bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Protein Kinase B (AKT) DNA Hypermethylation with Maintenance Atypical Antipsychotic Treatment in Patients with Bipolar Disorder
Authors: Burghardt Kyle J. , Seyoum Berhane , Dass Sabrina E. , Sanders Elani , Mallisho Abdullah , Yi Zhengping
Published: February 2018

Study Objective

Atypical antipsychotics cause insulin resistance that leads to an increased risk of diabetes mellitus and cardiovascular disease. Skeletal muscle is the primary tissue for uptake of glucose, and its dysfunction is considered one of the primary defects in the development of insulin resistance. Protein kinase B (AKT) plays an important role in overall skeletal muscle health and glucose uptake into the muscle. The objective of this study was to measure AKT isoform–specific gene methylation differences in the skeletal muscle of patients with bipolar disorder treated with atypical antipsychotic or mood stabilizer maintenance therapy.

Design

Cross‐sectional observational study.

Setting

Clinical research services center at an academic center.

Patients

Thirty patients with a confirmed diagnosis of bipolar disorder who were treated with either an atypical antipsychotic (16 patients) or mood stabilizer (14 patients) at a consistent dose for at least 3 months.

Interventions

A fasting skeletal muscle biopsy was performed in the vastus lateralis in each patient. Patients also underwent fasting blood sample collection and a standard 75‐g oral glucose tolerance test.

Measurements and Main Results

Skeletal muscle DNA methylation near the promoter region for three genes, AKT1, AKT2, and AKT3, was measured by methylation‐sensitive high‐resolution melting. Gene methylation was analyzed based on atypical antipsychotic versus mood stabilizer maintenance therapy. Associations between gene methylation, insulin resistance, and glucose tolerance were also analyzed. In patients treated with atypical antipsychotics, AKT1 and AKT2 methylation was increased compared with patients treated with mood stabilizers (p=0.03 and p=0.02, respectively). In addition, for patients receiving atypical antipsychotics, a positive trend for AKT2 hypermethylation with increasing insulin resistance was observed, whereas for patients receiving mood stabilizers, a trend for decreased AKT2 methylation with increasing insulin resistance was observed.

Conclusion

Overall, our findings suggest that the AKT gene is differentially methylated in the skeletal muscle of patients taking atypical antipsychotics or mood stabilizer maintenance therapy. These results may direct future approaches to reduce the harmful adverse effects of atypical antipsychotic treatment.
Antifungal constituents of the plant family Amaryllidaceae
Authors: Nair Jerald J. , van Staden Johannes
Published: February 2018

Globalization, the modern lifestyle, immuno‐suppressive agents, invasive surgical procedures, the loss of efficacies of existing drugs, and multidrug resistance are some of the factors used to explain the rise in fungal infections in recent years. Significant advances have been made in attempts to replace existing antifungal schedules, especially with synthetic targets. The identification of other platforms for drug discovery is now entrenched in research programs across the globe. Plants offer significant benefits owing to their numerical superiority, exceedingly broad chemical basis and appealing sustainability characteristics. Furthermore, plants have a long and rich historical association with traditional approaches towards fungal diseases. These have in numerous instances served as markers in the bioassay‐guided identification of the active constituents. Although the plant family Amaryllidaceae is conventionally associated with cancer and motor‐neuron disease chemotherapies, around 30 of its species have been examined for antifungal activities with microgram per millilitre inhibitory activities detected in several instances. This review focuses on the nearly 40 constituents from the family, mainly isoquinoline alkaloids, which have been screened against around 50 fungal pathogens. Encouragingly, microgram per millilitre growth inhibitory activities were applicable for several of the compounds with a minimum inhibitory concentration of 4 μg/ml seen to be the lowest.
System and path planning algorithm for low‐kV X‐ray free‐form surface irradiation
Authors: Rothfuss Andreas , Oesterle Oliver , Bürgy Daniel , Nwankwo Charles , Schneider Frank , van Poelgeest Auguste , Wenz Frederik , Stallkamp Jan , Clausen Sven
Published: February 2018

Objective: Intraoperative radiotherapy (IORT) after surgical resection using a low‐kV‐X‐ray source is a proven method used in cancer treatment. However, the shape and size of the targeted surface area are limited to the size of the available applicators. This can lead to nonconformal and therefore suboptimal treatment for many patients.

Methods: A system is proposed comprising an X‐ray source with an applicator for surface irradiation mounted on a robotic arm. This is controlled by an algorithm designed for planning the required continuous path, enabling irradiation of any desired shape with a controlled dose distribution.

Results: The system is shown to be capable of irradiating areas composed of rectangles on a flat surface with a homogeneity index of less than 7% inside the targeted area.

Conclusion: The presented results demonstrate the potential of the proposed setup to eliminate the current limitations, leading to better treatment of patients.
A closed‐loop nonlinear control and sliding mode estimation strategy for fluid flow regulation
Authors: Kidambi Krishna Bhavithavya , Ramos‐Pedroza Natalie , MacKunis William , Drakunov Sergey V.
Published: February 2018

Novel sliding mode observer (SMO) and robust nonlinear control methods are presented, which are shown to achieve finite‐time state estimation and asymptotic regulation of a fluid flow system. To facilitate the design and analysis of the closed‐loop active flow control (AFC) system, proper orthogonal decomposition–based model order reduction is utilized to express the Navier‐Stokes partial differential equations as a set of nonlinear ordinary differential equations. The resulting reduced‐order model contains a measurement equation that is in a nonstandard mathematical form. This challenge is mitigated through the detailed design and analysis of an SMO. The observer is shown to achieve finite‐time estimation of the unmeasurable states of the reduced‐order model using direct sensor measurements of the flow field velocity. The estimated states are utilized as feedback measurements in a closed‐loop AFC system. To address the practical challenge of actuator bandwidth limitations, the control law is designed to be continuous. A rigorous Lyapunov‐based stability analysis is presented to prove that the closed‐loop flow estimation and control method achieves asymptotic regulation of a fluid flow field to a prescribed state. Numerical simulation results are also provided to demonstrate the performance of the proposed closed‐loop AFC system, comparing 2 different designs for the SMO.
Re‐imagining the client‐side insight function
Authors: Geoghegan Andrew
Published: February 2018

Dealing with massive change provides exciting opportunities to innovate and transform how we work with insights.
MoS2‐QD‐Based Dual‐Model Photoluminescence Sensing Platform for Effective Determination of Al3+ and Fe3+ Simultaneously in Various Environment
Authors: Wu Qian , Wang Xiaojie , Jiang Yingnan , Sun Weiyi , Wang Chuanxi , Yang Minghui , Zhang Chi
Published: February 2018

The development of a sensitive sensing platform with multiple ions recognition ability in various environment is of great importance. In this paper, cysteine‐functionalized MoS2 quantum dots (Cys‐MoS2 QDs) with stable fluorescence are synthesized by a simple amidation reaction. The resultant Cys‐MoS2 QDs show good dispersion in aqueous solution and blue emission (λem= 428 nm) with a quantum yield (∼5%). The Cys‐MoS2 QDs drastically have improved the surface chemical reactivities, which exhibit sensitive and selective “turn‐on” response to Al3+ and “turn‐off” response to Fe3+ simultaneously. Furthermore, we testify the feasibility of applying this fluorescent probe for real sample analysis through the detection of Al3+ and Fe3+ ions in lake water and tap water. Moreover, using HeLa cells as the model, the resultant nanosensor is demonstrated to monitor Al3+ and Fe3+ ions in living cells. Thus, resultant Cys‐MoS2 QDs could be used as a “turn‐on” and “turn‐off” dual‐model photoluminescence sensing platform for effective determination of Al3+ and Fe3+ simultaneously in various environment.
New Heteropolycyclic Structures for Fluoride Anion Sensing by Naked‐Eye Visualization
Authors: Zhu Lei , Wen Ying , Liu Haoran , Zeng Zebing , Zhao Jingzhe , Jiang Jianhui , Miao Shaobin
Published: February 2018

Fluoride anion (F−) plays an important and fundamental role in chemical, biological, pathological, and environmental processes. It is highly desired to develop new methods for facial and efficient F− detection. Herein we present the synthesis and characterization of two effective fluoride ion probes and their selective F− sensing by naked‐eye visualization. A N‐heteroannelated anthraquinone derivative, compound I, was prepared by a cyclocondensation reaction of 1,2‐diaminoanthraquinone with 1,6‐bis(triisopropylsilyl)‐hexa‐l,5‐diyne‐3,4‐dione. Compound I was treated with malononitrile in the presence of Lehnert reagent to afford an HCl adduct, compound II, and an aza‐polycyclic aromatic compound III. All three compounds were characterized crystallographically and were studied photochemically. Similarly, 2,3‐diamino‐1,4‐anthraquinone reacted with 1,6‐bis(triisopropylsilyl)‐hexa‐l,5‐diyne‐3,4‐dione to afford compound IV, which reacted with malononitrile in the presence of Lehnert reagent to yield compound V. Compounds III and V are sensitive and selective probes for the detection of F− with significant color changes. The detection by naked eye visualization is rapid and facile, showing both compounds are potential probes for fluoride ion sensing.
pH‐Triggered 4,4′,4′′,4′′′‐(Ethene‐1,1,2,2‐tetrayl)tetrakis(N,N‐diethylaniline) with Aggregation‐Induced Emission (AIE) for Ablation of Cancer Cells
Authors: Yun Li Qiao , Yong Yang Zhan , Ting Su Wan , Yu Chen Dian , Wen Yang Gao , Feng Zou Deng
Published: February 2018

It is of great significance to develop compounds that can be soluble or dispersible in water and simultaneously remain high fluorescent in aqueous media. Compounds with aggregation induced emission (AIE) have a great potential as cell imaging agents. In this paper, 4,4′,4′′,4′′′‐(ethene‐1,1,2,2‐tetrayl)tetrakis(N,N‐diethylaniline) (denoted as ETTDA) with AIE was designed and prepared. DSPE‐PEG‐2000 (1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐(polyethylene glycol)‐Folate (sodium salt)‐2000) coated ETTDA nanoparticles (NPs) were used for treatment of four different kinds of cancer cells (HCT‐116 (human colon cancer cell), A549 (human caucasian lung carcinoma), Hela (human cervical cancer cells) and A2780 (ovarian carcinoma cells)) and cytotoxicity investigation shows it is highly sensitive to Hela, moderate sensitive to A549 and A2780 but low sensitive to HCT‐116. Furthermore, cell migration of ETTDA nanoparticles (NPs) on Hela shows that ETTDA NPs are capable of inhibiting the migration of Hela in vitro, indicating its potential ability to interfere with the transfer of tumor in vivo.
Hybrid NiCo2O4‐NiCo2S4 Nanoflakes as High‐Performance Anode Materials for Lithium‐Ion Batteries
Authors: Raj Shipra , Dong Yifan , Kar Pradip , Mai Liqiang , Jin Song , Roy Poulomi
Published: February 2018

The hybrid electrode with the combination of NiCo2O4 of inverse spinel structure and more conducting NiCo2S4 of normal spinel structure has been developed for next generation Li‐ion batteries. The hybrid nanostructures with the accessibility of both NiCo2O4 as well as NiCo2S4 showed almost 2‐fold better performance compared to pristine NiCo2O4. Apart from the doubled performance for hybrid materials, a significant cycling stability with 91.6% coulombic efficiency was achieved over 200 cycles. Such a high storage performance for the hybrid materials can be attributed not only to their normal spinel/inverse spinel combination, but also to the binder‐free direct deposition of materials on to the conductive 3D open Ni‐frame resulting high electrical conductivity and easy ionic diffusion.
Novel 1,2,3‐Triazole‐Functionalized 1,2‐Benzothiazine 1,1‐Dioxide Derivatives: Regioselective Synthesis, Biological Evaluation and Docking Studies
Authors: Swaroop Desireddy Krishna , Kumar Nagiri Ravi , Ratnakarreddy Kuchukulla , Raja Gopoju , Srigiridhar Kotamraju , Poornachandra Yedla , Kumar Chityal Ganesh , Babu Nanubolu Jagadeesh , Kumar Gunda Shravan , Narsaiah Banda
Published: February 2018

A series of novel 1,2‐benzothiazine‐1,1‐dioxide derivatives (Z)‐3‐hydroxy‐1‐(4‐hydroxy‐2‐methyl‐1,1‐dioxido‐2H‐benzo[e][1, 2]thiazin‐3‐yl)‐3‐phenyl substituted prop‐2‐en‐1‐one (6 a‐d) were synthesized starting from sodium salt of saccharin 1 in series of steps via 3‐acetyl‐2‐methyl‐1,1‐dioxido‐2H‐benzo[e][1, 2]thiazin‐4‐yl substituted benzoates (5 a‐d). Compound 6 e was obtained alternately from 1‐(4‐Hydroxy‐2‐methyl‐1,1‐dioxo‐1,2‐dihydro‐1λ6‐benzo[e][1, 2]thiazin‐3‐yl)‐ethanone (4). Compounds 6 a‐e were further reacted with aromatic azides to form (4‐hydroxy‐2‐methyl‐1,1‐dioxido‐2H‐benzo[e][1, 2]thiazin‐3‐yl)(1‐substitutedphenyl)‐5‐ substituted pheny or methyl‐1H‐1,2,3‐triazol‐4‐yl)methanone derivatives (7 a‐o) by regioselective cyclization. All the compounds were evaluated for anti‐inflammatory and anti‐cancer activities. Compounds 5 a‐b, 6 a‐b, 7 a, 7 c‐d, 7 i and 7 k‐l which showed significant anti‐inflammatory activity at micro molar concentration have been identified. Also screened for cytotoxic activity against four human cancer cells and one normal cell such as prostate cancer (PC‐3), breast adenocarcinoma (MDA‐MB‐231), liver hepatocellular carcinoma (Hep G2), cervical cancer (HeLa) and normal umbilical vein endothelial cell (HUVEC). Compounds 6 a, 7 g, 7 h and 7 k have been identified as promising candidates. Further, anti‐inflammatory activity is also validated by docking studies and compounds 5 a, 5 b and 7 d found to show good interactions when docked with IL‐1β signaling complex.
Synergistic Nanotubular Copper‐Doped Nickel Catalysts for Hydrogen Evolution Reactions
Authors: Sun Qiangqiang , Dong Yujuan , Wang Zenglin , Yin Shiwei , Zhao Chuan
Published: February 2018

Developing highly active electrocatalysts with low cost and high efficiency for hydrogen evolution reactions (HERs) is of great significance for industrial water electrolysis. Herein, a 3D hierarchically structured nanotubular copper‐doped nickel catalyst on nickel foam (NF) for HER is reported, denoted as Ni(Cu), via facile electrodeposition and selective electrochemical dealloying. The as‐prepared Ni(Cu)/NF electrode holds superlarge electrochemical active surface area and exhibits Pt‐like electrocatalytic activity for HER, displaying an overpotential of merely 27 mV to achieve a current density of 10 mA cm−2 and an extremely small Tafel slope of 33.3 mV dec−1 in 1 m KOH solution. The Ni(Cu)/NF electrode also shows excellent durability and robustness in both continuous and intermittent bulk water electrolysis. Density functional theory calculations suggest that Cu substitution and the formation of NiO on the surface leads to more optimal free energy for hydrogen adsorption. The lattice distortion of Ni caused by Cu substitution, the increased interfacial activity induced by surface oxidation of nanoporous Ni, and numerous active sites at Ni atom offered by the 3D hierarchical porous structure, all contribute to the dramatically enhanced catalytic performance. Benefiting from the facile, scalable preparation method, this highly efficient and robust Ni(Cu)/NF electrocatalyst holds great promise for industrial water–alkali electrolysis.
Retracted: Dual Effects of Nanostructuring and Oxygen Vacancy on Photoelectrochemical Water Oxidation Activity of Superstructured and Defective Hematite Nanorods
Authors: Wang Lei , Marcus Kyle , Huang Xiaojuan , Shen Zhiqiang , Yang Yang , Bi Yingpu
Published: February 2018

An Ar atmospheric treatment is rationally used to etch and activate hematite nanoflakes (NFs) as photoanodes toward enhanced photoelectrochemical water oxidation. The formation of a highly ordered hematite nanorods (NRs) array containing a high density of oxygen vacancy is successfully prepared through in situ reduction of NFs in Ar atmosphere. Furthermore, a hematite (104) plane and an iron suboxide layer at the absorber/back‐contact interface are formed. The material defects produced by a thermal oxidation method can be critical for the morphology transformation from 2D NFs to 1D NRs. The resulting hematite NR photoanodes show high efficiency toward solar water splitting with improved light harvesting capabilities, leading to an enhanced photoresponse due to the artificially formed oxygen vacancies.
A Flexible Stretchable Hydrogel Electrolyte for Healable All‐in‐One Configured Supercapacitors
Authors: Guo Ying , Zheng Kaiqiang , Wan Pengbo
Published: February 2018

The development of integrated high‐performance supercapacitors with all‐in‐one configuration, excellent flexibility and autonomously intrinsic self‐healability, and without the extra healable film layers, is still tremendously challenging. Compared to the sandwich‐like laminated structures of supercapacitors with augmented interfacial contact resistance, the flexible healable integrated supercapacitor with all‐in‐one structure could theoretically improve their interfacial contact resistance and energy densities, simplify the tedious device assembly process, prolong the lifetime, and avoid the displacement and delamination of multilayered configurations under deformations. Herein, a flexible healable all‐in‐one configured supercapacitor with excellent flexibility and reliable self‐healing ability by avoiding the extra healable film substrates and the postassembled sandwich‐like laminated structures is developed. The healable all‐in‐one configured supercapacitor is prepared from in situ polymerization and deposition of nanocomposites electrode materials onto the two‐sided faces of the self‐healing hydrogel electrolyte separator. The self‐healing hydrogel film is obtained from the physically crosslinked hydrogel with enormous hydrogen bonds, which can endow the healable capability through dynamic hydrogen bonding. The assembled all‐in‐one configured supercapacitor exhibits enhanced capacitive performance, good cycling stability, reliable self‐healing capability, and excellent flexibility. It holds broad prospects for obtaining various flexible healable all‐in‐one configured supercapacitors for working as portable energy storage devices in wearable electronics.
The Vasoreparative Function of Myeloid Angiogenic Cells Is Impaired in Diabetes Through the Induction of IL1β
Authors: Chambers Sarah E. J. , O'Neill Christina L. , Guduric-Fuchs Jasenka , McLoughlin Kiran J. , Liew Aaron , Egan Aoife M. , O'Brien Timothy , Stitt Alan W. , Medina Reinhold J.
Published: February 2018

Myeloid angiogenic cells (MACs) promote revascularization through the paracrine release of angiogenic factors and have been harnessed as therapeutic cells for many ischemic diseases. However, their proangiogenic properties have been suggested to be diminished in diabetes. This study investigates how the diabetic milieu affects the immunophenotype and function of MACs. Both MACs isolated from diabetic conditions and healthy cells exposed to a diabetic environment were used to determine the potential of MACs as a cell therapy for diabetic-related ischemia. MACs were isolated from human peripheral blood and characterized alongside proinflammatory macrophages M (LPS + IFNγ) and proangiogenic macrophages M (IL4). Functional changes in MACs in response to high-d-glucose were assessed using an in vitro 3D-tubulogenesis assay. Phenotypic changes were determined by gene and protein expression analysis. Additionally, MACs from type 1 diabetic (T1D) patients and corresponding controls were isolated and characterized. Our evidence demonstrates MACs identity as a distinct macrophage subtype that shares M2 proangiogenic characteristics, but can be distinguished by CD163hi expression. High-d-glucose treatment significantly reduced MACs proangiogenic capacity, which was associated with a significant increase in IL1β mRNA and protein expression. Inhibition of IL1β abrogated the antiangiogenic effect induced by high-d-glucose. IL1β was also significantly upregulated in MACs isolated from T1D patients with microvascular complications compared to T1D patients without microvascular complications or nondiabetic volunteers. This study demonstrates that Type 1 diabetes and diabetic-like conditions impair the proangiogenic and regenerative capacity of MACs, and this response is mediated by IL-1β.
Identification of Adult Mesodermal Progenitor Cells and Hierarchy in Atherosclerotic Vascular Calcification
Authors: Cho Hyun-Jai , Lee Jin-Woo , Cho Hyun-Ju , Lee Choon-Soo , Kim Hyo-Soo
Published: February 2018

The nature of calcifying progenitor cells remains elusive. In this study, we investigated the developmental hierarchy and dynamics of progenitor cells. In vitro and in vivo reconstitution assays demonstrated that Sca-1+/PDGFRα– cells in the bone marrow (BM) are the ancestors of Sca-1+/PDGFRα+ cells. Cells of CD29 + Sca-1+/PDGFRα– lineage in the BM showed both hematopoietic potential with osteoclastic differentiation ability as well as mesenchymal stem cell-like properties with osteoblastic differentiation potential. Clonally-isolated BM-derived artery-infiltrated Sca-1+/PDGFRα– cells maintained osteoblastic/osteoclastic bipotency but lost hematopoietic activity. In hypercholesterolemic apolipoprotein-E-deficient (Apoe-/-) mice, the mobilization from BM to peripheral circulation, followed by migration into atherosclerotic plaques of Sca-1+/PDGFRα– cells, but not Sca-1+/PDGFRα+ cells, were significantly decreased, and Interleukin-1β (IL-1β) and Interleukin-5 (IL-5) mediated this response. Here, we demonstrated that Sca-1+/PDGFRα– cells are mesodermal progenitor cells in adults, and the dynamics of progenitor cells were regulated by atherosclerosis-related humoral factors. These results may contribute to better understanding of vascular homeostasis and assist in the development of novel therapies for atherosclerosis.
Synthesis, Characterization, Uses and Applications of Porous Clays Heterostructures: A Review
Authors: Cecilia J. A. , García‐Sancho C. , Vilarrasa‐García E. , Jiménez‐Jiménez J. , Rodriguez‐Castellón E.
Published: February 2018

Porous clay heterostructures (PCH) are obtained by the insertion of an organic bulky cation in the interlayer spacing of a smectite, causing a swelling of the clay mineral. Right after, oxides species, mainly silicon oxide, are incorporated as pillars galleries between adjacent layers to form a porous structure after the removal of the template. The ordering of the clay mineral as well the organic cation incorporated in the synthetic step favors the modulation of the textural properties of the PCH. In addition, the incorporation of heteroatoms in the pillars galleries can also modulate the acidity of the PCH. The modulation of the pore size and the acid properties provides to these materials a wide range of applications in the fields of adsorption and catalysis. This paper carries out a detailed review of the synthesis of PCH, characterization as well as uses and application reported in the literature.
NF‐κB/p53‐activated inflammatory response involves in diquat‐induced mitochondrial dysfunction and apoptosis
Authors: Choi Su Eun , Park Yun Sun , Koh Hyun Chul
Published: February 2018

Inflammation generated by environmental toxicants including pesticides could be one of the factors underlying neuronal cell damage in neurodegenerative diseases. In this study, we investigated the mechanisms by which inflammatory responses contribute to apoptosis in PC12 cells treated with diquat. We found that diquat induced apoptosis, as demonstrated by the activation of caspases and nuclear condensation, inhibition of mitochondrial complex I activity, and decreased ATP level in PC12 cells. Diquat also reduced the dopamine level, indicating that cell death induced by diquat is due to cytotoxicity of dopaminergic neuronal components in these cells. Exposure of PC12 cells to diquat led to the production of reactive oxygen species (ROS), and the antioxidant N‐acetyl‐cystein attenuated the cytotoxicity of caspase‐3 pathways. These results demonstrate that diquat‐induced apoptosis is involved in mitochondrial dysfunction through production of ROS. Furthermore, diquat increased expression of cyclooxygenase‐2 (COX‐2) and tumor necrosis factor‐α (TNF‐α) via inflammatory stimulation. Diquat induced nuclear accumulation of NF‐κB and p53 proteins. Importantly, an inhibitor of NF‐κB nuclear translocation blocked the increase of p53. Both NF‐κB and p53 inhibitors also blocked the diquat‐induced inflammatory response. Pretreatment of cells with meloxicam, a COX‐2 inhibitor, also blocked apoptosis and mitochondrial dysfunction. These results represent a unique molecular characterization of diquat‐induced cytotoxicity in PC12 cells. Our results demonstrate that diquat induces cell damage in part through inflammatory responses via NF‐κB‐mediated p53 signaling. This suggests the potential to generate mitochondrial damage via inflammatory responses and inflammatory stimulation‐related neurodegenerative disease.
Accuracy and reproducibility of fetal‐fraction measurement using relative quantitation at polymorphic loci with microarray
Authors: Schmid M. , White K. , Stokowski R. , Miller D. , Bogard P. E. , Valmeekam V. , Wang E.
Published: February 2018

Objectives

Various methods of fetal‐fraction measurement have been employed in conjunction with different approaches to cell‐free DNA testing for fetal aneuploidy. In this study, we determined the accuracy and reproducibility of fetal‐fraction measurement using polymorphic assays that are incorporated into the test design as part of the Harmony® prenatal test and evaluated whether the single nucleotide polymorphisms selected for and used in these assays can be applied broadly to all patient populations.

Methods

Clinical maternal plasma samples were assayed using a custom microarray with Digital ANalysis of Selected Regions (DANSR) assays designed to cover non‐polymorphic targets on chromosomes of interest for aneuploidy assessment (13, 18, 21, X and Y) and polymorphic targets for fetal‐fraction assessment. In a consecutive series of 47 512 maternal plasma samples, fetal‐fraction measurements based on polymorphic assays were compared with those from Y‐sequence quantitation. Reproducibility was examined between first‐ and second‐tube measurements for the same patient sample in 734 cases. The fraction of informative loci was calculated for 13 988 samples.

Results

There was a strong correlation between fetal fractions determined using the polymorphic assays and using Y‐chromosome sequence quantitation (r = 0.97). Fetal‐fraction measurement between the first and second tubes was highly reproducible (r = 0.98). The fraction of informative loci observed in a clinical series was consistent with predictions based on assay design.

Conclusions

The method based on relative quantitation at polymorphic loci on a microarray is accurate and reproducible for fetal‐fraction estimation and is equally informative across global populations. This study provides a useful benchmark for ensuring the reliability and accuracy of fetal‐fraction measurement. © 2018 Roche Sequencing Solutions. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
Outcome of fetuses with prenatal diagnosis of isolated severe bilateral ventriculomegaly: systematic review and meta‐analysis
Authors: Carta S. , Kealin Agten A. , Belcaro C. , Bhide A.
Published: February 2018

Objective

To quantify from the published literature survival and neurodevelopmental outcome of fetuses with prenatally detected isolated severe bilateral ventriculomegaly.

Methods

MEDLINE, EMBASE and the Cochrane Library were searched electronically. Only cases with a prenatal diagnosis of apparently isolated severe ventriculomegaly and postnatal neurodevelopmental assessment were selected and included. Severe ventriculomegaly was defined as enlargement of the ventricular atria, with a diameter of greater than 15 mm in the transventricular plane. All cases in which the investigators were unable to detect associated structural abnormality, chromosomal abnormality or fetal infection, and in which the ventriculomegaly was therefore regarded as apparently isolated, were included. Those for which the etiology was identified prenatally were excluded, whereas those with postnatal identification of the underlying cause were not excluded, since this information was not available prenatally. The quality of the included studies was assessed using the Newcastle–Ottawa Scale (NOS) for cohort studies. Pregnancy outcomes such as termination, stillbirth, neonatal survival and developmental outcome of the baby, were recorded. The degree of disability was classified as no, mild or severe disability. Statistical assessment was performed by meta‐analysis of proportions to combine data, weighting the studies using the inverse variance method and a random‐effects model. Proportions and CIs were reported.

Results

Eleven studies including 137 fetuses were found. Twenty‐seven pregnancies underwent termination and were excluded. The remaining 110 fetuses with apparently isolated severe ventriculomegaly for which continuation of pregnancy was intended, form the study population. Overall quality assessed using NOS for cohort studies was good. Survival was reported in 95/110 (pooled proportion 87.9% (95% CI, 75.6–96.2%)) cases. In 15/110 (pooled proportion 12.1% (95% CI, 3.8–24.4%)), either stillbirth or neonatal demise was reported. No disability was reported in 41/95 survivors (pooled proportion 42.2% (95% CI, 27.5–57.6%)). However, 17/95 showed mild/moderate disability (pooled proportion 18.6% (95% CI, 7.2–33.8%)) and 37/95 were reported to have severe disability (pooled proportion 39.6% (95% CI, 30.0–50.0%)).

Conclusions

Four‐fifths of fetuses with severe ventriculomegaly survive and, of these, just over two‐fifths show normal neurodevelopment. The overall survivors without disability account for more than one third of the total. Given that many cases undergo termination of pregnancy and require longer follow‐up in order to detect subtle abnormalities, mortality and prevalence of developmental delay may be even higher than that reported in this paper. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Substrate preferences of coexisting invasive amphipods, Dikerogammarus villosus and Dikerogammarus haemobaphes, under field and laboratory conditions
Authors: Clinton K. E. , Mathers K. L. , Constable D. , Gerrard C. , Wood P. J.
Published: February 2018

Two Ponto-Caspian amphipods, Dikerogammarus villosus and Dikerogammarus haemobaphes, have expanded their geographical ranges from eastern Europe into Great Britain in recent years. This study represents one of the first examining the distribution and habitat preferences of coexisting populations of D. haemobaphes and D. villosus via field and laboratory experiments in the UK. Field surveys of a recently invaded lowland reservoir in the UK are complimented with ex situ laboratory mesocosm experiments examining the substrate preferences of coexisting populations of D. villosus and D. haemobaphes. Results from the field study indicated that D. haemobaphes dominated the macroinvertebrate community within the reservoir and demonstrated a strong affinity for large cobble and artificial substrates. D. villosus occurred at lower abundances but displayed a strong preference for coarse cobble substrates. A third invasive amphipod, Crangonyx pseudogracilis, was largely confined to sand/silt habitats. Laboratory mesocosm experiments clearly supported the field observations of D. villosus and D. haemobaphes with both species demonstrating a preference for cobble substrates. Results from the study highlight the importance of characterising physical habitat when investigating biological invasions and suggest that habitat availability may influence the extent and speed at which range expansion of new amphipod invaders occurs.
The Massive Online Needs Assessment (MONA) to inform the development of an emergency haematology educational blog series
Authors: Chan Teresa M. , Jo David , Shih Andrew W. , Bhagirath Vinai C. , Castellucci Lana A. , Yeh Calvin , Thoma Brent , Tseng Eric K. , De Wit Kerstin
Published: February 2018

Background Online educational resources are criticized as being teacher-centred, failing to address learner’s needs. Needs assessments are an important precursor to inform curriculum development, but these are often overlooked or skipped by developers of online educational resources due to cumbersome measurement tools. Novel methods are required to identify perceived and unperceived learning needs to allow targeted development of learner-centred curricula.
Objectives To evaluate the feasibility of performing a novel technique dubbed the Massive Online Needs Assessment (MONA) for the purpose of emergency haematology online educational curricular planning, within an online learning community (affiliated with the Free Open Access Medical education movement).
Methods An online survey was launched on CanadiEM.org using an embedded Google Forms survey. Participants were recruited using the study website and a social media campaign (utilizing Twitter, Facebook, Blogs, and a poster) targeting a specific online community. Web analytics were used to monitor participation rates in addition to survey responses.
Results The survey was open from 20 September to 10 December 2016 and received 198 complete responses representing 6 medical specialties from 21 countries. Most survey respondents identified themselves as staff physicians (n = 109) and medical trainees (n = 75). We identified 17 high-priority perceived needs, 17 prompted needs, and 10 topics with unperceived needs through our MONA process.
Conclusions A MONA is a feasible, novel method for collecting data on perceived, prompted, and unperceived learning needs to inform an online emergency haematology educational blog.
i-Assess: Evaluating the impact of electronic data capture for OSCE
Authors: Monteiro Sandra , Sibbald Debra , Coetzee Karen
Published: February 2018

Introduction Tablet-based assessments offer benefits over scannable-paper assessments; however, there is little known about the impact to the variability of assessment scores.

Methods Two studies were conducted to evaluate changes in rating technology. Rating modality (paper vs tablets) was manipulated between candidates (Study 1) and within candidates (Study 2). Average scores were analyzed using repeated measures ANOVA, Cronbach’s alpha and generalizability theory. Post-hoc analyses included a Rasch analysis and McDonald’s omega.

Results Study 1 revealed a main effect of modality (F (1,152) = 25.06, p < 0.01). Average tablet-based scores were higher, (3.39/5, 95% CI = 3.28 to 3.51), compared with average scan-sheet scores (3.00/5, 95% CI = 2.90 to 3.11). Study 2 also revealed a main effect of modality (F (1, 88) = 15.64, p < 0.01), however, the difference was reduced to 2% with higher scan-sheet scores (3.36, 95% CI = 3.30 to 3.42) compared with tablet scores (3.27, 95% CI = 3.21 to 3.33). Internal consistency (alpha and omega) remained high (>0.8) and inter-station reliability remained constant (0.3). Rasch analyses showed no relationship between station difficulty and rating modality.

Discussion Analyses of average scores may be misleading without an understanding of internal consistency and overall reliability of scores. Although updating to tablet-based forms did not result in systematic variations in scores, routine analyses ensured accurate interpretation of the variability of assessment scores.

Conclusion This study demonstrates the importance of ongoing program evaluation and data analysis.
Delayed Tibial-platform Periprosthetic Stress Fracture after Unicompartmental Knee Arthroplasty: Uncommon and Devastating Complication
Authors: Yuk-Wah Hung , Jason Chi-Ho Fan , Carson Ka-Bon Kwok , Ellis Lok-Fai Wong , Carman Ka-Man Lo
Published: February 2018

Periprosthetic fracture around total knee arthroplasty (TKA) is a well-described complication. Yet, report of medial tibial plateau stress fracture after unicompartmental knee arthroplasty (UKA) is limited. One case of delayed stress fracture of medial tibial plateau after UKA, which was salvaged by conversion to TKA was reported. To the best of our knowledge, this is the first report related to Zimmer Unicompartmental High Flex Knee system (fixed bearing). The possible reasons were analysed, and tips and tricks to avoid this complication were shared. With reference to our case, osteoporosis should be considered as one of the relative contraindication for UKA. Meticulous surgical technique and avoiding multiple pin holes for tibial tray cannot be overlooked.
Investigation on microstructure evolution of a new disk superalloy under different hot process
Authors: Jia Chonglin , Zhang Fenglin , Li Yang , Lv Shaomin , Ge Changchun
Published: February 2018

Over the course of this paper, a FGH100L nickel based alloy, which was prepared by spray forming, had been treated by hot isostatic pressing, followed by an optimized heat treatment. The microstructure evolution of gamma prime phase under different conditions was systematically analyzed. In conclusion, both the temperature and cooling rate during the heat treatment can affect gamma prime phase on its morphology, size and distribution. By varying solution treatment temperature, size variation of γ′ phase and fine-grain microstructure was obtained at a relatively low solution treatment temperature. As for changing cooling rate, a doublet morphology of splitting γ′ phase appeared at a relatively slow cooling rate under hot isostatic pressing progress. Based on microstructural characterization of γ′ phase, the reasonable heat treatment regime of FGH100L alloy was determined. The deformation recrystallization occurred when the as-deposited alloy was treated by hot isostatic pressing, which results in grain morphology changing from spherical or sphere-like to polygon. It can be obtained multi-sized γ′ precipitates for the hot isostatic pressing alloy which treated by optimized heat treatment regime. The results indicate that the multi-sized γ′ phase microstructure is beneficial to obtain ideal comprehensive mechanical properties.
Comparing the Bioburden Measured by Adenosine Triphosphate (ATP) Luminescence Technology to Contact Plate–Based Microbiologic Sampling to Assess the Cleanliness of the Patient Care Environment
Authors: Salsgiver Elizabeth , Bernstein Daniel , Simon Matthew S. , Greendyke William , Jia Haomiao , Robertson Amy , Salter Selma , Schuetz Audrey N. , Saiman Lisa , Furuya E. Yoko , Calfee David P.
Published: February 2018

The correlation between ATP concentration and bacterial burden in the patient care environment was assessed. These findings suggest that a correlation exists between ATP concentration and bacterial burden, and they generally support ATP technology manufacturer-recommended cutoff values. Despite relatively modest discriminative ability, this technology may serve as a useful proxy for cleanliness.

Infect Control Hosp Epidemiol 2018;39:622–624
Dynamic stall in vertical axis wind turbines: scaling and topological considerations
Authors: Buchner Abel-John , Soria Julio , Honnery Damon , Smits Alexander J.
Published: February 2018

Vertical axis wind turbine blades are subject to rapid, cyclical variations in angle of attack and relative airspeed which can induce dynamic stall. This phenomenon poses an obstacle to the greater implementation of vertical axis wind turbines because dynamic stall can reduce turbine efficiency and induce structural vibrations and noise. This study seeks to provide a more comprehensive description of dynamic stall in vertical axis wind turbines, with an emphasis on understanding its parametric dependence and scaling behaviour. This problem is of practical relevance to vertical axis wind turbine design but the inherent coupling of the pitching and velocity scales in the blade kinematics makes this problem of more broad fundamental interest as well. Experiments are performed using particle image velocimetry in the vicinity of the blades of a straight-bladed gyromill-type vertical axis wind turbine at blade Reynolds numbers of between 50 000 and 140 000, tip speed ratios between $\unicode[STIX]{x1D706}=1$ to $\unicode[STIX]{x1D706}=5$, and dimensionless pitch rates of $0.10\leqslant K_{c}\leqslant 0.20$. The effect of these factors on the evolution, strength and timing of vortex shedding from the turbine blades is determined. It is found that tip speed ratio alone is insufficient to describe the circulation production and vortex shedding behaviour from vertical axis wind turbine blades, and a scaling incorporating the dimensionless pitch rate is proposed.
Performance tests of IPPLM's krypton Hall thruster
Authors: Kurzyna Jacek , Jakubczak Maciej , Szelecka Agnieszka , Dannenmayer Käthe
Published: February 2018

The Institute of Plasma Physics and Laser Microfusion's (IPPLM) Hall effect thruster (Krypton Large IMpulse Thruster, KLIMT) is a 500 W class plasma engine with a mean diameter of discharge channel of 42 mm. KLIMT was developed within ESA/PECS project aiming to provide relatively small thruster for satellites that would be able to effectively operate with krypton propellant. Being several times less expensive than xenon, which is regarded as a propellant of choice for electric propulsion of electrostatic type, krypton since years has been suggested as an attractive alternative. In this paper, a design as well as performance tests of the laboratory model of KLIMT are discussed. It is shown that precise adjustment of magnetic field topography results in the stable operation of the thruster in wide range of operating conditions providing similar thrust and specific impulse production for both propellants. Maximum thrust produced with the use of xenon and krypton reached about 16–17 mN for mass flow rate of 1.15–1.2 mg/s resulting in specific impulse in the range of 1300–1500 s (13–15 km/s). However, for krypton the anode efficiency drops by ~10% in comparison with xenon. For krypton plasma beam divergence as measured by an average half-angle with respect to the beam axis was found to remain within the range of 19–23° for the whole set of the examined operating conditions. The reported characteristics are reasonable for Hall thruster of the discussed size and power.
Clearance-driven motion planning for mobile robots with differential constraints
Authors: Plaku Evis , Plaku Erion , Simari Patricio
Published: February 2018

This paper presents an approach that integrates the geometric notion of clearance (distance to the closest obstacle) into sampling-based motion planning to enable a robot to safely navigate in challenging environments. To reach the goal destination, the robot must obey geometric and differential constraints that arise from the underlying motion dynamics and the characteristics of the environment. To produce safe paths, the proposed approach expands a motion tree of collision-free and dynamically feasible motions while maintaining locally maximal clearance. In distinction from related work, rather than explicitly constructing the medial axis, the proposed approach imposes a grid or a triangular tessellation over the free space and uses the clearance information to construct a weighted graph where edges that connect regions with low clearance have high cost. Minimum-cost paths over this graph produce high-clearance routes that tend to follow the medial axis without requiring its explicit construction. A key aspect of the proposed approach is a route-following component which efficiently expands the motion tree to closely follow such high-clearance routes. When expansion along the current route becomes difficult, edges in the tessellation are penalized in order to promote motion-tree expansions along alternative high-clearance routes to the goal. Experiments using vehicle models with second-order dynamics demonstrate that the robot is able to successfully navigate in complex environments. Comparisons to the state-of-the-art show computational speedups of one or more orders of magnitude.
Report on Spiritualism of the Committee of the London Dialectical Society, together with the Evidence, oral and written, and a Selection from the Correspondence. Longman and Co. 1871
Authors: Huxley T. H.
Published: February 2018

The London Dialectical Society appointed a committee to examine the phenomena of so-called Spiritualism, the result of which has been a report that is not unlikely to be quoted by future historians, as striking evidence of the credulity and ignorance of many persons who had received the average education of the time. It is of some interest, scientifically, in relation to the doctrine of evolution, as it proves the persistence, in modern thought, of ideas and feelings which belong properly to the stage of mental evolution of our savage ancestors. It is, in fact, like the custom of wearing ear-rings, decided evidence of our descent from savages; we have plainly not yet outgrown some of their superstitions, just as we have not yet got rid of the little point of the ear which betrays our descent from a hairy animal with pointed ears.
The Physiognomy of Insanity
Authors: Conolly John , C. L. R.
Published: February 2018

Dr. Conolly has recently concluded a series of thirteen papers on the Physiognomy of Insanity, in the Medical Times and Gazette, illustrated by some very beautiful photographs from the portfolio of our accomplished associate Dr. Diamond, of Twickenham. We shall in this place make a few selections from the observations bearing on the general question of mental disease, and its exciting causes, with which Dr. Conolly has interspersed his special remarks on the individual portraits before him. The several papers are written with that grace and felicity of expression all Dr. Conolly's literary contributions.
Crystal structure of pemetrexed disodium heptahydrate, C20H33N5Na2O13 (Alimta)
Authors: Kaduk James A. , Gindhart Amy M. , Blanton Thomas N.
Published: February 2018

The crystal structure of pemetrexed disodium heptahydrate has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Pemetrexed disodium heptahydrate crystallizes in space group P21 (#4) with a = 11.732 697(27), b = 5.244 195(14), c = 21.689 00(6) Å, β = 92.663 90(20)°, V = 1333.051(6) Å3, and Z = 2. Each of the two ionized carboxylate groups acts as a unidentate ligand to a Na cation. The remaining five positions of the octahedral coordination spheres are occupied by water molecules. The Na octahedra share an edge to form pairs. These pairs share corners to form chains along the b-axis. All of the water molecule hydrogen atoms act as hydrogen bond donors. In addition the hydrogen atoms associated with the nitrogen atoms and amino groups of the pemetrexed anion were also observed to act as hydrogen bond donors. The powder pattern has been submitted to the International Centre for Diffraction Data (ICDD) for inclusion in the Powder Diffraction File™.