bluuebunny/crossref_metadata_2025 huggingface dataset:
A quantitative benefit–risk assessment approach to improve decision making in drug development: Application of a multicriteria decision analysis model in the development of combination therapy for overactive bladder
Authors: de Greef‐van der Sandt I , Newgreen D , Schaddelee M , Dorrepaal C , Martina R , Ridder A , van Maanen R
Published: September 2015

A multicriteria decision analysis (MCDA) approach was developed and used to estimate the benefit–risk of solifenacin and mirabegron and their combination in the treatment of overactive bladder (OAB). The objectives were 1) to develop an MCDA tool to compare drug effects in OAB quantitatively, 2) to establish transparency in the evaluation of the benefit–risk profile of various dose combinations, and 3) to quantify the added value of combination use compared to monotherapies. The MCDA model was developed using efficacy, safety, and tolerability attributes and the results of a phase II factorial design combination study were evaluated. Combinations of solifenacin 5 mg and mirabegron 25 mg and mirabegron 50 (5+25 and 5+50) scored the highest clinical utility and supported combination therapy development of solifenacin and mirabegron for phase III clinical development at these dose regimens. This case study underlines the benefit of using a quantitative approach in clinical drug development programs.
Highly Efficient Organocatalyzed Conversion of Oxiranes and CO2 into Organic Carbonates
Authors: Sopeña Sergio , Fiorani Giulia , Martín Carmen , Kleij Arjan W.
Published: September 2015

Invited for the cover of this issue is the group of Arjan Kleij at the Institute of Chemical Research of Catalonia (ICIQ). The image shows how naturally occurring compounds such as tannic acid can be used to devise highly efficient CO2 conversion catalysis. The Full Paper itself is available at 10.1002/cssc.201500710.
Fast‐scale stability limits of a two‐stage boost power converter
Authors: El Aroudi Abdelali , Mandal Kuntal , Giaouris Damian , Banerjee Soumitro , Abusorrah Abdullah , Al Hindawi Mohammed , Al‐Turki Yusuf
Published: September 2015

There are many applications in power electronics that demand high step‐up conversion ratio between the source and the load. A simple way of achieving such a high voltage ratio is by cascading DC–DC boost converters in a few stages. The individual converters in such a cascaded system are usually designed separately applying classical design criteria. This paper investigates the stability of the overall system of a cascade connection of two boost converters under current mode control. We first demonstrate the bifurcation behavior of the system, and it is shown that the desired periodic orbit can undergo fast‐scale period doubling bifurcation leading to subharmonic oscillations and chaotic regimes under parameter variation. The value of the intermediate capacitor is taken as a design parameter, and we determine the minimum ramp slope in the first stage required to maintain stability. It is shown that smaller capacitance values give rise to wider stability range. We explain the bifurcation phenomena using a full‐order model. Then, in order to simplify the analysis and to obtain a closed‐form expression to explain the previous observation, we develop a reduced‐order model by treating the second stage as a current sink. This allows us to obtain design‐oriented stability boundaries in the parameter space by taking into account slope interactions between the state variables in the two stages. Copyright © 2015 John Wiley & Sons, Ltd.
Fish attraction to artificial reefs not always harmful: a simulation study
Authors: Smith James A. , Lowry Michael B. , Suthers Iain M.
Published: September 2015

The debate on whether artificial reefs produce new fish or simply attract existing fish biomass continues due to the difficulty in distinguishing these processes, and there remains considerable doubt as to whether artificial reefs are a harmful form of habitat modification. The harm typically associated with attraction is that fish will be easier to harvest due to the existing biomass aggregating at a newly deployed reef. This outcome of fish attraction has not progressed past an anecdotal form, however, and is always perceived as a harmful process. We present a numerical model that simulates the effect that a redistributed fish biomass, due to an artificial reef, has on fishing catch per unit effort (CPUE). This model can be used to identify the scenarios (in terms of reef, fish, and harvest characteristics) that pose the most risk of exploitation due to fish attraction. The properties of this model were compared to the long‐standing predictions by Bohnsack (1989) on the factors that increase the risk or the harm of attraction. Simulations revealed that attraction is not always harmful because it does not always increase maximum fish density. Rather, attraction sometimes disperses existing fish biomass making them harder to catch. Some attraction can be ideal, with CPUE lowest when attraction leads to an equal distribution of biomass between natural and artificial reefs. Simulations also showed that the outcomes from attraction depend on the characteristics of the target fish species, such that transient or pelagic species are often at more risk of harmful attraction than resident species. Our findings generally agree with Bohnsack's predictions, although we recommend distinguishing “mobility” and “fidelity” when identifying species most at risk from attraction, as these traits had great influence on patterns of harvest of attracted fish biomass.
Evidence of niche shift and global invasion potential of the Tawny Crazy ant, Nylanderia fulva
Authors: Kumar Sunil , LeBrun Edward G. , Stohlgren Thomas J. , Stabach Jared A. , McDonald Danny L. , Oi David H. , LaPolla John S.
Published: September 2015

Analysis of an invasive species' niche shift between native and introduced ranges, along with potential distribution maps, can provide valuable information about its invasive potential. The tawny crazy ant, Nylanderia fulva, is a rapidly emerging and economically important invasive species in the southern United States. It is originally from east‐central South America and has also invaded Colombia and the Caribbean Islands. Our objectives were to generate a global potential distribution map for N. fulva, identify important climatic drivers associated with its current distribution, and test whether N. fulva's realized climatic niche has shifted across its invasive range. We used MaxEnt niche model to map the potential distribution of N. fulva using its native and invaded range occurrences and climatic variables. We used principal component analysis methods for investigating potential shifts in the realized climatic niche of N. fulva during invasion. We found strong evidence for a shift in the realized climatic niche of N. fulva across its invasive range. Our models predicted potentially suitable habitat for N. fulva in the United States and other parts of the world. Our analyses suggest that the majority of observed occurrences of N. fulva in the United States represent stabilizing populations. Mean diurnal range in temperature, degree days at ≥10°C, and precipitation of driest quarter were the most important variables associated with N. fulva distribution. The climatic niche expansion demonstrated in our study may suggest significant plasticity in the ability of N. fulva to survive in areas with diverse temperature ranges shown by its tolerance for environmental conditions in the southern United States, Caribbean Islands, and Colombia. The risk maps produced in this study can be useful in preventing N. fulva's future spread, and in managing and monitoring currently infested areas.
Prognostic implication of right ventricular involvement in peripartum cardiomyopathy: a cardiovascular magnetic resonance study
Authors: Haghikia Arash , Röntgen Philipp , Vogel‐Claussen Jens , Schwab Johannes , Westenfeld Ralf , Ehlermann Philipp , Berliner Dominik , Podewski Edith , Hilfiker‐Kleiner Denise , Bauersachs Johann
Published: September 2015

Aims

Peripartum cardiomyopathy (PPCM) is a major cause of acute heart failure in the peripartum period and considered potentially life threatening. While many aspects of its clinical profiles have been frequently reported, functional analysis, in particular of the right ventricle, and tissue characterization by cardiovascular magnetic resonance (CMR) imaging have been only sporadically described. The aim of the present study was to analyse pathological alterations and their prognostic relevance found in CMR imaging of patients newly diagnosed with PPCM.

Methods and results

In this multicenter study 34 patients with confirmed PPCM underwent CMR imaging at the time of diagnosis and at 5 ± 1 months follow‐up. Cine imaging of PPCM patients showed moderate to severe reduction of systolic left ventricular (LV) function (mean LVEF: 29.7 ± 12.8%). In 35% of the patients right ventricular (RV) systolic function was also reduced with a mean RVEF of 42.9 ± 13.9%. Dilatation of the LV was observed in 91% (mean LV‐EDV/BSA 128.5 ± 32.1 mL/m2), and dilatation of the RV was present in 24% (mean RV‐EDV/BSA 87.4 ± 18.5 mL/m2) of the patients. Focal non‐ischemic late gadolinium enhancement (LGE) was visible in 71%, and regional wall motion abnormalities were evident in 88% of the patients. LGE and wall motion abnormalities were predominantly located in the anteroseptal and basal to midventricular segments. RV dysfunction at baseline was associated with reduced probability of full cardiac recovery at 5 ± 1 months follow‐up.

Conclusions

Besides LV systolic dysfunction, RV dysfunction and dilatation are observed in about one third of PPCM patients at the time of diagnosis. RV dysfunction is associated with unfavourable outcome. A distinct pattern of LV wall motion abnormalities and myocardial scar is evident in most PPCM patients. The present study may help to establish a set of CMR criteria suitable for diagnosis in patients with suspected PPCM and may add further knowledge to the pathology of the disease.
Clinical presentation and outcome by age categories in acute heart failure: results from an international observational cohort
Authors: Teixeira Antonio , Parenica Jiri , Park Jin Joo , Ishihara Shiro , AlHabib Khalid F. , Laribi Said , Maggioni Aldo , Miró Òscar , Sato Naoki , Kajimoto Katsuya , Cohen‐Solal Alain , Fairman Enrique , Lassus Johan , Mueller Christian , Peacock William F. , Januzzi James L. , Choi Dong‐Ju , Plaisance Patrick , Spinar Jindrich , Mebazaa Alexandre , Gayat Etienne ,   on behalf of the GREAT (Global Research on Acute Conditions Team) Network
Published: September 2015

Aims

To assess, according to age groups, patients' characteristics according to region of origin, the chronic therapeutic management, prognostic utility of clinical variables, and natriuretic peptides.

Methods and results

The GREAT registry consisted of patients identified as presenting with acute heart failure at the emergency department. Four groups of patients were defined according to age: the young patient group (<65 years); ‘middle‐old’ (65–74 years), ‘old‐old’ (75–84 years) and the ‘oldest‐old’ (85–94 years). Follow‐up at 1 year was performed via personal contact or national data registries at 1 year. Dataset consisted of 14 758 patients aged up to 95 years, with the ‘oldest‐old’ group being more prevalent in North America and Western Europe. The 30‐day mortality rate were, respectively, 8.1%, 8.9%, 10.3%, and 16.3% among the four age groups and 1‐year mortality rates were, respectively, 3.1%, 17.1%, 24.7%, and 39.9%. Chronic heart failure treatment was less frequently administered with age (percentage of the ‘fully treated’ group was 14% in the ‘young’ compared with 2% in the ‘oldest‐old’ patient group). Reduced left ventricular ejection fraction was present in 70%, 62.3%, 52.5%, and 46.8% among the four age groups, respectively. The prognostic utility of most variables for short‐ and long‐term outcome was attenuated with age, with the exception of natriuretic peptides.

Conclusion

This study found a large heterogeneity in age among geographic regions and that the eldest are less likely to be treated in accordance with recommendations of current heart failure guidelines. Natriuretic peptide concentrations retained prognostic value in patients across age strata.
Crystal and Magnetic Structure of Sr2BIrO6 (B = Sc, Ti, Fe, Co, In) in the Framework of Multivalent Iridium Double Perovskites
Authors: Kayser Paula , Alonso Jose A. , Mompeán Federico J. , Retuerto Maria , Croft Mark , Ignatov Alexander , Fernández‐Díaz Maria T.
Published: September 2015

The preparation, crystal structure and magnetic properties of Sr2BIrO6 (B = In, Sc, Fe, Co or Ti) oxides are reported. For B = Sc, Fe, Co or In materials, X‐ray and neutron powder diffraction (NPD) studies confirm the presence of 1:1 B‐ordered perovskite‐like structures crystallizing in the monoclinic I2/m and P21/n space groups, with unit‐cell parameters a ≈ √2a0, b ≈ √2a0, c ≈ 2a0 and β ≈ 90°. Sr2TiIrO6 is described as a disordered perovskite with orthorhombic symmetry in the Pbnm space group. For B = Fe and Co, low‐temperature NPD data and magnetic measurements indicate the existence of an antiferromagnetic structure resulting from the Fe3+/Co3+ magnetic moment interaction. X‐ray absorption spectroscopy corroborates that the oxidation states of B and Ir are 3+ and 5+, respectively. The bond lengths and other structural features are discussed in the framework of other recently reported iridium double perovskites where iridium adopts tetravalent, pentavalent and hexavalent oxidation states, and in the wider context of Sr double perovskites.
Synthesis of Naphthofurans by tBuOK‐Catalyzed Intramolecular Anionic Cycloaddition of Unsymmetrical Bis‐propargyl Ethers
Authors: Grimaldi Tamíris B. , Back Davi F. , Zeni Gilson
Published: September 2015

The tBuOK‐catalyzed intramolecular anionic cycloaddition of unsymmetrical bis‐propargyl ethers has been applied to the synthesis of naphthofurans. A systematic study of the cyclization system revealed that the amount of base and solvent played an essential role in this reaction. The results showed that the cyclization preceded cleanly and smoothly under mild reaction conditions, employing a catalytic amount of tBuOK as base, THF as solvent, at room temperature in a short reaction time (15 min). The reaction was regioselective, giving only naphthofurans as the unique regioisomer through an initial intramolecular 5‐endo‐dig process followed by an intramolecular 6‐endo‐dig process. The method tolerates the presence of neutral, electron‐donating and ‐withdrawing as well as heteroaryl groups in any part of the substrates. More importantly, this methodology requires only one synthetic step to prepare the conjugated polycyclic compounds.
Preparation of 6‐Difluoromethylphosphonated Phenanthridines by Visible‐Light‐Driven Radical Cyclization of 2‐Isocyanobiphenyls
Authors: Wang Shuang , Jia Wen‐Liang , Wang Lin , Liu Qiang
Published: September 2015

A protocol to obtain a variety of 6‐difluoromethylenephosphonated phenanthridines through a radical cyclization process was explored. These reactions, performed with the use of diethyl bromodifluoromethylphosphonate as a radical resource and 2‐isocyanobiphenyls as radical acceptors, were smoothly triggered by visible‐light photocatalysis. Electron‐withdrawing and electron‐donating groups were well tolerated, and the target molecules were obtained in excellent to moderate yields.
D–A–A‐Type Organic Dyes for NiO‐Based Dye‐Sensitized Solar Cells
Authors: Wu Fei , Liu Jianlin , Li Xi , Song Qunliang , Wang Min , Zhong Cheng , Zhu Linna
Published: September 2015

Three new D–A–A‐type organic sensitizers – W1, W2, and W3 – have been synthesized and applied for p‐type dye‐sensitized solar cells. For the first time, the electron‐withdrawing 2,1,3‐benzothiadiazole (BT) unit has been applied as the π‐bridge between the triphenylamine donor and different acceptors in these dye molecules. It turns out that these dyes all exhibit power conversion efficiencies exceeding 0.1 %, and that the best performance is achieved by the dye W2, with an octyl 2‐cyanoacrylate acceptor. It shows a power conversion efficiency of 0.166 %, with a short circuit current of 4.16 mA cm–2 and an open circuit voltage of 0.121 V. The higher light‐harvesting efficiency leads to a higher photocurrent in W2. In addition, electrochemical impedance spectroscopy (EIS) studies suggest slower charge recombination at the metal oxide/electrolyte interface and a faster hole‐transporting ability of W2. The factors together may account for the higher power conversion efficiency of W2. This work demonstrates rational design of these dye molecules for the construction of efficient p‐type sensitizers.
Enhanced detection of quantum dots labeled protein by simultaneous bismuth electrodeposition into microfluidic channel
Authors: Medina‐Sánchez Mariana , Miserere Sandrine , Cadevall Miquell , Merkoçi Arben
Published: September 2015

In this study, we propose an electrochemical immunoassay into a disposable microfluidic platform, using quantum dots (QDs) as labels and their enhanced detection using bismuth as an alternative to mercury electrodes. CdSe@ZnS QDs were used to tag human IgG as a model protein and detected through highly sensitive stripping voltammetry of the dissolved metallic component (cadmium in our case). The modification of the screen printed carbon electrodes (SPCEs) was done by a simple electrodeposition of bismuth that was previously mixed with the sample containing QDs. A magneto‐immunosandwich assay was performed using a micromixer. A magnet placed at its outlet in order to capture the magnetic beads used as solid support for the immunoassay. SPCEs were integrated at the end of the channel as detector. Different parameters such as bismuth concentration, flow rate, and incubation times, were optimized. The LOD for HIgG in presence of bismuth was 3.5 ng/mL with a RSD of 13.2%. This LOD was about 3.3‐fold lower than the one obtained without bismuth. Furthermore, the sensitivity of the system was increased 100‐fold respect to experiments carried out with classical screen‐printed electrodes, both in presence of bismuth.
Acute and chronic toxicity of neonicotinoids to nymphs of a mayfly species and some notes on seasonal differences
Authors: Van den Brink Paul J. , Van Smeden Jasper M. , Bekele Robel S. , Dierick Wiebe , De Gelder Daphne M. , Noteboom Maarten , Roessink Ivo
Published: September 2015

Mayfly nymphs are among the most sensitive taxa to neonicotinoids. The present study presents the acute and chronic toxicity of 3 neonicotinoids (imidacloprid, thiacloprid, and thiamethoxam) to a mayfly species (Cloeon dipterum) and some notes on the seasonality of the toxicity of imidacloprid to C. dipterum and 5 other invertebrate species. Imidacloprid and thiamethoxam showed equal acute and chronic toxicity to a winter generation of C. dipterum, whereas thiacloprid was approximately twice as toxic. The acute and chronic toxicity of imidacloprid was much higher for the C. dipterum summer generation than for the winter one. The acute toxicity differs by a factor of 20 for the 96-h 50% effective concentration (EC50) and by a factor of 5.4 for the chronic 28-d EC50. Temperature had only a slight effect on the sensitivity of C. dipterum to imidacloprid because we only found a factor of 1.7 difference in the 96-h EC50 between tests performed at 10 °C and 18 °C. The difference in sensitivity between summer and overwintering generations was also found for 3 other insect species. The results indicate that if the use and environmental fate of the 3 neonicotinoids are comparable, replacing imidacloprid by another neonicotinoid might not reduce the environmental impact on the mayfly nymph C. dipterum. The results also show the importance of reporting which generation is tested because sensitivity values of insects in the summer might be underestimated by the experiments performed with neonicotinoids and an overwintering population. Environ Toxicol Chem 2016;35:128–133. © 2015 SETAC
The cost‐effectiveness of grip on challenging behaviour: an economic evaluation of a care programme for managing challenging behaviour
Authors: Zwijsen S. A. , Bosmans J. E. , Gerritsen D. L. , Pot A. M. , Hertogh C. M. P. M. , Smalbrugge M.
Published: September 2015

Objective

The objective of the study was to evaluate the cost‐effectiveness of implementing the Grip on Challenging Behaviour care programme (GRIP) on dementia special care units in comparison with usual care.

Methods

A stepped wedge design was used. Challenging behaviour and quality of life were measured using the Cohen Mansfield Agitation Inventory (CMAI) and the QUALIDEM. Quality‐adjusted life years (QALYs) were calculated using the EuroQol‐5D. Psychoactive medication use (range 0–5 per measurement) and sick leave were registered. Costs included medication, time spent on challenging behaviour and education. Costs and effects were analysed using linear multilevel regression. Incremental cost‐effectiveness ratios were calculated. Statistical uncertainty was estimated using bootstrapping.

Results

Seventeen dementia special care units participated. GRIP led to improvement on the QUALIDEM subscale social relations (1.6; 95% CI 0.18 to 3.4) and on the use of psychoactive medication (−0.73; 95% CI −1.1 to −0.46) and to a decrease in QALYs (−0.02; 95% CI −0.06 to −0.003). No significant effects on CMAI, sick leave and other QUALIDEM subscales were found. The intervention was not cost‐effective in comparison with usual care with regard to CMAI score, QALYs and sick leave. The willingness to pay should be 320€/point improvement on the QUALIDEM subscale social relations and 370€/psychoactive medication less to reach a 0.95 probability of cost‐effectiveness.

Conclusion

It depends on how much society is willing to pay whether GRIP can be considered cost‐effective. Because the appropriateness of the current methods for analysing cost‐effectiveness in this specific population is uncertain, the positive effects on behaviour, medication and job satisfactions should also be taken in account in the decision making. Copyright © 2015 John Wiley & Sons, Ltd.
Deficits in hippocampal‐dependent transfer generalization learning accompany synaptic dysfunction in a mouse model of amyloidosis
Authors: Montgomery Karienn S. , Edwards George , Levites Yona , Kumar Ashok , Myers Catherine E. , Gluck Mark A. , Setlow Barry , Bizon Jennifer L.
Published: September 2015

Elevated β‐amyloid and impaired synaptic function in hippocampus are among the earliest manifestations of Alzheimer's disease (AD). Most cognitive assessments employed in both humans and animal models, however, are insensitive to this early disease pathology. One critical aspect of hippocampal function is its role in episodic memory, which involves the binding of temporally coincident sensory information (e.g., sights, smells, and sounds) to create a representation of a specific learning epoch. Flexible associations can be formed among these distinct sensory stimuli that enable the “transfer” of new learning across a wide variety of contexts. The current studies employed a mouse analog of an associative “transfer learning” task that has previously been used to identify risk for prodromal AD in humans. The rodent version of the task assesses the transfer of learning about stimulus features relevant to a food reward across a series of compound discrimination problems. The relevant feature that predicts the food reward is unchanged across problems, but an irrelevant feature (i.e., the context) is altered. Experiment 1 demonstrated that C57BL6/J mice with bilateral ibotenic acid lesions of hippocampus were able to discriminate between two stimuli on par with control mice; however, lesioned mice were unable to transfer or apply this learning to new problem configurations. Experiment 2 used the APPswePS1 mouse model of amyloidosis to show that robust impairments in transfer learning are evident in mice with subtle β‐amyloid‐induced synaptic deficits in the hippocampus. Finally, Experiment 3 confirmed that the same transfer learning impairments observed in APPswePS1 mice were also evident in the Tg‐SwDI mouse, a second model of amyloidosis. Together, these data show that the ability to generalize learned associations to new contexts is disrupted even in the presence of subtle hippocampal dysfunction and suggest that, across species, this aspect of hippocampal‐dependent learning may be useful for early identification of AD‐like pathology. © 2015 Wiley Periodicals, Inc.
Retrieval flexibility and reinstatement in the developing hippocampus
Authors: DeMaster Dana , Coughlin Christine , Ghetti Simona
Published: September 2015

Episodic memory improves during childhood and this improvement has been associated with age differences in hippocampal function, but previous research has not manipulated the possible underlying mechanisms. We tested the hypothesis that age‐related differences in hippocampal activation may reflect changes in retrieval flexibility. We expected these activation differences to be observed most prominently in the anterior hippocampus. Functional magnetic resonance imaging (fMRI) data were collected from children ages 8 and 10, and adults (N = 63) during an associative recognition task that required participants to recognize pairs of pictures which either appeared in the same location as during encoding (Same location), or in a flipped location, such that each picture switched their location with the other member of the pair (Flipped location). Recognition of same‐location pairs placed lower demands on flexible retrieval compared to recognition of flipped‐location pairs. Behaviorally, 8‐year‐olds exhibited the strongest correct recognition gains for same‐location compared to flipped‐location pairs, and females unexpectedly outperformed males across all ages. When we examined correct recognition, adults recruited the hippocampal head more strongly for flipped‐ versus same‐location pairs compared to both groups of children; in contrast both adults and 10‐year‐olds recruited the hippocampal tail more strongly for flipped‐ versus same‐location pairs compared to 8‐year‐olds. This pattern was stronger in the left hippocampus and for females. Moreover hippocampal discrimination between recognized and forgotten items in the same‐location condition was stronger in 8‐year‐olds compared to adults, and was stronger in the flipped‐location condition in adults compared to 8‐year‐olds; this pattern was stronger in the left hippocampus. Individual differences in this discrimination contrast for flipped‐location trials in the head and body predicted performance on an index of creative thinking. Overall, these results lend new support to the idea that hippocampal development may reflect change in retrieval flexibility with implications for additional forms of flexible cognition. © 2015 Wiley Periodicals, Inc.
Effectiveness of novel, lower cost molecular human papillomavirus‐based tests for cervical cancer screening in rural china
Authors: Valdez Melissa , Jeronimo Jose , Bansil Pooja , Qiao You‐Lin , Zhao Fang‐Hui , Chen Wen , Zhang Xun , Kang Le‐Ni , Paul Proma , Bai Ping , Peck Roger , Li Jing , Chen Feng , Stoler Mark H. , Castle Philip E.
Published: September 2015

This study examined the efficacy of the OncoE6™ Cervical Test, careHPV™ and visual inspection with acetic acid (VIA) in identifying women at risk for cervical cancer and their capability to detect incident cervical precancer and cancer at 1‐year follow‐up. In a population of 7,543 women living in rural China, women provided a self‐collected and two clinician‐collected specimens and underwent VIA. All screen positive women for any of the tests, a ∼10% random sample of test‐negative women that underwent colposcopy at baseline, and an additional ∼10% random sample of test‐negative women who did not undergo colposcopy at baseline (n = 3,290) were recruited. 2,904 women were rescreened 1 year later using the same tests, colposcopic referral criteria, and procedures. Sensitivities of baseline tests to detect 1‐year cumulative cervical intraepithelial neoplasia Grade 3 or cancer (CIN3+) were 96.5% and 81.6% for careHPV™ on clinician‐collected and self‐collected specimens, respectively, and 54.4% for OncoE6™ test. The OncoE6™ test was very specific (99.1%) and had the greatest positive predictive value (PPV; 47.7%) for CIN3+. Baseline and 1‐year follow‐up cervical specimens testing HPV DNA positive was sensitive (88.0%) but poorly predictive (5.5–6.0%) of incident CIN2+, whereas testing repeat HPV16, 18 and 45 E6 positive identified only 24.0% of incident CIN2+ but had a predictive value of 33.3%. This study highlights the different utility of HPV DNA and E6 tests, the former as a screening and the latter as a diagnostic test, for detection of cervical precancer and cancer.
Panaxydol, a component of Panax ginseng, induces apoptosis in cancer cells through EGFR activation and ER stress and inhibits tumor growth in mouse models
Authors: Kim Hee Suk , Lim Jang Mi , Kim Joo Young , Kim Yongjin , Park Serkin , Sohn Jeongwon
Published: September 2015

We reported previously that panaxydol, a component of Panax ginseng roots, induced mitochondria‐mediated apoptosis preferentially in transformed cells. This study demonstrates that EGFR activation and the resulting ER stress mediate panaxydol‐induced apoptosis, and that panaxydol suppresses in vivo tumor growth in syngeneic and xenogeneic mouse tumor models. In addition, we elucidated that CaMKII and TGF‐β‐activated kinase (TAK1) participate in p38/JNK activation by elevated cytoplasmic Ca2+ concentration ([Ca2+]c). In MCF‐7 cells, EGFR was activated immediately after exposure to panaxydol, and this activation was necessary for induction of apoptosis, suggesting that panaxydol might be a promising anticancer candidate, especially for EGFR‐addicted cancer. Activation of PLCγ followed EGFR activation, resulting in Ca2+ release from the endoplasmic reticulum (ER) via inositol triphosphate and ryanodine receptors. ER Ca2+ release triggered mitochondrial Ca2+ uptake indirectly through oxidative stress and ensuing ER stress. Elevated [Ca2+]c triggered sequential activation of calmodulin/CaMKII, TAK1 and p38/JNK. As shown previously, p38 and JNK activate NADPH oxidase. Here, it was shown that the resulting oxidative stress triggered ER stress. Among the three signaling branches of the unfolded protein response, protein kinase R‐like ER kinase (PERK), but not inositol‐requiring enzyme 1 or activating transcription factor 6, played a role in transmitting the apoptosis signal. PERK induced C/EBP homologous protein (CHOP), and CHOP elevated Bim expression, initiating mitochondrial Ca2+ uptake and apoptosis. In summary, we identified roles of EGFR, the CAMKII‐TAK1‐p38/JNK pathway, and ER stress in panaxydol‐induced apoptosis and demonstrated the in vivo anticancer effect of panaxydol.
Adoption of Small‐Scale Irrigation and Its Livelihood Impacts in Northern Ethiopia
Authors: Zeweld Woldegebrial , Huylenbroeck Guido Van , Hidgot Assefa , Chandrakanth M. G. , Speelman Stijn
Published: September 2015

The potential of smallholder‐irrigated agriculture to enhance food security and improve livelihoods has led the government of Ethiopia to invest significantly in irrigation establishment. This article aims to investigate the impact of small‐scale irrigation on households' livelihood. To deal with the problems of purposive targeting and self‐selection which are likely to occur for this type of intervention, we use a sophisticated econometric technique called ‘propensity score matching’ to study this impact. Our findings confirm the presence of a statistically significant difference in income, overall expenditure, asset accumulation and expenditures on agricultural inputs between the treated and control households. In contrast, no statistically significant differences in livestock resources, food consumption, and expenditure on education and health were found. Furthermore, the proportion of poor is respectively 20 and 30% for the treated and control households. So, overall it can be concluded that participation in the small‐scale irrigation has robust and positive effect on most of the livelihood indices and that an expansion of irrigation schemes is a good strategy in the water‐stressed and drought‐prone areas of Ethiopia. Copyright © 2015 John Wiley & Sons, Ltd.
Soil‐Hydrological Responses to Rainfall Variation in a Subtropical Australian Landscape
Authors: Kodur S. , Robinson J. B. , Foley J. L. , Silburn D. M.
Published: September 2015

Reliable water supply for farming is a global concern, including the Lockyer Valley region, Australia. Knowledge of rainfall variation and resulting irrigation demand and deep drainage can improve crop water use and minimize salinity. Therefore, we modelled irrigation demand and deep drainage for different land‐use types of the Lockyer Valley and classified them according to rainfall. During the periods of extremely low rainfall (mean = 468 mm yr‐1), deep drainage fell by 35–239 mm yr‐1, whereas irrigation demand rose by 160–310 mm yr‐1, relative to extremely high rainfall (1138 mm yr‐1). With all land‐use types, deep drainage rose with water input, but it was consistent in the order (mean, mm yr‐1): lucerne (8–11), native grass (13), sorghum–wheat sequence (37–64), bare fallow (169) and sweetcorn–broccoli–bean sequence (225). Decadal trends in irrigation demand and deep drainage signalled a raising future irrigation demand; and in turn potential deep drainage risks if irrigation is not managed wisely. These findings will have broader implications for crop and environment management under rainfall variation. Copyright © 2015 John Wiley & Sons, Ltd.
Lethal bacterial trap: Cationic surface for endodontic sealing
Authors: Kesler Shvero Dana , Zaltsman Nathan , Weiss Ervin I. , Polak David , Hazan Ronen , Beyth Nurit
Published: September 2015

Insoluble antibacterial cationic nanoparticles have been previously shown to have potent and long‐lasting antibacterial properties. Our tested hypothesis was that root canal pathogens will be attracted to and eliminated when exposed to epoxy resin‐based surfaces incorporating cationic nanoparticles. In our research, an epoxy resin‐based surface incorporating quaternary ammonium polyethyleneimine (QPEI) nanoparticles was evaluated. Surface characterization was performed using atomic force microscopy and X‐ray photoelectron spectra. The surface anti‐Enterococcus faecalis effect was evaluated in an anti‐gravitational model. Cell membrane potential, viability, biofilm thickness, and biomass were tested using flow cytometry and confocal laser scanning microscopy. Additionally, the antibiofilm activity of the bacterial supernatant was assessed. The surface characterization showed QPEI nanoparticle embedment on the modified sealer. The epoxy resin‐based surface incorporating the QPEI nanoparticles actively attracted bacteria, causing membrane destabilization, and bacterial death. The supernatant of bacteria pre‐exposed to QPEI showed an antibacterial effect. In conclusion, the tested epoxy resin‐based surface incorporating QPEI nanoparticles traps and kills bacteria. The nanoparticles attracted bacteria, reducing their viability, and promoting cell death. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 427–434, 2016.
Ethanol Enhances TGF‐β Activity by Recruiting TGF‐β Receptors From Intracellular Vesicles/Lipid Rafts/Caveolae to Non‐Lipid Raft Microdomains
Authors: Huang Shuan Shian , Chen Chun‐Lin , Huang Franklin W. , Johnson Frank E. , Huang Jung San
Published: September 2015

Regular consumption of moderate amounts of ethanol has important health benefits on atherosclerotic cardiovascular disease (ASCVD). Overindulgence can cause many diseases, particularly alcoholic liver disease (ALD). The mechanisms by which ethanol causes both beneficial and harmful effects on human health are poorly understood. Here we demonstrate that ethanol enhances TGF‐β‐stimulated luciferase activity with a maximum of 0.5–1% (v/v) in Mv1Lu cells stably expressing a luciferase reporter gene containing Smad2‐dependent elements. In Mv1Lu cells, 0.5% ethanol increases the level of P‐Smad2, a canonical TGF‐β signaling sensor, by ∼2‐3‐fold. Ethanol (0.5%) increases cell‐surface expression of the type II TGF‐β receptor (TβR‐II) by ∼2‐3‐fold from its intracellular pool, as determined by I125‐TGF‐β‐cross‐linking/Western blot analysis. Sucrose density gradient ultracentrifugation and indirect immunofluorescence staining analyses reveal that ethanol (0.5% and 1%) also displaces cell‐surface TβR‐I and TβR‐II from lipid rafts/caveolae and facilitates translocation of these receptors to non‐lipid raft microdomains where canonical signaling occurs. These results suggest that ethanol enhances canonical TGF‐β signaling by increasing non‐lipid raft microdomain localization of the TGF‐β receptors. Since TGF‐β plays a protective role in ASCVD but can also cause ALD, the TGF‐β enhancer activity of ethanol at low and high doses appears to be responsible for both beneficial and harmful effects. Ethanol also disrupts the location of lipid raft/caveolae of other membrane proteins (e.g., neurotransmitter, growth factor/cytokine, and G protein‐coupled receptors) which utilize lipid rafts/caveolae as signaling platforms. Displacement of these membrane proteins induced by ethanol may result in a variety of pathologies in nerve, heart and other tissues. J. Cell. Biochem. 117: 860–871, 2016. © 2015 Wiley Periodicals, Inc.
Optimal visualization of the fetal four‐chamber and outflow tract views with transabdominal ultrasound in the morbidly obese: Are we there yet?
Authors: Adekola Henry , Soto Eleazar , Dai Jing , Lam‐Rachlin Jennifer , Gill Navleen , Leon‐Peters Jocelyn , Puder Karoline , Abramowicz Jacques S.
Published: September 2015

Background

To compare optimal visualization of the four‐chamber and outflow‐tract views of the fetal heart on sonographic examination between morbidly obese (body mass index [BMI] ≥ 40 kg/m2) and nonobese (BMI < 25 kg/m2) pregnant women.

Methods

In this retrospective cohort study, we included records and images from 509 pregnant women who had first undergone sonographic examination between 18 and 36 weeks' fetal gestational age.

Results

Compared with the nonobese women, morbidly obese women had lower optimal visualization of the four‐chamber and outflow‐tract heart views: four‐chamber view, morbidly obese, 83/186 (44.6%), versus nonobese, 283/323 (87.6%), and outflow‐tract view, morbidly obese, 80/186 (43%) versus nonobese, 258/290 (89%); p < 0.0001 for each comparison. Similar outcomes were observed when the results from each subcategory of morbidly obese women (ie, BMI 40–49.9, 50–59.9, and ≥60 kg/m2) were compared with that from nonobese women; p < 0.0001 for each comparison. These outcomes remained the same regardless of whether this comparison was made among those who had their examination before or at 19 weeks' or more gestational age. Among the morbidly obese women, there was no difference in optimal visualization of the four‐chamber or outflow‐tract views regardless of whether the examination was performed at <23 weeks' or at ≥23 weeks' gestational age: four‐chamber view <23 weeks, 44.8% (78/174), versus four‐chamber view ≥23 weeks, 41.7% (5/12); p = 0.8, and outflow‐tract view <23 weeks, 43.1% (75/174), versus outflow‐tract view ≥23 weeks, 41.7% (5/12); p = 0.9. After controlling for maternal age and race, the odds of visualizing the four‐chamber and outflow‐tract views in the morbidly obese were reduced compared with those in their nonobese counterparts: odds ratio (OR) for four‐chamber, 0.13; 95% confidence interval (CI), 0.08–0.21, and OR for outflow‐tract, 0.11; 95% CI, 0.07–0.17.

Conclusions

Optimal visualization of the fetal four‐chamber and outflow‐tract views was achieved in less than 50% of morbidly obese women, compared with almost 90% in nonobese women. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 43:548–555, 2015
Preference pulses and the win–stay, fix‐and‐sample model of choice
Authors: Hachiga Yosuke , Sakagami Takayuki , Silberberg Alan
Published: September 2015

Two groups of six rats each were trained to respond to two levers for a food reinforcer. One group was trained on concurrent variable‐ratio 20 extinction schedules of reinforcement. The second group was trained on a concurrent variable‐interval 27‐s extinction schedule. In both groups, lever‐schedule assignments changed randomly following reinforcement; a light cued the lever providing the next reinforcer. In the next condition, the light cue was removed and reinforcer assignment strictly alternated between levers. The next two conditions redetermined, in order, the first two conditions. Preference pulses, defined as a tendency for relative response rate to decline to the just‐reinforced alternative with time since reinforcement, only appeared during the extinction schedule. Although the pulse's functional form was well described by a reinforcer‐induction equation, there was a large residual between actual data and a pulse‐as‐artifact simulation (McLean, Grace, Pitts, & Hughes, 2014) used to discern reinforcer‐dependent contributions to pulsing. However, if that simulation was modified to include a win–stay tendency (a propensity to stay on the just‐reinforced alternative), the residual was greatly reduced. Additional modifications of the parameter values of the pulse‐as‐artifact simulation enabled it to accommodate the present results as well as those it originally accommodated. In its revised form, this simulation was used to create a model that describes response runs to the preferred alternative as terminating probabilistically, and runs to the unpreferred alternative as punctate with occasional perseverative response runs. After reinforcement, choices are modeled as returning briefly to the lever location that had been just reinforced. This win–stay propensity is hypothesized as due to reinforcer induction.
Synthesis, Antimicrobial Evaluations, and DNA Photo Cleavage Studies of New Bispyranopyrazoles
Authors: Yusuf Mohamad , Kaur Manvinder , Sohal Harvinder Singh
Published: September 2015

The bispyranopyrazoles (4a, 4b, 4c, 4d, 4e, 4f, 4g) were synthesized from the reactions of dibenzaldehydes (2a, 2b, 2c, 2d, 2e, 2f, 2g) with 3‐methylpyrazole‐5‐one 3 and malononitrile by refluxing under alcoholic medium. The dibenzaldehydes were obtained from the O‐alkylation of 3‐hydroxybenzaldehyde with suitable 1,ω‐dibromoalkanes under the alkaline conditions in the presence of dry EtOH/DMF. The structures of bisheterocyclics were determined from rigorous analysis of their spectral parameters (IR, 1H‐NMR, 13C‐NMR, and ESI‐MS). The newly prepared compounds were screened for their antimicrobial activity against seven bacterial and five fungal strains. The DNA photo cleavage potential of these compounds was also evaluated by using agarose gel electrophoresis, and bispyranopyrazoles 4b, 4d and 4e exhibited significant level of DNA photocleavage activity.
Synthesis and Evaluation of Novel 5‐cyclohexyl‐2‐(4″‐substitutedphenyl)‐3‐(2″‐substitutedphenyl)4H‐2,3,3a,5,6,6a‐hexahydropyrrolo[3,4‐d]isoxazole‐4,6‐dione Derivatives for Their In Vitro Antioxidant and Antibacterial Activities
Authors: Kaur Manpreet , Kaur Anjandeep , Singh Baldev , Singh Baljit
Published: September 2015

1,3‐Dipolar cycloaddition reactions of N‐cyclohexyl maleimide (1) with azomethine N‐oxide (2) have afforded novel isoxazolidine (3) in excellent yield. Their structures have been characterized from their IR, 1H‐NMR, 13C‐NMR, 1H,1H‐COSY, MS(ESI), and elemental analysis techniques. In vitro antibacterial activity of the synthesized compounds were investigated against a representative panel of pathogenic strains specifically two Gram‐positive bacteria (Staphylococcus aureus and Streptococcus pyogenes) and two Gram‐negative bacteria (Pseudomonas aeruginosa and Escherichia coli) using agar‐well diffusion assay. Some of the compounds (3a, 3k, 3n, and 3o) exhibited promising antibacterial activities. All the synthesized compounds have also been screened for their antioxidant activities and were found to be significantly active.
Cloning, expression and biochemical characterization of recombinant superoxide dismutase from Antarctic psychrophilic bacterium Pseudoalteromonas sp. ANT506
Authors: Wang Quan‐Fu , Wang Yi‐Fan , Hou Yan‐Hua , Shi Yong‐Lei , Han Han , Miao Miao , Wu Ying‐Ying , Liu Yuan‐Ping , Yue Xiao‐Na , Li Yu‐Jin
Published: September 2015

In this study, a superoxide dismutase gene (PsSOD) from Pseudoalteromonas sp. ANT506 was cloned and over expressed in Escherichia coli. The PsSOD has an open reading frame of 582 bp with a putative product of 193 amino acid residue and an estimated molecular size of 21.4 kDa. His‐tagged PsSOD was subsequently purified 12.6‐fold by Ni‐affinity chromatography and the yield of 22.9%. The characterization of the purified rPsSOD exhibited maximum activity at 30 °C and pH 8.0. The enzyme exhibited 13.9% activity at 0 °C and had high‐thermo lability at higher than 50 °C. rPsSOD exhibited well capability to 2.5 M NaCl (62.4%). These results indicated that rPsSOD exhibited special catalytic properties.
Variability and trends in England and Wales precipitation
Authors: de Leeuw Johannes , Methven John , Blackburn Mike
Published: September 2015

The England and Wales precipitation (EWP) dataset is a homogeneous time series of daily accumulations from 1931 to 2014, composed from rain gauge observations spanning the region. The daily regional‐average precipitation statistics are shown to be well described by a Weibull distribution, which is used to define extremes in terms of percentiles. Computed trends in annual and seasonal precipitation are sensitive to the period chosen, due to large variability on interannual and decadal timescales. Atmospheric circulation patterns associated with seasonal precipitation variability are identified. These patterns project onto known leading modes of variability, all of which involve displacements of the jet stream and storm‐track over the eastern Atlantic. The intensity of daily precipitation for each calendar season is investigated by partitioning all observations into eight intensity categories contributing equally to the total precipitation in the dataset. Contrary to previous results based on shorter periods, no significant trends of the most intense categories are found between 1931 and 2014. The regional‐average precipitation is found to share statistical properties common to the majority of individual stations across England and Wales used in previous studies. Statistics of the EWP data are examined for multi‐day accumulations up to 10 days, which are more relevant for river flooding. Four recent years (2000, 2007, 2008 and 2012) have a greater number of extreme events in the 3‐ and 5‐day accumulations than any previous year in the record. It is the duration of precipitation events in these years that is remarkable, rather than the magnitude of the daily accumulations.
Amino acids, peptides, and proteins as chemically bonded stationary phases – A review
Authors: Bocian Szymon , Skoczylas Magdalena , Buszewski Bogusław
Published: September 2015

The selectivity of chromatographic separation depends mostly on the stationary phase and mobile phase composition. Despite being a material with bonded simple organic molecule, a wide group of stationary phases contain immobilized compound that possesses biological activity. Stationary phases that contain amino acids and peptides as well as enzymes and proteins are alternative materials that may be used for liquid chromatographic separations and are reviewed in this work. In the case of peptide‐bonded stationary phases, most of these types of materials were elaborated in the 1970s and 1980s; however, over the last few years a growing interest has been observed which is connected with hydrophilic interaction liquid chromatography. The most important application of amino acid and peptide‐bonded stationary phases is connected with separation of amino acids, their derivatives, and peptides. The main advantage of such materials is the ability for chiral separations.