bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambient atomic resolution atomic force microscopy with qPlus sensors: Part 1
Authors: Wastl Daniel S.
Published: December 2016

Atomic force microscopy (AFM) is an enormous tool to observe nature in highest resolution and understand fundamental processes like friction and tribology on the nanoscale. Atomic resolution in highest quality was possible only in well‐controlled environments like ultrahigh vacuum (UHV) or controlled buffer environments (liquid conditions) and more specified for long‐term high‐resolution analysis at low temperatures (∼4 K) in UHV where drift is nearly completely absent. Atomic resolution in these environments is possible and is widely used. However, in uncontrolled environments like air, with all its pollutants and aerosols, unspecified thin liquid films as thin as a single molecular water‐layer of 200 pm or thicker condensation films with thicknesses up to hundred nanometer, have been a problem for highest resolution since the invention of the AFM. The goal of true atomic resolution on hydrophilic as well as hydrophobic samples was reached recently. In this manuscript we want to review the concept of ambient AFM with atomic resolution. The reader will be introduced to the phenomenology in ambient conditions and the problems will be explained and analyzed while a method for scan parameter optimization will be explained. Recently developed concepts and techniques how to reach atomic resolution in air and ultra‐thin liquid films will be shown and explained in detail, using several examples. Microsc. Res. Tech. 80:50–65, 2017. © 2016 Wiley Periodicals, Inc.
The function of NOD‐like receptors in central nervous system diseases
Authors: Kong Xiangxi , Yuan Zengqiang , Cheng Jinbo
Published: December 2016

NOD‐like receptors (NLRs) are critical cytoplasmic pattern‐recognition receptors (PRRs) that play an important role in the host innate immune response and immunity homeostasis. There is a growing body of evidence that NLRs are involved in a wide range of inflammatory diseases, including cancer, metabolic diseases, and autoimmune disorders. Recent studies have indicated that the proteins of the NLR family are linked with the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), and psychological diseases. In this review, we mainly focus on the role of NLRs and the underlying signaling pathways in central nervous system (CNS) diseases. © 2016 Wiley Periodicals, Inc.
Morphological brain measures of cortico‐limbic inhibition related to resilience
Authors: Gupta Arpana , Love Aubrey , Kilpatrick Lisa A. , Labus Jennifer S. , Bhatt Ravi , Chang Lin , Tillisch Kirsten , Naliboff Bruce , Mayer Emeran A.
Published: December 2016

Resilience is the ability to adequately adapt and respond to homeostatic perturbations. Although resilience has been associated with positive health outcomes, the neuro‐biological basis of resilience is poorly understood. The aim of the study was to identify associations between regional brain morphology and trait resilience with a focus on resilience‐related morphological differences in brain regions involved in cortico‐limbic inhibition. The relationship between resilience and measures of affect were also investigated. Forty‐eight healthy subjects completed structural MRI scans. Self‐reported resilience was measured using the Connor and Davidson Resilience Scale. Segmentation and regional parcellation of images was performed to yield a total of 165 regions. Gray matter volume (GMV), cortical thickness, surface area, and mean curvature were calculated for each region. Regression models were used to identify associations between morphology of regions belonging to executive control and emotional arousal brain networks and trait resilience (total and subscales) while controlling for age, sex, and total GMV. Correlations were also conducted between resilience scores and affect scores. Significant associations were found between GM changes in hypothesized brain regions (subparietal sulcus, intraparietal sulcus, amygdala, anterior mid cingulate cortex, and subgenual cingulate cortex) and resilience scores. There were significant positive correlations between resilience and positive affect and negative correlations with negative affect. Resilience was associated with brain morphology of regions involved in cognitive and affective processes related to cortico‐limbic inhibition. Brain signatures associated with resilience may be a biomarker of vulnerability to disease. © 2016 Wiley Periodicals, Inc.
Potential to improve precipitation forecasts in Texas through the incorporation of multiple teleconnections
Authors: Tian Liyan , Leasor Zachary , Quiring Steven M.
Published: December 2016

ABSTRACT

Climate oscillations are one of the primary factors that influence precipitation. This study uses canonical correlation analysis (CCA) to examine how El Niño‐Southern Oscillation (ENSO), Atlantic Multidecadal Oscillation, North Atlantic Oscillation, Pacific Decadal Oscillation, and the Pacific‐North American pattern influence precipitation in Texas. This study identifies the months, regions, and time lags where the relationships between climate oscillations and precipitation are strongest. Correlation results indicate that ENSO accounts for the greatest amount of precipitation variance in Texas. However, including all five climate oscillations is important and together they account for a greater amount of the variance in precipitation than any individual climate oscillation. Precipitation in southern Texas is more strongly influenced by climate oscillations than other regions in Texas. The CCA results demonstrate that there are statistically significant relationships between the climate oscillations and precipitation at time lags longer than 6 months during the summer and at time lags shorter than 6 months during the winter. Based on the CCA results, a precipitation forecast model was developed for the three climate regions that we defined. In the cases of January, the Heidke Skill Score (HSS) of our model is comparable or higher to those achieved by the Climate Prediction Center (CPC) in each region. For all of the 36 month/region cases (12 months × 3 regions), there are 50% cases that the HSS of our model is comparable or higher to those achieved by the CPC. The results of this study illustrate that including multiple teleconnections can increase forecast skill, and statistical methods are useful for precipitation forecasting at a 0‐month lead time.
Climatology of the premonsoon Indian dryline
Authors: Akter Nasreen , Tsuboki Kazuhisa
Published: December 2016

A northeast‐ to southwest‐oriented surface dryline with a dew point gradient of 1 °C per 10 km develops along the eastern Indian coast during the entire premonsoon season. Deep, hot, dry air of up to 500 hPa moves from arid regions in Southwest Asia and Western India to the Bay of Bengal (BoB), and warm, shallow, moist air from the BoB penetrates below the dry air, forming an inclined moisture gradient aloft to the east and reaching the surface to the west. The slope of the gradient depends on the vertically increased southwesterly wind over the BoB, which gradually intensifies from March to May. Diurnal low‐level temperature variations over the land cause periodic movements of the dry‐moist air convergence zone at the surface in the zonal direction. During the premonsoon, the average east–west diurnal oscillation of the surface dryline is approximately 100 km, and the eastward movement is almost three times faster than the westward movement.
Climatology of cross‐tropopause mass exchange over the Tibetan Plateau and its surroundings
Authors: Tian Hongying , Tian Wenshou , Luo Jiali , Zhang Jiankai , Zhang Min
Published: December 2016

The cross‐tropopause mass flux (CTMF) and long‐term trends in stratosphere–troposphere exchange (STE) over the Tibetan Plateau (TP) and its surroundings were analyzed using European Centre for Medium‐Range Weather Forecasts reanalysis data. The gross CTMF (the sum of upward and downward mass flux) shows an evident wave train structure over the TP, which is mainly related to the horizontal exchange of air masses along the tropopause associated with the sharp meridional gradient in tropopause pressure or vertical discontinuity of the thermal tropopause in winter. The seasonal cycle of the STE over the TP shows that the gross mass flux is downwards in Northern Hemisphere (NH) winter and upwards in NH summer. The gross CTMF over the TP accounts for 2.96% of the global total CTMF arising from STE processes resolved by Wei method. Both the upward and downward CTMF over the TP exhibit statistically significant positive trends in winter during the period 1979–2009. The strong positive trends of STE in winter over the TP are resulted from the combined effects of the rising tropopause height, enhanced westerlies and decreasing plateau winter monsoon. In summer, both the upward and downward CTMF exhibit statistically significant negative trends over the northern TP, while the trend in upward CTMF is positive over the southern TP, in accordance with the increasing intensity of Asian summer monsoon in recent decades. The sensitivity simulations with a climate model confirm that changes in the Asian monsoon can significantly affect the tropopause and the CTMF over the TP.
Tracing Sediment Sources Using Mid‐infrared Spectroscopy in Arvorezinha Catchment, Southern Brazil
Authors: Tiecher Tales , Caner Laurent , Minella Jean Paolo Gomes , Evrard Olivier , Mondamert Leslie , Labanowski Jérôme , Rheinheimer Danilo dos Santos
Published: December 2016

The widespread adoption of the sediment fingerprinting approach to guide catchment management has been limited by the cost and the difficulty to prepare and process samples for geochemical and radionuclide analyses. Spectral properties have recently been shown to provide a rapid and cost‐efficient alternative for this purpose. The current research objective was (i) to quantify the sediment source contributions in a 1∙19‐km2 rural catchment of Southern Brazil by using mid‐infrared (MIR) spectroscopy and (ii) to compare these results with those obtained with geochemical approach and near‐infrared and ultraviolet–visible spectroscopy methods. The sediment sources to discriminate were cropland surface (n = 20), unpaved roads (n = 10) and stream channel banks (n = 10). Twenty‐nine suspended sediment samples were collected at the catchment outlet during nine significant flood events. The sources could be distinguished by MIR spectroscopy. Cropland and channel bank sources mainly differed in their clay mineral contents, but their similar organic matter content complicated the MIR‐model predictions. Unpaved road contributions were discriminated from the other sources by their lower organic carbon content. When the results of the current research based on MIR spectroscopy are compared with those obtained using other sediment fingerprinting approaches, based on geochemistry and near‐infrared and ultraviolet–visible spectroscopy, an overestimation of channel banks contribution and an underestimation of cropland and unpaved road contributions is found. These results suggest that MIR spectroscopy can provide a useful tool that is non‐destructive, rapid and cheap for tracing sediment sources in rural catchments and for guiding the implementation of soil and water conservation measures. Copyright © 2016 John Wiley & Sons, Ltd.
How are coastal benthos fed?
Authors: Waples James T. , Bootsma Harvey A. , Klump J. Val
Published: December 2016

Water movement can influence the distribution of benthos, in part, by increasing food delivery; however, the impact of advective transport and turbulent diffusion on organic matter flux to nearshore benthic communities is not well quantified. In this study, we measured the vertical particulate organic carbon (POC) and particulate phosphorus (PP) flux in nearshore Lake Michigan using two naturally occurring daughter/parent radionuclide pairs (234Th/238U and 90Y/90Sr) and compared these fluxes to coincident benthic chamber estimates of respiration and total phosphorus efflux by quagga mussels on the lakebed. We found that advective onshore transport and vertical convective mixing increased POC and PP flux to the nearshore benthos by a factor of ∼ 15 and ∼ 30 over offshore trap‐derived estimates of flux. From these results, we hypothesize that high benthos population densities are related to an edge effect created when the dominant mechanism of particle delivery transitions from gravitational settling to convection.
Is size the only determinant of delayed abdominal closure in pediatric liver transplant?
Authors: Khorsandi Shirin Elizabeth , Day Arthur William Raven , Cortes Miriam , Deep Akash , Dhawan Anil , Vilca‐Melendez Hector , Heaton Nigel
Published: December 2016

The aim was to determine the factors associated with the use of delayed abdominal closure in pediatric liver transplantation (LT) and whether this affected outcome. From a prospectively maintained database, transplants performed in children (≤18 years) were identified (October 2010 to March 2015). Primary abdominal closure was defined as mass closure performed at time of transplant. Delayed abdominal closure was defined as mass closure not initially performed at the same time as transplant; 230 children underwent LT. Of these, 176 (76.5%) had primary closure. Age was similar between the primary and delayed groups (5.0 ± 4.9 versus 3.9 ± 5.0 years; P = 0.13). There was no difference in the graft‐to‐recipient weight ratio (GRWR) in the primary and delayed groups (3.4 ± 2.8 versus 4.1 ± 2.1; P = 0.12). Children with acute liver failure (ALF) were more likely to experience delayed closure then those with chronic liver disease (CLD; P < 0.001). GRWR was similar between the ALF and CLD (3.4 ± 2.4 versus 3.6 ± 2.7; P = 0.68). Primary closure children had a shorter hospital stay (P < 0.001), spent fewer days in pediatric intensive care unit (PICU; P = 0.001), and required a shorter duration of ventilation (P < 0.001). Vascular complications (arterial and venous) were similar (primary 8.2% versus delayed 5.6%; P = 0.52). Graft (P = 0.42) and child survival (P = 0.65) in the primary and delayed groups were similar. Considering timing of mass closure after transplant, patients in the early delayed closure group (<6 weeks) were found to experience a shorter time of ventilation (P = 0.03) and in PICU (P = 0.003). In conclusion, ALF was the main determinant of delayed abdominal closure rather than GRWR. The optimal time for delayed closure is within 6 weeks. The use of delayed abdominal closure does not adversely affect graft/child survival. Liver Transplantation 23 352–360 2017 AASLD.
Survival implications of opioid use before and after liver transplantation
Authors: Randall Henry B. , Alhamad Tarek , Schnitzler Mark A. , Zhang Zidong , Ford‐Glanton Sophia , Axelrod David A. , Segev Dorry L. , Kasiske Bertram L. , Hess Gregory P. , Yuan Hui , Ouseph Rosemary , Lentine Krista L.
Published: December 2016

Implications of prescription opioid use for outcomes after liver transplantation (LT) have not been described. We integrated national transplant registry data with records from a large pharmaceutical claims clearinghouse (2008‐2014; n = 29,673). Opioid fills on the waiting list were normalized to morphine equivalents (MEs), and exposure was categorized as follows: > 0‐2 ME/day (level 1), > 2‐10 ME/day (level 2), > 10‐70 ME/day (level 3), and >70 ME/day (level 4). Associations (adjusted hazard ratio [aHR], 95% LCL aHR 95% UCL) of pretransplant ME level with patient and graft survival over 5 years after transplant were quantified by multivariate Cox regression including adjustment for recipient, donor, and transplant factors, as well as propensity adjustment for opioid use. Overall, 9.3% of recipients filled opioids on the waiting list. Compared with no use, level 3 (aHR 1.061.281.55) and 4 (aHR 1.161.521.98) opioid use during listing were associated with increased mortality over 5 years after transplant. These associations were driven by risk after the first transplant anniversary, such that mortality >1‐5 years increased in a graded manner with higher use on the waiting list (level 2, aHR, 1.001.271.62; level 3, aHR, 1.081.381.77; level 4, aHR, 1.492.012.72). Similar patterns occurred for graft failure. Of recipients with the highest level of opioids on the waiting list, 65% had level 3 or 4 use in the first year after transplant, including 55% with use at these levels from day 90‐365 after transplant. Opioid use in the first year after transplant also bore graded associations with subsequent death and graft loss >1‐5 years after transplant. Opioid use history may be relevant in assessing and providing care to LT candidates. Liver Transplantation 23 305–314 2017 AASLD.
Decision modeling in donation after circulatory death liver transplantation
Authors: McLean Kenneth A. , Camilleri‐Brennan Julian , Knight Stephen R. , Drake Thomas M. , Ots Riinu , Shaw Catherine A. , Wigmore Stephen J. , Harrison Ewen M.
Published: December 2016

Donation after circulatory death (DCD) liver allografts are increasingly used for transplantation. However, the posttransplantation clinical and quality of life outcomes of DCD recipients are traditionally considered to be inferior compared with donation after brain death (DBD) allograft recipients. Decision making for such marginal organs can be difficult. This study investigated the optimal decision to accept or decline a DCD liver allograft for a patient based on their current health. A Markov decision process model was constructed to predict the 5‐year clinical course of patients on the liver transplant waiting list. Clinical outcomes were determined from the UK transplant registry or appropriate literature. Quality‐adjusted life years (QALYs) were determined using the condition‐specific short form of liver disease quality of life (SF‐LDQoL) questionnaire. There were 293/374 (78.3%) eligible patients who completed the SF‐LDQoL questionnaire. A total of 73 respondents (24.9%) were before transplant and 220 were after transplant (DBD recipient, 56.3%; DCD recipient, 8.5%; ischemic cholangiopathy patient, 2.4%; retransplant recipient, 7.9%). Predictive modeling indicated that QALYs gained at 5 years were significantly higher in DCD recipients (3.77; 95% confidence interval [CI], 3.44‐4.10) compared with those who remained on the waiting list for a DBD transplant with Model for End‐Stage Liver Disease (MELD) scores of 15‐20 (3.36; 95% CI, 3.28‐3.43), or >20 (3.07; 95% CI, 3.00‐3.14). There was no significant advantage for individuals with MELD scores <15 (3.55; 95% CI, 3.47‐3.63). In conclusion, this model predicts that patients on the UK liver transplant waiting list with MELD scores >15 should receive an offered DCD allograft based on the QALYs gained at 5 years. This analysis only accounts for donor‐recipient risk pairings seen in current practice. The optimal decision for patients with MELD scores <15 remains unclear. However, a survival benefit was observed when a DCD organ was accepted. Liver Transplantation 23 594–603 2017 AASLD.
Estimates of blow‐up times of a system of semilinear SPDEs
Authors: Li Mei , Gao Hongjun
Published: December 2016

In this paper, blow‐up property to a system of nonlinear stochastic PDEs driven by two‐dimensional Brownian motions is investigated. The lower and upper bounds for blow‐up times are obtained. When the system parameters satisfy certain conditions, the explicit solutions of a related system of random PDEs are deduced, which allows us to use Yor's formula to obtain the distribution functions of several blow‐up times. Particularly, the impact of noises on the life span of solutions is studied as the system parameters satisfy different conditions. Copyright © 2016 John Wiley & Sons, Ltd.
Expression of tamoxifen‐inducible CRE recombinase in Lcn5‐CreERT2 transgenic mouse caput epididymis
Authors: Xu Juan , Yao Guangxin , Ru Yanfei , Xie Shengsong
Published: December 2016

The epididymis, which connects the testis to vas deferens, plays a crucial role regulating sperm maturation and fertilization. Here, a tamoxifen‐inducible CreERT2 recombinase transgenic mouse was generated to study the function of genes in the caput epididymis using the Cre/LoxP system, which is driven by the 1.8‐kb Lcn5 promoter (Lcn5‐CreERT2). Both CRE recombinase and ERT2 mRNA were specifically expressed in the caput epididymis, beginning at postnatal Day 30 and increasing thereafter. Crossing these Lcn5‐CreERT2 transgenic mice with Rosa26; mT/mG reporter mice, which express membrane‐bound GFP (mGFP) only after CRE is active at its genetic locus, resulted in the presence of GFP only in the middle/distal caput epididymis after tamoxifen induction. Efficiency of the CRE recombinase production in the caput epididymis was dose‐ and time‐dependent. These tamoxifen‐inducible caput epididymis‐specific CRE recombinase transgenic mice thus provides a simple approach to modulate epididymal principal cells in vivo, allowing for the genetic investigation of caput epididymis‐specific gene functions during sperm maturation. 84: 257–264, 2017. © 2016 Wiley Periodicals, Inc.
Recovery of pectoralis major and triceps brachii after bench press exercise
Authors: Ferreira Diogo V. , Gentil Paulo , Soares Saulo Rodrigo Sampaio , Bottaro Martim
Published: December 2016

Introduction

The present study evaluated and compared the recovery of pectoralis major (PM) and triceps brachii (TB) muscles of trained men after bench press exercise.

Methods

Eighteen volunteers performed eight sets of bench press exercise to momentary muscle failure and were evaluated for TB and PM peak torque and total work on an isokinetic dynamometer.

Results

PM peak torque and total work remained lower than baseline for 72 and 96 h, respectively. TB peak torque was only different from baseline immediately post training, while total work was significantly lower than baseline immediately and 48 h after training. Normalized peak torque values were only different between TB and PM at 48 h after training.

Conclusions

Considering the small and nonsignificant difference between the recovery of TB and PM muscles, the results suggest that bench press exercise may promote a similar stress on these muscles. Muscle Nerve 56: 963–967, 2017
Evaluation of transmit efficiency and SAR for a tight fit transceiver human head phased array at 9.4 T
Authors: Avdievich N.I. , Hoffmann J. , Shajan G. , Pfrommer A. , Giapitzakis I.A. , Scheffler K. , Henning A.
Published: December 2016

Ultra‐high field (UHF, ≥7 T) tight fit transceiver phased arrays improve transmit (Tx) efficiency (B1+/√P) in comparison with Tx‐only arrays, which are usually larger to fit receive (Rx)‐only arrays inside. One of the major problems limiting applications of tight fit arrays at UHFs is the anticipated increase of local tissue heating, which is commonly evaluated by the local specific absorption rate (SAR). To investigate the tradeoff between Tx efficiency and SAR when a tight fit UHF human head transceiver phased array is used instead of a Tx‐only/Rx‐only RF system, a single‐row eight‐element prototype of a 400 MHz transceiver head phased array was constructed. The Tx efficiency and SAR of the array were evaluated and compared with that of a larger Tx‐only array, which could also be used in combination with an 18‐channel Rx‐only array. Data were acquired on the Siemens Magnetom whole body 9.4 T human MRI system.

Depending on the head size, positioning and the RF shim strategy, the smaller array provides from 11 to 23% higher Tx efficiency. In general, the Tx performance, evaluated as B1+/√SAR, i.e. the safety excitation efficiency (SEE), is also not compromised. The two arrays provide very similar SEEs evaluated over 1000 random RF shim sets.

We demonstrated that, in general, the tight fit transceiver array improves Tx performance without compromising SEE. However, in specific cases, the SEE value may vary, favoring one of the arrays, and therefore must be carefully evaluated.
Neurometabolic profiles of the substantia nigra and striatum of MPTP‐intoxicated common marmosets: An in vivo proton MRS study at 9.4 T
Authors: Heo Hwon , Ahn Jae‐Bum , Lee Hyeong Hun , Kwon Euna , Yun Jun‐Won , Kim Hyeonjin , Kang Byeong‐Cheol
Published: December 2016

Given the strong coupling between the substantia nigra (SN) and striatum (STR) in the early stage of Parkinson's disease (PD), yet only a few studies reported to date that have simultaneously investigated the neurochemistry of these two brain regions in vivo, we performed longitudinal metabolic profiling in the SN and STR of 1‐methyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐intoxicated common marmoset monkey models of PD (n = 10) by using proton MRS (1H–MRS) at 9.4 T. T2 relaxometry was also performed in the SN by using MRI. Data were classified into control, MPTP_2weeks, and MPTP_6‐10 weeks groups according to the treatment duration. In the SN, T2 of the MPTP_6‐10 weeks group was lower than that of the control group (44.33 ± 1.75 versus 47.21 ± 2.47 ms, p < 0.05). The N‐acetylaspartate to total creatine ratio (NAA/tCr) and γ‐aminobutyric acid to tCr ratio (GABA/tCr) of the MPTP_6‐10 weeks group were lower than those of the control group (0.41 ± 0.04 versus 0.54 ± 0.08 (p < 0.01) and 0.19 ± 0.03 versus 0.30 ± 0.09 (p < 0.05), respectively). The glutathione to tCr ratio (GSH/tCr) was correlated with T2 for the MPTP_6‐10 weeks group (r = 0.83, p = 0.04). In the STR, however, GABA/tCr of the MPTP_6‐10 weeks group was higher than that of the control group (0.25 ± 0.10 versus 0.16 ± 0.05, p < 0.05). These findings may be an in vivo depiction of the altered basal ganglion circuit in PD brain resulting from the degeneration of nigral dopaminergic neurons and disruption of nigrostriatal dopaminergic projections. Given the important role of non‐human primates in translational studies, our findings provide better understanding of the complicated evolution of PD.
Understanding communication in disaster response: A marketing strategy formulation and implementation perspective
Authors: Pitt Christine Sarah , Treen Emily
Published: December 2016

An analysis of communication disaster response in four well‐known natural disasters explores at what stage a disaster communication plan can fail. Based on a marketing strategy formulation–implementation framework, four different outcomes are used to examine what makes a disaster communication plan succeed or fail. This leads to an identification of barriers to the implementation of disaster communication plans. Very often in disaster communication plan failures the strategy formulation is blamed. However, often it is implementation at fault. This makes it hard to diagnose the reason for the communication plan failure. By taking heed of the barriers identified here, disaster response executives can hopefully overcome some of the causes of disaster communication plan failure. Avenues for future research are identified.
Reverse Iontophoretic Extraction of Metabolites from Living Plants and their Identification by Ion‐chromatography Coupled to High Resolution Mass Spectrometry
Authors: Sánchez Maria Isabel González , McCullagh James , Guy Richard H. , Compton Richard G.
Published: December 2016

Introduction

The identification and characterisation of cellular metabolites has now become an important strategy to obtain insight into functional plant biology. However, the extraction of metabolites for identification and analysis is challenging and, at the present time, usually requires destruction of the plant.

Objective

To detect different plant metabolites in living plants with no pre‐treatment using the combination of iontophoresis and ion‐chromatography with mass spectrometry detection.

Methodology

In this work, the simple and non‐destructive method of reverse iontophoresis has been used to extract in situ multiple plant metabolites from intact Ocimum basilicum leaves. Subsequently, the analysis of these metabolites has been performed with ion chromatography coupled directly to high resolution mass spectrometric detection (IC‐MS).

Results

The application of reverse iontophoresis to living plant samples has avoided the need for complex pre‐treatments. With this approach, no less than 24 compounds, including organic acids and sugars as well as adenosine triphosphate (ATP) were successfully detected.

Conclusion

The research demonstrates that it is feasible to monitor, therefore, a number of important plant metabolites using a simple, relatively fast and non‐destructive approach. Copyright © 2016 John Wiley & Sons, Ltd.
Phytochemical Analysis of a Cytotoxic Fraction of Quassia silvestris using LC‐HR‐ESI‐MSn
Authors: Tala Michel Feussi , Talontsi Ferdinand Mouafo , Zeng Guang‐Zhi , Wabo Hippolyte Kamdem , Spiteller Michael , Tan Ning‐Hua , Tane Pierre
Published: December 2016

Introduction

The genus Quassia is a promising source of secondary metabolites with biological potential including antimalarial and cytotoxic activities. Limited data are available on the phytochemistry and pharmacology of Quassia silvestris Cheek & Jongkind, a Cameroonian medicinal plant used to treat various ailments.

Objectives

To carry out the bioassay‐guided fractionation and LC‐HR‐ESI‐MS analyses of the leaves extract from Q. silvestris; to purify the active fractions and isolate the major compounds using different chromatographic and spectroscopic methods. The obtained compounds will be evaluated for their biological activity.

Material and methods

Following the cytotoxic screening and LC‐HR‐ESI‐MS profiling of fractions obtained from partition of the methanolic extract of Q. silvestris leaves, the CH2Cl2‐soluble fraction which exhibited the highest cytotoxicity was retained for further investigations.

Results

Sixteen squalene‐derived metabolites were identified with oxasqualenoid derivatives being the most predominant. Among the isolates, structure elucidation of two new oxasqualenoids quassiols E (1) and F (2), were achieved by NMR (one‐dimensional (1D) and two‐dimensional (2D)) and MS methods. The newly characterised compounds 1 and 2, together with the known tetraol (3) and 3‐oxo‐oleanoic acid (16) displayed moderate cytotoxicity.

Conclusion

The identification and structural characterisation of highly oxidised squalene derived metabolites from this plant may provide important insight data for further pharmacological investigations. The LC‐HR‐ESI‐MSn method reported here could be developed as a rapid and efficient tool for the analyses of structurally related compounds in the genera Quassia, Simarouba, and Eurycoma of the subfamily Simarouboideae. Copyright © 2016 John Wiley & Sons, Ltd.
The clinical status and economic savings associated with remission among patients with rheumatoid arthritis: leveraging linked registry and claims data for synergistic insights
Authors: Curtis Jeffrey R. , Chen Lang , Greenberg Jeffrey D. , Harrold Leslie , Kilgore Meredith L. , Kremer Joel M. , Solomon Daniel H. , Yun Huifeng
Published: December 2016

Introduction

Treat to target guidelines recommend achieving remission or low disease activity in rheumatoid arthritis (RA). However, the reduction in adverse events and costs associated with lower disease activity is unclear.

Methods

We used Corrona linked to Medicare data to identify RA patients. Time varying disease activity was measured using Clinical Disease Activity Index (CDAI); outcomes included all‐cause hospitalization, a composite of hospitalization or emergency department (ED) visits, mortality, and medical costs. Outcome‐specific Cox proportional models evaluated the adjusted hazard ratios between disease activity and outcomes, controlling for potential confounders including comorbidities grouped into four patient phenotypes. Costs were analyzed with mixed models using a Gaussian distribution with log transformation.

Results

Depending on outcome, 4593 RA patients contributed up to 12 001 person years. Median age was 71 years, 75% women. At baseline, approximately 50–60% of patients were in remission or low disease activity. There was a dose‐response relationship between RA disease activity (remission, low, moderate, and high) and the incidence of hospitalizations (13.1, 17.8, 21.2, 27.5 per 100 py, respectively); all adjusted hazard ratios were significant: 0.68 (remission), 0.87 (low), and 1.24 (high) compared with moderate disease activity. Similar trends were observed for ED visits and mortality. The crude difference in annual medical costs between remission ($11 145) and moderate disease activity ($17 646) was $−6 500; the adjusted difference (95%CI) was $−3133 (−4737.72, −1528.43).

Conclusion

Leveraging the benefits of linking registry and administrative data together, lower disease activity in RA was associated with incrementally reduced risks of all‐cause hospitalization, ED visits, mortality, and medical costs in a dose‐dependent fashion. Copyright © 2016 John Wiley & Sons, Ltd.
Retrospective Evaluation of Postoperative Adverse Drug Events in Patients Receiving Rivaroxaban After Major Orthopedic Surgery Compared with Standard Therapy in a Community Hospital
Authors: Cieri Nicole E. , Kusmierski Kristen , Lackie Cynthia , Van Opdorp August , Hassan Amany K.
Published: December 2016

Study Objectives

To evaluate the occurrence of bleeding and venous thromboembolic (VTE) events in patients receiving rivaroxaban, warfarin, or warfarin with the addition of enoxaparin during the immediate postoperative period following major orthopedic surgery.

Methods

Patients older than 18 years who received at least one dose of rivaroxaban the morning following surgery, adjusted dose warfarin, or adjusted dose warfarin with the addition of enoxaparin for VTE prophylaxis after major orthopedic surgery between October 1, 2011, and February 28, 2015, were included. Data collected from the electronic health record included patient demographics, renal function, inpatient aspirin, P2Y12 inhibitor and/or nonsteroidal antiinflammatory drug (NSAID) use, type of surgery, postoperative analgesia, and presence of VTE risk factors. Adjusted incidence rate ratio for bleeding or VTE events was estimated using modified Poisson regression with robust standard errors. Covariates included in a multivariable model were age, sex, aspirin use, P2Y12 inhibitor use, NSAID use, obesity, VTE risk factors, and creatinine clearance.

Results

There were 3246 patients who met study inclusion criteria. Overall, incidences of bleeding and VTE events were rare. Bleeding event incidence ranged from 0.4% in the warfarin and warfarin with the addition of enoxaparin groups to 1.2% in the rivaroxaban group (p=0.088). There were two major bleeding events and 18 minor bleeding events (including hemorrhagic wound complications). VTE event incidence ranged from 0.2% in the warfarin with the addition of enoxaparin group to 0.6% in the rivaroxaban group (p=0.230). Two deep vein thromboses and 10 pulmonary emboli occurred. With use of the multivariable model, the warfarin and warfarin with the addition of enoxaparin groups had significantly lower incidence rates of bleeding compared with rivaroxaban (incidence rate ratio [IRR] = 0.218, p=0.0120, and IRR = 0.242, p=0.021, respectively).

Principal Conclusions

We observed a small, yet significant, increase in rivaroxaban‐related bleeding in the immediate postoperative period relative to warfarin or warfarin with the addition of enoxaparin for the prevention of VTE after major orthopedic surgery.
Risk of depression following uterine cancer: A nationwide population‐based study
Authors: Chen Chao‐Yu , Yang Yao‐Hsu , Lee Chuan‐Pin , Wang Ting‐Yao , Cheng Bi‐Hua , Huang Yin‐Cheng , Chen Pau‐Chung , Liang Sophie Hsin‐Yi , Dewey Michael , Chen Vincent Chin‐Hung
Published: December 2016

Background

Depression happens commonly in cancer patients. However, there is limited literature on uterine cancer. In this study, we aimed to evaluate the association between uterine cancer and depression as well as the moderating effect of age and hormone replacement therapy (HRT).

Methods

This was a population‐based study using Taiwan's National Health Insurance Research Database. We conducted a matched cohort study and identified 6526 patients with uterine cancer and 65 260 controls. We adopted the competing risk analysis model as the statistical method and adjusted for potential confounding factors.

Results

From 1997 to 2008, 71 786 patients were included (6526 patients with uterine cancer and 65 260 controls). In the study, uterine cancer was not linked to depression. However, when we stratified the different age groups, those cancer patients aged <40 and 40 to 49 years showed significant higher risk of developing depression (subdistribution hazard ratio 1.64 and 1.41, respectively). In addition, among uterine cancer patients, 4602 patients had never used HRT and 1921 patients were prescribed HRT. The analysis of time‐dependent Cox model showed that, compared with no use of HRT, patients with cumulative doses ≥168 DDD had significant lower risk of depression (hazard ratio 0.49, 95% confidence interval = 0.26‐0.92).

Conclusions

An increased risk of depression among younger uterine cancer patients was observed. Our preliminary finding suggests a possible protective factor for developing depression after HRT usage.
Statins ameliorate pulmonary hypertension secondary to left ventricular dysfunction through the Rho‐kinase pathway and NADPH oxidase
Authors: Chen I‐Chen , Tan Mian‐Shin , Wu Bin‐Nan , Chai Chee‐Yin , Yeh Jwu‐Lai , Chou Shah‐Hwa , Chen Ing‐Jun , Dai Zen‐Kong
Published: December 2016

Background

Pulmonary hypertension (PH) is a devastating disorder, for which no therapy is curative. It has been reported that pulmonary vascular remodeling, associated with increasing mean pulmonary arterial pressure and upregulated expression of endothelial nitric oxide synthase (eNOS), endothelin‐1 (ET‐1), RhoA/RhoH‐kinase results in the development of PH. Oxidative stress and the RhoA/Rho‐kinase pathway are also thought to be involved in the pathophysiology of PH. Statins are 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (HMG‐CoA reductase inhibitors) with pleiotropic effects and are potential agents for the treatment of PH. In this study, we investigated the beneficial effects of simvastatin on the development of PH secondary to left ventricular dysfunction.

Methods

A PH secondary to left ventricular dysfunction model was established in 6‐week‐old aortic‐banded rats. The pulmonary expression of Rho kinase, ET‐1, eNOS, p‐eNOS, nitrite/nitrate (NOx), cGMP, p47Phox, and p67Phox were investigated in the early‐treatment group, to which was administered simvastatin (30 mg/kg/day) from days 1 to 42 or the late‐treatment group, to which was administered simvastatin (30 mg/kg/day) from days 29 to 42.

Results

Simvastatin attenuated the mean pulmonary artery pressure, pulmonary arteriolar remodeling, plasma brain natriuretic peptide, ET‐1, reactive oxygen species, and the NADPH oxidase 2 regulatory subunits, p47Phox and p67Phox, and upregulated pulmonary p‐eNOS, NOx, and cGMP in both the early‐ and late‐treated groups.

Conclusions

Inhibiting HMG‐CoA reductase may have therapeutic potential for preventing and attenuating the development of PH in left ventricular dysfunction through the Rho‐kinase pathway and NADPH oxidase. A translational study in humans is needed to substantiate these findings. Pediatr Pulmonol. 2017;52:443–457. © 2016 Wiley Periodicals, Inc.
Pulmonary hemorrhage as a complication of Respiratory Syncyntial Virus (RSV) bronchiolitis
Authors: Soo Audrey K.S. , Inwald David P.
Published: December 2016

Respiratory Syncytial Virus (RSV) is a common cause of bronchiolitis. Although there are a number of recognized complications, pulmonary hemorrhage has not been reported previously. A retrospective case notes review was performed through an electronic search of a Pediatric Intensive Care Unit's medical records. Seven patients with RSV infection and pulmonary hemorrhage were identified and included in this case series. Six of the seven patients were born prematurely (30–36 weeks gestation). All patients required blood transfusion. The pulmonary hemorrhage events all occurred after a period of mechanical ventilation and following extubation. All of the patients required reintubation with a mean of 5 further days of mechanical ventilation. Pulmonary hemorrhage is an uncommon complication of RSV infection, which has not been reported previously in the literature. Further studies are required to determine incidence, pathogenesis, and outcome. Pediatr Pulmonol. 2017;52:E32–E36. © 2016 Wiley Periodicals, Inc.
In vitro labeling strategies for in cellulo fluorescence microscopy of single ribonucleoprotein machines
Authors: Custer Thomas C. , Walter Nils G.
Published: December 2016

RNA plays a fundamental, ubiquitous role as either substrate or functional component of many large cellular complexes—“molecular machines”—used to maintain and control the readout of genetic information, a functional landscape that we are only beginning to understand. The cellular mechanisms for the spatiotemporal organization of the plethora of RNAs involved in gene expression are particularly poorly understood. Intracellular single‐molecule fluorescence microscopy provides a powerful emerging tool for probing the pertinent mechanistic parameters that govern cellular RNA functions, including those of protein coding messenger RNAs (mRNAs). Progress has been hampered, however, by the scarcity of efficient high‐yield methods to fluorescently label RNA molecules without the need to drastically increase their molecular weight through artificial appendages that may result in altered behavior. Herein, we employ T7 RNA polymerase to body label an RNA with a cyanine dye, as well as yeast poly(A) polymerase to strategically place multiple 2′‐azido‐modifications for subsequent fluorophore labeling either between the body and tail or randomly throughout the tail. Using a combination of biochemical and single‐molecule fluorescence microscopy approaches, we demonstrate that both yeast poly(A) polymerase labeling strategies result in fully functional mRNA, whereas protein coding is severely diminished in the case of body labeling.
Streptococcus pneumoniae IgA1 protease: A metalloprotease that can catalyze in a split manner in vitro
Authors: Chi Ying‐Chih , Rahkola Jeremy T. , Kendrick Agnieszka A. , Holliday Michael J. , Paukovich Natasia , Roberts Thomas S. , Janoff Edward N. , Eisenmesser Elan Z.
Published: December 2016

IgA1 proteases (IgA1P) from diverse pathogenic bacteria specifically cleave human immunoglobulin A1 (IgA1) at the hinge region, thereby thwarting protective host immune responses. Streptococcus pneumoniae (S. pneumoniae) IgA1P shares no sequence conservation with serine or cysteine types of IgA1Ps or other known proteins, other than a conserved HExxH Zn‐binding motif (1604‐1608) found in metalloproteases. We have developed a novel expression system to produce the mature S. pneumoniae IgA1P and we have discovered that this form is both attached to the bacterial cell surface and released in its full form. Our data demonstrate that the S. pneumoniae IgA1P comprises two distinct regions that associate to form an active metalloprotease, the first such example of a metalloprotease that can be split in vitro and recombined to form an active enzyme. By capitalizing on this novel domain architecture, we show that the N‐terminal region of S. pneumoniae IgA1P comprises the primary binding region for IgA1, although the C‐terminal region of S. pneumoniae IgA1P is necessary for cleavage of IgA1. Our findings lend insight into the protein domain architecture of the S. pneumoniae IgA1P and function of this important virulence factor for S. pneumoniae infection.
Emerging critical behavior at a first‐order phase transition rounded by disorder
Authors: Ibrahim Ahmed K. , Vojta Thomas
Published: December 2016

We investigate the two‐dimensional four‐color Ashkin‐Teller model by means of large‐scale Monte‐Carlo simulations. We demonstrate that the first‐order phase transition of the clean system is destroyed by random disorder introduced via site dilution. The critical behavior of the emerging continuous transition belongs to the clean two‐dimensional Ising universality class, apart from logarithmic corrections. These results confirm perturbative renormalization‐group predictions; they also agree with recent findings for the three‐color case, indicating that the critical behavior is universal.
Electron and electron–hole excitations in a driven Fermi sea
Authors: Vanević Mihajlo , Nazarov Yuli V. , Belzig Wolfgang
Published: December 2016

We study the response of a degenerate Fermi sea to a time‐dependent perturbation. We find that elementary excitations in the Fermi sea are electrons and electron–hole quasiparticle pairs whose number and probability of creation depend on amplitude and shape of the drive. The excitations can be probed in a driven quantum contact at low temperature. While electronic excitations are associated to the dc voltage offset and determine the average current, the electron–hole pairs are created by the ac voltage component and give rise to the excess current noise power in a junction. We also obtain the many‐body state created by the drive. The constituent quasiparticle states can be probed by a Hong–Ou–Mandel type of correlation experiment where electrons emitted from the terminals with a relative time delay collide at the contact. The current noise power in the junction is directly related to the wave packet overlap at the contact. This is confirmed in recent experiments, demonstrating an unprecedented degree of control of elementary excitations in a coherent mesoscopic junction.
Point estimation and p‐values in phase II adaptive two‐stage designs with a binary endpoint
Authors: Kunzmann K. , Kieser M.
Published: December 2016

Clinical trials in phase II of drug development are frequently conducted as single‐arm two‐stage studies with a binary endpoint. Recently, adaptive designs have been proposed for this setting that enable a midcourse modification of the sample size. While these designs are elaborated with respect to hypothesis testing by assuring control of the type I error rate, the topic of point estimation has up to now not been addressed. For adaptive designs with a prespecified sample size recalculation rule, we propose a new point estimator that both assures compatibility of estimation and test decision and minimizes average mean squared error. This estimator can be interpreted as a constrained posterior mean estimate based on the non‐informative Jeffreys prior. A comparative investigation of the operating characteristics demonstrates the favorable properties of the proposed approach. Copyright © 2016 John Wiley & Sons, Ltd.
Time‐varying rankings with the Bayesian Mallows model
Authors: Asfaw Derbachew , Vitelli Valeria , Sørensen Øystein , Arjas Elja , Frigessi Arnoldo
Published: December 2016

We present new statistical methodology for analysing rank data, where the rankings are allowed to vary in time. Such data arise, for example, when the assessments are based on a performance measure of the items, which varies in time, or if the criteria, according to which the items are ranked, change in time. Items can also be absent when the assessments are made, because of delayed entry or early departure, or purely randomly. In such situations, also the dimension of the rank vectors varies in time. Rank data in a time‐dependent setting thus lead to challenging statistical problems. These problems are further complicated, from the perspective of computation, by the large dimension of the sample space consisting of all permutations of the items. Here, we focus on introducing and developing a Bayesian version of the Mallows rank model, suitable for situations in which the ranks vary in time and the assessments can be incomplete. The consequent missing data problems are handled by applying Bayesian data augmentation within Markov chain Monte Carlo. Our method is also adapted to the task of future rank prediction. The method is illustrated by analysing some aspects of a data set describing the academic performance, measured by a series of tests, of a class of high school students over a period of 4 years. Copyright © 2016 John Wiley & Sons, Ltd.