bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of signal‐to‐noise ratio estimation for scanning electron microscope using autocorrelation Levinson–Durbin recursion model
Authors: SIM K.S. , LIM M.S. , YEAP Z.X.
Published: February 2016

A new technique to quantify signal‐to‐noise ratio (SNR) value of the scanning electron microscope (SEM) images is proposed. This technique is known as autocorrelation Levinson–Durbin recursion (ACLDR) model. To test the performance of this technique, the SEM image is corrupted with noise. The autocorrelation function of the original image and the noisy image are formed. The signal spectrum based on the autocorrelation function of image is formed. ACLDR is then used as an SNR estimator to quantify the signal spectrum of noisy image. The SNR values of the original image and the quantified image are calculated. The ACLDR is then compared with the three existing techniques, which are nearest neighbourhood, first‐order linear interpolation and nearest neighbourhood combined with first‐order linear interpolation. It is shown that ACLDR model is able to achieve higher accuracy in SNR estimation.
The Suspected Macrosomic Fetus at Term: A Clinical Dilemma
Authors: Ray Ellen M. , Alhusen Jeanne L.
Published: February 2016

Estimation of fetal weight is an important component of antenatal and intrapartum management of pregnant women. While many clinicians use ultrasound estimates of fetal weight to assess fetal growth, there are inherent challenges in both the diagnosis and management of suspected fetal macrosomia. Given the inaccuracy in estimating fetal weight, and the risks that accompany cesarean birth or induction of labor, the management of suspected fetal macrosomia requires open communication and shared decision making between the woman and her health care providers. This case study and literature review highlight the current management and recommendations for suspected fetal macrosomia.
Acylated but not des‐acyl ghrelin is neuroprotective in an MPTP mouse model of Parkinson's disease
Authors: Bayliss Jacqueline A. , Lemus Moyra , Santos Vanessa V. , Deo Minh , Elsworth John D. , Andrews Zane B.
Published: February 2016

The gut hormone ghrelin is widely beneficial in many disease states. However, ghrelin exists in two distinctive isoforms, each with its own metabolic profile. In Parkinson's Disease (PD) acylated ghrelin administration is neuroprotective, however, the role of des‐acylated ghrelin remains unknown. In this study, we wanted to identify the relative contribution each isoform plays using the MPTP model of PD. Chronic administration of acylated ghrelin in mice lacking both isoforms of ghrelin (Ghrelin KO) attenuated the MPTP‐induced loss on tyrosine hydroxylase (TH) neuronal number and volume and TH protein expression in the nigrostriatal pathway. Moreover, acylated ghrelin reduced the increase in glial fibrillary acidic protein and Ionized calcium binding adaptor molecule 1 microglia in the substantia nigra. However, injection of acylated ghrelin also elevated plasma des‐acylated ghrelin, indicating in vivo deacetylation. Next, we chronically administered des‐acylated ghrelin to Ghrelin KO mice and observed no neuroprotective effects in terms of TH cell number, TH protein expression, glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 cell number. The lack of a protective effect was mirrored in ghrelin‐O‐acyltransferase KO mice, which lack the ability to acylate ghrelin and consequently these mice have chronically increased plasma des‐acyl ghrelin. Plasma corticosterone was elevated in ghrelin‐O‐acyltransferase KO mice and with des‐acylated ghrelin administration. Overall, our studies suggest that acylated ghrelin is the isoform responsible for in vivo neuroprotection and that pharmacological approaches preventing plasma conversion from acyl ghrelin to des‐acyl ghrelin may have clinical efficacy to help slow or prevent the debilitating effects of PD.

image

Ghrelin exists in the plasma as acyl and des‐acyl ghrelin. We determined the form responsible for in vivo neuroprotection in a mouse model of Parkinson's disease. Although exogenous acyl ghrelin is deacylated in situ to des‐acyl, only acyl ghrelin was neuroprotective by attenuating dopamine cell loss and glial activation. Acyl ghrelin is a therapeutic option to reduce Parkinson's Disease progression.

Cover Image for this issue: doi: 10.1111/jnc.13316.
Does prism adaptation affect visual search in spatial neglect patients: A systematic review
Authors: De Wit Liselotte , Ten Brink Antonia F. , Visser‐Meily Johanna M. A. , Nijboer Tanja C. W.
Published: February 2016

Prism adaptation (PA) is a widely used intervention for (visuo‐)spatial neglect. PA‐induced improvements can be assessed by visual search tasks. It remains unclear which outcome measures are the most sensitive for the effects of PA in neglect. In this review, we aimed to evaluate PA effects on visual search measures. A systematic literature search was completed regarding PA intervention studies focusing on patients with neglect using visual search tasks. Information about study content and effectiveness was extracted. Out of 403 identified studies, 30 met the inclusion criteria. The quality of the studies was evaluated: Rankings were moderate‐to‐high for 7, and low for 23 studies. As feature search was only performed by five studies, low‐to‐moderate ranking, we were limited in drawing firm conclusions about the PA effect on feature search. All moderate‐to‐high‐ranking studies investigated cancellation by measuring only omissions or hits. These studies found an overall improvement after PA. Measuring perseverations and total task duration provides more specific information about visual search. The two (low ranking) studies that measured this found an improvement after PA on perseverations and duration (while accuracy improved for one study and remained the same for the other). This review suggests there is an overall effect of PA on visual search, although complex visual search tasks and specific visual search measures are lacking. Suggestions for search measures that give insight in subcomponents of visual search are provided for future studies, such as perseverations, search path intersections, search consistency and using a speed–accuracy trade‐off.
Nurses' role in medical error recovery: an integrative review
Authors: Gaffney Theresa A , Hatcher Barbara J , Milligan Renee
Published: February 2016

Aims and objectives

The aim of this study was to conduct an integrative review of the literature to fully understand nurses' role in medical error recovery.

Background

Despite focused efforts on error prevention, the prevalence of medical errors occurring in the health care system remains a concern. Patient harm can be reduced or prevented by adequate recovery processes that include identifying, interrupting and correcting medical errors in a timely fashion. Both medical error prevention and recovery are critical components in advancing patient safety, yet little is known about nurses' role in medical error recovery.

Design

An integrative review of the literature, guided by Whittmore and Knafl's (Journal of Advanced Nursing, 5, 2005, 546) five‐step process, was conducted for the period between 2000–2015. A comprehensive search yielded twelve articles for this review.

Methods

The level and quality of evidence of the included articles was rated using a five‐level rating system and the Johns Hopkins Nursing Quality of Evidence Appraisal developed by ©The Johns Hopkins Hospital/The Johns Hopkins University.

Results

The medical error recovery rate varied across specialty nursing populations with nurses recovering, on average, as many as one error per shift to as few as one error per week. Nurses rely on knowing the patient, environment and plan of care to aid in medical error recovery.

Conclusions

Nurses play a unique yet invisible role in identifying, interrupting and recovering medical errors. Individual and organisational factors influencing nurses' ability to recover medical errors remain unclear.

Relevance to clinical practice

Greater understanding of nurse characteristics and organisational factors that influence error recovery can foster the development of effective strategies to detect and correct medical errors and enable organisations to reduce negative outcomes.
The perspectives of stakeholders of intellectual disability liaison nurses: a model of compassionate, person‐centred care
Authors: Brown Michael , Chouliara Zoë , MacArthur Juliet , McKechanie Andrew , Mack Siobhan , Hayes Matt , Fletcher Joan
Published: February 2016

Aims and objectives

To investigate the experiences of patients with intellectual disabilities, family and paid carers regarding the role of liaison nurses and the delivery of compassionate, person‐centred care. From this to propose a model of person‐centred care embedded in these experiences.

Background

People with intellectual disabilities have a high number of comorbidities, requiring multidisciplinary care, and are at high risk of morbidity and preventable mortality. Provision of compassionate, person‐centred care is essential to prevent complications and avoid death.

Design

A qualitative design was adopted with Interpretative Phenomenological Analysis for data analysis.

Methods

Semistructured interviews and focus groups were conducted. Data were analysed with a focus on compassionate, person‐centred care elements and components. Themes were modelled to develop a clinically meaningful model for practice.

Results

Themes identified vulnerability, presence and the human interface; information balance; critical points and broken trust; roles and responsibilities; managing multiple transitions; ‘flagging up’ and communication.

Conclusions

The findings provide the first ‘anatomy’ of compassionate, person‐centred care and provide a model for operationalising this approach in practice. The applicability of the model will have to be evaluated further with this and other vulnerable groups.

Relevance to clinical practice

This is the first study to provide a definition of compassionate, person‐centred care and proposes a model to support its application into clinical practice for this and other vulnerable groups.
Long Coronary Lesions Treated With Thin Strut Bioresorbable Polymer Drug Eluting Stent: Experience From Multicentre Randomized CENTURY II Study
Authors: Lesiak Maciej , Araszkiewicz Aleksander , Grajek Stefan , Colombo Antonio , Lalmand Jacques , Carstensen Steen , Namiki Atsuo , Tobaru Tetsuya , Merkely Béla , Moreno Raul , Barbato Emanuele , Wijns William , Saito Shigeru
Published: February 2016

Objectives

to assess performance of new, bioresorbable polymer sirolimus‐eluting stent (BP‐SES), in patients with long coronary lesions (LL) and to compare it to permanent polymer everolimus‐eluting stent (PP‐EES).

Background

LL have been associated with worse clinical outcomes in percutaneous coronary interventions (PCI). The impact of lesion length on the outcomes of drug eluting stent (DES) implantations is not as clear.

Methods

In the frame of a randomized, multicentre CENTURY II study, out of 1119 patients enrolled, 182 patients had LL (defined as ≥25 mm), and were assigned randomly to treatment with BP‐SES (101) or PP‐EES (81). Primary endpoint was target lesion failure (TLF, composite of cardiac death, target vessel related myocardial infarction [MI], and target lesion revascularization [TLR]) at 9 months. All data were 100% monitored and adverse events were adjudicated by an independent clinical event committee.

Results

The baseline patient and lesion characteristics were similar in the 2 study arms. At 9‐months, the rates of cardiac death (2.0% vs 1.2%; P = 0.70), MI (3.0% vs 4.9%; P = 0.49) and clinically driven TLR (2.0% vs 3.7%; P = 0.48) and TLF (6.9% vs 8.6%; P = 0.67) were similar for BP‐SES and PP‐EES, respectively. There was no stent thrombosis (ST) in BP‐SES group up to 9 months, while 1 case (1.2%) of ST was recorded in PP‐EES group (P = 0.44).

Conclusions

Patients with LL showed similar clinical outcomes when treated with Ultimaster BP‐SES and Xience PP‐EES. (J Interven Cardiol 2016;29:47–56)
Circulating Endothelial Cells and Endothelial Function Predict Major Adverse Cardiac Events and Early Adverse Left Ventricular Remodeling in Patients With ST‐Segment Elevation Myocardial Infarction
Authors: Abdel Hamid Magdy , Bakhoum Sameh WG , Sharaf Yasser , Sabry Dina , El‐Gengehe Ahmed T. , Abdel‐Latif Ahmed
Published: February 2016

Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) are mobilized from the bone marrow and increase in the early phase after ST‐elevation myocardial infarction (STEMI). The aim of this study was to assess the prognostic significance of CECs and indices of endothelial dysfunction in patients with STEMI. In 78 patients with acute STEMI, characterization of CD34+/VEGFR2+CECs, and indices of endothelial damage/dysfunction such as brachial artery flow mediated dilatation (FMD) were determined. Blood samples for CECs assessment and quantification were obtained within 24 hours of admission and FMD was assessed during the index hospitalization. At 30 days follow up, the primary composite end point of major adverse cardiac events (MACE) consisting of all‐cause mortality, recurrent nonfatal MI, or heart failure and the secondary endpoint of early adverse left ventricular (LV) remodeling were analyzed. The 17 patients (22%) who developed MACE had significantly higher CEC level (P = 0.004), von Willebrand factor (vWF) level (P = 0.028), and significantly lower FMD (P = 0.006) compared to the remaining patients. Logistic regression analysis showed that CECs level and LV ejection fraction were independent predictors of MACE. The areas under the receiver operating characteristic curves (ROC) for CEC level, FMD, and the logistic model with both markers were 0.73, 0.75, and 0.82, respectively, for prediction of the MACE. The 16 patients who developed the secondary endpoint had significantly higher CEC level compared to remaining patients (P = 0.038). In conclusion, increased circulating endothelial cells and endothelial dysfunction predicted the occurrence of major adverse cardiac events and adverse cardiac remodeling in patients with STEMI. (J Interven Cardiol 2016;29:89–98)
Reduced thermal threshold in patients with Temporomandibular Disorders
Authors: Carvalho G. F. , Chaves T. C. , Florencio L. L. , Dach F. , Bigal M. E. , Bevilaqua‐Grossi D.
Published: February 2016

Background

Many studies have demonstrated the presence of somatosensory modulation changes at different sites in patients with temporomandibular disorders (TMDs) using different modalities. However, the neck area, a well‐know condition related to TMD, remains unexplored.

Objective

To assess the thermal pain threshold in patients with TMD and controls at cephalic and extra‐cephalic areas, including the neck.

Methods

Twenty female patients with TMDs diagnosed by the Research Diagnostic Criteria for TMD (RDC/TMD) and twenty age‐matched controls underwent a first interview about neck pain and disability (NDI questionnaire). A blinded evaluator assessed the thermal pain threshold for cold (CPT) and heat (HPT) stimuli in accordance with an ascending method of limits of the Quantitative Sensory Testing at the following sites: periorbital, masseter, cervical posterior and ventral forearm. The groups were compared using a t‐test with α = 5%.

Results

Patients with TMDs reported pain at higher temperature for cold stimuli in all sites (P < 0·05) and at lower temperature for heat stimuli in the right periorbital site (P < 0·05) than controls. Pain and disability due tothis symptom were reported more often in the TMD group (P < 0·05).

Conclusion

Patients with TMD have pain modulation changes in the neck area as well, especially for cold stimuli, associated with higher disability and a higher report of neck pain than controls. These findings reinforce the evidence regarding the relationship between TMDs and neck pain.
Strategies for parenting by mothers and fathers with a mental illness
Authors: van der Ende P. C. , van Busschbach J. T. , Nicholson J. , Korevaar E. L. , van Weeghel J.
Published: February 2016

Accessible summary

What is known on the subject?

The combination of coping with their mental health problems and caring for children makes parents vulnerable.

Family‐centred practice can help to maintain and strengthen important family relationships, and to identify and enhance the strengths of a parent with a mental illness, all contributing to the recovery of the person with the mental illness.

What this paper adds to the existing knowledge?

Taking the strength and the opportunities formulated by parents themselves as a starting point is fairly new.

Parents with severe mental illness find strength for parenting in several ways. They feel responsible, and this helps them to stay alert while parenting, whereas parenthood also offers a basis for social participation through school contacts and the child's friendships.

Dedication to the parent role provides a focus; parents develop strengths and skills as they find a balance between attending to their own lives and caring for their children; and parenting prompts them to find adequate sources of social support.

In this study these strategies were found to be the fundamentals of recovery related to parenting.

What are the implications for practice?

Nurses can support and coach patients who are identified as parents, and self‐chosen parenting related goals are set and addressed.

A family‐focused approach by nurses can be used to prevent problems for children and their families, identify their strengths as well as vulnerabilities, and address the challenges to build resilience.

Introduction

Understanding of the problems of parents with mental illness is growing. Gaining insight into strategies for parenting, while taking the opportunities formulated by these parents themselves as a starting point is fairly new.

Question

What are the strategies of parents with a mental illness to be successful?

Method

Experiences of 19 mothers and eight fathers with a mental illness were explored with in‐depth interviews. Data were content analysed, using qualitative methods.

Results

Next to feelings of inadequacy, interviewees also describe how children enrich and structure their lives and are not only a burden but serve as distraction from problems. Developing activities that interest both child and parent provides avenues for emerging strength. Mental illness constrains fathers, but also gives opportunities to develop a meaningful relation with their children.

Discussion

Strategies like being fully dedicated to the parental role, finding a balance between attention for one's own life and parenting and finding adequate sources of support are found to be fundamental for recovery in the parent role.

Implications for practice

Peer groups can be of valuable help and mental health workers can support parents to set self‐chosen parenting related goals.
Effects of forage offering method on performance, rumen fermentation, nutrient digestibility and nutritional behaviour in Holstein dairy calves
Authors: EbnAli A. , Khorvash M. , Ghorbani G. R. , Mahdavi A. H. , Malekkhahi M. , Mirzaei M. , Pezeshki A. , Ghaffari M. H.
Published: February 2016

The potential effect of dietary forage supplementation on the performance and rumen development in dairy calves is well established. However, limited research has been directed to the comparative effects of forage offering methods on calf performance. The objective of the present study was to determine the effects of forage provision methods (total mixed ration or free choice) on the performance, nutrient digestibility, rumen fermentation and nutritional behaviour in newborn calves. Forty‐five Holstein dairy calves (3 days of age and 41 ± 2 kg of body weight) were assigned to the following three groups (n = 15): (i) starter without forage provision (CON), (ii) starter supplemented with 10% alfalfa hay (AH) as a total mixed ration (AH‐TMR) and (iii) starter and AH as a free‐choice provision (AH‐FC) for a period of 70 days. All the calves were offered 5 l of milk/day from day 3 to 50, and 2.5 l/day from day 50 until weaning on day 56. Dry matter intake (DMI) was greater (p < 0.01) in the AH‐TMR and AH‐FC treatments than in the CON during the pre‐ and post‐weaning periods. Calves fed the AH‐FC diet showed the highest post‐weaning DMI among the treatments. The calves receiving ad libitum forage tended (p = 0.08) to increase crude protein digestibility and overall volatile fatty acids (VFA) concentrations in the rumen. No differences were observed among the treatments at the time spent on standing, lying, eating and performing non‐nutritive oral behaviours. Compared to CON calves, animals in the AH‐TMR treatment spent more time (p < 0.05) ruminating. In conclusion, our data suggest that forage supplementation in both forage offering methods increased total DMI, ruminal pH and ruminating time in dairy calves. Hence, there is no benefit in the free‐choice provision of AH in dairy calves.
Prevalence of insomnia‐related symptoms continues to increase in the Finnish working‐age population
Authors: Kronholm Erkki , Partonen Timo , Härmä Mikko , Hublin Christer , Lallukka Tea , Peltonen Markku , Laatikainen Tiina
Published: February 2016

In 2008, we published epidemiological data from 1972 to 2005 that suggested an increase in insomnia‐related symptoms among the working‐age population. The results were based on the National FINRISK (FR) Study samples of the Finnish adult population aged 25–64, and on the Finnish Quality of Work Life Surveys (FQWLS), carried out among Finnish salary earners. Both of these ongoing studies have since provided two new estimates of insomnia‐related symptoms. Chronic insomnia‐related symptoms were 9.0% (95% CI 8.3–9.7), 9.6% (95% CI 8.8–10.4) in FR 2007 and 2012, respectively; and 9.1% (95% CI 8.3–10.0), 9.2% (95% CI 8.4–10.1) in FQWLS 2008 and 2013, respectively. Occasional insomnia‐related symptoms were 45.3% (95% CI 44.1–46.6), 42.5% (95% CI 41.1–43.9) in FR 2007 and 2012, respectively; and 40.3% (95% CI 38.8–41.7), 44.8% (95% CI 41.1–43.9) in FQWLS 2008 and 2013, respectively. The new estimates further strengthen the interpretation of the ongoing increase in occasional insomnia‐related symptoms among the Finnish general adult population. The increase in occasional symptoms was most prominent among employees. However, chronic insomnia symptoms showed no further increase.
Exactly/Nearly Unbiased Estimation of Autocovariances of a Univariate Time Series With Unknown Mean
Authors: Vogelsang Timothy J. , Yang Jingjing
Published: February 2016

This article proposes an exactly/nearly unbiased estimator of the autocovariance function of a univariate time series with unknown mean. The estimator is a linear function of the usual sample autocovariances computed using the observed demeaned data. The idea is to stack the usual sample autocovariances into a vector and show that the expectation of this vector is a linear combination of population autocovariances. A matrix that we label,A, collects the weights in these linear combinations. When the population autocovariances of high lags are zero (small), exactly (nearly) unbiased estimators of the remaining autocovariances can be obtained using the inverse of upper blocks of theAmatrix. TheA‐matrix estimators are shown to be asymptotically equivalent to the usual sample autocovariance estimators. TheA‐matrix estimators can be used to construct estimators of the autocorrelation function that have less bias than the usual estimators. Simulations show that theA‐matrix estimators can substantially reduce bias while not necessarily increasing mean square error. More powerful tests for the null hypothesis of white noise are obtained using theA‐matrix estimators.
Interacting effects of grazing and habitat conditions on seedling recruitment and establishment
Authors: Kladivová Anna , Münzbergová Zuzana
Published: February 2016

Questions

What is the effect of grazing on seedling recruitment and seedling establishment? To what extent is grazing dependent on local habitat conditions?

Location

Český Kras (Czech Karst), central Bohemia, Czech Republic.

Methods

In 2005, grazing was reintroduced on formerly grazed dry grassland. Twelve blocks of grazed and control plots were established. Seedlings of dicotyledonous plants were observed three times a year for 4 yrs, for a total of ten censuses. We tested the effects of grazing on seedling recruitment (entry of new individuals to the seedling stage) as well as seedling establishment (survival of seedlings for 1 yr after initial emergence). In addition, we explored the effect of soil depth – the most important environmental variable at our study site – on seedling response to grazing. The effects of grazing, soil depth and season on seedling number in plots were tested with generalized mixed effect models with a Poisson distribution. The effect of grazing on species composition was tested with canonical correspondence analysis.

Results

Grazing had a significant positive effect on seedling recruitment. Grazing affected the number of seedlings and species composition and facilitated the presence of dry grassland species. Seedlings of xerophilous species were primarily found in grazed plots, while control plots contained species preferring higher, closed sward. Grazing explained only 1.2% of the total variation in composition of recruited seedlings. We presume that the main factor determining species composition could be dispersal limitation. Grazing increased the number of recruited seedlings by 10.55%. The final number of established seedlings was unaffected by grazing. Furthermore, the interaction of grazing with soil depth had a significant positive effect on seedling recruitment, thus showing that the effect of grazing strongly depends on habitat conditions at the specific microsite within our location.

Conclusions

Our results indicate that predicting higher generative reproduction on pastures based on a larger number of seedlings may be misleading if the species are limited by establishment – but not recruitment – as at our study site. Furthermore, our findings show that varying habitat conditions on small spatial scales can modify the impact of management on seedling recruitment and establishment.
Electoral Rules and Legislative Parties in the Ukrainian Rada
Authors: Thames Frank
Published: February 2016

Critics of Ukraine's single‐member district majoritarian and mixed‐member majoritarian electoral systems argue that they undermined the efficiency of the Supreme Rada by permitting nonpartisan single‐member district deputies to enter the legislature in large numbers. Such deputies changed parties and ignored party positions. This article argues that the effect of the differences in how legislators are elected is dependent upon whether legislators are partisans. The statistical analysis of party switching and party cohesion in the Rada from 1998 to 2002 shows that nonpartisan single‐member district deputies were the most likely to switch parties and the least cohesive.
Mapping and Explaining Parliamentary Rule Changes in Europe: A Research Program
Authors: Sieberer Ulrich , Meißner Peter , Keh Julia F. , Müller Wolfgang C.
Published: February 2016

We outline a comprehensive research program on institutional reforms in European parliaments. Original data show that parliamentary rules in Western European parliaments have been changed frequently and massively during the period from 1945 to 2010 suggesting that actors use institutional reforms as a distinct strategy to pursue their substantive goals. We discuss how institutional instability affects existing theoretical and empirical arguments about institutional effects. Furthermore, we present four ideal‐typical approaches to analyzing rule changes, present new software tools for identifying and coding changes in large text corpora, and demonstrate their usefulness for valid measurement of the overall change between subsequent text versions.
Challenger Quality and the Incumbency Advantage
Authors: Ban Pamela , Llaudet Elena , Snyder James M.
Published: February 2016

Most estimates of the incumbency advantage and the electoral benefits of previous officeholding experience do not account for strategic entry by high‐quality challengers. We address this issue by using term limits as an instrument for challenger quality. Studying US state legislatures, we find strong evidence of strategic behavior by experienced challengers. However, we also find that such behavior does not appear to significantly bias the estimated effect of challenger experience or the estimated incumbency advantage. More tentatively, using our estimates, we find that 30–40% of the incumbency advantage in state legislative races is the result of “scaring off” experienced challengers.
Relay Requirement and Traffic Assignment of Electric Vehicles
Authors: Xie Chi , Jiang Nan
Published: February 2016

This article defines, formulates, and solves a new equilibrium traffic assignment problem with side constraints—the traffic assignment problem with relays. The relay requirement arises from the driving situation that the onboard fuel capacity of vehicles is lower than what is needed for accomplishing their trips and the number and distribution of refueling infrastructures over the network are under the expected level. We proposed this problem as a modeling platform for evaluating congested regional transportation networks that serve plug‐in electric vehicles (in addition to internal combustion engine vehicles), where battery‐recharging or battery‐swapping stations are scarce. Specifically, we presented a novel nonlinear integer programming formulation, analyzed its mathematical properties and paradoxical phenomena, and suggested a generalized Benders decomposition framework for its solutions. In the algorithmic framework, a gradient projection algorithm and a labeling algorithm are adopted for, respectively, solving the primal problem and the relaxed master problem—the shortest path problem with relays. The modeling and solution methods are implemented for solving a set of example network problems. The numerical analysis results obtained from the implementation clearly show how the driving range limit and relay station location reshape equilibrium network flows.
Listeria monocytogenes wall teichoic acid decoration in virulence and cell‐to‐cell spread
Authors: Spears Patricia A. , Havell Edward A. , Hamrick Terri S. , Goforth John B. , Levine Alexandra L. , Abraham S. Thomas , Heiss Christian , Azadi Parastoo , Orndorff Paul E.
Published: February 2016

Wall teichoic acid (WTA) comprises a class of glycopolymers covalently attached to the peptidoglycan of gram positive bacteria. In Listeria monocytogenes, mutations that prevent addition of certain WTA decorating sugars are attenuating. However, the steps required for decoration and the pathogenic process interrupted are not well described. We systematically examined the requirement for WTA galactosylation in a mouse oral‐virulent strain by first creating mutations in four genes whose products conferred resistance to a WTA‐binding bacteriophage. WTA biochemical and structural studies indicated that galactosylated WTA was directly required for bacteriophage adsorption and that mutant WTA lacked appreciable galactose in all except one mutant – which retained a level ca. 7% of the parent. All mutants were profoundly attenuated in orally infected mice and were impaired in cell‐to‐cell spread in vitro. Confocal microscopy of cytosolic mutants revealed that all expressed ActA on their cell surface and formed actin tails with a frequency similar to the parent. However, the mutant tails were significantly shorter – suggesting a defect in actin based motility. Roles for the gene products in WTA galactosylation are proposed. Identification and interruption of WTA decoration pathways may provide a general strategy to discover non‐antibiotic therapeutics for gram positive infections. © 2016 John Wiley & Sons Ltd
Low‐dose paclitaxel ameliorates renal fibrosis by suppressing transforming growth factor‐β1‐induced plasminogen activator inhibitor‐1 signaling
Authors: Jung Eun Sook , Lee Jeonghwan , Heo Nam Ju , Kim Sejoong , Kim Dong Ki , Joo Kwon Wook , Han Jin Suk
Published: February 2016

Aim

To investigate the effect of microtubule stabilization with low‐dose paclitaxel on renal fibrosis, focusing on the transforming growth factor‐β1 (TGF‐β1)‐induced plasminogen activator inhibitor‐1 (PAI‐1) signaling cascade.

Methods

Forty‐eight rats were randomly assigned to four groups: sham/vehicle, sham/paclitaxel, unilateral ureteral obstruction (UUO)/vehicle and UUO/paclitaxel. Rats were treated with a 0.3 mg/kg intraperitoneal dose of paclitaxel or vehicle twice per week for 14 days. Half of the rats in each group were sacrificed respectively on day 7 and 14 after operation. Inner medullar collecting duct (IMCD) cells stimulated with TGF‐β1 were incubated with 0, 1 and 2 nM paclitaxel for 24 and 72 hours. Histological changes were assessed using periodic acid‐Schiff and Masson's trichrome. The TGF‐β1‐induced PAI‐1 signaling and status of extracellular matrix proteins were evaluated by western blot analysis.

Results

In the UUO kidneys, paclitaxel significantly attenuated tubular damage and interstitial collagen deposition, as well as α‐smooth muscle actin (α‐SMA), TGF‐β1 and PAI‐1 protein expression. Paclitaxel also inhibited the UUO‐induced activation of Smad2/3 and c‐Jun N‐terminal kinase (JNK). However, paclitaxel treatment did not inhibit extracellular signal‐regulated kinase 1/2 (ERK1/2) or p38 expression. In TGF‐β1‐treated IMCD cells, treatment with 1 and 2 nM paclitaxel for 72 h reduced fibronectin, α‐SMA and PAI‐1 protein expression. Moreover, a 2 nM dose of paclitaxel for 24 h significantly inhibited the TGF‐β1‐stimulated activation of Smad2/3, JNK and ERK1/2 in IMCD cells.

Conclusion

Paclitaxel at low non‐cytotoxic doses ameliorates renal fibrosis by inhibiting multiple steps in the TGF‐β1‐induced PAI‐1 signaling including Smads and mitogen‐activated protein kinases.
Characterizing colonic motility in children with chronic intractable constipation: a look beyond high‐amplitude propagating sequences
Authors: Wessel S. , Koppen I. J. N. , Wiklendt L. , Costa M. , Benninga M. A. , Dinning P. G.
Published: February 2016

Background

Children with chronic intractable constipation experience severe and long‐lasting symptoms, which respond poorly to conventional therapeutic strategies. Detailed characterization of colonic motor patterns in such children has not yet been obtained.

Methods

In 18 children with chronic intractable constipation, a high‐resolution water‐perfused manometry catheter (36 sensors at 1.5‐cm intervals) was colonoscopically placed with the tip at the distal transverse colon. Colonic motor patterns were recorded for 2 h prior to and after a meal and then after colonic infusion of bisacodyl. These data were compared with previously published colonic manometry data from 12 healthy adult controls and 14 adults with slow‐transit constipation.

Key Results

The postprandial number of the retrograde cyclic propagating motor pattern was significantly reduced in these children compared with healthy adults (children, 3.1 ± 4.7/h vs healthy adults, 34.7 ± 45.8/h; p < 0.0001) but not constipated adults (4.5 ± 5.6/h; p = 0.9). The number of preprandial long‐single motor patterns was significantly higher (p = 0.003) in children (8.0 ± 13.2/h) than in healthy adults (0.4 ± 0.9/h) and in constipated adults (0.4 ± 0.7/h). Postprandial high‐amplitude propagating sequences (HAPSs) were rarely observed in children (2/18), but HAPS could be induced by bisacodyl in 16 of 18 children.

Conclusions & Inferences

Children with chronic intractable constipation show a similar impaired postprandial colonic response to that seen in adults with slow‐transit constipation. Children may have attenuated extrinsic parasympathetic inputs to the colon associated with an increased incidence of spontaneous long‐single motor patterns.
Colonic content in health and its relation to functional gut symptoms
Authors: Bendezú R. A. , Barba E. , Burri E. , Cisternas D. , Accarino A. , Quiroga S. , Monclus E. , Navazo I. , Malagelada J.‐R. , Azpiroz F.
Published: February 2016

Background

Gut content may be determinant in the generation of digestive symptoms, particularly in patients with impaired gut function and hypersensitivity. Since the relation of intraluminal gas to symptoms is only partial, we hypothesized that non‐gaseous component may play a decisive role.

Methods

Abdominal computed tomography scans were evaluated in healthy subjects during fasting and after a meal (n = 15) and in patients with functional gut disorders during basal conditions (when they were feeling well) and during an episode of abdominal distension (n = 15). Colonic content and distribution were measured by an original analysis program.

Key Results

In healthy subjects both gaseous (87 ± 24 mL) and non‐gaseous colonic content (714 ± 34 mL) were uniformly distributed along the colon. In the early postprandial period gas volume increased (by 46 ± 23 mL), but non‐gaseous content did not, although a partial caudad displacement from the descending to the pelvic colon was observed. No differences in colonic content were detected between patients and healthy subjects. Symptoms were associated with discrete increments in gas volume. However, no consistent differences in non‐gaseous content were detected in patients between asymptomatic periods and during episodes of abdominal distension.

Conclusions & Inferences

In patients with functional gut disorders, abdominal distension is not related to changes in non‐gaseous colonic content. Hence, other factors, such as intestinal hypersensitivity and poor tolerance of small increases in luminal gas may be involved.
Epigenetic regulation of subgenome dominance following whole genome triplication in Brassica rapa
Authors: Cheng Feng , Sun Chao , Wu Jian , Schnable James , Woodhouse Margaret R. , Liang Jianli , Cai Chengcheng , Freeling Michael , Wang Xiaowu
Published: February 2016

Subgenome dominance is an important phenomenon observed in allopolyploids after whole genome duplication, in which one subgenome retains more genes as well as contributes more to the higher expressing gene copy of paralogous genes.

To dissect the mechanism of subgenome dominance, we systematically investigated the relationships of gene expression, transposable element (TE) distribution and small RNA targeting, relating to the multicopy paralogous genes generated from whole genome triplication in Brassica rapa.

The subgenome dominance was found to be regulated by a relatively stable factor established previously, then inherited by and shared among B. rapa varieties. In addition, we found a biased distribution of TEs between flanking regions of paralogous genes. Furthermore, the 24‐nt small RNAs target TEs and are negatively correlated to the dominant expression of individual paralogous gene pairs. The biased distribution of TEs among subgenomes and the targeting of 24‐nt small RNAs together produce the dominant expression phenomenon at a subgenome scale.

Based on these findings, we propose a bucket hypothesis to illustrate subgenome dominance and hybrid vigor. Our findings and hypothesis are valuable for the evolutionary study of polyploids, and may shed light on studies of hybrid vigor, which is common to most species.
Alleviation of proton toxicity by nitrate uptake specifically depends on nitrate transporter 1.1 in Arabidopsis
Authors: Fang Xian Zhi , Tian Wen Hao , Liu Xing Xing , Lin Xian Yong , Jin Chong Wei , Zheng Shao Jian
Published: February 2016

Protons in acid soil are highly rhizotoxic to plants, but the mechanism of tolerance of plants to protons is largely unknown. Nitrate uptake by root cells is accompanied by the uptake of protons. Therefore, nitrate uptake transporters (NRTs) may be involved in plant tolerance to proton toxicity.

We investigated the root nitrate uptake response to proton stress in Arabidopsis and its association with proton tolerance using NRT‐related mutants and pharmacological methods.

Lack of NRT1.1 in knockout nrt1.1 mutants led to impaired proton tolerance in nitrate‐sufficient growth medium, whereas no difference was seen between wild‐type plants and NRT1.2‐, NRT2.1‐, NRT2.2‐, and NRT2.4‐null mutants. Another nrt1.1 point mutant, which is defective in nitrate uptake but has a normal nitrate‐sensing function, also had impaired proton tolerance compared with the wild‐type plant. Furthermore, proton stress induced NRT1.1‐mediated nitrate uptake. These results indicate that NRT1.1‐conferred proton tolerance depends on nitrate uptake activity. In addition, the rooting medium was alkalified by wild‐type plants, but not by knockout nrt1.1 mutants, and in pH‐buffered medium, there were no differences in proton tolerance between wild‐type plants and knockout nrt1.1 mutants.

We conclude that NRT1.1‐mediated nitrate uptake plays a crucial role in plant proton tolerance by alkalifying the rhizosphere.
Communication of information about oral and oropharyngeal cancer: the quality of online resources
Authors: Bánki F. , Thomas S.J. , Main B.G. , Waylen A.E.
Published: February 2016

Aim

To critically appraise the content, quality and readability of websites that provide online information about oral and oropharyngeal cancer and are accessible by people diagnosed with that condition.

Material and methods

Three popular search engines were used to find websites providing information about oral and oropharyngeal cancer, and all links that presented on the first page of the search were analysed. Included sites were assessed for content (intended audience, and evidence of quality assurance). The validated DISCERN tool was used to assess the quality of sites. A readability score was calculated. Descriptive and inferential statistical analyses were performed.

Results

A total of 162 web sites were examined. The majority (87%) were written for a clinical audience. Most (89%) did not display evidence of quality assurance. The median overall quality (DISCERN) score was 2.0, indicating potentially serious shortcomings. There was a correlation between the DISCERN scores and evidence of quality assurance certification, but this was not seen for readability.

Conclusion

The quality of online information that may be accessed by people with oral and oropharyngeal cancer when seeking information online remains poor.
The production of human glucocerebrosidase in glyco‐engineered Nicotiana benthamiana plants
Authors: Limkul Juthamard , Iizuka Sayoko , Sato Yohei , Misaki Ryo , Ohashi Takao , Ohashi Toya , Fujiyama Kazuhito
Published: February 2016

For the production of therapeutic proteins in plants, the presence of β1,2‐xylose and core α1,3‐fucose on plants’ N‐glycan structures has been debated for their antigenic activity. In this study, RNA interference (RNAi) technology was used to down‐regulate the endogenous N‐acetylglucosaminyltransferase I (GNTI) expression in Nicotiana benthamiana. One glyco‐engineered line (NbGNTI‐RNAi) showed a strong reduction of plant‐specific N‐glycans, with the result that as much as 90.9% of the total N‐glycans were of high‐mannose type. Therefore, this NbGNTI‐RNAi would be a promising system for the production of therapeutic glycoproteins in plants. The NbGNTI‐RNAi plant was cross‐pollinated with transgenic N. benthamiana expressing human glucocerebrosidase (GC). The recombinant GC, which has been used for enzyme replacement therapy in patients with Gaucher's disease, requires terminal mannose for its therapeutic efficacy. The N‐glycan structures that were presented on all of the four occupied N‐glycosylation sites of recombinant GC in NbGNTI‐RNAi plants (GCgnt1) showed that the majority (ranging from 73.3% up to 85.5%) of the N‐glycans had mannose‐type structures lacking potential immunogenic β1,2‐xylose and α1,3‐fucose epitopes. Moreover, GCgnt1 could be taken up into the macrophage cells via mannose receptors, and distributed and taken up into the liver and spleen, the target organs in the treatment of Gaucher's disease. Notably, the NbGNTI‐RNAi line, producing GC, was stable and the NbGNTI‐RNAi plants were viable and did not show any obvious phenotype. Therefore, it would provide a robust tool for the production of GC with customized N‐glycan structures.
De Novo Mutation in ABCC9 Causes Hypertrichosis Acromegaloid Facial Features Disorder
Authors: Afifi Hanan H. , Abdel‐Hamid Mohamed S. , Eid Maha M. , Mostafa Inas S. , Abdel‐Salam Ghada M.H.
Published: February 2016

A 13‐year‐old Egyptian girl with generalized hypertrichosis, gingival hyperplasia, coarse facial appearance, no cardiovascular or skeletal anomalies, keloid formation, and multiple labial frenula was referred to our clinic for counseling. Molecular analysis of the ABCC9 gene showed a de novo missense mutation located in exon 27, which has been described previously with Cantu syndrome. An overlap between Cantu syndrome, acromegaloid facial syndrome, and hypertrichosis acromegaloid facial features disorder is apparent at the phenotypic and molecular levels. The patient reported here gives further evidence that these syndromes are an expression of the ABCC9‐related disorders, ranging from hypertrichosis and acromegaloid facies to the severe end of Cantu syndrome.
Deep procedural sedation by a sedationist team for outpatient pediatric renal biopsies
Authors: Kamat Pradip P. , Ayestaran Frank W. , Gillespie Scott E. , Sanders Rebecca D. , Greenbaum Larry A. , Simon Harold K. , Stockwell Jana A.
Published: February 2016

To date, no study has analyzed the use of deep PS for pediatric renal biopsies by a dedicated sedation team in an outpatient setting. Retrospective analysis of renal biopsies performed at CHOA from 2009 to 2013. Patient demographics, procedure success, and sedation‐related events were analyzed. Logistic regression techniques were applied to identify characteristics associated with procedure safety and success. A total of 174 biopsies from 136 patients, aged 2–21 yr, were reviewed. Of the 174 biopsies, 63 of 174 (36%) were from native, and 111 of 174 (64%) were from transplanted kidneys, respectively. No deaths, allograft losses, or unanticipated hospital admissions occurred. The most commonly utilized interventions during sedation were blow‐by oxygen (29.9%) and CPAP (12.1%). Children receiving the combination of F + P had significantly higher biopsy success rates vs. other drug combinations (96.1% vs. 79%; p = 0.014). There was no difference in complication rates regardless of drug combination or biopsy type (transplanted vs. native). The combination of F + P yields a high procedural success rate for outpatient native and transplanted kidney biopsies. We identified a number of sedation‐related events that can be easily managed by a well‐trained sedationist team.
Codelivery of DNA vaccination encoding LeIF gene and IL‐12 increases protection against Leishmania major infection in BALB/c mice
Authors: Maspi N. , Ghaffarifar F. , Sharifi Z. , Dalimi A.
Published: February 2016

Previous studies have shown that Leishmania elongation initiation factor (LeIF) antigen causes a partial immunity against leishmaniasis. The antigen develops type I immunity by overexpression of inflammatory cytokines such as interleukin‐12 (IL‐12), IFN‐γ and TNF‐α. Therefore, We evaluated immune responses induced by the LeIF gene against Leishmania major infection. Immunization with LeIF gene alone or with IL‐12 induced Th1 response and produced higher IFN‐γ and lower IL‐4 levels by splenocytes than control groups (P < 0·05) and also ratios of IFN‐γ/IL‐4 were 11·68 to 18·53 times more in immunized groups than control groups after challenge. In addition, analysis of humoral immune response revealed that immunized mice had more IgG2a levels than both control groups (P < 0·05). On the other hand, lesion size was less for immunized animals than control groups from 4th week after challenge (P < 0·05). The percentage reduction in lesion size was 29·30% for LeIF and 51·98% for LeIF + IL‐12 than PBS at 12th week post‐infection. Spleen parasite burden decreased in all immunized groups in comparison with control groups (P < 0·05). The results indicated that LeIF gene induced partial immunity against L. major infection in BALB/c mice. However, LeIF plus IL‐12 group showed more potent immunity with smaller lesions than other groups.