bluuebunny/crossref_metadata_2025 huggingface dataset:
Building a sustainable higher education sector in the UAE
Authors: Jose Saju , Chacko Jacob
Published: July 2017

Purpose

The purpose of this paper is to examine the relevant economic aspects that could affect the sustainability of the HE sector in the UAE.

Design/methodology/approach

Data are collected mainly through secondary sources and based on the relevant information. Two constructs, namely, market factors and educational governance are identified from the literature. An empirical model depicting the different factors that contribute to these two variables is outlined.

Findings

Educational governance and market factors are identified as the key pillars which contribute to the economic efficiency in the HE sector in the UAE. These constructs are affected by relevant factors. Some of the issues relating to educational governance could be controlled. Though factors contributing to market conditions could be deemed uncontrollable, HE institutions could come up with better strategies to deal with those issues.

Research limitations/implications

The UAE HE sector could be a major contributor to the economy in the future, it is important to identify the main constructs and the associated forces which could impact the economic efficiency of the HE sector. The model proposed could be empirically tested in future studies.

Originality/value

This study is a novel attempt to examine sustainability in the HE sector in terms of economic efficiency, while previous studies have focused on the social and environmental aspect of the sustainability in the HE sector. Thus this study tries to address this lacuna in this domain by focusing on the economic efficiency aspect which is an important contributor to the sustainable development. The results may provide valuable insights for universities and regulators in developing appropriate strategies to improve the HE sector.
Revenue management for Canadian professional sports organizations
Authors: Willie Paul A.
Published: July 2017

Purpose

This paper aims to recommend opportunities for professional sport leagues in the USA and Canada to apply the art and science of revenue management in order to minimize potential losses and maximize profits.

Design/methodology/approach

The evolution of current key revenue management concepts is presented from their initial stages to their current level of implementation. In addition, the literature regarding the strongest business models is reviewed and examined in the context of current successes and challenges across the major sport leagues in North America.

Findings

Five revenue streams in sports organizations are identified and analysed. Five key elements for revenues are highlighted as strategic tools used to maximize effectiveness in achieving revenue management goals. A series of recommendations is made to best use revenue management including careful negotiation of television contracts, the use of dynamic pricing models, maximization of partnerships and sponsorships, acceptance of new approaches to food and beverage and accessibility of sport merchandise to customers.

Practical implications

At the regional, national and international levels, sports organizations should review their current business practices to identify areas to improve their revenue management in light of the recommendations in this paper.

Originality/value

Although the use of the concept of revenue management in sectors of tourism has evolved since early 1970s, its application in professional sports is relatively new. Therefore, this paper provides value to professional sports organizations to optimize their profitability.
Human resource challenges in Canada’s hospitality and tourism industry
Authors: Murray William C. , Elliot Statia , Simmonds Keith , Madeley Donnalea , Taller Martin
Published: July 2017

Purpose

This paper aims to explore the challenges encountered by the hospitality and tourism industry in managing the labour challenges it faces presently and will face in the coming years. Although there are several issues at play, there are actions that industry members can take both internally and by advocating externally for change.

Design/methodology/approach

This paper draws on insights from three industry members and two academics to explore key areas in which action can be taken to address labour demand challenges in the hospitality and tourism workforce. The identified action items combine these various types of expertise to provide a holistic frame of action.

Findings

The Canadian hospitality and tourism industry is facing an ever-increasing labour demand shortage. Industry members can confront this on multiple fronts, from front-line employee satisfaction to more regional and national advocacy efforts. A combination of activities is recommended.

Practical implications

Hospitality and tourism industry members can take numerous actions from this analysis, including developing stronger organization cultures that align with employee needs, exerting effort in balancing wage gap issues and maintaining pressure on government partners to provide support for establishing hospitality and tourism, so that it is viewed as a valuable career path.

Originality/value

This paper increases knowledge in the hospitality and tourism field by combining the current human resource management theory with observations from industry experts on the needs that exist now and are predicted in the coming years.
Amenamevir, a novel helicase–primase inhibitor, for treatment of herpes zoster: A randomized, double‐blind, valaciclovir‐controlled phase 3 study
Authors: Kawashima Makoto , Nemoto Osamu , Honda Mariko , Watanabe Daisuke , Nakayama Juichiro , Imafuku Shinichi , Kato Toshiyuki , Katsuramaki Tsuneo ,   the study investigators
Published: July 2017

Amenamevir is a potent helicase–primase inhibitor and a novel class of antiviral agent other than nucleoside compounds, such as aciclovir, valaciclovir and famciclovir. This study is the first randomized, double‐blind, valaciclovir‐controlled phase 3 study to evaluate the efficacy and safety of amenamevir in Japanese patients with herpes zoster when treated within 72 h after onset of rash. A total of 751 patients were randomly assigned to receive either amenamevir 400 mg or 200 mg p.o. once daily or valaciclovir 1000 mg three times daily (daily dose, 3000 mg) for 7 days. The primary efficacy end‐point was the proportion of cessation of new lesion formation by day 4 (“day 4 cessation proportion”). The day 4 cessation proportions for amenamevir 400 and 200 mg and valaciclovir were 81.1% (197/243), 69.6% (172/247) and 75.1% (184/245), respectively. Non‐inferiority of amenamevir 400 mg to valaciclovir was confirmed by a closed testing procedure. Days to cessation of new lesion formation, complete crusting, healing, pain resolution and virus disappearance were evaluated as secondary end‐points. No significant differences were observed in any of the treatment groups. Amenamevir 400 and 200 mg were well tolerated as well as valaciclovir. The proportions of patients who experienced drug‐related adverse events were 10.0% (25/249), 10.7% (27/252) and 12.0% (30/249) with amenamevir 400 and 200 mg and valaciclovir, respectively. In conclusion, amenamevir 400 mg appears to be effective and well tolerated for treatment of herpes zoster in immunocompetent Japanese patients.
Strategies for managing rival bacterial communities: Lessons from burying beetles
Authors: Duarte Ana , Welch Martin , Swannack Chris , Wagner Josef , Kilner Rebecca M.
Published: July 2017

The role of bacteria in animal development, ecology and evolution is increasingly well understood, yet little is known of how animal behaviour affects bacterial communities. Animals that benefit from defending a key resource from microbial competitors are likely to evolve behaviours to control or manipulate the animal's associated external microbiota.

We describe four possible mechanisms by which animals could gain a competitive edge by disrupting a rival bacterial community: “weeding,” “seeding,” “replanting” and “preserving.” By combining detailed behavioural observations with molecular and bioinformatic analyses, we then test which of these mechanisms best explains how burying beetles, Nicrophorus vespilloides, manipulate the bacterial communities on their carcass breeding resource.

Burying beetles are a suitable species to study how animals manage external microbiota because reproduction revolves around a small vertebrate carcass. Parents shave a carcass and apply antimicrobial exudates on its surface, shaping it into an edible nest for their offspring. We compared bacterial communities in mice carcasses that were either fresh, prepared by beetles or unprepared but buried underground for the same length of time. We also analysed bacterial communities in the burying beetle's gut, during and after breeding, to understand whether beetles could be “seeding” the carcass with particular microbes.

We show that burying beetles do not “preserve” the carcass by reducing bacterial load, as is commonly supposed. Instead, our results suggest they “seed” the carcass with bacterial groups which are part of the Nicrophorus core microbiome. They may also “replant” other bacteria from the carcass gut onto the surface of their carrion nest. Both these processes may lead to the observed increase in bacterial load on the carcass surface in the presence of beetles. Beetles may also “weed” the bacterial community by eliminating some groups of bacteria on the carcass, perhaps through the production of antimicrobials themselves.

Whether these alterations to the bacterial community are adaptive from the beetle's perspective, or are simply a by‐product of the way in which the beetles prepare the carcass for reproduction, remains to be determined in future work. In general, our work suggests that animals might use more sophisticated techniques for attacking and disrupting rival microbial communities than is currently appreciated.
Effects of host species and environment on the skin microbiome of Plethodontid salamanders
Authors: Muletz Wolz Carly R. , Yarwood Stephanie A. , Campbell Grant Evan H. , Fleischer Robert C. , Lips Karen R.
Published: July 2017

The amphibian skin microbiome is recognized for its role in defence against pathogens, including the deadly fungal pathogen Batrachochytrium dendrobatidis (Bd). Yet, we have little understanding of evolutionary and ecological processes that structure these communities, especially for salamanders and closely related species. We investigated patterns in the distribution of bacterial communities on Plethodon salamander skin across host species and environments.

Quantifying salamander skin microbiome structure contributes to our understanding of how host‐associated bacteria are distributed across the landscape, among host species, and their putative relationship with disease.

We characterized skin microbiome structure (alpha‐diversity, beta‐diversity and bacterial operational taxonomic unit [OTU] abundances) using 16S rRNA gene sequencing for co‐occurring Plethodon salamander species (35 Plethodon cinereus, 17 Plethodon glutinosus, 10 Plethodon cylindraceus) at three localities to differentiate the effects of host species from environmental factors on the microbiome. We sampled the microbiome of P. cinereus along an elevational gradient (n = 50, 700–1,000 m a.s.l.) at one locality to determine whether elevation predicts microbiome structure. Finally, we quantified prevalence and abundance of putatively anti‐Bd bacteria to determine if Bd‐inhibitory bacteria are dominant microbiome members.

Co‐occurring salamanders had similar microbiome structure, but among sites salamanders had dissimilar microbiome structure for beta‐diversity and abundance of 28 bacterial OTUs. We found that alpha‐diversity increased with elevation, beta‐diversity and the abundance of 17 bacterial OTUs changed with elevation (16 OTUs decreasing, 1 OTU increasing). We detected 11 putatively anti‐Bd bacterial OTUs that were present on 90% of salamanders and made up an average relative abundance of 83% (SD ± 8.5) per salamander. All salamanders tested negative for Bd.

We conclude that environment is more influential in shaping skin microbiome structure than host differences in these congeneric species, and suggest that environmental characteristics that covary with elevation influence microbiome structure. High prevalence and abundance of anti‐Bd bacteria may contribute to low Bd levels in these populations of Plethodon salamanders.
Validity of the Assistance to Participate Scale with Parents of typically developing Australian children aged three to eight years
Authors: Joyce Kahli , Bourke‐Taylor Helen , Wilkes‐Gillan Sarah
Published: July 2017

Background/aim

The Assistance to Participate Scale (APS) measures the assistance parents provide to children with disability to participate in play and leisure. The primary aim of this study was to extend the psychometric development of theAPSthrough application to a typically developing sample.

Methods

Parents (N = 125) of typically developing Australian children aged three to eight years completed an online questionnaire comprising theAPS, Pediatric Evaluation of Disability Inventory (PEDI), Pediatric Quality of Life Scale (PedsQL) (caregiver scales) and demographic questions. Guided by theCOnsensus‐based Standards for the selection of health MeasurementINstruments (COSMIN), structural validity of theAPSwas investigated using principal components analysis; internal consistency reliability through calculation of Cronbach's α; construct validity through convergence with previously validated measures of paediatric occupational performance and quality of life (PEDI, PedsQL) and investigation of five research hypotheses developed a priori.

Results

Structural validity of theAPSwas confirmed. Internal consistency (Cronbach's α = 0.76) was good for this unidimensional scale. Construct validity was substantiated by moderate correlations with thePEDIand PedsQL(physical), and data that supported all research hypotheses. Statistically significant differences were found inAPSscores based on sex (P = 0.018), age (P < 0.001), school attendance (P < 0.001) and elder sibling (P = 0.006).

Conclusions

Results of this study indicate theAPSis a valid and reliable measure of the parental role in a typically developing child's play. Validation upon a typically developing sample offers preliminary guidelines regarding the normative pattern of assistance provided to children during play. Further research in line with theCOSMINis required.
Role of peripheral vascular resistance as an indicator of cardiovascular abnormalities in patients with Parkinson's disease
Authors: Zawadka‐Kunikowska Monika , Słomko Joanna , Tafil‐Klawe Małgorzata , Klawe Jacek J , Cudnoch‐Jędrzejewska Agnieszka , Newton Julia L , Zalewski Paweł
Published: July 2017

The aim of this study was to evaluate cardiovascular autonomic modulation in response to an orthostatic stress in healthy subjects and Parkinson's disease (PD). The study included 47 controls and 56 PD patients divided into groups (vasoconstrictor PD, vasodilator PD, control) according to vasodilation/vasoconstriction response during 70° head up tilt test. Using impedance cardiography (ICG) and electrocardiography (ECG) we measured stroke volume, cardiac output, left ventricular work index, left ventricular ejection time, acceleration index, index of contractility, Heather index, thoracic fluid content, total peripheral resistance, total arterial compliance. We also analyzed heart rate variability (HRV), using spectral analysis and continuous blood pressure (contBP). At rest, the vasodilator PD group showed significantly higher values of total peripheral resistance and lower values of stroke volume and cardiac output, compared to the vasoconstrictor PD and the control groups. A post‐tilt drop in ∆ (change rest – tilt) systolic blood pressure, ∆mean blood pressure, ∆total peripheral resistance and ∆Heather index, and a significantly lower increase in ∆diastolic blood pressure was observed in subjects from the vasodilator PD group compared to the vasoconstrictor PD and the control groups. No statistically significant differences were observed for HRV parameters between the vasoconstrictor and vasodilator PD groups, P > .05. Longer duration and higher disease stage of PD correlated with a reduction in post‐tilt systolic blood pressure changes in vasodilator group. Positive inotropy of the cardiac muscle represents a significant factor preventing orthostatic hypotension in PD subjects with a concurrent drop in peripheral vascular resistance during orthostatic stress.
Consumers’ Preferences for Bread: Transgenic, Cisgenic, Organic or Pesticide‐free?
Authors: Edenbrandt Anna K. , Gamborg Christian , Thorsen Bo J.
Published: July 2017

Consumers are apprehensive about transgenic technologies, so cisgenics, which limit gene transfers to sexually compatible organisms, have been suggested to address consumer concerns. We study consumer preferences for rye bread alternatives based on transgenic or cisgenic rye, grown conventionally or without the use of pesticides, relative to traditionally bred rye, grown with conventional or organic farming methods. Stated preference (SP) data from a choice experiment are combined with revealed preference (RP) data from market purchases from the same respondents. Results show that respondents prefer pesticide‐free production methods, and that while cisgenics is preferred over transgenics, the majority of respondents favour traditional breeding methods. The distribution in preferences suggests that some respondents prefer bread from cisgenic crops produced without pesticides over traditional crops produced using pesticides. Preferences for organic bread are stronger than for pesticide‐free products. From a policy perspective results suggest that excluding cisgenics from mandatory labeling in the EU, or including it in the voluntary non‐GM labelling in the US, would cause welfare losses for consumers.
Labor Unions and Income Smoothing
Authors: Hamm Sophia J. W. , Jung Boochun , Lee Woo‐Jong
Published: July 2017

We study labor unions, an important stakeholder group that has not been a focus of the earnings smoothing literature. We posit that managers strike a balance between sheltering resources from employees’ profit sharing demands and catering to employees’ aversion to downside risk by smoothing earnings. We then hypothesize that a strong labor union would intensify managerial incentives to smooth earnings. Consistent with our hypothesis, we find that union strength is positively associated with earnings smoothing activities through management of both accruals and R&D expenditures.
Parents’ Use of Subsidiaries to “Push Down” Earnings Management: Evidence from Italy
Authors: Bonacchi Massimiliano , Cipollini Fabrizio , Zarowin Paul
Published: July 2017

We find evidence consistent with Italian nonlisted subsidiaries engaging in accrual and real earnings management, so that their listed parents can meet or beat benchmarks. Thus, the parent firm drives the earnings management of the subsidiaries. We identify parents that are more likely to have managed earnings as the ones that avoid a small loss or meet or beat analyst forecast by a few cents. Cross‐sectional analysis reveals that Big 4 auditors mitigate accrual earnings management at the subsidiary level and that family‐owned firms use earnings management through nonlisted subsidiaries mainly to avoid reporting losses. Finally, we find that parent firms communicate earnings management strategies to their subsidiaries using board proximity. Our evidence shows that business groups manage earnings differently from single firms, pushing earnings management down to subsidiaries. It also supports the monitoring role of Big 4 auditors in a business group setting and contributes to understanding financial reporting decisions in family‐owned firms.
Delirium after fast‐track hip and knee arthroplasty – a cohort study of 6331 elderly patients
Authors: Petersen P. B. , Jørgensen C. C. , Kehlet H. ,   the Lundbeck Foundation Centre for Fast‐track Hip and Knee Replacement Collaborative Group
Published: July 2017

Background

Postoperative delirium (PD) is a well‐known complication among elderly surgical patients and associated with increased morbidity, mortality and length of stay (LOS). In elective orthopedic surgery, including hip and knee arthroplasty (THA/TKA), most studies report incidences between 5% and 10%. The multimodal optimization of perioperative care (fast‐track) aims to enhance recovery and reduce morbidity and LOS, but limited data are available on the effect on PD. Consequently, the study investigated signs of PD associated with LOS > 4 days.

Methods

Prospective risk assessment study with retrospective analysis of discharge notes or medical records of signs of PD in 6331 elective primary unilateral THA and TKA patients ≥ 70 years, and LOS > 4 days. Preoperative patient characteristics collected from eight high volume centers with similar standardized fast‐track protocols from January 2010 to November 2013.

Results

We identified 43 (0.7%) cases of PD symptoms mentioned as a reason for LOS > 4 days among the 789 patients with LOS > 4 days (12.5% of all THA and TKA). PD patients had a mean age of 80.7 [[95% CI] 79.3–82.1] years, being 4.0 [[95% CI] 2.5–5.5] years older compared to patients without PD (P < 0.001). LOS was median 10 [[Q2–Q3] 7–14] days in the PD group vs. 3 [2–3] days in the non‐PD group (P < 0.001), without differences in gender or site of arthroplasty (P = 0.139 and 0.499, respectively).

Conclusion

Postoperative delirium symptoms contributing to LOS > 4 days in fast‐track THA and TKA are rare in elderly patients.
Akt2 ablation prolongs life span and improves myocardial contractile function with adaptive cardiac remodeling: role of Sirt1‐mediated autophagy regulation
Authors: Ren Jun , Yang Lifang , Zhu Li , Xu Xihui , Ceylan Asli F. , Guo Wei , Yang Jian , Zhang Yingmei
Published: July 2017

Aging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulation of Akt and autophagy. This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca2+ properties were evaluated using echocardiography, IonOptix® edge‐detection and fura‐2 techniques. Levels of Sirt1, mitochondrial integrity, autophagy, and mitophagy markers were evaluated using Western blot. Our results revealed that Akt2 ablation prolonged life span (by 9.1%) and alleviated aging (24 months)‐induced unfavorable changes in myocardial function and intracellular Ca2+ handling (SERCA2a oxidation) albeit with more pronounced cardiac hypertrophy (58.1%, 47.8%, and 14.5% rises in heart weight, wall thickness, and cardiomyocyte cross‐sectional area). Aging downregulated levels of Sirt1, increased phosphorylation of Akt, and the nuclear transcriptional factor Foxo1, as well as facilitated acetylation of Foxo1, the effects of which (except Sirt1 and Foxo1 acetylation) were significantly attenuated or negated by Akt2 ablation. Advanced aging disturbed autophagy, mitophagy, and mitochondrial integrity as evidenced by increased p62, decreased levels of beclin‐1, Atg7, LC3B, BNIP3, PTEN‐induced putative kinase 1 (PINK1), Parkin, UCP‐2, PGC‐1α, and aconitase activity, the effects of which were reversed by Akt2 ablation. Aging‐induced cardiomyocyte contractile dysfunction and loss of mitophagy were improved by rapamycin and the Sirt1 activator SRT1720. Activation of Akt using insulin or Parkin deficiency prevented SRT1720‐induced beneficial effects against aging. In conclusion, our data indicate that Akt2 ablation protects against cardiac aging through restored Foxo1‐related autophagy and mitochondrial integrity.
Factors Associated with Self‐Estimated Breath Alcohol Concentration Among Bar Patrons
Authors: Rossheim Matthew E. , Barry Adam E. , Thombs Dennis L. , Weiler Robert M. , Krall Jenna R. , Stephenson Caroline J. , Walters Scott T. , Reed Mark B. , Clapp John D. , Suzuki Sumihiro , Barnett Tracey E. , Cannell M. Brad
Published: July 2017

Background

Few studies have examined the context in which drinkers underestimate their breath alcohol concentration (BrAC) in natural drinking environments. This study examined factors associated with bar patrons’ self‐estimated BrAC in high‐risk college town settings.

Methods

Guided interview and BrAC data were collected from 510 participants recruited as they exited bars located close to large universities: 1 in Florida and 1 in Texas.

Results

Participants with the highest measured BrACs underestimated their BrAC levels the most. Findings from multivariable linear regression analysis indicated that BrAC (std β = 0.014, p < 0.001), number of alcoholic drinks consumed (std β = 0.006, p < 0.01), and perceived drunkenness (std β = 0.024, p < 0.001) had significant positive associations with BrAC self‐estimates, where the regression coefficients were scaled by values approximately equal to each variable's interquartile range. Among the 321 participants with BrAC levels ≥ 0.08 g/dl, 21.2% believed their BrAC was below the legal per se driving limit of 0.08 g/dl. Results from a logistic regression analysis indicated that higher levels of perceived drunkenness were associated with better self‐recognition that one's BrAC level exceeded the legal driving threshold (OR = 3.312, p < 0.001). Further, participants under 26 years of age had reduced odds of recognizing that their BrAC was greater than 0.079 g/dl (OR = 0.245, p < 0.05).

Conclusions

These findings highlight the inaccuracy of self‐estimated BrAC when drinking, particularly among younger drinkers. Adjusting for BrAC, situational factors were strongly associated with self‐estimated BrAC. Future research is needed to better understand how altering drinking environments may improve accuracy of BrAC self‐estimates and deter driving after drinking.
The effects of board gender diversity on a firm's risk strategies
Authors: Chen Linda H. , Gramlich Jeffrey , Houser Kimberly A.
Published: July 2017

We study whether board gender diversity (BGD) affects corporate risk strategies. Specifically, we investigate the association between BGD and firms’ reputation risk and financial risk. Using S&P data from 1997 to 2013, we find that BGD is negatively associated with tax avoidance, suggesting firms with gender‐diverse boards are more cautious about potential reputation risks associated with aggressive tax strategies. However, we find that BGD is positively associated with firms’ financial risk. The combined findings illustrate that BGD aligns a firm's risk exposure closer to risk‐neutral shareholders’ preferences by reducing reputation risk exposure while enabling necessary financial risk exposure.
Cocaine and HIV are independently associated with neural activation in response to gain and loss valuation during economic risky choice
Authors: Meade Christina S. , Addicott Merideth , Hobkirk Andrea L. , Towe Sheri L. , Chen Nan‐Kuei , Sridharan Sriramkumar , Huettel Scott A.
Published: July 2017

Stimulant abuse is disproportionately common in HIV‐positive persons. Both HIV and stimulants are independently associated with deficits in reward‐based decision making, but their interactive and/or additive effects are poorly understood despite their prevalent co‐morbidity. Here, we examined the effects of cocaine dependence and HIV infection in 69 adults who underwent functional magnetic resonance imaging while completing an economic loss aversion task. We identified two neural networks that correlated with the evaluation of the favorable characteristics of the gamble (i.e. higher gains/lower losses: ventromedial prefrontal cortex, anterior cingulate, anterior and posterior precuneus and visual cortex) versus unfavorable characteristics of the gamble (i.e. lower gains/higher losses: dorsal prefrontal, lateral orbitofrontal, posterior parietal cortex, anterior insula and dorsal caudate). Behaviorally, cocaine and HIV had additive effects on loss aversion scores, with HIV‐positive cocaine users being the least loss averse. Cocaine users had greater activation in brain regions that tracked the favorability of gamble characteristics (i.e. increased activation to gains, but decreased activation to losses). In contrast, HIV infection was independently associated with lesser activation in regions that tracked the unfavorability of gamble characteristics. These results suggest that cocaine is associated with an overactive reward‐seeking system, while HIV is associated with an underactive cognitive control system. Together, these alterations may leave HIV‐positive cocaine users particularly vulnerable to making unfavorable decisions when outcomes are uncertain.
Proliferation of endogenous regulatory T cells improve the pathophysiology associated with placental ischaemia of pregnancy
Authors: Ibrahim Tarek , Przybyl Lukasz , Harmon Ashlyn C. , Amaral Lorena M. , Faulkner Jessica L. , Cornelius Denise C. , Cunningham Mark W. , Hünig Thomas , Herse Florian , Wallukat Gerd , Dechend Ralf , LaMarca Babbette
Published: July 2017

Problem

Preeclampsia (PE) is associated with inflammation and decreased Treg cells and IL‐10. The reduced uterine perfusion pressure (RUPP) rat model of PE exhibits these characteristics, and we hypothesized that induction of endogenous Tregs by a specific stimulus (CD28 superagonistic monoclonal antibody) would reduce inflammation, vasoactive factors, and hypertension in RUPP rats.

Method of study

RUPP was performed at gestation day (GD) 14; CD28 superagonist was administered intraperitoneally GD15; GD18 carotid catheters were inserted, and GD19 MAP and pup weight, blood, and tissues were collected.

Results

MAP (mmHg) in NP rats was 99±5 and 122±2 in RUPPs and was 111±1 mmHg in RUPP+SA. Circulating Tregs were 6±2% in NP rats and 0.77±0.49% in RUPP rats but increased to 11± 3% in RUPP+SA rats. Circulating IL‐6 and IL‐2 were decreased while IL‐10 and TGF‐B were significantly increased in RUPP+SA compared to RUPP controls. Vasoactive pathways such as ET‐1, AT1‐AA, and ROS were all reduced in RUPP+SA compared to RUPP. Pup weight was 2.4±0.05 mg in NP and 1.94±0.062 mg in RUPP and increased to 2.1± 0.05 mg in RUPP+SA.

Conclusion

These data suggest that stimulating endogenous Tregs lower factors causing hypertension and can improve fetal weight in response to PE.
Accelerated fetal growth in early pregnancy and risk of severe large‐for‐gestational‐age and macrosomic infant: a cohort study in a low‐risk population
Authors: Simic Marija , Wikström Anna‐Karin , Stephansson Olof
Published: July 2017

Introduction

Our objective was to examine the association between fetal growth in early pregnancy and risk of severe large‐for‐gestational‐age (LGA) and macrosomia at birth in a low‐risk population.

Material and methods

Cohort study that included 68 771 women with non‐anomalous singleton pregnancies, without history of diabetes or hypertension, based on an electronic database on pregnancies and deliveries in Stockholm–Gotland Region, Sweden, 2008–2014. We performed multivariable logistic regression to estimate the association between accelerated fetal growth occurring in the first through early second trimester as measured by ultrasound and LGA and macrosomia at birth. Restricted analyses were performed in the groups without gestational diabetes and with normal body mass index (18.5–24.9 kg/m2).

Results

When adjusting for confounders, the odds of having a severely LGA or macrosomic infant were elevated in mothers with fetuses that were at least 7 days larger than expected as compared with mothers without age discrepancy at the second‐trimester scan (adjusted odds ratio 1.80; 95% CI 1.23–2.64 and adjusted odds ratio 2.15; 95% CI 1.55–2.98, respectively). Additionally, mothers without gestational diabetes and mothers with normal weight had an elevated risk of having a severely LGA or macrosomic infant when the age discrepancy by second‐trimester ultrasound was at least 7 days.

Conclusions

In a low‐risk population, ultrasound‐estimated accelerated fetal growth in early pregnancy was associated with an increased risk of having a severely LGA or macrosomic infant.
Laparoscopic dissection of Merkel cell carcinoma recurrence at the pelvic lymph node
Authors: Watanabe Genki , Fukunaga Yosuke , Nagasaki Toshiya , Akiyoshi Takashi , Konishi Tsuyoshi , Fujimoto Yoshiya , Nagayama Satoshi , Ueno Masashi
Published: July 2017

Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin. It has a high propensity for recurrence and metastasis, and there is no clearly defined treatment. MCC recurrence at the pelvic lymph node has rarely been reported. Herein, we report a patient with pelvic lymph node recurrence of MCC that was dissected laparoscopically. Nine years before presenting to us, a 76‐year‐old male patient had been diagnosed with MCC, and since then, he had had two recurrences. The most recent recurrence—the third recurrence—involved a tumor that had been detected at the right pelvic lymph node, and MCC recurrence was suspected after several imaging studies. Laparoscopic right pelvic lymph node dissection was conducted, and pathological findings confirmed MCC recurrence. The patient was discharged on postoperative day 8 and had no recurrence for 2 years as detected by imaging. This case report demonstrates the benefits of laparoscopic treatment of MCC recurrence with respect to intraoperative magnified vision and a more comfortable postoperative course for the patient.
A call to incorporate systems theory and human factors into the existing investigation of harm in clinical research involving healthcare products
Authors: Edwards Brian D. , Bégaud Bernard , Daemen Esther , Dokas Ioannis , Fishbein Jonathan M. , Greenberg Howard E. , Hochberg Alan , Le Louet Hervé , Lyngvig Jytte , Mogles Nataliya , Owen Kathryn , Prendergast Christine , Rejzek Martin , Trantza Sophia , Webb David J. , Whalen Matthew , Whiteley Simon
Published: July 2017

This is a joint statement from individual pharmacology and pharmaceutical professionals acting in their own capacity, including members of the Alliance for Clinical Research Excellence and Safety (ACRES) and the International Society of Pharmacovigilance (ISoP). By building on the extensive pharmacological and regulatory investigations that already take place, we are calling for a fuller and more robust systems‐based approach to the independent investigation of clinical research when serious incidents of harm occur, starting with first‐in‐human clinical trials. To complement existing activities and regulations, we propose an additional approach blending evidence derived from both pharmacological and organizational science, which addresses human factors and transparency, to enhance organizational learning and continuous improvement. As happens with investigations in other sectors of society, such as the chemical and aviation sector, this systems approach should be seen as an additional way to understand how problems occur and how they might be prevented in the future. We believe that repetition of potentially preventable and adverse outcomes during clinical research, by failing to identify and act upon all systematic vulnerabilities, is a situation that needs urgent change. As we will discuss further on, approaches based on applying systems theory and human factors are much more likely to improve objectivity and transparency, leading to better system design.
Covariate-adjusted Response-adaptive Randomization for Multi-arm Clinical Trials Using a Modified Forward Looking Gittins Index Rule
Authors: Villar Sofía S. , Rosenberger William F.
Published: July 2017

We introduce a non-myopic, covariate-adjusted response adaptive (CARA) allocation design for multi-armed clinical trials. The allocation scheme is a computationally tractable procedure based on the Gittins index solution to the classic multi-armed bandit problem and extends the procedure recently proposed in Villar et al. (2015). Our proposed CARA randomization procedure is defined by reformulating the bandit problem with covariates into a classic bandit problem in which there are multiple combination arms, considering every arm per each covariate category as a distinct treatment arm. We then apply a heuristically modified Gittins index rule to solve the problem and define allocation probabilities from the resulting solution. We report the efficiency, balance, and ethical performance of our approach compared to existing CARA methods using a recently published clinical trial as motivation. The net savings in terms of expected number of treatment failures is considerably larger and probably enough to make this design attractive for certain studies where known covariates are expected to be important, stratification is not desired, treatment failures have a high ethical cost, and the disease under study is rare. In a two-armed context, this patient benefit advantage comes at the expense of increased variability in the allocation proportions and a reduction in statistical power. However, in a multi-armed context, simple modifications of the proposed CARA rule can be incorporated so that an ethical advantage can be offered without sacrificing power in comparison with balanced designs.
The impact of education on dental health — Ways to measure causal effects
Authors: Grytten Jostein
Published: July 2017

To our knowledge, there are no studies in which a possible causal effect of education on dental health has been examined. Such studies are needed to predict whether more schooling for people with poor dental health improves their dental health. Within social science, and in economics in particular, several methods have been developed to make causal inferences of the relationship between education and general health. These methods, which are based on observational data, are relevant to use for estimating a possible causal effect of education on dental health. This commentary provides an overview of the state of the art of the following methods: the use of instrumental variables, twin studies and a regression discontinuity design. Using these methods, reversed causality and the omission of a third variable that influences both education and dental health can be controlled for. In that way, an unbiased estimate of the effect of education on dental health can be obtained. To implement each of the methods correctly, several criteria have to be fulfilled. These criteria are outlined and discussed below.
Safety and pharmacodynamics of intranasal GSK2245035, a TLR7 agonist for allergic rhinitis: A randomized trial
Authors: Ellis A. K. , Tsitoura D. C. , Quint D. , Powley W. , Lee L. A.
Published: July 2017

Background

Toll‐like receptor 7 (TLR7) stimulation in the airways may reduce responses to aeroallergens by induction of type 1 interferons (IFNs). GSK2245035 is a novel selective TLR7 agonist in pharmaceutical development.

Objective

Assessment of safety, pharmacodynamics and nasal allergic reactivity following repeated weekly intranasal (i.n.) GSK2245035.

Methods

This randomized, double‐blind, placebo‐controlled study (TL7116958) was conducted over two pollen seasons (2013‐2014) and follow‐up study (204509) conducted 1 year later. Participants with allergic rhinitis (n=42) were randomized to receive eight weekly doses of i.n. GSK2245035 (20 ng [2014 Cohort; n=14] or 80 ng [2013 Cohort; n=14]) or placebo (n=14). Adverse events (AEs) including cytokine release syndrome AEs (CytoRS‐AEs) and nasal symptoms were assessed. Nasal and serum IFN‐inducible protein 10 (IP‐10) were measured after doses 1 and 8, then 1 (follow‐up visit [FUV] 1) and 3 (FUV2) weeks after final dose. Nasal allergen challenges (NACs) and allergic biomarker assessment (nasal, serum) were conducted at baseline, FUV1, FUV2 and at a FUV 1 year after final dose (FUV3; 2014 Cohort only). A Bayesian framework enabled probability statements for mean effect sizes.

Results

GSK2245035 induced CytoRS‐AEs (most commonly headache, median duration <1 day) in 93% of participants at 80 ng, while AE incidence at 20 ng was similar to placebo. There was no evidence of nasal inflammation. Dose‐related increases in nasal and serum IP‐10 were observed 24 hours after doses 1 and 8 (>95% certainty). Both doses showed a trend in reducing total nasal symptom score 15 minutes post‐NAC at FUV1 and FUV2, but there was no reduction evident at FUV3. Nasal levels of selected allergic biomarkers demonstrated trends for reductions at FUV1, FUV2 and FUV3.

Conclusions and clinical relevance

Weekly i.n. GSK2245035 20 ng was well tolerated and reduced allergic reactivity to nasal challenge for 3 weeks post‐treatment.
Time to glucose peak during an oral glucose tolerance test identifies prediabetes risk
Authors: Chung Stephanie T. , Ha Joon , Onuzuruike Anthony U. , Kasturi Kannan , Galvan‐De La Cruz Mirella , Bingham Brianna A. , Baker Rafeal L. , Utumatwishima Jean N. , Mabundo Lilian S. , Ricks Madia , Sherman Arthur S. , Sumner Anne E.
Published: July 2017

Context

Morphological characteristics of the glucose curve during an oral glucose tolerance test (OGTT) (time to peak and shape) may reflect different phenotypes of insulin secretion and action, but their ability to predict diabetes risk is uncertain.

Objective

To compare the ability of time to glucose peak and curve shape to detect prediabetes and β‐cell function.

Design and participants

In a cross‐sectional evaluation using an OGTT, 145 adults without diabetes (age 42±9 years (mean±SD), range 24‐62 years, BMI 29.2±5.3 kg/m2, range 19.9‐45.2 kg/m2) were characterized by peak (30 minutes vs >30 minutes) and shape (biphasic vs monophasic).

Main outcome measures

Prediabetes and disposition index (DI)—a marker of β‐cell function.

Results

Prediabetes was diagnosed in 36% (52/145) of participants. Peak>30 minutes, not monophasic curve, was associated with increased odds of prediabetes (OR: 4.0 vs 1.1; P<.001). Both monophasic curve and peak>30 minutes were associated with lower DI (P≤.01). Time to glucose peak and glucose area under the curves (AUC) were independent predictors of DI (adjR2=0.45, P<.001).

Conclusion

Glucose peak >30 minutes was a stronger independent indicator of prediabetes and β‐cell function than the monophasic curve. Time to glucose peak may be an important tool that could enhance prediabetes risk stratification.
Developing a national colorectal educational agenda: a survey of the Association of Coloproctology of Great Britain and Ireland
Authors: Francis N. K. , Curtis N. J. , Weegenaar C. , Boorman P. A. , Brook A. , Thorpe G. , Keogh K. , Grainger J. , Davies J. , Wheeler J. , Brown S. R. , Steele R. J. , Dawson P. ,   the ACPGBI Education Training Committee
Published: July 2017

Aim

In order to develop its education agenda, the Association of Coloproctology of Great Britain and Ireland (ACPGBI) sought the opinion of its members on current coloproctology training needs. The aims of this study were to canvass multidisciplinary needs and explore the perceived gaps and barriers to meeting them.

Method

A learner‐needs analysis was performed between July 2015 and October 2016. A bespoke electronic survey was sent to 1453 colorectal healthcare professionals [ACPGBI membership (1173), colorectal nurse specialists and allied health professionals (NAHPs) (261) and regional chapter‐leads (19)] seeking their needs, experiences and barriers to training across the coloproctology disciplines.

Results

In all, 390 responses were received [26.8% overall; 180 consultants/trainees (15%); 196 NAHPs (75%); 14 (74%) chapter‐leads]. Lack of funding and difficulties in obtaining study leave were the most frequently reported barriers to course and conference attendance. Transanal total mesorectal excision and laparoscopic training were the top educational needs for consultants and trainees respectively. 79% of NAHP respondents reported education gaps on a broad range of clinical and non‐clinical topics. NAHPs lacked information on relevant training opportunities and 27% felt available courses were insufficient to meet their educational needs. Wide heterogeneity in ACPGBI chapter composition and activity was reported. All groups felt the ACPGBI should increase the number of courses offered with coloproctology knowledge updates commonly requested.

Conclusion

A series of training needs across the coloproctology disciplines have been identified. These will underpin the development of the educational agenda for the ACPGBI.
Bone marrow endothelial progenitor cells activate hepatic stellate cells and aggravate carbon tetrachloride induced liver fibrosis in mice via paracrine factors
Authors: Garg Manali , Kaur Savneet , Banik Arpita , Kumar Vikash , Rastogi Archana , Sarin Shiv K. , Mukhopadhyay Asok , Trehanpati Nirupma
Published: July 2017

Objectives

Bone marrow derived endothelial progenitor cells (BM‐EPCs) are increased in chronic liver disease (CLD). Their role in hepatic fibrosis and regeneration remains an area of intense studies. We investigated the migration and secretory functions of BM‐EPCs in fibrotic mice liver.

Materials and methods

Bone marrow cells from C57BL6‐GFP mice were transplanted into the femur of irradiated C57BL6 mice, followed by CCl4 doses for 8 weeks, to develop hepatic fibrosis (n = 36). Transplanted C57BL6 mice without CCl4 treatment were used as controls. EPCs were analyzed in BM, blood and liver by flow cytometry and immunofluorescence. VEGF and TGF‐β were analysed in the hepatic stellate cells (HSCs) and BM‐EPCs co‐cultures using ELISAs.

Results

There was a significant migration of EPCs from BM to blood and to the liver (P ≤ 0.01). Percentage of GFP+CD31+ EPCs and collagen proportionate area was substantially increased in the liver at 4th week of CCl4 dosage compared to the controls (19.8% vs 1.9%, P ≤ 0.05). Levels of VEGF (533.6 pg/ml) and TGF‐β (327.44 pg/ml) also increased significantly, when HSCs were treated with the EPC conditioned medium, as compared to controls (25.66 pg/ml and 5.87 pg/ml, respectively; P ≤ 0.001).

Conclusions

Present findings suggest that BM‐EPCs migrate to the liver during CCl4‐induced liver injury and contribute to fibrosis.
Developmental trajectory of neural specialization for letter and number visual processing
Authors: Park Joonkoo , van den Berg Berry , Chiang Crystal , Woldorff Marty G. , Brannon Elizabeth M.
Published: July 2017

Adult neuroimaging studies have demonstrated dissociable neural activation patterns in the visual cortex in response to letters (Latin alphabet) and numbers (Arabic numerals), which suggest a strong experiential influence of reading and mathematics on the human visual system. Here, developmental trajectories in the event‐related potential (ERP) patterns evoked by visual processing of letters, numbers, and false fonts were examined in four different age groups (7‐, 10‐, 15‐year‐olds, and young adults). The 15‐year‐olds and adults showed greater neural sensitivity to letters over numbers in the left visual cortex and the reverse pattern in the right visual cortex, extending previous findings in adults to teenagers. In marked contrast, 7‐ and 10‐year‐olds did not show this dissociable neural pattern. Furthermore, the contrast of familiar stimuli (letters or numbers) versus unfamiliar ones (false fonts) showed stark ERP differences between the younger (7‐ and 10‐year‐olds) and the older (15‐year‐olds and adults) participants. These results suggest that both coarse (familiar versus unfamiliar) and fine (letters versus numbers) tuning for letters and numbers continue throughout childhood and early adolescence, demonstrating a profound impact of uniquely human cultural inventions on visual cognition and its development.