bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Human Immunodeficiency Virus on the Severity of Buruli Ulcer Disease: Results of a Retrospective Study in Cameroon
Authors: Christinet Vanessa , Comte Eric , Ciaffi Laura , Odermatt Peter , Serafini Micaela , Antierens Annick , Rossel Ludovic , Nomo Alain-Bertrand , Nkemenang Patrick , Tsoungui Akoa , Delhumeau Cecile , Calmy Alexandra
Published: April 2014

Background.  Buruli ulcer is the third most common mycobacterial disease after tuberculosis and leprosy and is particularly frequent in rural West and Central Africa. However, the impact of HIV infection on BU severity and prevalence remains unclear.

Methods.  This was a retrospective study of data collected at the Akonolinga District Hospital, Cameroon, from January 1, 2002 to March 27, 2013. Human immunodeficiency virus prevalence among BU patients was compared with regional HIV prevalence. Baseline characteristics of BU patients were compared between HIV-negative and HIV-positive patients and according to CD4 cell count strata in the latter group. Buruli ulcer time-to-healing was assessed in different CD4 count strata, and factors associated with BU main lesion size at baseline were ide.jpegied.

Results.  Human immunodeficiency virus prevalence among BU patients was significantly higher than the regional estimated prevalence in each group (children, 4.00% vs 0.68% [P < .001]; men, 17.0% vs 4.7% [P < .001]; women, 36.0% vs 8.0% [P < .001]). Individuals who were HIV positive had a more severe form of BU, with an increased severity in those with a higher level of immunosuppression. Low CD4 cell count was significantly associated with a larger main lesion size (β-coefficient, −0.50; P = .015; 95% confidence interval [CI], −0.91–0.10). Buruli ulcer time-to-healing was more than double in patients with a CD4 cell count below 500 cell/mm3 (hazard ratio, 2.39; P = .001; 95% CI, 1.44–3.98).

Conclusion.  Patients who are HIV positive are at higher risk for BU. Human immunodeficiency virus-induced immunosuppression seems to have an impact on BU clinical presentation and disease evolution.
Diagnostic Value of Histamine and Tryptase Concentrations in Severe Anaphylaxis with Shock or Cardiac Arrest during Anesthesia
Authors: Laroche Dominique , Gomis Philippe , Gallimidi Emmanuel , Malinovsky Jean-Marc , Mertes Paul Michel
Published: April 2014

Background:

The diagnosis of acute life-threatening allergic reactions during anesthesia relies on clinical signs, histamine and/or tryptase measurements, and allergic testing. In patients who die after the reaction, skin tests cannot be performed, and the effect of resuscitation manoeuvres on mediator concentrations is unknown. The authors compared plasma histamine and tryptase concentrations in patients with severe allergic reactions during anesthesia with those measured in patients with shock due to other causes.

Methods:

Patients with life-threatening allergic reactions were retrieved from a previous database (Group ALLERGY). All had positive allergy tests to administered agents. Patients with severe septic/cardiogenic shock or cardiac arrest (Group CONTROL) had histamine and tryptase measurements during resuscitation manoeuvres. Receiver operating characteristics curves were built to calculate the optimal mediator thresholds differentiating allergic reactions from others.

Results:

One hundred patients were included, 75 in Group ALLERGY (cardiovascular collapse, 67; cardiac arrest, 8) and 25 in Group CONTROL (shock, 11; cardiac arrest, 14). Mean histamine and tryptase concentrations remained unchanged throughout resuscitation in Group CONTROL and were significantly higher in Group ALLERGY. The optimal thresholds indicating an allergic mechanism were determined as 6.35 nmol/l for histamine (sensitivity: 90.7% [95% CI, 81.7 to 96.1]; specificity: 91.7% [73.0 to 98.9]) and 7.35 μg/l for tryptase (sensitivity: 92% [83.4 to 97.0]; specificity: 92% [73.9 to 99.0]).

Conclusions:

Resuscitation manoeuvres by themselves did not modify mediator concentrations. Virtually all life-threatening reactions during anesthesia associated with mediator concentrations exceeding the thresholds were allergic events. These findings have potential forensic interest when a patient dies during anesthesia.
On the reliability of seasonal climate forecasts
Authors: Weisheimer A. , Palmer T. N.
Published: April 2014

Seasonal climate forecasts are being used increasingly across a range of application sectors. A recent UK governmental report asked: how good are seasonal forecasts on a scale of 1–5 (where 5 is very good), and how good can we expect them to be in 30 years time? Seasonal forecasts are made from ensembles of integrations of numerical models of climate. We argue that ‘goodness’ should be assessed first and foremost in terms of the probabilistic reliability of these ensemble-based forecasts; reliable inputs are essential for any forecast-based decision-making. We propose that a ‘5’ should be reserved for systems that are not only reliable overall, but where, in particular, small ensemble spread is a reliable indicator of low ensemble forecast error. We study the reliability of regional temperature and precipitation forecasts of the current operational seasonal forecast system of the European Centre for Medium-Range Weather Forecasts, universally regarded as one of the world-leading operational institutes producing seasonal climate forecasts. A wide range of ‘goodness’ rankings, depending on region and variable (with summer forecasts of rainfall over Northern Europe performing exceptionally poorly) is found. Finally, we discuss the prospects of reaching ‘5’ across all regions and variables in 30 years time.
Diet quality in a wild grazer declines under the threat of an ambush predator
Authors: Barnier Florian , Valeix Marion , Duncan Patrick , Chamaillé-Jammes Simon , Barre Philippe , Loveridge Andrew J. , Macdonald David W. , Fritz Hervé
Published: April 2014

Predators influence prey populations not only through predation itself, but also indirectly through prompting changes in prey behaviour. The behavioural adjustments of prey to predation risk may carry nutritional costs, but this has seldom been studied in the wild in large mammals. Here, we studied the effects of an ambush predator, the African lion (Panthera leo), on the diet quality of plains zebras (Equus quagga) in Hwange National Park, Zimbabwe. We combined information on movements of both prey and predators, using GPS data, and measurements of faecal crude protein, an index of diet quality in the prey. Zebras which had been in close proximity to lions had a lower quality diet, showing that adjustments in behaviour when lions are within short distance carry nutritional costs. The ultimate fitness cost will depend on the frequency of predator–prey encounters and on whether bottom-up or top-down forces are more important in the prey population. Our finding is the first attempt to our knowledge to assess nutritionally mediated risk effects in a large mammalian prey species under the threat of an ambush predator, and brings support to the hypothesis that the behavioural effects of predation induce important risk effects on prey populations.
Glucan, Water Dikinase Exerts Little Control over Starch Degradation in Arabidopsis Leaves at Night
Authors: Skeffington Alastair W. , Graf Alexander , Duxbury Zane , Gruissem Wilhelm , Smith Alison M.
Published: April 2014

The first step on the pathway of starch degradation in Arabidopsis (Arabidopsis thaliana) leaves at night is the phosphorylation of starch polymers, catalyzed by glucan, water dikinase (GWD). It has been suggested that GWD is important for the control of starch degradation, because its transcript levels undergo strong diel fluctuations, its activity is subject to redox regulation in vitro, and starch degradation is strongly decreased in gwd mutant plants. To test this suggestion, we analyzed changes in GWD protein abundance in relation to starch levels in wild-type plants, in transgenic plants in which GWD transcripts were strongly reduced by induction of RNA interference, and in transgenic plants overexpressing GWD. We found that GWD protein levels do not vary over the diel cycle and that the protein has a half-life of 2 d. Overexpression of GWD does not accelerate starch degradation in leaves, and starch degradation is not inhibited until GWD levels are reduced by 70%. Surprisingly, this degree of reduction also inhibits starch synthesis in the light. To discover the importance of redox regulation, we generated transgenic plants expressing constitutively active GWD. These plants retained normal control of degradation. We conclude that GWD exerts only a low level of control over starch degradation in Arabidopsis leaves.
Application of best practices in university entrepreneurship education
Authors: A. Gedeon Steven
Published: April 2014

Purpose

– The purpose of this paper is to identify and apply best practices in university entrepreneurship education to the creation of a new MBA in entrepreneurship and innovation management. It is a direct response to calls for a total re-envisioning of entrepreneurship education and criticism that existing programs lack rigour, content, pedagogy, measurement and an established definition.

Design/methodology/approach

– This article uses reviews of the literature to identify normative best practices and how to apply them to the new program. An entrepreneurship program design framework (EPDF) was created and applied to a new MBA program being developed in central Germany.

Findings

– Most studies describe aspects of current programs (e.g. lists of courses) but almost none say what should be in a program. Others provide abstract guidance (e.g. programs should define entrepreneurship) but do not give specific recommendations (e.g. what the definition should be). The proposed EPDF provided a rigorous structure for reviewing the literature, designing the new program and establishing specific best practice recommendations for defining program goals, content, pedagogy and measurement of student transformation.

Research limitations/implications

– The entrepreneurship literature is largely silent on normative best practice guidance, so the proposed application of best practices should be evaluated in that context.

Originality/value

– Previous articles present relatively abstract frameworks and concepts, whereas this article is a direct application of the practical implications of these concepts. The proposed normative best practice guidelines may be somewhat controversial, but should stimulate useful discussion.
A framework for assessing entrepreneurial outcomes: an international perspective
Authors: Watson John , J. Gatewood Elizabeth , Lewis Kate
Published: April 2014

Purpose

– In this paper, the authors aim to develop a framework that provides a holistic approach to the assessment of entrepreneurial performance outcomes (EPOs) incorporating the multitude of factors (such as entrepreneurial goals and cultural norms) that research suggests can impact the entrepreneurial process.

Design/methodology/approach

– In developing the suggested framework, the authors draw on both the existing literature and the findings provided in the five papers selected for this special issue.

Findings

– The framework the authors advance suggests that the satisfaction male and female entrepreneurs derive from their ventures is principally determined by a combination of the goals they set for their business and the outcomes/outputs achieved. There is also some evidence to suggest that, other things equal, females may experience higher levels of satisfaction with their ventures than males. Other key issues the authors have incorporated into the framework that are important to a better understanding of the entrepreneurial process include the resources the entrepreneur has available (human, financial and social); various external environmental factors (for example, government support programmes); and gender (for example, to the extent that women are more risk averse than men they may set more modest goals for their ventures).

Originality/value

– The holistic framework the authors present for assessing (and better understanding) the entrepreneurial process should help direct/focus: future research concerned with assessing, evaluating and understanding EPOs; government policies designed to promote entrepreneurial initiatives; and those providing advice to the sector.
Patient satisfaction and resident postgraduate year status
Authors: N. Nadkarni Girish , Singh Sabharwal Manpreet , Reddy Ammakkanavar Natraj , Annapureddy Narender , Malhan Rishi , Mehta Bijal , Naag Kanakadandi Vijay , Kumar Agarwal Shiv , D. Fried Ethan
Published: April 2014

Purpose

– Patient satisfaction has been recognized as an important variable affecting healthcare behavior. However, there are limited data on the relationship between doctor post-graduate year (PGY) status and patient satisfaction with provider interpersonal skills and humanistic qualities. The authors aims to assess this relationship using an American Board of Internal Medicine (ABIM) questionnaire.

Design/methodology/approach

– Participants were: patients attending a primary care clinic at a large urban academic hospital; and physicians treating them. The survey questionnaire was the ABIM patient satisfaction instrument; ten questions pertaining to humanistic qualities and communication skills with responses from poor to excellent. Mann Whitney U test and multi-variable logistic regression analyses were used to explore score differences by PGY level.

Findings

– The postgraduate year one (PGY1) had higher patient-satisfaction levels compared to PGY2/PGY3 residents. The PGY1 level residents were more likely to score in the 90th percentile and this remained constant even after adjusting for confounders.

Research limitations/implications

– The research was a single-center study and may have been subject to confounding factors such as patient personality types and a survey ceiling effect. The survey's cross-sectional nature may also be a potential limitation.

Practical implications

– Patient satisfaction varies significantly with PGY status. Though clinical skills may improve with increasing experience, findings imply that interpersonal and humanistic qualities may deteriorate.

Originality/value

– The study is the first to assess patient satisfaction with PGY status and provides evidence that advanced trainees may need support to keep their communication skills and humanistic qualities from deteriorating as stressors increase to ensure optimal patient satisfaction.
Social media in the 2011 Egyptian uprising
Authors: Brym Robert , Godbout Melissa , Hoffbauer Andreas , Menard Gabe , Zhang Tony Huiquan
Published: May 2014

This paper uses Gallup poll data to assess two narratives that have crystallized around the 2011 Egyptian uprising: (1) New electronic communications media constituted an important and independent cause of the protests in so far as they enhanced the capacity of demonstrators to extend protest networks, express outrage, organize events, and warn comrades of real‐time threats. (2) Net of other factors, new electronic communications media played a relatively minor role in the uprising because they are low‐cost, low‐risk means of involvement that attract many sympathetic onlookers who are not prepared to engage in high‐risk activism. Examining the independent effects of a host of factors associated with high‐risk movement activism, the paper concludes that using some new electronic communications media was associated with being a demonstrator. However, grievances, structural availability, and network connections were more important than was the use of new electronic communications media in distinguishing demonstrators from sympathetic onlookers. Thus, although both narratives have some validity, they must both be qualified.
Methods for Constructing and Assessing Propensity Scores
Authors: Garrido Melissa M. , Kelley Amy S. , Paris Julia , Roza Katherine , Meier Diane E. , Morrison R. Sean , Aldridge Melissa D.
Published: April 2014

Objectives

To model the steps involved in preparing for and carrying out propensity score analyses by providing step‐by‐step guidance and Stata code applied to an empirical dataset.

Study Design

Guidance, Stata code, and empirical examples are given to illustrate (1) the process of choosing variables to include in the propensity score; (2) balance of propensity score across treatment and comparison groups; (3) balance of covariates across treatment and comparison groups within blocks of the propensity score; (4) choice of matching and weighting strategies; (5) balance of covariates after matching or weighting the sample; and (6) interpretation of treatment effect estimates.

Empirical Application

We use data from the Palliative Care for Cancer Patients (PC4C) study, a multisite observational study of the effect of inpatient palliative care on patient health outcomes and health services use, to illustrate the development and use of a propensity score.

Conclusions

Propensity scores are one useful tool for accounting for observed differences between treated and comparison groups. Careful testing of propensity scores is required before using them to estimate treatment effects.
‘Lonely and Voiceless Your Halls Must Remain’: Romantic‐Era National Song and Felicia Hemans's Welsh Melodies (1822)
Authors: Edwards Elizabeth
Published: May 2014

This article places Felicia Hemans's little‐discussed song collection A Selection of Welsh Melodies (1822) in the expanding field of eighteenth‐ and early nineteenth‐century national melody in Britain. Drawing on recent studies of Romantic paratext, it discusses the layered, contingent and interstitial nature of Welsh Melodies, via a series of close readings of the song texts. It argues that Hemans's approach to Wales in her songs reveals the collaborative and translational nature of her work, involving cultural and historical transmission, as well as the models of female subjectivity, professional authorship and (at times) feminist sentiment for which she is better known.
SNP discovery in wild and domesticated populations of blue catfish, Ictalurus furcatus, using genotyping‐by‐sequencing and subsequent SNP validation
Authors: Li Chao , Waldbieser Geoff , Bosworth Brian , Beck Benjamin H. , Thongda Wilawan , Peatman Eric
Published: May 2014

Blue catfish, Ictalurus furcatus, are valued in the United States as a trophy fishery for their capacity to reach large sizes, sometimes exceeding 45 kg. Additionally, blue catfish × channel catfish (I. punctatus) hybrid food fish production has recently increased the demand for blue catfish broodstock. However, there has been little study of the genetic impacts and interaction of farmed, introduced and stocked populations of blue catfish. We utilized genotyping‐by‐sequencing (GBS) to capture and genotype SNP markers on 190 individuals from five wild and domesticated populations (Mississippi River, Missouri, D&B, Rio Grande and Texas). Stringent filtering of SNP‐calling parameters resulted in 4275 SNP loci represented across all five populations. Population genetics and structure analyses revealed potential shared ancestry and admixture between populations. We utilized the Sequenom MassARRAY to validate two multiplex panels of SNPs selected from the GBS data. Selection criteria included SNPs shared between populations, SNPs specific to populations, number of reads per individual and number of individuals genotyped by GBS. Putative SNPs were validated in the discovery population and in two additional populations not used in the GBS analysis. A total of 64 SNPs were genotyped successfully in 191 individuals from nine populations. Our results should guide the development of highly informative, flexible genotyping multiplexes for blue catfish from the larger GBS SNP set as well as provide an example of a rapid, low‐cost approach to generate and genotype informative marker loci in aquatic species with minimal previous genetic information.
Measuring the relative effect of factors affecting species distribution model predictions
Authors: Thibaud Emeric , Petitpierre Blaise , Broennimann Olivier , Davison Anthony C. , Guisan Antoine
Published: May 2014

Species distribution models are increasingly used to address conservation questions, so their predictive capacity requires careful evaluation. Previous studies have shown how individual factors used in model construction can affect prediction. Although some factors probably have negligible effects compared to others, their relative effects are largely unknown.

We introduce a general ’virtual ecologist’ framework to study the relative importance of factors involved in the construction of species distribution models.

We illustrate the framework by examining the relative importance of five key factors – a missing covariate, spatial autocorrelation due to a dispersal process in presences/absences, sample size, sampling design and modelling technique – in a real study framework based on virtual plants in a mountain landscape at regional scale, and show that, for the parameter values considered here, most of the variation in prediction accuracy is due to sample size and modelling technique. Contrary to repeatedly reported concerns, spatial autocorrelation has only comparatively small effects.

This study shows the importance of using a nested statistical framework to evaluate the relative effects of factors that may affect species distribution models.
Pest fencing or pest trapping: A bio‐economic analysis of cost‐effectiveness
Authors: Norbury Grant , Hutcheon Andy , Reardon James , Daigneault Adam
Published: May 2014

Scofield et al. discredited the utility of pest‐exclusion fences for restoring biodiversity partly on the grounds of unquantified costs and benefits. We estimated the discounted costs of mammal exclusion fences, semi‐permeable (‘leaky’) fences and trapping, over 50 years and adjusted costs by their observed effectiveness at reducing mammalian predator abundance. We modelled data from two large predator management programmes operated by the New Zealand Department of Conservation. Using typical baseline costs and predator control efficacies (scale 0 to 1), the model predicted that an exclusion fence (efficacy 1.0) is the cheapest and most cost‐effective option for areas below about 1 ha, a leaky fence (efficacy 0.9) is most cost‐effective for 1–219 ha, and trapping (efficacy 0.6, based on 0.2 traps per hectare and a 1500‐m buffer to reduce predator reinvasion) for areas above 219 ha. This ranking was insensitive to adjustments in efficacy, but reducing efficacy of leaky fences to 0.8 or increasing trapping efficacy to 0.7 reduced the cost‐effective range of leaky fences by about 90 ha. Reducing trap maintenance costs from $300 to $100 per trap per year (e.g. using long‐life lures), or reducing trap buffer widths to 500 m, significantly elevated trapping as the most cost‐effective method for areas greater than 11–15 ha. These results were largely consistent with an ecological measure of effectiveness based on observed rates of recovery of two indigenous skink species inside exclusion fences or with trapping. The results support criticisms that exclusion fences are generally not cost‐effective, but highlight the value of considering cheaper leaky designs for small‐ to medium‐sized areas. Because this study is based largely on reductions in predator abundance, it has general application to broader biodiversity protection interests, but not to indigenous species that are highly sensitive to predation and only ever adequately protected on the mainland by exclusion fences.
Transfer of blood urea nitrogen to cecal microbes and nitrogen retention in mature rabbits are increased by dietary fructooligosaccharides
Authors: Min Xiao , Xiao Jin , Kawasaki Kiyonori , Li Xiao , Sakaguchi Ei
Published: May 2014

To estimate the effect of fructooligosaccharides (FOS) on N utilization, seven mature rabbits were fed a diet containing 5% glucose or FOS for 8 days. During the last 5 days, total feces and urine were collected to measure N levels (Experiment 1). To examine N transfer from the blood to cecal microbes, eight rabbits were fed the same diets as in Experiment 1. After 9 days of feeding, 2 g of glucose or FOS was given orally. Two hours later 20 mg of 15N‐urea was administered via the ear vein, and 1 h later cecal and blood samples were collected (Experiment 2). Urinary N excretion was lowered by FOS feeding (P < 0.05). Total bacterial N and 15N in the cecum was significantly higher in FOS‐fed animals (P < 0.05). Urea N in the cecum was lower in FOS‐fed rabbits (P < 0.05). Similarly, 15N atom % excess of cecal urea N was also lower in FOS‐fed rabbits than in glucose‐fed rabbits. These results suggest that FOS in the diet increases the transfer of blood urea N to the cecum for bacterial synthesis, thereby increasing N utilization.
Dietary copper supplementation improves pelt characteristics of female silver fox (Vulpes fulva) during the winter fur‐growing season
Authors: Zhong Wei , Liu Hanlu , Luo Guoliang , Chang Zhongjuan , Liu Fenghua , Zhao Jingbo , Li Danli , Yue Zhigang , Zhang Haihua , Li Guangyu
Published: May 2014

Copper has an essential role in normal fur pigmentation and fur quality. This study evaluated the effects of cupric citrate (CuCit) supplementation on growth, nutrients metabolism and pelt characteristics of the female silver fox (Vulpes fulva). Fifty age‐matched female silver foxes with similar body weights were randomly divided into five dietary groups for 58 days during the winter fur‐growing season. The basal diet contained 4.92 mg/kg copper. Groups I‐V were supplemented with 6, 30, 60, 90 or 150 mg Cu from CuCit per 1 kg dry matter basal diet. Serum alkaline phosphatase activity was significantly higher (P < 0.05) in those fed 90 mg/kg Cu than those fed 150 mg/kg Cu. Pelt total thickness was significantly higher (P < 0.05) in those fed 30 mg/kg Cu than foxes fed 6 mg/kg Cu supplemented diet, but were similar to the other groups. Length of guard hair was significantly lower (P < 0.05) in those fed 90 mg/kg Cu than fed 6 mg/kg Cu and 30 mg/kg Cu, but were similar to the other groups. Length of underhair was significantly higher (P < 0.05) in those fed 6 mg/kg Cu than those fed 90 mg/kg Cu, but was similar to the other groups. Considering decreasing environmental contamination and improving pelt performance, supplementing 30 mg/kg Cu from CuCit (actual copper 35 mg/kg dry matter) is appropriate for female silver fox.
Why don't they accept non‐invasive ventilation?: Insight into the interpersonal perspectives of patients with motor neurone disease
Authors: Ando Hikari , Williams Carl , Angus Robert M. , Thornton Everard W. , Chakrabarti Biswajit , Cousins Rosanna , Piggin Lucy H. , Young Carolyn A.
Published: May 2014

Objectives

Although non‐invasive ventilation (NIV) can benefit survival and quality of life, it is rejected by a substantial proportion of people with motor neurone disease (MND). The aim of this study was to understand why some MND patients decline or withdraw from NIV.

Method

Nine patients with MND (male = 7, mean age = 67 years) participated in this study. These patients, from a cohort of 35 patients who were offered NIV treatment to support respiratory muscle weakness, did not participate in NIV treatment when it was clinically appropriate. Semi‐structured interviews and interpretative phenomenological analysis (IPA) were employed to explore these patient's experience of MND and their thoughts and understanding of NIV treatment.

Results

Using IPA, four themes were identified: preservation of the self, negative perceptions of NIV, negative experience with health care services, and not needing NIV. Further analysis identified the fundamental issue to be the maintenance of perceived self, which was interpreted to consist of the sense of autonomy, dignity, and quality of life.

Conclusions

The findings indicate psychological reasons for disengagement with NIV. The threat to the self, the sense of loss of control, and negative views of NIV resulting from anxiety were more important to these patients than prolonging life in its current form. These findings suggest the importance of understanding the psychological dimension involved in decision‐making regarding uptake of NIV and a need for sensitive holistic evaluation if NIV is declined.

Statement of contribution

What is already known on this subject?

Non‐invasive ventilation is widely used as an effective symptomatic therapy in MND, yet about a third of patients decline the treatment.

Psychological disturbance generated by NIV use leads to negative experiences of the treatment.

Decision‐making about treatment potentials is complex and unique to each individual affected by perceived impact of disease.

What does this study add?

A decision concerning NIV uptake was influenced by perceived impact on individuals' sense of self.

Sense of self was influenced by the maintenance of autonomy, dignity, and quality of life.

Individuals' sense of self was identified to have been challenged by the disease, NIV, and their experience of health care service.
The tyrosine kinase inhibitor bafetinib inhibits PAR2‐induced activation of TRPV4 channels in vitro and pain in vivo
Authors: Grace M S , Lieu T , Darby B , Abogadie F C , Veldhuis N , Bunnett N W , McIntyre P
Published: April 2014

Background and Purpose

Protease‐activated receptor 2 (PAR2) is expressed on nociceptive neurons, and can sensitize transient receptor potential (TRP) ion channels to amplify neurogenic inflammation and pain. The mechanisms by which this occurs are not fully understood. PAR2 causes receptor‐operated activation of TRPV4 channels and TRPV4 null mice have attenuated PAR2‐stimulated neurogenic inflammation and mechanical hyperalgesia. Here we investigate the intracellular signalling mechanisms underlying PAR2‐induced TRPV4 channel activation and pain.

Experimental Approach

Responses of non‐transfected and TRPV4‐transfected HEK293 cells to agonists of PAR2 (trypsin and SLIGRL) and TRPV4 channels (GSK1016790A) were determined using calcium imaging. Inhibitors of TRPV4 channels (HC067047), sarcoendoplasmic reticulum calcium transport ATPase (thapsigargin), Gαq (UBO‐QIC), tyrosine kinases (bafetinib and dasatinib) or PI3 kinases (wortmannin and LY294002) were used to investigate signalling mechanisms. In vivo effects of tyrosine kinase inhibitors on PAR2‐induced mechanical hyperalgesia were assessed in mice.

Key Results

In non‐transfected HEK293 cells, PAR2 activation transiently increased intracellular calcium ([Ca2+]i). Functional expression of TRPV4 channels caused a sustained increase of [Ca2+]i, inhibited by HC067047, bafetinib and wortmannin; but not by thapsigargin, UBO‐QIC, dasatinib or LY294002. Bafetinib but not dasatinib inhibited PAR2‐induced mechanical hyperalgesia in vivo.

Conclusions and Implications

This study supports a role for tyrosine kinases in PAR2‐mediated receptor‐operated gating of TRPV4 channels, independent of Gαq stimulation. The ability of a tyrosine kinase inhibitor to diminish PAR2‐induced activation of TRPV4 channels and consequent mechanical hyperalgesia identifies bafetinib (which is in development in oncology) as a potential novel analgesic therapy.
Space, People, Interventions and Time (SPIT): A Model for Understanding Children's Outdoor Play in Post‐Disaster Contexts Based On a Case Study from the Triple Disaster Area of Tohoku in North‐East Japan
Authors: Woolley Helen , Kinoshita Isami
Published: May 2014

Play in the outdoor environment is important for children as part of their childhood and is particularly important for children in a post‐disaster situation. This article explores issues around outdoor play opportunities in the Tohoku region of north‐east Japan, 13 months after the triple disaster of earthquake, tsunami and nuclear power plant failure. A model of space, people, interventions and time (SPIT) is used to understand the situation in this unique case study.
Comparison of two methods of assessing total body water at sea level and increasing high altitude
Authors: Boos C. J. , Holdsworth D. A. , Hall D. P. , Mellor A. , O'Hara J. , Woods D. R.
Published: May 2014

Fluid retention is a recognized feature of acute mountain sickness. However, accurate assessment of hydration, including the quantification of body water, has traditionally relied on expensive and non‐portable equipment limiting its utility in the field setting. We compared the assessment of total body water (TBW) and their relationship to total body weight using two non‐invasive methods using the NICas single‐frequency bioimpedance analysis (SF‐BIA) system and the BodyStat QuadScan 4000 multifrequency BIA system (MF‐BIA). TBW measurements were performed at rest at sea level and at high altitude (HA) at 3833 m postexercise and at rest and thereafter at rest at 4450 m and 5129 m on 47 subjects. The average age was 34·5 ± 9·3 years with an age range of 21–54 years (70·2% male). There were strong correlations between TBW assessment with both methods at sea level (r = 0·90; 95% CI 0·78–0·95: P<0·0001) and at HA (r = 0·92; 0·89–0·94: P<0·0001), however, TBW readings were 0·2 l and 1·91 l lower, respectively, with the NICaS. There was a stronger correlation between TBW and body weight with the QuadScan (r = 0·91; P<0·0001) than with the NICaS (r = 0·83; P<0·0001). The overall agreement between the two TBW methods was good, but the 95% confidence intervals around these agreements were relatively wide. We conclude that there was reasonable agreement between the two methods of BIA for TBW, but this agreement was lower at HA.
A visual grading study for different administered activity levels in bone scintigraphy
Authors: Gustafsson Agnetha , Karlsson Henrik , Nilsson Kerstin A. , Geijer Håkan , Olsson Anna
Published: May 2014

Introduction

The aim of the study is to assess the administered activity levels versus visual‐based image quality using visual grading regression (VGR) including an assessment of the newly stated image criteria for whole‐body bone scintigraphy.

Materials and methods

A total of 90 patients was included and grouped in three levels of administered activity: 400, 500 and 600 MBq. Six clinical image criteria regarding image quality was formulated by experienced nuclear medicine physicians. Visual grading was performed in all images, where three physicians rated the fulfilment of the image criteria on a four‐step ordinal scale. The results were analysed using VGR. A count analysis was also made where the total number of counts in both views was registered.

Results

The administered activity of 600 MBq gives significantly better image quality than 400 MBq in five of six criteria (P<0·05). Comparing the administered activity of 600 MBq to 500 MBq, four criteria of six show significantly better image quality (P<0·05). The administered activity of 500 MBq gives no significantly better image quality than 400 Mbq (P<0·05). The count analysis shows that none of the three levels of administrated activity fulfil the recommendations by the EANM.

Conclusion

There was a significant improvement in perceived image quality using an activity level of 600 MBq compared to lower activity levels in whole‐body bone scintigraphy for the gamma camera equipment end set‐up used in this study. This type of visual‐based grading study seems to be a valuable tool and easy to implement in the clinical environment.
Are proprioceptive functions affected in Duchenne muscular dystrophy?
Authors: Green Dido
Published: May 2014

This commentary is on the original article by Troise et al. on pages 882–887 of this issue.
Residual effect of reductions in red blood cell count and haematocrit and haemoglobin levels after 10‐month withdrawal of pioglitazone in patients with Type 2 diabetes
Authors: Lin K.‐D. , Lee M.‐Y. , Feng C.‐C. , Chen B. K. , Yu M.‐L. , Shin S.‐J.
Published: May 2014

Aim

To investigate the recovery of thiazolidinedione‐induced body weight gain and haematopoietic changes after stopping pioglitazone treatment in patients with Type 2 diabetes.

Methods

This retrospective cohort study included 214 patients divided into three groups according to pioglitazone treatment status. The first study arm included patients who received pioglitazone for 38 months then interrupted this for 10 months (pioglitazone‐interruption group). The second arm consisted of patients who received pioglitazone throughout the 48 months (pioglitazone‐continuous group); the third arm included patients who had never received pioglitazone therapy (control group).

Results

Red blood cell count and haematocrit and haemoglobin levels decreased significantly, while body weight increased in the two pioglitazone‐treated groups as compared with the control group at 38 months. Multivariate regression analysis showed that the reductions in red blood cell count/haemoglobin levels were associated with pioglitazone use. In the pioglitazone‐interruption group, no recoveries of red blood cells, or haematocrit or haemoglobin levels were observed after stopping pioglitazone for 10 months compared with the pioglitazone‐continuous group, but body weight gain decreased to a level that was significantly lower than that in the pioglitazone‐continuous group and did not differ significantly from the control group.

Conclusion

In this study, we observed a reversal of body weight gain but no recoveries in red blood cells or haematocrit or haemoglobin levels after stopping pioglitazone for 10 months in patients treated with pioglitazone for 38 months. This finding should prompt a reconsideration of the sustained effect of thiazolidinediones on the haematopoietic system in patients with Type 2 diabetes.
Prediction of gestational diabetes in obese pregnant women from the UK Pregnancies Better Eating and Activity (UPBEAT) pilot trial
Authors: Maitland R. A. , Seed P. T. , Briley A. L. , Homsy M. , Thomas S. , Pasupathy D. , Robson S. C. , Nelson S. M. , Sattar N. , Poston L. ,   the UPBEAT trial consortium
Published: May 2014

Aim

To examine the prediction of gestational diabetes in obese women using routine clinical measures and measurement of biomarkers related to insulin resistance in the early second trimester.

Methods

A total of 117 obese pregnant women participating in a pilot trial of a complex intervention of dietary advice and physical activity were studied. Blood samples were obtained at recruitment (15+0–17+6 weeks' gestation) and demographic, clinical history and anthropometric measures recorded. The biomarkers analysed were plasma lipids (HDL cholesterol, LDL cholesterol, triglycerides), high‐sensitivity C‐reactive protein, alanine transaminase, aspartate transaminase, ferritin, fructosamine, insulin, adiponectin, tissue plasminogen activator, interleukin‐6, visfatin and leptin. Univariate and logistic regression analyses were performed to determine independent predictors and area under the receiver‐operating curve was calculated for the model.

Results

Of the 106 participants included in the analysis, 29 (27.4%) developed gestational diabetes. Participants with gestational diabetes were older (P = 0.002), more often of parity ≥ 2, had higher systolic (P = 0.02) and diastolic blood pressure (P = 0.02) and were more likely to be black (P = 0.009). Amongst the blood biomarkers measured, plasma adiponectin alone remained independently associated with gestational diabetes in adjusted models (P = 0.002). The area under the receiver‐operating curve for clinical factors alone (0.760) increased significantly (area under the curve 0.834, chi‐square statistic (1) = 4.00, P = 0.046) with the addition of adiponectin.

Conclusions

A combination of routinely measured clinical factors and adiponectin measured in the early second trimester in obese women may provide a useful approach to the prediction of gestational diabetes. Validation in a large prospective study is required to determine the usefulness of this algorithm in clinical practice. (Clinical Trial Registry No: ISRCTN89971375)
Challenges contributing to disrupted transition from paediatric to adult diabetes care in young adults with Type 1 diabetes
Authors: Pyatak E. A. , Sequeira P. A. , Whittemore R. , Vigen C. P. , Peters A. L. , Weigensberg M. J.
Published: May 2014

Aim

To examine challenges contributing to disruptions in care during the transition from paediatric to adult care among young adults with Type 1 diabetes who are primarily in ethnic minority groups and have low socio‐economic status.

Methods

Participants (n = 20) were newly enrolled patients in a transition clinic for young adults with Type 1 diabetes with a history of loss to medical follow‐up. Participants completed qualitative semi‐structured interviews detailing their transition experiences in addition to demographic, HbA1c and psychosocial measures. Descriptive statistics were completed for quantitative data, and narrative thematic analysis of interviews was used to identify common themes. A mixed‐method analysis was used to identify the associations between stressors identified in interviews and clinical and psychosocial variables.

Results

Three categories of challenges contributing to loss to follow‐up were identified: psychosocial challenges, health provider and health system challenges and developmental challenges. Participants experienced a high degree of stressful life circumstances which were associated with higher HbA1c (r = 0.60, P = 0.005), longer duration of loss to follow‐up (r = 0.51, P = 0.02), greater emergency department utilization (r = 0.45, P = 0.05), and lower life satisfaction (r = ‐0.62, P = 0.003).

Conclusions

A confluence of challenges, including stressful life circumstances, healthcare system barriers and the developmental trajectory of young adulthood, contributes to a high risk of loss to follow‐up and poor health in this population of young adults with Type 1 diabetes. An integrated approach to transition addressing medical and psychosocial needs may facilitate improved follow‐up and health outcomes in clinical settings.
Features of an effective operative dentistry learning environment: students' perceptions and relationship with performance
Authors: Suksudaj N. , Lekkas D. , Kaidonis J. , Townsend G. C. , Winning T. A.
Published: April 2014

Objective

Students' perceptions of their learning environment influence the quality of outcomes they achieve. Learning dental operative techniques in a simulated clinic environment is characterised by reciprocal interactions between skills training, staff‐ and student‐related factors. However, few studies have examined how students perceive their operative learning environments and whether there is a relationship between their perceptions and subsequent performance. Therefore, this study aimed to clarify which learning activities and interactions students perceived as supporting their operative skills learning and to examine relationships with their outcomes.

Methods

Longitudinal data about examples of operative laboratory sessions that were perceived as effective or ineffective for learning were collected twice a semester, using written critical incidents and interviews. Emergent themes from these data were identified using thematic analysis. Associations between perceptions of learning effectiveness and performance were analysed using chi‐square tests.

Results

Students indicated that an effective learning environment involved interactions with tutors and peers. This included tutors arranging group discussions to clarify processes and outcomes, providing demonstrations and constructive feedback. Feedback focused on mistakes, and not improvement, was reported as being ineffective for learning. However, there was no significant association between students' perceptions of the effectiveness of their learning experiences and subsequent performance.

Conclusions

It was clear that learning in an operative technique setting involved various factors related not only to social interactions and observational aspects of learning but also to cognitive, motivational and affective processes. Consistent with studies that have demonstrated complex interactions between students, their learning environment and outcomes, other factors need investigation.
High headache‐related disability in patients with systemic lupus erythematosus and primary Sjögren's syndrome
Authors: Tjensvoll A. B. , Gøransson L. G. , Harboe E. , Kvaløy J. T. , Omdal R.
Published: April 2014

Background and purpose

It is often argued that patients with systemic lupus erythematosus (SLE) have more headaches than healthy subjects, but this association remains controversial. Thus the magnitude and severity of headaches in SLE were evaluated in comparison with another autoimmune disease, namely primary Sjögren's syndrome (pSS).

Methods

Sixty‐seven patients with SLE, 71 pSS patients and 108 healthy subjects were included. The International Classification of Headache Disorders, Headache Impact Test‐6 (HIT‐6), and the Migraine Disability Assessment (MIDAS) questionnaire were used to classify and assess headache‐related disability.

Results

Primary headaches were more prevalent in SLE patients than in healthy subjects (82% vs. 69%, P = 0.01). Amongst the headache sufferers, SLE patients (N = 55) and pSS patients (N = 51) had higher HIT‐6 scores (median 51, range 36–67, and median 54, range 36–72, respectively) than healthy subjects (N = 69) (median 46, range 36–72; P = 0.02 and P = 0.0009, respectively). Also, MIDAS scores were higher in SLE (median 0, range 0–110) and pSS patients (median 1, range 0–40) than in healthy subjects (median 0, range 0–10; P = 0.04 and P = 0.003, respectively).

Conclusion

Patients with SLE and pSS have a higher burden from headaches and more severe headaches than headache sufferers without these diseases. However, evidence of a specific bothersome SLE headache was not possible to identify as the headaches had the same characteristics and similar impact and severity in pSS patients. Depressive mood significantly influenced headache severity.
Dentate nuclei T2 relaxometry is a reliable neuroimaging marker in Friedreich's ataxia
Authors: Bonilha da Silva C. , Bergo F. P. G. , D'Abreu A. , Cendes F. , Lopes‐Cendes I. , França M. C.
Published: April 2014

Background and purpose

In Friedreich's ataxia (FRDA), frataxin deficiency results in iron redistribution in the dentate nuclei (DNC). Clusters of iron cause inhomogeneities in a magnetic field and result in a reduction in T2 relaxation time (T2).

Methods

T2 was prospectively evaluated in DNC, putamen, substantia nigra (SN), cerebellar white matter (CWM) and caudate and the correlation with clinical parameters was investigated. Thirty‐five patients (range 9–51 years) and 44 controls (12–49 years) underwent T2 multi‐echo sequence in a 3T scanner. Twenty‐three patients (12–50 years) and 19 controls (14–49 years) were reassessed after 1 year. T2 was evaluated using specialized software (Aftervoxel) and severity of disease was quantified with the Friedreich Ataxia Rating Scale (FARS).

Results

T2 of both DNC was significantly shorter in the FRDA group at baseline (right, 58.6 ± 8.3 ms vs. 63.7 ± 8.1 ms, P = 0.013; left, 56.7 ± 7.7 ms vs. 62.6 ± 6.8 ms, P = 0.001). No significant difference was found between groups regarding the SN, putamen, CWM and caudate T2. DNC T2 values correlated with age, FARS total score and FARS III subscore on both sides. Prospectively, there was a significant reduction of T2 in FRDA patients in right and left DNC (P = 0.001 and 0.009) but not in other structures. Amongst controls, none of the regions significantly changed after 1 year. DNC T2 change over time correlated with GAA expansions and clinical deterioration (expressed by a change in FARS scores).

Conclusions

DNC T2 values are abnormal in FRDA, progress over time and correlate with ataxia severity. These results strongly suggest that DNC relaxometry can be a useful neuroimaging marker in FRDA.