bluuebunny/crossref_metadata_2025 huggingface dataset:
Overvalued equity, benchmark beating and unexpected accruals
Authors: Coulton Jeffrey J. , Saune Naibuka , Taylor Stephen L.
Published: March 2014

We investigate the extent to which the overvaluation hypothesis provides incentives for managers to beat earnings benchmarks, and whether this benchmark beating can be reliably interpreted as evidence of earnings management. We carefully identify firms immediately above earnings benchmarks that have a priori, overvaluation‐based incentives to achieve the benchmark. We therefore focus on benchmark‐beating observations where manipulation is most likely, providing a more powerful test of the existence of opportunistic financial reporting. Consistent with overvaluation‐related incentives encouraging earnings management, we find that overvalued firms that just exceed levels‐related earnings benchmarks have higher unexpected accruals than firms with less extreme valuations.
Footprints of recent selection and variability in breed composition in the Göttingen Minipig genome
Authors: Gärke C. , Ytournel F. , Sharifi A. R. , Pimentel E. C. G. , Ludwig A. , Simianer H.
Published: March 2014

The Göttingen Minipig (GMP) developed at the University of Göttingen is a synthetic breed that is widely used in medical research and toxicology. It combines the high fertility of the Vietnamese potbellied pig, the low body weight of the Minnesota Minipig and the white coat colour of the German Landrace pig. The aim of this study was to find genomic regions that may have undergone selection since the creation of the breed in the 1960s. Therefore, the whole genome was screened for footprints of recent selection based on single nucleotide polymorphism (SNP) genotypes from the Illumina Porcine SNP60 BeadChip using two methods: the extended haplotype homozygosity (EHH) test and the estimation of the genomic proportion of the three original breeds at each SNP using a Bayesian approach. Local deviations from the average genome‐wide breed composition were tested with a permutation‐based empirical test. Results for a comprehensive whole‐genome scan for both methods are presented. Several regions showing the highest P‐values in the EHH test are related to breeding goals relevant in the GMP, such as growth (SOCS2, TXN, DDR2 and GRB10 genes) and white colour (PRLR gene). Additionally, the calculated proportion of the founder breeds diverged significantly in many regions from the pedigree‐based expectations and the genome average. The results provide a genome‐wide map of selection signatures in the GMP, which leads to a better understanding of selection that took place over the last decades in GMP breed development.
Regulation of Speech and Media Coverage of Corruption: An Empirical Analysis of the Mexican Press
Authors: Stanig Piero
Published: March 2014

Restrictions to media freedom, in the form of repressive defamation legislation, are thought to affect the amount of information about corruption that the media report. Exploiting variation in regulation of speech across states in a federal country, Mexico, and using a novel data set based on content analysis of the local press, I estimate the effect of lack of freedom on the coverage devoted to acts of malfeasance by public officials. Corruption receives significantly less attention in states with a more repressive defamation law. Instrumental variable models corroborate the interpretation of the negative association between regulation and coverage as a causal “chilling effect.”
Influence of maternal body mass index on accuracy and reliability of external fetal monitoring techniques
Authors: Cohen Wayne R. , Hayes‐Gill Barrie
Published: March 2014

Objective

To evaluate the performance of external electronic fetal heart rate and uterine contraction monitoring according to maternal body mass index.

Design

Secondary analysis of prospective equivalence study.

Setting

Three US urban teaching hospitals.

Sample

Seventy‐four parturients with a normal term pregnancy.

Methods

The parent study assessed performance of two methods of external fetal heart rate monitoring (abdominal fetal electrocardiogram and Doppler ultrasound) and of uterine contraction monitoring (electrohystero‐graphy and tocodynamometry) compared with internal monitoring with fetal scalp electrode and intrauterine pressure transducer. Reliability of external techniques was assessed by the success rate and positive percent agreement with internal methods. Bland–Altman analysis determined accuracy. We analyzed data from that study according to maternal body mass index.

Main outcome measures

We assessed the relationship between body mass index and monitor performance with linear regression, using body mass index as the independent variable and measures of reliability and accuracy as dependent variables.

Results

There was no significant association between maternal body mass index and any measure of reliability or accuracy for abdominal fetal electrocardiogram. By contrast, the overall positive percent agreement for Doppler ultrasound declined (p = 0.042), and the root mean square error from the Bland–Altman analysis increased in the first stage (p = 0.029) with increasing body mass index. Uterine contraction recordings from electrohysterography and tocodynamometry showed no significant deterioration related to maternal body mass index.

Conclusions

Accuracy and reliability of fetal heart rate monitoring using abdominal fetal electrocardiogram was unaffected by maternal obesity, whereas performance of ultrasound degraded directly with maternal size. Both electrohysterography and tocodynamometry were unperturbed by obesity.
Three‐dimensional reconstruction of the human skeletal muscle mitochondrial network as a tool to assess mitochondrial content and structural organization
Authors: Dahl R. , Larsen S. , Dohlmann T. L. , Qvortrup K. , Helge J. W. , Dela F. , Prats C.
Published: March 2014

Aim

Mitochondria undergo continuous changes in shape as result of complex fusion and fission processes. The physiological relevance of mitochondrial dynamics is still unclear. In the field of mitochondria bioenergetics, there is a need of tools to assess cell mitochondrial content. To develop a method to visualize mitochondrial networks in high resolution and assess mitochondrial volume.

Methods

Confocal fluorescence microscopy imaging of mitochondrial network stains in human vastus lateralis single muscle fibres and focused ion beam/ scanning electron microscopy (FIB/SEM) imaging, combined with 3D reconstruction was used as a tool to analyse mitochondrial morphology and measure mitochondrial fractional volume.

Results

Most type I and type II muscle fibres have tubular highly interconnected profusion mitochondria, which are thicker and more structured in type I muscle fibres (Fig. 1). In some muscle fibres, profission‐isolated ellipsoid‐shaped mitochondria were observed. Mitochondrial volume was significantly higher in type I muscle fibres and showed no correlation with any of the investigated molecular and biochemical mitochondrial measurements (Fig. 2). Three‐dimensional reconstruction of FIB/SEM data sets shows that some subsarcolemmal mitochondria are physically interconnected with some intermyofibrillar mitochondria (Fig. 3).

Conclusion

Two microscopy methods to visualize skeletal muscle mitochondrial networks in 3D are described and can be used as tools to investigate mitochondrial dynamics in response to life‐style interventions and/or in certain pathologies. Our results question the classification of mitochondria into subsarcolemmal and intermyofibrillar pools, as they are physically interconnected.
Severe 25‐hydroxyvitamin D deficiency identifies a poor prognosis in patients with hepatocellular carcinoma – a prospective cohort study
Authors: Finkelmeier F. , Kronenberger B. , Köberle V. , Bojunga J. , Zeuzem S. , Trojan J. , Piiper A. , Waidmann O.
Published: March 2014

Background

Vitamin D is involved in many biological processes. The role of vitamin D in patients with hepatocellular carcinoma (HCC) remains inconclusive, although there is evolving evidence that vitamin D may modulate cancer development and progression.

Aim

To evaluate serum vitamin D as prognostic parameter in HCC, we performed a prospective cohort study.

Methods

HCC patients were prospectively recruited and 25‐hydroxyvitamin D3 (25(OH)D3) levels were determined. 25(OH)D3 levels were compared to stages of cirrhosis and HCC stages with nonparametric Kruskal–Wallis tests and Spearman correlations in 200 HCC patients. The association of the 25(OH)D3 levels and overall survival (OS) was assessed in uni‐ and multivariate Cox regression models.

Results

Two‐hundred patients with HCC were included. The mean follow‐up time was 322 ± 342 days with a range of 1–1508 days. Nineteen patients underwent liver transplantation and 60 patients died within the observation time. The mean serum 25(OH)D3 concentration was 17 ± 13 ng/mL with a range of 1–72 ng/mL. 25(OH)D3 serum levels negatively correlated with the stage of cirrhosis as well as with stages of HCC. Patients with severe 25(OH)D3 deficiency had the highest mortality risk (hazard ratio 2.225, 95% confidence interval 1.331–3.719, P = 0.002). Furthermore, very low 25(OH)D3 levels were associated with mortality independently from the MELD score and high alpha‐Fetoprotein levels (>400 ng/mL) in a multivariate Cox regression model.

Conclusions

We conclude that 25(OH)D3 deficiency is associated with advanced stages of hepatocellular carcinoma and it is a prognostic indicator for a poor outcome.
Beyond activism/academia: militant research and the radical climate and climate justice movement(s)
Authors: Russell Bertie
Published: March 2014

The problematic of the activist/academic relationship has been a source of sustained concern for radicalGeographers over the past 15 years. Drawing on my personal experience within the radical climate movement(s), this paper looks to develop on the commitments of militant research, contribute to the development of militant ethnography as a research approach and consider the subsequent implications for thinking through the activist/academic problematic. Elaborating on the epistemological distinction between ‘truth relaying’ and ‘knowledge production’, it is contended that militant research is an orientation and process synonymous with the disavowal of positivist knowledge and the construction of situated partisan knowledge(s). Rather than the (social) science of transmitting truth, research thus becomes the art of producing tools you can fight with. From this perspective, the activist/academic problematic is not a ‘neutral’ problem but a product of a certain way of knowing associated with the academy. The paper concludes that our concern should not be to navigate between (and thus reiterate) the fields of ‘activism’ and ‘academy’, but to surpass the problematic altogether. We are tasked not with reproducing the university in its current form, but reimagining it as a machine for the production of otherworlds.
In Vitro and Modelling Approaches to Risk Assessment from the U.S. Environmental Protection Agency ToxCast Programme
Authors: Judson Richard , Houck Keith , Martin Matt , Knudsen Thomas , Thomas Russell S. , Sipes Nisha , Shah Imran , Wambaugh John , Crofton Kevin
Published: March 2014

A significant challenge in toxicology is the ‘too many chemicals’ problem. Human beings and environmental species are exposed to tens of thousands of chemicals, only a small percentage of which have been tested thoroughly using standard in vivo test methods. This study reviews several approaches that are being developed to deal with this problem by the U.S. Environmental Protection Agency, under the umbrella of the ToxCast programme (http://epa.gov/ncct/toxcast/). The overall approach is broken into seven tasks: (i) identifying biological pathways that, when perturbed, can lead to toxicity; (ii) developing high‐throughput in vitro assays to test chemical perturbations of these pathways; (iii) identifying the universe of chemicals with likely human or ecological exposure; (iv) testing as many of these chemicals as possible in the relevant in vitro assays; (v) developing hazard models that take the results of these tests and identify chemicals as being potential toxicants; (vi) generating toxicokinetics data on these chemicals to predict the doses at which these hazard pathways would be activated; and (vii) developing exposure models to identify chemicals for which these hazardous dose levels could be achieved. This overall strategy is described and briefly illustrated with recent examples from the ToxCast programme.
At the Centennial of Michaelis and Menten, Competing Michaelis–Menten Steps Explain Effect of GLP‐1 on Blood–Brain Transfer and Metabolism of Glucose
Authors: Gejl Michael , Rungby Jørgen , Brock Birgitte , Gjedde Albert
Published: March 2014

Glucagon‐like peptide‐1 (GLP‐1) is a potent insulinotropic incretin hormone with both pancreatic and extrapancreatic effects. Studies of GLP‐1 reveal significant effects in regions of brain tissue that regulate appetite and satiety. GLP‐1 mimetics are used for the treatment of type 2 diabetes mellitus. GLP‐1 interacts with peripheral functions in which the autonomic nervous system plays an important role, and emerging pre‐clinical findings indicate a potential neuroprotective role of the peptide, for example in models of stroke and in neurodegenerative disorders. A century ago, Leonor Michaelis and Maud Menten described the steady‐state enzyme kinetics that still apply to the multiple receptors, transporters and enzymes that define the biochemical reactions of the brain, including the glucose‐dependent impact of GLP‐1 on blood–brain glucose transfer and metabolism. This MiniReview examines the potential of GLP‐1 as a molecule of interest for the understanding of brain energy metabolism and with reference to the impact on brain metabolism related to appetite and satiety regulation, stroke and neurodegenerative disorders. These effects can be understood only by reference to the original formulation of the Michaelis–Menten equation as applied to a chain of kinetically controlled steps. Indeed, the effects of GLP‐1 receptor activation on blood–brain glucose transfer and brain metabolism of glucose depend on the glucose concentration and relative affinities of the steps both in vitro and in vivo, as in the pancreas.
Executive functioning: Developmental consequences on adolescents with histories of maltreatment
Authors: Kirke‐Smith Mimi , Henry Lucy , Messer David
Published: March 2014

Research suggests that children exposed to maltreatment have deficits in executive functioning (EF) but few studies have focused on the adolescent age group. We investigated whether maltreated adolescents had lower EF abilities compared to a group of non‐maltreated adolescents. Forty adolescents with histories of child maltreatment, together with a comparison group of 40 non‐maltreated adolescents matched for age, completed a comprehensive battery of EF tasks. Hierarchical multiple regression analyses, controlling for IQ, were carried out using each of the EF measures as dependent variables to examine group differences. Maltreated adolescents had significantly lower performance than non‐maltreated adolescents on tasks assessing executive loaded working memory, fluency, and inhibition, although switching was not impaired. Emotional and behavioural difficulties (EBD) were included in additional regression analyses to examine whether these variables would explain the group differences. The inclusion of EBD variables had some effect on group differences, as expected, but did not eliminate them. These findings support the theory that impairments in EF may be one underlying reason why adolescents with histories of maltreatment struggle to cope both inside and outside the classroom.
Age disparities in survival from lymphoma and myeloma: a comparison between US and England
Authors: Pulte Dianne , Redaniel Maria T. , Lowry Lisa , Bird Jenny , Jeffreys Mona
Published: March 2014

Population‐level survival in older patients with lymphoma is significantly lower than in younger patients. In this study, data were obtained from cancer registries in England and the United States (US) for patients diagnosed with Hodgkin lymphoma (HL), non‐Hodgkin lymphoma (NHL) and myeloma. Five‐year relative survival was calculated using period analysis. Generalised linear models were used to determine excess hazard ratios (EHR) for older compared to younger patients. Five‐year relative survival was lower for older patients diagnosed with HL, NHL and myeloma in both countries. The greatest age‐related survival inequality was observed for patients with HL: in 2006–10 the EHR comparing patients aged 75 + years with those aged 15–24 years was 14·02 in the US and 15·69 in England. For NHL, the EHR was 1·91 in the US and 3·81 in England. For myeloma, comparing patients aged 75 + years with those aged 25–44 years, the EHR was 2·79 in the US and 3·60 in England. Survival of patients with lymphoma is lower for older patients in both the US and England but the discrepancy is less in the US. Physicians should be encouraged to evaluate patients' frailty and co‐morbidities as well as their age when considering treatment options for patients with lymphoma and myeloma.
Clinical presentation and molecular basis of congenital antithrombin deficiency in children: a cohort study
Authors: Kumar Riten , Chan Anthony K. C. , Dawson Jennifer E. , Forman‐Kay Julie D. , Kahr Walter H. A. , Williams Suzan
Published: March 2014

In this study we report the largest descriptive cohort of congenital antithrombin (AT) deficiency in children, its clinical presentation, molecular basis and genotype‐phenotype correlation. Paediatric patients diagnosed with AT deficiency at two tertiary care children's hospitals over a 10‐year period were retrospectively reviewed. SERPINC1 gene sequencing was offered to subjects who did not already have the test performed. Molecular modelling and stability simulations were performed for the novel mutations identified. Twenty‐nine subjects from 18 pedigrees were identified. Mean age (± standard deviation) at diagnosis and mean duration of follow‐up were 8·4 (± 6·6) years and 6·6 (± 5·7) years respectively. Most recent mean AT activity and AT antigen levels (n = 20) were 0·53 (± 0·09) iu/ml and 0·60 (± 0·17) iu/ml respectively. Ten subjects were diagnosed secondary to low AT activity measured following venous thrombo‐embolism (VTE). All 10 subjects had additional risk factors at the time of VTE. None of the 19 subjects diagnosed with AT deficiency in the setting of positive family history have had VTE with 7·4 (± 5·8) years follow‐up. Mutation analysis has been completed on 19 subjects from 16 pedigrees. Nine unique mutations, including 4 novel mutations were identified.
SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma – a Nordic Lymphoma Group study
Authors: Nordström Lena , Sernbo Sandra , Eden Patrik , Grønbæk Kirsten , Kolstad Arne , Räty Riikka , Karjalainen Marja‐Liisa , Geisler Christian , Ralfkiær Elisabeth , Sundström Christer , Laurell Anna , Delabie Jan , Ehinger Mats , Jerkeman Mats , Ek Sara
Published: March 2014

Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the NordicMCL2/3 protocols. In 2008, aMCLinternational prognostic index (MIPI) was created to enable stratification of the clinical diverseMCLpatients into three risk groups. So far, use of theMIPIin clinical routine has been limited, as it has been shown that it inadequately separates low and intermediate risk group patients. To improve outcome and minimize treatment‐related morbidity, additional parameters need to be evaluated to enable risk‐adapted treatment selection. We have investigated the individual prognostic role of theMIPIand molecular markers includingSOX11,TP53 (p53),MKI67 (Ki‐67) and CCND1 (cyclin D1). Furthermore, we explored the possibility of creating an improved prognostic tool by combining theMIPIwith information on molecular markers.SOX11 was shown to significantly add prognostic information to theMIPI, but in multivariate analysisTP53 was the only significant independent molecular marker. Based on these findings, we propose thatTP53 andSOX11 should routinely be assessed and that a combinedTP53/MIPIscore may be used to guide treatment decisions.
Mitochondrial pharmacology: energy, injury and beyond
Authors: Davidson S M , Lopaschuk G D , Spedding M , Beart P M
Published: March 2014

While the mitochondrion has long fascinated biologists and the sheer diversity of druggable targets has made it attractive for potential drug development, there has been little success translatable to the clinic. Given the diversity of inborn errors of metabolism and mitochondrial diseases, mitochondrially mediated oxidative stress (myopathies, reperfusion injury, Parkinson's disease, ageing) and the consequences of disturbed energetics (circulatory shock, diabetes, cancer), the potential for meaningful gain with novel drugs targeting mitochondrial mechanisms is huge both in terms of patient quality of life and health care costs. In this themed issue of the British Journal of Pharmacology, we highlight the key directions of the contemporary advances in the field of mitochondrial biology, emerging drug targets and new molecules which are close to clinical application. Authors' contributions are diverse both in terms of species and organs in which the mitochondrially related studies are performed, and from the perspectives of mechanisms under study. Defined roles of mitochondria in disease are updated and previously unknown contributions to disease are described in terms of the interface between basic science and pathological relevance.

Linked Articles

This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue‐8
Olfaction evaluation and correlation with brain atrophy in Bardet‐Biedl syndrome
Authors: Braun J.‐J. , Noblet V. , Durand M. , Scheidecker S. , Zinetti‐Bertschy A. , Foucher J. , Marion V. , Muller J. , Riehm S. , Dollfus H. , Kremer S.
Published: March 2014

Bardet‐Biedl syndrome (BBS) is a well‐recognized ciliopathy characterized by cardinal features namely: early onset retinitis pigmentosa, polydactyly, obesity, hypogonadism, renal and cognitive impairment. Recently, disorders of olfaction (anosmia, hyposmia) have been also described in BBS patients. Moreover, morphological brain anomalies have been reported and prompt for further investigations to determine whether they are primary or secondary to peripheral organ involvement (i.e. visual or olfactory neuronal tissue). The objective of this article is to evaluate olfactory disorders in BBS patients and to investigate putative correlation with morphological cerebral anomalies. To this end, 20 BBS patients were recruited and evaluated for olfaction using the University of Pennsylvania Smell Identification Test (UPSIT). All of them underwent a structural magnetic resonance imaging (MRI) scan. We first investigated brain morphological differences between BBS subjects and 14 healthy volunteers. Then, we showed objective olfaction disorders in BBS patients and highlight correlation between gray matter volume reduction and olfaction dysfunction in several brain areas.
Evaluating Children's Conservation Biology Learning at the Zoo
Authors: JENSEN ERIC
Published: March 2014

Millions of children visit zoos every year with parents or schools to encounter wildlife firsthand. Public conservation education is a requirement for membership in professional zoo associations. However, in recent years zoos have been criticized for failing to educate the public on conservation issues and related biological concepts, such as animal adaptation to habitats. I used matched pre‐ and postvisit mixed methods questionnaires to investigate the educational value of zoo visits for children aged 7–15 years. The questionnaires gathered qualitative data from these individuals, including zoo‐related thoughts and an annotated drawing of a habitat. A content analysis of these qualitative data produced the quantitative data reported in this article. I evaluated the relative learning outcomes of educator‐guided and unguided zoo visits at London Zoo, both in terms of learning about conservation biology (measured by annotated drawings) and changing attitudes toward wildlife conservation (measured using thought‐listing data). Forty‐one percent of educator‐guided visits and 34% of unguided visits resulted in conservation biology‐related learning. Negative changes in children's understanding of animals and their habitats were more prevalent in unguided zoo visits. Overall, my results show the potential educational value of visiting zoos for children. However, they also suggest that zoos’ standard unguided interpretive materials are insufficient for achieving the best outcomes for visiting children. These results support a theoretical model of conservation biology learning that frames conservation educators as toolmakers who develop conceptual resources to enhance children's understanding of science.

Evaluación del Aprendizaje de Biología de la Conservación por Niños en el Zoológico Jensen
Estimating How Many Undescribed Species Have Gone Extinct
Authors: TEDESCO P. A. , BIGORNE R. , BOGAN A. E. , GIAM X. , JÉZÉQUEL C. , HUGUENY B.
Published: March 2014

Because both descriptions of species and modern human‐driven extinctions started around the same time (i.e., eighteenth century), a logical expectation is that a large proportion of species may have gone extinct without ever having been recorded. Despite this evident and widely recognized assumption, the loss of undescribed species has never been estimated. We quantified this loss for several taxonomic groups and regions for which undescribed species extinctions are likely to have occurred. Across a wide range of taxonomic groups, we applied known extinction rates computed from recorded species losses to assumed exponential decay in the proportion of species remaining undiscovered. Because all previous modeling attempts to project total species richness implicitly assumed that undescribed species extinctions could be neglected, we also evaluated the effect of neglecting them. Finally, because we assumed constant description and extinction probabilities, we applied our model to simulated data that did not conform to this assumption. Actual species losses were severely underestimated by considering only known species extinctions. According to our estimates, the proportion of undiscovered extinct species over all extinctions ranged from 0.15 to 0.59, depending on the taxonomic group and the region considered. This means that recent extinctions may be up to twice as large as the number recorded. When species differed in their extinction or description probabilities, our model underestimated extinctions of undescribed species by up to 20%.

Estimación de Cuántas Especies sin Describir Se Han Extinguido
Testing Focus Groups as a Tool for Connecting Indigenous and Local Knowledge on Abundance of Natural resources with Science‐Based Land Management Systems
Authors: Danielsen Finn , Jensen Per M. , Burgess Neil D. , Coronado Indiana , Holt Sune , Poulsen Michael K. , Rueda Ricardo M. , Skielboe Thomas , Enghoff Martin , Hemmingsen Louise H. , Sørensen Marten , Pirhofer‐Walzl Karin
Published: March 2014

One of the clearly stated intentions of the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) is to bring both “western scientific” and “indigenous and local” knowledge systems within synthetic global, regional, and thematic assessments. A major challenge will be how to use, and quality‐assure, information derived from different knowledge systems. We test how indigenous and local knowledge on natural resources in Miskito and Mayangna communities in Nicaragua, validated through focus groups with community members, compares with information collected on line transects by trained scientists. Both provide comparable data on natural resource abundance, but focus groups are eight times cheaper. Such approaches could increase the amount and geographical scope of information available for assessments at all levels, while simultaneously empowering indigenous and local communities who generally have limited engagement in such processes.
Space matters when defining effective management for invasive plants
Authors: Meier Eliane S. , Dullinger Stefan , Zimmermann Niklaus E. , Baumgartner Daniel , Gattringer Andreas , Hülber Karl
Published: March 2014

Aim

Invasive alien species are a threat to biodiversity and can harm resident plants, animals, humans and infrastructure. To reduce deleterious effects, effective management planning for invasive plants is required. Currently, the effectiveness of management is primarily optimized locally through eradication of individual populations. By contrast, spatial prioritization of control activities at the landscape level has received less attention, despite its potential to improve management planning in complex landscapes, especially under budget constraints.

Location

North‐eastern Switzerland, Europe.

Methods

We used a dynamic simulation model to evaluate the effectiveness of spatially designed management planning for controlling the expansion of three invasive alien plants (IAPs;Heracleum mantegazzianum, Impatiens glanduliferaandReynoutria japonica) across a heterogeneous landscape in North‐eastern Switzerland. The model predicted the spread ofIAPs from their current distribution under constraints of 361 control options differing in local intensity, frequency, duration, area and spatial prioritization of eradication measures.

Results

Our results demonstrate thatIAP‐control actions under a restricted budget are more effective if control actions are spatially prioritized. Most effective spatial treatments generally prioritized small populations in the case of the annual species and large populations in the case of the perennial species. Further, applying intensive control at early stages generally increased effectiveness of control.

Main conclusions

ForIAP‐management planning, our findings suggest that control should be applied early whenIAPs start spreading, to maximize success or minimize costs. Further, spatial prioritization schemes are particularly useful under limited financial means forIAP‐management. Finally, our modelling approach may serve as a proof of concept to evaluate the effectiveness of control actions of variousIAPs in complex landscapes.
Modified bowel preparation regimen for use in second‐generation colon capsule endoscopy in patients with ulcerative colitis
Authors: Usui Shingo , Hosoe Naoki , Matsuoka Katsuyoshi , Kobayashi Taku , Nakano Masaru , Naganuma Makoto , Ishibashi Yuka , Kimura Kayoko , Yoneno Kazuaki , Kashiwagi Kazuhiro , Hisamatsu Tadakazu , Inoue Nagamu , Serizawa Hiroshi , Hibi Toshifumi , Ogata Haruhiko , Kanai Takanori
Published: March 2014

Background and Aim

We have reported that second‐generation colon capsule endoscopy (CCE‐2) might be feasible for assessing the severity of mucosal inflammation in ulcerative colitis (UC). However, because of the low rate (69%) of complete evaluation of the colon and owing to inadequate cleansing. We believe that the method of bowel preparation could be improved by reducing volume. In the present study, we attempted to improve the colon‐cleansing regimen in order to optimize the usefulness of CCE‐2 in the management of UC patients.

Methods

Twenty patients with histologically confirmed UC were enrolled. Patients took a maximum 2.2 L lavage solution (polyethylene glycol solution and magnesium citrate) in two or three divided doses. To assess the effectiveness of the modified bowel preparation regimen, we evaluated the rate of total colonobservation, the effectiveness of bowel cleansing, andinterobserver agreement in assessing UC disease activity. We used a four‐point grading scale (poor, fair, good, and excellent) for evaluating the quality of bowel cleansing. Matts' endoscopic score was used to evaluate disease activity.

Results

The rate of total colon observation was 85%, and 15 patients (75%) excreted the CCE‐2 within 8 h. The proportion of excellent plus good cleansing was approximately 60%. There was a substantial interobserver agreement (κ = 0.777) in assessment of overall cleansing, which was still substantial at the fair cleansing level (κ = 0.700).

Conclusion

Using CCE‐2, the modified bowel preparation regimen, with reduced volume has the potential to succeed in the evaluation of mucosal severity in UC.
Have infant gross motor abilities changed in 20 years? A re‐evaluation of the Alberta Infant Motor Scale normative values
Authors: Darrah Johanna , Bartlett Doreen , Maguire Thomas O , Avison William R , Lacaze‐Masmonteil Thierry
Published: March 2014

Aim

To compare the original normative data of the Alberta Infant Motor Scale (AIMS) (n=2202) collected 20 years ago with a contemporary sample of Canadian infants.

Method

This was a cross‐sectional cohort study of 650 Canadian infants (338 males, 312 females; mean age 30.9wks [SD 15.5], range 2wks–18mo) assessed once on the AIMS. Assessments were stratified by age, and infants proportionally represented the ethnic diversity of Canada. Logistic regression was used to place AIMS items on an age scale representing the age at which 50% of the infants passed an item on the contemporary data set and the original data set. Forty‐three items met the criterion for stable regression results in both data sets.

Results

The correlation coefficient between the age locations of items on the original and contemporary data sets was 0.99. The mean age difference between item locations was 0.7 weeks. Age values from the original data set when converted to the contemporary scale differed by less than 1 week.

Interpretation

The sequence and age at emergence of AIMS items has remained similar over 20 years and current normative values remain valid. Concern that the ‘back to sleep’ campaign has influenced the age at emergence of gross motor abilities is not supported.
STRATEGIC EXCLUSION OF THE HIGHEST‐VALUED BIDDERS IN WHOLESALE AUTOMOBILE AUCTIONS
Authors: HAMMOND ROBERT G. , MORRILL THAYER
Published: March 2014

By restricting bidders to be qualified dealers, wholesale automobile auctions exclude the bidders who place the highest value on the vehicles: consumers. This article provides an explanation for this puzzling entry restriction by modeling the inventory‐management decisions of a firm. If an automobile dealer has more vehicles in inventory than is optimal, it cannot reduce its inventory by selling directly to consumers without impacting the demand for the automobiles that remain. However, if the dealer sells his/her excess inventory to a competitor, the demand for his/her remaining vehicles increases as the competitor responds by acquiring fewer additional vehicles. We demonstrate that for any market demand function and any cost of the competitor acquiring additional vehicles, a dealer with excess inventory does better by selling a subset of its vehicles to a competitor rather than directly to consumers. We discuss the market for wholesale automobiles in relation to other markets where goods are also auctioned but where entry is not restricted to qualified dealers. Doing so allows us to compare our inventory‐management explanation to common explanations provided by industry practitioners. We find that intuitive alternative stories do not consistently explain practices across markets. (JEL D44, L11, L62)
Glucose‐6‐phosphate dehydrogenase deficiency: an unusual cause of acute jaundice after paracetamol overdose
Authors: Phillpotts Simon , Tash Elliot , Sen Sambit
Published: March 2014

Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is the commonest human enzyme defect causing haemolytic anaemia after exposure to specific triggers. Paracetamol‐induced haemolysis in G6PD deficiency is a rare complication and mostly reported in children. We report the first case (to the best of our knowledge) of acute jaundice without overt clinical features of a haemolytic crisis, in an otherwise healthy adult female following paracetamol overdose, due to previously undiagnosed G6PD deficiency. It is important that clinicians consider this condition when a patient presents following a paracetamol overdose with significant and disproportionate jaundice, without transaminitis or coagulopathy.
Neurofilament heavy chain as a marker of neuroaxonal pathology and prognosis in acute encephalitis
Authors: Sellner J. , Davies N. W. , Howard R. S. , Petzold A.
Published: March 2014

Background and purpose

The neurological outcome of acute encephalitis can be devastating and early prognosis remains difficult. Biomarkers that quantify the extent of early brain injury are needed to improve the prognostic accuracy and aid patient management. Our objective was to assess whether cerebrospinal fluid (CSF) protein biomarkers of neuroaxonal and glial cell injury are elevated in distinct forms of acute encephalitis and predictive of poor outcome.

Methods

This was a prospective study of patients presenting with acute encephalitis to three teaching hospitals in London, UK. Levels of neurofilament heavy chain (NfH, SMI35) and S100B were quantified in CSF using enzyme‐linked immunosorbent assay. The outcome was assessed by the Glasgow Outcome Scale (GOS).

Results

Fifty‐six patients with acute encephalitis were recruited and classified into the following diagnostic categories: infectious (n = 20), inflammatory (n = 14) and unknown etiology (n = 22). Pathological levels of NfH and S100B were observed in 24/56 (43%) and 54/56 (96%), respectively. Patients with infectious encephalitis had significantly higher NfH levels compared with the other two groups (P < 0.05). A poor outcome (GOS < 5) was associated with significantly higher CSF NfH levels within samples taken 2 weeks after symptom onset.

Conclusions

This study suggests that longitudinal CSF NfH levels are of superior prognostic value compared with CSF S100B levels. Prolonged release of NfH, a marker of neuroaxonal damage, was associated with poor outcome. Potentially there is a window of opportunity for future neuroprotective treatment strategies in encephalitis.
Oral doxycycline for Lyme neuroborreliosis with symptoms of encephalitis, myelitis, vasculitis or intracranial hypertension
Authors: Bremell D. , Dotevall L.
Published: March 2014

Background and purpose

The treatment recommendation for Lyme neuroborreliosis with central nervous system (CNS) symptoms is intravenous ceftriaxone, according to current American and European guidelines. For Lyme neuroborreliosis with peripheral nervous system (PNS) symptoms, treatment with intravenous ceftriaxone and oral doxycycline is considered equally effective. The purpose of this study was to evaluate the efficacy of oral doxycycline in the treatment of Lyme neuroborreliosis with CNS symptoms.

Methods

Patients with Lyme neuroborreliosis who had undergone cerebrospinal fluid (CSF) sampling before and after treatment at the Department of Infectious Diseases, Sahlgrenska University Hospital, during the period 1990–2012, were included in this retrospective study. The CSF mononuclear cell count was used as a surrogate marker of treatment outcome. Comparisons of CSF mononuclear cell counts were made between patients with CNS symptoms and patients with PNS symptoms before and after treatment with oral doxycycline.

Results

Twenty‐six patients classified as having CNS symptoms and 115 patients classified as having PNS symptoms were included. The decline in CSF mononuclear cell counts did not differ significantly between the two groups of patients. All patients with CNS disease showed a marked clinical improvement after treatment, even though 62% had remaining symptoms at the end of follow‐up.

Conclusion

Treatment with oral doxycycline resulted in a similar decrease in CSF mononuclear cell counts in patients with Lyme neuroborreliosis with CNS symptoms compared with patients with Lyme neuroborreliosis with PNS symptoms. The results indicate that oral doxycycline is an effective treatment for Lyme neuroborreliosis irrespective of the severity of symptoms.
Functional polymorphisms in COMT and SLC6A4 genes influence the prognosis of patients with medication overuse headache after withdrawal therapy
Authors: Cargnin S. , Viana M. , Ghiotto N. , Bianchi M. , Sances G. , Tassorelli C. , Nappi G. , Canonico P. L. , Genazzani A. A. , Terrazzino S.
Published: March 2014

Background and purpose

It is currently unknown if common genetic variants influence the prognosis of patients with medication overuse headache (MOH). Here the role of two common single nucleotide polymorphisms in the COMT gene (rs4680 and rs6269), as well as the STin2 variable number tandem repeat (VNTR) polymorphism in the SLC6A4 gene, were evaluated as predictors for long‐term outcomes of MOH patients after withdrawal therapy.

Methods

Genotyping was conducted by polymerase chain reaction (PCR), PCR restriction fragment length polymorphism analysis or real‐time PCR allelic discrimination assay on genomic DNA extracted from peripheral blood. Gene variants association was evaluated by logistic regression analysis adjusted for clinical confounding factors, and the threshold of statistical significance for multiple testing was set at P < 0.012.

Results

Sixty‐five MOH patients with unsuccessful detoxification and 83 MOH patients with effective drug withdrawal therapy were available for the analysis. rs4680G allele carriers or the COMT rs6269G‐rs4680G haplotype were found to be associated with a lower risk of relapse within the first year after successful detoxification therapy, in comparison with homozygous rs4680A allele carriers [odds ratio (OR) 0.17, 95% confidence interval (CI) 0.05–0.61, P = 0.007] or with the COMT rs6269A‐rs4680A haplotype (OR 0.19, 95% CI 0.06–0.54, P = 0.003), respectively. In addition, carriers of the STin2 VNTR short allele were found at higher odds for the composite poor outcome including unsuccessful withdrawal therapy and relapse within 12 months of follow‐up after successful detoxification (OR 2.81, 95%CI 1.26–6.25, P = 0.009).

Conclusions

Our results indicate that genotyping for COMT rs4680 and SLC6A4 STin2 VNTR could be useful for the identification of MOH patients at higher risk of poor prognosis after drug withdrawal.
Melanoma never says die
Authors: Haass Nikolas K. , Schumacher Udo
Published: March 2014

Drug resistance in melanoma is commonly attributed to ineffective apoptotic pathways. Targeting apoptosis regulators is thus considered a promising approach to sensitizing melanoma to therapy. In the previous issue of Experimental Dermatology, Plötz and Eberle discuss the role that apoptosis plays in melanoma progression and drug resistance and the utility of apoptosis‐inducing BH3‐mimetics as targeted therapy. There are a number of compounds in clinical development and the field seems close to translating recent findings into benefits for patients with melanoma. Thus, this viewpoint is timely and achieves a valuable summary of the current state of apoptosis‐inducing therapy of melanoma.
Face‐to‐face with anti‐inflammatory therapy for rosacea
Authors: Salzer Suzanna , Ruzicka Thomas , Schauber Jürgen
Published: March 2014

In the past, our understanding of rosacea has been inadequate and limited to descriptions of factors that exacerbate and improve the disease. While the pathophysiology of rosacea is complex and multifactorial, cathelicidin peptides have emerged as key players in the pathogenesis of this common dermatological disorder. This article correlates recent findings in abnormal cathelicidin production and proteolytic processing in rosacea with therapeutic actions of current treatment options and, in this way, highlights potential points of intervention for the development of efficient therapeutic alternatives.
Expression of AID in malignant melanoma with BRAFV600E mutation
Authors: Okura Risa , Yoshioka Haruna , Yoshioka Manabu , Hiromasa Kana , Nishio Daisuke , Nakamura Motonobu
Published: March 2014

BRAF‐activating somatic mutations often exist in malignant melanoma. The underlying molecular mechanism of somatic BRAF mutation inductions remained to be clear. Activation‐induced cytidine deaminase (AID), a member of a cytidine deaminase family, and APOBEC3B induce somatic mutations and recently have been indicated to be involved in the pathomechanism of several kinds of cancers. The aim of this study was to explore the expression level of AID and APOBEC3B in BRAF‐mutation‐ containing malignant melanoma. Immunohistochemical study demonstrated that 9 of 10 malignant melanomas with high AID expression had BRAFV600E mutation. Eight of them developed multiorgan metastases or multiple lymph node metastases afterwards. Although the size of the patient panel was small, the results indicate that there might be an association between AID expression and BRAF mutation in melanoma.
Climate change may have limited effect on global risk of potato late blight
Authors: Sparks Adam H. , Forbes Gregory A. , Hijmans Robert J. , Garrett Karen A.
Published: March 2014

Weather affects the severity of many plant diseases, and climate change is likely to alter the patterns of crop disease severity. Evaluating possible future patterns can help focus crop breeding and disease management research. We examined the global effect of climate change on potato late blight, the disease that caused the Irish potato famine and still is a common potato disease around the world. We used a metamodel and considered three global climate models for the A2 greenhouse gas emission scenario for three 20‐year time‐slices: 2000–2019, 2040–2059 and 2080–2099. In addition to global analyses, five regions were evaluated where potato is an important crop: the Andean Highlands, Indo‐Gangetic Plain and Himalayan Highlands, Southeast Asian Highlands, Ethiopian Highlands, and Lake Kivu Highlands in Sub‐Saharan Africa. We found that the average global risk of potato late blight increases initially, when compared with historic climate data, and then declines as planting dates shift to cooler seasons. Risk in the agro‐ecosystems analyzed, varied from a large increase in risk in the Lake Kivu Highlands in Rwanda to decreases in the Southeast Asian Highlands of Indonesia.
‘I'm happy that I can still walk’ – Participation of the elderly in home care as a specific group with specific needs and wishes
Authors: Bagchus Charlotte , Dedding Christine , Bunders Joske F. G.
Published: March 2014

Background

Taking the needs, wishes and experiential knowledge of clients into account is considered to result in a better fit between the supply and demand of modern health care, contributing to the improvement of individual care, organizations, institutions and policy. However, the current generation of the elderly have had little experience of consumer‐oriented public services. They are said to be less likely to discuss their needs and wishes with individual caregivers and health‐care organisations. As a result, they might not receive care matching their needs and wishes.

Aim

To examine how the elderly themselves refer to their age and their needs and wishes for individual and collective participation in home‐based care to get a better understanding of their participation in their own health care.

Methods

Content analysis of 20 semi‐structured in‐depth interviews with elderly recipients of care in the Netherlands.

Results

The need and ability of the elderly to discuss their experiences are strongly affected by physical and mental limitations, social cultural characteristics and their experiences of life. As a result, the elderly encounter many limitations in discussing their experiences with their individual caregivers and their home‐care organisation. However, this does not mean that the elderly do not have needs and wishes that they want taken into account.

Conclusion

The challenge is to create a more responsive environment and to find new, creative ways of facilitating the expression of the needs and wishes of the elderly, according to the specific values and norms of their generation.