bluuebunny/crossref_metadata_2025 huggingface dataset:
Intermodal synchrony as a form of maternal responsiveness
Authors: Rohlfing Katharina J. , Nomikou Iris
Published: July 2014

Research findings indicate that synchrony between events in two different modalities is a key concept in early social learning. Our longitudinal pilot study with 14 mother–child dyads is the first to support the idea that synchrony between action and language as a form of responsive behaviour in mothers relates to later language acquisition in their children. We conducted a fine-grained coding of multimodal behaviour within the dyad during an everyday diapering activity when the children were three and six months old. When the children attained 24 months, their mothers completed language surveys; this data was then related to the dyadic measures in early interaction. We propose a ‘role-switching’ model according to which it is important for three-month-olds to be exposed to multimodal input for a great deal of time, whereas for six-month-old infants, the mother should respond to the infant’s attention and provide multimodal input when her child is gazing at her.
Chapter 1. Towards technology-mediated TBLT
Authors: González-Lloret Marta , Ortega Lourdes
Published: July 2014

Computer and online-communication technologies have given rise to new tasks in the real world. The present collection* is based on two premises: (a) that rapid digital technological change fuels constant transformations in learning and language use, continually creating new language education needs, and (b) that these developments in turn demand suitable curricular and instructional responses, whereby tasks and technology are genuinely and productively integrated. In this introduction, we present our vision for how the canonical principles of task-based language teaching (TBLT) can be fitted integrally into the new language education and digital technology realities, and we outline a new framework that we call “technology-mediated TBLT” and which the book seeks to open up for new research. We also introduce each chapter and highlight connections among them as they provide relevant empirical evidence and help envision future needed research into technology-mediated TBLT.
Chapter 4. Textbooks, tasks, and technology
Authors: Solá Simón Elena
Published: July 2014

This chapter reports on an action research study conducted in the context of English as a foreign language (EFL) tertiary education in Mexico. It examines the educational value of blending technology into a task-based instruction module that was designed around a pre-during-post-task model, following the main tenets of task-based language teaching (Ellis 2003; Van den Branden,Bygate & Norris 2009). The participants were three intact classes of pre-intermediate-level EFL students at the National Autonomous University of Mexico (UNAM) who completed 8 two-hour classes on a module of their textbook targeting grammar learning (simple past, past continuous, and used to). The module culminated with a writing activity, which served as the springboard for the design of an innovative Story Telling Contest task online. At the end of the textbook module, Group A (N = 25) engaged in this task-based, technology-mediated instructional design, Group B (N = 23) experienced the same task-based design but with no digital tools, and Group C (N = 25) did the writing activity in the original design offered in the textbook. The three groups were compared by collecting student perceptions through questionnaires and by measuring grammar learning via a pre- and post-test of narrative past tense use. A subset of 7 learners who experienced the task with the support of technology was also interviewed a few months later. The triangulated evidence suggests that, while all three instructional approaches led to similar linguistic gains in the use of narrative tenses, Groups A and B perceived the task design to have helped them develop rich new competencies, more so than the technological element. Students in Group A reported some additional value in the technology-mediated TBLT experience, including the improvement of their digital skills and the easy delivery of instructional material to carry out the task. This action research study contributes to the understanding of ways in which a task mediated by digital tools can enhance language learning in the context of traditional textbook-bound curricula.
Chapter 8. The third dimension
Authors: Gánem-Gutiérrez Gabriela Adela
Published: July 2014

This chapter describes a theoretical framework for the design and evaluation of pedagogical tasks for 3D virtual world environments. The proposed framework is informed by Vygotskian Sociocultural Theory (SCT) and Activity Theory, two related sociocultural approaches to second (L2) language learning which, I argue, offer a particularly suitable paradigm for the design, implementation, and evaluation of technology-mediated tasks. Firstly, I provide an overview of what characterises 3D virtual worlds (3D VWs) and of current research into the potential of this technological application in the service of second language learning and teaching, and the range of tasks that this research has thus far inspected. Secondly, I briefly review core SCT concepts underlying the proposed framework and point out how they apply to 3D VW tasks. I then identify pedagogical principles derived from this approach to L2 learning and discuss their relevance in the context of technology-mediated task-based language teaching (TBLT) with specific reference to the current state and capabilities of 3D VWs. I also outline a task example designed to capitalise on the potential of 3D VWs for L2 learning. I conclude with a proposal for the application of Activity Theory to the evaluation of 3D VWs tasks. At a theoretical level, my goal in the chapter is to bring key sociocultural perspectives to TBLT and show how SCT can inform theoretically sound pedagogical design in TBLT. At a practical level, I hope to offer a framework for practitioners to support the design and evaluation of technology-mediated tasks in general and 3D VWs tasks in particular.
Chapter 10. Formative, task-based oral assessments in an advanced Chinese-language class
Authors: Winke Paula
Published: July 2014

This chapter reports on task-based, formative assessments of oral proficiency that were designed to help students self-monitor their oral development in a fourth-year, university foreign-language Chinese classroom. Seventeen advanced learners of Chinese completed two group role-play tasks two times during their 15-week semester. Both tasks were designed to follow a pre-task, main-task, post-task cycle and culminated within the same 90-minute lesson in individual oral assessments. Computerized tools aided in the design and delivery of both tasks and assessments. Immediately after completing each formative assessment, the learners were asked to self-rate their performances, which were then rated by two Chinese language experts as well. Finally, for each task and assessment cycle, a 30-minute reflective lesson was conducted by the teacher subsequently in class, in which students discussed their self-ratings and compared them to the expert ratings. The statistical comparison of student and expert ratings on the two task cycles suggests that students were realistic judges in their self-assessment and largely agreed with the expert raters in their estimations of the quality (i.e. accuracy, fluency, complexity, and accent/tones) of their task-based assessment performances. The chapter closes with a discussion of pedagogical implications and a call for oral formative assessments that are brought into the language classroom on a regular basis as part of task work, so as to support learners’ self-regulation and to increase their chances of language improvement.
Chapter 11. Evaluation of an online, task-based Chinese course
Authors: Brown Nielson Katharine
Published: July 2014

This chapter describes and evaluates an intermediate online, task-based Chinese course through an analysis of learner performance on the course tasks and assessments, including the performance-based assessments (PBAs) developed specifically for the course. After a brief consideration of online instruction and task-based language teaching (TBLT), the online TBLT course is described in some depth and the technology-mediated pedagogic tasks and associated PBAs are presented. The findings from these tasks and assessments are then reported, followed by a discussion of what the outcomes data revealed about online language instruction, TBLT, and technology-mediated tasks. The goal of this research is to evaluate this particular course in order to provide insights into how best to structure and assess learners during online foreign language classes, offering a model for instruction as well as empirical findings related to the effectiveness of both online and task-based foreign language courses.
Investigating the problem-solving strategies of revisers through triangulation
Authors: Robert Isabelle S.
Published: July 2014

This article reports on an exploratory follow-up study on the use of problem-solving strategies of professional revisers, and in particular the use of ‘rereading,’ ‘reflection-reformulation,’ and ‘search’ problem-solving strategies. The study focuses on the frequency of these strategies, on the effect of the revision procedure on the use of these strategies, and on the relationship between the use of these strategies and revision quality and duration. Results based on Think Aloud Protocols (TAPs) and keystroke logging data show that the reflection-reformulation and the search strategies are the most frequent. It seems that the more revisers use the reflection-reformulation strategy, whether alone or in combination with another strategy, the better they revise, but the longer they work. Results also show that the type of revision procedure employed does not seem to have any effect on the use of problem-solving strategies.
Fostering self-reflection in translation students
Authors: Norberg Ulf
Published: July 2014

The objective of this paper is to examine students’ understanding of the processes involved in translation if they are asked to write self-reflections on the strategies and procedures that they have employed and to submit these with their translations. The material analyzed in this study comprises retrospective, guided commentaries submitted during two terms by a group of undergraduate students studying translation. The results indicate that commentaries can foster heightened self-awareness of several aspects of the process, such as initial reading and revision. It is argued that the design of instructions for commentaries, including their variation and built-in progression, is of great importance for process-oriented translation teaching and deserves further experimental study.
A Case for Accelerated Reestablishment of American Eel in the Lake Ontario and Champlain Watersheds
Authors: Busch Wolf-Dieter N , Braun David P
Published: July 2014

The catadromous, panmictic American Eel (Anguilla rostrata) historically comprised nearly 25% of fish biomass in Atlantic coastal streams, supporting sizeable fisheries for centuries. However, the population has collapsed in its primary range. It is now proposed or listed as “endangered” by various North American governments, with its fisheries declared “depleted” along the U.S. Atlantic coast. The causes of decline include fragmented governance, loss of physical access to and/or degraded quality of freshwater habitats, lethal entrainment in hydroelectric turbines, changes in marine currents, and excessive harvest. Large gaps exist in knowledge of species biology and the effectiveness of management approaches. Prior to the collapse of eel production, the Lake Ontario and Champlain watersheds of the St. Lawrence River basin produced abundant, large, highly fecund female eels that contributed disproportionately to species-wide reproduction. Abatement of key threats specifically across these two particular watersheds therefore could contribute significantly to range-wide recovery from Greenland to Venezuela.

RESUMEN

la anguila americana (Anguilla rostrata) se considera una especie catádroma y panmíctica e históricamente ha constituido cerca del 25% de la biomasa de peces en los ríos costeros de Norte América, soportando durante siglos importantes pesquerías. Sin embargo, la población ha colapsado a lo largo de su rango principal de distribución. Actualmente, la especie se ha propuesto o bien listado como “en peligro” por varios gobiernos de Norte América, cuyas pesquerías se han declarado agotadas a lo largo de la costa atlántica de los EEUU. Las causas de la reducción incluyen la fragmentación de la gobernanza, pérdida del acceso físico hacia y/o degradación de la calidad de los hábitats dulceacuícolas, arrastre letal hacia turbinas hidroeléctricas, cambios en las corrientes marinas y extracción excesiva. Existen grandes huecos de conocimiento en cuanto a la biología de la especie y la efectividad de los enfoques de manejo. Antes del colapso en la producción de anguila, en el lago Ontario y en la cuenca hidrológica Champlain del río San Lorenzo se producían cantidad de hembras de anguila grandes y fecundas que contribuían de forma desproporcionada a la reproducción de la especie en todo su rango. Por lo tanto, la disminución de amenazas clave en estas dos cuencas en particular, puede contribuir importantemente a la recuperación de la especie en todo su rango de distribución, desde Groenlandia hasta Venezuela.
Practical application of flavonoid-poor menu meals to the study of the bioavailability of bilberry anthocyanins in human subjects
Authors: Sakakibara Hiroyuki , Ichikawa Yoko , Tajima Sanae , Makino Yoshie , Wakasugi Yusuke , Shimoi Kayoko , Kobayashi Saori , Kumazawa Shigenori , Goda Toshinao
Published: July 2014

Practical application of flavonoid-poor menus was evaluated on the bioavailability of anthocyanins as model flavonoids. Detectable amounts of flavonoids were not found in plasma and urine collected from 13 participants, who took the menus. After ingesting bilberry anthocyanins (919 μmol), average plasma AUC0-6h, Cmax, Tmax values and urinary recovery were 386.0 nmol h/mL, 139.1 nM, 1.31 h and 0.21%, respectively.
Jung's ‘secret knowledge’: commentary on works by contemporary Irish artist Gavin Hogg
Authors: Mather Mathew
Published: July 2014

Jung's ‘secret knowledge’ is identified as including three interrelated threads: precessional astrology, alchemy and anopus divinum. This is interpreted, broadly, in terms of an astro-alchemical myth. An extrapolation of this myth is then used as a basis from which to interpret a sample of works by contemporary Irish artist Gavin Hogg. The argument developed is that such an astro-alchemical myth finds visionary expression in such artworks, and that it offers a valuable perspective from which to critique a religious problematic such as a Catholic Ireland in crisis. The related notion of integrating a ‘missing fragment’ as an Eastern and also a Celtic holistic spirituality into the Western world picture is also briefly developed.
Characterization and Epidemiology of Outbreaks of Impatiens necrotic spot virus on Lettuce in Coastal California
Authors: Kuo Yen-Wen , Gilbertson Robert L. , Turini Tom , Brennan Eric B. , Smith Richard F. , Koike Steven T.
Published: July 2014

California is the leading producer of lettuce (Lactuca sativa) for the United States and grows 77% of the country's supply. Prior to 2006, coastal California lettuce was only periodically and incidentally infected by a single tospoviruses species: Tomato spotted wilt virus (TSWV). However, beginning in 2006 and continuing through 2012, severe outbreaks of disease caused by Impatiens necrotic spot virus (INSV) have affected the coastal lettuce crop, though TSWV was also present. In contrast, TSWV was the only tospovirus associated with disease outbreaks in Central Valley lettuce during this period. Disease surveys conducted over two seasons (2008 and 2009) in 10 commercial fields (acreage of 6 to 20 ha) indicated that INSV was the only tospovirus associated with economically damaging disease outbreaks in lettuce in the coastal region, with incidences of 0.5 to 27% (mean = 5.7%). Molecular characterization of INSV isolates associated with these disease outbreaks revealed little genetic diversity and indicated that lettuce-infecting INSV isolates were nearly identical to those previously characterized from ornamental or other hosts from different locations in the United States and the world. Monitoring of thrips revealed moderate to large populations in all surveyed lettuce fields, and the majority of thrips identified from these fields were western flower thrips, Frankliniella occidentalis. There was significant positive correlation (r2 = 0.91, P = 0.003) between thrips populations and INSV incidence in the most commonly encountered type of commercial lettuce (romaine, direct seeded, conventional) included in this study. A reverse-transcription polymerase chain reaction assay developed for detection of INSV in thrips showed promise as a monitoring tool in the field. Surveys for INSV reservoir hosts in the coastal production area revealed that the weeds little mallow (Malva parvifolia) and shepherd's purse (Capsella bursa-pastoris) were commonly infected. M. parvifolia plants infected in the field did not show obvious symptoms, whereas plants of this species inoculated in the laboratory with INSV by sap transmission developed necrotic spots and chlorosis. Eleven other weed species growing in the lettuce production areas were found to be hosts of INSV. Coastal crops found to be infected with INSV included basil (Ocimum basilicum), bell pepper (Capsicum annuum), calla lily (Zantedeschia aethiopica), faba bean (Vicia faba), radicchio (Cichorium intybus), and spinach (Spinacia oleracea). Thus, it is likely that INSV was introduced into coastal California lettuce fields via viruliferous thrips that initially acquired the virus from other local susceptible plant species. Results of this study provide a better understanding of INSV epidemiology in coastal California and may help growers devise appropriate disease management strategies.
Notification that new names of prokaryotes, new combinations and new taxonomic opinions have appeared in volume 64, part 4, of the IJSEM
Authors: Oren Aharon , Garrity George M.
Published: July 2014

This listing of names of prokaryotes published in a previous issue of the IJSEM is provided as a service to bacteriology to assist in the recognition of new names and new combinations. This procedure was proposed by the Judicial Commission [Minute 11(ii), Int J Syst Bacteriol
41 (1991), p. 185]. The names given herein are listed according to the Rules of priority (i.e. page number and order of valid publication of names in the original articles).
Are threatened plant species specialists, or just more vulnerable to disturbance?
Authors: Monks Adrian , Burrows Larry
Published: July 2014

Many studies report an association between species rarity and/or threat status, and habitat specialization. However, specialization is often inferred from a species' narrow realized range and may be confounded with landscape disturbance history.

We test whether threatened species are more specialized than non‐threatened plants using patterns of plant species turnover sampled at three occasions over 13 years in a lake shore ecosystem in Fiordland, New Zealand. If threatened plants are more specialized than non‐threatened plants, then we expect their rate of turnover to be higher than non‐threatened species in the same habitat across multiple time periods and changes to the disturbance gradient.

The first sampling occasion (1997) was associated with high water levels and a low rate of change in maximum inundation period with elevation. The second two sampling occasions (2005 & 2010) were associated with periods of lower water levels and steep hydrological gradients. Changes along the disturbance gradient created by shifts in the hydrological regime were associated with a movement of threatened and non‐threatened plants downslope (up to 0·8 m in elevation) and a decline in overall cover over the 13 years of the study. Threatened species had higher rates of turnover in only the last of the three sampling periods, suggesting that threatened species were not more likely to be habitat specialists than non‐threatened species.

Synthesis and applications. We suggest that threatened plant species are less resilient to disturbance than non‐threatened species and that these plants were slower to expand their range from the short‐term contraction caused by perturbation to the hydrological gradient. Disturbance history has implications for patterns of turnover more generally, and we suggest that species resilience may be a useful conceptual tool to identify species at risk of decline and inform pre‐emptive management action.
Type 1 diabetes‐associated cognitive decline: A meta‐analysis and update of the current literature 1型糖尿病相关的认知能力下降：一项对最新文献的meta分析
Authors: Tonoli Cajsa , Heyman Elsa , Roelands Bart , Pattyn Nathalie , Buyse Luk , Piacentini Maria Francesca , Berthoin Serge , Meeusen Romain
Published: July 2014

Background

Type 1 diabetes (T1D) can have a significant impact on brain structure and function, which is referred to as T1D‐associated cognitive decline (T1DACD). Diabetes duration, early onset disease, and diabetes‐associated complications are all proposed as factors contributing to T1DACD. However, there have been no comparisons in T1DACD between children and adults with T1D. To obtain a better insight into the occurrence and effects of T1DACD in T1D, the aim of the present meta‐analysis was to investigate differences between children and adults and to analyse factors contributing T1DACD.

Methods

Two electronic databases were consulted: PubMed and ISI Web of Knowledge. Literature published up until the end of 2013 was included in the analysis. Effect sizes (Cohen's d), which are standardized differences between experimental and control groups, were calculated.

Results

There was a small to modest decrease in cognitive performance in T1D patients compared with non‐diabetic controls. Children with T1D performed worse while testing for executive function, full intelligence quotient (IQ), and motor speed, whereas adults with T1D performed worse while testing the full, verbal and performance IQ, part of the executive function, memory, spatial memory, and motor speed. Episodes of severe hypoglycemia, chronic hyperglycemia, and age of onset can be significant factors influencing cognitive function in T1D.

Conclusions

The findings in the literature suggest that T1DACD is more severe in adults than children, indicating that age and diabetes duration contribute to this T1DACD.
Effects of climate change on species turnover and body mass frequency distributions ofSouthAfrican bird communities
Authors: Walther Bruno A. , van Niekerk Adriaan
Published: July 2014

Climate change will lead to substantial shifts in species distributions. Most of the predictions of shifting distributions rely on modelling future distributions with ecological niche models. We used these models to investigate (i) the expected species turnover, loss and gain within bird communities of fourSouthAfrican biomes and (ii) the expected changes in the body mass frequency distributions of these communities. We used distributional data of theSouthernAfricanBirdAtlasProject, current climate data and two scenarios of future climate change for 2050 to build ensemble models of bird distributions. Our results indicate that future species loss, gain and turnover within the four biomes will be considerable. Climate change will also have statistically significant effects on body mass frequency distributions, and these effects differ substantially depending on the severity of future climate change. We discuss the possible ecological effects of these predicted changes on ecosystem interactions and functions.
Predictive Value of a Fragmented QRS Complex in Patients Undergoing Primary Angioplasty for ST Elevation Myocardial Infarction
Authors: Akgul Ozgur , Uyarel Huseyin , Pusuroglu Hamdi , Surgit Ozgur , Turen Selahattin , Erturk Mehmet , Ayhan Erkan , Bulut Umit , Baycan Omer Faruk , Demir Ali Riza , Uslu Nevzat
Published: July 2014

Objectives

The aim of this study was to evaluate the prognostic value of fragmented QRS (fQRS) on electrocardiography (ECG) patients with acute ST‐segment elevation in myocardial infarction (STEMI), who are undergoing primary percutaneous coronary intervention (PCI).

Methods

We prospectively enrolled 414 consecutive STEMI patients (mean age of 55.2 ± 12.2 years old, range of 26–91‐years old) undergoing primary PCI. The study patients were divided into two groups according to the presence or absence of fQRS as shown by ECG in the first 48 hours. The presence of fQRS group was defined as fQRS(+) (n = 91), and the absence of fQRS group was defined as the fQRS(–) (n = 323) group. Clinical characteristics and the one‐year outcome of the primary PCI were analyzed.

Results

The patients in the fQRS(+) group were older (mean age 60.7 ± 12.5 vs. 53.6 ± 11.6 years old, P < 0.001). Higher one‐year all‐cause mortality rates were observed in the fQRS group upon ECG (23.1% vs. 2.5%, P < 0.001, respectively). When using the Cox multivariate analysis, the presence of fQRS on the ECG was found to be a powerful independent predictor of one‐year all‐cause mortality (hazard ratio: 5.24, 95% confidence interval: 1.43–19.2, P = 0.01).

Conclusions

These results suggest that the presence of fQRS on ECG was associated with an increased in‐hospital cardiovascular mortality, and one‐year all‐cause mortality in patients with STEMI who are under primary PCI.
Unusual Conduction Disorder: Left Posterior Fascicular Block + Left Septal Fascicular Block
Authors: Pérez‐Riera Andres Ricardo , Baranchuk Adrian
Published: July 2014

A 44‐year‐old man with aortic valve insufficiency and stenosis underwent aortic valve replacement depicting interesting ECG changes. This unique case is discussed, contributing to the understanding of a trifascicular left intraventricular conduction system.
Evaluation of the impact of persistent subepithelial corneal infiltrations on the visual performance and corneal optical quality after epidemic keratoconjunctivitis
Authors: Aydin Kurna Sevda , Altun Ahmet , Oflaz Aynur , Karatay Arsan Aysu
Published: July 2014

Purpose

Aim was to measure the effect of persistent subepithelial corneal infiltrates (SEIs) after epidemic keratoconjunctivitis (EKC) on visual performance and corneal optical quality.

Methods

We examined 53 patients divided into two groups. Patients with previous EKC constituted the study group (Group 1, n: 27). Healthy age matched subjects constituted the control group (Group 2, n: 26). Study group was subdivided into eyes with SEI (Group 1A, 40 eyes) and healthy fellow eyes (Group 1B, 14 eyes). Patients were submitted to a complete examination including high‐ and low‐contrast visual acuities (HCVA, LCVA), corneal topography and aberrometry.

Results

The mean interval between epidemic conjunctivitis and examination was 7.25 ± 5.63 months. Mean number of corneal infiltrates was 17.30 ± 14.38. The mean HCVA and LCVA were significantly lower in the eyes with SEI than fellow eyes and control group (p = 0.001). LCVA value was also worse in the fellow eyes when compared to control (p = 0.048). Corneal topography values were significantly higher in the eyes with SEI from both fellow eyes and control group. During corneal aberrometry, the mean root mean square value of spheric aberration, irregular astigmatism and total aberration were significantly higher in SEI group when compared to fellow eyes and control group (p < 0.05). Total aberrations were higher than control subjects in the fellow eyes. Trefoil aberration was higher in SEI group only when compared to control subjects, while there was no significant difference in coma aberration values between the groups (p > 0.05).

Conclusion

Results of this study suggested that visual performance is compromised in patients with EKC by aberrations and changes in topographic variables.
Histomorphometric study of the goat stomach during prenatal development
Authors: Garcia Angela , Rodriguez Pedro , Masot Javier , Franco Antonio , Redondo Eloy
Published: July 2014

The aim of this study was to perform a morphometric analysis of the different structural tissue layers of the goat stomach to study their prenatal growth from mathematical models fitted to these morphometric data. A total of 90 embryos and fetuses were used, from the early stages of prenatal life until birth. The growth rate of the gastric wall was slower than that of body length; rumen was the stomach compartment displaying slowest growth. In the three non‐glandular compartments, the epithelial layer grew faster than the gastric wall itself, while the growth rate of the abomasal epithelium declined in the early stages of development. A decline in growth rate was also observed for the lamina propria and submucosa in rumen and reticulum from the early embryonic stages, whereas in omasum and abomasum these layers continued to grow as gestation progressed. The tunica muscularis displayed consistent growth in all compartments, growing faster than the gastric wall. Serosa thickness increased as gestation progressed, displaying a decline in growth‐rate only in the omasum. In conclusion, the dynamics of gastric wall growth were governed by the growth rate of each of the component tissue layers.
Diagnostic dilemmas in Fabry disease: a case series study on GLA mutations of unknown clinical significance
Authors: Smid B.E. , Hollak C.E.M. , Poorthuis B.J.H.M. , van den Bergh Weerman M.A. , Florquin S. , Kok W.E.M. , Lekanne Deprez R.H. , Timmermans J. , Linthorst G.E.
Published: July 2014

Fabry disease' (FD) phenotype is heterogeneous: alpha‐galactosidase A gene mutations (GLA) can lead to classical or non‐classical FD, or no FD. The aim of this study is to describe pitfalls in diagnosing non‐classical FD and assess the diagnostic value of plasma globotriaosylsphingosine. This is a case series study. Family 1 (p.A143T) presented with hypertrophic cardiomyopathy (HCM), absent classical FD signs, high residual alpha‐galactosidase A activity (AGAL‐A) and normal plasma globotriaosylsphingosine. Co‐segregating sarcomeric mutations were found. Cardiac biopsy excluded FD. In family 2 (p.P60L), FD was suspected after kidney biopsy in a female with chloroquine use. Males had residual AGAL‐A, no classical FD signs and minimally increased plasma globotriaosylsphingosine, indicating that p.P60L is most likely non‐pathogenic. Non‐specific complications and histology can be explained by chloroquine and alternative causes. Males of two unrelated families (p.R112H) show AGAL‐A <5%, but slightly elevated plasma globotriaosylsphingosine (1.2–2.0 classical males >50 nmol/l). Histological evidence suggests a variable penetrance of this mutation. Patients with GLA mutations and non‐specific findings such as HCM may have non‐classical FD or no FD. Other (genetic) causes of FD‐like findings should be excluded, including medication inducing FD‐like storage. Plasma globotriaosylsphingosine may serve as a diagnostic tool, but histology of an affected organ is often mandatory.
Ataxia telangiectasia: more variation at clinical and cellular levels
Authors: Taylor A.M.R. , Lam Z. , Last J.I. , Byrd P.J.
Published: July 2014

Ataxia telangiectasia (A‐T) is a rare recessively inherited disorder resulting in a progressive neurological decline. It is caused by biallelic mutation of the ATM gene that encodes a 370 kDa serine/threonine protein kinase responsible for phosphorylating many target proteins. ATM is activated by auto(trans)phosphorylation in response to DNA double strand breaks and leads to the activation of cell cycle checkpoints and either DNA repair or apoptosis as part of the cellular response to DNA damage. The allelic heterogeneity in A‐T is striking. While the majority of mutations are truncating, leading to instability and loss of the ATM protein from the allele, a significant proportion of patients carry one of a small number of mutations that are either missense or leaky splice site mutations resulting in retention of some ATM with activity. The allelic heterogeneity in ATM, therefore, results in an equally striking clinical heterogeneity. There is also locus heterogeneity because mutation of the MRE11 gene can cause an obvious A‐T like disorder both clinically and also at the cellular level and mutation of the RNF168 gene results in a much milder clinical phenotype, neurologically, with the major clinical feature being an immunological defect.
Height estimation using long bone segment length is unlikely to play a role in the routine measurement of healthy preschool children
Authors: Elder Charlotte J , Wright Neil P
Published: July 2014

This commentary is on the original article by Weidauer et al. on pages 995–1000 of this issue.
Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non‐diabetic controls
Authors: Bannister C. A. , Holden S. E. , Jenkins‐Jones S. , Morgan C. Ll. , Halcox J. P. , Schernthaner G. , Mukherjee J. , Currie C. J.
Published: July 2014

Aims

Clinical and observational studies have shown an increased risk of cardiovascular events and death associated with sulphonylureas versus metformin. However, it has never been determined whether this was due to the beneficial effects of metformin or detrimental effects of sulphonylureas. The objective of this study was therefore to compare all‐cause mortality in diabetic patients treated first‐line with either sulphonylurea or metformin monotherapy with that in matched individuals without diabetes.

Methods

We used retrospective observational data from the UK Clinical Practice Research Datalink (CPRD) from 2000. Subjects with type 2 diabetes who progressed to first‐line treatment with metformin or sulphonylurea monotherapy were selected and matched to people without diabetes. Progression to all‐cause mortality was compared using parametric survival models that included a range of relevant co‐variables.

Results

We identified 78 241 subjects treated with metformin, 12 222 treated with sulphonylurea, and 90 463 matched subjects without diabetes. This resulted in a total, censored follow‐up period of 503 384 years. There were 7498 deaths in total, representing unadjusted mortality rates of 14.4 and 15.2, and 50.9 and 28.7 deaths per 1000 person‐years for metformin monotherapy and their matched controls, and sulphonylurea monotherapy and their matched controls, respectively. With reference to observed survival in diabetic patients initiated with metformin monotherapy [survival time ratio (STR) = 1.0], adjusted median survival time was 15% lower (STR = 0.85, 95% CI 0.81–0.90) in matched individuals without diabetes and 38% lower (0.62, 0.58–0.66) in diabetic patients treated with sulphonylurea monotherapy.

Conclusions

Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non‐diabetic controls. Those treated with sulphonylurea had markedly reduced survival compared with both matched controls and those receiving metformin monotherapy. This supports the position of metformin as first‐line therapy and implies that metformin may confer benefit in non‐diabetes. Sulphonylurea remains a concern.
Modulation of NADPH oxidase activity by known uraemic retention solutes
Authors: Schulz Anna Marta , Terne Cindy , Jankowski Vera , Cohen Gerald , Schaefer Mandy , Boehringer Falko , Tepel Martin , Kunkel Desiree , Zidek Walter , Jankowski Joachim ,   European Uremic Toxin Work Group (EUTox)
Published: July 2014

Background

Uraemia and cardiovascular disease appear to be associated with an increased oxidative burden. One of the key players in the genesis of reactive oxygen species (ROS) is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Based on initial experiments demonstrating a decreased inhibitory effect on NADPH oxidase activity in the presence of plasma from patients with CKD‐5D after dialysis compared with before dialysis, we investigated the effect of 48 known and commercially available uraemic retention solutes on the enzymatic activity of NADPH oxidase.

Methods

Mononuclear leucocytes isolated from buffy coats of healthy volunteers were isolated, lysed and incubated with NADH in the presence of plasma from healthy controls and patients with CKD‐5D. Furthermore, the leucocytes were lysed and incubated in the presence of uraemic retention solute of interest and diphenyleneiodonium chloride (DPI), an inhibitor of NADPH oxidase. The effect on enzymatic activity of NADPH oxidase was quantified within an incubation time of 120 min.

Results

Thirty‐nine of the 48 uraemic retention solutes tested had a significant decreasing effect on NADPH oxidase activity. Oxalate has been characterized as the strongest inhibitor of NADPH oxidase (90% of DPI inhibition). Surprisingly, none of the uraemic retention solutes we investigated was found to increase NADPH oxidase activity. Furthermore, plasma from patients with CKD‐5D before dialysis caused significantly higher inhibitory effect on NADPH oxidase activity compared with plasma from healthy subjects. However, this effect was significantly decreased in plasma from patients with CKD‐5D after dialysis.

Conclusions

The results of this study show that uraemic retention solutes modulated the activity of the NADPH oxidase. The results of this study might be the basis for the development of inhibitors applicable as drug in the situation of increased oxidative stress.
Cooperative investment in public goods is kin directed in communal nests of social birds
Authors: van Dijk René E. , Kaden Jennifer C. , Argüelles‐Ticó Araceli , Dawson Deborah A. , Burke Terry , Hatchwell Ben J.
Published: July 2014

The tragedy of the commons predicts social collapse when public goods are jointly exploited by individuals attempting to maximize their fitness at the expense of other social group members. However, animal societies have evolved many times despite this vulnerability to exploitation by selfish individuals. Kin selection offers a solution to this social dilemma, but in large social groups mean relatedness is often low. Sociable weavers (Philetairus socius) live in large colonies that share the benefits of a massive communal nest, which requires individual investment for construction and maintenance. Here, we show that despite low mean kinship within colonies, relatives are spatially and socially clustered and that nest‐building males have higher local relatedness to other colony members than do non‐building males. Alternative hypotheses received little support, so we conclude that the benefits of the public good are shared with kin and that cooperative investment is, despite the large size and low relatedness of these communities, kin directed.
Subcutaneous immunoglobulin preserves muscle strength in chronic inflammatory demyelinating polyneuropathy
Authors: Markvardsen L. H. , Harbo T. , Sindrup S. H. , Christiansen I. , Andersen H. , Jakobsen J. ,   The Danish CIDP and MMN Study Group
Published: July 2014

Background and purpose

Subcutaneous immunoglobulin (SCIG) is superior to placebo treatment for maintenance of muscle strength during 12 weeks in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The present study evaluated whether SCIG preserves muscle strength for 1 year in an open‐label follow‐up study.

Methods

Seventeen responders to intravenous immunoglobulin (IVIG) who had participated in the previous study of SCIG versus placebo in CIDP were included. After one IVIG infusion 2 weeks prior to baseline, all continued on SCIG treatment at weekly equal dosage and were evaluated after 3, 6 and 12 months. Primary end‐points were changes in muscle strength evaluated by isokinetic dynamometry in four affected muscle groups and a composite score of muscle performance and function tests, including Medical Research Council (MRC) score, grip strength, 40‐m walking test (40‐MWT) and nine‐hole peg test (9‐HPT). Secondary end‐points were changes of each of the listed parameters at each time point as well as an overall disability sum score (ODSS).

Results

The dose of SCIG was significantly unaltered during the follow‐up period. Overall the isokinetic dynamometry value increased by 7.2% (P = 0.033) and after 3, 6 and 12 months by 5.7%, 8.2% and 6.8% (ns). The overall composite score at all time intervals and for each interval remained unchanged. Amongst the secondary parameters the MRC score increased significantly by 1.7% (P = 0.007), whereas grip strength, 40‐MWT, 9‐HPT and ODSS remained unchanged.

Conclusion

SCIG preserves muscle strength and functional ability in patients with CIDP who previously responded to IVIG. SCIG should be considered as an alternative in long‐term treatment of CIDP patients.
Structural analysis of human soluble adenylyl cyclase and crystal structures of its nucleotide complexes – implications for cyclase catalysis and evolution
Authors: Kleinboelting Silke , van den Heuvel Joop , Steegborn Clemens
Published: July 2014

The ubiquitous second messenger cAMP regulates a wide array of functions, from bacterial transcription to mammalian memory. It is synthesized by six evolutionarily distinct adenylyl cyclase (AC) families. In mammals, there are two AC types: nine transmembrane ACs (tmACs) and one soluble AC (sAC). Both AC types belong to the widespread cyclase class III, which has members in numerous organisms from archaeons to mammals. Class III also contains all known guanylyl cyclases (GCs), which synthesize the cAMP‐related messenger cGMP in many eukaryotes and possibly some prokaryotes. Among mammalian ACs, sAC is uniquely regulated by bicarbonate, and has been proposed to be more closely related to a bacterial AC subfamily than to mammalian ACs, on the basis of sequence comparisons. Here, we used crystal structures of human sAC catalytic domains to analyze its relationships with other class III ACs and GCs, and to study its substrate selection mechanisms. Structural comparisons revealed a similarity within an sAC‐like subfamily but no family‐specific structure elements, and an unexpected sAC similarity to eukaryotic GCs and a potential bacterial GC. We further solved novel crystal structures of sAC catalytic domains in complex with a substrate analog, unprocessed ATP substrate, and product after soaking with ATP or GTP. The structures show a novel ATP‐binding conformation, and suggest mechanisms for substrate association and recognition. Our results could explain the limited substrate specificity of sAC, suggest how specificity is increased in other cyclases, and indicate evolutionary relationships among class III enzymes, with sAC being close to a putative ‘ancestor’ cyclase.

Database

Coordinates and structure factors for the novel sAC‐cat structures described have been deposited with the Worldwide PDB (www.pdb.org): ApCpp soak (entry 4usu), ATP + Ca2+ soak (entry 4usv), GTP + Mg2+ soak (entry 4ust), ATP soak (entry 4usw).
The isotopic biosignatures of photo‐ vs. thiotrophic bivalves: are they preserved in fossil shells?
Authors: Dreier A. , Loh W. , Blumenberg M. , Thiel V. , Hause‐Reitner D. , Hoppert M.
Published: July 2014

Symbiont‐bearing and non‐symbiotic marine bivalves were used as model organisms to establish biosignatures for the detection of distinctive symbioses in ancient bivalves. For this purpose, the isotopic composition of lipids (δ13C) and bulk organic shell matrix (δ13C, δ34S, δ15N) from shells of several thiotrophic, phototrophic, or non‐symbiotic bivalves were compared (phototrophic: Fragum fragum, Fragum unedo, Tridacna maxima; thiotrophic: Codakia tigerina, Fimbria fimbriata, Anodontia sp.; non‐symbiotic: Tapes dorsatus, Vasticardium vertebratum, Scutarcopagia sp.). ∆13C values of bulk organic shell matrices, most likely representing mainly original shell protein/chitin biomass, were depleted in thio‐ and phototrophic bivalves compared to non‐symbiotic bivalves. As the bulk organic shell matrix also showed a major depletion of δ15N (down to –2.2 ‰) for thiotrophic bivalves, combined δ13C and δ15N values are useful to differentiate between thio‐, phototrophic, and non‐symbiotic lifestyles. However, the use of these isotopic signatures for the study of ancient bivalves is limited by the preservation of the bulk organic shell matrix in fossils. Substantial alteration was clearly shown by detailed microscopic analyses of fossil (late Pleistocene) T. maxima and Trachycardium lacunosum shell, demonstrating a severe loss of quantity and quality of bulk organic shell matrix with time. Likewise, the composition and δ13C‐values of lipids from empty shells indicated that a large part of these compounds derived from prokaryotic decomposers. The use of lipids from ancient shells for the reconstruction of the bivalve's life style therefore appears to be restricted.
Transcription factor NF‐E2‐related factor 1 impairs glucose metabolism in mice
Authors: Hirotsu Yosuke , Higashi Chika , Fukutomi Toshiaki , Katsuoka Fumiki , Tsujita Tadayuki , Yagishita Yoko , Matsuyama Yuka , Motohashi Hozumi , Uruno Akira , Yamamoto Masayuki
Published: July 2014

Nrf1 (NF‐E2‐related factor 1) is a basic region leucine zipper‐type transcription factor belonging to the CNC (cap‐'n'‐collar) family. Major pathophysiological contribution of Nrf1 remains unclear. As single nucleotide polymorphism rs3764400 in 5′‐flanking region of NRF1 gene appears to associate with obesity, in this study, we focused on the Nrf1 function on metabolism. We found that the risk C allele of rs3764400 increased NRF1 gene transcriptional activity compared with the T allele in hepatoma cell lines. Therefore, we newly established Nrf1 transgenic (Nrf1‐Tg) mouse lines and examined roles that Nrf1 plays on the obesity and metabolism. Unexpectedly, Nrf1 over‐expression repressed bodyweight gain in both lean and diet‐induced obesity mice. Of note, Nrf1‐Tg mice showed rise in blood glucose levels; Nrf1 strongly reduced glucose infusion rate in euglycemic–hyperinsulinemic clamp test and increased blood glucose levels in insulin tolerance test, indicating that Nrf1 induces insulin resistance in mice. Nrf1 repressed insulin‐regulated glycolysis‐related gene expression and gave rise to loss of glucose‐6‐phosphate and fructose‐6‐phosphate contents in liver. Consistently, Nrf1 heterozygote improved impaired glucose regulations in diet‐induced obesity model. These results showed that Nrf1 contributes to metabolic regulation, which gain‐of‐function develops diabetes mellitus in mice.
Assessment of vaccination‐related information for consumers available on Facebook®
Authors: Buchanan Rachel , Beckett Robert D.
Published: July 2014

Objectives

To assess the magnitude, interest, purpose and validity of vaccination‐related information on Facebook and to determine whether information varies by site viewpoint.

Methods

The 10 largest vaccination‐focused Facebook® pages, groups and places in each category were identified and classified by viewpoint (i.e. anti‐, pro‐, neutral) and purpose. Number of members, posts per week, likes, comments and shares per post were recorded. Posts were assessed for concordance with CDC and FDA recommendations.

Results

Of 30 sites, 43% (n = 13) were anti‐vaccination, 7% (n = 2) neutral and 50% (n = 15) pro‐vaccination. Most sites were most popular with American users. Median members were similar between anti‐vaccination (2703 members, range 337–33 631 members) and pro‐vaccination sites (2142 members, range 456–61 565 members, P = 0.262); however, anti‐vaccination sites accumulated more posts per week by authors (median 15 vs. 3, P = 0.031) and members (median 33 vs. 1, P < 0.001). Pro‐vaccination sites more commonly had commercial purpose (53% [n = 8] vs. 8% [n = 1], P = 0.02). Anti‐vaccination sites more commonly gave medical advice (54% [n = 7] vs. 0%, P = 0.004). Overall, 48% (n = 22) of author posts were concordant with regulatory recommendations; concordance was more common on pro‐vaccination sites (78% [n = 21] vs. 5% [n = 1], P = 0.0002).

Conclusion

Vaccination‐related information is prevalent on Facebook regardless of viewpoint; however, anti‐vaccination information generates more interest. Anti‐vaccination sites were likely to provide medical advice and disagree with regulatory bodies.