bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of 13 developmentally toxic chemicals on the migration of rat cephalic neural crest cells in vitro
Authors: Usami Makoto , Mitsunaga Katsuyoshi , Miyajima Atsuko , Takamatu Mina , Kazama Shugo , Irie Tomohiko , Doi Osamu , Takizawa Tatsuya
Published: July 2015

The inhibition of neural crest cell (NCC) migration has been considered as a possible pathogenic mechanism underlying chemical developmental toxicity. In this study, we examined the effects of 13 developmentally toxic chemicals on the migration of rat cephalic NCCs (cNCCs) by using a simple in vitro assay. cNCCs were cultured for 48 h as emigrants from rhombencephalic neural tubes explanted from rat embryos at day 10.5 of gestation. The chemicals were added to the culture medium at 24 h of culture. Migration of cNCCs was measured as the change in the radius (radius ratio) calculated from the circular spread of cNCCs between 24 and 48 h of culture. Of the chemicals examined, 13‐cis‐retinoic acid, ethanol, ibuprofen, lead acetate, salicylic acid, and selenate inhibited the migration of cNCCs at their embryotoxic concentrations; no effects were observed for acetaminophen, caffeine, indium, phenytoin, selenite, tributyltin, and valproic acid. In a cNCC proliferation assay, ethanol, ibuprofen, salicylic acid, selenate, and tributyltin inhibited cell proliferation, suggesting the contribution of the reduced cell number to the inhibited migration of cNCCs. It was determined that several developmentally toxic chemicals inhibited the migration of cNCCs, the effects of which were manifested as various craniofacial abnormalities.
Why Research ‘by’ Children? Rethinking the Assumptions Underlying the Facilitation of Children as Researchers
Authors: Kim Chae‐Young
Published: July 2015

Research ‘by’ children, where children conduct research as primary investigators, may be seen as an ideal form of children's participation in research. This paper examines the methodological and normative assumptions that underlie such research and identifies some ambiguities which require clarification and questions which need answering for better theorisations of its purposes and more robust evaluations of the associated research practices to occur. It concludes that tensions between these assumptions and the research practices mean the role of children as ‘researchers’ has been limited, while further explorations of the potentials of research ‘by’ children need stronger reflexivity.
Living with Duchenne Muscular Dystrophy: Relational Autonomy and Decision‐Making
Authors: Skyrme Sarah
Published: July 2015

Interviews were conducted with boys and young men who have Duchenne muscular dystrophy, exploring their thoughts on making a decision to participate in medical research. This article focuses on one of the key findings, discussing how the participants identified their parents as carers, spokespersons and advisors. The term ‘relational autonomy’ encapsulates these co‐operative relationships, illustrating how they can help young people living with a degenerative disability to exercise some agency and autonomy. The boys and their families have demonstrated how disabled children who are physically dependent can be supported by their parents, without compromising independence.
Laying the foundations of evolutionary and systematic studies in crickets (Insecta, Orthoptera): a multilocus phylogenetic analysis
Authors: Chintauan‐Marquier Ioana C. , Legendre Frédéric , Hugel Sylvain , Robillard Tony , Grandcolas Philippe , Nel André , Zuccon Dario , Desutter‐Grandcolas Laure
Published: July 2015

Orthoptera have been used for decades for numerous evolutionary questions but several of its constituent groups, notably crickets, still suffer from a lack of a robust phylogenetic hypothesis. We propose the first phylogenetic hypothesis for the evolution of crickets sensu lato, based on analysis of 205 species, representing 88% of the subfamilies and 71% tribes currently listed in the database Orthoptera Species File (OSF). We reconstructed parsimony, maximum likelihood and Bayesian phylogenies using fragments of 18S, 28SA, 28SD, H3, 12S, 16S, and cytb (~3600 bp). Our results support the monophyly of the cricket clade, and its subdivision into two clades: mole crickets and ant‐loving crickets on the one hand, and all the other crickets on the other (i.e. crickets sensu stricto). Crickets sensu stricto form seven monophyletic clades, which support part of the OSF families, “subfamily groups”, or subfamilies: the mole crickets (OSF Gryllotalpidae), the scaly crickets (OSF Mogoplistidae), and the true crickets (OSF Gryllidae) are recovered as monophyletic. Among the 22 sampled subfamilies, only six are monophyletic: Gryllotalpinae, Trigonidiinae, Pteroplistinae, Euscyrtinae, Oecanthinae, and Phaloriinae. Most of the 37 tribes sampled are para‐ or polyphyletic. We propose the best‐supported clades as backbones for future definitions of familial groups, validating some taxonomic hypotheses proposed in the past. These clades fit variously with the morphological characters used today to identify crickets. Our study emphasizes the utility of a classificatory system that accommodates diagnostic characters and monophyletic units of evolution. Moreover, the phylogenetic hypotheses proposed by the present study open new perspectives for further evolutionary research, especially on acoustic communication and biogeography.
A morphological supermatrix‐based phylogeny for the Neotropical fish superfamily Anostomoidea (Ostariophysi: Characiformes): phylogeny, missing data and homoplasy
Authors: Dillman Casey B. , Sidlauskas Brian L. , Vari Richard P.
Published: July 2015

Although 11 studies have addressed the systematics of the four families and 281 fish species of the ecomorphologically diverse Anostomoidea, none has proposed a global hypothesis of relationships. We synthesized these studies to yield a supermatrix with 463 morphological characters among 174 ingroup species, and inferred phylogeny with parsimony and Bayesian optimization. We evaluated the applicability of the supermatrix approach to morphological datasets, tested its sensitivity to missing data, determined the impact of homoplastic characters on phylogenetic resolution, and determined the distribution of homologies and homoplasies on the topology. Despite more than 60% missing data, analyses supported the monophyly of all families, and phylogenetic structure degraded only with inclusion of species with high percentages of missing data and in analyses limited to homoplasies. The latter differs modestly from the full matrix indicating phylogenetic signal in homoplastic characters. Character distributions differ across the phylogeny, with a greater prevalence of homologies at deeper nodes and homoplasies nearer the tips than expected by chance. This may suggest early diversification into distinct bauplans with subsequent diversification of faster evolving character systems. The morphological supermatrix approach is powerful and allows integration of classical data with modern methods to examine the evolution of multiple character systems.
Dental implants treatment outcomes in patient under active therapy with alendronate: 3‐year follow‐up results of a multicenter prospective observational study
Authors: Tallarico Marco , Canullo Luigi , Xhanari Erta , Meloni Silvio Mario
Published: July 2015

Objective

To evaluate the 3‐year clinical and radiographic data of fixed implant‐supported dental prosthesis delivered to patients having taken alendronate 35–70 mg weekly for at least 3 years before implant placement.

Materials and Methods

Forty consecutive patients treated with oral bisphosphonates and requiring an implant‐supported restoration were recruited in two private centers between January 2008 and December 2011. Implants were inserted through minimally invasive approach under antibacterial and antibiotic treatment, 6 months after alendronate administration stopping. After 4 months of submerged healing, implants underwent prosthetic loading. Hygiene maintenance and clinical assessments were scheduled every 4 months for 3 years. Outcome measures were the following: implant and prosthetic success, survival rates, any observed clinical complications, marginal bone remodeling, probing pocket depth and bleeding‐on‐probing.

Results

At the end of the study, eight patients dropped out. The final sample size resulted in 32 consecutive partially or fully edentulous patients (32 females; mean age 64.6 years) with 98 submerged implants. In only one patient, maxillary implant failed during healing period. No prosthesis failed during the entire follow‐up, and no major complications were recorded. Implant and prostheses success resulted in an overall survival rate of 98, 98% and 100%, respectively. Three‐year mean marginal bone loss was 1.35 ± 0.21 (CI 95% 1.24–1.38). Successful soft tissue parameters were found around all implants.

Conclusions

Oral bisphosphonate therapy did not appear to significantly affect implant survival and success in case of accurate treatment time selection, minimally invasive surgical approach and constant follow‐up. Further prospective studies involving larger sample sizes and longer durations of follow‐up are required to confirm these results.
Minimum area requirements for an at‐risk butterfly based on movement and demography
Authors: Brown Leone M. , Crone Elizabeth E.
Published: July 2015

Determining the minimum area required to sustain populations has a long history in theoretical and conservation biology. Correlative approaches are often used to estimate minimum area requirements (MARs) based on relationships between area and the population size required for persistence or between species’ traits and distribution patterns across landscapes. Mechanistic approaches to estimating MAR facilitate prediction across space and time but are few. We used a mechanistic MAR model to determine the critical minimum patch size (CMP) for the Baltimore checkerspot butterfly (Euphydryas phaeton), a locally abundant species in decline along its southern range, and sister to several federally listed species. Our CMP is based on principles of diffusion, where individuals in smaller patches encounter edges and leave with higher probability than those in larger patches, potentially before reproducing. We estimated a CMP for the Baltimore checkerspot of 0.7–1.5 ha, in accordance with trait‐based MAR estimates. The diffusion rate on which we based this CMP was broadly similar when estimated at the landscape scale (comparing flight path vs. capture‐mark‐recapture data), and the estimated population growth rate was consistent with observed site trends. Our mechanistic approach to estimating MAR is appropriate for species whose movement follows a correlated random walk and may be useful where landscape‐scale distributions are difficult to assess, but demographic and movement data are obtainable from a single site or the literature. Just as simple estimates of lambda are often used to assess population viability, the principles of diffusion and CMP could provide a starting place for estimating MAR for conservation.
Prophylactic mesh at end‐colostomy construction reduces parastomal hernia rate: a randomized trial
Authors: Lambrecht J. R. , Larsen S. G. , Reiertsen O. , Vaktskjold A. , Julsrud L. , Flatmark K.
Published: July 2015

Aim

Parastomal hernia (PSH) is the most common complication of an end‐colostomy and about one‐quarter of patients need operative repair, which is often unsuccessful. A randomized trial was carried out to compare the results of using mesh or no mesh at the time of formation of a colostomy with the clinical identification of PSH as the primary outcome.

Method

In this two‐centre randomized trial (Oslo University Hospital and Sykehuset Innlandet Hospital Trust, Norway), patients with rectal cancer undergoing open pelvic surgery were randomized to receive a retromuscular synthetic mesh (study group, n = 32) or no mesh (control group, n = 26) at the time of end‐colostomy formation. Postoperative follow up was not blinded and included clinical examination and routine CT.

Results

The median period of follow up was 40 (range: 84) months. There were no differences in demographic variables or complications between the study and control groups. PSH developed in two patients of the study group and in 12 of the control group [OR = 0.04 (95% CI: 0.01–0.30) and hazard ratio 0.134 (95% CI: 0.030–0.603); P < 0.001]. The number needed to treat to avoid one PSH was 2.5 patients. CT demonstrated an increase over time in the size of the fascial orifice in patients with PSH without mesh prophylaxis, in contrast to a stable size in patients with mesh and in the control patients who did not develop PSH.

Conclusion

The retromuscular insertion of synthetic mesh at the time of formation of an end‐colostomy reduced the risk of PSH.
Training techniques in laparoscopic donor nephrectomy: a systematic review
Authors: Raque Jessica , Billeter Adrian T. , Lucich Elizabeth , Marvin Michael M. , Sutton Erica
Published: July 2015

The learning curve to achieve competency in laparoscopic donor nephrectomy (LDN) is poorly outlined. Online databases were searched for training in LDN. Abstracts and manuscripts were excluded if they did not address introduction of a laparoscopic technique for donor nephrectomy. Relevant manuscripts were reviewed for surgical technique, use of animal models, co‐surgeons, surgeon specialty and training, institution type/volume, and assessment of training method. Forty‐four met inclusion criteria, with 75% describing the evolution from open to LDN. Eighty‐two percent were from academic centers, and 36% were from centers performing <25 donor nephrectomies each year. The learner was an attending surgeon 80% of the time, mostly urologists with prior laparoscopy or open nephrectomy experience. The learning curve, defined by decreased operating time, averaged 35 cases. Improved intra‐operative, patient, and recipient outcomes were observed for centers performing ≥50 LDNs annually. The United Network of Organ Sharing requires 15 cases as surgeon or assistant to be certified as the primary LDN surgeon. This falls below the described learning curve for LDN. The assessment of training and competency for LDN is heterogeneous, and objective learner‐based metrics could help surgeons and institutions reach a quality standard for performing this operation.
Recruiting for addiction research via Facebook
Authors: Thornton Louise K. , Harris Keith , Baker Amanda L. , Johnson Martin , Kay‐Lambkin Frances J.
Published: July 2015

Introduction and Aims

This study aimed to examine the feasibility of recruiting participants to addiction research via Facebook.

Design and Methods

Participants were recruited via an advertisement on Facebook, a local research register and university psychology courses. Participants completed a self‐report survey regarding substance use, history of mental health issues and current psychological distress.

Results

The 524 participants recruited via Facebook cost $1.86 per participant; and 418 participants were recruited via more traditional methods. There were significantly fewer women in the Facebook sample compared with the non‐Facebook sample (χ2 = 196.61, P < 0.001), but no differences on age. Significantly more Facebook participants reported current use of tobacco (women: Facebook = 57%, non‐Facebook = 21%, χ2 = 39.71, P < 0.001; men: Facebook = 62%, non‐Facebook = 21%, χ2 = 32.429, P < 0.001) and cannabis (women: Facebook = 26%, non‐Facebook = 7%, χ2 = 14.364, P < 0.001; men: Facebook = 46%, non‐Facebook = 24%, χ2 = 6.765, P < 0.01). They also reported significantly more harmful use of tobacco [women: F degrees of freedom (d.f.) = 6.07, P < 0.05; men: F(d.f.) = 9.03, P < 0.01] and cannabis [women: F(d.f.) = 11.00, P < 0.01; men: F(d.f.) = 6.40, P < 0.05]. The Facebook sample contained a higher percentage of high‐severity cannabis users (women: Facebook = 24%, non‐Facebook = 4%, χ2 = 18.12, P < 0.001; men: Facebook = 43%, non‐Facebook = 16%, χ2 = 10.00, P < 0.01) and reported significantly more severe depressive symptoms [women: F(d.f.) = 26.38, P < 0.001; men: F(d.f.) = 7.44, P < 0.05].

Discussion and Conclusions

Through Facebook, we were able to capture a greater proportion of people with high‐severity substance use and mental health issues and were able to capture a greater and more severe range of substance use behaviours. This suggests social networking sites are efficient, cost‐effective ways to recruit large numbers of participants, with relevant behaviours and conditions, to addiction research. [Thornton LK, Harris K, Baker AL, Johnson M, Kay‐Lambkin FJ. Recruiting for addiction research via Facebook. Drug Alcohol Rev 2016;35:494–502]
Predicting perceived safety to drive the morning after drinking: The importance of hangover symptoms
Authors: Cameron Elaine , French David P.
Published: July 2015

Introduction and Aims

People driving the day after drinking are at risk of impaired performance and accidents due to continued intoxication or the effects of alcohol hangover. Drivers are poor at estimating their own blood alcohol concentration, and some drive despite believing they are over the legal limit. It is therefore important to identify other factors influencing perceived ability to drive ‘the morning after’. This study tested how accurately participants estimated their legal driving status, and the contribution of beliefs and hangover symptoms to the prediction of perceived driving safety.

Design and Methods

This cross‐sectional study involved 193 students completing a questionnaire and alcohol breath test the morning after heavy alcohol consumption. Indicators of subjective intoxication, severity of hangover symptoms, estimated legal status and perceived safety to drive were measured. A hierarchical linear regression analysis was conducted.

Results

No participants thought they were under the English legal limit when they were not, and 47% thought they were over the limit when they were in fact legally permissible to drive. However, 20% of those believing they were over the limit nevertheless rated themselves as safe to drive. Hangover symptoms added 17% variance to the prediction of perceived safety to drive, over and above objective and subjective measures of intoxication.

Discussion and Conclusions

Perceived severity of hangover symptoms influence beliefs about driving ability: When judging safety to drive, people experiencing less severe symptoms believe they are less impaired. If this finding is robust, health promotion campaigns should aim to correct this misapprehension. [Cameron E, French D. Predicting perceived safety to drive the morning after drinking: The importance of hangover symptoms. Drug Alcohol Rev 2016;35:442–446]
Gastroesophageal reflux disease after peroral endoscopic myotomy: Analysis of clinical, procedural and functional factors, associated with gastroesophageal reflux disease and esophagitis
Authors: Familiari Pietro , Greco Santi , Gigante Giovanni , Calì Anna , Boškoski Ivo , Onder Graziano , Perri Vincenzo , Costamagna Guido
Published: July 2015

Background and Aim

Peroral endoscopic myotomy (POEM) does not include any antireflux procedure, resulting in a certain risk of iatrogenic gastroesophageal reflux disease (GERD). The aim of the present study was to evaluate the incidence of iatrogenic GERD after POEM and identify preoperative, perioperative and postoperative factors associated with GERD.

Methods

All patients treated at a single center who had a complete GERD evaluation after POEM were included in the study. Demographics, preoperative and follow‐up data, results of functional studies and procedural data were collected and analyzed.

Results

A total of 103 patients (mean age 46.6 years, 47 males) were included. Postoperative altered esophageal acid exposure was attested in 52 patients (50.5%). A total of 19 patients (18.4%) had heartburn and 21 had esophagitis (20.4%). Overall, a clinically relevant GERD (altered esophageal acid exposure, associated with heartburn and/or esophagitis) was diagnosed in 30 patients (29.1%).

Correlation between the severity of esophageal acid exposure with heartburn and esophagitis after POEM was found. Patients with heartburn had a lower postoperative 4‐second integrated relaxation pressure compared to patients without symptoms (7.6 ± 3.8 mmHg vs 10.01 ± 4.4 mmHg, p<0.05). No correlations were identified with patient sex, age, postoperative body mass index, esophageal shape (sigmoid vs non sigmoid), lower esophageal sphincter pressure, length of myotomy, previous therapies and type of achalasia at high‐resolution manometry.

Conclusions

Preoperative, perioperative or postoperative factors minimally correlated with GERD after POEM. Clinically relevant GERD was identified in less than one‐third of patients, but all patients were well controlled with medical therapy.
Identification of tool use acquisition‐associated genes in the primate neocortex
Authors: Matsunaga Eiji , Nambu Sanae , Oka Mariko , Tanaka Michio , Taoka Miki , Iriki Atsushi
Published: July 2015

Japanese macaques are able to learn how to use rakes to take food after only a few weeks of training. Since tool‐use training induced rapid morphological changes in some restricted brain areas, this system will be a good model for studying the neural basis of plasticity in human brains. To examine the mechanisms of tool‐use associated brain expansion on the molecular and cellular level, here, we performed comprehensive analysis of gene expressions with microarray. We identified various transcripts showing differential expression between trained and untrained monkeys in the region around the lateral and intraparietal sulci. Among candidates, we focused on genes related to synapse formation and function. Using quantitative reverse transcription–polymerase chain reaction and histochemical analysis, we confirmed at least three genes (ADAM19, SPON2, and WIF1) with statistically different expression levels in neurons and glial cells. Comparative analysis revealed that tool use‐associated genes were more obviously expressed in macaque monkeys than marmosets or mice. Thus, our findings suggest that cognitive tasks induce structural changes in the neocortex via gene expression, and that learning‐associated genes innately differ with relation to learning ability.
The histopathology of polymicrogyria: a series of 71 brain autopsy studies
Authors: Jansen Anna C , Robitaille Yves , Honavar Mrinalini , Mullatti Nandini , Leventer Richard J , Andermann Eva , Andermann Frederick , Squier Waney
Published: July 2015

Aim

Polymicrogyria (PMG) is one of the most common forms of cortical malformation yet the mechanism of its development remains unknown. This study describes the histopathological aspects of PMG in a large series including a significant proportion of fetal cases.

Method

We have reviewed the neuropathology and medical records of 44 fetuses and 27 children and adults in whom the cortical architecture was focally or diffusely replaced by one or more festooning bands of neurons.

Results

The pial surface of the brain overlying the polymicrogyric cortex was abnormal in almost 90% of cases irrespective of the aetiology. This accords with animal studies indicating the importance of the leptomeninges in cortical development. The aetiology of PMG was highly heterogeneous and there was no correlation between cortical layering patterns and aetiology. PMG was almost always associated with other brain malformations.

Interpretation

The inclusion of many fetal cases has allowed us to examine the early developmental stages of PMG. The study indicates the significance of surface signals responsible for human corticogenesis and the complex interaction between genetic and environmental factors leading to this common endpoint of cortical maldevelopment.
Translation of the Diabetes Prevention Program for diabetes risk reduction in Chinese immigrants in New York City
Authors: Yeh M.‐C. , Heo M. , Suchday S. , Wong A. , Poon E. , Liu G. , Wylie‐Rosett J.
Published: July 2015

Aims

To evaluate the effectiveness and feasibility of implementing a linguistically and culturally tailored Diabetes Prevention Program among Chinese immigrants with prediabetes living in New York City.

Methods

A total of 60 Chinese immigrants with prediabetes were randomized into either a Diabetes Prevention Program lifestyle intervention (n = 30) consisting of 12 bi‐weekly core sessions and six monthly post‐core sessions or the control intervention (n = 30), consisting of quarterly mailing of diabetes prevention information. Each Diabetes Prevention Program intervention session lasted 1.5–2 h and covered topics such as healthy eating, physical activity, stress reduction and problem‐solving skills. Outcomes such as percent change in weight, BMI, and HbA1c concentration were assessed at baseline, 6 and 12 months. A mixed‐effects linear regression was applied to test the intervention effect at months 6 and 12. Data were collected in the period 2012–2013 and analysed in 2014.

Results

The participant attrition rate was < 5% (2 out of 60) at 12 months. There was a significantly greater percent weight loss in the intervention group (−3.5 vs. −0.1%; P = 0.0001) at 6 months, which was largely maintained at 12 months (−3.3 vs. 0.3%; P = 0.0003).

Conclusions

Participants in a Diabetes Prevention Program‐based intervention achieved greater weight loss and improvements in HbA1c concentration than control participants. Evaluation of the Chinese Diabetes Prevention Program curriculum in a larger trial is warranted.
Low levels of C‐peptide have clinical significance for established Type 1 diabetes
Authors: Kuhtreiber W. M. , Washer S. L. L. , Hsu E. , Zhao M. , Reinhold P. , Burger D. , Zheng H. , Faustman D. L.
Published: July 2015

Aim

To determine whether the low C‐peptide levels (< 50 pmol/l) produced by the pancreas for decades after onset of Type 1 diabetes have clinical significance.

Methods

We evaluated fasting C‐peptide levels, duration of disease and age of onset in a large cross‐sectional series (n = 1272) of people with Type 1 diabetes. We then expanded the scope of the study to include the relationship between C‐peptide and HbA1c control (n = 1273), as well as diabetic complications (n = 324) and presence of hypoglycaemia (n = 323). The full range of C‐peptide levels was also compared with 1,5‐Anhydroglucitol, a glucose responsive marker.

Results

C‐peptide levels declined for decades after diagnosis, and the rate of decline was significantly related to age of onset (P < 0.0001), after adjusting for disease duration. C‐peptide levels > 10 pmol/l were associated with protection from complications (e.g. nephropathy, neuropathy, foot ulcers and retinopathy; P = 0.03). Low C‐peptide levels were associated with poor metabolic control measured by HbA1c (P < 0.0001). Severe hypoglycaemia was associated with the lowest C‐peptide levels compared with mild (P = 0.049) or moderate (P = 0.04) hypoglycaemia. All levels of measurable C‐peptide were responsive to acute fluctuations in blood glucose levels as assessed by 1,5‐Anhydroglucitol (P < 0.0001).

Conclusions

Low C‐peptide levels have clinical significance and appear helpful in characterizing groups at‐risk for faster C‐peptide decline, complications, poorer metabolic control and severe hypoglycaemia. Low C‐peptide levels may be a biomarker for characterizing at‐risk patients with Type 1 diabetes.
People with diabetic peripheral neuropathy display a decreased stepping accuracy during walking: potential implications for risk of tripping
Authors: Handsaker J. C. , Brown S. J. , Bowling F. L. , Marple‐Horvat D. E. , Boulton A. J. M. , Reeves N. D.
Published: July 2015

Aim

To examine the stepping accuracy of people with diabetes and diabetic peripheral neuropathy.

Methods

Fourteen patients with diabetic peripheral neuropathy (DPN), 12 patients with diabetes but no neuropathy (D) and 10 healthy non‐diabetic control participants (C). Accuracy of stepping was measured whilst the participants walked along a walkway consisting of 18 stepping targets. Preliminary data on visual gaze characteristics were also captured in a subset of participants (diabetic peripheral neuropathy group: n = 4; diabetes‐alone group: n = 4; and control group: n = 4) during the same task.

Results

Patients in the diabetic peripheral neuropathy group, and patients in the diabetes‐alone group were significantly less accurate at stepping on targets than were control subjects (P < 0.05). Preliminary visual gaze analysis identified that patients diabetic peripheral neuropathy were slower to look between targets, resulting in less time being spent looking at a target before foot‐target contact.

Conclusions

Impaired motor control is theorized to be a major factor underlying the changes in stepping accuracy, and potentially altered visual gaze behaviour may also play a role. Reduced stepping accuracy may indicate a decreased ability to control the placement of the lower limbs, leading to patients with neuropathy potentially being less able to avoid observed obstacles during walking.
Are hepatic and soleus lipid content, assessed by magnetic resonance spectroscopy, associated with low birth weight or insulin resistance in a rural Indian population of healthy young men?
Authors: Livingstone R. S. , Grunnet L. G. , Thomas N. , Eapen A. , Antonisamy B. , Mohan V. R. , Spurgeon R. , Frank I. D. , Bygbjerg I. C. , Vaag A.
Published: July 2015

Aims

To assess young healthy men from rural India, who had normal or low birth weights, using magnetic resonance spectroscopy to determine the potential differences in ectopic fat storage between birth weight groups, and to determine if ectopic fat storage was associated with insulin resistance in this population.

Methods

A total of 54 lean men with normal birth weight and 49 lean men with low birth weight (age range 18–22 years) from rural India were recruited. All the men underwent anthropometry, magnetic resonance spectroscopy, a hyperinsulinaemic‐euglycaemic clamp and a dual‐energy X‐ray absorptiometry.

Results

The median (interquartile range) values for hepatic cellular lipids, intramyocellular lipids and extramyocellular lipids, measured using magnetic resonance spectroscopy were 0.76 (0.1–1.8)%, 1.27 (1.0–2.3)% and 1.89 (1.3–3.2)%, respectively, for the normal birth weight group and 0.4 (0.1–1.3)%, 1.38 (0.9–2.2)% and 2.07 (1.2–2.8)%, respectively, for the low birth weight group (P > 0.05). No difference in ectopic fat storage was observed between the low and normal birth weight groups, with or without adjustment for age and total fat percentage. Homeostatic model assessment of insulin resistance values were not associated with hepatic cellular, intramyocellular or extramyocellular lipid content in any of the groups. Total fat percentage was the only independent predictor of intramyocellular and extramyocellular lipid content.

Conclusion

Young and lean men from rural India with low birth weight were not observed to have ectopic fat storage in the liver or muscle, and the amount of liver and muscle fat was unrelated to insulin resistance. Older age and/or an urban affluent lifestyle may be required to show a potential role of ectopic fat storage on insulin resistance in Indian people with low or normal birth weight.
Academic abilities and glycaemic control in children and young people with Type 1 diabetes mellitus
Authors: Semenkovich K. , Patel P. P. , Pollock A. B. , Beach K. A. , Nelson S. , Masterson J. J. , Hershey T. , Arbeláez A. M.
Published: July 2015

Aims

To determine if children and young people aged < 23 years with Type 1 diabetes differ in academic ability from age‐matched control subjects without Type 1 diabetes and whether academic scores are related to glycaemic control.

Methods

Using a cross‐sectional study design, we administered cognitive and academic tests (Woodcock‐Johnson III Spatial Relations, General Information, Letter‐Word Recognition, Calculation and Spelling tests) to young people with Type 1 diabetes (n=61) and control subjects (n=26) aged 9–22 years. The groups did not differ in age or gender. Participants with Type 1 diabetes had a disease duration of 5–17.7 years. History of glycaemic control (HbA1c, diabetic ketoacidosis and severe hypoglycaemic episodes) was obtained via medical records and interviews.

Results

The participants with Type 1 diabetes had a lower mean estimated verbal intelligence (IQ) level compared with those in the control group (P=0.04). Greater exposure to hyperglycaemia over time was associated with lower spelling abilities within the group with Type 1 diabetes (P=0.048), even after controlling for age, gender, socio‐economic status, blood glucose level at time of testing and verbal IQ (P=0.01). History of severe hypoglycaemia or ketoacidosis was not associated with differences in academic abilities.

Conclusions

In children and young people, Type 1 diabetes was associated with a lower verbal IQ. Moreover, increased exposure to hyperglycaemia was associated with lower spelling performance. These results imply that hyperglycaemia can affect cognitive function and/or learning processes that may affect academic achievement.
Diabetes as a risk factor for carpal tunnel syndrome: a systematic review and meta‐analysis
Authors: Pourmemari M. H. , Shiri R.
Published: July 2015

Aims

To assess whether diabetes increases the risk of carpal tunnel syndrome and to estimate the magnitude of the association with Type 1 and Type 2 diabetes.

Methods

We conducted a systematic search of PubMed, Embase, Web of Science, Scopus, Google Scholar and ResearchGate for articles published between 1950 and January 2015. A total of 36 studies (eight cross‐sectional, 21 case–control and seven cohort studies) qualified for meta‐analysis. We used a random‐effects meta‐analysis and assessed heterogeneity and publication bias.

Results

The pooled odds ratio of 25 studies (including a total of 92 564 individuals) that reported unadjusted estimates for the association between diabetes and carpal tunnel syndrome or carpal tunnel release was 1.97 (95% CI 1.56–2.49). The pooled odds ratio of 18 case–control or cohort studies consisting of >37 million individuals that reported estimates after controlling for potential confounders was 1.69 (95% CI 1.45–1.96). The association did not differ for Type 1 and Type 2 diabetes. Furthermore, there was no publication bias.

Conclusion

This meta‐analysis suggests that both Type 1 and Type 2 diabetes are risk factors for carpal tunnel syndrome.
Glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus insulin glargine 100 U/ml in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: the EDITION 2 randomized 12‐month trial including 6‐month extension
Authors: Yki‐Järvinen H. , Bergenstal R. M. , Bolli G. B. , Ziemen M. , Wardecki M. , Muehlen‐Bartmer I. , Maroccia M. , Riddle M. C.
Published: July 2015

Aims

To compare the efficacy and safety of new insulin glargine 300 U/ml (Gla‐300) with insulin glargine 100 U/ml (Gla‐100) over 12 months of treatment in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs (OADs).

Methods

EDITION 2 (NCT01499095) was a randomized, 6‐month, multicentre, open‐label, two‐arm, phase IIIa study investigating once‐daily Gla‐300 versus Gla‐100, plus OADs (excluding sulphonylureas), with a 6‐month safety extension.

Results

Similar numbers of participants in each group completed 12 months of treatment [Gla‐300, 315 participants (78%); Gla‐100, 314 participants (77%)]. The reduction in glycated haemoglobin was maintained for 12 months with both treatments: least squares (LS) mean (standard error) change from baseline −0.55 (0.06)% for Gla‐300 and −0.50 (0.06)% for Gla‐100; LS mean difference −0.06 [95% confidence interval (CI) −0.22 to 0.10)%]. A significant relative reduction of 37% in the annualized rate of nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia was observed with Gla‐300 compared with Gla‐100: rate ratio 0.63 [(95% CI 0.42–0.96); p = 0.031], and fewer participants experienced ≥1 event [relative risk 0.84 (95% CI 0.71–0.99)]. Severe hypoglycaemia was infrequent. Weight gain was significantly lower with Gla‐300 than Gla‐100 [LS mean difference −0.7 (95% CI −1.3 to −0.2) kg; p = 0.009]. Both treatments were well tolerated with a similar pattern of adverse events (incidence of 69 and 60% in the Gla‐300 and Gla‐100 groups).

Conclusions

In people with type 2 diabetes treated with Gla‐300 or Gla‐100, and non‐sulphonylurea OADs, glycaemic control was sustained over 12 months, with less nocturnal hypoglycaemia in the Gla‐300 group.
A novel and selective sodium‐glucose cotransporter‐2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus
Authors: Ikeda S. , Takano Y. , Cynshi O. , Tanaka R. , Christ A. D. , Boerlin V. , Beyer U. , Beck A. , Ciorciaro C. , Meyer M. , Kadowaki T.
Published: July 2015

Aim

To assess the efficacy, safety and tolerability of different doses of tofogliflozin, a novel, highly selective sodium‐glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM).

Methods

In a 12‐week, multicentre, multinational, randomized, double‐blind, parallel‐group, placebo‐controlled, dose‐finding study, patients with inadequate glycaemic control from diet and exercise alone, or from diet and exercise plus a stable dose of metformin, were randomized to one of five doses of tofogliflozin (2.5, 5, 10, 20, or 40 mg) or placebo. The primary efficacy endpoint was absolute change at week 12 from baseline in glycated haemoglobin (HbA1c), minus the change in the placebo group.

Results

Statistically significant dose‐dependent reductions in HbA1c were shown in all treated groups except the 2.5‐mg dose group, with a maximum reduction of 0.56% (placebo‐subtracted) at the 40‐mg dose, along with increased urinary glucose excretion. Metformin treatment had no substantial influence on tofogliflozin efficacy. Dose‐dependent reductions in fasting plasma glucose and body weight were observed, and glucose intolerance was improved, with a trend towards blood pressure reduction. Slight increases were observed for mean ketone bodies with no abnormal change in ketone body ratio. No deaths or treatment‐related serious adverse events were reported. The incidence of adverse events was similar in the placebo (37.9%) to that in the tofogliflozin group (35.9–46.3%). Withdrawal because of adverse events was rare (≤2 patients per treatment group), with similar rates of withdrawal in the placebo and tofogliflozin groups.

Conclusions

A once‐daily dose of tofogliflozin for 12 weeks was an effective, safe and well‐tolerated treatment for T2DM.
Efficacy and safety of once‐weekly dulaglutide in combination with sulphonylurea and/or biguanide compared with once‐daily insulin glargine in Japanese patients with type 2 diabetes: a randomized, open‐label, phase III, non‐inferiority study
Authors: Araki E. , Inagaki N. , Tanizawa Y. , Oura T. , Takeuchi M. , Imaoka T.
Published: July 2015

Aims

To evaluate 0.75 mg of dulaglutide, a once‐weekly glucagon‐like peptide‐1 receptor agonist, compared with once‐daily insulin glargine for glycaemic control in Japanese patients with type 2 diabetes (T2D).

Methods

In this phase III, randomized, open‐label, parallel‐group, 26‐week study, 361 patients with inadequately controlled T2D receiving sulphonylureas and/or biguanides, aged ≥20 years, with glycated haemoglobin (HbA1c) levels 7.0–10.0% (53–86 mmol/mol), inclusive, were randomized (1 : 1) to receive dulaglutide or glargine. Participants and investigators were not masked to treatment allocation. The primary measure was change from baseline in HbA1c at 26 weeks, analysed using a mixed‐effects model for repeated measures, with a predefined non‐inferiority margin of 0.4%.

Results

At week 26, least‐squares (LS) mean (standard error) reductions in HbA1c were −1.44 (0.05)% [−15.74 (0.55) mmol/mol] in the dulaglutide group and −0.90 (0.05)% [−9.84 (0.55) mmol/mol] in the glargine group. The mean between‐group treatment difference in HbA1c was −0.54% (95% CI −0.67, −0.41) [−5.90 mmol/mol (95% CI −7.32, −4.48)]; p < 0.001. Dulaglutide significantly reduced body weight compared with glargine at week 26 (LS mean difference −1.42 kg, 95% CI −1.89, −0.94; p < 0.001). The most frequent adverse events with dulaglutide treatment were nasopharyngitis and gastrointestinal symptoms. The incidence of hypoglycaemia was significantly lower with dulaglutide [47/181 (26%)] compared with glargine [86/180 (48%)], p < 0.001.

Conclusion

In Japanese patients with T2D uncontrolled on sulphonylureas and/or biguanides, once‐weekly dulaglutide was superior to once‐daily glargine for reduction in HbA1c at 26 weeks. Although dulaglutide increased gastrointestinal symptoms, it was well tolerated, with an acceptable safety profile.
Are There Myths on Road Impact and Transport in Sub‐Saharan Africa?
Authors: Beuran Monica , Gachassin Marie , Raballand Gaël
Published: July 2015

Large investments in road infrastructure continue to be high on the agenda of many African countries, only a few of which have actually amended their investment strategy. In many cases, there seems to be a preference for a status quo that can easily be explained by political‐economy factors driving policies in the sector. After presenting data on the state of roads in sub‐Saharan Africa (length, density, condition), this article demonstrates how most countries’ transport strategies are based on certain misperceptions and recommends better prioritisation of investments, better procurement and contract management, better projects implementation and better monitoring to improve the developmental impact of recent road investments.
The Design of Conditional Cash Transfers: Experiences from Argentina's Universal Child Allowance
Authors: Rabinovich Lila , Diepeveen Stephanie
Published: July 2015

Conditional cash transfers (CCTs) have spread rapidly in developing countries in the past decade. While there is extensive literature assessing their impacts health, education and other outcomes, little attention has been paid to beneficiaries' subjective experiences of CCT design. This article addresses this issue by exploring how beneficiaries of Argentina's flagship CCT, the Universal Child Allowance, perceive the programme's unique design features. We find male and female beneficiaries tend to support targeted transfers to female carers, and that confusion about payment schedules has important implications for beneficiary engagement. Analysis of these findings offers useful insights into how CCT programme design may affect outcomes.
New Regimes of Responsibilization: Practicing Product Carbon Footprinting in the New Carbon Economy
Authors: Ormond Jim
Published: July 2015

This article discusses how by voluntarily adopting new dimensions of corporate responsibility—for the greenhouse gas (GHG) emissions generated by its products—global retailers not only position their organizations as responsible in the battle to win the hearts, minds, and wallets of their consumers, but also articulate a new solution for the mitigation of climate change aligned with their commercial interests. As part of this solution, retailers (and other brands) reimagined how GHG emissions should be allocated—shifting from a productionist‐based to a consumptionist‐based perspective—and redefined what they are responsible for and what their supply chains must care about. The article argues that the complexity involved in engaging tens, hundreds, or even thousands of individual organizations across numerous products’ supply chains means that requirements to measure and reduce a product's carbon footprint cannot, and are not, simply pushed down a supply chain. Rather through a confluence of the practices of translation, observation, and normalization retailers are creating, fostering, and articulating new regimes of responsibilization within which actors across successive tiers of a product's supply chains must measure, monitor, and reduce their own carbon footprints independently, conscientiously, and diligently, thereby enabling retailers to achieve carbon reductions at a distance. Seen through the Foucauldian‐inspired lens of the technologies of the self and self‐government under neoliberal governance regimes, this article suggests that, through the control of what is in a product's carbon footprint, how this should be measured, and how it should be reduced—what are called here carbon truths—global retailers are working to consolidate their socioeconomic powers as sustainability leaders that fundamentally direct society's response to, and mitigation of, climate change.© 2014 Clark University
Metastatic pheochromocytoma and paraganglioma
Authors: Angelousi Anna , Kassi Evanthia , Zografos Georgios , Kaltsas Gregory
Published: July 2015

Background

Metastatic pheochromocytomas (PCs) and paragangliomas (PGLs) are rare neuroendocrine tumours with a strong genetic background.

Design

We searched the PubMed database through February 2015 to identify studies characterizing metastatic PCs/PGLs as well as currently established and evolving therapies.

Results

Large size tumours (> 5 cm), PASS score > 6 and Ki‐67 labelling index > 3% are the most robust indices of metastatic PCs/PGLs albeit with great variability. Germline succinate dehydrogenase complex, subunit B (SDHB) mutation constitutes the main reliable molecular predictor of malignancy. Plasma and urinary methoxytyramine are the biochemical markers characterizing metastatic PCs/PGLs along with evolving molecular markers such as miRNAs and SNAIL. Conventional imaging is used for tumour localization, whereas 18F‐FDG‐PET for staging of metastatic PCs/PGLs especially those related to SDHB gene mutations. In addition, 68 Ga‐DOTATATE PET/CT is emerging as a highly sensitive alternative. Surgery remains the gold standard treatment in reducing tumour bulk and/or controlling the clinical syndrome. Treatment with 131I‐MIBG or radiolabelled somatostatin analogues is considered for unresectable disease. Conventional chemotherapy is reserved for more advanced and refractory to other therapies disease although new schemes are currently evolving. Recent genetic studies have highlighted a number of pathways involved in PCs/PGLs pathogenesis directing towards the use of targeted therapies which have still to be validated in clinical practice.

Conclusions

Metastatic PCs/PGLs remain an orphan disease that is only curable by surgery. However, advances in genomic analyses have improved the pathogenesis of these tumours and may lead to effective and more personalized treatments in the near future.
ECONOMIC DETERMINANTS OF THE TIMING OF PREFERENTIAL TRADE AGREEMENT FORMATIONS AND ENLARGEMENTS
Authors: Bergstrand Jeffrey H. , Egger Peter , Larch Mario
Published: July 2015

Preferential trade agreements (PTAs) have proliferated over the past 60 years. While a small number of recent studies have examined empirically the economic determinants of the likelihood of a pair of countries having a PTA, this study explains empirically the timing of all PTA formations and enlargements from 1950 through 2006 using duration analysis. Our main and novel goal is to predict (in‐ and out‐of‐sample) a substantive share of these 1,560 PTA events using a parsimonious model with mainly economic variables, taking selection dynamics into account. Our analysis reveals that we can predict correctly in‐sample the actual year of entry into force for 26% of the 1,560 bilateral PTA formations/enlargements in the period 1950–2006 among 10,518 pairings of 146 countries using only a few economic and political variables. Moreover, we can predict correctly in‐sample 57% of these PTA events within a 10‐year window leading up to the event using this model. The model also performs well out‐of‐sample for the near term (82%), but not if the out‐of‐sample period is very long. We conclude with an evaluation of the model's ability to predict the timing of the North American Free Trade Agreement, the European Union's formation and enlargements, and the model's ten most likely post‐2006 PTA events. (JEL F14, F15)