bluuebunny/crossref_metadata_2025 huggingface dataset:
CO2 laser‐assisted sclerectomy surgery compared with trabeculectomy in primary open‐angle glaucoma and exfoliative glaucoma. A 1‐year follow‐up
Authors: Jankowska‐Szmul Judyta , Dobrowolski Dariusz , Wylegala Edward
Published: April 2018

Purpose

To report on the efficacy and safety of CO2 laser‐assisted sclerectomy surgery (CLASS) compared with trabeculectomy in primary open‐angle glaucoma and exfoliative glaucoma.

Methods

One hundred and thirty‐one patients underwent CLASS (66 patients) or trabeculectomy (65 patients) and were followed up for 12 months. ‘Complete success’ was defined as intraocular pressure (IOP) between 10 and 18 mmHg and reduced by at least 30% from the baseline without medications, while ‘qualified success’ was compliant with the above criteria with or without the medications.

Results

Comparing CLASS with trabeculectomy at 1 year, the mean IOP reduction rate was 32.6 ± 10.8% versus 40.6 ± 15.9% (p < 0.001) and the average use of medications was 1.4 ± 1.4 versus 0.7 ± 1.1 (p < 0.05). At 12 months, the complete success rate was 35% for CLASS versus 60% for trabeculectomy (p < 0.01), while the qualified success rate was 74% versus 75%, respectively, with no significant difference in qualified success rate between the groups at any time‐point (p > 0.05). Compared with CLASS, patients after trabeculectomy developed a higher rate of early complications (9.1% versus 29.2%, p = 0.004), higher endothelial cell density (ECD) loss (1.4 ± 1.4% versus 6.5 ± 4.8%, p < 0.001), higher astigmatism (0.0 ± 0.1 versus 0.1 ± 0.2, p < 0.001) and significant visual acuity deterioration (0.1 ± 0.1; range 0–2 lines versus 0.4 ± 0.6; range 0–3 lines, p = 0.016).

Conclusion

Although CLASS shows a less potent hypotensive effect, it is similar to trabeculectomy in the qualified success rate and offers the reduction in medications up to 12 months. With a more attractive complications profile, CLASS may be an alternative to trabeculectomy, especially at the earlier glaucoma stage and in patients with a low ECD.
Fluocinolone acetonide intravitreal implant (Retisert®) in the treatment of sight threatening macular oedema of juvenile idiopathic arthritis‐related uveitis
Authors: Leinonen Sanna , Immonen Ilkka , Kotaniemi Kaisu
Published: April 2018

Purpose

We describe eight patients with juvenile idiopathic arthritis‐related chronic uveitis, who received a fluocinolone acetonide implant (FAI, Retisert®, Bausch&Lomb) in one eye. All patients had poor visual acuity (VA) due to persistent macular oedema in one or both eyes despite treatment with antirheumatic medication.

Methods

Median age of the patients was 22.9 years (range, 14.1–39.7) and duration of uveitis 13.0 years (range, 6.8–28.4) at FAI implantation. Median preoperative best‐corrected visual acuity (BCVA) was 0.1 (range, 0.05–0.4) and Standardization of Uveitis Nomenclature, SUN‐grade was SUN 2+ (range, 0.5–4.0). All patients had been treated extensively with systemic corticosteroids and antirheumatic drugs by the time of FAI implantation. The median follow‐up time was 5.3 years (range, 4.4–6.3).

Results

Macular edema resolved in a median time of 0.2 years (range, 0.04–0.39) after the FAI implantation. The median BCVA was 0.5–0.63 (range, 0.1–1.0) from 1 to 5 years of follow‐up. Macular edema did not recur in 5 eyes after the implantation. In three eyes, the macular oedema relapsed at 2.7, 2.9 and 5.5 years of follow‐up. All our patients needed antirheumatic drugs in addition to the FAI to treat their macular edema. During the follow‐up, 7 eyes required further intraocular operations: 4 cataract operations, 4 intraocular pressure ‐lowering operations and 1 retinal detachment surgery were performed.

Conclusion

Fluocinolone acetonide implant is a valuable option in the treatment of persistent macular edema associated with JIA‐related uveitis refractory to systemic treatments.
Contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients on nonsteroidal anti‐inflammatory drugs, antiplatelet agents, anticoagulants, corticosteroids and selective serotonin reuptake inhibitors
Authors: Venerito M. , Schneider C. , Costanzo R. , Breja R. , Röhl F.‐W. , Malfertheiner P.
Published: April 2018

Background

Nonsteroidal anti‐inflammatory drugs, low‐dose aspirin, non‐aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors and corticosteroids increase the risk of gastroduodenal bleeding.

Aim

To determine in a retrospective cohort study the contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients taking these drugs.

Methods

Among patients with peptic ulcer disease diagnosed by endoscopy from 01/2004 to 12/2014 (N = 1719, 60% males, age 65.8 ± 14.5), 56.9% had peptic ulcer bleeding (cases) and 43.1% uncomplicated peptic ulcer disease (controls). Demographics, intake of nonsteroidal anti‐inflammatory drugs, aspirin, non‐aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors, proton pump inhibitors and corticosteroids were documented. H. pylori status was determined by histology, rapid urease test or serology. Adjusted odds ratios (OR) were estimated by logistic regression analysis.

Results

Helicobacter pylori infection increased the risk of peptic ulcer bleeding in nonsteroidal anti‐inflammatory drug and aspirin users (OR = 2.91, 95% CI = 1.71‐4.98 and OR = 2.23, 95% CI = 1.52‐3.28, respectively), but not in patients on anticoagulants, selective serotonin reuptake inhibitor or corticosteroid therapy. H. pylori‐positive status substantially increased the risk of peptic ulcer bleeding in patients on non‐aspirin antiplatelet agents (OR = 4.37, 95% CI = 1.28‐14.99), concomitant aspirin/nonsteroidal anti‐inflammatory drug intake (OR = 5.85, 95% CI = 1.68‐20.36) and combined antiplatelet therapy (OR = 8.43, 95% CI = 1.09‐65.17). After further adjustment for proton pump inhibitor intake, H. pylori infection was still a risk factor for peptic ulcer bleeding in nonsteroidal anti‐inflammatory drug and aspirin users.

Conclusions

Helicobacter pylori infection increases the risk of peptic ulcer bleeding in peptic ulcer disease patients on nonsteroidal anti‐inflammatory drugs, aspirin and non‐aspirin antiplatelet agents. H. pylori‐positive patients on combined antiplatelet therapy carry the highest risk for peptic ulcer bleeding.
Urban Roma, segregation and place attachment in Szeged, Hungary
Authors: Málovics György , Creţan Remus , Méreiné Berki Boglárka , Tóth Janka
Published: April 2018

Recent research in segregated areas has shown that Romani people are marginalised in Central Eastern Europe and that desegregation has become an important part of the agenda in local development policy‐making. This paper aims to push forward this issue and to better understand how Roma living in segregated urban areas relate to the places and communities in which they live. The research therefore links the particular field of Romani Studies to wider developments in the social sciences, and especially to global debates on insecure/informal housing and (neo‐)ghettoisation, by ascertaining how Roma people's personal attachment to place functions as a basis for their everyday activities in the ghetto and surrounding area(s). The analysis is based on a participatory action research (PAR) process carried out in Szeged, Hungary, with local scholar–activists, Roma representatives and Roma families living in local segregated spaces. The findings suggest that the world of Roma in segregated neighbourhoods is characterised by a strong feeling of place attachment fundamentally shaped by social relations and the features of those neighbourhoods, but certain centripetal forces alienate inhabitants from these spaces. This is important because existing place attachment to segregated Roma communities as a living environment is a contradictory situation for the affected Roma, which is characterised by “dual bonds”: traditional relationships based on strong bonding capital and reciprocity still exist and represent significant material and emotional support for families and the places they inhabit, while at the same time communities are becoming more fragmented, with the most marginalised often being excluded from this “net of space protection.”
Culture‐specific links between maternal executive function, parenting, and preschool children's executive function in South Korea
Authors: Lee Min Kyung , Baker Sara , Whitebread David
Published: April 2018

Background

Research on the relationships between parental factors and children's executive function (EF) has been conducted mainly in Western cultures.

Aim

This study provides the first empirical test, in a non‐Western context, of how maternal EF and parenting behaviours relate to child EF.

Sample

South Korean mothers and their preschool children (N = 95 dyads) completed EF tasks.

Method

Two aspects of parental scaffolding were observed during a puzzle task: contingency (i.e., adjusting among levels of scaffolding according to the child's ongoing evidence of understanding) and intrusiveness (i.e., directive, mother‐centred interactions).

Results and Conclusions

Maternal EF and maternal contingency each accounted for unique variance in child EF, above and beyond child age, child language and maternal education. Maternal intrusiveness, however, was not significantly related to child EF. Additionally, no mediating role of parenting was found in the maternal and child EF link. However, child language was found to partially mediate the link between maternal contingency and child EF. These results complement prior findings by revealing distinctive patterns in the link between maternal EF, parenting behaviours, and child EF in the Korean context.
Emotion regulation and well‐being in primary classrooms situated in low‐socioeconomic communities
Authors: Somerville Matthew P. , Whitebread David
Published: April 2018

Background

Although emotion is central to most models of children's well‐being, few studies have looked at how well‐being is related to the ways in which children regulate their emotions.

Aims

The aim of this study was to examine the associations among children's emotion regulation strategy choice and their emotional expression, behaviour, and well‐being. The study also investigated whether contextual factors influenced the emotion regulation strategies children chose to use.

Sample

Participants (N = 33) were selected from four Year 5/6 composite classrooms situated in low‐socioeconomic urban communities in New Zealand.

Method

Questionnaires were used to measure children's well‐being and teacher‐reported emotional and behavioural problems. Emotional expression and emotion regulation strategies were measured through video‐recorded observations in the classroom. A total of 1,184 instances of emotion regulation strategy use were coded using a framework based on Gross' process model of emotion regulation.

Results

The findings highlight the complexity of the relations among emotion regulation, emotion expression, and well‐being. Some strategies, such as Cognitive Reappraisal, were effective at upregulating negative emotion in the short term, yet not strongly associated with well‐being. Others, such as Situation Modification: Physical, were positively associated with well‐being, yet not with an immediate change in a child's emotional experience. The findings also suggest children flexibly use different strategies in relation to different contextual demands.

Conclusion

These findings may be used to guide future intervention efforts which target emotion regulation strategy use as well as those which focus on teachers' support of children during emotionally challenging situations.
The diverse origins of circulating cell‐free DNA in the human body: a critical re‐evaluation of the literature
Authors: Aucamp Janine , Bronkhorst Abel J. , Badenhorst Christoffel P. S. , Pretorius Piet J.
Published: April 2018

Since the detection of cell‐free DNA (cfDNA) in human plasma in 1948, it has been investigated as a non‐invasive screening tool for many diseases, especially solid tumours and foetal genetic abnormalities. However, to date our lack of knowledge regarding the origin and purpose of cfDNA in a physiological environment has limited its use to more obvious diagnostics, neglecting, for example, its potential utility in the identification of predisposition to disease, earlier detection of cancers, and lifestyle‐induced epigenetic changes. Moreover, the concept or mechanism of cfDNA could also have potential therapeutic uses such as in immuno‐ or gene therapy. This review presents an extensive compilation of the putative origins of cfDNA and then contrasts the contributions of cellular breakdown processes with active mechanisms for the release of cfDNA into the extracellular environment. The involvement of cfDNA derived from both cellular breakdown and active release in lateral information transfer is also discussed. We hope to encourage researchers to adopt a more holistic view of cfDNA research, taking into account all the biological pathways in which cfDNA is involved, and to give serious consideration to the integration of in vitro and in vivo research. We also wish to encourage researchers not to limit their focus to the apoptotic or necrotic fraction of cfDNA, but to investigate the intercellular messaging capabilities of the actively released fraction of cfDNA and to study the role of cfDNA in pathogenesis.
Small montane cloud forest fragments are important for conserving tree diversity in the Ecuadorian Andes
Authors: Wilson Sarah Jane , Rhemtulla Jeanine M.
Published: April 2018

Montane tropical cloud forests, with their complex topography, biodiversity, high numbers of endemic species, and rapid rates of clearing, are a top global conservation priority. However, species distributions at local and landscape scales in cloud forests are still poorly understood, in part because few regions have been surveyed. Empirical work has focused on species distributions along elevation gradients, but spatial variation among forests at the same elevation is less commonly investigated. In this study, the first to compare tree communities across multiple Andean cloud forests at similar elevations, we surveyed trees in five ridge‐top forest reserves at the upper end of the ‘mid‐elevation diversity bulge’ (1900–2250 masl) in the Intag Valley, a heavily deforested region in the Ecuadorian Andes. We found that tree communities were distinct in reserves located as close as 10 to 35 km apart, and that spatially closer forests were not more similar to one another. Although larger (1500 to 6880 ha), more intact forests contained significantly more tree species (108–120 species/0.1 ha) than smaller (30 to 780 ha) ones (56–87 species/0.1 ha), each reserve had unique combinations of more common species, and contained high proportions of species not found in the others. Results thus suggest that protecting multiple cloud forest patches within this narrow elevational band is essential to conserve landscape‐level tree diversity, and that even small forest reserves contribute significantly to biodiversity conservation. These findings can be applied to create management plans to conserve and restore cloud forests in the Andes and tropical montane cloud forests elsewhere.
Exploring Indigenous youth perspectives of mobility and social relationships: A Photovoice approach
Authors: Goodman Ashley , Snyder Marcie , Wilson Kathi
Published: April 2018

Growing rates of urbanization among young Indigenous populations have been associated with frequent geographic mobility between urban and rural areas, as well as within cities. Little is known of the context of this mobility, or its impacts on social relationships. With nearly half the urban Indigenous population under the age of 25, gaps persist in understanding the mobility experiences of Indigenous youth, who tend to be more mobile than non‐Indigenous youth and move more often than their older counterparts. The voice of Indigenous youth remains under‐represented, and research with mobile Indigenous youth is limited. To address these gaps, Photovoice was used to better understand how mobility shapes social relationships among a group of Indigenous youth living in Winnipeg, Manitoba. Key findings reveal mobility is common and persistent, often rooted in colonization and intergenerational trauma. As a result, this mobility is often linked to unstable living conditions and displacement from family and social connections. The frequent and uncertain nature of this mobility impacts the ability to develop and sustain positive and supportive social relationships. Findings point to the importance of culturally safe spaces and Indigenous mentorship that fosters resilience and self‐empowerment.
Improving classical scoring functions using random forest: The non‐additivity of free energy terms’ contributions in binding
Authors: Afifi Karim , Al‐Sadek Ahmed Farouk
Published: April 2018

Despite recent efforts to improve the scoring performance of scoring functions, accurately predicting the binding affinity is still a challenging task. Therefore, different approaches were tried to improve the prediction performance of four scoring functions (x‐score, vina, autodock, and rf‐score) by substituting the linear regression model of classical scoring function by random forest to examine the performance improvement if an additive functional form is not imposed, and by combining different scoring functions into hybrid ones. The datasets were derived from the PDBbind‐CN database version 2016. When evaluating the original scoring functions on the generic dataset, rf‐score has outperformed classical scoring functions, which shows the superiority of descriptor‐based scoring functions. Substituting linear regression as a linear model by random forest as a nonlinear model had largely improved the scoring performance of autodock and vina while x‐score had only a slight performance increase. All hybrid scoring functions had only a slight improvement—if any—on both of the combined scoring functions, which is not worth the slower calculation time.
Subclinical thyroid dysfunction and circulating thyroid hormones are not associated with bone turnover markers or incident hip fracture in older men
Authors: Siru Ranita , Alfonso Helman , Chubb S. A. Paul , Golledge Jonathan , Flicker Leon , Yeap Bu B.
Published: April 2018

Objective

Overt thyroid dysfunction is a risk factor for osteoporosis and fractures. Subclinical hyperthyroidism has also been associated with fracture. It remains unclear whether variation in thyroid hormones within the euthyroid range modulates bone health, particularly among older men. We assessed whether thyroid stimulating hormone (TSH) and free thyroxine (FT4) are associated with bone turnover markers (BTMs) and predict hip fracture risk in community‐dwelling older men without known thyroid disease.

Design

Prospective cohort study.

Patients

Four thousand two hundred forty‐eight men aged 70‐89 years.

Measurements

Baseline blood samples were assayed for TSH, FT4, total osteocalcin (TOC), undercarboxylated osteocalcin (ucOC), N‐terminal propeptide of type I collagen (P1NP) and collagen type I C‐terminal cross‐linked telopeptide (CTX). Incidence of hip fracture events was ascertained to 2012. Associations of TSH and FT4 with BTMs were analysed at baseline using Pearson correlation coefficients, and with incident hip fracture using Cox proportional hazards regression.

Results

After excluding men with pre‐existing thyroid or bone disease, there were 3, 338 men for analysis. Of these, 3, 117 were euthyroid, 135 had subclinical hypothyroidism, and 86 had subclinical hyperthyroidism. Men with subclinical thyroid disease were older, and those with subclinical hyperthyroidism had lower creatinine than the other groups. After multivariate analysis, there were no associations found between FT4, TSH or subclinical thyroid dysfunction and BTMs at baseline. Neither subclinical thyroid dysfunction, TSH nor FT4 were predictive of incident hip fracture in our study population.

Conclusions

In euthyroid older men, TSH and FT4 were not associated with BTMs or incident hip fracture. Our findings differ from those previously described in postmenopausal women.
A Survey on 3D Virtual Object Manipulation: From the Desktop to Immersive Virtual Environments
Authors: Mendes D. , Caputo F. M. , Giachetti A. , Ferreira A. , Jorge J.
Published: April 2018

Interactions within virtual environments often require manipulating 3D virtual objects. To this end, researchers have endeavoured to find efficient solutions using either traditional input devices or focusing on different input modalities, such as touch and mid‐air gestures. Different virtual environments and diverse input modalities present specific issues to control object position, orientation and scaling: traditional mouse input, for example, presents non‐trivial challenges because of the need to map between 2D input and 3D actions. While interactive surfaces enable more natural approaches, they still require smart mappings. Mid‐air gestures can be exploited to offer natural manipulations mimicking interactions with physical objects. However, these approaches often lack precision and control. All these issues and many others have been addressed in a large body of work. In this article, we survey the state‐of‐the‐art in 3D object manipulation, ranging from traditional desktop approaches to touch and mid‐air interfaces, to interact in diverse virtual environments. We propose a new taxonomy to better classify manipulation properties. Using our taxonomy, we discuss the techniques presented in the surveyed literature, highlighting trends, guidelines and open challenges, that can be useful both to future research and to developers of 3D user interfaces.
Management of patients with incurable colorectal cancer: a retrospective audit
Authors: Thavanesan N. , Abdalkoddus M. , Yao C. , Lai C. W. , Stubbs B. M.
Published: April 2018

Aim

Counselling patients and their relatives about non‐curative management options in colorectal cancer is difficult because of a paucity of published data. This study aims to determine outcomes in patients unsuitable for curative surgery and the rates of subsequent surgical intervention.

Method

This was an analysis of all colorectal cancers managed without curative surgery in a district general hospital from a prospectively maintained cancer registry between 2009 and 2016, as decided by a multidisciplinary team. Primary outcomes were overall survival and secondary outcomes were subsequent intervention rates and impact of tumour stage.

Results

In all, 183 patients out of 976 patients (18.8%) were identified. The median age at diagnosis was 81 years [interquartile range (IQR) 71–87 years]. Overall median survival from diagnosis was 205 days (IQR 60–532 days). One‐year mortality was 62.3%. Patients were classified into two groups depending on the reason for a non‐curable approach: patient‐related (PR) or disease‐related (DR). The difference in survival between PR (median 277 days, IQR 70–593) and DR (median 179 days, IQR 51–450) was 98 days (P = 0.023). Twenty‐four patients were alive at the end of the study period; 19 out of 91 cases in PR (20.8%) and five out of 92 cases in DR (5.4%). Overall intervention rates were 11.9%, with higher rates in the DR group (P = 0.005). Disease stage was not associated with subsequent surgical intervention between the two groups (P = 0.392).

Conclusion

Life expectancy for non‐curatively managed patients within our unit was 6.8 months with one in nine patients requiring subsequent surgical admission for palliation. This information may be useful when counselling patients with incurable colorectal malignancy.
Climate change‐driven extinctions of tree species affect forest functioning more than random extinctions
Authors: García‐Valdés Raúl , Bugmann Harald , Morin Xavier
Published: April 2018

Aim

Climate change affects forest functioning not only through direct physiological effects such as modifying photosynthesis and growing season lengths, but also through indirect effects on community composition related to species extinctions and colonizations. Such indirect effects remain poorly explored in comparison with the direct ones. Biodiversity–ecosystem functioning (BEF) studies commonly examine the effects of species loss by eliminating species randomly. However, species extinctions caused by climate change will depend on the species’ vulnerability to the new environmental conditions, thus occurring in a specific, non‐random order. Here, we evaluated whether successive tree species extinctions, according to their vulnerability to climate change, impact forest functions differently than random species losses.

Location

Eleven temperate forests across a gradient of climatic conditions in central Europe.

Methods

We simulated tree community dynamics with a forest succession model to study the impact of species loss on the communities’ aboveground biomass, productivity and temporal stability. Tree species were removed from the local pool (1) randomly, and according to (2) their inability to be recruited under a warmer climate or (3) their increased mortality under drier conditions.

Results

Results showed that non‐random species loss (i.e., based on their vulnerability to warmer or drier conditions) changed forest functioning at a different rate, and sometimes direction, than random species loss. Furthermore, directed extinctions, unlike random, triggered tipping points along the species loss process where forest functions were strongly impacted. These tipping points occurred after fewer extinctions in forests located in the coldest areas, where ecosystem functioning relies on fewer species.

Main conclusions

We showed that the extinction of species in a deterministic and mechanistically motivated order, in this case the species vulnerability to climate change, strengthens the selection effect of diversity on ecosystem functioning. BEF studies exploring the impact of species loss on ecosystem functioning using random extinctions thus possibly underestimate the potential effect of biodiversity loss when driven by a directional force, such as climate change.
Effects of El Niño Southern Oscillation on avian breeding phenology
Authors: Englert Duursma Daisy , Gallagher Rachael V. , Griffith Simon C.
Published: April 2018

Aim

Climate oscillations are known to influence the reproductive phenology of birds. Here, we quantify the effects of cyclic climatic variation, specifically El Niño Southern Oscillation (ENSO), on birds that breed opportunistically. We aim to show how inter‐decadal climate fluctuations influence opportunistic breeding. This knowledge is essential for tracking the phenological responses of birds to climate change.

Location

Temperate and arid Australia.

Methods

We assessed variation in egg‐laying (start, peak, conclusion, length) during the three phases of ENSO (El Niño, La Niña and Neutral) for 64 temperate and 15 arid region species using ~80,000 observations. Linear mixed‐effect models and analysis of variance were used to (1) determine if, on average within each region, egg‐laying dates differed significantly among species between Neutral‐El Niño and Neutral‐La Niña phases, and (2) assess how La Niña and El Niño episodes influence egg‐laying in birds which breed early in the year.

Results

During La Niña phases, which are characterized by mild/wet conditions, most bird species in the temperate and arid regions exhibited longer egg‐laying periods relative to Neutral phases. However, there was substantial variation across species. This effect was strongly seasonal; species breeding in spring experienced the greatest increases in egg‐laying periods during La Niña. Further, we found only small differences in peak egg‐laying dates during Neutral and La Niña in the arid region; suggesting that hot temperatures may constrain breeding regardless of rainfall. The effects of El Niño on breeding phenology were not consistent in the temperate and arid regions and may be confounded by highly mobile species opportunistically moving and breeding with localized rainfall during dry periods.

Main conclusions

In both arid and temperate regions, increased rainfall associated with La Niña phases positively influences avian breeding, and likely recruitment. However, dry El Niño phases may not have the dramatic impacts on breeding phenology that are commonly assumed.
Sleep as therapy in neurodevelopmental disorders
Authors: Dan Bernard
Published: April 2018

Video Podcast: https://www.youtube.com/watch?v=EHjUqMbRHqU&feature=youtu.be
Improved survival after paediatric stroke – but at what price?
Authors: Steinlin Maja
Published: April 2018

This commentary is on the original article by Fiume et al. on pages 587–595 of this issue.
Differentiating arterial ischaemic stroke from migraine in the paediatric emergency department
Authors: Mackay Mark T , Lee Michelle , Yock‐Corrales Adriana , Churilov Leonid , Donnan Geoffrey A , Monagle Paul , Babl Franz E
Published: April 2018

Aim

To estimate the strengths of association between clinical features and migraine or arterial ischaemic stroke (AIS) in children presenting to the emergency department.

Method

Eighty‐four children with migraine, prospectively recruited from 2009 to 2010, were compared with 55 children with AIS, prospectively/retrospectively recruited from 2003 to 2010. Odds ratios were calculated via logistic regression to measure associations between clinical features and process‐of‐care factors, and migraine and AIS.

Results

Median age was 13 years 5 months (interquartile range 12y 11mo–13y 10mo) for migraine and 5 years (interquartile range 3y 7mo–8y) for patients with AIS. All cases of AIS and 30% of migraine cases underwent neuroimaging. Over 40% of children with migraine had vomiting, numbness, or visual disturbance; other symptoms were uncommon. Fifty‐five per cent had no signs on physician assessment. Weakness or speech disturbance were common in patients with AIS. Significant clinical features associated with increased odds of AIS included sudden symptom onset, weakness, seizures, speech disturbance, and ataxia, and signs of face, arm, or leg weakness, inability to walk, dysarthria, dysphasia, and altered consciousness (p<0.05). Significant features associated with decreased odds of AIS included older age, vomiting, visual, sensory, other symptoms, and absent focal signs on assessment (p<0.05).

Interpretation

Presenting features can discriminate childhood AIS from migraine. These differences inform decisions about urgency and type of neuroimaging in children presenting to the emergency department with brain attack symptoms.

What the paper adds

Weakness, seizures, ataxia, speech, or walking difficulties are more frequent in arterial ischaemic stroke (AIS).

Vomiting, visual, or sensory disturbance and absent focal signs are more frequent in migraine.

Identifying features of AIS and migraine guides neuroimaging in children with brain attack symptoms.
Treatment of hallux deformities in adolescents with cerebral palsy
Authors: Bouchard Maryse
Published: April 2018

This commentary is on the original article by van de Velde et al. on pages 624–628 of this issue.
Acute encephalopathy after febrile status epilepticus: an underdiagnosed, misunderstood complication of Dravet syndrome
Authors: Dravet Charlotte
Published: April 2018

This commentary is on the original article by Tian et al. (Editor's Choice) on pages 566–573 of this issue.
Classifying paroxysmal movement disorders: more genotypes and phenotypes
Authors: Babiker Mohamed O E
Published: April 2018

This commentary is on the invited review by Silveira‐Moriyama et al. on
pages 559–565 of this issue.
Pharmacokinetic and pharmacodynamic profile of the sodium‐glucose co‐transporter‐2 inhibitor empagliflozin in young people with Type 2 diabetes: a randomized trial
Authors: Laffel L. M. B. , Tamborlane W. V. , Yver A. , Simons G. , Wu J. , Nock V. , Hobson D. , Hughan K. S. , Kaspers S. , Marquard J.
Published: April 2018

Aims

To assess the pharmacokinetic and pharmacodynamic profile of a single dose of empagliflozin in young people with Type 2 diabetes to identify the appropriate doses for further paediatric development.

Methods

We conducted a single‐dose, open‐label, randomized, parallel‐group study with empagliflozin 5 mg, 10 mg and 25 mg in young people with Type 2 diabetes aged 10–17 years.

Results

Of 39 participants screened, 27 were randomized and completed the study; their mean (± sd) age was 14.1±2.0 years and body weight was 96.7±23.5 kg. Compared with similar studies in adults with Type 2 diabetes, the maximum observed plasma concentrations were slightly lower with the 10‐mg and 25‐mg doses, and the area under the plasma concentration–time curve was slightly lower with the 10‐mg but slightly higher with the 25‐mg dose. The adjusted mean increases in urinary glucose excretion were 53 g/24 h (95% CI 32,74), 73 g/24 h (95% CI 52,94) and 87 g/24 h (95% CI 68,107), and the adjusted mean decreases in fasting plasma glucose were 0.9 mmol/l (95% CI –1.6,–0.1), 0.9 mmol/l (95% CI –1.7,–0.2) and 1.1 mmol/l (95% CI –1.8,–0.5) for the 5‐ 10‐ and 25‐mg doses, respectively. There were no serious adverse events and one investigator‐reported drug‐related event (dehydration).

Conclusions

After a single oral dose of empagliflozin, adults and young people with Type 2 diabetes had similar exposure–response relationships after adjusting for significant covariates. These data support testing 10‐mg and/or 25‐mg doses of empagliflozin in an upcoming paediatric phase III Type 2 diabetes trial.

(ClinicalTrials.gov registration no.: NCT02121483).
Is glucagon‐like peptide‐1 fully protected by the dipeptidyl peptidase 4 inhibitor sitagliptin when administered to patients with type 2 diabetes?
Authors: Andersen Emilie S. , Lund Asger , Bagger Jonatan I. , Andreasen Camilla , Grøndahl Magnus F. , Deacon Carolyn F. , Hartmann Bolette , Holst Jens J. , Knop Filip K. , Vilsbøll Tina
Published: April 2018

Aim

To evaluate the relationship between plasma dipeptidyl‐peptidase 4 (DPP‐4) activity and its protection of glucagon‐like peptide‐1 (GLP‐1) using the DPP‐4 inhibitor sitagliptin.

Methods

On four separate days, patients with type 2 diabetes (T2D) (n = 8; age: 59.9 ±10.8 [mean ±SD] years; body mass index [BMI]: 28.8 ±4.6 kg/m2; glycated haemoglobin A1c [HbA1c]: 43.1 ±0.5 mmol/mol [6.6% ±1.7%]) received a 380‐minute continuous intravenous infusion of GLP‐1 (1.0 pmol × kg bodyweight−1 × minutes−1) and a double‐blind, single‐dose oral administration of sitagliptin in doses of 0 (placebo), 25, 100 and 200 mg.

Results

Plasma DPP‐4 activity decreased compared to baseline (placebo) with increasing doses of sitagliptin (P < .01), reaching a maximal inhibition with the 100 mg dose. Levels of intact GLP‐1 increased with increasing doses of sitagliptin from placebo to 100 mg (area under curve [AUC] 7.2 [95%, CI; 12.1, 16.4] [placebo], 10.7 [16.1, 21.4] [25 mg], 11.7 [17.8, 23.6] [100 mg] nmol/L × 360 minutes [P < .01]), but no further increase in intact GLP‐1 levels was observed with 200 mg of sitagliptin (11.5 [17.6, 23.4] nmol/L × 360 minutes) (P = .80).

Conclusion

Our findings suggest that the sitagliptin dose of 100 mg is sufficient to inhibit both plasma and membrane‐bound DPP‐4 activity, presumably also leading to complete protection of endogenous GLP‐1 in patients with T2D.
LABOR'S SHARE, THE FIRM'S MARKET POWER, AND TOTAL FACTOR PRODUCTIVITY
Authors: Dixon Robert , Lim Guay C.
Published: April 2018

We investigate the relationship between labor's share, firm's market power, and the elasticity of output with respect to labor input using an approach based on an unobserved components model. The approach yields time‐varying estimates of market power and the elasticity. Evidence on the market power of firms (which we find to be rising since 2000) gives a deeper understanding of movements in labor's share and the labor wedge. The generated values of the elasticity yield revised estimates of total factor productivity growth which is informative about the extent of the downward bias inherent in traditional estimates which use labor's share as a proxy for the elasticity. (JEL O47, C32, E25)
Optimal Monetary Policy in Inflation Targeting Open Economies
Authors: Makin Anthony J.
Published: April 2018

This paper presents a simple framework for analysing the operation and effectiveness of monetary policy in open economies in the spirit of aggregative approaches that are the mainstay of intermediate macroeconomic theory. Combining standard macroeconomic relations with precepts from international finance, it provides new lessons for the conduct of monetary policy under inflation targeting. It first confirms the classic Mundell‐Fleming result that monetary policy is only effective as a short run stabilization instrument under floating exchange rates, yet goes further in showing that countercyclical monetary policy is incompatible with inflation targeting under fixed exchange rates. Second, it highlights the importance of anchoring inflation expectations as a means of inflation control. Third, it suggests how central banks should react to changes in the monetary stance abroad. Lastly, it demonstrates how monetary policy should respond to productivity improvement at home under floating exchange rates.
Political business cycles and construction licensing
Authors: Imami Drini , Uberti Luca J. , Lami Endrit , Zhllima Edvin
Published: April 2018

We analyze the effects of opportunistic and partisan politics on the licensing of construction activities, which in turn determines the level of housing supply. In line with Political Business Cycle theory, we hypothesize that the municipal incumbent may manipulate the supply of construction permits before (general and local) elections in order to boost economic activity and voter satisfaction, or to accommodate special‐interest groups. Our findings, based on time‐series data from post‐socialist Tirana (Albania), are consistent with opportunistic and partisan incentives’ creating cycle effects in the licensing of construction permits. However, we find that the direction of opportunistic election cycles depends critically on the interaction between the municipal incumbent and the central‐level government. Our paper raises important questions about the effects of transition politics on spatial development in post‐socialist cities.
The tethered flight technique as a tool for studying life‐history strategies associated with migration in insects
Authors: Minter Melissa , Pearson Aislinn , Lim Ka S. , Wilson Kenneth , Chapman Jason W. , Jones Christopher M.
Published: April 2018

1. Every year billions of insects engage in long‐distance, seasonal mass migrations which have major consequences for agriculture, ecosystem services and insect‐vectored diseases. Tracking this movement in the field is difficult, with mass migrations often occurring at high altitudes and over large spatial scales.

2. As such, tethered flight provides a valuable tool for studying the flight behaviour of insects, giving insights into flight propensity (e.g. distance, duration and velocity) and orientation under controlled laboratory settings. By experimentally manipulating a variety of environmental and physiological traits, numerous studies have used this technology to study the flight behaviour of migratory insects ranging in size from aphids to butterflies. Advances in functional genomics promise to extend this to the identification of genetic factors associated with flight. Tethered flight techniques have been used to study migratory flight characteristics in insects for more than 50 years, but have never been reviewed.

3. This study summarises the key findings of this technology, which has been employed in studies of species from six Orders. By providing detailed descriptions of the tethered flight systems, the present study also aims to further the understanding of how tethered flight studies support field observations, the situations under which the technology is useful and how it might be used in future studies.

4. The aim is to contextualise the available tethered flight studies within the broader knowledge of insect migration and to describe the significant contribution these systems have made to the literature.
How do invasive species affect native species? Experimental evidence from a carrion blowfly (Diptera: Calliphoridae) system
Authors: Carmo Rodrigo F. R. , Vasconcelos Simão D. , Brundage Adrienne L. , Tomberlin Jeffery K.
Published: April 2018

1. The necrobiome is a unique microcosm in which various organisms interact and compete for access to an ephemeral resource, such as carrion, that ultimately determines the structure and composition of these assemblages.

2. Blowfly species exhibit different competitive abilities which, when associated with other types of behaviour, such as predation or cannibalism, influence coexistence. Knowledge of the effects of competition between native and invasive species on development and survival is essential to understanding the dynamics of insect communities and to assess biological invasions.

3. Laboratory experiments were performed to evaluate the effect of interspecific competition on the bionomics and survival of a native (Cochliomyia macellaria) and an invasive (Chrysomya rufifacies) blowfly species at different population densities.

4. The deleterious effect of competition on the larval parameters of C. macellaria increased proportionally with increases in the larval density of C. rufifacies. When exposed to increased densities of C. rufifacies, larvae of C. macellaria accelerated their development and, as a trade‐off for this strategy, surviving adults were smaller and had reduced wing size, which were likely to reduce dispersal and reproductive capacity.

5. Larval competition – both as species‐dependent and density‐dependent phenomena – influences morphological and biological traits of surviving individuals. The impact of the invasive species has consequences at the population level, such as displacement or local population depletion of native species, a phenomenon likely to occur in other systems involving insects and ephemeral resources.
Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders
Authors: Lindy Amanda S. , Stosser Mary Beth , Butler Elizabeth , Downtain‐Pickersgill Courtney , Shanmugham Anita , Retterer Kyle , Brandt Tracy , Richard Gabriele , McKnight Dianalee A.
Published: April 2018

Objective

We evaluated >8500 consecutive, unselected patients with epilepsy and neurodevelopmental disorders who underwent multigene panel testing to determine the average age at molecular diagnosis and diagnostic yield of 70 genes.

Methods

We reviewed molecular test results for 70 genes known to cause epilepsy and neurodevelopmental disorders using next generation sequencing (NGS) and exon‐level array comparative genomic hybridization (aCGH). A positive result was defined as the presence of 1 or 2 pathogenic or likely pathogenic (P/LP) variants in a single gene, depending on the mode of inheritance of the associated disorder.

Results

Overall, 22 genes were found to have a high yield of positive findings by genetic testing, with SCN1A and KCNQ2 accounting for the greatest number of positive findings. In contrast, there were no positive findings in 16 genes. Most of the P/LP variants were sequence changes identified by NGS (90.9%), whereas ~9% were gross deletions or duplications detected by exon‐level aCGH. The mean age of molecular diagnosis for the cohort was 5 years, 8 months (ranging from 1 week to 47 years). Recurrent P/LP variants were observed in 14 distinct genes, most commonly in MECP2, KCNQ2, SCN1A, SCN2A, STXBP1, and PRRT2. Parental testing was performed in >30% of positive cases. All variants identified in CDKL5, STXBP1, SCN8A, GABRA1, and FOXG1 were de novo, whereas 85.7% of variants in PRRT2 were inherited.

Significance

Using a combined approach of NGS and exon‐level aCGH, testing identified a genetic etiology in 15.4% of patients in this cohort and revealed the age at molecular diagnosis for patients. Our study highlights both high‐ and low‐yield genes associated with epilepsy and neurodevelopmental disorders, indicating which genes may be considered for molecular diagnostic testing.
The development of in vitro embryo production in the horse
Authors: Morris L. H. A.
Published: April 2018

The development of techniques to produce equine embryos in vitro is reviewed with specific reference to intracytoplasmic sperm injection (ICSI). Unexplored 50 years ago, this technology has progressed rapidly in the last 20 years to become a commercial reality for the equine breeding industry. Improvements in our understanding of oocyte and embryo competence in the horse have been key factors in overcoming some of the initial problems associated with ICSI. It is now possible to obtain high nuclear maturation and cleavage rates in vitro and the most limiting factor, presently, is the low rate of development to the blastocyst stage. However, in spite of this, once obtained, these in vitro‐derived blastocysts can result in pregnancy rates in excess of 60% following transfer.
A study of the environmental survival of Streptococcus equi subspecies equi
Authors: Durham A. E. , Hall Y. S. , Kulp L. , Underwood C.
Published: April 2018

Background

Streptococcus equi represents a common hazard to equids worldwide. Environmental contamination with bacteria shed from an infected horse may represent a significant source of contagion and further knowledge of ex vivo bacterial survival under different conditions is important for disinfection and isolation protocols.

Objectives

To determine the potential duration of survival and vigour of growth of S. equi inoculated onto surfaces relevant to equine veterinary practice and stabling in summer and winter.

Study design

Repeat sampling of environmental inocula of S. equi.

Methods

Cultures of S. equi were inoculated onto wood, a shoe sole, cotton overalls, inside a nasogastric tube, inside a dental rasp, in a wet plastic bucket and onto a fence post both in the summer and winter seasons. Frequent resampling and culture from the inoculated sites was conducted until no viable bacteria were found. Bacterial viability was determined by both duration (time to first negative culture) and vigour of growth (growth score over the first 3 days of culture) and compared between inoculated sites and times of year.

Results

Bacterial viability was enhanced by a wet local environment and by the winter season. Survival tended to be short in the summer (up to 9 days in wet sites and up to 2 days in dry sites) but much longer in the winter (up to 34 days in wet sites and up to 13 days in dry sites). Vigour of bacterial growth was also greater in the winter than in the summer as judged by 3‐day‐growth scores.

Main limitations

Direct comparison with the variable size and nature of naturally shed infectious material is difficult.

Conclusions

Veterinarians and personnel handling horses should be aware that S. equi may survive in an equine environment for longer than previously found, especially when protected by wet and cold conditions.