bluuebunny/crossref_metadata_2025 huggingface dataset:
Employees’ eldercare demands, strain, and perceived support
Authors: Zacher Hannes , Schulz Heiko
Published: February 2015

Purpose

– In many countries, both the number of older people in need of care and the number of employed caregivers of elderly relatives will increase over the next decades. The purpose of this paper is to examine the extent to which perceived organizational, supervisor, and coworker support for eldercare reduce employed caregivers’ strain and weaken the relationship between eldercare demands and strain.

Design/methodology/approach

– Survey data were collected from 100 employed caregivers from one organization.

Findings

– Results showed that eldercare demands were positively related to strain, and perceived organizational eldercare support (POES) was negatively related to strain. In addition, high POES weakened the relationship between eldercare demands and strain.

Research limitations/implications

– The cross-sectional design and use of self-report scales constitute limitations of the study.

Practical implications

– POES is a resource for employed caregivers, especially when their eldercare demands are high.

Originality/value

– This research highlights the relative importance of different forms of perceived support for reducing employed caregivers’ strain and weakening the relationship between eldercare demands and strain.
Effects of feedback motives on inquiry and performance
Authors: Dahling Jason , O'Malley Alison L , Chau Samantha L
Published: February 2015

Purpose

– The purpose of this paper is to examine how two motives for feedback-seeking behavior, the instrumental and image enhancement motives, impact the feedback-seeking process and supervisor ratings of task performance.

Design/methodology/approach

– Correlational data were collected from supervisor-subordinate dyads and analysed with path analysis.

Findings

– Results show that perceptions of a supportive supervisory feedback environment are associated with both higher instrumental and image enhancement motives. The instrumental motive fully mediates the relationship between the feedback environment and feedback-seeking behavior. However, the positive effect of feedback-seeking behavior on task performance ratings made by supervisors is only significant when the image enhancement motive is low. Contrary to expectations, no direct or moderating effects were found for the instrumental motive on performance ratings.

Practical implications

– These results demonstrate that many instances of feedback-seeking behavior are motivated by a desire to enhance one’s public image, and that high image enhancers can earn strong performance ratings even with low feedback-seeking behavior. Overall, the findings highlight the critical importance of measuring employees’ motives in research on feedback and performance management.

Originality/value

– This is the first study to explicitly examine how motives mediate and moderate the relationships between feedback environment perceptions, feedback-seeking behavior, and performance in the workplace. The findings suggest that future research on feedback-seeking behavior should measure and model the effects of motives on feedback processes.
‘MetaTaal’: enhancing complex syntax in children with specific language impairment—a metalinguistic and multimodal approach
Authors: Zwitserlood Rob , Wijnen Frank , van Weerdenburg Marjolijn , Verhoeven Ludo
Published: February 2015

Background

Currently, most research on the effective treatment of morphosyntax in children with specific language impairment (SLI) pertains to younger children. In the last two decades, several studies have provided evidence that intervention for older school‐age children with SLI can be effective. These metalinguistic intervention approaches teach grammatical rules explicitly and use shapes and colours as two‐dimensional visual support. Reading or writing activities form a substantial part of these interventions. However, some children with SLI are poor readers and might benefit more from an approach that is less dependent on literacy skills.

Aims

To examine the effectiveness of a combined metalinguistic and multimodal approach in older school‐age children with SLI. The intervention was adapted to suit poor readers and targeted the improvement of relative clause production, because relative clauses still pose difficulties for older children with SLI.

Methods & Procedures

Participants were 12 monolingual Dutch children with SLI (mean age 11;2). All children visited a special school for children with speech and language disorders in the Netherlands. A quasi‐experimental multiple‐baseline design was chosen to evaluate the effectiveness of the intervention. A set of tasks was constructed to test relative clause production and comprehension. Two balanced versions were alternated in order to suppress a possible learning effect from multiple presentations of the tasks. After 3 monthly baseline measurements, the children received individual treatment with a protocolled intervention programme twice a week during 5 weeks. The tests were repeated directly post‐therapy and at a retention measurement 3 months later. During the intervention programme, the speech therapist delivering the treatment remained blind to the test results.

Outcomes & Results

No significant changes were found during the baseline measurements. However, measurement directly post‐therapy showed that 5 h of intervention produced significant improvement on the relative clause production tasks, but not on the relative clause comprehension task. The gains were also maintained 3 months later.

Conclusions & Implications

The motor and tactile/kinesthetic dimensions of the ‘MetaTaal’ metalinguistic intervention approach are a valuable addition to the existing metalinguistic approaches. This study supports the evidence that grammatical skills in older school‐age children with SLI can be remediated with direct intervention using a metalinguistic approach. The current tendency to diminish direct intervention for older children with SLI should be reconsidered.
Spoken language comprehension of phrases, simple and compound‐active sentences in non‐speaking children with severe cerebral palsy
Authors: Geytenbeek Joke J. M. , Heim Margriet J. M. , Knol Dirk L. , Vermeulen R. Jeroen , Oostrom Kim J.
Published: February 2015

Background

Children with severe cerebral palsy (CP) (i.e. ‘non‐speaking children with severely limited mobility’) are restricted in many domains that are important to the acquisition of language.

Aims

To investigate comprehension of spoken language on sentence type level in non‐speaking children with severe CP.

Methods & Procedures

From an original sample of 87 non‐speaking children with severe CP, 68 passed the pre‐test (i.e. they matched at least five spoken words to the corresponding objects) of a specifically developed computer‐based instrument for low motor language testing (C‐BiLLT), admitting them to the actual C‐BiLLT computer test. As a result, the present study included 68 children with severe CP (35 boys, 33 girls; mean age 6;11 years, SD 3;0 years; age range 1;9–11;11 years) who were investigated with the C‐BiLLT for comprehension of different sentence types: phrases, simple active sentences (with one or two arguments) and compound sentences. The C‐BiLLT provides norm data of typically developing (TD) children (1;6–6;6 years). Binomial logistic regression analyses were used to compare the percentage correct of each sentence type in children with severe CP with that in TD children (subdivided into age groups) and to compare percentage correct within the CP subtypes.

Outcomes & Results

Sentence comprehension in non‐speaking children with severe CP followed the developmental trajectory of TD children, but at a much slower rate; nevertheless, they were still developing up to at least age 12 years. Delays in sentence type comprehension increased with sentence complexity and showed a large variability between individual children and between subtypes of CP. Comprehension of simple and syntactically more complex sentences were significantly better in children with dyskinetic CP than in children with spastic CP. Of the children with dyskinetic CP, 10–13% showed comprehension of simple and compound sentences within the percentage correct of TD children, as opposed to none of the children with spastic CP.

Conclusion & Implications

In non‐speaking children with severe CP sentence comprehension is delayed rather than deviant. Results indicate the importance of following comprehension skills across all age groups, even beyond age 12 years. Moreover, the subtype of CP should be considered when establishing an educational programme for sentence comprehension, and augmentative and alternative communication support. In addition, educational programmes for children with severe CP should take into account the linguistic hierarchy of sentence comprehension when focusing on the input and understanding of spoken language comprehension.
The effect of lowering salt on the physicochemical, microbiological and sensory properties of São João cheese of Pico Island
Authors: Soares Catarina , Fernando Ana Luisa , Mendes Benilde , Martins António P L
Published: February 2015

São João cheeses with varying curd dry salting treatments were made with decreasing levels of salt (sodium chloride): 4 (control), 3, 2 and 1% (w/w), along with the salt‐free version. The cheeses were ripened at 11 °C over a 40‐day period, and the effect of lowering salt on the physicochemical, microbiological and sensory properties of the cheese was studied. Reduced salt resulted in a concomitant moisture decrease with protein increase, ash and sodium reduction among experimental cheeses at the same ripening day, but there were no significant differences in pH, acidity and fat, or in the microbiological quality. Triangle tests indicated perceptible differences between test and control cheeses at the level of 2% NaCl (w/w) or less, but not with the cheese salted with 3 g NaCl/100 g. Considering the sensory, the physicochemical and the microbiological results, the cheese formulated at 3% NaCl (w/w) (presenting a reduction of 25% in salt) is feasible on an industrial scale, being indistinguishable by the regular consumer.
The Dividend Substitution Hypothesis: Australian Evidence
Authors: Brown Christine , Handley John , O'Day James
Published: February 2015

In a perfect capital market firms are indifferent to either dividends or repurchases as payout mechanisms, suggesting that the two payout methods should be perfect substitutes. Empirical research at the single country level, as well as cross country studies, provide evidence that dividends and repurchases act as substitutes (the dividend substitution hypothesis), and that the tax treatment of dividends versus capital gains affects this relation. Australia, which operates under a full dividend imputation system, has two types of repurchases: on‐ and off‐market. On‐market repurchases are taxed as capital gains while off‐market repurchases comprise a large dividend component carrying valuable tax credits. Australia thus provides a natural setting to investigate how the tax treatment of proceeds affects the dividend substitution hypothesis. Dividend substitution is found to exist for on‐market repurchases but not for off‐market repurchases, thus providing further support for the idea that the tax treatment of proceeds affects the substitutability of repurchases and dividends.
The Purpose of Financial Reporting: The Case for Coherence in the Conceptual Framework and Standards
Authors: Sutton David B. , Cordery Carolyn J. , van Zijl Tony
Published: February 2015

This paper proposes a basis for progress in the development of the conceptual framework (CF) as a foundation for developing accounting standards. This topic has gained increased prominence following theIASB's (2013) release of itsReview of the Conceptual Framework for Financial Reporting(RCFFR) proposing changes to theCF. In this paper the broad socio‐economic environment is seen as determining the primary purpose ofGeneralPurposeFinancialReporting (GPFR), which, in turn, establishes the high‐level properties of aCFsuitable to meet that primary purpose. This is to support market stability and efficiency through the provision of an account of the financial position and performance of an entity that accords with economic reality.

The case is made that the primary purpose of aCFis to provide the principles for the development of accounting standards that will result inGPFRthat is useful. This requires theoretical coherence. TheCFshould drive the standards and if standards depart from theCFprinciples, such departures should be justified. This proposal is consistent with the position adopted in theRCFFR. However, in contrast to theRCFFR, this paper accents the purposive approach and links the formation of standards directly to theCF. This approach implies that standards are subordinate toCFprinciples; therefore compliance with standards should not provide a basis for compromising the faithful representation of economic reality. From the purpose identified forGPFR, the paper argues for a default presumption in favour ofFairValueAccounting, a retreat from the asset/liability approach, and a re‐casting of the income statement to focus on operational flows.
Earnings Surprises in Analysts' Forecasts, Mandatory Disclosure, and Share Repurchases
Authors: Liu Chi‐Chun , Chen Ni‐Yun
Published: February 2015

This paper examines the impact of forecast errors and the mandatory disclosure of repurchase transactions required by 2003 Securities and Exchange Commission (SEC) regulations on share repurchases. We define forecast errors as the difference between analysts' forecasted earnings and actual earnings. We argue that firms with positive forecast errors imply greater information asymmetry, which may induce them to signal through share repurchases. We show that both the repurchase target and analysts' forecast revision are positively related to forecast errors. Furthermore, these associations are more pronounced in the low disclosure period (1989–2003) where greater information asymmetry between managers and outside investors is found, while increased transparency in the high disclosure period (2004–2006) leads to more significant improvement in long‐term performances for firms with positive forecast errors. The results are consistent with our expectations that the information asymmetry implied in forecast errors, along with a shock change from the introduction of the 2003 SEC regulation, affect both corporate and analysts' behaviour.
Comparison of streamlined liner of the pharynx airway (SLIPA™) and laryngeal mask airway: a systematic review and meta‐analysis
Authors: Choi G. J. , Kang H. , Baek C. W. , Jung Y. H. , Woo Y. C. , Kim S. H. , Kim J. G.
Published: February 2015

We performed a systematic review to compare the efficacy and safety of the streamlined liner of the pharynx airway and laryngeal mask airway used in adults during general anaesthesia. We included 14 studies with studies with 1273 patients in total. There was no evidence of a difference between the two devices in insertion success rate on the first attempt (13 studies, 1143 patients), insertion time (seven studies, 576 patients), ease of insertion (five studies, 466 patients), oropharyngeal leak pressure (eight studies, 771 patients) and the quality of the fibreoptic view of the larynx through the device (three studies, 281 patients). The relative risk (95% CI) of bloodstaining of the device (nine studies, 859 patients) was 2.09 (1.46–3.00) for the streamlined liner of the pharynx airway compared with the laryngeal mask airway. Other adverse events were comparable. Subgroup analysis suggested that the insertion by novice users might be faster and more successful with the streamlined liner of the pharynx airway than the laryngeal mask airway; however, this was from only two studies and 186 patients. The method of size selection of the streamlined liner of the pharynx airway device might also affect the speed of insertion: choosing according to the width of the patient's thyroid cartilage, rather than height, may produce better results.
Markedly raised levels of C‐reactive protein are associated with culture‐proven sepsis or necrotising enterocolitis in extremely preterm neonates
Authors: Keane Michelle , Fallon Rachel , Riordan Andrew , Shaw Ben
Published: February 2015

Aim

A serious inflammatory process is suspected when C‐reactive protein (CRP) is very high, and we established the causes and outcomes when CRP was >100 mg/L in neonates.

Methods

We retrospectively reviewed all 277 episodes where CRP exceeded 100 mg/L between January 2007 and December 2011 at a tertiary neonatal unit.

Results

Of the 6025 neonates admitted during the study period, 258 had CRP >100 mg/L at least once. The overall mortality rate was 44/258 (17%); 36 died within 7 days of CRP >100 mg/L, and 34 were extremely preterm infants. CRP exceeded 100 mg/L in 106 infants within the first 3 days of life – 74 term, 25 preterm and seven extremely preterm – with no infection identified in 81%. In contrast, infections were found in 87% of the 171 episodes from day four of life – 129 extremely preterm, 23 preterm and 19 term – predominantly coagulase‐negative staphylococcus sepsis and necrotising enterocolitis.

Conclusion

Markedly elevated CRP in the first 3 days of life was most likely to affect term neonates (74/106) with no infectious cause (81%). However, CRP >100 mg/L from the fourth day of life was most likely to affect extremely preterm neonates (129/171) and have an infectious cause (87%).
Randomised clinical trial: the 5‐HT4 agonist revexepride in patients with gastro‐oesophageal reflux disease who have persistent symptoms despite PPI therapy
Authors: Shaheen N. J. , Adler J. , Dedrie S. , Johnson D. , Malfertheiner P. , Miner P. , Meulemans A. , Poole L. , Tack J. , Thielemans L. , Troy S. , Vakil N. , Zerbib F. , Ruth M.
Published: February 2015

Background

A substantial proportion of patients with gastro‐oesophageal reflux disease (GERD) have only a partial response to proton pump inhibitor (PPI) therapy. Prokinetic drugs may improve reflux symptoms by enhancing oesophageal motility and gastric emptying.

Aim

To evaluate the effect of revexepride, a novel prokinetic 5‐hydroxytryptamine type 4 (5‐HT4) receptor agonist, compared with placebo, in patients with GERD who have a partial response to PPIs.

Methods

A phase 2b, double‐blind, parallel‐group study was conducted, in which patients were randomised to one of three revexepride treatment groups (0.1, 0.5 and 2.0 mg three times daily) or placebo (1:1:1:1 ratio). Daily e‐diary data captured patients' symptoms over an 8‐week treatment period. The primary efficacy outcome was the weekly percentage of regurgitation‐free days in the second half of the study (weeks 5–8).

Results

In total, 480 patients were randomised and 477 received treatment (mean age 47.9 years; 61% women). The mean percentage of regurgitation‐free days increased from baseline (range, 15.0–18.8%) to week 8 (62.3–70.5%) in all four study arms; however, there were no statistically significant differences in this change between placebo and the three treatment arms. No dose‐dependent relationship in treatment effect was observed for any of the study endpoints. The incidence of treatment‐emergent adverse events (TEAEs) was revexepride dose‐dependent. Only one serious TEAE occurred and none resulted in death.

Conclusions

Revexepride was no more effective than placebo in controlling regurgitation in patients with GERD symptoms partially responsive to PPIs. Revexepride was well tolerated. ClinicalTrials.gov Identifier: NCT01472939.
Basophil infiltration in eosinophilic oesophagitis and proton pump inhibitor‐responsive oesophageal eosinophilia
Authors: Iwakura N. , Fujiwara Y. , Tanaka F. , Tanigawa T. , Yamagami H. , Shiba M. , Tominaga K. , Watanabe T. , Iijima K. , Koike T. , Walls A. F. , Arakawa T.
Published: February 2015

Background

The features of proton pump inhibitor‐responsive oesophageal eosinophilia (PPI‐REE) are similar to those of eosinophilic oesophagitis (EoE), but PPI‐REE demonstrates symptomatic and histological responses to PPI therapy. Several studies have shown that basophils play a crucial role in the pathogenesis of allergic diseases.

Aim

To identify and compare basophil infiltration in the oesophageal epithelium in patients with EoE, PPI‐REE, gastroesophageal reflux disease (GERD) and normal oesophagus (controls).

Methods

Biopsy specimens from 43 patients, including 12 with EoE, 11 with PPI‐REE, 10 with GERD and 10 normal oesophagus, were analysed. Immunohistochemistry was performed to quantify the number of basophils and mast cells in the oesophageal epithelium. Double immunofluorescence staining for thymic stromal lymphopoietin (TSLP) and basophils was performed. Patients with EoE were treated with swallowed fluticasone.

Results

There were no differences in clinical, endoscopic or histological features between patients with EoE and PPI‐REE. There were more basophils and mast cells in patients with EoE and PPI‐REE than in patients with GERD and control subjects. Basophil infiltration of the oesophageal epithelium in patients with EoE was higher than that in patients with PPI‐REE (3.6 ± 2.8 per high power field vs. 1.2 ± 0.9 per high power field respectively; P = 0.02); however, there was no significant difference in mast cell infiltration between the two groups. TSLP was highly expressed in the oesophageal epithelium in areas infiltrated by basophils. Steroid therapy significantly decreased intraepithelial basophils in patients with EoE.

Conclusion

Basophils may play an important role in the pathogenesis of eosinophilic oesophagitis.
Impact of dietary deviation on disease progression and gut microbiome composition in lupus-prone SNF1 mice
Authors: Johnson B M , Gaudreau M-C , Al-Gadban M M , Gudi R , Vasu C
Published: February 2015

Environmental factors, including microbes and diet, play a key role in initiating autoimmunity in genetically predisposed individuals. However, the influence of gut microflora in the initiation and progression of systemic lupus erythematosus (SLE) is not well understood. In this study, we have examined the impact of drinking water pH on immune response, disease incidence and gut microbiome in a spontaneous mouse model of SLE. Our results show that (SWR × NZB) F1 (SNF1) mice that were given acidic pH water (AW) developed nephritis at a slower pace compared to those on neutral pH water (NW). Immunological analyses revealed that the NW-recipient mice carry relatively higher levels of circulating autoantibodies against nuclear antigen (nAg) as well as plasma cells. Importantly, 16S rRNA gene-targeted sequencing revealed that the composition of gut microbiome is significantly different between NW and AW groups of mice. In addition, analysis of cytokine and transcription factor expression revealed that immune response in the gut mucosa of NW recipient mice is dominated by T helper type 17 (Th17) and Th9-associated factors. Segmented filamentous bacteria (SFB) promote a Th17 response and autoimmunity in mouse models of arthritis and multiple sclerosis. Interestingly, however, not only was SFB colonization unaffected by the pH of drinking water, but also SFB failed to cause a profound increase in Th17 response and had no significant effect on lupus incidence. Overall, these observations show that simple dietary deviations such as the pH of drinking water can influence lupus incidence and affect the composition of gut microbiome.
Evaluation of the first maxillary molar post‐extraction socket as a model for dental implant osseointegration research
Authors: Du Zhibin , Lee Ryan S. B. , Hamlet Stephen , Doan Nghiem , Ivanovski Saso , Xiao Yin
Published: February 2015

Objectives

Published information regarding the use of rat jawbones for dental implant osseointegration research is limited and often inconsistent. This study assessed the suitability and feasibility of placing dental implants into the rat maxilla and to establish parameters to be used for dental implant research using this model.

Materials and methods

Forty‐two customized titanium implants (2 × 3 mm) were placed bilaterally in the maxillary first molar area of 21 Sprague–Dawley rats. Every animal received two implants. The animals were subsequently sacrificed at days 3, 7, 14, 28 and 56 post‐surgery. Resin‐embedded sections of the implant and surrounding maxilla were prepared for histological and histomorphometric analyses.

Results

The mesial root of the first molar in the rat maxilla was the optimal site to place the implant. Although the most apical 2–3 threads of the implant penetrated into the sinus cavity, 2 mm of the remaining implant was embedded in the bone. New bone formation at day 7 around the implant increased further at day 14, as measured by the percentage of bone‐to‐implant contact (%BIC) and new bone area (%BA) in the implant thread chambers (55.1 ± 8.9% and 63.7 ± 7.7%, respectively). There was a further significant increase between day 14 and 28 (P < 0.05), however, no significant differences were found between day 28 and 56 in either %BIC or %BA.

Conclusions

The mesial root socket of the first molar in the rat maxilla is a useful model for dental implant research. Osseointegration following implant placement as measured by BIC plateaued after 28 days. The recommended implant dimensions are 1.5 mm in diameter and 2 mm in length.
Hypomagnesaemia and its potential impact on thiamine utilisation in patients with alcohol misuse at the Alice Springs Hospital
Authors: Dingwall Kylie Maree , Delima Jennifer Flavia , Gent Debra , Batey Robert Gordon
Published: February 2015

Introduction and Aims

Alcohol rapidly reduces thiamine among alcohol‐dependent individuals. Poor diet and alcohol's impact on absorption, storage, activation and excretion of thiamine are thought to be the mechanisms. Previous literature identifies magnesium as an important cofactor in thiamine utilisation, which might also be compromised in alcohol dependent patients. The aim was to describe the thiamine status and clinical profile for a sample of heavy alcohol users entering the Alice Springs Hospital in the Northern Territory of Australia and to examine the relationship between thiamine deficiency, magnesium deficiency and cognitive functioning.

Design and Methods

Cross‐sectional study examining thiamine pyrophosphate (TPP) and magnesium concentrations for a sample of 62 males and 43 females (N = 105; n = 88 Aboriginal, n = 13 non‐Indigenous). Cognition was assessed using the Rowland Universal Dementia Assessment Scale.

Results

TPP concentrations were within or above the reference range. Aboriginal patients had significantly lower TPP than non‐Indigenous patients. A marginally significant difference was found between individuals with thiamine supplementation recorded within the previous 20 days compared with those without. Mean serum magnesium was in the low normal range with magnesium deficiency (i.e. <0.80 mmol L−1) present in 48% of those tested. Serum magnesium (but not TPP) concentrations correlated positively with cognitive test scores.

Discussion and Conclusions

Despite increased exposure to risk factors for Wernicke Korsakoff Syndrome, no patient had TPP concentrations below the reference range. High patient readmission and aggressive thiamine treatment policies may explain this finding. However, low magnesium may be prevalent and could contribute to impaired thiamine utilisation. [Dingwall KM, Delima JF, Gent D, Batey RG. Hypomagnesaemia and its potential impact on thiamine utilisation in patients with alcohol misuse at the Alice Springs Hospital. Drug Alcohol Rev 2015]
Effects of lowering the alcohol minimum purchasing age on weekend hospitalised assaults of young Māori in New Zealand
Authors: Kypri Kypros , Davie Gabrielle , McElduff Patrick , Langley John , Connor Jennie
Published: February 2015

Introduction and Aims

We examine the association between reducing the alcohol minimum purchasing age from 20 to 18 years in December 1999 and rates of weekend assault hospitalisation among young Māori in the following 12 years. Our previous work showed deleterious effects for young people overall. In keeping with Treaty of Waitangi principles, we sought to determine whether the policy was similarly detrimental for Māori.

Design and Methods

We used Poisson regression to examine data from 1995 to 2011 on Māori hospitalised on Friday–Sunday following assault, separately by gender among 15‐ to 17‐year‐olds and 18‐ to 19‐year‐olds, versus 20‐ to 21‐year‐olds as a control for changes in economic and environmental factors.

Results

There was no evidence to suggest weekend assault hospitalisations increased significantly more among 15‐ to 17‐year‐old or 18‐ to 19‐year‐old Māori males in the post‐change periods (incidence rate ratios varied between 0.83 and 1.13; P values >0.25) compared with increases observed in 20‐ to 21‐year‐old Māori males. For Māori females, estimates were more variable, but overall, there was no evidence of the hypothesised effect (incidence rate ratios between 0.60 and 1.09; P values >0.07).

Discussion and Conclusions

Overall, we find no evidence that lowering the minimum alcohol purchasing age increased weekend hospitalised assaults among young Māori. Inferences are compromised by lack of statistical power which underlines the importance of planning for evaluation of important policies well before they are implemented, particularly with a view to meeting obligations to Māori arising from the Treaty of Waitangi. [Kypri K, Davie G, McElduff P, Langley J, Connor J. Effects of lowering the alcohol minimum purchasing age on weekend hospitalised assaults of young Māori in New Zealand. Drug Alcohol Rev 2015]
Periostin, a neurite outgrowth‐promoting factor, is expressed at high levels in the primate cerebral cortex
Authors: Matsunaga Eiji , Nambu Sanae , Oka Mariko , Tanaka Michio , Taoka Miki , Iriki Atsushi
Published: February 2015

Periostin (POSTN or osteoblast specific factor) is an extracellular matrix protein originally identified as a protein highly expressed in osteoblasts. Recently, periostin has been reported to function in axon regeneration and neuroprotection. In the present study, we focused on periostin function in cortical evolution. We performed a comparative gene expression analysis of periostin between rodents (mice) and primates (marmosets and macaques). Periostin was expressed at higher levels in the primate cerebral cortex compared to the mouse cerebral cortex. Furthermore, we performed overexpression experiments of periostin in vivo and in vitro. Periostin exhibited neurite outgrowth activity in cortical neurons. These results suggested the possibility that prolonged and increased periostin expression in the primate cerebral cortex enhances the cortical plasticity of the mammalian cerebral cortex.
Size control during organogenesis: Development of the lateral line organs in zebrafish
Authors: Wada Hironori , Kawakami Koichi
Published: February 2015

Many genes that play essential roles in organ growth have been identified across a range of organisms. However, the mechanisms by which growing organs can sense their sizes and stop growing when they reach their proper sizes remain poorly understood. The mechanosensory organs of the fish lateral line system (neuromasts) provide an ideal system to address this question for the following reasons. First, each superficial neuromast is composed of a small number of cells situated on the body surface, making it relatively easy to quantify organ size throughout development. Second, while the sensory cells of superficial neuromasts are continuously renewed, overall organ size is homeostatically maintained. Third, there is another type of neuromast showing an opposite mode of growth: that is, canal neuromasts increase in size in proportion to organism body size. Here, we review recent findings regarding the mechanisms that control organ size in the zebrafish lateral line.
Roles of Hoxb5 in the development of vagal and trunk neural crest cells
Authors: Kam Mandy K. M. , Lui Vincent C. H.
Published: February 2015

Neural crest cells (NC) are a group of multipotent stem cells uniquely present in vertebrates. They are destined to form various organs according to their anterior‐posterior (A‐P) levels of origin in the neural tube (NT). They develop into a wide spectrum of cell lineages under the influence of signaling cascades, neural plate border genes and NC specifier genes. Although this complex gene regulatory network (GRN) specifies the fate of NC and the combinatory action of Hox genes executed at the time of NC induction governs the patterning of NC for the formation of specific structures along the A‐P axis, not much information on how GRN and Hox genes directly interact and orchestrate is available. This review summarizes recent findings on the multiple roles of Hoxb5 on the survival and cell lineage differentiation of vagal and trunk NC cells during early development, by direct transcriptional regulation of NC specifier genes (Sox9 and Foxd3) of the GRN. We will also review findings on the transcriptional regulation of Ret by Hoxb5 in the population of the vagal NC that are committed to the enteric neuron and glia lineages. Functional redundancy between Hox proteins (Hoxa5 and Hoxc5) from the same paralogue group as Hoxb5, and the cooperative effects of Hox cofactors, collaborators and transcription factors in the Hoxb5 transcriptional regulation of target genes will also be discussed.
Effects of sitagliptin on counter‐regulatory and incretin hormones during acute hypoglycaemia in patients with type 1 diabetes: a randomized double‐blind placebo‐controlled crossover study
Authors: Schopman J. E. , Hoekstra J. B. L. , Frier B. M. , Ackermans M. T. , de Sonnaville J. J. J. , Stades A. M. , Zwertbroek R. , Hartmann B. , Holst J. J. , Knop F. K. , Holleman F.
Published: February 2015

Aims

To assess whether the dipeptidyl peptidase‐4 (DPP‐4) inhibitor sitagliptin affects glucagon and other counter‐regulatory hormone responses to hypoglycaemia in patients with type 1 diabetes.

Methods

We conducted a single‐centre, randomized, double‐blind, placebo‐controlled, three‐period crossover study. We studied 16 male patients with type 1 diabetes aged 18–52 years, with a diabetes duration of 5–20 years and intact hypoglycaemia awareness. Participants received sitagliptin (100 mg/day) or placebo for 6 weeks and attended the hospital for three acute hypoglycaemia studies (at baseline, after sitagliptin treatment and after placebo). The primary outcome was differences between the three hypoglycaemia study days with respect to plasma glucagon responses from the initialization phase of the hypoglycaemia intervention to 40 min after onset of the autonomic reaction.

Results

Sitagliptin treatment significantly increased active levels of glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1. No significant differences were observed for glucagon or adrenergic counter‐regulatory responses during the three hypoglycaemia studies. Growth hormone concentration at 40 min after occurrence of autonomic reaction was significantly lower after sitagliptin treatment [median (IQR) 23 (0.2–211.0) mEq/l] compared with placebo [median (IQR) 90 (8.8–180) mEq/l; p = 0.008].

Conclusions

Sitagliptin does not affect glucagon or adrenergic counter‐regulatory responses in patients with type 1 diabetes, but attenuates the growth hormone response during late hypoglycaemia.
Embryology and Anatomy of Intrapulmonary Shunts
Authors: McMullan David Michael , Riemer R. Kirk
Published: February 2015

Pulmonary vascular shunting poses a major clinical risk. In this brief overview, we discuss the morphological aspects of shunting vessels in the lung, their development, and the regulation of their patency.
Using multiple traits to estimate the effects of heat shock on the fitness of Aphidius colemani
Authors: Jerbi‐Elayed Mey , Lebdi‐Grissa Kaouthar , Foray Vincent , Muratori Frédéric , Hance Thierry
Published: February 2015

Extreme temperature events are a great challenge for most ectotherms, particularly for the immature stages of parasitoids, as they do not possess the ability to behaviourally thermoregulate. In this study, we measured the effect of an acute heat shock, combined with desiccation stress (34 °C and 35% r.h. during 10 h) during the mummy stage on several fitness‐related traits of emerging adults of the aphid parasitoid Aphidius colemani Viereck (Hymenoptera: Braconidae: Aphidiinae). Our results showed that the emergence rate was strongly affected by the heat shock (63 ± 2.3 vs. 96.1 ± 0.7% for stress vs. control conditions, respectively), and the resulting population was male biased. Heat stress reduced the lifespan of emerged parasitoids but had no effect on fat reserves and female size. Egg load at emergence and parasitism rate were also reduced by heat treatment. The antennal symmetry was disturbed by the heat treatment, and stressed individuals had reduced mating success compared to control parasitoids. Specifically, time before wing fanning, a typical male courtship behaviour, was significantly longer in parasitoid pairs involving females that had emerged from heat‐treated mummies. Additionally, olfactometry tests on experimental females indicated that their response to host odour was similar to that of control individuals, but they required a longer time for perception. These results highlight that exposure to high temperatures during the mummy stage has cumulative detrimental effects that may strongly impact parasitoid populations under natural conditions and hinder the success of biological control programs.
A prospective analysis of clinical efficacy and safety in chronic myeloid leukemia‐chronic phase patients with imatinib resistance or intolerance as evaluated using European LeukemiaNet 2013 criteria
Authors: Murai Kazunori , Akagi Tomoaki , Shimosegawa Kenji , Sugawara Tomohiro , Ishizawa Kenichi , Ito Shigeki , Murai Keiko , Motegi Mutsuhito , Yokoyama Hisayuki , Noji Hideyoshi , Tajima Katsushi , Kimura Jun , Chou Takaaki , Ogawa Kazuei , Harigae Hideo , Kubo Kohmei , Oba Koji , Sakamoto Junichi , Ishida Yoji
Published: February 2015

Background

We conducted a phase II study to evaluate the efficacy and safety of dasatinib in Japanese patients with imatinib‐resistant or imatinib‐intolerant chronic myeloid leukemia (CML).

Methods

From 2009 to 2011, 54 CML‐chronic phase (CP) patients with resistance (n = 40) or intolerance (n = 25) to imatinib were registered to undergo dasatinib treatment. Eleven patients showed both resistance and intolerance to imatinib. Coincidentally, the resistance criteria in this study were the same as a non‐optimal response to tyrosine kinase inhibitors (TKIs) as defined in the European LeukemiaNet (ELN) 2013 recommendations.

Results

The overall incidence rate of major molecular response (MMR) at 12 months was 62.3% (n = 47). Forty patients with resistance to imatinib who were ‘warning’ and ‘failure’ patients based on the ELN 2013 recommendations were assessed; cumulative MMR and MR4.5 rates were 62.5% (n = 39) and 21.0% (n = 40), respectively, at 12 months. Twelve patients who showed a BCR‐ABL transcript level >1% on the international scale did not achieve a MMR or discontinued dasatinib treatment because of insufficient effects. With regard to safety issues, grade 3/4 non‐hematologic adverse events (AEs) were infrequent.

Conclusions

Patients with non‐optimal responses (who meet ELN 2013 warning and failure criteria) to imatinib should be switched quickly to dasatinib, which is less toxic in CML‐CP patients, to improve their prognoses. A BCR‐ABL1 IS of <1% at 3 months of dasatinib administration is a landmark for good therapeutic outcome.
Adenosine A2b receptors control A1 receptor‐mediated inhibition of synaptic transmission in the mouse hippocampus
Authors: Gonçalves Francisco Q. , Pires Johny , Pliassova Anna , Beleza Rui , Lemos Cristina , Marques Joana M. , Rodrigues Ricardo J. , Canas Paula M. , Köfalvi Attila , Cunha Rodrigo A. , Rial Daniel
Published: February 2015

Adenosine is a neuromodulator mostly acting through A1 (inhibitory) and A2A (excitatory) receptors in the brain. A2B receptors (A2BR) are Gs/q‐protein‐coupled receptors with low expression in the brain. As A2BR function is largely unknown, we have now explored their role in the mouse hippocampus. We performed electrophysiological extracellular recordings in mouse hippocampal slices, and immunological analysis of nerve terminals and glutamate release in hippocampal slices and synaptosomes. Additionally, A2BR‐knockout (A2BR‐KO) and C57/BL6 mice were submitted to a behavioural test battery (open field, elevated plus‐maze, Y‐maze). The A2BR agonist BAY60‐6583 (300 nm) decreased the paired‐pulse stimulation ratio, an effect prevented by the A2BR antagonist MRS 1754 (200 nM) and abrogated in A2BR‐KO mice. Accordingly, A2BR immunoreactivity was present in 73 ± 5% of glutamatergic nerve terminals, i.e. those immunopositive for vesicular glutamate transporters. Furthermore, BAY 60‐6583 attenuated the A1R control of synaptic transmission, both the A1R inhibition caused by 2‐chloroadenosine (0.1–1 μm) and the disinhibition caused by the A1R antagonist DPCPX (100 nm), both effects prevented by MRS 1754 and abrogated in A2BR‐KO mice. BAY 60‐6583 decreased glutamate release in slices and also attenuated the A1R inhibition (CPA 100 nm). A2BR‐KO mice displayed a modified exploratory behaviour with an increased time in the central areas of the open field, elevated plus‐maze and the Y‐maze and no alteration of locomotion, anxiety or working memory. We conclude that A2BR are present in hippocampal glutamatergic terminals where they counteract the predominant A1R‐mediated inhibition of synaptic transmission, impacting on exploratory behaviour.
Hydroxylated histidine of human ribosomal protein uL2 is involved in maintaining the local structure of 28S rRNA in the ribosomal peptidyl transferase center
Authors: Yanshina Darya D. , Bulygin Konstantin N. , Malygin Alexey A. , Karpova Galina G.
Published: February 2015

Protein uL2 is essential for the catalytic activity of the ribosome and has a conserved shape in ribosomes from all domains of life. However, the sequence of its unstructured C‐terminal loop apex that contacts the conserved 23S/28S rRNA helix (H) 93 near the ribosomal peptidyl transferase center differs in bacteria, archaea and eukaryotes. Eukaryote‐specific residue His216 located in this loop in mammalian uL2 is hydroxylated in ribosomes. We used a set of chemical probes to explore the structure of an RNA that mimicked a segment of 28S rRNA domain V containing part of the uL2 binding site including H93, complexed with either natural (hydroxylated) or recombinant (unmodified) human uL2. It was found that both protein forms engage H93 during binding, but only natural uL2 (uL2n) protects it from hydroxyl radicals. The association of uL2n with RNA leads to changes in its structure at U4532 adjacent to the universally conserved U4531 (U2585, Escherichia coli numbering) involved in peptidyl transferase center formation, and at the universally conserved C4447 (2501) located in the ribosome near A4397 (2451) and C3909 (2063) belonging to the peptidyl transferase center. As a result, both nucleotides become strongly exposed to hydroxyl radicals. Our data argue that the hydroxyl group at His216 in the C‐terminal loop apex of mammalian uL2 contributes to stabilization of a protein conformation that is favorable for binding to H93 of 28S rRNA and that this binding induces structural rearrangement in the regions close to the peptidyl transferase center in the mature ribosome.
Predicting early life connectivity of Antarctic silverfish, an important forage species along the Antarctic Peninsula
Authors: La Mesa Mario , Piñones Andrea , Catalano Barbara , Ashford Julian
Published: February 2015

The early life stages of the Antarctic silverfish (Pleuragramma antarctica), an important prey species for higher predators in the Southern Ocean ecosystem, dominate the larval fish assemblages of the Bransfield Strait, one of the most important areas for larval retention off the Antarctic Peninsula. Nevertheless, the spatial location of areas where they were spawned and the timing of larval hatching remain unknown. By linking Lagrangian particle tracking simulations with age data obtained using otolith microincrements from fish caught north of Joinville Island in a pelagic survey, we estimated the distribution of hatch dates and subsequent growth rates of silverfish reaching the Bransfield Strait, and predicted the areas where they were spawned. Larval hatching peaked during the last week of December, and the inner shelf and shelf break, east of the Larsen Ice shelf, were the dominant areas predicted to contribute to larval assemblages in the Bransfield Strait. Over simulated periods of 600–630 days, 35–40% of particles remained within the Bransfield Strait, suggesting an important source of supply to higher predators feeding off the northern Antarctic Peninsula. The daily growth rate at the mean size of 22.3 mm was 0.18 mm, corresponding to a daily change in size of approximately 0.82% standard length (SL), and large variability in growth rate suggested a wide range of environmental conditions experienced during the period of advection from the spawning areas. These results provide spatial predictions that can be tested empirically in future studies, using the simulated trajectories to inform sampling design and spatial coverage.
Methyl‐donor deficiency in adolescence affects memory and epigenetic status in the mouse hippocampus
Authors: Tomizawa H. , Matsuzawa D. , Ishii D. , Matsuda S. , Kawai K. , Mashimo Y. , Sutoh C. , Shimizu E.
Published: February 2015

DNA methylation is one of the essential factors in the control of gene expression. Alteration of the DNA methylation pattern has been linked to various neurological, behavioral and neurocognitive dysfunctions. Recent studies have pointed out the importance of epigenetics in brain development and functions including learning and memory. Nutrients related to one‐carbon metabolism are known to play important roles in the maintenance of genomic DNA methylation. Previous studies have shown that the long‐term administration of a diet lacking essential one‐carbon nutrients such as methionine, choline and folic acid (methyl donors) caused global DNA hypermethylation in the brain. Therefore, the long‐term feeding of a methyl‐donor‐deficient diet may cause abnormal brain development including learning and memory. To confirm this hypothesis, 3‐week‐old mice were maintained on a folate‐, methionine‐ and choline‐deficient (FMCD) or control (CON) diet for 3 weeks. We found that the methyl‐donor deficiency impaired both novel object recognition and fear extinction after 3 weeks of treatment. The FMCD group showed spontaneous recovery of fear that differed from that in CON. In addition, we found decreased Gria1 gene expression and specific CpG hypermethylation of the Gria1 promoter region in the FMCD hippocampus. Our data suggest that a chronic dietary lack of methyl donors in the developmental period affects learning, memory and gene expressions in the hippocampus.