bluuebunny/crossref_metadata_2025 huggingface dataset:
How hotel responses to online reviews differ by hotel rating: an exploratory study
Authors: Lee HyeRyeon , Blum Shane C.
Published: June 2015

Purpose

– The purpose of this paper is to investigate how hotels respond to online reviews on a third-party Web site (such as TripAdvisor) based on the hotel’s star rating.

Design/methodology/approach

– Content analysis was used to compare responses to online hotel reviews at five different levels of hotel based on a star-rating system ranging from one star to five stars.

Findings

– Most hotel managers’ response rates were low, and they paid the most attention to positive comments. Managers at four- and five-star hotels more often responded to negative online reviews. Guest service manager was the most common job title of managers who responded to guests’ reviews.

Research limitations/implications

– This paper is limited to an analysis of ten hotels, two for each of the five-star ratings. More hotel cases with long-term data collection involving the use of the star-rating system may provide more insights on this discussion.

Practical implications

– The exploratory study sought to identify strategies for managing online reviews in the lodging industry. Hotel managers should respond to negative online reviews with appreciation, apology and an explanation of what went wrong. Moreover, hotels may need a designated person to observe and respond to guest comments on their Web sites and third-party Web sites. A designated person is also needed to monitor online comments and communicate with guests to better manage the hotel’s online reputation.

Originality/value

– As an exploratory research project, this paper expands the understanding of hotel managers’ responses to their guests’ online reviews in an attempt to identify best practices for the industry.
Costs of sleeping in: circadian rhythms influence cuckoldry risk in a songbird
Authors: Greives Timothy J. , Kingma Sjouke A. , Kranstauber Bart , Mortega Kim , Wikelski Martin , van Oers Kees , Mateman A. Christa , Ferguson Glen A. , Beltrami Giulia , Hau Michaela
Published: June 2015

Circadian (i.e. daily) regulation of behaviours is thought to provide fitness benefits to organisms by enabling them to anticipate diel changes in the environment, such as sunrise.

A common behaviour among socially monogamous songbirds that usually takes place in the early mornings is extra‐pair mating, that is copulating with partners outside of the social pair bond.

Thus, variation in when individuals begin their daily activity may influence their reproductive success; early risers may be better able to gain copulations and guard their partners, thus minimizing their risk of being cuckolded compared with late risers. Sexual selection may thus play an important role in shaping circadian behaviours, but this assumption has yet to be tested in free‐living animals.

Here, we experimentally weakened endogenous circadian rhythmicity, and thus, anticipation of dawn in male great tits (Parus major) in the wild through the subcutaneous administration of implants filled with melatonin shortly before egg‐laying began in this population. Melatonin is a hormone released during the dark phase at night and is one important cue animals use to entrain their circadian clock.

Experimental individuals delayed the onset of daily activity compared with controls and were more likely to be cuckolded compared with control males. Manipulation did not alter other behavioural traits observed; no difference between treatments was observed in activity levels during the day or in the end time of daily activity.

These results strongly support the assumption that selection, particularly sexual selection, shapes the circadian phenotypes of wild vertebrates which enable anticipation of important and predictive diel changes in an individual's biotic and abiotic environment.
Northern Ireland Representation at Westminster: Constitutional Conundrums and Political Manœuvres
Authors: Walker Graham , Mulvenna Gareth
Published: June 2015

This article focuses on the issue of Northern Ireland's representation at Westminster. It investigates the political context of the decision to increase Northern Ireland's representation in the house of commons at Westminster from 12 members to 17 in 1978–9. Exploring this episode in more detail, it is argued, provides a more informed overall understanding of the history of devolution in the UK and of the way issues concerning Northern Ireland often overlapped with questions of constitutional change in Scotland and Wales. The article also throws light on the matter of Northern Ireland MPs and their voting rights at Westminster during Northern Ireland's experience of devolution prior to 1972.
When is an acoustic neuroma not an acoustic neuroma? Pitfalls for radiosurgeons
Authors: Roos Daniel E , Patel Sandy G , Potter Andrew E , Zacest Andrew C
Published: June 2015

Introduction

Because acoustic neuroma (AN), also termed vestibular schwannoma, constitutes by far the commonest intracranial schwannoma and cerebello‐pontine angle (CPA) tumour, there is a risk of overlooking rarer alternative diagnoses with similar clinical and/or radiological features. The purpose of this article is to highlight to radiosurgeons the potentially serious implications of this problem through illustrative case studies.

Methods

Our linac stereotactic radiosurgery (SRS) technique has been previously described, with stereotactic headring fixation and treatment delivered via cones or micro‐multileaf collimators using multiple arcs or static beams.

Results

Between November 1993 and October 2014, we treated 132 patients referred with a clinical diagnosis of AN, the vast majority with 12 Gy marginal dose. Three of these (2.3%), evident either at the time of treatment (2) or subsequently (1), had features instead consistent with cochlear schwannoma, facial schwannoma and meningioma, respectively. Each warranted significant modification to standard AN outlining and fields. The meningioma progressed due to geographic miss. One other patient with recurrent facial schwannoma (not yet needing SRS) was also referred with an incorrect diagnosis of AN.

Conclusion

When rare variants of common medical problems are not identified before referral, there is a risk that ‘blinkering’ can lead to misdiagnosis and suboptimal treatment. Radiosurgeons need to be particularly mindful of this issue with AN, which can mimic several other tumours occurring in the CPA region, albeit with different patterns of spread. Optimal imaging, high‐quality radiology reporting and neuroradiology input at the time of SRS planning within the setting of a specialised multidisciplinary team are highly desirable.
Would you bet on PET? Evaluation of the significance of positive PET scan results post‐microwave ablation for non‐small cell lung cancer
Authors: Zaheer Syed N , Whitley Justin M , Thomas Paul A , Steinke Karin
Published: June 2015

Fluodeoxyglucose‐positron emission tomography (FDG‐PET) imaging is an acknowledged modality for the follow‐up of solid tumours treated with thermal ablation, with persistent or new FDG uptake at the ablation site considered to be a reliable indicator of local recurrence. Several cases of proven false‐positive FDG‐PET scans are illustrated in this pictorial essay with uptake at the site of the ablated tumour, remote from the ablated lesion and in mediastinal and hilar lymph nodes. Positive FDG‐PET scans post‐thermal ablation of lung tumours therefore cannot always reliably predict local tumour recurrence or nodal spread. It is important to be familiar with FDG uptake patterns post‐ablation and their significance. FDG‐PET avid lesions post‐ablation may require histological confirmation before further therapy is planned or management is changed.
A randomized clinical trial of the effects of ultra‐low‐dose naloxone infusion on postoperative opioid requirements and recovery
Authors: Xiao Y. , Wu L. , Zhou Q. , Xiong W. , Duan X. , Huang X.
Published: June 2015

Background

Tolerance to remifentanil during sevoflurane anesthesia may increase postoperative analgesic requirements. Low‐dose naloxone not only has been shown to block the development of acute opioid tolerance but also to ameliorate undesired opioid‐induced side effects. We hypothesized that naloxone prevents the acute opioid tolerance produced by a large dose of remifentanil, and reduces the incidence of opioid‐induced side effects.

Methods

Seventy‐two patients undergoing open colorectal surgery were randomly assigned to receive intraoperative remifentanil (1) small dose at 0.1 μg/kg/min; (2) large dose at 0.30 μg/kg/min; or (3) large dose at 0.30 μg/kg/min combined with low‐dose naloxone at 0.25 μg/kg/h just after the induction. Cumulative morphine consumption, postoperative pain scores, incidence of opioid‐related side effects, time to recovery of bowel function, and length of hospital stay were recorded.

Results

Cumulative morphine consumption at 24 h after surgery was higher in the large‐dose remifentanil group (28 ± 12 mg) compared with the small‐dose remifentanil group (17 ± 12 mg), and large‐dose remifentanil–naloxone group (18 ± 9 mg), (P < 0.001). The median time to return of bowel function was shorter in the large‐dose remifentanil–naloxone group than the other two groups (P < 0.05). The median length of hospital stay was lower in the large‐dose remifentanil–naloxone group (8 [interquartile range: 8–12] days) compared with the small‐dose remifentanil group (12 [interquartile range: 9–15] days) and large‐dose remifentanil group (12 [interquartile range: 10–13] days), (P < 0.001).

Conclusion

Naloxone infusion prevented the acute opioid tolerance, provided a quicker recovery of bowel function, and reduced the length of hospital stay after open colorectal surgery.
Genomewide Association Study for Maximum Number of Alcoholic Drinks in European Americans and African Americans
Authors: Xu Ke , Kranzler Henry R. , Sherva Richard , Sartor Carolyn E. , Almasy Laura , Koesterer Ryan , Zhao Hongyu , Farrer Lindsay A. , Gelernter Joel
Published: June 2015

Background

We conducted a genomewide association study (GWAS) for maximum number of alcoholic drinks consumed in a 24‐hour period (“MaxDrinks”), in 2 independent samples comprised of over 9,500 subjects, following up on our GWAS for alcohol dependence (AD) in European Americans (EAs) and African Americans (AAs).

Methods

The samples included our GWAS samples (Yale‐UPenn) recruited for studies of the genetics of drug or AD, and a publicly available sample: the Study of Addiction: Genetics and Environment (SAGE). Genomewide association analysis was performed for ~890,000 single nucleotide polymorphisms (SNPs) using linear association random effects models. EAs and AAs were separately analyzed.

Results

The results confirmed significant associations of the well‐known functional loci at ADH1B with MaxDrinks in EAs (rs1229984 Arg48His p = 5.96 × 10−15) and AAs (rs2066702 Arg370Cys, p = 2.50 × 10−10). The region of significant association on chromosome 4 was extended to LOC100507053 in AAs but not EAs. We also identified potentially novel significant common SNPs for MaxDrinks in EAs in the Yale‐UPenn sample: rs1799876 at SERPINC1 on chromosome 1 (4.00 × 10−8) and rs2309169 close to ANKRD36 on chromosome 2 (p = 5.58 × 10−9). After adjusting for the peak SNP rs1229984 on ADH1B, rs1799876 was nearly significant (p = 1.99 × 10−7) and rs2309169 remained highly significant (2.12 × 10−9).

Conclusions

The results provide further support that ADH1B modulates alcohol consumption. Future replications of potential novel loci are warranted. This is the largest MaxDrinks GWAS to date, the first in AAs.
Corporate governance and the probability of default
Authors: Schultz Emma L. , Tan David T. , Walsh Kathleen D.
Published: June 2015

We employ Merton's probability of default as a continuous ex‐ante measure of the likelihood of firm failure and dynamic panel generalised method of moments to better characterise the relationship between corporate governance and the chance of default. In doing so, we overcome limitations of discrete proxies widely used in previous studies and more completely account for endogeneity issues permeating this area of research. While initial testing designed to facilitate comparison with previous studies suggests a significant relationship between the probability of default and executive pay, board structure and ownership structure, once endogeneity concerns are accounted for, no such relationship remains.
Comparison of striatal dopamine transporter levels in chronic heroin‐dependent and methamphetamine‐dependent subjects
Authors: Yuan Jie , Liu Xing Dang , Han Mei , Lv Rong Bin , Wang Yuan Kai , Zhang Guang Ming , Li Yu
Published: June 2015

To compare the effects of heroin and methamphetamine (METH) addiction on dopamine transporters (DATs) in the same dose and duration, we assessed DAT levels in the striatum by 99mTc‐TRODAT‐1 single‐photon emission computed tomography (SPECT) brain images in people with heroin and METH dependence. We recruited 21 healthy human controls, 23 heroin‐dependent subjects and 25 METH abusers. The heroin‐ and METH‐dependent subjects exhibited negative urine toxicology after undergoing physiological detoxification. All subjects underwent SPECT brain imaging, and specific tracer uptake ratios (SURs) were assessed bilaterally in the regions of interest. A significant SUR reduction in heroin‐dependent subjects and METH‐dependent subjects compared with healthy controls was found in the left striatum, right striatum, left caudate nucleus, right caudate nucleus, left putamen and right putamen. There were no significant differences in the heroin group and METH group for the left striatum, right striatum, left caudate nucleus, right caudate nucleus, left putamen and right putamen. The scores of craving, HAMA (Hamilton Anxiety Rating Scale), in heroin abusers were lower than in the METH abusers. Our results show that people with heroin and METH dependence who are currently abstinent had lower DAT levels in the striatum than healthy controls. There were no differences in striatal DAT in heroin and METH users. These results suggest that chronic heroin and METH abuse appears to produce similar effects in striatal DAT in humans. METH users may have more serious craving and anxiety symptoms than heroin users with prolonged abstinence.
Griffith Edwards’ rigorous sympathy with Alcoholics Anonymous
Authors: Humphreys Keith
Published: June 2015

Griffith Edwards made empirical contributions early in his career to the literature on Alcoholics Anonymous (AA), but the attitude he adopted towards AA and other peer‐led mutual help initiatives constitutes an even more important legacy. Unlike many treatment professionals who dismissed the value of AA or were threatened by its non‐professional approach, Edwards was consistently respectful of the organization. However, he never became an uncritical booster of AA or overgeneralized what could be learnt from it. Future scholarly and clinical endeavors concerning addiction‐related mutual help initiatives will benefit by continuing Edwards’ tradition of ‘rigorous sympathy’.
The Prime Minister and the Bomb: John Gorton, W.C. Wentworth and the Quest for an Atomic Australia
Authors: Clohesy Lachlan , Deery Phillip
Published: June 2015

The efforts of the Liberal government led by John Gorton to acquire a locally built nuclear deterrent stretch back into the 1950s when Robert Menzies preferred to rely on the American or British nuclear umbrella for protection. Gorton took a different view and the advocates of an independent Australian nuclear capability rejoiced upon his elevation to the Liberal leadership. We argue that Gorton's ambitions advanced as far as they did in the latter 1960s due to the support, or urgings, from an informal coalition of scientists (particularly Philip Baxter) and discontented fringes of the parliamentary Liberal Party. In particular, the maverick backbencher, W.C. Wentworth, played a key role in mobilising support for Gorton's controversial quest to acquire an independent nuclear capacity.
Basophils exhibit antibacterial activity through extracellular trap formation
Authors: Yousefi S. , Morshed M. , Amini P. , Stojkov D. , Simon D. , von Gunten S. , Kaufmann T. , Simon H.‐U.
Published: June 2015

Basophils are primarily associated with immunomodulatory functions in allergic diseases and parasitic infections. Recently, it has been demonstrated that both activated human and mouse basophils can form extracellular DNA traps (BETs) containing mitochondrial DNA and granule proteins. In this report, we provide evidence that, in spite of an apparent lack of phagocytic activity, basophils can kill bacteria through BET formation.
Inverse Adaptive Cluster Sampling with Unequal Selection Probabilities: Case Studies on Crab Holes and Arsenic Pollution
Authors: Salehi Mohammad , Moradi Mohammad , Al Khayat Jassim A. , Brown Jennifer , Yousif Adil Eltayeb Mohamed
Published: June 2015

Adaptive cluster sampling is an efficient method of estimating the parameters of rare and clustered populations. The method mimics how biologists would like to collect data in the field by targeting survey effort to localised areas where the rare population occurs. Another popular sampling design is inverse sampling. Inverse sampling was developed so as to be able to obtain a sample of rare events having a predetermined size. Ideally, in inverse sampling, the resultant sample set will be sufficiently large to ensure reliable estimation of population parameters. In an effort to combine the good properties of these two designs, adaptive cluster sampling and inverse sampling, we introduce inverse adaptive cluster sampling with unequal selection probabilities. We develop an unbiased estimator of the population total that is applicable to data obtained from such designs. We also develop numerical approximations to this estimator. The efficiency of the estimators that we introduce is investigated through simulation studies based on two real populations: crabs in Al Khor, Qatar and arsenic pollution in Kurdistan, Iran. The simulation results show that our estimators are efficient.
Prevention of transient liver damage after laparoscopic gastrectomy via modification of the liver retraction technique using the Nathanson liver retractor
Authors: Kitajima Toshihiro , Shinohara Hisashi , Haruta Shusuke , Momose Kota , Ueno Masaki , Udagawa Harushi
Published: June 2015

Introduction

Although laparoscopic radical gastrectomy has several advantages over conventional surgery, postoperative liver dysfunction is an unwanted complication. The major cause is considered to be use of mechanical liver retraction. To prevent liver damage after laparoscopic gastrectomy, we modified the liver retraction method: the retractor was used only after lymph node dissection along the greater curvature had been completed, and it was released before reconstruction and intermittent repositioning to avoid discoloration of the liver parenchyma. This study sought to determine whether postoperative liver dysfunction could be prevented by making these simple modifications.

Methods

In this retrospective study involving 114 laparoscopic gastrectomy patients, postoperative serum aspartate aminotransferase, alanine aminotransferase (ALT), and total bilirubin levels were compared between laparoscopic gastrectomy patients who had undergone the modified procedure and those who had not. Discoloration of the liver was classified into three groups just before the retractor was released at the end of surgery.

Results

Aspartate aminotransferase and ALT levels on postoperative days 1 and 2 and the proportion of patients with elevated aspartate aminotransferase or ALT levels on postoperative day 1 were significantly lower after the modifications. ALT level on postoperative day 1 was significantly higher in the subgroup with broad liver discoloration.

Conclusions

Reducing the duration of liver retraction and moving the position of the retractor or releasing it intermittently before discoloration of the liver parenchyma may be effective for preventing postoperative liver damage.
Corporate charitable contributions: business award winners' giving behaviors
Authors: Yoo Choong‐Yuel , Pae Jinhan
Published: June 2015

We investigate corporate giving behaviors of prestigious business award winners in Korea. In particular, we examine whether firms strategically use corporate giving to enhance corporate reputation. We find that (1) award winners generally make more charitable contributions than nonwinners prior to winning awards and maintain significant charitable contributions after winning awards; (2) multiple award winners make even more charitable contributions than single‐award winners; and (3) an increase in charitable contributions does not raise the probability of winning awards in the year after the increase. The results suggest that CEOs of award‐winning firms do not use corporate giving opportunistically to enhance their status and reputation. Rather, significant charitable contributions by award winners may be indicative of a sound business strategy to maximize long‐term firm value.
Incorporating risk assessment into the formative evaluation of an authentic e‐learning program
Authors: Vesper James L. , Kartoğlu Ümit , Herrington Jan , Reeves Thomas C.
Published: June 2015

This paper describes the use of two different risk assessment strategies during the design and development of a complex authentic task‐based e‐learning program developed by the World Health Organization (WHO). The first strategy involved the use of expert reviewers and the second strategy employed the engagement of a risk assessment expert facilitator. This approach enabled the WHO design team to identify risks in advance and employ control and mitigation strategies to eliminate or reduce the risks that were revealed by the two risk assessments.
Neurorestoration induced by the HDAC inhibitor sodium valproate in the lactacystin model of Parkinson's is associated with histone acetylation and up‐regulation of neurotrophic factors
Authors: Harrison Ian F , Crum William R , Vernon Anthony C , Dexter David T
Published: June 2015

Background and Purpose

Histone hypoacetylation is associated with Parkinson's disease (PD), due possibly to an imbalance in the activities of enzymes responsible for histone (de)acetylation; correction of which may be neuroprotective/neurorestorative. This hypothesis was tested using the anti‐epileptic drug sodium valproate, a known histone deacetylase inhibitor (HDACI), utilizing a delayed‐start study design in the lactacystin rat model of PD.

Experimental Approach

The irreversible proteasome inhibitor lactacystin was unilaterally injected into the substantia nigra of Sprague–Dawley rats that subsequently received valproate for 28 days starting 7 days after lactacystin lesioning. Longitudinal motor behavioural testing, structural MRI and post‐mortem assessment of nigrostriatal integrity were used to track changes in this model of PD and quantify neuroprotection/restoration. Subsequent cellular and molecular analyses were performed to elucidate the mechanisms underlying valproate's effects.

Key Results

Despite producing a distinct pattern of structural re‐modelling in the healthy and lactacystin‐lesioned brain, delayed‐start valproate administration induced dose‐dependent neuroprotection/restoration against lactacystin neurotoxicity, characterized by motor deficit alleviation, attenuation of morphological brain changes and restoration of dopaminergic neurons in the substantia nigra. Molecular analyses revealed that valproate alleviated lactacystin‐induced histone hypoacetylation and induced up‐regulation of brain neurotrophic/neuroprotective factors.

Conclusions and Implications

The histone acetylation and up‐regulation of neurotrophic/neuroprotective factors associated with valproate treatment culminate in a neuroprotective and neurorestorative phenotype in this animal model of PD. As valproate induced structural re‐modelling of the brain, further research is required to determine whether valproate represents a viable candidate for disease treatment; however, the results suggest that HDACIs could hold potential as disease‐modifying agents in PD.
Effects of acute and chronic sunitinib treatment on cardiac function and calcium/calmodulin‐dependent protein kinase II
Authors: Mooney L , Skinner M , Coker S J , Currie S
Published: June 2015

Background and Purpose

Calcium/calmodulin‐dependent protein kinase IIδ (CaMKIIδ) is an important regulator of cardiac contractile function and dysfunction and may be an unwanted secondary target for anti‐cancer drugs such as sunitinib and imatinib that have been reported to alter cardiac performance. This study aimed to determine whether anti‐cancer kinase inhibitors may affect CaMKII activity and expression when administered in vivo.

Experimental Approach

Cardiovascular haemodynamics in response to acute and chronic sunitinib treatment, and chronic imatinib treatment, were assessed in guinea pigs and the effects compared with those of the known positive and negative inotropes, isoprenaline and verapamil. Parallel studies from the same animals assessed CaMKIIδ expression and CaMKII activity following drug treatments.

Key Results

Acute administration of sunitinib decreased left ventricular (LV) dP/dtmax. Acute administration of isoprenaline increased LVdP/dtmax dose‐dependently, while LVdP/dtmax was decreased by verapamil. CaMKII activity was decreased by acute administration of sunitinib and was increased by acute administration of isoprenaline, and decreased by acute administration of verapamil. CaMKIIδ expression following all acute treatments remained unchanged. Chronic imatinib and sunitinib treatments did not alter fractional shortening; however, both CaMKIIδ expression and CaMKII activity were significantly increased. Chronic administration of isoprenaline and verapamil decreased LV fractional shortening with parallel increases in CaMKIIδ expression and CaMKII activity.

Conclusions and Implications

Chronic sunitinib and imatinib treatment increased CaMKIIδ expression and CaMKII activity. As these compounds are associated with cardiac dysfunction, increased CaMKII expression could be an early indication of cellular cardiotoxicity marking potential progression of cardiac contractile dysfunction.
How Does Landscape Modification Induce Biological Homogenization in Tropical Stream Metacommunities?
Authors: Siqueira Tadeu , Lacerda Camila Giaj‐Levra Teixeira , Saito Victor S.
Published: June 2015

Habitat modification can homogenize biological communities. Beta diversity analyses provide key information for understanding biotic homogenization, especially given recent conceptual and methodological advances. Here, we investigated if landscape modification was associated with taxonomic homogenization in 32 stream insect communities from the Brazilian Atlantic Forest. We investigated: (1) if the way we defined landscape affected our estimates of beta diversity; (2) to what extent changes in species composition versus relative abundance caused the observed homogenization; and (3) if environmental heterogeneity among modified habitats influenced homogenization. We detected taxonomic homogenization caused by landscape modification only when we used refined landscape categorizations and abundance‐based diversity measures. For forested streams, changes in relative abundance rather than absolute taxonomic composition increased the biological variation. Forested streams were generally more heterogeneous, with a variable set of abundant genera; by contrast, non‐forested streams were more homogeneous, with the same set of genera being more or less abundant. We suggest that landscape modification by agriculture, pasture, and silviculture reduces beta diversity by limiting the colonization of potential species, and, ultimately, causing taxonomic homogenization. Studies investigating biotic homogenization should include multiple dissimilarity measures representing changes in relative species abundance and community composition.
Combination with third‐generation bisphosphonate (YM529) and interferon‐alpha can inhibit the progression of established bone renal cell carcinoma
Authors: Kurabayashi Atsushi , Inoue Keiji , Fukuhara Hideo , Karashima Takashi , Fukata Satoshi , Kawada Chiaki , Shuin Taro , Furihata Mutsuo
Published: June 2015

The aim of this study was to investigate whether the third‐generation nitrogen‐containing bisphosphonate (YM529) can inhibit the progression of established bone renal cell carcinoma (RCC) and to elucidate its mechanism. Antiproliferative effect and apoptosis induction of RCC cells and mouse osteoclasts by YM529 and/or interferon‐alpha (IFN‐α) were evaluated in vitro using cell counting and in vivo using soft X‐ray, the TUNEL method and tartrate‐resistant acid phosphatase stain. For the in vivo study, male athymic BALB/cA Jc1‐nu nude mice bearing human RCC cell line RBM1‐IT4 cells were treated with YM529 and/or IFN‐α. The biological activity of osteoclasts was evaluated using the pit formation assay. The antiangiogenetic effect by YM529 and/or IFN‐α was analyzed using micro‐vessel density and in situ mRNA hybridization. Osteoclast number in bone tumors was decreased in YM529‐treated mouse. YM529 also inhibited osteoclast activity and proliferation in vitro, whereas basic fibroblast growth factor expressions and micro‐vessel density within tumors were inhibited by IFN‐α. Neither YM529 nor IFN‐α alone significantly inhibited the growth of established bone metastatic tumors. Combined treatment with YM529 and IFN‐α may be beneficial in patients with human RCC bone metastasis. Their effects are mediated by osteoclast recruitment inhibition and inactivation by YM529 and antiangiogenesis by IFN‐α.
Effects of maternal subtotal nephrectomy on the development of the fetal kidney: A morphometric study
Authors: Kondo Tomohiro , Kitano‐Amahori Yoko , Nagai Hiroaki , Mino Masaki , Takeshita Ai , Kusakabe Ken Takeshi , Okada Toshiya
Published: June 2015

The present study was designed to explore if maternal subtotal (5/6) nephrectomy affects the development of fetal rat kidneys using morphometric methods and examining whether there are any apoptotic changes in the fetal kidney. To generate 5/6 nephrectomized model rats, animals underwent 2/3 left nephrectomy on gestation day (GD) 5 and total right nephrectomy on GD 12. The fetal kidneys were examined on GDs 16 and 22. A significant decrease in fetal body weight resulting from maternal 5/6 nephrectomy was observed on GD 16, and a significant decrease in fetal renal weight and fetal body weight caused by maternal nephrectomy was observed on GD 22. Maternal 5/6 nephrectomy induced a significant increase in glomerular number, proximal tubular length, and total proximal tubular volume of fetuses on GD 22. Maternal 5/6 nephrectomy resulted in an increase in the number of apoptotic cells in the metanephric mesenchyme of the kidney on GD 16, and in the collecting tubules on GD 22. These findings suggest that maternal 5/6 nephrectomy stimulates the development of the fetal kidney while suppressing fetal growth.
Bone formation in mono cortical mandibular critical size defects after augmentation with two synthetic nanostructured and one xenogenous hydroxyapatite bone substitute – in vivo animal study
Authors: Dau Michael , Kämmerer Peer W. , Henkel Kai‐Olaf , Gerber Thomas , Frerich Bernhard , Gundlach Karsten K. H.
Published: June 2015

Objectives

Healing characteristics as well as level of tissue integration and degradation of two different nanostructured hydroxyapatite bone substitute materials (BSM) in comparison with a deproteinized hydroxyapatite bovine BSM were evaluated in an in vivo animal experiment.

Material and methods

In the posterior mandible of 18 minipigs, bilateral mono cortical critical size bone defects were created. Randomized augmentation procedures with NanoBone® (NHA1), Ostim® (NHA2) or Bio‐Oss® (DBBM) were conducted (each material n = 12). Samples were analyzed after five (each material n = 6) and 8 months (each material n = 6). Defect healing, formation of soft tissue and bone as well as the amount of remaining respective BSM were quantified both macro‐ and microscopically.

Results

For NHA2, the residual bone defect after 5 weeks was significantly less compared to NHA1 or DBBM. There was no difference in residual BSM between NHA1 and DBBM, but the amount in NHA2 was significantly lower. NHA2 also showed the least amount of soft tissue and the highest amount of new bone after 5 weeks. Eight months after implantation, no significant differences in the amount of residual bone defects, in soft tissue or in bone formation were detected between the groups. Again, NHA2 showed significant less residual material than NHA1 and DBBM.

Discussion

We observed non‐significant differences in the biological hard tissue response of NHA1 and DBBM. The water‐soluble NHA2 initially induced an increased amount of new bone but was highly compressed which may have a negative effect in less stable augmentations of the jaw.
A prospective study evaluating cochlear implant management skills: development and validation of the Cochlear Implant Management Skills survey
Authors: Bennett R.J. , Jayakody D.M.P. , Eikelboom R.H. , Taljaard D.S. , Atlas M.D.
Published: June 2015

Objective

To investigate the ability of cochlear implant (CI) recipients to physically handle and care for their hearing implant device(s) and to identify factors that may influence skills. To assess device management skills, a clinical survey was developed and validated on a clinical cohort of CI recipients.

Design

Survey development and validation. A prospective convenience cohort design study.

Setting

Specialist hearing implant clinic.

Participants

Forty‐nine post‐lingually deafened, adult CI recipients, at least 12 months postoperative.

Main outcome measures

Survey test–retest reliability, interobserver reliability and responsiveness. Correlations between management skills and participant demographic, audiometric, clinical outcomes and device factors.

Results

The Cochlear Implant Management Skills survey was developed, demonstrating high test–retest reliability (0.878), interobserver reliability (0.972) and responsiveness to intervention (skills training) [t(20) = −3.913, P = 0.001]. Cochlear Implant Management Skills survey scores range from 54.69% to 100% (mean: 83.45%, sd: 12.47). No associations were found between handling skills and participant factors.

Conclusions

This is the first study to demonstrate a range in cochlear implant device handling skills in CI recipients and offers clinicians and researchers a tool to systematically and objectively identify shortcomings in CI recipients' device handling skills.
Pleomorphic spindle cell dermal neoplasm with dot‐like keratin reactivity: keratin‐positive AFX or carcinoma?
Authors: Ellis Ransom , Chase Elizabeth , Barland Alycia , Rajpara Anand , Fraga Garth R.
Published: June 2015

Atypical fibroxanthoma (AFX) is an uncommon cutaneous neoplasm of pleomorphic myofibroblast‐like cells. Diagnosis requires exclusion of other undifferentiated spindle and pleomorphic cell neoplasms by immunohistochemistry. We report two patients with p63‐non‐reactive spindle cell neoplasms which resembled AFX but demonstrated anomalous dot‐like immunolabeling with antibodies to high molecular weight keratin and keratin 5. One case recurred locally, suggesting such lesions may behave aggressively. Whether these lesions represent keratin‐positive dermal sarcomas or poorly differentiated carcinomas is debatable. Regardless of exact classification, our experience suggests such cases should be managed as high‐risk non‐melanoma skin cancers.
Proper muscle layer damage affects ulcer healing after gastric endoscopic submucosal dissection
Authors: Horikawa Yohei , Mimori Nobuya , Mizutamari Hiroya , Kato Yuhei , Shimazu Kazuhiro , Sawaguchi Masayuki , Tawaraya Shin , Igarashi Kimihiro , Okubo Syunji
Published: June 2015

Background and Aim

Endoscopic submucosal dissection (ESD) is the established therapy for superficial gastrointestinal neoplasms. However, management of the artificial ulcers associated with ESD has become important and the relationship between ulcer healing factors and treatment is still unclear. We aimed to evaluate ESD‐related artificial ulcer reduction ratio at 4 weeks to assess factors associating with ulcer healing after ESD that may lead to optimal treatment.

Methods

Between January 2009 and December 2013, a total of 375 lesions fulfilled the expanded criteria for ESD. We defined ulcer reduction rate <90% as (A) poor‐healing group; and rate ≥90% as (B) well‐healing group. After exclusion, 328 lesions were divided into two groups and analyzed. These two groups were compared based on clinicopathological/endoscopic features, concomitant drugs, and treatment.

Results

Ulcer reduction rate was significantly correlated with factors related to the ESD procedure (i.e. procedure time, submucosal fibrosis, and injury of the proper muscle layer, in univariate analysis. Multivariate logistic regression analysis showed that submucosal fibrosis (F2) (P = 0.03; OR, 16.46; 95% CI, 1.31–206.73) and injury of the proper muscle layer (P = 0.01; OR, 4.27; 95% CI, 2.04–8.92) were statistically significant predictors of delayed healing.

Conclusion

This single‐center retrospective study indicated that ESD‐induced artificial ulcer healing was affected by submucosal fibrosis and injury of the proper muscle layer, which induced damage to the muscle layer. Therefore, the preferable pharmacotherapy can be determined on completion of the ESD procedure.
C‐Reactive protein and insulin growth factor 1 serum levels during the menstrual cycle in adolescents with Type 1 diabetes
Authors: Codner E. , Merino P. M. , Martínez D. , Lopez P. , Godoy C. , Iñiguez G. , Cassorla F. , Perez‐Bravo F.
Published: June 2015

Aims

To evaluate C–reactive protein, insulin growth factor 1 and lipid levels during the follicular and luteal phases in adolescents with Type 1 diabetes.

Methods

Adolescents with Type 1 diabetes (N = 40) and healthy controls (C; N = 43) were studied during the follicular and luteal phases of their menstrual cycles. C–Reactive protein, insulin growth factor 1 and lipid levels were measured.

Results

Adolescents with Type 1 diabetes exhibited higher C–reactive protein levels than the C group during the follicular (P < 0.0001) and luteal phases (P < 0.01). The elevation of C–reactive protein levels was more pronounced in overweight adolescents with Type 1 diabetes than in adolescents in the C group. More adolescents with Type 1 diabetes were classified as having an elevated risk of cardiovascular disease (C–reactive protein > 3 mg/l) in the luteal phase than in the follicular phase (37.5% and 17.5%, respectively); half of the overweight adolescents with Type 1 diabetes in the luteal phase reached this level. BMI was the only significant factor affecting follicular and luteal phase C–reactive protein levels in adolescents with Type 1 diabetes. Lower insulin growth factor 1 levels were observed during both phases of the menstrual cycle in adolescents with Type 1 diabetes compared with controls. An elevation in insulin growth factor 1 levels in the luteal phase relative to the follicular phase was observed in controls, but not in adolescents with Type 1 diabetes. Luteal insulin growth factor 1 and C–reactive protein exhibited an inverse correlation (r = –0.4, P = 0.01).

Conclusions

Adolescents with Type 1 diabetes have higher C–reactive protein levels and lower insulin growth factor 1 levels relative to controls, especially during the luteal phase. Type 1 diabetes diminishes the natural elevation in insulin growth factor 1 levels observed during the luteal phase in controls. Excess weight exacerbates the subclinical inflammatory state observed during both phases of the menstrual cycle in adolescents with Type 1 diabetes.
Properties and bioavailability of particulate and mineral‐associated organic matter in Arctic permafrost soils, Lower Kolyma Region, Russia
Authors: Gentsch N. , Mikutta R. , Shibistova O. , Wild B. , Schnecker J. , Richter A. , Urich T. , Gittel A. , Šantrůčková H. , Bárta J. , Lashchinskiy N. , Mueller C. W. , Fuß R. , Guggenberger G.
Published: June 2015

Permafrost degradation may cause strong feedbacks of arctic ecosystems to global warming, but this will depend on if, and to what extent, organic matter (OM) is protected against biodegradation by mechanisms other than freezing and anoxia. Here, we report on the amount, chemical composition and bioavailability of particulate (POM) and mineral‐associated OM (MOM) in permafrost soils of the East Siberian Arctic. The average total organic carbon (OC) stock across all soils was 24.0 ± 6.7 kg m−2 within 100 cm soil depth. Density fractionation (density cut‐off 1.6 g cm−3) revealed that 54 ± 16% of the total soil OC and 64 ± 18% of OC in subsoil horizons was bound to minerals. As well as sorption of OM to clay‐sized minerals (R2 = 0.80; P < 0.01), co‐precipitation of OM with hydrolyzable metals may also transfer carbon into the mineral‐bound fraction. Carbon:nitrogen ratios, stable carbon and nitrogen isotopes, 13C‐NMR and X‐ray photoelectron spectroscopy showed that OM is transformed in permafrost soils, which is a prerequisite for the formation of mineral‐organic associations. Mineral‐associated OM in deeper soil was enriched in 13C and 15N, and had narrow C:N and large alkyl C:(O‐/N‐alkyl C) ratios, indicating an advanced stage of decomposition. Despite being up to several thousands of years old, when incubated under favourable conditions (60% water‐holding capacity, 15°C, adequate nutrients, 90 days), only 1.5–5% of the mineral‐associated OC was released as CO2. In the topsoils, POM had the largest mineralization but was even less bioavailable than the MOM in subsoil horizons. Our results suggest that the formation of mineral‐organic associations acts as an important additional factor in the stabilization of OM in permafrost soils. Although the majority of MOM was not prone to decomposition under favourable conditions, mineral‐organic associations host a readily accessible carbon fraction, which may actively participate in ecosystem carbon exchange.
Antinuclear antibodies in neuromyelitis optica: guardians of the brain?
Authors: Monson N.
Published: June 2015

Click here to view the accompanying paper in this issue.
A prospective study of direct medical costs in a large cohort of consecutively enrolled patients with refractory epilepsy in Italy
Authors: Luoni Chiara , Canevini Maria Paola , Capovilla Giuseppe , De Sarro Giovambattista , Galimberti Carlo Andrea , Gatti Giuliana , Guerrini Renzo , La Neve Angela , Mazzucchelli Iolanda , Rosati Eleonora , Specchio Luigi Maria , Striano Salvatore , Tinuper Paolo , Perucca Emilio ,   Study of Outcome of PHarmacoresistance In Epilepsy (SOPHIE) collaborators
Published: June 2015

Objective

To evaluate direct medical costs and their predictors in patients with refractory epilepsy enrolled into the SOPHIE study (Study of Outcomes of PHarmacoresistance In Epilepsy) in Italy.

Methods

Adults and children with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers and followed for 18 months. At entry, all subjects underwent a structured interview and a medical examination, and were asked to keep records of diagnostic examinations, laboratory tests, specialist consultations, treatments, hospital admissions, and day‐hospital days during follow‐up. Study visits included assessments every 6 months of seizure frequency, health‐related quality of life (Quality of Life in Epilepsy Inventory 31), medication‐related adverse events (Adverse Event Profile) and mood state (Beck Depression Inventory‐II). Cost items were priced by applying Italian tariffs. Cost estimates were adjusted to 2013 values.

Results

Of 1,124 enrolled individuals, 1,040 completed follow‐up. Average annual cost per patient was € 4,677. The highest cost was for antiepileptic drug (AED) treatment (50%), followed by hospital admissions (29% of overall costs). AED polytherapy, seizure frequency during follow‐up, grade III pharmacoresistance, medical and psychiatric comorbidities, and occurrence of status epilepticus during follow‐up were identified as significant predictors of higher costs. Age between 6 and 11 years, and genetic (idiopathic) generalized epilepsies were associated with the lowest costs. Costs showed prominent variation across centers, largely due to differences in the clinical characteristics of cohorts enrolled at each center and the prescribing of second‐generation AEDs. Individual outliers associated with high costs related to hospital admissions had a major influence on costs in many centers.

Significance

Refractory epilepsy is associated with high costs that affect individuals and society. Costs differ across centers in relation to the characteristics of patients and the extent of use of more expensive, second‐generation AEDs. Epilepsy‐specific costs cannot be easily differentiated from costs related to comorbidities.
Building sustainable cities: tools for developing new building practices?
Authors: GEORG SUSSE
Published: June 2015

Urban professionals have a widespread interest in sustainable cities and the use of assessment tools to monitor performance. Much of the research on such assessment tools focuses on gauging their differences and similarities. Scholars give insufficient attention to what the tools ‘do’ to those who use them and to how this affects building practices. Drawing on insights from actor‐network theory and an empirical study of two Danish urban development competitions in which design teams were required to use a sustainability assessment tool, the analysis shows how this artefact mediated interaction among different professionals and initiated iterative, dialogical processes that affected building practices. The analysis emphasizes a number of aspects that the construction and urban development literature often overlook: such tools can facilitate and mediate knowledge creation and flow, but the entanglement of relationships, the assemblages, in which the designers are situated conditions the outcome.
Increased CD1D polymorphism: identification of two novel alleles, CD1D*03 and *04, in individuals from Morocco
Authors: Aureli A. , Oumhani K. , Del Beato T. , Di Rocco M. , Tessitore A. , El Aouad R. , Piancatelli D.
Published: June 2015

Two novel CD1D alleles were identified in unrelated individuals from Morocco. They differ each from the common CD1D*01 allele by one nucleotide substitution in exon 2 resulting in one amino acid change in the G‐ALPHA1‐LIKE domain. According to the IMGT unique numbering for G domain, CD1D*03 has one nucleotide transition c136 > t in codon 46, with an arginine‐to‐cysteine amino acid change (R46 > C) in the D‐STRAND, whereas CD1D*04 has one transition c98 > t in codon 33, with a threonine‐to‐methionine amino acid change (T33 > M) in the C‐STRAND. This suggests that CD1D is more polymorphic than previously assumed.
You can go your own way! The long‐term effectiveness of a self‐employment programme for welfare recipients in Germany
Authors: Wolff Joachim , Nivorozhkin Anton , Bernhard Stefan
Published: June 2015

In this study, we examined the long‐term effects of supporting welfare recipients by means of a subsidy to start their own business. We used administrative data and propensity score matching to estimate the impact of the subsidy on the probability of receiving welfare benefits and on unemployment status up to 72 months after programme start. We supplemented our estimation results with the results of a qualitative survey which provided insights into the diversity of entrepreneurial activities and the recipients' motivation for starting a business. Our results are encouraging. We found a stable positive effect on the outcomes of interest. We further found that foreign nationals and the long‐term unemployed benefit the most. We conclude that the subsidy allows some people to successfully start a business who would not have otherwise done so and who would have been less successful by choosing the alternative of continued job search.