bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in the provision of residential educational placements available for young people with learning disabilities/autism in England
Authors: Tomlinson Serena Rose Louisa , McGill Peter , Gore Nick , Humphreys Jessie
Published: August 2017

Purpose

Little is known about the characteristics of residential educational settings for young people with intellectual or developmental disabilities (IDD) in England. Previous research has focussed on the characteristics and experiences of the young people attending such settings rather than the setting itself; therefore, an overview of national provision is needed. The paper aims to discuss these issues.

Design/methodology/approach

As part of a larger project, data were collected for all residential schools and colleges in England. Data relate to settings offering residential provision for at least 4 nights per week for 30 weeks per year, either at the school/college itself, or in an associated residential home. Due to the remit of the main project, settings offering placements only to young people aged under 16 were excluded. Data were collected from a range of sources, including school/college websites, Ofsted and Department for Education resources, and liaison directly with the setting.

Findings

In total, 342 residential educational settings were identified with 57 of these offering post-16 provisions only. A range of data is presented about these settings, including location, placement numbers and types available, age range catered for, special educational needs categories registered for, governance arrangements (e.g. LA maintained, privately owned, and charitable organisation), and Ofsted educational ratings.

Originality/value

These data provide a national overview of residential educational settings for young people with IDD. This enables a clearer picture of the location and type of provision offered and allows comparisons both within and between areas.
Adult autism advocacy in the UK: a policy review
Authors: Watts Georgina
Published: August 2017

Purpose

The need for advocacy for autistic adults is emphasised in many government policy and good practice guidelines. The purpose of this paper is to investigate legislation and policy relevant to advocacy for autistic adults in England and explore whether this translates into practice. It also seeks to clarify which policies can be enforced under current legislation and highlight the gaps in legislative power to ensure implementation of good practice.

Design/methodology/approach

This paper aims to define what is meant by autism advocacy. Relevant legislation, including human rights, disability and autism-specific guidelines, are discussed in respect to autistic adults in England.

Findings

Implementation of autism advocacy policy appears to vary greatly according to local and individual resources.

Originality/value

Autistic adults, and services that support them, may be unaware of the policies and guidelines relevant to advocacy, they may also be confused by the plethora of different guidelines or unsure how to implement these. Further research is needed to review obstacles to the practical application of autism advocacy policy.
Valorization of Apple Pomace by Extraction of Valuable Compounds
Authors: Perussello Camila A. , Zhang Zhihang , Marzocchella Antonio , Tiwari Brijesh K.
Published: August 2017

Apple pomace is a promising source of carbohydrates, proteins, amino acids, fatty acids, phenolic compounds, vitamins, and other compounds with a vast range of food applications. This review focuses on the valorization of apple pomace towards the recovery of the main compounds, namely pectin and polyphenols. Applications, advantages, and drawbacks of conventional extraction (acidic medium under high temperatures) compared with novel extraction technologies are presented. The comparison is based on an extensive literature review of research on extraction of valuable compounds from plant matrixes, particularly apple pomace. Novel extraction techniques involving enzymes, electric field, ultrasound, microwave heating, pressurized liquid, and super/subcritical fluid are also discussed. These techniques offer several advantages, including shorter extraction time, increased yield, reduction—or suppression—of solvents, and minimization of the environmental impact. This paper may help researchers and food industry professionals on the scaling‐up and optimization of eco‐friendly extractions of pectin and phenolic compounds.
Distribution of Selected Soil and Water Conservation Practices in the U.S. as Identified with Google Earth
Authors: White Michael , Haglund Leighton , Gloe Marcus , Bieger Katrin , Namphong Brandon , Gambone Marilyn , Hardy Eric , Gao Jungang , Yen Haw , Arnold Jeff
Published: August 2017

The proper representation of conservation practices on agricultural lands is an important factor in large‐scale assessments of water quality in the United States. Unfortunately, there are few publicly available data sources at the local level and even fewer at the national scale. In this research, randomly selected points within agricultural lands were examined for selected conservation practices using Google Earth aerial imagery by a team of interpreters. In total, 13,530 points had field boundaries digitized, and were subsequently examined and classified. The presence of terraces, grassed waterways, contour farming, center pivot irrigation, strip cropping, ponds, riparian vegetation, filter strips, and land cover were noted. Subjectivity among interpreters was evaluated using duplicate samples and was found to be similar to image misclassification rates in other research. Conservation practice adoption rates for selected major river basins compared favorably with data collected by the Conservation Effects Assessment Project. The frequency of occurrence of each conservation practice was summarized and presented by ecoregion. To facilitate future research, point level data and software source code developed in this research are available via the web at http://nlet.brc.tamus.edu/Conservation. Aerial imagery was found to be a powerful, inexpensive, and easily accessible tool to assess large‐scale conservation practice implementation for certain conservation practices.
Mapping Outlets of Iowa Flood Center and National Water Center River Networks for Hydrologic Model Comparison
Authors: Quintero Felipe , Krajewski Witold F.
Published: August 2017

River networks based on Digital Elevation Model (DEM) data differ depending on the DEM resolution, accuracy, and algorithms used for network extraction. As spatial scale increases, the differences diminish. This study explores methods that identify the scale where networks obtained by different methods agree within some margin of error. The problem is relevant for comparing hydrologic models built around the two networks. An example is the need to compare streamflow prediction from the Hillslope Link Model (HLM) operated by the Iowa Flood Center (IFC) and the National Water Model (NWM) operated by the National Water Center of the National Oceanic and Atmospheric Administration. The HLM uses landscape decomposition into hillslopes and channel links while the NWM uses the NHDPlus dataset as its basic spatial support. While the HLM resolves the scale of the NHDPlus, the outlets of the latter do not necessarily correspond to the nodes of the HLM model. The authors evaluated two methods to map the outlets of NHDPlus to outlets on the IFC network. The methods compare the upstream areas of the channels and their spatial location. Both methods displayed similar performance and identified matches for about 80% of the outlets with a tolerance of 10% in errors in the upstream area. As the aggregation scale increases, the number of matches also increases. At the scale of 100 km2, 90% of the outlets have matches with tolerance of 5%. The authors recommend this scale for comparing the HLM and NWM streamflow predictions.
Concurrent epidermal growth factor receptor T790M secondary mutation and epithelial‐mesenchymal transition in a lung adenocarcinoma patient with EGFR‐TKI drug resistance
Authors: Xu Song , Liu Xia , Liu Renwang , Shi Tao , Li Xiongfei , Zhong Diansheng , Wang Yan , Chen Gang , Chen Jun
Published: August 2017

Almost all epidermal growth factor receptor (EGFR)‐mutant lung cancers develop resistance to EGFR‐tyrosine kinase inhibitors. Several mechanisms for this acquired resistance have been identified, including development of an EGFR T790M mutation, MET amplification, hepatocyte growth factor overexpression, loss of phosphatase and tensin homolog expression, epithelial–mesenchymal transition, and transformation to small cell lung cancer. Herein, we report a case of a lung cancer patient with EGFR exon 19 deletion who was resistant to EGFR‐tyrosine kinase inhibitor treatment during disease progression. Using histological and gene sequencing analysis, we observed that the primary adenocarcinoma acquired T790M mutation in EGFR exon 20, and a secondary sarcomatoid carcinoma developed in the vicinity. Assessment of E‐cadherin and Vimentin expression confirmed that the sarcomatoid carcinoma had undergone an epithelial–mesenchymal transition. Therefore, it is important to perform a tissue re‐biopsy after the development of resistance to identify the best treatment options. Surgical resection might be a better “salvage” treatment in cases of oligometastatic progression.
International Diversification, SFAS 131 and Post‐Earnings‐Announcement Drift
Authors: Kang Tony , Khurana Inder K. , Wang Changjiang
Published: August 2017

Using 1990 through 2013 data of U.S. firms with foreign operations, we show that (i) the serial correlation of analyst forecast errors increases in the extent of international diversification, (ii) post‐earnings‐announcement drift (PEAD) based on analyst forecast errors increases in the extent of international diversification, and (iii) the impact of international diversification on the serial correlation of analyst forecast errors and its associated drift is significantly reduced after the implementation of SFAS 131 on segment disclosures. When we replicate our tests using seasonally differenced earnings, we fail to observe similar patterns. Overall, our results suggest that investors’ underreaction to announced earnings is a likely explanation for PEAD. Our findings also indicate that disclosures required under SFAS 131 are useful to analysts in forming efficient earnings expectations, thereby helping capital market participants in the pricing of internationally diversified firms’ earnings.
Prevalence of Mutations in Deafness‐Causing Genes in Cochlear Implanted Patients with Profound Nonsyndromic Sensorineural Hearing Loss in Shandong Province, China
Authors: Luo Jianfen , Bai Xiaohui , Zhang Fengguo , Xiao Yun , Gu Lintao , Han Yuechen , Fan Zhaomin , Li Jianfeng , Xu Lei , Wang Haibo
Published: August 2017

The mutations of GJB2, SLC26A4, and mtDNA12SrRNA are the most common inherited causes of nonsyndromic sensorineural hearing loss (NSHL) in China, yet previous genetic screenings were mainly carried on patients with moderate‐to‐profound impairment. We aimed to detect the mutation frequencies in NSHL population within a more specified range of severity. Patients with profound NSHL who had undergone cochlear implantation in the Shandong Provincial Hospital (Shandong, China) were recruited. The majority (n  =  472) were between 0.7 and 6 years old, and the remaining (n  =  63) were between 6 and 70 years old. In total, 115 mutation alleles of the three genes were screened with SNP scan assay. Of the patients, 19.44% (104/535) were found to have GJB2 mutations, and the most common allele was c.235delC, followed by c.299_300delAT and c.109G>A. SLC26A4 mutations were detected in 13.46% patients (72/535), and the most common allele was c.919‐2A>G (IVS7‐2A>G), followed by c.1174A>T and c.2168A>G. Seven patients (1.31%) carried mutations in mtDNA12SrRNA, with the alleles of m.1555A>G and m.1494C>T. We found the allele frequency of c.109G>A (GJB2) was relatively lower in the profound NSHL population in comparison to the moderate‐to‐profound ones, and the c.1174A>T (SLC26A4) relatively higher. It suggests those mutations may be connected with the degree of deafness, which needs more observations and analyses to support.
No Need to Watch: How the Effects of Partisan Media Can Spread via Interpersonal Discussions
Authors: Druckman James N. , Levendusky Matthew S. , McLain Audrey
Published: August 2017

To what extent do partisan media sources shape public opinion? On its face, it would appear that the impact of partisan media is limited, given that it attracts a relatively small audience. We argue, however, that its influence may extend beyond its direct audience via a two‐step communication flow. Specifically, those who watch and are impacted by partisan media outlets talk to and persuade others who did not watch. We present experimental results that demonstrate this process. We therefore show that previous studies may have significantly underestimated the effect of these outlets. We also illustrate that how the two‐step communication flow works is contingent upon the precise composition of the discussion group (e.g., is it consistent of all fellow partisans or a mix of partisans?). We conclude by highlighting what our results imply about the study of media, preference formation, and partisan polarization.
Allergens displayed on virus‐like particles are highly immunogenic but fail to activate human mast cells
Authors: Engeroff P. , Caviezel F. , Storni F. , Thoms F. , Vogel M. , Bachmann M. F.
Published: August 2017

Background

The goal of allergen‐specific immunotherapy is the induction of protective immune responses in the absence of anaphylactic reactions. We have previously shown that Fel d 1, the major cat allergen, displayed in a repetitive fashion on virus‐like particles (VLPs) may fulfill these criteria. Specifically, Fel d 1 on VLPs induced strongly increased protective IgG responses compared to free allergen in mice while anaphylactic reactions were essentially abolished. Here we extend these findings to human mast cells and offer a mechanistic explanation for the reduced anaphylactic activity.

Methods

We differentiated human mast cells in vitro from blood‐derived stem cell progenitors and sensitized the cells with a monoclonal Fel d 1‐specific IgE. We compared the capability of Fel d 1 to induce mast cell activation in its free form versus displayed on VLPs and we performed allergen binding studies by surface plasmon resonance as well as flow cytometry.

Results

We show that free Fel d 1 induces degranulation of IgE‐sensitized mast cells whereas Fel d 1 displayed on VLPs fails to induce mast cell activation. We demonstrate that this inability to activate mast cells is based on a biophysical as well as a biochemical mechanism. Firstly, Fel d 1 on VLPs showed a strongly impaired ability to bind to surface‐bound IgE. Secondly, despite residual binding, repetitively displayed allergen on VLPs failed to cause mast cell activation.

Conclusion

These findings indicate that repetitively displaying allergens on VLPs increases their immunogenicity while reducing their potential to cause anaphylactic reactions by essentially eliminating IgE‐mediated activation of mast cells.
Erectile function recovery in men treated with phosphodiesterase type 5 inhibitor administration after bilateral nerve‐sparing radical prostatectomy: a systematic review of placebo‐controlled randomized trials with trial sequential analysis
Authors: Limoncin E. , Gravina G. L. , Corona G. , Maggi M. , Ciocca G. , Lenzi A. , Jannini E. A.
Published: August 2017

The impact of phosphodiesterase type 5 inhibitor (PDE5I) treatment modality (on‐demand vs. daily), PDE5I half‐life and time from surgery to PDE5I prescription on the achievement of drug‐assisted erectile function (EF) recovery is uncertain. We systematically reviewed published randomized clinical trials (RCTs). We performed meta‐analyses of data on 2317 men treated with PDE5Is after nerve‐sparing radical prostatectomy (NSRP). A PubMed and SCOPUS search was performed for trials published from 1 January 1969 to 30 June 2016. PDE5Is are effective in achieving drug‐assisted recovery of erectile function (EF). From a statistical standpoint, these studies were subjected to Trial Sequential Analysis to determine whether the pooled data were adequately powered to verify the study outcomes. On‐demand treatment with PDE5Is was significantly better than daily treatment in recovering drug‐assisted EF. This effect was maintained even when the drugs were stratified according with half‐life. Although not based on head‐to‐head trials, Avanafil used on‐demand was the most effective PDE5I in recovering drug‐assisted EF. Whereas tadalafil was equally effective when used both on‐demand and daily, vardenafil significantly improved drug‐assisted EF recovery only when used on‐demand. The start of PDE5I treatment six months or more after surgery compared to treatment started earlier did not negatively affect the rate of drug‐assisted EF recovery or the possibility to have successful intercourse based on the Sexual Encounter Profile question‐3 (SEP‐3). Current trials do not support the hypothesis that PDE5I use recovers drug‐unassisted EF, although chronic low‐dose tadalafil administration may help to preserve erectile tissue integrity. Potential shortcomings in the trials design may partially explain these disappointing results and several questions concerning the recovery of drug‐unassisted EF remain unanswered. Thus, there is a need for well‐designed new RCTs requiring changes in the timing of PDE5I administration as well as in the dose and the treatment duration.
Preliminary results of a new tool to evaluate cavernous body fibrosis following radical prostatectomy: penile elastography
Authors: Hamidi N. , Altinbas N. K. , Gokce M. I. , Suer E. , Yagci C. , Baltaci S. , Turkolmez K.
Published: August 2017

Development of cavernous tissue fibrosis due to neurovascular bundle damage during radical prostatectomy has been shown in many trials with invasive methods. In this study, we evaluated the changes in cavernous tissue elasticity by elastography in patients who underwent radical prostatectomy with or without neurovascular bundle preservation. Data from 65 patients underwent open retropubic radical prostatectomy between April 2014 and December 2015 was collected prospectively. Patients were grouped with respect to nerve‐sparing status (non‐, unilateral, and bilateral nerve sparing). International Index of Erectile Function scores, penile lengths, and elasticity scores were recorded at preoperative and postoperative follow‐up visits (at 3rd and 6th months). The primary endpoint of the study was to evaluate the changes of the elasticity scores in all groups. Elasticity scores were measured with real‐time elastography by a single experienced radiologist. Mean age, baseline total testosterone level, IIEF‐5 score, elasticity scores of the cavernous body, and penile length were comparable in all groups. At postoperative 3rd and 6th months, statistically significant higher (in favor for fibrosis) mean cavernous body elasticity scores (p = 0.0001), lower mean IIEF‐5 scores (p = 0.0001), and shorter penile lengths (p < 0.05) were observed in non‐nerve‐sparing group compared to other groups while there were no statistically significant differences between unilateral and bilateral nerve‐sparing groups. Very strong negative correlation was detected between IIEF‐5 and elasticity scores (p = 0.0001). According to our results, preservation of the neurovascular bundle in at least one side mediates lower elasticity scores, better International Index of Erectile Function scores, and penile lengths. Preliminary results of the penile elastography studies are promising for prediction of erectile functions and cavernous tissue fibrosis.
Study of termination of postprandial gastric contractions in humans, dogs and Suncus murinus: role of motilin‐ and ghrelin‐induced strong contraction
Authors: Mikami T. , Ito K. , Diaz‐Tartera H. O. , Hellström P. M. , Mochiki E. , Takemi S. , Tanaka T. , Tsuda S. , Jogahara T. , Sakata I. , Sakai T.
Published: August 2017

Aim

Stomach contractions show two types of specific patterns in many species, that is migrating motor contraction (MMC) and postprandial contractions (PPCs), in the fasting and fed states respectively. We found gastric PPCs terminated with migrating strong contractions in humans, dogs and suncus. In this study, we reveal the detailed characteristics and physiological implications of these strong contractions of PPC.

Methods

Human, suncus and canine gastric contractions were recorded with a motility‐monitoring ingestible capsule and a strain‐gauge force transducer. The response of motilin and ghrelin and its receptor antagonist on the contractions were studied by using free‐moving suncus.

Results

Strong gastric contractions were observed at the end of a PPC in human, dog and suncus models, and we tentatively designated this contraction to be a postprandial giant contraction (PPGC). In the suncus, the PPGC showed the same property as those of a phase III contraction of MMC (PIII‐MMC) in the duration, motility index and response to motilin or ghrelin antagonist administration. Ghrelin antagonist administration in the latter half of the PPC (LH‐PPC) attenuated gastric contraction prolonged the duration of occurrence of PPGC, as found in PII‐MMC.

Conclusion

It is thought that the first half of the PPC changed to PII‐MMC and then terminated with PIII‐MMC, suggesting that PPC consists of a digestive phase (the first half of the PPC) and a discharge phase (LH‐PPC) and that LH‐PPC is coincident with MMC. In this study, we propose a new approach for the understanding of postprandial contractions.
A day in the life of a Geographer: ‘lone’1, black, female
Authors: Tolia‐Kelly Divya P
Published: August 2017

This piece is a narrative representation of the experience of being black and female in the discipline of Geography in the UK and beyond. The aim is to share an ethnographic research on race in Geography, based on day‐to‐day experience in the academy. The piece expresses some of the morphologies of black geographical life in everyday academia. The material has originally been shared in coaching and mentoring relationships with me. The quotes included have been sanctioned for use in this particular piece and were sent to me in individual emails in January 2017.
Decolonising geographical knowledges: the incommensurable, the university and democracy
Authors: Baldwin Andrew
Published: August 2017

This short intervention argues that Eve Tuck and Wayne Yang's notion of an ethic of incommensurability might serve as the basis for rethinking the democratic function of the university in the context of calls to decolonialise geographical knowledge and higher education.
‘Free, decolonised education’: a lesson from the South African student struggle
Authors: Elliott‐Cooper Adam
Published: August 2017

This commentary places British geography within transnational currents of student‐focused decolonisation movements. In October 2015, the author travelled to South Africa for the first time, visiting Witwatersrand University (Johannesburg), University of Cape Town (UCT) and Rhodes University in Grahamstown. This paper draws on historical accounts of the British colonisation of what is now South Africa, contextualising both the domestic and global inequalities which it’s students are currently challenging. British imperial history also provides a basis for understanding the roots of British geography, offering the campaigns to decolonise the South African university as an opportunity to critically reflect on how our own discipline produces knowledge. The commentary asks this timely question: as geographers, particularly those based in the old centre of Empire, how can our work be used to dismantle the colonialism our discipline has been implicated in since its formal inception?
Comparison of the impact of laparoscopic endometriotic cystectomy and vaporization on postoperative serum anti‐Mullerian hormone levels
Authors: Saito Natsuho , Yamashita Yoshiki , Okuda Kiyoji , Kokunai Kana , Terai Yoshito , Ohmichi Masahide
Published: August 2017

Introduction

The aim of this study was to investigate the effect of laparoscopic endometriotic cystectomy and vaporization on ovarian reserve.

Methods

We prospectively analyzed the serum level of anti‐Mullerian hormone (AMH) in 62 patients at four different time points— preoperatively and at 1 month, 6 months, and 1 year postoperatively. Among the 62 cases, a bilateral cystectomy was performed in 10, bilateral vaporization in 16, a unilateral cystectomy in 24, and unilateral vaporization in 12.

Results

The rate of AMH decline after unilateral cystectomy or bilateral cystectomy was higher than that after unilateral vaporization or bilateral vaporization. Age and bilaterality were associated with an AMH decline at 1 month, and age alone was associated with an AMH decline at 1 year. Moreover, being older than 38 years of age and having a revised American Society for Reproductive Medicine score >80 were independent risk factors for the non‐recovery of AMH.

Conclusion

The rate of AMH decline after laparoscopic endometriotic vaporization is significantly lower than that after cystectomy. Both methods, however, have the potential to lower ovarian reserve, especially in cases of severe endometriosis or in patients older than 38 years of age.
Family firms and the interests of non‐family stakeholders: The influence of family managers' affective commitment and family salience in terms of power
Authors: Déniz‐Déniz María de la Cruz , Cabrera‐Suárez María Katiuska , Martín‐Santana Josefa D.
Published: August 2017

The goal of this research is to analyze the heterogeneity of family firms in the normative attention to their non‐family stakeholders. With this aim, we suggest that the psychological process of top family managers in terms of individual affective commitment to their firms is a key variable to explain that heterogeneity. However, we also suggest a moderator effect of the family stakeholder salience in the relationship between the managers' affective commitment to the firm and the establishment of firm goals toward non‐family stakeholders. The results of a hierarchical regression analysis on data obtained from 207 family executives show a significant positive influence of managers' affective commitment on the establishment of goals related both to internal (employees) and external (customers and community) non‐family stakeholders. In addition, we can observe a negative moderator effect of the family utilitarian power—as an indicator of the family stakeholder salience—on the relationship between the family managers' affective commitment and the goals related to non‐family employees.
First, do no harm: Generalized procreative non‐maleficence
Authors: Saunders Ben
Published: August 2017

New reproductive technologies allow parents some choice over their children. Various moral principles have been suggested to regulate such choices. This article starts from a discussion of Julian Savulescu's Principle of Procreative Beneficence (PPB), according to which parents ought to choose the child expected to have the best quality of life, before combining two previously separate lines of attack against this principle. First, it is suggested that the appropriate moral principles of guiding reproductive choices ought to focus on general wellbeing rather than prioritizing that of the child and, second, that they ought to be non‐maximizing (e.g. seeking the ‘good enough’ or to avoid harm). Though neither of these suggestions is entirely novel, combining them results in a new, and arguably more plausible, principle to regulate procreative choices, which I call the Principle of Generalized Procreative Non‐Maleficence (PGPNM). According to this principle, the primary obligation on parents is not to cause harm to other people through their reproductive choices.
Euthanasia and cryothanasia
Authors: Minerva Francesca , Sandberg Anders
Published: August 2017

In this article we discuss the moral and legal aspects of causing the death of a terminal patient in the hope of extending their life in the future. We call this theoretical procedure cryothanasia. We argue that administering cryothanasia is ethically different from administering euthanasia. Consequently, objections to euthanasia should not apply to cryothanasia, and cryothanasia could also be considered a legal option where euthanasia is illegal.
Metabolic tumor volume of primary tumor predicts survival better than T classification in the larynx preservation approach
Authors: Miyabe Junji , Hanamoto Atsushi , Tatsumi Mitsuaki , Hamasaki Toshimitsu , Takenaka Yukinori , Nakahara Susumu , Kishikawa Toshihiro , Suzuki Motoyuki , Takemoto Norihiko , Michiba Takahiro , Yoshioka Yasuo , Isohashi Fumiaki , Konishi Koji , Ogawa Kazuhiko , Hatazawa Jun , Inohara Hidenori
Published: August 2017

We aimed to determine whether pretreatment metabolic tumor volume of the primary tumor (T‐MTV) or T classification would be a better predictor of laryngectomy‐free survival (LFS) and overall survival (OS) after chemoradiotherapy in patients with locally advanced laryngeal or hypopharyngeal cancer requiring total laryngectomy. We analyzed 85 patients using a Cox proportional hazards model and evaluated its usefulness by Akaike's information criterion. A T‐MTV cut‐off value was determined by time‐dependent receiver operating characteristic curve analysis. Interobserver reliability for measuring T‐MTV was estimated by the intraclass correlation coefficient (ICC). After adjustment for covariables, T‐MTV, irrespective of whether a continuous or dichotomized variable, and T classification remained independent predictors of LFS and OS. Large T‐MTV (>28.7 mL) was associated with inferior LFS (hazard ratio [HR], 4.16; 95% confidence interval [CI], 1.97–8.70; P = 0.0003) and inferior OS (HR, 3.18; 95% CI, 1.47–6.69; P = 0.004) compared with small T‐MTV (≤28.7 mL). The T‐MTV model outperformed the T classification model in predicting LFS and OS (P = 0.007 and 0.01, respectively). Three‐year LFS and OS rates for patients with small versus large T‐MTV were 68% vs 9% (P < 0.0001) and 77% vs 25% (P < 0.0001), respectively, whereas those for patients with T2‐T3 versus T4a were 61% vs 31% (P = 0.003) and 71% vs 48% (P = 0.10), respectively. ICC was 0.99 (95% CI, 0.99–1.00). Given the excellent interobserver reliability, T‐MTV is better than T classification to identify patients who would benefit from the larynx preservation approach.
Discordance between imaging and immunohistochemistry in unilateral primary aldosteronism
Authors: Nanba Aya T. , Nanba Kazutaka , Byrd James B. , Shields James J. , Giordano Thomas J. , Miller Barbara S. , Rainey William E. , Auchus Richard J. , Turcu Adina F.
Published: August 2017

Objective

Correct subtyping of primary aldosteronism (PA) is essential for good surgical outcomes. Adrenal vein sampling (AVS) and/or computed tomography (CT) are used for PA subclassification. Clinical and/or biochemical improvement after surgery, however, is not always achieved in patients with presumed unilateral PA. We aimed to identify the pitfalls in PA subclassification leading to surgical treatment failures.

Patients and Design

We retrospectively studied 208 patients who underwent adrenal vein sampling (AVS) for PA subclassification in a tertiary referral centre, between January 2009 and August 2016. Simultaneous bilateral AVS was performed before and after cosyntropin administration. We implemented immunohistochemistry for aldosterone synthase (CYP11B2) and 17α‐hydroxylase/17,20 lyase (CYP17A1) in adrenal glands resected from patients without improvement of PA after surgical treatment and from those with limitations in AVS interpretation.

Results

Of 55 patients who underwent adrenalectomy, three (5.5%) had no improvement of PA. All three patients underwent partial adrenalectomy to remove a CT‐detected nodule present on the same side with AVS lateralization. Immunohistochemistry revealed a CYP11B2‐negative nodule in both cases available. All patients who underwent total adrenalectomy based on AVS lateralization benefitted from surgery, including three patients with unilateral unsuccessful AVS and aldosterone suppression in the catheterized side vs inferior vena cava.

Conclusions

Radiographically identified adrenal nodules are not always a source of PA, even when ipsilateral with AVS lateralization. These data caution against reliance on imaging findings, either alone or in conjunction with AVS, to guide surgery for PA.
Bone health and SATB2‐associated syndrome
Authors: Zarate Y.A. , Steinraths M. , Matthews A. , Smith W.E. , Sun A. , Wilson L.C. , Brain C. , Allgove J. , Jacobs B. , Fish J.L. , Powell C.M. , Wasserman W.W. , van Karnebeek C.D. , Wakeling E.L. , Ma N.S.
Published: August 2017

SATB2‐associated syndrome (SAS) is a rare disorder caused by alterations in the special AT‐rich sequence‐binding protein 2 (SATB2). Skeletal abnormalities such as tibial bowing, osteomalacia, osteopenia or osteoporosis have been reported suggesting a higher frequency of skeletal complications in SAS. The optimal timing, necessity, and methodology for routine assessment of bone health in individuals with SAS, however, remain unclear. We report molecular and phenotypic features of 7 individuals with SAS documented to have low bone mineral density (BMD) ascertained by dual‐energy X‐ray absorptiometry (DXA), often preceded by tibial bowing. The lowest BMD Z‐scores ranged −2.3 to −5.6. In 4 individuals, total alkaline phosphatase levels were elevated (2 with elevated bone fraction) around the time of low BMD documentation. A clinically significant fracture history and a diagnosis of pediatric osteoporosis were present in 4 individuals. Pamidronate treatment in 2 children improved BMD. In conclusion, low BMD, fractures, and tibial bowing are relatively common skeletal complications in individuals with SAS. DXA is a useful tool when evaluating a child with SAS suspected to have low BMD and the results might alter clinical management.
Hippocampal synaptic and neural network deficits in young mice carrying the human APOE4 gene
Authors: Sun Guo‐Zhu , He Yong‐Chang , Ma Xiao Kuang , Li Shuang‐Tao , Chen De‐Jie , Gao Ming , Qiu Shen‐Feng , Yin Jun‐Xiang , Shi Jiong , Wu Jie
Published: August 2017

Introduction

Apolipoprotein E4 (APOE4) is a major genetic risk factor for late‐onset sporadic Alzheimer disease. Emerging evidence demonstrates a hippocampus‐associated learning and memory deficit in aged APOE4 human carriers and also in aged mice carrying human APOE4 gene. This suggests that either exogenous APOE4 or endogenous APOE4 alters the cognitive profile and hippocampal structure and function. However, little is known regarding how Apoe4 modulates hippocampal dendritic morphology, synaptic function, and neural network activity in young mice.

Aim

In this study, we compared hippocampal dendritic and spine morphology and synaptic function of young (4 months) mice with transgenic expression of the human APOE4 and APOE3 genes.

Methods

Hippocampal dendritic and spine morphology and synaptic function were assessed by neuronal imaging and electrophysiological approaches.

Results

Morphology results showed that shortened dendritic length and reduced spine density occurred at hippocampal CA1 neurons in Apoe4 mice compared to Apoe3 mice. Electrophysiological results demonstrated that in the hippocampal CA3‐CA1 synapses of young Apoe4 mice, basic synaptic transmission, and paired‐pulse facilitation were enhanced but long‐term potentiation and carbachol‐induced hippocampal theta oscillations were impaired compared to young Apoe3 mice. However, both Apoe genotypes responded similarly to persistent stimulations (4, 10, and 40 Hz for 4 seconds).

Conclusion

Our results suggest significant alterations in hippocampal dendritic structure and synaptic function in Apoe4 mice, even at an early age.
Identification and measurement of dystonia in cerebral palsy
Authors: Rice James , Skuza Pawel , Baker Felicity , Russo Remo , Fehlings Darcy
Published: August 2017

Aim

To establish the prevalence and severity of dystonia in a population of children with cerebral palsy (CP) with hypertonia assessment and measurement tools.

Method

A cross‐sectional study of 151 children (84 males, 67 females) withCPwho were assessed with the Hypertonia Assessment Tool (HAT) and Barry‐Albright Dystonia scale (BAD) for identification and measurement of severity of dystonia.HATdystonia items were assessed for construct and convergent validity.

Results

Distribution by predominant motor type (PMT) was: 85% spastic, 14% dyskinetic, and 1% ataxic. Spastic and dyskinetic groups showed widespread evidence of dystonia according toHATprofiles andBADscores. The dyskineticPMTgroup had a higher meanBADscore than the spastic group (difference of 13 units, 95%CI9.1–16.4). Dystonia severity (BADscore) increased linearly across gross motor (p<0.001), manual ability (p<0.001) and communication functional levels (p<0.001). Divergence was noted in howHATitem six identified dystonia compared to items one and two.

Interpretation

TheHATprovided an estimate of the prevalence of both spasticity and dystonia in a largeCPpopulation, beyond predominant motor type. Dystonia is a common finding in the spasticPMTgroup, and its severity increases as motor function worsens.

What this paper adds

Dystonia is readily identified in cerebral palsy (CP) using the Hypertonia Assessment Tool, regardless of the predominant motor type.

Spasticity and dystonia frequently coexist in the CP population.

Severity of dystonia is inversely related to motor function.
The bile acid‐sequestering resin sevelamer eliminates the acute GLP‐1 stimulatory effect of endogenously released bile acids in patients with type 2 diabetes
Authors: Brønden Andreas , Albér Anders , Rohde Ulrich , Gasbjerg Lærke S. , Rehfeld Jens F. , Holst Jens J. , Vilsbøll Tina , Knop Filip K.
Published: August 2017

Aims

Discovery of the specific bile acid receptors farnesoid X receptor (FXR) and Takeda G protein‐coupled receptor 5 (TGR5) in enteroendocrine L cells has prompted research focusing on the impact of bile acids on glucagon‐like peptide‐1 (GLP‐1) secretion and glucose metabolism. The aim of the present study was to assess the GLP‐1 secretory and gluco‐metabolic effects of endogenously released bile, with and without concomitant administration of the bile acid‐sequestering resin, sevelamer, in patients with type 2 diabetes.

Materials and Methods

We performed a randomized, placebo‐controlled, double‐blinded cross‐over study including 15 metformin‐treated patients with type 2 diabetes. During 4 experimental study days, either sevelamer 3200 mg or placebo in combination with intravenous infusion of cholecystokinin (CCK) (0.4 pmol sulfated CCK‐8/kg/min) or saline was administered in randomized order. The primary endpoint was plasma GLP‐1 excursions as measured by incremental area under the curve. Secondary endpoints included plasma responses of glucose, triglycerides, insulin, CCK, fibroblast growth factor‐19 and 7α‐hydroxy‐4‐cholesten‐3‐one (C4). In addition, gallbladder dynamics, gastric emptying, resting energy expenditure, appetite and ad libitum food intake were assessed.

Results

CCK‐mediated gallbladder emptying was demonstrated to elicit a significant induction of GLP‐1 secretion compared to saline, whereas concomitant single‐dose administration of the bile acid sequestrant sevelamer was shown to eliminate the acute bile acid‐induced increase in plasma GLP‐1 excursions.

Conclusions

Single‐dose administration of sevelamer eliminated bile acid‐mediated GLP‐1 secretion in patients with type 2 diabetes, which could be explained by reduced bile acid stimulation of the basolaterally localized TGR5 on enteroendocrine L cells.
A spectrum of sinus of Valsalva aneurysm—From the young to the old
Authors: McGregor Pei‐Chun , Temtanakitpaisan Yutthapong , Hiltbolt Aimee , Aragam Jayashri R.
Published: August 2017

Sinus of Valsalva aneurysm (SVA) is a rare but potentially serious condition. Proper and timely diagnosis is crucial to the outcome of patients, particularly when rupture has occurred. Echocardiography is often the initial diagnostic imaging modality of choice as it is ubiquitous, relatively inexpensive, and without need for radiation or iodinated contrast administration. There are several congenital abnormalities that can appear similar to SVA on echocardiography, making the diagnosis challenging especially if providers are unfamiliar with these conditions. Here, we present a case series of three patients with SVA, representing a wide spectrum ranging from a young man presenting with acute rupture and decompensated heart failure to an elderly asymptomatic male with an incidental unruptured aneurysm. We will also present a brief literature overview and our approach to differentiating SVA from other congenital abnormalities on echocardiography.
Suicidal ideation and burnout among psychiatric trainees in Japan
Authors: Tateno Masaru , Jovanović Nikolina , Beezhold Julian , Uehara‐Aoyama Kumi , Umene‐Nakano Wakako , Nakamae Takashi , Uchida Naoki , Hashimoto Naoki , Kikuchi Saya , Wake Yosuke , Fujisawa Daisuke , Ikari Keisuke , Otsuka Kotaro , Takahashi Katsuyoshi , Okugawa Gaku , Watanabe Norio , Shirasaka Tomohiro , Kato Takahiro A.
Published: August 2017

Aim

Burnout is a psychological condition that may occur in all workers after being exposed to excessive work‐related stresses. We investigated suicidal ideation and burnout among Japanese psychiatric trainees as a part of the Burnout Syndrome Study (BoSS) International.

Methods

In the Japanese branch, 91 trainees fully completed suicide ideation and behaviour questionnaire (SIBQ) and Maslach Burnout Inventory—General Survey (MBI‐GS).

Results

Passive suicidal ideation was reported by 38.5% of Japanese trainees and 22.0% of them had experienced active suicidal ideation. The burnout rate among Japanese subjects was 40.0%. These results were worse compared to the all 1980 trainees who fully completed the main outcome measure in BoSS International, 25.9%, 20.4% and 36.7%, respectively.

Conclusions

Our results suggest a higher risk of suicide among Japanese residents. Japan has a higher suicide rate than other countries. Early detection of, and appropriate intervention for, suicidal ideation is important in preventing suicide in psychiatry residents.
Self‐Knowledge and Knowledge of Mankind in Hobbes' Leviathan
Authors: Renz Ursula
Published: August 2017

In the introduction to the Leviathan, Hobbes famously defends the anthropological point of departure of his theory of the state by invoking the Delphic injunction ‘Know thyself!’ of which he presents a peculiar reading thereafter. In this paper, I present a reading of the anthropology of the Leviathan that takes this move seriously. In appealing to Delphic injunction, Hobbes wanted to prompt a particular way of reading his anthropology for which it is crucial that the reader relate the presented anthropological views to his self‐conception. The anthropology of the Leviathan is thus a kind of manual for a certain kind of self‐reflection by which the reader's self‐knowledge is to be improved. Furthermore, I will argue that Hobbes' interpretation of the Delphic injunction illuminates several theoretical issues relevant to the epistemology of that kind of ‘self‐knowledge’ that was demanded by the Delphic injunction. While Hobbes does not solve all the epistemological problems related with the ideal appealed to by this inscription, he does provide some interesting insights into some general requirements that any epistemological account of Socratic self‐knowledge has to meet.
Elapid snake envenomation in horses: 52 cases (2006–2016)
Authors: Bamford N. J. , Sprinkle S. B. , Cudmore L. A. , Cullimore A. M. , van Eps A. W. , Verdegaal E. J. M. M. , Tennent‐Brown B. S.
Published: August 2017

Background

Snake envenomation is a cause of morbidity and mortality in domestic animals worldwide. The clinical features of crotalid snake (pit viper) envenomation are widely reported and well described in horses but elapid snake envenomation is poorly characterised.

Objectives

To describe the presentation, clinical and laboratory findings, treatment and outcome of horses with a diagnosis of elapid snake envenomation in Australia.

Study design

Retrospective case series.

Methods

Medical records of horses with a diagnosis of elapid snake envenomation (2006–2016) at several university and private veterinary practices were reviewed. Inclusion criteria comprised one or more of the following: 1) observed snakebite, 2) positive snake venom detection kit (SVDK) result, 3) appropriate clinical response to treatment with antivenom or 4) supportive post‐mortem findings.

Results

Fifty‐two cases met the inclusion criteria. Most cases (94%) demonstrated clinical signs of neurotoxicity, characterised by generalised neuromuscular weakness. Associated neurologic signs included staggering gait, muscle fasciculations, recumbency, mydriasis, ptosis and tongue paresis. Concurrent clinically important conditions included rhabdomyolysis (50%) and haemolysis (19%). Of 18 urine samples evaluated with aSVDK, only three (17%) were positive. Overall survival was favourable (86%) among 49 horses who received antivenom. Eighteen surviving horses (43%) required more than one vial of antivenom.

Main limitations

Possible cases within the searchable database were not included if horses died acutely or responded to symptomatic treatment without receiving antivenom.

Conclusions

Elapid snake envenomation is primarily a syndrome of neuromuscular weakness. Supportive anamnesis or an obvious bite site is rarely encountered. In endemic areas, this diagnosis should be considered for horses with generalised neuromuscular weakness, altered mentation, rhabdomyolysis and/or haemolysis; especially during spring and summer months. Diagnostic suspicion is best confirmed by response to treatment with antivenom.
Mast cells are critical for the limitation of thrombin‐induced skin inflammation
Authors: Suender Cathleen A. , Leist Mandy , Åbrink Magnus , Valentin Patricia , Geldmacher Astrid , Steinhoff Martin , Metz Martin , Maurer Marcus
Published: August 2017

Thrombin, a key player in coagulation, is widely held to induce and promote inflammation. As of now, the features, kinetics and control of thrombin's proinflammatory effects on the skin remain to be characterized in detail. We, therefore, injected thrombin into the ear skin of mice and observed strong, dose‐dependent and transient ear swelling responses as well as mast cell (MC) degranulation. Unexpectedly, thrombin induced even stronger, not reduced, ear swelling in MC‐deficient KitW‐sh/W‐sh mice. Prior local reconstitution of KitW‐sh/W‐sh mice with MCs inhibited this effect, indicating that MCs may contribute to the control of thrombin‐induced skin inflammation. In line with previous studies, we found that MCs express the thrombin receptors PAR1, PAR3 and PAR4, thrombin induces direct and dose‐dependent MC degranulation, and that degranulated MCs inactivate thrombin. Further findings suggested that MC‐mediated protection from thrombin‐induced inflammation is likely to rely on the effects of MC proteases. We show for the first time that MC‐deficient mice and MC protease 4‐deficient mice with normal numbers of MCs show markedly increased ear swelling in response to thrombin as compared to wild‐type mice. Taken together, these results suggest that thrombin‐induced skin inflammation is controlled, in part, by MC protease 4 released from activated MCs. For MC‐driven diseases such as chronic spontaneous urticaria, which has been linked to increased thrombin generation, this might mean that MCs may contribute to the resolution of skin inflammatory responses.