bluuebunny/crossref_metadata_2025 huggingface dataset:
“You don't want to peer over people's shoulders, it feels too rude!” The moral geographies of using participants’ personal smartphones in research
Authors: Holton Mark , Harmer Nichola
Published: April 2018

This paper examines the moralities of using participants’ personal mobile technologies in research. While smartphones bring novel benefits to research in terms of their labour‐saving, innovative, intuitive and low‐cost virtues, they also raise unique spatial, ethical and moral issues that can have implications for how research is conducted. Using morality as a conceptual tool, this paper explores the smartphone as a geographical space that is simultaneously private/public, personal/shared and material/imagined. By examining the observations made during a study which tested a mobile walking tour app, this paper questions the moral implications for, and the consequences of, researching using participants’ personal technologies and how researchers might access and interpret behaviours within these private digital “spaces.” This paper advocates the importance of recognising the complexities of moving into participants’ private digital spaces and how a diverse range of behaviours may become part of the research encounter through the ways in which participants form interactions with technologies, the environment and with each other. Finally, this paper contributes to discussions of moral geographies by examining the asymmetric power relations that are evident when examining moral behaviours that are performed simultaneously in digital and geographical spaces, and questions whether these may be functions of hegemonic systems of “acceptable” behaviour.
The other side of electronic monitoring: Ethics of care in a control‐oriented technology
Authors: Ollivon Franck
Published: April 2018

This paper aims to question the role of an ethics of care when using a technology of control such as electronic monitoring. Qualitative research based on semi‐structured interviews and ethnographic observation was conducted in two French probation services in order to understand how this alternative to imprisonment is used by State agents. It is argued that, whereas such a technology was designed to ensure an automatic and omniscient control over the probationer, the technical operation of the device leaves room for an interpersonal relationship between the probationer and probation staff. These interactions encourage judges, probation counsellors and surveillance agents to adapt the spatiotemporal frame of the surveillance and therefore make it less difficult to bear.
Staff perceptions of borderline personality disorder and recovery: A Q‐sort method approach
Authors: Dean Rebecca , Siddiqui Sara , Beesley Frank , Fox John , Berry Katherine
Published: April 2018

Objectives

This study was the first to explore how staff that work with people diagnosed with borderline personality disorder (BPD) perceive recovery in this client group. These views are important because of the crucial role that staff play in the care of people with BPD, and the challenges that staff experience with these clients.

Design

A Q methodology design was used, containing 58 statements about recovery.

Methods

Twenty‐nine mental health staff sorted recovery statements according to perceived importance to recovery in BPD.

Results

There were two different viewpoints about recovery in BPD. A medically oriented group viewed coping with symptoms and behaviours specific to BPD as being most important to recovery, whereas participants who were more well‐being oriented viewed achieving overall well‐being that was universally valued regardless of diagnosis as more important. Both groups reported that engaging in socially valued activities such as work and education was not an important aspect of recovery and that people with BPD could be considered to have recovered despite continued impairments in everyday functioning.

Conclusions

Staff perceptions of recovery in BPD can differ, which poses risks for consistent team working, a particularly important issue in this client group due to the relational difficulties associated with the diagnosis. Multidisciplinary teams working with people diagnosed with BPD therefore need to find a forum to promote a shared understanding of each patient's needs and support plans. We advocate that team formulation is a promising approach to achieve more consistent ways of working within teams.

Practitioner points

Findings

Multidisciplinary teams working with people with borderline personality disorder should use team formulations to create a shared understanding of individual patient's needs and goals for recovery, so they can deliver a consistent approach to care.

Recovery questionnaires should be used to develop an understanding of a patient's individual recovery goals.

Limitations

Opportunity sampling was utilized in recruitment, and the sample was not representative of the general population of staff working with borderline personality disorder.

Although views from a wide range of professions were sampled in this research, the views of psychiatrists were not represented.
Aberrant methylation of EYA4 promotes epithelial‐mesenchymal transition in esophageal squamous cell carcinoma
Authors: Luo Mei , Li Yuan , Shi Xuejiao , Yang Wenhui , Zhou Fang , Sun Nan , He Jie
Published: April 2018

EYA4, one of the four members of the EYA gene family, is associated with several human cancers. However, its biological functions and molecular mechanisms in the progression of cancer, particularly in esophageal squamous cell carcinoma (ESCC), remain unknown. In the present study, we found that EYA4 was underexpressed and hypermethylated in most of the ESCC cell lines tested (85.7%, 6/7). Treatment with 5‐aza‐dC and/or trichostatin A (TSA) restored EYA4 expression in ESCC cell lines, which indicates that EYA4 expression was epigenetically regulated. Similarly, EYA4 was aberrantly hypermethylated in ESCC tissues (78%, 39/50) and downregulation of EYA4 occurred in approximately 65% of primary ESCC at protein level where it was associated significantly with TNM stage and lymph node metastases. Knockdown of EYA4 in KYSE30 and KYSE70 ESCC cells using small hairpin RNA increased migration and invasive motility in vitro. Conversely, the overexpression of EYA4 in KYSE180 and KYSE450 promoted an epithelial phenotype, which consisted of decreased migration and invasion abilities and a decrease in TGF‐β1‐induced epithelial‐mesenchymal transition. Mechanistically, EYA4 overexpression reduced the phosphorylation of Akt and glycogen synthase kinase (GSK) 3β, which led to the inactivation of slug. In addition, we found that TGF‐β1 decreased EYA4 expression in both a dose‐dependent and a time‐dependent manner in KYSE30 cells, accompanied by an increase in the expression of DNA methyltransferases, especially DNMT3A. In summary, EYA4 is frequently hypermethylated in ESCC and may function as a tumor suppressor gene in the development of ESCC.
Bone fragility in Turner syndrome: Fracture prevalence and risk factors determined by a national patient survey
Authors: Wasserman Halley , Backeljauw Philippe F. , Khoury Jane C. , Kalkwarf Heidi J. , Gordon Catherine M.
Published: April 2018

Objective

Osteoporosis is considered a comorbidity of adult women with Turner syndrome (TS). Limited data are available on fracture prevalence in girls and women with this diagnosis. We aimed to determine the prevalence of fractures in individuals with TS in the United States and identify risk factors for fracture.

Design

Girls and women with TS were invited to participate in an anonymous, self‐report, national survey from November 2016 to March 2017. Non‐TS controls were obtained through direct contacts of TS participants.

Results

During childhood (0‐12 years), adolescence (13‐25 years) and young adulthood (26‐45 years), there was no difference between TS and controls in fracture prevalence. Girls and women with TS were more likely to report upper extremity fractures, whereas controls were more likely to report phalangeal fractures. Older women (>45 years) with TS were more likely to fracture than non‐TS controls (P = .01). Balance problems were more common in individuals with TS than controls (26.5% vs 14.8%, P = .0006). In TS, those reporting balance problems were 54% more likely to have a prior fracture than those without balance problems (OR=1.54, 95% CI 1.03, 2.30), even after controlling for age. There was no significant association between balance problems and fractures among controls.

Conclusions

In a nationwide survey, there was no difference in fracture prevalence in younger women with TS compared with controls. However, the location of fractures differed. After controlling for age, impaired balance was associated with an increased fracture risk in TS and may be an underrecognized risk factor for fracture in this population.
Serving clients and the community better: A mixed‐methods analysis of benefits experienced when organizations collaborate in child welfare
Authors: Colvin Marianna L. , Miller Shari E.
Published: April 2018

Data from extensive qualitative interviews (n = 67) and a survey instrument (n = 80) are used in this study to examine the perceived benefits experienced when organizations interact in community‐wide child welfare practice. Three prominent findings are organized into an evidence‐informed model detailing the benefits of collaboration whereby, (a) relationships between organizations were perceived to improve client and community services, (b) network‐level benefits were newly identified and distinguished separately, and (c) the benefits at the organizational level in a child welfare context were clarified. Fifteen overall benefits emerged, and findings have numerous implications, such as demonstrating a flaw in using any single measure of network performance. A model is presented to organize the results of this study, and findings are discussed for their relevance to policy, practice, and theory development, with particular emphasis on future directions for examining the complex interorganizational interactions in child welfare practice.
Clinical characteristics of peri‐implant mucositis and peri‐implantitis
Authors: Ramanauskaite Ausra , Becker Kathrin , Schwarz Frank
Published: April 2018

Objectives

To evaluate and correlate clinical parameters associated with peri‐implant diseases based on established case definitions.

Materials and Methods

A total of 75 patients exhibiting 269 implants (healthy: 77; peri‐implant mucositis: 77; peri‐implantitis: 115) were included in this observational study. Clinical parameters included bleeding on probing (BOP), probing depths (PDs), and suppuration (Supp).

Results

Healthy sites were associated with the absence of BOP, while mean BOP in peri‐implant mucositis and peri‐implantitis patients amounted to 20.83% and 71.33%, corresponding to 43% and 86% at the implant level (p < .001), respectively. Peri‐implantitis patients exhibited significantly higher mean PD values (4.46 mm) when compared with the peri‐implant mucositis group (2.70 mm, p < .001). Supp was limited to peri‐implantitis cases and detected in 30.16% of the patients (implant level: 17.39%). The regression model revealed a significant linear association between the number of BOP‐positive sites around the implant (minimum 0, maximum 6) and mean PD values at peri‐implant mucositis and peri‐implantitis sites at both patient and implant levels.

Conclusions

The clinical parameters investigated were shown to be associated with the severity of peri‐implant diseases.
Social license as an emergent property of political interactions: response to Kendal and Ford 2017
Authors: Garnett Stephen T. , Zander Kerstin K. , Robinson Catherine J.
Published: April 2018

Article impact statement: Recognition that conservation, like mining, needs a social license to operate can help avoid dangerous assumptions of approval.
COPD is independently associated with 6‐month survival in patients who have life support withheld in intensive care
Authors: Maamar Adel , Chevalier Stéphanie , Fillâtre Pierre , Botoc Vlad , Le Tulzo Yves , Gacouin Arnaud , Tadié Jean‐Marc
Published: April 2018

Background

In‐hospital outcomes following decisions of withholding or withdrawing in Intensive Care Unit (ICU) patients have been previously assessed, little is known about outcomes after ICU and hospital discharge. Our objective was to report the 6‐month outcomes of discharged patients who had treatment limitations in a general ICU and to identify prognostic factors of survival.

Methods

We retrospectively collected the data of patients discharged from the ICU for whom life support was withheld from 2009 to 2011. We assessed the survival status of all patients at 6 months post‐discharge and their duration of survival. Survivors and non‐survivors were compared using univariate and multivariate analyses by Cox's proportional hazard model.

Results

One hundred fourteen patients were included. The survival rate at 6 months was 58.8%. Survival was associated with acute respiratory failure (48% vs 19%, P = .006), a history of COPD (40% vs 21%, P = .03) and a lower SAPS II score (44 vs 49, P = .006). We identified a history of COPD as a prognostic factor for survival in the multivariate analysis (HR = 2.1; IC 95% 1.02‐4.36, P = .04).

Conclusion

A total of 58.8% of patients for whom life‐sustaining therapies were withheld in the ICU survived for at least 6 months after discharge. Patients with COPD appeared to have a significantly higher survival rate. The decision to withhold life support in patients should not lead to a cessation of post‐ICU care and to non‐readmission of COPD patients.
Lymphomatoid papulosis with folliculotropism, eccrinotropism and neurotropism
Authors: Ba Wei , Yang Yi , Zhang Ziyan , Wei Xuanjin , Wang Wenjuan , Zhao Zigang , Zheng Liqiang , Li Chengxin
Published: April 2018

The histopathological characteristics of lymphomatoid papulosis (LyP) vary. Currently, 6 subtypes have been reported, including a new subtype with perifollicular infiltration and different degrees of folliculotropism of CD30+ atypical lymphocytes, known as follicular LyP. However, LyP pathologically manifesting with folliculotropism, eccrinotropism and neurotropism has been rarely reported. We present a case of LyP showing CD30+ atypical lymphocytes around the hair follicle, eccrine gland and nerve fiber, with varying degrees of infiltrates. The pathological characteristics of folliculotropism and eccrinotropism are often associated with mycosis fungoides (MF). This case suggests that differential diagnosis is necessary when atypical lymphocytes infiltrate the follicle and eccrine gland. As folliculotropism and eccrinotropism can occur in both MF and LyP, it may represent a conceptual intersection between the 2 disease processes.
Diagnosis of primary peritoneal high‐grade serous carcinoma in a man by cytology
Authors: Umphress B. , Philip J. , Zhang Y. , Lin X.
Published: April 2018

Primary peritoneal serous carcinoma (PPSC) is an uncommon entity, almost exclusively diagnosed in women. In this case report, we present the clinical, radiographic, cytomorphologic, histologic and immunohistochemical (IHC) findings of a primary peritoneal high grade serous carcinoma (PPSC) in a 70‐year‐old male with a history of prostatic adenocarcinoma.
Lessons from Queensland's last‐drinks legislation: The use of extended trading permits
Authors: Zahnow Renee , Miller Peter , Coomber Kerri , de Andrade Dominique , Ferris Jason
Published: April 2018

Introduction and Aims

The association between alcohol availability, alcohol consumption and, in turn, alcohol‐related harms is well established. Policies to reduce alcohol‐related harms focus on limiting accessibility through the regulation of the liquor industry, including trading hours. On 1 July 2016, the Queensland Government introduced legislation to reduce ordinary liquor trading hours, replacing 5 am closing times with 3 am cessation of liquor sales in designated entertainment precincts and 2 am cessation of sales across the rest of the state. However, the amendment was under‐inclusive and did not apply to temporary extended trading permits, a provision of the Liquor Act 1992 allowing one‐off variations in trading hours for special events.

Design and Methods

We use 24 months of data (1 January 2015 to 31 December 2016) from the Office of Liquor Gaming and Regulation to explore patterns of extended trading permit use across Queensland, pre‐ and post‐ 1 July 2016.

Results

We find that following the Amendment in 2016 there was also a distinct shift in the utilisation of temporary extended trading permits, with a 63% increase in approved permits between 2015 and 2016. Temporal clustering around key calendar events dissipated following 1 July 2016 with consistent concentration of permit utilisation over consecutive weeks.

Discussion and Conclusions

Using temporary extended trading permits venue owners avoided earlier closing times and continued to operate until 5 am. The findings provide lessons for future policy implementation by illustrating the capacity for under‐inclusive legislation to result in the dilution of intended effects.
Population structure of caribou in an ice‐bound archipelago
Authors: Jenkins Deborah. A. , Yannic Glenn , Schaefer James A. , Conolly James , Lecomte Nicolas
Published: April 2018

Aim

Archipelagos provide ideal natural systems for testing the effects of isolation and fragmentation of habitats on the genetic makeup of populations—an important consideration, given that many insular species are of conservation concern. Two theories predominate: Island Biogeography Theory (IBT) posits that proximity to the mainland drives the potential for migrants and gene flow. The Central Marginal Hypothesis (CMH) predicts that island populations at the periphery of a species range may experience low gene flow, small population size and high rates of genetic drift. We investigated population genetic structure, genetic diversity and key drivers of diversity for Arctic island‐dwelling caribou (Rangifer tarandus). Our aim was to inform intraspecific units for conservation and decipher how IBT and CMH could act in an archipelago where isolation is highly variable due to sea ice and open water.

Location

Canadian Arctic Archipelago, Canada (Latitude, 55–82°N; Longitude, 61–123°W).

Methods

We genotyped 447 caribou at 16 microsatellite loci; these caribou represented two subspecies (R. t. groenlandicus, R. t. pearyi) and three designatable units. We used hierarchical Bayesian clustering and ordination to determine genetic groups. We evaluated the influence of ecological and geographic variables on genetic diversity using linear mixed‐effects models and compared diversity among mainland and island herds.

Results

Bayesian clustering revealed nine genetic clusters with differentiation among and within caribou subspecies. Genetic differentiation was explained predominantly by isolation‐by‐distance across all caribou, even at the scale of subspecies. Island caribou were less genetically diverse than mainland herds; individual heterozygosity was negatively correlated with distance‐to‐mainland and the extent of autumn ice‐free coastline and positively correlated with unglaciated island size.

Main conclusions

Our findings underscore the importance of hierarchical analysis when investigating genetic population structure. Genetic diversity and its key drivers lend support to both IBT and CMH and highlight the pending threat of climate change for Arctic island caribou.
Endoscopic full‐thickness resection for gastrointestinal submucosal tumors
Authors: Cai Ming‐Yan , Martin Carreras‐Presas Francisco , Zhou Ping‐Hong
Published: April 2018

Endoscopic full‐thickness resection (EFTR) is a “changing‐concept” endoscopic resection technique, which safely allows resecting deep submucosal tumors (SMTs) in the gastrointestinal (GI) wall. It's a highly promising endoscopic procedure that allows full‐thickness excision of a small piece of the complete GI wall by using only a flexible endoscope. EFTR is a meeting point between surgery and endoscopy and probably the onset of many prospective combined minimally invasive therapeutic techniques that science will explore. In this review, use of the EFTR technique for gastrointestinal SMTs is highlighted, focusing on some technical aspects, indications, contraindications and outcomes.
Comparison between endoscopic and laparoscopic removal of gastric submucosal tumor
Authors: Abe Nobutsugu , Takeuchi Hirohisa , Ohki Atsuko , Hashimoto Yoshikazu , Mori Toshiyuki , Sugiyama Masanori
Published: April 2018

Background and Aim

A retrospective study was conducted to compare two resection methods, namely, endoscopic resection (ER) procedures (endoscopic submucosal dissection [ESD], endoscopic muscularis dissection [EMD], and endoscopic full‐thickness resection [EFTR]) and laparoscopic resections (LR) (laparoscopic endoscopic cooperative surgery [LECS] and laparoscopic wedge resection).

Methods

Seventy‐three patients who underwent ER (N = 33: ESD, N = 4; EMD, N = 15; EFTR, N = 14) or LR (N = 39: LECS, N = 16; wedge resection, N = 23) for gastric submucosal tumor (G‐SMT) smaller than 50 mm were included in this study. Patient/tumor characteristics and intra/postoperative factors were compared between the ER and LR groups.

Results

The ER group had a significantly higher percentage of intraluminal growing type of tumor (100% vs 41%) and smaller tumor size (23 vs 33 mm) than the LR group. The ER group had a significantly shorter operative time (93 vs 145 min) and less blood loss (13 vs 30 mL) than the LR group. In the ER group, three patients who had tumors located on the anterior wall of the stomach required laparoscopic closure after EFTR because of difficulty in endoscopic closure of the gastric‐wall defect. Postoperative complication rates and duration of postoperative hospital stays did not differ between the two groups.

Conclusions

ER may be technically feasible, safe, less invasive, and oncologically appropriate options for selected patients with the intraluminal growing type of G‐SMT smaller than 30 mm. EFTR may be more reasonable alternatives to LR in selected patients with a small G‐SMT located on the lesser curvature side.
Age differences in the prosocial influence effect
Authors: Foulkes Lucy , Leung Jovita T , Fuhrmann Delia , Knoll Lisa J , Blakemore Sarah‐Jayne
Published: April 2018

Social influence occurs when an individual's thoughts or behaviours are affected by other people. There are significant age effects on susceptibility to social influence, typically a decline from childhood to adulthood. Most research has focused on negative aspects of social influence, such as peer influence on risky behaviour, particularly in adolescence. The current study investigated the impact of social influence on the reporting of prosocial behaviour (any act intended to help another person). In this study, 755 participants aged 8–59 completed a computerized task in which they rated how likely they would be to engage in a prosocial behaviour. Afterwards, they were told the average rating (in fact fictitious) that other participants had given to the same question, and then were asked to rate the same behaviour again. We found that participants' age affected the extent to which they were influenced by other people: children (8–11 years), young adolescents (12–14 years) and mid‐adolescents (15–18 years) all significantly changed their ratings, while young adults (19–25 years) and adults (26–59 years) did not. Across the three youngest age groups, children showed the most susceptibility to prosocial influence, changing their reporting of prosocial behaviour the most. The study provides evidence that younger people's increased susceptibility to social influence can have positive outcomes.
Estimation of soil organic carbon in arable soil in Belgium and Luxembourg with the LUCAS topsoil database
Authors: Castaldi F. , Chabrillat S. , Chartin C. , Genot V. , Jones A. R. , van Wesemael B.
Published: April 2018

Quantification of the soil organic carbon (SOC) content over large areas is mandatory to obtain accurate soil characterization and classification, which can improve site‐specific management at local or regional scales. In this context, soil spectroscopy is a well‐consolidated and widespread method to estimate soil variables, and in particular SOC content, at a low cost for routine analysis. The increasing number of large soil spectral libraries collected worldwide reflects the importance of spectroscopy in soil science. These large libraries contain soil samples derived from a large number of pedological regions and thus from different parent materials and soil types. In the light of the huge variation in the spectral responses to SOC content and composition, a rigorous process is necessary to subdivide large spectral libraries to avoid calibration with global models that fail to predict local variation in SOC content. Here, we propose to classify the European LUCAS topsoil database with a cluster analysis based on a large number of soil properties. The soil samples collected from arable land in the LUCAS database were chosen to apply a standardized multivariate calibration approach, valid for large areas, to calibrate local models without the need for further field and laboratory work. Cluster analysis detected seven soil classes and the samples belonging to each class were used to calibrate specific partial least squares regression (PLSR) models to estimate SOC content in three spectral libraries collected in Belgium and Luxembourg. Soil organic carbon was predicted with good accuracy, both within each library (root mean square error (RMSE), 1.2–5.1 g kg−1; ratio of performance to prediction (RPD), 1.41–2.24) and for the samples of the three libraries together (RMSE, 3.7 g kg−1; RPD, 2.54). The proposed approach could enable SOC to be estimated for arable soils in Europe with only the spectra of soil samples and without the need for laboratory analyses.

Highlights

We investigated the potential of the LUCAS database to estimate SOC in spectral libraries.

We proposed a routine approach to estimate SOC with less laboratory work.

The classification of the LUCAS topsoil dataset improved estimation accuracy of SOC

SOC content can be predicted from soil spectra with models calibrated on the LUCAS database.
Biochemical and biomechanical characterisation of equine cervical facet joint cartilage
Authors: O'Leary S. A. , White J. L. , Hu J. C. , Athanasiou K. A.
Published: April 2018

Background

The equine cervical facet joint is a site of significant pathology. Located bilaterally on the dorsal spine, these diarthrodial joints work in conjunction with the intervertebral disc to facilitate appropriate spinal motion. Despite the high prevalence of pathology in this joint, the facet joint is understudied and thus lacking in viable treatment options.

Objective

The goal of this study was to characterise equine facet joint cartilage and provide a comprehensive database describing the morphological, histological, biochemical and biomechanical properties of this tissue.

Study design

Descriptive cadaver studies.

Methods

A total of 132 facet joint surfaces were harvested from the cervical spines of six skeletally mature horses (11 surfaces per animal) for compiling biomechanical and biochemical properties of hyaline cartilage of the equine cervical facet joints. Gross morphometric measurements and histological staining were performed on facet joint cartilage. Creep indentation and uniaxial strain‐to‐failure testing were used to determine the biomechanical compressive and tensile properties. Biochemical assays included quantification of total collagen, sulfated glycosaminoglycan andDNAcontent.

Results

The facet joint surfaces were ovoid in shape with a flat articular surface. Histological analyses highlighted structures akin to articular cartilage of other synovial joints. In general, biomechanical and biochemical properties did not differ significantly between the inferior and superior joint surfaces as well as among spinal levels. Interestingly, compressive and tensile properties of cervical facet articular cartilage were lower than those of articular cartilage from other previously characterised equine joints. Removal of the superficial zone reduced the tissue's tensile strength, suggesting that this zone is important for the tensile integrity of the tissue.

Main limitations

Facet surfaces were sampled at a single, central location and do not capture the potential topographic variation in cartilage properties.

Conclusions

This is the first study to report the properties of equine cervical facet joint cartilage and may serve as the foundation for the development of future tissue‐engineered replacements as well as other treatment strategies.
The FGF‐23/klotho axis and its relationship with phosphorus, calcium, vitamin D, PTH, aldosterone, severity of disease, and outcome in hospitalised foals
Authors: Kamr A. M. , Dembek K. A. , Hildreth B. E. , Morresey P. R. , Rathgeber R. A. , Burns T. A. , Zaghawa A. A. , Toribio R. E.
Published: April 2018

Background

Fibroblast growth factor‐23 (FGF‐23) and klotho are key regulators of vitamin D and parathyroid hormone (PTH) synthesis as well as phosphorus and calcium homeostasis; however, information on the FGF‐23/klotho axis in healthy and hospitalised foals is lacking.

Objectives

The aims of this study were to measure serum FGF‐23 and klotho concentrations and determine their association with serum phosphorus, total calcium (TCa), vitamin D metabolite [25(OH)D, 1,25(OH)2D], PTH, and aldosterone concentrations, disease severity, and mortality in hospitalised foals.

Study design

Prospective, multicentre, cross‐sectional study.

Methods

A total of 91 foals ≤72 h old were classified as hospitalised (n = 81; 58 septic; 23 sick non‐septic [SNS]) and healthy (n = 10). Blood samples were collected on admission. Hormone concentrations were determined by immunoassays.

Results

Serum FGF‐23, PTH, phosphorus, and aldosterone concentrations were higher while klotho, 25(OH)D, 1,25(OH)2D, and TCa concentrations were lower in septic and SNS compared to healthy foals (P<0.05). In hospitalised and septic foals, increased FGF‐23 and aldosterone concentrations were associated with high phosphorus and PTH but not with TCa and vitamin D metabolite concentrations. Hospitalised foals with the highest FGF‐23 and lowest klotho concentrations were more likely to die (odds ratio (OR): 3.3; 95% confidence interval (CI): 1.1–10.3 and OR: 3.1; CI: 1.1–8.0, respectively).

Main limitations

Blood gas, ionised calcium, blood culture information not being available for many foals, and use of the sepsis score to classify hospitalised foals.

Conclusions

Imbalances in the FGF‐23/klotho axis may contribute to mineral dyshomeostasis and disease progression in critically ill foals. Elevated FGF‐23 and reduced klotho, together with high phosphorus and PTH concentrations suggests FGF‐23 resistance. FGF‐23 and klotho are good markers of disease severity and likelihood of mortality in hospitalised foals. Aldosterone may influence phosphorus and PTH dynamics in hospitalised foals. Routine measurement of phosphorus concentrations in sick foals is recommended.
Descriptive vs mechanistic scientific approach to study wound healing and its inhibition: Is there a value of translational research involving human subjects?
Authors: Pastar Irena , Wong Lulu L. , Egger Andjela N. , Tomic‐Canic Marjana
Published: April 2018

The clinical field of wound healing is challenged by numerous hurdles. Not only are wound‐healing disorders complex and multifactorial, but the corresponding patient population is diverse, often elderly and burdened by multiple comorbidities such as diabetes and cardiovascular disease. The care of such patients requires a dedicated, multidisciplinary team of physicians, surgeons, nurses and scientists. In spite of the critical clinical need, it has been over 15 years since a treatment received approval for efficacy by the FDA in the United States. Among the reasons contributing to this lack of effective new treatment modalities is poor understanding of mechanisms that inhibit healing in patients. Additionally, preclinical models do not fully reflect the disease complexity of the human condition, which brings us to a paradox: if we are to use a “mechanistic” approach that favours animal models, we can dissect specific mechanisms using advanced genetic, molecular and cellular technologies, with the caveat that it may not be directly applicable to patients. Traditionally, scientific review panels, for either grant funding or manuscript publication purposes, favour such “mechanistic” approaches whereby human tissue analyses, deemed “descriptive” science, are characterized as a “fishing expedition” and are considered “fatally flawed.” However, more emerging evidence supports the notion that the use of human samples provides significant new knowledge regarding the molecular and cellular mechanisms that control wound healing and contribute to inhibition of the process in patients. Here, we discuss the advances, benefits and challenges of translational research in wound healing focusing on human subject research.
Structural and molecular dynamics studies of a C1‐oxidizing lytic polysaccharide monooxygenase from Heterobasidion irregulare reveal amino acids important for substrate recognition
Authors: Liu Bing , Kognole Abhishek A. , Wu Miao , Westereng Bjørge , Crowley Michael F. , Kim Seonah , Dimarogona Maria , Payne Christina M. , Sandgren Mats
Published: April 2018

Lytic polysaccharide monooxygenases (LPMOs) are a group of recently discovered enzymes that play important roles in the decomposition of recalcitrant polysaccharides. Here, we report the biochemical, structural, and computational characterization of an LPMO from the white‐rot fungus Heterobasidion irregulare (HiLPMO9B). This enzyme oxidizes cellulose at the C1 carbon of glycosidic linkages. The crystal structure of HiLPMO9B was determined at 2.1 Å resolution using X‐ray crystallography. Unlike the majority of the currently available C1‐specific LPMO structures, the HiLPMO9B structure contains an extended L2 loop, connecting β‐strands β2 and β3 of the β‐sandwich structure. Molecular dynamics (MD) simulations suggest roles for both aromatic and acidic residues in the substrate binding of HiLPMO9B, with the main contribution from the residues located on the extended region of the L2 loop (Tyr20) and the LC loop (Asp205, Tyr207, and Glu210). Asp205 and Glu210 were found to be involved in the hydrogen bonding with the hydroxyl group of the C6 carbon of glucose moieties directly or via a water molecule. Two different binding orientations were observed over the course of the MD simulations. In each orientation, the active‐site copper of this LPMO preferentially skewed toward the pyranose C1 of the glycosidic linkage over the targeted glycosidic bond. This study provides additional insight into cellulose binding by C1‐specific LPMOs, giving a molecular‐level picture of active site substrate interactions.

Database

The atomic coordinates and structure factors for HiLPMO9B have been deposited in the Protein Data Bank with accession code 5NNS.
Spatial extent of analysis influences observed patterns of population genetic structure in a widespread darter species (Percidae)
Authors: Argentina Jane E. , Angermeier Paul L. , Hallerman Eric M. , Welsh Stuart A.
Published: April 2018

Connectivity among stream fish populations allows for exchange of genetic material and helps maintain genetic diversity, adaptive potential and population stability over time. Changes in species demographics and population connectivity have the potential to permanently alter the genetic patterns of stream fish, although these changes through space and time are variable and understudied in small‐bodied freshwater fish.

As a spatially widespread, common species of benthic freshwater fish, the variegate darter (Etheostoma variatum) is a model species for documenting how patterns of genetic structure and diversity respond to increasing isolation due to large dams and how scale of study may shape our understanding of these patterns. We sampled variegate darters from 34 sites across their range in the North American Ohio River basin and examined how patterns of genetic structure and diversity within and between populations responded to historical population changes and dams within and between populations.

Spatial scale and configuration of genetic structure varied across the eight identified populations, from tributaries within a watershed, to a single watershed, to multiple watersheds that encompass Ohio River mainstem habitats. This multiwatershed pattern of population structuring suggests genetic dispersal across large distances was and may continue to be common, although some populations remain isolated despite no apparent structural dispersal barriers. Populations with low effective population sizes and evidence of past population bottlenecks showed low allelic richness, but diversity patterns were not related to watershed size, a surrogate for habitat availability. Pairwise genetic differentiation (FST) increased with fluvial distance and was related to both historic and contemporary processes. Genetic diversity changes were influenced by underlying population size and stability, and while instream barriers were not strong determinants of genetic structuring or loss of genetic diversity, they reduce population connectivity and may impact long‐term population persistence.

The broad spatial scale of this study demonstrated the large spatial extent of some variegate darter populations and indicated that dispersal is more extensive than expected given the movement patterns typically observed for small‐bodied, benthic fish. Dam impacts depended on underlying population size and stability, with larger populations more resilient to genetic drift and allelic richness loss than smaller populations.

Other darters that inhabit large river habitats may show similar patterns in landscape‐scale studies, and large river barriers may impact populations of small‐bodied fish more than previously expected. Estimation of dispersal rates and behaviours is critical to conservation of imperilled riverine species such as darters.
Polygenic risk for psychiatric disorders correlates with executive function in typical development
Authors: Schork A.J. , Brown T.T. , Hagler D.J. , Thompson W.K. , Chen C.‐H. , Dale A.M. , Jernigan T.L. , Akshoomoff N. ,   for the Pediatric Imaging, Neurocognition and Genetics Study
Published: April 2018

Executive functions are a diverse and critical suite of cognitive abilities that are often disrupted in individuals with psychiatric disorders. Despite their moderate to high heritability, little is known about the molecular genetic factors that contribute to variability in executive functions and how these factors may be related to those that predispose to psychiatric disorders. We examined the relationship between polygenic risk scores built from large genome‐wide association studies of psychiatric disorders and executive functioning in typically developing children. In our discovery sample (N = 417), consistent with previous reports on general cognitive abilities, polygenic risk for autism spectrum disorder was associated with better performance on the Dimensional Change Card Sort test from the NIH Cognition Toolbox, with the largest effect in the youngest children. Polygenic risk for major depressive disorder was associated with poorer performance on the Flanker test in the same sample. This second association replicated for performance on the Penn Conditional Exclusion Test in an independent cohort (N = 3681). Our results suggest that the molecular genetic factors contributing to variability in executive function during typical development are at least partially overlapping with those associated with psychiatric disorders, although larger studies and further replication are needed.
A global climate niche for giant trees
Authors: Scheffer Marten , Xu Chi , Hantson Stijn , Holmgren Milena , Los Sietse O. , van Nes Egbert H.
Published: April 2018

Rainforests are among the most charismatic as well as the most endangered ecosystems of the world. However, although the effects of climate change on tropical forests resilience is a focus of intense research, the conditions for their equally impressive temperate counterparts remain poorly understood, and it remains unclear whether tropical and temperate rainforests have fundamental similarities or not. Here we use new global data from high precision laser altimetry equipment on satellites to reveal for the first time that across climate zones ‘giant forests’ are a distinct and universal phenomenon, reflected in a separate mode of canopy height (~40 m) worldwide. Occurrence of these giant forests (cutoff height > 25 m) is negatively correlated with variability in rainfall and temperature. We also demonstrate that their distribution is sharply limited to situations with a mean annual precipitation above a threshold of 1,500 mm that is surprisingly universal across tropical and temperate climates. The total area with such precipitation levels is projected to increase by ~4 million km2 globally. Our results thus imply that strategic management could in principle facilitate the expansion of giant forests, securing critically endangered biodiversity as well as carbon storage in selected regions.
High‐grade PanIN presenting with localised stricture of the main pancreatic duct: A clinicopathological and molecular study of 10 cases suggests a clue for the early detection of pancreatic cancer
Authors: Yokode Masataka , Akita Masayuki , Fujikura Kohei , Kim Mi‐Ju , Morinaga Yukiko , Yoshikawa Seiichi , Terada Takuro , Matsukiyo Hiroshi , Tajiri Takuma , Abe‐Suzuki Shiho , Itoh Tomoo , Hong Seung‐Mo , Zen Yoh
Published: April 2018

Aims

This study aimed to identify the pathological features of high‐grade PanIN that presents with imaging‐detectable abnormalities.

Methods and results

Ten cases of isolated, main‐duct, high‐grade PanIN as the primary clinical presentation were identified. All patients presented with stenosis of the main pancreatic duct, with two being associated with extensive upstream duct dilatation (>5 mm in diameter). Pancreatic juice cytology suggested adenocarcinoma in all seven cases examined. In resected specimens, high‐grade PanIN was present chiefly in the main pancreatic duct, with longitudinal extension ranging between 3 and 40 mm in length (median = 18 mm). In four cases, in which hypoechoic or hypovascular masses were observed on imaging, radiopathology correlations suggested that they represented parenchymal atrophy and subsequent fibrosis around affected ducts, but not invasive malignancy. On immunohistochemistry, the loss of p16 expression was found in five (50%), p53 overexpression in two (20%) and loss of SMAD4 expression in none (0%). KRAS mutations were detected in nine cases, with two dominant clones being found in three by ultrasensitive droplet digital polymerase chain reaction, suggesting the genetic heterogeneity of dysplastic cells composing individual lesions. Mutant GNAS was also observed in one case.

Conclusions

Isolated high‐grade PanIN may present with pancreatic duct stenosis. Therefore, intensive investigations including pancreatic juice cytology will be required for patients with unexplained pancreatic duct stenosis. The abnormal expression of p53 and SMAD4 is infrequent, while GNAS may be mutated in premalignant lesions mainly affecting the main pancreatic duct, similar to KRAS.
DICER1 hot‐spot mutations in ovarian gynandroblastoma
Authors: Wang Yemin , Karnezis Anthony N , Magrill Jamie , Tessier‐Cloutier Basile , Lum Amy , Senz Janine , Gilks C Blake , McCluggage W Glenn , Huntsman David G , Kommoss Friedrich
Published: April 2018

Aims

Gynandroblastoma is a rare ovarian sex cord‐stromal tumour characterised by the presence of both male (Sertoli and/or Leydig cells) and female (granulosa cells) components. We investigated the mutational status of DICER1, FOXL2 and AKT1 genes at hot‐spot regions that are known to be the key driving events in the development of Sertoli–Leydig cell tumour (SLCT), adult granulosa cell tumour (aGCT) and juvenile granulosa cell tumour (jGCT), respectively, to gain insights into the molecular pathogenesis of gynandroblastoma.

Methods and results

Sixteen cases of gynandroblastoma were studied. All contained SLCT or Sertoli cell tumour components. aGCT and jGCT components were identified in seven and 10 cases, respectively, with one presenting both components. Heterozygous hot‐spot mutations in the RNase IIIb domain of DICER1 were discovered in three cases, including one case with heterologous mucinous elements, all of which were composed of moderately or poorly differentiated SLCT and jGCT components, and harboured the mutations in both histological components. None of the 16 cases displayed mutations at the p.C134W (c.402C→G) of FOXL2 or within the pleckstrin‐homology domain of AKT1. All cases showed FOXL2 immunostaining in both male and female components.

Conclusion

DICER1 hot‐spot mutation is the key‐driving event in a subset of gynandroblastomas containing components of SLCT and jGCT. Gynandroblastomas composed of SLCT and jGCT may represent morphological variants of SLCT. The molecular basis of gynandroblastoma containing a component of aGCT is different from pure aGCT.
Geochemical and geochronological studies of the Muong Hum alkaline granitic pluton from the Phan Si Pan Zone, northwest Vietnam: Implications for petrogenesis and tectonic setting
Authors: Minh Pham , Hieu Pham T. , Hoang Nguyen K.
Published: April 2018

The Phan Si Pan zone in northwest Vietnam is an important tectonic unit for understanding the geological evolution of the southeast Asian Block. Numerous late Permian A‐type granites outcrop in this zone. In this study, new geochemical and geochronological data derived from the Muong Hum alkaline granitic pluton in the Phan Si Pan zone were investigated for its petrogenesis and tectonic setting. Zircon U–Pb analyses of three samples yielded 206Pb/238U ages of (251.1 ±3.5) Ma, (251.2 ±3.8) Ma, and (253.9 ±1.5) Ma, respectively, coinciding with the ages of the acid member of magma from Emeishan large igneous province, southwest China. The Muong Hum granite has 10 000 × Ga/Al and A/CNK values of 4.70–4.93 and 0.87–0.90, respectively, as well as negative Eu anomalies. It shows significant depletion of Ba, Sr, Ti, and P, similar to features of A‐type granite. Zircons have positive εHf(t) values (+1.9 to +8.6) and Hf model ages (TDM1) of 595–846 Ma, originating a mantle source. Compared with the Panzhihua A‐type granite of the southwest China domain and other A‐type plutons of the Phan Si Pan zone, including Ye Yen Sun, Phu Sa Phin, Nam Xe, Tam Duong Phan Si Pan, and Taihe, the geochemical characteristics and zircon Hf isotopic compositions of the Muong Hum granite demonstrate an affinity of mantle magma. It is believed that the Phan Si Pan zone is an important part of Emeishan large igneous province. It was reworked by the Cenozoic Aillaoshan‐Red River shear fault to its present location.