bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuous vital sign monitoring after major abdominal surgery—Quantification of micro events
Authors: Duus C. L. , Aasvang E. K. , Olsen R. M. , Sørensen H. B. D. , Jørgensen L. N. , Achiam M. P. , Meyhoff C. S.
Published: July 2018

Introduction

Millions of patients undergo major abdominal surgery worldwide each year, and the post‐operative phase carries a high risk of respiratory and circulatory complications. Standard ward observation of patients includes vital sign registration at regular intervals. Patients may deteriorate between measurements, and this may be detected by continuous monitoring. The aim of this study was to compare the number of micro events detected by continuous monitoring to those documented by the widely used standardized Early Warning Score (EWS).

Methods

Fifty patients were continuously monitored with peripheral arterial oxygen saturation (SpO2), heart rate (HR), and respiratory rate (RR) the first 4 days after major abdominal cancer surgery. EWS was monitored as routine practice. Number and duration of events were analyzed using Fisher's exact test and Wilcoxon rank sum test.

Results

Continuous monitoring detected a SpO2 <92% in 98% of patients vs 16% of patients detected by EWS (P < .0001). Micro events of SpO2 <92% lasting longer than 60 minutes were found in 58% of patients by continuous monitoring vs 16% by the EWS (P < .0001). Fifty‐two percent of patients had micro events of SpO2 <85% lasting longer than 10 minutes. Continuous monitoring found tachycardia in 60% of patients vs 6% by the EWS. Frequency of events for bradycardia, tachypnea, and bradypnea showed similar patterns.

Conclusion

Very low SpO2 and tachycardia in post‐operative patients are common and under‐diagnosed by the EWS. Continuous monitoring can discover these micro events and potentially contribute to earlier detection and, potentially, result in prevention of clinical complications.
Aging and Alzheimer’s disease: Comparison and associations from molecular to system level
Authors: Xia Xian , Jiang Quanlong , McDermott Joseph , Han Jing‐Dong J.
Published: July 2018

Alzheimer's disease is the most prevalent cause of dementia, which is defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality proposed by the original amyloid hypothesis. Aging is the main risk factor for Alzheimer's disease that cannot be explained by amyloid hypothesis. To evaluate how aging and Alzheimer's disease are intrinsically interwoven with each other, we review and summarize evidence from molecular, cellular, and system level. In particular, we focus on study designs, treatments, or interventions in Alzheimer's disease that could also be insightful in aging and vice versa.
Non‐Destructive Survey of Early Roman Copper‐Alloy Brooches using Portable X‐ray Fluorescence Spectrometry
Authors: Roxburgh M. A. , Heeren S. , Huisman D. J. , Van Os B. J. H.
Published: July 2018

This paper argues that portable X‐ray fluorescence spectrometry (pXRF) is a suitable elemental measurement technique to study the production of copper‐alloy artefacts. However, rather than try to imitate the accuracy and precision of laboratory techniques, it is more beneficial to deploy it in a survey role, one that attempts to model chronological and geographical changes within large quantities of artefacts. To achieve this, it was investigated to what extent corrosion and the issues surrounding surface measurements affect the potential of this type of research. Analyses on early Roman period brooches gathered in the Nijmegen region of the Netherlands were subsequently compared with published data.
From Alloy Composition to Alloying Practice: Chinese Bronzes
Authors: Pollard A. M. , Liu R. , Rawson J. , Tang X.
Published: July 2018

We propose a new methodology based on standard statistical processes for displaying and rigorously comparing the alloy composition of archaeological bronze alloys. Although traditional approaches using visual comparisons of histograms of alloying elements in an assemblage of archaeological objects are adequate for observing differences between these distributions, we argue that differences in sample size cannot be adequately accounted for without using a statistical approach. We demonstrate this methodology by comparing the alloy composition of bronzes from the sequence of Bronze Age cultures in Central China—Erlitou, Erligang (Zhengzhou, or early Shang), Anyang (late Shang) and Western Zhou. We suggest that this approach allows the identification and rigorous comparison of ‘regional alloying practices’, which in turn enables us to link the alloy composition of the objects with the intentions and skills of foundry workers.
Haploidentical haematopoietic stem cell transplantation for thalassaemia major based on an FBCA conditioning regimen
Authors: Sun Qixin , Wu Bingyi , Lan Hekui , Meng Fanyi , Ma Xiaoxiao , Chen Xinxin , Huang Zhiwei , Yao Qianqian , Xu Jianhui , Huang Yuxian , Wu Shaojie , Zhu Zhigang
Published: July 2018

Allogeneic haematopoietic stem cell transplantation (HSCT) is the only available curative therapy for patients with thalassaemia major. With the progress in human leucocyte antigen (HLA) antigen typing technology and supportive care, the outcomes of thalassaemia major have greatly improved in recent years, even in high‐risk patients. However, the problem of finding a suitable donor is still a major obstacle to curing these patients. In recent decades, the lack of available HSCT donors has led to the increased use of haploidentical donors (HDs) for HSCT in haematological malignancies. Recently, we explored the effect of HD HSCT to eight children with thalassaemia major based on the FBCA conditioning regimen (fludarabine, busulphan, cyclophosphamide, antithymocyte globulin), which is usually used in leukaemia patients receiving haploidentical HSCT in our centre. So far, all of the transplanted patients have a stable engraftment and are transfusion independent in daily life. This encouraging result has revised our previous conception about haploidentical HCST for thalassaemia major and strongly suggests that HD HSCT is a feasible and safe method for thalassaemia major patients.
An attempt to incorporate effect of direct interaction between a ligand and explicit water molecules into MM/3D‐RISM
Authors: Gohda Keigo
Published: July 2018

Endpoint methods using continuum‐solvent models are widely used to estimate protein–ligand affinity. A recently developed method, MM/3D‐RISM, estimates the solvation energy using statistical mechanics by 3D‐RISM. This method is theoretically expected to accurately describe solvation effects and to also be less dependent on protein–ligand systems. In this study, we examined the performance of MM/3D‐RISM for a set of α‐thrombin inhibitors with a non‐congeneric series of ligands, containing three diverse chemical scaffolds. The standard MM/3D‐RISM showed a weak correlation (R2 = 0.191) but correctly estimated affinity for two of the three scaffolds. However, the simplest inhibitor, benzamidine, was not ranked appropriately. From visual inspection of inhibitor‐binding modes, an attempt was made to incorporate the direct interaction between a ligand and water molecules into MM/3D‐RISM. A model (Model‐1) dealing with directly interacting water molecules (Wat) as an independent component of a protein (R)–ligand (L) complex‐formation, that is, R + L + Wat → R–L–Wat, showed a better linearity (R2 = 0.422) than that of the standard MM/3D‐RISM model and achieved a good ranking of all three scaffolds of α‐thrombin inhibitors. Additionally, an attempt was made to model avidin–biotin system with a congeneric series of inhibitors, and results showed that both the standard MM/3D‐RISM model (R2 = 0.839) and Model‐1 (R2 = 0.695) satisfactorily estimated the affinity.
Fluoride intake and cortical and trabecular bone characteristics in adolescents at age 17: A prospective cohort study
Authors: Oweis Reem Reda , Levy Steven M. , Eichenberger‐Gilmore Julie M. , Warren John J. , Burns Trudy L. , Janz Kathleen F. , Torner James C. , Saha Punam K. , Letuchy Elena
Published: July 2018

Objective

To investigate the associations between period‐specific and cumulative fluoride (F) intakes from birth to age 17 years, and radial and tibial bone measures obtained using peripheral quantitative computed tomography (pQCT).

Methods

Participants (n = 380) were recruited from hospitals at birth and continued their participation in the ongoing Iowa Fluoride Study/Iowa Bone Development Study until age 17. Fluoride intakes from water, other beverages, selected foods, dietary fluoride supplements and dentifrice were determined every 1.5‐6 months using detailed questionnaires. Associations between F intake and bone measures (cortical and trabecular bone mineral content [BMC], density and strength) were determined in bivariate and multivariable analyses adjusted for height, weight, maturity offset, physical activity, and daily calcium and protein intake using robust regression analysis.

Results

Fluoride intake ranged from 0.7 to 0.8 mg F/d for females and from 0.7 to 0.9 mg F/d for males. Spearman correlations between daily F intake and pQCT bone measures were weak. For females, Spearman correlations ranged from r = −.08 to .21, and for males, they ranged from r = −.03 to .30. In sex‐specific, height‐, weight‐ and maturity offset‐ partially adjusted regression analyses, associations between females’ fluoride intake and bone characteristics were almost all negative; associations for males were mostly positive. In the fully adjusted models, which also included physical activity, and protein and calcium intakes, no significant associations were detected for females; significant positive associations were detected between F intake from 14 to 17 years and tibial cortical bone content (β = 21.40, P < .01) and torsion strength (β = 175.06, P < .01) for males.

Conclusion

In this cohort of 17‐year‐old adolescents, mostly living in optimally fluoridated areas, lifelong F intake from combined sources was weakly associated with bone pQCT measures.
Why less complexity produces better forecasts: an independent data evaluation of kelp habitat models
Authors: Gregr Edward J. , Palacios Daniel M. , Thompson Allison , Chan Kai M. A.
Published: July 2018

Understanding how species are distributed in the environment is increasingly important for natural resource management, particularly for keystone and habitat – forming species, and those of conservation concern. Habitat suitability models are fundamental to developing this understanding; however their use in management continues to be limited due to often‐vague model objectives and inadequate evaluation methods. Along the Northeast Pacific coast, canopy kelps (Macrocystis pyrifera and Nereocystis luetkeana) provide biogenic habitat and considerable primary production to nearshore ecosystems. We investigated the distribution of these species by examining a series of increasingly complex habitat suitability models ranging from process‐based models based on species’ ecology to complex generalised additive models applied to purpose‐collected survey data. Seeking empirical limits to model complexity, we explored the relationship between model complexity and forecast skill, measured using both cross‐validation and independent data evaluation. Our analysis confirmed the importance of predictors used in models of coastal kelp distributions developed elsewhere (i.e. depth, bottom type, bottom slope, and exposure); it also identified additional important factors including salinity, and potential interactions between exposure and salinity, and slope and tidal energy. Comparative results showed how cross‐validation can lead to over‐fitting, while independent data evaluation clearly identified the appropriate model complexity for generating habitat forecasts. Our results also illustrate that, depending on the evaluation data, predictions from simpler models can out‐perform those from more complex models. Collectively, the insights from evaluating multiple models with multiple data sets contribute to the holistic assessment of model forecast skill. The continued development of methods and metrics for evaluating model forecasts with independent data, and the explicit consideration of model objectives and assumptions, promise to increase the utility of model forecasts to decision makers.
A common environment experiment reveals plastic and genetic contributions to the fast life‐history strategy of an invasive fish
Authors: Rooke Anna C. , Fox Michael G.
Published: July 2018

Invasive species often exhibit a suite of life‐history traits that promote rapid population growth, including early age and small size at maturation, and high reproductive investment. The common expression of these “fast” life‐history traits in invasive populations could be the result of plastic and/or genetic responses to the non‐native environment, or in response to the process of range expansion. To determine the relative importance of plastic and genetic contributions to the expression of life‐history traits, we reared two native Canadian and two invasive Spanish populations of Pumpkinseed sunfish (Lepomis gibbosus) in a common environment in central Ontario, Canada. In the wild, European Pumpkinseed tend to exhibit faster juvenile growth rates, younger age and smaller size at maturity, and higher reproductive investment than native North American populations. When reared in a common environment, both native and invasive populations exhibited similar juvenile growth rates, and similar age and size at maturity, suggesting that the differences seen among wild populations are a plastic response to the warmer non‐native environment. However, reproductive investment was consistently higher in the Spanish populations regardless of rearing environment, suggesting a genetic difference in reproductive investment between native and invasive populations. Selection for greater reproductive investment in non‐native Pumpkinseed may have contributed to their widespread success in Europe.
Quantifying trophic interactions and niche sizes of juvenile fishes in an invaded riverine cyprinid fish community
Authors: Gutmann Roberts Catherine , Britton J. Robert
Published: July 2018

Quantifying feeding interactions between nonindigenous and indigenous fishes in invaded fish communities is important for determining how introduced species integrate into native food webs. Here, the trophic interactions of invasive 0+ European barbelBarbus barbus(L.) and the three other principal 0+ fishes in the community,Squalius cephalus(L.),Leuciscus leuciscus(L.) andPhoxinus phoxinus(L.), were investigated in the River Teme, a River Severn tributary in Western England.B. barbushas been present in the River Teme for approximately 40 years. Analyses of stomach contents from samples collected from three sites between June and September 2015 revealed that, overall, fishes displayed a generalist feeding strategy, with most prey having low frequency of selection. Relationships of diet composition versus body length and gape height were species‐specific, with increasing dietary specialisms apparent as the 0+ fishes increased in length and gape height. The trophic niche size of invasiveB. barbuswas always significantly smaller thanS. cephalusandL. leuciscusand was significantly smaller thanP. phoxinusat two sites. This was primarily due to differences in the functional morphology of the fishes; 0+B. barbuswere generally restricted to foraging on the benthos, whereas the other fishes were able to forage on prey present throughout the water column. Nevertheless, the invasiveB. barbuswere exploiting very similar prey items to populations in their native range, suggesting these invaders were strongly pre‐adapted to the River Teme and this arguably facilitated their establishment and invasion.
Trophic ecology of speckled peacock bass Cichla temensis Humboldt 1821 in the middle Negro River, Amazon, Brazil
Authors: Aguiar‐Santos Jamerson , deHart Pieter A. P. , Pouilly Marc , Freitas Carlos E. C. , Siqueira‐Souza Flávia K.
Published: July 2018

The aim of this study was to analyse the trophic ecology of speckled peacock bass Cichla temensis inhabiting two tributaries of the middle Negro River, the Aracá River and the Demeni River. Using an analysis of stomach contents and stable isotope composition (δ15N, δ13C) of scales, we describe the diet and evaluate the trophic position of subadult and adult individuals. We then test whether diet shifts and trophic positions occurred among successive size classes and among sample locations. The stomach content analysis confirmed the piscivorous feeding habit of the species and showed that the speckled peacock bass preyed on a variety species belonging to different trophic guilds. The length of the ingested prey increased with the size of the speckled peacock bass. Diet composition and trophic position were not different among size classes. δ13C values yielded significant shifts among the size classes: larger individuals displayed higher δ13C values than smaller individuals. Trophic position varied between locations, with lowest values observed in fish from the Aracá River. This study demonstrated that diet of C. temensis may vary according to the size of the fish, even at the subadult or adult stages, and according to the river/locality, even within a same basin. We then suggest that further studies take into account local availability of food resources to better explore C. temensis diet and tropic ecology.
Integrating threshold concepts with reflective practice: Discussing a theory‐based approach for curriculum refinement in dental education
Authors: Hyde S. , Flatau A. , Wilson D.
Published: July 2018

Introduction

The theory of threshold concepts (TCs) is a burgeoning area of educational research and curriculum reform. This study describes and reviews the TCs literature, describes the differences between TCs and threshold learning outcomes (TLOs) and seeks to promote discussion on using an integrated reflective practice approach to facilitate the translation of TCs into fulfilment of TLOs. A worked example is included in this study to explore the challenges inherent in this task but also the learning gains to be made for both staff and students in this endeavour.

Intersection of reflective clinical practice and threshold concepts

Reflection is intrinsic to all aspects of learning and is a vital characteristic of developing competence in the health professions. Further, the need for explicit teaching and assessment of reflection in health professions education is recognised. We suggest that the identification of TCs can help to scaffold reflective processes in dentistry and argue that TCs may achieve a bridging function between theory and practice when used in conjunction with reflective writing and dialogue. This study provides a discussion of the complexities and challenges involved as well as an explicit example of the process involved for 1 TC in 1 particular discipline—removable prosthodontics.

Discussion

Reflective practice is recognised by the authors as a pedagogical tool to support the acquisition of threshold concepts. An example is provided of integrating reflective practice tasks with identified TCs in curricula which shows the potential of reflective dialogue and discourse as vehicles to make TCs explicit as well as facilitate the attainment of threshold learning outcomes or graduate attributes. This is an ongoing process, and although the fully revised curriculum is not ready to be translated to other contexts, we suggest it is beneficial to start working towards the integration of reflective practice tasks and identified TLOs as part of curriculum refinement—rather than adding to a crowded curriculum. We suggest such an integrated approach can harness the challenges inherent in discipline‐specific contexts to bridge the theory‐practice nexus for students and permit staff greater flexibility in the teaching and assessment of such traditionally difficult areas.

We propose a way of thinking about curriculum change by integrating threshold concepts with the explicit use and assessment of reflective practice tasks as a means to achieve threshold learning outcomes and professional attributes identified by accrediting bodies. We provide an overview of the literature in this area and an example of our approach in linking reflective practice with newly identified threshold concepts in our School. We welcome further discussion, debate and collaboration in this area.
Tree cricket baffles are manufactured tools
Authors: Mhatre Natasha
Published: July 2018

Tree crickets use sound to attract mates and make acoustic baffles to increase their sound production efficiency. It has been recently discovered that these insects use a flexible yet inherited behavioural programme to make acoustically optimal baffles. Whether these baffles qualify as tools, however, remains controversial. Here, baffle‐using and baffle‐making behaviours are analysed using the most current and authoritative definition of tool use. The current definition of tool use does not require the tool to be detached from the substrate and includes attached but manipulable external objects. Given this schema, tree cricket baffles, which are attached but manipulated prior to use, must be considered tools. The mode of manufacture for a baffle is “Subtract,” and the mode of use is “Drape”.
FAM83G/Fam83g genetic variants affect canine and murine hair formation
Authors: Balmer Pierre , Fellay Auxanne K. , Sayar Beyza S. , Hariton William V. J. , Wiener Dominique J. , Galichet Arnaud , Müller Eliane J. , Roosje Petra J.
Published: July 2018

FAM83G/Fam83g genetic variants have been described in dogs, mice and recently also in humans. They are associated with palmoplantar keratoderma and altered hair or coat phenotype, reported as wooly phenotype in mice. FAM83G/Fam83g is an unexplored effector of temporally and spatially coordinated Wnt and BMP signalling which are key pathways in pre‐ and postnatal hair follicle morphogenesis and differentiation. The aim of this study was to unravel phenotypic consequences of FAM83G/Fam83g variants on hair coat formation in dogs and mice. Our results show differences in hair types and hair shaft structures in both species. Additionally, mice exhibit deregulated hair cycle progression which timely correlates with defective Wnt signalling (Axin2) and Bmp2/4 expression. These results affirm the involvement of FAM83G in hair morphogenesis, hair follicle differentiation and cycling.
Drivers of postfire soil organic carbon accumulation in the boreal forest
Authors: Andrieux Benjamin , Beguin Julien , Bergeron Yves , Grondin Pierre , Paré David
Published: July 2018

The accumulation of soil carbon (C) is regulated by a complex interplay between abiotic and biotic factors. Our study aimed to identify the main drivers of soil C accumulation in the boreal forest of eastern North America. Ecosystem C pools were measured in 72 sites of fire origin that burned 2–314 years ago over a vast region with a range of ∆ mean annual temperature of 3°C and one of ∆ 500 mm total precipitation. We used a set of multivariate a priori causal hypotheses to test the influence of time since fire (TSF), climate, soil physico‐chemistry and bryophyte dominance on forest soil organic C accumulation. Integrating the direct and indirect effects among abiotic and biotic variables explained as much as 50% of the full model variability. The main direct drivers of soil C stocks were: TSF >bryophyte dominance of the FH layer and metal oxide content >pH of the mineral soil. Only climate parameters related to water availability contributed significantly to explaining soil C stock variation. Importantly, climate was found to affect FH layer and mineral soil C stocks indirectly through its effects on bryophyte dominance and organo‐metal complexation, respectively. Soil texture had no influence on soil C stocks. Soil C stocks increased both in the FH layer and mineral soil with TSF and this effect was linked to a decrease in pH with TSF in mineral soil. TSF thus appears to be an important factor of soil development and of C sequestration in mineral soil through its influence on soil chemistry. Overall, this work highlights that integrating the complex interplay between the main drivers of soil C stocks into mechanistic models of C dynamics could improve our ability to assess C stocks and better anticipate the response of the boreal forest to global change.
Dynamic responses of tree‐ring growth to multiple dimensions of drought
Authors: Gao Shan , Liu Ruishun , Zhou Tao , Fang Wei , Yi Chuixiang , Lu Ruijie , Zhao Xiang , Luo Hui
Published: July 2018

Droughts, which are characterized by multiple dimensions including frequency, duration, severity, and onset timing, can impact tree stem radial growth profoundly. Different dimensions of drought influence tree stem radial growth independently or jointly, which makes the development of accurate predictions a formidable challenge. Measurement‐based tree‐ring data have obvious advantages for studying the drought responses of trees. Here, we explored the use of abundant tree‐ring records for quantifying regional response patterns to key dimensions of drought. Specifically, we designed a series of regional‐scaled “natural experiments,” based on 357 tree‐ring chronologies from Southwest USA and location‐matched monthly water balance anomalies, to reveal how tree‐ring responds to each dimension of drought. Our results showed that tree‐ring was affected significantly more by the water balance condition in the current hydrological year than that in the prior hydrological year. Within the current hydrological year, increased drought frequency (number of dry months) and duration (maximum number of consecutive dry months) resulted in “cumulative effects” which amplified the impacts of drought on trees and reduced the drought resistance of trees. Drought events that occurred in the pregrowing seasons strongly affected subsequent tree stem radial growth. Both the onset timing and severity of drought increased “legacy effects” on tree stem radial growth, which reduced the drought resilience of trees. These results indicated that the drought impact on trees is a dynamic process: even when the total water deficits are the same, differences among the drought processes could lead to considerably different responses from trees. This study thus provides a conceptual framework and probabilistic patterns of tree‐ring growth response to multiple dimensions of drought regimes, which in turn may have a wide range of implications for predictions, uncertainty assessment, and forest management.
Acceleration of global vegetation greenup from combined effects of climate change and human land management
Authors: Wang Lanhui , Tian Feng , Wang Yuhang , Wu Zhendong , Schurgers Guy , Fensholt Rasmus
Published: July 2018

Global warming and human land management have greatly influenced vegetation growth through both changes in spring phenology and photosynthetic primary production. This will presumably impact the velocity of vegetation greenup (Vgreenup, the daily rate of changes in vegetation productivity during greenup period), yet little is currently known about the spatio‐temporal patterns of Vgreenup of global vegetation. Here, we define Vgreenup as the ratio of the amplitude of greenup (Agreenup) to the duration of greenup (Dgreenup) and derive global Vgreenup from 34‐year satellite leaf area index (LAI) observations to study spatio‐temporal dynamics of Vgreenup at the global, hemispheric, and ecosystem scales. We find that 19.9% of the pixels analyzed (n = 1,175,453) experienced significant trends toward higher greenup rates by an average of 0.018 m2 m−2 day−1 for 1982–2015 as compared to 8.6% of pixels with significant negative trends (p < 0.05). Global distribution and dynamics of Vgreenup show high spatial heterogeneity and ecosystem‐specific patterns, which is primarily determined by the high spatial variation in Agreenup, while the temporal dynamics of Vgreenup are directly controlled by both changes in Dgreenup and Agreenup. Areas with the largest Vgreenup and largest positive trends are both observed in deciduous and mixed forests as compared to nonforest ecosystems showing both lower Vgreenup and trends. For nonforest ecosystems, human‐managed ecosystems (e.g., rangelands and rainfed croplands) exhibited higher Vgreenup and positive trends than those of natural counterparts, suggesting strong imprints of human land management on terrestrial ecosystem functioning. Globally, warming has accelerated Vgreenup in temperature‐constrained high latitude forest ecosystems and arctic regions, but decelerated Vgreenup in temperate and arid/semiarid areas. These results suggest that the combined effects of climate change and human land management have greatly accelerated global vegetation greenup, with important implications for changes in terrestrial ecosystem functioning and global carbon cycling.
High‐resolution, Quantitative Element Imaging of an Upper Crust, Low‐angle Cataclasite (Zuccale Fault, Northern Apennines) by Laser Ablation ICP Time‐of‐Flight Mass Spectrometry
Authors: Gundlach‐Graham Alexander , Garofalo Paolo S. , Schwarz Gunnar , Redi Daniele , Günther Detlef
Published: July 2018

Laser ablation inductively coupled plasma time‐of‐flight mass spectrometry (LA‐ICP‐ToF‐MS) was used to generate quantitative elemental images of a mineralogically and texturally complex fault rock of the Northern Apennines of Italy (Zuccale Fault, eastern Island of Elba). Using LA‐ICP‐ToF‐MS combined with a low‐dispersion LA cell, we were able to generate large format (4 mm × 2 mm), high‐resolution (5 μm), high dynamic range (1–106 μg g−1) and quantitative multi‐elemental two‐dimensional compositional maps within a data acquisition time of a few hours. To quantify element mass fractions across the heterogeneous sample of the Zuccale Fault, we used a 100% species‐mass normalisation approach that took into account different mineral phases across the specimen. To assign mineral phase directly from LA‐ICP‐ToF‐MS data, we exploited the segregation of sulfur and calcium between distinct phases to threshold element images and develop mineral‐phase‐specific masks. Moreover, we demonstrate agreement between elemental mass fractions determined by LA‐ICP‐ToF‐MS imaging with 100% normalisation quantification and conventional LA‐ICP‐MS analysis with internal standard element‐based quantification. Finally, we discuss how this elemental imaging provides unique insights into the genesis of the Zuccale Fault.
MicroRNA‐137‐mediated Src oncogenic signaling promotes cancer progression
Authors: Kokuda Rie , Watanabe Risayo , Okuzaki Daisuke , Akamatsu Hiroki , Oneyama Chitose
Published: July 2018

The tyrosine kinase c‐Src is frequently overexpressed and activated in a wide variety of human cancers. However, the molecular mechanisms responsible for the upregulation of c‐Src remain elusive. To examine whether microRNA‐mediated c‐Src upregulation promotes cancer progression, we screened miRNAs with complementarity to the 3′‐UTR of c‐Src mRNA. Among these miRNAs, down‐regulation of miR‐137 was tightly associated with c‐Src‐mediated tumor progression of human colon cancer cells/tissues. Re‐expression of miR‐137 in human colon cancer cells suppressed tumor growth and caused the disruption of focal contacts, suppression of cell adhesion, and invasion, although restoration of c‐Src in miR‐137‐treated cells could not fully rescue the tumor‐suppressive effect of miR‐137. We found that miR‐137 targets AKT2 and paxillin also and miR‐137‐mediated regulation of c‐Src /AKT2 is crucial for controlling tumor growth, whereas that of c‐Src/paxillin contributes to malignancy. miR‐137 suppressed Src‐related oncogenic signaling and changed the expression of miRNAs that are regulated by Src activation. miR‐137 controls the expression of c‐Src/AKT2/paxillin and synergistically suppresses Src oncogenic signaling evoked from focal adhesions. In various human cancers that harbor c‐Src upregulation, the dysfunction of this novel mechanism would serve as a critical trigger for tumor progression.
BAY 94‐9027, a PEGylated recombinant factor VIII, exhibits a prolonged half‐life and higher area under the curve in patients with severe haemophilia A: Comprehensive pharmacokinetic assessment from clinical studies
Authors: Shah A. , Coyle T. , Lalezari S. , Fischer K. , Kohlstaedde B. , Delesen H. , Radke S. , Michaels L. A.
Published: July 2018

Introduction

Recombinant factor VIII (rFVIII) products with extended half‐lives, such as BAY 94‐9027, can potentially maintain higher FVIII levels for longer periods of time, thus providing improved bleeding protection vs standard‐acting FVIII products.

Aim

To characterize the pharmacokinetic (PK) profile of BAY 94‐9027 from phase 1, phase 2/3 (PROTECT VIII) and phase 3 (PROTECT VIII Kids) clinical trials in adults, adolescents and children with severe haemophilia A

Methods

Patients with severe haemophilia A (FVIII <1%) with >50 FVIII exposure days (EDs) and no history of inhibitors were included in the phase 1 (18–65 years, ≥150 EDs), PROTECT VIII (12–65 years, ≥150 EDs) and PROTECT VIII Kids (<12 years, >50 EDs) trials. PK parameters were assessed following a 25‐IU/kg or 60‐IU/kg BAY 94‐9027 dose in the phase 1 study after the first and repeated infusion, in PROTECT VIII after the first and repeated 60‐IU/kg infusion and in PROTECT VIII Kids after a single 60‐IU/kg infusion. The chromogenic assay was used to assess FVIII activity.

Results

Compared with sucrose‐formulated rFVIII, BAY 94‐9027 had reduced clearance that resulted in a ~1.4‐fold increase in half‐life and dose‐normalized area under the curve (AUC). The BAY 94‐9027 PK profile was comparable after single‐ and repeated‐dose administrations. Dose‐proportional increases were observed between 25‐ and 60‐IU/kg administrations. BAY 94‐9027 PK characteristics were age dependent, consistent with other FVIII products.

Conclusions

BAY 94‐9027 shows an extended half‐life and increased AUC vs standard‐acting FVIII products. These PK characteristics will result in higher FVIII levels for longer duration.
Barriers and facilitators to implementing a process to enable parent escalation of care for the deteriorating child in hospital
Authors: Gill Fenella J. , Leslie Gavin D. , Marshall Andrea P.
Published: July 2018

Objective

To identify barriers and facilitators to implementing a parent escalation of care process: Calling for Help (C4H).

Design

Audits, semi‐structured interviews and focus groups guided by the Theoretical Domains Framework.

Setting

Australian paediatric hospital where a parent escalation of care process was introduced in the previous 6 months.

Participants

Four children, 13 parents, 91 nurses and doctors including Medical Emergency Team (MET) members.

Main outcome measures

Parent awareness and involvement in escalating care and factors impacting implementation of C4H.

Results

Two audits identified low level of parent awareness (16/88, 19% and 5/85, 6%). Parent involvement in escalation of care was documented in 11/62 (18%) events. The main facilitators included uniformly positive views that C4H was in the child's best interest, acknowledgement that parents had skills to recognize deterioration and would take action. C4H was considered to add to patient safety and being reviewed by the MET was a patient benefit. Key barriers were the low level of awareness, doubt about parent capabilities, concern about parents’ information overload, anticipated overuse of resources, staff unease about possible repercussions and anticipated difficulty for parents to question staff with potential negative effects on parent‐staff relationships. Overall C4H presents a challenge to traditional hospital hierarchy and culture.

Conclusions

Although there was a low level of awareness about C4H in practice, there was in‐principle support for the concept. Initial strategies had primarily targeted policy change without taking into account the need for practice and organizational behaviour changes. Using a theoretical approach to identify key factors will enable a targeted approach to implementation.
Superb Lyrebird Menura novaehollandiae mycophagy, truffles and soil disturbance
Authors: Elliott Todd F. , Vernes Karl
Published: July 2018

We observed foraging behaviour and collected 18 faecal samples of Superb Lyrebirds Menura novaehollandiae at two National Park locations in high‐elevation Nothofagus forests in the New England Tablelands of New South Wales, Australia. Based on microscopic examination of faecal samples, we provide the first report of mycophagy by this bird species. We hypothesize that this association is representative of a much more widespread relation between ground‐foraging birds and fungi. We apply methods not typically used by ornithologists to demonstrate the potential prevalence of mycophagy among ground‐foraging birds and its possible nutritional value. We additionally show the ecological significance that this and associated bird–fungus interactions have in the dispersal of symbiotic fungi.
The Rufous‐thighed KiteHarpagus diodonis not an endemic breeder of the Atlantic Forest: lessons to assess Wallacean shortfalls
Authors: Areta Juan I. , Juhant Matías A.
Published: July 2018

The migratory Rufous‐thighed KiteHarpagus diodonis widely distributed in South America, and a recent spatiotemporal analysis of its distribution that was largely based on citizen science data concluded that it breeds (almost) exclusively in the Atlantic Forest, constituting a ‘hidden endemism’, and that it is a complete migrant, overwintering in the eastern Amazonian lowlands. However, that study missed key data from large areas that would have resulted in a different biogeographical pattern. Here, we reject the ‘hidden endemism’ hypothesis and show that the Rufous‐thighed Kite is a more widespread breeder. We propose that to uncover Wallacean shortfalls of migratory birds correctly, (1) citizen science data must be integrated with thorough bibliographical searches and specimen examination and (2) life‐cycle categories should be critically determined: failing to recognize the importance of these two key issues can undermine the ability of researchers to uncover the true extent of breeding ranges and timing of migration, resulting in erroneous ecogeographical patterns. By proposing and following a set of recommendations, and using previously unpublished and published documented records mostly from the southwestern portion of the distribution of Rufous‐thighed Kite, we here show that this species breeds in the Cerrado of eastern Bolivia and is present during the austral spring and summer in the Austral Yungas but largely absent during the austral autumn and winter, mirroring the seasonality of the species in the Atlantic Forest.
Differences in semen characteristics between patients with testicular cancer and other malignancies using various cut‐off values
Authors: Hamano Itsuto , Hatakeyama Shingo , Nakamura Rika , Fukuhara Rie , Noro Daisuke , Tanaka Toshikazu , Yoneyama Tohru , Yamamoto Hayato , Yoneyama Takahiro , Hashimoto Yasuhiro , Koie Takuya , Yokoyama Yoshihito , Ohyama Chikara
Published: July 2018

Objectives

To compare semen parameters between patients with testicular cancer and other malignancies using various cut‐off values, and to evaluate the correlation between semen parameters and intracytoplasmic sperm injection outcomes.

Methods

We retrospectively investigated semen parameters before cancer treatment in 117 patients with malignancies who cryopreserved sperm at Hirosaki University Hospital between November 1999 and May 2016. We compared semen parameters between patients with testicular cancer and other malignancies (non‐testicular cancer), seminoma and non‐seminoma, and stage I testicular cancer and stage II/III testicular cancer. The assessment of cut‐off values recommended by the World Health Organization and the total motile sperm count was carried out between the testicular cancer and non‐testicular cancer groups. The intracytoplasmic sperm injection outcomes in those using preserved sperm were assessed.

Results

Of the 111 patients enrolled, 29 (26%) had testicular cancer and 82 (74%) had non‐testicular cancer. Patients with testicular cancer showed significantly lower total sperm concentration than non‐testicular cancer patients. The cut‐off value of total sperm concentration distinguished the patient proportions exceeding the cut‐off between patients with testicular cancer (41%) and non‐testicular cancer (66%). The comparison between patients with seminoma versus non‐seminoma and stage I versus stage II/III testicular cancer presented no significant differences in semen parameters. No correlation between pretreatment semen parameters and intracytoplasmic sperm injection outcomes was observed.

Conclusions

Although testicular cancer patients show lower total sperm concentration, intracytoplasmic sperm injection outcomes are acceptable. Further studies on the fertility potential of testicular cancer patients are warranted.
Wage Gap Paradox: The Case of Immigrants from the FSU in Israel
Authors: Kushnirovich Nonna
Published: July 2018

The purpose of this article was to investigate whether some groups of immigrants are particularly disadvantaged in their earnings compared to other population groups, to what extent wage gaps arise from discriminatory remuneration, and how immigrants’ wages change over time. The contribution of this study is twofold: it conceptualizes a wage gap paradox and delineates the indicators of discrimination in terms of earnings. Data from the 2010‐2014 Social Surveys in Israel were used. The results revealed evidence of a wage gap paradox for immigrants from the former Soviet Union: the wage gaps between them and other population groups do not close during time living in the host country, despite the high level of their formal credentials. Applying the Blinder‐Oaxaca decomposition, the study revealed that a sufficient part of the wage gap is attributable to discrimination, which prevented immigrants from full economic integration.
Macrophage targeting: opening new possibilities for cancer immunotherapy
Authors: Cassetta Luca , Kitamura Takanori
Published: July 2018

Tumour‐infiltrating immune cells regulate tumour development and progression either negatively or positively. For example, cytotoxic lymphocytes (CTL) such as CD8+ T and natural killer (NK) cells can recognize and eliminate cancer cells, and thereby restrict the tumour growth and metastasis, if they exert full cytotoxicity. In contrast, tumour‐infiltrating myeloid cells such as tumour‐associated macrophages (TAM) promote the expansion and dissemination of cancer cells depending on their functional states. Given the tumour‐killing ability of CTL, the augmentation of CTL‐induced antitumour immune reactions has been considered as an attractive therapeutic modality for lethal solid tumours and several promising strategies have emerged, which include immune checkpoint inhibitors, cancer vaccines and adoptive CTL transfer. These immunotherapies are now tested in clinical trials and have shown significant antitumour effects in patients with lymphoma and some solid tumours such as melanoma and lung cancer. Despite these encouraging results, these therapies are not efficient in a certain fraction of patients and tumour types with tumour cell‐intrinsic mechanisms such as impaired antigen presentation and/or tumour cell‐extrinsic mechanisms including the accumulation of immunosuppressive cells. Several animal studies suggest that tumour‐infiltrating myeloid cells, especially TAM, are one of the key targets to improve the efficacy of immunotherapies as these cells can suppress the functions of CD8+ T and NK cells. In this review, we will summarize recent animal studies regarding the involvement of TAM in the immune checkpoint, cancer vaccination and adoptive CTL transfer therapies, and discuss the therapeutic potential of TAM targeting to improve the immunotherapies.
‘Hiding in plain sight’: Exploring the complexity of sexual safety within an acute mental health setting
Authors: McGarry Julie
Published: July 2018

It is increasingly being recognized that individuals who access acute mental health services are at risk of sexual assault. Assaults may be perpetrated by other patients but also by staff working in mental health environments, although this latter group remain largely under‐researched. Following a reported professional sexual assault and review of an acute inpatient mental health setting in the UK, the overall aim of this study was to explore the mechanisms and structures that were put into place following the investigation and in so doing examine the wider questions of sexual safety in acute mental health settings. A qualitative approach was utilized and involved interviews with clinical staff (n = 8). Thematic analysis was used to analyse the data resulting in four main themes: ‘Feeling betrayed’: The relational context of the ward environment’; ‘Doing what we were meant to be doing’: Quality of leadership’; ‘Covering yourself’: Safeguarding practice; ‘The subtleties of abuse’: Complexities of safeguarding ‘. The findings of the study highlight the need for clear organizational structures of support, a clearer understanding of ‘sexual safety’, and education and training which explicitly addresses recognition and complexity of sexual violence.
Development and applicability of a tool for identification of people with intellectual disabilities in need of palliative care (PALLI)
Authors: Vrijmoeth Cis , Echteld Michael A. , Assendelft Pim , Christians Milou , Festen Dederieke , van Schrojenstein Lantman‐de Valk Henny , Vissers Kris , Groot Marieke
Published: July 2018

Background

Timely identifying people with intellectual disabilities in need of palliative care is important. Therefore, we developed PALLI: a screening tool for deteriorating health, indicative of a limited life expectancy. Here, we aimed to describe development of PALLI and to explore its applicability.

Method

We used a five‐stage mixed‐methods procedure to develop PALLI based on knowledge from practice. For exploring applicability, professionals caring for people with intellectual disabilities completed PALLI for 185 people with intellectual disabilities and provided information on applicability after 5–6 months.

Results

The final version of PALLI included 39 questions relevant for people with intellectual disabilities. Applicability was adequate: Most professionals found PALLI relevant and reported no ambiguous questions. Added value of PALLI was reflecting on and becoming aware of the process of decline in health.

Conclusions

PALLI shows promising applicability and has potential as a tool for timely identifying people with intellectual disabilities who may benefit from palliative care.
Factors associated with leucism in the common blackbird Turdus merula
Authors: Izquierdo Lucía , Thomson Robert L. , Aguirre José I. , Díez‐Fernández Alazne , Faivre Bruno , Figuerola Jordi , Ibáñez‐Álamo Juan Diego
Published: July 2018

Leucism is the total or partial lack of melanins in the skin and associate structures (i.e. hair or feathers). Little is known about the factors influencing this chromatic aberration although some local studies suggest that there is an effect of habitat, age and sex. To test these hypotheses and expand our knowledge on leucism, we carried out a large‐scale study using common blackbirds Turdus merula as our model species. Given the poor information available on this topic and the variability of methodological approaches, we used three different methods to assess the effect of these variables in the presence of leucism: transects, bird captures and citizen science information (pictures from internet). We found an effect of habitat indicating that there are more leucistic blackbirds in cities than in non‐urban areas. In addition, we found a positive association between presence of white feathers and age providing the first large‐scale support for the progressive graying hypothesis in birds. This chromatic aberration was also influenced by sex, with males showing higher probability of leucism than females, although only for the capture data, indicating that the method used to study this phenomenon can partly influence our conclusions, and therefore suggesting caution when planning future studies in this topic.