bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of changed paradigms in CRE research – a systematic literature review 2005-2015
Authors: Jylhä Tuuli , Remøy Hilde , Arkesteijn Monique
Published: March 2019

Purpose

As corporations change their way of working, the importance of corporate real estate (CRE) management has increased. Hence, there is a need to structure the existing knowledge and to identify the latest developments in CRE research. This paper aims to identify the major developments and changed paradigms in CRE research in 2005-2015.

Design/methodology/approach

A systematic literature review is conducted, including papers from seven journals. In three sequential scans, papers were identified for the final analysis, keeping 99 of 1,667 papers.

Findings

Based on nine identified developments, two paradigm shifts were found. The shift from cost minimisation to value delivery was identified. Besides solving current problems, value delivery aims to capture the future value and prevent future problems. The second paradigm shift is from buildings to people. Before the shift, buildings refer to value delivery as a transaction, while the shift to people highlights the aim to provide value-in-use.

Research limitations/implications

This paper focusses on corporate offices, excluding retail, health care, education, publicly owned facilities, etc. This research is limited to CRE research. Therefore, the results are applicable to CRE research but do not cover the developments in practice.

Practical implications

For practitioners, this paper offers a possibility to develop their RE strategies by reflecting their current practices with the identified developments and paradigms in the CRE literature. This paper suggests to conduct a similar research in practice to compare the underlying paradigms.

Originality/value

This paper is based on a systematic literature study, and summarises developments in CRE research over the past 10 years.
Medicare expenditures attributable to dementia
Authors: White Lindsay , Fishman Paul , Basu Anirban , Crane Paul K. , Larson Eric B. , Coe Norma B.
Published: March 2019

Objective

To estimate dementia's incremental cost to the traditional Medicare program.

Data Sources

Health and Retirement Study (HRS) survey‐linked Medicare part A and B claims from 1991 to 2012.

Study Design

We compared Medicare expenditures for 60 months following a claims‐based dementia diagnosis to those for a randomly selected, matched comparison group.

Data Collection/Extraction Methods

We used a cost estimator that accounts for differential survival between individuals with and without dementia and decomposes incremental costs into survival and cost intensity components.

Principal Findings

Dementia's five‐year incremental cost to the traditional Medicare program is approximately $15 700 per patient, nearly half of which is incurred in the first year after diagnosis. Shorter survival with dementia mitigates the incremental cost by about $2650. Increased costs for individuals with dementia were driven by more intensive use of Medicare part A covered services. The incremental cost of dementia was about $7850 higher for females than for males because of sex‐specific differential mortality associated with dementia.

Conclusions

Dementia's cost to the traditional Medicare program is significant. Interventions that target early identification of dementia and preventable inpatient and post‐acute care services could produce substantial savings.
Financial Gatekeepers and Investor Protection: Evidence from Criminal Background Checks
Authors: LAW KELVIN K. F. , MILLS LILLIAN F.
Published: March 2019

We examine whether financial advisors with pre‐advisor criminal records pose a greater risk to investors than those without. We find that financial advisors with pre‐advisor criminal records are more likely to receive future customer complaints. Their complaints are more likely to receive arbitration awards or settlements and are more likely to involve large settlements exceeding $100,000. Finally, clients are more likely to suffer service disruptions from engaging advisors with pre‐advisor criminal records, even incremental to the brokerage firm being high‐risk. Although we do not have performance data of individual advisors, mutual funds of those firms that employ advisors with criminal records do not provide their clients with superior returns nor charge lower fees, suggesting that there are not compensating benefits to offset the investor harm. Overall, pre‐advisor criminal record serves as an important ex ante characteristic available to regulators, investors, and employers for risk‐assessment purposes.
Functional analysis of a miRNA‐like small RNA derived from Bombyx mori cytoplasmic polyhedrosis virus
Authors: Guo Jian‐Yong , Wang Yong‐Sheng , Chen Tian , Jiang Xiao‐Xu , Wu Ping , Geng Tao , Pan Zhong‐Hua , Shang Meng‐Ke , Hou Cheng‐Xiang , Gao Kun , Guo Xi‐Jie
Published: March 2019

Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) is a major pathogen of the economic insect silkworm, Bombyx mori. Virus‐encoded microRNAs (miRNAs) have been proven to play important roles in host–pathogen interactions. In this study we identified a BmCPV‐derived miRNA‐like 21 nt small RNA, BmCPV‐miR‐1, from the small RNA deep sequencing of BmCPV‐infected silkworm larvae by stem‐loop quantitative real‐time PCR (qPCR) and investigated its functions with qPCR and lentiviral expression systems. Bombyx mori inhibitor of apoptosis protein (BmIAP) gene was predicted by both target prediction software miRanda and Targetscan to be one of its target genes with a binding site for BmCPV‐miR‐1 at the 5′ untranslated region. It was found that the expression of BmCPV‐miR‐1 and its target gene BmIAP were both up‐regulated in BmCPV‐infected larvae. At the same time, it was confirmed that BmCPV‐miR‐1 could up‐regulate the expression of BmIAP gene in HEK293T cells with lentiviral expression systems and in BmN cells by transfecting mimics. Furthermore, BmCPV‐miR‐1 mimics could up‐regulate the expression level of BmIAP gene in midgut and fat body in the silkworm. In the midgut of BmCPV‐infected larvae, BmCPV‐miR‐1 mimics could be further up‐regulated and inhibitors could lower the virus‐mediated expression of BmIAP gene. With the viral genomic RNA segments S1 and S10 as indicators, BmCPV‐miR‐1 mimics could up‐regulate and inhibitors down‐regulate their replication in the infected silkworm. These results implied that BmCPV‐miR‐1 could inhibit cell apoptosis in the infected silkworm through up‐regulating BmIAP expression, providing the virus with a better cell circumstance for its replication.
Improving nutrition care for neurosurgery patients through a nurse‐led transition feeding protocol
Authors: Dux Claire , Lim Shu‐Chuin , Jeffree Rosalind , Heaydon Sandra , de Jersey Susan
Published: March 2019

Aim

Neurosurgical patients often transition from enteral nutrition (EN) to oral nutrition (ON) as they recover. Implementing a nurse‐led feeding protocol to guide this transition may improve consistency of nutrition care and dietitian workload efficiency. This pragmatic study aimed to evaluate the effect of such a protocol on these outcomes and on nurses’ nutrition care attitudes, practices and knowledge.

Methods

Data were collected retrospectively for 1 year pre‐ and prospectively for 1 year post‐implementation of the transition feeding protocol (TFP). Participants who transitioned from EN to ON were included in the study. Post‐implementation nurses in the neurosurgery ward were invited to complete a self‐administered questionnaire to investigate attitudes, practices and knowledge.

Results

One hundred and thirteen participants, 55 pre‐ and 58 post‐implementation, took part in the study. Significantly more patients received transition feeding (TF) post‐implementation (58% vs 93%, P < 0.001), there was a statistically significant improvement in the commencement of TF (0 vs 1 day after ON clearance; P = 0.029), and all patients consumed adequate oral intake 1‐week post‐EN cessation (92.3% vs 100%, P = 0.078). There was no difference in dietetic occasions of service post‐implementation (2 vs 1.5; P = 0.204). A 38% survey response rate from nursing staff (n = 15) was achieved. More nurses were found to be initiating TF (P < 0.001) and a majority reported a perceived increase in knowledge and confidence in providing nutrition support.

Conclusions

A TFP can optimise the transition from EN to ON by improving consistency and commencement of TF and nurses’ confidence and knowledge in overall nutrition care.
Association of plant development to organic matter and fungal presence in soils of horticultural crops
Authors: Marín‐Guirao Jose Ignacio , de Cara‐García Miguel , Crisol‐Martínez Eduardo , Gómez‐Tenorio Miguel Ángel , García‐Raya Pablo , Tello‐Marquina Julio César
Published: March 2019

Soil microbial communities are a crucial link between soil nutrient availability and plant productivity. They particularly depend on soil organic matter (SOM) content, which is considered one of the main components of soil fertility. But agricultural intensification and the increase in the use of fertilisers of mineral origin in recent decades (to the detriment of the incorporation of organic materials in agricultural soils) have resulted in a continuous loss of agricultural soil quality and fertility, which is considered one of the greatest challenges to addressing global food security. Therefore, a better understanding of the mechanisms driving soil improvement via soil microbiota could result in a sustainable improvement in crop yields. Soils were sampled in 40 intensively managed greenhouses in southeast Spain to understand how SOM influences soil fungal community and how both these factors influence plant development. The values of three out of four growth‐related variables (plant height, aerial dry weight and leaf area, but not root dry weight) in both tomato and cucumber plants showed a positive relation with SOM content and soil fungal diversity. This study concludes that SOM is key for the maintenance of soil fertility in intensive horticulture and that it is linked to the composition and diversity of soil fungal community. Both SOM and soil fungal communities should be considered as essential factors in achieving high soil fertility, and ultimately, to ensure an optimum crop development.
Has GnRH a direct role in AMH regulation?
Authors: van Helden Josef , Evliyaoglu Osman , Weiskirchen Ralf
Published: March 2019

Objective

Anti‐Mullerian hormone (AMH) together with luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) plays crucial roles in gonadal functions. However, the possible effects of GnRH on AMH via the hypothalamic‐pituitary‐gonadal (HPG) axis remain unexplored. We aimed to explore the changes in AMH levels after bolus GnRH stimulation and understand the relationship of AMH with FSH and LH in healthy subjects.

Methods

Thirty‐one prepubertal children (15 males/16 females) and 78 adults (36 males/42 females) were included. We collected basal (0 minute) samples for determining levels of hormones. After GnRH treatment at a dose of 2.5 μg/kg body weight (maximum of 100 μg/kg body weight) intravenously, blood was collected at 30 minutes intervals for 120 minutes. Serum LH, FSH and AMH were measured by electrochemiluminometric assays.

Results

After injection of GnRH, AMH levels were significantly decreased in 30 minutes (P < 0.001) in all groups with parallel increase of FSH and LH. In the second 30 minutes, all hormones levels reversed. There was also a moderate correlation between AMH and FSH (r = −0.430, P < 0.001).

Conclusions

GnRH lowers serum AMH levels, which have a negative correlation with the increase in gonadotrophins. These data pinpoint GnRH as an important factor of the AMH regulation, leading new opportunities for the understanding of AMH role in reproductive function and dysfunction.
Evaluation of outcomes in renal transplantation with hypothermic machine perfusion for the preservation of kidneys from expanded criteria donors
Authors: Savoye Emilie , Macher Marie‐Alice , Videcoq Michel , Gatault Philippe , Hazzan Marc , Abboud Imad , Thierry Antoine , Bertrand Dominique , Drouin Sarah , Sayegh Johnny , Barrou Benoit , Badet Lionel , Bastien Olivier , Huot Olivier , Lamotte Christian , Logerot Hélène , Legeai Camille , Antoine Corinne
Published: March 2019

In 2012, an expert working group from the French Transplant Health Authority recommended the use of hypothermic machine perfusion (HMP) to improve kidney preservation and transplant outcomes from expanded criteria donors, deceased after brain death. This study compares HMP and cold storage (CS) effects on delayed graft function (DGF) and transplant outcomes. We identified 4,316 kidney transplants from expanded criteria donors (2011‐2014) in France through the French Transplant Registry. DGF occurrence was analyzed with a logistic regression, excluding preemptive transplants. One‐year graft failure was analyzed with a Cox regression. A subpopulation of 66 paired kidneys was identified: one preserved by HMP and the other by CS from the same donor. Kidneys preserved by HMP (801) vs CS (3515) were associated with more frequent recipient comorbidities and older donors and recipients. HMP had a protective effect against DGF (24% in HMP group and 38% in CS group, OR = 0.49 [0.40‐0.60]). Results were similar in the paired kidneys (OR = 0.23 [0.04‐0.57]). HMP use decreased risk for 1‐year graft failure (HR = 0.77 [0.60‐0.99]). Initial hospital stays were shorter in the HMP group (P < 0.001). Our results confirm the reduction in DGF occurrence among expanded criteria donors kidneys preserved by HMP.
A novel classification system for research reporting in rare and progressive genetic conditions
Authors: van Karnebeek Clara D M , Beumer Daniël , Pawliuk Colleen , Goez Helly , Mostafavi Sara , Andrews Gail , Steele Rose , Siden Harold
Published: March 2019

Aim

To create a classification system for severe, rare, and progressive genetic conditions for use in research reporting.

Method

A modified Delphi consensus technique was used to create and reach agreement on a new system of condition categories. Interrater reliability was tested via two rounds of an online survey whereby physicians classified a subset of conditions using our novel system. Overall percentage agreement and agreement above chance were calculated using Fleiss’ kappa (κ).

Results

Eleven physicians completed the first Delphi, with an overall agreement of 76.4%, the κ value was 0.57 (95% confidence interval 0.51–0.63), indicating moderate agreement (0.41–0.60) above chance. Based on the first survey several categories were described in more detail. The second survey confirmed a classification system with 12 categories, with an overall percentage agreement among the participants of 82.6%. The overall mean κ value was 0.71 (95% confidence interval 0.65–0.77), indicating substantial agreement (0.61–0.80).

Interpretation

Our new system was useful in categorizing a broad range of rare childhood diseases and may be applicable to other rare disease studies; further validation in larger cohorts is required.

What this paper adds

This novel 12‐category classification system can be used in research reporting in rare and progressive genetic conditions.
Evaluation of early myocardial dysfunction with strain echocardiography in chronic hepatitis B patients
Authors: Özdemir Emre , Demirdal Tuna , Emren Sadık Volkan , Tokaç Mehmet
Published: March 2019

Introduction

It is well known that chronic hepatitis B virus infection (CHBV) can be associated with cirrhosis and hepatocellular carcinoma but it can also be associated with extra‐hepatic effects, of which cardiac manifestations are the one of the least known. There is a limited amount of data about myocardial dysfunction in CHBV and insufficient data of strain echocardiography in CHBV. The aim of this study was to detect early myocardial dysfunction in CHBV using strain echocardiography.

Method

This prospective study included 40 CHBV patients without anti‐viral treatment, 40 CHBV patients under anti‐viral treatment, and 40 healthy volunteers as control group from 2017 October to 2018 May. The patients in all groups were aged 30–60 years, with no co‐morbid diseases. Any patients with pathologies that would cause myocardial dysfunction were excluded from the study. All patients were evaluated with transthoracic two‐dimensional (2D), tissue Doppler, and strain echocardiography.

Results

The mean age and gender distribution were similar in all groups (P = 0.677). A statistically significant difference was determined between the groups in respect of the global circumferential strain and global longitudinal strain values (P < 0.01). The difference in the mean lateral s′ was of statistical significance between the CHBV patients and the control group (P = 0.035). No statistically significant difference was determined in respect of the other echocardiographic parameters.

Conclusion

As it is a chronic necro‐inflammatory period, chronic HBV can affect myocardial functions. Traditional echocardiographic parameters may not be useful in the detection of early myocardial dysfunction. The results of this study showed that strain echocardiography may be more valuable in early myocardial dysfunction rather than routine 2D echocardiography in CHBV patients.
Species identity dominates over environment in shaping the microbiota of small mammals
Authors: Knowles S. C. L. , Eccles R. M. , Baltrūnaitė L.
Published: March 2019

The mammalian gut microbiota is considered pivotal to host fitness, yet the determinants of community composition remain poorly understood. Laboratory studies show that environmental factors, particularly diet, are important, while comparative work emphasises host genetics. Here, we compare the influence of host genetics and the environment on the microbiota of sympatric small mammal species (mice, voles, shrews) across multiple habitats. While sharing a habitat caused some microbiota convergence, the influence of species identity dominated. In all three host genera examined, an individual's microbiota was more similar to conspecifics living elsewhere than to heterospecifics at the same site. Our results suggest this species‐specificity arises in part through host‐microbe codiversification. Stomach contents analysis suggested that diet also shapes the microbiota, but where diet is itself influenced by species identity. In this way, we can reconcile the importance of both diet and genetics, while showing that species identity is the strongest predictor of microbiota composition.
Abortion in donkeys associated with Salmonella abortus equi infection
Authors: Wang H. , Liu K. J. , Sun Y. H. , Cui L. Y. , Meng X. , Jiang G. M. , Zhao F. W. , Li J. J.
Published: March 2019

Background

Salmonella enterica subspecies enterica serovar abortus equi (S. abortus equi) is well known as the aetiological agent of equine abortion. However, abortion caused by S. abortus equi has not been previously described in donkeys.

Objectives

To investigate whether S. abortus equi was correlated with an abortion outbreak consisting of 61 abortions.

Study design

Investigation of the clinical cases using pathoanatomical, bacteriological, serological and molecular approaches.

Methods

Autopsies on nine aborted foetuses were performed. Tissue specimens from seven aborted foetuses and two mares were cultured and subjected to detection of equine herpesvirus 1 (EHV‐1), equine herpesvirus 4 (EHV‐4) and equine arteritis virus (EAV) by polymerase chain reaction. The isolates were serotyped according to the Kaufmann−White scheme and analysed by multi‐locus sequence typing (MLST). Detection of EHV and EAV antibodies was performed in all pregnant mares.

Results

No obvious gross lesions were observed in the foetuses. Nine Gram‐negative isolates were obtained from all nine tissue samples and were identified as Salmonella spp. All of the isolates belonged to the B group, the O antigen epitope was 4, 12 and H antigen was not obtained. The isolates of Salmonella were characterised as sequence type (ST) 251. Detection of EHV‐1, EHV‐4 and EAV was negative.

Main limitations

The mechanism that causes abortion in donkeys needs further study and the lack of histological examination.

Conclusion

Salmonella abortus equi was isolated as the single agent and was responsible for the abortions. Equine practitioners should be aware of S. abortus equi infection as a cause of abortion in donkeys.
Differential regulation of myc homologs by Wnt/β‐Catenin signaling in the early metazoan Hydra
Authors: Hartl Markus , Glasauer Stella , Gufler Sabine , Raffeiner Andrea , Puglisi Kane , Breuker Kathrin , Bister Klaus , Hobmayer Bert
Published: March 2019

The c‐Myc protein is a transcription factor with oncogenic potential controlling fundamental cellular processes. Homologs of the human c‐myc protooncogene have been identified in the early diploblastic cnidarian Hydra (myc1, myc2). The ancestral Myc1 and Myc2 proteins display the principal design and biochemical properties of their vertebrate derivatives, suggesting that important Myc functions arose very early in metazoan evolution. c‐Myc is part of a transcription factor network regulated by several upstream pathways implicated in oncogenesis and development. One of these signaling cascades is the Wnt/β‐Catenin pathway driving cell differentiation and developmental patterning, but also tumorigenic processes including aberrant transcriptional activation of c‐myc in several human cancers. Here, we show that genetic or pharmacological stimulation of Wnt/β‐Catenin signaling in Hydra is accompanied by specific downregulation of myc1 at mRNA and protein levels. The myc1 and myc2 promoter regions contain consensus binding sites for the transcription factor Tcf, and Hydra Tcf binds to the regulatory regions of both promoters. The myc1 promoter is also specifically repressed in the presence of ectopic Hydra β‐Catenin/Tcf in avian cell culture. We propose that Hydra myc1 is a negative Wnt signaling target, in contrast to vertebrate c‐myc, which is one of the best studied genes activated by this pathway. On the contrary, myc2 is not suppressed by ectopic β‐Catenin in Hydra and presumably represents the structural and functional c‐myc ortholog. Our data implicate that the connection between β‐Catenin‐mediated signaling and myc1 and myc2 gene regulation is an ancestral metazoan feature. Its impact on decision making in Hydra interstitial stem cells is discussed.
Incidence of hip fracture and 30‐day hospital readmissions in a region of central Italy from 2006 to 2015
Authors: Di Giovanni Pamela , Di Martino Giuseppe , Zecca Isaia AL , Porfilio Italo , Romano Ferdinando , Staniscia Tommaso
Published: March 2019

Aim

Increased life expectancy causes a higher prevalence of chronic and degenerative diseases, and greater frailty among older people. Hip fracture is a common event for older people, and 1‐year mortality after hip fracture is high. The present study was carried out in the Abruzzo region, Italy, over the years from 2006 to 2015, entailing as its main objectives the assessment of age and sex‐specific trends in the incidence of hip fractures, with the subsequent hospital mortality. Causes of 30‐day hospital readmissions were assessed.

Methods

Data were collected from all hospital discharge records. Information on all 30‐day readmissions was also retrieved.

Results

Overall, 23 075 patients were admitted to hospital for hip fracture (mean age 81.0 ± 11.7 years,72.6% women). The overall hip fracture incidence remained constant over the study period, varying from 175.9 cases in 2006 to 179.3 cases per 100 000 in 2015. However, the incidence progressively increased from 40.0 to 51.0 among men, and from 61.6 to 80.9 among patients aged >85 years. The in‐hospital mortality rate was 3.8%. Within 30 days from the hip fracture discharge, 10 526 patients (45.6%) had a second hospitalization, related to the condition of interest in >80% of the patients. Additionally, 414 (3.9%) patients died during the second hospitalization.

Conclusions

Although women aged >65 years remain the category of patients at highest risk of hip fracture, an increasing trend is observed among men and patients aged >85 years. Hip fracture is frequently associated with early hospital readmission and is responsible for elevated in‐hospital mortality. Geriatr Gerontol Int 2019; 19: 483–486.
A pilot feasibility randomised clinical trial comparing dialkylcarbamoylchloride‐coated dressings versus standard care for the primary prevention of surgical site infection
Authors: Totty Joshua P. , Hitchman Louise H. , Cai Paris L. , Harwood Amy E. , Wallace Tom , Carradice Dan , Smith George E. , Chetter Ian C.
Published: March 2019

A surgical site infection (SSI) may occur in up to 30% of procedures and results in significant morbidity and mortality. We aimed to assess the feasibility of conducting a randomised controlled trial (RCT) examining the use of dialkylcarbamoylchloride (DACC)‐impregnated dressings, which bind bacteria at the wound bed, in the prevention of SSI in primarily closed incisional wounds. This pilot RCT recruited patients undergoing clean or clean‐contaminated vascular surgery. Participants were randomised intraoperatively on a 1:1 basis to either a DACC‐coated dressing or a control dressing. Outcomes were divided into feasibility and clinical outcomes. The primary clinical outcome was SSI at 30 days (assessed using Centers for Disease Control criteria and Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of the deep tissues, Isolation of bacteria and duration of inpatient Stay scoring methods). This study recruited 144 patients in 12 months at a median rate of 10 per month. Eligibility was 73% and recruitment 60%. At 30 days, there was a 36.9% relative risk reduction in the DACC‐coated arm (16.22% versus 25.71%, odds ratio 0.559, P = 0.161). The number needed to treat was 11 patients. A large‐scale RCT is both achievable and desirable given the relative risk reduction shown in this study. Further work is needed to improve the study protocol and involve more centres in a full‐scale RCT.
Multilocus phylogeny of the Crocidura poensis species complex (Mammalia, Eulipotyphla): Influences of the palaeoclimate on its diversification and evolution
Authors: Nicolas Violaine , Jacquet François , Hutterer Rainer , Konečný Adam , Kan Kouassi Stephane , Durnez Lies , Lalis Aude , Colyn Marc , Denys Christiane
Published: March 2019

Aim

This study aims to reconstruct the evolutionary history of the Crocidura poensis species complex and to identify factors driving diversification within it. We tested whether: (a) there is a pattern of allopatric differentiation coincident with the location of hypothesized Pleistocene forest refugia, (b) sister taxa are separated by broad rivers, (c) sister taxa occupy adjacent but distinct habitat.

Location

Sub‐Saharan African forests and adjacent savanna.

Taxon

Shrews.

Methods

Analyses were based on 247 specimens collected from across the distribution of the species complex. We reconstructed the phylogeny (Bayesian and maximum likelihood methods) and assessed historical biogeography of this taxonomic group using a combination of mitochondrial and nuclear markers. We mapped the genetic diversity and estimated the divergence times by a relaxed clock model. Informed by multilocus species delimitation methods, we discussed possible taxonomic implications.

Results

This complex is composed of nine major genetic lineages (proposed species). The earliest split within this complex occurred after 2.0–2.4 Ma, which corresponds to a period of increased aridity and/or extreme environmental variability. Most other divergence events occurred after the Early‐Middle Pleistocene Transition (1.2–0.8 Ma). Divergent selection across ecological gradients could explain diversification within the West African lineage. In Central Africa, the observed phylogeographic pattern fits the Pleistocene refuge hypothesis and supports the existence of multiple small rather than a few large forest refugia during glacial maxima. Large rivers, like the Congo and Sanaga Rivers, are important barriers to gene flow for several lineages but probably were not the primary cause of differentiation.

Main conclusions

Both geographic isolation in distinct forest refugia and divergent selection along ecological gradients could explain Pleistocene diversification within this complex.
Tetraspanin 1 as a mediator of fibrosis inhibits EMT process and Smad2/3 and beta‐catenin pathway in human pulmonary fibrosis
Authors: Liu Gang , Wang Yahong , Yang Lawei , Zou Baoan , Gao Shenglan , Song Zeqing , Lin Ziying
Published: March 2019

Tetraspanin 1(TSPAN1) as a clinically relevant gene target in cancer has been studied, but there is no direct in vivo or vitro evidence for pulmonary fibrosis (PF). Using reanalysing Gene Expression Omnibus data, here, we show for the first time that TSPAN1 was markedly down‐regulated in lung tissue of patient with idiopathic PF (IPF) and verified the reduced protein expression of TSPAN1 in lung tissue samples of patient with IPF and bleomycin‐induced PF mice. The expression of TSPAN1 was decreased and associated with transforming growth factor‐β1 (TGF‐β1)‐induced molecular characteristics of epithelial‐to‐mesenchymal transition (EMT) in alveolar epithelial cells (AECs). Silencing TSPAN1 promoted cell migration, and the expression of alpha‐smooth muscle actin, vimentin and E‐cadherin in AECs with TGF‐β1 treatment, while exogenous TSPAN1 has the converse effects. Moreover, silencing TSPAN1 promotes the phosphorylation of Smad2/3 and stabilizes beta‐catenin protein, however, overexpressed TSPAN1 impeded TGF‐β1‐induced activation of Smad2/3 and beta‐catenin pathway in AECs. Together, our study implicates TSPAN1 as a key regulator in the process of EMT in AECs of IPF.
Modeling Response Styles in Cross‐Country Self‐Reports: An Application of a Multilevel Multidimensional Nominal Response Model
Authors: Ju Unhee , Falk Carl F.
Published: March 2019

We examined the feasibility and results of a multilevel multidimensional nominal response model (ML‐MNRM) for measuring both substantive constructs and extreme response style (ERS) across countries. The ML‐MNRM considers within‐country clustering while allowing overall item slopes to vary across items and examination of whether certain items were more prone to ERS. We applied this model to survey items from TALIS 2013. Results indicated that self‐efficacy items were more likely to trigger ERS compared to need for professional development, and the between‐country relationships among constructs can change due to ERS. Simulations assessed the estimation approach and found adequate recovery of model parameters and factor scores. We stress the importance of additional validity studies to improve the cross‐cultural comparability of substantive constructs.
Behavioural and physiological effects of methadone in the perioperative period on the Nile tilapia Oreochromis niloticus
Authors: Crivelaro Roberta M. , Thiesen Roberto , Aldrovani Marcela , Silva Paloma E.S. , Barros Sobrinho Alexandre A.F. , Moraes Paola C.
Published: March 2019

Through the analysis of behavioural changes, this study demonstrates that methadone has behavioural, but not analgesic, effects on Oreochromis niloticus. It provides information that suggests the drug has sedative abilities, as the recovery time was shorter in the fish receiving methadone. Future research, with different doses and stimuli, is required to provide more information about analgesia.
The suppressive role of HYAL1 and HYAL2 in the metastasis of colorectal cancer
Authors: Jin Zhiming , Zhang Guoliang , Liu Yiwen , He Yiqing , Yang Cuixia , Du Yan , Gao Feng
Published: March 2019

Background

Hyaluronidases (HAases), enzymes that degrade hyaluronan, have been widely investigated in cancer biology. However, whether HAases serve as tumor promoters or suppressors has been controversial in different cancers, and the exact role of HAases in colorectal cancer (CRC) has not been elucidated.

Methods

The expression levels of HYAL1, HYAL2, and HYAL3 in cancer and corresponding normal tissues from CRC patients were examined via immunohistochemistry. Then the correlation between HAases levels and pathological characteristics of CRC patients was analyzed. To verify the clinical data, HYAL1 and HYAL2 were downregulated or overexpressed in colon cancer cells LOVO and HCT116 to observe their influences on cell invasion and migration. For the mechanism study, we investigated the effects of HYAL1 and HYAL2 on the expression of matrix metalloproteases (MMPs)/tissue inhibitor of metalloproteases (TIMPs) and distribution of F‐actin.

Results

All the three HAases were abnormally elevated in cancer tissues. Interestingly, HYAL1 and HYAL2, but not HYAL3, were negatively correlated with lymphatic metastasis and TNM stage. When HYAL1 and HYAL2 were knocked down, the invasion and migration abilities of colon cancer cells were accelerated, whereas overexpression of HYAL1 and HYAL2 had the opposite effects. In addition, colon cancer cells with HYAL1 and HYAL2 downregulation showed increased levels of MMP2 and MMP9, decreased levels of TIMP1 and TIMP2, and more intense F‐actin stress fibers.

Conclusions

Our study suggests that HYAL1 and HYAL2 suppress CRC metastasis through regulating MMPs/TIMPs balance and rearranging F‐actin distribution, further inhibiting invasion and migration of cancer cells.
Emerging Genetic and Epigenetic Mechanisms Underlying Pubertal Maturation in Adolescence
Authors: Aylwin Carlos F. , Toro Carlos A. , Shirtcliff Elizabeth , Lomniczi Alejandro
Published: March 2019

The adolescent transition begins with the onset of puberty which, upstream in the brain, is initiated by the gonadotropin‐releasing hormone (GnRH) pulse generator that activates the release of peripheral sex hormones. Substantial research in human and animal models has revealed a myriad of cellular networks and heritable genes that control the GnRH pulse generator allowing the individual to begin the process of reproductive competence and sexual maturation. Here, we review the latest knowledge in neuroendocrine pubertal research with emphasis on genetic and epigenetic mechanisms underlying the pubertal transition.
Paediatric asylum seekers in Western Australia: Identification of adversity and complex needs through comprehensive refugee health assessment
Authors: Hanes Gemma , Chee Jessica , Mutch Raewyn , Cherian Sarah
Published: March 2019

Aim

Asylum seekers (ASs) report high rates of trauma and difficulty accessing health and educational services. This study aims to ascertain the needs of paediatric ASs managed by the tertiary Western Australian paediatric Refugee Health Service (RHS), including demographic features, the range of health and psychosocial issues and ongoing management challenges.

Methods

An audit of multidisciplinary RHS assessments, health records and hospital admissions for new AS patients (<16 years) between July 2012 and June 2016 was undertaken.

Results

Records for 110 ASs were reviewed (mean age 6 years, standard deviation 4.72 years). Multiple issues (medical, psychological, developmental, educational) were identified after the first tertiary assessment (median 4, interquartile range (IQR) 3–6) compared to referral sources (median 1, IQR 0–2, P < 0.001). The median number of issues per child at audit completion was 6 (IQR 4–7, P < 0.001). Multiple refugee adverse childhood experiences were identified, with all experiencing >3 (median 4, IQR 4–5). Most had detention experience (107/110, 97.2%), family separation (91/108, 84%) and interrupted education (41/46, 89.2%). The median duration of detention was 7 months (IQR 3–12.5 months) at time of initial review across multiple sites (median 2, IQR 1–3 locations). High rates of hospital interaction were evident, with 45.4% requiring hospital admission and 36% presenting to the emergency department. The median number of outpatient appointments attended per child was 5 (IQR 2–8). Parental and child mental health concerns were identified in 53.6 and 46.3%, respectively.

Conclusions

Paediatric ASs have complex trauma backgrounds with exposure to multiple adverse events within disrupted family units. The majority of Western Australian ASs assessed demonstrated negative health or education sequelae compounded by detention not previously identified prior to comprehensive paediatric review. Our data support the urgent removal of ASs from held detention. Ongoing holistic assessment and management engaging multidisciplinary trauma‐informed paediatric refugee services to optimise health and well‐being is recommended.
Rapidly progressive miliary brain metastasis of lung cancer after EGFR tyrosine kinase inhibitor discontinuation: An autopsy report
Authors: Kurihara Masanori , Koda Hirotomo , Aono Hiromi , Sugimoto Izumi , Sakurai Yasuhisa , Sano Terunori , Saito Yuko , Murayama Shigeo , Mori Masaya
Published: March 2019

Miliary brain metastasis is a rare type of brain metastasis, in which carcinoma cells disseminate to numerous foci confined to Virchow–Robin/subpial spaces. Symptoms usually progress within several months, and magnetic resonance imaging (MRI) shows multiple small contrast‐enhancing lesions. We report an autopsy case of a patient who rapidly deteriorated within a week due to miliary brain metastasis after epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) discontinuation, without contrast‐enhancing lesions on MRI. A 74‐year‐old woman was diagnosed with stage IV lung adenocarcinoma with EGFR L868R mutation 2 years before presentation. Gefitinib, an EGFR‐TKI was started. After 7 months, multiple new punctate contrast‐enhancing lesions in the cerebral cortex appeared. After switching to another EGFR‐TKI, erlotinib, these lesions disappeared. One year later, erlotinib was discontinued because of disease progression in the lung and docetaxel was initiated. Sixteen days later, cognitive decline appeared which rapidly progressed to bedridden state in 4 days. MRI showed multiple cortical small fluid‐attenuated inversion recovery high intensity lesions which lacked contrast enhancement. The patient exhibited a state of akinetic mutism within a few days, and died 52 days after the appearance of neurological symptoms. The rapid progression indicated disease flare after EGFR‐TKI discontinuation. Autopsy revealed numerous foci of metastasis in the cerebral cortex, basal ganglia, thalamus, and cerebellum, in which cancer cells were mostly confined to the Virchow–Robin/subpial spaces. These pathological findings were compatible with previous reports of miliary brain metastasis. Recent reports suggest that early disseminated cancer cells can survive for a long time and even remain after chemotherapy in supportive niches, and Virchow–Robin spaces are the niches in the brain. Our case suggests that these cancer cells may rapidly proliferate as a withdrawal burst after discontinuation of molecular targeted drugs, and show pathological findings of miliary brain metastasis.
Demystifying dominant species
Authors: Avolio Meghan L. , Forrestel Elisabeth J. , Chang Cynthia C. , La Pierre Kimberly J. , Burghardt Karin T. , Smith Melinda D.
Published: March 2019

The pattern of a few abundant species and many rarer species is a defining characteristic of communities worldwide. These abundant species are often referred to as dominant species. Yet, despite their importance, the term dominant species is poorly defined and often used to convey different information by different authors. Based on a review of historical and contemporary definitions we develop a synthetic definition of dominant species. This definition incorporates the relative local abundance of a species, its ubiquity across the landscape, and its impact on community and ecosystem properties. A meta‐analysis of removal studies shows that the loss of species identified as dominant by authors can significantly impact ecosystem functioning and community structure. We recommend two metrics that can be used jointly to identify dominant species in a given community and provide a roadmap for future avenues of research on dominant species. In our review, we make the case that the identity and effects of dominant species on their environments are key to linking patterns of diversity to ecosystem function, including predicting impacts of species loss and other aspects of global change on ecosystems.
Malignant transformation of neurocutaneous melanosis (NCM) following immunosuppression
Authors: Schaff Lauren R. , Marghoob Ashfaq , Rosenblum Marc K. , Meyer Rina , Khakoo Yasmin
Published: March 2019

Neurocutaneous melanosis (NCM) is the condition of abnormal melanocyte deposition in the leptomeninges and brain parenchyma. Associated with congenital melanocytic nevi, NCM can result in neurologic deficits, hydrocephalus, and rarely, malignant transformation of cells. We present the case of a 16‐year‐old boy with NCM who developed malignant leptomeningeal melanoma following immunosuppression with a TNFα inhibitor. To our knowledge, this is the first reported case of a patient with known NCM undergoing malignant transformation after anti‐TNF therapy for inflammatory bowel disease.
The past, present and future of pulmonary rehabilitation
Authors: Troosters Thierry , Blondeel Astrid , Janssens Wim , Demeyer Heleen
Published: March 2019

Abundant evidence supports the use of pulmonary rehabilitation as a treatment for stable and exacerbated chronic obstructive pulmonary disease. Several questions around the science base of rehabilitation in other patient groups as well as the role of rehabilitation as a component in other comprehensive care trajectories remain to be addressed. The impact of a rehabilitation programme could also perhaps be enhanced if clear guidance would be available on how to individualize the components of a rehabilitation programme in individual patients. The rehabilitation community, in an attempt to increase access to programmes, has developed less rigorous interventions. These may serve specific patients (e.g. less severe patients or may be used as a maintenance programme), but in order to have conceptual clarity they should not be called substitutes for rehabilitation if they do not meet the definition of rehabilitation. Reaching clarity on the best format for maintenance programmes in order to achieve long‐lasting health benefits for patients is another challenge. Furthermore, as many patients as possible should be referred to adequate rehabilitation programmes within their reach with fair reimbursement. Programmes should take into account the burden of the disease of a patient, the required components to tackle the problems, adequate assessment to document the outcome and the patient's preference. In summary, pulmonary rehabilitation is one of the most potent evidence‐based therapies for patients with respiratory diseases. Researchers should continue to fine tune the interventions, get clarity on terminology as well as the ultimate outcomes for rehabilitation to ensure sustainable health effects.
Conflict and Contraception in Colombia
Authors: Svallfors Signe , Billingsley Sunnee
Published: March 2019

This study explores how armed conflict relates to contraceptive use in Colombia, combining data from the Uppsala Conflict Data Program and Demographic and Health Surveys 1990–2016. Our study is the first systematic effort to investigate whether and how violent conflict influences women's contraceptive use, using nationally representative data across all stages of women's reproductive careers. With fixed effects linear probability models, we adjust for location‐specific cultural, social, and economic differences. The results show that although modern contraceptive use increased over time, it declined according to conflict intensity across location and time. We find no evidence that this relationship varied across socioeconomic groups. Increased fertility demand appears to explain a small portion of this relationship, potentially reflecting uncertainty about losing a partner, but conflict may also result in lack of access to contraceptive goods and services.
Sequence diversity of major histo‐compatibility complex class II DQA1 in Indian Tharparkar cattle: novel alleles and in‐silico analysis
Authors: Sahoo Nihar R. , Kumar Pushpendra , Khan Mohd. F. , Mourya Ranjeeta , Ravikumar G. V. P. P. S. , Tiwari Ashok K.
Published: March 2019

Exon 2 of MHC class II gene codes for the first domain of the molecule that forms the peptide‐binding groove and its polymorphism partly explains functional MHC diversity. A 850 bp DQA1 gene fragment spanning from intron I to exon III was typed by sequencing of 40 Tharparkar cattle of various agro‐climatic zones of northern India along with 10 Tharparkar crossbreds. On analysis of nucleotide sequences, a total of 30 polymorphic sites (1 insertion and 29 SNPs) were identified in 14 MHC alleles leading to amino acid changes in 5 places in 249 bp (exon 2). Five new BoLa DQA1 alleles were identified and reported. The within group mean distance was highest in Tharparkar herd of Bikaner (0.045) and lowest (0.020) in that of Surathgarh (breeding tract) whereas, between groups mean distance was highest in Bikaner Tharparkar—Suratgarh Tharparkar pair. There was excess of nonsynonymous over synonymous nucleotide substitutions in the present study. The effects of these substitutions were predicted using I‐Mutant and Panther online resources. The mean ratio of dN/dS was found to be >1.0 at 12 codons with two mutation hotspots at 13th codon (P = 0.002) and 64th codon (P = 0.01). The phylo‐geographic analysis revealed that alleles 5, 7 and 13 formed a different cluster with alleles 7 and 13 grouped by the most frequent allele (BoLa‐DQA*1401).
Improving surface-wetting characterization
Authors: Liu Kai , Vuckovac Maja , Latikka Mika , Huhtamäki Tommi , Ras Robin H. A.
Published: March 2019

Awareness of instrument inaccuracies will boost the development of liquid-repellent coatings
Efficacy, immunogenicity and safety of a recombinant tetravalent dengue vaccine (CYD-TDV) in children aged 2–17 years: systematic review and meta-analysis
Authors: Rosa Bruno Rodrigues , Cunha Antonio José Ledo Alves da , Medronho Roberto de Andrade
Published: March 2019

Background

Randomised controlled trials have evaluated the recombinant tetravalent dengue vaccine (CYD-TDV). However, individual results may have little power to identify differences among the populations studied.

Objective

To evaluate efficacy, immunogenicity and safety of CYD-TDV in the prevention of dengue in children aged 2–17 years.

Design

Systematic review and meta-analysis.

Data sources

MEDLINE (from 1950 to 5 December 2018), EMBASE (from 1947 to 5 December 2018) and Cochrane (from 1993 to 5 December 2018).

Eligibility criteria of studies

Randomised trials comparing efficacy, immunogenicity and safety of CYD-TDV with placebo or other vaccines for preventing dengue cases in children aged 2–17 years.

Outcome measures

Efficacy, immunogenicity and safety of CYD-TDV.

Study appraisal and methods

Calculations were made of relative risk (RR) and mean difference (MD) for dichotomous and continuous outcomes, respectively. All estimates were calculated considering a 95% CI estimate. A p<0.05 was considered statistically significant.

Results

Nine studies involving 34 248 participants were included. The overall efficacy of CYD-TDV was 60% (RR 0.40 (0.30 to 0.54)). Serotype-specific efficacy of the vaccine was 51% for dengue virus type-1 (DENV-1) (RR 0.49 (0.39 to 0.63)); 34% for DENV-2 (RR 0.66 (0.50 to 0.86)); 75% for DENV-3 (RR 0.25 (0.18 to 0.35)) and 77% for DENV-4 (RR 0.23 (0.15 to 0.34)). Overall immunogenicity (MD) of CYD-TDV was 225.13 (190.34 to 259.93). Serotype-specific immunogenicity was: DENV-1: 176.59 (123.36 to 229.83); DENV-2: 294.21 (181.98 to 406.45); DENV-3: 258.78 (146.72 to 370.84) and DENV-4: 189.35 (141.11 to 237.59). The most common adverse events were headache and pain at the injection site.

Limitations

The main limitation of this study was unclear or incomplete data.

Conclusions and implications of key findings

CYD-TDV is considered safe and able to partially protect children and adolescents against four serotypes of DENV for a 1-year period. Despite this, research should prioritise improvements in vaccine efficacy, thus proving higher long-term protection against all virus serotypes.

PROSPERO registration number

CRD42016043628.