bluuebunny/crossref_metadata_2025 huggingface dataset:
miR‐34c‐3p functions as a tumour suppressor by inhibiting eIF4E expression in non‐small cell lung cancer
Authors: Liu Fang , Wang Xuefeng , Li Jiebing , Gu Kuo , Lv Liyan , Zhang Shuai , Che Dehai , Cao Jingyan , Jin Shi , Yu Yan
Published: August 2015

Objectives

MicroRNAs (miRNAs) are small non‐coding RNAs that post‐transcriptionally regulate gene expression and mediate diverse physiological processes. In this study, we investigated functions of miRNA miR‐34c‐3p in non‐small cell lung cancer (NSCLC).

Materials and methods

miR‐34c‐3p expression was evaluated by qPCR. Cell viability was examined by MTT and proliferation by cell cycle analysis. Cell migration and invasion were tested using Transwells with/without Matrigel coating. Western blot analysis was performed for eIF4E, c‐Myc, Cyclin D1, survivin and Mcl‐1 protein expression.

Results

miR‐34c‐3p expression was significantly reduced in tissues and serum samples from NSCLC patients and in NSCLC cell lines A549, H460, H23, H157 and H1299. Overexpression of miR‐34c‐3p in A549 and H157 cells reduced cell proliferation, migration and invasion, whereas transfection with miR‐34c‐3p inhibitor (miR‐34c‐3p‐in) produced opposite effects. Target analysis using algorithms miRanda, TargetScan and DIANA identified eIF4E as a potential target of miR‐34c‐3p. Luciferase assay using the eIF4E 3′‐UTR reporter carrying a putative miR‐34c‐3p target sequence revealed eIF4E to be a specific target of miR‐34c‐3p. Overexpression of miR‐34c‐3p in NSCLS cell lines led to significant reduction in mRNA and protein levels of eIF4E, whereas inhibition of miR‐34c‐3p resulted in significant increase in eIf4e protein levels, confirming eIF4E to be a direct target of miR‐34c‐3p in NSCLS. Overexpression of eIF4E in A549 cells promoted cell proliferation, migration and invasion, which were partially reversed by miR‐34c‐3p.

Conclusion

miR‐34c‐3p directly targeted eIF4E and reduced miR‐34c‐3p expression in NSCLC, promoting cell cycle progression, proliferation, migration and invasion.
Who gains clinical benefit from using insulin pump therapy? A qualitative study of the perceptions and views of health professionals involved in the Relative Effectiveness of Pumps over MDI and Structured Education (REPOSE) trial
Authors: Lawton J. , Kirkham J. , Rankin D. , White D. A. , Elliott J. , Jaap A. , Smithson W. H. , Heller S. ,   the REPOSE Group
Published: August 2015

Aims

To explore health professionals' views about insulin pump therapy [continuous subcutaneous insulin infusion (CSII)] and the types of individuals they thought would gain greatest clinical benefit from using this treatment.

Methods

In‐depth interviews with staff (n = 18) who delivered the Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE) trial. Data were analysed thematically.

Results

Staff perceived insulin pumps as offering a better self‐management tool to some individuals due to the drip feed of insulin, the ability to alter basal rates and other advanced features. However, staff also noted that, because of the diversity of features on offer, CSII is a more technically complex therapy to execute than multiple daily injections. For this reason, staff described how, alongside clinical criteria, they had tended to select individuals for CSII in routine clinical practice based on their perceptions about whether they possessed the personal and psychological attributes needed to make optimal use of pump technology. Staff also described how their assumptions about personal and psychological suitability had been challenged by working on the REPOSE trial and observing individuals make effective use of CSII who they would not have recommended for this type of therapy in routine clinical practice.

Conclusions

Our findings add to those studies that highlight the difficulties of using patient characteristics and variables to predict clinical success using CSII. To promote equitable access to CSII, attitudinal barriers and prejudicial assumptions amongst staff about who is able to make effective use of CSII may need to be addressed.
Fiscal Shocks and the Exchange Rate in a Generalized Redux Model
Authors: Di Giorgio Giorgio , Nisticò Salvatore , Traficante Guido
Published: August 2015

This paper studies how the interaction between the monetary policy regime and the degree of home bias in public consumption affects the exchange‐rate response to fiscal shocks in a generalized version of the Redux model of Obstfeld and Rogoff (). We show that the joint presence of home bias in public consumption and endogenous monetary policy overturns the result of the Redux model implying an exchange‐rate appreciation in response to an expansionary fiscal shock.
Robustness despite uncertainty: regional climate data reveal the dominant role of humans in explaining global extinctions of Late Quaternary megafauna
Authors: Bartlett Lewis J. , Williams David R. , Prescott Graham W. , Balmford Andrew , Green Rhys E. , Eriksson Anders , Valdes Paul J. , Singarayer Joy S. , Manica Andrea
Published: August 2015

Debate over the Late Quaternary megafaunal extinctions has focussed on whether human colonisation or climatic changes were more important drivers of extinction, with few extinctions being unambiguously attributable to either. Most analyses have been geographically or taxonomically restricted and the few quantitative global analyses have been limited by coarse temporal resolution or overly simplified climate reconstructions or proxies. We present a global analysis of the causes of these extinctions which uses high‐resolution climate reconstructions and explicitly investigates the sensitivity of our results to uncertainty in the palaeological record. Our results show that human colonisation was the dominant driver of megafaunal extinction across the world but that climatic factors were also important. We identify the geographic regions where future research is likely to have the most impact, with our models reliably predicting extinctions across most of the world, with the notable exception of mainland Asia where we fail to explain the apparently low rate of extinction found in in the fossil record. Our results are highly robust to uncertainties in the palaeological record, and our main conclusions are unlikely to change qualitatively following minor improvements or changes in the dates of extinctions and human colonisation.
Patients with multiple myeloma have excellent long‐term outcomes after recovery from dialysis‐dependent acute kidney injury
Authors: Yadav Punit , Hutchison Colin A. , Basnayake Kolitha , Stringer Stephanie , Jesky Mark , Fifer Lesley , Snell Kym , Pinney Jennifer , Drayson Mark T. , Cook Mark , Cockwell Paul
Published: August 2015

Objectives

The aim of this study was to report the long‐term outcomes in patients with multiple myeloma (MM) who receive dialysis treatment for acute kidney injury (AKI) due to myeloma cast nephropathy and subsequently recover renal function.

Methods

Patients presenting with dialysis‐dependent AKI secondary to myeloma cast nephropathy and subsequently recovering independent renal function between January 2005 and December 2012 were included in this study. Both renal and haematological parameters were collected at multiple time points as part of routine clinic practice. Factors associated with renal function and overall survival (OS) were determined.

Results

Twenty‐four patients fulfilled the criteria for inclusion. Mean age was 62.1 years; 75% were male and 75% were of White ethnicity. The median OS was 64.1 months (95% confidence interval [CI] 34.8–93.3). Twenty‐three (95.8%) patients remained dialysis‐independent until death or end of follow‐up; one patient required further haemodialysis treatment during the follow‐up period. The independent determinant of worse OS was a known history of chronic kidney disease (CKD) at presentation. Shorter length of time on haemodialysis and higher percentage reduction in clonal serum FLC at day 21 from baseline predicted better excretory renal function (estimated glomerular filtration rate) at 6 months.

Conclusion

In this series, the large majority of patients with MM and dialysis‐dependent AKI secondary to myeloma cast nephropathy who recovered independent renal function had no requirement for further dialysis. Survival following recovery of renal function is good, and early variables are independently associated with survival and future renal function.
Microbial ecosystems are dominated by specialist taxa
Authors: Mariadassou Mahendra , Pichon Samuel , Ebert Dieter
Published: August 2015

Abundance and specificity are two key characteristics of species distribution and biodiversity. Theories of species assembly aim to reproduce the empirical joint patterns of specificity and abundance, with the goal to explain patterns of biodiversity across habitats. The specialist‐generalist paradigm predicts that specialists should have a local advantage over generalists and thus be more abundant. We developed a specificity index to analyse abundance–specificity relationships in microbial ecosystems. By analysing microbiota spanning 23 habitats from three very different data sets covering a wide range of sequencing depths and environmental conditions, we find that habitats are consistently dominated by specialist taxa, resulting in a strong, positive correlation between abundance and specificity. This finding is consistent over several levels of taxonomic aggregation and robust to errors in abundance measures. The relationship explains why shallow sequencing captures similar β‐diversity as deep sequencing, and can be sufficient to capture the habitat‐specific functions of microbial communities.
Rapid local adaptation mediates zooplankton community assembly in experimental mesocosms
Authors: Pantel Jelena H. , Duvivier Cathy , Meester Luc De
Published: August 2015

Adaptive evolution can occur over similar timescales as ecological processes such as community assembly, but its particular effects on community assembly and structure and their magnitude are poorly understood. In experimental evolution trials, Daphnia magna were exposed to varying environments (presence and absence of fish and artificial macrophytes) for 2 months. Then, in a common gardening experiment, we compared zooplankton community composition when either experimentally adapted or D. magna from the original population were present. Local adaptation of D. magna significantly altered zooplankton community composition, leading to a suppression of abundances for some zooplankton taxa and facilitation for others. The effect size of D. magna adaptation was similar to that of adding fish or macrophytes to mesocosms, two important drivers of zooplankton community structure. Our results suggest that substantial amounts of variation in community composition in natural systems may be unexplained if evolutionary dynamics are ignored.
Different axes of environmental variation explain the presence vs. extent of cooperative nest founding associations in Polistes paper wasps
Authors: Sheehan Michael J , Botero Carlos A , Hendry Tory A , Sedio Brian E , Jandt Jennifer M , Weiner Susan , Toth Amy L , Tibbetts Elizabeth A
Published: August 2015

Ecological constraints on independent breeding are recognised as major drivers of cooperative breeding across diverse lineages. How the prevalence and degree of cooperative breeding relates to ecological variation remains unresolved. Using a large data set of cooperative nesting in Polistes wasps we demonstrate that different aspects of cooperative breeding are likely to be driven by different aspects of climate. Whether or not a species forms cooperative groups is associated with greater short‐term temperature fluctuations. In contrast, the number of cooperative foundresses increases in more benign environments with warmer, wetter conditions. The same data set reveals that intraspecific responses to climate variation do not mirror genus‐wide trends and instead are highly heterogeneous among species. Collectively these data suggest that the ecological drivers that lead to the origin or loss of cooperation are different from those that influence the extent of its expression within populations.
Gut physiology mediates a trade‐off between adaptation to malnutrition and susceptibility to food‐borne pathogens
Authors: Vijendravarma Roshan K. , Narasimha Sunitha , Chakrabarti Sveta , Babin Aurelie , Kolly Sylvain , Lemaitre Bruno , Kawecki Tadeusz J.
Published: August 2015

The animal gut plays a central role in tackling two common ecological challenges, nutrient shortage and food‐borne parasites, the former by efficient digestion and nutrient absorption, the latter by acting as an immune organ and a barrier. It remains unknown whether these functions can be independently optimised by evolution, or whether they interfere with each other. We report that Drosophila melanogaster populations adapted during 160 generations of experimental evolution to chronic larval malnutrition became more susceptible to intestinal infection with the opportunistic bacterial pathogen Pseudomonas entomophila. However, they do not show suppressed immune response or higher bacterial loads. Rather, their increased susceptibility to P. entomophila is largely mediated by an elevated predisposition to loss of intestinal barrier integrity upon infection. These results may reflect a trade‐off between the efficiency of nutrient extraction from poor food and the protective function of the gut, in particular its tolerance to pathogen‐induced damage.
Using Test Scores From Students With Disabilities in Teacher Evaluation
Authors: Buzick Heather M. , Jones Nathan D.
Published: August 2015

Much of the recent focus of educational policymakers has been on improving the measurement of teacher effectiveness. Linking student growth to teacher effects has been a large part of reform efforts. To date, neither researchers nor practitioners have arrived at a consensus on how to treat test scores from students with disabilities in growth‐based teacher effectiveness indicators, despite the fact that these students make up approximately 13% of the K‐12 student population. In this study, we leverage longitudinal data from the population of teachers in one state to explore practical questions related to including general assessment scores from students with disabilities in teacher evaluation. Findings suggest that including test scores from students with disabilities allows more teachers to be evaluated and does not substantially affect teachers’ scores. Moreover, including disability‐related covariates can allow for fairer evaluations for teachers with many students with disabilities in their class.
Control Structures Used in Family Business to Manage Wealth: Operationalization of Antecedent and Outcome Variables
Authors: Chandler Gaylen N.
Published: August 2015

This commentary extends the work of Zellweger and Kammerlander by describing how the relationships they hypothesize might be operationalized and tested. It more clearly defines and provides suggestions for how to measure the heterogeneity and complexity of family members and family relationships. It discusses how to operationalize the scope, scale, and complexity of assets controlled by the family, and the characteristics of agents who manage the process. In addition the commentary discusses outcome measures for the family such as family wealth, family communication, family happiness, and family functionality. It describes financial and operational measures of performance for the businesses controlled by the family. The commentary concludes by discussing outcome measures for individual family members and for the agents they employ.
Contrasting genetic structure between mitochondrial and nuclear markers in the dengue fever mosquito from Rio de Janeiro: implications for vector control
Authors: Rašić Gordana , Schama Renata , Powell Rosanna , Maciel‐de Freitas Rafael , Endersby‐Harshman Nancy M. , Filipović Igor , Sylvestre Gabriel , Máspero Renato C. , Hoffmann Ary A.
Published: August 2015

Dengue is the most prevalent global arboviral disease that affects over 300 million people every year. Brazil has the highest number of dengue cases in the world, with the most severe epidemics in the city of Rio de Janeiro (Rio). The effective control of dengue is critically dependent on the knowledge of population genetic structuring in the primary dengue vector, the mosquito Aedes aegypti. We analyzed mitochondrial and nuclear genomewide single nucleotide polymorphism markers generated via Restriction‐site Associated DNA sequencing, as well as traditional microsatellite markers in Ae. aegypti from Rio. We found four divergent mitochondrial lineages and a strong spatial structuring of mitochondrial variation, in contrast to the overall nuclear homogeneity across Rio. Despite a low overall differentiation in the nuclear genome, we detected strong spatial structure for variation in over 20 genes that have a significantly altered expression in response to insecticides, xenobiotics, and pathogens, including the novel biocontrol agent Wolbachia. Our results indicate that high genetic diversity, spatially unconstrained admixing likely mediated by male dispersal, along with locally heterogeneous genetic variation that could affect insecticide resistance and mosquito vectorial capacity, set limits to the effectiveness of measures to control dengue fever in Rio.
National Culture and Profit Reinvestment: Evidence from Small and Medium‐Sized Enterprises
Authors: El Ghoul Sadok , Guedhami Omrane , Kwok Chuck , Shao Liang
Published: August 2015

We examine the role of national culture—an important informal institution—in the profit reinvestment decisions of small firms in emerging markets. Prior economic development literature focuses on formal institutions as determinants of growth. However, in emerging markets where formal institutions are less developed, informal institutions should have more of a direct versus indirect impact through formal institutions. We find that Schwartz's cultural dimensions of Embeddedness and Hierarchy negatively affect profit reinvestment, and that access to external financing (strength of property rights) is more important for reinvestment decisions in countries with low (high) Embeddedness and Hierarchy.
Discharge, legacy effects and nutrient availability as determinants of temporal patterns in biofilm metabolism and accrual in an arctic river
Authors: Kendrick Michael R. , Huryn Alexander D.
Published: August 2015

Significant changes in the timing of thawing and freezing, annual discharge and nutrient supply are anticipated for arctic river ecosystems due to climate warming. Our understanding of the effects of such changes, however, is poor. Since biofilms are both critical to ecosystem processes and subject to control by combinations of freezing dynamics, discharge and nutrient supply, the effects of climate warming on arctic river ecosystems may be substantial.

We studied biofilm accrual and metabolism in the Kuparuk River of Alaska with three objectives. First, we assessed biofilm activity during the open‐water season, including the poorly known ‘shoulder seasons’ (periods shortly after the spring thaw and then before autumn freezing). Second, we assessed how discharge and freezing dynamics may affect temporal patterns in biofilm activity. Third, we assessed biofilm response to increases in concentrations predicted as the climate warms.

Our study consisted of an upstream reference reach and a downstream treatment reach where H3PO4 was experimentally added for two years (2011–2012; ˜0.3 μm increase). We used archived reference‐reach data from 1983 to 2014 to assess discharge–chlorophyll relationships.

Mean biofilm gross primary production (GPP) in the reference reach during 2011 and 2012 was 15.4 ± 2.2 (mean ± S.E.) and 13.4 ± 2.5 mg C m−2 h−1, respectively, with spring shoulder season values being significantly higher than the summer values that are more routinely measured. An analysis of a 31‐year record from the reference reach revealed that biofilm chlorophyll biomass was significantly (R2 = 0.39, P < 0.001) related to the discharge regime of the previous summer. This ‘legacy effect’ is attributable to bedfast ice within the river channel during winter that protects biofilms from scour during the spring thaw. Before–after‐control–impact (BACI) analysis showed significant and positive effects on mean biofilm chl‐a biomass in the treatment reach. This treatment effect was associated with a parallel increase in GPP.

High biofilm activity in the Kuparuk River during the shoulder seasons indicates its potential significance to the energetics of arctic river ecosystems, particularly in the context of climate change. The related ‘legacy effect’ probably underlies the scope for rapid recovery of biofilm activity during the spring. Finally, increases in at concentrations predicted as the climate warms are likely to result in increases in summer biofilm biomass and metabolism. Further studies of biofilm processes during the shoulder seasons, and how these are affected by shifts in discharge, freezing dynamics and nutrient supply, are required for a comprehensive understanding of the effects of climate warming on arctic river ecosystems.
Slow life history and rapid extreme flood: demographic mechanisms and their consequences on population viability in a threatened amphibian
Authors: Cayuela Hugo , Arsovski Dragan , Boitaud Sylvain , Bonnaire Eric , Boualit Laurent , Miaud Claude , Joly Pierre , Besnard Aurelien
Published: August 2015

In the Northern Hemisphere, an increase in both the frequency and magnitude of violent flooding events has been reported due to climate change. According to life history theory, one might postulate that in ‘slow’ species: (i) environmental canalisation may act as a selective force that minimises to some extent adult survival variations caused by catastrophic flood and (ii) extreme flooding events would cause important variations in recruitment and young survival. Hence, it may be hypothesised that (iii) the population growth rate of ‘slow’ species might be relatively insensitive to changes in the frequency of extreme climatic events if adult survival remains largely unaffected.

In this study, we investigated how extreme rainfall events resulting in severe flood impact population dynamics of a long‐lived endangered amphibian, the yellow‐bellied toad (Bombina variegata: Bombinatoridae). To address this issue, we used capture–recapture (CR) data collected on two populations (768 and 1154 individuals identified) in southern France and developed multi‐event CR models.

Our results indicated that extreme flooding did not cause any variation in sub‐adult or adult survival, whereas recruitment and juvenile survival were negatively impacted. Furthermore, our simulations indicated that the population growth rate was only marginally sensitive to potential changes in the frequency of extreme flooding in the future.

Hence, we suggest that extreme flooding does not appear to be a proximal factor of extinction risk for this endangered amphibian species.
A humanized version of Foxp2 does not affect ultrasonic vocalization in adult mice
Authors: Hammerschmidt K. , Schreiweis C. , Minge C. , Pääbo S. , Fischer J. , Enard W.
Published: August 2015

The transcription factor FOXP2 has been linked to severe speech and language impairments in humans. An analysis of the evolution of the FOXP2 gene has identified two amino acid substitutions that became fixed after the split of the human and chimpanzee lineages. Studying the functional consequences of these two substitutions in the endogenous Foxp2 gene of mice showed alterations in dopamine levels, striatal synaptic plasticity, neuronal morphology and cortico‐striatal‐dependent learning. In addition, ultrasonic vocalizations (USVs) of pups had a significantly lower average pitch than control littermates. To which degree adult USVs would be affected in mice carrying the ‘humanized’ Foxp2 variant remained unclear. In this study, we analyzed USVs of 68 adult male mice uttered during repeated courtship encounters with different females. Mice carrying the Foxp2hum/hum allele did not differ significantly in the number of call elements, their element structure or in their element composition from control littermates. We conclude that neither the structure nor the usage of USVs in adult mice is affected by the two amino acid substitutions that occurred in FOXP2 during human evolution. The reported effect for pup vocalization thus appears to be transient. These results are in line with accumulating evidence that mouse USVs are hardly influenced by vocal learning. Hence, the function and evolution of genes that are necessary, but not sufficient for vocal learning in humans, must be either studied at a different phenotypic level in mice or in other organisms.
The biogeography of fertilization mode in the sea
Authors: Monro Keyne , Marshall Dustin J.
Published: August 2015

Aim

Knowledge of the biogeography of life histories is central to understanding and predicting the impacts of global change on key functional traits that shape species distributions and transcend taxonomic boundaries. Whether species are internal or external fertilizers is a fundamental aspect of reproductive diversity in the sea, and has profound ecological and evolutionary consequences. However, geographic variation in this trait and the factors that potentially drive it (e.g. transitions in associated life‐history traits, ecological conditions that favour one mode over the other or the evolutionary history of species) remain poorly characterized.

Location

Oceans world‐wide.

Methods

We collated life‐history data (modes of fertilization and development), geographic data and biophysical data (sea‐surface temperatures and food availability) for 1532 marine species spanning 17 invertebrate phyla. We used standard and phylogenetic logistic regressions to evaluate latitudinal gradients in fertilization mode, plus their interactions with development (transitions from planktonic to aplanktonic development, or from feeding to non‐feeding larvae) and taxonomy. We also explored the dependence of fertilization mode on biophysical variables to understand how ecology potentially contributes to geographic variation in this trait.

Results

Fertilization mode often varies predictably with latitude, but the exact nature of this relationship depends on developmental mode and the phylum under consideration. Some commonalities were evident, however, with the likelihood of internal fertilization declining at higher latitudes forAnnelida andEchinodermata with aplanktonic development, but increasing at higher latitudes forCnidaria and Porifera with non‐feeding, planktonic larvae. Synergistic effects of temperature and food availability may potentially shape some of these patterns.

Main conclusions

There are latitudinal gradients in fertilization mode in the sea. The variation among phyla and developmental modes, however, is a complexity that is unexplained by existing theory. Combined effects of recent adaptation and deeper phylogenetic history have probably shaped this systematic variation in the reproductive ecology of marine organisms.
Differences in lifestyle, physical performance and quality of life between frail and robust Brazilian community‐dwelling elderly women
Authors: Sewo Sampaio Priscila Yukari , Sampaio Ricardo Aurélio Carvalho , Coelho Júnior Hélio José , Teixeira Luis Felipe M , Tessutti Vitor D , Uchida Marco Carlos , Arai Hidenori
Published: August 2015

Aim

To investigate the lifestyles, physical performance and quality of life (QOL) of frail and robust Brazilian community‐dwelling older women, and to identify risk factors for frailty.

Methods

Frailty was assessed using the Kihon Checklist. Lifestyles were assessed using a questionnaire. Physical performance was assessed by measuring walking speeds, performance on the one‐leg stand test and the five‐times chair stand test and handgrip strength. QOL was assessed using the Short Form‐8 questionnaire. Participants were divided into frail and robust groups based on their total Kihon Checklist scores.

Results

A total of 109 participants (age 70.8 ± 6.87 years) were included in this study (robust n = 85, frail n = 24). Differences in living structures (P < 0.001), financial satisfaction (P = 0.004) and the frequencies with which participants leave the house (P < 0.001) were found between groups. The frail group had more fallers (P = 0.047), and lower engagement in physical activity (P = 0.044), lower body mass indices (P = 0.043) and poorer nutritional status (P = 0.002), whereas robust older people showed better physical performance (walking speed P < 0.001, one‐leg stand P = 0.021, handgrip strength P = 0.002) and higher QOL scores (general health P = 0.005, role‐physical P = 0.013, bodily pain P = 0.002, vitality P = 0.001, social functioning P = 0.001, role‐emotional P = 0.008). Multivariate regression analysis identified a slow usual walking speed and bodily pain as risk factors for frailty.

Conclusions

Frail participants had higher indices for being housebound, and having financial dissatisfaction, a sedentary lifestyle, falls, and malnutrition. Furthermore, they showed poorer physical performance and QOL. An early, well‐focused approach is crucial, especially for older adults who walk slowly and have bodily pain to preserve health and QOL. Geriatr Gerontol Int 2016; 16: 829–835.
Relationship between white matter lesions and regional cerebral blood flow changes during longitudinal follow up in Alzheimer's disease
Authors: Hanaoka Takuya , Kimura Noriyuki , Aso Yasuhiro , Takemaru Makoto , Kimura Yuki , Ishibashi Masato , Matsubara Etsuro
Published: August 2015

Aim

The aim of the present study was to evaluate the relationship between baseline white matter lesions (WML) and changes in regional cerebral blood flow during longitudinal follow up of patients with Alzheimer's disease (AD).

Methods

A total of 38 patients with AD were included in the study (16 men, 22 women; mean age 77.8 years). All patients were evaluated using the Mini‐Mental State Examination and brain perfusion single‐photon emission computed tomography at baseline with an approximately 2‐year follow up. The patients were divided into two subgroups according to the presence of WML on magnetic resonance imaging. Single‐photon emission computed tomography data were analyzed using a voxel‐by‐voxel group analysis with Statistical Parametric Mapping 8 and region of interest analysis using FineSRT. Changes in Mini‐Mental State Examination scores and regional cerebral blood flow were analyzed using the Wilcoxon signed‐rank test.

Results

Mean Mini‐Mental State Examination scores in AD patients with WML significantly decreased from 19.4 ± 4.8 to 15.5 ± 6.5 (P = 0.003). Statistical Parametric Mapping 8 and FineSRT analysis showed more severe and widespread regional cerebral blood flow reduction, mainly in the frontal and mesial temporal regions in AD patients with WML compared with those without WML.

Conclusion

Baseline WML could predict a rapid progression of cognitive and brain functional impairment during longitudinal follow up in AD. Geriatr Gerontol Int 2016; 16: 836–842.
Classification and regression tree analysis vs. multivariable linear and logistic regression methods as statistical tools for studying haemophilia
Authors: Henrard S. , Speybroeck N. , Hermans C.
Published: August 2015

Introduction

Haemophilia is a rare genetic haemorrhagic disease characterized by partial or complete deficiency of coagulation factor VIII, for haemophilia A, or IX, for haemophilia B. As in any other medical research domain, the field of haemophilia research is increasingly concerned with finding factors associated with binary or continuous outcomes through multivariable models. Traditional models include multiple logistic regressions, for binary outcomes, and multiple linear regressions for continuous outcomes. Yet these regression models are at times difficult to implement, especially for non‐statisticians, and can be difficult to interpret.

Aims

The present paper sought to didactically explain how, why, and when to use classification and regression tree (CART) analysis for haemophilia research.

Materials & methods

The CART method is non‐parametric and non‐linear, based on the repeated partitioning of a sample into subgroups based on a certain criterion. Breiman developed this method in 1984. Classification trees (CTs) are used to analyse categorical outcomes and regression trees (RTs) to analyse continuous ones.

Results

The CART methodology has become increasingly popular in the medical field, yet only a few examples of studies using this methodology specifically in haemophilia have to date been published. Two examples using CART analysis and previously published in this field are didactically explained in details.

Conclusion

There is increasing interest in using CART analysis in the health domain, primarily due to its ease of implementation, use, and interpretation, thus facilitating medical decision‐making. This method should be promoted for analysing continuous or categorical outcomes in haemophilia, when applicable.
Concordance of absolute and relative plasma volume changes and stability of Fcells in routine hemodialysis
Authors: Schneditz Daniel , Ribitsch Werner , Schilcher Gernot , Uhlmann Matthias , Chait Yossi , Stadlbauer Vanessa
Published: August 2015

Central hematocrit (H) measurements are currently used to track the degree of ultrafiltration‐induced hemoconcentration with the aim to detect and prevent excessive intravascular fluid depletion during hemodialysis (HD). Failure to maintain hemodynamic stability is commonly attributed to the misinterpretation of H caused by an unaccountable increase in Fcells, the ratio of whole‐body hematocrit to H. It was the aim to examine Fcells under everyday conditions in a group of stable HD patients. Absolute plasma volume (Vp) and H were concomitantly measured during routine HD in the extracorporeal system in hourly intervals by noninvasive and continuous technology (CritLine‐Instrument‐III) and indocyanine green dye dilution to derive relative plasma volumes from Vp and H (RPVp, RPVH), respectively, and to calculate Fcells. Thirteen patients were studied during two midweek treatments (n = 26). Both absolute Vp (P < 0.05) and relative plasma volumes RPVH (P < 0.001) decreased during HD. Vp at any time point was positively correlated to RPVH (r = 0.52). Moreover, relative plasma volumes RPVH and RPVp determined by independent techniques were identical and showed negligible bias (−0.2%) but considerable limits of agreement (−15.6% to +15.3%). Fcells was stable and in the range of 0.9 ± 0.05 throughout HD and not different from the value assumed at the beginning of HD. Although Fcells remains constant in patients on routine dialysis and relative plasma volumes (RPVH and RPVp) determined by independent techniques are therefore comparable, the variability of experimental conditions during dialysis and the limited accuracy of absolute volume measurements using available technology continues to complicate the ultrafiltration control problem.
A semi‐automated method to assess intraepidermal nerve fibre density in human skin biopsies
Authors: Seger Shanon , Stritt Manuel , Doppler Kathrin , Frank Stephan , Panaite Adrian , Kuntzer Thierry , Steck Andreas , Pagenstecher Axel , Sommer Claudia , Stalder Anna K
Published: August 2015

Aims

Evaluation of intraepidermal nerve fibres (IENFs) in skin biopsies is used in the diagnosis of small‐fibre neuropathies. The number of IENFs is assessed manually under a microscope, with an inter‐rater variability of ~25%. Unless the images are digitized, there is no documentation. Our aim was to develop a method for standardized semi‐automated quantification (SAQ) and documentation of IENF density.

Methods and results

We analysed samples from four different university centres that were immunostained according to local protocols. Images were acquired through the Z‐plane with a whole slide scanner. orbit image analysis software was used to create an analysable image and develop a reliable algorithm for IENF detection. Rebuilt images revealed well‐contrasted nerves, allowing detection of IENFs (automated). The software presented the detected nerves for confirmation by the operator (manual). As compared with the conventional microscopy count, the SAQ achieved correlation coefficients of 0.99 and 0.96 and interfacility variabilities of 19% and 23%, respectively. We found better reproducibility with fluorescence‐stained specimens than with bright‐field images.

Conclusions

The new semi‐automated method has high experimenter‐independent reproducibility when based on nerve detection by fluorescence and is easy to perform, even by untrained users. The IENF counting is electronically well documented.
Phase Formation, Microstructure, and Densification of Yttrium‐Doped Barium Zirconate Prepared by the Sonochemical Method
Authors: Seeharaj Panpailin , Charoonsuk Thitirat , Pasupong Patchara , Kim‐Lohsoontorn Pattaraporn , Vittayakorn Naratip
Published: August 2015

Spherical monodispersed yttrium‐doped barium zirconate (BaY0.1Zr0.9O3; BYZ) particles were successfully prepared in single step without the requirement of calcination process by the sonochemical method in highly basic aqueous solution. The stoichiometric solution of BaCl2.2H2O, ZrOCl2.8H2O, and YCl4.6H2O was precipitated in a 20 M NaOH under high‐intensity ultrasonic irradiation (20 kHz, 150 W/cm2) for 15, 30, and 60 min. As‐prepared powders were identified by XRD, FT‐IR, and Raman spectroscopy as cubic perovskite BYZ. The microstructure examined by SEM and TEM showed spherical‐shaped BYZ particles formed by aggregation of primary nanocrystals, and this unique morphology was induced by the effects of the ultrasonication and the strong alkaline environment. BYZ powders prepared under ultrasonication for 60 min had narrow‐sized distribution with the average particle size of 267 ± 26 nm and the specific surface area of 40.2 m2/g. BYZ ceramics sintered in the air at 1550°C for 20 h showed good densification (95%) and consisted of large grain size (7.67 ± 2.79 μm).
Prevalence of hepatic osteodystrophy and vitamin D deficiency in cirrhosis
Authors: Chinnaratha M. A. , Chaudhary S. , Doogue M. , McCormick R. J. , Woodman R. J. , Wigg A. J.
Published: August 2015

Background

Hepatic osteodystrophy (HO) is a major complication of cirrhosis. However, the prevalence of HO in a general cirrhotic patient population is not well defined as previous studies were in single aetiology or pre‐liver transplant patients.

Aims

The aims of this study were to investigate the prevalence of HO and vitamin D deficiency in patients with cirrhosis of mixed aetiology and disease severity and to determine the risk factors for HO.

Methods

This is a single‐centre cross‐sectional study of all patients newly diagnosed with cirrhosis between September 2009 and December 2012. All patients underwent bone mineral density assessment using dual energy X‐ray absorptiometry within 3 months of diagnosis. Demographic and biochemical factors, severity of underlying liver disease, previous fragility fractures, smoking status and alcohol use were collected on diagnosis. Logistic regression analysis was used to assess risk factors for HO.

Results

Among the 406 patients (67% males), the median (range) age was 56 years (21–85) and most (84%) were Childs–Pugh A or B with a median (range) model for end‐stage liver disease score of 11 (5–40). Alcohol (41%) was the most common underlying aetiology. The prevalence of HO and vitamin D deficiency (≤50 nmol/L) was 56% and 54%, respectively, and previous fragility fractures had occurred in 3%. Increasing age (odds ratio (95% confidence interval): 1.49 per 10 years (1.02–2.18), P = 0.04), excessive alcohol intake (2.34 (1.03–5.32), P = 0.04) and lower body mass index (0.92 per kg/m2 (0.87–0.98), P = 0.009) were independent risk factors for HO.

Conclusion

There is a high prevalence of HO and vitamin D deficiency in patients with cirrhosis at presentation irrespective of disease severity or underlying aetiology.
Highly (100)‐Oriented Bi(Ni1/2Hf1/2)O3‐PbTiO3 Relaxor‐Ferroelectric Films for Integrated Piezoelectric Energy Harvesting and Storage System
Authors: Xie Zhenkun , Peng Bin , Zhang Jie , Zhang Xiaohua , Yue Zhenxing , Li Longtu
Published: August 2015

Highly (100)‐oriented 0.38Bi(Ni1/2Hf1/2)O3‐0.62PbTiO3 relaxor‐ferroelectric films were fabricated on Pt(111)/Ti/SiO2/Si(111) substrates by introducing a lead oxide seeding layer. A moderate relative permittivity , a low dissipation factor (tan δ < 5%), and strong relaxor‐like behavior (γ = 0.74) over a broad temperature region were observed. The energy storage density of approximately 45.1 ± 2.3 J/cm3 was achieved for films with (100) preferential orientation, which is much higher than the value ~33.5 ± 1.7 J/cm3 obtained from films with random orientation. Furthermore, the PbO‐seeded films are more capable of providing larger piezoelectric response (~113 ± 10 pm/V) compared to the films without seeds (~85 ± 8 pm/V). These excellent features indicate that the highly (100)‐oriented 0.38Bi(Ni1/2Hf1/2)O3‐0.62PbTiO3 films could be promising candidates for applications in high‐energy storage capacitors, high‐performance MEMS devices, and particularly for potential applications in the next‐generation integrated multifunctional piezoelectric energy harvesting and storage system.
Ferroelectric Phase Transition, Interfaces Quality, and Stress Evolution of TiOx/BaxSr1−xTiO3 Structures
Authors: Ghalem Areski , Ponchel Freddy , Rémiens Denis , Lasri Tuami
Published: August 2015

Ba(Sr,Ti)O3 material presents a remarkable property that lies in the possibility to change the permittivity by applying a dc electric field, i.e., BST is a tunable material. That makes BST a very interesting material for the development of reconfigurable devices in microelectronics. In this study, we focus our work on Ba(Sr,Ti)O3 with Ba/Sr = 30/70, the films are deposited by radio‐frequency magnetron sputtering on Al2O3 (0001). A buffer layer of TiOx is used to control the film orientation. The influence of this buffer layer on the dielectric properties, the interfaces quality with respect to the film thickness, and the temperature is analyzed. An increase of 30% of the relative permittivity was measured and a tunability of 50% was attained at 300 KV/cm. The dielectric measurements on BST/TiOx as a function of the temperature show a shift of the Curie temperature (Tc = −40°C) in comparison to BST without TiOx layer (Tc = −80°C). We demonstrate that the Curie temperature does not correspond to the maximum permittivity. The important stress measured on the films (930 MPa) could explain this behavior.
Hybrid Sol–Gel Glasses with Glass‐Transition Temperatures Below Room Temperature
Authors: Jitianu Andrei , Gonzalez Guadalupe , Klein Lisa C.
Published: August 2015

Melting gels are hybrid gels that have the ability to soften and flow at around 100°C for some combinations of mono‐ and di‐substituted alkoxysiloxanes, where substitutions are either all aromatic or all aliphatic. In this study, melting gels were prepared using phenyltriethoxysilane (PhTES) and dimethyldiethoxysilane (DMDES), meaning both an aromatic and aliphatic substitution. Differential scanning calorimetry was performed to identify glass‐transition temperatures, and thermal gravimetric analysis coupled with differential thermal analysis (TGA‐DTA) was performed to measure weight loss. The glass‐transition temperatures (Tg) ranged from −61°C to +5.6°C, which are between the values in the methyl only system, where all Tg values are less than 0°C, and those values in the phenyl only system, where Tg values are greater than 0°C. The Tg decreased with an increase in the DMDES fraction. Below 450°C, the gels lost little weight, but around 600°C there was a drop in weight. This temperature is lower than the temperature for gels prepared with only aromatic substitutions, but higher than that for gels prepared with only aliphatic substitutions. Final heat treatment was carried out at 150°C for the gel with 80%PhTES‐20%DMDES (in mol%), and the consolidation temperature increased with increasing DMDES content to 205°C for the gel with 50%PhTES‐50%DMDES. After this heat treatment, the melting gels no longer soften.
Diverse Fibrosis Architecture and Premature Stimulation Facilitate Initiation of Reentrant Activity Following Chronic Atrial Fibrillation
Authors: ANGEL NATHAN , LI LI , MACLEOD ROB S. , MARROUCHE NASSIR , RANJAN RAVI , DOSDALL DEREK J.
Published: August 2015

Fibrosis Architecture and Conduction in Chronic AF

Introduction

Patients with paroxysmal atrial fibrillation (AF) often transition between sinus rhythm and AF. For AF to initiate there must be both a trigger and a substrate that facilitates reentrant activity. This trigger is often caused by a premature atrial contraction or focal activations within the atrium. We hypothesize that specific architectures of fibrosis alter local conduction to enable AF.

Methods and Results

Control goats (n = 13) and goats in chronic AF (for an average of 6 months, n = 6) had a high‐density electrode plaque placed on the LA appendage. Conduction patterns following a premature atrial contraction, caused by an electrical stimulation, were quantified to determine regions of conduction slowing. These regions were compared to architecture, either diffuse fibrosis or regions of obstructive fibrosis, and overall fibrosis levels as determined by histology from the mapped region. The chronic AF goats had more obstructive fibrosis than the controls (17.5 ± 8.0 fibers/mm2 vs. 8.6 ± 3.0 fibers/mm2). Conduction velocity of the AF goats was significantly slowed compared to the control goats in the transverse direction (0.40 ± 0.04 m/s vs. 0.53 ± 0.15 m/s) but not in the longitudinal direction (0.70 ± 0.27 m/s vs. 0.76 ± 0.18 m/s).

Conclusions

AF‐induced atrial remodeling leads to increased obstructive fibrosis and conduction velocity slowing transverse to fiber orientation following premature stimuli. The decrease in conduction velocity causes a decrease in the cardiac wavelength, and increases the likelihood of reentry and AF onset.
Age, Body Mass Index, and Daytime and Nocturnal Hypoxia as Predictors of Hypertension in Patients With Obstructive Sleep Apnea
Authors: Natsios Georgios , Pastaka Chaido , Vavougios Georgios , Zarogiannis Sotirios G. , Tsolaki Vasiliki , Dimoulis Andreas , Seitanidis Georgios , Gourgoulianis Konstantinos I.
Published: August 2015

A growing body of evidence links obstructive sleep apnea (OSA) with hypertension. The authors performed a retrospective cohort study using the University Hospital of Larissa Sleep Apnea Database (1501 patients) to determine predictors of in‐laboratory diagnosed OSA for development of hypertension. Differences in continuous variables were assessed via independent samples t test, whereas discrete variables were compared by Pearson's chi‐square test. Multivariate analysis was performed via discriminant function analysis. There were several significant differences between hypertensive and normotensive patients. Age, body mass index, comorbidity, daytime oxygen saturation, and indices of hypoxia during sleep were deemed the most accurate predictors of hypertension, whereas apnea‐hypopnea index and desaturation index were not. The single derived discriminant function was statistically significant (Wilk's lambda=0.771, χ2=289.070, P<.0001). Daytime and nocturnal hypoxia as consequences of chronic intermittent hypoxia play a central role in OSA‐related hypertension and should be further evaluated as possible severity markers in OSA.