bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabinoid‐1 receptor deletion in podocytes mitigates both glomerular and tubular dysfunction in a mouse model of diabetic nephropathy
Authors: Jourdan Tony , Park Joshua K. , Varga Zoltán V. , Pálóczi János , Coffey Nathan J. , Rosenberg Avi Z. , Godlewski Grzegorz , Cinar Resat , Mackie Ken , Pacher Pal , Kunos George
Published: November 2017

Aims

To determine the specific role of podocyte‐expressed cannabinoid‐1 receptor (CB1R) in the development of diabetic nephropathy (DN), relative to CB1R in other renal cell types.

Material and methods

We developed a mouse model with a podocyte‐specific deletion of CB1R (pCB1Rko) and challenged this model with streptozotocin (STZ)‐induced type‐1 DN. We also assessed the podocyte response to high glucose in vitro and its effects on CB1R activation.

Results

High glucose exposure for 48 hours led to an increase in CB1R gene expression (CNR1) and endocannabinoid production in cultured human podocytes. This was associated with podocyte injury, reflected by decreased podocin and nephrin expression. These changes could be prevented by Cnr1‐silencing, thus identifying CB1R as a key player in podocyte injury. After 12 weeks of chronic hyperglycaemia, STZ‐treated pCB1Rko mice showed elevated blood glucose similar to that of their wild‐type littermates. However, they displayed less albuminuria and less podocyte loss than STZ‐treated wild‐type mice. Unexpectedly, pCB1Rko mice also have milder tubular dysfunction, fibrosis and reduction of cortical microcirculation compared to wild‐type controls, which is mediated, in part, by podocyte‐derived endocannabinoids acting via CB1R on proximal tubular cells.

Conclusions

Activation of CB1R in podocytes contributes to both glomerular and tubular dysfunction in type‐1 DN, which highlights the therapeutic potential of peripheral CB1R blockade.
Right heart function in impaired left ventricular diastolic function: 2D speckle tracking echocardiography–based and Doppler tissue imaging–based analysis of right atrial and ventricular function
Authors: Brand Anna , Bathe Marny , Oertelt‐Prigione Sabine , Seeland Ute , Rücke Mirjam , Regitz‐Zagrosek Vera , Stangl Karl , Knebel Fabian , Stangl Verena , Dreger Henryk
Published: November 2017

Aim

The aim of our study was to describe right atrial (RA) and right ventricular (RV) function, assessed by Doppler tissue imaging and 2D speckle tracking echocardiography (2DSTE), in women with signs of early impaired left ventricular diastolic function (DD).

Methods and Results

In a cross‐sectional trial, standard parameters of diastolic and right heart function were investigated in 438 women of the Berlin Female Risk Evaluation (BEFRI) study. In a subset of women, average peak systolic RA strain (RAS), as well as the average peak systolic RV strain of the free wall (RVS free wall) and of all RV segments (average RV strain; RVS Avg), was analyzed using 2DSTE. Compared to women with normal diastolic function (DD0), RAS, RVS free wall and RVS Avg were significantly reduced in DD (43.1% ± 11.9%, −26.7% ± 5.6%, and −23.3% ± 3.5% in DD0; vs 35.1% ± 10.4%, −23.9% ± 5.5%, and −20.6% ± 3.8% in DD; P < .01). Peak RV myocardial velocity (RV‐IVV) and acceleration during isovolumetric contraction (RV‐IVA) were markedly higher in DD (15.0 ± 3.9 cm/s and 3.1 ± 1.0 m/s² in DD vs 11.9 ± 3.2 cm/s and 2.8 ± 0.8 m/s² in DD0; P < .05). RAS and RV‐IVV were significantly associated with DD after adjustment to age, BMI, and left atrial strain in multivariate regression analysis.

Conclusion

Systolic right heart function is significantly altered in DD. DTI as well as 2DSTE constitute sensitive echocardiographic tools that enable the diagnosis of impaired right heart mechanics in early‐staged DD.
Forecasting range shifts of a cold‐adapted species under climate change: are genomic and ecological diversity within species crucial for future resilience?
Authors: Theodoridis Spyros , Patsiou Theofania S. , Randin Christophe , Conti Elena
Published: November 2017

Cold‐adapted taxa are experiencing severe range shifts due to climate change and are expected to suffer a significant reduction of their climatically suitable habitats in the next few decades. However, it has been proposed that taxa with sufficient standing genetic and ecologic diversity will better withstand climate change. These taxa are typically more broadly distributed in geographic and ecological niche space, therefore they are likely to endure higher levels of populations loss than more restricted, less diverse taxa before the effects of those losses impact their overall diversity and resilience. Here, we explore the potential relationship between intraspecific genetic and ecological diversity and future resilience, using the cold‐adapted plant Primula farinosa. We employ high‐throughput sequencing to assess the genomic diversity of phylogeographic lineages in P. farinosa. Additionally, we use current climatic variables to define niche breadth and niche differentiation across lineages. Finally, we calibrate species distribution models (SDMs) and project the climatic preferences of each lineage on future climate to predict lineage‐specific shifts in climatically suitable habitats. Our study predicts relative persistence of future suitable habitats for the most genetically and ecologically diverse lineages of the cold‐adapted P. farinosa, but significant reduction of them for two out of its four lineages. While we do not provide specific experiments aimed at identifying the causal links between genetic diversity and resilience to climate change, our results indicate that greater genetic diversity and wider ecological breadth may buffer species responses to rapid climatic changes. This study further highlights the importance of integrating knowledge of intraspecific diversity for predicting species fate in response to climate change.
Disentangling the effects of spring anomalies in climate and net primary production on body size of temperate songbirds
Authors: Dubos Nicolas , Le Viol Isabelle , Robert Alexandre , Teplitsky Céline , Ghislain Manon , Dehorter Olivier , Julliard Romain , Henry Pierre Yves
Published: November 2017

Body size is implicated in individual fitness and population dynamics. Mounting interest is being given to the effects of environmental change on body size, but the underlying mechanisms are poorly understood. We tested whether body size and body condition are related to ambient temperature (heat maintenance hypothesis), or/and explained by variations in primary production (food availability hypothesis) during the period of body growth in songbirds. We also explored whether annual population‐level variations of mean body size are due to changes of juvenile growth and/or size‐dependent mortality during the first year. For 41 species, from 257 sites across France, we tested for relationships between wing length (n = 107 193) or body condition (n = 82 022) and local anomalies in temperature, precipitation and net primary production (NDVI) during the breeding period, for juveniles and adults separately. Juvenile body size was best explained by primary production: wings were longer in years with locally high NDVI, but not shorter in years with low NDVI. Temperature showed a slightly positive effect. Body condition and adult wing length did not covary with any of the other tested variables. We found no evidence of climate‐driven size‐dependent mortality for the breeding season. In our temperate system, local climatic anomalies explained little of the body size variation. A large part of wing length variance was site‐specific, suggesting that avian size was more dependent on local drivers than global ones. Net primary production influenced juvenile size the most through effects on body growth. We suggest that, during the breeding season in temperate systems, thermoregulatory mechanisms are less involved in juvenile growth than food assimilation.
Study of bone metabolism and angiogenesis in patients undergoing high‐dose chemotherapy/autologous hematopoietic stem cell transplantation
Authors: Boutsikas Georgios , Terpos Evangelos , Papatheodorou Athanasios , Tsirkinidis Pantelis , Tsirigotis Panayiotis , Meletiou Anastasia , Lalou Eleni , Telonis Vasileios , Zannou Anna , Kanellopoulos Alexander , Galani Zacharoula , Stefanou Angeliki , Tsaftaridis Panayiotis , Viniou Nora‐Athina , Panayiotidis Panayiotis , Kyrtsonis Marie‐Christine , Meletis John , Vassilakopoulos Theodoros P. , Angelopoulou Maria K.
Published: November 2017

Objectives

As the interaction between hematopoietic stem cells (HSCs) and endosteal and endothelial niches in HSCs homing is essential, we aimed to study bone turnover and angiogenesis in 29 patients with lymphoma/multiple myeloma undergoing hematopoietic stem cell transplantation (HSCT).

Methods

Serum samples were collected before high‐dose chemotherapy (HDT), at the end of HDT, after HSC infusion, at the nadir of myelotoxicity, and at engraftment. Bone metabolism (CTX, TRACP‐5b, bALP, OC, DKK1, RANKL, OPG), and angiogenesis (Ang1, Ang2) markers were measured. These markers were also measured in 21 control patients before and after conventional chemotherapy.

Results and Conclusions

Bone resorption declined during HSCT (decrease in TRACP‐5b [P < .001] and CTX [P = .006]). Bone formation declined as well (decrease in bALP and OC [P < .001 for both]). RANKL/OPG ratio, an indicator of osteoclastic activation, did not change significantly (P = .5). Ang1/Ang2 ratio, a vessel equilibrium marker, decreased significantly (P < .001) suggesting endothelial destabilization. The changes observed in the control group were similar except of bALP and RANKL/OPG ratio. Moreover, Ang1/Ang2 ratio on the day after HSC infusion strongly correlated with time to neutrophil and platelet engraftment (P < .001 for both). Conclusively, bone turnover and vessel destabilization represent important events during HSCT probably reflecting the effect of chemotherapy.
Cost–effectiveness analysis of interventions for prevention of invasive aspergillosis among leukemia patients during hospital construction activities
Authors: Combariza Juan F. , Toro Luis F. , Orozco John J. , Arango Marcos
Published: November 2017

Objectives

Invasive Aspergillosis (IA) is a serious problem among hematological patients and it is associated with high mortality. This situation can worsen at times of hospital construction, however there are several preventive measures available. This work aims to define the cost‐effectiveness of some of these interventions.

Patients and methods

A decision tree model was used, it was divided into four arms according to each 1 of the interventions performed. A cost‐effectiveness incremental analysis comparing environmental control measures, high efficiency particulate absorption (HEPA) filter installation and prophylaxis with posaconazole was done. Probabilistic and deterministic sensitivity analyses were also carried out.

Results

Among 86 patients with 175 hospitalization episodes, the incidence of IA with environmental protection measures, antifungal prophylaxis and hospitalization in rooms with HEPA filters was 14.4%, 6.3% and 0%, respectively. An Incremental Cost Effectiveness Ratio analysis was performed and it was found that HEPA filtered rooms and environmental protection measures are cost saving interventions when compared with posaconazole prophylaxis (−$2665 vs −$4073 vs $42 531 US dollars, respectively) for IA episode prevented.

Conclusion

The isolation of inpatients with acute leukemia during hospital construction periods in HEPA filtered rooms could reduce the incidence of IA and might be a cost‐effective prevention strategy.
Predictors of symptomatic intracranial haemorrhage in off‐label thrombolysis: an analysis of the Safe Implementation of Treatments in Stroke registry
Authors: Mundiyanapurath S. , Hees K. , Ahmed N. , Wahlgren N. , Uhlmann L. , Kieser M. , Ringleb P. A. , Hacke W. , Nagel S.
Published: November 2017

Background and purpose

Intravenous thrombolysis (IVT) is the only approved pharmacological treatment for acute ischemic stroke. Off‐label IVT for ischemic stroke is common. We aimed to analyse its safety in a large database.

Methods

This was a retrospective analysis of the safe implementation of treatments in stroke (SITS) thrombolysis registry with regard to 11 off‐label criteria according to the European licence for alteplase. Symptomatic intracranial haemorrhage (SICH) according to SITS was defined as primary safety endpoint and SICH according to the European Cooperative Acute Stroke Study (ECASS II) definition and the National Institute of Neurological Disorders and Stroke definition as secondary safety endpoints. Multivariable logistic regression analyses after replacing missing values using multiple imputations were performed.

Results

Patients from 793 centres in 44 countries were included, mainly (95%) in Europe. A total of 56 258 patients who were treated with intravenous alteplase were included. Median age was 71 (IQR 61–78) years and median National Institutes of Health Stroke Scale score was 12 (IQR 7–17). A total of 16 740 (30%) patients received off‐label IVT and 1037 (1.8%) patients suffered from SICH according to the SITS definition (SICH SITS). Median percentage of missing values per variable was 0.4%. The only two off‐label criteria constituting independent positive and negative predictors for SICH SITS were high blood pressure (odds ratio, 1.39; 95% confidence interval, 1.08–1.80; P = 0.012) and minor stroke (odds ratio, 0.51; 95% confidence interval, 0.33–0.78; P = 0.002). Very severe stroke, previous stroke and diabetes, age and high glucose levels were additional independent predictors of SICH according to the ECASS II and National Institute of Neurological Disorders and Stroke definitions.

Conclusions

Thrombolysis appears to be safe with regard to SICH for most of the off‐label criteria, especially for minor stroke, but is risky in patients with high blood pressure. Individual risk–benefit evaluation should be performed.
Methodological standards for in vitro models of epilepsy and epileptic seizures. A TASK1‐WG4 report of the AES/ILAE Translational Task Force of the ILAE
Authors: Raimondo Joseph V. , Heinemann Uwe , de Curtis Marco , Goodkin Howard P. , Dulla Chris G. , Janigro Damir , Ikeda Akio , Lin Chou‐Ching K. , Jiruska Premysl , Galanopoulou Aristea S. , Bernard Christophe
Published: November 2017

In vitro preparations are a powerful tool to explore the mechanisms and processes underlying epileptogenesis and ictogenesis. In this review, we critically review the numerous in vitro methodologies utilized in epilepsy research. We provide support for the inclusion of detailed descriptions of techniques, including often ignored parameters with unpredictable yet significant effects on study reproducibility and outcomes. In addition, we explore how recent developments in brain slice preparation relate to their use as models of epileptic activity.
Harmonization in preclinical epilepsy research: A joint AES/ILAE translational initiative
Authors: Galanopoulou Aristea S. , French Jacqueline A. , O'Brien Terence , Simonato Michele
Published: November 2017

Among the priority next steps outlined during the first translational epilepsy research workshop in London, United Kingdom (2012), jointly organized by the American Epilepsy Society (AES) and the International League Against Epilepsy (ILAE), are the harmonization of research practices used in preclinical studies and the development of infrastructure that facilitates multicenter preclinical studies. The AES/ILAE Translational Task Force of the ILAE has been pursuing initiatives that advance these goals. In this supplement, we present the first reports of the working groups of the Task Force that aim to improve practices of performing rodent video–electroencephalography (vEEG) studies in experimental controls, generate systematic reviews of preclinical research data, and develop preclinical common data elements (CDEs) for epilepsy research in animals.
Comparison of different cryopreservation methods for horse and donkey embryos
Authors: Pérez‐Marín C. C. , Vizuete G. , Vazquez‐Martinez R. , Galisteo J. J.
Published: November 2017

Background

Few studies have been published about cryopreservation and embryo assessment in horses and donkeys.

Objectives

To evaluate the viability of embryos collected from mares and jennies that were cryopreserved by slow freezing or by vitrification.

Study design

Randomised controlled experiment.

Methods

Horse (n=19) and donkey (n=16) embryos (≤300 μm) were recovered on days 6.5–7.5 post‐ovulation and assigned to control or cryopreservation protocols of slow freezing or vitrification. For slow freezing, 1.5 mol/L ethylene glycol (EG) was used. For vitrification, horse embryos were exposed to 1.4 mol/L glycerol, 1.4 mol/L glycerol + 3.6 mol/L EG and 3.4 mol/L glycerol + 4.6 mol/L EG, using Fibreplug or a 0.25 mL straw; donkey embryos were vitrified using Fibreplug with similar EG–glycerol solutions to above or 7.0 mol/L EG. Dead cells, apoptotic and fragmented nuclei, and cytoskeleton quality were assessed on thawed/warmed embryos.

Results

A significant decrease in embryo quality was observed after cryopreservation (P<0.05). Although the percentage of dead cells was lower (P<0.05) in control than in cryopreserved embryos, no differences were observed between freezing protocols used for horse or donkey embryos. While no differences were detected in the number of apoptotic cells in warmed horse embryos, in donkey embryos a higher incidence of apoptosis was measured after vitrification with EG–glycerol in Fibreplug (P<0.05). Vitrified horse embryos had a significantly (P<0.05) higher percentage of nonviable cells than donkey embryo. Actin cytoskeleton quality did not differ between treatments.

Main limitations

Difficulties in obtaining a large number of embryos meant that the number of embryos per group was low.

Conclusions

Vitrified horse and donkey embryos did not show higher susceptibility to cell damage than those preserved by slow freezing, whether using straws or Fibreplug. However, Fibreplug with EG 7 mol/L resulted in fewer nonviable and apoptotic cells in donkey embryos. Donkey embryos showed lower susceptibility to vitrification than horse embryos.

The Summary is available in Spanish ‐ See Supporting Information
The late‐stage “ferruginization” of the Ediacara Member (Rawnsley Quartzite, South Australia): Insights from uranium isotopes
Authors: Tarhan L. G. , Planavsky N. J. , Wang X. , Bellefroid E. J. , Droser M. L. , Gehling J. G.
Published: November 2017

The paleoenvironmental setting in which the Ediacara Biota lived, died, and was preserved in the eponymous Ediacara Member of the Rawnsley Quartzite of South Australia is an issue of long‐standing interest and recent debate. Over the past few decades, interpretations have ranged from deep marine to shallow marine to terrestrial. One of the key features invoked by adherents of the terrestrial paleoenvironment hypothesis is the presence of iron oxide coatings, inferred to represent the upper horizons of paleosols, along fossiliferous sandstone beds of the Ediacara Member. We find that these surficial oxides are characterized by (234U/238U) values which are not in secular equilibrium, indicating extensive fluid‐rich alteration of these surfaces within the past approximately 2 million years. Specifically, the oxide coatings are characterized by (234U/238U) values >1, indicating interaction with high‐(234U/238U) fluids derived from alpha‐recoil discharge. These oxides are also characterized by light “stable” δ238/235U values, consistent with a groundwater U source. These U isotope data thus corroborate sedimentological observations that ferric oxides along fossiliferous surfaces of the Ediacara Member consist of surficial, non‐bedform‐parallel staining, and sharply irregular patches, strongly reflecting post‐depositional, late‐stage processes. Therefore, both sedimentological and geochemical evidence indicate that Ediacara iron oxides do not reflect synsedimentary ferruginization and that the presence of iron oxides cannot be used to either invoke a terrestrial paleoenvironmental setting for or reconstruct the taphonomic pathways responsible for preservation of the Ediacara Biota. These findings demonstrate that careful assessment of paleoenvironmental parameters is essential to the reconstruction of the habitat of the Ediacara Biota and the factors that led to the fossilization of these early complex ecosystems.
The economic geography of immigrant diversity: Disparate impacts and new directions
Authors: Cooke Abigail , Kemeny Thomas
Published: November 2017

Increasing immigrant diversity, both in the number of immigrants and the diversity of sending countries, is helping reshape the economic landscape in many countries, most notably in their urban regions. This paper provides a succinct introduction to the existing research on the economic effects, particularly productivity, of immigrant diversity, focusing on a recent wave of empirical work. It identifies outstanding questions in the research, offering several ways to push current lines of inquiry ahead and suggesting areas as yet underexplored. To motivate these new directions for geographers to pursue, it presents empirical results that raise more questions than they answer. In doing so, it sets the stage for future work that can generate a deeper understanding of the role of immigrant diversity in shaping economic welfare in cities.
Solitary fibrous tumour of the female genital tract: a clinicopathological analysis of 25 cases
Authors: Yang Eric J , Howitt Brooke E , Fletcher Christopher D M , Nucci Marisa R
Published: November 2017

Aims

Solitary fibrous tumour (SFT) is an uncommon spindle cell neoplasm of fibroblastic origin, first described as a tumour of the pleura and now well established at extrapleural sites. However, SFT in the female genital tract is rare and therefore not fully characterised. Here, we describe a series of 25 SFTs arising throughout the gynaecological tract, including the vulva (14 cases), vagina (one), cervix (one), uterus (six), ovary (two), and fallopian tube (one).

Methods and results

The tumours showed classic histology as well as known variant morphological features, including a fatty component, diffuse stromal hyalinisation, myxoid stroma, and giant‐cell angiofibroma‐like features. Eleven (11/25, 44%) were considered to be histologically malignant on the basis of mitotic counts of ≥4 per 10 high‐power fields. Follow‐up data were available for nine (3–56 months; mean 25 months). Six patients are alive with no evidence of disease, and three are alive with disease. Both SFT and other spindle cell lesions of the gynaecological tract were stained for STAT6. Ninety per cent of SFTs showed nuclear expression of STAT6. The majority of other tumour types were negative for STAT6, except for a subset of inflammatory myofibroblastic tumours (1/3; 33%), fibroma/thecoma (3/56; 5%), and sclerosing stromal tumour (1/3; 33%), which showed weak/focal staining.

Conclusion

Gynaecological SFT can be diagnosed reliably with careful morphological evaluation and judicious use of immunohistochemical stains, and should be considered in the diagnostic workup of spindle cell tumours of unclear lineage in the female genital tract.
Determination of optimum Al content in HA‐Al2O3 nanocomposites coatings prepared by electrophoretic deposition on titanium substrate
Authors: Askari Nayereh , Yousefpour Mardali , Rajabi Masoud
Published: November 2017

In this research work, Hydroxyapatite (HA)‐Al2O3 bio nanocomposite coatings were coated on titanium substrate by electrophoretic deposition (EPD) and reaction bonding process. The reaction bonding process densifies the coating and creates small uniform porosities. HA‐Al2O3 bio nanocomposite coatings were analyzed by X‐ray diffraction (XRD) and field emission scanning electron microscopy (FE‐SEM). For the coatings sintered for 2 hours at 850°C, XRD results demonstrated no significant HA decomposition. The adhesion strength increased from 10.2 MPa to 25 MPa. It was determined that 50 wt.% of Al is the optimum content for producing free‐of‐crack composite coatings on the titanium surface as shown by SEM examination.
Resource allocation with partial responsibilities for initial endowments
Authors: Chambers Christopher P. , Hayashi Takashi
Published: November 2017

This paper studies a resource allocation problem in which each individual is responsible but in general only partially for his initial endowment. We consider pure‐exchange economies with initial endowments but we do not assume the individual rationality axiom, taking the society to consist of citizens who cannot opt out of it. We characterize a class of allocation rules which are parametrized by income redistribution codes. In particular, we characterize a one‐parameter family of income redistribution codes, in which one extreme corresponds to the case where everybody is 100% responsible for his initial endowment and the other extreme corresponds to the case where nobody is responsible for his endowment at all.
Competitive equilibrium in the random assignment problem
Authors: Le Phuong
Published: November 2017

This paper studies the problem of random assignment with fractional endowments. Fractional endowments complicate matters because the assignment has to make an agent weakly better off than his endowment. I first formulate an exchange economy that resembles the random assignment problem and prove the existence of competitive equilibrium in this economy. I then propose a pseudo‐market mechanism for the random assignment problem that is based on the competitive equilibrium. This mechanism is individually rational, Pareto optimal and justified envy‐free but not incentive compatible.
Competition versus collusion: The impact of consumer inertia
Authors: Bos Iwan , Peeters Ronald , Pot Erik
Published: November 2017

A model of dynamic price competition is analyzed to assess how consumer inertia may impact the ability of firms to sustain high prices. Three main consequences are identified: maintaining high prices does not require punishment strategies when firms are sufficiently myopic; for sufficiently high levels of inertia, high prices can be sustained at all discount factors; and the ability to maintain high prices may depend non‐monotonically on the level of the discount factor. Our findings offer implications for strategic firm behavior and public policy. For example, measures aiming to reduce the degree of consumer inertia are unambiguously effective in traditional markets, but may facilitate collusion in network industries.
Health insurance, market power, and social welfare
Authors: Liang Run , Wang Hao
Published: November 2017

This paper considers the welfare effects of health insurance. With a rather general model, we show that the presence of traditional health insurance makes consumers worse off when the marginal cost of health care is low enough, while always making the health care provider better off. The presence of traditional health insurance increases social welfare, but cannot achieve the socially optimal outcome. Furthermore, we consider a market structure called “integrated health insurance” and show that in a health care market where a firm provides not only health care but also health insurance, the socially optimal outcome can be achieved.
Multiple centre evaluation study of ADAMTS13 activity and inhibitor assays
Authors: Langley K. , Fretwell R. , Kitchen S. , MacDonald S. , Dutt T. , Baker P. , Singh D. , McDonald V. , Hughes C. , Murphy P. , Scully M.
Published: November 2017

Introduction

Accurate evaluation of ADAMTS13 activity is required for the diagnosis and clinical management of thrombotic microangiopathies, and commercial kits are available for routine laboratory use.

Methods

Our study compares the results from Technoclone (Technoclone GmbH, Austria) activity and Inhibitor kits with specialist laboratory reference methods (FRETS and ELISA IgG) and the impact of transporting frozen samples and comparison of results.

Results

This multicentre study identified differences in Technoclone activity results compared to specialist testing, which could potentially impact diagnosis. A change in the commercial kit during the study period appears to have rectified the detection levels. Frozen samples provided comparable results between sites.

Conclusion

With close attention to normal ranges, commercial kits are suitable for use in the clinical diagnosis of thrombotic microangiopathies and frozen transportation of samples between sites is a suitable approach. However, a robust external quality control system is essential to provide an independent evaluation of changes in kit production.
Evaluation of NovoRapid infusion as a treatment option in the management of diabetic ketoacidosis
Authors: Kwok Raylene , Sztal‐Mazer Shoshana , Hopkins Ria E. , Poole Susan G. , Grannell Louise , Coutsouvelis John , Topliss Duncan J.
Published: November 2017

This study evaluates the clinical efficacy and safety of NovoRapid (insulin aspart) compared to Actrapid™ (human neutral insulin) for diabetic ketoacidosis (DKA). In this retrospective study involving 40 patients, no statistically significant differences were observed between biochemical variables, infusion duration or complications in patients treated with insulin aspart or human neutral insulin. These results support the use of insulin aspart as an effective and safe alternative to human neutral insulin in DKA.
Inappropriate inhaled corticosteroid prescribing in chronic obstructive pulmonary disease patients
Authors: Harrison Amelia , Borg Brigitte , Thompson Bruce , Hew Mark , Dabscheck Eli
Published: November 2017

The Australian National Chronic Obstructive Pulmonary Disease (COPD) guidelines recommend that inhaled corticosteroids (ICS) be reserved for patients with a post‐bronchodilator forced expiratory volume in 1 s (FEV1) less than 50% predicted and those who experience ≥2 exacerbations in 12 months. In total, 707 COPD patients were identified from the lung function test database at our tertiary hospital; 52.4% of patients with a post‐bronchodilator FEV1 ≥50% were prescribed an ICS. Significant discordance exists between guideline recommendations and inhaler prescription.
Optimizing multiship routing and scheduling with constraints on inventory levels in a Brazilian oil company
Authors: Stanzani Amélia de Lorena , Pureza Vitória , Morabito Reinaldo , Silva Bruno Jensen Virginio da , Yamashita Denise , Ribas Paulo César
Published: November 2017

This study addresses a real‐life multiship routing and scheduling application with inventory constraints that arises in pickup and delivery operations of different types of crude oil from various offshore oil rigs (platforms) to coastal terminals. Oil transportation largely results from the need to maintain inventories at each supply point (platform) between minimum and maximum levels, considering production rates in these operational points, and to meet demands of different oils in the terminals within the planning time horizon. Routing and scheduling of the available fleet aims to obtain solutions of minimum total costs, subject to various constraints such as the maximum volume of cargo carried on each ship, simultaneous cargo unloading in some terminals, conditions that rule ship docking in offshore platforms and terminal berths, among others. In this research, we modify and extend inventory constrained maritime routing and scheduling models to appropriately represent the problem of a case study at a Brazilian company and to solve small‐to‐moderate instances based on real data. We also present a matheuristic to deal with larger problem instances. Solution evaluation by company experts indicates that the model and this hybrid heuristic properly represent the problem and highlights the potential of their application in practice.
Effect of interfacial energy on microstructure of a directionally solidified Al2O3/YAG eutectic ceramic
Authors: Wang Xu , Zhong Yujie , Wang Dong , Sun Luchao , Jiang Bailing , Wang Jingyang
Published: November 2017

An Al2O3/Y3Al5O12 eutectic ceramic was prepared with a c‐axis sapphire seed by an optical floating zone furnace. The crystallographic relationships in the initial and the steady growth sections of the as‐grown eutectic ceramic were investigated by electron backscattering diffraction and transmission electron microscopy. The corresponding results were: <111 > {101}Y3Al5O12 || <0001 > {}Al2O3 and <110 > {}Y3Al5O12 || < > {0001}Al2O3, respectively. The steady orientation of the latter one shows smaller planar disregistry. Interfacial strain played the decisive role in affecting the solidification behavior of the Al2O3/Y3Al5O12 eutectic ceramic. The stability of interfaces with minimum interfacial strain and better ionic charge balance in irregular microstructure prevail upon the constraint of the seed. These results might cast light for the interfacial design of the Al2O3/Y3Al5O12 binary eutectic ceramic.
Inhibition of mitochondrial complex I improves glucose metabolism independently of AMPK activation
Authors: Hou Wo‐Lin , Yin Jun , Alimujiang Miriayi , Yu Xue‐Ying , Ai Li‐Gen , Bao Yu‐qian , Liu Fang , Jia Wei‐Ping
Published: November 2017

Accumulating evidences showed metformin and berberine, well‐known glucose‐lowering agents, were able to inhibit mitochondrial electron transport chain at complex I. In this study, we aimed to explore the antihyperglycaemic effect of complex I inhibition. Rotenone, amobarbital and gene silence of NDUFA13 were used to inhibit complex I. Intraperitoneal glucose tolerance test and insulin tolerance test were performed in db/db mice. Lactate release and glucose consumption were measured to investigate glucose metabolism in HepG2 hepatocytes and C2C12 myotubes. Glucose output was measured in primary hepatocytes. Compound C and adenoviruses expressing dominant negative AMP‐activated protein kinase (AMPK) α1/2 were exploited to inactivate AMPK pathway. Cellular NAD+/NADH ratio was assayed to evaluate energy transforming and redox state. Rotenone ameliorated hyperglycaemia and insulin resistance in db/db mice. It induced glucose consumption and glycolysis and reduced hepatic glucose output. Rotenone also activated AMPK. Furthermore, it remained effective with AMPK inactivation. The enhanced glycolysis and repressed gluconeogenesis correlated with a reduction in cellular NAD+/NADH ratio, which resulted from complex I suppression. Amobarbital, another representative complex I inhibitor, stimulated glucose consumption and decreased hepatic glucose output in vitro, too. Similar changes were observed while expression of NDUFA13, a subunit of complex I, was knocked down with gene silencing. These findings reveal mitochondrial complex I emerges as a key drug target for diabetes treatment. Inhibition of complex I improves glucose homoeostasis via non‐AMPK pathway, which may relate to the suppression of the cellular NAD+/NADH ratio.
Renal function after intravitreal administration of vascular endothelial growth factor inhibitors in patients with diabetes and chronic kidney disease
Authors: Kameda Yusuke , Babazono Tetsuya , Uchigata Yasuko , Kitano Shigehiko
Published: November 2017

The present study aimed to determine whether intravitreal administration of vascular endothelial growth factor inhibitors is associated with deterioration of renal function, as seen with systemic administration, in patients with diabetes and chronic kidney disease. Estimated glomerular filtration rates before and after 160 intravitreal injections of vascular endothelial growth factor inhibitors (aflibercept, bevacizumab or ranibizumab) were compared in 69 patients with diabetes and with a baseline estimated glomerular filtration rate <60 mL/min/1.73 m2. We also determined the incidence of acute kidney injury. The data showed no significant difference in the estimated glomerular filtration rate before and after vascular endothelial growth factor inhibitor administration in all patients and in patient subgroups based on each inhibitor. Furthermore, no episodes of acute kidney injury occurred. In conclusion, intravitreal administration of vascular endothelial growth factor inhibitors is unlikely to be associated with a deterioration of renal function in patients with diabetes and chronic kidney disease.
Retrospective analysis of liraglutide and basal insulin combination therapy in Japanese type 2 diabetes patients: The association between remaining β‐cell function and the achievement of the glycated hemoglobin target 1 year after initiation
Authors: Usui Ryota , Sakuramachi Yui , Seino Yusuke , Murotani Kenta , Kuwata Hitoshi , Tatsuoka Hisato , Hamamoto Yoshiyuki , Kurose Takeshi , Seino Yutaka , Yabe Daisuke
Published: November 2017

Aims/Introduction

The glucose‐lowering effects of the glucagon‐like peptide‐1 receptor agonist, liraglutide, have been shown to rely on remaining β‐cell function. However, the possible associations of remaining β‐cell function with the glucose‐lowering effects of liraglutide in combination with basal insulin remain unknown and warrant investigation.

Materials and Methods

This was a single‐center, retrospective, observational study carried out in a private hospital in Osaka, Japan. Type 2 diabetes patients who received a prescription change from insulin therapy, both multiple‐dose insulin and basal insulin‐supported oral therapy, to liraglutide and basal insulin combination and continued the therapy for 54 weeks without additional oral antidiabetic drugs or bolus insulin were retrospectively analyzed.

Results

Among the 72 participants who received a prescription change from multiple‐dose insulin and basal insulin‐supported oral therapy to liraglutide and basal insulin combination, 57 continued the therapy for 54 weeks. Of those who continued the therapy without receiving additional oral antidiabetic drugs or bolus insulin, seven participants achieved glycated hemoglobin < 7.0% at 54 weeks, but 30 participants did not. The participants who achieved glycated hemoglobin < 7.0% at 54 weeks had a significantly higher C‐peptide immunoreactivity index, a β‐cell function‐related index frequently used in Japanese clinical settings. The receiver operating curve analysis showed that the C‐peptide immunoreactivity index cut‐off value for the achievement of glycated hemoglobin <7.0% at 54 weeks is 1.103.

Conclusions

The current findings show that the glucose‐lowering effects of liraglutide rely on remaining β‐cell function, even when used with basal insulin; and suggest that liraglutide and basal insulin combination might require additional bolus insulin to fully compensate insulin insufficiency in individuals with reduced β‐cell function.
Pheromones do regulate sexual development in Dictyostelium discoideum
Authors: O'Day D. H.
Published: November 2017

Based on negative data, Douglas et al refuted earlier work by the O’Day laboratory on the role of pheromones in the sexual development of Dictyostelium discoideum. This letter addresses some of the issues with their study.
Resting Cysts of the Pigmented Ciliate Blepharisma sinuosum Sawaya, 1940 (Ciliophora: Heterotrichea)
Authors: Cavaleiro Jéssica , Fernandes Noemi Mendes , da Silva‐Neto Inácio D. , Soares Carlos Augusto Gomes
Published: November 2017

The morphology of Blepharisma sinuosum resting cysts and the dynamics of pigmentation at different stages of encystment are presented for the first time. Cyst morphometrics are similar to other Blepharisma species, with three‐wall layers, bacteria surrounding the ectocyst, a conical plug, and wrinkly surface toward the plug in mature stages. The vegetative moniliform macronucleus changes to a horseshoe shape, and at early stages, the cystic cytoplasm is homogeneously pigmented, comprising a contractile vacuole; later, pigments polarize toward the plug, decorate the cortical layer, and become brownish. This work reinforces the potential role of pigment dynamics on cyst biology.
Moderate‐ to long‐term therapeutic outcomes of treated aggressive periodontitis patients without regular supportive care
Authors: Goh V. , Nihalani D. , Yeung K. W. S. , Corbet E. F. , Leung W. K.
Published: November 2017

Background and Objective

Risk for deterioration in treated aggressive periodontitis (AgP) individuals remained unclear. This retrospective cohort study investigated 7‐26 years of periodontal outcomes and oral health‐related quality of life (OHRQoL) of young adults with advanced periodontitis.

Material and Methods

Eighty‐nine previously treated patients with AgP were re‐examined. Clinical and radiographic parameters before treatment discontinuation and at re‐examination were compared. OHRQoL at re‐call was assessed with the short‐form Oral Health Impact Profile (OHIP‐14S).

Results

None of the subjects adhered to suggested periodontal therapy and maintenance after discharge. Mean percentage of sites with probing pocket depth (PPD) ≥6 mm at re‐examination was 4.5 ± 5.9%. A total of 182 teeth had been lost over time. Tooth loss rate was 0.14/patient/year. From 68 subjects with documented favorable treatment outcomes, higher percentage of sites with PPD ≥6 mm at re‐examination and higher radiographic proximal bone loss was associated with current smoking status. Patients with AgP with <20 teeth at re‐call had worse OHRQoL than those with ≥20 teeth. Patients with higher full‐mouth mean PPD also reported poorer OHRQoL.

Conclusion

Treatment in patients with AgP who smoke and neglect proper supportive care, risk periodontal disease progression. Substantial tooth loss and higher full‐mouth mean PPD led to poorer OHRQoL in this cohort.
External Voting Rights in Latin America and the Caribbean: The Influence of Remittances, Globalization, and Partisan Control
Authors: Erlingsson Hafthor , Tuman John P.
Published: November 2017

This article attempts to explain the decision of governments in Latin America and the Caribbean to grant expatriates voting rights in their country of origin. Focusing on 24 Latin American and Caribbean countries from 1980 to 2012, the study investigates the effects of remittance flows, globalization, leftist‐party control of the executive branch, and several other controls on the likelihood that governments will grant voting rights for their citizens residing abroad. The statistical models are estimated with Cox proportional hazard regression. The results add to the literature on migration by demonstrating that remittance flows influence the likelihood that governments will adopt policies granting expatriate voting rights, although the influence is non‐linear. Partisan control is also shown to be important, although the level of wealth, globalization, policy diffusion, and other controls were not found to be significant.
Venezuela's Economic and Social Development in the Era of Chavism
Authors: Gutiérrez S. Alejandro
Published: November 2017

This article analyzes the economic and social development of Venezuela during the Chavism period, considering the main political events, institutional changes, economic and social policies, and evolution of economic and social indicators from 1999 to 2016. The article's conclusion is that the Chavism development project, based on so‐called socialism of the 21st century, was not useful to overcome the crisis of the oil‐rent‐based capital‐accumulation model. Despite the increase in oil revenue throughout most of the Chavism era, institutional changes and economic policies of socialism of the 21st century have worsened the crisis of the oil‐rent‐based development model. The outcome has been a setback in the main leading economic and social indicators and in democratic institutions, and increased discontent among the population. The regime has evolved toward authoritarianism, with less respect for democratic principles. Today, the crisis in Venezuela is worse than the one experienced during the period preceding Chavism, and the country faces the challenge of recovering democracy, stabilizing the economy, and changing the extremely oil‐rent‐dependent capital‐accumulation model.
Oxygen delivery from the cerebral microvasculature to tissue is governed by a single time constant of approximately 6 seconds
Authors: Payne Stephen John , Lucas Claire
Published: November 2017

Objective

The cerebral microvasculature plays a key role in the coupling between cerebral blood flow and metabolism. Although experimental imaging techniques now allow for finely detailed measurements of flow and oxygenation, within humans measurements remain confined to a voxel‐level scale, of order 1 mm. Mathematical models are thus key in interpreting such data. However, these can be highly complicated, due to the large number of vessels and the nonlinearities in the governing equations.

Methods

We thus propose here a new model of the cerebral microvasculature and show how its behavior can be simplified based on the order of magnitude arguments.

Results

The resulting model shows a dependence upon just two time constants, termed “slow” and “metabolic” time constants; the tissue oxygenation response can be characterized by convolution of the difference between the fractional flow and metabolic responses with a single exponential, with time constant equal to half the ratio of tissue volume to blood flow multiplied by the ratio of effective oxygen solubility in tissue and blood.

Conclusions

The overall response time for the whole network is approximately 6 seconds; this value indicates that the flow response to increases in metabolic activity cannot be driven solely by changes in tissue oxygenation.
Frontotemporal lobar degeneration due to P301L tau mutation showing apathy and severe frontal atrophy but lacking other behavioral changes: A case report and literature review
Authors: Miki Tomoko , Yokota Osamu , Takenoshita Shintaro , Mori Yoko , Yamazaki Kiyohiro , Ozaki Yuki , Ueno Shu‐ichi , Haraguchi Takashi , Ishizu Hideki , Kuroda Shigetoshi , Terada Seishi , Yamada Norihito
Published: November 2017

The clinical features in cases that have mutations in the microtubule‐associated protein tau gene but lack prominent behavioral changes remain unclear. Here, we describe detailed clinical and pathological features of a case carrying the P301L tau mutation that showed only apathy until the middle stage of the course. The mother of this case was suspected to have mild cognitive decline at age 46. However, before she was fully examined, she had a subarachnoid hemorrhage at age 49 and died at age 53. An autopsy was not done. The proband of this pedigree, a 60‐year‐old right‐handed Japanese man at the time of death, began to make mistakes at work at the age of 51 years. Until age 54, he showed only mild apathy with bradykinesia. Insight was well spared. Parkinsonism and echolalia developed at age 55, and pyramidal signs and oral tendency at age 57. Personality change, disinhibition, stereotypy, or semantic memory impairment was not found throughout the course. The final neurological diagnosis was unspecified dementia. Pathological examination demonstrated numerous round four‐repeat tau‐positive three‐repeat tau‐negative or perinuclear ring‐like neuronal cytoplasmic inclusions with many ballooned neurons in the frontal and temporal cortices and hippocampus. Genetic analysis using frozen brain tissue demonstrated a P301L tau mutation. Among 31 previously reported cases bearing the P301L tau mutation for which the data regarding initial symptoms are available, one clinical case showed only apathy with depression in the early stage. Given these findings, clinicians should be aware that a clinical course characterized only by apathy for several years, which can be misdiagnosed as a psychiatric disorder, is one of the clinical presentations associated with P301L tau mutation.