bluuebunny/crossref_metadata_2025 huggingface dataset:
CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV‐positive patients
Authors: Lu Wei , Mehraj Vikram , Vyboh Kishanda , Cao Wei , Li Taisheng , Routy Jean‐Pierre
Published: June 2015

Introduction

Absolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy. Following long‐term therapy, patients generally present with significant CD4 T cell recovery contrasting with persistently elevated CD8 T cell counts, which leads to a partial restoration of CD4:CD8 ratio. This review focuses on the relevance of the CD4:CD8 ratio on clinical outcomes, immune dysfunction and HIV reservoir size in long‐term treated patients.

Method

We conducted a comprehensive literature review of publications in English language using major electronic databases. Our search was focused on factors contributing to CD4:CD8 T cell ratio and clinical outcome in adult HIV‐positive patients in the context of treated infection.

Discussion

Low CD4:CD8 ratio has been linked to ageing and acts as a predictor of mortality in the general population. This ratio may represent the combined effects of inflammation and immunological changes called “inflammaging.” Although the mechanisms underlying partial correction of the CD4:CD8 ratio and persistently elevated CD8 T cell count in long‐term treated patients remain poorly understood, it has been recently indicated that patients with optimal CD4 T cell recovery and low CD4:CD8 ratio still harbour increased immune activation, an immune senescent phenotype and have a higher risk of non‐AIDS morbidity and mortality. This review reconsiders CD4:CD8 ratio in the light of advances in the understanding of immune dysfunction and examines its pathophysiological features and implications on clinical outcome and HIV reservoir size in long‐term treated HIV‐positive adults.

Conclusion

The CD4:CD8 ratio can contribute to the immunological evaluation of treated patients in a long‐term follow‐up and may be applied for monitoring both immune dysfunction and viral reservoir size in immune‐based clinical trials.
Analysis of convergent flow tracer tests in a heterogeneous sandy box with connected gravel channels
Authors: Molinari Antonio , Pedretti D. , Fallico C.
Published: June 2015

We analyzed the behavior of convergent flow tracer tests performed in a 3‐D heterogeneous sandbox in presence of connected gravel channels under laboratory‐controlled conditions. We focused on the evaluation of connectivity metrics based on characteristic times calculated from experimental breakthrough curves (BTCs), and the selection of upscaling model parameters related to connectivity. A conservative compound was injected from several piezometers in the box, and depth‐integrated BTCs were measured at the central pumping well. Results show that transport was largely affected by the presence of gravel channels, which generate anomalous transport behavior such as BTC tailing and double peaks. Connectivity indicators based on BTC peak times provided better information about the presence of connected gravel channels in the box. One of these indicators, β, was defined as the relative temporal separation of the BTCs peaks from the BTCs centers of mass. The mathematical equivalence between β and the capacity coefficient adopted in mass transfer‐based formulations suggests how connectivity metrics could be directly embedded in mass transfer formulations. This finding is in line with previous theoretical studies and was corroborated by reproducing a few representative experimental BTCs using a 1‐D semianalytical bimodal solution embedding a mass transfer term. Model results show a good agreement with experimental BTCs when the capacity coefficient was constrained by measured β. Models that do not embed adequate connectivity metrics or do not adequately reproduce connectivity showed poor matching with observed BTCs.
Energy considerations in the Community Atmosphere Model (CAM)
Authors: Williamson David L. , Olson Jerry G. , Hannay Cécile , Toniazzo Thomas , Taylor Mark , Yudin Valery
Published: June 2015

An error in the energy formulation in the Community Atmosphere Model (CAM) is identified and corrected. Ten year AMIP simulations are compared using the correct and incorrect energy formulations. Statistics of selected primary variables all indicate physically insignificant differences between the simulations, comparable to differences with simulations initialized with rounding sized perturbations. The two simulations are so similar mainly because of an inconsistency in the application of the incorrect energy formulation in the original CAM. CAM used the erroneous energy form to determine the states passed between the parameterizations, but used a form related to the correct formulation for the state passed from the parameterizations to the dynamical core. If the incorrect form is also used to determine the state passed to the dynamical core the simulations are significantly different. In addition, CAM uses the incorrect form for the global energy fixer, but that seems to be less important. The difference of the magnitude of the fixers using the correct and incorrect energy definitions is very small.
Current Progress in Nanotechnology Applications for Diagnosis and Treatment of Kidney Diseases
Authors: Lee Sue Hyun , Lee Jung Bok , Bae Min Soo , Balikov Daniel A. , Hwang Amy , Boire Timothy C. , Kwon Il Keun , Sung Hak‐Joon , Yang Jae Won
Published: June 2015

Significant progress has been made in nanomedicine, primarily in the form of nanoparticles, for theranostic applications to various diseases. A variety of materials, both organic and inorganic, have been used to develop nanoparticles with promise to achieve improved efficacy in medical applications as well as reduced systemic side effects compared to current standard of care medical practices. In particular, this article highlights the recent development and application of nanoparticles for diagnosing and treating nephropathologies.
Physical growth of the shuar: Height, Weight, and BMI references for an indigenous amazonian population
Authors: Urlacher Samuel S. , Blackwell Aaron D. , Liebert Melissa A. , Madimenos Felicia C. , Cepon‐Robins Tara J. , Gildner Theresa E. , Snodgrass J. Josh , Sugiyama Lawrence S.
Published: June 2015

Objectives

Information concerning physical growth among small‐scale populations remains limited, yet such data are critical to local health efforts and to foster basic understandings of human life history and variation in childhood development. Using a large dataset and robust modeling methods, this study aims to describe growth from birth to adulthood among the indigenous Shuar of Amazonian Ecuador.

Methods

Mixed‐longitudinal measures of height, weight, and body mass index (BMI) were collected from Shuar participants (n = 2,463; age: 0–29 years). Centile growth curves and tables were created for each anthropometric variable of interest using Generalized Additive Models for Location, Scale, and Shape (GAMLSS). Pseudo‐velocity and Lambda‐Mu‐Sigma curves were generated to further investigate Shuar patterns of growth and to facilitate comparison with United States Center for Disease Control and Prevention and multinational World Health Organization growth references.

Results

The Shuar are small throughout life and exhibit complex patterns of growth that differ substantially from those of international references. Similar to other Amazonians, Shuar growth in weight compares more favorably to references than growth in height, resulting in BMI curves that approximate international medians. Several additional characteristics of Shuar development are noteworthy, including large observed variation in body size early in life, significant infant growth faltering, extended male growth into adulthood, and a markedly early female pubertal growth spurt in height. Phenotypic plasticity and genetic selection in response to local environmental factors may explain many of these patterns.

Conclusions

Providing a detailed reference of growth for the Shuar and other Amazonian populations, this study possesses direct clinical application and affords valuable insight into childhood health and the ecology of human growth. Am. J. Hum. Biol. 28:16–30, 2016. © 2015 Wiley Periodicals, Inc.
ALG3‐CDG: Report of two siblings with antenatal features carrying homozygous p.Gly96Arg mutation
Authors: Lepais Laureline , Cheillan David , Frachon Sophie Collardeau , Hays Stéphane , Matthijs Gert , Panagiotakaki Eleni , Abel Carine , Edery Patrick , Rossi Massimiliano
Published: June 2015

Congenital disorders of glycosylation (CDG) are a group of inborn errors of metabolism presenting with heterogeneous multisystemic clinical manifestations. To date, more than 60 different types of CDG have been reported. ALG3‐CDG is very rare, with only nine patients described so far. We report two affected siblings presenting prenatally with skeletal abnormalities associated with dysmorphic features, cerebellar vermis hypoplasia, corpus callosum agenesis, hepatic fibrosis and poor prognosis. This is the first detailed report of an affected fetus including clinical, radiographic and pathological findings. The patients showed some clinical features previously unreported in ALG3‐CDG, such as bone dysplasia, cataract, corneal opacities, and pons hypoplasia. Both patients were homozygous for the previously unreported p.Gly96Arg mutation of the ALG3 gene. One patient showed chondrodysplasia punctata (CDP), which has not been previously reported in CDG. An exhaustive genetic and metabolic assessment, performed in order to rule out other possible causes of CDP, showed abnormally raised levels of anti‐nuclear antibodies in the mother who, nevertheless, did not show any clinical sign of autoimmune disease during a 7 years follow‐up. We speculate that the observed CDP may be explained by the maternal anti‐nuclear antibodies; alternatively, a possible link to the underlying metabolic disorder cannot be ruled out. In conclusion, we report the clinical, pathological, biochemical and molecular characterization of two further patients affected by ALG3‐CDG, expanding the phenotypic spectrum of this very rare disease. © 2015 Wiley Periodicals, Inc.
Pediatric brain death in a Japanese pediatric hospital
Authors: Toida Chiaki , Muguruma Takashi
Published: June 2015

Aim

The Organ Transplantation Act was revised in Japan in 2010, which permitted the organs of children younger than 15 years to be donated after brain death. As of August 2012, 2 years after the Act was revised, only two children had become brain dead donors.In our hospital, we used a basic determination of brain death in order to predict the neurological outcome. We evaluated the incidence and characteristics of pediatric brain death treated at our hospital in order to investigate why there are so few pediatric brain deaths in Japan.

Methods

We evaluated the characteristics of patients undergoing a basic determination of brain death and the procedure for the determination was compared retrospectively by reviewing their medical records. We enrolled 3,721 patients aged younger than 15 years who were admitted to the pediatric intensive care unit between 2008 and 2012.

Results

A basic determination of brain death had been enacted in 35 patients. Many of the patients undergoing the determination were admitted after resuscitation (pre‐group / post‐group, 50%/74%) and many of them had been transferred from the emergency department (94%/89%). After revision of the Act, only three children were deemed to be brain dead in our hospital, which was 0.1% of total pediatric intensive care unit admissions and 7% of total pediatric intensive care unit deaths.

Conclusions

The low incidence of pediatric brain death in Japan may be due to differences in exclusion criteria for determination of brain death and personal views regarding life and death compared with other countries.
Fragment‐Based Discovery of a Dual pan‐RET/VEGFR2 Kinase Inhibitor Optimized for Single‐Agent Polypharmacology
Authors: Frett Brendan , Carlomagno Francesca , Moccia Maria Luisa , Brescia Annalisa , Federico Giorgia , De Falco Valentina , Admire Brittany , Chen Zhongzhu , Qi Wenqing , Santoro Massimo , Li Hong‐yu
Published: June 2015

Oncogenic conversion of the RET (rearranged during transfection) tyrosine kinase is associated with several cancers. A fragment‐based chemical screen led to the identification of a novel RET inhibitor, Pz‐1. Modeling and kinetic analysis identified Pz‐1 as a type II tyrosine kinase inhibitor that is able to bind the “DFG‐out” conformation of the kinase. Importantly, from a single‐agent polypharmacology standpoint, Pz‐1 was shown to be active on VEGFR2, which can block the blood supply required for RET‐stimulated growth. In cell‐based assays, 1.0 nM of Pz‐1 strongly inhibited phosphorylation of all tested RET oncoproteins. At 1.0 mg kg−1 day−1 per os, Pz‐1 abrogated the formation of tumors induced by RET‐mutant fibroblasts and blocked the phosphorylation of both RET and VEGFR2 in tumor tissue. Pz‐1 featured no detectable toxicity at concentrations of up to 100.0 mg kg−1, which indicates a large therapeutic window. This study validates the effectiveness and usefulness of a medicinal chemistry/polypharmacology approach to obtain an inhibitor capable of targeting multiple oncogenic pathways.
10‐Step Asymmetric Total Synthesis and Stereochemical Elucidation of (+)‐Dragmacidin D
Authors: Jackson Jeffrey J. , Kobayashi Hiroyuki , Steffens Sophia D. , Zakarian Armen
Published: June 2015

The asymmetric synthesis of dragmacidin D (1) was completed in 10 steps. Its sole stereocenter was set by using direct asymmetric alkylation enabled by a C2‐symmetric tetramine and lithium N‐(trimethylsilyl)‐tert‐butylamide as the enolization reagent. A central Larock indole synthesis was employed in a convergent assembly of the heterocyclic subunits. The stereochemical evidence from this work strongly supports the predicted S configuration at the 6′′′ position, which is consistent with other members of the dragmacidin family of natural products.
A Mixed‐Valence Tri‐Zinc Complex, [LZnZnZnL] (L=Bulky Amide), Bearing a Linear Chain of Two‐Coordinate Zinc Atoms
Authors: Hicks Jamie , Underhill Emma J. , Kefalidis Christos E. , Maron Laurent , Jones Cameron
Published: June 2015

Reduction of a variety of extremely bulky amido Group 12 metal halide complexes, [LMX(THF)0,1] (L=amide; M=Zn, Cd, or Hg; X=halide) with a magnesium(I) dimer gave a homologous series of two‐coordinate metal(I) dimers, [L′MML′] (L′=N(Ar†)(SiMe3), Ar†=C6H2{C(H)Ph2}2Pri‐2,6,4); and the formally zinc(0) complex, [L*ZnMg(MesNacnac)] (L*=N(Ar*)(SiPri3); Ar*=C6H2{C(H)Ph2}2Me‐2,6,4; MesNacnac=[(MesNCMe)2CH]−, Mes=mesityl), which contains the first unsupported ZnMg bond. Two equivalents of [L*ZnMg(MesNacnac)] react with ZnBr2 or ZnBr2(tmeda) to give the mixed valence, two‐coordinate, linear tri‐zinc complex, [L*ZnIZn0ZnIL*], and the first zinc(I) halide complex, [L*ZnZnBr(tmeda)], respectively. The analogues [L*ZnMZnL*] (M=Cd or Hg), were also prepared, the Cd species contains the first ZnCd bond in a molecular compound. Metal–metal bonding was studied by DFT calculations.
Forming Stereogenic Centers in Acyclic Systems from Alkynes
Authors: Vabre Roxane , Island Biana , Diehl Claudia J. , Schreiner Peter R. , Marek Ilan
Published: June 2015

The combined carbometalation/zinc homologation followed by reactions with α‐heterosubstituted aldehydes and imines proceed through a chair‐like transition structure with the substituent of the incoming aldehyde residue preferentially occupying a pseudo‐axial position to avoid the two gauche interactions. The heteroatom in the axial position produces a chelated intermediate (and not a Cornforth–Evans transition structure for α‐chloro aldehydes and imines) leading to a face differentiation in the allylation reaction. This method provides access to functionalized products in which three new carbon–carbon bonds and two to three stereogenic centers, including a quaternary one, were created in acyclic systems in a single‐pot operation from simple alkynes.
Role of acrylic acid in the synthesis of core‐shell fluorine‐containing polyacrylate latex with spherical and plum blossom‐like morphology
Authors: Li Kunquan , Zeng Xingrong , Li Hongqiang , Lai Xuejun
Published: June 2015

The core‐shell fluorine‐containing polyacrylate latex was successfully synthesized by two‐stage semicontinuous emulsion copolymerization of methyl methacrylate (MMA), butylacrylate (BA), acrylic acid (AA), and dodecafluoroheptyl methacrylate (DFMA). The fluorine‐containing polyacrylate latex was characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential, thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC). The effects of AA content on monomer conversion, polymerization stability, particle size, corsslinking degree, carboxyl groups distributions (latex surface, aqueous phase or buried in latex), as well as mechanical properties and water absorption rate of latex film were investigated. The obtained fluorine‐containing polyacrylate latex exhibited core‐shell structure with a particle size of 120–150 nm. The introduction of AA was beneficial for the increase of monomer conversion and the polymerization stability, and had little effects on the mechanical property of latex film. However, the hydrophilicity of AA made the water resistance of latex film get bad. With the increase of AA content, the carboxyl groups preferred to distribute on aqueous phase, and the possibility of homogeneous nucleation increased and more oligomers particles were formed. Moreover, the oligomers would distribute to the latex and continued to grow up, making the latex morphology changed from spherical to plum blossom‐like. The core‐shell latex had two Tg corresponding to the rubber polyacrylate core and hard fluorine‐containing polyacrylate shell, and the latex film possessed excellent thermal stability. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42527.
Study on flax fiber toughened poly (lactic acid) composites
Authors: Xia Xuelian , Liu Wentao , Zhou Liyong , Liu Hao , He Suqin , Zhu Chengshen
Published: June 2015

Poly (lactic acid) (PLA) is a renewable and biodegradable polymer with high modulus, high strength but low toughness. Blending PLA with plant fiber has been believed an available strategy to improve the toughness of PLA. PLA/Flax composites were fabricated by extrusion and injection molding processes. The flax fiber surfaces were modified before blending to improve the compatibility, and the chemical structures of both untreated and treated fiber were characterized by Fourier transform infrared spectroscopy. Results of mechanical test showed that the impact strength and elongation at break of PLA/Flax composites were remarkably higher than PLA. The impact fractures of PLA/Flax composites were also observed by scanning electron microscope. The results showed uniform dispersion of fibers in PLA matrix and good compatibility between treated fibers and PLA matrix. Moreover, it can be observed that crazing propagation was hindered by fibers and transcrystalline developed along fibers by polarized optical microscope. Differential scanning calorimetry analysis was carried out to study the crystallinity of PLA and it was found that incorporation of fiber improved the crystallinity of PLA. The toughening mechanism of PLA/Flax composites was discussed according to the results. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42573.
In‐situgrown silica/water‐borne epoxy shape memory composite foams prepared without blowing agent addition
Authors: Dong Yubing , Fu Yaqin , Ni Qing‐Qing
Published: June 2015

Shape memory (SM) silica/epoxy composite foams were successfully synthesized via latex technology and prepared without blowing agent addition. Silica was synthesized via tetraethoxysilane (TEOS) hydrolysis. Silica/epoxy foams were obtained from the TEOS solution and water‐borne epoxy mixtures after freeze‐drying and foaming in the presence of residual moisture as the blowing agent under a vacuum at 110°C. The morphologies of the resulting foams were evaluated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Compression and thermo‐mechanical cycle tests were performed to measure the mechanical and SM properties of the foams. Experimental results indicated that the micrographs and mechanical properties of the foams were closely related to freeze‐drying time. The final composite foams exhibited high shape recovery and fixity ratios and could maintain both properties at more than 90% even after five thermo‐mechanical cycles. The properties obtained in the epoxy foams may offer new opportunities for their use in future structural applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2015,132, 42599.
Design, Synthesis, and Biological Evaluation of Dabigatran Etexilate Mimics, a Novel Class of Thrombin Inhibitors
Authors: Wang Shaochi , Dai Peng , Xu Yungen , Chen Qiufang , Zhu Qihua , Gong Guoqing
Published: June 2015

Human α‐thrombin is a particularly promising target for anticoagulant therapy, and identification of oral small‐molecular inhibitors of thrombin remains a research focus. On the basis of the X‐ray crystal structure of human α‐thrombin and its inhibitor dabigatran, we designed and synthesized a series of dabigatran etexilate mimics containing a novel tricyclic fused scaffold. The biological evaluations reveal that all of the compounds possess moderate activity of antiplatelet aggregation induced by thrombin in vitro. Moreover, compound I‐8, which contains 2‐hydroxymethyl‐3,5,6‐trimethylpyrazine (HTMP), a cleavable moiety with antiplatelet activity, shows the best anticoagulant effect among the tested compounds in vivo. Those synthesized compounds that have better in vitro activity were subjected to bleeding complication tests, and the results demonstrate that the novel compounds are less likely to have bleeding risk than dabigatran etexilate.
Carbon Monoxide Addition to Ruthenium–Dithiolene Complex and Polysiloxane Hybrid Film Formation
Authors: Tsukada Satoru , Sagawa Takuya , Gunji Takahiro
Published: June 2015

The addition of carbon monoxide to the ruthenium center of [(η6‐C6Me6)Ru(S2C6H4)] (1) has been investigated. [(η6‐C6Me6)Ru(CO)(S2C6H4)] (2) was obtained by the addition of CO gas to the ruthenium center of 1 in both solution and solid states. 1 was reproduced by treating 2 with an oxidant. A 1/polysiloxane self‐standing hybrid film was also prepared and showed a dramatic color change upon transformation of 1 to 2 in polysiloxane hybrid film.
Significance of transcytosis in Alzheimer's disease: BACE1 takes the scenic route to axons
Authors: Buggia‐Prévot Virginie , Thinakaran Gopal
Published: June 2015

Neurons have developed elaborate mechanisms for sorting of proteins to their destination in dendrites and axons as well as dynamic local trafficking. Recent evidence suggests that polarized axonal sorting of β‐site converting enzyme 1 (BACE1), a type I transmembrane aspartyl protease involved in Alzheimer's disease (AD) pathogenesis, entails an unusual journey. In hippocampal neurons, BACE1 internalized from dendrites is conveyed in recycling endosomes via unidirectional retrograde transport towards the soma and sorted to axons where BACE1 becomes enriched. In comparison to other transmembrane proteins that undergo transcytosis or elimination in somatodendritic compartment, vectorial transport of internalized BACE1 in dendrites is unique and intriguing. Dysfunction of protein transport contributes to pathogenesis of AD and other neurodegenerative diseases. Therefore, characterization of BACE1 transcytosis is an important addition to the multiple lines of evidence that highlight the crucial role played by endosomal trafficking pathway as well as axonal sorting mechanisms in AD pathogenesis.
Interventions to Improve the Response of Professionals to Children Exposed to Domestic Violence and Abuse: A Systematic Review
Authors: Turner William , Hester Marianne , Broad Jonathan , Szilassy Eszter , Feder Gene , Drinkwater Jessica , Firth Adam , Stanley Nicky
Published: June 2015

Exposure of children to domestic violence and abuse (DVA) is a form of child maltreatment with short‐ and long‐term behavioural and mental health impact. Health care professionals are generally uncertain about how to respond to domestic violence and are particularly unclear about best practice with regards to children's exposure and their role in a multiagency response. In this systematic review, we report educational and structural or whole‐system interventions that aim to improve professionals' understanding of, and response to, DVA survivors and their children. We searched 22 bibliographic databases and contacted topic experts for studies reporting quantitative outcomes for any type of intervention aiming to improve professional responses to disclosure of DVA with child involvement. We included interventions for physicians, nurses, social workers and teachers. Twenty‐one studies met the inclusion criteria: three randomised controlled trials (RCTs), 18 pre‐post intervention surveys. There were 18 training and three system‐level interventions. Training interventions generally had positive effects on participants' knowledge, attitudes towards DVA and clinical competence. The results from the RCTs were consistent with the before‐after surveys. Results from system‐level interventions aimed to change organisational practice and inter‐organisational collaboration demonstrates the benefit of coordinating system change in child welfare agencies with primary health care and other organisations. Implications for policy and research are discussed. © 2015 The Authors.Child Abuse Reviewpublished by John Wiley & Sons Ltd.

‘We searched 22 bibliographic databases and contacted topic experts’

Key Practitioner Messages

We reviewed published evidence on interventions aimed at improving professionals' practice with domestic violence survivors and their children.

Training programmes were found to improve participants' knowledge, attitudes and clinical competence up to a year after delivery.

Key elements of successful training include interactive discussion, booster sessions and involving specialist domestic violence practitioners.

Whole‐system approaches aiming to promote coordination and collaboration across agencies appear promising but require funding and high levels of commitment from partners.

‘Training programmes were found to improve participants' knowledge, attitudes and clinical competence up to a year after delivery’
Beyond Ethics to Morality: Choices and Relationships in Bicultural Research Settings
Authors: Furness Jane , Nikora Linda Waimarie , Hodgetts Darrin , Robertson Neville
Published: June 2015

As community and applied social psychologists, it is crucial that we know ourselves as cultural beings, appreciate the values and beliefs of those with whom we work and understand the history of relations among those in our work settings. In New Zealand, research by non‐Māori involving Māori has often mirrored the harmful colonising practices of the nation's wider history. In response, several frameworks have been developed setting out conditions and guidelines in which non‐Māori might conduct research in Māori settings responsibly and usefully. Nevertheless, views differ on the ways, and extent to which, non‐Māori might be involved. Most guidelines do not provide answers to ethical nuances that may arise. This article discusses the experiences of a non‐Māori community psychologist engaging in research in a predominantly Māori setting. It describes how the first author carefully negotiated entry into the setting, built relationships based on mutuality, sought expert guidance, exercised an ethic of caring, and ensured that the research was accountable to the community. We believe that there are important lessons here for researchers from dominant groups undertaking research in indigenous and minority communities. Copyright © 2015 John Wiley & Sons, Ltd.
A case of antithrombin replacement using recombinant human antithrombin in an adult patient supported with extracorporeal membrane oxygenation
Authors: Lavandosky Gerald J.
Published: June 2015

Key Clinical Message

In the critically ill patient on extracorporeal life support, antithrombin production and activity can be decreased and may require replacement to therapeutic levels in order to maintain appropriate anticoagulation and prevent thrombosis.
Efficient Total Synthesis of Bongkrekic Acid and Apoptosis Inhibitory Activity of Its Analogues
Authors: Matsumoto Kenji , Suyama Masaki , Fujita Satoshi , Moriwaki Takuya , Sato Yukiko , Aso Yoshifumi , Muroshita Satoshi , Matsuo Hiroshi , Monda Keishi , Okuda Katsuhiro , Abe Masato , Fukunaga Hiroyuki , Kano Arihiro , Shindo Mitsuru
Published: June 2015

Bongkrekic acid (BKA), isolated from the bacterium Burkholderia cocovenenans, is an inhibitor of adenine nucleotide translocator, which inhibits apoptosis, and is thus an important tool for the mechanistic investigation of apoptosis. An efficient total synthesis of BKA has been achieved by employing a three‐component convergent strategy based on Kocienski–Julia olefination and Suzuki–Miyaura coupling. It is noteworthy that segment B has been prepared as a new doubly functionalized coupling partner, which contributes to shortening of the number of steps. Torquoselective olefination with an ynolate has also been applied for the efficient construction of an unsaturated ester. Furthermore, it is revealed that 1‐methyl‐2‐azaadamantane N‐oxyl is an excellent reagent for final oxidation to afford BKA in high yield. Based on the total synthesis, several BKA analogues were prepared for structure–activity relationship studies, which indicated that the carboxylic acid moieties were essential for the apoptosis inhibitory activity of BKA. More easily available BKA analogues with potent apoptosis inhibitory activity were also developed.
A Well‐Defined Aluminum‐Based Lewis Acid as an Effective Catalyst for Diels–Alder Transformations
Authors: Liu Zhizhou , Lee Jazreen Hui Qi , Ganguly Rakesh , Vidović Dragoslav
Published: June 2015

A catalytically active aluminum‐based system for Diels–Alder transformations is reported. The system was generated by mixing a β‐diketiminate‐stabilized aluminum bistriflate compound with Na[BArCl4] (ArCl=3,5‐Cl2C6H3). Solid‐state analysis of the catalytic system reveals a unique structure incorporating a two‐dimensional coordination polymer. According to the experimental results obtained from several Diels–Alder transformations, the aluminum‐based system appears to be a more practical and more robust alternative to the recently reported compounds based on carbon and silicon cations.
Structure determination from powder diffraction data: past, present and future challenges
Authors: Meden Anton , Radosavljevic Evans Ivana
Published: June 2015

Structural information is crucial for understanding and tailoring the materials properties. When the materials are available only in the polycrystalline form, powder diffraction is the method of choice for structure determination. Compared to the single crystal data, the powder pattern contains less information due to the overlap problem and the reduction of the information content is even larger if only the low resolution data are available. Several data analysis approaches are available to address this problem, including reciprocal, direct and dual space methods. They are discussed and illustrated by a number of examples, including cases where other techniques, such as IR and NMR spectroscopy, electron microscopy and crystal‐chemical knowledge have to be applied to solve the structure.
Global Invader Impact Network (GIIN): toward standardized evaluation of the ecological impacts of invasive plants
Authors: Barney Jacob N. , Tekiela Daniel R. , Barrios‐Garcia Maria Noelia , Dimarco Romina D. , Hufbauer Ruth A. , Leipzig‐Scott Peter , Nuñez Martin A. , Pauchard Aníbal , Pyšek Petr , Vítková Michaela , Maxwell Bruce D.
Published: June 2015

Terrestrial invasive plants are a global problem and are becoming ubiquitous components of most ecosystems. They are implicated in altering disturbance regimes, reducing biodiversity, and changing ecosystem function, sometimes in profound and irreversible ways. However, the ecological impacts of most invasive plants have not been studied experimentally, and most research to date focuses on few types of impacts, which can vary greatly among studies. Thus, our knowledge of existing ecological impacts ascribed to invasive plants is surprisingly limited in both breadth and depth. Our aim was to propose a standard methodology for quantifying baseline ecological impact that, in theory, is scalable to any terrestrial plant invader (e.g., annual grasses to trees) and any invaded system (e.g., grassland to forest). The Global Invader Impact Network (GIIN) is a coordinated distributed experiment composed of an observational and manipulative methodology. The protocol consists of a series of plots located in (1) an invaded area; (2) an adjacent removal treatment within the invaded area; and (3) a spatially separate uninvaded area thought to be similar to pre‐invasion conditions of the invaded area. A standardized and inexpensive suite of community, soil, and ecosystem metrics are collected allowing broad comparisons among measurements, populations, and species. The method allows for one‐time comparisons and for long‐term monitoring enabling one to derive information about change due to invasion over time. Invader removal plots will also allow for quantification of legacy effects and their return rates, which will be monitored for several years. GIIN uses a nested hierarchical scale approach encompassing multiple sites, regions, and continents. Currently, GIIN has network members in six countries, with new members encouraged. To date, study species include representatives of annual and perennial grasses; annual and perennial forbs; shrubs; and trees. The goal of the GIIN framework is to create a standard yet flexible platform for understanding the ecological impacts of invasive plants, allowing both individual and synthetic analyses across a range of taxa and ecosystems. If broadly adopted, this standard approach will offer unique insight into the ecological impacts of invasive plants at local, regional, and global scales.
Cocoa polyphenols treatment ameliorates visceral obesity by reduction lipogenesis and promoting fatty acid oxidation genes in obese rats through interfering with AMPK pathway
Authors: Ali Faisal , Ismail Amin , Esa Norhaizan Mohd , Pei Chong
Published: June 2015

This study was conducted to investigate the pharmacological activity of cocoa polyphenols (CPs) on visceral obesity markers and the possible mechanisms. In this study, Sprague–Dawley (SD) rats were fed either a low‐fat diet (LFD) or a high‐fat diet (HFD). After 12 wk of diet intervention, only one group of HFD rats (n = 10/group) were treated at a dose of 600 mg/kg bw/day CPs (HFD + CPs) for 4 wk. The gene and protein expression levels of phosphorylation of AMPK‐activated protein kinase α/β (AMPK α/β) were measured using real time‐PCR and Western blotting. The mRNA expression of lipogenic key enzymes (Acaca, Fasn, Mcat, and Scd‐1), and β‐oxidation key enzymes (CPT1, Prkaa1, Acox1) were investigated. In addition, the upstream transcription factors (PPARα, PPARγ, C/EBPα, and SREBP‐1c) were also examined. In accordance with these findings, CPs treatment improved visceral adiposity, adipocytes hypertrophy, and liver steatosis. AMP‐activated protein kinase α/β (AMPK α/β) phosphorylation in liver and adipose tissue of HFD + CPs‐treated rats was activated compared with HFD‐fed rats. The expression of lipogensis related‐genes was decreased, while expression levels of β‐oxidation‐related genes were increased compared with HFD‐fed rats. Together, these data partially unravel the ameliorative effects of CPs treatment on visceral obesity markers by inhibiting lipogenesis and promoting β‐oxidation related‐genes through activation of the AMPK pathway.

Practical applications: There is a metabolic logic linking the expended visceral or abdominal fat depot to dyslipidemia. The conceivability of using a natural dietary supplement to regulate lipid metabolism homeostasis is appealing as this by product of the defatted cocoa juice industry is non‐toxic, cheap, and has shown hypolipidemic properties. This is essentially significant in the context of the rising costs of obesity and its related diseases care. The ability of polyphenolics to suppress SREBP‐1c, the target of statins, while activating PPARα, the target of fibrates, suggest it can naturally find its role in the treatment of hyperlipidemia.

The molecular mechanism underlying the therapeutic actions of polyphenolics ‐derived cocoa against visceral obesity has been partially unveiled in this research. Our findings suggest that CPs treatment attenuated diet‐induced visceral obesity via transcriptional regulation of AMPK mediating lipid metabolism‐related genes in the liver and visceral white adipose tissue.
Double Deposition and Stripping Steps for Trace Determination of Au(III) Using Anodic Stripping Voltammetry
Authors: Rutyna Iwona , Ochab Mateusz , Korolczuk Mieczysław
Published: June 2015

A new way of decreasing the detection limit ‐ double deposition and stripping steps was proposed to determine trace amounts of gold(III) by anodic stripping voltammetry. Two carbon composite electrodes that differed drastically in their surface areas were used for the measurements. The calibration graph was linear from 1×10−9 to 1×10−8 mol L−1 following deposition time of 300 s at the first and the second electrode. The detection limit was found to be 2.3×10−10 and 1.4×10−11 mol L−1 for deposition time 600 and 2400 s, respectively. It is the lowest detection limit obtained so far for gold(III) determination in stripping voltammetry.
Auf den Geschmack kommen
Authors: Unterstell Rembert
Published: June 2015

Wolfgang Meyerhof erforscht die grundlegenden Mechanismen des lange vernachlässigten Geschmackssinns. Doch damit nicht genug: Der Biochemiker versucht auch, das Wechselspiel von Geschmack und Ernährung zu verstehen. Im Gespräch über die Welt der Bitterstoffrezeptoren, die Hinterleiber von Honigbienen als Süßersatz, Geschmacksvorlieben und ‐aversionen.
Angriff und Gegenwehr
Authors: Marchfelder Anita
Published: June 2015

CRISPR‐Cas: Was als Abwehrsystem von Einzellern gegen Viren entdeckt wurde, macht jetzt Karriere als genetisches Schneidewerkzeug. Doch wie funktioniert das erstaunlich lernfähige Immunsystem? Eine Forschergruppe versucht die grundlegenden Mechanismen zu klären.
So global wie national
Authors: Strohschneider Peter
Published: June 2015

Jahrestreffen des Global Research Council in Tokyo, intensive Konsultationen mit Partnern in Argentinien, Brasilien und Russland, wissenschaftliche Politikberatung bei den Vereinten Nationen in New York — auch in den internationalen Dimensionen ihres Handelns ist die Förderung bester erkenntnisgeleiteter Forschung Aufgabe und Verpflichtung der DFG.
Can performance‐based financing help reaching the poor with maternal and child health services? The experience of rural Rwanda
Authors: Lannes Laurence , Meessen Bruno , Soucat Agnes , Basinga Paulin
Published: June 2015

More than 20 countries in Africa are scaling up performance‐based financing (PBF), but its impact on equity in access to health services remains to be documented. This paper draws on evidence from Rwanda to examine the capacity of PBF to ensure equal access to key health interventions especially in rural areas where most of the poor live. Specifically, it focuses on maternal and child health services, distinguishing two wealth groups, and uses data from a rigorous impact evaluation.

Difference‐in‐difference technique is used, and different model specifications are tested: control for unobserved heterogeneity and common random error using linear probability model, seemingly unrelated regression equations, and clustering and fixed effects.

Results suggest that in Rwanda, PBF improved efficiency rather than equity for most health services. We find that PBF achieved efficiency gains by improving access to health services for those easier to reach, generally the relatively more affluent. It turns out to be less effective in reaching the poorest. Our results illustrate the advantages of rigorous randomized impact evaluation data as results published earlier using a nationally representative survey (Demographic and Health Survey) were not able to capture the pro‐rich nature of the PBF scheme in Rwanda.

Our paper advocates for building mechanisms targeting the vulnerable groups in PBF strategies. It also highlights the need to understand the impact of PBF together with the specific development of health insurance coverage and the organization of the health system.
Antitumor and antimetastasis effects of macerating solutions from an injectable chitosan‐based hydrogel on hepatocarcinoma
Authors: Wang Hui , Song Fulai , Chen Quan , Hu Rui , Jiang Zhiwen , Yang Yan , Han Baoqin
Published: June 2015

In our previous studies, injectable chitosan‐based hydrogel (CH) was prepared and its application in surgery removal of tumor was studied. In this study, the antitumor and antimetastasis effects of the macerating solutions from CH were investigated. Our in vitro results showed that macerating solutions from CH significantly increased the proliferation of human normal liver L02 cells. In contrast, macerating solutions from CH showed significant inhibitory effects on the growth of human hepatoma Bel‐7402 cells. In a mouse H22 tumor model, intraperitoneal injection of macerating solutions from CH decreased tumor growth and prevented tumor diffusion. Tumor weight was decreased dramatically in mice treated with macerating solutions from CH. The thymus index and spleen index were significantly increased by treatment with macerating solutions from CH. Administration of macerating solutions from CH also remarkably increased serum levels of TNF‐α, IL‐2, IFN‐γ, and decreased serum VEGF content as compared with the control group treated with saline. The antimetastasis studies showed that the number of pulmonary nodules, pulmonary metastases index, and lymph nodes index were significantly decreased in experimental groups treated with macerating solutions from CH. This study provided more supporting data for the potential clinical application of CH after surgical removal of tumor. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3879–3885, 2015.
Discharge before noon: Effect on throughput and sustainability
Authors: Wertheimer Benjamin , Jacobs Ramon E. A. , Iturrate Eduardo , Bailey Martha , Hochman Katherine
Published: June 2015

BACKGROUND

Late afternoon hospital discharges are thought to contribute to admission bottlenecks. We previously described an intervention that resulted in a statistically significant increase in the discharge before noon (DBN) rate on 2 inpatient medicine units.

OBJECTIVE

To evaluate (1) the effect of an increased DBN rate on the admission arrival time and the number of admissions per hour and (2) the sustainability of our DBN initiative.

DESIGN

Pre‐/postintervention retrospective analysis.

SETTING

Two acute‐care inpatient medicine units in a tertiary care, urban, academic medical center.

PATIENTS: For the admission arrival time and admissions per hour analysis, all inpatients admitted to the medical units from June 1, 2011 to June 31, 2013. For the sustainability analysis, all patients discharged from July 1, 2013 to December 31, 2014.

INTERVENTION

A multidisciplinary intervention to increase the DBN rate.

MEASUREMENTS: Date and time of arrival to all inpatient sites, and discharge date and time of all patients from 2 inpatient medicine units.

RESULTS

Concurrent with our increase in DBN rate, we found a statistically significant change in the median arrival time of emergency department (ED) admissions and transfers from 5 pm to 4 pm. High‐frequency admission peaks were statistically significantly reduced for ED admissions. The statistically significant increase in DBN rate is sustained at 35%.

CONCLUSIONS

Increasing the DBN rate correlates with admissions arriving earlier in the day and reductions in high‐frequency peaks of ED admissions. Statistically significant improvements in DBN rates are sustainable. Journal of Hospital Medicine 2015;10:664–669. © 2015 Society of Hospital Medicine
Magnetic resonance elastography of frontotemporal dementia
Authors: Huston John , Murphy Matthew C. , Boeve Bradley F. , Fattahi Nikoo , Arani Arvin , Glaser Kevin J. , Manduca Armando , Jones David T. , Ehman Richard L.
Published: June 2015

Purpose

To investigate the feasibility of utilizing brain stiffness as a potential biomarker for behavioral variant frontotemporal dementia (bvFTD) patients. Magnetic resonance elastography (MRE) is a noninvasive technique for evaluating the mechanical properties of brain tissue in vivo. MRE has demonstrated decreased brain stiffness in patients with Alzheimer's disease.

Materials and Methods

We examined five male subjects with bvFTD and nine cognitively normal age‐matched male controls (NC) with brain 3T MRE. Stiffness was calculated in nine regions of interest (ROIs): whole brain (entire cerebrum excluding cerebellum), frontal lobes, occipital lobes, parietal lobes, temporal lobes, deep gray matter / white matter (GM/WM; insula, deep gray nuclei and white matter tracts), cerebellum, sensorimotor cortex (pre‐ and postcentral gyri), and a composite region labeled FT (frontal and temporal lobes excluding the pre‐ and postcentral gyri).

Results

Significantly lower stiffness values were observed in the whole brain (P = 0.007), frontal lobe (P = 0.001), and temporal lobes (P = 0.005) of bvFTD patients compared to NC. No significant stiffness differences were observed in any other ROIs of bvFTD patients compared to NC (P > 0.05). These results demonstrate that statistically significant brain softening occurs in the frontal and temporal lobes of bvFTD patients, which corresponds to the expected pathophysiology of bvFTD.

Conclusion

Future studies evaluating the feasibility of brain MRE for early disease detection and monitoring disease progression could shed new insights into understanding the mechanisms involved in bvFTD. J. Magn. Reson. Imaging 2016;43:474–478.
Crimean‐Congo hemorrhagic fever with hyperbilirubinemia and ascites: An unusual presentation
Authors: Ture Zeynep , Ulu Kılıç Ayşegül , Celik Ilhami , Tok Tugba , Yağcı‐Çağlayık Dilek
Published: June 2015

Crimean‐Congo hemorrhagic fever (CCHF) is a fatal systemic viral infection which is an important health problem in Turkey. Many systemic symptoms have been reported including fever, hemorrhage, headache, fatigue, muscle ache, abdominal pain, nausea and vomiting. A 45‐year‐old male farmer with CCHF presented with massive peritoneal effusion and hyperbilirubinemia. To our knowledge, this is the first case of peritoneal effusion and hyperbilirubinemia in an adult patient with CCHF. His clinical symptoms successfully improved with supportive therapy. In patients who live in endemic areas with atypical presentation for the diagnosis of CCHF should be kept in mind. J. Med. Virol. 88:159–162, 2016. © 2015 Wiley Periodicals, Inc.
Study of phase coexistence in YVO3 and LaVO3
Authors: Roberge Benoit , Jandl Serge , Nugroho Agung A. , Palstra Thomas T. M. , Tung Le D. , Balakrishnan Geetha
Published: June 2015

The coexistence at low temperature in YVO3 and LaVO3 of two competing phases with defined orbital and spin orientations is studied by Raman spectroscopy. The temperature evolution of the phonons indicates that phase coexistence, due to strain in YVO3 and fluctuations in LaVO3, is not restricted to small R ionic radius in RVO3 compounds. Also, a typical temperature at 50 K is inferred from the temperature dependence of the intensities in LaVO3. Copyright © 2015 John Wiley & Sons, Ltd.