bluuebunny/crossref_metadata_2025 huggingface dataset:
Cigarette smoking increases the risk of mortality from liver cancer: A clinical‐based cohort and meta‐analysis
Authors: Pang Qing , Qu Kai , Zhang Jingyao , Xu Xinsen , Liu Sushun , Song Sidong , Wang Ruitao , Zhang Lingqiang , Wang Zhixin , Liu Chang
Published: May 2015

Background and Aim

Although the influence of cigarette smoking on the incident risk of liver cancer has been determined, the association between smoking and liver cancer mortality remains uncertain.

Methods

We searched Pubmed, EmBase, and Web of Science databases to obtain eligible studies. Hazard ratio (HR) value and 95% confidential intervals (CI) were pooled by using a random‐effects model, and dose–response analyses were conducted to quantify associations between smoking and mortality from liver cancer.

Results

A total of 27 articles involving four million participants from seven countries by retrieval (published 1986–2014) were finally included. Pooled HR values for liver cancer mortality was 1.45 (95% CI: 1.33–1.59), 1.22 (95% CI: 1.11–1.34) and 1.16 (95% CI: 1.01–1.32) for current, former, and ever smokers, respectively, when compared with nonsmokers. The risk increased by 7.1% (95% CI: 1.4–13.2) for per additional 10 cigarettes per day and by 5.2% (95% CI: 0.02–11.2) for per additional 10 pack‐years. In our population recruiting 597 patients with liver cancer, smoking status was further identified as a significant determinant factor of tumor size and serum level of gamma‐glutamyl transpeptidase, but not a significant prognostic factor.

Conclusions

Cigarette smoking, especially current smoking, significantly increased mortality risk from liver cancer.
Reduced gland mucin‐specific O‐glycan in gastric atrophy: A possible risk factor for differentiated‐type adenocarcinoma of the stomach
Authors: Yamada Shigenori , Okamura Takuma , Kobayashi Satoshi , Tanaka Eiji , Nakayama Jun
Published: May 2015

Background and Aims

O‐glycans exhibiting terminal α1,4‐linked N‐acetylglucosamine (αGlcNAc) are attached to MUC6 in gastric gland mucins and serve as a tumor suppressor for gastric adenocarcinoma. Gastric atrophy is associated with risk for gastric cancer. However, the significance of αGlcNAc expression in pyloric glands of chronic atrophic gastritis remains unknown. Here, we asked whether reduced αGlcNAc expression in chronic atrophic gastritis is associated with risk for gastric cancer.

Methods

We quantitatively analyzed expression of αGlcNAc relative to MUC6 in pyloric glands by immunohistochemistry in 67 patients with normal mucosa, 70 with chronic atrophic gastritis, 68 with intramucosal differentiated‐type adenocarcinoma, and 11 with intramucosal undifferentiated‐type adenocarcinoma. We also compared the Ki‐67 labeling index in gastric epithelial cells between chronic atrophic gastritis and normal gastric mucosa with respect to αGlcNAc reduction.

Results

In normal pyloric mucosa, αGlcNAc was co‐expressed with MUC6. By contrast, in chronic atrophic gastritis, pyloric gland αGlcNAc expression was significantly reduced relative to MUC6. In intramucosal gastric cancer, αGlcNAc expression in pyloric glands found just beneath differentiated‐type adenocarcinoma was also reduced relative to MUC6. However, pyloric glands present beneath undifferentiated‐type adenocarcinoma exhibited no αGlcNAc decrease. The Ki‐67 labeling index in chronic atrophic gastritis showing αGlcNAc reduction was significantly increased relative to that in normal gastric mucosa.

Conclusions

Because αGlcNAc prevents the gastric cancer development, reduced αGlcNAc expression in chronic atrophic gastritis is a possible risk factor for differentiated‐type adenocarcinoma of the stomach.
Optimizing use of the structural chemical analyser (variable pressure FESEM‐EDX raman spectroscopy) on micro‐size complex historical paintings characterization
Authors: GUERRA I. , CARDELL C.
Published: May 2015

The novel Structural Chemical Analyser (hyphenated Raman spectroscopy and scanning electron microscopy equipped with an X‐ray detector) is gaining popularity since it allows 3‐D morphological studies and elemental, molecular, structural and electronic analyses of a single complex micro‐sized sample without transfer between instruments. However, its full potential remains unexploited in painting heritage where simultaneous identification of inorganic and organic materials in paintings is critically yet unresolved. Despite benefits and drawbacks shown in literature, new challenges have to be faced analysing multifaceted paint specimens. SEM−Structural Chemical Analyser systems differ since they are fabricated ad hoc by request. As configuration influences the procedure to optimize analyses, likewise analytical protocols have to be designed ad hoc. This paper deals with the optimization of the analytical procedure of a Variable Pressure Field Emission scanning electron microscopy equipped with an X‐ray detector Raman spectroscopy system to analyse historical paint samples. We address essential parameters, technical challenges and limitations raised from analysing paint stratigraphies, archaeological samples and loose pigments. We show that accurate data interpretation requires comprehensive knowledge of factors affecting Raman spectra. We tackled: (i) the in‐FESEM−Raman spectroscopy analytical sequence, (ii) correlations between FESEM and Structural Chemical Analyser/laser analytical position, (iii) Raman signal intensity under different VP‐FESEM vacuum modes, (iv) carbon deposition on samples under FESEM low‐vacuum mode, (v) crystal nature and morphology, (vi) depth of focus and (vii) surface‐enhanced Raman scattering effect. We recommend careful planning of analysis strategies prior to research which, although time consuming, guarantees reliable results. The ultimate goal of this paper is to help to guide future users of a FESEM‐Structural Chemical Analyser system in order to increase applications.
The Effects of Melatonin on Brain Arginine Vasotocin: Relationship with Sex and Seasonal Differences in Melatonin Receptor Type 1 in Green Treefrogs (Hyla cinerea)
Authors: Howard C. M. , Lutterschmidt D. I.
Published: May 2015

The neuroendocrine mechanisms by which animals synchronise their physiological state with environmental cues are vital to timing life‐history events appropriately. One important endocrine transducer of environmental cues in vertebrates is the pineal hormone melatonin, the secretion of which is directly sensitive to photoperiod and temperature. Melatonin modulates arginine vasotocin (AVT)‐immunoreactive (‐IR) cell number in the brain of green treefrogs (Hyla cinerea) during the summer breeding season, and this modulation is sexually dimorphic. In the present study, we investigated whether the influence of melatonin on vasotocin varies seasonally. We show that treatment of nonreproductive male green treefrogs with melatonin‐filled silastic implants for 4 weeks during the winter does not alter vasotocin‐IR cell number in any brain region (i.e. nucleus accumbens, amygdala, preoptic area, suprachiasmatic nucleus or ventral hypothalamus). Taken together, these results suggest that the influence of melatonin on AVT is associated with sex and seasonal variation in melatonin receptor expression. We tested this hypothesis by using immunohistochemistry to characterise the distribution of melatonin receptor type 1 (MT1, also known as Mel1a) in the brain of reproductive and nonreproductive male and female frogs. We quantified MT1‐IR cell number in regions known to contain AVT cell populations. Reproductive males had significantly more MT1‐IR cells than nonreproductive males in all brain regions, including the combined nucleus accumbens, diagonal band of Broca and septum, striatum, amygdala, combined preoptic area and suprachiasmatic nucleus, as well as the ventral hypothalamus. In the accumbens region, where the effect of melatonin on AVT is known to be sexually dimorphic, males had significantly more MT1‐IR cells than females during the summer breeding season. Based on these findings, we suggest that MT1 plays a role in mediating the interactions between melatonin and vasotocin that regulate seasonal and sexually dimorphic changes in sociosexual behaviour.
Pegylated interferon alfa for chronic hepatitis B: systematic review and meta‐analysis
Authors: Kim V. , Abreu R. M. , Nakagawa D. M. , Baldassare R. M. , Carrilho F. J. , Ono S. K.
Published: May 2015

Conventional interferon alfa and nucleos(t)ide analogues, such as lamivudine, are frequently used for chronic hepatitis B (CHB) treatment, but are associated with adverse effects and viral resistance. Here we performed a systematic review and meta‐analysis evaluating all studies of pegylated interferon alfa (PEG‐IFNα) treatment in hepatitis B e antigen (HBeAg)‐positive and HBeAg‐negative patients with CHB. We searched electronic databases – PubMed, EMBASE, Cochrane Library and LILACS – for randomized controlled trials evaluating PEG‐IFNα therapy between 1999 and September 2014. Virological response was the primary outcome. We identified 14 studies involving 2829 patients. Our analysis revealed that PEG‐IFNα + lamivudine combination therapy produced better virological and biochemical responses than PEG‐IFNα monotherapy in HBeAg‐positive and HBeAg‐negative patients at the end of treatment. PEG‐IFNα + adefovir dipivoxil achieved better seroconversion rate than PEG‐IFNα in HBeAg‐positive patients at the end of treatment. The present findings demonstrated a beneficial response rate following PEG‐IFNα combination therapy with nucelos(t)ides among HBeAg‐positive and HBeAg‐negative patients with CHB. Further trials are needed to investigate simultaneous and sequential therapy strategies.
Work Rules: How International NGOs Build Law in War-Torn Societies
Authors: Massoud Mark Fathi
Published: May 2015

Drawing on socio-legal literature and fieldwork in South Sudan, this article argues that international aid groups operating in conflict settings create and impose a rules-based order on the local people they hire and on the domestic organizations they fund. Civil society actors in these places experience law'ssoftpower through their daily, tangible, and mundane contact with aid agencies. As employees they are subject to contracts and other rules of employment, work under management and finance teams, document routine activity, and abide by organizational constitutions. In analyzing how South Sudanese activists confront, understand, conform to, or resist these externally imposed legal techniques and workplace practices, this article decenters state institutions as sites for understanding law's power and exposes how aid organizations themselves become arenas of significant legal and political struggle in war-torn societies.
Linking root traits to nutrient foraging in arbuscular mycorrhizal trees in a temperate forest
Authors: Eissenstat David M. , Kucharski Joshua M. , Zadworny Marcin , Adams Thomas S. , Koide Roger T.
Published: May 2015

The identification of plant functional traits that can be linked to ecosystem processes is of wide interest, especially for predicting vegetational responses to climate change. Root diameter of the finest absorptive roots may be one plant trait that has wide significance. Do species with relatively thick absorptive roots forage in nutrient‐rich patches differently from species with relatively fine absorptive roots?

We measured traits related to nutrient foraging (root morphology and architecture, root proliferation, and mycorrhizal colonization) across six coexisting arbuscular mycorrhizal (AM) temperate tree species with and without nutrient addition.

Root traits such as root diameter and specific root length were highly correlated with root branching intensity, with thin‐root species having higher branching intensity than thick‐root species. In both fertilized and unfertilized soil, species with thin absorptive roots and high branching intensity showed much greater root length and mass proliferation but lower mycorrhizal colonization than species with thick absorptive roots. Across all species, fertilization led to increased root proliferation and reduced mycorrhizal colonization.

These results suggest that thin‐root species forage more by root proliferation, whereas thick‐root species forage more by mycorrhizal fungi. In mineral nutrient‐rich patches, AM trees seem to forage more by proliferating roots than by mycorrhizal fungi.
A randomized controlled trial of ProRoot MTA, OrthoMTA and RetroMTA for pulpotomy in primary molars
Authors: Kang C‐M , Kim S‐H , Shin Y , Lee H‐S , Lee J‐H , Kim GT , Song JS
Published: May 2015

Objectives

The aim of this study was to determine the clinical efficacy of the newly developed OrthoMTA and RetroMTA, compared to conventionally used ProRoot MTA, for pulpotomy in primary teeth.

Material and Methods

In this randomized clinical trial, 151 molars from 102 children, who met the inclusion criteria and were 3–10 years old, were enrolled. Ultimately, 143 teeth were divided in a randomized, single‐blind manner into three groups according to the planned treatment: RetroMTA (n = 49 teeth), OrthoMTA (n = 47 teeth) or ProRoot MTA (n = 47 teeth). Clinical and radiographic follow‐up examinations were conducted at 3, 6 and 12 months postoperatively.

Results

By the end of the study period, 109 teeth were evaluated at 12 months. The radiographic success rates in these three groups were 100%, 94.7% and 94.7%, respectively; the corresponding clinical success rates were 100%, 97.4% and 100%. The Kaplan–Meier survival function curves relative to clinical and radiographic cumulative survival rates did not differ significantly between the three groups.

Conclusions

The success rates of RetroMTA, OrthoMTA and ProRoot MTA are indistinguishable, indicating that pulpotomy can be carried out successfully in primary molars with the newly developed materials.
Monitoring the impact of cow's milk allergy on children and their families with the FLIP questionnaire – a six‐month follow‐up study
Authors: Mikkelsen Andrea , Mehlig Kirsten , Borres Magnus P. , Oxelmark Lena , Björkelund Cecilia , Lissner Lauren
Published: May 2015

Background

Many children with cow's milk allergy (CMA) develop tolerance, but, challenges in daily life may remain. Using the Food hypersensitivity famiLy ImPact questionnaire (FLIP), we sought to monitor changes in the impact of CMA over time.

Methods

Families of children with CMA, who participated in the validation of the FLIP, were re‐approached 6 months later for follow‐up. Change in reported difficulties was assessed by paired sample t‐test and mixed models, stratifying by outgrown vs. persistent CMA.

Results

Impact on families with children who had outgrown CMA (n = 20) decreased in the FLIP's total score (p = 0.0001) and in two subscales; Health and Emotions (p = 0.0001) and Everyday Life (p = 0.0001). In contrast, no significant improvements were registered in nutritional concerns. Impact on the group with persistent CMA (n = 57) was unchanged at follow‐up except for more impact on Everyday Life (p = 0.001). In the final analysis comparing longitudinal changes in the groups, the strongest differences were observed for the subscales Health & Emotions and Everyday Life; for the Nutrition subscale, the between‐group changes also differed, but to lesser extent.

Conclusions

We have documented the varying impact of CMA on parents and children over time. Families who were still affected continued to experience impact in daily life. Despite development of tolerance, families who were no longer affected revealed continuing nutritional concerns. Follow‐ups should be offered even after outgrown CMA to encourage progression to unrestricted diet, to prevent eating disorders and to promote healthy growth.
HARKing's Threat to Organizational Research: Evidence From Primary and Meta‐Analytic Sources
Authors: Bosco Frank A. , Aguinis Herman , Field James G. , Pierce Charles A. , Dalton Dan R.
Published: May 2015

We assessed presumed consequences of hypothesizing after results are known (HARKing) by contrasting hypothesized versus nonhypothesized effect sizes among 10 common relations in organizational behavior, human resource management, and industrial and organizational psychology research. In Study 1, we analyzed 247 correlations representing 9 relations with individual performance in 136 articles published in Journal of Applied Psychology and Personnel Psychology and provide evidence that correlations are significantly larger when hypothesized compared to nonhypothesized. In Study 2, we analyzed 281 effect sizes from a meta‐analysis on the job satisfaction–job performance relation and provide evidence that correlations are significantly larger when hypothesized compared to nonhypothesized. In addition, in Study 2, we documented that hypothesized variable pairs are more likely to be mentioned in article titles or abstracts. We also ruled out 13 alternative explanations to the presumed HARKing effect pertaining to methodological (e.g., unreliability, publication year, research setting, research design, measure contextualization, publication source) and substantive (e.g., predictor–performance pair, performance measure, satisfaction measure, occupation, job/task complexity) issues. Our results suggest that HARKing seems to pose a threat to research results, substantive conclusions, and practical applications. We offer recommended solutions to the HARKing threat.
Mining new resources for grape resistance against Botryosphaeriaceae: a focus on Vitis vinifera subsp. sylvestris
Authors: Guan X. , Essakhi S. , Laloue H. , Nick P. , Bertsch C. , Chong J.
Published: May 2015

Botryosphaeria dieback is an important grapevine trunk disease with global impact. Susceptibility differences between grape varieties manifest as different expression of canopy symptoms in the field. However, the cause of these dieback symptoms and their relation with wood necrosis remain only partially understood. As a first step towards future strategies for resistance breeding, wood necrosis was investigated over a large selection of the Vitaceae family members following artificial inoculation of the Botryosphaeriaceae fungi Neofusicoccum parvum and Diplodia seriata into woody internodes. Large variation of resistance levels was found, with good performance in several accessions from V. vinifera subsp. sylvestris, the ancestor of cultivated grapevine. To get insight into the mechanisms of this apparent resistance, expression of defence genes was studied in V. vinifera cv. Chardonnay, Gewürztraminer and different V. vinifera subsp. sylvestris genotypes, in both green and necrotic areas of inoculated woods. Resistance to Botryosphaeriaceae in V. vinifera subsp. sylvestris correlated with earlier and higher induction of some defence genes, both in green and necrotic wood. Moreover, leaves of several V. vinifera subsp. sylvestris accessions were also less susceptible to necrosis induced by treatment with a culture filtrate of Botryosphaeriaceae, compared to commercial cultivars of V. vinifera. The results show that V. vinifera subsp. sylvestris provides interesting genetic resources for breeding new varieties with enhanced resistance to botryosphaeria dieback.
Phakopsora myrtacearum sp. nov., a newly described rust (Pucciniales) on eucalypts in eastern and southern Africa
Authors: Maier W. , McTaggart A. R. , Roux J. , Wingfield M. J.
Published: May 2015

Outbreaks of a rust disease in eucalypt forestry plantations and nurseries in Kenya, Mozambique and South Africa occurred between 2009 and 2014. The pathogen was identified using morphology and molecular phylogenetic analyses as an undescribed species in the Phakopsoraceae. A systematic study, based on nuclear ribosomal DNA, showed that it is a species of Phakopsora, herein named Phakopsora myrtacearum sp. nov. This new species of rust is the second validly described species on Eucalyptus, along with Puccinia psidii. Phakopsora myrtacearum is distinguished from P. psidii by leaf symptoms, morphology of the urediniospores and distinct phylogenetic placement. Phakopsora myrtacearum has been found on three species of Eucalyptus in Kenya, Mozambique and South Africa, and it may have future negative implications for commercial forestry in these areas.
SSR assessment of Phytophthora infestans populations on tomato and potato in British gardens demonstrates high diversity but no evidence for host specialization
Authors: Stroud J. A. , Shaw D. S. , Hale M. D. , Steele K. A.
Published: May 2015

Phytophthora infestans populations can differ in composition as a result of host specialization on tomato and potato hosts. In Great Britain many amateur gardeners grow outdoor tomatoes but there is little or no commercial tomato production outdoors. This study analysed isolates of P. infestans from British gardens with 12 multiplexed simple sequence repeat markers that are used to monitor the disease on commercial potato crops. Samples of P. infestans from tomato hosts were collected in 3 years and from potato in 1 year from across Great Britain. Seven previously unreported clonal lineages were detected in garden populations and higher frequencies of unique clonal lineages (28–40%) were present compared with populations from British commercial potato crops reported elsewhere. Garden populations had a lower proportion (11–48% less) of the most common lineages (13_A2 and 6_A1) that together made up at least 86% of the commercial potato populations during the sampling period. Host species accounted for only 2·0% of molecular variance detected between garden potato‐ and tomato‐hosted samples. No significant difference in clonal lineage composition was found between host species in Great Britain and this could be due to the whole P. infestans population overwintering on potato. British garden populations on both hosts were much more diverse than those on commercial potato crops; this finding may be influenced by less frequent fungicide use by gardeners and a higher diversity of unsprayed susceptible potato cultivars, enabling metalaxyl‐sensitive and less aggressive genotypes to survive in gardens.
Colour Doppler Ultrasonography as a Tool to Assess Luteal Function in Santa Inês Ewes
Authors: Figueira LM , Fonseca JF , Arashiro EKN , Souza‐Fabjan JMG , Ribeiro ACS , Oba E , Viana JHM , Brandão FZ
Published: May 2015

Contents

The aim of this study was to evaluate luteal dynamics in the Santa Inês ewes using colour Doppler (CD) ultrasonography. Oestrus was synchronized in nulliparous females (n = 18), and subsequently, they were only teased (n = 6) or teased and mated (n = 12). Blood samples were collected daily for plasma progesterone (P4) concentrations. Ultrasonographic images of corpora lutea (CL) in CD mode were obtained for further analysis in its largest diameter. The CD mode allowed an early sequential monitoring of CL that was visualized by the first time 0.77 ± 0.62 days after ovulation, with luteal area 29.68 ± 13.21 mm2. During the luteogenesis, a progressive increase was observed, followed by a plateau of luteal area, vascularization area and plasma concentrations of P4 reaching maximum values in D11 (124.0 ± 38.0 mm2, 52.78 ± 24.08 mm2 and 11.23 ± 4.89 ng/ml, respectively). In the luteolysis, the plasma concentrations of P4 decreased sharply, whereas luteal and vascularization area gradually. The vascularization area was positively correlated with plasma concentrations of P4 during the luteogenesis (r = 0.22) and luteolysis (r = 0.48). The luteal dynamics of Santa Inês ewes showed patterns similar to those observed in other sheep breeds studied. The CD ultrasonography has the potential to be used as a tool to assess luteal function in sheep.
Neoproterozoic peritidal phosphorite from the Sete Lagoas Formation (Brazil) and the Precambrian phosphorus cycle
Authors: Drummond Justin B. R. , Pufahl Peir K. , Porto Claudio G. , Carvalho Mariana
Published: May 2015

The Neoproterozoic Sete Lagoas Formation (ca 610 Ma) of the São Francisco Basin, Brazil, is a succession of siltstone, limestone and phosphorite. Phosphorite forms part of a previously unrecognized 150 to 200 m thick, unconformity bounded depositional sequence. Lithofacies stacking patterns indicate that deposition was punctuated by higher order fluctuations in base level that produced aggradational parasequences. These shallowing‐upward cycles record the progradation of phosphate‐rich intertidal flats over shallow subtidal deposits as accommodation filled. The presence of mudcracks, authigenic chert nodules, lack of coarse terrigenous clastics and the abundance of silt with fine, abraded quartz grains suggests accumulation along an arid coastline with significant aeolian input. Delivery of phosphorus adsorbed on aeolian Fe‐(oxyhydr)oxide and clay is interpreted as having stimulated phosphogenesis in peritidal environments. Lithofacies associations indicate that windblown phosphorus promoted the establishment of cyanobacterial communities along the coast, which produced photosynthetic oxygen and the suboxic conditions necessary for the precipitation of authigenic carbonate fluorapatite. As in other Precambrian phosphatic systems, nearshore oxygen oases were a prerequisite for phosphorite accumulation because redox sensitive phosphogenic processes were pushed into the sediment to concentrate phosphorus. In more distal, anoxic environments phosphorite could not form because these biotic and abiotic processes were suspended in the water column, which cycled phosphorus in sea water rather than at the sediment–water interface. Such shallow‐water phosphorite is unlike larger, younger Neoproterozoic–Phanerozoic phosphatic deposits inferred to have formed in deeper‐upwelling related environments. The increasing size of phosphatic deposits through the latest Precambrian is interpreted as reflecting the progressive ventilation of the oceans during the Neoproterozoic Oxygenation Event, and resultant expansion of phosphogenic environments into distal settings. The widespread cycling of bioavailable phosphorus at the sea floor not only produced the first true phosphorite giants, but may have also been an important precondition for the evolution of multicellular animals.
Depositional controls on mixed carbonate–siliciclastic cycles and sequences on gently inclined shelf profiles
Authors: Zeller Michael , Verwer Klaas , Eberli Gregor P. , Massaferro Jose Luis , Schwarz Ernesto , Spalletti Luis
Published: May 2015

The interplay between carbonate production and siliciclastic input produces mixed systems that typically contain a very high degree of lateral and vertical facies heterogeneity. This heterogeneity complicates the sequence stratigraphic analysis of mixed systems. Outcrop studies facilitate the deciphering of controls and understanding of facies distributions within sedimentary successions. The Picún Leufú Anticline in the Neuquén Basin (Argentina) offers the opportunity to integrate large‐scale depositional architecture with detailed facies descriptions of the shelf to basin successions of the Upper Jurassic – Lower Cretaceous Quintuco – Picún Leufú – Vaca Muerta System. The strata in the system are mixed and range in depositional environments from shallow marine sandstones and limestones to deep basinal shales. These environments are arranged in metre‐scale shallowing upward cycles and cycle sets, with increasing carbonate proportions in regressive hemicycles. Increased input of siliciclastic material from the volcanic arc area occurred during phases of relative sea‐level rise and was controlled by the intensity of along‐shelf currents. The shelf transport was driven by the available accommodation space on the shelf, and therefore was a function of the eustatic sea‐level fluctuations. Within the studied section, a pure carbonate depositional system developed because siliciclastic input was shut down either due to long‐lived highstand settings or a sudden climatic change to more arid conditions. Carbonate–siliciclastic mixing in this setting is a function of siliciclastic dilution of the carbonate sedimentation and differs from the classical reciprocal sedimentation model, which typically includes shut‐off of carbonate production during lowstand periods. In the regional context, the subsurface strata of time‐equivalent reservoirs in the Eastern Neuquén Embayment display strong similarities of architecture, indicating that similar mixing processes occurred along most of the Neuquén Basin.
Spiegelmer Inhibition of MCP‐1/CCR2 – Potential as an Adjunct Immunosuppressive Therapy in Transplantation
Authors: Kalnins A. , Thomas M. N. , Andrassy M. , Müller S. , Wagner A. , Pratschke S. , Rentsch M. , Klussmann S. , Kauke T. , Angele M. K. , Bazhin A. V. , Fischereder M. , Werner J. , Guba M. , Andrassy J.
Published: May 2015

The rejection process remains the key unsolved issue after transplantation of disparate tissue. The CC chemokine monocyte chemoattractant protein‐1 (MCP‐1/CCL2) has been reported to be involved in the process of alloimmune interaction. Spiegelmers are l‐oligonucleotides that can be designed to bind to pharmacologically relevant target molecules. Here, we tested a high‐affinity Spiegelmer‐based MCP‐1 inhibitor (mNOX‐E36) in an allogeneic heart transplant model. Fully vascularized allogeneic heterotopic heart transplantations from BALB/c to C57BL/6 mice were performed. Mice were either treated with the anti‐MCP‐1‐Spiegelmer (mNOX‐E36) in monotherapy or in combination with subtherapeutic doses of cyclosporine A (CsA) (10 mg/kgBW/day) for 10 days. Controls received equivalent doses of a non‐functional Spiegelmer (revmNOX‐E36). Graft survival of allogeneic heart transplants was slightly but significantly prolonged under mNOX‐E36 monotherapy (median graft survival 10 day ± 0.7) compared to revmNOX‐E36 (median graft survival 7 day ± 0.3; P = 0.001). A synergistic beneficial effect could be seen when mNOX‐E36 was administered in combination with subtherapeutic doses of CsA (18 day ± 2.8 versus 7 day ± 0.3; P < 0.0001). Levels of inflammatory cytokines and ‘alarmins’ were significantly reduced, and the number of F4/80+ cells was lower under combination therapy (1.8% ± 1.3%; versus 14.6% ± 4.4%; P = 0.0002). This novel inhibitor of the MCP‐1/CCR2 axis (mNOX‐E36), which has already proven efficacy and tolerability in early clinical trials, alleviates acute rejection processes in allogeneic transplantation especially when combined with subtherapeutic doses of CsA. Thus, mNOX‐E36 may have potential as an adjunct immunomodulatory agent.
Stored red blood cell susceptibility to in vitro transfusion‐associated stress conditions is higher after longer storage and increased by storage in saline‐adenine‐glucose‐mannitol compared to AS‐1
Authors: Mittag Diana , Sran Amrita , Chan Kasey S. , Boland Martin P. , Bandala‐Sanchez Esther , Huet Olivier , Xu William , Sparrow Rosemary L.
Published: May 2015

BACKGROUND

Biochemical changes induced in red blood cells (RBCs) during storage may impair their function upon transfusion. Transfusion‐associated stresses may further amplify storage lesion effects including increased phosphatidylserine (PS) exposure at the RBC membrane, microparticle (MP) release, and adhesion to endothelial cells (ECs). RBC stress susceptibility in vitro was investigated in relation to storage time and additive solution.

STUDY DESIGN AND METHODS

Leukoreduced whole blood donations (n = 18) were paired, mixed, and resplit before separating the RBCs for storage in saline‐adenine‐glucose‐mannitol (SAGM) or AS‐1. Samples were taken after 3, 21, or 35 days. For oxidative stress treatment, RBCs were exposed to 0.5 mmol/L tert‐butylhydroperoxide. Transfusion‐associated stress was simulated by overnight culture at 37 °C with plasma containing inflammatory mediators. PS exposure and MPs were measured by flow cytometry and adhesion to ECs was tested under flow conditions. PS specificity of adhesion was tested by blocking with PS‐containing lipid vesicles.

RESULTS

Oxidative stress induced significantly higher PS exposure and adhesion to ECs in RBCs stored for 35 days compared to 3 days (p < 0.04). PS‐containing vesicles blocked RBC‐EC adhesion. After overnight culture with or without plasma, PS exposure and EC adhesion were significantly increased (p < 0.05). MP numbers increased with longer RBC storage and after RBC culture with plasma. Culture conditions influenced MP numbers from Day 35 RBCs. RBCs stored in SAGM had significantly higher PS exposure after stress treatment than AS‐1 RBCs (p < 0.02).

CONCLUSION

Storage for 35 days significantly increased RBC susceptibility to oxidative and in vitro transfusion‐associated stresses and was higher for RBCs stored in SAGM compared to AS‐1.
Necessary and Sufficient Conditions for Agribusiness Success of Small-scale Farming Systems in Northern Vietnam
Authors: Ha Tuan M. , Bosch Ockie J. H. , Nguyen Nam C.
Published: May 2015

This study was conducted in Haiphong (Vietnam) during 2013-2014 to analyse the requirements for the success of small-scale agribusinesses. Following two baseline studies on the current state of the local farming systems and market situations, various stakeholders were engaged in a number of workshops with support of a causal loop diagram (CLD) modelling tool to redefine the pre-requisites for agribusiness success and their interplays. As a result, multi-stakeholder collaboration and government support via its policies and development programs were identified as the necessary conditions for success. Nonetheless, strengthening the capacity of local cooperatives and investing in human and social capitals are of equal importance as sufficient conditions, which generate multiple benefits towards achieving agribusiness success. Values of full participation by all stakeholders and the use of the CLD in defining systemic interventions are also discussed.
Steady‐state tilt has no effect on cerebrovascular CO2 reactivity in anterior and posterior cerebral circulations
Authors: Tymko Michael M. , Skow Rachel J. , MacKay Christina M. , Day Trevor A.
Published: May 2015

New Findings

What is the central question of this study?

We investigated the effects of superimposed tilt and hypercapnia‐induced cerebral arteriolar dilatation on anterior and posterior cerebrovascular CO2 reactivity using hyperoxic rebreathing in human participants.

What is the main finding and its importance?

The main findings are threefold: (i) cerebrovascular CO2 reactivity in the anterior and posterior cerebrovasculature is unchanged with tilt; (ii) cerebral autoregulation is unlikely responsible due to unchanging cerebrovascular resistance reactivity between positions; and (iii) cerebral blood flow is not pressure passive during tilt as it is with pharmacological or lower body negative pressure‐induced changes in mean arterial pressure, suggesting that sympathetic activation or balanced transmural pressures during head‐down tilt regulate cerebral blood flow.

Cerebral autoregulation is a protective feature of the cerebrovasculature that maintains relatively constant cerebral perfusion in the face of static and dynamic fluctuations in mean arterial pressure (MAP). However, the extent that the cerebrovasculature can autoregulate in the face of superimposed steady‐state orthostasis‐induced changes in MAP (e.g. head‐up and head‐down tilt; HUT and HDT) and CO2‐mediated arteriolar dilatation is unknown. We tested the effects of steady‐state tilt on cerebrovascular CO2 reactivity in the middle and and posterior cerebral artery in the following five body positions: 90 deg HUT, 45 deg HUT, supine, 45 deg HDT and 90 deg HDT on a tilt table during a modified hyperoxic rebreathing test. Absolute and relative cerebrovascular CO2 reactivity [cerebral blood velocity (CBV)/CO2], cerebrovascular resistance (CVR) reactivity (CVR/CO2) and MAP reactivity (MAP/CO2) were quantified using linear regression. Mean arterial pressure was significantly elevated in 90 deg HDT compared with other positions during baseline steady‐state tilt (P < 0.01). Absolute CBV/CO2 and CVR/CO2 were greater in the middle cerebral artery than the posterior cerebral artery (P < 0.01) in all body positions, but relative measures were not different (P = 0.143 and P = 0.360, respectively), nor was there any interaction with tilt position. In addition, there was no difference in absolute (P = 0.556) and relative MAP/CO2 (P = 0.308) between positions. Our data demonstrate that cerebral blood flow remains well regulated during superimposed steady‐state orthostatic stress and dynamic changes in the partial pressure of end‐tidal CO2 during rebreathing. Cerebral autoregulation is likely not the mechanism responsible, but rather sympathetic nervous system activation or a balanced cerebrovascular transmural pressure with HDT maintains resting cerebral blood flow and cerebrovascular CO2 reactivity during rebreathing.
Voltage‐gated sodium channels contribute to action potentials and spontaneous contractility in isolated human lymphatic vessels
Authors: Telinius Niklas , Majgaard Jens , Kim Sukhan , Katballe Niels , Pahle Einar , Nielsen Jørn , Hjortdal Vibeke , Aalkjaer Christian , Boedtkjer Donna Briggs
Published: May 2015

Key points

Initial studies have described the electrical properties of lymphatic smooth muscle cells from different animal species and the ion channels contributing to these properties. However, there is a translational gap to the human situation where studies on human tissue are lacking.

Voltage‐gated sodium channels are essential for the generation of action potentials, and thus spontaneous contractions in human lymphatic vessels, but not noradrenaline‐induced contractions. A sodium channel opener elicited contractions as a result of calcium influx via voltage‐gated calcium channels and the sodium–calcium exchanger.

Pharmacological characterization and the mRNA expression profile indicate that Nav1.3 is the most prevalent sodium channel.

These results provide support for an important role of sodium channels in spontaneous human lymphatic vessel electrical activity and contractility.

Voltage‐gated sodium channels (VGSC) play a key role for initiating action potentials (AP) in excitable cells. VGSC in human lymphatic vessels have not been investigated. In the present study, we report the electrical activity and APs of small human lymphatic collecting vessels, as well as mRNA expression and function of VGSC in small and large human lymphatic vessels. The VGSC blocker TTX inhibited spontaneous contractions in six of 10 spontaneously active vessels, whereas ranolazine, which has a narrower VGSC blocking profile, had no influence on spontaneous activity. TTX did not affect noradrenaline‐induced contractions. The VGSC opener veratridine induced contractions in a concentration‐dependent manner (0.1–30 μm) eliciting a stable tonic contraction and membrane depolarization to −18 ± 0.6 mV. Veratridine‐induced depolarizations and contractions were reversed ∼80% by TTX, and were dependent on Ca2+ influx via L‐type calcium channels and the sodium–calcium exchanger in reverse mode. Molecular analysis determined NaV1.3 to be the predominantly expressed VGSC isoform. Electrophysiology of mesenteric lymphatics determined the resting membrane potential to be −45 ± 1.7 mV. Spontaneous APs were preceded by a slow depolarization of 5.3 ± 0.6 mV after which a spike was elicited that almost completely repolarized before immediately depolarizing again to plateau. Vessels transiently hyperpolarized prior to returning to the resting membrane potential. TTX application blocked APs. We have shown that VGSC are necessary for initiating and maintaining APs and spontaneous contractions in human lymphatic vessels and our data suggest the main contribution from comes NaV1.3. We have also shown that activation of these channels augments the contractile activity of the vessels.
Small-Scale Wind Turbine Testing in Wind Tunnels Under Low Reynolds Number Conditions
Authors: Van Treuren Kenneth W.
Published: May 2015

Much of the aerodynamic design of wind turbines is accomplished using computational tools such as XFOIL. These codes are not robust enough for predicting performance under the low Reynolds numbers found with small-scale wind turbines. Wind tunnels can experimentally test wind turbine airfoils to determine lift and drag data over typical operating Reynolds numbers. They can also test complete small wind turbine systems to determine overall performance. For small-scale wind turbines, quality experimental airfoil data at the appropriate Reynolds numbers are necessary for accurate design and prediction of power production.
On Necessary Pumping Pressures for Industrial Process-Driven Particle-Laden Fluid Flows
Authors: Zohdi T. I.
Published: May 2015

Due to increasing demands for faster and faster manufacturing of new complex materials, such as casting of particulate composites, the determination of pumping pressures needed for particle-laden fluids through channels is critical. In particular, the increase in viscosity as a function of the particle volume fraction can lead to system malfunction, due to an inability to deliver necessary pressures to pump the more viscous fluid through the system. This paper studies the pressure gradient needed to maintain a given flow rate, explicitly as a function of the volume fraction of particles present in the fluid. It is also crucial to control voids in the casted products, which can be traced to air-entrainment, spurious internal reactions, dewetting, etc., which can be traced to high Reynolds numbers. Accordingly, an expression for the resulting Reynolds number as a function of the particle volume fraction and flow rate is also developed. Numerical examples are provided to illustrate the practical use of the derived relations to characterize the necessary pumping pressures for process-driven, particle-laden fluid flows.
Using Rigid-Body Mechanism Topologies to Design Path Generating Compliant Mechanisms
Authors: Zhao Kai , Schmiedeler James P.
Published: May 2015

For a path generation problem, this paper uses the base topology of a single degree-of-freedom (DOF) rigid-body mechanism solution to synthesize fully distributed compliant mechanisms that can trace the same path. Two different strategies are proposed to employ the base topology in the structural optimization so that its design space size can be intelligently reduced from an arbitrary complexity. In the first strategy, dimensional synthesis directly determines the optimal size and shape of the compliant mechanism solution while maintaining the exact base topology. In the second, the base topology establishes an initial mesh network to determine the optimal topology and dimensions simultaneously. To increase the possibility of converging to an optimal design, the objective metrics to evaluate the path generation ability are computed in a novel manner. A section-by-section analysis with a rigid-body transformation is implemented to examine the full path of each candidate mechanism. A two-objective genetic algorithm (GA) is employed to find a group of viable designs that tradeoff minimizing the average Euclidean distance between the desired and actual paths with minimizing the peak distance between corresponding points on those paths. Two synthesis examples generating straight-line and curved paths are presented to demonstrate the procedure's utility.
Reliability of the Spatiotemporal Determinants of Maximal Sprint Speed in Adolescent Boys Over Single and Multiple Steps
Authors: Meyers Robert W. , Oliver Jon L. , Hughes Michael G. , Lloyd Rhodri S. , Cronin John
Published: May 2015

The purpose of this study was to examine the reliability of the spatiotemporal determinants of maximal sprinting speed in boys over single and multiple steps. Fifty-four adolescent boys (age = 14.1 ± 0.7 years [range = 12.9–15.7 years]; height = 1.63 ± 0.09 m; body mass = 55.3 ± 13.3 kg; -0.31 ± 0.90 age from Peak Height Velocity (PHV) in years; mean ± s) volunteered to complete a 30 m sprint test on 3 occasions over a 2-week period. Speed, step length, step frequency, contact time, and flight time were assessed via an optical measurement system. Speed and step characteristics were obtained from the single-fastest step and average of the 2 and 4 fastest consecutive steps. Pairwise comparison of consecutive trials revealed the coefficient of variation (CV) for speed was greater in 4-step (CV = 7.3 & 7.5%) compared with 2-step (CV = 4.2 & 4.1%) and 1-step (CV = 4.8 & 4.6%) analysis. The CV of step length, step frequency and contact time ranged from 4.8 to 7.5% for 1-step, 3.8–5.0% for 2-step and 4.2–7.5% for 4-step analyses across all trials. An acceptable degree of reliability was achieved for the spatiotemporal and performance variables assessed in this study. Two-step analysis demonstrated the highest degree of reliability for the key spatiotemporal variables, and therefore may be the most suitable approach to monitor the spatiotemporal characteristics of maximal sprint speed in boys.
How to know when physicians are ready for genomic medicine
Authors: Vassy Jason L. , Korf Bruce R. , Green Robert C.
Published: May 2015

Despite perceptions to the contrary, physicians are as prepared for genomic medicine as they are for other medical innovations.
Stimulated sight
Authors: Bhatti Pamela
Published: May 2015

Electrical stimulation of retinal neurons using photovoltaics restores sight in rats with retinal degradation.
It takes two to tango
Authors: Parekkadan Biju
Published: May 2015

An engineered IL-2 fusion protein collaborates with T cell therapy to induce a multifaceted immune response in mouse tumor models.
Acute STEMI in the setting of a single coronary artery anomaly
Authors: McCarthy Cian , Khider Wisam , Caplice Noel
Published: May 2015

We report a case of a patient admitted with an acute ST elevation myocardial infarction following occlusion of his right coronary artery, successfully treated with thrombectomy and percutaneous coronary intervention (PCI). Coronary angiography and multislice CT revealed a single right coronary artery with two anomalous branches (constituting the left coronary system); one branch passed between the pulmonary trunk and the aorta before dividing into three separate branches, while the other anomalous branch passed anterior to the pulmonary trunk, consistent with a Yamanaka R-IIIC classification. The course of this Yamanaka R-IIIC subtype is unusual as both anomalous branches combine to form a dual origin left anterior descending artery. The course of these anomalous branches places the patient at an increased risk of future myocardial ischaemia, infarction and sudden cardiac death. As symptoms typically develop on exertion, this cohort may benefit from exercise myocardial perfusion imaging to identify high-risk patients.