bluuebunny/crossref_metadata_2025 huggingface dataset:
The complete chloroplast genome of the spring ephemeral plant Alyssum desertorum and its implications for the phylogenetic position of the tribe Alysseae within the Brassicaceae
Authors: Li Yan , Lv Guanghui , He Xueming , Zhang Xueni , Yang Xiaodong
Published: August 2017

Alyssum desertorum (Alysseae, Brassicaceae) is an annual spring ephemeral plant whose life cycle is only 2–3 months. It typically has high photosynthetic capacity and a high growth rate. However, little was known about the chloroplast (cp) genome structure of this species. Furthermore, the phylogenetic position of the tribe Alysseae relative to other tribes in the Brassicaceae has not been established and there appear to be inconsistences between different DNA markers. This study is the first report on a cp genome of the genus Alyssum and discusses the phylogenetic relationships of the tribe Alysseae relative to other tribes in the family. The complete cp genome of A. desertorum was 151 677 bp in size and is thus the smallest cp genome of Brassicaceae sequenced to date. The genome includes a large single‐copy region of 81 551 bp, a small single‐copy region of 17 804 bp, and two inverted repeats of 26 161 bp each. The genome contains 132 genes, including 86 protein‐coding genes (PCGs), 38 tRNA genes and 8 rRNA genes. A total of 16 genes contained introns, including 10 PCGs and 6 tRNA genes; the ycf3 and clpP genes contained two introns, and the remaining genes each contained one. Compared to the cp genomes of 21 other Brassicaceae species, the cp genome of Alyssum desertorum was the smallest, as due to variation in gene content and gene length, such as a lack of the rps16 gene and the deletion of some coding genes. Additionally, deletions of introns and intergenic spacers were observed, but their total length was not significantly shorter than those of other taxa. Phylogenetic analysis at the tribal level based on a cp genome dataset revealed that the tribe Alysseae is an early‐diverging lineage that is sister to other species within subclade B of clade II.
Learning the Natural Numbers as a Child
Authors: Buijsman Stefan
Published: August 2017

How do we get out knowledge of the natural numbers? Various philosophical accounts exist, but there has been comparatively little attention to psychological data on how the learning process actually takes place. I work through the psychological literature on number acquisition with the aim of characterising the acquisition stages in formal terms. In doing so, I argue that we need a combination of current neologicist accounts and accounts such as that of Parsons. In particular, I argue that we learn the initial segment of the natural numbers on the basis of the Fregean definitions, but do not learn the natural number structure as a whole on the basis of Hume's principle. Therefore, we need to account for some of the consistency of our number concepts with the Dedekind‐Peano axioms in other terms.
How to support the endurance of long‐term networks: The pivotal role of the network manager
Authors: Macciò Laura , Cristofoli Daniela
Published: August 2017

This article focuses on interorganizational networks in an attempt to contribute to the research on network endurance. Specifically, we will focus on service delivery networks created to endure, and explore the impact on network endurance of some key variables, such as the configuration of the modes of network governance, the formalization of coordination mechanisms and the concentration of managerial skills in the network manager. Our results show that a Network Administrative Organization alone is not sufficient to enable network endurance. Having skilful network managers who can activate formalized coordination mechanisms is also important. Hence, skilful network managers seem to be pivotal for long‐term public networks, thanks to their ability to link network structures to network mechanisms and bring about network endurance.
Cost of asthma in children: A nationwide, population‐based, cost‐of‐illness study
Authors: Ferreira de Magalhães Manuel , Amaral Rita , Pereira Ana M. , Sá‐Sousa Ana , Azevedo Inês , Azevedo Luís F. , Fonseca João A.
Published: August 2017

Background

Childhood asthma is very prevalent and costs can be high, especially in severe disease. This study aimed to estimate the cost of asthma in Portuguese children and the variations by level of asthma control.

Methods

A nationwide, population‐ and prevalence‐based cost‐of‐illness study with a societal perspective was conducted. We measured direct and indirect costs using a bottom‐up approach and a human capital method, respectively, for 208 children (<18 years), from two national repositories. Generalized linear modelling for analysis of asthma costs’ determinants and sensitivity analysis to assess uncertainty were performed.

Results

The mean annualized asthma cost per child was €929.35 (95%CI, 809.65‐1061.11): €698.65 (95%CI, 600.88‐798.27) for direct costs and €230.70 (95%CI, 197.36‐263.81) for indirect costs. Extrapolations for the Portuguese children amounted to €161 410 007.61 (95%CI, 140 620 769.55‐184 293 968.55) for total costs. Direct costs represent 75.2% with the costliest domain (51.1% of total costs) being the healthcare service use: 20.7% for scheduled medical visits and 30.4% for acute asthma care—non‐scheduled medical visits (7.9%, €12 766 203.20), emergency department visits (11.7%, €18 932 464.80) and hospitalizations (10.8%, €17 406 946.00).

Children with partly controlled and uncontrolled asthma had higher mean costs per year (adjusted coefficients: 1.46 [95%CI, 1.12‐1.90] and 2.25 [95%CI, 1.56‐3.24], respectively).

Conclusions

Costs of childhood asthma are high (0.9% of the healthcare expenditures in Portugal). Direct costs represented three‐fourth of total costs, mainly related to the use of healthcare services for acute asthma care. Policies and interventions to improve asthma control and reduce acute use of healthcare services have the potential to reduce asthma costs.
Vitamin D intake during the first 4 years and onset of asthma by age 5: A nested case‐control study
Authors: Nwaru Bright I. , Hadkhale Kishor , Hämäläinen Niina , Takkinen Hanna‐Mari , Ahonen Suvi , Ilonen Jorma , Toppari Jorma , Niemelä Onni , Haapala Anna‐Maija , Veijola Riitta , Knip Mikael , Virtanen Suvi M.
Published: August 2017

Background

Early‐life vitamin D intake has been linked to asthma risk in childhood, but the role of longitudinal vitamin D exposure has not been previously evaluated. We investigated the association between vitamin D intake during the first 4 years of life and asthma risk by age 5.

Methods

Within a Finnish population‐based birth cohort, 182 incident asthma cases were matched to 728 controls on sex, genetic risk for type 1 diabetes, delivery hospital, and time of birth. Vitamin D intake was assessed by age‐specific 3 day food records. Parents completed a validated version of the International Study of Asthma and Allergies in Childhood questionnaire at 5 years.

Results

At 3 months, supplements were the main source of vitamin D intake; intake from foods increased from 3 months on, mainly from fortified milk products. Vitamin D intake at each specific age was associated with an increased risk of any asthma, atopic, and non‐atopic asthma, but only intake at 1 and 2 years was statistically significantly associated with asthma. Longitudinal vitamin D intake was associated with an increased risk of asthma (OR 1.24; 95%CI 1.00‐1.53).

Conclusions

Increased vitamin D intake in childhood, particularly intake at 1 and 2 years of age, may increase risk of childhood asthma. This might reflect a true effect or residual confounding by lifestyle or environmental factors. Repeated assessment of vitamin D intake allowed evaluation of the longitudinal and age‐dependent impact of vitamin D on the risk of asthma. Further longitudinal studies are required to confirm or question these findings.
Infant spinal anesthesia: Do girls need a larger dose of local anesthetic?
Authors: Frawley Geoff , Huque Md Hamidul
Published: August 2017

Background

Gender differences in absorption, distribution, and metabolism of a number of anesthetic agents have been identified in adults. Clinically, adult studies suggest women demonstrate slower onset of opioid analgesic effects, lower spinal and epidural dose requirements, and greater sensitivity to neuromuscular blocking agents. Sex‐related differences in the pharmacokinetics and pharmacodynamics of local anesthetics in neonates and infants, however, have not been well documented. As a result, it is not known whether modification of the dose of local anesthetic for awake spinal anesthesia in infants is required.

Aims

Our aim was to determine whether the ED50 and ED95 of local anesthetics used for infant spinal anesthesia are different between sexes.

Methods

This was a retrospective analysis of data previously collected during dose‐response studies of levobupivacaine and ropivacaine spinal anesthetics. The doses were reanalyzed using generalized linear regression analysis to determine whether there is a discernible difference in dose requirements between male and female infants.

Results

One hundred and twenty infant spinal anesthetics were reviewed. For levobupivacaine, the ED50 (95% CI) was 0.49 (0.33‐0.65) mg vs 0.69 (0.49‐0.88), whereas the ED95 (95% CI) was 1.07 (0.73‐1.41) vs 0.93 (0.64‐1.22) for girls and boys, respectively. For ropivacaine spinal anesthesia, the ED50 (95% CI) was 0.64 (0.35‐0.92) mg vs 0.30 (−0.32‐0.92), whereas the ED95 (95% CI) was 1.30 (0.73‐1.87) vs 1.66 (0.55‐2.76) for girls and boys, respectively.

Conclusion

There is no evidence that sex differences occur at the ED50 dose range or at the clinically relevant ED95 dose. Modification of spinal anesthetic dose is not required for infant girls.
Mapping quantitative trait loci associated with starch paste viscosity in rice (Oryza sativa L.) under different environmental conditions
Authors: Yao Xiaoyun , Wang Jiayu , Liu Jin , Zhang Jia , Ren Chunyuan , Ma Dianrong , Xu Hai , Xu Zhengjin
Published: August 2017

A recombinant inbred line (RIL) population consisting of 153 lines derived from a cross between indica ‘Zhongyouzao8’ and japonica ‘Toyonishiki’ rice was used to detect stable quantitative trait loci (QTL) for rapid visco analyser (RVA) characteristics under four environmental conditions. We identified 93 QTL for RVA profiles, and four pleiotropic regions harbouring stably expressed QTL were detected on chromosomes 2, 6, 7 and 11. These newly identified and stable QTL will facilitate further research into the genetic mechanism regulating RVA profiles. Amylose content (AC) was correlated with RVA traits. AC and RVA traits were unaffected by indica–japonica subspecies differentiation, suggesting that RVA profiles were mainly influenced by the Wx gene. The RIL population was divided into two subpopulations according to Wx genotypes. A total of 106 QTL associated with RVA profiles were detected in the subpopulations. These QTL differed from those detected in the whole population in terms of their genomic location, number, logarithm of odds values and amount of phenotypic variance explained. Using this strategy, we detected QTL with minor effects and eliminated false due to the Wx gene.
The potential of genomic‐assisted breeding to improve Fusarium head blight resistance in winter durum wheat
Authors: Miedaner Thomas , Sieber Alisa‐Naomi , Desaint Henry , Buerstmayr Hermann , Longin C. Friedrich H. , Würschum Tobias
Published: August 2017

Durum wheat is the most important tetraploid wheat mainly used for semolina and pasta production, but is notorious for its high susceptibility to Fusarium head blight (FHB). Our objectives were to identify and characterize quantitative trait loci (QTL) in winter durum and to evaluate the potential of genomic approaches for the improvement ofFHBresistance. Here, we employed an international panel of 170 winter and 14 spring durum lines, phenotyped forFusarium culmorumresistance at five environments. Heading date, plant height and meanFHBseverity showed significant genotypic variation with high heritabilities andFHBresistance was negatively correlated with both heading date and plant height. The dwarfing geneRht‐B1significantly affectedFHBresistance and the genome‐wide association scan identified eight additionalQTLaffectingFHBresistance, explaining between 1% and 14% of the genotypic variation. A genome‐wide prediction approach yielded only a slightly improved predictive ability compared to marker‐assisted selection based on the four strongestQTL. In conclusion,FHBresistance in durum wheat is a highly quantitative trait and in breeding programmes may best be tackled by classical high‐throughput recurrent phenotypic selection that can be assisted by genomic prediction if marker profiles are available.
White matter alterations associate with onset symptom dimension in obsessive–compulsive disorder
Authors: Bollettini Irene , Mazza Mario G. , Muzzarelli Laura , Dallaspezia Sara , Poletti Sara , Vai Benedetta , Smeraldi Enrico , Benedetti Francesco
Published: August 2017

Aim

The high heterogeneity of obsessive–compulsive disorder (OCD) is best described by a multidimensional model involving symptom dimensions. We aimed to investigate white matter alterations associated with OCD, focusing on the impact of long‐lasting effect of symptom dimensions assessed at onset of illness. Furthermore, we investigated white matter alterations associated with this disorder, controlling for the impact of medications and for the prevailing current symptom dimension.

Methods

We studied 58 patients affected by OCD and 58 age‐ and sex‐matched healthy controls. We divided patients according to symptom dimension at onset of illness, assessed with the five‐factor model. T‐tests were performed in order to investigate differences between subgroups. Similar analyses were performed considering the prevailing current symptom dimension. Analyses were conducted with tract‐based spatial statistics on diffusion tensor imaging.

Results

Doubt/checking and rituals/superstition symptom dimensions at onset and symmetry/perfectionism current symptom dimensions were characterized by significant alterations in diffusion tensor imaging measures. An association of white matter alterations and symmetry/perfectionism current dimension was found only when controlling for the effect of doubt/checking dimension at onset. Finally, results pointed out that the observed differences between patients and healthy controls were carried by the effect of previous and current medications.

Conclusion

Our findings evidenced that onset symptom dimensions are associated with enduring alterations of white matter microstructure. Onset symptom dimensions may reflect underlying endophenotypes. In addition, present results confirm the effect of medications on white matter in OCD, showing a large effect of current treatment on myelination.
Childhood cancer survivors: Anxieties felt after treatment and the need for continued support
Authors: Iwai Naoko , Shimada Akira , Iwai Atsushi , Yamaguchi Sonoe , Tsukahara Hirokazu , Oda Megumi
Published: August 2017

Background

Childhood cancer survivors (CCS) and their family members continue to live in fear even after treatment is concluded due to concerns about late effects and recurrences. The consequent long‐term psychological burden requires long‐term follow up suited to the anxieties and needs of CCS, hence the need for the present survey.

Methods

We conducted a questionnaire survey at medical facilities in the Chugoku and Shikoku regions of Japan with CCS who had survived for at least 5 years following treatment, and their family members.

Results

A total of 30 CCS (53%) and 27 CCS family members (47%) answered the questionnaires. The median age of the CCS and their family members (CCS parents) was 23 years and 51.5 years, respectively. The most common diagnosis was acute lymphoblastic leukemia (47%) and the median length of follow up after the conclusion of treatment was 11 years. The percentage of participants who responded that they knew about late effects was significantly lower among CCS than among CCS parents. Almost no significant difference was observed between CCS and CCS parents regarding anxieties at specific life stages. The main consultants for CCS and CCS parents were their family, but they sought opportunities for casual consultation for current worries outside the family.

Conclusions

It is necessary for medical facilities not only to provide medical support, but also to establish a place where they can provide centralized consultation for the anxieties of CCS and their parents.
Risks of Adverse Perinatal Outcomes after Repeat Terminations of Pregnancy by their Methods: a Nationwide Register‐based Cohort Study in Finland 1996–2013
Authors: KC S. , Gissler M. , Virtanen S. M. , Klemetti R.
Published: August 2017

Background

Repeat terminations of pregnancy (TOPs) are associated with an increased risk of adverse outcomes in the subsequent birth. The perinatal outcomes after repeat TOPs by their methods have not yet been properly studied. This study aimed to examine perinatal outcomes in subsequent pregnancy among the women with a singleton birth and a history of TOPs.

Methods

All the first‐time mothers (n = 419 879) with a singleton birth during 1996–2013 in Finland were identified from the Medical Birth Register and linked to the Abortion Register. Adjusted multivariable logistic regression analysis was used to estimate risks of adverse perinatal outcomes.

Results

The increased incidence of adverse perinatal outcomes was found with increasing number of surgical TOPs. After adjusting for confounders, the women with one surgical TOP had slightly increased but significant odds of 1.07 (95% CI 1.02, 1.13) for being small for gestational age compared with the women having no TOP. A significantly high risk for extremely preterm birth (OR 1.51, 95% CI 1.03, 2.23) was found among the women having had repeat surgical TOPs when compared to the women with no TOP. Non‐significant risks were found for adverse perinatal outcomes after women's repeat surgical TOPs than repeat medical TOPs.

Conclusion

Information regarding the consequences of repeat induced TOPs will be significant in sexual health education as well as counselling women after first termination.
Molecular aspects of uterine diseases in dogs
Authors: Hagman R
Published: August 2017

Contents

Uterine diseases are common in dogs, particularly in countries where elective spaying is not usually performed. The associated clinical illnesses may be of varying degree ranging from merely decreased fertility to a critical pyometra requiring intensive care to survive. The diagnosis of some uterine diseases is generally uncomplicated, such as in a classic pyometra presenting with enlarged, fluid‐filled uterus, purulent vaginal discharge and characteristic signs of illness or in other disorders associated with uterine enlargement. However, it can be more puzzling in diseases with normal uterine size and very mild or obscure clinical signs. It is important to recognize the uterine diseases early because of the risk of potentially life‐threatening complications such as sepsis developing if treatment is delayed in cases where bacterial infection is present. In breeding bitches, an early diagnosis, that is when the disease has not developed extensively, will increase the possibility of non‐surgical treatment options without increased risk and thereby also increasing chances of maintained fertility. Early diagnosis and treatment initiation are thus favourable for complete recovery, also in less severe uterine diseases and those without infection. Molecular markers are molecules in biological samples that can be measured for diagnostic purposes, outcome prediction, and for gaining more information about different physiological and pathological conditions. Examples of commonly evaluated markers include laboratory variables analysed in blood, urine, cytological or tissue biopsy samples. Regarding the genetic pre‐disposition for different uterine diseases in dogs, information is lacking. Recently, the global gene expression in uterine tissue in dogs has been investigated more closely, and newly developed technologies provide excellent opportunities for identifying molecular markers worth exploring further. The focus of this review article is to highlight findings on markers relevant for diagnosis, prediction of prognosis and treatment outcome in the most common uterine diseases in dogs.
Post‐crisis reforms in banking: Regulators at the interface between domestic and international governance
Authors: Quaglia Lucia , Spendzharova Aneta
Published: August 2017

Post‐crisis international standards have been agreed on in certain areas of banking regulation, namely capital, liquidity, and resolution, but not others, namely bank structure – why? We articulate a two‐step analytical framework that links the domestic and international levels of governance. In particular, we focus on the role of domestic regulators at the interface between the two levels. At the domestic level, regulators evaluate externalities and adjustment costs before engaging in cooperation at the international level. This analysis explains why regulators in the United States and the European Union act as pacesetters, foot‐draggers, or fence‐sitters in international standard setting; that is to say, why they promote, resist, or are neutral toward international financial standards. At the international level, we explain the outcome of international standard setting by considering the interaction of pacesetters and foot‐draggers.
Depositional Age of a Fossil Whale Bone from São Paulo Ridge, South Atlantic Ocean, Based on Os Isotope Stratigraphy of a Ferromanganese Crust
Authors: Nozaki Tatsuo , Takaya Yutaro , Toyofuku Takashi , Tokumaru Ayaka , Goto Kosuke T. , Chang Qing , Kimura Jun‐ichi , Kato Yasuhiro , Suzuki Katsuhiko , Augustin Adolpho Herbert , Kitazato Hiroshi
Published: August 2017

Whale carcasses (whale falls) deposited on the deep seafloor are associated with a distinctive biotic community. A fossil whale bone recovered from São Paulo Ridge, South Atlantic Ocean, during cruise YK13–04 Leg 1 of R/V Yokosuka was covered by a ferromanganese (Fe–Mn) crust approximately 9 mm thick. Here, we report an age constraint for this fossil bone on the basis of Os isotopic stratigraphy (187Os/188Os ratio) of the Fe–Mn crust. Major‐ and trace‐element compositions of the crust are similar to those of Fe–Mn crusts of predominantly hydrogenous origin. Rare earth element concentrations in samples of the crust, normalized with respect to Post‐Archean average Australian Shale, exhibit flat patterns with positive Ce and negative Y anomalies. These results indicate that the Fe–Mn crust consists predominantly of hydrogenous components and that it preserves the Os isotope composition of seawater at the time of its deposition. 187Os/188Os ratios of three Fe–Mn crust samples increased from 0.904 to 1.068 in ascending stratigraphic order. The value of 1.068 from the surface slice (0–3 mm depth in the crust) was identical to that of present‐day seawater within error (~1.06). The value of 0.904 from the basal slice (6–9 mm) equaled seawater values from ca. 4–5 Ma. Because it is unknown how long the bone lay on the seafloor before the Fe–Mn crust was deposited, the Os stratigraphic age of ca. 5 Ma is a minimum age of the fossil. This is the first application, to our knowledge, of marine Os isotope stratigraphy for determining the age of a fossil whale bone. Such data may offer valuable insights into the evolution of the whale‐fall biotic community.
Another Look at Distance-Weighted Discrimination
Authors: Wang Boxiang , Zou Hui
Published: August 2017

Distance-weighted discrimination (DWD) is a modern margin-based classifier with an interesting geometric motivation. It was proposed as a competitor to the support vector machine (SVM). Despite many recent references on DWD, DWD is far less popular than the SVM, mainly because of computational and theoretical reasons. We greatly advance the current DWD methodology and its learning theory. We propose a novel thrifty algorithm for solving standard DWD and generalized DWD, and our algorithm can be several hundred times faster than the existing state of the art algorithm based on second-order cone programming. In addition, we exploit the new algorithm to design an efficient scheme to tune generalized DWD. Furthermore, we formulate a natural kernel DWD approach in a reproducing kernel Hilbert space and then establish the Bayes risk consistency of the kernel DWD by using a universal kernel such as the Gaussian kernel. This result solves an open theoretical problem in the DWD literature. A comparison study on 16 benchmark data sets shows that data-driven generalized DWD consistently delivers higher classification accuracy with less computation time than the SVM.
Effect on gene expression of three allelic variants in GATA motifs of ABO, RHD, and RHCE regulatory elements
Authors: Fennell Katie , Hoffman Roser , Yoshida Ken , Iwamoto Sadahiko , Govender Lavendri , Vather Kuben , Sookraj Ashika , Jentsch Ute , Pambrun Chantale , McAuley Catherine , Keller Margaret A. , Ochoa‐Garay Gorka
Published: August 2017

BACKGROUND

Only a few genetic variants have been reported in regulatory elements of blood group genes. Most of them affect GATA motifs, binding sites for the GATA‐1 transcription factor.

STUDY DESIGN AND METHODS

Samples from two patients and one donor with unusual or discrepant serology for ABO, RhD, and RhCE antigens were analyzed by DNA sequencing. Analyzed regions included the coding sequence and portions of regulatory elements. The effect of some variants on gene expression was evaluated in reporter gene assays.

RESULTS

Three new alleles were identified. Their key variants are located in the ABO Intron 1 enhancer, the RHD proximal promoter, and the RHCE proximal promoter. IVS1 + 5859A was found in an African American patient with a group O forward type and a group B reverse type. 5′UTR‐115C was the only RHD variant sequence found in a mixed‐race black and Caucasian prenatal patient showing mixed‐field agglutination with anti‐D. 5′UTR‐83T was found in several black donors and patients in the context of the genetically related RHCE*ceBI and RHCE*ceSM alleles. Reporter assays of promoter constructs including 5′UTR‐115C or 5′UTR‐83T showed a significant reduction in RH gene expression.

CONCLUSION

Three new alleles in the ABO, RHD, and RHCE genes consist of single‐nucleotide changes within GATA motifs, emphasizing the key role of GATA transcription factors in the expression of blood group genes.
The impact of intergenerational transfers on wealth inequality in Japan and the United States
Authors: Niimi Yoko , Horioka Charles Yuji
Published: August 2017

Our paper sheds light on the implications of intergenerational transfers for wealth inequality by examining whether or not individuals who receive intergenerational transfers from their parents are more likely to leave bequests to their children than those who do not using microdata for Japan and the United States. The estimation results show that the receipt of intergenerational transfers from parents and/or parents‐in‐law increases the likelihood of individuals leaving bequests to their children in both Japan and the United States, which in turn is likely to contribute to the persistence or widening of wealth disparities. However, such a tendency is found to be stronger among less better‐off households in both countries, and this may help alleviate the disequalising effect of intergenerational transfers on the distribution of wealth, at least to some extent.
Infection with a novel derogenid trematode in a Flap‐necked chameleon (Chamaeleo dilepis)
Authors: Collicutt Nancy B. , Stacy Nicole I. , Walden Heather Stockdale , Childress April , Dill Jennifer , Anderson Marita , Wellehan James F.X.
Published: August 2017

A 2‐year‐old female Flap‐necked chameleon (Chamaeleo dilepis) was presented with a history of anorexia. On physical examination, three 11×4×2 mm, light tan‐pink, raised, gelatinous, freely movable, poorly demarcated, raised nodules were identified within the oral cavity. An impression smear contained multiple, light blue to green structures exhibiting an 18×35 μm, elliptical‐shaped anterior portion and a single 1×150 μm filament with a tapered end. Initial differential etiologies included trematode ova, flagellate protozoa, fungal sporangia, plant material, and sperm. Fungal culture yielded no growth. The structures described above did not stain with Gomori methenamine silver stain. A calcofluor white stain yielded positive fluorescence. The DNA was extracted from the impression smears and pan‐trematode PCR was performed; products were directly sequenced and phylogenetic analysis revealed maximum similarity with a digenean trematode in the family Derogenidae that was distinct from other trematodes for which a reference sequence was available. To our knowledge, this is the first description of cytologic features of trematode ova from an oral lesion in a chameleon.
Pullout strength of 2.0 mm cancellous and cortical screws in synthetic bone
Authors: Moser John E. , Kunkel Kevin A. R. , Gerard Patrick D.
Published: August 2017

Objective

To determine whether 2.0 mm cancellous screws are superior to 2.0 mm cortical screws when inserted into cancellous and bicortical bone.

Study design

Biomechanical study.

Methods

The 2.0 mm cancellous screws and 2.0 mm cortical screws were inserted according to the recommended guidelines in synthetic cancellous and bicortical blocks. Fifteen screw‐block constructs per group were tested to failure in axial pullout. Axial pullout strength and yield strength were calculated. Data were analyzed using a one‐way ANOVA.

Results

The 2.0 mm cortical screws achieved lower axial pullout strength than 2.0 mm cancellous screws in cancellous blocks. The 2.0 mm cortical screws achieved greater pullout strength than 2.0 mm cancellous screws in bicortical blocks.

Conclusion

The 2.0 mm cancellous screws may offer a biomechanical advantage in bone with thin cortices (<1 mm thick), whereas 2.0 mm cortical screws may be preferred in cortical bone with cortices measuring at least 1 mm in thickness.
Cardiac action potential repolarization revisited: early repolarization shows all‐or‐none behaviour
Authors: Trenor Beatriz , Cardona Karen , Saiz Javier , Noble Denis , Giles Wayne
Published: August 2017

In healthy mammalian hearts the action potential (AP) waveform initiates and modulates each contraction, or heartbeat. As a result, AP height and duration are key physiological variables. In addition, rate‐dependent changes in ventricular AP duration (APD), and variations in APD at a fixed heart rate are both reliable biomarkers of electrophysiological stability. Present guidelines for the likelihood that candidate drugs will increase arrhythmias rely on small changes in APD and Q–T intervals as criteria for safety pharmacology decisions. However, both of these measurements correspond to the final repolarization of the AP. Emerging clinical evidence draws attention to the early repolarization phase of the action potential (and the J‐wave of the ECG) as an additional important biomarker for arrhythmogenesis. Here we provide a mechanistic background to this early repolarization syndrome by summarizing the evidence that both the initial depolarization and repolarization phases of the cardiac action potential can exhibit distinct time‐ and voltage‐dependent thresholds, and also demonstrating that both can show regenerative all‐or‐none behaviour. An important consequence of this is that not all of the dynamics of action potential repolarization in human ventricle can be captured by data from single myocytes when these results are expressed as ‘repolarization reserve’. For example, the complex pattern of cell‐to‐cell current flow that is responsible for AP conduction (propagation) within the mammalian myocardium can change APD and the Q–T interval of the electrocardiogram alter APD stability, and modulate responsiveness to pharmacological agents (such as Class III anti‐arrhythmic drugs).

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Chronic morphine reduces the readily releasable pool of GABA, a presynaptic mechanism of opioid tolerance
Authors: Wilson‐Poe Adrianne R. , Jeong Hyo‐Jin , Vaughan Christopher W.
Published: August 2017

Key points

Chronic treatment with opioids, such as morphine, leads to analgesic tolerance.

While postsynaptic opioid tolerance is well documented, the involvement of presynaptic mechanisms remains unclear.

We show that chronic morphine reduces the ability of periaqueductal grey (PAG) neurons to maintain GABAergic transmission.

This depression of GABAergic transmission was due to a reduction in the effective size of the readily releasable pool.

This also led to a reduction in opioid presynaptic inhibition; these presynaptic adaptations need to be considered in the development of strategies to reduce opioid tolerance.

The midbrain periaqueductal grey (PAG) plays a critical role in tolerance to the analgesic actions of opioids such as morphine. While numerous studies have identified the postsynaptic adaptations induced by chronic morphine treatment in this and other brain regions, the presence of presynaptic adaptations remains uncertain. We examined GABAergic synaptic transmission within rat PAG brain slices from animals which underwent a low dose morphine treatment protocol which produces tolerance, but not withdrawal. Evoked GABAergic IPSCs (inhibitory postsynaptic currents) were less in morphine compared to control saline treated animals. Postsynaptic GABAA receptor mediated currents and desensitization, presynaptic release probability (Pr), and inhibition by endogenous neurotransmitters were similar in morphine and saline treated animals. By contrast, the effective size of the readily releasable pool (RRP) was smaller in morphine treated animals. While the μ‐opioid agonist DAMGO produced a reduction in Pr and RRP size in saline treated animals, it only reduced Pr in morphine treated animals. Consequently, DAMGO‐induced inhibition of evoked IPSCs during short burst stimulation was less in morphine, compared to saline treated animals. These results indicate that low dose chronic morphine treatment reduces presynaptic μ‐opioid inhibition by reducing the size of the pool of vesicles available for action potential dependent release. This novel presynaptic adaptation may provide important insights into the development of efficacious pain therapies that can circumvent the development of opioid tolerance.
Pulmonary artery wave propagation and reservoir function in conscious man: impact of pulmonary vascular disease, respiration and dynamic stress tests
Authors: Su Junjing , Manisty Charlotte , Simonsen Ulf , Howard Luke S. , Parker Kim H. , Hughes Alun D.
Published: August 2017

Key points

Wave travel plays an important role in cardiovascular physiology. However, many aspects of pulmonary arterial wave behaviour remain unclear.

Wave intensity and reservoir‐excess pressure analyses were applied in the pulmonary artery in subjects with and without pulmonary hypertension during spontaneous respiration and dynamic stress tests.

Arterial wave energy decreased during expiration and Valsalva manoeuvre due to decreased ventricular preload. Wave energy also decreased during handgrip exercise due to increased heart rate.

In pulmonary hypertension patients, the asymptotic pressure at which the microvascular flow ceases, the reservoir pressure related to arterial compliance and the excess pressure caused by waves increased. The reservoir and excess pressures decreased during Valsalva manoeuvre but remained unchanged during handgrip exercise.

This study provides insights into the influence of pulmonary vascular disease, spontaneous respiration and dynamic stress tests on pulmonary artery wave propagation and reservoir function.

Detailed haemodynamic analysis may provide novel insights into the pulmonary circulation. Therefore, wave intensity and reservoir‐excess pressure analyses were applied in the pulmonary artery to characterize changes in wave propagation and reservoir function during spontaneous respiration and dynamic stress tests. Right heart catheterization was performed using a pressure and Doppler flow sensor tipped guidewire to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery in control subjects and patients with pulmonary arterial hypertension (PAH) at rest. In controls, recordings were also obtained during Valsalva manoeuvre and handgrip exercise. The asymptotic pressure at which the flow through the microcirculation ceases, the reservoir pressure related to arterial compliance and the excess pressure caused by arterial waves increased in PAH patients compared to controls. The systolic and diastolic rate constants also increased, while the diastolic time constant decreased. The forward compression wave energy decreased by ∼8% in controls and ∼6% in PAH patients during expiration compared to inspiration, while the wave speed remained unchanged throughout the respiratory cycle. Wave energy decreased during Valsalva manoeuvre (by ∼45%) and handgrip exercise (by ∼27%) with unaffected wave speed. Moreover, the reservoir and excess pressures decreased during Valsalva manoeuvre but remained unaltered during handgrip exercise. In conclusion, reservoir‐excess pressure analysis applied to the pulmonary artery revealed distinctive differences between controls and PAH patients. Variations in the ventricular preload and afterload influence pulmonary arterial wave propagation as demonstrated by changes in wave energy during spontaneous respiration and dynamic stress tests.
Engineering defined membrane‐embedded elements of AMPA receptor induces opposing gating modulation by cornichon 3 and stargazin
Authors: Hawken Natalie M. , Zaika Elena I. , Nakagawa Terunaga
Published: August 2017

Key points

The AMPA‐type ionotropic glutamate receptors (AMPARs) mediate the majority of excitatory synaptic transmission and their function impacts learning, cognition and behaviour.

The gating of AMPARs occurs in milliseconds, precisely controlled by a variety of auxiliary subunits that are expressed differentially in the brain, but the difference in mechanisms underlying AMPAR gating modulation by auxiliary subunits remains elusive and is investigated.

The elements of the AMPAR that are functionally recruited by auxiliary subunits, stargazin and cornichon 3, are located not only in the extracellular domains but also in the lipid‐accessible surface of the AMPAR.

We reveal that the two auxiliary subunits require a shared surface on the transmembrane domain of the AMPAR for their function, but the gating is influenced by this surface in opposing directions for each auxiliary subunit.

Our results provide new insights into the mechanistic difference of AMPAR modulation by auxiliary subunits and a conceptual framework for functional engineering of the complex.

During excitatory synaptic transmission, various structurally unrelated transmembrane auxiliary subunits control the function of AMPA receptors (AMPARs), but the underlying mechanisms remain unclear. We identified lipid‐exposed residues in the transmembrane domain (TMD) of the GluA2 subunit of AMPARs that are critical for the function of AMPAR auxiliary subunits, stargazin (Stg) and cornichon 3 (CNIH3). These residues are essential for stabilizing the AMPAR–CNIH3 complex in detergents and overlap with the contacts made between GluA2 TMD and Stg in the cryoEM structures. Mutating these residues had opposite effects on gating modulation and complex stability when Stg‐ and CNIH3‐bound AMPARs were compared. Specifically, in detergent the GluA2‐A793F formed an unstable complex with CNIIH3 but in the membrane the GluA2‐A793F–CNIH3 complex expressed a gain of function. In contrast, the GluA2‐A793F–Stg complex was stable, but had diminished gating modulation. GluA2‐C528L destabilized the AMPAR–CNIH3 complex but stabilized the AMPAR–Stg complex, with overall loss of function in gating modulation. Furthermore, loss‐of‐function mutations in this TMD region cancelled the effects of a gain‐of‐function Stg carrying mutation in its extracellular loop, demonstrating that both the extracellular and the TMD elements contribute independently to gating modulation. The elements of AMPAR functionally recruited by auxiliary subunits are, therefore, located not only in the extracellular domains but also in the lipid accessible surface of the AMPAR. The TMD surface we defined is a potential target for auxiliary subunit‐specific compounds, because engineering of this hotspot induces opposing functional outcomes by Stg and CNIH3. The collection of mutant‐phenotype mapping provides a framework for engineering AMPAR gating using auxiliary subunits.
Errors in Calculating Anterior–Posterior Tibial Contact Locations in Total Knee Arthroplasty Using Three-Dimensional Model to Two-Dimensional Image Registration in Radiographs: An In Vitro Study of Two Methods
Authors: Ross Derrick S. , Howell Stephen M. , Hull Maury L.
Published: August 2017

Knowledge of anterior–posterior (A-P) tibial contact locations provides an objective assessment of the relative motion of the tibia on the femur following total knee arthroplasty (TKA), which can be used to compare the effects of different components, surgical techniques, and alignment goals on knee function in vivo. Both the lowest point method and the penetration method have been used to calculate A-P tibial contact locations using three-dimensional (3D) model to two-dimensional (2D) image registration. The primary objective of this study was to quantify errors in calculating the A-P tibial contact location using the lowest point and penetration methods because the errors in calculating the A-P tibial contact locations using these two methods are unknown. The A-P tibial contact locations were calculated with the two methods and simultaneously measured with a tibial force sensor in ten fresh-frozen cadaveric knee specimens with a TKA. Single-plane radiographs of the knee specimens were acquired at 0 deg, 30 deg, 60 deg, and 90 deg of flexion in neutrally, internally, and externally rotated orientations. While the radiographs were exposed, reference A-P tibial contact locations were simultaneously collected using the tibial force sensor to be compared to the calculated A-P tibial contact locations. The overall root-mean-squared-errors (RMSEs) in the A-P tibial contact location calculated with the lowest point method, the penetration method with penetration, and penetration method without penetration were 5.5 mm, 3.6 mm, and 8.9 mm, respectively. The overall RMSE was lowest for the penetration method with penetration, making it the superior method for calculating A-P tibial contact locations.
Using X-Ray Diffraction and Finite Element Method to Analyze Residual Stress of Tube-to-Tubesheet Welded Joints in a Shell and Tube Heat Exchanger
Authors: Wan Yu , Jiang Wenchun , Luo Yun
Published: August 2017

A lot of failures have been generated in the tube-to-tubesheet joints of a shell and tube heat exchanger, which are greatly affected by the weld residual stresses. In order to ensure the structure integrity, it is very important to predict and decrease the residual stress in the joint between tube and tubesheet. In this paper, a combination of X-ray diffraction and finite element method (FEM) was used to analysis the residual stress distribution in the tube-to-tubesheet joints. The formation mechanism of residual stress before and after cosmetic welding was explicated. The effects of heat input and welding sequence on residual stresses were studied. The results show that the large tensile residual stresses which are in excess of yield strength, are generated in the tube-to-tubesheet joints. The residual stresses at the bottom surface and the edge of the tubesheet are relatively small even become compressive. The formation of the weld residual stress is mainly induced by the cosmetic welding rather than the back welding. The residual stresses increase as the heat input increases. The duplex welding method is recommended to decrease the residual stress.
Design of Directional Probes for High-Frequency Turbine Measurements
Authors: Liu Z. , Paniagua G.
Published: August 2017

Aerodynamic probes are prevalent in turbomachinery research and gas turbine monitoring. Regrettably, this measurement technique experiences limitations not only in the transonic range but also in the high frequency range. Calibrated numerical tools offer an alternative procedure in the design of suitable instrumentation for turbine applications. First, two different probe geometries, oval and trapezoidal shapes, were characterized at different incidence angles. In particular, the pressure recovery, angle sensitivity, and induced vortex shedding unsteadiness at several yaw angles were evaluated. The studies were performed over a wide range of Mach numbers from subsonic to the transonic regime. The vortex shedding of the probe was also carefully analyzed. In a second evaluation, we selected the oval probe geometry including the line-cavity effects into the pressure tappings. The resonance frequency of line-cavity system was evaluated and compared with analytical calculations, as well as with the detailed analysis of Bergh and Tijdeman. The comparison of the pressure tapping readings with the actual input signal allowed the identification of the transfer functions, as well as the physical mechanisms that should be corrected during the measurements. Finally, three-dimensional (3D) unsteady evaluations were implemented to compute the blockage effects, as well as the final frequency attenuation experienced by the piezo-resistive sensors. All numerical analyses were performed using unsteady Reynolds-averaged Navier–Stokes (URANS) models.
Optimal Structural Design of a Heat Sink With Laminar Single-Phase Flow Using Computational Fluid Dynamics-Based Multi-Objective Genetic Algorithm
Authors: Ge Ya , Shan Feng , Liu Zhichun , Liu Wei
Published: August 2017

This paper proposes a general method combining evolutionary algorithm and decision-making technique to optimize the structure of a minichannel heat sink (MCHS). Two conflicting objectives, the thermal resistance θ and the pumping power P, are simultaneously considered to assess the performance of the MCHS. In order to achieve the ultimate optimal design, multi-objective genetic algorithm is employed to obtain the nondominated solutions (Pareto solutions), while technique for order preference by similarity to an ideal solution (TOPSIS) is employed to determine which is the best compromise solution. Meanwhile, both the material cost and volumetric flow rate are fixed where this nonlinear problem is solved by applying the penalty function. The results show that θ of Pareto solutions varies from 0.03707 K W−1 to 0.10742 K W−1, while P varies from 0.00307 W to 0.05388 W, respectively. After the TOPSIS selection, it is found that P is significantly reduced without increasing too much θ. As a result, θ and P of the optimal MCHS determined by TOPSIS are 35.82% and 52.55% lower than initial one, respectively.