bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary fibrolysis in a patient with idiopathic pulmonary fibrosis: improvement of clinical and radiological pattern after treatment with pirfenidone
Authors: Varone Francesco , Mastrobattista Annelisa , Franchi Paola , Viglietta Luca , Poletti Venerino , Tomassetti Sara , Dubini Alessandra , Tagliaboschi Linda , Calandriello Lucio , Farchione Alessandra , Larici Anna Rita
Published: June 2016

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia associated with the histologic and/or radiologic pattern of usual interstitial pneumonia (UIP). Nowadays, the high‐resolution computed tomography pattern of “definite UIP” is enough to define a diagnosis of UIP without histological proof. This is pivotal especially in elderly patients with comorbidities. Early recognition of IPF is relevant for its prognostic implication. Some pharmacological strategies have been proposing novel molecules that tend to slow lung function decline, even though without healing fibrosis. We report a case of ex‐heavy smoker male with IPF showing clinical and radiological improvement after 11 months of treatment with Pirfenidone. The definite diagnosis was challenging and it was reached by a multidisciplinary approach.
Bilingual children's long‐term outcomes in English as a second language: language environment factors shape individual differences in catching up with monolinguals
Authors: Paradis Johanne , Jia Ruiting
Published: June 2016

Bilingual children experience more variation in their language environment than monolingual children and this impacts their rate of language development with respect to monolinguals. How long it takes for bilingual children learning English as a second language (L2) to display similar abilities to monolingual age‐peers has been estimated to be 4–6 years, but conflicting findings suggest that even 6 years in school is not enough. Most studies on long‐term L2 development have focused on just one linguistic sub‐domain, vocabulary, and have not included multiple individual difference factors. For the present study, Chinese first language‐English L2 children were given standardized measures of vocabulary, grammar and global comprehension every year from 4 ½ to 6 ½ years of English in school (ages 8½ to 10½); language environment factors were obtained through an extensive parent questionnaire. Children converged on monolingual norms differentially according to the test, with the majority of children reaching monolingual levels of performance on the majority of tests by 5 ½ years of English exposure. Individual differences in outcomes were predicted by length of English exposure, mother's education, mother's English fluency, child's use of English in the home, richness/quality of the English input outside school and age of arrival in Canada. In sum, the timeframe for bilinguals to catch up to monolinguals depends on linguistic sub‐domain, task difficulty and on individual children's language environment, making 4–6 years an approximate estimate only. This study also shows that language environment factors shape not only early‐stage but also late‐stage bilingual development.
Part‐based representations of the body in early childhood: evidence from perceived distortions of tactile space across limb boundaries
Authors: Le Cornu Knight Frances , Cowie Dorothy , Bremner Andrew J.
Published: June 2016

Studies show that touch in adults is referenced to a representation of the body that is structured topologically according to body parts; the perceived distance between two stimuli crossing over a body part boundary is elongated relative to the perceived distance between two stimuli presented within one body part category. Here we investigate this influence of body parts on tactile space perception in children of 5, 6 and 7 years of age. We presented children with pairs of tactile stimuli on the left hand/arm, either within the hand, within the forearm, or over the wrist. With their eyes closed children were asked to adjust the distance between the thumb and forefinger of their right hand to represent the felt distance between the two tactile stimuli. Like adults, the children perceived the distance between two stimuli that cross the body part boundary to be further apart than those that were presented within the hand or arm. They also perceive tactile distance to be greater on the hand than the arm which is the first observation of Weber's illusion in young children. We propose that a topological mode of body representation is particularly advantageous during early life given that body part categories remain constant while the metric proportions of the body change substantially as the child grows.
Aberrant topologies and reconfiguration pattern of functional brain network in children with second language reading impairment
Authors: Liu Lanfang , Li Hehui , Zhang Manli , Wang Zhengke , Wei Na , Liu Li , Meng Xiangzhi , Ding Guosheng
Published: June 2016

Prior work has extensively studied neural deficits in children with reading impairment (RI) in their native language but has rarely examined those of RI children in their second language (L2). A recent study revealed that the function of the local brain regions was disrupted in children with RI in L2, but it is not clear whether the disruption also occurs at a large‐scale brain network level. Using fMRI and graph theoretical analysis, we explored the topology of the whole‐brain functional network during a phonological rhyming task and network reconfigurations across task and short resting phases in Chinese children with English reading impairment versus age‐matched typically developing (TD) children. We found that, when completing the phonological task, the RI group exhibited higher local network efficiency and network modularity compared with the TD group. When switching between the phonological task and the short resting phase, the RI group showed difficulty with network reconfiguration, as reflected in fewer changes in the local efficiency and modularity properties and less rearrangement of the modular communities. These findings were reproducible after controlling for the effects of in‐scanner accuracy, participant gender, and L1 reading performance. The results from the whole‐brain network analyses were largely replicated in the task‐activated network. These findings provide preliminary evidence supporting that RI in L2 is associated with not only abnormal functional network organization but also poor flexibility of the neural system in responding to changing cognitive demands.
Pubertal development shapes perception of complex facial expressions
Authors: Motta‐Mena Natalie V. , Scherf K. Suzanne
Published: June 2016

We previously hypothesized that pubertal development shapes the emergence of new components of face processing (Scherf et al., 2012; Garcia & Scherf, 2015). Here, we evaluate this hypothesis by investigating emerging perceptual sensitivity to complex versus basic facial expressions across pubertal development. We tested pre‐pubescent children (6–8 years), age‐ and sex‐matched adolescents in early and later stages of pubertal development (11–14 years), and sexually mature adults (18–24 years). Using a perceptual staircase procedure, participants made visual discriminations of both socially complex expressions (sexual interest, contempt) that are arguably relevant to emerging peer‐oriented relationships of adolescence, and basic (happy, anger) expressions that are important even in early infancy. Only sensitivity to detect complex expressions improved as a function of pubertal development. The ability to perceive these expressions is adult‐like by late puberty when adolescents become sexually mature. This pattern of results provides the first evidence that pubertal development specifically influences emerging affective components of face perception in adolescence.
Termite cohabitation: the relative effect of biotic and abiotic factors on mound biodiversity
Authors: MARINS ALESSANDRA , COSTA DIOGO , RUSSO LAURA , CAMPBELL COLIN , DESOUZA OG , BJØRNSTAD OTTAR N. , SHEA KATRIONA
Published: June 2016

1. Termites are important ecosystem engineers that improve primary productivity in trees and animal diversity outside their mounds. However, their ecological relationship with the species nesting inside their mounds is poorly understood.

2. The presence of termite cohabitant colonies inside 145Cornitermes cumulansmounds of known size and location was recorded. Using network‐theoretical methods in conjunction with a suite of statistical analyses, the relative influence of biotic and abiotic drivers of termite within‐mound diversity on the composition and species richness of the termite community was investigated, specifically builder presence and physical aspects of the mound.

3. We found that richness inside the mound increases with mound size, and the species similarity between mounds decreases with distance. The physical attributes (abiotic drivers) of termite mounds (size and relative distance to other mounds) are the strongest predictors of termite species richness and composition. The biotic driver (presence of a builder colony) has an important, though smaller, negative effect on within‐mound termite species richness.

4. The findings suggest that the termites' physical manipulation of their environment is an important driver of within‐mound community diversity. More generally, the approach taken here, using a combination of statistical and network‐theoretical methods, can be used to determine the relative importance of abiotic and biotic drivers of diversity in a wide range of communities of interacting species.
Direct finance in the Dutch Golden Age†
Authors: Gelderblom Oscar , Jonker Joost , Kool Clemens
Published: June 2016

This article analyses private credit operations in Amsterdam in the seventeenth century to explain the absence of deposit banks. The financial system was highly segmented and a combination of declining business margins and narrow interest rate spreads cut the scope for deposit taking. Moreover, merchants had easy access to credit in the form of short‐term loans which could be easily rolled over, or replaced at will. This technique worked well because a market developed providing key functions to control risk and price loans accordingly.
First evidence of Wolbachia infection in populations of grasshopper Podisma sapporensis (Orthoptera: Acrididae)
Authors: Bugrov Alexander G. , Ilinsky Yury Yu. , Strunov Anton , Zhukova Mariya , Kiseleva Elena , Akimoto Shin‐ichi , Tatsuta Haruki
Published: June 2016

The brachypterous grasshopper Podisma sapporensis (Orthoptera: Acrididae) is distributed throughout the Sakhalin, Kunashir and Hokkaido Islands. Karyotypes of this species consist of two major chromosomal races with different sex chromosome systems, XO/XX and XY/XX. Molecular phylogeographic analysis of the chromosome races and subraces confirms the genetic divergence of the races and subraces in P. sapporensis. Here we first report that P. sapporensis is infected with Wolbachia consisting of three variants on wsp locus, while gatB locus was monomorphic. Furthermore, observation of cell tissue of P. sapporensis using electron microscopy confirmed the infection of Wolbachia that was inferred from polymerase chain reaction and revealed the distribution of the bacteria in the head, thorax and abdomen of P. sapporensis embryos. Our finding may shed new light on Wolbachia as a possible agent causing hybrid dysfunction resulting from experimental crosses between chromosome races or subraces of P. sapporensis.
Rapid evolution of photoperiodic response in a recently introduced insect Ophraella communa along geographic gradients
Authors: Tanaka Koichi , Murata Kouhei
Published: June 2016

The introduced beetle Ophraella communa was first found in 1996 in Japan and has rapidly expanded its distribution to include regions that encompass a wide range of latitude and altitude and are dominated by different host‐plants. In this study, we investigated geographic variation in its photoperiodic response for the induction of reproductive diapause, with which the beetle adjusts its life cycle to local climate and host‐plant phenology. The beetle lines were collected from 18 sites in Japan. The diapause incidence under a photoperiodic condition of 13 h light : 11 h dark (LD 13:11) and the critical day length differed among the beetle lines. Analysis with the generalized linear model showed that latitude, altitude and host‐plant species (Ambrosia artemisiifolia vs. Ambrosia trifida) had significant effects on diapause incidence under LD 13:11. These results suggest that the O. communa populations have rapidly adapted to local environmental conditions after their colonization. However, the photoperiodic response of the O. communa population in Tomakomai, the northernmost part of its distribution range in Japan, deviated significantly from the general trend. We suggest that this deviation is attributed to either: (i) that this beetle has colonized Tomakomai more recently compared to the other sites; or (ii) that the Tomakomai population has adapted to local environments in a different way from other populations.
Constitutional Pluralism Revisited
Authors: Walker Neil
Published: June 2016

This essay revisits the theory of constitutional pluralism. This theory was first developed in the EU context as a way of understanding and defending the absence of a broadly agreed source of final authority in the relationship between national and supranational (EU) legal systems and their respective appellate courts in the context of the significant increase in supranational jurisdiction around the time of the Maastricht Treaty 25 years ago. The essay argues that the theory of constitutional pluralism remains relevant today, in particular offering better explanatory and justificatory accounts of the EU than any of the singularist (or monist), holist or federalist alternatives. Its continuing relevance, however, depends on a more explicit focus on the political underpinnings of the legal and judicial dimensions of constitutional pluralism than has typically been the case in the literature, and on more detailed consideration of the preconditions, forms and limits of constitutional initiative in the contemporary phase of unprecedented challenge to the legitimacy of the EU.
Another Look at Constitutional Pluralism in the European Union
Authors: Baquero Cruz Julio
Published: June 2016

Constitutional pluralism is a theory, or movement, or idea, for some perhaps even an ideal, about the relationship between the legal system of the European Union and those of its Member States. In this paper, Julio Baquero Cruz analyses its assumptions and implications in the light of historical experience and of the consequences it could have for the practice of law in Europe. To do so, constitutional pluralism is compared with the other main positions about that relationship: the national constitutional position and the position of Union law.
Politicising EU Lawmaking? The Spitzenkandidaten Experiment as a Cautionary Tale
Authors: Goldoni Marco
Published: June 2016

The Spitzenkandidaten experiment has elicited much interest in academic and political circles as a move towards further politicisation of important aspects of EU lawmaking. This article puts forward a sobering account of the normative and instrumental reasons that explain why these expectations were grounded on shaky premises and the experiment could not have delivered its promises. In particular, the article stresses (1) the failure in creating a channel for political opposition through the indirect election of the President of the Commission; (2) the adoption of a formal understanding of the institutions involved in the process, that is, a conception detached from their social basis and (3) the choice of the wrong institution for the purpose of politicisation. The article concludes with a modest proposal for the consolidation of the channels for political action already available at the level of the Member States.
A new conception for enhancement of fatigue life of large number of fastener holes in aircraft structures
Authors: Duncheva G. V. , Maximov J. T. , Ganev N.
Published: June 2016

A new conception for increasing fatigue life of large number of fastener holes in aircraft structures is developed. It is accomplished by a new method, called friction stir hole expansion (FSHE). This method not only reduces labour and time consumption, but it also decreases the overall cost for processing a large number of holes in structures made of aerospace grade 2024‐T3 aluminium alloy. FSHE combines the advantages of friction stir processing with these of mandrel cold working methods in two ways: a micro effect, expressed in hole surface modification, and a macro effect, expressed by the introduction of beneficial compressive residual macro stresses. The effectiveness of the method has been assessed by fatigue tests. Finite element simulations have been carried out. It has been proven that the greater fatigue life of fastener holes, processed by FSHE, is a consequence of the obtained micro effect.
Stoichiometric constraints modulate impacts of silver contamination on stream detritivores: an experimental test with Gammarus fossarum
Authors: Arce‐Funck Julio , Crenier Clément , Danger Michael , Cossu‐Leguille Carole , Guérold François , Felten Vincent
Published: June 2016

Organisms commonly face multiple stresses in ecosystems, among which are toxic substances that add to natural ecological constraints such as insufficient resource quality. The combined effects of these stressors on species and ecosystems remain poorly investigated.

We hypothesised that feeding on high‐quality resources in terms of phosphorus (P) content will improve the physiological state of consumers and thus increase tolerance to episodic metal stress by silver (Ag). We used a detritivorous crustacean from streams, Gammarus fossarum, to test this hypothesis.

The experimental design involved two phases. In the first phase, gammarids were fed ad libitum for 15 days to evaluate the effect of food quality on their energetic status. Gammarids were placed in laboratory microcosms and allowed to feed on two leaf species, alder and sycamore, that were colonised by aquatic fungi and experimentally enriched with P. At the end of this feeding period, we determined (i) food consumption, (ii) energetic reserves and (iii) physiological and behavioural states. In the second phase, gammarids previously consuming food of different quality were exposed to dissolved Ag (0, 0.5 and 1 μg L−1) for 4 days to investigate the physiological and behavioural responses of the consumers.

Elevated P concentrations in leaf litter increased the energetic reserves and locomotor activity of G. fossarum. Gammarids exposed to Ag had a low glycogen content, regardless of the Ag concentration and leaf P concentration, suggesting significant energy allocation to several aspects of organism maintenance (e.g. detoxification or compensatory mechanisms). In most cases, this investment appeared to prevent gammarids from carrying out lipid peroxidation (indicating cell membrane damage), except for those gammarids feeding on leaves with the highest P concentration.

Higher energetic storage (measured as glycogen content), related to higher elemental food quality, did not lead to a systematic increase in consumer tolerance to Ag, gammarids being unable to compensate for negative effects of Ag at the concentrations tested.
Persistence of Crime Hot Spots: An Ordered Probit Analysis
Authors: He Li , Páez Antonio , Liu Desheng
Published: June 2016

The temporal persistence of crime hot spots is recognized as a valuable indicator of consistent problem areas. The current literature has not adequately addressed the mechanisms that perpetuate or interrupt persistent crime hot spots. Investigating the persistence of violent crime hot spots in Columbus, Ohio, from 1994 to 2002, this study fills a gap in the literature by identifying neighborhood structural correlates that drive the persistence of hot spots. Specifically, this study identifies yearly crime hot spots, and estimates an ordered probit model to explore the neighborhood structural determinants. The results indicate that socio‐economic factors, identified from a synthesis of social disorganization theory and routine activity theory, significantly correlate with persistent patterns of violent crime hot spots. This gives evidence that a combination of the two ruling spatial theories of crime provides an applicable framework for understanding the temporal dimension of violent crime hot spots. By identifying the factors that contribute to the persistence of hot spots of crime, insights gained from the results can help to inform focused crime prevention efforts.
How to Apply the AHS Evidence Assessment of the Acute Treatment of Migraine in Adults to your Patient with Migraine
Authors: Pringsheim Tamara , Davenport William Jeptha , Marmura Michael J. , Schwedt Todd J. , Silberstein Stephen
Published: June 2016

The “Acute Treatment of Migraine in Adults: The American Headache Society Evidence Assessment of Migraine Pharmacotherapies” provides levels of evidence for medication efficacy for acute treatment of migraine. The goal of this companion paper is to provide guidance on how to choose between evidence‐based treatment options, and, based on the clinical characteristics of the patient and their migraine attacks, to provide guidance on designing an individualized strategy for managing migraine attacks. The acute pharmacological treatments described in the American Headache Society evidence assessment can be divided into those initially taken by the patient during the headache phase of the migraine attack, those taken by the patient later in the attack when initial treatments fail, and those administered intravenously or intramuscularly in urgent care settings. Medications taken initially by patients in the headache phase include nonspecific analgesics such as acetaminophen and nonsteroidal anti‐inflammatory drugs (NSAIDs), triptans, and dihydroergotamine (DHE). A stratified approach to treatment is advised, with the choice of medication based on the patient's treatment needs, taking into consideration the attack severity, presence of associated symptoms such as nausea and vomiting, and the degree of migraine‐related disability. Individuals with migraine may find reassurance in having a “back‐up plan” in the event of an initial acute treatment failure. For those individuals who had a partial response to the initial acute treatment, a second dose might be indicated. When the initial treatment does not provide meaningful and sustained benefits, a treatment from a different medication class is typically chosen. Depending upon the initial treatment used, this might include NSAIDs, triptans, or DHE. Opioids or acetaminophen in combination with codeine or tramadol can be considered as part of the “back‐up plan,” provided they are used infrequently. When all patient administered treatments have failed and moderate to severe migraine symptoms remain, some individuals seek treatment in urgent care settings. The intravenous administration of antiemetics with or without an intravenous or intramuscular NSAID or DHE, or an intramuscular opioid can be considered. Patients with migraine should be encouraged to treat migraine pain early, and avoid overuse of medications.
Clinical and virological features of acute hepatitis E in Gunma prefecture, Japan between 2004 and 2015
Authors: Yamazaki Yuichi , Naganuma Atsushi , Arai Yosuke , Takeuchi Suguru , Kobayashi Takeshi , Takakusagi Satoshi , Hatanaka Takeshi , Hoshino Takashi , Namikawa Masashi , Hashizume Hiroaki , Takizawa Daichi , Ohyama Tatsuya , Suzuki Hideyuki , Horiguchi Norio , Takagi Hitoshi , Sato Ken , Kakizaki Satoru , Kusano Motoyasu , Nagashima Shigeo , Takahashi Masaharu , Okamoto Hiroaki , Yamada Masanobu
Published: June 2016

Aim

To evaluate the clinical and virological features of acute hepatitis E (AH‐E) in Gunma prefecture and focus on the hepatitis E virus (HEV) infection in immunocompromised patients.

Methods

A total of 30 patients with AH‐E diagnosed at our Gunma University Hospital, and located in 3‐39‐15 Showa‐machi, Maebashi, Gunma 371‐8511 Japan, and its affiliated hospitals from 2004 to 2015, were studied. We evaluated the detailed medical histories, laboratory examinations and virological features of these participants.

Results

Of the 30 patients, 21 patients were men, with a median age of 61 years. Three of these patients had a history of recent oversea travel. A total of 14 patients had eaten raw or undercooked meat/viscera from animals, and two patients had contracted transfusion‐transmitted AH‐E. Eight patients were immunocompromised, including those with hematological disease, cancer receiving systemic chemotherapy and kidney transplant or connective tissue disease undergoing immunosuppressive medications. The alanine aminotransferase and total bilirubin levels were more significantly reduced in these immunocompromised patients than in the non‐immunocompromised patients. Severe thrombocytopenia, an extra‐hepatic manifestation of AH‐E, occurred in one case. Among the 22 HEV strains whose subgenotype was determined, two were imported strains (1a and 1f), and 11 strains formed four distinct phylogenetic clusters within subgenotype 3b. The remaining nine strains differed from each other by 9.8–22.4%, and were classified into four subgenotypes (3a, 3b, 3e and 3f).

Conclusion

Markedly divergent HEV strains (3a, 3b, 3e and 3f) were found to circulate in Gunma. Although immunosuppression appears to play a crucial role in establishing chronic sequels, AH‐E in eight immunocompromised patients, including transfusion‐transmitted HEV infection in two patients, did not become chronic.
Oct2 and Bob1 are sensitive and specific markers in lineage determination of B cell lymphomas with no expression of conventional B cell markers
Authors: Yin Liqun , Xu Jie , Li Min , Reddy Vishnu , Zhou Quan , Liu Huanxin , Chu Peiguo , Zhang Qianyun , Huang Qin , Gao Zifen , Liang Xiayuan , Wang Huan‐You , Pan Zenggang
Published: June 2016

Aims

Rare cases of B cell lymphomas do not express conventional B cell markers (CD20, CD79a and PAX5), and these types of lymphomas include anaplastic lymphoma kinase (ALK)‐positive large B cell lymphoma, plasmablastic lymphoma, primary effusion lymphoma and the solid variant of primary effusion lymphoma, extracavitary human herpesvirus 8 (HHV8)‐positive large B cell lymphoma. Establishing accurate diagnoses of these B cell lymphomas can be challenging, and often requires a large panel of immunohistochemical stains, molecular assays and cytogenetic studies. B cell‐specific transcription factors, Oct2 and Bob1, have been shown to be expressed consistently in most, if not all, B cell lymphomas, and therefore we investigated the utility of Oct2 and Bob1 immunohistochemistry in lineage determination of the aforementioned B cell lymphomas.

Methods and results

We selected 34 cases of previously diagnosed B cell lymphomas with no or weak expression of CD20, CD79a and PAX5. Oct2 and Bob1 were positive in 74% (25 of 34) and 85% (29 of 34) of the cases, respectively. When we combined the results of these two immunostains, 94% (32 of 34) cases expressed at least one of these two markers. We also included 51 control cases of non‐B cell neoplasms, and none of them expressed either Oct2 or Bob1.

Conclusions

Oct2 and Bob1 are very reliable in determining B cell lineage in the absence of expression of other pan‐B cell markers, and it should provide great diagnostic benefit to include them both in a panel of immunohistochemistry to assess undifferentiated malignant neoplasms.
Non‐breeding Cackling, Ross's and Snow Geese on Baffin Island show no loss of body mass during wing moult
Authors: Fox Anthony D. , Leafloor James O. , Balsby Thorsten J. S. , Dickson Kathryn M. , Johnson Michael A. , Nicolai Christopher A.
Published: June 2016

Non‐breeding Cackling Branta hutchinsii, Ross's Anser rossii and Lesser Snow Geese Anser caerulescens caerulescens captured during remigial moult on Baffin Island in 2015 showed no loss of body mass with moult stage, and individual variation in mass was largely explained by sex and measures of body size (tarsus length). Exceptional conditions in 2015 resulted in almost no reproductive effort or success in that year, so captured geese of all three species were likely to have been non‐breeding individuals that initiated moult early, whereas there were almost no failed or successful breeders, which would normally moult later. This suggests that in a non‐breeding year (i.e. in the absence of competition from large numbers of goslings), locally moulting geese can obtain sufficient exogenous energy to meet their needs during the flightless wing moult period without losing body mass. This also is consistent with the hypothesis that in other species of geese, accumulation of fat stores prior to, and depletion of such stores during, wing moult is adaptive and likely to be a feature of individual plasticity to meet particular needs, such as undertaking moult migration to remote sites where precise foraging and predation conditions cannot be anticipated, or where competition from more dominant individuals may restrict their access to a reliable food supply.
Molecular diagnosis of thrombocytopenia‐absent radius syndrome using next‐generation sequencing
Authors: Nicchia E. , Giordano P. , Greco C. , De Rocco D. , Savoia A.
Published: June 2016

Introduction

Thrombocytopenia‐absent radius (TAR) syndrome is a rare autosomal recessive disease. Patients are compound heterozygotes for a loss‐of‐function allele, which in most cases is a large genomic deletion on chromosome 1q21.1 containing the RBM8A gene, and a noncoding variant located in the 5′UTR (rs139428292) or intronic (rs201779890) regions of RBM8A. As the molecular genetic testing in TAR requires multiple techniques for detection of copy‐number variations (CNV) and nucleotide substitutions, we tested whether a next‐generation sequencing (NGS) approach could identify both alterations.

Methods

Two unrelated families were analyzed with Ion PGM sequencing using a target panel of genes responsible for different forms of inherited thrombocytopenia. A statistical quantitative evaluation of amplicon coverage was performed to detect CNV, in particular those on the RBM8A gene.

Results

All the probands were apparently homozygous for the rare allele inherited by the father at the rs139428292 locus, suggesting the presence of a deletion on the maternal chromosome. The statistical analysis confirmed the hemizygous condition of RBM8A.

Conclusion

We concluded that NGS approaches could be used as a cost‐effective method for molecular investigation of TAR as they could simultaneously detect CNV and point mutations.
Performance evaluation of the Sysmex®XP‐300 in an oncology setting: evaluation and comparison of hematological parameters with the Sysmex®XN‐3000
Authors: van Dievoet M. A. , Louagie H. , Ghys T.
Published: June 2016

Introduction

The Sysmex XP‐300® (XP‐300) is a new, fully automated hematology analyzer, designed to generate complete blood counts (CBC) with 3‐part differential. In our study, the XP‐300 was evaluated as a point‐of‐care (POC) analyzer in an oncology setting. In which blood samples from patients with different pathologies and treatments, affecting hematopoiesis, were analyzed.

Methods

Performance was evaluated according to the International Council for Standardization in Haematology (ICSH) guidelines and CLSI protocol H20‐A2 . Beside precision, linearity and carry‐over, a comparison study with the Sysmex® XN‐3000 (XN‐3000) and a manual reference leukocyte differential was performed. Flagging performance was also evaluated.

Results

XP‐300 showed excellent precision and linearity results. For within‐ and between‐run precision, the criteria, according to Ricos et al. , were met for all parameters tested, except for platelets in the low level. Less than or equal to 0.5% carry‐over was seen for all parameters tested. Comparison studies showed an acceptable correlation with both XN‐3000 and the manual reference leukocyte count. A suboptimal flagging performance was demonstrated.

Conclusion

In the context of diagnosing cytopenia due to myelosuppressing agents or leukocytosis due to infection, the XP‐300 showed good analytical performance. However, in the thrombocytopenic range, precision was suboptimal. In follow‐up of hematological malignancies with the occurrence of abnormal cells, we advise verification with a more advanced analyzer or with microscopic review, although further studies with a higher prevalence of abnormal cells are needed.
Evaluation of a new PT‐INR monitoring system in patients with the antiphospholipid syndrome
Authors: Braham S. , Novembrino C. , Moia M. , Torresani E. , Tripodi A.
Published: June 2016

Introduction

Patients on anticoagulant therapy with vitamin K antagonists (VKA) need frequent INR monitoring. Reliability of point‐of‐care (POC) devices for measuring INR needs rigorous evaluation, particularly in patient with the antiphospholipid syndrome (APS). The aim of this study was to evaluate the accuracy of the ProTime InRhythm™ System (here called device) for INR measurement in patients with APS on VKA.

Methods

We compared the device INR vs. the laboratory INR measurement for blood samples from 29 APS‐positive and 31 APS‐negative patients consecutively enrolled. APS was confirmed by positive serological and/or phospholipid‐dependent coagulation tests. Chromogenic factor X assay was used to evaluate anticoagulation. Bland–Altman difference plot for paired INR (POC vs. laboratory) was used to evaluate agreement between the device and the laboratory. The device INR relationship with factor X chromogenic assay was evaluated by orthogonal regression analysis.

Results

Overall, 97% of the device INR measurements were similar to laboratory INR values with an absolute difference less than 0.4 units. Correlation coefficient for the device INR vs. factor X was −0.69 (P < 0.0001, CI 95% −0.80 to −0.52).

Conclusions

The ProTime InRhythm System™ is an accurate point‐of‐care device for measuring INR also in patients with and without APS.
Queen pheromone regulates programmed cell death in the honey bee worker ovary
Authors: Ronai I. , Oldroyd B. P. , Vergoz V.
Published: June 2016

In social insect colonies the presence of a queen, secreting her pheromones, is a key environmental cue for regulating the reproductive state of workers. However, until recently the proximate molecular mechanisms underlying facultative worker sterility were unidentified. Studies into worker oogenesis in the honey bee (Apis mellifera) have indicated that programmed cell death is central to the regulation of oogenesis. Here we investigate how queen pheromone, age of the worker and ovary state affect both programmed cell death and cell number in worker ovaries. We describe a novel method to simultaneously measure programmed cell death (caspase activity) and live cell number (estimated from the amount of adenosine triphosphate) in an insect tissue. Workers exposed to queen pheromone have higher levels of caspase activity in the ovary than those not exposed. Our results suggest that queen pheromone triggers programmed cell death at the mid‐oogenesis checkpoint causing the abortion of worker oocytes and reproductive inhibition of the worker caste. Nonetheless, high caspase activity is present in activated ovaries from workers not exposed to queen pheromone. This caspase activity is most likely to be from the nurse cells undergoing programmed cell death, in late oogenesis, for normal oocyte development. Our study shows that the social environment of an organism can influence programmed cell death within a tissue.
Emerging roles for antigen presentation in establishing host–microbiome symbiosis
Authors: Bessman Nicholas J. , Sonnenberg Gregory F.
Published: June 2016

Trillions of beneficial bacteria inhabit the intestinal tract of healthy mammals from birth. Accordingly, mammalian hosts have evolved a series of complementary and redundant pathways to limit pathologic immune responses against these bacteria, while simultaneously protecting against enteric pathogen invasion. These pathways can be generically responsive to the presence of any commensal bacteria and innate in nature, as for IL‐22‐related pathways. Alternatively, specific bacterial antigens can drive a distinct set of adaptive immune cell responses, including IgA affinity maturation and secretion, and a recently described pathway of intestinal selection whereby MHCII+ ILC3 deletes commensal bacteria‐reactive CD4 T cells. These pathways can either promote or inhibit colonization by specific subsets of commensal bacteria, and cooperatively maintain intestinal homeostasis. In this review, we will highlight recent developments in understanding how these diverse pathways complement each other to cooperatively shape the symbiotic relationship between commensal bacteria and mammalian hosts.
The processing and presentation of lipids and glycolipids to the immune system
Authors: Vartabedian Vincent F. , Savage Paul B. , Teyton Luc
Published: June 2016

The recognition of CD1–lipid complexes by T cells was discovered 20 years ago and has since been an emerging and expanding field of investigation. Unlike protein antigens, which are presented on MHC class I and II molecules, lipids can only be presented by CD1 molecules, a unique family of MHC‐like proteins whose singularity is a hydrophobic antigen‐binding groove. The processing and loading of lipid antigens inside this groove of CD1 molecules require localization to endosomal and lysosomal subcellular compartments and their acidic pHs. This particular environment provides the necessary glycolytic enzymes and lipases that process lipid and glycolipid antigens, as well as a set of lipid transfer proteins that load the final version of the antigen inside the groove of CD1. The overall sequence of events needed for efficient presentation of lipid antigens is now understood and presented in this review. However, a large number of important details have been elusive. This elusiveness is linked to the inherent technical difficulties of studying lipids and the lipid–protein interface in vitro and in vivo. Here, we will expose some of those limitations and describe new approaches to address them during the characterization of lipids and glycolipids antigen presentation.
Antigen‐specific impairment of adoptive T‐cell therapy against cancer: players, mechanisms, solutions and a hypothesis
Authors: Villadangos Jose A.
Published: June 2016

Adoptive cell therapy (ACT) destroys tumors with infused cytotoxic T lymphocytes (CTLs). Although successful in some settings, ACT is compromised due to impaired survival or functional inactivation of the CTL. To better understand the mechanisms involved, we have exploited a mouse model of leukemia expressing ovalbumin as a tumor neoantigen to address these questions: (i) Is CTL impairment during ACT antigen specific? (ii) If yes, which are the antigen‐presenting cells responsible? (iii) Can this information assist the development of complementary therapies to improve ACT? Our results indicate that the target (tumor) cells, not cross‐presenting cells, are the main culprits of antigen‐specific CTL inactivation. We find that the affinity/avidity of the CTL‐tumor cell interaction has little influence on ACT outcomes, while tumor density is a major determinant. Reduction of tumor burden with mild non‐lymphoablative and non‐inflammatory chemotherapy can dramatically improve the efficacy of ACT and may minimize side‐effects. We propose a general mechanism for the inactivation of anti‐self CTL in the same tissues where the activity of anti‐foreign CTL is preserved, based on the density of target cells. This mechanism, which we tentatively call stunning, may have evolved to protect infected sites from self‐destruction and is exploited by tumors to inactivate CTL.
Nowhere to hide: unconventional translation yields cryptic peptides for immune surveillance
Authors: Starck Shelley R. , Shastri Nilabh
Published: June 2016

Effective immune surveillance by CD8+ cytotoxic T cells of intracellular microbes and cancer depends on the antigen presentation pathway. This pathway produces an optimal peptide repertoire for presentation by major histocompatibility (MHC) class I molecules (pMHCs I) on the cell surface. We have known for years that the pMHC I repertoire is a reflection of the intracellular protein pool. However, many studies have revealed that pMHCs I present peptides not only from precursors encoded in open‐reading frames of mRNA transcripts but also cryptic peptides encoded in apparently ‘untranslated’ regions. These sources vastly increase the availability of peptides for presentation and immune evasion. Here, we review studies on the composition of the cryptic pMHC I repertoire, the immunological significance of these pMHC I, and the novel translational mechanisms that generate cryptic peptides from unusual sources.
Association between quantitative measures obtained using fluorescence‐based methods and activity status of occlusal caries lesions in primary molars
Authors: Novaes Tatiane Fernandes , Reyes Alessandra , Matos Ronilza , Antunes‐Pontes Laura Regina , Marques Renata Pereira de Samuel , Braga Mariana Minatel , Diniz Michele Baffi , Mendes Fausto Medeiros
Published: June 2016

Background

Fluorescence‐based methods (FBM) can add objectiveness to diagnosis strategy for caries. Few studies, however, have focused on the evaluation of caries activity.

Aim

To evaluate the association between quantitative measures obtained with FBM, clinical parameters acquired from the patients, caries detection, and assessment of activity status in occlusal surfaces of primary molars.

Design

Six hundred and six teeth from 113 children (4–14 years) were evaluated. The presence of a biofilm, caries experience, and the number of active lesions were recorded. The teeth were assessed using FBM: DIAGNOdent pen (Lfpen) and Quantitative light‐induced fluorescence (QLF). As reference standard, all teeth were evaluated using the ICDAS (International Caries Detection and Assessment System) associated with clinical activity assessments. Multilevel regressions compared the FBM values and evaluated the association between the FBM measures and clinical variables related to the caries activity.

Results

The measures from the FBM were higher in cavitated lesions. Only, ∆F values distinguished active and inactive lesions. The LFpen measures were higher in active lesions, at the cavitated threshold (56.95 ± 29.60). Following regression analyses, only the presence of visible biofilm on occlusal surfaces (adjusted prevalence ratio = 1.43) and ∆R values of the teeth (adjusted prevalence ratio = 1.02) were associated with caries activity.

Conclusion

Some quantitative measures from FBM parameters are associated with caries activity evaluation, which is similar to the clinical evaluation of the presence of visible biofilm.
Analysis of stochastic local search methods for the unrelated parallel machine scheduling problem
Authors: Santos Haroldo G. , Toffolo Túlio A.M. , Silva Cristiano L.T.F. , Vanden Berghe Greet
Published: June 2016

This work addresses the unrelated parallel machine scheduling problem with sequence‐dependent setup times, in which a set of jobs must be scheduled for execution by one of the several available machines. Each job has a machine‐dependent processing time. Furthermore, given multiple jobs, there are additional setup times, which vary based on the sequence and machine employed. The objective is to minimize the schedule's completion time (makespan). The problem is NP‐hard and of significant practical relevance. The present paper investigates the performance of four different stochastic local search (SLS) methods designed for solving the particular scheduling problem: simulated annealing, iterated local search, late acceptance hill‐climbing, and step counting hill‐climbing. The analysis focuses on design questions, tuning effort, and optimization performance. Simple neighborhood structures are considered. All proposed SLS methods performed significantly better than two state‐of‐the‐art hybrid heuristics, especially for larger instances. Updated best‐known solutions were generated for 901 of the 1000 large benchmark instances considered, demonstrating that particular SLS methods are simple yet powerful alternatives to current approaches for addressing the problem. Implementations of the contributed algorithms have been made available to the research community.
Becoming Teacher: A/r/tographical Inquiry and Visualising Metaphor
Authors: Boulton Adrienne , Grauer Kit , L. Irwin Rita
Published: June 2016

A great deal has been written about the representational use of metaphor to understand teacher candidates’/new teachers’ conceptions of teacher practice. This article will discuss recent research that explored secondary visual art teacher candidates’/new teachers’visualisingof visual metaphors to provoke their a/r/tographical inquiry into their perceptions of practice. This article engages with the Deleuzian conceptionbecomingas well as the ontology of difference to provoke the reimagination of metaphor in research. We offer new understandings about visualising the visual in research and the methodological implications of relational research practices.
Top 10 research priorities relating to stroke nursing: a rigorous approach to establish a national nurse‐led research agenda
Authors: Rowat Anne , Pollock Alex , St George Bridget , Cowey Eileen , Booth Joanne , Lawrence Maggie ,   the Scottish Stroke Nurses Forum (SSNF)
Published: June 2016

Aim

To determine the top 10 research priorities specific to stroke nursing.

Background

It is important that stroke nurses build their research capability and capacity. This project built on a previous James Lind Alliance prioritization project, which established the shared stroke research priorities of stroke survivors, carers and health professionals.

Design

Research priority setting project using James Lind Alliance methods; a survey for interim prioritization and a consensus meeting for final priority setting.

Methods

Between September ‐ November 2014, stroke nurses were invited to select their top 10 priorities from a previously established list of 226 unique unanswered questions. These data were used to generate a list of shared research priorities (interim priority setting stage). A purposefully selected group of stroke nurses attended a final consensus meeting (April 2015) to determine the top 10 research priorities.

Results

During the interim prioritization stage, 97 stroke nurses identified 28 shared priority treatment uncertainties. At the final consensus meeting, 27 stroke nurses reached agreement on the top 10 stroke nursing research priorities. Five of the top 10 questions relate to stroke‐specific impairments and five relate to rehabilitation and long‐term consequences of stroke.

Conclusions

The research agenda for stroke nursing has now been clearly defined, facilitating nurses to undertake research, which is of importance to stroke survivors and carers and central to supporting optimal recovery and quality of life after stroke.