bluuebunny/crossref_metadata_2025 huggingface dataset:
Acquired Haemophilia: Functional Study of Antibodies to Factor VIII
Authors: Allain J P , Gaillandre A , Frommel D
Published: July 2018

Factor VIII complex and its interaction with antibodies to factor VIII have been studied in 17 non-haemophilic patients with factor VIII inhibitor. Low VIII:C and high VIIIR.Ag levels were found in all patients. VIII:WF levels were 50% of those of VTIIRrAg, possibly related to an increase of poorly aggregated and electrophoretically fast moving VIIIR:Ag oligomers.

Antibody function has been characterized by kinetics of VIII :C inactivation, saturability by normal plasma and the slope of the affinity curve. Two major patterns were observed:

1) Antibodies from 6 patients behaved similarly to those from haemophiliacs by showing second order inhibition kinetics, easy saturability and steep affinity slope (> 1).

2) Antibodies from other patients, usually with lower titres, inactivated VIII :C according to complex order kinetics, were not saturable, and had a less steep affinity slope (< 0.7). In native plasma, or after mixing with factor VIII concentrate, antibodies of the second group did not form immune complexes with the whole factor VIII molecular complex. However, dissociation procedures did release some antibodies from apparently low molecular weight complexes formed in vivo or in vitro. For appropriate management of non-haemophilic patients with factor VIII inhibitor, it is important to determine the functional properties of their antibodies to factor VIII.
Acute and Chronic Changes in Platelet Volume and Count After Cardiopulmonary Bypass Induced Thrombocytopenia in Man
Authors: Martin J F , Daniel T D , Trowbridge E A
Published: July 2018

Patients undergoing surgery for coronary artery bypass graft or heart valve replacement had their platelet count and mean volume measured pre-operatively, immediately post-operatively and serially for up to 48 days after the surgical procedure. The mean pre-operative platelet count of 1.95 ± 0.11 × 1011/1 (n = 26) fell significantly to 1.35 ± 0.09 × 1011/1 immediately post-operatively (p <0.001) (n = 22), without a significant alteration in the mean platelet volume. The average platelet count rose to a maximum of 5.07 ± 0.66 × 1011/1 between days 14 and 17 after surgery while the average mean platelet volume fell from preparative and post-operative values of 7.25 ± 0.14 and 7.20 ± 0.14 fl respectively to a minimum of 6.16 ± 0.16 fl by day 20. Seven patients were followed for 32 days or longer after the operation. By this time they had achieved steady state thrombopoiesis and their average platelet count was 2.44 ± 0.33 × 1011/1, significantly higher than the pre-operative value (p <0.05), while their average mean platelet volume was 6.63 ± 0.21 fl, significantly lower than before surgery (p <0.001). The pre-operative values for the platelet volume and counts of these patients were significantly different from a control group of 32 young males, while the chronic post-operative values were not. These long term changes in platelet volume and count may reflect changes in the thrombopoietic control system secondary to the corrective surgery.
Investigation of the Interaction of Blood Platelets with the Coagulation System at the Site of Plug Formation In Vivo in Man - Effect of Low-Dose Aspirin
Authors: Kyrle P A , Westwick J , Scully M F , Kakkar V V , Lewis G P
Published: July 2018

In 7 healthy volunteers, formation of thrombin (represented by fibrinopeptide A (FPA) generation, α-granule release (represented by β-thromboglobulin [βTG] release) and the generation of thromboxane B2 (TxB2) were measured in vivo in blood emerging from a template bleeding time incision. At the site of plug formation, considerable platelet activation and thrombin generation were seen within the first minute, as indicated by a 110-fold, 50-fold and 30-fold increase of FPA, TxB2 and PTG over the corresponding plasma values. After a further increase of the markers in the subsequent 3 minutes, they reached a plateau during the fourth and fifth minute. A low-dose aspirin regimen (0.42 mg.kg-1.day-1 for 7 days) caused >90% inhibition of TxB2formation in both bleeding time blood and clotted blood. At the site of plug formation, a-granule release was substantially reduced within the first three minutes and thrombin generation was similarly inhibited. We conclude that (a) marked platelet activation and considerable thrombin generation occur in the early stages.of haemostasis, (b) α-granule release in vivo is partially dependent upon cyclo-oxygenase-controlled mechanisms and (c) thrombin generation at the site of plug formation is promoted by the activation of platelets.
Deficient t-PA Release and Elevated PA Inhibitor Levels in Patients with Spontaneous or Recurrent Deep Venous Thrombosis
Authors: Juhan-Vague I , Valadier J , Alessi M C , Aillaud M F , Ansaldi J , Philip-Joet C , Holvoet P , Serradimigni A , Collen D
Published: July 2018

The fibrinolytic system was investigated in 120 patients with spontaneous or recurrent deep vein thrombosis (DVT) without any known organic disease able to explain by itself the occurrence of a thrombosis and without any known defect of antithrombin III, Heparin Cofactor II, Protein C, or Protein S. The assays included: Euglobulin fibrinolytic activity (EFA), tissue-type plasminogen activator related antigen (t-PA-Ag) and plasminogen activator inhibitor activity (PA inhibitor), which were measured before and after 10 min of venous occlusion (V. O.). On the basis of the results, the patients could be classified in 3 groups:good responders with an at least two-fold increase of EFA after venous occlusion (n = 76), poor responders with a lesser increase of EFA due to deficient release of t-PA (n = 12), and poor responders with a normal t-PA release but an increased level of PA-Inhibitor (n = 32).

The poor responders due to deficient t-PA release (10% of total) had a higher incidence of recurrence of deep vein thrombosis, than the other groups (p <0.01). An overall correlation was found between the level of PA-Inhibitor activity and the triglyceride level (r = 0.40, p <0.01), suggesting that these elevations may be due to a common cause, at least in some of the patients.

It is concluded that a poor fibrinolytic response to venous occlusion occurs in 35 percent of DVT patients. Poor responders however fall into two categories, one fourth with deficient t-PA release who have a high risk for recurrent venous thrombosis, and three fourth with increased PA-Inhibitor levels which may be associated with underlying diseases also causing hypertriglyceridemia. Further elucidation of the correlation between recurrent venous thrombosis and deficient fibrinolysis is expected to result in more specific and adequate treatment and prevention of DVT.
Catalysis of Thrombin Inhibition Provides an Index for Estimating the Antithrombotic Potential of Glycosaminoglycans in Rabbits
Authors: Fernandez F A , Buchanan M R , Hirsh J , Fenton II J W , Ofosu F A
Published: July 2018

Previous studies have demonstrated that standard anticoagulant tests are poor indices of the antithrombotic potential of glycosaminoglycans which are weak catalysts of the thrombinantithrombin III reaction. In this study we investigated whether the catalysis of thrombin inhibition by plasma could serve as a reliable index for assessing the antithrombotic effectiveness of glycosaminoglycans. Equal volumes of 125I-thrombin and control or test plasma were incubated for up to 10 min at 37° C. Inactivation of thrombin was then determined after 7.9% SDS-polyacrylamide gel electrophoresis and subsequent autoradiography. Increasing concentrations of heparin (>0.066 μg/mL or 0.01 USP units/mL) and dermatan sulfate (>0.1 μg/mL) could be readily demonstrated in undiluted plasma by enhanced formation of complexes of thrombin with antithrombin III and heparin cofactor II respectively. However, the detection of any catalytic effect of the two glycosaminoglycans decreased significantly with increasing plasma dilutions. When ex vivo plasmas obtained from rabbits that had been injected with the minimum dose of any one of seven glycosaminoglycans required to achieve their optimal antithrombotic effect were assessed for their ability to catalyse thrombin inhibition, there was approximately a 2-fold increase in the amount of thrombin inactivated 30 s after the thrombin had been added to the plasma. The enhanced inhibition of thrombin was achieved by catalysis of antithrombin III and/or heparin cofactor II activities. These results suggest that measurement of the catalysis of thrombin inactivation in undiluted plasma is a sensitive and reliable index for estimating the antithrombotic potential of glycosaminoglycans in rabbits.
Increased Plasma Thrombomodulin in Cancer Patients
Authors: Lindahl Anne Karin , Boffa Marie-Claire , Abildgaard Ulrich
Published: July 2018

Plasma samples from 35 patients with colorectal cancer, 16 patients with pancreatic cancer and 46 patients with various cancers in the terminal stage were analysed for soluble plasma thrombomodulin with an ELISA method. At time of diagnosis and before primary treatment, the patients with colorectal cancer had normal plasma TM levels. In the patients who developed disseminated disease, the mean plasma TM level increased significantly. In the patients with pancreatic cancer, the mean plasma TM level was increased already at time of primary treatment. The TM level increased further with progress of the pancreatic cancer. In the patients with various cancer types in the terminal stage, the mean TM was also significantly increased compared to healthy controls. Great individual variation in the plasma TM level was observed, as well as great variation of mean TM level between the various cancer types. There was no significant correlation between the TM levels and the levels of tissue factor pathway inhibitor, another endothelial coagulation inhibitor, which increased with progress of malignant disease. This may indicate different underlying mechanisms for the increased plasma levels.
ADP Receptor Induced Activation of Guanine Nucleotide Binding Proteins in Rat Platelet Membranes– An Effect Selectively Blocked by the Thienopyridine Clopidogrel
Authors: Gachet C , Savi P , Ohlmann P , Maffrand J-P , Jakobs K H , Cazenave J-P
Published: July 2018

The thienopyridine clopidogrel, a potent analog of ticlopidine, is a powerful inhibitor of ADP induced platelet aggregation and ADP induced inhibition of cyclic AMP accumulation in intact platelets but not of ADP induced shape change. We have recently demonstrated that ADP stimulates the binding of GTPγS to GTP binding proteins (G proteins) in human platelet membranes. We now studied the effects of clopidogrel, a specific inhibitor of ADP induced platelet aggregation on the stimulation of GTPγS binding to rat platelet membranes by ADP. Using the non hydrolyzable stable analog of ADP, 2MeSADP, we demonstrate that 2MeSADP stimulates the binding of [35S]GTPγS to rat platelet membranes in a concentration dependent manner, that this effect is inhibited by the specific ADP receptor antagonist Sp-ATPαS and that clopidogrel completely and selectively blocks the stimulation by 2MeSADP of [35S]GTPγS binding to platelet membranes of treated rats. We conclude that: i) rat platelet membranes possess an ADP receptor coupled to unidentified G protein(s) and ii) the thienopyridine clopidogrel impairs the interaction of the ADP receptor with its G protein by an irreversible modification the ADP receptor itself or its putative G protein.
Development of angle-resolved spectroscopy system of electrons emitted from a surface with negative electron affinity state
Authors: Ichihashi Fumiaki , Dong Xinyu , Inoue Akito , Kawaguchi Takahiko , Kuwahara Makoto , Ito Takahiro , Harada Shunta , Tagawa Miho , Ujihara Toru
Published: July 2018

We developed an angle-resolved photoemission spectroscopy system for the analysis of conduction-band electrons. By forming a negative electron affinity surface on a semiconductor surface, electrons in conduction bands are emitted into a vacuum and measured by using an analyzer. This method enables us to determine the energy and momentum of the conduction electrons. Furthermore, it can be used to determine unoccupied conduction band structures. The main challenges of this method are that the energies of the emitted electrons are extremely low and the trajectories of the electrons change due to various influences. We overcame these problems by placing the shielding mesh close to the sample and parallel to the sample surface. The entire chambers, including the shielding mesh, were grounded, and a negative bias voltage was applied only to the sample. This configuration realizes the acceleration of electrons while preserving the momentum component parallel to the sample surface. Another problem is the establishment of a method for converting a detected angle into the corresponding wavevector. We focused on the emission angle of electrons emitted from a sample and their minimum energy and then established an analytical method for converting detected angles into corresponding wavevectors on the basis of the minimum energy.
Proof of concept for an optogalvanic gas sensor for NO based on Rydberg excitations
Authors: Schmidt J. , Fiedler M. , Albrecht R. , Djekic D. , Schalberger P. , Baur H. , Löw R. , Fruehauf N. , Pfau T. , Anders J. , Grant E. R. , Kübler H.
Published: July 2018

We demonstrate the applicability of 2-photon Rydberg excitations of nitric oxide (NO) at room temperature in a gas mixture with helium (He) as an optogalvanic gas sensor. The charges created initially from preceding collisions of excited NO Rydberg molecules with free electrons are measured as a current on metallic electrodes inside a glass cell and amplified using a custom-designed high-bandwidth transimpedance amplifier attached to the cell. We find that this gas sensing method is capable of detecting NO concentrations lower than 10 ppm even at atmospheric pressures, currently only limited by the way we prepare gas dilutions.
H-mode access and the role of spectral shift with electrode biasing in the TCABR tokamak
Authors: Grenfell G. G. , Nascimento I. C. , Oliveira D. S. , Guimarães-Filho Z. O. , Elizondo J. I. , Reis A. P. , Galvão R. M. O. , Baquero W. A. H. , Oliveira A. M. , Ronchi G. , de Sá W. P. , Severo J. H. F. ,   T CABR Team
Published: July 2018

The transition from the ohmic heating L-mode to the H-mode in the tokamak TCABR induced by an external electrode biasing is addressed in this work. A gradual improvement in the plasma confinement with the biasing voltage was observed as a result of the enhancement of the E × B shear flow at the edge. This result was supported by the measurement of plasma parameters in different radial locations by two electrostatic probes. Radial profiles of the electron temperature (from the standard sweeping voltage technique), electron density, and radial electric field, as well as the local turbulence features, were measured. We observed that the electron density profile became steeper as the voltage on the electrode increased, while no significant change in the temperature profile was noticed. In addition, the data were compared with the spectral shift model [G. M. Staebler et al., Phys. Rev. Lett. 110, 055003 (2013)] at different bias voltages, i.e., different E × B shear flows, showing a good agreement. Particularly, the gradual improvement was held: the higher the biasing voltage, the larger the radial wavenumber shift and so the turbulence suppression. Moreover, by studying the edge radial profile of the mean radial wavenumber, we show that the large shift occurs in the same position where the transport barrier is created.
Macroscopic superhydrophobicity achieved by atomic decoration with silicones
Authors: Huang Yongfeng , Meng Sheng
Published: July 2018

Modulating wetting states of water droplets on a solid surface has great potential in numerous applications such as self-cleaning, heat transfer, and water purification. Present strategies to achieve controlled wettability usually employ surface roughness and/or chemical coating at the nanometer-to-micrometer scale. Here we propose that atomic-scale decoration and patterning with silicones can be used to fabricate superhydrophobic surfaces. Atomic decoration, differing from chemical coatings in the characteristic size and partial coverage, controls wetting states with the atomic precision (several angstroms) at low cost and maintains a long lifetime. We attribute the mechanism of atomic decoration to the decrease in effective potential-well depth, inducing weak interactions between the substrate and water droplet. Our work pushes water wetting to the limit of atomic scales, hinting for a paradigm shift from macroscopic to atomically-precise engineering of wetting states and providing new insights for fabricating superhydrophobic surfaces.
Infrared spectra of 3-hydroxy-(1H)-pyridinium cation and 3-hydroxy-(1H)-pyridinyl radical isolated in solid para-hydrogen
Authors: Tsuge Masashi , Lai Chia-Peng , Lee Yuan-Pern
Published: July 2018

As pyridine and its derivatives are regarded as building blocks of nitrogen-containing polycyclic aromatic hydrocarbons, spectral identifications of their protonated and hydrogenated species are important. The infrared (IR) absorption spectra of the 3-hydroxy-(1H)-pyridinium cation, 3-C5H4(OH)NH+, and the 3-hydroxy-(1H)-pyridinyl radical, 3-C5H4(OH)NH, produced on electron bombardment during deposition of a mixture of 3-hydroxypyridine, 3-C5H4(OH)N, and para-H2 to form a matrix at 3.2 K were recorded. Intense IR absorption lines of trans-3-C5H4(OH)NH+ at 3594.4, 3380.0, 1610.6, 1562.2, 1319.4, 1193.8, 1167.5, and 780.4 cm−1 and eleven weaker ones decreased in intensity after the matrix was maintained in darkness for 20 h, whereas lines of trans-3-C5H4(OH)NH at 3646.2, 3493.4, 3488.7, 1546.7, 1349.6, 1244.1, 1209.1, 1177.3, 979.8, and 685.2 cm−1 and nine weaker ones increased. The intensities of lines of trans-3-C5H4(OH)NH decreased upon irradiation at 520 nm and diminished nearly completely upon irradiation at 450 nm, whereas those of trans-3-C5H4(OH)NH+ remained unchanged upon irradiation at 370, 450, and 520 nm. Observed vibrational wavenumbers and relative intensities of these species agree satisfactorily with the scaled harmonic vibrational wavenumbers and IR intensities predicted with the B3LYP/aug-cc-pVTZ method. The observed 3-C5H4(OH)NH+ cation and 3-C5H4(OH)NH radical are predicted to be the most stable species among all possible isomers by quantum-chemical calculations.
The innovative progressive aspect of Black South African English: The role of language proficiency and normative processes
Authors: van Rooy Bertus , Kruger Haidee
Published: July 2018

Conflicting findings are reported for New Englishes and Learner Englishes:
similarities are identified mainly on psycholinguistic grounds and differences on sociolinguistic grounds. This chapter offers an analysis of the progressive form in Black South African English, in which the interaction between gradual increases in proficiency and normative interventions by explicit feedback and editing of published texts is examined to establish the route towards conventionalisation of innovative features. The results indicate that one innovative feature, the extension of the progressive to longer time spans, becomes established as a feature of the variety, but other potential innovations gradually disappear under normative influence and with increased proficiency. Innovations are likely to be accepted if they are insufficiently salient to be targeted for normative correction and sufficiently present in the written and spoken input to become entrenched in the grammatical representations of learners as they turn into advanced users of the New English.
The position of the verb in Gothic
Authors: Falluomini Carla
Published: July 2018

The aim of this paper is to offer a descriptive analysis of the position of the verb in the recently discovered Gothic fragment of Bologna (Gothica Bononiensia) – a text that seems to be independent of Greek or Latin models – in order to highlight analogies to and differences from other Gothic texts. The analysis shows that the position of the verb is relatively free, both in main and in subordinate clauses, with some exceptions (negatives,wh-questions and imperatives). The text exhibits the coexistence of competing grammatical constructions, used to satisfy pragmatic and stylistic requirements.
Gothic graffiti from the Mangup basilica
Authors: Vinogradov Andrey , Korobov Maksim
Published: July 2018

For more than a millennium there have been reports testifying to the presence of Goths in the Crimea. However, until a few years ago, the
only evidence of a Gothic or Germanic idiom spoken in the peninsula stems from the list of words recorded between 1560 and 1562 by Ogier de
Busbecq. Significant new evidence, however, has become available through the recent discovery of five Gothic graffiti scratched on two
reused fragments of a cornice belonging to the early Byzantine basilica at Mangup-Qale in the Crimea. The graffiti, datable to between about
850 and the end of the 10th century, exhibit words in Gothic known from Wulfila’s Bible translation, the script used being an archaic
variant of Wulfila’s alphabet and the only specimen of this alphabet attested outside Pannonia and Italy. There would seem to be evidence
for assuming that, among educated Crimean Goths, Gothic served as a spoken vernacular in a triglossic situation along with a purely literary
type of Gothic and with Greek in the second half of the 9th century.
The Spanish quotative según across written genres
Authors: Llopis Cardona Ana
Published: July 2018

This research aims to provide an insight into characterization of quotative markers from a specific and prototypical Spanish one, según. The analysis is corpus-based, specifically the data comes from four different genres (academic articles, essays, news and novels). Our study examines the linguistic features, the source of information, the combination with reporting verbs, and the frequency in relation to genres. Thus, it underlines that, in contrast to the counterpart in other languages, the evidential function of según is fulfilled by means of a prepositional phrase or a clause bringing a reporting verb. Also, it demonstrates the modification of the prototypical specific source (3d person) causes a reduction of reliability as a pragmatic extension, and it shows the evidential function is the most frequent across written genres and has increased significantly in news.
Positioning through address practice in Finland-Swedish and Sweden-Swedish service encounters
Authors: Norrby Catrin , Wide Camilla , Nilsson Jenny , Lindström Jan K.
Published: July 2018

This chapter investigates social positioning through the use (or non-use) of address pronouns in Finland-Swedish and Sweden-Swedish service encounters recorded at theatre and event booking venues in Finland and Sweden. The results demonstrate some compelling variation in address practices which can be attributed to participant roles (customer or staff), national variety (Finland-Swedish or Sweden-Swedish), age (younger or older speaker and addressee) and situational circumstances, such as type of venue and type of transaction, as well as micro-situational aspects which occur during the course of the interaction (complications, problems or topics treated as sensitive). The study highlights that different forms of address cannot be associated a priori with a certain level of formality, but should be interpreted in their micro and macro contexts in order to understand existing cultural norms for appropriate address.
Closeness at a distance
Authors: Debray Carolin , Reissner-Roubicek Sophie
Published: July 2018

Social relationships are argued to have a special importance in Brazilian workplaces, as in Brazil generally (Amado and Brasil 1991; Fonseca and Castor 2005; Tanure and Duarte 2005), but scarce attention has been paid to the way such relationships are indexed through language. This research explores the way employees position themselves and others in emails to shape and influence relationships, highlighting how features that are specific to the medium index workplace identities. The analysis of 77 emails from a range of workplaces focuses on phatic aspects occurring frequently in our sample, greetings and closings. Employees used these strategically to emphasise closeness or distance, and with different degrees of formality, fulfilling diverse positioning functions including contesting power, enhancing relationships, or emphasising others’ independence. In addition, the relatively high frequency of greetings and closings compared to findings from other settings appears to confirm the importance claimed for relating at work in Brazil.
Direct speech, subjectivity and speaker positioning in London English and Paris French
Authors: Secova Maria
Published: July 2018

This paper examines functional similarities and differences in the use of pragmatic features – in particular quotatives and general extenders – on the right and left periphery of direct quotations. This comparative study, based on the analysis of a contemporary corpus of London English and Paris French (MLE – MPF),1 finds that the form and frequency of these particles tend to vary not only with respect to social factors such as speakers’ age and gender, but also with respect to the different pragmatic functions they come to perform in different interactional settings. The contemporary data is analysed both qualitatively and quantitatively to show how different variants position the speaker in relation to: (i) the content of the quote, (ii) the interlocutors, (iii) the presumed author of the quote. The paper aims to contribute to a better understanding of pragmatic universals and variability in the use of direct speech.
Constellation of indexicalities and social meaning
Authors: Ghezzi Chiara
Published: July 2018

This chapter analyses the evolution of Italian cioè lit. ‘that is’ in recent diachrony. Cioè developed a social indexicality as in the 1980s it was associated with a young speech style. Through a corpus-based analysis of listeners’ phone-ins to a radio station, this study analyses the functions of cioè in the speech styles of different age-cohorts and its diachronic evolution over the last thirty years. The evolution of cioè shows that speakers employ it creatively, through a progressive bleaching of its original semantic and pragmatic values. The expansion of its functions and contexts of occurrence is so extensive that the expression became stigmatized as a ‘verbal tic’ characteristic of the language spoken by an age-cohort of speakers. These same social values are at the origin of the progressive decline of cioè in new generations of young speakers and in the community as a whole.
Representations of self and other in narratives of return migration
Authors: Nikolaou Alexander , Sclafani Jennifer
Published: July 2018

This paper examines self and other representations in interviews conducted with second-generation Greek return migrants, (in their majority Greek Americans) who relocated to their parents’ homeland as adults within a decade prior to the interviews. Through the analysis of stories of linguistic and cultural assimilation, conflict and transition, authenticity and hybridity, we explore how return migrants construct and negotiate identity positions vis-à-vis other members of their immigrant community, native Greeks, and the interviewer through the employment of indexical devices during the interview. Return migrants constitute an understudied group, especially from a sociolinguistic perspective, and we argue that understanding the complex positioning of identities among this group may provide unique insights into the broader ideologies that mediate hybrid and hyphenated identities in general.
The building blocks of Catalan ‘at least’
Authors: Castroviejo Miró Elena , Mayol Laia
Published: July 2018

This paper deals with the meaning of a Catalan expression that is partially analogous to English at least, namely si més no (literally ‘if more not’). We aim to derive its concessive and epistemic readings, and explain its lack of complete overlap with at least by appealing to si més no’s building blocks: a conditional, an additive morpheme, and negation. Specifically, we argue that ‘si més no φ’ is a biscuit conditional whose consequent contains a VERUM operator. It conveys that if it is not true that there is a ψ such that ψ + φ holds, there is a relevant assertion that it is indeed true that φ. The epistemic and concessive readings are pragmatically derived by appealing to the relevance of the assertion of the consequent under the circumstances described by the antecedent.
The acquisition of variation
Authors: Geveler Jasmin , Gil Laia Arnaus , Müller Natascha
Published: July 2018

Bilingual children do not have problems with variation across languages, one of the most convincing kind of evidence that they are able to separate their two languages from early on. Natural languages exhibit another kind of variation, namely intra-linguistic variation, as in the case of adjective placement in Romance (French, Spanish). The acquisition of the distribution of adjectives implies a fine analysis of different factors which determine the probability with which an adjective occurs pre- or postnominally. An analysis of 12 German-Romance (French, Spanish) or Romance-Romance (French, Spanish, Italian) bilingual children from birth from the age of 1;4 until the age of 5;4 and 3 adults (Spanish, French) shows that it is important to distinguish between French and Spanish. In French, the children are able to acquire the fine distinctions of the adult systems from early on, both with respect to variation across languages and intra-linguistic variation. The French bilingual data lack any signs of cross-linguistic influence. In contrast, bilingual children with Spanish do not always reflect the input frequencies.
DREAM-Yara: an exact read mapper for very large databases with short update time
Authors: Dadi Temesgen Hailemariam , Siragusa Enrico , Piro Vitor C , Andrusch Andreas , Seiler Enrico , Renard Bernhard Y , Reinert Knut
Published: July 2018

Motivation

Mapping-based approaches have become limited in their application to very large sets of references since computing an FM-index for very large databases (e.g. >10 GB) has become a bottleneck. This affects many analyses that need such index as an essential step for approximate matching of the NGS reads to reference databases. For instance, in typical metagenomics analysis, the size of the reference sequences has become prohibitive to compute a single full-text index on standard machines. Even on large memory machines, computing such index takes about 1 day of computing time. As a result, updates of indices are rarely performed. Hence, it is desirable to create an alternative way of indexing while preserving fast search times.

Results

To solve the index construction and update problem we propose the DREAM (Dynamic seaRchablE pArallel coMpressed index) framework and provide an implementation. The main contributions are the introduction of an approximate search distributor via a novel use of Bloom filters. We combine several Bloom filters to form an interleaved Bloom filter and use this new data structure to quickly exclude reads for parts of the databases where they cannot match. This allows us to keep the databases in several indices which can be easily rebuilt if parts are updated while maintaining a fast search time. The second main contribution is an implementation of DREAM-Yara a distributed version of a fully sensitive read mapper under the DREAM framework.

Availability and implementation

https://gitlab.com/pirovc/dream_yara/
SPhyR: tumor phylogeny estimation from single-cell sequencing data under loss and error
Authors: El-Kebir Mohammed
Published: July 2018

Motivation

Cancer is characterized by intra-tumor heterogeneity, the presence of distinct cell populations with distinct complements of somatic mutations, which include single-nucleotide variants (SNVs) and copy-number aberrations (CNAs). Single-cell sequencing technology enables one to study these cell populations at single-cell resolution. Phylogeny estimation algorithms that employ appropriate evolutionary models are key to understanding the evolutionary mechanisms behind intra-tumor heterogeneity.

Results

We introduce Single-cell Phylogeny Reconstruction (SPhyR), a method for tumor phylogeny estimation from single-cell sequencing data. In light of frequent loss of SNVs due to CNAs in cancer, SPhyR employs the k-Dollo evolutionary model, where a mutation can only be gained once but lost k times. Underlying SPhyR is a novel combinatorial characterization of solutions as constrained integer matrix completions, based on a connection to the cladistic multi-state perfect phylogeny problem. SPhyR outperforms existing methods on simulated data and on a metastatic colorectal cancer.

Availability and implementation

SPhyR is available on https://github.com/elkebir-group/SPhyR.

Supplementary information

Supplementary data are available at Bioinformatics online.
Functional analysis of synovial fluid from osteoarthritic knee and carpometacarpal joints unravels different molecular profiles
Authors: Barreto Goncalo , Soliymani Rabah , Baumann Marc , Waris Eero , Eklund Kari K , Zenobi-Wong Marcy , Lalowski Maciej
Published: July 2018

Objective

In this work, we aimed to elucidate the molecular mechanisms driving primary OA. By studying the dynamics of protein expression in two different types of OA joints we searched for similarities and disparities to identify key molecular mechanisms driving OA.

Methods

For this purpose, human SF samples were obtained from CMC-I OA and knee joint of OA patients. SF samples were analysed by label-free quantitative liquid chromatography mass spectrometry. Disease-relevant proteins identified in proteomics studies, such as clusterin, paraoxonase/arylesterase 1 (PON1) and transthyretin were validated by enzyme-linked immunosorbent assays, and on the mRNA level by droplet digital PCR. Functional studies were performed in vitro using primary chondrocytes.

Results

Differential proteomic changes were observed in the concentration of 40 proteins including clusterin, PON1 and transthyretin. Immunoassay analyses of clusterin, PON1, transthyretin and other inflammatory cytokines confirmed significant differences in protein concentration in SF of CMC-I and knee OA patients, with primarily lower protein expression levels in CMC-I. Functional studies on chondrocytes unequivocally demonstrated that stimulation with SF obtained from knee OA, in contrast to CMC-I OA joint, caused a significant upregulation in pro-inflammatory response, cell death and hypertrophy.

Conclusion

This study demonstrates that differential expression of molecular players in SF from different OA joints evokes diverse effects on primary chondrocytes. The pathomolecular mechanisms of OA may significantly differ in various joints, a finding that brings a new dimension into the pathogenesis of primary OA.
Mycobacterium tuberculosis type III‐A CRISPR/Cas system crRNA and its maturation have atypical features
Authors: Wei Wenjing , Zhang Shuai , Fleming Joy , Chen Ying , Li Zihui , Fan Shanghua , Liu Yi , Wang Wei , Wang Ting , Liu Ying , Ren Baiguang , Wang Ming , Jiao Jianjian , Chen Yuanyuan , Zhou Ying , Zhou Yafeng , Gu Shoujin , Zhang Xiaoli , Wan Li , Chen Tao , Zhou Lin , Chen Yong , Zhang Xian-En , Li Chuanyou , Zhang Hongtai , Bi Lijun
Published: July 2018

Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated protein (Cas) systems are prokaryotic adaptive immune systems against invading nucleic acids. CRISPR locus variability has been exploited in evolutionary and epidemiological studies of Mycobacterium tuberculosis, the causative agent of tuberculosis, for over 20 yr, yet the biological function of this type III‐A system is largely unexplored. Here, using cell biology and biochemical, mutagenic, and RNA‐seq approaches, we show it is active in invader defense and has features atypical of type III‐A systems: mature CRISPR RNA (crRNA) in its crRNA‐CRISPR/Cas protein complex are of uniform length (∼71 nt) and appear not to be subject to 3′‐end processing after Cas6 cleavage of repeat RNA 8 nt from its 3′ end. crRNAs generated resemble mature crRNA in type I systems, having both 5′ (8 nt) and 3′ (28 nt) repeat tags. Cas6 cleavage of repeat RNA is ion dependent, and accurate cleavage depends on the presence of a 3′ hairpin in the repeat RNA and the sequence of its stem base nucleotides. This study unveils further diversity among CRISPR/Cas systems and provides insight into the crRNA recognition mechanism in M. tuberculosis, providing a foundation for investigating the potential of a type III‐A–based genome editing system.—Wei, W., Zhang, S., Fleming, J., Chen, Y., Li, Z., Fan, S., Liu, Y., Wang, W., Wang, T., Liu, Y., Ren, B., Wang, M., Jiao, J., Chen, Y., Zhou, Y., Zhou, Y., Gu, S., Zhang, X., Wan, L., Chen, T., Zhou, L., Chen, Y., Zhang, X.‐E., Li, C., Zhang, H., Bi, L. Mycobacterium tuberculosis type III‐A CRISPR/Cas system crRNA and its maturation have atypical features. FASEB J. 33, 1496–1509 (2019). www.fasebj.org
Myofascial Release and Muscle Retraining for Dropped Head Syndrome Attributed to Radiation Fibrosis in Hodgkin Lymphoma: A Case Series
Authors: Dixey Joanne , Purohit Kash , Greenfield Diana M.
Published: July 2018

Background and Purpose:

This article reviews the current knowledge base of dropped head syndrome and presents the case histories of 7 patients with a diagnosis of this condition at the Royal Hallamshire Hospital, Sheffield, through the Late Effects Clinic. All patients were referred for physiotherapy, and the assessment findings and subsequent treatment provided are discussed in detail.

Case Description:

Seven patients who were consecutively referred to physiotherapy and presented with signs and symptoms of suspected dropped head syndrome following previous treatment with mantle radiotherapy for Hodgkin lymphoma are discussed. Physiotherapy was delivered at various time intervals and duration on a one-to-one basis. Interventions were delivered to restore soft tissue length, rehabilitate proprioception, increase neck stabilizer strength, and retraining of muscles through range both locally and distally.

Outcomes:

All 7 patients reported subjective improvements in pain and function, with objective improvements in local and distal posture, tolerance to maintain head on neck position, and ability to grade through range neck movement locally. No formal outcome measures were used, as this is a retrospective report.

Conclusion:

Physiotherapy can offer short-term subjective and objective improvements in head on neck posture and control and effect more distal postural changes. Longer-term maintenance of improvements gained has yet to be determined. The most effective time point posttreatment for therapy intervention requires further research as does the type of physiotherapy intervention to be offered.
Oncology Section EDGE Task Force on Urogenital Cancer: A Systematic Review of Clinical Measures for Incontinence
Authors: Jeffrey Alicia , Harrington Shana E. , Hill Alexandra , Roscow Amanda , Alappattu Meryl
Published: July 2018

Background:

Compared with the general population, women and men with urogenital and colorectal cancers experience higher rates of urinary and fecal incontinence. Although a variety of measures exist to assess these areas, currently, there are no guidelines recommending which outcomes rehabilitation professionals should administer to examine these impairments in those with cancer.

Purpose:

To identify outcome measures for assessing urinary and fecal incontinence and evaluate their psychometric data and applicability to the cancer population.

Methods:

Multiple electronic databases (CINAHL, MEDLINE, PsycINFO) were reviewed using specific search terms to locate articles that identify outcome measures assessing urinary and fecal incontinence. As part of a larger effort to identify outcome measures for both incontinence and sexual dysfunction, 1118 articles were initially identified, 228 articles were reviewed, and 37 outcome measures were selected for analysis, 13 of which were related to urinary and fecal incontinence. Each incontinence outcome measure was independently reviewed and rated by 2 reviewers using the Cancer Evaluation Database to Guide Effectiveness (EDGE) Task Force Outcome Measure Rating Form. Any discrepancies between reviewers were discussed, and an overall recommendation for each outcome measure was made using the 4-point Cancer EDGE Task Force Rating Scale.

Results:

The Task Force was able to highly recommend 1 measure addressing urinary incontinence (American Urological Association Symptom Index) and 2 measures assessing urinary and fecal incontinence (Pelvic Floor Distress Inventory–Short Form, and Pelvic Floor Impact Questionnaire–Short Form). The Task Force also recommended 2 measures of urinary incontinence that demonstrated strong psychometric properties but had not yet been evaluated in the cancer population (Incontinence Quality-of-Life Questionnaire, International Consultation on Incontinence Questionnaire–Short Form). The Task Force was unable to recommend any measures that solely addressed fecal incontinence.

Conclusions:

Five of the 13 outcome measures assessing urinary incontinence and 2 of the 13 measures assessing urinary and fecal incontinence demonstrated satisfactory psychometric properties and application to the urogenital cancer population and are thereby recommended for use by the Task Force.
A Descriptive Report of Early Mobilization for Critically Ill Ventilated Patients With Cancer
Authors: Weeks Amanda , Campbell Claudine , Rajendram Prabalini , Shi Weiji , Voigt Louis P.
Published: July 2018

Background:

Early mobilization protocols have been successfully implemented to improve function in critically ill patients; however, no study has focused on the oncology population.

Objectives:

To investigate the feasibility of early mobilization and describe the rehabilitation interventions and discharge outcomes in a cohort of critically ill patients with cancer.

Design:

Retrospective review.

Methods:

A retrospective analysis of patients with cancer who participated in occupational and physical therapy while on mechanical ventilation, using an institutional early mobilization protocol from June 2010 to July 2011, was completed. Demographic and clinical variables were abstracted, as well as occupational and physical therapy interventions.

Results:

A cohort of 42 patients with cancer on mechanical ventilation in the mixed medical/surgical intensive care unit of a comprehensive cancer center received early mobilization during the study period. The majority of participants demonstrated improved cognitive and functional status from the intensive care unit to hospital discharge. There were no reported adverse events during the occupational and physical therapy sessions. Among the 30 hospital survivors, 53% required continued rehabilitation services in their home environment and 40% were transferred to a rehabilitation facility.

Limitations:

Because of the small sample size, these findings are not generalizable to all critically ill patients with cancer. There was no post–acute care follow-up of cognitive and physical functional performance.

Conclusion:

Early mobilization appears to be feasible in addressing the cognitive and functional needs of oncology patients in the intensive care unit.
Gross Motor Function at 10 Years of Age in Children With Clubfoot Following the French Physical Therapy Method and the Ponseti Technique
Authors: Zapata Karina A. , Karol Lori A. , Jeans Kelly A. , Jo Chan-Hee
Published: July 2018

Purpose:

To evaluate gross motor skills [Bruininks-Oseretsky Test of Motor Proficiency, 2nd ed (BOT-2)] of patients with idiopathic clubfoot initially treated nonoperatively with either the French functional physical therapy (PT) method or the Ponseti technique, at age 10 years.

Methods:

The BOT-2 was administered by trained physical therapists on patients with idiopathic clubfoot at age 10 years. The cohort was divided by initial treatment method (PT or Ponseti), and compared. Subsequent analyses included comparisons of: initial clubfoot severity (Dimeglio scores: ≤13 vs. >13), laterality (unilateral vs. bilateral), and surgical versus nonoperative outcome.

Results:

Of the 183 patients tested, 172 were included. The Ponseti and PT groups did not significantly differ according to age, height, weight, body mass index, ankle dorsiflexion, sex, average initial Dimeglio score, laterality, or surgical versus nonsurgical outcome. Overall, patients with treated clubfoot had average gross motor BOT-2 scores compared with age-matched peers. Patients in the PT group scored higher on Running Speed/Agility (P=0.019), Body Coordination percentile rank (P=0.038), and Strength and Agility percentile rank (P=0.007) than patients treated by the Ponseti technique. Patients with bilateral clubfoot scored significantly lower on the Balance subtest (P<0.01), and Body Coordination percentile rank (P<0.01), than those with unilateral clubfoot. Patients who required surgery scored significantly lower on the Balance subtest (P=0.04) than those who did not require surgery.

Conclusions:

Clubfoot may impair balance in 10 year olds with bilateral involvement and those requiring surgery. Future research should evaluate whether components of the PT method may improve gross motor outcomes as a supplement to the Ponseti technique.

Levels of Evidence:

Level II.
Uniportal Thoracoscopic Approach For Pulmonary Hydatid Cyst: Preliminary Results
Authors: Ocakcioglu Ilhan , Sayir Fuat
Published: July 2018

Purpose:

Pulmonary hydatid cyst is a preventable parasitary disease with high prevalence in low-medium income countries. Thoracoscopic approach is seen in the literature as small-case groups and multiple-port incisions are observed in these studies. Unlike other thoracoscopic approaches for the surgical treatment, we describe the single-port technique for the first time in our study. We attempt to compare the clinical outcomes and preliminary results of patients with pulmonary hydatid cyst treated with either minimally invasive or thoracotomy.

Methods:

The medical records of 66 patients undergoing surgery for pulmonary hydatid cyst disease between January 2013 and July 2017 were reviewed. The number of patients who underwent thoracotomy was 48, whereas 18 were managed by single-port video-assisted thoracoscopic surgery. Variables statistically compared between the 2 groups were age, diameter of the cystic, operation time, volume and duration of the drainage, postoperative complications, length of stay, duration of narcotic analgesic usage, and pain score.

Results:

Thoracoscopic approach was superior to conventional thoracotomy in terms of operation time, drainage volume, time to drain removal, hospital stay, narcotic analgesic treatment duration, and postoperative pain scores. All thoracoscopic procedures were concluded successfully, and conversion to open surgery was not required. No postoperative mortality was seen in either group. During the follow-up period, no recurrence was encountered in either group.

Conclusions:

Uniportal thoracoscopic approach is a safe option for the treatment of hydatid cyst disease. It can be used as an alternative to thoracotomy, depending on the size and location of the lesion.