bluuebunny/crossref_metadata_2025 huggingface dataset:
Concatenated channel‐and‐network coding scheme for two‐path successive relay network
Authors: Chen Shaolei , Zhang Zhaoyang , Yin Rui , Chen Xiaoming , Wang Wei
Published: February 2013

Two‐path successive relaying (TPSR) is an effective way to reduce the multiplex loss induced by the half‐duplex operation of the relay node in a conventional relay network. One crucial issue in TPSR network is that the listening relay always suffers inevitable inter‐relay interference (IRI), which degrades detection performance at the destination. In this study, a concatenated channel‐and‐network coding approach is proposed to solve the problem. In particular, a highly flexible channel code, namely, rateless code, is employed at the source to provide resilience to the residual IRI and reduce the retransmissions, which might break the system steady state of successive relaying. Then recognising the special interference structure, physical‐layer network coding is incorporated into the forwarding scheme of the relay nodes to exploit network diversity and improve system efficiency. By extrinsic information transfer analysis, the minimum number of required code symbols for successful data recovery are calculated, and degree distribution of the rateless code is optimised.
Flirting and ‘normative’ sexualities
Authors: Kiesling Scott F.
Published: February 2013

In this article I explore the effects of heteronormative assumptions on the interpretation of interaction. I consider two pieces of data that, based on the kinds of alignments shown, might be seen as flirting. However, through both perception experiments and discourse analysis, I show that these are rarely considered to be flirting if they take place for ‘same-gender’ interactions. These results demonstrate the power and effect of ‘background knowledge’ about sexualities on the interpretation of talk.
“We aren’t really that different”
Authors: Phillips Robert
Published: February 2013

Singapore is one of a few nations in Asia that has yet to decriminalize homosexuality yet has a queer scene that rivals other more liberal cosmopolitan centers. Since the introduction of the Internet into Singapore in 1994, queer Singaporeans have been exposed to a variety of regional and transnational discourses of sexual subjectivity and rights. In this article, I examine the ways that individuals and activists in Singapore reject the “globalization” of sexuality and instead create unique ways of speaking about queer rights. In the process, they are creating a rights movement that is beginning to find limited success.
Slang registers, code-switching and restructured urban varieties in South Africa
Authors: Mesthrie Rajend , Hurst Ellen
Published: February 2013

This paper examines the status of an informal urban variety in Cape Town known as Tsotsitaal. Similar varieties, going by a plethora of names (Flaaitaal, Iscamtho, Ringas) have been described in other South African cities, especially Johannesburg, Pretoria and Durban (see also Sheng in Kenyan cities). This paper seeks to describe the essential characteristics of Cape Town Tsotsitaal, which is based on Xhosa, and to argue for its continuity with similar varieties in other South African cities. However, this continuity eventually calls into question many of the previous assumptions in the literature about Tsotsitaal and its analogues: e.g. the thesis that these varieties necessarily involve code-switching, or that they are pidgins, even ones that are creolising in some areas. More generally, this paper serves several purposes: (a) to comment on and elucidate why there is a proliferation of often contradictory names, (b) to examine the degree and types of switching in the different varieties, and (c) to clarify the relationship between what are essentially tsotsitaal registers and the urban languages they are part of.
No need for instinct
Authors: Gibbs Raymond W. , Clark Nathaniel
Published: February 2013

Language serves many purposes in our individual lives and our varied interpersonal interactions. Daniel Everett’s claim that language primarily emerges from an “interactional instinct” and not a classic “language instinct” gives proper weight to the importance of coordinated communication in meeting our adaptive needs. Yet the argument that language is a “cultural tool”, motivated by an underlying “instinct”, does not adequately explain the complex, yet complementary nature of both linguistic regularities and variations in everyday speech. Our alternative suggestion is that language use, and coordinated communication more generally, is an emergent product of human self-organization processes. Both broad regularities and specific variations in linguistic structure and behavior can be accounted for by self-organizational processes that operate without explicit internal rules, blueprints, or mental representations. A major implication of this view is that both linguistic patterns and behaviors, within and across speakers, emerge from the dynamical interactions of brain, body, and world, which gives rise to highly context-sensitive and varied linguistic performances.
Cognition, communication, and readiness for language
Authors: Allwood Jens
Published: February 2013

This review article discusses some problems and needs for clarification that are connected with the use of the concepts culture, language, tool, and communication in Daniel Everett’s recently published book, Language: The Cultural Tool. It also discusses whether the idea of biological readiness and preparedness for language (rather than grammar) can really be disposed of as a result of Everett’s very convincing arguments against a specific genetic predisposition for the syntactic component of a grammar. Finally, it calls into question whether Everett really is true to his professed ideology of scientific ideographical pragmatism.
Regulation of AQP0 water permeability is enhanced by cooperativity
Authors: Németh-Cahalan Karin L. , Clemens Daniel M. , Hall James E.
Published: February 2013

Aquaporin 0 (AQP0), essential for lens clarity, is a tetrameric protein composed of four identical monomers, each of which has its own water pore. The water permeability of AQP0 expressed in Xenopus laevis oocytes can be approximately doubled by changes in calcium concentration or pH. Although each monomer pore functions as a water channel, under certain conditions the pores act cooperatively. In other words, the tetramer is the functional unit. In this paper, we show that changes in external pH and calcium can induce an increase in water permeability that exhibits either a positive cooperativity switch-like increase in water permeability or an increase in water permeability in which each monomer acts independently and additively. Because the concentrations of calcium and hydrogen ions increase toward the center of the lens, a concentration signal could trigger a regulatory change in AQP0 water permeability. It thus seems plausible that the cooperative modes of water permeability regulation by AQP0 tetramers mediated by decreased pH and elevated calcium are the physiologically important ones in the living lens.
Flavonoid regulation of EAG1 channels
Authors: Carlson Anne E. , Brelidze Tinatin I. , Zagotta William N.
Published: February 2013

The voltage-gated, K+-selective ether á go-go 1 (EAG1) channel is expressed throughout the brain where it is thought to regulate neuronal excitability. Besides its normal physiological role in the brain, EAG1 is abnormally expressed in several cancer cell types and promotes tumor progression. Like all other channels in the KCNH family, EAG1 channels have a large intracellular carboxy-terminal region that shares structural similarity with cyclic nucleotide–binding homology domains (CNBHDs). EAG1 channels, however, are not regulated by the direct binding of cyclic nucleotides and have no known endogenous ligands. In a screen of biological metabolites, we have now identified four flavonoids as potentiators of EAG1 channels: fisetin, quercetin, luteolin, and kaempferol. These four flavonoids shifted the voltage dependence of activation toward more hyperpolarizing potentials and slowed channel deactivation. All four flavonoids regulated channel gating with half-maximal concentrations of 2–8 µM. The potentiation of gating did not require the amino-terminal or post-CNBHD regions of EAG1 channels. However, in fluorescence resonance energy transfer and anisotropy-based binding assays, flavonoids bound to the purified CNBHD of EAG1 channels. The CNBHD of KCNH channels contains an intrinsic ligand, a conserved stretch of residues that occupy the cyclic nucleotide–binding pocket. Mutations of the intrinsic ligand in EAG1 (Y699A) potentiated gating similar to flavonoids, and flavonoids did not further potentiate EAG1-Y699A channels. Furthermore, the Y699A mutant CNBHD bound to flavonoids with higher affinity than wild-type CNBHD. These results suggest that the flavonoids identified here potentiated EAG1 channels by binding to the CNBHD, possibly by displacing their intrinsic ligand. EAG1 channels should be considered as a possible target for the physiological effects of flavonoids.
The voltage-sensing domain of a phosphatase gates the pore of a potassium channel
Authors: Arrigoni Cristina , Schroeder Indra , Romani Giulia , Van Etten James L. , Thiel Gerhard , Moroni Anna
Published: February 2013

The modular architecture of voltage-gated K+ (Kv) channels suggests that they resulted from the fusion of a voltage-sensing domain (VSD) to a pore module. Here, we show that the VSD of Ciona intestinalis phosphatase (Ci-VSP) fused to the viral channel Kcv creates KvSynth1, a functional voltage-gated, outwardly rectifying K+ channel. KvSynth1 displays the summed features of its individual components: pore properties of Kcv (selectivity and filter gating) and voltage dependence of Ci-VSP (V1/2 = +56 mV; z of ∼1), including the depolarization-induced mode shift. The degree of outward rectification of the channel is critically dependent on the length of the linker more than on its amino acid composition. This highlights a mechanistic role of the linker in transmitting the movement of the sensor to the pore and shows that electromechanical coupling can occur without coevolution of the two domains.
QuikScan formatting as a means to improve text recall
Authors: van der Meij Hans , van der Meij Jan , Farkas David K.
Published: February 2013

Purpose

QuikScan is an innovative text format that employs three prominent signaling devices – summaries, headings, and access cues – to make the reading of medium‐to‐long texts more productive. The experiments reported in this paper aim to examine the claim that QuikScan contributes to text recall.

Design/methodology/approach

In two consecutive experiments a QuikScanned text (experimental condition) was compared to a non‐QuickScanned text (control condition). In Experiment one, 41 university students read the text and then answered ten open recall questions. In Experiment two, 58 university students read the text and then wrote a summary and answered four recall questions.

Findings

In Experiment one, a statistically significant overall effect on text recall favoring QuikScan was found. Detailed analyses revealed that QuikScan mainly affected the readers' responses to higher‐order questions (d= 1.24). Experiment two showed that QuikScan led to significantly higher recall scores for the summaries. Just as in the first experiment, a strong effect on the higher‐order questions was found (d= 1.27).

Research limitations/implications

Further studies of QuikScan should include studies in naturalistic settings and should address selective reading and information navigation as well as text recall. SARA, a recent comprehensive theory of signaling, makes it possible to identify the individual functions of QuikScan's signaling devices and conduct revealing studies of QuikScan.

Practical implications

QuikScan and other innovations that improve the reading experience can potentially increase the willingness of readers to read longer documents.

Originality/value

QuikScan provides a unique combination of signaling devices. It can facilitate access and enhance text comprehension.
Flow and stability of natural pest control services depend on complexity and crop rotation at the landscape scale
Authors: Rusch Adrien , Bommarco Riccardo , Jonsson Mattias , Smith Henrik G. , Ekbom Barbara
Published: February 2013

Increasing landscape complexity can enhance biodiversity and ecosystem services in agroecosystems. However, policies based on conversion of arable land into semi‐natural habitats to increase landscape complexity and ecosystem services can be difficult to implement. Although it appears to be a promising management option, nothing is known about the effect of increasing landscape diversity through crop rotations on the delivery of ecosystem services.

In this study, we examined how landscape complexity and crop rotation intensity in the landscape at different spatial scales affect the flow and the stability of natural pest control services in barley fields using manipulative cage experiments.

Exclusion experiments revealed that natural enemies can have a strong impact on aphid population growth and that the delivery of pest control services is strongly dependent on the landscape context.

We found that the overall level of pest control increased with landscape complexity and that this effect was independent of crop rotation intensity. In addition, the within‐field stability in pest control services increased with crop rotation intensity in the landscape, although stability in parasitism rates decreased.

Multiple spatial scales analyses showed that the mean level of natural pest control was best predicted by landscape complexity at the 0·5‐km and the 1‐km spatial scales. The stability in overall pest control decreased with proportion of ley at the 2·5‐km and the 3‐km spatial scales.

Synthesis and applications. Our study disentangled, for the first time, the relative effects of landscape complexity and crop rotation intensity on the delivery of an ecosystem service. We show that combined management of semi‐natural habitat and crop rotation can stabilize and enhance natural pest control in agricultural landscapes. Our findings have important implications in terms of management options to maintain and enhance ecosystem services in agroecosystems. They suggest that conservation of heterogeneous landscapes, characterized by a higher proportion of semi‐natural habitats such as pastures and relatively small fields, is essential for maintaining and enhancing effective biological control in agroecosystems.
Landscape composition, connectivity and fragment size drive effects of grassland fragmentation on insect communities
Authors: Rösch Verena , Tscharntke Teja , Scherber Christoph , Batáry Péter
Published: February 2013

Calcareous grasslands are among the most species‐rich habitats in Europe, but are increasingly threatened due to abandonment and fragmentation. Little is known about how the surrounding landscape influences fragmentation effects. Here, we focus on the interaction between habitat fragmentation and landscape composition on leafhoppers, a highly diverse group of insects, including many species that are likely to be vulnerable to changes in their environment.

We selected 14 small and 14 large fragments of calcareous grassland in Central Germany, differing in isolation from other calcareous grasslands and in composition of the surrounding landscape. Leafhoppers, sampled by sweep netting, were either specialists that depended on calcareous grasslands or generalists that could use the landscape matrix, but still required low‐productivity habitats.

Increasing habitat isolation reduced leafhopper species richness in simple (dominated by arable crops), but not in complex landscapes. This effect was driven by the generalist species. In simple landscapes, leafhoppers may find it more difficult to reach the next suitable fragment due to a lack of alternative resources during dispersal.

Moreover, we found that generalist species richness increased with increasing connectivity on small fragments, whereas it remained stable with increasing connectivity on large fragments. In small, isolated fragments, a higher extinction rate combined with a lower probability of recolonization is thought to cause the reduced species richness.

Synthesis and applications. Our results show for the first time that insect species richness can be negatively affected by increasing habitat isolation in simplified but not in complex landscapes and in small but not in large fragments. We provide evidence that mitigating the negative effects of habitat fragmentation needs to take the surrounding landscape into account. Management efforts should prioritize (i) an increase in connectivity of small, isolated fragments, (ii) an increase in connectivity of fragments in simple landscapes and (iii) enhanced dispersal by increasing heterogeneity of both landscape composition and configuration. Moreover, extensive management of fragments by grazing or mowing to increase local habitat quality for leafhoppers would benefit other insect groups as well.
Children with developmental language impairment have vocabulary deficits characterized by limited breadth and depth
Authors: McGregor Karla K. , Oleson Jacob , Bahnsen Alison , Duff Dawna
Published: February 2013

Background

Deficient vocabulary is a frequently reported symptom of developmental language impairment, but the nature of the deficit and its developmental course are not well documented.

Aims

To describe the nature of the deficit in terms of breadth and depth of vocabulary knowledge and to determine whether the nature and the extent of the deficit change over the school years.

Methods & Procedures

A total of 25 681 oral definitions produced by 177 children with developmental language impairment (LI) and 325 grade‐mates with normally developing language (ND) in grades 2, 4, 8 and 10 were taken from an existing longitudinal database. We analysed these for breadth by counting the number of words defined correctly and for depth by determining the amount of information in each correct definition. Via a linear mixed model, we determined whether breadth and depth varied with language diagnosis independent of non‐verbal IQ, mothers’ education level, race, gender, income and (for depth only) word.

Outcomes & Results

Children with LI scored significantly lower than children with ND on breadth and depth of vocabulary knowledge in all grades. The extent of the deficit did not vary significantly across grades. Language diagnosis was an independent predictor of breadth and depth and as strong a predictor as maternal education. For the LI group, growth in depth relative to breadth was slower than for the ND group.

Conclusions & Implications

Compared with their grade‐mates, children with LI have fewer words in their vocabularies and they have shallower knowledge of the words that are in their vocabularies. This deficit persists over developmental time.
Characterization of water and wildlife strains as a subgroup of Campylobacter jejuni using DNA microarrays
Authors: Stabler Richard A. , Larsson Jonas T. , Al‐Jaberi Suaad , Nielsen Eva M. , Kay Emily , Tam Clarence C. , Higgins Craig D. , Rodrigues Laura C. , Richardson Judith F. , O'Brien Sarah J. , Wren Brendan W.
Published: February 2013

Campylobacter jejuni is the leading cause of human bacterial gastroenteritis worldwide, but source attribution of the organism is difficult. Previously, DNA microarrays were used to investigate isolate source, which suggested a non‐livestock source of infection. In this study we analysed the genome content of 162 clinical, livestock and water and wildlife (WW) associated isolates combined with the previous study. Isolates were grouped by genotypes into nine clusters (C1 to C9). Multilocus sequence typing (MLST) data demonstrated that livestock associated clonal complexes dominated clusters C1–C6. The majority of WW isolates were present in the C9 cluster. Analysis of previously reported genomic variable regions demonstrated that these regions were linked to specific clusters. Two novel variable regions were identified. A six gene multiplex PCR (mPCR) assay, designed to effectively differentiated strains into clusters, was validated with 30 isolates. A further five WW isolates were tested by mPCR and were assigned to the C7‐C9 group of clusters. The predictive mPCR test could be used to indicate if a clinical case has come from domesticated or WW sources. Our findings provide further evidence that WW C. jejuni subtypes show niche adaptation and may be important in causing human infection.
DNA barcoding for conservation, seed banking and ecological restoration of Acacia in the Midwest of Western Australia
Authors: Nevill Paul G. , Wallace Mark J. , Miller Joseph T. , Krauss Siegfried L.
Published: February 2013

We used DNA barcoding to address an important conservation issue in the Midwest of Western Australia, working on Australia's largest genus of flowering plant. We tested whether or not currently recommended plant DNA barcoding regions (matK and rbcL) were able to discriminate Acacia taxa of varying phylogenetic distances, and ultimately identify an ambiguously labelled seed collection from a mine‐site restoration project. Although matK successfully identified the unknown seed as the rare and conservation priority listed A. karina, and was able to resolve six of the eleven study species, this region was difficult to amplify and sequence. In contrast, rbcL was straightforward to recover and align, but could not determine the origin of the seed and only resolved 3 of the 11 species. Other chloroplast regions (rpl32‐trnL, psbA‐trnH, trnL‐F and trnK) had mixed success resolving the studied taxa. In general, species were better resolved in multilocus data sets compared to single‐locus data sets. We recommend using the formal barcoding regions supplemented with data from other plastid regions, particularly rpl32‐trnL, for barcoding in Acacia. Our study demonstrates the novel use of DNA barcoding for seed identification and illustrates the practical potential of DNA barcoding for the growing discipline of restoration ecology.
A life‐course perspective on economic stress and tobacco smoking: a population‐based study
Authors: Lindström Martin , Modén Birgit , Rosvall Maria
Published: February 2013

Aims

To investigate the associations between economic stress in childhood and adulthood and tobacco smoking, with reference to the accumulation, critical period and social mobility hypotheses from life‐course epidemiology.

Design, settingparticipants and measurements

The 2008 public health survey inSkåne,Sweden is a cross‐sectional postal questionnaire study based on a random sample which yielded 28 198 participants aged 18–80 years (55% participation). Logistic regression models were used to investigate associations between economic stress in childhood and adulthood and tobacco smoking.

Findings

A 17.4% prevalence of men and 19.1% of women reported tobacco smoking. Tobacco smoking was more prevalent among middle‐aged men and young women, among those born outsideSweden, with low occupational status, low social support, low trust, economic stress in childhood and adulthood. The accumulation hypothesis was confirmed because combined childhood and adulthood exposures to economic stress were associated (P < 0.001) with tobacco smoking in a graded manner. The critical period hypothesis was not supported because the associations between economic stress in childhood as well as adulthood, respectively, and tobacco smoking were significant (P = 0.004 andP < 0.001) throughout the analyses. The social mobility hypothesis was confirmed because upward social mobility was associated significantly (P < 0.001) with lower odds of smoking, while downward social mobility was associated significantly (P < 0.001) with higher odds of smoking.

Conclusions

Downward social mobility and economic stress in both childhood and adulthood should be considered as risk factors for tobacco smoking over the life‐course.
Woody plants' diversity, structural analysis and regeneration status of Wof Washa natural forest, North‐east Ethiopia
Authors: Fisaha Gebremicael , Hundera Kitessa , Dalle Gemedo
Published: February 2013

Wof‐Washa forest is one of the few remaining dry Afromontane forests in the central plateau of Ethiopia. Woody species composition, structure and regeneration patterns of this forest were studied to generate information essential for formulating feasible management options for the forest. Vegetation data were collected from 64 quadrats of size 20 m × 20 m, 10 m × 10 m and 5 m × 5 m for tree/shrub, sapling and seedling, respectively, laid systematically along transects. A total of 62 woody species belonging to 54 genera and 40 families were recorded. Rosaceae was the most diverse family with five (12.5%) species followed by Anacardiaceae, Euphorbiaceae and Myrsinaceae with three (7.5%) species each. Tree/shrub, sapling and seedling densities were 699, 1178 and 7618.7 individuals/ha. About 56.7% of the importance value index was contributed by Juniperus procera, Maytenus arbutifolia, Podocarpus falcatus and Ilex mitis. Vegetation classification resulted in five plant communities: Ilex mitis – Maytenus obscura, Galiniera saxifraga – Maesa lanceolata, Juniperus procera – Erica arborea, Podocapus falcatus – Allophylus abyssinicus and Pittosporum viridiflorum – Polycias fulva community types. Regeneration status of all the woody plant species was categorized as ‘Good’ (28%), ‘Fair’ (19%), ‘Poor’ (8%), ‘None’ (40%) and ‘New’ (5%).
Fetal Regulatory T Cells and Peripheral Immune Tolerance In Utero: Implications for Development and Disease
Authors: Burt Trevor D.
Published: February 2013

The developing fetus must actively learn to tolerate benign antigens or suffer the consequences of broken tolerance. Tolerance of self‐antigens prevents development of autoimmune diseases and is achieved by both deletion of autoreactive T cell clones in the thymus (central tolerance) and by the suppressive influence of CD4+ CD25+ FoxP3+ regulatory T cells (Tregs) in the periphery. Fetal CD4+ T cells have a strong predisposition to differentiate into tolerogenic Tregs that actively promote self‐tolerance, as well as tolerance to non‐inherited antigens on chimeric maternal cells that reside in fetal tissues. As the fetus nears birth, a crucial transition must occur between the tolerogenic fetal immune system and a more defensive adult‐type immune system that is able to combat pathogens. This paper will review the unique tolerogenic nature of fetal T cells and will examine evidence for a novel model of fetal immune development: the layered immune system hypothesis.
Is that femur really short? A survey of current and best practice in fetal biometry
Authors: McCarthy Elizabeth A. , Shub Alexis , Walker Susan P.
Published: February 2013

A web‐based survey of Royal Australian and New Zealand College of Obstetricians and Gynaecologists fellows and trainees enquired about fetal femur length reporting and found:

Heterogeneous (including unpublished) chart choices.

Popular charts are not always of highest quality.

z‐score rarely used despite World Health Authority endorsement.

Potential clinical risks include false‐positive and false‐negative diagnosis and confusion for both patient and staff. We recommend developing high‐quality charts, publishing unpublished charts and describe methods to support best practice.
Political Competition, Path Dependence, and the Strategy of Sustainable Energy Transitions
Authors: Aklin Michaël , Urpelainen Johannes
Published: February 2013

Previous research emphasizes the importance of path dependence for sustainable energy transitions, but their strategic nature is frequently overlooked. We examine formally how exogenous shocks, such as changes in international energy prices, interact with positive reinforcement factors, such as the growing strength of the renewables advocacy coalition. We find that political competition modifies the effect of path dependence on policy and outcomes. Specifically, while “green” governments can use positive reinforcement mechanisms to lock in policy commitments (by creating green constituencies), “brown” governments strategically underprovide public support for renewable energy (to avoid creating green constituencies). The effect of positive reinforcement also decreases with international energy prices. Our empirical analysis shows that (1) political competition conditions the policy response to exogenous shocks and market failures, while (2) governments strategically exploit path dependence for political gain.
Moderate, excessive or heavy alcohol consumption: each is significantly associated with increased mortality in patients with chronic hepatitis C
Authors: Younossi Z. M. , Zheng L. , Stepanova M. , Venkatesan C. , Mir H. M.
Published: February 2013

Background

The impact of moderate alcohol consumption on long‐term outcomes of chronic hepatitis C (CH‐C) infected patients remains controversial.

Aim

To assess the impact of moderate alcohol consumption on long‐term outcomes of CH‐C patients using population‐based data.

Methods

Data were obtained from the Third National Health and Nutrition Examination Survey (NHANES III)‐mortality linked files. Alcohol consumption was estimated as grams/day. Multivariate Cox proportional hazards model was utilized to assess the effects of CH‐C and alcohol consumption on mortality (all causes, cardiovascular disease, and liver disease).

Results

A total of 8985 participants were included as the study cohort. Of these, 218 had CH‐C. The follow‐up time was 162.95 months for CH‐C and 178.27 months for controls. CH‐C patients had increased risk for both overall mortality and liver‐related mortality. CH‐C patients with excessive alcohol consumption had even higher risks for overall mortality and liver‐related mortality. The risk of overall mortality associated with CH‐C increased with moderate alcohol consumption of 1–19 g/day and heavy alcohol consumption ≥30 g/day.

Conclusion

Although chronic hepatitis C is associated with increased risks for overall and liver‐related mortality, these risks are even higher for patients consuming moderate and excessive amounts of alcohol.
Model‐based evaluation of the pharmacokinetic differences between adults and children for lopinavir and ritonavir in combination with rifampicin
Authors: Zhang Chao , Denti Paolo , Decloedt Eric H. , Ren Yuan , Karlsson Mats O. , McIlleron Helen
Published: February 2013

Aims

Rifampicin profoundly reduces lopinavir concentrations. Doubled doses of lopinavir/ritonavir compensate for the effect of rifampicin in adults, but fail to provide adequate lopinavir concentrations in young children on rifampicin‐based antituberculosis therapy. The objective of this study was to develop a population pharmacokinetic model describing the pharmacokinetic differences of lopinavir and ritonavir, with and without rifampicin, between children and adults.

Methods

An integrated population pharmacokinetic model developed in nonmem 7 was used to describe the pharmacokinetics of lopinavir and ritonavir in 21 HIV infected adults, 39 HIV infected children and 35 HIV infected children with tuberculosis, who were established on lopinavir/ritonavir‐based antiretroviral therapy with and without rifampicin‐containing antituberculosis therapy.

Results

The bioavailability of lopinavir was reduced by 25% in adults whereas children on antituberculosis treatment experienced a 59% reduction, an effect that was moderated by the dose of ritonavir. Conversely, rifampicin increased oral clearance of both lopinavir and ritonavir to a lesser extent in children than in adults. Rifampicin therapy in administered doses increased CL of lopinavir by 58% in adults and 48% in children, and CL of ritonavir by 34% and 22% for adults and children, respectively. In children, the absorption half‐life of lopinavir and the mean transit time of ritonavir were lengthened, compared with those in adults.

Conclusions

The model characterized important differences between adults and children in the effect of rifampicin on the pharmacokinetics of lopinavir and ritonavir. As adult studies cannot reliably predict their magnitude in children, drug–drug interactions should be evaluated in paediatric patient populations.
MicroRNAs in myeloproliferative neoplasms
Authors: Zhan Huichun , Cardozo Christopher , Raza Azra
Published: February 2013

The chronic myeloproliferative neoplasms (MPN), including polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF), are clonal stem cell disorders characterized by dysregulated haematopoietic stem cell expansion and production of red cells, white cells and platelets alone or in combination. An acquired mutation JAK2V617F can be found in all three disorders and shows many of the phenotypic abnormalities of the diseases in murine models. The disease phenotype is also influenced by other unknown genetic or epigenetic factors. MicroRNAs (miRNA) are 18–24 nucleotide single‐stranded non‐protein‐coding RNAs that function primarily as gene repressors by binding to their target messenger RNAs. There is growing evidence that miRNAs regulate haematopoiesis in both haematopoietic stem cells and committed progenitor cells. Here, we review the field of miRNA biology and its regulatory roles in normal haematopoiesis with an emphasis on miRNA deregulations in MPNs. Continued research into how miRNAs impact JAK2V617F clonal expansion, differential haematopoiesis among different MPNs, disease progression and leukaemia transformation will lead to a better understanding of the development of these disorders, their clinical manifestations, and their treatment.
Flow cytometry thresholds of myeloperoxidase detection to discriminate between acute lymphoblastic or myeloblastic leukaemia
Authors: Guy Julien , Antony‐Debré Iléana , Benayoun Emmanuel , Arnoux Isabelle , Fossat Chantal , Le Garff‐Tavernier Magali , Raimbault Anna , Imbert Michèle , Maynadié Marc , Lacombe Francis , Béné Marie C , Wagner‐Ballon Orianne ,   GEIL (Groupe d'Etude Immunologique des Leucémies)
Published: February 2013

The World Health Organization 2008 Classification emphasizes myeloperoxidase (MPO) detection as sufficient for assigning a blast population to the myeloid lineage. Published MPO positivity thresholds are 10% for flow cytometry (FCM) but 3% for cytochemistry. Here we re‐evaluated the FCM‐MPO threshold by comparing retrospectively 128 acute lymphoblastic leukaemias and 75 acute myeloid leukaemias without maturation, all assessed by benzidine‐based cytochemistry. A 13% threshold was found to be relevant using an isotype control as background‐reference (sensitivity 95·1%, specificity 91·7%). Residual normal lymphocytes proved to be an advantageous alternative reference, a threshold of 28% yielding improved 97·4% sensitivity and 96·1% specificity.
R‐CHOP therapy alone in limited stage diffuse large B‐cell lymphoma
Authors: Tomita Naoto , Takasaki Hirotaka , Miyashita Kazuho , Fujisawa Shin , Ogusa Eriko , Matsuura Shiro , Kishimoto Kumiko , Numata Ayumi , Fujita Atsuko , Ohshima Rika , Kuwabara Hideyuki , Hagihara Maki , Hashimoto Chizuko , Takemura Sachiya , Koharazawa Hideyuki , Yamazaki Etsuko , Fujimaki Katsumichi , Taguchi Jun , Sakai Rika , Ishigatsubo Yoshiaki
Published: February 2013

Long‐term observation has identified a pattern of continuing relapse in limited stage diffuse large B‐cell lymphoma (DLBCL) treated by three cycles of R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) plus involved‐field irradiation. We retrospectively analysed 190 untreated patients with limited stage DLBCL treated by R‐CHOP alone. All the patients were scheduled to undergo primary therapy with six cycles of full‐dose R‐CHOP. Cases with a dose reduction of more than 20% were excluded from the study. Additional local irradiation was allowed in patients with partial response (PR). Five patients received additional local irradiation after PR at the end of the R‐CHOP therapy. The median observation period was 52 months. Median age at diagnosis was 63 years. The responses to therapy were 180 complete responses, eight PR, and two progression of disease (PD). The 5‐year progression‐free survival and 5‐year overall survival rates were 84% and 90%, respectively, both in plateau. During the observation period, 29 patients experienced PD. The progression sites were the primary sites in 15 patients, outside the primary sites in 10, and undetermined in four patients. These results suggest that the ‘standard’ strategy of three cycles of R‐CHOP followed by involved‐field radiotherapy for limited stage DLBCL could be effectively replaced by six cycles of R‐CHOP alone.
Metabolic Modulation of Epigenetics in Gliomas
Authors: Venneti Sriram , Thompson Craig B.
Published: February 2013

Cancer metabolism and epigenetics are two relatively new areas of cancer research. Recent years have seen an explosion of studies implicating either altered tumor metabolism or epigenetic mechanisms in the pathogenesis or maintenance of brain tumors. A new paradigm is emerging in cancer biology that represents a convergence of these themes, the metabolic regulation of epigenetics. We discuss this interrelationship in the context of two metabolic enzymes that can influence the pathogenesis of gliomas by altering the epigenetic state. The first of these enzymes is isocitrate dehydrogenase 1 (IDH1), which is mutated in secondary glioblastomas and ∼70% of grade II/III astrocytomas and oligodendrogliomas. Mutant IDH1 results in the production of a metabolite 2‐hydroxyglutarate (2‐HG) that can inhibit DNA and histone demethylating enzymes resulting in the glioma‐CpG island phenotype (G‐CIMP) and increased histone methylation marks. Pyruvate kinase M2 (PKM2), an enzyme that plays a critical role in the glycolytic pathway, is a second example of a metabolic enzyme that can affect histone modifications. In epidermal growth factor receptor (EGFR)‐driven glioblastoma, PKM2 translocates to the nucleus and phosphorylates histone 3 at threonine 11 (H3‐T11). This causes dissociation of HDAC3 from the CCND1 (Cyclin D1) and c‐MYC promoters and subsequent histone acetylation, leading to transcription of Cyclin‐D1 and c‐MYC, and subsequent cell proliferation. Modification of the epigenetic state by alterations in metabolic enzymes is a novel phenomenon that contributes to the pathogenesis of gliomas and may help in the identification of new therapeutic targets.
Sleep and Cognition in Preschool Years: Specific Links to Executive Functioning
Authors: Bernier Annie , Beauchamp Miriam H. , Bouvette‐Turcot Andrée‐Anne , Carlson Stephanie M. , Carrier Julie
Published: February 2013

This study investigated the prospective links between sleep in infancy and preschoolers' cognitive performance. Mothers of 65 infants completed a sleep diary when infants were aged 1 year, and children completed two subscales of the Wechsler Preschool and Primary Scale of Intelligence at 4 years, indexing general cognitive ability and complex executive functioning. Consistent with hypotheses, children getting higher proportions of their sleep at night as infants were found to perform better on executive functions, but did not show better general cognition. Relations held after controlling for family socioeconomic status and prior cognitive functioning. These findings suggest that the special importance of sleep for higher order cognition, documented among adults, may appear very early in life.
Loss‐of‐function mutations in CCDC114 cause primary ciliary dyskinesia
Authors: Wu DH , Singaraja RR
Published: February 2013

Splice‐site mutations in the axonemal outer dynein arm docking complex gene CCDC114 cause primary ciliary dyskinesia

Onoufriadis et al. (2013)

American Journal of Human Genetics 92:88–98.

Exome sequencing identifies mutations in CCDC114 as a cause of primary ciliary dyskinesia

Knowles et al. (2013)

American Journal of Human Genetics 92:99–106.
Exome sequencing is a useful diagnostic tool for complicated forms of hereditary spastic paraplegia
Authors: Bettencourt C. , López‐Sendón J.L. , García‐Caldentey J. , Rizzu P. , Bakker I.M.C. , Shomroni O. , Quintáns B. , Dávila J.R. , Bevova M.R. , Sobrido M.‐J. , Heutink P. , de Yébenes J.G.
Published: February 2013

Hereditary spastic paraplegias constitute a heterogeneous group of neurodegenerative diseases encompassing pure and complicated forms, for which at least 52 loci and 31 causative genes have been identified. Although mutations in the SPAST gene explain approximately 40% of the pure autosomal dominant forms, molecular diagnosis can be challenging for the sporadic and recessive forms, which are often complicated and clinically overlap with a broad number of movement disorders. The validity of exome sequencing as a routine diagnostic approach in the movement disorder clinic needs to be assessed. The main goal of this study was to explore the usefulness of an exome analysis for the diagnosis of a complicated form of spastic paraplegia. Whole‐exome sequencing was performed in two Spanish siblings with a neurodegenerative syndrome including upper and lower motor neuron, ocular and cerebellar signs. Exome sequencing revealed that both patients carry a novel homozygous nonsense mutation in exon 15 of the SPG11 gene (c.2678G>A; p.W893X), which was not found in 584 Spanish control chromosomes. After many years of follow‐up and multiple time‐consuming genetic testing, we were able to diagnose these patients by making use of whole‐exome sequencing, showing that this is a cost‐efficient diagnostic tool for the movement disorder specialist.
SCHOOL CHOICE: SUPPORTERS AND OPPONENTS
Authors: BRASINGTON DAVID M. , HITE DIANE
Published: February 2013

We examine the attitudes of Ohio homeowners about school choice, which includes open enrollment programs, school vouchers, tuition tax credits, and charter schools. Previous studies examine more limited forms of choice and investigate fewer possible influences. Overall we report at least five new findings and five findings that contradict previous studies. We find the strongest predictors of opposition for school choice are people having graduate degrees and living in high‐performing public school districts. We find people living in blue collar areas and using private schools to be the strongest predictors of support. Males tend to oppose choice and African Americans support it. We find no role for income, the convenience of alternative schools, or the protection of house values in support for school choice. Overall we report at least five new findings and five findings that contradict previous studies. (JEL H44, I22)
Hidradenocarcinoma showing prominent mucinous and squamous differentiation and associated pagetoid cells
Authors: Honda Yumi , Tanigawa Hiroki , Harada Miho , Fukushima Satoshi , Masuguchi Shinichi , Ishihara Tsuyoshi , Ihn Hironobu , Iyama Ken‐ichi
Published: February 2013

Herein, we report a 63‐year‐old man presenting with hidradenocarcinoma showing prominent mucinous and squamous differentiation on his back. The tumor was dermal‐based, solid and cystic. Tumor cells with squamous differentiation and with keratin pearl formation were identified predominantly in the superficial dermis, and mucinous cells were identified principally in the cystic lesion in the deep dermis. Interestingly, the additional feature of pagetoid cells was identified in the overlying epidermis. Both the mucinous cells in hidradenocarcinoma and pagetoid cells had intracytoplasmic mucin; however, they had different histopathologic findings and immunophenotypes. Mucinous cells in hidradenocarcinoma had small nuclei and abundant intracytoplasmic mucin presenting goblet cells with low rate of positive immunostaining for p53 and Ki67. In contrast, pagetoid cells had larger nuclei with less intracytoplasmic mucin. Both p53‐ and Ki67‐positive cells were increased in pagetoid cells. Additionally, mucinous cells in hidradenocarcinoma were MUC1(+)/MUC2(−)/MUC5AC(+)/MUC6(+), but pagetoid cells were MUC1(+; focal)/MUC2(−)/MUC5AC(−)/MUC6(+; focal). The derivation of pagetoid cells is unclear; however, the localized small region of pagetoid cells over the hidradenocarcinoma in the present case may suggest a common histogenesis of these two malignant neoplasms.
Subchronic exposure of titanium dioxide nanoparticles to hairless rat skin
Authors: Adachi Koji , Yamada Nanako , Yoshida Yuichi , Yamamoto Osamu
Published: February 2013

The evaluation of the biological effects of industrial nanoparticles on the skin is necessary for their risk assessment. To clarify the influence of TiO2 nanoparticles on the skin, we carried out a subchronic exposure study of TiO2 nanoparticles to hairless rat skin. W/O emulsion containing 10 wt% TiO2 nanoparticles and control emulsion was applied to the dorsal skin of Hairless Wistar Yagi rats once a day for a maximum period of 56 consecutive days. After 2, 4 and 8 weeks, skin samples were taken from the exposed skin area. Histopathologically, the particles were only located in the stratum corneum layer of epidermis and follicular epithelium. Focal parakeratosis and spongiosis were observed in the epidermis. Transmission electron microscopy with energy‐dispersive X‐ray spectrometry (EDX) analysis failed to show TiO2 nanoparticles in the viable skin areas. There was no evidence of TiO2 penetration in the viable skin areas. In addition, titanium contents in several organs were determined using inductively coupled plasma mass spectroscopy. Increased titanium concentration was detected in lung samples of the TiO2 emulsion‐treated groups after 8 weeks. It was most likely that the presence of TiO2 in the lungs was not caused by direct absorption of nanoparticles from the skin but was due to rats inhaling the nanoparticle. We did not find any obvious evidences of nano‐TiO2 particle skin penetration using several morphological methods after the subchronic exposure. We believe that the influence of subchronic exposure of TiO2 is not significant based on our study.
The antimanic‐like effect of phenytoin and carbamazepine on methylphenidate‐induced hyperlocomotion: role of voltage‐gated sodium channels
Authors: Tonelli Denise A.G. , Pereira Marcela , Siba Isadora P. , Martynhak Bruno J. , Correia Diego , Casarotto Plínio C. , Biojone Caroline , Guimarães Francisco S. , Joca Samia L.R. , Andreatini Roberto
Published: February 2013

The objective of this study was to verify whether phenytoin modifies methylphenidate‐induced hyperlocomotion, an animal model for screening antimanic‐like drugs, and also evaluate the effect of veratrine, a voltage‐gated sodium channel opener, pretreatment on the effect of phenytoin in this model. Carbamazepine was used as a positive control. Methylphenidate (5 mg/kg, s.c.) increased open‐field locomotion, and phenytoin (5–10 mg/kg, i.p.) and carbamazepine (20 mg/kg, i.p.) blocked this effect. Veratrine (0.4 mg/kg, s.c.) pretreatment reversed the effects of phenytoin (10 mg/kg, i.p.) and carbamazepine (20 mg/kg, i.p.). Phenytoin (1–50 mg/kg, i.p.) and carbamazepine (10–20 mg/kg i.p.) alone did not change spontaneous locomotor activity. These results indicate that voltage‐gated sodium channels play an important role in antimanic‐like effects of phenytoin and carbamazepine on psychostimulant‐induced hyperlocomotion model.