bluuebunny/crossref_metadata_2025 huggingface dataset:
Teachers' knowing how to use technology: exploring a conceptual framework for purposeful learning activity
Authors: Fisher Tony , Denning Tim , Higgins Chris , Loveless Avril
Published: August 2012

This article describes a project to apply and validate a conceptual framework of clusters of purposeful learning activity involving ICT tools. The framework, which is based in a socio‐cultural perspective, is described as ‘DECK’, and comprises the following major categories of the use of digital technologies to support learning: distributed thinking and knowing; engagement; community and communication; and knowledge building. Small‐scale research to test the framework was carried out with 12 teachers in English primary and secondary schools. The methods involved mind mapping, ‘think aloud’ procedures and interviews. The framework was modified in the light of teachers' responses and offers a way of describing and thinking about the diverse uses of digital technologies to support learning in various contexts.
Imageability and age of acquisition effects in disyllabic word recognition
Authors: Cortese Michael J. , Schock Jocelyn
Published: August 2012

Imageability and age of acquisition (AoA) effects, as well as key interactions between these variables and frequency and consistency, were examined via multiple regression analyses for 1,936 disyllabic words, using reaction time and accuracy measures from the English Lexicon Project. Both imageability and AoA accounted for unique variance in lexical decision and naming reaction time performance. In addition, across both tasks, AoA and imageability effects were larger for low-frequency words than high-frequency words, and imageability effects were larger for later acquired than earlier acquired words. In reading aloud, consistency effects in reaction time were larger for later acquired words than earlier acquired words, but consistency did not interact with imageability in the reaction time analysis. These results provide further evidence that multisyllabic word recognition is similar to monosyllabic word recognition and indicate that AoA and imageability are valid predictors of word recognition performance. In addition, the results indicate that meaning exerts a larger influence in the reading aloud of multisyllabic words than monosyllabic words. Finally, parallel-distributed-processing approaches provide a useful theoretical framework to explain the main effects and interactions.
MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells
Authors: Ochi Atsuo , Nguyen Andrew H. , Bedrosian Andrea S. , Mushlin Harry M. , Zarbakhsh Saman , Barilla Rocky , Zambirinis Constantinos P. , Fallon Nina C. , Rehman Adeel , Pylayeva-Gupta Yuliya , Badar Sana , Hajdu Cristina H. , Frey Alan B. , Bar-Sagi Dafna , Miller George
Published: August 2012

The transition of chronic pancreatic fibroinflammatory disease to neoplasia is a primary example of the paradigm linking inflammation to carcinogenesis. However, the cellular and molecular mediators bridging these entities are not well understood. Because TLR4 ligation can exacerbate pancreatic inflammation, we postulated that TLR4 activation drives pancreatic carcinogenesis. In this study, we show that lipopolysaccharide accelerates pancreatic tumorigenesis, whereas TLR4 inhibition is protective. Furthermore, blockade of the MyD88-independent TRIF pathway is protective against pancreatic cancer, whereas blockade of the MyD88-dependent pathway surprisingly exacerbates pancreatic inflammation and malignant progression. The protumorigenic and fibroinflammatory effects of MyD88 inhibition are mediated by dendritic cells (DCs), which induce pancreatic antigen–restricted Th2-deviated CD4+ T cells and promote the transition from pancreatitis to carcinoma. Our data implicate a primary role for DCs in pancreatic carcinogenesis and illustrate divergent pathways in which blockade of TLR4 signaling via TRIF is protective against pancreatic cancer and, conversely, MyD88 inhibition exacerbates pancreatic inflammation and neoplastic transformation by augmenting the DC–Th2 axis.
Skin-like self-assembled monolayers on InAs/GaSb superlattice photodetectors
Authors: Salihoglu Omer , Muti Abdullah , Kutluer Kutlu , Tansel Tunay , Turan Rasit , Aydinli Atilla
Published: August 2012

We report on the effects of monolayer (ML) thick skin-like octadecanethiol (ODT, CH3[CH2]17SH) on type-II InAs/GaSb MWIR photodetectors. Circumventing the ageing effects of conventional sulfur compounds, we use ODT, a self-assembling, long molecular chain headed with a sulfur atom. Photodiodes coated with and without the self-assembled monolayer (SAM) ODT were compared for their electrical and optical performances. For ODT-coated diodes, the dark current density was improved by two orders of magnitude at 77 K under −100 mV bias. The zero bias responsivity and detectivity were 1.04 A W−1 and 2.15 × 1013 Jones, respectively, at 4 µm and 77 K. The quantum efficiency was determined to be 37% for a cutoff wavelength of 5.1 µm.
Snakemake—a scalable bioinformatics workflow engine
Authors: Köster Johannes , Rahmann Sven
Published: August 2012

Summary: Snakemake is a workflow engine that provides a readable Python-based workflow definition language and a powerful execution environment that scales from single-core workstations to compute clusters without modifying the workflow. It is the first system to support the use of automatically inferred multiple named wildcards (or variables) in input and output filenames.

Availability:  http://snakemake.googlecode.com.

Contact:  johannes.koester@uni-due.de
Mitochondrial DNA and microsatellite genetic differentiation in the European anchovy Engraulis encrasicolus L.
Authors: Borrell Yaisel J. , Piñera Jorge A. , Sánchez Prado José A. , Blanco Gloria
Published: August 2012

Borrell, Y. J., Piñera, J. A., Sanchez Prado, J. A., and Blanco, G. 2012. Mitochondrial DNA and microsatellite genetic differentiation in the European anchovy Engraulis encrasicolus L. – ICES Journal of Marine Science, 69: .

The European anchovy Engraulisencrasicolus is currently one of the principal target species for commercial fisheries in Europe, and most stocks are overfished at present. In this work, specimens were sampled in the Bay of Biscay (Cantabrian, Basque Country, and French coasts) in 2009 and also in the Mediterranean (Adriatic Sea). Mitochondrial DNA (mtDNA; cytochrome b and 16S) was sequenced, and 14 nuclear microsatellites showing high and low levels of polymorphism were arranged in three multiplex polymerase chain reaction (PCR) systems and genotyped. Two main ancient mitochondrial clades were found. These clades are separated by 15 mutational steps and 1.7% sequence divergence, corresponding to a separation time of ∼0.5 million years ago. Our results using both mtDNA and microsatellites suggest the presence of at least three genetically differentiated groups: the west Cantabrian Sea, the rest of the populations in the Bay of Biscay, and the Mediterranean. Although it is known that western Iberian Atlantic populations of E. encrasicolus may be genetically different from those of the Bay of Biscay, the results suggest that the transition between these groups may be as close as a 100 km and that a recent genetic homogenization process in the eastward area of the Bay of Biscay has probably occurred.
Despite poor interferon response in advanced hepatitis C virus infection, models of protease inhibitor treatment predict maximum treatment benefit
Authors: Rowe I. A. , Houlihan D. D. , Mutimer D. J.
Published: August 2012

Background

Protease inhibitors have improved sustained virological response (SVR) rates for subjects with genotype 1 hepatitis C virus infection (HCV). There is however uncertainty regarding how, and in whom, these agents should be used. In previously treated subjects, prior response to interferon has a major effect on SVR rates with protease inhibitor therapy.

Aim

To assess the benefits of treatment and to understand the utility of a stopping rule for subjects with a poor interferon response following a 4‐week lead‐in with pegylated interferon and ribavirin.

Methods

Treatment responses and long‐term outcomes were modelled using hypothetical 1000 subject cohorts with 5 years of follow‐up. Treatment strategies were compared with number needed to treat (NNT) and comparative effectiveness approaches.

Results

Over 5 years of follow‐up the NNT to prevent liver‐related mortality for subjects with advanced fibrosis was substantially lower than that for subjects with all fibrosis stages (18 vs. 60) indicating particular benefit in this high‐risk population. The use of a stopping rule for subjects with advanced fibrosis and a poor interferon response after a 4‐week lead‐in reduces the number of subjects exposed to a protease inhibitor by 55%. However, 33% fewer liver‐related deaths are prevented using this strategy, indicating that there is unacceptable harm associated with this approach over a 5‐year follow‐up period.

Conclusions

Subjects with advanced fibrosis should be prioritised for triple therapy on the basis of need. Treatment should be continued regardless of initial interferon response to maximise the early prevention of hepatitis C virus‐related mortality.
Biotic modifiers, environmental modulation and species distribution models
Authors: Linder H. Peter , Bykova Olga , Dyke James , Etienne Rampal S. , Hickler Thomas , Kühn Ingolf , Marion Glenn , Ohlemüller Ralf , Schymanski Stanislaus J. , Singer Alexander
Published: August 2012

The ability of species to modulate environmental conditions and resources has long been of interest. In the past three decades the impacts of these biotic modifiers have been investigated as ‘ecosystem engineers’, ‘niche constructors’, ‘facilitators’ and ‘keystone species’. This environmental modulation can vary spatially from extremely local to global, temporally from days to geological time, and taxonomically from a few to a very large number of species. Modulation impacts are pervasive and affect, inter alia, the climate, structural environments, disturbance rates, soils and the atmospheric chemical composition. Biotic modifiers may profoundly transform the projected environmental conditions, and consequently have a significant impact on the predicted occurrence of the focal species in species distribution models (SDMs). This applies especially when these models are projected into different geographical regions or into the future or the past, where these biotic modifiers may be absent, or other biotic modifiers may be present. We show that environmental modulation can be represented in SDMs as additional variables. In some instances it is possible to use the species (e.g. biotic modifiers) in order to reflect the modulation. This would apply particularly to cases where the effect is the result of a single or a small number of species (e.g. elephants transforming woodland to grassland). Where numerous species generate an effect (such as tree species making a forest, or grasses facilitating fire) that modulates the abiotic environment, the effect itself might be a better descriptor for the aggregated action of the numerous species. We refer to this ‘effect’ as the modulator. Much of the information required to incorporate environmental modulation effects in SDMs is already available from remote‐sensing data and vegetation models.
Oral status and the need for oral health care among patients hospitalised with acute medical conditions
Authors: Hanne Konradsen , Ingelise Trosborg , Linda Christensen , Ulrich Pedersen P
Published: August 2012

Aims and objectives.  To investigate the prevalence of oral health problems in patients hospitalised with acute medical conditions.

Background.  Increases in our knowledge of oral health and its effects on overall well‐being have helped us elucidate the relationship between oral health, disease and treatment. Currently, little is known regarding the number of patients requiring oral care at the time of hospitalisation.

Design.  This was a cross‐sectional study that assessed patients hospitalised with acute medical conditions using the Revised Oral Assessment Guide (ROAG).

Methods.  The ROAG was translated into Danish, and three experienced nurses performed the assessments. A visual guide was used to calibrate the assessments. The data were analysed with spss to determine the percentage of participants who exhibited specific clinical characteristics.

Results.  Ninety‐one per cent of the newly admitted patients in this study had one or more oral health problems. Common oral problems, listed in order of the most frequent first, included the following: local plaque or debris, decayed teeth or damaged dentures and dryness and/or changes in the colour of the tongue. There was a correlation between age and the number of oral health problems.

Conclusions.  In this study, oral health was severely affected at the time that patients were hospitalised for acute medical issues.

Relevance to clinical practice.  Highlights the need for standardised oral health assessments of acutely hospitalised patients, which should begin as soon as the patient’s condition allows. Without these oral health assessments, a number of oral problems may not be detected and may increase in severity.
Targeting hospitalised patients for early discharge planning intervention
Authors: Holland Diane E , Knafl George J , Bowles Kathryn H
Published: August 2012

Aims and objectives.  The purpose of the study was to describe the ability of an evidence‐based discharge planning (DP) decision support tool to identify and prioritise patients appropriate for early DP intervention. Specifically, we aimed to determine whether patients with a high Early Screen for Discharge Planning (ESDP) score report more problems and continuing care needs in the first few weeks after discharge than patients with low ESDP scores.

Background.  Improved methods are needed to efficiently and accurately identify hospitalised patients at risk of complex discharge plans.

Design.  A descriptive cross‐sectional study was designed using a quality health outcomes framework.

Methods.  The ESDP was administered to 260 adults hospitalised in an academic health centre who returned home after discharge. Problems and continuing care needs were self‐reported on the Problems After Discharge Questionnaire – English Version, mailed 6–10 days after discharge.

Results.  Patients with high ESDP scores reported significantly more problems [mean, 16·3 (standard deviation ±8·7)] than those with low scores [12·2 (±8·4)]. Within the Problems After Discharge Questionnaire subscales, patients with high ESDP scores reported significantly more problems with personal care, household activities, mobility and physical difficulties than patients with low screen scores. Significantly more of the patients with a high ESDP score received consults to a Discharge Planner and referrals for postacute services than patients with low screen scores.

Conclusion.  The ESDP is effective as a decision support tool in identifying patients to prioritise for early DP intervention.

Relevance to clinical practice.  Use of an evidence‐based DP decision support tool minimises biases inherent in decision‐making, promotes efficient use of hospital DP resources, and improves the opportunity for patients to access community resources they need to promote successful recovery after hospitalisation.
The Saccharomyces cerevisiae BEM1 homologue in Neurospora crassa promotes co‐ordinated cell behaviour resulting in cell fusion
Authors: Schürg Timo , Brandt Ulrike , Adis Christian , Fleißner André
Published: August 2012

Directed growth or movement is a common feature of microbial development and propagation. In polar growing filamentous fungi, directed growth requires the interaction of signal sensing machineries with factors controlling polarity and cell tip extension. In Neurospora crassa an unusual mode of cell–cell signalling mediates mutual attraction of germinating spores, which subsequently fuse. During directed growth of the two fusion partners, the cells co‐ordinately alternate between two physiological stages, probably associated with signal sending and receiving. Here, we show that the Saccharomyces cerevisiae BEM1 homologue in N. crassa is essential for the robust and efficient functioning of this MAP kinase‐based signalling system. BEM1 localizes to growing hyphal tips suggesting a conserved function as a polarity component. In the absence of BEM1, activation of MAK‐2, a MAP kinase essential for germling fusion, is strongly reduced and delayed. Germling interactions become highly instable and successful fusion is greatly reduced. In addition, BEM1 is actively recruited around the forming fusion pore, suggesting potential functions after cell–cell contact has been established. By genetically dissecting the contribution of BEM1 to additional various polarization events, we also obtained first hints that BEM1 might function in different protein complexes controlling polarity and growth direction.
Early quality of life outcomes in patients with prostate cancer managed by high‐dose‐rate brachytherapy as monotherapy
Authors: Komiya Akira , Fujiuchi Yasuyoshi , Ito Takatoshi , Morii Akihiro , Yasuda Kenji , Watanabe Akihiko , Nozaki Tetsuo , Iida Hiroaki , Nomura Kuninori , Fuse Hideki
Published: August 2012

Objectives:  To evaluate the early quality of life outcomes in prostate cancer patients managed by high‐dose‐rate brachytherapy as monotherapy.

Methods:  A total of 51 patients with cT1c–T3aN0M0 prostate cancer treated between July 2007 and January 2010 were included in this study. The average age was 69 years, and the average initial serum prostate‐specific antigen was 10.98 ng/mL. A total of 25, 18 and eight patients were considered to be low, intermediate and high risk, respectively. All patients received one implant of Ir‐192 and seven fractions of 6.5 Gy within 3.5 days for a total prescribed dose of 45.5 Gy. For high‐risk prostate cancer, neoadjuvant androgen deprivation therapy was carried out for at least 6 months, and continued after high‐dose‐rate brachytherapy. Quality of life outcomes were measured by using the International Prostate Symptom Score, the Functional Assessment of Cancer Therapy‐Prostate and the International Index of Erectile Function Questionnaire. The oncological outcome was assessed by serum prostate‐specific antigen and diagnostic imaging. Adverse events were also recorded.

Results:  The Functional Assessment of Cancer Therapy‐Prostate scores decreased for a few months after high‐dose‐rate brachytherapy, and recovered to pretreatment condition thereafter. The International Prostate Symptom Score significantly increased 2 weeks after treatment for each of its items and their sum, and it returned to baseline after 12 weeks. Sexual function decreased at 2 and 4 weeks, and recovered after 12 weeks. Severe complications were rare. Within a median follow up of 17.2 months, two patients showed a prostate‐specific antigen recurrence.

Conclusions:  High‐dose‐rate brachytherapy for prostate cancer is a feasible treatment modality with acceptable toxicity and only a limited impact on the quality of life.
Case of syndrome of headache with neurological deficits and cerebrospinal fluid lymphocytosis (HaNDL) with focal slowing on electroencephalogram
Authors: Tsang B. K.‐T. , Kwong J. C. , Dewey H. M.
Published: August 2012

We describe a case of headache and neurological deficits with cerebrospinal fluid (CSF) lymphocytosis in a patient presenting with a 3‐week history of recurrent severe headaches associated with negative sensory symptoms and dysphasia. The patient had no cardiovascular risk factors and no family history of migraines. Neurological examination was unremarkable. Cerebral magnetic resonance imaging was unremarkable. CSF analysis revealed lymphocytosis (leucocytes 84 × 106/L, 100% lymphocytes). Extensive laboratory investigations of CSF and serum did not reveal an infectious, autoimmune or metabolic cause. Visual evoked potentials were normal. Awake electroencephalogram revealed intermittent 3–5 Hz generalised slowing and frontal intermittent rhythmic delta activity, without epileptiform discharges. Repeat CSF analysis showed marked reduction of the total leucocyte count and remained negative for infectious aetiology. Propranolol was commenced, and no recurrence of headache or neurological symptoms was observed at follow‐up. An extensive literature review on the topic is discussed.
Dispersal polymorphisms from natal phenotype–environment interactions have carry‐over effects on lifetime reproductive success of a tropical parrot
Authors: Tarwater Corey E. , Beissinger Steven R.
Published: August 2012

We examined how interactions between an individual's phenotype and its environment affect natal dispersal at multiple scales and the effects on lifetime reproductive success using a 22‐year study of green‐rumped parrotlets (Forpus passerinus). Dispersal increased or decreased lifetime reproductive success depending upon an individual's natal environment and phenotype. Many of the phenotypic traits and environmental conditions that influenced lifetime reproductive success also influenced dispersal, such as clutch size and competition, and this differed with scale. By examining phenotype–environment interactions, we observed both positive and negative effects of rainfall, habitat quality and competition on dispersal depending upon phenotype. The dispersal behaviours of juveniles typically resulted in higher lifetime reproductive success. Thus, individuals commonly exhibit ideal free behaviour and results provide support for the occurrence and maintenance of dispersal polymorphisms. This study highlights the long‐term, carry‐over effects of natal environment, natal phenotype and dispersal tactic on lifetime reproductive success.
A predictive model of community assembly that incorporates intraspecific trait variation
Authors: Laughlin Daniel C. , Joshi Chaitanya , van Bodegom Peter M. , Bastow Zachary A. , Fulé Peter Z.
Published: August 2012

Community assembly involves two antagonistic processes that select functional traits in opposite directions. Environmental filtering tends to increase the functional similarity of species within communities leading to trait convergence, whereas competition tends to limit the functional similarity of species within communities leading to trait divergence. Here, we introduce a new hierarchical Bayesian model that incorporates intraspecific trait variation into a predictive framework to unify classic coexistence theory and evolutionary biology with recent trait‐based approaches. Model predictions exhibited a significant positive correlation (r = 0.66) with observed relative abundances along a 10 °C gradient in mean annual temperature. The model predicted the correct dominant species in half of the plots, and accurately reproduced species' temperature optimums. The framework is generalizable to any ecosystem as it can accommodate any species pool, any set of functional traits and multiple environmental gradients, and it eliminates some of the criticisms associated with recent trait‐based community assembly models.
Becoming a researcher
Authors: Flood Samantha , Bennett Davey , Melsome Melissa , Northway Ruth
Published: August 2012

Accessible summary

This paper is about three people with learning disabilities. They work as co‐researchers.

They have written this paper with support.

Support is important to them. It has helped them to do the research. They each have a personal assistant. Other people working on the project also help them.

They have had training and practised what they needed to do before asking other people questions.

They have learnt a lot of new skills and have made a lot of decisions about the project.

They enjoy their work and hope that other people will learn from their stories.

They hope that other people with learning disabilities will want to do research.

People with learning disabilities are increasingly taking on the role of researcher within participatory research projects. This paper talks about what it means to be a researcher using the words, views and experiences of three people with learning disabilities who are currently working as co‐researchers. It talks about what they have found helpful, and what they have found challenging. It compares their experiences to those of other people and highlights the importance of support. Overall they report that it has been a positive experience which has helped them to learn a great deal and they provide advice that they hope will help others thinking about taking on such a role.
Vesicular uptake blockade generates the toxic dopamine metabolite 3,4‐dihydroxyphenylacetaldehyde in PC12 cells: relevance to the pathogenesis of Parkinson's disease
Authors: Goldstein David S. , Sullivan Patti , Cooney Adele , Jinsmaa Yunden , Sullivan Rachel , Gross Daniel J. , Holmes Courtney , Kopin Irwin J. , Sharabi Yehonatan
Published: August 2012

Parkinson's disease entails profound loss of nigrostriatal dopaminergic terminals, decreased vesicular uptake of intraneuronal catecholamines, and relatively increased putamen tissue concentrations of the toxic dopamine metabolite, 3,4‐dihydroxyphenylacetaldehyde (DOPAL). The objective of this study was to test whether vesicular uptake blockade augments endogenous DOPAL production. We also examined whether intracellular DOPAL contributes to apoptosis and, as α‐synuclein oligomers may be pathogenetic in Parkinson's disease, oligomerizes α‐synuclein. Catechols were assayed in PC12 cells after reserpine to block vesicular uptake, with or without inhibition of enzymes metabolizing DOPAL—daidzein for aldehyde dehydrogenase and AL1576 for aldehyde reductase. Vesicular uptake was quantified by a method based on 6F‐ or 13C‐dopamine incubation; DOPAL toxicity by apoptosis responses to exogenous dopamine, with or without daidzein+AL1576; and DOPAL‐induced synuclein oligomerization by synuclein dimer production during DOPA incubation, with or without inhibition of L‐aromatic‐amino‐acid decarboxylase or monoamine oxidase. Reserpine inhibited vesicular uptake by 95–97% and rapidly increased cell DOPAL content (p = 0.0008). Daidzein+AL1576 augmented DOPAL responses to reserpine (p = 0.004). Intracellular DOPAL contributed to dopamine‐evoked apoptosis and DOPA‐evoked synuclein dimerization. The findings fit with the ‘catecholaldehyde hypothesis,’ according to which decreased vesicular sequestration of cytosolic catecholamines and impaired catecholaldehyde detoxification contribute to the catecholaminergic denervation that characterizes Parkinson's disease.
Adolescent rats are resistant to adaptations in excitatory and inhibitory mechanisms that modulate mesolimbic dopamine during nicotine withdrawal
Authors: Natividad Luis A. , Buczynski Matthew W. , Parsons Loren H. , Torres Oscar V. , O'Dell Laura E.
Published: August 2012

Adolescent smokers report enhanced positive responses to tobacco and fewer negative effects of withdrawal from this drug than adults, and this is believed to propel higher tobacco use during adolescence. Differential dopaminergic responses to nicotine are thought to underlie these age‐related effects, as adolescent rats experience lower withdrawal‐related deficits in nucleus accumbens (NAcc) dopamine versus adults. This study examined whether age differences in NAcc dopamine during withdrawal are mediated by excitatory or inhibitory transmission in the ventral tegmental area (VTA) dopamine cell body region. In vivo microdialysis was used to monitor extracellular levels of glutamate and gamma‐aminobutyric acid (GABA) in the VTA of adolescent and adult rats experiencing nicotine withdrawal. In adults, nicotine withdrawal produced decreases in VTA glutamate levels (44% decrease) and increases in VTA GABA levels (38% increase). In contrast, adolescents did not exhibit changes in either of these measures. Naïve controls of both ages did not display changes in NAcc dopamine, VTA glutamate, or VTA GABA following mecamylamine. These results indicate that adolescents display resistance to withdrawal‐related neurochemical processes that inhibit mesolimbic dopamine function in adults experiencing nicotine withdrawal. Our findings provide a potential mechanism involving VTA amino acid neurotransmission that modulates age differences during withdrawal.
Size and sulfation are critical for the effect of heparin on APP processing and Aβ production
Authors: Cui Hao , Hung Amos C. , Freeman Craig , Narkowicz Christian , Jacobson Glenn A. , Small David H.
Published: August 2012

Alzheimer's disease is associated with abnormal accumulation of Aβ, which is produced from the β‐amyloid precursor protein (APP) by the β‐site APP‐cleaving enzyme (BACE1) and γ‐secretase. Our previous studies showed that heparin can decrease APP processing by decreasing the levels of BACE1 and ADAM10. In this study, we examined the effects of glycosaminoglycans (GAGs) on APP processing and Aβ production with the aim of understanding the specificity of the effects. Various GAG analogs were incubated with primary cortical cells derived from APP (SW)Tg2576 mice and the level of APP, proteolytic products of APP and APP‐cleavage enzymes were measured. The effect of GAGs on APP processing was both size‐ and sulfation‐dependent. 6‐O‐Sulfation was important for the effect on APP processing as heparin lacking 6‐O sulfate were less potent than native heparin. However, deletion of carboxyl groups on heparin had no significant effect on APP processing. Our studies suggest that there is structural specificity to the effect of GAGs on APP processing and that certain GAGs have a greater effect on Aβ production than others. This suggests that it might be possible to alter the structure of GAGs to achieve more specific inhibitors of APP processing that can cross the blood–brain barrier.
A horizon scanning assessment of current and potential future threats to migratory shorebirds
Authors: Sutherland William J. , Alves Jose A. , Amano Tatsuya , Chang Charlotte H. , Davidson Nicholas C. , Max Finlayson C. , Gill Jennifer A. , Gill Robert E. , González Patricia M. , Gunnarsson Tómas Grétar , Kleijn David , Spray Chris J. , Székely Tamás , Thompson Des B. A.
Published: August 2012

We review the conservation issues facing migratory shorebird populations that breed in temperate regions and use wetlands in the non‐breeding season. Shorebirds are excellent model organisms for understanding ecological, behavioural and evolutionary processes and are often used as indicators of wetland health. A global team of experienced shorebird researchers identified 45 issues facing these shorebird populations, and divided them into three categories (natural, current anthropogenic and future issues). The natural issues included megatsunamis, volcanoes and regional climate changes, while current anthropogenic threats encompassed agricultural intensification, conversion of tidal flats and coastal wetlands by human infrastructure developments and eutrophication of coastal systems. Possible future threats to shorebirds include microplastics, new means of recreation and infectious diseases. We suggest that this review process be broadened to other taxa to aid the identification and ranking of current and future conservation actions.
BD750, a benzothiazole derivative, inhibits T cell proliferation by affecting the JAK3/STAT5 signalling pathway
Authors: Liu Y , Yang T , Li H , Li M‐H , Liu J , Wang Y‐T , Yang S‐X , Zheng J , Luo X‐Y , Lai Y , Yang P , Li L‐M , Zou Q
Published: August 2012

Background and Purpose

A series of benzothiazole derivatives were screened for immunosuppressive activity; of these compounds BD750 was found to be the most effective immunosuppressant. The purpose of the current study was to determine the immunosuppressive activity of BD750 on T cell proliferation and its potential mode of action.

Experimental Approach

T cell proliferation, CD25 and CD69 expression and cell cycle distribution were measured in vitro by flow cytometry. Cell viability was determined by CCK‐8 assay. Cytokine levels were measured by elisa. The activation of signal‐regulated molecules was assessed by Western blot analysis. The effects of BD750 were evaluated in vivo in a mouse model of delayed‐type hypersensitivity.

Key Results

BD750 significantly inhibited mouse and human T cell proliferation, stimulated either by anti‐CD3/anti‐CD28 monoclonal antibodies or by an alloantigen, in a dose‐dependent manner in vitro. No obvious cytotoxic effects of BD750 were observed in our experimental conditions. Furthermore, BD750 did not inhibit CD25 and CD69 expression or IL‐2 and IL‐4 secretion, but induced cell cycle arrest at the G0/G1 phase in activated T cells. In IL‐2‐stimulated CTLL‐2 cells and primary activated T cells, BD750 inhibited cell proliferation and STAT5 phosphorylation, but not Akt or p70S6K phosphorylation. BD750 also reduced the T cell‐mediated delayed‐type hypersensitivity response in mice in a dose‐dependent manner.

Conclusion and Implications

These data indicate that BD750 inhibits IL‐2‐induced JAK3/STAT5‐dependent T cell proliferation. BD750 has the potential to be used as a lead compound for the design and development of new immunosuppressants for preventing graft rejection and treating autoimmune diseases.
Genome sizes of three species in the subtribe Carabina (Coleoptera: Carabidae)
Authors: Sota Teiji , Konuma Junji , Fujiwara Mayuki , Shoguchi Eiichi
Published: August 2012

Genome sizes of three species in the subtribe Carabina (Coleoptera: Carabidae: tribe Carabini) were estimated from nuclei of spermatozoa using a flow cytometry. The estimated haploid genome sizes were about 330 megabases (Mb) for Damaster blaptoides, about 280 Mb for Carabus uenoi and about 260 Mb for Carabus yamato.
Should the Model for Risk‐Informed Regulation be Game Theory Rather than Decision Theory?
Authors: Bier Vicki M. , Lin Shi‐Woei
Published: August 2012

Risk analysts frequently view the regulation of risks as being largely a matter of decision theory. According to this view, risk analysis methods provide information on the likelihood and severity of various possible outcomes; this information should then be assessed using a decision‐theoretic approach (such as cost/benefit analysis) to determine whether the risks are acceptable, and whether additional regulation is warranted. However, this view ignores the fact that in many industries (particularly industries that are technologically sophisticated and employ specialized risk and safety experts), risk analyses may be done by regulated firms, not by the regulator. Moreover, those firms may have more knowledge about the levels of safety at their own facilities than the regulator does. This creates a situation in which the regulated firm has both the opportunity—and often also the motive—to provide inaccurate (in particular, favorably biased) risk information to the regulator, and hence the regulator has reason to doubt the accuracy of the risk information provided by regulated parties. Researchers have argued that decision theory is capable of dealing with many such strategic interactions as well as game theory can. This is especially true in two‐player, two‐stage games in which the follower has a unique best strategy in response to the leader's strategy, as appears to be the case in the situation analyzed in this article. However, even in such cases, we agree with Cox that game‐theoretic methods and concepts can still be useful. In particular, the tools of mechanism design, and especially the revelation principle, can simplify the analysis of such games because the revelation principle provides rigorous assurance that it is sufficient to analyze only games in which licensees truthfully report their risk levels, making the problem more manageable. Without that, it would generally be necessary to consider much more complicated forms of strategic behavior (including deception), to identify optimal regulatory strategies. Therefore, we believe that the types of regulatory interactions analyzed in this article are better modeled using game theory rather than decision theory. In particular, the goals of this article are to review the relevant literature in game theory and regulatory economics (to stimulate interest in this area among risk analysts), and to present illustrative results showing how the application of game theory can provide useful insights into the theory and practice of risk‐informed regulation.
Real‐World Data on the Lifespan of Implantable Cardioverter‐Defibrillators Depending on Manufacturers and the Amount of Ventricular Pacing
Authors: HORLBECK FRITZ W. , MELLERT FRITZ , KREUZ JENS , NICKENIG GEORG , SCHWAB JOERG O.
Published: August 2012

Real‐World Data on the Lifespan of ICDs Introduction: Implantable cardioverter‐defibrillator (ICD) longevity is crucial for both patients and public health systems because it determines the number of surgical ICD replacements, which can generally be considered an additional risk factor for complications, and the cost‐effectiveness of ICD therapy. Our objective was to obtain insight into the “real‐world” longevities of implantable cardioverter‐defibrillators, which quite often differ from those stated in the manufacturers’ declarations.

Methods and Results: On the basis of a prospective database, we analyzed all ICD implantations performed in our hospital from June 1988 to June 2009. We studied 980 patients (follow‐up 58 ± 51 months) with 1,502 ICDs and all respective data until August 2010. We compared the percentage of still operating ICDs at different points in time in relation to manufacturers, types of device (single chamber 623, dual chamber 588, cardiac resynchronization therapy ICDs [CRT‐D] 291), and amount of right ventricular pacing (VP). We found distinct differences between the mean lifespans of ICDs of different manufacturers (Biotronik 4.3 years, Sorin 4.5 years, Guidant/Boston Scientific 4.7 years, St. Jude Medical 5 years, Medtronic 5.8 years). CRT‐D devices (hazard ratio [HR] 1.778, P = 0.0005) were associated with an elevated annual relative risk for device replacement while a decrease in the proportion of VP (HR 0.934 for each 10% decrease in VP, P < 0.0001) and Medtronic ICDs were associated with a reduced risk of device replacement (HR 0.544, P < 0.0001).

Conclusion: CRT‐Ds and an elevated percentage of VP are associated with a significantly elevated risk for device replacement, while Medtronic ICDs showed the longest lifespans. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1336‐1342, December 2012)
Arrhythmogenic Right Ventricular Cardiomyopathy 2012: Diagnostic Challenges and Treatment
Authors: MARCUS FRANK I. , ABIDOV AIDEN
Published: August 2012

ARVC 2012. The most common presentation of arrhythmogenic right ventricular cardiomyopathy (ARVC) is palpitations or ventricular tachycardia (VT) of left bundle branch morphology in a young or middle‐aged individual. The 12‐lead electrocardiogram may be normal or have T‐wave inversion beyond V1 in an otherwise healthy person who is suspected of having ARVC. The most frequent imaging abnormalities are an enlarged right ventricle, decrease in right ventricular (RV) function, and localized wall motion abnormalities. Risk factors for implantable cardioverter defibrillator include a history of aborted sudden death, syncope, young age, decreased left ventricular function, and marked decrease in RV function. Recent results of treatment with epicardial ablation are encouraging. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1149‐1153, October 2012)
“Better to Be Hot than Caught”: Excavating the Conflicting Roles of Migrant Material Culture
Authors: De León Jason
Published: August 2012

ABSTRACT  Since the mid‐1990s, heightened U.S. border security in unauthorized crossing areas near urban ports of entry has shifted undocumented migration toward remote regions such as the Sonoran Desert of Arizona, where security is more penetrable but crossing conditions are more difficult. Subsequently, a complex smuggling industry has developed in Northern Mexico that profits from helping migrants cross the desert on foot to enter the United States undetected. Desert crossing is now a well‐established social process whereby items such as dark clothes and water bottles have been adopted as tools used for subterfuge and survival by migrants. This article highlights ethnographic data on the experiences of migrants and archaeological data collected along the migrant trails that cross the Arizona desert to illustrate the routinized techniques and tools associated with the violent process of border crossing, as well as the dialectical and often oppressive relationship that exists between migrants and objects. [material culture, undocumented migration, border crossing, U.S.–Mexico, archaeology of the contemporary]
“We Have Been Sensitized”: Ex‐Combatants, Marginalization, and Youth in Postwar Sierra Leone
Authors: Bolten Catherine
Published: August 2012

ABSTRACT  Civilians in Makeni, Sierra Leone, describe their relationship with the ex‐combatants of the rebel RUF as a state of being “sensitized” to their presence. I argue that “sensitization” connotes civilians’acceptance of ex‐combatants living among them, while they refuse to incorporate ex‐combatants into the social order. Civilians, although treating the war as a “state of exception,” refuse to grant ex‐combatants the grace of belonging to this exceptional time. They question whether youth socialized to violence against elders ever belonged to the social world, thus the possibility of their reintegration is suspended. Ex‐combatants’ assertive demands for social acceptance, adoption of reintegration discourse and development practices, and disdain for “useful” work mark them apart from “mainstream” youth, rendering them socially and economically marginal. They are threatening not because of the war but because they represent the vanguard of youth who disdain manual labor and elder control, a long‐emergent social trend. [Sierra Leone, states of exception, ex‐combatants, youth, transitional justice]
Secondary review of external histopathology on cutaneous oncology patients referred for sentinel lymph node biopsy: how often does it happen and is it worth it?
Authors: Haws Bryn , Romain Paul St , Mammen Joshua , Fraga Garth R. 
Published: August 2012

Background

We reviewed the data on external histopathology review for patients referred to our institution for sentinel lymph node biopsy (SLNB) associated with melanoma, Merkel cell carcinoma and adnexal carcinoma.

Methods

We calculated the incidence of external histopathology review and the rate of discordance between internal and external histopathology diagnoses between January 1, 2010 and February 28, 2011. We conducted an anonymous poll of our community pathologists' experience with external histopathology review prior to SLNB. Financial charges and payments from 10 Medicare patients who underwent SLNB were obtained from our hospital's finance department.

Results

Sixty‐eight cases were identified (63 melanomas, 4 Merkel cell carcinomas and 1 spiradenocarcinoma). The external histopathology was reviewed as part of the patient's care in 14 of 68 cases. In 3 of 14 reviewed cases, SLNB was deemed unnecessary. Nine of eleven community pathologists reported reviewing external histopathology material in less than 11% SLNB patients in their hospitals. The average Medicare reimbursement for SLNB and secondary pathology review was $5738 and $80 respectively.

Conclusions

Our data show that review of external cutaneous histopathology diagnoses on patients referred for SLNB is uncommon in our practice area, but is cost‐effective and should be required to reduce unnecessary treatment.
Adult T‐cell leukemia/lymphoma with follicular mucinosis: an unusual histopathological finding and a commentary
Authors: Camp Brendan , Horwitz Steven , Pulitzer Melissa P.
Published: August 2012

Follicular mucinosis is currently recognized as a histopathological finding characterized by the accumulation of mucin within follicular epithelium and is commonly associated with follicular mycosis fungoides (MF). We report the finding of follicular mucinosis in a cutaneous nodule of human T‐lymphotropic virus type 1 (HTLV‐1) associated adult T‐cell leukemia/lymphoma (ATLL). The patient was a 69‐year‐old female of Caribbean descent with a history of ATLL who presented with erythematous nodules on the chest and abdomen. Histopathologic examination showed a pan‐dermal infiltrate of medium‐to‐large sized atypical lymphocytes extending into follicular epithelium where they associated with large mucin deposits. Immunohistochemical stains showed that the atypical lymphocytes were positive for CD3, CD4 and CD25 and negative for CD30. Cutaneous lesions of ATLL, which often present histopathologically as an epidermotropic lymphoma with Pautrier‐type collections, are often difficult to distinguish from MF. Until recently, lymphoma‐associated follicular mucinosis seemed specific to MF and Sézary syndrome (SS), being reported only once in a lesion of ATLL. We report a second case of ATLL‐associated follicular mucinosis to increase awareness of this possible association, and briefly review the literature of follicular mucinosis‐associated hematologic malignancies, ultimately cautioning against the interpretation of all cutaneous lymphoma‐related follicular mucinosis as MF/SS.
A visible response to an invisible tattoo
Authors: Tsang Matthew , Marsch Amanda , Bassett Katrina , High Whitney , Fitzpatrick James , Prok Lori
Published: August 2012

Invisible (or blacklight) tattoos are fast becoming the trend in the world of tattoo art, and with their rise comes the onset of associated complications. Though there have been many reports of cutaneous reactions to traditional tattoo pigments, literature regarding reactions to invisible tattoos is scarce. We report the case of a 28‐year‐old man who presented with an inflammatory eruption of 2 months' duration confined to the area of a recently placed invisible tattoo; the eruption was diagnosed as granulomatous dermatitis to a foreign material. Under fluorescent light, a refractile foreign material was identified in the biopsy specimen, which we believe to be melamine, one of the invisible tattoo's five ingredients. Previous cases of cutaneous reactions to invisible tattoos were attributed to polymethylmethacrylate, not a component of the tattoo in this case. To our knowledge, this is the first case implicating melamine as the cause of a granulomatous tattoo reaction. Given the rising popularity of invisible tattoos, we present this case to raise awareness of the risks associated with this alternative tattoo trend.
The effect of season on inflammatory response in captive baboons
Authors: McFarlane Dianne , Wolf Roman F. , McDaniel Kristen A. , White Gary L.
Published: August 2012

Introduction

Highly seasonal animals demonstrate predictable changes in immune function that coincide with changes in photoperiod. Little is known about the effect of season on immune response in baboons. The objective of this study was to determine the effect of season on inflammatory response in baboons.

Materials and Methods

Peripheral blood mononuclear cell cytokine response following immune stimulation and serum markers of inflammation were assessed during each season in two groups of young male baboons: one housed under natural light and one in a controlled environment of 12 hours light:12 hours dark.

Results

A seasonal immune rhythm was evident in both groups, with a greater TNF‐α and IL‐6 response to stimulation and serum CRP concentration in June and September compared with December.

Conclusions

Season is an important experimental confounder, and therefore, time of year should be controlled when designing studies and analyzing data from immune studies in baboons.