bluuebunny/crossref_metadata_2025 huggingface dataset:
A cellular genome-wide association study reveals human variation in microtubule stability and a role in inflammatory cell death
Authors: Salinas Raul E. , Ogohara Cassandra , Thomas Monica I. , Shukla Kajal P. , Miller Samuel I. , Ko Dennis C.
Published: October 2013

Pyroptosis is proinflammatory cell death that occurs in response to certain microbes. Activation of the protease caspase-1 by molecular platforms called inflammasomes is required for pyroptosis. We performed a cellular genome-wide association study (GWAS) using Salmonella typhimurium infection of human lymphoblastoid cell lines as a means of dissecting the genetic architecture of susceptibility to pyroptosis and identifying unknown regulatory mechanisms. Cellular GWAS revealed that a common human genetic difference that regulates pyroptosis also alters microtubule stability. An intergenic single-nucleotide polymorphism on chromosome 18 is associated with decreased pyroptosis and increased expression of TUBB6 (tubulin, β 6 class V). TUBB6 is unique among tubulin isoforms in that its overexpression can completely disrupt the microtubule network. Cells from individuals with higher levels of TUBB6 expression have lower microtubule stability and less pyroptosis. Reducing TUBB6 expression or stabilizing microtubules pharmacologically with paclitaxel (Taxol) increases pyroptosis without affecting the other major readout of caspase-1 activation, interleukin-1β secretion. The results reveal a new role for microtubules and possibly specific tubulin isoforms in the execution of pyroptosis. Furthermore, the finding that there is common diversity in TUBB6 expression and microtubule stability could have broad consequences for other microtubule-dependent phenotypes, diseases, and pharmacological responses.
Substrate stiffness regulates solubility of cellular vimentin
Authors: Murray Maria E. , Mendez Melissa G. , Janmey Paul A.
Published: October 2013

The intermediate filament protein vimentin is involved in the regulation of cell behavior, morphology, and mechanical properties. Previous studies using cells cultured on glass or plastic substrates showed that vimentin is largely insoluble. Although substrate stiffness was shown to alter many aspects of cell behavior, changes in vimentin organization were not reported. Our results show for the first time that mesenchymal stem cells (hMSCs), endothelial cells, and fibroblasts cultured on different-stiffness substrates exhibit biphasic changes in vimentin detergent solubility, which increases from nearly 0 to 67% in hMSCs coincident with increases in cell spreading and membrane ruffling. When imaged, the detergent-soluble vimentin appears to consist of small fragments the length of one or several unit-length filaments. Vimentin detergent solubility decreases when these cells are subjected to serum starvation, allowed to form cell–cell contacts, after microtubule disruption, or inhibition of Rac1, Rho-activated kinase, or p21-activated kinase. Inhibiting myosin or actin assembly increases vimentin solubility on rigid substrates. These data suggest that in the mechanical environment in vivo, vimentin is more dynamic than previously reported and its assembly state is sensitive to stimuli that alter cellular tension and morphology.
Characteristics of community-onset NDM-1-producing Klebsiella pneumoniae isolates
Authors: Kim So Yeon , Rhee Ji-Young , Shin Sang Yop , Ko Kwan Soo
Published: October 2013

Multilocus sequence typing and in vitro antimicrobial susceptibility testing were performed for three community-onset New Delhi metallo-β-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae isolates from Korea. The genetic structure surrounding the bla
NDM-1 gene was determined in bla
NDM-1-harbouring plasmids. Three NDM-1-producing K. pneumoniae isolates were found to belong to the same clone (sequence type 340). Each of these isolates showed the same genetic structure surrounding the bla
NDM-1 gene. The genes bla
NDM-1, ble
MBL, trpF and dsbC were flanked by two intact insertion sequences, ISAba125 and IS26, which may promote horizontal gene transfer. The bla
NDM-1-harbouring plasmids conferred antimicrobial resistance to carbapenems, cephalosporins, aminoglycosides and aztreonam in transconjugants. It can be speculated that either the entire bla
NDM-1-harbouring plasmids or just the part of the plasmid containing the bla
NDM-1 gene may have transferred between K. pneumoniae and Escherichia
coli. Following the transfer, the isolate disseminated throughout Korea. This study suggests the need for monitoring the dissemination of NDM-1-producing isolates across countries or continents due to their potential transferability via ISAba125- and IS26-associated transposons.
Contribution of Gag and protease to variation in susceptibility to protease inhibitors between different strains of subtype B human immunodeficiency virus type 1
Authors: Sutherland Katherine A. , Mbisa Jean L. , Cane Patricia A. , Pillay Deenan , Parry Chris M.
Published: October 2013

Recent reports have shown that human immunodeficiency virus type 1 (HIV-1) Gag can directly affect susceptibility to protease inhibitors (PIs) in the absence of known resistance mutations in protease. Inclusion of co-evolved Gag alongside protease in phenotypic drug susceptibility assays can alter PI susceptibility in comparison with protease with a WT Gag. Using a single-replication-cycle assay encompassing full-length Gag together with protease we demonstrated significant variation in PI susceptibility between a number of PI-naïve subtype B viruses. Six publicly available subtype B molecular clones, namely HXB2, NL4-3, SF2, YU2, JRFL and 89.6, displayed up to nine-fold reduced PI susceptibility in comparison with the assay reference strain. For two molecular clones, YU2 and JRFL, Gag contributed solely to the observed reduction in susceptibility, with the N-terminal region of Gag contributing significantly. Gag and protease from treatment-naïve, patient-derived viruses also demonstrated significant variation in susceptibility, with up to a 17-fold reduction to atazanavir in comparison with the assay reference strain. In contrast to the molecular clones, protease was the main determinant of the reduced susceptibility. Common polymorphisms in protease, including I13V, L63P and A71T, were shown to contribute to this reduction in PI susceptibility, in the absence of major resistance mutations. This study demonstrated significant variation in PI susceptibility of treatment-naïve patient viruses, and provided further evidence of the independent role of Gag, the protease substrate and in particular the N-terminus of Gag in PI susceptibility. It also highlighted the importance of considering co-evolved Gag and protease when assessing PI susceptibility.
A hydrogen-bonded ribbon in 6-amino-3-methyl-5-nitroso-2-(pyrrolidin-1-yl)pyrimidin-4(3H)-one monohydrate and hydrogen-bonded sheets in 6-amino-2-dimethylamino-3-methyl-5-nitrosopyrimidin-4(3H)-one monohydrate. Corrigendum
Authors: Orozco Fabían , Insuasty Braulio , Cobo Justo , Glidewell Christopher
Published: October 2013

The permanent address of one of the authors in the paper by Orozcoet al.[Acta Cryst.(2009), C65, o549–o552] is corrected.
A novel one-dimensional copper(II) coordination polymer and a trinuclear nickel(II) complex with a one-dimensional hydrogen-bonded structure
Authors: Chen Xiao-Hua , Chen Shun-Yu , Xie Chun-Ling , Wu Qiong-Jie
Published: October 2013

In the CuIIcompoundcatena-poly[[copper(II)-μ-[2-({2-[2-(naphthalen-2-yloxy)-1-oxidoethylidene]hydrazin-1-ylidene}methyl)phenolato]] dimethylformamide monosolvate monohydrate], {[Cu(C19H14N2O3)]·C3H7NO·H2O}n, (I), the CuIIcation isO,N,O′-chelated by one ligand and furtherN,O-chelated by a second ligand, and exhibits a distorted square-pyramidal coordination environment. The ligand acts as an overall pentadentate bridge between two metal ions, thus forming a novel coordination polymer. In the trinuclear NiIIcompound diaquabis(1H-imidazole)bis[μ-2-oxido-N′-(1-oxido-2-phenoxyethylidene)benzohydrazidato]trinickel(II) dimethylformamide tetrasolvate, [Ni3(C15H11N2O4)2(C3H4N2)2(H2O)2]·4C3H7NO, (II), the three NiIIcations are directly linked by twotransdiazine (N—N) bridges and are strictly collinear by symmetry. The central NiIIcation, located on an inversion centre, is coordinated by two water O atoms and is furtherN,O-chelated by two 2-oxido-N′-(1-oxido-2-phenoxyethylidene)benzohydrazidate(3−) ligands in an elongated octahedral coordination geometry. The two terminal centrosymmetrically related NiIIcations are coordinated by an imidazole ligand andO,N,O′-chelated by a hydrazidate ligand in a distorted square-planar coordination geometry. Hydrogen bonds link individual molecules of (II) into a chain along [100].
Achieving “One-Web” through customization and prioritization
Authors: Shaari Nassiriah , Charters Stuart , Churcher Clare
Published: October 2013

Purpose

– Accessing web sites from mobile devices has been gaining popularity but may often do not give the same results and experiences as accessing them from a personal computer. The paper aims to discuss these issues.

Design/methodology/approach

– To address these issues, the paper presents a server-side adaptation approach to prioritising adaptive pages to different devices through prioritisation system. The prioritisation approach allows users to prioritise page items for different devices. The prioritisation engine reorders, shows, and removes items based on its priority set by users or developers.

Findings

– With this approach, the overall web page's structure is preserved and the same terminology, content, and similar location of content are delivered to all devices. A user trial and a performance test were conducted. Results show that adaptive page and prioritisation provides a consistent and efficient web experience across different devices.

Originality/value

– The approach provides advantages over both client-side and proxy and has conducted significant experimentation to determine the applicability and effectiveness of the approach.
A comparison framework for service-oriented software engineering approaches
Authors: Baghdadi Youcef
Published: October 2013

Purpose

– Many service-oriented software engineering (SOSE) methods from industry and academia claim their compliance with SOA and SO, but there is a lack of framework to assess the existing methods or to provide new ones. First, the paper questions: (Q1) to what extent an approach would consider the three aspect: service, composition, and management to deliver software solutions that are conformed to SO and SOA principles; (Q2) to what extent an approach would consider the aggregates of a method, including representation techniques, assisting tools, and inspection techniques to assess the delivered solution (service and composition), in addition to the process; and (Q3) to what extent an approach would consider the alignment of business and IT through the application of model-driven development by using standards such as model-driven architecture. Then, the paper compares four generic approaches: top-down, bottom-up, green-field, and meet-in-the-middle, within a framework, to highlight their strengths and weaknesses. Finally, the paper aims to propose a business-oriented approach that focuses on the value a business can add to its customers, whereby the value must be specified in a contract to be largely re-used.

Design/methodology/approach

– This work develops a framework as an abstract model for SOSE generic methods. Then, it uses the framework as an analytical study to compare the generic methods and come up with research issues and a new method for SOSE.

Findings

– A set of guidelines that a SOSE method develops should consider when selecting or developing a new method.

Research limitations/implications

– Comparison of existing SOSE methods within the findings of the proposed framework. The paper has theoretical implications as the open issues provide a research roadmap towards the realization of SOA in accordance with a maturity model.

Practical implications

– This has practical implications as it: provides a better understanding of the approaches, as they are ambiguously used by the existing methods; and assists developers in deciding an approach having the necessary knowledge related to its process, strengths and weaknesses.

Originality/value

– None of the existing comparison framework has raised the level of abstraction up to generic methods such as top-down, green-filed, meet-in-the-middle and bottom-up.
Compliant multi-fingered passively adaptive robotic gripper
Authors: Petkovic´ Dalibor , D. Pavlovic´ Nenad
Published: October 2013

Purpose

– The paper aims to discuss a new design methodology for multi-fingered robotic grippers.

Design/methodology/approach

– Optimization of the compliant mechanism with underactuation.

Findings

– A new robotic gripper principle without active control.

Originality/value

– Design of multi-fingered robotic gripper as a monolithic structure without joints.
Social media provides a megaphone for organizations intent on shaping the corporate environment
Authors: Mark R. Kennedy Hon.,
Published: October 2013

Purpose

– The author offers a leaders' guide to managing relations with “shapeholders” the political, regulatory, media and activist actors in the firm's operating environment that shape, constrain, or expand a firm's opportunities and raise certain risks.

Design/methodology/approach

– The author, a former US congressman, shows how companies can adopt a program of analysis, foresight and preparation, and successfully engage shapeholders to advance mutual goals and preempt open conflict.

Findings

– The author warns that seeking unjustified advantage for your company or industry often trades transient benefits for long-term risks and reduced standing in seeking a level playing field in international markets.

Practical implications

– The author suggests several practical preparation techniques, citing the need to train for a rapid response to shapeholder pressures in today's hyper-connected world. When a controversy goes viral on social media, it's too late to debate options, policy and tactics.

Originality/value

– Leaders can use the author's WinWin Shapeholders Decision Matrix and other models introduced in the article to analyze and prepare for shapeholder interactions in advance.
Landscape scale variation in nectar amino acid and sugar composition in a Lepidoptera pollinated orchid species and its relation with fruit set
Authors: Gijbels Pieter , Van den Ende Wim , Honnay Olivier
Published: October 2013

Understanding landscape scale variation in reproductive and pollination success is a major aim of plant population biology. A potential determinant of reproductive success that has received surprisingly little attention so far is variation in nectar chemical composition across plant individuals and populations. Using theLepidoptera pollinated fragrant orchid (Gymnadenia conopsea) as a model species, we aimed at providing a first account of landscape scale variation in nectar amino acid and sugar composition, its environmental drivers, and how it may affect plant fruit set.

Nectar was sampled from 986 flowers from 296 individuals across eleven discrete populations of theG. conopsea. The proportions of sugars and amino acids were determined using high‐performance anion‐exchange chromatography. Nectar composition was related to soil characteristics of the populations, and to fruit set, using linear mixed models.

Approximately, 20% of the variance in nectar traits was situated between populations, whereas the highest proportion of variance (c. 45%) was found among flowers within individuals. Soil carbon and nitrogen content affected both nectar concentration and composition. Furthermore, fruit set ofG. conopseaindividuals was found to be significantly related to nectar amino acid and sugar composition.

Synthesis. These results show that landscape scale variation in nectar amino acid and sugar composition should be taken into account in future studies of plant reproductive success. Furthermore, there is also high within‐plant variation in both nectar amino acid and sugar composition. This variation may reduce geitonogamous pollination, but it may also limit rapid pollinator‐mediated selection on nectar composition.
Supply Elasticity and the Housing Cycle of the 2000s
Authors: Davidoff Thomas
Published: October 2013

There is no evidence that differences in supply elasticity caused cross‐sectional variation among U.S. housing markets in the severity of the 2000s housing cycle. This is true in three sets of empirical specifications: a first that assumes identical demand changes in the 2000s across markets, a second that proxies for supply elasticity and demand changes in the 2000s with estimates based on price and quantity changes in the 1980s and a third that uses physical and regulatory constraints to proxy for supply elasticity and uses state fixed effects to capture variation in demand conditions.
Relationship between platelet volume indices with macrovascular and peripheral neuropathy complications in type 2 diabetic patients (2型糖尿病患者血小板容积参数与大血管及外周神经并发症的相关性研究)
Authors: Xiao Wenjin , Huang Yun , Dong Jixiang , Zhang Xiaoyan , Hu Ji
Published: October 2013

Background

The relationship of platelet volume indices including mean platelet volume (MPV) and platelet distribution width (PDW) with carotid intima‐media thickness (IMT) as well as vibration perception threshold (VPT) was investigated in type 2 diabetic patients.

Methods

A total of 500 type 2 diabetic patients (298 male, 202 female) were enrolled. Clinical and laboratory data were collected from hospital records.

Results

Both MPV and PDW were significantly associated with carotid IMT, after adjustment for confounding factors including age, systolic blood pressure, total cholesterol and creatinine (0.833 ± 0.029 mm vs 0.955 ± 0.030 mm; 0.839 ± 0.029 mm vs 0.955 ± 0.030 mm; P = 0.0015 and P = 0.022, respectively). Agreed with carotid IMT analysis results, significant association was found between PDW and VPT as tertiles (15.760 ± 1.091V vs 20.187 ± 1.094V, P = 0.016). In multivariable analysis, both MPV and PDW were significantly associated with VPT (P = 0.021 and P = 0.007, respectively). However, only PDW, but not MPV, was significantly associated with carotid IMT (P = 0.002).

Conclusions

These findings implied the predictive value of platelets volume indices in vascular and peripheral neuropathy complications in type 2 diabetes.
Part 1: MRI features of focal nodular hyperplasia with an emphasis on hepatobiliary contrast agents
Authors: Sutherland Tom , Seale Melanie , Yap Kelvin
Published: October 2013

Focal nodular hyperplasia (FNH) is the second most common benign liver tumour and typically do not require any treatment. An accurate non‐invasive diagnosis is therefore vital to avoid unnecessary intervention and to reassure patients. This article discusses the demographics and pathology of FNH and reviews the appearance of FNH at MRI using liver‐specific contrast agents.
A Primary Cause of Partisanship? Nomination Systems and Legislator Ideology
Authors: McGhee Eric , Masket Seth , Shor Boris , Rogers Steven , McCarty Nolan
Published: October 2013

Many theoretical and empirical accounts of representation argue that primary elections are a polarizing influence. Likewise, many reformers advocate opening party nominations to nonmembers as a way of increasing the number of moderate elected officials. Data and measurement constraints, however, have limited the range of empirical tests of this argument. We marry a unique new data set of state legislator ideal points to a detailed accounting of primary systems in the United States to gauge the effect of primary systems on polarization. We find that the openness of a primary election has little, if any, effect on the extremism of the politicians it produces.
Astaxanthin modulates osteopontin and transforming growth factor β1 expression levels in a rat model of nephrolithiasis: a comparison with citrate administration
Authors: Alex Manju , Sauganth Paul M.V. , Abhilash M. , Mathews Varghese V. , Anilkumar T.V. , Nair R. Harikumaran
Published: October 2013

Objectives

To evaluate the effect of astaxanthin on renal angiotensin‐I converting enzyme (ACE) levels, osteopontin (OPN) and transforming growth factor β1 (TGF‐β1) expressions and the extent of crystal deposition in experimentally induced calcium oxalate kidney stone disease in a male Wistar rat model.

To compare the efficacy of astaxanthin treatment with a currently used treatment strategy (citrate administration) for kidney stones.

Materials and Methods

The expression of OPN was assessed by immunohistochemistry. One step reverse transcriptase polymerase chain reaction followed by densitometry was used to assess renal OPN and TGF‐β1 levels.

Renal ACE levels were quantified by an enzyme‐linked immunosorbent assay method.

Crystal deposition in kidney was analysed by scanning electron microscopic (SEM)‐energy‐dispersive X‐ray (EDX).

Results

The renal ACE levels and the expression of OPN and TGF‐β1 were upregulated in the nephrolithiasis‐induced rats.

Astaxanthin treatment reduced renal ACE levels and the expression OPN and TGF‐β1.

SEM‐EDX analysis showed that crystal deposition was reduced in the astaxanthin‐treated nephrolithiatic group.

Astaxanthin treatment was more effective than citrate administration in the regulation of renal ACE levels, OPN and TGF‐β1 expressions.

Conclusions

Astaxanthin administration reduced renal calcium oxalate crystal deposition possibly by modulating the renal renin‐angiotensin system (RAS), which reduced the expression of OPN and TGF‐β1 levels.

Astaxanthin administration was more effective than citrate treatment in reducing crystal deposition and down‐regulating the expression of OPN and TGF‐β1.
Type IV sensitizations in physical therapists: Patch test results of the Information Network of Departments of Dermatology (IVDK) 2007–2011
Authors: Girbig Maria , Hegewald Janice , Seidler Andreas , Bauer Andrea , Uter Wolfgang , Schmitt Jochen
Published: October 2013

Background

Physical therapists frequently come in contact with materials that can potentially cause skin irritation and/or allergies. Nevertheless analyses of professionally relevant sensitization patterns are currently lacking.

Patients and methods

A descriptive analysis of the patch test results from the Information Network of Departments of Dermatology (IVDK) was carried out considering patients employed full‐time as physical therapists during the years 2007–2011. Information includes dermatologic diagnoses, possible contact substances and cofactors as well as the “hit list” of the most common allergens.

Results

Among the patients (n = 134) the most common diagnoses (1st and 2nd) were allergic contact dermatitis (23.9 %), chronic irritant dermatitis (17.2 %) and atopic dermatitis (19.4 %). In 80 of the 134 patients (59.7 %), the skin lesions were located on the hands. In 62 (46.3 %) of the cases, skin disease was considered work‐related. The contact with cosmetics, creams, disinfectants, topical medications and the use of gloves were relevant as putative triggering factors for the respondents. The most common allergens were nickel (II) sulfate (16.5 %), fragrance mix (12.2 %) and fragrance mix II (13.0 %).

Conclusions

In this first comprehensive study of contact allergies among physical therapists in German‐speaking countries, a link between skin disease and work was felt likely in nearly 50 % of the tested cohort. To which extent the results shown in this work can be confirmed and which consequences these have for occupational preventive measures should be examined in additional, preferably longitudinal studies.
A historical case of amelogenesis imperfecta: Giovanna of Austria, Grand Duchess of Tuscany (1547–1578)
Authors: Giuffra Valentina , Panetta Daniele , Salvadori Piero A. , Fornaciari Gino
Published: October 2013

The skeletal remains of Giovanna of Austria (1547–1578), daughter of the Emperor Ferdinand I of Habsburg (1503–1564) and first wife of the Grand Duke of Tuscany, Francesco I (1541–1587), exhumed from the Basilica of San Lorenzo in Florence, were submitted to paleopathological study. Examination of the dentition, which was in a good state of preservation, showed maxillary retrognathism, together with a caries lesion, moderate periodontal disease, malposition of the upper second premolars and tooth wear. Furthermore, several horizontal grooves were observed in both the buccal and the lingual crown surfaces of almost all teeth, especially the anterior ones. The orthopantomogram showed hypomineralized enamel and alveolar bone loss. Two third‐molar teeth were investigated using micro‐computed tomography (micro‐CT) analysis, revealing highly irregular enamel caps with reduced average thickness. The observed features suggest a diagnosis of hypoplastic amelogenesis imperfecta, a developmental condition affecting enamel formation.
Soil and crop response to stover removal from rainfed and irrigated corn
Authors: Kenney Ian , Blanco‐Canqui Humberto , Presley Deann R. , Rice Charles W. , Janssen Keith , Olson Brian
Published: October 2013

Excessive corn (Zea mays L.) stover removal for biofuel and other uses may adversely impact soil and crop production. We assessed the effects of stover removal at 0, 25, 50, 75, and 100% from continuous corn on water erosion, corn yield, and related soil properties during a 3‐year study under irrigated and no‐tillage management practice on a Ulysses silt loam at Colby, irrigated and strip till management practice on a Hugoton loam at Hugoton, and rainfed and no‐tillage management practice on a Woodson silt loam at Ottawa in Kansas, USA. The slope of each soil was <1%. One year after removal, complete (100%) stover removal resulted in increased losses of sediment by 0.36–0.47 Mg ha−1 at the irrigated sites, but, at the rainfed site, removal at rates as low as 50% resulted in increased sediment loss by 0.30 Mg ha−1 and sediment‐associated carbon (C) by 0.29 kg ha−1. Complete stover removal reduced wet aggregate stability of the soil at the irrigated sites in the first year after removal, but, at the rainfed site, wet aggregate stability was reduced in all years. Stover removal at rates ≥ 50% resulted in reduced soil water content, increased soil temperature in summer by 3.5–6.8 °C, and reduced temperature in winter by about 0.5 °C. Soil C pool tended to decrease and crop yields tended to increase with an increase in stover removal, but 3 years after removal, differences were not significant. Overall, stover removal at rates ≥50% may enhance grain yield but may increase risks of water erosion and negatively affect soil water and temperature regimes in this region.
Characteristics and determinants of T‐cell phenotype normalization in HIV‐1‐infected individuals receiving long‐term antiretroviral therapy
Authors: Ndumbi P , Gillis J , Raboud J , Cooper C , Hogg RS , Montaner JSG , Burchell AN , Loutfy MR , Machouf N , Klein MB , Tsoukas C ,   The Canadian Observational Cohort (CANOC) Collaboration
Published: October 2013

Objectives

Although combination antiretroviral therapy (cART) can restore CD4 T‐cell numbers in HIV infection, alterations in T‐cell regulation and homeostasis persist. We assessed the incidence and predictors of reversing these alterations with cART.

Methods

ART‐naïve adults (n = 4459) followed within the Canadian Observational Cohort and exhibiting an abnormal T‐cell phenotype (TCP) prior to cART initiation were studied. Abnormal TCP was defined as having (1) a low CD4 T‐cell count (< 532 cells/μL), (2) lost T‐cell homeostasis (CD3 < 65% or > 85%) or (3) CD4:CD8 ratio dysregulation (ratio < 1.2). To thoroughly evaluate the TCP, CD4 and CD8 T‐cell percentages and absolute counts were also analysed for a median duration of 3.14 years [interquartile range (IQR) 1.48–5.47 years]. Predictors of TCP normalization were assessed using adjusted Cox proportional hazards models.

Results

At baseline, 96% of pateints had CD4 depletion, 32% had lost homeostasis and 99% exhibited ratio dysregulation. With treatment, a third of patients had normalized CD4 T‐cell counts, but only 85 individuals (2%) had normalized their TCP. In a multivariable model adjusted for age, measurement frequency and baseline regimen, higher baseline CD4 T‐cell counts and time‐dependent viral suppression independently predicted TCP normalization [hazard ratio (HR) for baseline CD4 T‐cell count = 1.42 (1.31–1.54) per 100 cells/μL increase; P ≤ 0.0001; HR for time‐dependent suppressed viral load = 3.69 (1.58–8.61); P‐value ≤ 0.01].

Conclusions

Despite effective cART, complete TCP recovery occurred in very few individuals and was associated with baseline CD4 T‐cell count and viral load suppression. HIV‐induced alterations of the TCP are incompletely reversed by long‐term ART.
Expanded HIV testing in high‐prevalence areas in England: results of a 2012 audit of sexual health commissioners
Authors: Hartney T , Kennedy I , Crook P , Nardone A
Published: October 2013

Objectives

The aim of the study was to examine whether UK HIV testing guidelines which recommend the expansion of HIV testing in high HIV prevalence areas have been implemented in England.

Methods

An online survey tool was used to conduct an audit of sexual health commissioners in 40 high HIV prevalence areas (diagnosed prevalence > 2 per 1000) between May and June 2012. Responders were asked to provide details of expanded HIV testing programmes that they had commissioned in nontraditional settings and perceived barriers and facilitators involved in introducing expanded testing.

Results

The response rate was 88% (35 of 40). Against the key audit standards, 31% (11 of 35) of areas had commissioned routine testing of new registrants in general practice, and 14% (five of 35) routine testing of general medical admissions. The majority of responders (80%; 28 of 35) had commissioned some form of expanded testing, often targeted at risk groups. The most common setting for commissioning of testing was the community (51%; 18 of 35), followed by general practice (49%; 17 of 35) and hospital departments (36%; 13 of 35). A minority (11%; four of 35) of responders had commissioned testing in all three settings. Where testing in general practice took place this was typically in a minority of practices (median 10–20%). Most (77%; 27 of 35) expected the rate of HIV testing to increase over the next year, but lack of resources was cited as a barrier to testing by 94% (33 of 35) of responders.

Conclusions

Not all high HIV prevalence areas in England have fully implemented testing guidelines. Scale‐up of existing programmes and continued expansion of testing into new settings will be necessary to achieve this.
Factors Associated with Sex Hormones and Erectile Dysfunction in Male Taiwanese Participants with Obesity
Authors: Shi Ming-Der , Chao Jian-Kang , Ma Mi-Chia , Hao Lyh-Jyh , Chao I.-Chen
Published: October 2013

Introduction

Obesity has been receiving an increasing amount of attention recently, but investigations regarding the potential impact of obesity, sexual behaviors, and sex hormones on erectile dysfunction (ED) in men have not completely clarified the association.

Aim

To identify the relationship between ED, sexual behavior, sexual satisfaction, sex hormones, and obesity in older adult males in Taiwan.

Methods

Data were obtained from a baseline survey of 476 older adult males (≧40 years old). Their demographic data, body mass index (BMI), sex hormones, sexual desire, sexual satisfaction, and ED status were assessed.

Main Outcome Measures

The International Index of Erectile Function-5 (IIEF-5), Sexual Desire Inventory (SDI), and Sexual Satisfaction Scale (SSS) were used to assess ED, sexual desire, and sexual satisfaction.

Results

In all, 476 men were available for analysis. The mean age of the sample was 51.34 ± 7.84 years (range 40 to 70 years). The IIEF total score had a mean of 19.44 ± 4.98; 264 (55.5%) subjects had ED, 250 (52.9%) were currently obese (BMI ≧27), and 297 (62.4%) had metabolic syndrome. The results showed an increased risk of ED among obese men and subjects with lower levels of sex hormones and lower sexual desire. Testosterone levels were lower in subjects with obesity (P < 0.001). Among the predictors of ED, obesity (odds ratio [OR] = 1.62, 95% CI = 1.07–2.44, P = 0.021), abnormal high sensitivity C-reactive protein (hs-CRP) (OR = 10.59, 95% CI = 4.70–23.87, P < 0.001), and lower serum full testosterone (OR = 3.27, 95% CI = 2.16–4.93, P < 0.001) were significantly independent factors.

Conclusions

This study supports the idea of a close relationship between low levels of sex hormones, sexual desire, sexual satisfaction, obesity, and ED, and also shows that low free testosterone and hs-CRP may predict ED, even in obese populations.
Hepatitis B and survival after renal transplant: meta‐analysis of observational studies
Authors: Fabrizi F. , Dixit V. , Martin P. , Messa P.
Published: October 2013

Recent evidence has been accumulated suggesting that HBsAg seropositive status is significantly linked to lower patient and graft survival after renal transplant even if conflicting data on this point exist. The aim of this study was to conduct a systematic review of the published medical literature concerning the impact of HBV surface antigen seropositive status on all‐cause mortality and graft loss after RT. The relative risk of all‐cause mortality and graft loss was regarded as the most reliable outcome end‐point. Study‐specific relative risks were weighted by the inverse of their variance to obtain fixed‐ and random‐effect pooled estimates for mortality and graft loss with HBsAg across the published studies. We identified ten observational studies involving 82 690 unique renal transplant recipients. The summary estimate for adjusted relative risk (aRR) of all‐cause mortality was 2.214 with a 95% confidence interval (CI) of 1.56; 3.137 (P < 0.0001); heterogeneity statistics, Ri = 0.98 (P‐value by Q‐test = 0.0001). The overall estimate for adjusted RR of all‐cause graft loss was 1.44 (95% CI, 1.26; 1.63) (P < 0.0001) and heterogeneity statistics, Ri = 0.05 (P‐value by Q‐test = 0.4). Stratified analysis changed marginally the results. Meta‐regression showed that diabetes mellitus had a detrimental role on patient survival (P = 0.02). This meta‐analysis of observational studies supports the notion that HBsAg‐positive patients after RT have an increased risk of mortality and graft loss. The mechanisms underlying the relationship between HBsAg and mortality or graft dysfunction after renal transplant are an area of avid research.
Wavelet Denoising of TSD Deflection Slope Measurements for Improved Pavement Structural Evaluation
Authors: Katicha Samer Wehbe , Flintsch Gerardo , Bryce James , Ferne Brian
Published: October 2013

Continuous deflection devices (CDDs) can safely measure pavement deflection (or other related properties) while traveling at highway speed, which reduces traffic disruption. CDD measurements are contaminated with relatively high noise levels compared to stop‐and‐go devices such as the Falling Weight Deflectometer. In this article, we use wavelet transform denoising to remove the noise and estimate the true deflection slope measurements obtained from the Traffic Speed Deflectometer. Results show that failure to denoise deflection slope measurements can lead to calculated Effective Structural Number values that are highly variable (unstable). Attempting to filter these highly variable measurements can lead to erroneous results. We also use wavelet transform denoising to identify localized weak spots such as those that are caused by pavement reflection cracking. Identifying weak spots with wavelets is possible because wavelets are spatially adaptive to local features. In contrast, a linear filter is not capable of adapting to local features.
Network Model for Rural Roadway Tolling with Pavement Deterioration and Repair
Authors: Saha Promothes , Liu Ruoyu , Melson Christopher , Boyles Stephen D.
Published: October 2013

The objective of roadway tolling in rural areas is often tied to revenue generation for roadway maintenance. Thus, rural pricing models should directly incorporate a pavement deterioration and maintenance model. However, the interactions between these models are not simple, because tolls cause traffic diversion, which in turn affects deterioration rates and forecasted revenue. This article describes a rural pricing model which calculates diversion endogenously with a network assignment model. This model captures deterioration rates and pavement condition in the toll‐setter's objective function, maximizing long‐run net present value of the highway infrastructure. A novel deterioration model is used which is particularly suitable for computational efficiency. The resulting model is discontinuous and nondifferentiable, and involves solving a combinatorial knapsack problem as a subproblem. Thus, a simulated annealing‐based algorithm is presented to solve it, in the framework of a new solution method built upon partitioning the feasible region. A demonstration is made using a network representing the state of Wyoming (28 zones, 60 nodes, and 188 links). Sensitivity analyses reveal that although the locations for optimal tolling are relatively stable as demand changes, the revenue collected can vary substantially. Relatively simple models are used throughout for computational reasons, and future research should investigate strategies for incorporating more advanced pavement and network models.
Voice and Expressivity in Free Indirect Thought Representations: Imitation and Representation
Authors: BLAKEMORE DIANE
Published: October 2013

This article addresses issues in the philosophy of fiction from the perspective of a relevance theoretic approach to communication: first, how should we understand the notion of ‘voice’ as it is used in the analysis of free indirect style narratives; and, second, in what sense can the person responsible for free indirect representations of fictional characters' thoughts be regarded as a communicator?

The background to these questions is the debate about the roles of pretence and attribution in free indirect style. I argue that the role of expressives in sustaining the illusion that fictional characters speak their inner thoughts suggests that ‘voice’ should be understood in two distinct ways. On the one hand, there are cases in which the use of expressive devices leads to the formation of thoughts which are understood to resemble other (attributed) thoughts. On the other hand, there are other cases in which expressives are used as a means of simulating a fictional character's behaviour or style.

At the same time, I argue that in order to accommodate free indirect thought representation in a relevance theoretic model of communication, the responsibility for ensuring that the effort of processing the text will be rewarded by optimal relevance must be decoupled from the point of view that is being represented. While the (constructed) author is responsible for orchestrating our interpretation of free indirect thought representations so that the effort of processing will result in optimal relevance, the reader does not necessarily assume this function is being performed by someone who intends to communicate their own thoughts: the relevance of the act of narration may instead lie in the sense of mutuality achieved between reader and character.
Two Types of Implicature: Material and Behavioural
Authors: JARY MARK
Published: October 2013

This article argues that what Grice termed ‘particularized conversational implicatures’ can be divided into two types. In some cases, it is possible to reconstruct the inference from the explicit content of the utterance to the implicature without employing a premise to the effect that that the speaker expressed that content (by means of an utterance). I call these ‘material implicatures’. Those whose reconstruction relies on a premise about the speaker's verbal behaviour, by contrast, I call ‘behavioural implicatures’. After showing that the division is theoretically significant, I ask whether current pragmatic theory is able to accommodate it. I conclude that, while (neo)‐Gricean pragmatics cannot do so straightforwardly, the distinction is already implicit in Relevance Theory. The article ends by considering the question of whether, in the light of previous discussion, speaker meaning really is always an instance of non‐natural meaning.
Nursing and human freedom
Authors: Risjord Mark
Published: October 2013

Debates over how to conceptualize the nursing role were prominent in the nursing literature during the latter part of the twentieth century. There were, broadly, two schools of thought. Writers likeHenderson andOrem used the idea of a self‐care deficit to understand the nurse as doing for the patient what he or she could not do alone. Later writers found this paternalistic and emphasized the importance of the patient's free will. This essay uses the ideas of positive and negative freedom to explore the differing conceptions of autonomy which are implicit in this debate. The notion of positive freedom has often been criticized as paternalistic, and the criticisms of self‐care in the nursing literature echo criticisms from political philosophy. Recent work on relational autonomy and on the relationship between autonomy and identity are used to address these objections. This essay argues for a more nuanced conception of the obligation to support autonomy that includes both positive (freedomto) and negative (freedomfrom) dimensions. This conception of autonomy provides a moral foundation for conceptualizing nursing in something like Henderson's terms: as involving the duty to expand the patient's capacities. The essay concludes by generalizing the lesson. Respect for autonomy on the part of any health care provider requires both respect for the patient's choices and a commitment to expand the patient's ability to actualize their choices.
Contemporary nursing wisdom in theUKand ethical knowing: difficulties in conceptualising the ethics of nursing
Authors: Newham Roger , Curzio Joan , Carr Graham , Terry Louise
Published: October 2013

This paper's philosophical ideas are developed from a General Nursing Council for England and Wales Trust‐funded study to explore nursing knowledge and wisdom and ways in which these can be translated into clinical practice and fostered in junior nurses. Participants using Carper's (1978) ways of knowing as a framework experienced difficulty conceptualizing a link between the empirics and ethics of nursing. The philosophical problem is how to understandpraxisas a moral entity with intrinsic value when so much of value seems to be technical and extrinsic depending on desired ends. Using the Aristotelian termspoesisandpraxiscan articulate the concerns that the participants as well as Carper (1978) and Dreyfus (in Flyvbjerg, 1991) among others share that certain actions or ways of knowing important for nursing are being devalued and deformed by the importance placed on quantitative data and measurable outcomes. The sense ofpraxisis a moralized one and most of what nurses do is plausibly on any account of normative ethics a morally good thing; the articulation of the idea ofpraxiscan go some way in showing how it is a part of the discipline of nursing. Nursing's acts aspoesiscan be a part of how practitioners come to havepraxisasphronesisor practical wisdom. So to be a wise nurse, one needs be a wise person.
Motor control, habits, complex motor stereotypies, and Tourette syndrome
Authors: Singer Harvey S.
Published: October 2013

Tourette syndrome (TS) and primary complex motor stereotypies (CMS) are two relatively common, distinctly different movement disorders of childhood. Despite their frequency, the precise underlying pathophysiological mechanism(s) for tics and stereotypies remains unknown. Both are likely to involve cortical–striatal–thalamo–cortical (CSTC) pathways or their interconnecting brain regions. In recent studies, distinct, separate cortical–striatal pathways have been identified for goal‐directed and habitual behavioral activity with important influences from structures, such as the hippocampus, amygdala, dorsolateral prefrontal cortex, cerebellum, ventral tegmental area, and substantia nigra pars compacta. Determining the specific site of abnormality within these circuits remains an active area of research. At the synaptic level, numerous neurotransmitters are involved in the transmission of messages through CSTC pathways, and many have been proposed as potential pathophysiological mechanisms. Which, if any, transmitter is the primary pathological factor in TS and primary CMS remains to be definitively determined.
Food industry: friend or foe?
Authors: Yach D.
Published: October 2013

Open discourse and tolerance between the food industry and public sector is limited. As a result, the public and private sectors are reluctant to collaborate on pressing nutritional issues. Those in the public sector have never heard what they could do to encourage a food company's transition towards healthier foods and beverages, whereas many in the private sector dismissed policies and actions initiated within the public sector. During my career, I have sought to engage the broadest possible stakeholder groups required to develop evidence‐based policies and with the aim of improving public health. My recent experience in industry confirmed my view about the need for scientific exchange regardless of the disagreements about policy. Open discourse and partnering is essential if we are to tackle complex food and health issues and improve the global food system. Private–public engagement can provide faster and more sustainable results than government alone without impacting profits. Moreover, a high‐quality product in smaller portions will have higher profit margins than a bargain‐sized product of lower quality. The food industry and private sector must come together to implement innovative strategies to address urgent nutritional needs.
Modeling the Adenoma and Serrated Pathway to Colorectal CAncer (ASCCA)
Authors: Greuter Marjolein J. E. , Xu Xiang‐Ming , Lew Jie‐Bin , Dekker Evelien , Kuipers Ernst J. , Canfell Karen , Meijer Gerrit A. , Coupé Veerle M. H.
Published: October 2013

Several colorectal cancer (CRC) screening models have been developed describing the progression of adenomas to CRC. Currently, there is increasing evidence that serrated lesions can also develop into CRC. It is not clear whether screening tests have the same test characteristics for serrated lesions as for adenomas, but lower sensitivities have been suggested. Models that ignore this type of colorectal lesions may provide overly optimistic predictions of the screen‐induced reduction in CRC incidence. To address this issue, we have developed the Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) model that includes the adenoma‐carcinoma pathway and the serrated pathway to CRC as well as characteristics of colorectal lesions. The model structure and the calibration procedure are described in detail. Calibration resulted in 19 parameter sets for the adenoma‐carcinoma pathway and 13 for the serrated pathway that match the age‐ and sex‐specific adenoma and serrated lesion prevalence in the COlonoscopy versus COlonography Screening (COCOS) trial, Dutch CRC incidence and mortality rates, and a number of other intermediate outcomes concerning characteristics of colorectal lesions. As an example, we simulated outcomes for a biennial fecal immunochemical test screening program and a hypothetical one‐time colonoscopy screening program. Inclusion of the serrated pathway influenced the predicted effectiveness of screening when serrated lesions are associated with lower screening test sensitivity or when they are not removed. To our knowledge, this is the first model that explicitly includes the serrated pathway and characteristics of colorectal lesions. It is suitable for the evaluation of the (cost)effectiveness of potential screening strategies for CRC.