bluuebunny/crossref_metadata_2025 huggingface dataset:
New therapeutic options in metastatic castration-resistant prostate cancer: Can cost-effectiveness analysis help in treatment decisions?
Authors: Wilson Leslie , Tang Jun , Zhong Lixian , Balani Gregory , Gipson Gregory , Xiang Pin , Yu Dawn , Srinivas Sandy
Published: November 2013

Objective:

To evaluate the cost-effectiveness of abiraterone, cabazitaxel, and enzalutamide compared to placebo for treatment of metastatic castration-resistant prostate cancer.

Material and methods:

A decision-tree model compared three treatment options for metastatic castration-resistant prostate cancer patients over 18 months from a societal perspective in 2012 USD. Chance nodes included baseline pain as a severity indicator, significant adverse effects (neutropenia, cardiac events, or seizures), and survival. Probabilities, survival rates, and health utilities were from clinical trials (COU-AA, TROPIC, and AFFIRM) and other published studies. Survival of enzalutamide was adjusted to match placebo groups across trials. Probabilistic sensitivity analyses, acceptability curves and net benefit calculations were performed.

Results:

Abiraterone was the most cost-effective of the treatments ($123.4 K/quality-adjusted life year) compared to placebo, enzalutamide was $437.6 K/quality-adjusted life year compared to abiraterone, and cabazitaxel was $351.9 K/quality-adjusted life year compared to enzalutamide. Enzalutamide and cabazitaxel were not cost-effective compared to placebo at $154.3 K/quality-adjusted life year and $163.2 K/quality-adjusted life year, respectively. Acceptability curves showed abiraterone was cost-effective 29.3% of the time with a willingness to pay threshold of $100 K. The model was sensitive to changes in cost of the drugs, life expectancy, and survival rate. Sensitivity analysis shows that enzalutamide can become the most cost-effective option if the price of the medication decreased by 26% and other drug costs remained the same.

Conclusion:

Based on the cost-effective analysis, and survival adjustments necessary to match placebo groups, we would recommend abiraterone for treatment of metastatic castration-resistant prostate cancer despite not quite falling under the usually accepted willingness to pay threshold. Further analysis should examine comparative survival across the three drugs.
Incidence of cetuximab-related infusion reactions in oncology patients treated at the University of North Carolina Cancer Hospital
Authors: Keating Karen , Walko Christine , Stephenson Briana , O’Neil Bert H , Weiss Jared
Published: November 2013

Purpose

The primary purpose of this study was to determine the rate of infusion reactions to cetuximab in oncology patients treated at the University of North Carolina Cancer Hospital. Secondarily, we sought to evaluate predictors of grade 3–4 hypersensitivity, including geography.

Methods

Data were collected by retrospective chart review for patients treated with cetuximab at the University of North Carolina Cancer Hospital between 15 November 2006 and 31 December 2010. Data were analyzed for occurrence of hypersensitivity reaction in 125 patients with various cancer types.

Results

Of the 125 subjects, 31 (24.8%) experienced an infusion reaction of any grade. Of 125, 18 (14.4%) experienced a grade 3 or 4 reaction. The odds ratio for patients with an allergy history having a grade 3 or 4 reaction was 2.57 (95% CI 0.93 to 7.09, p = 0.07). Pretreatment with steroids was associated with absence of grade 3 or 4 reaction with an odds ratio of 0.21 (95% CI 0.05 to 0.83, p = 0.04). Mapping of reaction rates by county revealed higher rates in some of the more rural counties of North Carolina, however, statistical power was lacking.

Conclusions

Rates of hypersensitivity reaction at UNC are similar to rates seen in other areas of the southeastern United States and higher than in other regions of the United States and Europe. Rates of both hypersensitivity reactions and grade 3 to 4 hypersensitivity reactions have not substantially changed over time. Geography, allergy history, and perhaps smoking or cancer type may help predict who will react to cetuximab. Steroids should be strongly considered as premedication in addition to diphenhydramine.
How effects on party unity vary across votes
Authors: Stecker Christian
Published: November 2013

Our current knowledge of the causes of party unity rests heavily on the analysis of average unity scores of party groups from different countries. This study design invites two related problems: By aggregating unity scores we miss valuable variance at the level of disaggregated votes, and by comparing these aggregate scores across time and countries we might confound institutional effects with an unobserved case-specific selection bias of roll-call votes. In taking advantage of the laboratory-like conditions of the 16 sub-national parliaments of Germany and shifting the level of analysis to party unity in every single vote this article addresses both problems. Analysing 8607 unity scores, it is shown that the voting context is an important moderator of institutional effects on party unity. Specifically, it is shown that government status boosts party unity particularly within legislative important votes. Furthermore, the unity-boosting effect of slim majorities is only present for government parties and particularly strong when legislative consequential decisions are taken. Beyond that I also show that roll-call vote request, increasing ideological distances and norms of party loyalty increase party unity.
The uses of universalism. ‘Diversity Statistics’ and the race issue in contemporary France
Authors: Cervulle Maxime
Published: November 2013

In France, the emergence of the issue of ‘diversity’ since the 2000s has deeply renewed public debates around racial and ethnic discriminations. Tracing the debates that appeared in this context around ‘diversity statistics’ and the possibility of integrating racial and/or ethnic data in the national census, this essay aims at delineating the conflicting universalisms that shape different positions around a ‘race issue’ that France alternatively engages with and blissfully ignores. By tracking the trends and changes in public lexicons, in the mediated public sphere as well as in institutional language, through an approach inspired by E. Laclau and C. Mouffe’s Discourse Theory and S. Hall’s theory of articulation, it describes competing notions of citizenship in the French context and presents a critical analysis of the current public redefinitions of antidiscrimination policies.
Reading the faces of hunger: Disturbing images of child malnutrition in the World Press Photo competition
Authors: Mannevuo Mona
Published: November 2013

This article explores the images of starving children through a case study, the annual World Press Photo competition. The figure of a child in need is familiar from humanitarian discourses, but despite its familiar trope, it bears powerful affective meanings, especially in relation to the notions of innocence, vulnerability and futurity. In this study, the notions are discussed in the framework of five photographs of child malnutrition that were selected as the World Press Photo of the year in 1974, 1980, 1992, 2001, and 2005. The aim of this article is to discuss the complex and disturbing ways these photographs affect the viewer. While they invite the viewer to take part in a global project of constructing a better world, they also may hide difficult questions of global inequality and structural violence behind a series of individual events about personal suffering and loss.
In pursuit of pop culture: Reception of pop culture in the People’s Republic of Poland as opposition to the political system – Example of the science fiction fandom
Authors: Siuda Piotr
Published: November 2013

Researching the fans of pop culture texts, it is worth considering a direction that has been neglected in fan studies: the treatment of fan practices as opposition to the polity of a country. Such considerations are particularly crucial in the context of fan communities functioning in non-democratic countries. The author describes the conditions of reception of pop culture texts in Poland under communism. It was in this era that access to such transmissions was restricted, and since fans sought to get access to those rationed cultural assets, their reception ought to be viewed as a symbolic opposition to the politics of the country. The article illustrates this using the example of science fiction fans functioning in the 1980s. The mechanism that governs their community is discussed as exemplified by issues of the literary magazine Fantastyka between 1982 and 1989. The fans’ opposition to the political system has been presented as an escape from the everyday difficulties connected with functioning in a communist polity. The fans facing the conditions of the time strived to get their favourite texts and overcame some institutional obstacles connected with organising their activities.
Circulating social imaginaries: Theoretical and methodological reflections
Authors: Valaskivi Katja , Sumiala Johanna
Published: November 2013

In this introductory article for the special section on circulation, we examine the concept of circulation from theoretical and methodological perspectives. By drawing on media and social theory, we argue for the relevance of circulation in theorizing current on-the-move social dynamics. Three particular perspectives are introduced in this exercise: non-linearity, action and materiality. As a methodological tool, circulation refers to the tracking and tracing of social actions. In this article, we examine in particular the creation and maintenance of social imaginaries. Our context of analysis is contemporary highly media-saturated society. A case study on media circulation of the 2011 death of Apple CEO Steve Jobs illustrates our theoretical and methodological reflection.
Confidence game: Marketing well-being in economic surveys
Authors: Aronczyk Melissa
Published: November 2013

The recent global financial crisis has also been widely characterized as a massive crisis of confidence. This article examines how economic surveys of well-being are deployed to maintain confidence in market institutions and activities. It argues that these economic surveys, which are ostensibly designed to measure confidence, happiness and other states of subjective well-being, are in fact responsible for enacting confidence among its respondents and the general public. The article employs a framework of ‘marketization’, connecting this framework to broader cultural studies of economics and economies that focus on the ways in which markets and the context in which they are received are ‘made’. Economic surveys work to create confidence in the current economic system by positing that positive social and cultural attitudes toward market activity are not merely related to but are actually responsible for market growth. As such, these surveys accomplish a double objective: they maintain economic expertise, infrastructures and devices as legitimate and necessary; and they maintain the notion that economic growth is central to the maintenance of social welfare and progress. The article concludes that the inculcation of confidence among individuals and institutions precludes the task of reflecting on and recognizing the inadequacy of the current economic situation and diminishes the seeming necessity for political action and reform.
‘The fruits of my own labor’: A case study on clashing models of co-creativity in the new media landscape
Authors: Roig Antoni , San Cornelio Gemma , Sánchez-Navarro Jordi , Ardèvol Elisenda
Published: November 2013

This article deals with the engagement of new media users in specific forms of participatory content production, focusing on productive and labour aspects in co-creative endeavours. We present a case analysis of a community-based filmmaking software, Moviestorm, focused on a specific set of practices – modding – and following the controversy that took place when a shift in the company’s business model altered the rules that tacitly constituted modders’ practices, particularly the notion of control over their own labour. We pay attention to motivations and expected rewards expressed by both modders and the company as a part of a negotiation process around the ownership and the affective and economic value of user-generated content. Our central argument is that through the analysis of practices, particularly in moments of conflict and change, we can acquire a more subtle understanding of an economy of affections in co-creative processes as well as observing the clashing models of co-creativity, with different approaches to peer production and hierarchy.
Evaluation of total concentration and size distribution of bacterial and fungal aerosol in healthcare built environments
Authors: Nasir Zaheer Ahmad , Mula Viswanath , Stokoe Jane , Colbeck Ian , Loeffler Mark
Published: November 2013

This study aims to assess the levels and size distribution of airborne bacteria and fungi in two different types of orthopaedic theatres (conventionally ventilated and laminar flow), a general ward and outdoors in a hospital. The sampling was carried out with an Andersen six-stage viable impactor over a period of eight weeks. The highest mean concentration of total bacteria was found outdoors followed by the general ward, conventionally ventilated theatre and laminar flow theatre. With reference to Gram-negative bacteria, the general ward had the highest mean concentration followed by outdoors and the conventionally ventilated theatre. No Gram-negative bacteria were detected in the operating theatre with laminar flow. Similar to bacteria, the higher concentration of fungi was present outdoors and in the general ward as compared to the operation theatres. In general, higher concentrations were found in the conventionally ventilated theatre than the laminar flow theatre. In terms of size distribution, in the ward and outdoors the dominant bacteria, Gram-negative bacteria and fungi were in the size range of 3.3–4.7 µm or 2.1–3.3 µm. The bacterial concentrations in the conventionally ventilated operating theatre were mostly in coarse size fraction compared to fine fraction for the theatre with laminar flow.
Reflections on teaching ethnographic fieldwork: Building community participatory practices
Authors: Gioia Deborah
Published: November 2013

This article presents how the classical roots of ethnographic fieldwork can be considered and adapted when teaching ethnography in social work and public health courses. The experiential community engagement component of the course is discussed in-depth (with ten classroom examples), as well as how to enhance fieldwork skills through classroom activities, which Master's of Social Work (MSW) and Bachelor's of Social Work (BSW) students will need in preparation for entering the field. Students who have undergraduate experiences in ethnography with faculty mentors are often taught ‘how’ to use the elements of fieldwork but not the ‘why’ of the methods. Two books reviewed in this issue of the journal are viewed as exemplars for student learning and can be used in the classroom. Researcher reflection is highlighted as a necessary skill, and the need to consider the community as partners is essential for the design, rigor and understanding of classroom projects in ethnography.
Upstairs and Downstairs
Authors: Borooah Vani K.
Published: November 2013

Under cricket’s decision review system (DRS) a player may request a review of dismissal decisions taken by on-field umpires. Reviews of leg before wicket decisions, the focus of this article, occur through a ball-tracking technology popularly called “Hawk-Eye.” If Hawk-Eye makes mistakes, in the face of such errors, the overall error rate can be decomposed into a “technology error rate” and a “human error rate.” Consequently, improved decision can be achieved through better technology or better umpires. We argue that, given the costs of DRS, the same gains could be obtained, at lower cost, by investing in umpires rather than technology.
Coding the (Digital) Flows
Authors: Tiessen Matthew
Published: November 2013

In this article, I will engage the contested terrain of contemporary (online) transparency by looking at it through the lens of a “cultural studies of finance.” I will focus here especially on the conflicting but complementary tactics of technologically enhanced transparency and how it is being strategically mobilized by, on the one hand, an increasingly vocal macroeconomically informed and invested online community of bloggers and online activists (“econo-bloggers”) and, on the other hand, by one of the primary targets of their transparency-seeking attacks: the Federal Reserve (the Fed)—the central bank of the United States. I want to show how the transparency tactics being pursued by both parties at once conflict with and complement one another as both parties play the transparency game with the same objective: to win the monetary policy debate and thereby achieve a sort of monetarily significant ontological legitimacy. This legitimacy is premised upon a monopolization of the very nature of monetary “truth”: a form of truth that’s becoming increasingly important to control and manage in light of, for instance, recent economic catastrophes, the faith-based nature of contemporary credit- and fiat-based money, and ever-inflating commodity costs (e.g., gold and oil). But while both the econo-blogosphere and the Fed champion transparency-promoting agendas, their allegedly transparency-promoting tactics are not so much about getting at “objective” realities concerning money as they are about controlling the message. Transparency in this online macroeconomically inflected infowar is a tool used both offensively and defensively either to maintain or subvert status quo monetary policy; more prosaically, transparency—and the appeal to transparency as a sort of moral or ethical “good”—has today become a technologically necessitated public relations tool masquerading behind a veil of authenticity and unadulterated exposure.
Cardiovascular Function After Spinal Cord Injury
Authors: Ravensbergen Henrike J. C. (Rianne) , de Groot Sonja , Post Marcel W. M. , Slootman Hans J. , van der Woude Lucas H. V. , Claydon Victoria E.
Published: November 2013

Background. Autonomic dysfunction after spinal cord injury (SCI) is an under-researched area when compared with motor and sensory dysfunction. Cardiovascular autonomic dysfunction is a particular concern, leading to impaired control of blood pressure and heart rate. Objectives. (1) To determine the prevalence of hypotension in individuals with SCI during and after rehabilitation; (2) To investigate changes in cardiovascular variables during and after rehabilitation; (3) To evaluate the influence of personal and lesion characteristics on cardiovascular variables. Methods. Cardiovascular variables (resting systolic [SAP] and diastolic [DAP] arterial pressures and resting [HRrest] and peak heart rates [HRpeak]) were measured on 5 test occasions: start of inpatient rehabilitation, 3 months later, at discharge, and at 1 and 5 years after discharge. The time course and effects of personal and lesion characteristics on cardiovascular variables were studied using multilevel regression analyses. Results. The prevalence of hypotension was unchanged during rehabilitation and for 5 years after discharge. Odds for hypotension were highest in those with cervical and high thoracic lesions, younger individuals, and men. DAP increased during the 5 years after discharge. HRrest decreased during and after rehabilitation. SAP, DAP, HRrest, and HRpeak were lowest in those with cervical and high thoracic lesions. SAP and DAP increased with age; HRpeak decreased with age. Conclusions. These longitudinal data provide normative values for blood pressure and heart rate changes with time after injury according to lesion and personal characteristics. These results can be used to guide clinical practice and place changes in cardiovascular function caused by interventions in perspective.
Spatial and Temporal Asymmetries in Gait Predict Split-Belt Adaptation Behavior in Stroke
Authors: Malone Laura A. , Bastian Amy J.
Published: November 2013

Background. Step asymmetries during gait in persons after stroke can occur in temporal or spatial domains. Prior studies have shown that split-belt locomotor adaptation can temporarily mitigate these asymmetries. Objective. We investigated whether baseline gait asymmetries affected how patients adapt and store new walking patterns. Methods. Subjects with stroke and age-matched controls were studied walking at a 2:1 speed ratio on the split-belt during adaptation and assessed for retention of the learned pattern (the after-effect) with both belts at the same speed. Results. Those with stroke adapted more slowly ( P < .0001), though just as much as healthy older adults. During split-belt walking, the participants with stroke adapted toward their baseline asymmetry (eg, F = 14.02, P < .01 for step symmetry), regardless of whether the subsequent after-effects improved or worsened their baseline step asymmetries. No correlation was found between baseline spatial and temporal measures of asymmetry ( P = .38). Last, the initial spatial and temporal asymmetries predicted after-effects independently of one another. The after-effects in the spatial domain (ie, center of oscillation difference) are only predicted by center of oscillation difference baseline ( F = 15.3, P = .001), while all other parameters were nonsignificant (all Ps > .17). Temporal coordination (ie, phasing) after-effects showed a significant effect only from phasing baseline ( F = 26.92, P < .001, all others P > .33). Conclusion. This work demonstrates that stroke patients adapt toward their baseline temporal and spatial asymmetries of walking independently of one another. We define how a given split-belt training session would affect asymmetries in these domains, which must be considered when developing rehabilitation interventions for stroke patients.
The Relative Contribution of Physical and Cognitive Fall Risk Factors in People With Parkinson’s Disease
Authors: Paul Serene S. , Sherrington Catherine , Canning Colleen G. , Fung Victor S. C. , Close Jacqueline C. T. , Lord Stephen R.
Published: November 2013

Background. In order to develop multifaceted fall prevention strategies for people with Parkinson’s disease (PD), greater understanding of the impact of physical and cognitive performance on falls is required. Objective. We aimed to identify the relative contribution of a comprehensive range of physical and cognitive risk factors to prospectively-measured falls in a large sample of people with PD and develop an explanatory multivariate fall risk model in this group. Methods. Measures of PD signs and symptoms, freezing of gait, balance, mobility, proprioception, leg muscle strength, and cognition were collected on 205 community-dwelling people with PD. Falls were monitored prospectively for 6 months using falls diaries. Results. A total of 120 participants (59%) fell during follow-up. Freezing of gait ( P < .001), dyskinesia ( P = .02), impaired anticipatory and reactive balance ( P < .001), impaired cognition ( P = .002), reduced leg muscle strength ( P = .006), and reduced proprioception ( P = .04) were significantly associated with future falls in univariate analyses. Freezing of gait (risk ratio [RR] = 1.03, 95% confidence interval [CI] = 1.00-1.05, P = .02), impaired anticipatory (RR = 1.01, 95% CI = 1.00-1.02, P = .03) and reactive (RR = 1.26, 95% CI = 1.01-1.58, P = .04) balance, and impaired orientation (RR = 1.28, 95% CI = 1.01-1.62, P = .04) maintained significant associations with falls in multivariate analysis. Conclusion. The study findings elucidate important physical and cognitive determinants of falls in people with PD and may assist in developing efficacious fall prevention strategies for this high-risk group.
Excitatory Deep Transcranial Magnetic Stimulation With H-Coil Over the Right Homologous Broca’s Region Improves Naming in Chronic Post-stroke Aphasia
Authors: Chieffo Raffaella , Ferrari Federico , Battista Petronilla , Houdayer Elise , Nuara Arturo , Alemanno Federica , Abutalebi Jubin , Zangen Abraham , Comi Giancarlo , Cappa Stefano F. , Leocani Letizia
Published: November 2013

Background. The role of the right hemisphere in poststroke aphasia recovery is still controversial and the effects of repetitive transcranial magnetic stimulation (rTMS) over the right homologous Broca’s region have been seldom investigated. Objective. This study aimed to compare the effect of excitatory, inhibitory, and sham rTMS delivered with H-coil over the right inferior frontal gyrus in chronic aphasic patients. Methods. Five right-handed poststroke aphasic patients underwent a picture naming task before and immediately after each of 3 sessions of rTMS: excitatory (10 Hz), inhibitory (1 Hz), and sham rTMS, in random sequence and separated by at least 1 week. Results. Only the excitatory 10-Hz stimulation was associated with a significant improvement in naming performance ( P = .043) and was significantly more effective than 1-Hz rTMS ( P = .043). Conclusions. A single session of excitatory deep brain rTMS over the right inferior frontal gyrus with H-coil significantly improves naming in right-handed chronic poststroke aphasic patients. This result is in line with the hypothesis of a positive, rather than detrimental, role of the right hemisphere in chronic aphasia due to a left-hemispheric stroke.
Political interviews in public television and commercial broadcasters: A comparison
Authors: Roca-Cuberes Carles
Published: November 2013

In this article I examine the differences between broadcast political interviews in commercial and public service broadcasters in Spain. The study focuses in particular on political interviews broadcast on ‘morning show’ type programmes. The analysis distinguishes the characteristics that make up the news interview turn-taking system in order to explore the degree to which information and entertainment come together in political interviews broadcast on morning shows. The results show, primarily, that political interviews shown on public service broadcasters’ morning shows adhere to the journalistic standards of neutralism and adversarialness. This is precisely how they strive to make the politician publicly accountable. In political interviews broadcast by commercial broadcasters, however, these rules are followed intermittently. The aim of these interviews appears to be different: to penetrate politicians’ personal sphere with the discernible purpose of entertaining. These differences reflect different interview styles which, in turn, reveal different conceptions of journalism, politics and society. This investigation utilizes the research tools developed in conversation analysis (CA).
Magnetic Resonance Imaging Findings After Acute Patellar Dislocation in Children
Authors: Wilson Addison , Afarin Afshin , Shaw Corey , Shirley Eric , Pierce Jennifer , Slakey Joseph B.
Published: November 2013

Background:

Acute patellar dislocation (APD) is a common knee injury in children. The pattern and frequency of injury to the medial patellofemoral ligament (MPFL) is different in pediatric compared with adult populations.

Purpose:

To report on injury patterns sustained to the MPFL after APD in children and to determine whether predisposing factors for APD cited in adults hold true in the pediatric population.

Study Design:

Case series; Level of evidence, 4.

Methods:

Magnetic resonance imaging (MRI) studies were reviewed for 36 children sustaining APD. Evidence of injury to the MPFL was documented, and when the MPFL was torn, the location of tear was determined. Presence of trochlear dysplasia, patella alta, tibial tubercle–trochlear groove (TTTG) distance, and thickness of the lateral patellofemoral retinaculum (LPR) were recorded and correlated with MPFL tear.

Results:

Of the 36 patients sustaining APD, only 16 tore the MPFL. The location of MPFL tear was equally divided between the origin, the insertion, or both, with no case of midsubstance tear. There was a significant correlation identified between MPFL rupture and both LPR thickness greater than 3 mm and TTTG distance greater than 19 mm.

Conclusion:

The MPFL does not always tear in children who sustain APD, and the tear location is variable. A thickened LPR and increased TTTG distance predispose to MPFL tear.
Velocity Changes in the Extracranial Artery Examination After Arteriovenous Fistula Placement
Authors: Green Judi C.
Published: November 2013

As the population ages, sonographers will be required to do increasing numbers of examinations for patients undergoing dialysis. The hemodynamic changes that result from the placement of an arteriovenous fistula (AVF) or a dialysis access graft in the upper extremity can significantly influence the final diagnosis of an extracranial carotid arterial sonographic evaluation. The case study presented demonstrates the importance of obtaining a complete patient history on the resulting differential diagnosis.
Myosin IIA is critical for organelle distribution and F-actin organization in megakaryocytes and platelets
Authors: Pertuy Fabien , Eckly Anita , Weber Josiane , Proamer Fabienne , Rinckel Jean-Yves , Lanza François , Gachet Christian , Léon Catherine
Published: November 2013

Key Points

Myosin IIA deficiency affects F-actin structuration and organelle distribution in MKs which leads to abnormal platelet organelle content.
Mortalin and DJ-1 coordinately regulate hematopoietic stem cell function through the control of oxidative stress
Authors: Tai-Nagara Ikue , Matsuoka Sahoko , Ariga Hiroyoshi , Suda Toshio
Published: November 2013

Key Points

Mitochondrial heat shock protein, mortalin, is essential for the maintenance of HSCs via the control of oxidative stress. Mortalin directly interact with DJ-1 to regulate ROS levels in the mitochondria of HSCs.
Blood stem cell fate regulation by Delta-1–mediated rewiring of IL-6 paracrine signaling
Authors: Csaszar Elizabeth , Wang Weijia , Usenko Tatiana , Qiao Wenlian , Delaney Colleen , Bernstein Irwin D. , Zandstra Peter W.
Published: November 2013

Key Points

The Notch ligand Delta-1 reduces membrane bound IL-6R expression, inhibiting IL-6 cis-signaling and the production of myeloid cells. Combined with a dynamically fed culture system that minimizes IL-6 trans-signaling, Delta-1 produces rapid and sustained HSC engraftment.
The planarian regeneration transcriptome reveals a shared but temporally shifted regulatory program between opposing head and tail scenarios
Authors: Kao Damian , Felix Daniel , Aboobaker Aziz
Published: November 2013

Background

Planarians can regenerate entire animals from a small fragment of the body. The regenerating fragment is able to create new tissues and remodel existing tissues to form a complete animal. Thus different fragments with very different starting components eventually converge on the same solution. In this study, we performed an extensive RNA-seq time-course on regenerating head and tail fragments to observe the differences and similarities of the transcriptional landscape between head and tail fragments during regeneration.

Results

We have consolidated existing transcriptomic data for S. mediterranea to generate a high confidence set of transcripts for use in genome wide expression studies. We performed a RNA-seq time-course on regenerating head and tail fragments from 0 hours to 3 days. We found that the transcriptome profiles of head and tail regeneration were very different at the start of regeneration; however, an unexpected convergence of transcriptional profiles occurred at 48 hours when head and tail fragments are still morphologically distinct. By comparing differentially expressed transcripts at various time-points, we revealed that this divergence/convergence pattern is caused by a shared regulatory program that runs early in heads and later in tails.

Additionally, we also performed RNA-seq on smed-prep(RNAi) tail fragments which ultimately fail to regenerate anterior structures. We find the gene regulation program in response to smed-prep(RNAi) to display the opposite regulatory trend compared to the previously mentioned share regulatory program during regeneration. Using annotation data and comparative approaches, we also identified a set of approximately 4,800 triclad specific transcripts that were enriched amongst the genes displaying differential expression during the regeneration time-course.

Conclusion

The regeneration transcriptome of head and tail regeneration provides us with a rich resource for investigating the global expression changes that occurs during regeneration. We show that very different regenerative scenarios utilize a shared core regenerative program. Furthermore, our consolidated transcriptome and annotations allowed us to identity triclad specific transcripts that are enriched within this core regulatory program. Our data support the hypothesis that both conserved aspects of animal developmental programs and recent evolutionarily innovations work in concert to control regeneration.
Identification and characterization of the three homeologues of a new sucrose transporter in hexaploid wheat (Triticum aestivum L.)
Authors: Deol Kirandeep K , Mukherjee Shalini , Gao Feng , Brûlé-Babel Anita , Stasolla Claudio , Ayele Belay T
Published: November 2013

Background

Sucrose transporters (SUTs) play important roles in regulating the translocation of assimilates from source to sink tissues. Identification and characterization of new SUTs in economically important crops such as wheat provide insights into their role in determining seed yield. To date, however, only one SUT of wheat has been reported and functionally characterized. The present study reports the isolation and characterization of a new SUT, designated as TaSUT2, and its homeologues (TaSUT2A, TaSUT2B and TaSUT2D) in hexaploid wheat (Triticum aestivum L.).

Results

TaSUT2A and TaSUT2B genes each encode a protein with 506 amino acids, whereas TaSUT2D encodes a protein of 508 amino acids. The molecular mass of these proteins is predicted to be ~ 54 kDA. Topological analysis of the amino acid sequences of the three homeologues revealed that they contain 12 transmembrane spanning helices, which are described as distinct characteristic features of glycoside-pentoside-hexuronide cation symporter family that includes all known plant SUTs, and a histidine residue that appears to be localized at and associated conformationally with the sucrose binding site. Yeast SUSY7/ura3 strain cells transformed with TaSUT2A, TaSUT2B and TaSUT2D were able to uptake sucrose and grow on a medium containing sucrose as a sole source of carbon; however, our subcellular localization study with plant cells revealed that TaSUT2 is localized to the tonoplast. The expression of TaSUT2 was detected in the source, including flag leaf blade, flag leaf sheath, peduncle, glumes, palea and lemma, and sink (seed) tissues. The relative contributions of the three genomes of wheat to the total expression of TaSUT2 appear to differ with tissues and developmental stages. At the cellular level, TaSUT2 is expressed mainly in the vein of developing seeds and subepidermal mesophyll cells of the leaf blade.

Conclusion

This study demonstrated that TaSUT2 is a new wheat SUT protein. Given that TaSUT2 is localized to the tonoplast and sucrose is temporarily stored in the vacuoles of both source and sink tissues, our data imply that TaSUT2 is involved in the intracellular partitioning of sucrose, particularly between the vacuole and cytoplasm.
Effects of a combination of amlodipine and imipenem on 42 clinical isolates of Acinetobacter baumannii obtained from a teaching hospital in Guangzhou, China
Authors: Li Yu jun , Pan Chu zhi , Zhao Zi wen , Zhao Zhu xiang , Chen Hui ling , Lu Wei bo
Published: November 2013

Background

The clonal spread of Acinetobacter baumannii is a global problem, and carbapenems, such as imipenem, remain the first-choice agent against A. baumannii. Using synergy to enhance the antibiotic activity of carbapenems could be useful. Here, amlodipine (AML) was tested alone and with imipenem against A. baumannii isolates.

Methods

Forty-two isolates of A. baumannii were collected. Multilocus sequence typing (MLST) assessed the genetic relationship of the isolates. The resistance phenotypes were determined using disc diffusion. The minimum inhibitory concentrations (MICs) of the drugs were determined by broth microdilution. The combined effects of the drugs were determined by a checkerboard procedure. Metallo-β-lactamase (MBL) was determined using the MBL Etest.

Results

Forty-two A. baumannii isolates were collected from 42 patients who were mostly older than 65 years and had long inpatient stays (≥7 days). A. baumannii was mostly recovered from the respiratory system (N = 35, 83.3%). Most patients (N = 27, 64.3%) received care in intensive care units (ICUs). Disc diffusion testing demonstrated that A. baumannii susceptibility to polymyxin B was 100%, while susceptibility to other antimicrobial agents was less than 30%, classifying the isolates into 10 MDR and 32 XDR strains. MLST grouped the A. baumannii isolates into 4 existing STs and 6 new STs. STn4 carried allele G1, with a T → C mutation at nt3 on the gpi111 locus. STn5 carried allele A1, possessing A → C mutations at nt156 and nt159 on the gltA1 locus. ST195 and ST208 accounted for 68.05% (29/42) of the isolates. Clonal relation analysis showed that ST195 and ST208 belonged to clonal complex (CC) 92. The inhibitory concentration of imipenem ranged from 0.5 to 32 μg/ml, and that of AML ranged from 40 to 320 μg/ml. In combination, the susceptibility rate of A. baumannii isolates increased from 16.7% to 54.8% (P = 0.001). In the checkerboard procedure, half of the isolates (N = 21, 50.0%) demonstrated synergy or partial synergy with the drug combination. The MBL Etest revealed that 1 A. baumannii strain (N = 1, 2.4%) produced MBL.

Conclusions

CC92 was the major clone spreading in our hospital. AML improved the activity of imipenem against A. baumannii isolates in vitro but did not inhibit MBL.
Pattern of HIV testing and multiple sexual partnerships among men who have sex with men in China
Authors: Chow Eric P F , Jing Jun , Feng Yuji , Min Dai , Zhang Jun , Wilson David P , Zhang Xiaohu , Zhang Lei
Published: November 2013

Background

Men who have sex with men (MSM) are a hidden but emerging population susceptible to HIV infection against a background of rapidly increasing HIV prevalence in China. Low HIV testing levels and multiple partnerships among MSM are two major contributing factors to HIV transmission.

Methods

We conducted a cross-sectional survey among 447 Chinese MSM in Changsha and Tianjin cities from November to December 2011 using an anonymous questionnaire. We aim to investigate (1) the trend of HIV testing rates among Chinese MSM during 2009 to 2011; and (2) the patterns of multiple sexual relationships with male, female and commercial partners.

Results

The self-reported past-12-months HIV testing level among Chinese MSM increased from 16.6% in 2009 to 46.3% in 2010 and 58.6% in 2011 (χ2 = 173.49, p < 0.001). Compared with men who have tested for HIV, the never-tested MSM were generally younger, never married, students, and more likely to have unprotected anal intercourse with non-commercial male partners. Furthermore, 21.3% (56/263) MSM reported having multiple regular male and female sexual partnerships and 6.2% (16/257) reported having commercial male partners in the past six months. However, individuals who were never-tested for HIV are consistently less likely to engage in multiple sexual relationships.

Conclusions

HIV testing rates have increased substantially among Chinese MSM in the period 2009–2011, although significant barriers to testing remain. Multiple sexual partnerships, and especially bisexual behaviours, are common among Chinese MSM.
Prevalence of chronic kidney disease across levels of glycemia among adults in Pudong New Area, Shanghai, China
Authors: Zhou Yi , Echouffo-Tcheugui Justin B , Gu Jian-jun , Ruan Xiao-nan , Zhao Gen-ming , Xu Wang-hong , Yang Li-ming , Zhang Hong , Qiu Hua , Narayan K M Venkat , Sun Qiao
Published: November 2013

Background

Few population-based studies have examined the relationship between glycemic status and chronic kidney disease (CKD) in China. We examined the prevalence of CKD across categories of glycemia [diagnosed diabetes, undiagnosed diabetes (fasting plasma glucose [FPG] ≥ 126 mg/dL), prediabetes (FPG 100–126 mg/dL) and normal glycemia (FPG <100 mg/dL)] among Chinese adults and assessed the relative contribution of dysglycemia (prediabetes and/or diabetes) to the burden of CKD.

Methods

5,584 Chinese adults aged 20–79 years were selected from the Pudong New Area of Shanghai through a multistage random sampling. Demographic and lifestyle characteristics, anthropometry and blood pressure were measured. Biochemical assays included FPG, serum creatinine and lipids, urinary creatinine and albumin. Prevalence of albuminuria [urine albumin-to-creatinine ratio (ACR) ≥ 30 mg/g], decreased kidney function and CKD (either decreased kidney function or albuminuria) across levels of glycemia were estimated.

Results

The prevalence of albuminuria, decreased kidney function and CKD each increased with higher glycemic levels (P < 0.001). Based on the MDRD Study equation, the unadjusted CKD prevalence was 30.9%, 28.5%, 14.1% and 9.2% in those with diagnosed diabetes, undiagnosed diabetes, prediabetes and normoglycemia, respectively. The corresponding age-, gender- and hypertension-adjusted CKD prevalence were 25.8%, 25.0%, 12.3% and 9.1%, respectively. In a multivariable analysis, the factors associated with CKD were hypertension (Odds ratio [OR] 1.70, 95% confidence interval [CI]: 1.42-2.03), dysglycemia (OR 1.65, 95% CI: 1.39-1.95), female gender (OR 1.48, 95% CI: 1.25-1.75), higher triglycerides (OR 1.14, 95% CI: 1.08-1.20 per mmol/L), higher body mass index (OR 1.08, 95% CI: 1.05-1.10 per kg/m2), and older age (OR 1.02, 95% CI: 1.01 -1.03 per year). The population attributable risks (PARs) associated with diabetes, prediabetes, dysglycemia (diabetes and prediabetes) and hypertension were 18.4%, 19.7%, 30.3% and 44.5% for CKD as defined by the MDRD study equation, and 15.8%, 24.4%, 29.2% and 10.0% with the CKD-EPI equation. Estimates of prevalence and ORs of the relative contribution of various risk factors to CKD obtained with the CKD-EPI equation were similar.

Conclusions

As much as 30% of the CKD burden may be associated with dysglycemia among Chinese adults, independent of age, gender and hypertension status. Prevention and control of diabetes and prediabetes should be a high priority in reducing the CKD burden in China.
Performance on the Frontal Assessment Battery is sensitive to frontal lobe damage in stroke patients
Authors: Kopp Bruno , Rösser Nina , Tabeling Sandra , Stürenburg Hans Jörg , de Haan Bianca , Karnath Hans-Otto , Wessel Karl
Published: November 2013

Background

The Frontal Assessment Battery (FAB) is a brief battery of six neuropsychological tasks designed to assess frontal lobe function at bedside [Neurology 55:1621-1626, 2000]. The six FAB tasks explore cognitive and behavioral domains that are thought to be under the control of the frontal lobes, most notably conceptualization and abstract reasoning, lexical verbal fluency and mental flexibility, motor programming and executive control of action, self-regulation and resistance to interference, inhibitory control, and environmental autonomy.

Methods

We examined the sensitivity of performance on the FAB to frontal lobe damage in right-hemisphere-damaged first-ever stroke patients based on voxel-based lesion-behavior mapping.

Results

Voxel-based lesion-behavior mapping of FAB performance revealed that the integrity of the right anterior insula (BA13) is crucial for the FAB global composite score, for the FAB conceptualization score, as well as for the FAB inhibitory control score. Furthermore, the FAB conceptualization and mental flexibility scores were sensitive to damage of the right middle frontal gyrus (MFG; BA9). Finally, the FAB inhibitory control score was sensitive to damage of the right inferior frontal gyrus (IFG; BA44/45).

Conclusions

These findings indicate that several FAB scores (including composite and item scores) provide valid measures of right hemispheric lateral frontal lobe dysfunction, specifically of focal lesions near the anterior insula, in the MFG and in the IFG.
Identification of the IGF1/PI3K/NF κB/ERK gene signalling networks associated with chemotherapy resistance and treatment response in high-grade serous epithelial ovarian cancer
Authors: Koti Madhuri , Gooding Robert J , Nuin Paulo , Haslehurst Alexandria , Crane Colleen , Weberpals Johanne , Childs Timothy , Bryson Peter , Dharsee Moyez , Evans Kenneth , Feilotter Harriet E , Park Paul C , Squire Jeremy A
Published: November 2013

Background

Resistance to platinum-based chemotherapy remains a major impediment in the treatment of serous epithelial ovarian cancer. The objective of this study was to use gene expression profiling to delineate major deregulated pathways and biomarkers associated with the development of intrinsic chemotherapy resistance upon exposure to standard first-line therapy for ovarian cancer.

Methods

The study cohort comprised 28 patients divided into two groups based on their varying sensitivity to first-line chemotherapy using progression free survival (PFS) as a surrogate of response. All 28 patients had advanced stage, high-grade serous ovarian cancer, and were treated with standard platinum-based chemotherapy. Twelve patient tumours demonstrating relative resistance to platinum chemotherapy corresponding to shorter PFS (< eight months) were compared to sixteen tumours from platinum-sensitive patients (PFS > eighteen months). Whole transcriptome profiling was performed using an Affymetrix high-resolution microarray platform to permit global comparisons of gene expression profiles between tumours from the resistant group and the sensitive group.

Results

Microarray data analysis revealed a set of 204 discriminating genes possessing expression levels which could influence differential chemotherapy response between the two groups. Robust statistical testing was then performed which eliminated a dependence on the normalization algorithm employed, producing a restricted list of differentially regulated genes, and which found IGF1 to be the most strongly differentially expressed gene. Pathway analysis, based on the list of 204 genes, revealed enrichment in genes primarily involved in the IGF1/PI3K/NF κB/ERK gene signalling networks.

Conclusions

This study has identified pathway specific prognostic biomarkers possibly underlying a differential chemotherapy response in patients undergoing standard platinum-based treatment of serous epithelial ovarian cancer. In addition, our results provide a pathway context for further experimental validations, and the findings are a significant step towards future therapeutic interventions.