bluuebunny/crossref_metadata_2025 huggingface dataset:
Transnational Tamil networks: Mapping engagement opportunities on the Web
Authors: Kumar Priya
Published: November 2012

This article focuses on the Tamil diaspora in the context of virtual networks. Contemporary linkages stem from decades of civil unrest within Sri Lanka. The Tamil community has found much unity in perceived injustices and marginalization following a violent mass exodus during the 1980s. Quests for political validation and statehood in North-East Sri Lanka have transferred to virtual platforms. Subsequent networks are both sophisticated and dynamic, proactively transcending borders, propelling transnational linkages forward. Between the virtual and physical, the article investigates how respective communities network and expand online. This includes mapping online activities, which characteristically focus on current affairs and ground realities. Indeed, the Web provides a platform of engagement, which in a quest for legitimacy has expanded the networked opportunities available for the greater Tamil diaspora.
Egyptian e-diaspora: Migrant websites without a network?
Authors: Severo Marta , Zuolo Eleonora
Published: November 2012

The definition of Egyptian migration as a diaspora has been much debated and often denied. This article investigates the phenomenon of the Egyptian diaspora through an innovative approach based on an analysis of the digital activity and the presence of Egyptian connected migrants. Following the methodology of the e-Diaspora project, we found a weakly connected network of websites, with many isolated nodes, little clusterization and no authorities or hubs. The fact that the traditional approach of the e-diaspora yielded few results prompted us to follow a new research strategy combining data from Web 1.0 and Web 2.0. Because of a particularly fortuitous coincidence with the Egyptian revolt, we could investigate the mobilization of Egyptian migrants in pursuit of their voting rights on the micro-blogging platform Twitter. Through Twitter data, we identified links that were not visible through traditional Web-mapping techniques, and we could observe the emergence of a transnational Egyptian community debating and fighting for a common cause.
What remains of Yugoslavia? From the geopolitical space of Yugoslavia to the virtual space of the Web Yugosphere
Authors: Mazzucchelli Francesco
Published: November 2012

This article works from the double hypothesis that: (1) a Yugoslav socio-cultural space still exists in spite of the dissolution of the former Socialist Federal Republic of Yugoslavia; and (2) the communities ‘occupying’ this space can be considered, in some measure, ‘diasporic’, if the ‘Yugoslav diaspora’ is defined by not only the geographic displacement of people but also by the loosening of connections between members of an ex-nation who still consider themselves a national community. The ‘space’ mapped in the article is the so-called ‘virtual space’ of the Web, including all websites that reconnect to the ‘cultural languages’ of the ‘past-country’. The author observes how these ‘different Yugoslavias’ are ‘staged’ and linked together on the Web, and verifies how some far-flung communities rally around the ‘virtual re-foundation’ and ‘virtual representations’ of Yugoslavia. The corpus is constituted mainly of ‘yugonostalgic’ websites that are subjected to a content analysis. The 191 websites of the corpus and the hypertextual map of their edges are analysed using semantic features together with other tools of categorization.
Common Topics and Commonplaces of Environmental Rhetoric
Authors: Ross Derek G.
Published: November 2012

Common topics are words or phrases used to develop argument, and commonplaces aid memory or catalyze frames of understanding. When used in argumentation, each may help interested parties more effectively communicate valuable scientific and environment-related information. This article describes 12 modern topics of environmental rhetoric, identified from 125 interviews, and discusses them in relation to their topical fluidity and managerial, generative, and encapsulated utility: “Al Gore,” “balance,” “common sense,” “environment as setting,” “experience,” “extremism,” “man’s achievements,” “pragmatism,” “proof,” “religion,” “recycling,” and “seeing is believing.” Findings suggest that “environment” is a complex topic with many potential implications—using topics common to environmental rhetoric to shape argumentation may facilitate more productive environment-related communication.
Interdistrict Variation in the Implementation of the Crack Retroactivity Policy by U.S. District Courts
Authors: Reitler Angela K. , Frank James
Published: November 2012

In 2007, after years of dissatisfaction with the 100-to-1 disparity between crack cocaine and powder cocaine, the U.S. Sentencing Commission amended the U.S. Sentencing Guidelines, reducing by two levels the base offense level assigned to threshold quantities of crack cocaine. The amendment was subsequently made retroactive, which required the federal courts to process approximately 20,000 prisoner motions for sentence reduction. Using data collected from a case study of one particular district as well as a survey of representatives from the 94 federal judicial districts, this study examines the process of “crack retroactivity” implementation. The authors found that court communities varied greatly with respect to their organizational arrangements, procedures, and motivations. Although U.S. Probation and Pretrial Services played an important role in every district, how and why districts organized to respond to crack retroactivity varied. The study findings also indicate that sentencing procedures may be another mechanism through which location affects sentencing outcomes.
Legal and Extra-Legal Factors Related to the Imposition of Blended Sentences
Authors: Brown Joe M. , Sorensen Jon R.
Published: November 2012

This study sought to determine whether legal and extra-legal factors such as type and severity of offense, prior criminal history, age, gender, and race influence decision making in juvenile court. Specifically, the study focused on the imposition of a blended, “determinate” sentence rather than a traditional indeterminate sentence, controlling for adult court transfers. Data for this study were obtained from the largest county in the state of Texas. The results indicated that juveniles sentenced to a blended sentence had committed more serious offenses than those sentenced to traditional indeterminate sentences. Unlike with transfers to adult court, however, minority juveniles (Black and Hispanic) were no more likely than non-Hispanic White youth to receive a blended sentence. Although findings from the current study generally support the imposition of blended sentences, the true test of their utility lies further downstream in the implementation process.
What Makes You the “Worst of the Worst?” An Examination of State Policies Defining Supermaximum Confinement
Authors: Butler H. Daniel , Griffin O. Hayden , Johnson W. Wesley
Published: November 2012

As a response to an increasing prison population and as a counteractive measure to problematic inmates, many states within the United States have established supermaximum (supermax) prisons or supermax units within existing prison facilities. Many criminal justice researchers have questioned the efficacy of these specialized units. Although the National Institute for Corrections has established model criteria to dictate what types of inmates should be placed in supermax custody, existing research has not yet examined if the states have chosen to follow the criteria or substitute their own criteria for admission to supermax custody. The current study examines 42 individual state policies in an attempt to ascertain how states determine which inmates are considered the “worst of the worst” and deserve segregation in supermax facilities and/or units. Implications of these policies and directions for future research are discussed.
Machining characteristics of Inconel 718 under several cutting conditions based on Taguchi method
Authors: Thirumalai R , Senthilkumaar JS , Selvarani P , Ramesh S
Published: November 2012

Extensive researchers have conducted several experiments in the past for selecting the optimum parameters in machining nickel based alloy – Inconel 718. These experiments conducted so far are dealt with dry machining and flooded coolant machining of nickel alloy Inconel 718. In this research study, the usage of refrigerated coolant is also dealt with and it is compared with dry machining and flooded coolant machining. Cutting speed, feed and depth of cut are considered as the machining parameters. The effectiveness of the refrigerated coolant in machining the heat resistant super alloy material Inconel 718 with respect to these machining parameters are described in this article. The machinability studies parameters were generated with surface roughness and flank wear. The performance of uncoated carbide cutting tool was investigated at various cutting condition under dry, flooded coolant and refrigerated coolant machining. The relationship between the machining parameters and the performance measures were established and using analysis of variance significant machining parameters determined. This article made an attempt to Taguchi optimization technique to study the machinability performances of Inconel 718. Taguchi approach is an efficient and effective experimental method in which a response variable can be optimized, given various control and noise factors, using fewer experiments than a factorial design. Taguchi’s optimization analysis indicates that the factors level, its significance to influence the surface roughness and flank wear for the machining processes. Confirmation tests were conducted at an optimal condition to make a comparison between the experimental results foreseen from the mentioned correlations.
A note on the generation of a compressible vortex rings using helium as driver gas
Authors: Mariani R , Quinn MK , Kontis K
Published: November 2012

An experimental study has been conducted on the generation and propagation of compressible vortex rings using helium as a driver gas, with the aim of evaluating the effects of multi-gas operations for real-life applications. The advantage of such system, when compared to a constant gas system based on ambient air, is to effectively increase the Mach number while keeping the pressure ratio constant. Three pressure ratios of ∼4, 8 and 12 were set, corresponding to experimental Mach numbers of approximately 1.50, 1.81 and 2.05. The increase in incident Mach number resulted in the variation of the vortex ring and trailing jet structure, and an increase in both the velocity magnitude and vorticity field. Results showed a transition from the regular-reflection shock-cell system at the experimental Mach number approximately 1.50 to the presence of a Mach reflection with a central Mach disc, which grew in size with further increase in incident Mach number. The presence of the Mach disc resulted in the formation of a subsonic jet, internal to the main trailing jet. Its velocity was measured to be in the order of magnitude of 550 m/s, with the speed of sound of helium at 1005 m/s. Results also demonstrated that shear layers formed between the subsonic and main trailing jet have opposing vorticity, with that of the subsonic jet being approximately half in magnitude. Secondary counter-rotating vortex rings were generated ahead of the main vortex and orbited around it. The analysis of the vorticity field has shown that these secondary vortices have a magnitude approximately half of that of the vorticity of the main vortex, and has confirmed that they have an opposite direction of rotation.
Experimental study of a small partial admission axial turbine with low aspect ratio blade
Authors: Varma AK , Soundranayagam S
Published: November 2012

Experimental study of a small partial admission axial turbine with low aspect ratio blade has been done. Tests were also performed with full admission stator replacing the partial one for the same rotor to assess the losses occurring due to partial admission. Further tests were conducted with stator admission area split into two and three sectors to study the effects of multiple admission sectors. The method of Ainley and Mathieson with suitable correction for aspect ratio in secondary losses, as proposed by Kacker and Okapuu, gives a good estimate of the efficiency. Estimates of partial admission losses are made and compared with experimentally observed values. The Suter and Traupel correlations for partial admission losses yielded reasonably accurate estimates of efficiency even for small turbines though limited to the region of design u/ cis. Stenning’s original concept of expansion losses in a single sector is extended to include multiple sectors of opening. The computed efficiency debit due to each additional sector opened is compared with test values. The agreement is observed to be good. This verified Stenning’s original concept of expansion losses. When the expression developed on this extended concept is modified by a correction factor, the prediction of partial admission efficiencies is nearly as good as that of Suter and Traupel. Further, performance benefits accrue if the turbine is configured with increased aspect ratio at the expense of reduced partial admission.
A comparison of incomplete-data methods for categorical data
Authors: van der Palm Daniël W , van der Ark L Andries , Vermunt Jeroen K
Published: November 2012

We studied four methods for handling incomplete categorical data in statistical modeling: (1) maximum likelihood estimation of the statistical model with incomplete data, (2) multiple imputation using a loglinear model, (3) multiple imputation using a latent class model, (4) and multivariate imputation by chained equations. Each method has advantages and disadvantages, and it is unknown which method should be recommended to practitioners. We reviewed the merits of each method and investigated their effect on the bias and stability of parameter estimates and bias of the standard errors. We found that multiple imputation using a latent class model with many latent classes was the most promising method for handling incomplete categorical data, especially when the number of variables used in the imputation model is large.
The importance of moral sensitivity when including persons with dementia in qualitative research
Authors: Heggestad Anne Kari T , Nortvedt Per , Slettebø Åshild
Published: November 2012

The aim of this article is to show the importance of moral sensitivity when including persons with dementia in research. The article presents and discusses ethical challenges encountered when a total of 15 persons with dementia from two nursing homes and seven proxies were included in a qualitative study. The examples show that the ethical challenges may be unpredictable. As researchers, you participate with the informants in their daily life and in the interviews, and it is not possible to plan all that may happen during the research. A procedural proposal to an ethical committee at the beginning of a research project based on traditional research ethical principles may serve as a guideline, but it cannot solve all the ethical problems one faces during the research process. Our main argument in this article is, therefore, that moral sensitivity is required in addition to the traditional research ethical principles throughout the whole process of observing and interviewing the respondents.
Professional values, self-esteem, and ethical confidence of baccalaureate nursing students
Authors: Iacobucci Trisha A , Daly Barbara J , Lindell Debbie , Griffin Mary Quinn
Published: November 2012

Professional identity and competent ethical behaviors of nursing students are commonly developed through curricular inclusion of professional nursing values education. Despite the enactment of this approach, nursing students continue to express difficulty in managing ethical conflicts encountered in their practice. This descriptive correlational study explores the relationships between professional nursing values, self-esteem, and ethical decision making among senior baccalaureate nursing students. A convenience sample of 47 senior nursing students from the United States were surveyed for their level of internalized professional nursing values (Revised Professional Nursing Values Scale), level of self-esteem (Rosenberg’s Self-Esteem Scale), and perceived level of confidence in ethical decision making. A significant positive relationship (p < 0.05) was found between nursing students’ professional nursing values and levels of self-esteem. The results of this study can be useful to nursing educators whose efforts are focused on promoting professional identity development and competent ethical behaviors of future nurses.
Differentiating the Associations of Waist Circumference and Body Mass Index With Cardiovascular Disease Risk in a Chinese Population
Authors: Li Rui , Shi Liang , Jia Jian , Li Yanyun , Yang Qundi , Ruan Ye , Chen Renjie , Kan Haidong
Published: November 2012

It is not known which obesity index best explains variations in cardiovascular disease risk across populations. The objective of this study was to differentiate the associations of waist circumference (WC) and body mass index (BMI) with cardiovascular disease risk in a Chinese population. Cardiovascular risk factors, WC, and BMI were measured in 13 817 adults aged more than 18 years in Shanghai. Higher WC tertiles were associated with higher blood pressure and higher cholesterol, triacylglycerol, and glucose concentrations within each tertile of BMI and vice versa. The odds ratios (ORs) of hypertension, dyslipidemia, and metabolic syndrome increased with successive WC (or BMI) tertiles after adjustment for BMI (or WC) and several covariates. However, BMI tertiles were not associated with the ORs of diabetes after adjustment for WC. WC may be better than BMI as an alternative measure of body fatness or fat distribution for predicting diabetic risks in Chinese adults.
Comparison of fecal DNA extraction kits for the detection of Mycobacterium avium subsp. paratuberculosis by polymerase chain reaction
Authors: Leite Fernando L. , Stokes Kevin D. , Robbe-Austerman Suelee , Stabel Judith R.
Published: November 2012

Culture of Mycobacterium avium subsp. paratuberculosis (MAP) from feces has been considered the gold standard for the diagnosis of paratuberculosis for many years. However, direct fecal polymerase chain reaction (PCR) is becoming more widely used, demonstrating similar sensitivity and specificity to culture. To ensure efficient and reproducible PCR results from a difficult sample matrix such as feces, there are many obstacles that a DNA extraction method must overcome, including the presence of inhibitors and the thick waxy cell wall of MAP. In the current study, 6 commercial DNA extraction kits were evaluated using fecal samples from naturally infected cattle shedding various amounts of MAP. Upon extraction, DNA purity and yield were measured, and real-time PCR was performed for detection of the insertion sequence (IS)900 and ISMAP02 targets. The kits evaluated showed significant differences in the purity and yield of DNA obtained. The best results were observed with kits E and A, having identified 94% (16/17) and 76% (13/17) of the positive samples by IS900 PCR, respectively. Both of these kits utilized bead beating in a lysis solution for cell disruption, followed by spin column technology (kit E) or magnetic bead–based technology (kit A) for nucleic acid isolation and purification. Two kits (A and F) demonstrated improved performance when used in conjunction with the respective manufacturer’s PCR test. The present study demonstrates the importance of choosing the correct methodology for the most accurate diagnosis of paratuberculosis through fecal PCR.
Retrospective swine influenza serological surveillance in the four highest pig density provinces of Thailand before the introduction of the 2009 pandemic Influenza A virus subtype H1N1 using various antibody detection assays
Authors: Sreta Donruethai , Jittimanee Suphattra , Charoenvisal Nataya , Amonsin Alongkorn , Kitikoon Pravina , Thanawongnuwech Roongroje
Published: November 2012

Genetic characterization of the hemagglutinin gene of the 6 selected Thai Swine influenza virus (SIV) isolates (4 H1 and 2 H3 isolates) used in the establishment of a hemagglutination inhibition (HI) assay was analyzed. Based on the phylogenetic analysis, Thai SIVs could be divided into 3 clusters of the H1 viruses (clusters I and II belonging to classical swine H1α, and cluster III belonging to classical swine H1γ), and 2 clusters of the H3 viruses both belonging to human-like 1970s. The serological results indicated that swH1N1-06 (H1 cluster I) is a suitable representative SIV for the HI test antigen to detect H1 SIV-specific antibodies in the Thai swine population, while both swH3N2-05 and swH3N2-07 should be used for Thai H3 SIV-specific antibody detection. The HI test results of swine sera collected from pigs in the 4 highest pig population provinces of Thailand indicated that the percentage of pigs seropositive to swH3N2-07 was highest compared to swH1N1-06, swH1N1-09, and swH3N2-05 (85.4%, 50.1%, 18.6%, and 15.8%, respectively). It should be noted that countries lacking SIV genetic information should be concerned with determining the most suitable HI test antigens to use when performing the tests due to the genetic variation and limited cross-reaction of SIVs. The results of the current study demonstrated that HI tests should be implemented with the suitable field strains as the representative test antigen to ascertain accurate SIV serostatus in Thailand and that test antigens should be genetically analyzed and compared with circulating strains regularly.
Myocardial fibrosis associated with previous ingestion of yew (Taxus sp.) in a Holstein heifer
Authors: Burcham Grant N. , Becker Kyle J. , Tahara John M. , Wilson Christina R. , Hooser Stephen B.
Published: November 2012

Twenty-six 5-month-old Holstein calves were accidentally exposed to discarded branches of yew bushes ( Taxus sp.). Several calves were found dead approximately 24 hr after exposure; however, a few calves died several days after exposure. One calf died 18 days after the initial exposure to Taxus sp. and was examined on the farm via necropsy. Gross lesions included ascites, and dilated and flaccid myocardial ventricles. Sections of formalin-fixed heart were submitted to the Indiana Animal Disease Diagnostic Laboratory for histopathologic examination; fresh rumen contents were submitted for toxicologic testing. Histologically, large areas of myocardium were replaced by fibrous connective tissue, suggesting previous myocardial necrosis. Taxus alkaloids were identified in the rumen contents using gas chromatography–mass spectrometry. Based on the clinical history, the gross and histologic lesions, the identification of Taxus alkaloids in the rumen contents, and lack of exposure to other known cardiotoxic agents, yew toxicity was considered the cause of death in this calf. Ingestion of taxines is known to cause acute and subacute toxicity in human beings and animals; however, a chronic clinical course and severe histologic lesions have not been previously associated with yew toxicity. Although only 1 calf was examined, this case suggests that yew toxicity can result in a prolonged clinical course in cattle and can cause histologic myocardial lesions.
Forecasting and observing: A cross-methodological consideration of Internet and mobile phone diffusion in the Egyptian revolt
Authors: Groshek Jacob
Published: November 2012

This study examines the Egyptian revolt (see Zhuo et al., 2011) of January/February 2011 from two discrete perspectives. The first perspective is a contextual marker that takes into account long-term and forecast trends in democracy from 1952 through 2011. The second perspective reports the opinions and viewpoints of Egyptian citizens living in a remote fishing village and resort town through impromptu in-person interviews conducted between 23 and 30 January 2011. The statistical findings evidence that the Internet and mobile phones have helped to facilitate sociopolitical instability and democratic change over time, while the personal interviews paradoxically suggest circumspection in making generalizations about how these events have proceeded across a large population and through a period of tightly suppressed communication when Internet access was shut down. Taken together, characterizing the events in Egypt as having been just a social media revolution therefore appears to misrepresent the evolution of political change in the country through this time period.
Current Concepts in Examination and Treatment of Elbow Tendon Injury
Authors: Ellenbecker Todd S. , Nirschl Robert , Renstrom Per
Published: November 2012

Context:

Injuries to the tendons of the elbow occur frequently in the overhead athlete, creating a significant loss of function and dilemma to sports medicine professionals. A detailed review of the anatomy, etiology, and pathophysiology of tendon injury coupled with comprehensive evaluation and treatment information is needed for clinicians to optimally design treatment programs for rehabilitation and prevention.

Evidence Acquisitions:

The PubMed database was searched in January 2012 for English-language articles pertaining to elbow tendon injury.

Results:

Detailed information on tendon pathophysiology was found along with incidence of elbow injury in overhead athletes. Several evidence-based reviews were identified, providing a thorough review of the recommended rehabilitation for elbow tendon injury.

Conclusions:

Humeral epicondylitis is an extra-articular tendon injury that is common in athletes subjected to repetitive upper extremity loading. Research is limited on the identification of treatment modalities that can reduce pain and restore function to the elbow. Eccentric exercise has been studied in several investigations and, when coupled with a complete upper extremity strengthening program, can produce positive results in patients with elbow tendon injury. Further research is needed in high-level study to delineate optimal treatment methods.
Considerations for Providing Counseling Services in Second Life
Authors: Russ Debra P.
Published: November 2012

Second Life is a multiuser environment that can be found on the Internet. There are hundreds of counselors using Second Life as a service delivery mode. Currently, Second Life remains an unregulated avenue for practice. Counselors considering opening a practice need to investigate the benefits and disadvantages for using this medium. The author will discuss the opportunities, issues, and steps for establishing a counseling practice in Second Life.
From “Chastity As a Gift” to “Doing It As a Sign of Love”
Authors: Dias Ana Rita Conde , Machado Carla , Gonçalves Miguel
Published: November 2012

This study aims to analyze the media discourse about feminine sexuality produced by Portuguese magazines. Texts about female sexuality published in six types of magazines between 1965 and 2006 were content analyzed. The results showed that Portuguese media’s discourse on sexuality is not only becoming more liberal but is also characterized by ambiguity and contradiction. Within a “progressive” discursive framework for sexuality, tensions and double standards for women are still noticeable. The media discourse in Portugal continues to reinforce the established gender hierarchy and inequality in heterosexual relationships and maintain traditional gender roles.
Survey of heavy metal contamination in recycled polyethylene terephthalate used for food packaging
Authors: Whitt M , Vorst K , Brown W , Baker S , Gorman L
Published: November 2012

Polyethylene terephthalate food-product containers made with post-consumer materials have been found contaminated with heavy metals due to the recycling and sorting process. The increased use of recycled plastic flake from international suppliers, and subsequent commingling with electronic waste, has been suspected as the source of the increased levels of heavy metal contamination. In this study, nickel, chromium, cadmium, antimony, and lead were quantified in post-consumer polyethylene terephthalate extruded sheet and thermoformed samples, using inductively coupled plasma-atomic emission spectrometry. Recycled polyethylene terephthalate samples were digested using trace-metal grade hydrochloric, perchloric, and nitric acids. Samples were analyzed per ASTM E1613-04, standard test method for determination of lead by inductively coupled plasma atomic emission spectrometry, flame atomic absorption spectrometry, or graphite furnace atomic absorption spectrometry techniques. Two hundred samples were tested of which 29 were found to be contaminated with heavy metals. Chromium and cadmium were found in all 29 sample replicates. Nickel was found in 96.4% of the sample replicates and when it was found, the concentration averaged 11.59 ppm. Lead was found in 90.4% of the sample replicates and the average concentration was 0.15 ppm. Antimony was found in 97.6% of the sample replicates and concentrations were higher in rigid recycled polyethylene terephthalate containers compared to films. It was noted that the total contamination in all 29 samples was well below the threshold level set for the incidental presence of heavy metals in packaging materials as set forth in California’s Toxics in Packaging Prevention Act of 2006. The percentage of each heavy metal that would actually leach from the plastics to contaminate food products during normal processing, packaging, marketing, and consumer use was not determined in this study.
Targeted nanoparticle delivery overcomes off-target immunostimulatory effects of oligonucleotides and improves therapeutic efficacy in chronic lymphocytic leukemia
Authors: Yu Bo , Mao Yicheng , Bai Li-Yuan , Herman Sarah E. M. , Wang Xinmei , Ramanunni Asha , Jin Yan , Mo Xiaokui , Cheney Carolyn , Chan Kenneth K. , Jarjoura David , Marcucci Guido , Lee Robert J. , Byrd John C. , Lee L. James , Muthusamy Natarajan
Published: November 2012

Several RNA-targeted therapeutics, including antisense oligonucleotides (ONs), small interfering RNAs, and miRNAs, constitute immunostimulatory CpG motifs as an integral part of their design. The limited success with free antisense ONs in hematologic malignancies in recent clinical trials has been attributed to the CpG motif–mediated, TLR-induced prosurvival effects and inefficient target modulation in desired cells. In an attempt to diminish their off-target prosurvival and proinflammatory effects and specific delivery, as a proof of principle, in the present study, we developed an Ab-targeted liposomal delivery strategy using a clinically relevant CD20 Ab (rituximab)–conjugated lipopolyplex nanoparticle (RIT-INP)– and Bcl-2–targeted antisense G3139 as archetypical antisense therapeutics. The adverse immunostimulatory responses were abrogated by selective B cell–targeted delivery and early endosomal compartmentalization of G3139-encapsulated RIT-INPs, resulting in reduced NF-κB activation, robust Bcl-2 down-regulation, and enhanced sensitivity to fludarabine-induced cytotoxicity. Furthermore, significant in vivo therapeutic efficacy was noted after RIT-INP–G3139 administration in a disseminated xenograft leukemia model. The results of the present study demonstrate that CD20-targeted delivery overcomes the immunostimulatory properties of CpG-containing ON therapeutics and improves efficient gene silencing and in vivo therapeutic efficacy for B-cell malignancies. The broader implications of similar approaches in overcoming immunostimulatory properties of RNA-directed therapeutics in hematologic malignancies are also discussed.
Allogeneic, but not autologous, hematopoietic cell transplantation improves survival only among younger adults with acute lymphoblastic leukemia in first remission: an individual patient data meta-analysis
Authors: Gupta Vikas , Richards Sue , Rowe Jacob
Published: November 2012

Hematopoietic cell transplantation (HCT) and prolonged chemotherapy are standard postremission strategies for adult acute lymphoblastic leukemia in first complete remission, but the optimal strategy remains controversial. There are no randomized trials of allogeneic HCT. In the present study, updated individual patient data were collected and analyzed from studies with information on availability of matched sibling donor (used to mimic randomization) and from randomized trials of autograft versus chemotherapy. Data from 13 studies including 2962 patients, excluding Philadelphia chromosome–positive patients, showed a survival benefit for having a matched sibling donor for patients < 35 years of age (OR = 0.79; 95% CI, 0.70-0.90, P = .0003) but not for those ≥ 35 years of age (OR = 1.01; 95% CI, 0.85-1.19, P = .9; heterogeneity P = .03) because of the higher absolute risk of nonrelapse mortality for older patients. No differences were seen by risk group. There was a trend toward inferior survival for autograft versus chemotherapy (OR = 1.18; 95% CI, 0.99-1.41; P = .06). No beneficial effect of autografting was seen compared with chemotherapy in this analysis. We conclude that matched sibling donor myeloablative HCT improves survival only for younger patients, with an absolute benefit of approximately 10% at 5 years. Improved chemotherapy outcomes and reduced nonrelapse mortality associated with allogeneic HCT may change the relative effects of these treatments in the future.
Proteomic characterization of the Rph15 barley resistance gene-mediated defence responses to leaf rust
Authors: Bernardo Letizia , Prinsi Bhakti , Negri Alfredo Simone , Cattivelli Luigi , Espen Luca , Valè Giampiero
Published: November 2012

Background

Leaf rust, caused by the biotrophic fungal pathogen Puccinia hordei, is one of the most important foliar disease of barley (Hordeum vulgare) and represents a serious threat in many production regions of the world. The leaf rust resistance gene Rph15 is of outstanding interest for resistance breeding because it confers resistance to over 350 Puccinia hordei isolates collected from around the world. Molecular and biochemical mechanisms responsible for the Rph15 effectiveness are currently not investigated. The aim of the present work was to study the Rph15-based defence responses using a proteomic approach.

Results

Protein pattern changes in response to the leaf rust pathogen infection were investigated in two barley near isogenic lines (NILs), Bowman (leaf rust susceptible) and Bowman-Rph15 (leaf rust resistant), differing for the introgression of the leaf rust resistance gene Rph15. Two infection time points, 24 hours and four days post inoculation (dpi), were analysed. No statistically significant differences were identified at the early time point, while at 4 dpi eighteen protein spots were significantly up or down regulated with a fold-change equal or higher than two in response to pathogen infection. Almost all the pathogen-responsive proteins were identified in the Bowman-Rph15 resistant NIL. Protein spots were characterized by LC-MS/MS analysis and found to be involved in photosynthesis and energy metabolism, carbohydrate metabolism, protein degradation and defence. Proteomic data were complemented by transcriptional analysis of the respective genes. The identified proteins can be related to modulation of the photosynthetic apparatus components, re-direction of the metabolism to sustain defence responses and deployment of defence proteins.

Conclusions

The identification of leaf rust infection-modulated defence responses restricted to the resistant NIL support the hypothesis that basal defence responses of Bowman, but not the Rph15 resistance gene-based ones, are suppressed or delayed by pathogen effectors to levels below the detection power of the adopted proteomic approach. Additionally, Rph15-mediated resistance processes identified mainly resides on a modulation of primary metabolism, affecting photosyntesis and carbohydrate pool.
Synergies between RNA degradation and trans-translation in Streptococcus pneumoniae: cross regulation and co-transcription of RNase R and SmpB
Authors: Moreira Ricardo N , Domingues Susana , Viegas Sandra C , Amblar Mónica , Arraiano Cecília M
Published: November 2012

Background

Ribonuclease R (RNase R) is an exoribonuclease that recognizes and degrades a wide range of RNA molecules. It is a stress-induced protein shown to be important for the establishment of virulence in several pathogenic bacteria. RNase R has also been implicated in thetrans-translation process. Transfer-messenger RNA (tmRNA/SsrA RNA) and SmpB are the main effectors oftrans-translation, an RNA and protein quality control system that resolves challenges associated with stalled ribosomes on non-stop mRNAs.Trans-translation has also been associated with deficiencies in stress-response mechanisms and pathogenicity.

Results

In this work we study the expression of RNase R in the human pathogenStreptococcus pneumoniaeand analyse the interplay of this enzyme with the main components of thetrans-translation machinery (SmpB and tmRNA/SsrA). We show that RNase R is induced after a 37°C to 15°C temperature downshift and that its levels are dependent on SmpB. On the other hand, our results revealed a strong accumulation of thesmpBtranscript in the absence of RNase R at 15°C. Transcriptional analysis of theS. pneumoniae rnrgene demonstrated that it is co-transcribed with the flanking genes,secGandsmpB. Transcription of these genes is driven from a promoter upstream ofsecGand the transcript is processed to yield mature independent mRNAs. This genetic organization seems to be a common feature of Gram positive bacteria, and the biological significance of this gene cluster is further discussed.

Conclusions

This study unravels an additional contribution of RNase R to thetrans-translation system by demonstrating thatsmpBis regulated by this exoribonuclease. RNase R in turn, is shown to be under the control of SmpB. These proteins are therefore mutually dependent and cross-regulated. The data presented here shed light on the interactions between RNase R,trans-translation and cold-shock response in an important human pathogen.
The Plant Short-Chain Dehydrogenase (SDR) superfamily: genome-wide inventory and diversification patterns
Authors: Moummou Hanane , Kallberg Yvonne , Tonfack Libert Brice , Persson Bengt , van der Rest Benoît
Published: November 2012

Background

Short-chain dehydrogenases/reductases (SDRs) form one of the largest and oldest NAD(P)(H) dependent oxidoreductase families. Despite a conserved ‘Rossmann-fold’ structure, members of the SDR superfamily exhibit low sequence similarities, which constituted a bottleneck in terms of identification. Recent classification methods, relying on hidden-Markov models (HMMs), improved identification and enabled the construction of a nomenclature. However, functional annotations of plant SDRs remain scarce.

Results

Wide-scale analyses were performed on ten plant genomes. The combination of hidden Markov model (HMM) based analyses and similarity searches led to the construction of an exhaustive inventory of plant SDR. With 68 to 315 members found in each analysed genome, the inventory confirmed the over-representation of SDRs in plants compared to animals, fungi and prokaryotes. The plant SDRs were first classified into three major types — ‘classical’, ‘extended’ and ‘divergent’ — but a minority (10% of the predicted SDRs) could not be classified into these general types (‘unknown’ or ‘atypical’ types). In a second step, we could categorize the vast majority of land plant SDRs into a set of 49 families. Out of these 49 families, 35 appeared early during evolution since they are commonly found through all the Green Lineage. Yet, some SDR families — tropinone reductase-like proteins (SDR65C), ‘ABA2-like’-NAD dehydrogenase (SDR110C), ‘salutaridine/menthone-reductase-like’ proteins (SDR114C), ‘dihydroflavonol 4-reductase’-like proteins (SDR108E) and ‘isoflavone-reductase-like’ (SDR460A) proteins — have undergone significant functional diversification within vascular plants since they diverged from Bryophytes. Interestingly, these diversified families are either involved in the secondary metabolism routes (terpenoids, alkaloids, phenolics) or participate in developmental processes (hormone biosynthesis or catabolism, flower development), in opposition to SDR families involved in primary metabolism which are poorly diversified.

Conclusion

The application of HMMs to plant genomes enabled us to identify 49 families that encompass all Angiosperms (‘higher plants’) SDRs, each family being sufficiently conserved to enable simpler analyses based only on overall sequence similarity. The multiplicity of SDRs in plant kingdom is mainly explained by the diversification of large families involved in different secondary metabolism pathways, suggesting that the chemical diversification that accompanied the emergence of vascular plants acted as a driving force for SDR evolution.
A questionnaire-based survey to assess patient satisfaction, ease-of-learning, ease-of-use, injection site pain and overall patient satisfaction of the follitropin-alpha (Gonal-f) filled-by-mass (FbM) prefilled pen compared with other systems of gonadotrophin administration
Authors: Utsunomiya Takafumi , Tanaka Atsushi , Tatsumi Kenichi , Ezcurra Diego
Published: November 2012

Background

Gonadotrophins are used routinely for follicular stimulation during ovarian induction and assisted reproduction techniques. Developments in recombinant follicle-stimulating hormone preparations and their injection devices have improved patient quality of life by enabling patients to self-administer treatment at home. The objective of this study was to investigate patient experiences of learning to use and overall satisfaction with the follitropin-alpha (Gonal-f) filled-by-mass (FbM) prefilled pen.

Methods

This questionnaire-based survey study was conducted in 23 fertility centres in Japan over a period of 14 months. Patients who were receiving fertility treatment with the follitropin-alpha (FbM) prefilled pen were asked to complete a questionnaire to assess their satisfaction, ease of learning and use, and injection site pain following treatment.

Results

A total of 663 women participated in the study. The majority of patients found the instructions for administering follitropin-alpha with the prefilled pen easy to understand (83.0%; n = 546/658) and patients found that a hands-on demonstration by a nurse or doctor was the most useful tool for learning to use the follitropin-alpha (FbM) prefilled pen (80.0%; n = 497/621). Forty-eight percent (n = 318) of patients in the study had previous experience with different types of fertility medications and the majority of these patients found the follitropin-alpha (FbM) prefilled pen easier to use (75.1%; n = 232/309) and less painful (89.0%; n = 347/390) than their previous medication. The majority (80.2%; n = 521/650) of patients reported overall satisfaction with the follitropin-alpha (FbM) prefilled pen.

Conclusions

The follitropin-alpha (FbM) prefilled pen is an easy-to-use injection device according to this questionnaire-based survey. Patients who had experience of different types of fertility medication preferred the follitropin-alpha (FbM) prefilled pen to other injection devices.
Impact of evergreening on patients and health insurance: a meta analysis and reimbursement cost analysis of citalopram/escitalopram antidepressants
Authors: Alkhafaji Ali A , Trinquart Ludovic , Baron Gabriel , Desvarieux Moïse , Ravaud Philippe
Published: November 2012

Background

"Evergreening" refers to the numerous strategies whereby owners of pharmaceutical products use patent laws and minor drug modifications to extend their monopoly privileges on the drug. We aimed to evaluate the impact of evergreening through the case study of the antidepressant citalopram and its chiral switch form escitalopram by evaluating treatment efficacy and acceptability for patients, as well as health insurance costs for society.

Methods

To assess efficacy and acceptability, we performed meta-analyses for efficacy and acceptability. We compared direct evidence (meta-analysis of results of head-to-head trials) and indirect evidence (adjusted indirect comparison of results of placebo-controlled trials). To assess health insurance costs, we analyzed individual reimbursement data from a representative sample of the French National Health Insurance Inter-regime Information System (SNIIR-AM) from 2003 to 2010, which allowed for projecting these results to the whole SNIIR-AM population (53 million people).

Results

In the meta-analysis of seven head-to-head trials (2,174 patients), efficacy was significantly better for escitalopram than citalopram (combined odds ratio (OR) 1.60 (95% confidence interval 1.05 to 2.46)). However, for the adjusted indirect comparison of 10 citalopram and 12 escitalopram placebo-controlled trials, 2,984 and 3,777 patients respectively, efficacy was similar for the two drug forms (combined indirect OR 1.03 (0.82 to 1.30)). Because of the discrepancy, we could not combine direct and indirect data (test of inconsistency,P= 0.07). A similar discrepancy was found for treatment acceptability. The overall reimbursement cost burden for the citalopram, escitalopram and its generic forms was 120.6 million Euros in 2010, with 96.8 million Euros for escitalopram.

Conclusions

The clinical benefit of escitalopram versus citalopram remains uncertain. In our case of evergreening, escitalopram represented a substantially high proportion of the overall reimbursement cost burden as compared with citalopram and the generic forms.
The burden of breast cancer in Italy: mastectomies and quadrantectomies performed between 2001 and 2008 based on nationwide hospital discharge records
Authors: Piscitelli Prisco , Barba Maddalena , Crespi Massimo , Di Maio Massimo , Santoriello Antonio , D’Aiuto Massiliamo , Fucito Alfredo , Losco Arturo , Pentimalli Francesca , Maranta Pasquale , Chitano Giovanna , Argentiero Alberto , Neglia Cosimo , Distante Alessandro , Di Tanna Gian luca , Brandi Maria Luisa , Mazza Alfredo , Marino Ignazio R , Giordano Antonio
Published: November 2012

Background

Where population coverage is limited, the exclusive use of Cancer Registries might limit ascertainment of incident cancer cases. We explored the potentials of Nationwide hospital discharge records (NHDRs) to capture incident breast cancer cases in Italy.

Methods

We analyzed NHDRs for mastectomies and quadrantectomies performed between 2001 and 2008. The average annual percentage change (AAPC) and related 95% Confidence Interval (CI) in the actual number of mastectomies and quadrantectomies performed during the study period were computed for the full sample and for subgroups defined by age, surgical procedure, macro-area and singular Region. Re-admissions of the same patients were separately presented.

Results

The overall number of mastectomies decreased, with an AAPC of −2.1% (−2.3 -1.8). This result was largely driven by the values observed for women in the 45 to 64 and 65 to 74 age subgroups (−3.0%, -3.4 -3.6 and −3.3%, -3.8 -2.8, respectively). We observed no significant reduction in mastectomies for women in the remaining age groups. Quadrantectomies showed an overall +4.7 AAPC (95%CI:4.5–4.9), with no substantial differences by age. Analyses by geographical area showed a remarkable decrease in mastectomies, with inter-regional discrepancies possibly depending upon variability in mammography screening coverage and adherence. Quadrantectomies significantly increased, with Southern Regions presenting the highest average rates. Data on repeat admissions within a year revealed a total number of 46,610 major breast surgeries between 2001 and 2008, with an overall +3.2% AAPC (95%CI:2.8-3.6).

Conclusions

In Italy, NHDRs might represent a valuable supplemental data source to integrate Cancer Registries in cancer surveillance.