bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammation in dry eye associated with rheumatoid arthritis: Cytokine and in vivo confocal microscopy study
Authors: Villani Edoardo , Galimberti Daniela , Papa Nicoletta Del , Nucci Paolo , Ratiglia Roberto
Published: January 2013

The purpose of this research was to study ocular surface inflammation in relation to systemic disease activity in rheumatoid arthritis (RA) patients with or without secondary Sjögren’s syndrome (SSII and non-SSII respectively). The study was conducted in two phases. In phase I, 12 patients with active RA SSII and 12 with active RA non-SSII were consecutively enrolled. Each completed an Ocular Surface Disease Index (OSDI) questionnaire and underwent a full eye exam and in vivo confocal microscopy examination of the cornea. Tear fluid samples were collected in sponges and analyzed for IL-1α, -6, and -8, and TNF-α. When RA activity was suppressed by systemic treatment the patients entered phase II of the study in which all of the phase I examinations were repeated. In RA SSII patients, OSDI, fluorescein staining dendritic cell density, and concentrations of IL-1α and IL-6 decreased significantly ( P < 0.01) between phases I and II. Tear breakup time scores increased significantly. For RA non-SSII patients, there were no significant differences between phases I and II. Differences in the clinical, cellular and cytokine responsiveness to systemic RA treatments show that the ocular surface pathology is dissimilar for RA SSII and RA non-SSII patients.
What’s Better—R, SAS®, SPSS®, or Stata®? Thoughts for Instructors of Statistics and Research Methods Courses
Authors: Ward Brian W.
Published: January 2013

Knowledge of statistical software is an important skill for undergraduate sociology students to possess when seeking postgraduation employment; however, formal discussion of which software may be most beneficial to students and appealing to potential employers is lacking. The author’s goal in this teaching note is to provide the strengths and limitations of R, SAS, SPSS, and Stata software in a succinct and nontechnical manner, and discuss how these differences may influence an undergraduate instructor’s consideration of choosing which software is best for his or her statistics or research methods course. On reviewing these differences, the author argues that in most situations SAS would be the preferred software to use in one’s undergraduate course. However, there could be certain situations where R, SPSS, or Stata may be the preferred software. By giving consideration to the differences in these software packages, instructors can make an informed decision as to which is best for their course.
Mediating Program Evaluations
Authors: Fielding Stephen L.
Published: January 2013

Organizations conduct external evaluations for several reasons. They might want an independent assessment showing that their program is effective to garner community support, favorably influence public policy related to their mission, support their future bids for financial support, provide critical information for continuous quality assessment (although much of the latter is conducted internally by the organizations themselves), or because an external evaluation is required under the terms of a grant they received. The author focuses on the latter and argues that the quality of these evaluations is dependent on the continued involvement of funding agencies after the grant is awarded. He suggests four things that funders can do to address this challenge.
Responding to Welfare Reform
Authors: Latimer Melissa , Plein L. Christopher
Published: January 2013

This study compares administrative and caseworker perspectives on service delivery processes in rural areas in an Appalachian state with high levels of poverty and unemployment and limited economic resources for investment and development. The focus of this study is on the implementation of West Virginia Works, West Virginia’s public assistance program that was adopted in response to new federal welfare law enacted in 1996. The data source used in this research comes from focus groups with approximately 80 caseworkers and 5 West Virginia Department of Health and Human Resources administrators with key knowledge of welfare reform in West Virginia. Implications for service delivery and public policy are discussed.
Engaging Latinos in Access to Counseling and Education
Authors: Sandoval J. S. Onésimo , Jennings Joel , Rataj Meredith , Klein Erin
Published: January 2013

This article reports results from an applied research project between Catholic Charities Community Services Southside Center (CCCSSC) and the Department of Sociology and Anthropology (DSA) at Saint Louis University. In August 2010, CCCSSC and DSA began working on a project called Engaging Latinos in Access to Counseling and Education (EnLACE). The findings from this research were threefold: first, the empirical data suggest that quality of life among Latino immigrants was affected by perceived quality of health, money, transportation, enjoyment of life, perception of safety, leisure, work, and sex; second, based on our critical reflection, we have identified four lessons that we can build on to strengthen future Participatory Action Research (PAR); and third, we offer EnLACE as an example where applied academic research can be conducted while preserving the principles of PAR.
The management of refractory coeliac disease
Authors: Woodward Jeremy
Published: January 2013

A significant proportion of patients with coeliac disease are ‘nonresponsive’ to gluten withdrawal. Most cases of nonresponsive coeliac disease are due to persisting gluten ingestion. Refractory coeliac disease (RCD) is currently defined by persistent symptoms and signs of malabsorption after gluten exclusion for 12 months with ongoing intestinal villous atrophy. Primary (without initial response to diet) and secondary (relapse following response to diet) RCD is recognized. RCD is further classified as type I or type II based on the absence or presence of a population of aberrant intestinal lymphocytes. Quality of dietetic advice and support is fundamental, and lack of objective corroboration of gluten exclusion may result in over-identification of RCD I, particularly in those cases with persisting antibody responses. Over-reliance on lymphocyte clonality similarly may result in over-diagnosis of RCD II which requires careful quantification of aberrant lymphocyte populations. Management of RCD should be undertaken in specialist centres. It requires initial intensive dietary supervision, strict gluten exclusion and subsequent re-evaluation. There is currently insufficient evidence to recommend specific treatments. Steroids are often used in both RCD I and II (albeit with little objective evidence of benefit in RCD II), and azathioprine as steroid-sparing therapy in RCD I. There is growing evidence for the use of cladribine in RCD II with autologous stem cell transplantation in nonresponders, but this requires further multicentre evaluation. There remains considerable controversy regarding the diagnosis, treatment and surveillance of RCD: international consensus in these areas is urgently required to facilitate future therapeutic advances.
Canons, classics, and inclusion in the histories of geography
Authors: Monk Janice
Published: January 2013

In responding to reflections by Keighren et al. (2012) on the place of ‘classics’ within geographical literature and on the possibilities of identifying canonical works, I focus on the criteria for selection and how such works might be identified. As an example, I analyze the history of inclusion in the ‘Classics revisited’ series in the journal Progress in Human Geography, and pose questions to prompt reflection on the role of language of publication, national origins of authors, and interest in particular paradigms and subfields within the discipline as influences on selection. Additionally, I ask how the temporal and spatial contexts of readers and their motivations shape interpretations of works, what this implies in responses to ‘classics’, and for the possibilities of identifying a ‘canon’.
Locating contradictions in canonical geographies
Authors: Schein Richard H
Published: January 2013

This response to Keighren et al. (2012) challenges the distinction made between texts as ‘canonical’ or ‘classic’ to call for interrogating texts as interventions in broader disciplinary conversations, highlighting their place in mediating disagreements, challenges, contradictions, and the power relationships of intellectual and disciplinary winners and losers. This is especially important for graduate education, as a critical site where we construct the discipline’s dominant narratives and socially reproduce ourselves.
We have never been canonical
Authors: Keighren Innes M , Abrahamsson Christian , Dora Veronica della
Published: January 2013

In responding to the commentaries on Keighren et al. (2012), we discuss in this paper the nature of memory and forgetfulness in geography and examine what the implications of active forgetting are for the stories we tell about geography and geographers. We explore the role which fashion plays in directing the course of the discipline and what this means for our engagement with the work of past geographers. Finally, we consider how notions of inheritance and bequest can inform the ways in which we value the texts through which the discipline has defined and represented itself.
Aesthetics for post-human worlds
Authors: Lorimer Jamie
Published: January 2013

This short commentary briefly flags and develops three dimensions of an `aesthetics for post-human worlds', which are suggested by Dixon et al.'s (2012) paper. The first relates to questions of non-human difference – encouraging the authors to focus on what might be gained from comparing the different ontologies offered in their two case studies. The second examines questions of expertise, dwelling on the skills recounted in the paper under discussions and the epistemological politics that underpin science-art collaboration. The third observation explores the relationships between post-human aesthetics, ethics and politics. In short this commentary suggests that the authors have perhaps been a little humble about the import of their analysis. There are wider implications for geographical thought and practice after the relational turn raised here that are worthy of more extensive discussion.
Of human birds and living rocks
Authors: Dixon Deborah , Hawkins Harriet , Straughan Elizabeth
Published: January 2013

Geographers have long pondered post-human worlds. And yet, whilst such analyses have explored the natural and physical sciences as a means of articulating the relationalities and commonalities that span species and kingdoms, an explicit consideration of the aesthetic has been largely absent. To a degree, this is because the aesthetic has been understood as a `humanist remain'. Here, we want to make a stronger claim for the value of the aesthetic as a stepping off point for thinking through post-human geographies. We begin by acknowledging a productive tension within Kantian and post-Kantian accounts of sense-making: that is, a series of questions that speak directly to the post-human have been raised by dwelling upon how the aesthetic can be related to bodily needs and desires, as well as a feeling that emerges from the exercise of judgement. Then, we make the argument that, as a means of developing our aesthetic sensibility, geography can usefully further its engagement with art theory and practice. This leads us to ground our own exploration of the post-human in a discussion of two projects created by artist Perdita Phillips. Moving from a consideration of bowerbirds in the savanna to thrombolites in a saline lake, and from evolutionary biology to a Deleuzo -Guattarian geophilosophy, we ask, where is the artistry?
Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo
Authors: Harris James M. , Esain Virginie , Frechette Gregory M. , Harris Lauren J. , Cox Andrew G. , Cortes Mauricio , Garnaas Maija K. , Carroll Kelli J. , Cutting Claire C. , Khan Tahsin , Elks Philip M. , Renshaw Stephen A. , Dickinson Bryan C. , Chang Christopher J. , Murphy Michael P. , Paw Barry H. , Vander Heiden Matthew G. , Goessling Wolfram , North Trista E.
Published: January 2013

Key Points

Glucose metabolism enhances hematopoietic stem cell formation and function in the vertebrate embryo Glucose metabolism modulates hif1α activity via mitochondrial generation of reactive oxygen species to impact HSC-relevant gene expression
The role of PPARγ in carbon nanotube-elicited granulomatous lung inflammation
Authors: Huizar Isham , Malur Anagha , Patel Janki , McPeek Matthew , Dobbs Larry , Wingard Christopher , Barna Barbara P , Thomassen Mary Jane
Published: January 2013

Background

Although granulomatous inflammation is a central feature of many disease processes, cellular mechanisms of granuloma formation and persistence are poorly understood. Carbon nanoparticles, which can be products of manufacture or the environment, have been associated with granulomatous disease. This paper utilizes a previously described carbon nanoparticle granuloma model to address the issue of whether peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear transcription factor and negative regulator of inflammatory cytokines might play a role in granulomatous lung disease. PPARγ is constitutively expressed in alveolar macrophages from healthy individuals but is depressed in alveolar macrophages of patients with sarcoidosis, a prototypical granulomatous disease. Our previous study of macrophage-specific PPARγ KO mice had revealed an intrinsically inflammatory pulmonary environment with an elevated pro-inflammatory cytokines profile as compared to wild-type mice. Based on such observations we hypothesized that PPARγ expression would be repressed in alveolar macrophages from animals bearing granulomas induced by MWCNT instillation.

Methods

Wild-type C57Bl/6 and macrophage-specific PPARγ KO mice received oropharyngeal instillations of multiwall carbon nanotubes (MWCNT) (100 μg). Bronchoalveolar lavage (BAL) cells, BAL fluids, and lung tissues were obtained 60 days post-instillation for analysis of granuloma histology and pro-inflammatory cytokines (osteopontin, CCL2, and interferon gamma [IFN-γ] mRNA and protein expression.

Results

In wild-type mice, alveolar macrophage PPARγ expression and activity were significantly reduced in granuloma-bearing animals 60 days after MWCNT instillation. In macrophage-specific PPARγ KO mice, granuloma formation was more extensive than in wild-type at 60 days after MWCNT instillation. PPARγ KO mice also demonstrated elevated pro-inflammatory cytokine expression in lung tissue, laser-microdissected lung granulomas, and BAL cells/fluids, at 60 days post MWCNT exposure.

Conclusions

Overall, data indicate that PPARγ deficiency promotes inflammation and granuloma formation, suggesting that PPARγ functions as a negative regulator of chronic granulomatous inflammation.
Genome reannotation of the lizard Anolis carolinensis based on 14 adult and embryonic deep transcriptomes
Authors: Eckalbar Walter L , Hutchins Elizabeth D , Markov Glenn J , Allen April N , Corneveaux Jason J , Lindblad-Toh Kerstin , Di Palma Federica , Alföldi Jessica , Huentelman Matthew J , Kusumi Kenro
Published: January 2013

Background

The green anole lizard, Anolis carolinensis, is a key species for both laboratory and field-based studies of evolutionary genetics, development, neurobiology, physiology, behavior, and ecology. As the first non-avian reptilian genome sequenced, A. carolinesis is also a prime reptilian model for comparison with other vertebrate genomes. The public databases of Ensembl and NCBI have provided a first generation gene annotation of the anole genome that relies primarily on sequence conservation with related species. A second generation annotation based on tissue-specific transcriptomes would provide a valuable resource for molecular studies.

Results

Here we provide an annotation of the A. carolinensis genome based on de novo assembly of deep transcriptomes of 14 adult and embryonic tissues. This revised annotation describes 59,373 transcripts, compared to 16,533 and 18,939 currently for Ensembl and NCBI, and 22,962 predicted protein-coding genes. A key improvement in this revised annotation is coverage of untranslated region (UTR) sequences, with 79% and 59% of transcripts containing 5’ and 3’ UTRs, respectively. Gaps in genome sequence from the current A. carolinensis build (Anocar2.0) are highlighted by our identification of 16,542 unmapped transcripts, representing 6,695 orthologues, with less than 70% genomic coverage.

Conclusions

Incorporation of tissue-specific transcriptome sequence into the A. carolinensis genome annotation has markedly improved its utility for comparative and functional studies. Increased UTR coverage allows for more accurate predicted protein sequence and regulatory analysis. This revised annotation also provides an atlas of gene expression specific to adult and embryonic tissues.
Meta-analysis of randomized controlled trials on magnesium in addition to beta-blocker for prevention of postoperative atrial arrhythmias after coronary artery bypass grafting
Authors: Wu Xiaosan , Wang Congxia , Zhu Jinyun , Zhang Chunyan , Zhang Yan , Gao Yanhua
Published: January 2013

Background

Atrial arrhythmia (AA) is the most common complication after coronary artery bypass grafting (CABG). Only beta-blockers and amiodarone have been convincingly shown to decrease its incidence. The effectiveness of magnesium on this complication is still controversial. This meta-analysis was performed to evaluate the effect of magnesium as a sole or adjuvant agent in addition to beta-blocker on suppressing postoperative AA after CABG.

Methods

We searched the PubMed, Medline, ISI Web of Knowledge, Cochrane library databases and online clinical trial database up to May 2012. We used random effects model when there was significant heterogeneity between trials and fixed effects model when heterogeneity was negligible.

Results

Five randomized controlled trials were identified, enrolling a total of 1251 patients. The combination of magnesium and beta-blocker did not significantly decrease the incidence of postoperative AA after CABG versus beta-blocker alone (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.86-1.47,P= 0.40). Magnesium in addition to beta-blocker did not significantly affect LOS (weighted mean difference −0.14 days of stay, 95% CI −0.58 to 0.29,P= 0.24) or the overall mortality (OR 0.59, 95% CI 0.08-4.56,P= 0.62). However the risk of postoperative adverse events was higher in the combination of magnesium and beta-blocker group than beta-blocker alone (OR 2.80, 95% CI 1.66-4.71,P= 0.0001).

Conclusions

This meta-analysis offers the more definitive evidence against the prophylactic administration of intravenous magnesium for prevention of AA after CABG when beta-blockers are routinely administered, and shows an association with more adverse events in those people who received magnesium.
Potentiation of in vitro and in vivoantitumor efficacy of doxorubicin by cyclin-dependent kinase inhibitor P276-00 in human non-small cell lung cancer cells
Authors: Rathos Maggie J , Khanwalkar Harshal , Joshi Kavita , Manohar Sonal M , Joshi Kalpana S
Published: January 2013

Background

In the present study, we show that the combination of doxorubicin with the cyclin-dependent kinase inhibitor P276-00 was synergistic at suboptimal doses in the non-small cell lung carcinoma (NSCLC) cell lines and induces extensive apoptosis than either drug alone in H-460 human NSCLC cells.

Methods

Synergistic effects of P276-00 and doxorubicin on growth inhibition was studied using the Propidium Iodide (PI) assay. The doses showing the best synergistic effect was determined and these doses were used for further mechanistic studies such as western blotting, cell cycle analysis and RT-PCR. The in vivo efficacy of the combination was evaluated using the H-460 xenograft model.

Results

The combination of 100 nM doxorubicin followed by 1200 nM P276-00 showed synergistic effect in the p53-positive and p53-mutated cell lines H-460 and H23 respectively as compared to the p53-null cell line H1299. Abrogation of doxorubicin-induced G2/M arrest and induction of apoptosis was observed in the combination treatment. This was associated with induction of tumor suppressor protein p53 and reduction of anti-apoptotic protein Bcl-2. Furthermore, doxorubicin alone greatly induced COX-2, a NF-κB target and Cdk-1, a target of P276-00, which was downregulated by P276-00 in the combination. Doxorubicin when combined with P276-00 in a sequence-specific manner significantly inhibited tumor growth, compared with either doxorubicin or P276-00 alone in H-460 xenograft model.

Conclusion

These findings suggest that this combination may increase the therapeutic index over doxorubicin alone and reduce systemic toxicity of doxorubicin most likely via an inhibition of doxorubicin-induced chemoresistance involving NF-κB signaling and inhibition of Cdk-1 which is involved in cell cycle progression.
Clinical association between teeth malocclusions, wrong posture and ocular convergence disorders: an epidemiological investigation on primary school children
Authors: Silvestrini-Biavati Armando , Migliorati Marco , Demarziani Eleonora , Tecco Simona , Silvestrini-Biavati Piero , Polimeni Antonella , Saccucci Matteo
Published: January 2013

Background

As the various systems in the body are inter-connected to form a single structural unit, a pathological condition in one area can also affect other areas. There are many known correlations between the visual and motor system. The importance of visual function, particularly the paracentral peripheral field of view, in motor coordination, ambulation and the maintenance of balance has been amply demonstrated.

In line with current medical principles, which are moving towards a more holistic view of the human body, this study aims to investigate, in an interdisciplinary manner, the incidence of dental malocclusions together with posture and eye convergence disorders.

Methods

Six hundred and five children attending at the 3rd, 4th and 5th years of seven Genoa primary schools were examined. Each child underwent the following examinations: (i) dental/occlusal; (ii) orthoptic; and (iii) postural. Occlusal data concerned the presence of cross-bite, midline deviation with a mandibular shift, bad habits and deep or open bite.

Postural assessment involved frontal and lateral inspection, investigation during trunk flexion and ambulation, and note of any asymmetry in the lower limbs. The recorded orthoptic data included those pertaining to ocular dominance, a cover test, convergence and the Brock string test.

Results

A prevalence of cases with an unphysiological gait was found in patients with overjet (14.70%) or overbite (14.87%), while the percentage of patients with normal occlusion that showed an unphysiological gait was 13.08%. Also, about 93.8%–94.2% of children showed normal legs without dysmetry, with no difference in respect to the type of occlusion. Subjects with an open bite or deep bite showed a slightly different distribution of right or left dominant eyes.

Conclusion

About 13% of children showed a pathological gait and, among them, vertical anomalies of occlusion (deep bite or open bite) were prevalent with respect to the other occlusal defects. The vertical dimension of occlusion revealed a slight relationship with the proper dominant eye. Postural, orthoptic, osteopathic and occlusal variables were often clinically associated, and therefore these disorders appear to request a multidisciplinary medical approach for their treatment.
Efficacy and safety of moxifloxacin in acute exacerbations of chronic bronchitis: a prospective, multicenter, observational study (AVANTI)
Authors: Chuchalin Alexander , Zakharova Maryna , Dokic Dejan , Tokić Mahir , Marschall Hans-Peter , Petri Thomas
Published: January 2013

Background

Acute exacerbations of chronic bronchitis (AECB), including chronic obstructive pulmonary disease (AECOPD), represent a substantial patient burden. Few data exist on outpatient antibiotic management for AECB/AECOPD in Eastern/South Eastern Europe, in particular on the use of moxifloxacin (Avelox®), although moxifloxacin is widely approved in this region based on evidence from international clinical studies.

Methods

AVANTI (AVelox® in Acute Exacerbations of chroNic bronchiTIs) was a prospective, observational study conducted in eight Eastern European countries in patients > 35 years with AECB/AECOPD to whom moxifloxacin was prescribed. In addition to safety and efficacy outcomes, data on risk factors and the impact of exacerbation on daily life were collected.

Results

In the efficacy population (N = 2536), chronic bronchitis had been prevalent for > 10 years in 31.4% of patients and 66.0% of patients had concomitant COPD. Almost half the patients had never smoked, in contrast to data from Western Europe and the USA, where only one-quarter of COPD patients are non-smokers. The mean number of exacerbations in the last 12 months was 2.7 and 26.3% of patients had been hospitalized at least once for exacerbation. Physician compliance with the recommended moxifloxacin dose (400 mg once daily) was 99.6%. The mean duration of moxifloxacin therapy for the current exacerbation (Anthonisen type I or II in 83.1%; predominantly type I) was 6.4 ± 1.9 days. Symptom improvement was reported after a mean of 3.4 ± 1.4 days. After 5 days, 93.2% of patients reported improvement and, in total, 93.5% of patients were symptom-free after 10 days. In the safety population (N = 2672), 57 (2.3%) patients had treatment-emergent adverse events (TEAEs) and 4 (0.15%) had serious TEAEs; no deaths occurred. These results are in line with the known safety profile of moxifloxacin.

Conclusions

A significant number of patients in this observational study had risk factors for poor outcome, justifying use of moxifloxacin. The safety profile of moxifloxacin and its value as an antibiotic treatment were confirmed. Physicians complied with the recommended 400 mg once-daily dose in a large proportion of patients, confirming the advantages of this simple dosing regimen.

Trial registration

ClinicalTrials.gov identifier: NCT00846911
Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen Plasmodium falciparum FVO merozoite surface protein-1 (MSP142) administered intramuscularly with adjuvant system AS01
Authors: Otsyula Nekoye , Angov Evelina , Bergmann-Leitner Elke , Koech Margaret , Khan Farhat , Bennett Jason , Otieno Lucas , Cummings James , Andagalu Ben , Tosh Donna , Waitumbi John , Richie Nancy , Shi Meng , Miller Lori , Otieno Walter , Otieno Godfrey Allan , Ware Lisa , House Brent , Godeaux Olivier , Dubois Marie-Claude , Ogutu Bernhards , Ballou W Ripley , Soisson Lorraine , Diggs Carter , Cohen Joe , Polhemus Mark , Heppner D Gray , Ockenhouse Christian F , Spring Michele D
Published: January 2013

Background

The development of an asexual blood stage vaccine againstPlasmodium falciparummalaria based on the major merozoite surface protein-1 (MSP1) antigen is founded on the protective efficacy observed in preclinical studies and induction of invasion and growth inhibitory antibody responses. The 42 kDa C-terminus of MSP1 has been developed as the recombinant protein vaccine antigen, and the 3D7 allotype, formulated with the Adjuvant System AS02A, has been evaluated extensively in human clinical trials. In preclinical rabbit studies, the FVO allele of MSP142has been shown to have improved immunogenicity over the 3D7 allele, in terms of antibody titres as well as growth inhibitory activity of antibodies against both the heterologous 3D7 and homologous FVO parasites.

Methods

Two Phase 1 clinical studies were conducted to examine the safety, reactogenicity and immunogenicity of the FVO allele of MSP142in the adjuvant system AS01 administered intramuscularly at 0-, 1-, and 2-months: one in the USA and, after evaluation of safety data results, one in Western Kenya. The US study was an open-label, dose escalation study of 10 and 50 μg doses of MSP142in 26 adults, while the Kenya study, evaluating 30 volunteers, was a double-blind, randomized study of only the 50 μg dose with a rabies vaccine comparator.

Results

In these studies it was demonstrated that this vaccine formulation has an acceptable safety profile and is immunogenic in malaria-naïve and malaria-experienced populations. High titres of anti-MSP1 antibodies were induced in both study populations, although there was a limited number of volunteers whose serum demonstrated significant inhibition of blood-stage parasites as measured by growth inhibition assay. In the US volunteers, the antibodies generated exhibited better cross-reactivity to heterologous MSP1 alleles than a MSP1-based vaccine (3D7 allele) previously tested at both study sites.

Conclusions

Given that the primary effector mechanism for blood stage vaccine targets is humoral, the antibody responses demonstrated to this vaccine candidate, both quantitative (total antibody titres) and qualitative (functional antibodies inhibiting parasite growth) warrant further consideration of its application in endemic settings.

Trial registrations

Clinical Trials NCT00666380
Innovative DAMA algorithm for multimedia DVB-RCS system
Authors: de la Cuesta Borja , Albiol Lorena , Aguiar Javier M , Baladrón Carlos , Carro Belén , Sánchez-Esguevillas Antonio
Published: January 2013

Satellite is often used as an access network in the Next Generation Networks landscape, where multimedia and real-time services are supported by return channels. However, these satellite return channels are a very limited resource with many terminal stations competing for its use, making its efficient assignation one of the key problems to solve in order to increase network performance. This article presents an innovative implementation of the resource allocation mechanism demand assigned multiple access (DAMA) applied to satellite return channel assignment, which provides support for dynamic allocation and quality-of-service. This resource allocation mechanism has been validated with the special purpose advanced Internet network emulator, using the test lab implementation to optimize traffic mapping and queue parameters directly in the field. The numerical results for the different test cases considered are presented, showing that the DAMA algorithm provided is an efficient way of assigning resources, and also helping in the comparison of the different capacity request mechanisms described in the standard.
Old drugs, old problems: where do we stand in prediction of rheumatoid arthritis responsiveness to methotrexate and other synthetic DMARDs?
Authors: Romão Vasco Crispim , Canhão Helena , Fonseca João Eurico
Published: January 2013

Methotrexate (MTX) is the central drug in the management of rheumatoid arthritis (RA) and other immune mediated inflammatory diseases. It is widely used either in monotherapy or in association with other synthetic and biologic disease modifying anti-rheumatic drugs (DMARDs). Although comprehensive clinical experience exists for MTX and synthetic DMARDs, to date it has not been possible to preview correctly whether or not a patient will respond to treatment with these drugs. Predicting response to MTX and other DMARDs would allow the selection of patients based on their likelihood of response, thus enabling individualized therapy and avoiding unnecessary adverse effects and elevated costs. However, studies analyzing this issue have struggled to obtain consistent, replicable results and no factor has yet been recognized to individually distinguish responders from nonresponders at treatment start. Variables possibly influencing drug effectiveness may be disease-, patient- or treatment-related, clinical or biological (genetic and nongenetic). In this review we summarize current evidence on predictors of response to MTX and other synthetic DMARDs, discuss possible causes for the heterogeneity observed and address its translation into daily clinical practice.
Posterolateral inter-transverse lumbar fusion in a mouse model
Authors: Bobyn Justin , Rasch Anton , Little David G , Schindeler Aaron
Published: January 2013

Background

Spinal fusion is a common orthopaedic procedure that has been previously modeled using canine, lapine, and rodent subjects. Despite the increasing availability of genetically modified mouse strains, murine models have only been infrequently described.

Purpose

To present an efficient and minimally traumatic procedure for achieving spinal fusion in a mouse model and determine the optimal rhBMP-2 dose to achieve sufficient fusion mass.

Method

MicroCT reconstructions of the unfused mouse spine and human spine were compared to design a surgical approach. In phase 1, posterolateral lumbar spine fusion in the mouse was evaluated using 18 animals allocated to three experimental groups. Group 1 received decortication only (n = 3), Group 2 received 10 μg rhBMP-2 in a collagen sponge bilaterally (n = 6), and Group 3 received 10 μg rhBMP-2 + decortication (n = 9). The surgical technique was assessed for intra-operative safety, efficacy, access and reproducibility. Spines were harvested for analysis at 3 weeks (Groups 1, 2) and 1, 2, and 3 weeks (Group 3). In phase 2, a dose response study was carried out in an additional 18 animals with C57BL6 mice receiving sponges containing 0, 0.5, 1, 2.5, 5 μg of rhBMP-2 per sponge bilaterally.

Results

The operative procedure via midline access was rapid and reproducible, and fusion of the murine articular processes was found to be analogous to the human procedure. Unlike reports from other species, decortication alone (Group 1) yielded no new bone formation. Addition of rhBMP-2 (Groups 2 and 3) yielded a significant bone mass that bridged the L4-L6 vertebrae. The subsequent dose response experiment revealed that 0.5 μg rhBMP-2 per sponge was sufficient to create a fusion mass.

Conclusion

We describe a new approach for mouse lumbar spine fusion that is safe, efficient, and highly reproducible. The technique we employed is analogous to the human midline procedure and may be highly suitable for genetically modified mouse models.
Perspectives and concerns of clients at primary health care facilities involved in evaluation of a national mental health training programme for primary care in Kenya
Authors: Othieno Caleb , Jenkins Rachel , Okeyo Stephen , Aruwa Julyan , Wallcraft Jan , Jenkins Ben
Published: January 2013

Background

A cluster randomised controlled trial (RCT) of a national Kenyan mental health primary care training programme demonstrated a significant impact on the health, disability and quality of life of clients, despite a severe shortage of medicines in the clinics (Jenkins et al. Submitted 2012). As focus group methodology has been found to be a useful method of obtaining a detailed understanding of client and health worker perspectives within health systems (Sharfritz and Roberts. Health Transit Rev 4:81–85, 1994), the experiences of the participating clients were explored through qualitative focus group discussions in order to better understand the potential reasons for the improved outcomes in the intervention group.

Methods

Two ninety minute focus groups were conducted in Nyanza province, a poor agricultural region of Kenya, with 10 clients from the intervention group clinics where staff had received the training programme, and 10 clients from the control group where staff had not received the training during the earlier randomised controlled trial.

Results

These focus group discussions suggest that the clients in the intervention group noticed and appreciated enhanced communication, diagnostic and counselling skills in their respective health workers, whereas clients in the control group were aware of the lack of these skills. Confidentiality emerged from the discussions as a significant client concern in relation to the volunteer cadre of community health workers, whose only training comes from their respective primary care health workers.

Conclusion

Enhanced health worker skills conferred by the mental health training programme may be responsible for the significant improvement in outcomes for clients in the intervention clinics found in the randomised controlled trial, despite the general shortage of medicines and other health system weaknesses. These findings suggest that strengthening mental health training for primary care staff is worthwhile even where health systems are not strong and where the medicine supply cannot be guaranteed.

Trial registration

ISRCTN 53515024.
Short and long term gene expression variation and networking in human proximal tubule cells when exposed to cadmium
Authors: Garrett Scott H , Clarke Kaitlin , Sens Donald A , Deng Youping , Somji Seema , Zhang Ke K
Published: January 2013

Cadmium (Cd2+) is a known nephrotoxin causing tubular necrosis during acute exposure and potentially contributing to renal failure in chronic long-term exposure. To investigate changes in global gene expression elicited by cadmium, an in-vitro exposure system was developed from cultures of human renal epithelial cells derived from cortical tissue obtained from nephrectomies. These cultures exhibit many of the qualities of proximal tubule cells. Using these cells, a study was performed to determine the cadmium-induced global gene expression changes after short-term (1 day, 9, 27, and 45 μM) and long-term cadmium exposure (13 days, 4.5, 9, and 27 μM). These studies revealed fundamental differences in the types of genes expressed during each of these time points. The obtained data was further analyzed using regression to identify cadmium toxicity responsive genes. Regression analysis showed 403 genes were induced and 522 genes were repressed by Cd2+ within 1 day, and 366 and 517 genes were induced and repressed, respectively, after 13 days. We developed a gene set enrichment analysis method to identify the cadmium induced pathways that are unique in comparison to traditional approaches. The perturbation of global gene expression by various Cd2+ concentrations and multiple time points enabled us to study the transcriptional dynamics and gene interaction using a mutual information-based network model. The most prominent network module consisted of INHBA, KIF20A, DNAJA4, AKAP12, ZFAND2A, AKR1B10, SCL7A11, and AKR1C1.
An adult patient with Henoch-Schönlein purpura and non-occlusive mesenteric ischemia
Authors: Oshikata Chiyako , Tsurikisawa Naomi , Takigawa Masakazu , Omori Tomoko , Sugano Satoshi , Tsuburai Takahiro , Mitomi Hiroyuki , Takemura Tamiko , Akiyama Kazuo
Published: January 2013

Background

Onset of Henoch-Schönlein purpura (HSP) in middle age is uncommon, and adults with renal or gastrointestinal involvement present with more severe disease than do similar pediatric patients.

Case presentation

We present the case of a 69-year-old male with HSP who, after treatment with steroids, cyclophosphamide, and continuous intravenous prostaglandin E1 (PGE1), died as a result of severe gastrointestinal involvement with non-occlusive mesenteric ischemia (NOMI). Vascular narrowing associated with the NOMI improved after catheter injection of PGE1 and prednisolone, but the patient died of bleeding from an exposed small vessel. At autopsy there was no active vasculitis in the jejunal submucosa.

Conclusion

Treatment with PGE1 and prednisolone might improve small-vessel vasculitis associated with NOMI.
Blood CD33(+)HLA-DR(−) myeloid-derived suppressor cells are increased with age and a history of cancer
Authors: Verschoor Chris P , Johnstone Jennie , Millar Jamie , Dorrington Michael G , Habibagahi Mojtaba , Lelic Alina , Loeb Mark , Bramson Jonathan L , Bowdish Dawn M E
Published: January 2013

Myeloid-derived suppressor cells are increased with age and elevated in donors with a history of cancer; an age-related effect has never been shown in humans.

As we age, the composition of our peripheral leukocytes changes dramatically. Many of these alterations contribute to the general immune dysfunction that burdens the elderly, which in turn, contributes to increased susceptibility to disease. MDSCs represent a heterogeneous population of immunosuppressive leukocytes that are elevated in the peripheral blood of cancer patients. Given the relation between cancer incidence and age, this study examined the frequency of peripheral blood CD33(+)HLA-DR(−) MDSCs across three cohorts: healthy adults (19–59 years old), community-dwelling seniors (61–76 years old), and frail elderly (67–99 years old). This analysis is the first to demonstrate that MDSCs and specifically the CD11b(+)CD15(+) MDSC subset are increased with age. Proinflammatory cytokines that are required for the differentiation of MDSCs (e.g., TNF-α, IL-6, and IL-1β) were similarly found to be increased in the serum of the frail elderly. Furthermore, the proportion of MDSCs and the CD11b(+)CD15(+) subset were found to be elevated significantly in elderly donors with a history of cancer. This age-related elevation in the frequency of MDSCs may contribute to the increased cancer incidence that occurs with age. Further investigation into the functional consequences of elevated MDSCs will provide valuable insight into the progression of age-related pathologies.
Antiangiogenic Agents, Chemotherapy, and the Treatment of Metastatic Transitional Cell Carcinoma
Authors: Vogelzang Nicholas J.
Published: January 2013

A 69-year-old man with a 100 pack-year history of smoking developed gross hematuria. His medical history included hypertension, a silent myocardial infarction, and a cerebrovascular accident complicated by seizures. Cystoscopy and biopsy showed a 4-cm mass at the right ureteral orifice positive for a high-grade papillary transitional cell carcinoma (TCC) with muscularis propria invasion (Fig 1). The computed tomography (CT)/positron emission tomography (PET) scan of the chest, abdomen, and pelvis showed hydronephrosis and hydroureter with marked cortical thinning and multiple bilateral PET-avid pulmonary nodules, with the largest in the left upper lung measuring 3.0 × 2.5 cm (Figs 2A, 3A), biopsy of which showed invasive high-grade urothelial carcinoma. The patient consented to join a clinical trial for metastatic TCC (USON [US Oncology Network study] 06040) involving treatment with gemcitabine, cisplatin, and sunitinib (GCS) 37.5 mg per day.1 Four days later, he experienced a 10-day hospitalization for acute pancreatitis and neutropenia. Sunitinib was discontinued, and he completed four additional cycles of GC. CT/PET showed that the right ureteral mass and all lung nodules had regressed or disappeared (Figs 2B, 3B). The largest remaining lung nodule at 1.4 cm showed no metabolic activity. He underwent a radical cystoprostatectomy and right nephroureterectomy, disclosing residual high-grade urothelial carcinoma infiltrating the full thickness of the ureteral wall. There was carcinoma in situ of the bladder, and 42 nodes were negative for cancer. The surgery was followed by a small, uncomplicated myocardial infarction. A scheduled left thoracotomy to remove the remaining nodule was cancelled. No additional chemotherapy was administered, and the patient remains free of recurrence 2 years from initiation of chemotherapy. The 1.4-cm nodule has calcified and remains stable and metabolically inactive. He has no sequelae of chemotherapy or surgery, with a creatinine level of 1.35 mg/dL.
Randomized Phase III Multi-Institutional Study of TNFerade Biologic With Fluorouracil and Radiotherapy for Locally Advanced Pancreatic Cancer: Final Results
Authors: Herman Joseph M. , Wild Aaron T. , Wang Hao , Tran Phuoc T. , Chang Kenneth J. , Taylor Gretchen E. , Donehower Ross C. , Pawlik Timothy M. , Ziegler Mark A. , Cai Hongyan , Savage Dionne T. , Canto Marcia I. , Klapman Jason , Reid Tony , Shah Raj J. , Hoffe Sarah E. , Rosemurgy Alexander , Wolfgang Christopher L. , Laheru Daniel A.
Published: January 2013

Purpose

TNFerade biologic is a novel means of delivering tumor necrosis factor alpha to tumor cells by gene transfer. We herein report final results of the largest randomized phase III trial performed to date among patients with locally advanced pancreatic cancer (LAPC) and the first to test gene transfer against this malignancy.

Patients and Methods

In all, 304 patients were randomly assigned 2:1 to standard of care plus TNFerade (SOC + TNFerade) versus standard of care alone (SOC). SOC consisted of 50.4 Gy in 28 fractions with concurrent fluorouracil (200 mg/m2 per day continuous infusion). TNFerade was injected intratumorally before the first fraction of radiotherapy each week at a dose of 4 × 1011 particle units by using either a percutaneous transabdominal or an endoscopic ultrasound approach. Four weeks after chemoradiotherapy, patients began gemcitabine (1,000 mg/m2 intravenously) with or without erlotinib (100 to 150 mg per day orally) until progression or toxicity.

Results

The analysis included 187 patients randomly assigned to SOC + TNFerade and 90 to SOC by using a modified intention-to-treat approach. Median follow-up was 9.1 months (range, 0.1 to 50.5 months). Median survival was 10.0 months for patients in both the SOC + TNFerade and SOC arms (hazard ratio [HR], 0.90; 95% CI, 0.66 to 1.22; P = .26). Median progression-free survival (PFS) was 6.8 months for SOC + TNFerade versus 7.0 months for SOC (HR, 0.96; 95% CI, 0.69 to 1.32; P = .51). Among patients treated on the SOC + TNFerade arm, multivariate analysis showed that TNFerade injection by an endoscopic ultrasound-guided transgastric/transduodenal approach rather than a percutaneous transabdominal approach was a risk factor for inferior PFS (HR, 2.08; 95% CI, 1.06 to 4.06; P = .032). The patients in the SOC + TNFerade arm experienced more grade 1 to 2 fever and chills than those in the SOC arm (P < .001) but both arms had similar rates of grade 3 to 4 toxicities (all P > .05).

Conclusion

SOC + TNFerade is safe but not effective for prolonging survival in patients with LAPC.
Pharmacotherapy Considerations in Patients with HIV and Psychiatric Disorders: Focus on Antidepressants and Antipsychotics
Authors: Hill Lucas , Lee Kelly C
Published: January 2013

OBJECTIVE

To review the evidence for the efficacy and safety of pharmacologic agents for the treatment of depressive and psychotic disorders in patients with HIV infection and to provide clinical considerations for the treatment of depression and psychosis in these patients.

DATA SOURCES

PubMed was searched for articles published between 1966 and August 1, 2012, using the search terms antiretrovirals, HIV, AIDS, depression, psychosis, schizophrenia, antidepressant, antipsychotic, and individual drug names (fluoxetine, sertraline, paroxetine, citalopram, escitalopram, venlafaxine, duloxetine, mirtazapine, bupropion, haloperidol, perphenazine, fluphenazine, aripiprazole, asenapine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone).

STUDY SELECTION AND DATA EXTRACTION

For the purposes of evaluating efficacy data, we limited our selection to randomized placebo-controlled or active comparator–controlled trials for agents that have been used for depression and psychosis in HIV-infected patients.

DATA SYNTHESIS

We found 11 studies for depression treatment and 1 study for psychosis treatment that met our inclusion and exclusion criteria. Selective serotonin reuptake inhibitors (SSRIs; especially fluoxetine) and tricyclic antidepressants appear to be effective in treating depressive symptoms in patients with HIV infection without affecting immune status. Testosterone, stimulants, and dehydroepiandrosterone may also be effective in subsyndromal depression; however, studies on these agents in general were limited by small sample size. There are limited data for antipsychotics, with the only controlled study found for haloperidol and chlorpromazine used for AIDS delirium. Drug-drug interactions and potentiation of metabolic syndrome are concerns for the combined use of antidepressants and antipsychotics with antiretrovirals.

CONCLUSIONS

Larger controlled studies are needed to validate the current findings as well as expand knowledge for non-SSRI antidepressants and second-generation antipsychotics for use in HIV-infected patients.