bluuebunny/crossref_metadata_2025 huggingface dataset:
Survivors of Sex Trafficking in Andhra Pradesh
Authors: Vindhya U. , Dev V. Swathi
Published: June 2011

In the literature on trafficking in India there is a crucial dearth of primary data and micro studies that could be used for vulnerability mapping of the source areas and for addressing the risk factors identified. The article is a small attempt to contribute to plugging the gap in the context of Andhra Pradesh, identified as a ‘hot spot’ in the literature. It is based on case studies of 78 women who had been trafficked from their places of origin in Anantapur district to metropolitan cities across India and who have since returned to their homes. The article attempts to identify the individual and family circumstances that contribute to trafficking, to highlight in particular the gendered vulnerabilities that set these women up for trafficking, and to capture the process of the trafficking experience. The case studies reported here point to the compelling urgency of interventions that will go beyond the forced/voluntary divide in trafficking and sex work.
Climate Change and Asia’s Coastal Urban Cities
Authors: Fuchs Roland , Conran Mary , Louis Elizabeth
Published: June 2011

The scientific literature has documented the growing risks of flooding posed for Asia’s coastal cities by the combination of climate change, as reflected in sea level rise and intensified storms and storm surges, and ongoing urban growth in low-lying coastal zones. These issues were already elaborated in the 2007 IPCC (IPCC, 2007) reports but recent studies indicate that climate change, sea level rise and the sinking of the deltas on which most Asian mega urban regions have arisen, are all occurring at much faster rates than earlier projected and therefore pose even greater risks than previously indicated. Global warming appears to be accelerating and may increase to 4° C or more by the end of this century, twice the earlier IPCC projections. The sea level is now expected to rise by one meter or more by 2100; two or three times the earlier projections. The recent typhoons and rains striking Southeast Asia have been the most intense in decades as would be expected as a result of global warming. At the same time, Asia’s urban population is increasing at the rate of 140,000 per day, with much of this growth occurring in low-lying coastal regions and on deltas characterized by land subsidence that is further contributing to flooding risks. While these risks and vulnerabilities have been increasingly detailed in the scientific literature, recognition and effective responses on the part of the urban planning and policy community have been slow to develop. Barriers to adaptation, policy formation and response are reviewed and possible steps forward are outlined.
Health-Related Quality of Life of Hematopoietic Stem Cell Transplant Childhood Survivors
Authors: Tanzi Elizabeth M.
Published: June 2011

The notion of health-related quality of life (HRQoL) holds unique significance in the treatment of patients who have undergone hematopoietic stem cell transplantation (HSCT). Not only is transplant procedure inevitably associated with immediate and late medical effects along with high mortality and morbidity rates, but it can also significantly affect the HRQoL for the patient and family. This review of literature will assist advanced practice nurses and pediatric oncology nurses in distinguishing and targeting interventions for patients and families who are at high risk of encountering distress during and following HSCT. It provides information on the assessment of pre-HSCT variables to identify patient subgroups in need of more aggressive supportive care to improve HRQoL during transplant. Furthermore, it serves as a guideline for developing interventional strategies and the role of the advanced practice nurse and pediatric oncology nurse caring for the patient throughout and following transplant.
Evaluating the Productivity of Social Work Scholars Using the h-Index
Authors: Lacasse Jeffrey R. , Hodge David R. , Bean Kristen F.
Published: June 2011

Objectives: This article reports the first estimated h-index values for social work faculty. Methods: Multiple raters blindly assessed two samples of faculty (1) tenure-track faculty at institutions listed in the U.S. News and World Report top 10 (n = 337) and (2) tenure-track editorial board members of 5 highly ranked social work journals (n = 215). Results: Intraclass correlation coefficients for h-index values among the multiple raters ranged from .83 to .92, indicating good reliability. For faculty at top 10 institutions, mean estimated h-index values were 3.97 (SD = 2.87) for assistant professors; 8.59 (SD = 3.72) for associate professors; and 16.14 (SD = 8.35) for full professors. Values for editorial board members were generally similar. Conclusions: These are the first such published data; further research is needed.
The Adaptive Approach
Authors: Lee Ching-Fang , Tsai Stephen Dun-Hou , Amjadi Mansour
Published: June 2011

In this essay, the authors analyze two different knowledge management (KM) approaches in the semiconductor industry: the object-based KM (OBKM) and community-based KM (CBKM) models. This reveals that organizational knowledge is not only distributed differently in different workplaces but also embedded in the specific context of interactions. The authors then illustrate that the CBKM model complements the OBKM model based on the complex adaptive system perspective. Furthermore, the adaptive approach that allows actors to benefit from both models in their work practices is proposed. Finally, theoretical and practical implications, as well as potential areas for further inquiries, are identified.
Triple Synchronous Primary Gynecologic Carcinomas
Authors: Hale Christopher Stephen , Lee Lili , Mittal Khush
Published: June 2011

Double synchronous primaries are known to occasionally occur in gynecologic cancers. Cases of triple or quadruple synchronous primaries, with only 4 case reports in the literature, are extremely rare. The authors report the case of a 49-year-old para 2-0-0-2 woman who presented for surgical management of metastatic ovarian adenocarcinoma diagnosed at an outside institution. On examination of the surgical specimen, 3 synchronous primary carcinomas with multiple histologic features were identified within the ovaries, uterus, and cervix. Although rare, the possibility of triple synchronous primary malignancies should be considered when evaluating gynecologic malignancies.
Conflict and Cooperation in Municipalities
Authors: Nelson Kimberly L. , Nollenberger Karl
Published: June 2011

One measure of governance quality is the level of reported conflict and cooperation that is present between and among elected officials and administrators. High levels of conflict or low levels of cooperation can hinder the decision-making process. However, there are few attempts to assess the causes of conflict and cooperation in the existing literature. This study uses an expanded typology of local government form and additional independent variables to determine what factors are likely to lead to conditions conducive to cooperation and lower perceived conflict in the local governance process. Data on government performance and indicators of perceived conflict and cooperation were collected from a national survey of municipal mayors, council members, and chief administrators in cities with populations of 50,000 to 250,000. Our results suggest that form of government and proportion of council members elected by district are two factors that significantly influence governance at the local level.
Relationship Between Self-Reported Racial Composition of High School and Health Literacy Among Community Health Center Patients
Authors: Kaphingst Kimberly A. , Goodman Melody , Pyke Owen , Stafford Jewel , Lachance Christina
Published: June 2011

Intervention and policy approaches targeting the societal factors that affect health literacy (e.g., educational systems) could have promise to improve health outcomes, but little research has investigated these factors. This study examined the associations between self-reported racial composition of prior educational and neighborhood contexts and health literacy among 1,061 English- and Spanish-speaking adult community health center patients. The authors found that self-reported racial composition of high school was a significant predictor of health literacy among those who received schooling in the United States, controlling for race/ethnicity, education, age, country of birth, and survey language. Black and Hispanic patients had significantly lower health literacy than White patients within educational strata among those schooled in the United States. The findings revealed substantial disparities in health literacy. Self-reported racial composition of school context was a significant predictor of health literacy. Transdisciplinary, multilevel intervention approaches are likely to be needed to address the health literacy needs of this population.
Implementation of new diffusion/filtering operators in the CAM-FV dynamical core
Authors: Lauritzen Peter H. , Mirin Arthur A. , Truesdale John , Raeder Kevin , Anderson Jeffrey L. , Bacmeister Julio , Neale Richard B.
Published: June 2011

Two new filtering/diffusion operators have been implemented in the Community Atmosphere Model finite-volume dynamical core (CAM-FV). First, a fourth-order divergence damping operator has been added to optionally replace the second-order version that has traditionally been used. This provides more scale selective dissipation of divergent modes that can generate grid-scale noise in CAM-FV if not damped properly. For example, data assimilation runs using CAM-FV DART (Data Assimilation Research Testbed) have revealed potential noise problems at the grid scale that can be alleviated significantly using higher-order divergence damping. Second, a ‘Laplacian’-type damping operator has been implemented to increase the explicit momentum dissipation in the top-of-atmosphere sponge layers. This helps control the excessive polar night jets that have been observed in ultra-high-resolution CAM-FV simulations. Results from stand-alone CAM-FV and CAM-FV DART are presented in this paper along with details on the implementation of the new operators.
Anatomy of interaction experience: Distinguishing sensory, semantic, and behavioral dimensions of interactivity
Authors: Sohn Dongyoung
Published: June 2011

Understanding the experience people have in a direct or mediated interaction is essential to defining interactivity and theorizing its role in communication, but the question of what constitutes a person’s perceptual experience of interaction, namely perceived interactivity, has not been systematically inquired. The objective of this article is to define the general structure of perceived interactivity, which provides an integrative framework to compare and evaluate interaction forms or situations involving human actors as well as both old and new media. A major premise of this framework is that an interaction experience, whether direct or mediated, consists of three underlying dimensions – sensory, semantic, and behavioral.
Identifying the invisible: The experiences of prostitution among persons with intellectual disabilities: Implications for social work
Authors: Kuosmanen Jari , Starke Mikaela
Published: June 2011

• Summary: This article explores a relatively uncharted research area. The focus of the analysis is on how professionals working in care provision units, specialized prostitution units, the police, social services and special schools detect and deal with prostitution among people with intellectual disabilities. The data were obtained primarily through focus group interviews. The study shows that organizational specialization in different authorities and services makes it difficult to identify and work with this group. Clients with complex problems tend to find themselves in between the jurisdictional fields of different authorities, meaning that many do not receive the support that they need.

• Findings: In recent decades social work has undergone increasing balkanization and specialization. Each particular organization is regulated by specific legislation, regulations, forms of knowledge and normative assumptions. Professionals working with people with intellectual disabilities have difficulties in detecting prostitution among their clients, whilst those who work with prostitution lack the knowledge and methods to work with intellectual disabilities. At the same time, social work with these individuals is conducted within a field of tension between the client′s right of self-determination and professionals’ responsibilities for their well-being.

• Applications: The study demonstrates that, with this type of complex problem, it is important to establish different types of collaboration between different organizations. However, due to the risk of increased control being detrimental to clients, collaboration needs to be founded on the client’s needs and right to self-determination.
Masson’s disease in hand surgery: a clinicopathologic study of four cases
Authors: Sartore L. , Voltan A. , Tomat V. , Bassetto F. , Salmaso R.
Published: June 2011

Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson’s tumour, is an uncommon benign vascular lesion characterized by small multiple, endothelial-lined, papillary structures with hyaline stalks. It appears to be a reactive condition involving excessive proliferation of endothelial cells in normal blood vessels or in vascular malformations, perhaps in response to blood vessel injury or thrombosis. The lesions are small, superficial, reddish-blue nodules, usually in the head, neck or hand. Distinction from pyogenic granuloma and angiosarcoma usually requires pathological examination. Complete surgical excision is the treatment of choice. Four cases affecting the finger are presented together with histological features.
A new non-contact automatic inspection method for micro-structures
Authors: Castellani M , Landot R , Yang M , Beyeler F
Published: June 2011

This paper presents a new non-contact, non-destructive method for automatic inspection of micro-structures. A piezoelectric actuator is used to vibrate the devices under inspection. The frequency of the vibrations is swept within an interval that includes the resonance frequency of the parts. A microscope camera is used to monitor the vibrations of the structures. At resonance, functional devices undergo large oscillations and these are seen as a blur on the camera. Two image processing algorithms are used to measure the degree of blurring in the camera images, namely, Quadtree segmentation and Otsu's adaptive thresholding method. Using the Quadtree segmentation method, blurring is detected from a drop in the count of image partitions. Using Otsu's adaptive thresholding method, blurring is detected from an increase in the count of white pixels in the binarized image. In both cases, by setting a threshold on the number of partitions (white pixels), resonant parts can be distinguished from broken ones. Experimental tests proved the effectiveness of the proposed method, and indicate the feasibility of its application in a real time plant environment. This is believed to be the first fully automated quality control method for micro-structures based on the analysis of their resonance vibrations.
miR-181b is a biomarker of disease progression in chronic lymphocytic leukemia
Authors: Visone Rosa , Veronese Angelo , Rassenti Laura Z. , Balatti Veronica , Pearl Dennis K. , Acunzo Mario , Volinia Stefano , Taccioli Cristian , Kipps Thomas J. , Croce Carlo M.
Published: June 2011

MicroRNAs play a crucial role in chronic lymphocytic leukemia. We investigated whether microRNAs can discriminate patients with a progressive disease from patients with a stable disease. We analyzed microRNA expression on leukemic cells isolated from 358 sequential samples of 114 patients with either stable or progressive disease. We found that during the course of the disease the expression values of miR-181b, the most dysregulated microRNA, decreased in samples of patients with a progressive (P < .001, training and validation sets) but not in samples of patients with a stable disease (P = .3, training set; P = .2, validation set) over time. A drop of ≥ 50% between sequential samples and/or a miR-181b value ≤ 0.005 at the starting time point were significant to differentiate progressive from stable disease (P = .004, training set; P < .001, validation set). These parameters were associated with high risk of requiring treatment (risk ratio, 5.8; 95% confidence interval, 2.5-14.9). We also observed that miR-181b targets Mcl-1 protein and that the decrease of its expression inversely correlated with increased protein levels of MCL1 and BCL2 target genes. We conclude that parameters defined on the basis of the miR-181b expression values specify disease progression in chronic lymphocytic leukemia and are associated with clinical outcome.
Characterization of porcine dendritic cell response to Streptococcus suis
Authors: Lecours Marie-Pier , Segura Mariela , Lachance Claude , Mussa Tufaria , Surprenant Charles , Montoya Maria , Gottschalk Marcelo
Published: June 2011

Streptococcus suis is a major swine pathogen and important zoonotic agent causing mainly septicemia and meningitis. However, the mechanisms involved in host innate and adaptive immune responses toward S. suis as well as the mechanisms used by S. suis to subvert these responses are unknown. Here, and for the first time, the ability of S. suis to interact with bone marrow-derived swine dendritic cells (DCs) was evaluated. In addition, the role of S. suis capsular polysaccharide in modulation of DC functions was also assessed. Well encapsulated S. suis was relatively resistant to phagocytosis, but it increased the relative expression of Toll-like receptors 2 and 6 and triggered the release of several cytokines by DCs, including IL-1β, IL-6, IL-8, IL-12p40 and TNF-α. The capsular polysaccharide was shown to interfere with DC phagocytosis; however, once internalized, S. suis was readily destroyed by DCs independently of the presence of the capsular polysaccharide. Cell wall components were mainly responsible for DC activation, since the capsular polysaccharide-negative mutant induced higher cytokine levels than the wild-type strain. The capsular polysaccharide also interfered with the expression of the co-stimulatory molecules CD80/86 and MHC-II on DCs. To conclude, our results show for the first time that S. suis interacts with swine origin DCs and suggest that these cells might play a role in the development of host innate and adaptive immunity during an infection with S. suis serotype 2.
Comparative thermodynamic studies on substrate and product binding of O-Acetylserine Sulfhydrylase reveals two different ligand recognition modes†
Authors: Banerjee Shrijita , Ekka Mary K , Kumaran Sangaralingam
Published: June 2011

Background

The importance of understanding the detailed mechanism of cysteine biosynthesis in bacteria is underscored by the fact that cysteine is the only sulfur donor for all cellular components containing reduced sulfur. O-acetylserine sulfhydrylase (OASS) catalyzes this crucial last step in the cysteine biosynthesis and has been recognized as an important gene for the survival and virulence of pathogenic bacteria. Structural and kinetic studies have contributed to the understanding of mechanistic aspects of OASS, but details of ligand recognition features of OASS are not available. In the absence of any detailed study on the energetics of ligand binding, we have studied the thermodynamics of OASS from Salmonella typhimurium (St OASS), Haemophilus influenzae (Hi OASS), and Mycobacterium tuberculosis (MtOASS) binding to their substrate O-acetylserine (OAS), substrate analogue (methionine), and product (cysteine).

Results

Ligand binding properties of three OASS enzymes are studied under defined solution conditions. Both substrate and product binding is an exothermic reaction, but their thermodynamic signatures are very different. Cysteine binding to OASS shows that both enthalpy and entropy contribute significantly to the binding free energy at all temperatures (10-30°C) examined. The analyses of interaction between OASS with OAS (substrate) or methionine (substrate analogue) revealed a completely different mode of binding. Binding of both OAS and methionine to OASS is dominated by a favorable entropy change, with minor contribution from enthalpy change (ΔHSt-Met = -1.5 ± 0.1 kJ/mol; TΔSSt-Met = 8.2 kJ/mol) at 20°C. Our salt dependent ligand binding studies indicate that methionine binding affinity is more sensitive to [NaCl] as compared to cysteine affinity.

Conclusions

We show that OASS from three different pathogenic bacteria bind substrate and product through two different mechanisms. Results indicate that predominantly entropy driven methionine binding is not mediated through classical hydrophobic binding, instead, may involve desolvation of the polar active site. We speculate that OASS in general, may exhibit two different binding mechanisms for recognizing substrates and products.
Using affinity propagation for identifying subspecies among clonal organisms: lessons from M. tuberculosis
Authors: Borile Claudio , Labarre Mathieu , Franz Silvio , Sola Christophe , Refrégier Guislaine
Published: June 2011

Background

Classification and naming is a key step in the analysis, understanding and adequate management of living organisms. However, where to set limits between groups can be puzzling especially in clonal organisms. Within the Mycobacterium tuberculosis complex (MTC), the etiological agent of tuberculosis (TB), experts have first identified several groups according to their pattern at repetitive sequences, especially at the CRISPR locus (spoligotyping), and to their epidemiological relevance. Most groups such as "Beijing" found good support when tested with other loci. However, other groups such as T family and T1 subfamily (belonging to the "Euro-American" lineage) correspond to non-monophyletic groups and still need to be refined. Here, we propose to use a method called Affinity Propagation that has been successfully used in image categorization to identify relevant patterns at the CRISPR locus in MTC.

Results

To adequately infer the relative divergence time between strains, we used a distance method inspired by the recent evolutionary model by Reyes et al. We first confirm that this method performs better than the Jaccard index commonly used to compare spoligotype patterns. Second, we document the support of each spoligotype family among the previous classification using affinity propagation on the international spoligotyping database SpolDB4. This allowed us to propose a consensus assignation for all SpolDB4 spoligotypes. Third, we propose new signatures to subclassify the T family.

Conclusion

Altogether, this study shows how the new clustering algorithm Affinity Propagation can help building or refining clonal organims classifications. It also describes well-supported families and subfamilies among M. tuberculosis complex, especially inside the modern "Euro-American" lineage.
Computer-based fluorescence quantification: a novel approach to study nucleolar biology
Authors: Kodiha Mohamed , Bański Piotr , Stochaj Ursula
Published: June 2011

Background

Nucleoli are composed of possibly several thousand different proteins and represent the most conspicuous compartments in the nucleus; they play a crucial role in the proper execution of many cellular processes. As such, nucleoli carry out ribosome biogenesis and sequester or associate with key molecules that regulate cell cycle progression, tumorigenesis, apoptosis and the stress response. Nucleoli are dynamic compartments that are characterized by a constant flux of macromolecules. Given the complex and dynamic composition of the nucleolar proteome, it is challenging to link modifications in nucleolar composition to downstream effects.

Results

In this contribution, we present quantitative immunofluorescence methods that rely on computer-based image analysis. We demonstrate the effectiveness of these techniques by monitoring the dynamic association of proteins and RNA with nucleoli under different physiological conditions. Thus, the protocols described by us were employed to study stress-dependent changes in the nucleolar concentration of endogenous and GFP-tagged proteins. Furthermore, our methods were applied to measure de novo RNA synthesis that is associated with nucleoli. We show that the techniques described here can be easily combined with automated high throughput screening (HTS) platforms, making it possible to obtain large data sets and analyze many of the biological processes that are located in nucleoli.

Conclusions

Our protocols set the stage to analyze in a quantitative fashion the kinetics of shuttling nucleolar proteins, both at the single cell level as well as for a large number of cells. Moreover, the procedures described here are compatible with high throughput image acquisition and analysis using HTS automated platforms, thereby providing the basis to quantify nucleolar components and activities for numerous samples and experimental conditions. Together with the growing amount of information obtained for the nucleolar proteome, improvements in quantitative microscopy as they are described here can be expected to produce new insights into the complex biological functions that are orchestrated by the nucleolus.
Genetic basis of wing morphogenesis in Drosophila: sexual dimorphism and non-allometric effects of shape variation
Authors: Carreira Valeria P , Soto Ignacio M , Mensch Julián , Fanara Juan J
Published: June 2011

Background

The Drosophila wing represents a particularly appropriate model to investigate the developmental control of phenotypic variation. Previous studies which aimed to identify candidate genes for wing morphology demonstrated that the genetic basis of wing shape variation in D. melanogaster is composed of numerous genetic factors causing small, additive effects. In this study, we analyzed wing shape in males and females from 191 lines of D. melanogaster, homozygous for a single P-element insertion, using geometric morphometrics techniques. The analysis allowed us to identify known and novel candidate genes that may contribute to the expression of wing shape in each sex separately and to compare them to candidate genes affecting wing size which have been identified previously using the same lines.

Results

Our results indicate that more than 63% of induced mutations affected wing shape in one or both sexes, although only 33% showed significant differences in both males and females. The joint analysis of wing size and shape revealed that only 19% of the P-element insertions caused coincident effects on both components of wing form in one or both sexes. Further morphometrical analyses revealed that the intersection between veins showed the smallest displacements in the proximal region of the wing. Finally, we observed that mutations causing general deformations were more common than expected in both sexes whereas the opposite occurred with those generating local changes. For most of the 94 candidate genes identified, this seems to be the first record relating them with wing shape variation.

Conclusions

Our results support the idea that the genetic architecture of wing shape is complex with many different genes contributing to the trait in a sexually dimorphic manner. This polygenic basis, which is relatively independent from that of wing size, is composed of genes generally involved in development and/or metabolic functions, especially related to the regulation of different cellular processes such as motility, adhesion, communication and signal transduction. This study suggests that understanding the genetic basis of wing shape requires merging the regulation of vein patterning by signalling pathways with processes that occur during wing development at the cellular level.
Diverse and tissue-enriched small RNAs in the plant pathogenic fungus, Magnaporthe oryzae
Authors: Nunes Cristiano C , Gowda Malali , Sailsbery Joshua , Xue Minfeng , Chen Feng , Brown Douglas E , Oh YeonYee , Mitchell Thomas K , Dean Ralph A
Published: June 2011

Background

Emerging knowledge of the impact of small RNAs as important cellular regulators has prompted an explosion of small transcriptome sequencing projects. Although significant progress has been made towards small RNA discovery and biogenesis in higher eukaryotes and other model organisms, knowledge in simple eukaryotes such as filamentous fungi remains limited.

Results

Here, we used 454 pyrosequencing to present a detailed analysis of the small RNA transcriptome (~ 15 - 40 nucleotides in length) from mycelia and appressoria tissues of the rice blast fungal pathogen, Magnaporthe oryzae. Small RNAs mapped to numerous nuclear and mitochondrial genomic features including repetitive elements, tRNA loci, rRNAs, protein coding genes, snRNAs and intergenic regions. For most elements, small RNAs mapped primarily to the sense strand with the exception of repetitive elements to which small RNAs mapped in the sense and antisense orientation in near equal proportions. Inspection of the small RNAs revealed a preference for U and suppression of C at position 1, particularly for antisense mapping small RNAs. In the mycelia library, small RNAs of the size 18 - 23 nt were enriched for intergenic regions and repetitive elements. Small RNAs mapping to LTR retrotransposons were classified as LTR retrotransposon-siRNAs (LTR-siRNAs). Conversely, the appressoria library had a greater proportion of 28 - 35 nt small RNAs mapping to tRNA loci, and were classified as tRNA-derived RNA fragments (tRFs). LTR-siRNAs and tRFs were independently validated by 3' RACE PCR and northern blots, respectively.

Conclusions

Our findings suggest M. oryzae small RNAs differentially accumulate in vegetative and specialized-infection tissues and may play an active role in genome integrity and regulating growth and development.
Whole brain radiotherapy after local treatment of brain metastases in melanoma patients - a randomised phase III trial
Authors: Fogarty Gerald , Morton Rachael L , Vardy Janette , Nowak Anna K , Mandel Catherine , Forder Peta M , Hong Angela , Hruby George , Burmeister Bryan , Shivalingam Brindha , Dhillon Haryana , Thompson John F
Published: June 2011

Background

Cerebral metastases are a common cause of death in patients with melanoma. Systemic drug treatment of these metastases is rarely effective, and where possible surgical resection and/or stereotactic radiosurgery (SRS) are the preferred treatment options. Treatment with adjuvant whole brain radiotherapy (WBRT) following neurosurgery and/or SRS is controversial. Proponents of WBRT report prolongation of intracranial control with reduced neurological events and better palliation. Opponents state melanoma is radioresistant; that WBRT yields no survival benefit and may impair neurocognitive function. These opinions are based largely on studies in other tumour types in which assessment of neurocognitive function has been incomplete.

Methods/Design

This trial is an international, prospective multi-centre, open-label, phase III randomised controlled trial comparing WBRT to observation following local treatment of intracranial melanoma metastases with surgery and/or SRS. Patients aged 18 years or older with 1-3 brain metastases excised and/or stereotactically irradiated and an ECOG status of 0-2 are eligible. Patients with leptomeningeal disease, or who have had previous WBRT or localised treatment for brain metastases are ineligible. WBRT prescription is at least 30 Gy in 10 fractions commenced within 8 weeks of surgery and/or SRS. Randomisation is stratified by the number of cerebral metastases, presence or absence of extracranial disease, treatment centre, sex, radiotherapy dose and patient age. The primary endpoint is the proportion of patients with distant intracranial failure as determined by MRI assessment at 12 months. Secondary end points include: survival, quality of life, performance status and neurocognitive function.

Discussion

Accrual to previous trials for patients with brain metastases has been difficult, mainly due to referral bias for or against WBRT. This trial should provide the evidence that is currently lacking in treatment decision-making for patients with melanoma brain metastases. The trial is conducted by the Australia and New Zealand Melanoma Trials Group (ANZMTG-study 01-07), and the Trans Tasman Radiation Oncology Group (TROG) but international participation is encouraged. Twelve sites are open to date with 43 patients randomised as of the 31st March 2011. The target accrual is 200 patients.

Trial registration

Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000512426
Impact of changing the measles vaccine vial size on Niger's vaccine supply chain: a computational model
Authors: Assi Tina-Marie , Brown Shawn T , Djibo Ali , Norman Bryan A , Rajgopal Jayant , Welling Joel S , Chen Sheng-I , Bailey Rachel R , Kone Souleymane , Kenea Hailu , Connor Diana L , Wateska Angela R , Jana Anirban , Wisniewski Stephen R , Van Panhuis Willem G , Burke Donald S , Lee Bruce Y
Published: June 2011

Background

Many countries, such as Niger, are considering changing their vaccine vial size presentation and may want to evaluate the subsequent impact on their supply chains, the series of steps required to get vaccines from their manufacturers to patients. The measles vaccine is particularly important in Niger, a country prone to measles outbreaks.

Methods

We developed a detailed discrete event simulation model of the vaccine supply chain representing every vaccine, storage location, refrigerator, freezer, and transport device (e.g., cold trucks, 4 × 4 trucks, and vaccine carriers) in the Niger Expanded Programme on Immunization (EPI). Experiments simulated the impact of replacing the 10-dose measles vial size with 5-dose, 2-dose and 1-dose vial sizes.

Results

Switching from the 10-dose to the 5-dose, 2-dose and 1-dose vial sizes decreased the average availability of EPI vaccines for arriving patients from 83% to 82%, 81% and 78%, respectively for a 100% target population size. The switches also changed transport vehicle's utilization from a mean of 58% (range: 4-164%) to means of 59% (range: 4-164%), 62% (range: 4-175%), and 67% (range: 5-192%), respectively, between the regional and district stores, and from a mean of 160% (range: 83-300%) to means of 161% (range: 82-322%), 175% (range: 78-344%), and 198% (range: 88-402%), respectively, between the district to integrated health centres (IHC). The switch also changed district level storage utilization from a mean of 65% to means of 64%, 66% and 68% (range for all scenarios: 3-100%). Finally, accounting for vaccine administration, wastage, and disposal, replacing the 10-dose vial with the 5 or 1-dose vials would increase the cost per immunized patient from $0.47US to $0.71US and $1.26US, respectively.

Conclusions

The switch from the 10-dose measles vaccines to smaller vial sizes could overwhelm the capacities of many storage facilities and transport vehicles as well as increase the cost per vaccinated child.
Ultrasound in rheumatoid arthritis - volar versus dorsal synovitis evaluation and scoring
Authors: Vlad V , Berghea F , Libianu S , Balanescu A , Bojinca V , Constantinescu C , Abobului M , Predeteanu D , Ionescu R
Published: June 2011

Background

Assessment of synovitis in Rheumatoid Arthritis (RA) is a major issue for a proper treatment administration; it has been proven that ultrasound (US) examination could be of valuable help and it is currently being investigated as a possible outcome measure for the disease. It is, though, of greatest importance to accurately establish the place of US scores among the already validated outcome measures, according to Outcome Measures for Rheumatoid Arthritis in Clinical Trials (OMERACT) filter. The present study is designed to compare the results of gray-scale ultrasound (GSUS) and Power Doppler ultrasound (PDUS) additive scores, separately calculated for volar and dorsal aspects of the hand, with physical examination, patient's evaluation of disease pain and global activity on Visual Analogic Scale (VAS) and traditional scores for disease activity assessment (DAS28, CDAI, SDAI, HAQ). The final aim is to prove the advantages of volar US evaluation in RA patients.

Methods

42 RA patients have been clinically evaluated for pain and swelling of their hand joints, completed VAS and HAQ questionnaires and underwent both volar and dorsal sonography of the hands during the same day. The US examiner was blinded to clinical assessments and lab results. For each patient 20 joints were assessed by sonography (radiocarpal, intercarpal, metacarpophalangeal (MCP) 2-5, proximal interphalangeal (PIP) 2-5). Carpal joints were only evaluated from dorsal view, while MCPs and PIPs were evaluated both from dorsal and volar aspect resulting a total of 36 distinct evaluations for each patient. GSUS synovial hypertrophy was assessed both by quantitative measurement and semiquantitative scale (0-3 grades); Doppler signal (PDUS) was recorded on a semiquantitative scale (0-3 grades). The semiquantitative grades for both GSUS and PDUS evaluation of each joint were added and the sum was defined as the Echographic Score (ES) of each patient. Separately, we added the semiquantitative grades for volar and dorsal side, resulting in Volar ES (VES) and Dorsal ES (DES) of each patient.

Results

We found ESs correlated with other activity scores: DAS28, CDAI, SDAI, HAQ. Correlations with clinical indices as CDAI and SDAI were stronger for VES than for DES. US discovered more synovitis than clinical examination.

Conclusion

VES is a suitable reflection of RA activity and volar US examination should accompany the dorsal one both in clinical practice and in clinical trials.
Purification of functional baculovirus particles from silkworm larval hemolymph and their use as nanoparticles for the detection of human prorenin receptor (PRR) binding
Authors: Kato Tatsuya , Suzuki Fumiaki , Park Enoch Y
Published: June 2011

Background

Baculovirus, which has a width of 40 nm and a length of 250-300 nm, can display functional peptides, receptors and antigens on its surface by their fusion with a baculovirus envelop protein, GP64. In addition, some transmembrane proteins can be displayed without GP64 fusion, using the native transmembrane domains of the baculovirus. We used this functionality to display human prorenin receptor fused with GFPuv (GFPuv-hPRR) on the surface of silkworm Bombyx mori nucleopolyhedrovirus (BmNPV) and then tested whether these baculovirus particles could be used to detect protein-protein interactions.

Results

BmNPV displaying GFPuv-hPRR (BmNPV-GFPuv-hPRR) was purified from hemolymph by using Sephacryl S-1000 column chromatography in the presence of 0.01% Triton X-100. Its recovery was 86% and the final baculovirus particles number was 4.98 × 108 pfu. Based on the results of enzyme-linked immunosorbent assay (ELISA), 3.1% of the total proteins in BmNPV-GFPuv-hPRR were GFPuv-hPRR. This value was similar to that calculated from the result of western blot by a densitometry (2.7%). To determine whether BmNPV-GFPuv-hPRR particles were bound to human prorenin, ELISA results were compared with those from ELISAs using protease negative BmNPV displaying β1,3-N-acetylglucosaminyltransferase 2 fused with the gene encoding GFPuv (GGT2) (BmNPV-CP
--GGT2) particles, which do not display hPRR on their surfaces.

Conclusion

The display of on the surface of the BmNPV particles will be useful for the detection of protein-protein interactions and the screening of inhibitors and drugs in their roles as nanobioparticles.
Antibodies on demand: a fast method for the production of human scFvs with minimal amounts of antigen
Authors: Babel Ingrid , Barderas Rodrigo , Peláez-García Alberto , Casal J Ignacio
Published: June 2011

Background

Antibodies constitute a powerful tool to study protein function, protein localization and protein-protein interactions, as well as for diagnostic and therapeutic purposes. High-throughput antibody development requires faster methodologies with lower antigen consumption.

Results

Here, we describe a novel methodology to select human monoclonal recombinant antibodies by combining in vitro protein expression, phage display antibody libraries and antibody microarrays. The application of this combination of methodologies permitted us to generate human single-chain variable fragments (scFvs) against two proteins: green fluorescent protein (GFP) and thioredoxin (Trx) in a short time, using as low as 5 μg of purified protein. These scFvs showed specific reactivity against their respective targets and worked well by ELISA and western blot. The scFvs were able to recognise as low as 31 ng of protein of their respective targets by western blot.

Conclusion

This work describes a novel and miniaturized methodology to obtain human monoclonal recombinant antibodies against any target in a shorter time than other methodologies using only 5 μg of protein. The protocol could be easily adapted to a high-throughput procedure for antibody production.
Systematic development of a communication skills training course for physicians performing work disability assessments: from evidence to practice
Authors: van Rijssen H Jolanda , Schellart Antonius JM , Anema Johannes R , de Boer Wout EL , van der Beek Allard J
Published: June 2011

Background

Physicians require specific communication skills, because the face-to-face contact with their patients is an important source of information. Although physicians who perform work disability assessments attend some communication-related training courses during their professional education, no specialised and evidence-based communication skills training course is available for them. Therefore, the objectives of this study were: 1) to systematically develop a training course aimed at improving the communication skills of physicians during work disability assessment interviews with disability claimants, and 2) to plan an evaluation of the training course.

Methods

A physician-tailored communication skills training course was developed, according to the six steps of the Intervention Mapping protocol. Data were collected from questionnaire studies among physicians and claimants, a focus group study among physicians, a systematic review of the literature, and meetings with various experts. Determinants and performance objectives were formulated. A concept version of the training course was discussed with several experts before the final training course programme was established. The evaluation plan was developed by consulting experts, social insurance physicians, researchers, and policy-makers, and discussing with them the options for evaluation.

Results

A two-day post-graduate communication skills training course was developed, aimed at improving professional communication during work disability assessment interviews. Special focus was on active teaching strategies, such as practising the skills in role-play. An adoption and implementation plan was formulated, in which the infrastructure of the educational department of the institute that employs the physicians was utilised. Improvement in the skills and knowledge of the physicians who will participate in the training course will be evaluated in a randomised controlled trial.

Conclusions

The feasibility and practical relevance of the communication skills training course that was developed seem promising. Such a course may be relevant for physicians in many countries who perform work disability assessments. The development of the first training course of this type represents an important advancement in this field.
Protein Kinase C inhibition ameliorates functional endothelial insulin resistance and Vascular Smooth Muscle Cell hypersensitivity to insulin in diabetic hypertensive rats
Authors: Lu Xiao , Bean James S , Kassab Ghassan S , Rekhter Mark D
Published: June 2011

Objective

Insulin resistance, diabetes, and hypertension are considered elements of metabolic syndrome which is associated with vascular dysfunction. We investigated whether inhibition of protein kinase C (PKC) would affect vascular function in diabetic hypertensive (DH) rats.

Methods

A combination of type 2 diabetes and arterial hypertension was produced in male Sprague Dawley rats by intrauterine protein deprivation (IUPD) followed by high salt diet. At the age of 32 weeks, DH rats were treated for 2 weeks with the angiotensin-converting enzyme inhibitor captopril (Capto, 30 mg/kg), PKC inhibitor ruboxistaurin (RBX, 50 mg/kg) or vehicle (n = 8 per group) and blood pressure was monitored using telemetry. At the end of experiments, femoral arteries were dissected, and vascular reactivity was evaluated with isovolumic myography.

Results

The IUPD followed by high salt diet resulted in significant elevation of plasma glucose, plasma insulin, and blood pressure. Endothelium-dependent vascular relaxation in response to acetylcholine was blunted while vascular contraction in response to phenylephrine was enhanced in the DH rats. Neither Capto nor RBX restored endothelium-dependent vascular relaxation while both suppressed vascular contraction. Ex-vivo incubation of femoral arteries from control rats with insulin induced dose-response vasorelaxation while insulin failed to induce vasorelaxation in the DH rat arteries. In the control arteries treated with endothelial nitric oxide synthase inhibitor L-NAME, insulin induced vasoconstriction that was exacerbated in DH rats. Capto and RBX partially inhibited insulin-stimulated vascular contraction.

Conclusion

These findings suggest that PKC inhibition ameliorates functional endothelial insulin resistance and smooth muscle cell hypersensitivity to insulin, but does not restore acetylcholine-activated endothelium-dependent vasodilation in DH rats.
Echocardiographic predictors of early in-hospital heart failure during first ST-elevation acute myocardial infarction: does myocardial performance index and left atrial volume improve diagnosis over conventional parameters of left ventricular function?
Authors: Souza Lilian P , Campos Orlando , Peres Clovis A , Machado Cristiano V , Carvalho Antonio C
Published: June 2011

Background

Left ventricular ejection fraction (LVEF) has been considered a major determinant of early outcome in acute myocardial infarction (AMI). Myocardial performance index (MPI) has been associated to early evolution in AMI in a heterogeneous population, including non ST-elevation or previous AMI. Left atrial volume has been related with late evolution after AMI. We evaluated the independent role of clinical and echocardiographic variables including LVEF, MPI and left atrial volume in predicting early in-hospital congestive heart failure (CHF) specifically in patients with a first isolated ST-elevation AMI.

Methods

Echocardiography was performed within 30 hours of chest pain in 95 patients with a first ST-elevation AMI followed during the first week of hospitalization. Several clinical and echocardiographic variables were analyzed. CHF was defined as Killip class ≥ II. Multivariate regression analysis was used to select independent predictor of in-hospital CHF.

Results

Early in-hospital CHF occurred in 29 (31%) of patients. LVEF ≤ 0.45 was the single independent and highly significant predictor of early CHF among other clinical and echocardiographic variables (odds ratio 17.0; [95% CI 4.1 - 70.8]; p < 0.0001). MPI alone could not predict CHF in first ST-elevation AMI patients. Left atrial volume was not associated with early CHF in such patients.

Conclusion

For patients with first, isolated ST-elevation AMI, LVEF assessed by echocardiography still constitutes a strong and accurate independent predictor of early in-hospital CHF, superior to isolated MPI and left atrial volume in this particular subset of patients.