bluuebunny/crossref_metadata_2025 huggingface dataset:
The Moneylenders and Indebtedness
Authors: Saikia Arupjyoti
Published: July 2010

This article examines the dynamics of rural money lending in the Brahmaputra valley from 1881 to 1951. It begins with a question as to why the peasants in Assam borrowed, following it up with questions such as: Which section of the peasantry got involved in this process? To what extent did the local rich peasants participate in the money lending? How and to what extent were the Marwari businessmen involved in the process? Did the money lending lead to the transfer of land from the owner to the moneylenders? Did the arrival of the immigrant peasants from East Bengal accentuate the process? And finally, it tries to answer as to how it influenced the agrarian relations and legislative politics in the Brahmaputra valley. Despite the official claim of credit market operation through the banking sector becoming a success, the importance of usury never became marginal in the agrarian relations even after Independence. Assamese peasants treated the moneylenders with bitter distaste. The moneylenders were known as mahajans in rural vocabulary.
Technological Momentum
Authors: Sarkar Suvobrata
Published: July 2010

The nineteenth century was a very significant period in the history of modern India. It was during this period that the country witnessed the emergence of many intellectual currents in all aspects: religious, social, political, economic and cultural. For the colonial power, by the beginning of the nineteenth century, the empire had more or less been won. The job was to keep it, and to use it for profit. Colonialism was not the result of mere Western superiority, but of the unleashing of overwhelming force backed by technology at minimal cost. Technological changes affected the timing and location of European conquests and thus determined the economic relations of colonialism. It made European expansion swift, thorough and cheap. The new ability of Europeans in the nineteenth century to conquer other territories arose from relatively few inventions like iron-hulled steam ships, improved firearms, telegraph, railways and so on. With these tools, Europeans brought about a shift in global relations. The current study seeks to find answers as to how various technological tools and projects were used by the British in the nineteenth century Bengal and whether the relocation of Western technologies on Indian soil was really successful.
‘Rich India’ of Our Ancient Legends (India in the Russian Periodicals of the Second Half of the Nineteenth Century: Social and Economic Aspects)
Authors: Sidorova S.E.
Published: July 2010

In comparison with other countries, India and especially its social and economic life could hardly be placed among the subjects which were regularly discussed by the Russian press. Nevertheless, these publications offer an idea about what the image of India was in Russia, what the Russian people knew and thought about India’s socio-economic and particularly agrarian problems, what was the range of questions they were interested in, and in what perspective and context these questions were being considered. Russian interest in India was determined by several governing factors, such as existence of certain common tendencies in the social and economic life of both the countries, perception of their own path of development as different from the West, confrontation of Britain and Russia in Central Asia and by pure economic considerations, among them, competition of Russian and Indian commodities in the world market, desire of the Russian commercial circles to start direct trade with India and borrowing English agricultural practice in India. Russian journals became the source for this article, both literary monthly (‘fat magazines’) and economics journals.
Copper, stainless steel, glass core yarn, and ply yarn woven fabric composite materials properties
Authors: Perumalraj R. , Dasaradhan BS , Nalankilli G.
Published: July 2010

A study on physical and mechanical properties of copper core yarn, stainless core yarn, glass core yarn, and copper ply yarn woven fabric composite materials through ANOVA has been reported. Copper, stainless steel, and glass filaments are selected as the core, and cotton is selected as the sheath. The various combinations of copper, stainless, and glass core yarns are produced by DREF II Friction spinning machine, and core yarns are converted into woven fabric composite materials by loom. The physical and mechanical properties of copper core yarn, stainless core yarn, glass core yarn, and copper ply yarn woven fabric composite materials have been measured using various instruments. It is observed that there is strong and significant difference between the tensile strength of warp direction and weft direction of core yarn woven fabric composite materials. The flexural rigidity and bending modulus of core yarn fabric increases with an increase in core content of copper, stainless steel, and glass filament.
Effects of harsh weather and seawater on glass fiber reinforced epoxy composite
Authors: Merah N. , Nizamuddin S. , Khan Z. , Al-Sulaiman F. , Mehdi M.
Published: July 2010

The lack of reliable engineering data on the durability of glass fiber reinforced Epoxy (GFRE) pipes when exposed to harsh Arabian Gulf outdoor environment has limited their wide use for saltwater and crude oil handling and transportation. This article explores the combined effect of natural and accelerated weathering and seawater on tensile properties of GFRE pipe materials. Saltwater filled pipes were exposed to outdoor environment in Dhahran, Saudi Arabia for periods ranging from 6 to 12 months. Ring-shaped tensile test specimens were also immersed in oxygenated saltwater at room temperature for time periods ranging from 300 to 10,000 h. The natural exposures resulted in gradual reduction of tensile strength and fracture strain with exposure time in saltwater filled pipes. The exposure to oxygenated saltwater immersion also showed detrimental effects after 300 h of exposure. Longer immersion periods did not result in further strength degradation. The stiffness of the GFRE pipe specimens remained more or less unaffected by exposure to seawater. Fractographic analysis of unexposed specimens showed a combination of Mode I and Mode II failure characterized by inclined hackles as well as fiber breakage. High outdoor temperature and moisture absorption decreased fiber—matrix interface strength and caused degradation at the fiber level resulting in lower ultimate strength, fracture strain, and stiffness of the GFRE.
Tensile behavior of New Zealand flax (Phormium tenax) fibers
Authors: De Rosa Igor Maria , Kenny Josè Maria , Puglia Debora , Santulli Carlo , Sarasini Fabrizio
Published: July 2010

The objective of this study is to characterize the tensile properties of New Zealand flax (Phormium tenax) technical fibers to be used as potential reinforcement in polymer matrix composites. Single fiber tensile tests were performed at three gage lengths to assess the effect of gage length on tensile strength and Young’s modulus. The results were analyzed through a two-parameter Weibull distribution. The morphology, diameter, and fracture modes of P. tenax fibers were also characterized through optical and scanning electron microscopy.
Les « choix » du sociologue avec Alceste - Du paramétrage des unités de contexte aux résultats obtenus
Authors: Dalud-Vincent Monique
Published: July 2010

The ‘‘Choice’’ of the Sociologist with Alceste - From Determining Units of Context to the Results Obtained: In this article, we pose the question of the relationship between cutting up a corpus of semi-structured interviews in sociology by determing the units of content and the results obtained when the Alceste software analyzes the units of context. We show that the way the text is cut up has an influence on the results and thus the analysis produced.
Measuring and Comparing Levels of Education: Methodological Problems in the Classification of Educational Levels in the European Social Surveys and the French Labor Force Surveys
Authors: Kieffer Annick
Published: July 2010

Mesurer et comparer les niveaux d’éducation - Problèmes méthodologiques posés par le classement des niveaux d’études dans la European Social Survey et dans l’enquête Emploi française: Couramment utilisé en sciences sociales pour comprendre les représentations, les comportements ou les grandes évolutions sociales, le niveau d’éducation des individus, sa classification et ses mesures possibles font l’objet de peu de travaux méthodologiques. On montrerty a ici, sur la base d’une comparaison des différentes versions des European Social Surveys avec les enquêtes Emploi de l’Insee pour la France, l’importance des procédures de saisie, de classement, d’agrégation et d’harmonisation de l’éducation dans des catégories comparables, du niveau national jusqu’au niveau international (la classification Cite). Les mesures courantes s’attachent à comparer des niveaux d’éducation. La prise en compte de l’orientation des savoirs, notamment de la différence entre enseignement général et enseignemrnt professionnel et technique améliore nettement la qualité de la mesure. Cet article plaide pour un développement des travaux sociologiques sur ces questions.
Nontraumatic Coma in a Tertiary Pediatric Emergency Department in Egypt: Etiology and Outcome
Authors: Fouad Hala , Haron Mervat , Halawa Eman Fawzy , Nada Mona
Published: July 2010

Nontraumatic coma in childhood is an important pediatric emergency with a wide range of primary etiologies. This prospective descriptive study of 100 consecutive pediatric nontraumatic coma cases was done to identify etiology, clinical profile, and predictive outcome in a pediatric emergency department at a tertiary care university hospital. Most frequent etiologies were metabolic (33%), central nervous system infections (28%), and intracranial hemorrhage (13%). In the emergency department, 50% of those patients died. Hypothermia, hypotension, flaccidity, and poor Glasgow coma scale at admission correlated significantly with mortality. After 48 hours of admission, poor pulse volume, poor Glasgow coma scale, abnormal respiratory pattern/apnea, and seizures correlated significantly with mortality. On logistic regression, poor Glasgow coma scale at admission, abnormal respiratory pattern, and seizures after 48 hours of admission were independent significant predictors of mortality. Metabolic causes are the most common etiology in pediatrics nontraumatic coma. Simple clinical signs were good predictors of outcome.
The Examination of Peer Review and Publication in Neurology
Authors: Wong Victoria S. S.
Published: July 2010

Despite remarkable growth in the clinical neurology literature, there is little research on peer review and biomedical publication in neurology. Biomedical publication research encompasses every step of the research process, from the methodology to the publication of research findings. Some general medical journals have served as leaders in improving scientific publication. Many medical fields have taken it upon themselves to characterize journals and peer reviewers within their own fields. Not all of these data can be applied to the clinical neurology literature; research methodologies, article types, and the journals themselves are unique to every medical field. This article reviews current publication research in the neurology literature and concludes that, to sustain and improve upon the integrity of clinical neurology research, further study is needed of the journals and the peer review process in neurology. Otherwise, the value of clinical research findings and patient care guidelines will be diminished.
Capitalizing Knowledge: The Mind-Set of Academic Scientists
Authors: Dzisah James
Published: July 2010

Advances in generic forms of knowledge have reflexively transformed the form and content of knowledge production and academic institutions. This unique alteration has resulted in the initiation of steps by most universities and public policy regimes to increase the economic outcomes of their research. Utilizing qualitative in-depth interviews, the article explores the mind-set of academic scientists regarding the capitalization of knowledge. It notes that any critical analysis of patterns of knowledge capitalization will reveal that university, industry and government have all been influencing each other in varying forms and contexts. While it can be argued that universities are not idyllic islands now being crushed under industrial interests, the case for scientific integrity in all knowledge regimes must continue to be made by both proponents and critics of academic capitalism within the spirit of openness and scientific boundaries.
Complex Adaptive Systems and the Evolutionary Triple Helix
Authors: Viale Riccardo , Pozzali Andrea
Published: July 2010

Innovation dynamics are more and more considered to represent one of the most important processes in the development of modern economic systems. This perspective is at the root of the development of various innovation concepts. The systematic study of different systems of innovation has raised the awareness that each particular system has its own characteristics, and that it is not always possible to unilaterally define all the parameters that play a role in shaping innovation processes. The article describes the main obstacles facing public policy decision-making drawing on examples from innovation and research policy. It argues that Complex Adaptive Systems (CAS) research can teach us a series of useful lessons, especially those features necessitating the consideration of innovation systems as complex adaptive systems.
Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study
Authors: Zavada J. , Pešickova SS , Ryšava R. , Olejarova M. , Horák P. , Hrnčíř Z. , Rychlík I. , Havrda M. , Vítova J. , Lukáč J. , Rovensky J. , Tegzova D. , Böhmova J. , Zadražil J. , Hána J. , Dostál C. , Tesar V.
Published: July 2010

Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300) Lupus (2010) 19, 1281—1289.
Informed consent to research in persons with schizophrenia spectrum disorders
Authors: Humphrey Beebe Lora , Smith Kathlene
Published: July 2010

This manuscript describes the responses and correlates of outpatients with schizophrenia spectrum disorders to a tool designed to measure comprehension before obtaining informed consent for research participation. We used the Evaluation to Sign Consent form to document comprehension in 100 outpatients as part of their consent to participate in an ongoing study of an exercise intervention. The findings suggest that using this form is a feasible and acceptable approach to documenting comprehension of research procedures prior to obtaining informed consent. Age 49 years and older and the receipt of intramuscular antipsychotic medication predicted the need for additional assistance to complete the Evaluation to Sign Consent form successfully (χ2 = 8.29, P = 0.016). Nurse researchers should consider documenting comprehension with this tool owing to its availability, time efficiency and utility.
Ethical problems in nursing management: The role of codes of ethics
Authors: Aitamaa Elina , Leino-Kilpi Helena , Puukka Pauli , Suhonen Riitta
Published: July 2010

The aim of this study was to identify the ethical problems that nurse managers encounter in their work and the role of codes of ethics in the solutions to these difficulties. The data were collected using a structured questionnaire and analysed statistically. The target sample included all nurse managers in 21 specialized health care or primary health care organizations in two hospital districts in Finland (N = 501; response rate 41%). The most common ethical problems concerned resource allocation as well as providing and developing high quality care. This was the case in different managerial positions as well as in types of organization. Professional codes of ethics were used more often for problems related to patients’ care compared with issues of resource allocation. Nurse managers at middle or strategic management levels used codes of ethics more often than those in charge of a ward. More research is required to investigate ethical decision making in nursing management, especially with regard to problem solving. In addition, new guidelines and continuing education in ethics are important for management personnel.
Internal or external whistleblowing: Nurses’ willingness to report wrongdoing
Authors: Mansbach Abraham , Bachner Yaacov G
Published: July 2010

In Israel, whistleblowing in the nursing profession has been largely ignored. This topic is neither part of the professional—ethical discourse nor a subject for research. Focusing on the divide between internal and external whistleblowing, this article presents a study that explores nurses’ willingness to disclose an act that could jeopardize the rights or safety of patients. Internal disclosure entails reporting wrongdoing to an authority within the organization. External disclosure involves reporting the offense to an outside agency, such as a professional organization or the press. The study’s findings indicate that the nurse respondents viewed both the harmful misconduct of a colleague and that of a manager as being very serious. In such dilemmas the nurses reported a desire to correct the wrongdoing and a concomitant willingness to act. They were, however, much more likely to whistleblow internally rather than externally. This study revealed a pattern of nurses’ progressive retraction as the circle of disclosure widened.
Achieving Bologna Goals: Where Does Europe Stand Ahead of 2010
Authors: Rauhvargers Andrejs
Published: July 2010

Ten years have passed since the signature of the Bologna declaration. Seventeen countries have joined the process; since then, several new action lines have been added and the original action lines have often gained a new and more sophisticated content. The 2009 Bologna Stocktaking exercise included the traditional quantitative indicators, the criteria this time being designed to evaluate the goals set for 2010. In addition, particular emphasis was put on qualitative analysis on this occasion to provide a realistic picture of what has been achieved and which initiatives will take more time than anticipated to implement. The 2009 stocktaking shows that while there has indeed been important progress since 1999, following progress since 2007, not all the goals of the Bologna Process will be achieved by 2010.
Learning and Reversal Learning in the Subcortical Limbic System: A Computational Model
Authors: Thompson Adedoyin Maria , Porr Bernd , Wörgötter Florentin
Published: July 2010

We present a biologically inspired model of the subcortical nuclei of the limbic system that is capable of performing reversal learning in a food-seeking task. In contrast to previous models, the reversal is modeled by the inhibition of the previously learned behavior. This allows for the reinstatement of behavior to recur quickly, as observed in animal behavior. In this model learning is achieved by implementing isotropic sequence order learning and a third factor (ISO-3) that triggers learning at relevant moments. This third factor is modeled by phasic and tonic dopaminergic activity which respectively enable long-term potentiation to occur during acquisition, and long-term depression (LTD) to occur when adjustments in learned behaviors are required. It will be shown how the nucleus accumbens core uses conditioned reinforcers to invigorate instrumental responding while relatively strong LTD in the shell influences the core through a shell-ventral pallido-mediodorsal pathway. This pathway functions as a feed-forward switching mechanism and enables behavioral flexibility.
A Cohesive Law for Carbon Nanotube/Polymer Interface Accounting for Chemical Covalent Bonds
Authors: Jiang L.Y.
Published: July 2010

The influence of chemical bonds formed between a single-walled carbon nanotube (CNT) and a polymer matrix upon the interface behavior has been studied through the development of an interfacial cohesive law. By using the interatomic potential directly, the tensile cohesive stress and cohesive energy for the interface with opening mode separation are expressed in terms of the area density of the carbon atoms of the CNT, the volume density of the polymer molecules, the material constants of the CNT and the polymer matrix, the parameters in the van der Waals potential, and the Brenner potential and the chemical bond density. This cohesive law avoids any phenomenological assumption between the normal traction and interface opening displacement. For a CNT in an infinite polymer, the shear cohesive stress vanishes, and the tensile cohesive stress depends only on the opening displacement. The cohesive properties, such as the total cohesive energy, have increased significantly, which results in a stronger interfacial bonding due to the creation of new chemical bonds at the interface. The developed cohesive law is useful to study the interaction between the CNT and the polymer, such as in CNT-reinforced composites.
Genetic disruption of both Fancc and Fancg in mice recapitulates the hematopoietic manifestations of Fanconi anemia
Authors: Pulliam-Leath Anna C. , Ciccone Samantha L. , Nalepa Grzegorz , Li Xiaxin , Si Yue , Miravalle Leticia , Smith Danielle , Yuan Jin , Li Jingling , Anur Praveen , Orazi Attilio , Vance Gail H. , Yang Feng-Chun , Hanenberg Helmut , Bagby Grover C. , Clapp D. Wade
Published: July 2010

Fanconi anemia (FA) is an inherited chromosomal instability syndrome characterized by bone marrow failure, myelodysplasia (MDS), and acute myeloid leukemia (AML). Eight FA proteins associate in a nuclear core complex to monoubiquitinate FANCD2/FANCI in response to DNA damage. Additional functions have been described for some of the core complex proteins; however, in vivo genetic proof has been lacking. Here we show that double-mutant Fancc−/−;Fancg−/− mice develop spontaneous hematologic sequelae including bone marrow failure, AML, MDS and complex random chromosomal abnormalities that the single-mutant mice do not. This genetic model provides evidence for unique core complex protein function independent of their ability to monoubiquitinate FANCD2/FANCI. Importantly, this model closely recapitulates the phenotypes found in FA patients and may be useful as a preclinical platform to evaluate the molecular pathogenesis of spontaneous bone marrow failure, MDS and AML in FA.
An adult uterine hemangioblast: evidence for extramedullary self-renewal and clonal bilineage potential
Authors: Sun Zhuo , Zhang Yuemei , Brunt Keith R. , Wu Jun , Li Shu-Hong , Fazel Shafie , Weisel Richard D. , Keating Armand , Li Ren-Ke
Published: July 2010

Stem cells exhibit long-term self-renewal by asymmetric division and multipotent differentiation. During embryonic development, cell fate is determined with predictable orientation, differentiation, and partitioning to form the organism. This includes the formation of a hemangioblast from which 2 derivative cell clusters commit to either a hematopoietic or an endothelial lineage. Frequently, it is not clear whether tissue resident stem cells in the adult originate from the bone marrow. Here, we show that blast colony-forming cells exhibiting bilineage (hematopoietic and vascular) potential and long-term self-renewal originate from the uterus in the mouse. This is the first in vitro and in vivo evidence of an adult hemangioblast retained from development in the uterus. Our findings offer new understanding of uterine cell renewal and turnover and may provide insights and opportunities for the study of stem cell maintenance.
A transgenic mouse model demonstrates a dominant negative effect of a point mutation in the RPS19 gene associated with Diamond-Blackfan anemia
Authors: Devlin Emily E. , DaCosta Lydie , Mohandas Narla , Elliott Gene , Bodine David M.
Published: July 2010

Diamond Blackfan anemia (DBA) is an inherited erythroblastopenia associated with mutations in at least 8 different ribosomal protein genes. Mutations in the gene encoding ribosomal protein S19 (RPS19) have been identified in approximately 25% of DBA families. Most of these mutations disrupt either the translation or stability of the RPS19 protein and are predicted to cause DBA by haploinsufficiency. However, approximately 30% of RPS19 mutations are missense mutations that do not alter the stability of the RPS19 protein and are hypothesized to act by a dominant negative mechanism. To formally test this hypothesis, we generated a transgenic mouse model expressing an RPS19 mutation in which an arginine residue is replaced with a tryptophan residue at codon 62 (RPS19R62W). Constitutive expression of RPS19R62W in developing mice was lethal. Conditional expression of RPS19R62W resulted in growth retardation, a mild anemia with reduced numbers of erythroid progenitors, and significant inhibition of terminal erythroid maturation, similar to DBA. RNA profiling demonstrated more than 700 dysregulated genes belonging to the same pathways that are disrupted in RNA profiles of DBA patient cells. We conclude that RPS19R62W is a dominant negative DBA mutation.
Association of obesity risk SNPs in PCSK1with insulin sensitivity and proinsulin conversion
Authors: Heni Martin , Haupt Axel , Schäfer Silke A , Ketterer Caroline , Thamer Claus , Machicao Fausto , Stefan Norbert , Staiger Harald , Häring Hans-Ulrich , Fritsche Andreas
Published: July 2010

Background

Prohormone convertase 1 is involved in maturation of peptides. Rare mutations in gene PCSK1, encoding this enzyme, cause childhood obesity and abnormal glucose homeostasis with elevated proinsulin concentrations. Common single nucleotide polymorphisms (SNPs) within this gene, rs6232 and rs6235, are associated with obesity. We studied whether these SNPs influence the prediabetic traits insulin resistance, β-cell dysfunction, or glucose intolerance.

Methods

We genotyped 1498 German subjects for SNPs rs6232 and rs6235 within PCSK1. The subjects were metabolically characterized by oral glucose tolerance test with glucose, insulin, proinsulin, and C-peptide measurements. A subgroup of 512 subjects underwent a hyperinsulinemic-euglycemic clamp.

Results

The minor allele frequencies were 25.8% for SNP rs6235 and 6.0% for rs6232. After adjustment for sex and age, we found no association of SNPs rs6235 and rs6232 with BMI or other weight-related traits (all p ≥ 0.07). Both minor alleles, adjusted for sex, age, BMI and insulin sensitivity were associated with elevated AUCproinsulin and AUCproinsulin/AUCinsulin (rs6235: padditive model ≤ 0.009, effect sizes 8/8%, rs6232: pdominant model ≤ 0.01, effect sizes 10/21%). Insulin secretion was not affected by the variants (different secretion parameters, all p ≥ 0.08). The minor allele of SNP rs6232 was additionally associated with 15% higher OGTT-derived and 19% higher clamp-derived insulin sensitivity (pdom ≤ 0.0047), 4.5% lower HOMAIR (pdom = 0.02) and 3.5% lower 120-min glucose (pdom = 0.0003) independently of BMI and proinsulin conversion. SNP rs6235 was not associated with parameters of glucose metabolism.

Conclusions

Like rare mutations in PCSK1, the more common variants tested determine glucose-stimulated proinsulin conversion, but not insulin secretion. In addition, rs6232, encoding the amino acid exchange N221D, influences insulin sensitivity and glucose homeostasis.
Synuclein gamma predicts poor clinical outcome in colon cancer with normal levels of carcinoembryonic antigen
Authors: Liu Caiyun , Dong Bin , Lu Aiping , Qu Like , Xing Xiaofang , Meng Lin , Wu Jian , Eric Shi Y , Shou Chengchao
Published: July 2010

Background

Synuclein gamma (SNCG), initially identified as a breast cancer specific gene, is aberrantly expressed in many different malignant tumors but rarely expressed in matched nonneoplastic adjacent tissues. In this study, we investigated the prognostic potential of SNCG in colon cancer particularly in the patients with normal carcinoembryonic antigen (CEA) levels.

Methods

SNCG levels were assessed immunohistochemically in cancer tissues from 229 colon adenocarcinoma patients with a mean follow-up of 44 months. Correlations between SNCG levels and clinicopathologic features, preoperative serum CEA level, and clinical outcome were analyzed statistically using SPSS.

Results

SNCG levels in colon adenocarcinoma were closely associated with intravascular embolus and tumor recurrence but independent of preoperative serum CEA levels. SNCG expression was an independent prognostic factor of a shorter disease-free survival (DFS) and overall survival (OS) (P < 0.0001). Multivariate analysis revealed that both tissue SNCG and serum CEA were independent prognostic factors of DFS (P = 0.001, <0.0001, respectively) for 170 patients with colon adenocarcinomas. Importantly, SNCG remained a prognostic determinant of DFS and OS (P = 0.001, 0.002) for 97 patients with normal preoperative serum CEA level.

Conclusions

Our results suggest for the first time that SNCG is a new independent predicator for poor prognosis in patients with colon adenocarcinoma, including those with normal CEA levels. Combination of CEA with SNCG improves prognostic evaluation for patients with colon adenocarcinoma.
A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5α
Authors: Kuroishi Ayumu , Bozek Katarzyna , Shioda Tatsuo , Nakayama Emi E
Published: July 2010

Background

Human immunodeficiency virus type 1 (HIV-1) productively infects only humans and chimpanzees but not Old World monkeys, such as rhesus and cynomolgus (CM) monkeys. To establish a monkey model of HIV-1/AIDS, several HIV-1 derivatives have been constructed. We previously reported that efficient replication of HIV-1 in CM cells was achieved after we replaced the loop between α-helices 6 and 7 (L6/7) of the capsid protein (CA) with that of SIVmac239 in addition to the loop between α-helices 4 and 5 (L4/5) and vif. This virus (NL-4/5S6/7SvifS) was supposed to escape from host restriction factors cyclophilin A, CM TRIM5α, and APOBEC3G. However, the replicative capability of NL-4/5S6/7SvifS in human cells was severely impaired.

Results

By long-term cultivation of human CEMss cells infected with NL-4/5S6/7SvifS, we succeeded in rescuing the impaired replicative capability of the virus in human cells. Sequence analysis of the CA region of the adapted virus revealed a G-to-E substitution at the 116th position of the CA (G116E). Introduction of this substitution into the molecular DNA clone of NL-4/5S6/7SvifS indeed improved the virus' replicative capability in human cells. Although the G116E substitution occurred during long-term cultivation of human cells infected with NL-4/5S6/7SvifS, the viruses with G116E unexpectedly became resistant to CM, but not human TRIM5α-mediated restriction. The 3-D model showed that position 116 is located in the 6th helix near L4/5 and L6/7 and is apparently exposed to the protein surface. The amino acid substitution at the 116th position caused a change in the structure of the protein surface because of the replacement of G (which has no side chain) with E (which has a long negatively charged side chain).

Conclusions

We succeeded in rescuing the impaired replicative capability of NL-4/5S6/7SvifS and report a mutation that improved the replicative capability of the virus. Unexpectedly, HIV-1 with this mutation became resistant to CM TRIM5α-mediated restriction.
Gene expression profiling in circulating endothelial cells from systemic sclerosis patients shows an altered control of apoptosis and angiogenesis that is modified by iloprost infusion
Authors: Tinazzi Elisa , Dolcino Marzia , Puccetti Antonio , Rigo Antonella , Beri Ruggero , Valenti Maria Teresa , Corrocher Roberto , Lunardi Claudio
Published: July 2010

Introduction

Circulating endothelial cells are increased in patients affected by systemic sclerosis (SSc) and their number strongly correlates with vascular damage. The effects of iloprost in systemic sclerosis are only partially known. We aimed at studying the gene expression profile of circulating endothelial cells and the effects of iloprost infusion and gene expression in patients with systemic sclerosis.

Methods

We enrolled 50 patients affected by systemic sclerosis, 37 patients without and 13 patients with digital ulcers. Blood samples were collected from all patients before and 72 hours after either a single day or five days eight hours iloprost infusion. Blood samples were also collected from 50 sex- and age-matched healthy controls. Circulating endothelial cells and endothelial progenitors cells were detected in the peripheral blood of patients with systemic sclerosis by flow cytometry with a four-colour panel of antibodies. Statistical analysis was performed with the SPSS 16 statistical package.Circulating endothelial cells were then isolated from peripheral blood by immunomagnetic CD45 negative selection for the gene array study.

Results

The number of both circulating endothelial cells and progenitors was significantly higher in patients affected by systemic sclerosis than in controls and among patients in those with digital ulcers than in patients without them. Circulating endothelial cells and progenitors number increased after iloprost infusion. Gene array analysis of endothelial cells showed a different transcriptional profile in patients compared to controls. Indeed, patients displayed an altered expression of genes involved in the control of apoptosis and angiogenesis. Iloprost infusion had a profound impact on endothelial cells gene expression since the treatment was able to modulate a very high number of transcripts.

Conclusions

We report here that circulating endothelial cells in patients with systemic sclerosis show an altered expression of genes involved in the control of apoptosis and angiogenesis. Moreover we describe that iloprost infusion has a strong effect on endothelial cells and progenitors since it is able to modulate both their number and their gene expression profile.
Citrullinated vimentin as an important antigen in immune complexes from synovial fluid of rheumatoid arthritis patients with antibodies against citrullinated proteins
Authors: Van Steendam Katleen , Tilleman Kelly , De Ceuleneer Marlies , De Keyser Filip , Elewaut Dirk , Deforce Dieter
Published: July 2010

Introduction

Rheumatoid arthritis (RA) is an inflammatory disease, which results in destruction of the joint. The presence of immune complexes (IC) in serum and synovial fluid of RA patients might contribute to this articular damage through different mechanisms, such as complement activation. Therefore, identification of the antigens from these IC is important to gain more insight into the pathogenesis of RA. Since RA patients have antibodies against citrullinated proteins (ACPA) in their serum and synovial fluid (SF) and since elevated levels of citrullinated proteins are detected in the joints of RA patients, citrullinated antigens are possibly present in IC from RA patients.

Methods

IC from serum of healthy persons, serum of RA patients and IC from synovial fluid of RA patients and Spondyloarthropathy (SpA) patients were isolated by immunoprecipitation. Identification of the antigens was performed by SDS-PAGE, mass spectrometry and immunodetection. The presence of citrullinated proteins was evaluated by anti-modified citrulline (AMC) staining.

Results

Circulating IC in the serum of RA patients and healthy controls contain fibrinogenβ and fibronectin, both in a non-citrullinated form. Additionally, in IC isolated from RA SF, fibrinogenγ and vimentin were identified as well. More importantly, vimentin and a minor portion of fibrinogenβ were found to be citrullinated in the isolated complexes. Moreover these citrullinated antigens were only found in ACPA+ patients. No citrullinated antigens were found in IC from SF of SpA patients.

Conclusions

Citrullinated fibrinogenβ and citrullinated vimentin were found in IC from SF of ACPA+ RA patients, while no citrullinated antigens were found in IC from SF of ACPA- RA patients or SpA patients or in IC from serum of RA patients or healthy volunteers. The identification of citrullinated vimentin as a prominent citrullinated antigen in IC from SF of ACPA+ RA patients strengthens the hypothesis that citrullinated vimentin plays an important role in the pathogenesis of RA.
Disclosing a Diagnosis of Cancer: Where and How Does It Occur?
Authors: Figg William D. , Smith Erika K. , Price Douglas K. , English Bevin C. , Thurman Paul W. , Steinberg Seth M. , Emanuel Ezekiel
Published: July 2010

Purpose

While disclosing a cancer diagnosis to a patient is common practice, how it is disclosed and the impact it has on the patient are poorly understood. We examined how cancer diagnoses were first given to patients and the impact of different aspects of disclosure on patient satisfaction.

Patients and Methods

We provided a self-administered questionnaire to a total of 460 oncology patients of the National Cancer Institute (NCI) being treated at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD.

Results

Of the 437 patients who completed the survey, 54% were told their diagnosis in-person in the physician's office, 18% by phone, and 28% in the hospital. Forty-four percent of patients reported discussions of 10 minutes or fewer, 53% reported discussions lasting longer than 10 minutes, and 5% could not remember. Treatment options were not discussed for 31% of those who could clearly remember. Higher mean satisfaction scores were associated with diagnoses revealed in person rather than over the phone (68.2 ± 1.6 v 47.2 ± 3.7), diagnoses revealed in a personal setting rather than an impersonal setting (68.9 ± 1.6 v 55.7 ± 2.8), discussions lasting longer than 10 minutes rather than fewer than 10 minutes (73.5 ± 1.9 v 54.1 ± 2.4), and inclusion of treatment options rather than exclusion (72.0 ± 1.9 v 50.7 ± 3.2; P < .001 for each aspect).

Conclusion

Physicians should disclose a cancer diagnosis in a personal setting, discussing the diagnosis and treatment options for a substantial period of time whenever possible.
Pain and Emotional Well-Being Outcomes in Southwest Oncology Group–Directed Intergroup Trial S0205: A Phase III Study Comparing Gemcitabine Plus Cetuximab Versus Gemcitabine As First-Line Therapy in Patients With Advanced Pancreas Cancer
Authors: Moinpour Carol M. , Vaught Nancy L. , Goldman Bryan , Redman Mary W. , Philip Philip A. , Millwood Barbara , Lippman Scott M. , Seay Thomas E. , Flynn Patrick J. , O'Reilly Eileen M. , Rowland Kendrith M. , Wong Ralph P. , Benedetti Jacqueline , Blanke Charles D.
Published: July 2010

Purpose

S0205 was a randomized clinical trial that compared the therapeutic impact of gemcitabine versus gemcitabine plus cetuximab. Study results for patient-reported health-related quality of life (HRQL) outcomes are reported.

Patients and Methods

Patients completed the Brief Pain Inventory and a measure of emotional well-being (each measured on a 0 to 10 scale) at baseline and at weeks 5, 9, 13, and 17 postrandom assignment. Worst pain status was classified as palliated (worst pain scores < 5 maintained for 2 consecutive cycles) or not palliated (remaining patients) and tested with a χ2 test. Change in emotional well-being and worst pain (exploratory analysis) were assessed over 17 weeks using generalized estimating equations with inverse probability of censoring weights.

Results

Seven hundred twenty of 766 enrolled patients contributed baseline HRQL data. The two treatment arms did not differ statistically in the percentage of patients with successful worst pain palliation. Longitudinal analyses showed significantly improved emotional well-being for patients on both arms by weeks 13 and 17 (P < .01 and P < .001). An exploratory longitudinal analysis of worst pain showed significant decreases at all time points for both arms (P < .01 and P < .001). Significant treatment arm differences for either worst pain or emotional well-being were not observed at any of the assessment times.

Conclusion

We observed palliated pain and improved well-being for patients on this trial. However, these improvements were similar in both treatment arms, suggesting that the addition of cetuximab did not contribute to improvement in these HRQL outcomes.
T-Cell–Depleted Reduced-Intensity Transplantation Followed by Donor Leukocyte Infusions to Promote Graft-Versus-Lymphoma Activity Results in Excellent Long-Term Survival in Patients With Multiply Relapsed Follicular Lymphoma
Authors: Thomson Kirsty J. , Morris Emma C. , Milligan Don , Parker Anne N. , Hunter Ann E. , Cook Gordon , Bloor Adrian J.C. , Clark Fiona , Kazmi Majid , Linch David C. , Chakraverty Ronjon , Peggs Karl S. , Mackinnon Stephen
Published: July 2010

Purpose

Follicular lymphoma (FL) is an indolent disorder that is treatable but considered incurable with chemotherapy alone. The curative potential of allogeneic transplantation using conventional myeloablative conditioning has been demonstrated, but this approach is precluded in the majority of patients with FL because of excessive toxicity. Thus, reduced-intensity conditioning regimens are being explored.

Patients and Methods

This study reports the outcome of 82 consecutive patients with FL who underwent transplantation using fludarabine, melphalan, and alemtuzumab for in vivo T-cell depletion. Patients were heavily pretreated, having received a median of four lines of prior therapy, and 26% had experienced treatment failure with previous autologous transplantation. Median patient age was 45 years, and 52% of patients received stem cells from unrelated donors.

Results

With a median follow-up time of 43 months, the nonrelapse mortality was 15% at 4 years (8% for sibling and 22% for unrelated donor transplantations), acute grade 2 or 3 graft-versus-host disease (GVHD) occurred in 13%, and the incidence of extensive chronic GVHD was only 18%. Although relapse risk was 26%, this was significantly reduced where mixed chimerism had been converted to full donor chimerism by the use of donor lymphocyte infusion (DLI; P = .03). In addition, 10 (77%) of 13 patients given DLI for relapse after transplantation experienced remission, with nine of these responses being sustained. Current progression-free survival at 4 years was 76% for the whole cohort (90% for those with sibling donors and 64% for those with unrelated donors).

Conclusion

The excellent long-term survival with associated low rates of GVHD and the frequency and durability of DLI responses make this an extremely encouraging strategy for the treatment and potential cure of FL.
Somatic Mutations in BRCA1 and BRCA2 Could Expand the Number of Patients That Benefit From Poly (ADP Ribose) Polymerase Inhibitors in Ovarian Cancer
Authors: Hennessy Bryan T.J. , Timms Kirsten M. , Carey Mark S. , Gutin Alexander , Meyer Larissa A. , Flake Darl D. , Abkevich Victor , Potter Jennifer , Pruss Dmitry , Glenn Pat , Li Yang , Li Jie , Gonzalez-Angulo Ana Maria , McCune Karen Smith , Markman Maurie , Broaddus Russell R. , Lanchbury Jerry S. , Lu Karen H. , Mills Gordon B.
Published: July 2010

Purpose

The prevalence of BRCA½ mutations in germline DNA from unselected ovarian cancer patients is 11% to 15.3%. It is important to determine the frequency of somatic BRCA½ changes, given the sensitivity of BRCA-mutated cancers to poly (ADP ribose) polymerase-1 (PARP1) inhibitors and platinum analogs.

Patients and Methods

In 235 unselected ovarian cancers, BRCA½ was sequenced in 235, assessed by copy number analysis in 95, and tiling arrays in 65. 113 tumors were sequenced for TP53. BRCA½ transcript levels were assessed by quantitative polymerase chain reaction in 220. When available for tumors with BRCA½ mutations, germline DNA was sequenced.

Results

Forty-four mutations (19%) in BRCA1 (n = 31)/BRCA2 (n = 13) were detected, including one homozygous BRCA1 intragenic deletion. BRCA½ mutations were particularly common (23%) in high-grade serous cancers. In 28 patients with available germline DNA, nine (42.9%) of 21 and two (28.6%) of seven BRCA1 and BRCA2 mutations were demonstrated to be somatic, respectively. Five mutations not previously identified in germline DNA were more commonly somatic than germline (four of 11 v one of 17; P = .062). There was a positive association between BRCA1 and TP53 mutations (P = .012). BRCA½ mutations were associated with improved progression-free survival (PFS) after platinum-based chemotherapy in univariate (P = .032; hazard ratio [HR] = 0.65; 95% CI, 0.43 to 0.98) and multivariate (P = .019) analyses. BRCA½ deficiency, defined as BRCA½ mutations or expression loss (in 24 [13.3%] BRCA½–wild-type cancers), was present in 67 ovarian cancers (30%) and was also significantly associated with PFS in univariate (P = .026; HR = 0.67; 95% CI, 0.47 to 0.96) and multivariate (P = .008) analyses.

Conclusion

BRCA½ somatic and germline mutations and expression loss are sufficiently common in ovarian cancer to warrant assessment for prediction of benefit in clinical trials of PARP1 inhibitors.