bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurodevelopment and Schizophrenia
Authors: Walker Elaine , Shapiro Daniel , Esterberg Michelle , Trotman Hanan
Published: August 2010

Developmental changes in the brain are now a central feature of most etiological theories of schizophrenia. From the fetal period, in which vulnerability is presumed to originate, to the emergence of clinical illness in adolescence, brain changes are setting the stage for the first episode of psychosis. A host of factors that have the ability to alter fetal brain development have been linked with schizophrenia. Heritable genetic factors may increase risk for aberrant fetal brain development, and molecular genetic studies are now revealing mutations and epigenetic events that can also derail normal developmental processes. Prenatal complications also are now known to be associated with vulnerability. Later, adolescence and early adulthood are the critical periods for the onset of the prodrome, the period of decline before illness onset, and then the clinical syndrome. Here we summarize hypothesized elements of the neurodevelopmental process in schizophrenia in a model that spans both the prenatal and adolescent/young-adult periods. It is likely that future models will be much more complex as epigenetic processes and gene–environment interactions are incorporated.
Cognitive Functioning and Disability in Schizophrenia
Authors: Harvey Philip D.
Published: August 2010

Impairments in a variety of cognitive processes, including concentration and attention, learning and memory, processing speed, and problem solving, are present in people with schizophrenia. Also seen in the condition are notable impairments in the ability to perform everyday tasks and to achieve normal functional milestones such as work, stable social relationships, and living independently. In this article I discuss recent research that has focused on quantifying the predictors of disability in real-world functioning, with cognitive impairment being one of the major predictors. Other important developments include the development of direct measures of the ability to perform the skills required to achieve everyday functional goals—skills referred to as “functional capacity.” Studies have shown that these abilities may be influenced by cognitive impairments and may be better predictors of disability than are cognitive deficits. I also examine the current literature on the treatment of cognitive impairments and functional disability, including both pharmacological and behavioral interventions.
Schizophrenia Course, Long-Term Outcome, Recovery, and Prognosis
Authors: Jobe Thomas H. , Harrow Martin
Published: August 2010

Our 26-year longitudinal study and other longitudinal studies confirm older views that outcome for schizophrenia, while showing some variation for different schizophrenia patients, is still significantly poorer than that for other psychiatric disorders, with the exception of the dementias. Our research leads us to propose that risk factors, either stress related or those related to vulnerability to psychosis, account for the episodic course of periods of recovery followed by periods of recurrence that is experienced by most schizophrenia patients. These risk factors interact with personality, temperament, and cognitive traits that, while not causing psychosis, influence its course. It is these interactions that account for the heterogeneous outcome trajectories of different subgroups of people with this condition. Our research and that of others has focused on the contributions of these risk factors, such as vulnerability to trait anxiety, poor developmental achievements before the illness, personality traits such as locus of control, cognitive styles, neurocognitive impairments, length of untreated psychosis, and several others. Despite the proven efficacy of antipsychotic medications over the short term, there is a subgroup of schizophrenia patients who, a few years after the acute phase, function adequately or experience periods of recovery for a number of years, without treatment.
Would Better Institutional Quality Contribute towards Reducing the Size of Government in Sub-Saharan Africa?
Authors: Sobhee Sanjeev K.
Published: August 2010

Sub-Saharan Africa is concurrently characterised by low institutional quality and large-sized government sectors and both may keep the cost of doing business high. This paper revitalises the political economy literature on growth of governments in highlighting the essence of upgrading institutional quality to trim down government size in several sub-Saharan economies. It particularly contributes to existing knowledge by showing that failure to control for idiosyncrasies would lead to serious biases in regressions that try to explain growth of governments. Moreover, this paper challenges factors such as globalisation and population dynamics, often perceived as major drivers, of the size of public sector in developing countries. Empirical findings based on 42 economies, pertaining to this region, clearly indicate that, besides level of development, the quality of institutions matters tremendously in reducing growth of governments. Contrary to previous studies, weak evidence is found of trade openness, urbanisation and dependency ratio determining public sector growth once idiosyncratic elements are accounted for. Of the six indicators of institutional quality applied in this assessment, ‘Control of Corruption’ is found to be most significant that policy reforms should address to reduce the overwhelming sizes of government in sub-Saharan economies.
A Periodic Autoregressive Model of Indian WPI Inflation
Authors: Kar Sujata
Published: August 2010

A growing literature in the field of econometrics is on the treatment of seasonal variables. However, so far, very few studies in India have applied advanced seasonal modelling techniques to important macroeconomic variables. This paper examines the seasonal properties of Indian monthly WPI inflation and their usefulness in modelling the series more efficiently. Monthly WPI inflation was found to be a periodic process with 18 lags and periodic integration of order two. A comparison between the performances of a PAR (18) and an AR (18) model showed that the former performed substantially better in terms of R2, AIC, in-sample predictive ability and residual properties. However, the out-of-sample forecasts from the PAR model were only reasonable. The best forecasts obtained for a horizon of 22 months, however, had good ‘direction of change’ predictions. The model could also produce interval forecasts of modest accuracy.
India Protection Index
Authors: Shukla Rajesh , Rai Anil , Monga Nitasha
Published: August 2010

The success and failure of any democratic government is gauged in terms of how effectively it has fulfilled its constitutional obligation of enhancing social and economic well-being, particularly the common man. While developed economies use a set of indices to measure well-being, a systematic and comprehensive empirical assessment of well-being is found wanting in most developing countries, including India. This paper discusses the status of social and economic well-being of Indian families as measured by a primary survey-based composite index, the India Protection Index (IPI), which is an integration of the important dimensions of well-being. It finds that nearly 65 per cent of households and people in India have a reasonable degree of protection (i.e., the power of well-being) and that most of the less- and under-protected are daily wage earners, without any village–urban divide. The western states are better protected, as Maharashtra has the largest number of well-protected households (16 per cent), followed by Kartnataka and Kerala each accounting for 10 per cent. In terms of concentration, Kerala with 70,735 well-protected households per million is at the top, followed by Karnataka with 44,949 households—Uttar Pradesh and Bihar being at the bottom, with 14,621 and 26,908 households, respectively. The results show that the IPI can effectively be used to identify the status of households in terms of social and economic protection.
Centralized grassroots sport policy and ‘new governance’: A case study of County Sports Partnerships in the UK – unpacking the paradox
Authors: Phillpots Lesley , Grix Jonathan , Quarmby Tom
Published: August 2010

This article offers the first empirical account of the role of County Sport Partnerships (CSPs) in delivering grassroots sport policy in the UK. Current leading academic approaches to policy delivery in the UK suggest that we have witnessed a move from ‘big’ government to governance by and through networks and partnerships. Such a process is said to have led to a dispersal of power among many actors and diminished the ability of the state to control policy. Our empirical study of CSPs – including 10 in-depth interviews with key actors – suggests otherwise: grassroots sport policy delivery does take place via ‘partnerships’, but such arrangements are not to be confused with ‘new governance’. On the contrary, government policy delivery has never been so centrally managed, monitored and controlled.
“Snitches End Up in Ditches” and Other Cautionary Tales
Authors: Morris Edward W.
Published: August 2010

This article examines the “stop snitching” phenomenon in relation to teenagers and schooling. It shows evidence of a code against sharing information with formal authorities among students at two low-income schools: a predominately Black, urban school and a predominately White, rural school. Using Bourdieu’s concept of habitus, the analysis demonstrates how antisnitching is woven into the social fabric of these communities, prompting student ambivalence toward school-sanctioned methods of conflict resolution. The findings highlight the broad reach of the antisnitching phenomenon, situating this mentality as the result of community-based distrust of formal authority. The article assesses implications of antisnitching for school discipline and climate.
Racial Tensions and School Crime
Authors: Maume Michael O. , Kim-Godwin Yeoun Soo , Clements Caroline M.
Published: August 2010

This article uses data on school crime and other characteristics from a study of U.S. public schools to contribute to our knowledge about the extent and correlates of school violence and property crime. Following a brief review of the literature, the authors describe their efforts to examine the link between racial tensions and school crime. Relying on the macro version of general strain theory (GST) developed by Agnew and racial contact/threat perspectives on school race relations, a more specific purpose for their article is to determine the extent to which school-based crime is at least a partial function of extant racial tensions in schools. Analyses of violent and property-related incidents across a weighted sample of 1,936 middle and high schools indicate that racial tensions is a significant, positive correlate of both types of school crime, net of other school climate, organizational, and demographic characteristics. They discuss these findings and describe directions for future research with these data.
Game Engagement Theory and Adult Learning
Authors: Whitton Nicola
Published: August 2010

One of the benefits of computer game–based learning is the ability of certain types of game to engage and motivate learners. However, theories of learning and engagement, particularly in the sphere of higher education, typically fail to consider gaming engagement theory. In this article, the author examines the principles of engagement from games designed for entertainment, applies these principles to the design of learning activities, and presents a model of learning engagement. The article examines literature on computer games and engagement, draws together the findings from a series of interviews, and applies these in an educational context. The author hypothesizes five factors that contribute to engagement with a learning activity and provides an example of the use of these factors in practice. The article concludes by considering further potential applications of the model.
Learning About the Unit Cell and Crystal Lattice With Computerized Simulations and Games
Authors: Luealamai Sutha , Panijpan Bhinyo
Published: August 2010

The authors have developed a computer-based learning module on the unit cell of various types of crystal. The module has two components: the virtual unit cell (VUC) part and the subsequent unit cell hunter part. The VUC is a virtual reality simulation for students to actively arrive at the unit cell from exploring, from a broad view, the crystal lattice of atoms or ions displayed “three dimensionally.” The unit cell hunter (UCH) part, implemented after the VUC, is a board game with students competing in assembling the atomic pieces for two types of unit cell (cubic and hexagonal) framework. The students were evaluated for achievement after having benefited from working with the learning module and participating in the debriefing. Apart from identical pre- and posttests at the beginning and end of the activities, students also responded to a questionnaire. Active participation by the students and the researcher in the debriefing enhanced learning as set out by the objectives, for example, better visualization of the three-dimensional structures of various types of unit cell and crystal lattice.
Effects of Pegylated Interferon α on Fibrinolytic Parameters in Patients With Chronic Hepatitis C
Authors: Gokmen Ayla , Ustundag Yucel , Oztoprak Nefise , Aydemir Selim , Tekin Ishak Ozel , Cakal Basak , Kiran Sibel , Engin Huseyin
Published: August 2010

Interferon (IFN) interacts with endothelial cells and modulates the functions of these cells. In our study, we aimed to determine the effects of treatment with pegylated IFN-α (peg-IFN-α) on fibrinolytic parameters in patients with chronic hepatitis C. Fifteen patients with chronic hepatitis C were treated with peg-IFN-α once per week plus daily oral ribavirin. Euglobulin lysis time (ELT), plasma levels of d-dimer, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and thrombin activatable fibrinolysis inhibitor (TAFI) were determined before treatment, 2 weeks, 1 month, and 3 months after the initiation of the treatment. Plasma levels of t-PA increased significantly 1 month and 3 months after the treatment ( P < .05). The PAI-1 and TAFI levels in 2 weeks, 1 month and 3 months after treatment were not statistically different as compared with pretreatment levels ( P > .05) No significant difference in plasma d-dimer levels was observed during peg-IFN-α treatment ( P > .05). There was a significant decrease in ELT 1 month and 3 months after the treatment ( P < .05). Our results indicated that treatment with peg-IFN-α may be associated with enhanced fibrinolysis,
Low-Molecular-Weight Heparin Versus Unfractionated Heparin for Prophylaxis of Venous Thromboembolism in Medicine Patients—A Pharmacoeconomic Analysis
Authors: Wilbur Kerry , Lynd L. D. , Sadatsafavi M.
Published: August 2010

Background: Prevention of in-hospital venous thromboembolism (VTE) is identified internationally as a priority to improve patient safety. Advocated alternatives include low-dose unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Although LMWHs are as effective as UFH, less frequent administration and potentially safer adverse effect profile associated with LMWHs might off-set greater drug acquisition costs. The objective of this study was to determine the most cost-effective thromboprophylaxis strategy for hospitalized medicine patients and specific subgroups in Canada. Methods: A decision-analytic model assessed costs and outcomes of LMWH compared to UFH for thromboprophylaxis in at-risk hospitalized medicine patients from an institutional perspective. The outcome of interest was the incremental cost-effectiveness ratio (ICER) for preventing deep vein thrombosis (DVT) and combined untoward events (pulmonary embolism [PE], major bleed, and death). The time horizon of the model was the hospital stay. Results: In the base-case analysis, LMWH thromboprophylaxis resulted in higher costs ($7.40), but 3.6 and 1.1 fewer DVT and untoward events per 1000 patients, respectively, with associated ICERs of $2042 and $6832. Results remained predominantly stable when alternative assumptions were evaluated in the sensitivity analysis. Low-molecular-weight heparin had the most favorable economic profile in patients with a history of DVT. In the probabilistic sensitivity analysis, in 33% of simulations LMWH was less costly and more effective, whereas the reverse was true for UFH only in 13% of simulations. Conclusions: Low-molecular-weight heparin administration is a cost-effective alternative for thromboprophylaxis strategy in Canadian hospitalized medicine patients.
My Friend, Advocate Ellen Pence
Authors: Dasgupta Shamita Das
Published: August 2010

This is a tribute to Ellen Pence’s exemplary advocacy on behalf of battered women. It traces Ellen’s vital contributions to the field of antidomestic violence advocacy through two organizations, DAIP and Praxis. The history of Ellen’s relentless efforts to transform legal and social institutions that led her to create the coordinated community response (CCR) and the institutional audit tool to assess safety and accountability are also elaborated. The author characterizes Ellen Pence’s work as meta-advocacy.
Exploring the Measurement Quality of an Attitudinal Scale of Street Code-Related Violence: Similarities and Differences Across Groups and Contexts
Authors: Taylor Terrance J. , Esbensen Finn-Aage , Brick Bradley T. , Freng Adrienne
Published: August 2010

Elijah Anderson’s ‘‘code of the streets’’ has received considerable attention as a promising approach to understanding youths violence. One area which has received scant attention, however, is the measurement quality of the street code concept. Using data collected from more than 3,300 middle school youths residing in seven geographically and demographically diverse U.S. cities between 2007 and 2009, the authors seek to answer the following questions: (a) What are the psychometric properties of the attitudes toward street code-related violence scale (in terms of dimensionality and internal consistency) across demographic subgroups (i.e., race/ethnicity, sex, and age groups) and social contexts (i.e., cities)? and (b) To what extent does the level of acceptance of the attitudes associated with street code-related violence vary across demographic subgroups and social contexts? Results illustrate that the scale performs similarly across groups and contexts, but the actual level of acceptance of street code-related violence varies considerably.
Comparative Analyses of the YLS/CMI, SAVRY, and PCL:YV in Adolescent Offenders: A 10-year Follow-Up Into Adulthood
Authors: Schmidt Fred , Campbell Mary Ann , Houlding Carolyn
Published: August 2010

A growing body of research has been dedicated to developing adolescent risk assessment instruments, but much of this research has been limited to short-term tests of predictive validity. The current study examined the predictive and incremental validity of the Youth Level of Service/ Case Management Inventory (YLS/CMI), Structured Assessment of Violence Risk in Youth (SAVRY), and Psychopathy Checklist: Youth Version (PCL:YV) in adolescent offenders over a mean 10-year follow-up period. Each instrument predicted general recidivism with moderate- (YLS/CMI area under the curve [AUC] = .66) -to-large effect sizes (SAVRY AUC = .74; PCL:YV AUC = .79). However, there was variation in predictive validity across types of recidivism, and all three instruments were better at predicting recidivism in males than females. SAVRY total also demonstrated incremental validity over its structured professional judgment of risk. Clinical implications and future directions for youth risk assessment are discussed.
Hero takes a fall: A lesson from theatre for leadership
Authors: Biehl-Missal Brigitte
Published: August 2010

Comparing leaders to actors has a long tradition, and researchers and practitioners in the organizational field have tried to learn lessons from theatre. For developing this approach, this article takes an interdisciplinary theatre studies perspective and discusses how leaders in organizations compare to actors in the theatre. It makes the assertion that the actor’s role in (dramatic, epic and postdramatic) theatre over several historic epochs can be seen as a complementary, opposed practice that confronts and challenges audiences rather than ‘playing to them’. Theatre does not provide us with ideal or charismatic leader characters but, quite the opposite, teaches us about contentious and problematic heroes. Theatre presents a fundamental disrespect for tenability and positive affirmation and may offer more critical ideas about aesthetic interaction, leadership performance and leader-follower interaction. This illustrates that aesthetic features do not alone turn leadership into an art. ‘Leadership as an art’ through this lens includes critical interaction through increased aesthetic awareness from the viewpoint of followers.
MyD88-dependent pro-inflammatory cytokine response contributes to lethal toxicity of staphylococcal enterotoxin B in mice
Authors: Kissner Teri L , Ruthel Gordon , Cisney Emily D , Ulrich Robert G , Fernandez Stefan , Saikh Kamal U
Published: August 2010

An elevated pro-inflammatory cytokine response is the primary cause of death by toxic shock after exposure to staphylococcal enterotoxin B (SEB). Identifying an intracellular signal mediator that predominantly controls the pro-inflammatory response is important for developing a therapeutic strategy. We examined the role of the signaling adaptor MyD88 in cell culture and in a mouse model of toxic shock. Our results indicated that elevated tumor necrosis factor-α, interferon-γ, interleukin (IL)-1α/β and IL-6 production from mouse spleen cells treated with SEB alone or in combination with lipopolysaccharide (LPS) was regulated by MyD88. Elevated levels of MyD88 protein in spleen cells, as well as in CD11c+ or Mac3+ cells, and activation of nuclear factor-κB in spleen cells were observed in mice treated with SEB. An SEB-dose dependent lethality was observed in LPS-potentiated and in D-galactosamine-sensitized mice. D-Galactosamine treatment of spleen cells had no effect in cytokine induction but rather increased the sensitivity to toxic shock in mice. Our results demonstrated an impaired pro-inflammatory cytokine production by spleen cells of MyD88–/– mice in response to SEB or SEB plus LPS. Most importantly, MyD88–/– mice were resistant to SEB-induced death. These results demonstrate that MyD88-dependent pro-inflammatory signaling is responsible for SEB intoxication. In addition, our studies also demonstrated that LPS potentiation, in comparison to D-galactosamine sensitization, contributes to a stronger SEB–induced lethality. This is due to the pro-inflammatory cytokine response elicited by MyD88 after exposure to SEB and LPS. These findings offer an important insight upon SEB intoxication and subsequent therapy targeting MyD88.
Review: Replication of cortisol circadian rhythm: new advances in hydrocortisone replacement therapy
Authors: Chan Sharon , Debono Miguel
Published: August 2010

Cortisol has one of the most distinct and fascinating circadian rhythms in human physiology. This is regulated by the central clock located in the suprachiasmatic nucleus of the hypothalamus. It has been suggested that cortisol acts as a secondary messenger between central and peripheral clocks, hence its importance in the synchronization of body circadian rhythms. Conventional immediate-release hydrocortisone, either at twice- or thrice-daily doses, is not capable of replicating physiological cortisol circadian rhythm and patients with adrenal insufficiency or congenital adrenal hyperplasia still suffer from a poor quality of life and increased mortality. Novel treatments for replacement therapy are therefore essential. Proof-of-concept studies using hydrocortisone infusions suggest that the circadian delivery of hydrocortisone may improve biochemical control and life quality in patients lacking cortisol with an impaired cortisol rhythm. Recently oral formulations of modified-release hydrocortisone are being developed and it has been shown that it is possible to replicate cortisol circadian rhythm and also achieve better control of morning androgen levels. These new drug therapies are promising and potentially offer a more effective treatment with less adverse effects. Definite improvements clearly need to be established in future clinical trials.
InterLymph hierarchical classification of lymphoid neoplasms for epidemiologic research based on the WHO classification (2008): update and future directions
Authors: Turner Jennifer J. , Morton Lindsay M. , Linet Martha S. , Clarke Christina A. , Kadin Marshall E. , Vajdic Claire M. , Monnereau Alain , Maynadié Marc , Chiu Brian C.-H. , Marcos-Gragera Rafael , Costantini Adele Seniori , Cerhan James R. , Weisenburger Dennis D.
Published: August 2010

After publication of the updated World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues in 2008, the Pathology Working Group of the International Lymphoma Epidemiology Consortium (InterLymph) now presents an update of the hierarchical classification of lymphoid neoplasms for epidemiologic research based on the 2001 WHO classification, which we published in 2007. The updated hierarchical classification incorporates all of the major and provisional entities in the 2008 WHO classification, including newly defined entities based on age, site, certain infections, and molecular characteristics, as well as borderline categories, early and “in situ” lesions, disorders with limited capacity for clinical progression, lesions without current International Classification of Diseases for Oncology, 3rd Edition codes, and immunodeficiency-associated lymphoproliferative disorders. WHO subtypes are defined in hierarchical groupings, with newly defined groups for small B-cell lymphomas with plasmacytic differentiation and for primary cutaneous T-cell lymphomas. We suggest approaches for applying the hierarchical classification in various epidemiologic settings, including strategies for dealing with multiple coexisting lymphoma subtypes in one patient, and cases with incomplete pathologic information. The pathology materials useful for state-of-the-art epidemiology studies are also discussed. We encourage epidemiologists to adopt the updated InterLymph hierarchical classification, which incorporates the most recent WHO entities while demonstrating their relationship to older classifications.
Homologous illegitimate random integration of foreign DNA into the X chromosome of a transgenic mouse line
Authors: Yan Bowen , Li Defa , Gou Kemian
Published: August 2010

Background

It is not clear how foreign DNA molecules insert into the host genome. Recently, we have produced transgenic mice to investigate the role of the fad2 gene in the conversion of oleic acid to linoleic acid. Here we describe an integration mechanism of fad2 transgene by homologous illegitimate random integration.

Results

We confirmed that one fad2 line had a sole integration site on the X chromosome according to the inheritance patterns. Mapping of insertion sequences with thermal asymmetric interlaced and conventional PCR revealed that the foreign DNA was inserted into the XC1 region of the X chromosome by a homologous illegitimate replacement of an entire 45,556-bp endogenous genomic region, including the ovarian granulosa cell tumourigenesis-4 allele. For 5' and 3' junction sequences, there were very short (3-7 bp) common sequences in the AT-rich domains, which may mediate the recognition of the homologous arms between the transgene and the host genome. In addition, analysis of gene transcription indicated that the transgene was expressed in all tested fad2 tissues and that its transcription level in homozygous female tissues was about twice as high as in the heterozygous female (p < 0.05).

Conclusions

Taken together, the results indicated that the foreign fad2 behaved like an X-linked gene and that foreign DNA molecules were inserted into the eukaryotic genome through a homologous illegitimate random integration.
The two α-dox genes of Nicotiana attenuata: overlapping but distinct functions in development and stress responses
Authors: Steppuhn Anke , Gaquerel Emmanuel , Baldwin Ian T
Published: August 2010

Background

Plant fatty acid α-dioxygenases (α-DOX) are oxylipin-forming enzymes induced by biotic and abiotic stresses, which also participate in developmental processes. InNicotiana attenuata, herbivory strongly induces the expression of anα-dox1gene. To determine its role, we silenced its expression usingAgrobacterium-mediated plant transformation with an inverted repeat construct. More than half of the transformed lines showed a severe dwarf growth phenotype that was very similar to the phenotype of tomato plants mutated at a secondα-doxisoform. This led us to identify the correspondingα-dox2gene inN. attenuataand examine the regulation of bothα-doxgenes as well as the consequences of their silencing in plant development and anti-herbivore defense.

Results

The transformed lines exhibiting a dwarf growth phenotype are co-silenced for bothα-doxgenes resulting in a nearly complete suppression of α-DOX activity, which is associated with increases in ABA, JA and anthocyanin levels, all metabolic signatures of oxidative stress. The other lines, only silenced forα-dox1, developed similarly to wild-type plants, exhibited a 40% reduction of α-DOX activity resulting in a 50% reduction of its main productin planta(2-HOT) and showed no signs of oxidative stress. In contrast toα-dox1, the expression ofα-dox2gene is not induced by wounding or elicitors in the oral secretions ofManduca sexta. Instead,α-dox2is expressed in roots and flowers which lackα-dox1expression, but both genes are equally regulated during leaf maturation. We transiently silencedα-doxgene copies with gene-specific constructs using virus induced gene silencing and determined the consequences for plant development and phytohormone and 2-HOT levels. While individual silencing ofα-dox1orα-dox2had no effects on plant growth, the co-suppression of bothα-doxgenes decreased plant growth. Plants transiently silenced for bothα-doxgenes had increased constitutive levels of JA and ABA but silencingα-dox1alone resulted in lowerM. sexta-induced levels of JA, 2-HOT and ABA.

Conclusions

Thus, bothα-doxisoforms function in the development ofN. attenuata. In leaf maturation, the twoα-doxgenes have overlapping functions, but onlyα-dox2is involved in root and flower development and onlyα-dox1functions in anti-herbivore defense.
Infection with HIV and HCV enhances the release of fatty acid synthase into circulation: evidence for a novel indicator of viral infection
Authors: Aragonès Gerard , Alonso-Villaverde Carlos , Oliveras-Ferraros Cristina , Beltrán-Debón Raúl , Rull Anna , Rodríguez-Sanabria Fernando , Camps Jordi , Martín Alejandro Vázquez , Menéndez Javier A , Joven Jorge
Published: August 2010

Background

Fatty acid synthase (FASN) is an enzyme synthesized by the liver and plays an important role in lipogenesis. The present study aimed to investigate whether serum FASN concentration may provide a direct link between HIV and/or HCV viral infections and lipid metabolic disorders commonly observed in HIV/HCV-infected patients.

Methods

We evaluated serum FASN concentration in 191 consecutive HIV-infected patients in the absence or presence of HCV co-infection. For comparison, 102 uninfected controls were included. Metabolic and inflammatory phenotype was also compared with respect to the presence of HCV co-infection.

Results

Serum FASN concentration was significantly higher in HIV-infected patients than in healthy participants and HCV co-infected patients showed higher levels than those without co-infection. Levels were also affected by treatment regimen, but marginally influenced by virological variables. Insulin concentration was the sole variable among metabolic parameters that demonstrated a significant correlation with serum FASN concentrations. Serum alanine aminotransferase (ALT) values correlated significantly with serum FASN concentration and provided the best discrimination with respect to the presence or absence of HCV co-infection. In multivariate analysis, only ALT, monocyte chemoattractant protein-1 (MCP-1) and the presence of antiretroviral treatment regimen significantly contributed to explain serum FASN concentration in HIV/HCV co-infected patients.

Conclusion

Serum FASN concentration is significantly increased in HIV-infected individuals. The release of FASN into the circulation is further enhanced in patients who are co-infected with HCV. Subsequent studies should explore the usefulness of this indicator to monitor the effect of viral infections on disease progression and survival.
Impact of adjuvant chemotherapy for gliomatosis cerebri
Authors: Kong Doo-Sik , Kim Sung Tae , Lee Jung-Il , Suh Yeon-Lim , Lim Do Hoon , Kim Won Seog , Kwon Ki-Hoon , Park Kwan , Kim Jong Hyun , Nam Do-Hyun
Published: August 2010

Background

Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC.

Methods

Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy.

Results

Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008).

Conclusion

Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC.
Evaluation of mobile learning: Students' experiences in a new rural-based medical school
Authors: Nestel Debra , Ng Andre , Gray Katherine , Hill Robyn , Villanueva Elmer , Kotsanas George , Oaten Andrew , Browne Chris
Published: August 2010

Background

Mobile learning (ML) is an emerging educational method with success dependent on many factors including the ML device, physical infrastructure and user characteristics. At Gippsland Medical School (GMS), students are given a laptop at the commencement of their four-year degree. We evaluated the educational impact of the ML program from students' perspectives.

Methods

Questionnaires and individual interviews explored students' experiences of ML. All students were invited to complete questionnaires. Convenience sampling was used for interviews. Quantitative data was entered to SPSS 17.0 and descriptive statistics computed. Free text comments from questionnaires and transcriptions of interviews were thematically analysed.

Results

Fifty students completed the questionnaire (response rate 88%). Six students participated in interviews. More than half the students owned a laptop prior to commencing studies, would recommend the laptop and took the laptop to GMS daily. Modal daily use of laptops was four hours. Most frequent use was for access to the internet and email while the most frequently used applications were Microsoft Word and PowerPoint. Students appreciated the laptops for several reasons. The reduced financial burden was valued. Students were largely satisfied with the laptop specifications. Design elements of teaching spaces limited functionality. Although students valued aspects of the virtual learning environment (VLE), they also made many suggestions for improvement.

Conclusions

Students reported many educational benefits from school provision of laptops. In particular, the quick and easy access to electronic educational resources as and when they were needed. Improved design of physical facilities would enhance laptop use together with a more logical layout of the VLE, new computer-based resources and activities promoting interaction.
A comparison of the Charlson comorbidity index derived from medical records and claims data from patients undergoing lung cancer surgery in Korea: a population-based investigation
Authors: Seo Hyun-Ju , Yoon Seok-Jun , Lee Sang-Il , Lee Kun Sei , Yun Young Ho , Kim Eun-Jung , Oh In-Hwan
Published: August 2010

Background

Calculating the Charlson comorbidity index (CCI) from medical records is a time-consuming and expensive process. The objectives of this study are to 1) measure agreement between medical record and claims data for CCI in lung cancer patients and 2) predict health outcomes of lung cancer patients based on CCIs from both data sources.

Methods

We studied 392 patients who underwent surgery for pathologic stages I-III of lung cancer. The kappa value was used to measure the agreement between the 17 comorbidities of the CCI prevalence obtained from medical records and claims data. Multiple linear regression analyses were used to evaluate the relationships between CCI and length of stay and reimbursement cost.

Results

Out of 17 comorbidities identified in the Charlson comorbidity index, ten had a higher prevalence, four had a lower prevalence and three had a similar prevalence in claims data to those of medical records. The kappa values calculated from the two databases ranged from 0.093 to 0.473 for nine comorbidities. In predicting length of stay and reimbursement cost after surgical resection for lung cancer patients, the CCI scores derived from both the medical records and claims data were not statistically significant.

Conclusions

Poor agreement between medical record data and claims data may result from different motivations for collecting data. Further studies are needed to determine an appropriate method for predicting health outcomes based on these data sources.
3D collagen type I matrix inhibits the antimigratory effect of doxorubicin
Authors: Millerot-Serrurot Emilie , Guilbert Marie , Fourré Nicolas , Witkowski Wojciech , Said Georges , Van Gulick Laurence , Terryn Christine , Zahm Jean-Marie , Garnotel Roselyne , Jeannesson Pierre
Published: August 2010

Background

The cell microenvironment, especially extracellular matrix proteins, plays an important role in tumor cell response to chemotherapeutic drugs. The present study was designed to investigate whether this microenvironment can influence the antimigratory effect of an anthracycline drug, doxorubicin, when tumor cells are grown in a matrix of type I collagen, a three-dimensional (3D) context which simulates a natural microenvironment.

Methods

To this purpose, we studied the migratory parameters, the integrin expression, and the activation state of focal adhesion kinase (FAK) and GTPase RhoA involved in the formation of focal adhesions and cell movement. These parameters were evaluated at non toxic concentrations which did not affect HT1080 cell proliferation.

Results

We show that while doxorubicin decreased cell migration properties by 70% in conventional two-dimensional (2D) culture, this effect was completely abolished in a 3D one. Regarding the impact of doxorubicin on the focal adhesion complexes, unlike in 2D systems, the data indicated that the drug neither affected β1 integrin expression nor the state of phosphorylation of FAK and RhoA.

Conclusion

This study suggests the lack of antiinvasive effect of doxorubicin in a 3D environment which is generally considered to better mimic the phenotypic behaviour of cells in vivo. Consistent with the previously shown resistance to the cytotoxic effect in a 3D context, our results highlight the importance of the matrix configuration on the tumor cell response to antiinvasive drugs.
Optimization strategies for metabolic networks
Authors: Domingues Alexandre , Vinga Susana , Lemos João M
Published: August 2010

Background

The increasing availability of models and data for metabolic networks poses new challenges in what concerns optimization for biological systems. Due to the high level of complexity and uncertainty associated to these networks the suggested models often lack detail and liability, required to determine the proper optimization strategies. A possible approach to overcome this limitation is the combination of both kinetic and stoichiometric models. In this paper three control optimization methods, with different levels of complexity and assuming various degrees of process information, are presented and their results compared using a prototype network.

Results

The results obtained show that Bi-Level optimization lead to a good approximation of the optimum attainable with the full information on the original network. Furthermore, using Pontryagin's Maximum Principle it is shown that the optimal control for the network in question, can only assume values on the extremes of the interval of its possible values.

Conclusions

It is shown that, for a class of networks in which the product that favors cell growth competes with the desired product yield, the optimal control that explores this trade-off assumes only extreme values. The proposed Bi-Level optimization led to a good approximation of the original network, allowing to overcome the limitation on the available information, often present in metabolic network models. Although the prototype network considered, it is stressed that the results obtained concern methods, and provide guidelines that are valid in a wider context.
Evidence that adiponectin receptor 1 activation exacerbates ischemic neuronal death
Authors: Thundyil John , Tang Sung-Chun , Okun Eitan , Shah Kausik , Karamyan Vardan T , Li Yu-I , Woodruff Trent M , Taylor Stephen M , Jo Dong-Gyu , Mattson Mark P , Arumugam Thiruma V
Published: August 2010

Background-

Adiponectin is a hormone produced in and released from adipose cells, which has been shown to have anti-diabetic and anti-inflammatory actions in peripheral cells. Two cell surface adiponectin receptors (ADRs) mediate the majority of the known biological actions of adiponectin. Thus far, ADR expression in the brain has been demonstrated in the arcuate and the paraventricular nucleus of hypothalamus, where its activation affects food intake. Recent findings suggest that levels of circulating adiponectin increase after an ischemic stroke, but the role of adiponectin receptor activation in stroke pathogenesis and its functional outcome is unclear.

Methods-

Ischemic stroke was induced in C57BL/6 mice by middle cerebral artery occlusion (MCAO) for 1 h, followed by reperfusion. Primary cortical neuronal cultures were established from individual embryonic neocortex. For glucose deprivation (GD), cultured neurons were incubated in glucose-free Locke's medium for 6, 12 or 24 h. For combined oxygen and glucose deprivation (OGD), neurons were incubated in glucose-free Locke's medium in an oxygen-free chamber with 95% N2/5% CO2 atmosphere for either 3, 6, 9, 12 or 24 h. Primary neurons and brain tissues were analysed for Adiponectin and ADRs using reverse transcriptase polymerase chain reaction (RT-PCR), immunoblot and immunochemistry methods.

Results-

Cortical neurons express ADR1 and ADR2, and that the levels of ADR1 are increased in neurons in response to in vitro or in vivo ischemic conditions. Neurons treated with either globular or trimeric adiponectin exhibited increased vulnerability to oxygen and glucose deprivation which was associated with increased activation of a pro-apoptotic signaling cascade involving p38 mitogen-activated protein kinase (p38MAPK) and AMP-activated protein kinase (AMPK).

Conclusions-

This study reveals a novel pathogenic role for adiponectin and adiponectin receptor activation in ischemic stroke. We show that cortical neurons express ADRs and reveal a pro-apoptotic role for ADR1 activation in neurons, which may render them vulnerable to ischemic death.
Early combination disease-modifying antirheumatic drug therapy and tight disease control improve long-term radiologic outcome in patients with early rheumatoid arthritis: the 11-year results of the Finnish Rheumatoid Arthritis Combination Therapy trial
Authors: Rantalaiho Vappu , Korpela Markku , Laasonen Leena , Kautiainen Hannu , Järvenpää Salme , Hannonen Pekka , Leirisalo-Repo Marjatta , Blåfield Harri , Puolakka Kari , Karjalainen Anna , Möttönen Timo ,   the FIN-RACo Trial Group
Published: August 2010

Introduction

Early treatment of rheumatoid arthritis (RA) has been shown to retard the development of joint damage for a period of up to 5 years. The aim of this study was to evaluate the radiologic progression beyond that time in patients with early RA initially treated with a combination of three disease-modifying antirheumatic drugs (DMARDs) or a single DMARD.

Methods

A cohort of 199 patients with early active RA were initially randomized to receive treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone (FIN-RACo), or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone (SINGLE). After 2 years, the drug-treatment strategy became unrestricted, but still targeted remission. The radiographs of hands and feet were analyzed by using the Larsen score at baseline, 2, 5, and 11 years, and the radiographs of large joints, at 11 years.

Results

Sixty-five patients in the FIN-RACo and 65 in the SINGLE group had radiographs of hands and feet available at baseline and at 11 years. The mean change from baseline to 11 years in Larsen score was 17 (95% CI, 12 to 26) in the FIN-RACo group and 27 (95% CI, 22 to 33) in the SINGLE group (P = 0.037). In total, 87% (95% CI, 74 to 94) and 72% (95% CI, 58 to 84) of the patients in the FIN-RACo and the SINGLE treatment arms, respectively, had no erosive changes in large joints at 11 years.

Conclusions

Targeting to remission with tight clinical controls results in low radiologic progression in most RA patients. Patients treated initially with a combination of DMARDs have less long-term radiologic damage than do those treated initially with DMARD monotherapy.

Trial registration

Current Controlled Trials ISRCTN18445519.