bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopaminergic challenges in social anxiety disorder: evidence for dopamine D3 desensitisation following successful treatment with serotonergic antidepressants
Authors: Hood SD , Potokar JP , Davies SJC , Hince DA , Morris K. , Seddon KM , Nutt DJ , Argyropoulos SV
Published: October 2008

Serotonergic antidepressants (SSRIs) are first-line treatments for social anxiety disorder [SAnD], though there is evidence of dopaminergic system dysfunction. Twenty subjects with DSM-IV SAnD, untreated (n = 10) and SSRI-remitted DSM-IV SAnD (n = 10), were administered a single dose of 1) a dopamine agonist (pramipexole 0.5 mg) and 2) a dopamine antagonist (sulpiride 400 mg), followed by anxiogenic challenges (verbal tasks and autobiographical scripts) in a double-blind crossover design, the two test days being one week apart. Anxiety symptoms were measured by self-reported changes in Visual Analogue Scales, specific SAnD scales and anxiety questionnaires. Plasma levels of prolactin were obtained. Untreated SAnD subjects experienced significant increases in anxiety symptoms following behavioural challenges after either sulpiride or pramipexole. Following remission with SSRIs, the socially anxiogenic effect of behavioural provocation was significantly attenuated under pramipexole, whereas under sulpiride effects remained significantly elevated. There appears to be instability of the dopamine system under behavioural stress in social anxiety subjects that is only partly rectified by successful treatment with an SSRI, which may induce a desensitisation of postsynaptic dopamine D3 receptors.
Factor Structure of the Norwegian Version of the WAIS-III in a Clinical Sample
Authors: Egeland Jens , Bosnes Ole , Johansen Hans
Published: October 2008

Confirmatory Factor Analyses (CFA) of the Wechsler Adult Intelligence Scale—III (WAIS-III) lend partial support to the four-factor model proposed in the test manual. However, the Arithmetic subtest has been especially difficult to allocate to one factor. Using the new Norwegian WAIS-III version, we tested factor models differing in the number of factors and in the placement of the Arithmetic subtest in a mixed clinical sample ( n = 272). Only the four-factor solutions had adequate goodness-of-fit values. Allowing Arithmetic to load on both the Verbal Comprehension and Working Memory factors provided a more parsimonious solution compared to considering the subtest only as a measure of Working Memory. Effects of education were particularly high for both the Verbal Comprehension tests and Arithmetic.
Evaluating the Invariance and Validity of the Structure of Dysfunctional Attitudes in an Adolescent Population
Authors: Prenoveau Jason M. , Zinbarg Richard E. , Craske Michelle G. , Mineka Susan , Griffith James W. , Rose Raphael D.
Published: October 2008

Form A of the Dysfunctional Attitude Scale (DAS-A), a self-report measure of depressive beliefs, is widely used to test Beck's cognitive model of depression. The present study is the first to evaluate the DAS-A factor structure in an adolescent population of 542 high school juniors and the first to examine a hierarchical model. Findings support the existence of a hierarchical structure consisting of two conceptually meaningful group factors (Dysfunctional Attitudes About Achievement and Dysfunctional Attitudes About Needing Approval), a method factor consisting of reverse-worded items, and a general factor, which accounts for 65% of the variance in total scores. The general factor is related to sociotropy, autonomy, and neuroticism, whereas the Dysfunctional Attitudes About Achievement and Dysfunctional Attitudes About Needing Approval factors demonstrate convergent and discriminant validity with respect to autonomy and sociotropy. The structure displays partial metric invariance in female and male students as well as in Caucasian and Non-Caucasian students.
The Test Validation Summary
Authors: Frederick Richard I. , Bowden Stephen C.
Published: October 2008

Common rates employed in classificatory testing are the true positive rate (TPR), false positive rate (FPR), positive predictive power (PPP), and negative predictive power (NPP). FPR and TPR are estimated from research samples representing populations to be distinguished by classificatory testing. PPP and NPP are used by clinicians to classify test takers into populations. PPP and NPP depend on the base rate (BR) of population members in the clinician's sample. The authors introduce the test validation summary (TVS) as a means to report within a single graph the FPR and TPR and the ranges of PPP and NPP across all potential sample BRs for any chosen cut score. The authors investigate how the TVS has other applications, including the estimation of local BR for the condition of interest and the estimation of standard errors for FPR and TPR when estimated across multiple independent validation studies of the classificatory test.
Developing Infrastructure Through the Use of Tax Increment Financing
Authors: Leavitt William M. , Morris John C. , Lombard John R.
Published: October 2008

The use of tax increment finance (TIF) arrangements to finance capital-intensive infrastructure needs is not a new concept, but it is gaining traction in many states and municipalities. This article presents the case of the Town Center project in Virginia Beach, Virginia, and the use of a TIF to provide infrastructure for the project. The authors find that the success of the TIF is because of a combination of a reduction in public risk, careful planning, and close attention paid to the capabilities of the private sector partners. The authors conclude that the TIF mechanism is an appropriate and attractive means to fund infrastructure needs, provided the trade-offs and pitfalls are carefully considered and understood.
The Risks and Rewards of Private Equity in Infrastructure
Authors: Page Sasha N. , Ankner Dr. William , Jones Cheryl , Fetterman Robert
Published: October 2008

Many policymakers, operators and developers of public infrastructure (such as highways, airports, water utilities), and academics believe that there is a funding deficit for US infrastructure. Traditional funding sources, such as fuel taxes, are widely deemed inadequate and unlikely to be increased. Tolls and other user fees provide additional funding sources. Coupled with public-private partnership contracting and delivery methods (P3s), these fees can provide new funding sources and ways to reduce delivery costs, as many recent transactions demonstrate, such as the Chicago Skyway and the State of Texas transactions. Private equity is an important component of P3 financing and as much as $80 to $130 billion (B) is available in private equity investment funds (PEIFs). PEIFs impose certain requirements on the projects and companies they finance, most importantly on short duration of the investment, as little as ten years, in some cases, from initial investment to final payback. This causes potential conflicts with new, greenfield projects, which have a three to five year construction period and several years of ramp-up in the early operating years. PEIFs can serve as a useful funding source if: 1) policymakers anticipate this conflict, including anticipating short duration, allowing for novation of private contracts to other parties, are clear about re-gearing issues, seek ways to reduce project development periods and/or if 2) PEIFs can be structured with longer durations and/or PEIF funding partners, especially endowments and pension funds, can make direct, longer duration investments.
Chemical Metaphors in Sociological Discourse
Authors: Sousa Fernandes Teresa
Published: October 2008

This article addresses the role of chemical ideas in the formation of sociological discourse, focusing on the works of Rousseau and Durkheim. The opposition between physics and chemistry, as envisaged by Rousseau and the encyclopaedists, was transposed to social philosophy. This procedure is at the origin of contrasting sociological concepts. `Aggregation' and `association', in particular, are metaphors of the physical and the chemical object, respectively. It is shown that these Rousseauian constructions form the matrix of Durkheim's definition of the sui generis nature of collective representations. The interpretation is centred on the concept of synthesis as it relates to chemical notions of `affinity' and `combination'. I reassess, in this context, the continuity of Durkheim's thought.
Mystification of the Labor Process in Contemporary Consumer Culture
Authors: Borchard Kurt , Dickens David R.
Published: October 2008

An addition to an already diverse body of empirical work within cultural studies research is offered by analyzing the mystification of the labor process for children attending Build-A-Bear Workshops. First it is briefly described how customers "build" their own commodities at these Workshops and how the production of stuffed animals at the stores is constructed as an experience that hides the true nature of capitalist manufacturing and service work. It is argued that these Workshops place children in the role of supervisors engaged in facilitating the sort of flexible production that characterizes the contemporary work process. It is noted how the process of naming and creating "birth records" for the stuffed animals allows Build-A-Bear Workshops to collect valuable personal information on individuals and families. In sum, it is found that Build-A-Bear Workshops socialize children into the commodification of sentiment, the role of middle managers, and a lifestyle of consuming prefabricated products and experiences.
Careless Whispers: The Doubleness of Spanish Love
Authors: Farred Grant
Published: October 2008

This essay explores the "national" division of Spain, and Spanish football in particular, from the perspective of a long-distance Liverpool Football Club fan. The route to and through Spain, through its turbulent and bloody political history, is mediated by the persona of the Basque midfield maestro, Xabi Alonso. Marveling at Alonso's sublime skills, "Careless Whispers" reflects on the complicated and multiply divided nature of (international) football fandom. The path from Liverpool, England, to San Sebastian, Bizkaia, is riddled with many histories, but it is precisely because of the "diversions" and contradictions that map this journey that Xabi Alonso is able to stand as the figure of footballing explication.
Sport, Authenticity, Confession
Authors: Miller Toby
Published: October 2008

This article appeals for an end to drawing on personal experience as sports scholarship and pedagogy. It questions the value of autoethnography. Too much work on sport, in particular, is based on appeals to sporting ardor or expertise rather than analytic and political acuity. Instead, what is needed is a supple blend of political economy, ethnography, and textual analysis.
Cultural Studies and the Circuit of Culture: Advertising, Promotional Culture and the New Zealand All Blacks
Authors: Scherer Jay , Jackson Steven J.
Published: October 2008

Using a modified circuit of culture as a methodological and theoretical framework, this paper examines the interrelated moments associated with the production, representation, and consumption of a recent televised advertisement for adidas's sponsorship of the New Zealand All Blacks. The study suggests that each articulatory moment represents a key site for in-depth multiperspectival analyses, which can facilitate a broad contextual understanding of the complexities, contradictions, and power relations associated with contemporary culture in general and specifically in relation to indigenous culture.
Human Resource Development for Modernizing the Agricultural Workforce
Authors: Rivera William M. , Alex Gary E.
Published: October 2008

Greater commercialization of agricultural systems and increasing trade liberalization dictate the need for better capacity on the part of the agriculture workforce in the 21st century. Global changes in the roles of the public and private sectors and the dramatic advancements in technology have also strongly affected agricultural workforce development needs. These evolving changes have important policy, institutional and programmatic implications. This article therefore places human resource development in the context of current concerns for the development of national knowledge economies and “education for the knowledge economy.” First, the territory is defined. Then the part training plays in capacity development within organizations in the agriculture workforce is examined and suggests, in the view of the authors, the need for new and necessary policy, institutional, and program reform. Agricultural education systems, including extension, formal education, in-service training, and mass media/distance education programs are examined for their importance and their need to network to prepare the agricultural workforce to meet new challenges.
The Nephrotic Syndrome: An Unusual Case of Multiple Embolic Events
Authors: Schwartz Jean-Claude D. , Wyrzykowski Amy D. , Dente Christopher J. , Nicholas Jeffrey M.
Published: October 2008

The nephrotic syndrome is an unusual cause of the hypercoaguable state and thromboembolic complications. Here we report the case of a 42-year-old woman with nephrotic syndrome who presented with a pulseless lower extremity and a midpole renal infarct requiring urgent embolectomy of the leg. During her embolic evaluation, she was found to have an intracardiac thrombus. Over the course of her hospitalization, she developed a pulseless upper extremity and required an embolectomy of her arm. We believe that this represents the first case report of a patient with nephrotic syndrome, intracardiac thrombus, and evidence of embolization to 3 sites: kidney, arm, and leg.
STAT-3 and ERK 1/2 phosphorylation are critical for T-cell alloactivation and graft-versus-host disease
Authors: Lu Sydney X. , Alpdogan Onder , Lin Janine , Balderas Robert , Campos-Gonzalez Roberto , Wang Xiao , Gao Guo-Jian , Suh David , King Christopher , Chow Melanie , Smith Odette M. , Hubbard Vanessa M. , Bautista Johanne L. , Cabrera-Perez Javier , Zakrzewski Johannes L. , Kochman Adam A. , Chow Andrew , Altan-Bonnet Gregoire , van den Brink Marcel R. M.
Published: October 2008

Graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation, and donor T cells are indispensable for GVHD. Current therapies have limited efficacy, selectivity, and high toxicities. We used a novel flow cytometry technique for the analysis of intracellular phosphorylation events in single cells in murine BMT models to identify and validate novel GVHD drug targets.1-7 This method circumvents the requirement for large numbers of purified cells, unlike western blots. We defined a signaling profile for alloactivated T cells in vivo and identified the phosphorylation of ERK1/2 and STAT-3 as important events during T-cell (allo)activation in GVHD. We establish that interference with STAT-3 phosphorylation can inhibit T-cell activation and proliferation in vitro and GVHD in vivo. This suggests that phospho-specific flow cytometry is useful for the identification of promising drug targets, and ERK1/2 and STAT-3 phosphorylation in alloactivated T cells may be important for GVHD.
Adrenaline modulates the global transcriptional profile of Salmonella revealing a role in the antimicrobial peptide and oxidative stress resistance responses
Authors: Karavolos MH , Spencer H , Bulmer DM , Thompson A , Winzer K , Williams P , Hinton JCD , Khan CM Anjam
Published: October 2008

Background

The successful interaction of bacterial pathogens with host tissues requires the sensing of specific chemical and physical cues. The human gut contains a huge number of neurons involved in the secretion and sensing of a class of neuroendocrine hormones called catecholamines. Recently, in Escherichia coli O157:H7, the catecholamines adrenaline and noradrenaline were shown to act synergistically with a bacterial quorum sensing molecule, autoinducer 3 (AI-3), to affect bacterial virulence and motility. We wished to investigate the impact of adrenaline on the biology of Salmonella spp.

Results

We have determined the effect of adrenaline on the transcriptome of the gut pathogen Salmonella enterica serovar Typhimurium. Addition of adrenaline led to an induction of key metal transport systems within 30 minutes of treatment. The oxidative stress responses employing manganese internalisation were also elicited. Cells lacking the key oxidative stress regulator OxyR showed reduced survival in the presence of adrenaline and complete restoration of growth upon addition of manganese. A significant reduction in the expression of the pmrHFIJKLM antimicrobial peptide resistance operon reduced the ability of Salmonella to survive polymyxin B following addition of adrenaline. Notably, both phenotypes were reversed by the addition of the β-adrenergic blocker propranolol. Our data suggest that the BasSR two component signal transduction system is the likely adrenaline sensor mediating the antimicrobial peptide response.

Conclusion

Salmonella are able to sense adrenaline and downregulate the antimicrobial peptide resistance pmr locus through the BasSR two component signalling system. Through iron transport, adrenaline may affect the oxidative stress balance of the cell requiring OxyR for normal growth. Both adrenaline effects can be inhibited by the addition of the β-adrenergic blocker propranolol. Adrenaline sensing may provide an environmental cue for the induction of the Salmonella stress response in anticipation of imminent host-derived oxidative stress. However, adrenaline may also serve in favour of the host defences by lowering antimicrobial peptide resistance and hence documenting for the first time such a function for a hormone.
Transglutaminase activity in the hematopoietic tissue of a crustacean, Pacifastacus leniusculus, importance in hemocyte homeostasis
Authors: Lin Xionghui , Söderhäll Kenneth , Söderhäll Irene
Published: October 2008

Background

Transglutaminases (TGases) form a group of enzymes that have many different substrates and among the most well known are fibrin for Factor XIIIa and the clotting protein in crustaceans. We also found that TGase is an abundant protein in the hematopoietic tissue (Hpt) cells of crayfish and hence we have studied the possible function of this enzyme in hematopoiesis.

Results

TGase is one of the most abundant proteins in the Hpt and its mRNA expression as well as enzyme activity is very high in the Hpt cells, lesser in the semi-granular hemocytes and very low in the granular cells. In cultured hematopoietic tissues, high activity was present in cells in the centre of the tissue, whereas cells migrating out of the tissue had very low TGase activity. RNAi experiments using dsRNA for TGase completely knocked down the transcript and as a result the cell morphology was changed and the cells started to spread intensely. If astakine, a cytokine directly involved in hematopoiesis, was added the cells started to spread and adopt a morphology similar to that observed after RNAi of TGase. Astakine had no effect on TGase expression, but after a prolonged incubation for one week with this invertebrate cytokine, TGase activity inside and outside the cells was completely lost. Thus it seems as if astakine addition to the Hpt cells and RNAi of TGase in the cell culture will lead to the same results, i.e. loss of TGase activity in the cells and they start to differentiate and spread.

Conclusion

The results of this study suggest that TGase is important for keeping the Hpt cells in an undifferentiated stage inside the hematopoietic tissue and if expression of TGase mRNA is blocked the cells start to differentiate and spread.

This shows a new function for transglutaminase in preventing hematopoietic stem cells from starting to differentiate and migrate into the hemolymph, whereas their proliferation is unaffected. Astakine is also important for the hematopoiesis, since it induces hemocyte synthesis in the Hpt but now we also show that it in some unknown way participates in the differentiation of the Hpt cells.
Pocket Doppler and vascular laboratory equipment yield comparable results for ankle brachial index measurement
Authors: Nicolaï Saskia PA , Kruidenier Lotte M , Rouwet Ellen V , Wetzels-Gulpers Liliane , Rozeman Constantijn AM , Prins Martin H , Teijink Joep AW
Published: October 2008

Background

The ankle brachial index (ABI) is a well-established tool for screening and diagnosis of peripheral arterial disease (PAD). In this study we assessed the validity of ABI determination using a pocket Doppler device compared with automatic vascular laboratory measurement in patients suspected of PAD.

Methods

Consecutive patients with symptoms of PAD referred for ABI measurement between December 2006 and August 2007 were included. Resting ABI was determined with a pocket Doppler, followed by ABI measurement with automatic vascular laboratory equipment, performed by an experienced vascular technician. The leg with the lowest ABI was used for analysis.

Results

From 99 patients the mean resting ABI was 0.80 measured with the pocket Doppler and 0.85 measured with vascular laboratory equipment. A Bland-Altman plot demonstrated great correspondence between the two methods. The mean difference between the two methods was 0.05 (P < .001). Multivariate linear regression analysis showed no dependency of the difference on either the average measured ABI or affected or unaffected leg.

Conclusion

Since the small, albeit statistically significant, difference between the two methods is not clinically relevant, our study demonstrates that ABI measurements with pocket Doppler and vascular laboratory equipment yield comparable results and can replace each other. Results support the use of the pocket Doppler for screening of PAD, allowing initiation of cardiovascular risk factor management in primary care, provided that the equipment operator is experienced.
Screening for type 2 diabetes is feasible, acceptable, but associated with increased short-term anxiety: A randomised controlled trial in British general practice
Authors: Park Paul , Simmons Rebecca K , Prevost A Toby , Griffin Simon J
Published: October 2008

Background

To assess the feasibility and uptake of a diabetes screening programme; to examine the effects of invitation to diabetes screening on anxiety, self-rated health and illness perceptions.

Methods

Randomised controlled trial in two general practices in Cambridgeshire. Individuals aged 40–69 without known diabetes were identified as being at high risk of having undiagnosed type 2 diabetes using patient records and a validated risk score (n = 1,280). 355 individuals were randomised in a 2 to 1 ratio into non-invited (n = 238) and invited (n = 116) groups. A stepwise screening programme confirmed the presence or absence of diabetes. Six weeks after the last contact (either test or invitation), a questionnaire was sent to all participants, including non-attenders and those who were not originally invited. Outcome measures included attendance, anxiety (short-form Spielberger State Anxiety Inventory-STAI), self-rated health and diabetes illness perceptions.

Results

95 people (82% of those invited) attended for the initial capillary blood test. Six individuals were diagnosed with diabetes. Invited participants were more anxious than those not invited (37.6 vs. 34.1 STAI, p-value = 0.015), and those diagnosed with diabetes were considerably more anxious than those classified free of diabetes (46.7 vs. 37.0 STAI, p-value = 0.031). Non-attenders had a higher mean treatment control sub-scale (3.87 vs. 3.56, p-value = 0.016) and a lower mean emotional representation sub-scale (1.81 vs. 2.68, p-value = 0.001) than attenders. No differences in the other five illness perception sub-scales or self-rated health were found.

Conclusion

Screening for type 2 diabetes in primary care is feasible but may be associated with higher levels of short-term anxiety among invited compared with non-invited participants.

Trial registration

ISRCTN99175498
The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors
Authors: Rossi Fiorella , Querido Bianca , Nimmagadda Manideepthi , Cocklin Simon , Navas-Martín Sonia , Martín-García Julio
Published: October 2008

Background

HIV-1 infects macrophages and microglia in the brain and can cause neurological disorders in infected patients. We and others have shown that brain-derived envelope glycoproteins (Env) have lower CD4 dependence and higher avidity for CD4 than those from peripheral isolates, and we have also observed increased fusogenicity and reduced sensitivity to the fusion inhibitor T-1249. Due to the genetic differences between brain and spleen env from one individual throughout gp120 and in gp41's heptad repeat 2 (HR2), we investigated the viral determinants for the phenotypic differences by performing functional studies with chimeric and mutant Env.

Results

Chimeric Env showed that the V1/V2-C2-V3 region in brain's gp120 determines the low CD4 dependence and high avidity for CD4, as well as macrophage tropism and reduced sensitivity to the small molecule BMS-378806. Changes in brain gp41's HR2 region did not contribute to the increased fusogenicity or to the reduced sensitivity to T-1249, since a T-1249-based peptide containing residues found in brain's but not in spleen's HR2 had similar potency than T-1249 and interacted similarly with an immobilized heptad repeat 1-derived peptide in surface plasmon resonance analysis. However, the increased fusogenicity and reduced T-1249 sensitivity of brain and certain chimeric Env mostly correlated with the low CD4 dependence and high avidity for CD4 determined by brain's V1-V3 region. Remarkably, most but not all of these low CD4-dependent, macrophage tropic envelopes glycoproteins also had increased sensitivity to the novel allosteric entry inhibitor HNG-105. The gp120's C2 region asparagine 283 (N283) has been previously associated with macrophage tropism, brain infection, lower CD4 dependence and higher CD4 affinity. Therefore, we introduced the N283T mutation into an env clone from a brain-derived isolate and into a brain tissue-derived env clone, and the T283N change into a spleen-derived env from the same individual; however, we found that their phenotypes were not affected.

Conclusion

We have identified that the V1-V3 region of a brain-derived envelope glycoprotein seems to play a crucial role in determining not only the low CD4 dependence and increased macrophage tropism, but also the augmented fusogenicity and reduced sensitivity to T-1249 and BMS-378806. By contrast, increased sensitivity to HNG-105 mostly correlated with low CD4 dependence and macrophage tropism but was not determined by the presence of the brain's V1-V3 region, confirming that viral determinants of phenotypic changes in brain-derived envelope glycoproteins are likely complex and context-dependent.
The intracellular detection of MIP-1beta enhances the capacity to detect IFN-gamma mediated HIV-1-specific CD8 T-cell responses in a flow cytometric setting providing a sensitive alternative to the ELISPOT
Authors: Kutscher Sarah , Dembek Claudia J , Allgayer Simone , Heltai Silvia , Stadlbauer Birgit , Biswas Priscilla , Nozza Silvia , Tambussi Giuseppe , Bogner Johannes R , Stellbrink Hans J , Goebel Frank D , Lusso Paolo , Tinelli Marco , Poli Guido , Erfle Volker , Pohla Heike , Malnati Mauro , Cosma Antonio
Published: October 2008

Background

T-cell mediated immunity likely plays an important role in controlling HIV-1 infection and progression to AIDS. Several candidate vaccines against HIV-1 aim at stimulating cellular immune responses, either alone or together with the induction of neutralizing antibodies, and assays able to measure CD8 and CD4 T-cell responses need to be implemented. At present, the IFN-γ-based ELISPOT assay is considered the gold standard and it is broadly preferred as primary assay for detection of antigen-specific T-cell responses in vaccine trials. However, in spite of its high sensitivity, the measurement of the sole IFN-γ production provides limited information on the quality of the immune response. On the other hand, the introduction of polychromatic flow-cytometry-based assays such as the intracellular cytokine staining (ICS) strongly improved the capacity to detect several markers on a single cell level.

Results

The cumulative analysis of 275 samples from 31 different HIV-1 infected individuals using an ICS staining procedure optimized by our laboratories revealed that, following antigenic stimulation, IFN-γ producing T-cells were also producing MIP-1β whereas T-cells characterized by the sole production of IFN-γ were rare. Since the analysis of the combination of two functions decreases the background and the measurement of the IFN-γ+ MIP-1β+ T-cells was equivalent to the measurement of the total IFN-γ+ T-cells, we adopted the IFN-γ+ MIP-1β+ data analysis system to evaluate IFN-γ-based, antigen-specific T-cell responses. Comparison of our ICS assay with ELISPOT assays performed in two different experienced laboratories demonstrated that the IFN-γ+ MIP-1β+ data analysis system increased the sensitivity of the ICS up to levels comparable to the sensitivity of the ELISPOT assay.

Conclusion

The IFN-γ+ MIP-1β+ data evaluation system provides a clear advantage for the detection of low magnitude HIV-1-specific responses. These results are important to guide the choice for suitable highly sensitive immune assays and to build reagent panels able to accurately characterize the phenotype and function of responding T-cells. More importantly, the ICS assay can be used as primary assay to evaluate HIV-1-specific responses without losing sensitivity in comparison to the ELISPOT assay.
Iterative reconstruction of a global metabolic model of Acinetobacter baylyi ADP1 using high-throughput growth phenotype and gene essentiality data
Authors: Durot Maxime , Le Fèvre François , de Berardinis Véronique , Kreimeyer Annett , Vallenet David , Combe Cyril , Smidtas Serge , Salanoubat Marcel , Weissenbach Jean , Schachter Vincent
Published: October 2008

Background

Genome-scale metabolic models are powerful tools to study global properties of metabolic networks. They provide a way to integrate various types of biological information in a single framework, providing a structured representation of available knowledge on the metabolism of the respective species.

Results

We reconstructed a constraint-based metabolic model of Acinetobacter baylyi ADP1, a soil bacterium of interest for environmental and biotechnological applications with large-spectrum biodegradation capabilities. Following initial reconstruction from genome annotation and the literature, we iteratively refined the model by comparing its predictions with the results of large-scale experiments: (1) high-throughput growth phenotypes of the wild-type strain on 190 distinct environments, (2) genome-wide gene essentialities from a knockout mutant library, and (3) large-scale growth phenotypes of all mutant strains on 8 minimal media. Out of 1412 predictions, 1262 were initially consistent with our experimental observations. Inconsistencies were systematically examined, leading in 65 cases to model corrections. The predictions of the final version of the model, which included three rounds of refinements, are consistent with the experimental results for (1) 91% of the wild-type growth phenotypes, (2) 94% of the gene essentiality results, and (3) 94% of the mutant growth phenotypes. To facilitate the exploitation of the metabolic model, we provide a web interface allowing online predictions and visualization of results on metabolic maps.

Conclusion

The iterative reconstruction procedure led to significant model improvements, showing that genome-wide mutant phenotypes on several media can significantly facilitate the transition from genome annotation to a high-quality model.
Evaluation of the safety of high-frequency chest wall oscillation (HFCWO) therapy in blunt thoracic trauma patients
Authors: Anderson Casandra A , Palmer Cassandra A , Ney Arthur L , Becker Brian , Schaffel Steven D , Quickel Robert R
Published: October 2008

Background

Airway clearance is frequently needed by patients suffering from blunt chest wall trauma. High Frequency Chest Wall Oscillation (HFCWO) has been shown to be effective in helping to clear secretions from the lungs of patients with cystic fibrosis, bronchiectasis, asthma, primary ciliary dyskinesia, emphysema, COPD, and many others. Chest wall trauma patients are at increased risk for development of pulmonary complications related to airway clearance. These patients frequently have chest tubes, drains, catheters, etc. which could become dislodged during HFCWO. This prospective observational study was conducted to determine if HFCWO treatment, as provided by The Vest™ Airway Clearance System (Hill-Rom, Saint Paul, MN), was safe and well tolerated by these patients.

Methods

Twenty-five blunt thoracic trauma patients were entered into the study. These patients were consented. Each patient was prescribed 2, 15 minute HFCWO treatments per day using The Vest® Airway Clearance System (Hill-Rom, Inc., St Paul, MN). The Vest® system was set to a frequency of 10–12 Hz and a pressure of 2–3 (arbitrary unit). Physiological parameters were measured before, during, and after treatment. Patients were free to refuse or terminate a treatment early for any reason.

Results

No chest tubes, lines, drains or catheters were dislodged as a result of treatment. One patient with flail chest had a chest tube placed after one treatment due to increasing serous effusion. No treatments were missed and continued without further incident. Post treatment survey showed 76% experienced mild or no pain and more productive cough. Thirty days after discharge there were no deaths or hospital re-admissions.

Conclusion

This study suggests that HFCWO treatment is safe for trauma patients with lung and chest wall injuries. These findings support further work to demonstrate the airway clearance benefits of HFCWO treatment.
Acute renal failure and rhabdomyolysis in a patient with infectious mononucleosis: a case report
Authors: Aloizos Stavros , Gourgiotis Stavros , Oikonomou Konstantinos , Stakia Paraskevi
Published: October 2008

We report a very rare case of acute renal failure and rhabdomyolysis in an Intensive Care treated 20-years-old male with upper airway obstruction due to Epstein-Barr infection.

In our opinion this was a manifestation of the very rare and potentially lethal propofol infusion syndrome and not a direct complication of the underlying infection, although renal biopsy was not performed in our patient.
Burkholderia pseudomallei infection in a patient with diabetes presenting with multiple splenic abscesses and abscess in the foot: a case report
Authors: Dhodapkar Rahul , Sujatha S , Sivasangeetha K , Prasanth G , Parija Subhash Chandra
Published: October 2008

Introduction

Melioidosis or infection with Burkholderia pseudomallei presents with protean manifestations. We present a case of melioidosis in a diabetic patient from India. The case is presented to highlight the importance of early microbiologic diagnosis and subsequent institution of appropriate therapy to achieve a better prognosis

Case presentation

A male bachelor around 50 years of age from India presented with low grade fever, bilateral ankle swelling and hypochondrial pain. On examination patient had diabetes and had multiple abscesses in bilateral ankle, knee and splenic region. Microbiologic diagnosis revealed the etiologic agent to be Burkholderia pseudomallei. Patient was managed with iv ceftazidime and surgical excision.

Conclusion

The case report highlights the importance of early identification of etiologic agent. B. pseudomallei identification requires a great deal of clinical suspicion as well as alertness on the part of the medical microbiologist as these isolates are often reported as Pseudomonas spp. Correct identification of the etiologic agent is essential as B pseudomallei requires prolonged antimicrobial therapy for a better clinical outcome.
Involved-Nodal Radiation Therapy As a Component of Combination Therapy for Limited-Stage Hodgkin's Lymphoma: A Question of Field Size
Authors: Campbell Belinda A. , Voss Nick , Pickles Tom , Morris James , Gascoyne Randy D. , Savage Kerry J. , Connors Joseph M.
Published: October 2008

Purpose

Combined-modality therapy is the standard of care for limited-stage Hodgkin's lymphoma (HL). Radiation therapy has evolved from extended-field radiation therapy (EFRT) to involved-field radiation therapy (IFRT), reducing toxicity while maintaining high cure rates. Recent publications recommend a further reduction to involved-nodal radiation therapy (INRT), however, this has not been clinically validated.

Patients and Methods

We identified 325 patients with limited-stage HL, diagnosed between May 1, 1989 and April 1, 2005, and treated with chemotherapy and radiation therapy following era-specific guidelines: EFRT until 1996; IFRT from 1996 to 2001; INRT ≤ 5 cm from 2001 to the present. INRT ≤ 5 cm was defined as the prechemotherapy nodal volume with margins ≤ 5 cm to account for physiological movement, set-up variation, and the limitations of conventional simulation and radiation therapy techniques. Exclusion criteria were age younger than 16, fluorine-18 fluorodeoxyglucose positron emission tomography, non–doxorubicin, bleomycin, vinblastine, and dacarbazine-like chemotherapy, and/or more than four chemotherapy cycles.

Results

At diagnosis, median age was 35 years; 52% male; stage IA 29%; stage IIA 71%. Ninety-five percent of patients received two chemotherapy cycles. The three radiation therapy groups were: EFRT, 39%; IFRT, 30%; and INRT ≤ 5 cm, 31%. Median follow-up of living patients was 80 months. Median time to relapse was 37 months. Twelve relapses occurred: four after EFRT (3%); five after IFRT (5%); and three after INRT ≤ 5 cm (3%; P = .9). No marginal recurrences occurred after INRT ≤ 5 cm. Locoregional relapse (LRR) occurred in five patients: three after EFRT; two with IFRT; and none with INRT ≤ 5 cm. At 5 years, progression-free survival (PFS) was 97%, and overall survival (OS) was 95%. At 10 years, PFS and OS were 95% and 90%, respectively.

Conclusion

Reduction in field size appears to be safe, without an increased risk of LRR in patients receiving INRT ≤ 5 cm.
Population-Based Analysis of Incidence and Outcome of Transformed Non-Hodgkin's Lymphoma
Authors: Al-Tourah Abdulwahab J. , Gill Karamjit K. , Chhanabhai Mukesh , Hoskins Paul J. , Klasa Richard J. , Savage Kerry J. , Sehn Laurie H. , Shenkier Tamara N. , Gascoyne Randy D. , Connors Joseph M.
Published: October 2008

Purpose

To assess the incidence and predictive factors for development of transformed lymphoma in a population-based series of patients with follicular lymphoma (FL).

Patients and Methods

The Lymphoid Cancer Database was used to identify patients with FL diagnosed and treated in the province of British Columbia, Canada. Transformed lymphoma was defined as the development of aggressive non-Hodgkin's lymphoma (NHL) in patients with FL. Factors present at the time of initial diagnosis of indolent NHL and at transformation were analyzed for their impact on risk of transformation and subsequent outcome.

Results

Between 1986 and 2001, 600 patients with newly diagnosed FL met the inclusion criteria. With a median follow-up of 109 months (range, 10 to 244), 170 (28%) developed transformation, 107 (63%) based on biopsy confirmation. The annual risk of transformation was 3% continuously through 15 years. A multivariate analysis of clinical factors at diagnosis identified advanced stage as the only predictor of future transformation. The median post-transformation survival was 1.7 years. The 5-year survival was superior for patients with limited extent transformation compared with those with advanced cases (66% v 19%, P < .0001). Patients with transformation based on clinical versus histological criteria had an identical median survival of 1.8 years (P = .2).

Conclusion

The annual risk of transformation of FL is 3% continuing without plateau beyond 15 years. Advanced stage at diagnosis is predictive of future transformation. Clinically diagnosed transformation has an equal impact on outcome as biopsy proven transformation.
Immunoembolization of Malignant Liver Tumors, Including Uveal Melanoma, Using Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Sato Takami , Eschelman David J. , Gonsalves Carin F. , Terai Mizue , Chervoneva Inna , McCue Peter A. , Shields Jerry A. , Shields Carol L. , Yamamoto Akira , Berd David , Mastrangelo Michael J. , Sullivan Kevin L.
Published: October 2008

Purpose

We conducted a phase I study to investigate the feasibility and safety of immunoembolization with granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostim) for malignant liver tumors, predominantly hepatic metastases from patients with primary uveal melanoma.

Patients and Methods

Thirty-nine patients with surgically unresectable malignant liver tumors, including 34 patients with primary uveal melanoma, were enrolled. Hepatic artery embolization accompanied an infusion of dose-escalated GM-CSF (25 to 2,000 μg) given every 4 weeks. Primary end points included dose-limiting toxicity and maximum tolerated dose (MTD). Patients who completed two cycles of treatments were monitored for hepatic antitumor response. Survival rates of patients were also monitored.

Results

MTD was not reached up to the dose level of 2,000 μg, and there were no treatment-related deaths. Thirty-one assessable patients with uveal melanoma demonstrated two complete responses, eight partial responses, and 10 occurrences of stable disease in their hepatic metastases. The median overall survival of intent-to-treat patients who had metastatic uveal melanoma was 14.4 months. Multivariate analyses indicated that female sex, high doses of GM-CSF (≥ 1,500 μg), and regression of hepatic metastases (complete and partial responses) were correlated to longer overall survival. Moreover, high doses of GM-CSF were associated with prolonged progression-free survival in extrahepatic sites.

Conclusion

Immunoembolization with GM-CSF is safe and feasible in patients with hepatic metastasis from primary uveal melanoma. Encouraging preliminary efficacy and safety results warrant additional clinical study in metastatic uveal melanoma.
Prevalence of Lymphedema in Women With Breast Cancer 5 Years After Sentinel Lymph Node Biopsy or Axillary Dissection: Objective Measurements
Authors: McLaughlin Sarah A. , Wright Mary J. , Morris Katherine T. , Giron Gladys L. , Sampson Michelle R. , Brockway Julia P. , Hurley Karen E. , Riedel Elyn R. , Van Zee Kimberly J.
Published: October 2008

Purpose

Sentinel lymph node biopsy was adopted for the staging of the axilla with the assumption that it would reduce the risk of lymphedema in women with breast cancer. The aim of this study was to determine the long-term prevalence of lymphedema after SLN biopsy (SLNB) alone and after SLNB followed by axillary lymph node dissection (SLNB/ALND).

Patients and Methods

At median follow-up of 5 years, lymphedema was assessed in 936 women with clinically node-negative breast cancer who underwent SLNB alone or SLNB/ALND. Standardized ipsilateral and contralateral measurements at baseline and follow-up were used to determine change in ipsilateral upper extremity circumference and to control for baseline asymmetry and weight change. Associations between lymphedema and potential risk factors were examined.

Results

Of the 936 women, 600 women (64%) underwent SLNB alone and 336 women (36%) underwent SLNB/ALND. Patients having SLNB alone were older than those having SLNB/ALND (56 v 52 years; P < .0001). Baseline body mass index (BMI) was similar in both groups. Arm circumference measurements documented lymphedema in 5% of SLNB alone patients, compared with 16% of SLNB/ALND patients (P < .0001). Risk factors associated with measured lymphedema were greater body weight (P < .0001), higher BMI (P < .0001), and infection (P < .0001) or injury (P = .02) in the ipsilateral arm since surgery.

Conclusion

When compared with SLNB/ALND, SLNB alone results in a significantly lower rate of lymphedema 5 years postoperatively. However, even after SLNB alone, there remains a clinically relevant risk of lymphedema. Higher body weight, infection, and injury are significant risk factors for developing lymphedema.
Anti–Cytotoxic T-Lymphocyte Antigen-4 Antibody: The First in an Emerging Class of Immunomodulatory Antibodies for Cancer Treatment
Authors: Fong Lawrence , Small Eric J.
Published: October 2008

Purpose

To evaluate the emerging role of immunomodulatory antibodies in cancer treatment. Antibodies (ipilimumab and tremelimumab) targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), an inhibitory molecule on T cells, represent the vanguard of these new drugs.

Design

We performed a systematic review of the clinical studies examining the clinical activity of anti–CTLA-4 antibodies. We also review the potential mechanisms and toxicities associated with these treatments.

Results

Clinical activity with anti–CTLA-4 monoclonal antibodies (mAbs) has paved the way for additional T-cell immunomodulatory monoclonal antibody (mAb) approaches for the treatment of cancer to be investigated. Because anti–CTLA-4 mAbs target the immune system and not the tumor, they may provide significant potential advantages over traditional antitumor mAbs, chemotherapies, and immunotherapies (ie, vaccines and cytokines). Other antibodies, such as CD137 agonists, CD40 agonists, and PD-1 antagonists, are currently in various stages of preclinical and clinical development.

Conclusion

Available clinical data suggest that anti–CTLA-4 mAbs are very different from traditional mAbs, chemotherapies, and immunotherapies in terms of patterns of response, duration of response, and adverse event profile. Ongoing clinical studies aim to establish the efficacy and safety of anti–CTLA-4 mAbs as monotherapy or in combination with other drugs for the treatment of metastatic melanoma and a variety of other cancer types.
Ontogenetic changes in the structural stiffness of the tailstock of bottlenose dolphins (Tursiops truncatus)
Authors: Etnier S. A. , McLellan W. A. , Blum J. , Pabst D. A.
Published: October 2008

Late-term fetal bottlenose dolphins (Tursiops truncatus) are bent ventrolaterally en utero, requiring extreme flexibility of the axial skeleton and associated soft tissues. At birth, neonatal dolphins must immediately swim to the surface to breath, yet the dorsoventral oscillations used during locomotion may be compromised by the lateral flexibility evident in the fetus. The unique fetal position of dolphins, coupled with their need to swim at birth, places conflicting mechanical demands on the tailstock. Our previous research demonstrated that neonatal dolphins possess laterally placed, axial muscles that are functionally specialized to actively maintain the straightened posture of the tailstock. Here, we investigated the development of passive lateral stability in the tailstock of bottlenose dolphins by performing whole-body bending tests on an ontogenetic series of stranded dolphin specimens (N=15), including fetuses, neonates and juveniles (total length 58–171 cm). Structural stiffness increased,while overall body curvature decreased, with increasing body length. Scaling analyses suggest that increased structural stiffness is due to increases in size and probably changes in the passive material properties of the tailstock through ontogeny. The neutral zone was approximately constant with increasing size, while the relative neutral zone (neutral zone/total length) decreased. The lateral stability of the tailstock appears to be controlled by a combination of active and passive systems and the role of these systems varies through ontogeny. While neonates use active, muscular mechanisms to limit lateral deformations of the tailstock, the stability of the maturing tailstock is due primarily to its passive tissue properties.