bluuebunny/crossref_metadata_2025 huggingface dataset:
ebTrack: an environmental bioinformatics system built upon ArrayTrack™
Authors: Chen Minjun , Martin Jackson , Fang Hong , Isukapalli Sastry , Georgopoulos Panos G , Welsh William J , Tong Weida
Published: June 2009

ebTrack is being developed as an integrated bioinformatics system for environmental research and analysis by addressing the issues of integration, curation, management, first level analysis and interpretation of environmental and toxicological data from diverse sources. It is based on enhancements to the US FDA developed ArrayTrack™ system through additional analysis modules for gene expression data as well as through incorporation and linkages to modules for analysis of proteomic and metabonomic datasets that include tandem mass spectra. ebTrack uses a client-server architecture with the free and open source PostgreSQL as its database engine, and java tools for user interface, analysis, visualization, and web-based deployment. Several predictive tools that are critical for environmental health research are currently supported in ebTrack, including Significance Analysis of Microarray (SAM). Furthermore, new tools are under continuous integration, and interfaces to environmental health risk analysis tools are being developed in order to make ebTrack widely usable. These health risk analysis tools include the Modeling ENvironment for TOtal Risk studies (MENTOR) for source-to-dose exposure modeling and the DOse Response Information ANalysis system (DORIAN) for health outcome modeling. The design of ebTrack is presented in detail and steps involved in its application are summarized through an illustrative application.
Oncolytic adenovirus mediated Survivin knockdown by RNA interference suppresses human colorectal carcinoma growth in vitro and in vivo
Authors: Shen Wei , Wang Chun-Yi , Wang Xue-Hu , Fu Zhong-Xue
Published: June 2009

Background

Colorectal cancer is a one of the most common alimentary malignancies. Survivin has been proved by many studies to be an ideal target for cancer gene therapy because of its strong anti-apoptotic effect. The reduction of Survivin expression by means of chemically synthesized small interfering RNA or small hairpin RNA expressed from plasmid and resulted growth inhibition of cancer cells had been proved by many studies including ours, but the transfection efficiency was not encouraging. So for the first time we constructed the Survivin shRNA into an oncolytic adenovirus, tested its effects on colorectal cancer cell lines and nude mice xenograft model.

Methods

In this study, we constructed an oncolytic adenovirus with a Survivin targeted small hairpin RNA and a reporter gene (ZD55-Sur-EGFP). The expression of Survivin mRNA and protein were analyzed by RT-PCR and western blot. The cell growth and apoptosis were tested by in vitro cytopathic assay, MTT assay and flow cytometry respectively. The effect of the constructed virus on xenograft model was evaluated by tumor volume and western blot analysis.

Results

ZD55-Sur-EGFP replicated in cancer cells specifically, reduced the expression of Survivin mRNA and protein expression effectively (P < 0.0001), induced cancer cell apoptosis and inhibited SW480 cell growth both in vitro and in vivo significantly.

Conclusion

We conclude Survivin RNA interference combining with oncolytic adenovirus virotherapy to be a promising treatment for colorectal cancer.
Polymorphisms of TGFB1 and VEGF genes and survival of patients with gastric cancer
Authors: Guan Xiaoxiang , Zhao Hui , Niu Jiangong , Tan Dongfeng , Ajani Jaffer A , Wei Qingyi
Published: June 2009

Background

SomeTGFB1andVEGFpolymorphisms are believed to be functional. Given that these genes are involved in tumor growth and progression including angiogenesis, dissemination, and invasiveness, we hypothesized that these polymorphisms would be associated with survival in patients with gastric cancer.

Methods

We genotypedTGFB1-509 C>T, +1869 T>C, and +915 G>C andVEGF-1498T>C, -634G>C, and +936C>T in 167 patients with gastric cancer. Using the Kaplan and Meier method, log-rank tests, and Cox proportional hazard models, we evaluated associations amongTGFB1andVEGFvariants with overall, 1-year, and 2-year survival rates.

Results

Although there were no significant differences in overall survival rates among all polymorphisms tested, patients withTGFB1+915CG and CC genotypes had a poorer 2-year survival (adjusted hazard ratio (HR), 3.06; 95% confidence interval (CI), 1.09–8.62;P= 0.034) than patients with the GG genotype had. In addition, patients heterozygous forVEGF-634CG also had a poorer 1-year survival (adjusted HR, 2.08; 95% CI, 1.03–4.22;P= 0.042) than patients with the -634GG genotype.

Conclusion

Our study suggested thatTGFB1+915CG/CC andVEGF-634CG genotypes may be associated with short-term survival in gastric cancer patients. However, larger studies are needed to verify these findings.
Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia
Authors: Lequerré Thierry , Bansard Carine , Vittecoq Olivier , Derambure Céline , Hiron Martine , Daveau Maryvonne , Tron François , Ayral Xavier , Biga Norman , Auquit-Auckbur Isabelle , Chiocchia Gilles , Le Loët Xavier , Salier Jean-Philippe
Published: June 2009

Introduction

Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia.

Methods

Synovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of early, LS RA and healthy synovia were linked to the biological processes involved in each situation.

Results

Three combinations of 719, 116 and 52 transcripts discriminated, respectively, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA.

Conclusions

Early and LS RA have distinct molecular signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment.
Myeloid dendritic cells correlate with clinical response whereas plasmacytoid dendritic cells impact autoantibody development in rheumatoid arthritis patients treated with infliximab
Authors: Richez Christophe , Schaeverbeke Thierry , Dumoulin Chantal , Dehais Joël , Moreau Jean-François , Blanco Patrick
Published: June 2009

Introduction

The objective of our study was to identify the significance of the subtypes of dendritic cell (DC), specifically myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), in rheumatoid arthritis (RA) pathogenesis through their longitudinal follow-up in patients receiving infliximab.

Methods

Circulating mDC and pDC levels were evaluated by flow cytometry in RA patients (n = 61) and healthy volunteers (n = 30). In RA patients, these levels were measured before and during infliximab therapy. Their counts were correlated to RA disease activity markers and anti-nuclear antibody occurrence. IFNα production was measured by ELISA in serum of RA patients and, in vitro, in supernatant of peripheral blood mononuclear cells stimulated by influenza virus in the presence or absence of infliximab. Statistical evaluations were based on Mann–Whitney tests or Wilcoxon's signed-rank tests.

Results

RA patients with active disease were characterized by a baseline decrease in both circulating pDCs and mDCs. Disease activity markers inversely correlated only with mDC level. This level increased in RA patients responsive to infliximab therapy, to reach the level observed in controls. Conversely, anti-nuclear antibody appearance during infliximab therapy correlated inversely with pDC level and was associated with increased serum IFNα level and circulating plasma cells number. In vitro studies revealed that infliximab kept pDCs in an IFNα secreting state upon viral stimulation allowing differentiation of B cells into anti-nuclear antibody-secreting plasma cells.

Conclusions

This study reveals two distinct roles for pDC and mDC in RA. Circulating mDCs mainly contribute to RA activity, whereas pDCs seem to be involved in appearance of anti-nuclear antibodies under infliximab therapy through the ability of this drug to keep pDCs in an IFNα secreting state.
Targeting inhibitor of apoptosis proteins in combination with ErbB antagonists in breast cancer
Authors: Foster Fiona M , Owens Thomas W , Tanianis-Hughes Jolanta , Clarke Robert B , Brennan Keith , Bundred Nigel J , Streuli Charles H
Published: June 2009

Introduction

Inhibitor of apoptosis (IAPs) proteins are a family of proteins that can block apoptosis in normal cells and have been suggested to cause resistance to apoptosis in cancer. Overexpression of oncogenic receptor tyrosine kinases is common in breast cancer; in particular 20% of all cases show elevated Her2. Despite clinical success with the use of targeted therapies, such as Trastuzumab, only up to 35% of Her2-positive patients initially respond. We reasoned that IAP-mediated apoptosis resistance might contribute to this insensitivity to receptor tyrosine kinase therapy, in particular ErbB antagonists. Here we examine the levels of IAPs in breast cancer and evaluate whether targeting IAPs can enhance apoptosis in response to growth factor receptor antagonists and TRAIL.

Methods

IAP levels were examined in a breast cancer cell line panel and in patient samples. IAPs were inhibited using siRNA or cell permeable mimetics of endogenous inhibitors. Cells were then exposed to TRAIL, Trastuzumab, Lapatinib, or Gefitinib for 48 hours. Examining nuclear morphology and staining for cleaved caspase 3 was used to score apoptosis. Proliferation was examined by Ki67 staining.

Results

Four members of the IAP family, Survivin, XIAP, cIAP1 and cIAP2, were all expressed to varying extents in breast cancer cell lines or tumours. MDAMB468, BT474 and BT20 cells all expressed XIAP to varying extents. Depleting the cells of XIAP overcame the intrinsic resistance of BT20 and MDAMB468 cells to TRAIL. Moreover, siRNA-based depletion of XIAP or use of a Smac mimetic to target multiple IAPs increased apoptosis in response to the ErbB antagonists, Trastuzumab, Lapatinib or Gefitinib in Her2-overexpressing BT474 cells, or Gefitinib in EGFR-overexpressing MDAMB468 cells.

Conclusions

The novel findings of this study are that multiple IAPs are concomitantly expressed in breast cancers, and that, in combination with clinically relevant Her2 treatments, IAP antagonists promote apoptosis and reduce the cell turnover index of breast cancers. We also show that combination therapy of IAP antagonists with some pro-apoptotic agents (for example, TRAIL) enhances apoptosis of breast cancer cells. In some cases (for example, MDAMB468 cells), the enhanced apoptosis is profound.
The role of YY1 in reduced HP1α gene expression in invasive human breast cancer cells
Authors: Lieberthal Jason G , Kaminsky Marissa , Parkhurst Christopher N , Tanese Naoko
Published: June 2009

Introduction

Heterochromatin protein 1 (HP1) associates with chromatin by binding to histone H3 and contributes to gene silencing. There are three isoforms of HP1 in mammals: HP1α, β, and γ. Studies have shown that the level of HP1α is reduced in invasive human breast cancer cell lines such as MDA-MB-231 and HS578T compared with non-invasive cell lines such as MCF7 and T47D. It is hypothesized that reduced HP1α expression may lead to impaired epigenetic silencing of genes that are important in the acquisition of an invasive phenotype. We set out to determine whether reduced expression of HP1α in invasive breast cancer cell lines occurs at the level of transcription.

Methods

We used transient transfection assays to investigate the mechanism of differential transcriptional activity of the human HP1α gene promoter in different cell lines. Mutational analysis of putative transcription factor binding sites in an HP1α gene reporter construct was performed to identify transcription factors responsible for the differential activity. SiRNA-mediated knockdown and chromatin immunoprecipitation experiments were performed to determine the role of a specific transcription factor in regulating the HP1α gene.

Results

The transcription factor yin yang 1 (YY1) was found to play a role in differential transcriptional activity of the HP1α gene. Examination of the YY1 protein and mRNA levels revealed that both were reduced in the invasive cell line HS578T compared with MCF7 cells. YY1 knockdown in MCF7 cells resulted in a decreased level of HP1α mRNA, indicating that YY1 positively regulates HP1α expression. Chromatin immunoprecipitation experiments verified YY1 occupancy at the HP1α gene promoter in MCF7 cells but not HS578T cells. Overexpression of YY1 in HS578T cells decreased cell migration in a manner independent of HP1α overexpression.

Conclusions

Our data suggests that a reduction of YY1 expression in breast cancer cells could contribute to the acquisition of an invasive phenotype through increased cell migration as well as by reduced expression of HP1α.
Prevalence of endotoxemia after surgery and its association with ICU length of stay
Authors: Valenza Franco , Fagnani Lorella , Coppola Silvia , Froio Sara , Sacconi Francesca , Tedesco Cecilia , Maffioletti Micol , Pizzocri Marta , Salice Valentina , Ranzi Maria Luisa , Marenghi Cristina , Gattinoni Luciano
Published: June 2009

Introduction

The aim of this observational study was to investigate the prevalence of endotoxemia after surgery and its association with ICU length of stay.

Methods

102 patients admitted to a university ICU after surgery were recruited. Within four hours of admission, functional data were collected and APACHE II severity score calculated. Arterial blood samples were taken and endotoxemia was measured by chemiluminescence (Endotoxin Activity (EA)). Patients were stratified according to their endotoxin levels (low, intermediate and high) and according to their surgical procedures. Differences between endotoxin levels were assessed by ANOVA, accepting P < 0.05 as significant. Data are expressed as mean ± SD.

Results

EA levels were low in 68 (66%) patients, intermediate in 17 (17%) and high in 17 (17%). Age (61 ± 17 years) and APACHE II score 8.3 ± 3.7 (P = 0.542) were not significantly different in the three EA groups. Functional parameters on admission were similar between EA groups: white blood cells 11093 ± 4605 cells/mm3 (P = 0.385), heart rate 76 ± 16 bpm (P = 0.898), mean arterial pressure 88.8 ± 13.6 mmHg (P = 0.576), lactate 1.18 ± 0.77 mmol/L (P = 0.370), PaO2/FiO2 383 ± 109 mmHg (P = 0.474). Patients with high levels of EA were characterized by longer length of stay in the ICU: 1.9 ± 3.0 days in the low EA group, 1.8 ± 1.4 days in intermediate and 5.2 ± 7.8 days in high group (P = 0.038).

Conclusions

17% of our patients were characterized by high levels of endotoxemia as assessed by EA assay, despite their low level of complexity on admission. High levels of endotoxin were associated with a longer ICU length of stay.
Protein disulfide isomerase (PDI) associates with NADPH oxidase and is required for phagocytosis of Leishmania chagasi promastigotes by macrophages
Authors: Santos Célio X C , Stolf Beatriz S , Takemoto Paulo V A , Amanso Angélica M , Lopes Lucia R , Souza Edna B , Goto Hiro , Laurindo Francisco R M
Published: June 2009

Macrophage infection by Leishmania parasite is prone to oxidative stress in a redox-regulated way by protein disulfide isomerase which is closely associated to NADPH oxidase activity.

PDI, a redox chaperone, is involved in host cell uptake of bacteria/viruses, phagosome formation, and vascular NADPH oxidase regulation. PDI involvement in phagocyte infection by parasites has been poorly explored. Here, we investigated the role of PDI in in vitro infection of J774 macrophages by amastigote and promastigote forms of the protozoan Leishmania chagasi and assessed whether PDI associates with the macrophage NADPH oxidase complex. Promastigote but not amastigote phagocytosis was inhibited significantly by macrophage incubation with thiol/PDI inhibitors DTNB, bacitracin, phenylarsine oxide, and neutralizing PDI antibody in a parasite redox-dependent way. Binding assays indicate that PDI preferentially mediates parasite internalization. Bref-A, an ER-Golgi-disrupting agent, prevented PDI concentration in an enriched macrophage membrane fraction and promoted a significant decrease in infection. Promastigote phagocytosis was increased further by macrophage overexpression of wild-type PDI and decreased upon transfection with an antisense PDI plasmid or PDI siRNA. At later stages of infection, PDI physically interacted with L. chagasi, as revealed by immunoprecipitation data. Promastigote uptake was inhibited consistently by macrophage preincubation with catalase. Additionally, loss- or gain-of-function experiments indicated that PMA-driven NADPH oxidase activation correlated directly with PDI expression levels. Close association between PDI and the p22phox NADPH oxidase subunit was shown by confocal colocalization and coimmunoprecipitation. These results provide evidence that PDI not only associates with phagocyte NADPH oxidase but also that PDI is crucial for efficient macrophage infection by L. chagasi.
TLR4-mediated Cox-2 expression increases intestinal ischemia/reperfusion-induced damage
Authors: Moses Tiffany , Wagner Lynn , Fleming Sherry D
Published: June 2009

TLR4 stimulates Cox-2-mediated PGE2 production which is necessary but not sufficient for intestinal ischemia/reperfusion-induced damage and inflammation.

Mesenteric IR induces significant inflammation and immune-mediated mucosal damage. TLR4 is a critical receptor in the induction of the inflammatory response and plays a role in intestinal homeostasis. To determine the role of TLR4 in IR-induced epithelial damage, we performed IR studies using TLR4lps-def and TLR4lps-n mice and analyzed mucosal damage and inflammation. We found that the absence of TLR4 or TLR4-induced signaling attenuated local mucosal damage with significantly decreased cytokine and eicosanoid secretion including PGE2 production. Similar results were seen in MyD88−/− mice. Wild-type mice treated with NS-398 (a Cox-2 inhibitor) not only decreased PGE2 production but also attenuated tissue damage. In contrast, PGE2 was not sufficient to induce damage in the TLR4lps-def mice. Together, these data indicate that TLR4 stimulation of Cox-2 activation of PGE2 production is necessary but not sufficient for intestinal IR-induced damage and inflammation.
The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote inflammation
Authors: Hreggvidsdottir Hulda Sigridur , Östberg Therese , Wähämaa Heidi , Schierbeck Hanna , Aveberger Ann-Charlotte , Klevenvall Lena , Palmblad Karin , Ottosson Lars , Andersson Ulf , Harris Helena Erlandsson
Published: June 2009

A prototypic mechanism for enhancement of inflammation by an endogenous molecule is described.

The nuclear protein HMGB1 has previously been demonstrated to act as an alarmin and to promote inflammation upon extracellular release, yet its mode of action is still not well defined. Access to highly purified HMGB1 preparations from prokaryotic and eukaryotic sources enabled studies of activation of human PBMC or synovial fibroblast cultures in response to HMGB1 alone or after binding to cofactors. HMGB1 on its own could not induce detectable IL-6 production. However, strong enhancing effects on induction of proinflammatory cytokine production occurred when the protein associated with each of the separate proinflammatory molecules, rhIL-1β, the TLR4 ligand LPS, the TLR9 ligand CpG-ODN, or the TLR1-TLR2 ligand Pam3CSK4. The bioactivities were recorded in cocultures with preformed HMGB1 complexes but not after sequential or simultaneous addition of HMGB1 and the individual ligands. Individual A-box and B-box domains of HMGB1 had the ability to bind LPS and enhance IL-6 production. Heat denaturation of HMGB1 eliminated this enhancement. Cocultures with HMGB1 and other proinflammatory molecules such as TNF, RANKL, or IL-18 did not induce enhancement. HMGB1 thus acts broadly with many but not all immunostimulatory molecules to amplify their activity in a synergistic manner.
The antihypoxia–adenosinergic pathogenesis as a result of collateral damage by overactive immune cells
Authors: Hatfield Stephen , Belikoff Bryan , Lukashev Dmitriy , Sitkovsky Michail , Ohta Akio
Published: June 2009

The consumption of natural A2A adenosine receptor antagonists, such as caffeine, as well as the use of supplemental oxygen during acute inflammation episodes may have undesirable effects.

Here, we attract attention to the possibility of iatrogenic exacerbation of immune–mediated tissue damage as a result of the unintended weakening of the tissue–protecting, hypoxia–adenosinergic pathway. These immunosuppressive, anti–inflammatory pathways play a critical and nonredundant role in the protection of normal tissues from collateral damage during an inflammatory response. We believe that it is the tissue hypoxia associated with inflammatory damage that leads to local inhibition of overactive immune cells by activating A2AR and A2BR and stabilizing HIF–1α. We show in an animal model of acute lung injury that oxygenation (i.e., inspiring supplemental oxygen) reverses tissue hypoxia and exacerbates ongoing inflammatory lung tissue damage. However, little has been done to carefully investigate and prevent this in a clinical setting. Similarly, the consumption of caffeine antagonizes A2ARs, resulting in exacerbation of ongoing acute inflammation. It is suggested that although the elimination of hypoxia–adenosinergic immunosuppression is desirable to improve vaccines, it is important to take into account the unintentional effects of supplemental oxygen and caffeine, which may increase collateral, inflammatory tissue damage.
Assisted traveltime picking of crosshole GPR data
Authors: Giroux Bernard , Bouchedda Abderrezak , Chouteau Michel
Published: June 2009

We introduce two new traveltime picking schemes developed specifically for crosshole ground-penetrating radar (GPR) applications. The main objective is to automate, at least partially, the traveltime picking procedure and to provide first-arrival times that are closer in quality to those of manual picking approaches. The first scheme is an adaptation of a method based on cross-correlation of radar traces collated in gathers according to their associated transmitter-receiver angle. A detector is added to isolate the first cycle of the radar wave and to suppress secon-dary arrivals that might be mistaken for first arrivals. To improve the accuracy of the arrival times obtained from the crosscorrelation lags, a time-rescaling scheme is implemented to resize the radar wavelets to a common time-window length. The second method is based on the Akaike information criterion(AIC) and continuous wavelet transform (CWT). It is not tied to the restrictive criterion of waveform similarity that underlies crosscorrelation approaches, which is not guaranteed for traces sorted in common ray-angle gathers. It has the advantage of being automated fully. Performances of the new algorithms are tested with synthetic and real data. In all tests, the approach that adds first-cycle isolation to the original crosscorrelation scheme improves the results. In contrast, the time-rescaling approach brings limited benefits, except when strong dispersion is present in the data. In addition, the performance of crosscorrelation picking schemes degrades for data sets with disparate waveforms despite the high signal-to-noise ratio of the data. In general, the AIC-CWT approach is more versatile and performs well on all data sets. Only with data showing low signal-to-noise ratios is the AIC-CWT superseded by the modified crosscorrelation picker.
Multiridge analysis of potential fields: Geometric method and reduced Euler deconvolution
Authors: Fedi Maurizio , Florio Giovanni , Quarta Tatiana A.
Published: June 2009

A new method based on 3D multiridge analysis of potential fields assumes a 3D subset in the harmonic region and studies the behavior of potential field ridges, which are built by joining extreme points of the analyzed field computed at different altitudes. Three types of ridges are formed by searching for the zeros of the first horizontal and first vertical derivatives of the potential field (types I and II, respectively) and the zeros of the potential field itself (type III). This method uses a redundant set of ridges, called a multiridge set, to determine source type and location. For homogeneous potential fields generated by simple sources, all of the ridges are straight lines converging to the source position. This method analyzes the multiridges by using a geometric criterion to find the source position at the intersection of the multiridge set and by solving the three reduced Euler equations associated with ridge types I, II, and III. The reduced Euler type I and II equations are used to obtain the structural index and the vertical and horizontal source positions; equation type III estimates the horizontal and vertical source positions. Tests on synthetic as well as the Bishop model field yield good results even with noise-corrupted data. Results obtained using magnetic data collected over the wreck of a military ship in the Tyrrhenian Sea successfully determine its vertical and horizontal positions and the structural index.
Thin-bed prestack spectral inversion
Authors: Rubino J. Germán , Velis Danilo
Published: June 2009

Prestack seismic data has been used in a new method to fully determine thin-bed properties, including the estimation of its thickness, P- and S-wave velocities, and density. The approach requires neither phase information nor normal-moveout (NMO) corrections, and assumes that the prestack seismic response of the thin layer can be isolated using an offset-dependent time window. We obtained the amplitude-versus-angle (AVA) response of the thin bed considering converted P-waves, S-waves, and all the associated multiples. We carried out the estimation of the thin-bed parameters in the frequency (amplitude spectrum) domain using simulated annealing. In contrast to using zero-offset data, the use of AVA data contributes to increase the robustness of this inverse problem under noisy conditions, as well as to significantly reduce its inherent nonuniqueness. To further reduce the nonuniqueness, and as a means to incorporate a priori geologic or geophysical information (e.g., well-log data), we imposed appropriate bounding constraints to the parameters of the media lying above and below the thin bed, which need not be known accurately. We tested the method by inverting noisy synthetic gathers corresponding to simple wedge models. In addition, we stochastically estimated the uncertainty of the solutions by inverting different data sets that share the same model parameters but are contaminated with different noise realizations. The results suggest that thin beds can be characterized fully with a moderate to high degree of confidence below tuning, even when using an approximate wavelet spectrum.
Cognitive–behavioural therapy as an adjunctive treatment in chronic physical illness
Authors: Halford Judith , Brown Tom
Published: June 2009

Chronic physical illness is a significant risk factor for psychological symptoms, psychiatric disorder and suicide. Properly targeted cognitive–behavioural therapy (CBT) can improve outcomes for people with chronic physical illnesses. This article looks at practical aspects of the use of CBT as part of the overall medical and psychiatric management of chronic physical illness.
Why psychiatrists should watch films (or What has cinema ever done for psychiatry?)
Authors: Byrne Peter
Published: June 2009

Cinema is at once a powerful medium, art, entertainment, an industry and an instrument of social change; psychiatrists should neither ignore nor censor it. Representations of psychiatrists are mixed but psychiatric treatments are rarely portrayed positively. In this article, five rules of movie psychiatry are proposed, supported by over 370 films. Commercial and artistic pressures reduce verisimilitude in fictional and factual films, although many are useful to advance understanding of phenomenology, shared history and social contexts in psychiatry. Acknowledging some negative representations, three areas are explored where cinema gets it mostly right: addictions, bereavement and personality disorder. Although there are excellent representations of psychosis on film, film-makers have more often portrayed it violently – ultimately demonising people as psychokillers in more than 100 films cited. When people with mental illness are stigmatised through stereotypes, examining unwelcome depictions can uncover important truths. Psychiatrists' engagement with film will ensure professional and artistic gains.
Major depression: revisiting the concept and diagnosis
Authors: Jacob K. S.
Published: June 2009

The classification of depression has been debated for decades. The introduction of operational criteria and the category of major depression were significant advances in the 1970s. However, the validity of the major depression category is controversial. The article highlights the limitations of using severity criteria and cross-sectional evaluation to diagnose depression. It recommends the classic typologies (melancholia, dysthymia and adjustment disorder) for clinical presentations of depression, highlighting the need to use longitudinal clinical patterns and context for diagnosis. Major depression owes its success to its loose definition, to the subordinate status of adjustment disorders and dysthymia and to the mechanistic application of the diagnostic hierarchy and criteria. There is a need to focus more on the context of depression (stress, coping and support) and to reduce the medicalisation of distress.
Dementia in the acute hospital: prospective cohort study of
prevalence and mortality
Authors: Sampson Elizabeth L. , Blanchard Martin R. , Jones Louise , Tookman Adrian , King Michael
Published: June 2009

Background

Increasing numbers of people will die with dementia, many in the acute
hospital. It is often not perceived to be a life-limiting illness.

Aims

To investigate the prevalence of dementia in older people undergoing
emergency medical admission and its effect on outcomes.

Method

Longitudinal cohort study of 617 people (aged over 70). The main outcome
was mortality risk during admission.

Results

Of the cohort, 42.4% had dementia (only half diagnosed prior to
admission). In men aged 70–79, dementia prevalence was 16.4%, rising to
48.8% of those over 90. In women, 29.6% aged 70–79 had dementia, rising
to 75.0% aged over 90. Urinary tract infection or pneumonia was the
principal cause of admission in 41.3% of the people with dementia. These
individuals had markedly higher mortality; 24.0% of those with severe
cognitive impairment died during admission (adjusted mortality risk 4.02,
95% CI 2.24–7.36).

Conclusions

The rising prevalence of dementia will have an impact on acute hospitals.
Extra resources will be required for intermediate and palliative care and
mental health liaison services.
Local implementation of the crisis model: the Buckinghamshire community acute service
Authors: Allen Danny , Blaylock Wendy , Mieczkowski Stefan
Published: June 2009

Aims and Method

Buckinghamshire crisis and home treatment team was struggling to meet its commissioned care episodes and found itself detached from community mental health teams (CMHTs) and acute day hospitals. An operations management consultant, using ‘lean’ principles developed in industry, worked alongside staff to redesign the service.

Results

Improvements in staff capacity and ability contributed to more care episodes and reduced ward-stay times, compensating for the impact of a ward closure. Re-examination of individuals needs through case-review led to the development of ‘patient typing’, facilitating clear care pathways according to need. Finally, two proven modalities of community-based service were fused together.

Clinical Implications

Placing value to patients, carers and referrers ahead of old demarcations and practices has enabled a more flexible and responsive service to develop and grow.
NHS links: achievements of a scheme between one London mental health trust and Uganda
Authors: Baillie Dave , Boardman Jed , Onen Tom , Hall Cerdic , Gedde Maia , Parry Eldryd
Published: June 2009

This paper describes a link between a mental health trust (the East London Foundation Trust (ELFT)) in the UK and mental health services in Uganda which has developed since 2004. the aim of the link was to help support the development of mental health services in Uganda by establishing an educational partnership. During the first 3 years, nine staff from ELFT and nine staff from Butabika, from a variety of disciplines, have made short-term exchange visits. Evaluation of the link has demonstrated that benefits have been experienced in both London and Uganda. Such links can provide one way of strategically supporting and strengthening existing health services in low- and middle-income countries.
Substance use disorders and psychological trauma
Authors: Shora Shaheen , Stone Elizabeth , Fletcher Keron
Published: June 2009

Aims and Method

The Impact of Events Scale was administered to 104 in-patients detoxing from alcohol or opiates to determine the prevalence of psychological trauma, the severity of its symptoms and the types of trauma responsible for symptoms.

Results

Out of the 104 in-patients undergoing detoxification, 75 had symptoms of psychological trauma; in 60 patients the symptoms were in the treatable range. Patients with alcohol-dependence were more severely affected. ‘Life events’ traumatised a higher proportion of individuals than ‘traumatic events’.

Clinical Implications

Psychological trauma requiring treatment is commonly found in substance misusers. This is rarely addressed despite the cormorbid disorder running a complicated clinical course. There are conflicting opinions about best practice, but consideration should be given to providing patients with accessible treatments for psychological trauma.
Beyond consultation: the challenge of working with user/survivor and carer groups
Authors: Bracken Pat , Thomas Phil
Published: June 2009

Recent years have seen increased pressures on psychiatrists to work closely with user/survivor and carer groups. We argue that although many groups are happy for this to remain at the level of consultation, there are growing demands from more radical elements of the user/survivor movement for moves towards a more collaborative framework. A number of these groups challenge some of the central assumptions of psychiatry. for productive engagement and collaboration to take place, psychiatry will have to be able to react positively, not defensively, to these challenges. We suggest that this raises questions about how we should think about the nature of science, truth and expertise.
Is research just an optional extra in clinical psychiatry? Invited commentary on … Research as part of the career of a psychiatrist entering clinical practice
Authors: Tyrer Peter
Published: June 2009

A reassessment of the reasons for psychiatrists being reluctant to do research is made. It is suggested that a combination of inspiration and scepticism is required to both be a good researcher as well as a good clinician. These are seldom to be found in one individual but usually can be found if the trainee is prepared to scour. the benefits of success are many, and a long and productive life in clinical practice is likely with a positive attitude to research, not just to keep up with developments in an informed way but to prevent the ossifying process of clinical dogmatism from developing.
Intensity-Modulated Radiation Therapy With or Without Chemotherapy for Nasopharyngeal Carcinoma: Radiation Therapy Oncology Group Phase II Trial 0225
Authors: Lee Nancy , Harris Jonathan , Garden Adam S. , Straube William , Glisson Bonnie , Xia Ping , Bosch Walter , Morrison William H. , Quivey Jeanne , Thorstad Wade , Jones Christopher , Ang K. Kian
Published: June 2009

Purpose

To investigate the feasibility of intensity-modulated radiation therapy (IMRT) with or without chemotherapy, and to assess toxicities, failure patterns, and survivals in patients with nasopharyngeal carcinoma (NPC).

Patients and Methods

Radiation consisted of 70 Gy given to the planning target volumes of primary tumor plus any N+ disease and 59.4 Gy given to subclinical disease, delivered over 33 treatment days. Patients with stage T2b or greater or with N+ disease also received concurrent cisplatin (100 mg/m2) on days 1, 22, and 43 followed by adjuvant cisplatin (80 mg/m2) on day 1; fluorouracil (1,000 mg/m2/d) on days 1 through 4 administered every 4 weeks for three cycles. Tumor, clinical status, and acute/late toxicities were assessed. The primary objective was to test the transportability of IMRT to a multi-institutional setting.

Results

Between February 2003 and November 2005, 68 patients with stages I through IVB NPC (of which 93.8% were WHO types 2 and 3) were enrolled. Prescribed IMRT (target delineation) was given to 83.8%, whereas 64.9% received chemotherapy per protocol. The estimated 2-year local progression-free (PF), regional PF, locoregional PF, and distant metastasis–free rates were 92.6%, 90.8%, 89.3%, and 84.7%, respectively. The estimated 2-year PF and overall survivals were 72.7% and 80.2%, respectively. Acute grade 4 mucositis occurred in 4.4%, and the worst late grade 3 toxicities were as follows: esophagus, 4.7%; mucous membranes, 3.1%; and xerostomia, 3.1%. The rate of grade 2 xerostomia at 1 year from start of IMRT was 13.5%. Only two patients complained of grade 3 xerostomia, and none had grade 4 xerostomia.

Conclusion

It was feasible to transport IMRT with or without chemotherapy in the treatment of NPC to a multi-institutional setting with 90% LRPF rate reproducing excellent reports from single institutions. Minimal grade 3 and lack of grade 4 xerostomia were encouraging.
Postoperative Surveillance Recommendations for Early Stage Colon Cancer Based on Results From the Clinical Outcomes of Surgical Therapy Trial
Authors: Tsikitis Vassiliki L. , Malireddy Kishore , Green Erin A. , Christensen Brent , Whelan Richard , Hyder Jace , Marcello Peter , Larach Sergio , Lauter David , Sargent Daniel J. , Nelson Heidi
Published: June 2009

Purpose

Intensive postoperative surveillance is associated with improved survival and recommended for patients with late stage (stage IIB and III) colon cancer. We hypothesized that stage I and IIA colon cancer patients would experience similar benefits.

Patients and Methods

Secondary analysis of data from the Clinical Outcomes of Surgical Therapy trial was performed by analyzing results according to TNM stage; early (stage I and IIA, 537 patients) and late (stage IIB and III, 254 patients) stage disease. Five-year recurrence rates were higher in patients with late (35.7%) versus early stage disease (9.5%). Early and late stage salvage rates, recurrence patterns and methods of first detection were compared by χ2 test.

Results

Salvage rates for early- and late-stage disease patients with recurrence were the same (35.9% v 37%; P = .9, respectively). Median survival after second surgery after recurrence was 51.2 and 35.8 months for early- and late-stage patients, respectively. Single sites of first recurrence did not significantly differ between early and late stage, but multiple sites of recurrence occurred less often in early-stage patients (3.6% v 28.6%, for early v late, respectively; P < .001). Methods of first detection of recurrence were not significantly different: carcinoembryonic antigen (29.1% v 37.4%), computed tomography scan (23.6% v 26.4%), chest x-ray (7.3% v 12.1%), and colonoscopy (12.7% v 8.8%), for early versus late stage disease, respectively.

Conclusion

Patients with early-stage colon cancer have similar sites of recurrence, and receive similar benefit from postrecurrence therapy as late-stage patients; implementation of surveillance guidelines for early-stage patients is appropriate.
Thinking Afro-Futures: A Preamble to an Epistemic History
Authors: Olaniyan Tejumola
Published: June 2009

Africana thought within the orbit of Western discourses, from the eighteenth century to the 1970s, conceived the place of the black person in the world in essentially “political” terms. That is, it conceived it as the problematic of a dominated and disenfranchised people in a modern world it helped bring into being but whose benefits are controlled and appropriated primarily by Europe and America. This was the catalyst behind the exertions of the voice of the slave and the Pan African Congresses of the early twentieth century to the writings of W. E. B. Du Bois, Kwame Nkrumah, Richard Wright, C. L. R. James, and Eric Williams, to name just a few. The “political” approach, which I exemplify here with the writings of Richard Wright, would subsequently be challenged by a preoccupation with the affirmation of “culture.”
The Dead Zone: Stumbling at the Crossroads of Party Politics, Genocide, and Postracial Racism
Authors: James Joy
Published: June 2009

Examining the parameters of Africana thought with references to the 2008 presidential campaigns that led to the election of Barack Obama as the forty-fourth president of the United States, this essay explores the relationship of black elite leadership and black mass disenfranchisement. It identifies the intersection of these two formations as a “dead zone,” that is, a void in practical and theoretical politics, one that reveals central evasions in conventional discourse given its general inability or unwillingness to critique the simultaneous successes and failures of a multiracial democracy that enables antiblack racism and genocide.
Marx in the Vernacular: Abdel Khaliq Mahgoub and the Riddles of Localizing Leftist Politics in Sudanese Philosophies of Liberation
Authors: Abusharaf Rogaia Mustafa
Published: June 2009

In the thought of the late secretary-general of the Sudanese Communist Party, Abdel Khaliq Mahgoub, the intricacies of culture and politics are deftly interwoven in a thorough ethnographic and philosophical critique of state and society. Mahgoub's wide-ranging writings engaging questions of liberation led him to devote his life to localizing Marxist theory in the Sudanese context. His explication of the tools of translating Marxism challenges absolutist interpretations and applications of a single idea in a cultural context unfavorable to its growth. This essay draws on Mahgoub's impressive intellectual contributions to patterns and processes through which Marxist politics can be mobilized to defy egregious state transgressions of democratic rights. Throughout his work, which is analyzed in this essay, two preoccupations figure prominently: the commitment to creating a public culture that accommodates innovation and renewal in transforming a society shredded by exploitative discriminatory practices, and the struggle for the reinforcement of a vision of liberation more expansive than the one presented in the nationalist discourse, which Mahgoub critiqued as forlorn and unable to produce a coherent vision on political transformation. “Marx in the Vernacular” traces these intellectual and political concerns in Mahgoub's thought and links their pertinence to current issues in Sudanese and African politics. Multiple relevancies of Mahgoub's legacies are elucidated alongside analysis of tradition, humanism, Marxist anthropology, and the nature of the national democratic revolution.
“Our Duty to Conserve”: W. E. B. Du Bois's Philosophy of History in Context
Authors: Bernasconi Robert
Published: June 2009

When restored to its historical context, W. E. B. Du Bois's “The Conservation of Races” emerges less as a contribution to the debate about the legitimacy of the concept of race, which is how it tends to be read today, and more as an intervention in the debate about the impact of so-called miscegenation on the African American population. Du Bois's contribution is situated in relation to the positions held by Frederick Douglass, Edward Blyden, and Alexander Crummell. Particular attention is paid to the way Du Bois and Kelly Miller used the inaugural meeting of the American Negro Academy to respond to Frederick Hoffman's racist study, Race Traits and Tendencies of the American Negro, which in the context of social Darwinism had a dramatic impact on how mixed-race people were seen. Du Bois argued that African Americans should not divide on the basis of degrees of racial purity but unite around their common ideals and a hope for the future in the midst of continuing oppression.
“Thief's Theme”
Authors: Ralph Michael
Published: June 2009

Though voter theft is an American tradition as old as the right to vote, it has not yet become a key focus of scholarship in the field of political science. Thus, this line of inquiry might benefit from a position that is more critical and imaginative than the one professional political scientists tend to develop. This chapter uses hip-hop lyricism to measure how the concept of theft appears in the political philosophy of Malcolm X against the way this strategy for resource redistribution is discussed in the films The Departed and Scarface as a way to enrich political theory. If the concept of theft can be used to track deception in U.S. democracy, certain contemporary forms of lyrical and visual culture might enrich the academic study of politics, since they produce forms of “political distrust” that counteract the presumptions with which scholars in this disciplinary niche tend to proceed.

The looming threat of “theft” ironically reveals its own enchantment with democracy in that it suggests the U.S. system of electoral politics works perfectly well unless momentarily interrupted by rogue politicians, instead of framing duplicity as a problem that plagues this particular form of political representation at a fundamental level. Still, the idea of stolen democracy that surfaces in lyrical and visual culture illuminates a crucial challenge for political theory in its suggestion that, for the past few decades—but even more intensely during the past few elections—the U.S. government has been administered expressly, if not exclusively, by thieves and hustlers.
Not the Moment After, but the Moment Of
Authors: Farred Grant
Published: June 2009

Using the brief (ten-week) rule of Patrice Lumumba in the Congo as an instructive instance for thinking the post-, “Not the Moment After, but the Moment Of” argues that the post- is never the time after but the moment—impossible as it is to understand—of, that is, the moment itself. Grounded in a critique of “postcommunism,” this essay maps Lumumba's transition from bourgeois nationalist—the postcolonial leader—to the communist who did not name himself a communist, the anticolonialist transformed, by the force of history (the failure of the United Nations to protect the sovereignty of the newly independent Congo; the neoimperialist designs of the United States and Belgium; his struggle against the Belgian-sponsored secessionist movement in the copper-rich Katanga province), into a Lenin-like revolutionary. This essay thinks Lumumba both in relation to the African revolutionary tradition (Gamal Abdel Nasser, Julius Nyerere, and Agostinho Neto, among others) and the history of radical socialism (Lenin figures especially prominently in this regard).