bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct genotypic profiles of the two major clades of Mycobacterium africanum
Authors: Vasconcellos Sidra E Gonçalves , Huard Richard C , Niemann Stefan , Kremer Kristin , Santos Adalberto R , Suffys Philip N , Ho John L
Published: March 2010

Background

Mycobacterium tuberculosis is the principal etiologic agent of human tuberculosis (TB) and a member of the M. tuberculosis complex (MTC). Additional MTC species that cause TB in humans and other mammals include Mycobacterium africanum and Mycobacterium bovis. One result of studies interrogating recently identified MTC phylogenetic markers has been the recognition of at least two distinct lineages of M. africanum, known as West African-1 and West African-2.

Methods

We screened a blinded non-random set of MTC strains isolated from TB patients in Ghana (n = 47) for known chromosomal region-of-difference (RD) loci and single nucleotide polymorphisms (SNPs). A MTC PCR-typing panel, single-target standard PCR, multi-primer PCR, PCR-restriction fragment analysis, and sequence analysis of amplified products were among the methods utilized for the comparative evaluation of targets and identification systems. The MTC distributions of novel SNPs were characterized in the both the Ghana collection and two other diverse collections of MTC strains (n = 175 in total).

Results

The utility of various polymorphisms as species-, lineage-, and sublineage-defining phylogenetic markers for M. africanum was determined. Novel SNPs were also identified and found to be specific to either M. africanum West African-1 (Rv1332
523; n = 32) or M. africanum West African-2 (nat
751; n = 27). In the final analysis, a strain identification approach that combined multi-primer PCR targeting of the RD loci RD9, RD10, and RD702 was the most simple, straight-forward, and definitive means of distinguishing the two clades of M. africanum from one another and from other MTC species.

Conclusion

With this study, we have organized a series of consistent phylogenetically-relevant markers for each of the distinct MTC lineages that share the M. africanum designation. A differential distribution of each M. africanum clade in Western Africa is described.
Cholesterol treatment with statins: Who is left out and who makes it to goal?
Authors: Franks Peter , Tancredi Daniel , Winters Paul , Fiscella Kevin
Published: March 2010

Background

Whether patient socio-demographic characteristics (age, sex, race/ethnicity, income, and education) are independently associated with failure to receive indicated statin therapy and/or to achieve low density lipoprotein cholesterol (LDL-C) therapy goals are not known. We examined socio-demographic factors associated with a) eligibility for statin therapy among those not on statins, and b) achievement of statin therapy goals.

Methods

Adults (21-79 years) participating in the United States (US) National Health and Nutrition Examination Surveys, 1999-2006 were studied. Statin eligibility and achievement of target LDL-C was assessed using the US Third Adult Treatment Panel (ATP III) on Treatment of High Cholesterol guidelines.

Results

Among 6,043 participants not taking statins, 10.4% were eligible. Adjusted predictors of statin eligibility among statin non-users were being older, male, poorer, and less educated. Hispanics were less likely to be eligible but not using statins, an effect that became non-significant with adjustment for language usually spoken at home. Among 537 persons taking statins, 81% were at LDL-C goal. Adjusted predictors of goal failure among statin users were being male and poorer. These risks were not attenuated by adjustment for healthcare access or utilization.

Conclusion

Among person's not taking statins, the socio-economically disadvantaged are more likely to be eligible and among those on statins, the socio-economically disadvantaged are less likely to achieve statin treatment goals. Further study is needed to identify specific amenable patient and/or physician factors that contribute to these disparities.
Risk of hematological malignancies associated with magnetic fields exposure from power lines: a case-control study in two municipalities of northern Italy
Authors: Malagoli Carlotta , Fabbi Sara , Teggi Sergio , Calzari Mariagiulia , Poli Maurizio , Ballotti Elena , Notari Barbara , Bruni Maurizio , Palazzi Giovanni , Paolucci Paolo , Vinceti Marco
Published: March 2010

Background

Some epidemiologic studies have suggested an association between electromagnetic field exposure induced by high voltage power lines and childhood leukemia, but null results have also been yielded and the possibility of bias due to unmeasured confounders has been suggested.

Methods

We studied this relation in the Modena and Reggio Emilia municipalities of northern Italy, identifying the corridors along high voltage power lines with calculated magnetic field intensity in the 0.1-<0.2, 0.2-<0.4, and ≥ 0.4 microTesla ranges. We identified 64 cases of newly-diagnosed hematological malignancies in children aged <14 within these municipalities from 1986 to 2007, and we sampled four matched controls for each case, collecting information on historical residence and parental socioeconomic status of these subjects.

Results

Relative risk of leukemia associated with antecedent residence in the area with exposure ≥ 0.1 microTesla was 3.2 (6.7 adjusting for socioeconomic status), but this estimate was statistically very unstable, its 95% confidence interval being 0.4-23.4, and no indication of a dose-response relation emerged. Relative risk for acute lymphoblastic leukemia was 5.3 (95% confidence interval 0.7-43.5), while there was no increased risk for the other hematological malignancies.

Conclusions

Though the number of exposed children in this study was too low to allow firm conclusions, results were more suggestive of an excess risk of leukemia among exposed children than of a null relation.
Comparison of serum apolipoprotein A-I between Chinese multiple sclerosis and other related autoimmune disease
Authors: Zhang Bin , Pu ShuXiang , Li BinMei , Ying JianRui , Song Xing Wang , Gao Cong
Published: March 2010

Background

Serum apolipoprotein (apo) A-I was considered to be an immune regulator and could suppress pro-inflammatory cytokines generated by activated T cell in some autoimmune diseases. However, the change of serum apoA-I levels in multiple sclerosis (MS) patients is unknown.

Methods

In the presentation we performed a study on serum apoA-I levels in the patients with MS. We enrolled some age and gender matched patients with MS, autoimmune demyelinating diseases (Guillain-Barre Syndrome and Clinically Isolated Syndrome), neuroinflammatory diseases (viral encephalitis), autoimmune connective diseases (rheumatoid arthritis and systemic lupus erythematosus) and healthy control groups, and tested their serum lipids levels: total cholesterol (TC), triglyceride (TG), high-density lipoproteins (HDL), apolipoproteinB100 (apoB100), apolipoproteinA-I (apoA-I).

Results

For all patients, age had no effect on serum apoA-I levels (P > 0.05). Meanwhile, we proved the highest serum apoA-I levels in MS patients and the lowest serum apoA-I levels in SLE patients. Serum apoA-I levels was significantly elevated in female MS patients (P = 0.033; P < 0.05).

Conclusion

In short we believed that patients with MS and other autoimmune demyelination had significantly decreased serum levels of apo A-I.
Prediction of novel synthetic pathways for the production of desired chemicals
Authors: Cho Ayoun , Yun Hongseok , Park Jin Hwan , Lee Sang Yup , Park Sunwon
Published: March 2010

Background

There have been several methods developed for the prediction of synthetic metabolic pathways leading to the production of desired chemicals. In these approaches, novel pathways were predicted based on chemical structure changes, enzymatic information, and/or reaction mechanisms, but the approaches generating a huge number of predicted results are difficult to be applied to real experiments. Also, some of these methods focus on specific pathways, and thus are limited to expansion to the whole metabolism.

Results

In the present study, we propose a system framework employing a retrosynthesis model with a prioritization scoring algorithm. This new strategy allows deducing the novel promising pathways for the synthesis of a desired chemical together with information on enzymes involved based on structural changes and reaction mechanisms present in the system database. The prioritization scoring algorithm employing Tanimoto coefficient and group contribution method allows examination of structurally qualified pathways to recognize which pathway is more appropriate. In addition, new concepts of binding site covalence, estimation of pathway distance and organism specificity were taken into account to identify the best synthetic pathway. Parameters of these factors can be evolutionarily optimized when a newly proven synthetic pathway is registered. As the proofs of concept, the novel synthetic pathways for the production of isobutanol, 3-hydroxypropionate, and butyryl-CoA were predicted. The prediction shows a high reliability, in which experimentally verified synthetic pathways were listed within the top 0.089% of the identified pathway candidates.

Conclusions

It is expected that the system framework developed in this study would be useful for the in silico design of novel metabolic pathways to be employed for the efficient production of chemicals, fuels and materials.
Effects of lifestyle physical activity on perceived symptoms and physical function in adults with fibromyalgia: results of a randomized trial
Authors: Fontaine Kevin R , Conn Lora , Clauw Daniel J
Published: March 2010

Introduction

Although exercise is therapeutic for adults with fibromyalgia (FM), its symptoms often create obstacles that discourage exercise. We evaluated the effects of accumulating at least 30 minutes of self-selected lifestyle physical activity (LPA) on perceived physical function, pain, fatigue, body mass index, depression, tenderness, and the six-minute walk test in adults with FM.

Methods

Eighty-four minimally active adults with FM were randomized to either LPA or a FM education control (FME) group. LPA participants worked toward accumulating 30 minutes of self-selected moderate-intensity LPA, five to seven days per week, while the FME participants received information and support.

Results

Seventy-three of the 84 participants (87%) completed the 12-week trial. The LPA group increased their average daily steps by 54%. Compared to FME, the LPA group reported significantly less perceived functional deficits (P = .032) and less pain (P = .006). There were no differences between the groups on the six-minute walk test (P = .067), fatigue, depression, body mass index, or tenderness.

Conclusions

Accumulating 30 minutes of LPA throughout the day produces clinically relevant changes in perceived physical function and pain in previously minimally active adults with FM.

Trial Registration

clinicaltrials.gov NCT00383084
Evaluation of the rheumatoid arthritis susceptibility loci HLA-DRB1, PTPN22, OLIG3/TNFAIP3, STAT4 and TRAF1/C5 in an inception cohort
Authors: Morgan Ann W , Robinson James I , Conaghan Philip G , Martin Stephen G , Hensor Elizabeth MA , Morgan Michael D , Steiner Lori , Erlich Henry A , Gooi Hock-Chye , Barton Anne , Worthington Jane , Emery Paul ,   UKRAG Consortium and the YEAR Consortium
Published: March 2010

Introduction

This study investigated five confirmed rheumatoid arthritis (RA) susceptibility genes/loci (HLA-DRB1, PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5) for association with susceptibility and severity in an inception cohort.

Methods

The magnitude of association for each genotype was assessed in 1,046 RA subjects from the Yorkshire Early RA cohort and in 5,968 healthy UK controls. Additional exploratory subanalyses were undertaken in subgroups defined by autoantibody status (rheumatoid factor and anti-cyclic citrullinated peptide) or disease severity (baseline articular erosions, Health Assessment Questionnaire (HAQ) score and swollen joint count (SJC)).

Results

In the total RA inception cohort, the HLA-DRB1 shared epitope (per-allele odds ratio (OR) = 2.1, trend P < 0.0001), PTPN22 (per-allele OR = 1.5, trend P < 0.0001), OLIG3/TNFAIP3 locus (per-allele OR = 1.2, trend P = 0.009) and TRAF1/C5 locus (per-allele OR = 1.1, trend P = 0.04) were associated with RA. The magnitude of association for these loci was increased in those patients who were autoantibody-positive. PTPN22 was associated with autoantibody-negative RA (per-allele OR = 1.3, trend P = 0.04). There was no evidence of association between these five genetic loci and baseline erosions or SJC in the total RA cohort, after adjustment for symptom duration. TRAF1/C5 was significantly associated with baseline HAQ, however, following adjustment for symptom duration (P trend = 0.03).

Conclusions

These findings support the mounting evidence that different genetic loci are associated with autoantibody-positive and autoantibody-negative RA, possibly suggesting that many of the genes identified to date are associated with autoantibody production. Additional studies with a specific focus on autoantibody-negative RA will be needed to identify the genes predisposing to this RA subgroup. The TRAF1/C5 locus in particular warrants further investigation in RA as a potential disease severity locus.
Been There, Done That, Wrote the Blog: The Choices and Challenges of Supporting Adolescents and Young Adults With Cancer
Authors: Treadgold Claire L. , Kuperberg Aura
Published: March 2010

The purpose of this article is to review the current literature on the provision of support groups for adolescent and young adult (AYA) patients with cancer with a focus on the challenges that are faced by these initiatives. The value of group support to patients with cancer and particularly to this age group has been well documented. However, with the advent and increase in popularity of online support options, it is an opportune time to examine the options available to the AYA group and highlight areas that would benefit from further investigation. This article will review the literature on the need to provide support groups to this age group, the available options, and the challenges they face.
Phase III Trial Comparing Vinflunine With Docetaxel in Second-Line Advanced Non–Small-Cell Lung Cancer Previously Treated With Platinum-Containing Chemotherapy
Authors: Krzakowski Maciej , Ramlau Rodryg , Jassem Jacek , Szczesna Aleksandra , Zatloukal Petr , Von Pawel Joachim , Sun Xushan , Bennouna Jaafar , Santoro Armando , Biesma Bonne , Delgado François M. , Salhi Yacine , Vaissiere Nathalie , Hansen Olfred , Tan Eng-Huat , Quoix Elisabeth , Garrido Pilar , Douillard Jean-Yves
Published: March 2010

Purpose

To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non–small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy.

Patients and Methods

Randomized, multicenter, phase III study, 551 patients received either vinflunine 320 mg/m2or docetaxel 75 mg/m2every 21 days until disease progression or serious toxicity. The primary end point was progression-free survival (PFS). The noninferiority analysis was based on a 10% difference (types I/II error rates: 5%/20%). Secondary end points included response rate (ORR), response duration, overall survival (OS), clinical benefit, quality of life (QOL), and safety.

Results

Median PFS was 2.3 months for each arm (HR, 1.004; 95% CI, 0.841 to 1.199). ORR, stable disease, median OS, were 4.4% versus 5.5%, 36.0% versus 39.6%, 6.7 versus 7.2 months (HR, 0.973; 95% CI, 0.805 to 1.176), respectively. No significant difference in patient benefit and QOL (Functional Assessment of Cancer Therapy-Lung). No unexpected adverse events were observed. Grade higher than 0 (vinflunine v docetaxel) anemia (82.1% v 79.8%), neutropenia (49.3 v 39.02%), thrombocytopenia (30.6% v 14.3%), febrile neutropenia (3.3% v 4.7%), constipation (39.2% v 11.7%), fatigue (36.6% v 33.9%), injection site reaction (31.9% v 0.7%), nausea (26.7% v 23.7%), vomiting (23.8% v 14.2%), alopecia (19.8% v 35.4%), stomatis (19.4% v 12.4%), abdominal pain (20.1% v 3.6%), myalgia (14.7% v 6.6%), peripheral neuropathy (10.7% v 15.0%), arthralgia (7.0% v 7.7%), diarrhea (6.2% v 12.4%), edema (1.5% v 5.4%), and nail disorders (1.1% v 5;1%) were observed.

Conclusion

This noninferiority phase III study showed similar efficacy end points for vinflunine and docetaxel. Despite higher rates of some adverse effects (anemia, abdominal pain, constipation, fatigue) the overall toxicity profile of vinflunine was manageable. Therefore, VFL may be another option in the second-line treatment of patients with advanced NSCLC.
Insulin-like Growth Factor Receptor 1 (IGF1R) Gene Copy Number Is Associated With Survival in Operable Non–Small-Cell Lung Cancer: A Comparison Between IGF1R Fluorescent In Situ Hybridization, Protein Expression, and mRNA Expression
Authors: Dziadziuszko Rafal , Merrick Daniel T. , Witta Samir E. , Mendoza Adelita D. , Szostakiewicz Barbara , Szymanowska Amelia , Rzyman Witold , Dziadziuszko Katarzyna , Jassem Jacek , Bunn Paul A. , Varella-Garcia Marileila , Hirsch Fred R.
Published: March 2010

Purpose

The purpose of this study was to characterize insulin-like growth factor-1 receptor (IGF1R) protein expression, mRNA expression, and gene copy number in surgically resected non–small-cell lung cancers (NSCLC) in relation to epidermal growth factor receptor (EGFR) protein expression, patient characteristics, and prognosis.

Patients and Methods

One hundred eighty-nine patients with NSCLC who underwent curative pulmonary resection were studied (median follow-up, 5.3 years). IGF1R protein expression was evaluated by immunohistochemistry (IHC) with two anti-IGF1R antibodies (n = 179). EGFR protein expression was assessed with PharmDx kit. IGF1R gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 114 corresponding fresh-frozen samples. IGF1R gene copy number was assessed by fluorescent in situ hybridization using customized probes (n = 181).

Results

IGF1R IHC score was higher in squamous cell carcinomas versus other histologies (P < .001) and associated with stage (P = .03) but not survival (P = .46). IGF1R and EGFR protein expression showed significant correlation (r = 0.30; P < .001). IGF1R gene expression by qRT-PCR was higher in squamous cell versus other histologies (P = .006) and did not associate with other clinical features nor survival (P = .73). Employing criteria previously established for EGFR copy number, patients with IGF1R amplification/high polysomy (n = 48; 27%) had 3-year survival of 58%, patients with low polysomy (n = 87; 48%) had 3-year survival of 47% and patients with trisomy/disomy (n = 46; 25%) had 3-year survival of 35%, respectively (P = .024). Prognostic value of high IGF1R gene copy number was confirmed in multivariate analysis.

Conclusion

IGF1R protein expression is higher in squamous cell versus other histologies and correlates with EGFR expression. IGF1R protein and gene expression does not associate with survival, whereas high IGF1R gene copy number harbors positive prognostic value.
Phase I/II Trial of Preoperative Oxaliplatin, Docetaxel, and Capecitabine With Concurrent Radiation Therapy in Localized Carcinoma of the Esophagus or Gastroesophageal Junction
Authors: Spigel David R. , Greco F. Anthony , Meluch Anthony A. , Lane Cassie M. , Farley Cynthia , Gray James R. , Clark Bobby L. , Burris Howard A. , Hainsworth John D.
Published: March 2010

Purpose

Preoperative chemoradiotherapy is a primary treatment option for patients with resectable esophageal cancer. Combination regimens using newer agents may improve patient outcomes. This multicenter community-based phase I/II trial examined a modern triplet regimen comprised of oxaliplatin, docetaxel, and capecitabine (ODC) combined with radiation therapy (RT).

Patients and Methods

The primary end point was the pathologic complete response (pCR) rate. Eligibility criteria included resectable stage I to III cancer of the mid-/distal-esophagus or gastroesophageal junction, measurable disease, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. Treatment included oxaliplatin 40 mg/m2, docetaxel 20 mg/m2 (intravenous, weekly × 5); capecitabine 1,000 mg/m2 orally twice daily on days 1 to 7, 15 to 21, and 29 to 35; and concurrent RT (45 Gy). Resection was performed during weeks 9 to 12. ODC and RT safety was determined in a phase I portion (n = 10) preceding phase II.

Results

Fifty-nine patients were enrolled (September 2005 to February 2008; phase I/cohort 1, 10 patients; phase I/cohort 2/phase II, 49 patients). Baseline characteristics included median age of 63 years; 84% male; ECOG PS 0 and 1, 51% and 49%, respectively; adenocarcinoma and squamous cell, 69% and 18%, respectively; stage I, II, and III, 12%, 41%, and 45%, respectively. Phase I revealed no dose-limiting toxicity. Responses: pCR rate, 49%; objective response rate, 61% (24 complete and six partial responses); stable disease, 6%; and progressive disease, 2%. Sixty-nine percent of patients underwent surgery. Survival: median follow-up, 116 weeks; median disease-free survival (DFS) and overall survival (OS) were 16.3 and 24.1 months, respectively. Two-year DFS and OS were 45.1% and 52.2%, respectively. Most common (≥ 5%) grade 3 to 4 nonhematologic toxicities were anorexia (20%), dehydration (16%), diarrhea (8%), dysphagia (10%), esophagitis (20%), fatigue (12%), hyperglycemia (6%), nausea (16%), pulmonary symptoms (14%), sepsis (6%), and vomiting (16%). All other grade 3 to 4 hematologic and nonhematologic toxicities were uncommon (< 5%).

Conclusion

Preoperative ODC plus RT is active and relatively safe in patients with locoregional esophageal cancer. Importantly, this therapy can be administered within 8 weeks. This regimen warrants additional study in this setting and in combination with newer biologic agents.
Total Skin Electron Beam and Non-Myeloablative Allogeneic Hematopoietic Stem-Cell Transplantation in Advanced Mycosis Fungoides and Sézary Syndrome
Authors: Duvic Madeleine , Donato Michele , Dabaja Bouthaina , Richmond Heather , Singh Lotika , Wei Wei , Acholonu Sandra , Khouri Issa , Champlin Richard , Hosing Chitra
Published: March 2010

Purpose

Transformed mycosis fungoides (MF) and Sézary syndrome (SS) are currently incurable. We studied the safety and efficacy of total skin electron beam with allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with cutaneous T-cell lymphoma (CTCL).

Patients and Methods

Nineteen patients with advanced CTCL (median age, 50 years; four prior therapies) underwent total skin electron beam radiation followed by allogeneic HSCT between July 2001 and July 2008. Sixteen patients were conditioned with fludarabine (125 mg/m2) and melphalan (140 mg/m2) plus thymoglobulin (for mismatched donors). Graft-versus-host disease (GVHD) prophylaxis was with tacrolimus/mini methotrexate.

Results

Eighteen patients experienced engraftment, and one died as a result of sepsis on day 16. Median time to recovery of absolute neutrophil count (ANC) was 12 days. Fifteen achieved full donor chimerism, 12 had acute GVHD, and 12 were treated for chronic GVHD. The overall intent-to-treat response was 68%, and the complete response rate was 58%. Four of six patients died in complete remission as a result of bacterial sepsis (n = 2), chronic GVHD and fungal infection (n = 1), or lung cancer (n = 1); only two died as a result of progressive disease. Eight experienced relapse in skin; five regained complete response with reduced immunosuppression or donor lymphocyte infusions. Eleven of 13 are currently in complete remissions, with median follow-up of 19 months (range, 1.3 to 8.3 years). Median overall survival has not been reached.

Conclusion

Total skin electron beam followed by allogeneic stem-cell transplantation merits additional evaluation for a selected group of patients with refractory, advanced, cutaneous T-cell lymphoma with evidence for graft-versus-tumor effect.
Meta-Analysis of Concomitant Versus Sequential Radiochemotherapy in Locally Advanced Non–Small-Cell Lung Cancer
Authors: Aupérin Anne , Le Péchoux Cecile , Rolland Estelle , Curran Walter J. , Furuse Kiyoyuki , Fournel Pierre , Belderbos Jose , Clamon Gerald , Ulutin Hakki Cuneyt , Paulus Rebecca , Yamanaka Takeharu , Bozonnat Marie-Cecile , Uitterhoeve Apollonia , Wang Xiaofei , Stewart Lesley , Arriagada Rodrigo , Burdett Sarah , Pignon Jean-Pierre
Published: March 2010

Purpose

The previous individual patient data meta-analyses of chemotherapy in locally advanced non–small-cell lung cancer (NSCLC) showed that adding sequential or concomitant chemotherapy to radiotherapy improved survival. The NSCLC Collaborative Group performed a meta-analysis of randomized trials directly comparing concomitant versus sequential radiochemotherapy.

Methods

Systematic searches for trials were undertaken, followed by central collection, checking, and reanalysis of updated individual patient data. Results from trials were combined using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival; secondary outcomes were progression-free survival, cumulative incidences of locoregional and distant progression, and acute toxicity.

Results

Of seven eligible trials, data from six trials were received (1,205 patients, 92% of all randomly assigned patients). Median follow-up was 6 years. There was a significant benefit of concomitant radiochemotherapy on overall survival (HR, 0.84; 95% CI, 0.74 to 0.95; P = .004), with an absolute benefit of 5.7% (from 18.1% to 23.8%) at 3 years and 4.5% at 5 years. For progression-free survival, the HR was 0.90 (95% CI, 0.79 to 1.01; P = .07). Concomitant treatment decreased locoregional progression (HR, 0.77; 95% CI, 0.62 to 0.95; P = .01); its effect was not different from that of sequential treatment on distant progression (HR, 1.04; 95% CI, 0.86 to 1.25; P = .69). Concomitant radiochemotherapy increased acute esophageal toxicity (grade 3-4) from 4% to 18% with a relative risk of 4.9 (95% CI, 3.1 to 7.8; P < .001). There was no significant difference regarding acute pulmonary toxicity.

Conclusion

Concomitant radiochemotherapy, as compared with sequential radiochemotherapy, improved survival of patients with locally advanced NSCLC, primarily because of a better locoregional control, but at the cost of manageable increased acute esophageal toxicity.
Risk of Arterial Thromboembolic Events With Sunitinib and Sorafenib: A Systematic Review and Meta-Analysis of Clinical Trials
Authors: Choueiri Toni K. , Schutz Fabio A.B. , Je Youjin , Rosenberg Jonathan E. , Bellmunt Joaquim
Published: March 2010

Purpose

Sunitinib and sorafenib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) used in a vast range of cancers. Arterial thromboembolic events (ATE) have been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to determine the incidence and the relative risk (RR) associated with the use of sunitinib and sorafenib.

Patients and Methods

PubMed databases were searched for articles published from January 1966 to July 2009, and abstracts presented at the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) meetings held between 2004 and 2009 were searched for relevant clinical trials. Eligible studies included phase II and III trials and expanded access programs. Statistical analyses were conducted to calculate the summary incidence, RRs, and 95% CIs, using random-effects or fixed-effects models based on the heterogeneity of included studies.

Results

A total of 10,255 patients were selected for this meta-analysis. The incidence for ATE was 1.4% (95% CI, 1.2% to 1.6%). The RR of ATEs associated with sorafenib and sunitinib was 3.03 (95% CI, 1.25 to 7.37; P = .015) compared with control patients. The analysis was also stratified for the underlying malignancy (renal cell cancer v non-renal cell cancer) and TKI (sunitinib v sorafenib), but no significant differences in incidence or RR were observed.

Conclusion

Treatment with VEGFR TKIs sunitinib and sorafenib is associated with a significant increase in the risk of ATEs.
Estrogen Receptor-Related Receptor α Mediates Up-Regulation of Aromatase Expression by Prostaglandin E2 in Prostate Stromal Cells
Authors: Miao Lin , Shi Jiandang , Wang Chun-Yu , Zhu Yan , Du Xiaoling , Jiao Hongli , Mo Zengnan , Klocker Helmut , Lee Chung , Zhang Ju
Published: March 2010

Estrogen receptor-related receptor α (ERRα) is an orphan member of the nuclear receptor superfamily of transcription factors. ERRα is highly expressed in the prostate, especially in prostate stromal cells. However, little is known about the regulation and function of ERRα, which may contribute to the progression of prostatic diseases. We previously found that prostaglandin E2 (PGE2) up-regulated the expression of aromatase in prostate stromal cells. Here we show that PGE2 also up-regulates the expression of ERRα, which, as a transcription factor, further mediates the regulatory effects of PGE2 on the expression of aromatase. ERRα expression was up-regulated by PGE2 in prostate stromal cell line WPMY-1, which was mediated mainly through the protein kinase A signaling pathway by PGE2 receptor EP2. Suppression of ERRα activity by chlordane (an antagonist of ERRα) or small interfering RNA knockdown of ERRα blocked the increase of expression and promoter activity of aromatase induced by PGE2. Overexpression of ERRα significantly increased aromatase expression and promoter activity, which were further augmented by PGE2. Chromatin immunoprecipitation assay demonstrated that ERRα directly bound to the aromatase promoter in vivo, and PGE2 enhanced the recruitment of ERRα and promoted transcriptional regulatory effects on aromatase expression in WPMY-1. 17β-Estradiol concentration in WPMY-1 medium was up-regulated by ERRα expression, and that was further increased by PGE2. Our results provided evidence that ERRα contributed to local estrogen production by up-regulating aromatase expression in response to PGE2 and provided further insights into the potential role of ERRα in estrogen-related prostatic diseases.
Forjando Patrimonio: The Making of Archaeological Patrimony in Porfirian Mexico
Authors: Bueno Christina
Published: March 2010

This article examines the state project to gather pre-Hispanic artifacts in Mexico’s National Museum during the dictatorship of Porfirio Díaz (1876–1910). It focuses on the government project as part of a larger effort aimed at constructing an official national history and image. Through antiquity and the control of its remains, Porfirian elites sought to present Mexico as a modern, scientific, and sovereign nation with a sophisticated, ancient past. They based the government’s right to the artifacts on arguments that rested on appeals to nation and science. This article problematizes these claims. It demonstrates that far from an established science, archaeology was marked by a lack of technique and consensus about the meaning and display of artifacts. In addition, the official Indian past proved exclusionary in several ways. It celebrated certain ancient cultures and ignored others. It also negated the artifacts’ other uses and meanings. For many Mexicans the objects were not national but local patrimony, links to localized identities and histories. Although ordinary Mexicans aided the state, the transfer of artifacts to the museum did not go uncontested, a fact illustrated here by popular struggles to retain objects in Teotihuacán, Tepoztlán, and Tetlama, communities that battled with the inspector of monuments Leopoldo Batres, the principal state official in charge of gathering antiquities.
What Is the Institutional Form for Thinking?
Authors: Critchley Simon
Published: March 2010

This article considers the state of the humanities, particularly in disciplines like philosophy, in light of the institutional structure of the university. Arguing that the bureaucratization of the contemporary university is thwarting learning and thinking, the author suggests that we begin to consider academic institutions through lenses less focused on the production of measurable knowledge and more attentive to the practice of teaching as an end in itself. He invites readers to imagine alternatives to current academic institutions, challenging us to envision better, collaborative institutional forms for thinking. The increasingly corporate academic model needs to move away from its instrumentalizing emphasis on output, this essay suggests, to acknowledge, instead, the pleasures of teaching, of learning, and of thinking.
Between Irony and Revolution: Sexual Difference and the Case ofAufhebung
Authors: Nikolchina Miglena
Published: March 2010

In his discussion of the possible link between Hegel's term Aufhebung and Martin Luther's translation of the Greek word katargein as used by Saint Paul, Giorgio Agamben points out the Russian connection—via Alexandre Kojève and Alexandre Koyré—and hence the connection to Russian apocalyptic thinking in the reception of Hegelianism in France. This connection, however, has been marked by a striking contrast in the vicissitudes of Hegel's term in Russia and in France. Its first aspect is the invisibility of the issue of translation in the Russian case and the French hypersensitivity to this issue, which has resulted in a proliferation of suggested translations and discussions up to and beyond Derrida. The second aspect becomes manifest in the transformation the translation undergoes from Kojève to his self-professed disciple, Lacan. Kojève's “taking down” becomes “raising up” with Lacan, who, furthermore, inscribes this silent reversal in his theory of sexuation. It is the curious twist from apocalypse to sexual difference that the article addresses, moving from Alain Badiou's early views on dialectics to the groundbreaking debate on sexual difference between Judith Butler and Joan Copjec.
Thinking Differently
Authors: Cowie Elizabeth
Published: March 2010

This contribution to the twentieth anniversary issue of differences asks: What would not be theory? And what theory now? How does the contingent and conjunctural moment interact with or determine our theory and the understanding we seek from our theories? If theories are a form of representation, can one then say that representations are theories? Drawing on the work of Alain Badiou, Gilles Deleuze, and Slavoj Žižek, this essay explores these questions through the notion of the event, considering how our theories manage the terror of the contingency of events. Psychoanalysis, on the other hand, theorizes not the event but the drive to theorize the event—including the event of femininity—to make it precisely some thing, a symptom. But, as Lacan emphasized, the facts miss the point, and naming things is not the same as being able to articulate “the thing” of lack, the real of “missingness” constitutive of subjectivity. Various theorizations of difference, through concepts such as patriarchy or racism, come up against the problem of how difference can be different for us now. What, then, is the relation of the event to thinking the new? In her concluding discussion of Clio Barnard's mobile phone video, Dark Glass (2006), the author asks if film, as a time-based art that makes every recorded “then” a “now” in the experience of viewing, can also engage us in the contingent as the traumatic real to be made knowable. Would such a documentary event be what Badiou calls a poeticization, that is, would it constitute a “procedure of truth” that “throws us outside of ourselves”?
Unpacking the Archive: Ichthyology, Photography, and the Archival Record in Japan and Korea
Authors: Kim Gyewon
Published: March 2010

This essay examines the interlayered relations between photography, archive, and science in imperial Japan and postcolonial Korea. It specifically takes its cue from two archival contexts: the archive made by Uchida Keitarô, a Japanese ichthyologist who surveyed in colonial Korea during the 1930s, and that archive's reorganization in the form of an exhibition in Seoul in 2004. Uchida investigated “native Korean fish” for the colonial government for fifteen years beginning in 1927. He employed photography especially for identifying and historicizing the life of the native Korean fish. Uchida's photographs were missing for over seventy years, however, after being used by Jeong Moon-Ki, a representative Korean ichthyologist in the postcolonial era. Uchida's glass plates were discovered by chance and were archived and displayed in 2004 in an exhibition titled The Fish Locked in a Glass Plate. In this exhibition, Lee Gyeong-Min, the archivist and curator of Uchida's photographs, attempted to reveal the exhibition's connection to the power/knowledge equation in colonial science, while at the same time seeking to reground the site of the archive for writing a new history of the colonial past. This essay seeks to address what is entailed in this attempt to unpack the colonial archive in the postcolonial age, and how the new archive engages in the critical reflection of historiography of imperial Japan and colonial Korea.
The Double Scission of Mishima Yukio: Limits and Anxieties in the Autofictional Machine
Authors: Walker Gavin
Published: March 2010

As an author, a figure, and as an author who relied on figurations of himself as a primary device, Mishima Yukio (1925–1970) has existed in a complex relationship to criticism and literary history. Criticism of Mishima's work and life has often taken for granted the network of configurations, referrals, and affective structures set up by Mishima himself, and thus more often than not participates in the continuation and concretization of the Mishima myth. I argue that Taiyô to tetsu (Sun and Steel, 1968) contains a glimpse into the construction of this discursive machine, and that this work has largely been misread as what it purports to be: a kind of autobiography. Instead, Taiyô to tetsu is itself a reproduction schema for the project at its center: the careful correlation of Mishima the historical figure and Mishima as self-figured in his work. The theorizations of subjectivation, visuality, and collectivity in the text trace this project through its formation. By explicitly setting up this machine in his text, Mishima carefully ensured that even oppositional readings of his work would be co-opted into service on behalf of the discourse of his own myth. After drawing out the theoretical structures of Taiyô to tetsu, I conclude by suggesting that in terms of its relation to criticism and literary history, Mishima's project and the problematic posed by it closely parallels the question of the emperor-system (tennôsei) and its own problems of cultural representation.
The Birth of “Rok”: Cultural Imperialism, Nationalism, and the Glocalization of Rock Music in South Korea, 1964–1975
Authors: Kim Pil Ho , Shin Hyunjoon
Published: March 2010

Like any other genre of Western popular music in the postwar period, rock was introduced to South Korea via the U.S. Armed Forces, a powerful symbol of postwar American hegemony. Until the late 1960s the U.S. military camp shows, clubs, and radio broadcast remained the main source of Western pop, providing opportunities for Korean musicians to hone their skills and enrich their repertoire. While this might be seen as a classic example of cultural imperialism, it actually developed a much more complex pattern of glocalization, especially in the case of rock music. The Korean appropriation of rock—which we refer to as “rok”—unfolded new sensibilities of the youth counterculture, mounting a considerable challenge to the conservative, militaristic nationalism of the Park Chung Hee regime.

The supremely talented guitarist and composer Shin Joong Hyun and his band, the Add Four, led the way from the U.S. military base to the Korean audience in 1964, along with their rivals, the Key Boys. Other Korean rock bands, then known as the “group sounds,” followed suit. Group-sound rok flourished in the live music salons, outdoor festivals, and go-go dance clubs, captivating the youth in the 1960s and 1970s. As the authoritarian regime started noticing and clamping down on the “threat” of the youth culture, Shin Joong Hyun and other group-sound musicians were making a breakthrough in the mainstream popular culture. In 1975 the regime banned and censored Shin and other musicians, criminalizing the youth culture.

In analyzing what sparked off this monumental culture clash, we find that rok's reimagination of nation as a community of peace and love caused the harsh reaction from the regime, whose doctrine of “national culture” was heavily influenced by the militaristic vision of the Japanese Empire.
A City of Ten Years: Public/Private Internet Development in Nanhai
Authors: Qiu Jack Linchuan
Published: March 2010

Does the Internet, a key technological infrastructure in contemporary urban China, facilitate the emergence of private entrepreneurs and autonomous citizens? Who deserves the credit? Chinese national leaders answered “yes” to the first question and pointed to themselves as the answer to the second. This essay maintains, however, that local state actors played the central and effectively centralizing role in informatization (xinxihua) projects in Nanhai City, Guangdong province. Through local e-government projects and a series of policies regarding land use, financing, and personnel training, the Nanhai government was able to shape the emerging local e-conomy in a way that limited entrepreneurial autonomy for small-scale start-ups in the Internet industry. The highly centralized informatization campaign fundamentally reversed Nanhai's renowned decentralized model of rural industrialization.

Through this process, a fractured system emerged for the public and private meanings attached to informatization and to the city itself. This was manifested in everyday practice and discourse among local policymakers, entrepreneurs in both new and old economies, and average residents with different (mis)perceptions of the Internet influenced by their gender. At the formal policy level, the trend toward centralization was most obvious, revolving around the formation of a nebulous “public” network space being constructed by the city using technological, administrative, and rhetorical devices. Yet the “private” practices and perceptions of Internet that defined Nanhai's informational landscape persisted in a fractured manner at the same time, leading to major corruption scandals and the implosion of the grandiose technology campaign. To understand such a paradoxical process, this article examines the contextual and internal factors for Nanhai's Internet buildup. From a critical and historical perspective, it highlights a long-term seesaw battle along the problematic public-private borderline regarding issues of urbanization and informatization in contemporary Chinese cities.

This article reflects on the restructuring of local power relations and the role of “informatization” policy discourse therein. A crucial, yet often overlooked, dimension of reform in China today is the migration and subsequent transformation of technosocial meaning across different scales of public and private operations. The discursive process often has a transnational reach and tends to follow a political logic that usually only makes sense against the backdrop of the local history.
How Central Should the Central Bank Be?
Authors: Blinder Alan S
Published: March 2010

The nature and scope of the Federal Reserve's authority and the structure of its decision making are now “on the table” to an extent that has not been seen since 1935, and the Fed's vaunted independence is under some attack. This essay asks what the Federal Reserve should—and shouldn't—do, leaning heavily on the concept of economies of scope. In particular, I conclude that the central bank should monitor and regulate systemic risk because preserving financial stability is (a) closely aligned with the standard objectives of monetary policy and (b) likely to require lender of last resort powers. I also conclude that the Fed should supervise large financial institutions because that function is so closely to regulating systemic risk. However, several other functions now performed by the Fed could easily be done elsewhere. (JEL E52, E58, G21, G28)
Consensus Methods to Identify a Set of Potential Performance Indicators for Systems of Emergency and Urgent Care
Authors: Coleman Patricia , Nicholl Jon
Published: March 2010

Objectives

To identify a comprehensive set of indicators to enable Primary Care Trust (PCT) commissioners in England and other NHS decision-makers to monitor the performance of systems of emergency and urgent care for which they are responsible.

Methods

Using a combination of Delphi RAND methods in three successive rounds of consultation and nominal group review, we canvassed expert opinion on 70 potential indicators as good measures of system performance. The two Delphi panels consisted of senior clinicians and researchers, and urgent care leads and commissioners in PCTs and Strategic Health Authorities (SHAs). The indicators were formatted into a questionnaire according to whether they were outcome, process, structure, or equity-based measures. Participants scored each indicator on a Likert scale of 1-9 and had the opportunity to consider their scores informed by the group scores and feedback. The questionnaire was refined after each round. To ensure that the indicators rated most highly by the Delphi panels covered all dimensions of performance, the results of the Delphi were reviewed by a nominal group consisting of two researchers and three clinicians from the local health services research network (LHSR).

Results

Overall, the process yielded 16 candidate indicators. It also produced a core set of serious, emergency and urgent care-sensitive conditions (defined as conditions whose exacerbations should be managed by a well-performing system without admission to an inpatient bed), for use with the indicators.

Conclusions

System-wide measures to monitor performance across multiple services should encourage providers to work for patient benefit in an integrated way. They will also assist commissioners to monitor and improve emergency and urgent care for their local populations. The indicators are now being calculated using routinely available data, and tested for their responsiveness to capture change over time.
Economic Consequences for Other Family Members of Mental Health Problems in Older People
Authors: Wilcox-Gök Virginia , McNamee Paul
Published: March 2010

Objectives

We estimated the effects of poor mental health among older family members on the labour supply and incomes of younger family members living in the same household. Due to policy differences, effects for Scotland were compared with other parts of the UK.

Methods

Effects were estimated using the British Household Panel Survey (waves 1999-2006), with data from621 older respondents and 800 younger family members. Mental health was assessed using the General Health Questionnaire (GHQ), together with self-reported presence of depression, anxiety, orothermental health problems.

Results

The associations between labour supply and mental ill-health were found to vary by gender and region of the UK. For men, there were larger negative effects in Scotland relative to the rest of the UK. For women, mental ill-health was associated with increased labour supply in Scotland, while in the remainder of the UK, a negative association was observed. Income losses accrued across all groups except among Scottish females, with the largest significant negative effects observed among men living in the remainder of the UK.

Conclusions

Mental health problems among older family members are associated with significant labour market effects for younger family members. To reduce the economic consequences, better assessment of mental health among older people may be warranted. Further employment support for younger family members, in the form of more flexible work policies, might also serve to ameliorate economic losses.