bluuebunny/crossref_metadata_2025 huggingface dataset:
Theory and simulation of photogeneration and transport in Si-SiO
x
superlattice absorbers
Authors: Aeberhard Urs
Published: March 2011

Si-SiO
x
superlattices are among the candidates that have been proposed as high band gap absorber material in all-Si tandem solar cell devices. Owing to the large potential barriers for photoexited charge carriers, transport in these devices is restricted to quantum-confined superlattice states. As a consequence of the finite number of wells and large built-in fields, the electronic spectrum can deviate considerably from the minibands of a regular superlattice. In this article, a quantum-kinetic theory based on the non-equilibrium Green's function formalism for an effective mass Hamiltonian is used for investigating photogeneration and transport in such devices for arbitrary geometry and operating conditions. By including the coupling of electrons to both photons and phonons, the theory is able to provide a microscopic picture of indirect generation, carrier relaxation, and inter-well transport mechanisms beyond the ballistic regime.
Temperature- and thickness-dependent elastic moduli of polymer thin films
Authors: Ao Zhimin , Li Sean
Published: March 2011

The mechanical properties of polymer ultrathin films are usually different from those of their counterparts in bulk. Understanding the effect of thickness on the mechanical properties of these films is crucial for their applications. However, it is a great challenge to measure their elastic modulus experimentally with in situ heating. In this study, a thermodynamic model for temperature- (T) and thickness (h)-dependent elastic moduli of polymer thin films Ef(T,h) is developed with verification by the reported experimental data on polystyrene (PS) thin films. For the PS thin films on a passivated substrate, Ef(T,h) decreases with the decreasing film thickness, when h is less than 60 nm at ambient temperature. However, the onset thickness (h*), at which thickness Ef(T,h) deviates from the bulk value, can be modulated by T. h* becomes larger at higher T because of the depression of the quenching depth, which determines the thickness of the surface layer δ.
Defect-related hysteresis in nanotube-based nano-electromechanical systems
Authors: Tsetseris Leonidas , Pantelides Sokrates T
Published: March 2011

The electronic properties of multi-walled carbon nanotubes (MWCNTs) depend on the positions of their walls with respect to neighboring shells. This fact can enable several applications of MWCNTs as nano-electromechanical systems (NEMS). In this article, we report the findings of a first-principles study on the stability and dynamics of point defects in double-walled carbon nanotubes (DWCNTs) and their role in the response of the host systems under inter-tube displacement. Key defect-related effects, namely, sudden energy changes and hysteresis, are identified, and their relevance to a host of MWCNT-based NEMS is highlighted. The results also demonstrate the dependence of these effects on defect clustering and chirality of DWCNT shells.
Experimental study of combustion characteristics of nanoscale metal and metal oxide additives in biofuel (ethanol)
Authors: Jones Matthew , Li Calvin H , Afjeh Abdollah , Peterson GP
Published: March 2011

An experimental investigation of the combustion behavior of nano-aluminum (n-Al) and nano-aluminum oxide (n-Al2O3) particles stably suspended in biofuel (ethanol) as a secondary energy carrier was conducted. The heat of combustion (HoC) was studied using a modified static bomb calorimeter system. Combustion element composition and surface morphology were evaluated using a SEM/EDS system. N-Al and n-Al2O3 particles of 50- and 36-nm diameters, respectively, were utilized in this investigation. Combustion experiments were performed with volume fractions of 1, 3, 5, 7, and 10% for n-Al, and 0.5, 1, 3, and 5% for n-Al2O3. The results indicate that the amount of heat released from ethanol combustion increases almost linearly with n-Al concentration. N-Al volume fractions of 1 and 3% did not show enhancement in the average volumetric HoC, but higher volume fractions of 5, 7, and 10% increased the volumetric HoC by 5.82, 8.65, and 15.31%, respectively. N-Al2O3 and heavily passivated n-Al additives did not participate in combustion reactively, and there was no contribution from Al2O3 to the HoC in the tests. A combustion model that utilized Chemical Equilibrium with Applications was conducted as well and was shown to be in good agreement with the experimental results.
Viscosity affected by nanoparticle aggregation in Al2O3-water nanofluids
Authors: Duan Fei , Kwek Dingtian , Crivoi Alexandru
Published: March 2011

An investigation on viscosity was conducted 2 weeks after the Al2O3-water nanofluids having dispersants were prepared at the volume concentration of 1-5%. The shear stress was observed with a non-Newtonian behavior. On further ultrasonic agitation treatment, the nanofluids resumed as a Newtonian fluids. The relative viscosity increases as the volume concentrations increases. At 5% volume concentration, an increment was about 60% in the re-ultrasonication nanofluids in comparison with the base fluid. The microstructure analysis indicates that a higher nanoparticle aggregation had been observed in the nanofluids before re-ultrasonication.
Enhancing surface heat transfer by carbon nanofins: towards an alternative to nanofluids?
Authors: Chiavazzo Eliodoro , Asinari Pietro
Published: March 2011

Background

Nanofluids are suspensions of nanoparticles and fibers which have recently attracted much attention because of their superior thermal properties. Nevertheless, it was proven that, due to modest dispersion of nanoparticles, such high expectations often remain unmet. In this article, by introducing the notion of nanofin, a possible solution is envisioned, where nanostructures with high aspect-ratio are sparsely attached to a solid surface (to avoid a significant disturbance on the fluid dynamic structures), and act as efficient thermal bridges within the boundary layer. As a result, particles are only needed in a small region of the fluid, while dispersion can be controlled in advance through design and manufacturing processes.

Results

Toward the end of implementing the above idea, we focus on single carbon nanotubes to enhance heat transfer between a surface and a fluid in contact with it. First, we investigate the thermal conductivity of the latter nanostructures by means of classical non-equilibrium molecular dynamics simulations. Next, thermal conductance at the interface between a single wall carbon nanotube (nanofin) and water molecules is assessed by means of both steady-state and transient numerical experiments.

Conclusions

Numerical evidences suggest a pretty favorable thermal boundary conductance (order of 107 W·m-2·K-1) which makes carbon nanotubes potential candidates for constructing nanofinned surfaces.
Japanese encephalitis virus co-opts the ER-stress response protein GRP78 for viral infectivity
Authors: Wu Yi-Ping , Chang Chung-Ming , Hung Chun-Yu , Tsai Meng-Chieh , Schuyler Scott C , Wang Robert Yung-Liang
Published: March 2011

The serum-free medium from Japanese encephalitis virus (JEV) infected Baby Hamster Kidney-21 (BHK-21) cell cultures was analyzed by liquid chromatography tandem mass spectrometry (LC-MS) to identify host proteins that were secreted upon viral infection. Five proteins were identified, including the molecular chaperones Hsp90, GRP78, and Hsp70. The functional role of GRP78 in the JEV life cycle was then investigated. Co-migration of GRP78 with JEV particles in sucrose density gradients was observed and co-localization of viral E protein with GRP78 was detected by immunofluorescence analysis in vivo. Knockdown of GRP78 expression by siRNA did not effect viral RNA replication, but did impair mature viral production. Mature viruses that do not co-fractionate with GPR78 displayed a significant decrease in viral infectivity. Our results support the hypothesis that JEV co-opts host cell GPR78 for use in viral maturation and in subsequent cellular infections.
Isolation and complete genomic characterization of H1N1 subtype swine influenza viruses in southern China through the 2009 pandemic
Authors: Liu Yizhi , Ji Jun , Xie Qingmei , Wang Jing , Shang Huiqin , Chen Cuiying , Chen Feng , Xue Chunyi , Cao Yongchang , Ma Jingyun , Bi Yingzuo
Published: March 2011

Background

The swine influenza (SI) is an infectious disease of swine and human. The novel swine-origin influenza A (H1N1) that emerged from April 2009 in Mexico spread rapidly and caused a human pandemic globally. To determine whether the tremendous virus had existed in or transmitted to pigs in southern China, eight H1N1 influenza strains were identified from pigs of Guangdong province during 2008-2009.

Results

Based on the homology and phylogenetic analyses of the nucleotide sequences of each gene segments, the isolates were confirmed to belong to the classical SI group, with HA, NP and NS most similar to 2009 human-like H1N1 influenza virus lineages. All of the eight strains were low pathogenic influenza viruses, had the same host range, and not sensitive to class of antiviral drugs.

Conclusions

This study provides the evidence that there is no 2009 H1N1-like virus emerged in southern China, but the importance of swine influenza virus surveillance in China should be given a high priority.
Genetic characterization of avian influenza subtype H4N6 and H4N9 from live bird market, Thailand
Authors: Wisedchanwet Trong , Wongphatcharachai Manoosak , Boonyapisitsopa Supanat , Bunpapong Napawan , Kitikoon Pravina , Amonsin Alongkorn
Published: March 2011

A one year active surveillance program for influenza A viruses among avian species in a live-bird market (LBM) in Bangkok, Thailand was conducted in 2009. Out of 970 samples collected, influenza A virus subtypes H4N6 (n = 2) and H4N9 (n = 1) were isolated from healthy Muscovy ducks. All three viruses were characterized by whole genome sequencing with subsequent phylogenetic analysis and genetic comparison. Phylogenetic analysis of all eight viral genes showed that the viruses clustered in the Eurasian lineage of influenza A viruses. Genetic analysis showed that H4N6 and H4N9 viruses display low pathogenic avian influenza characteristics. The HA cleavage site and receptor binding sites were conserved and resembled to LPAI viruses. This study is the first to report isolation of H4N6 and H4N9 viruses from birds in LBM in Thailand and shows the genetic diversity of the viruses circulating in the LBM. In addition, co-infection of H4N6 and H4N9 in the same Muscovy duck was observed.
Use of the measure your medical outcome profile (MYMOP2) and W-BQ12 (Well-Being) outcomes measures to evaluate chiropractic treatment: an observational study
Authors: Polus Barbara I , Kimpton Amanda J , Walsh Max J
Published: March 2011

Background

The objective was to assess the use of the Measure Yourself Medical Outcome Profile (MYMOP2) and W-BQ12 well-being questionnaire for measuring clinical change associated with a course of chiropractic treatment.

Methods

Chiropractic care of the patients involved spinal manipulative therapy (SMT), mechanically assisted techniques, soft tissue therapy, and physiological therapeutic devices.

Outcome measures used were MYMOP2 and the Well-Being Questionnaire 12 (W-BQ12).

Results

Statistical and clinical significant changes were demonstrated with W-BQ12 and MYMOP2.

Conclusions

The study demonstrated that MYMOP2 was responsive to change and may be a useful instrument for assessing clinical changes among chiropractic patients who present with a variety of symptoms and clinical conditions.
Anti-T cell immunoglobulin and mucin domain-2 monoclonal antibody exacerbates collagen-induced arthritis by stimulating B cells
Authors: Kawamoto Toshio , Abe Yoshiyuki , Ito Jun , Makino Fumihiko , Kojima Yuko , Usui Yoshihiko , Ma Juan , Morimoto Shinji , Yagita Hideo , Okumura Ko , Takasaki Yoshinari , Akiba Hisaya
Published: March 2011

Introduction

T cell immunoglobulin and mucin domain-2 (TIM-2) has been shown to regulate CD4 T cell activation. However, the role of TIM-2 in the autoimmune disease models has not been clarified yet. In this study, we investigated the effects of anti-TIM-2 monoclonal antibodies (mAbs) in collagen-induced arthritis (CIA) to determine whether TIM-2 contributes to the development of T helper (Th) 1 or Th17 cells and joint inflammation.

Methods

DBA/1 mice were treated with anti-TIM-2 mAbs during the early or late phase of CIA. Type II collagen (CII)-specific CD4 T-cell proliferative response and cytokine production were assessed from lymph node cell culture. The serum levels of CII-specific antibody were measured by ELISA. The expression of TIM-2 on CD4 T cells or B cells was determined by flow cytometric analysis.

Results

Administration of anti-TIM-2 mAbs in early phase, but not late phase, significantly exacerbated the development of CIA. Although anti-TIM-2 mAbs treatment did not affect the development of Th1 or Th17 cells in the draining lymph node, the serum levels of anti-CII antibodies were significantly increased in the anti-TIM-2-treated mice. TIM-2 expression was found on splenic B cells and further up-regulated by anti-immunoglobulin (Ig)M, anti-CD40, and interleukin(IL)-4 stimulation. In contrast, CD4 T cells did not express TIM-2 even when stimulated with both anti-CD3 and anti-CD28 mAbs. Interestingly, anti-TIM-2 mAbs enhanced proliferation and antibody production of activated B cells in vitro.

Conclusions

TIM-2 signaling influences both proliferation and antibody production of B cells during the early phase of CIA, but not induction of Th1 or Th17 cells.
Acquired bloodstream infection in the intensive care unit: incidence and attributable mortality
Authors: Prowle John R , Echeverri Jorge E , Ligabo E Valentina , Sherry Norelle , Taori Gopal C , Crozier Timothy M , Hart Graeme K , Korman Tony M , Mayall Barrie C , Johnson Paul DR , Bellomo Rinaldo
Published: March 2011

Introduction

To estimate the incidence of intensive care unit (ICU)-acquired bloodstream infection (BSI) and its independent effect on hospital mortality.

Methods

We retrospectively studied acquisition of BSI during admissions of >72 hours to adult ICUs from two university-affiliated hospitals. We obtained demographics, illness severity and co-morbidity data from ICU databases and microbiological diagnoses from departmental electronic records. We assessed survival at hospital discharge or at 90 days if still hospitalized.

Results

We identified 6339 ICU admissions, 330 of which were complicated by BSI (5.2%). Median time to first positive culture was 7 days (IQR 5-12). Overall mortality was 23.5%, 41.2% in patients with BSI and 22.5% in those without. Patients who developed BSI had higher illness severity at ICU admission (median APACHE III score: 79 vs. 68, P < 0.001). After controlling for illness severity and baseline demographics by Cox proportional-hazard model, BSI remained independently associated with risk of death (hazard ratio from diagnosis 2.89; 95% confidence interval 2.41-3.46; P < 0.001). However, only 5% of the deaths in this model could be attributed to acquired-BSI, equivalent to an absolute decrease in survival of 1% of the total population. When analyzed by microbiological classification, Candida, Staphylococcus aureus and gram-negative bacilli infections were independently associated with increased risk of death. In a sub-group analysis intravascular catheter associated BSI remained associated with significant risk of death (hazard ratio 2.64; 95% confidence interval 1.44-4.83; P = 0.002).

Conclusions

ICU-acquired BSI is associated with greater in-hospital mortality, but complicates only 5% of ICU admissions and its absolute effect on population mortality is limited. These findings have implications for the design and interpretation of clinical trials.
Genome-wide assessment of imprinted expression in human cells
Authors: Morcos Lisanne , Ge Bing , Koka Vonda , Lam Kevin CL , Pokholok Dmitry K , Gunderson Kevin L , Montpetit Alexandre , Verlaan Dominique J , Pastinen Tomi
Published: March 2011

Background

Parent-of-origin-dependent expression of alleles, imprinting, has been suggested to impact a substantial proportion of mammalian genes. Its discovery requires allele-specific detection of expressed transcripts, but in some cases detected allelic expression bias has been interpreted as imprinting without demonstrating compatible transmission patterns and excluding heritable variation. Therefore, we utilized a genome-wide tool exploiting high density genotyping arrays in parallel measurements of genotypes in RNA and DNA to determine allelic expression across the transcriptome in lymphoblastoid cell lines (LCLs) and skin fibroblasts derived from families.

Results

We were able to validate 43% of imprinted genes with previous demonstration of compatible transmission patterns in LCLs and fibroblasts. In contrast, we only validated 8% of genes suggested to be imprinted in the literature, but without clear evidence of parent-of-origin-determined expression. We also detected five novel imprinted genes and delineated regions of imprinted expression surrounding annotated imprinted genes. More subtle parent-of-origin-dependent expression, or partial imprinting, could be verified in four genes. Despite higher prevalence of monoallelic expression, immortalized LCLs showed consistent imprinting in fewer loci than primary cells. Random monoallelic expression has previously been observed in LCLs and we show that random monoallelic expression in LCLs can be partly explained by aberrant methylation in the genome.

Conclusions

Our results indicate that widespread parent-of-origin-dependent expression observed recently in rodents is unlikely to be captured by assessment of human cells derived from adult tissues where genome-wide assessment of both primary and immortalized cells yields few new imprinted loci.
Community transcriptomics reveals universal patterns of protein sequence conservation in natural microbial communities
Authors: Stewart Frank J , Sharma Adrian K , Bryant Jessica A , Eppley John M , DeLong Edward F
Published: March 2011

Background

Combined metagenomic and metatranscriptomic datasets make it possible to study the molecular evolution of diverse microbial species recovered from their native habitats. The link between gene expression level and sequence conservation was examined using shotgun pyrosequencing of microbial community DNA and RNA from diverse marine environments, and from forest soil.

Results

Across all samples, expressed genes with transcripts in the RNA sample were significantly more conserved than non-expressed gene sets relative to best matches in reference databases. This discrepancy, observed for many diverse individual genomes and across entire communities, coincided with a shift in amino acid usage between these gene fractions. Expressed genes trended toward GC-enriched amino acids, consistent with a hypothesis of higher levels of functional constraint in this gene pool. Highly expressed genes were significantly more likely to fall within an orthologous gene set shared between closely related taxa (core genes). However, non-core genes, when expressed above the level of detection, were, on average, significantly more highly expressed than core genes based on transcript abundance normalized to gene abundance. Finally, expressed genes showed broad similarities in function across samples, being relatively enriched in genes of energy metabolism and underrepresented by genes of cell growth.

Conclusions

These patterns support the hypothesis, predicated on studies of model organisms, that gene expression level is a primary correlate of evolutionary rate across diverse microbial taxa from natural environments. Despite their complexity, meta-omic datasets can reveal broad evolutionary patterns across taxonomically, functionally, and environmentally diverse communities.
Total Cholesterol and Cancer Risk in a Large Prospective Study in Korea
Authors: Kitahara Cari M. , Berrington de González Amy , Freedman Neal D. , Huxley Rachel , Mok Yejin , Jee Sun Ha , Samet Jonathan M.
Published: March 2011

Purpose

To further clarify the relationship between total cholesterol and cancer, which remains unclear.

Methods

We prospectively examined the association between total cholesterol and site-specific and all-cancer incidence among 1,189,719 Korean adults enrolled in the National Health Insurance Corporation who underwent a standardized biennial medical examination in 1992 to 1995 and were observed for 14 years until cancer diagnosis or death.

Results

Over follow-up, 53,944 men and 24,475 women were diagnosed with a primary cancer. Compared with levels less than 160 mg/dL, high total cholesterol (≥ 240 mg/dL) was positively associated with prostate cancer (hazard ratio [HR], 1.24; 95% CI, 1.07 to 1.44; P trend = .001) and colon cancer (HR, 1.12; 95% CI, 1.00 to 1.25; P trend = .05) in men and breast cancer in women (HR, 1.17; 95% CI, 1.03 to 1.33; P trend = .03). Higher total cholesterol was associated with a lower incidence of liver cancer (men: HR, 0.42; 95% CI, 0.38 to 0.45; P trend < .001; women: HR, 0.32; 95% CI, 0.27 to 0.39; P trend < .001), stomach cancer (men: HR, 0.87; 95% CI, 0.82 to 0.93; P trend ≤ .001; women: HR, 0.86; 95% CI, 0.77 to 0.97; P trend = .06), and, in men, lung cancer (HR, 0.89; 95% CI, 0.82 to 0.96; P trend < .001). Results for liver cancer were slightly attenuated after additional adjustment for liver enzyme levels and hepatitis B surface antigen status (men: HR, 0.60; P trend < .001; women: HR, 0.46; P trend = .003) and exclusion of the first 10 years of follow-up (men: HR, 0.59; P trend < .001; women: HR, 0.44; P trend < .001). Total cholesterol was inversely associated with all-cancer incidence in both men (HR, 0.84; 95% CI, 0.81 to 0.86; P trend < .001) and women (HR, 0.91; 95% CI, 0.87 to 0.95; P trend < .001), but these associations were attenuated after excluding incident liver cancers (men: HR, 0.95; P trend < .001; women: HR, 0.98; P trend = .32).

Conclusion

In this large prospective study, we found that total cholesterol was associated with the risk of several different cancers, although these relationships differed markedly by cancer site.
Clotting Factor Gene Polymorphisms and Colorectal Cancer Risk
Authors: Vossen Carla Y. , Hoffmeister Michael , Chang-Claude Jenny C. , Rosendaal Frits R. , Brenner Hermann
Published: March 2011

Purpose

Increased coagulation has been associated with cancer onset and progression. Mainly small studies have addressed the association between clotting factor gene polymorphisms and the onset of colorectal cancer. We examined the association between six well-known clotting factor gene polymorphisms and colorectal cancer risk in a large case-control study.

Patients and Methods

Factor V Leiden (rs6025), prothrombin G20210A (rs1799963), PAI-1 4G/5G (rs1799889), MTHFR 677C>T (rs1801133), fibrinogen gamma 10034C>T (rs2066865), and factor XIII Val34Leu (rs5985) were genotyped in 1,801 patients with colorectal cancer and 1,853 healthy controls from a large German population-based study. The risk of colorectal cancer associated with gene variants was determined by calculating odds ratios (ORs) and their 95% CIs using logistic regression.

Results

Homozygous carriers of the prothrombotic factor V Leiden polymorphism showed a 5.8-fold increased risk (95% CI, 1.69 to 19.72) for colorectal cancer compared with noncarriers. A 30% reduced risk was found for heterozygous carriers of factor V Leiden (OR = 0.68; 95% CI, 0.52 to 0.90) and prothrombin G20210A (OR = 0.69; 95% CI, 0.49 to 0.96), implying an advantage for slightly increased thrombin generation. Carriers of the antithrombotic factor XIII Val34Leu polymorphism showed a 15% reduced risk of developing colorectal cancer (OR = 0.85; 95% CI, 0.74 to 0.97) compared with noncarriers. Our results did not support an effect of PAI-1 4G/5G, MTHFR 677C>T, and fibrinogen gamma 10034C>T on colorectal cancer risk.

Conclusion

Our results support a role of clotting factor polymorphisms and thereby the coagulation system in the risk of colorectal cancer.
Venous Thromboembolic Events With Chemotherapy Plus Bevacizumab: A Pooled Analysis of Patients in Randomized Phase II and III Studies
Authors: Hurwitz Herbert I. , Saltz Leonard B. , Van Cutsem Eric , Cassidy James , Wiedemann Jonas , Sirzén Florin , Lyman Gary H. , Rohr Ulrich-Peter
Published: March 2011

Purpose

Thromboembolism is a major source of morbidity and mortality in patients with cancer. The contribution of anti–vascular endothelial growth factor therapy to these events remains controversial.

Patients and Methods

Individual patient data were available for 6,055 patients in 10 randomized studies. Unadjusted and exposure-adjusted incidence of venous thromboembolisms (VTEs) was estimated for the overall population and by tumor type. Multivariate analysis was performed to identify risk factors for development of VTE. The safety of anticoagulant therapy in patients undergoing bevacizumab treatment was also examined.

Results

There were no statistically significant increases in the unadjusted or exposure-adjusted incidences of all-grade VTEs for bevacizumab versus controls in the overall population or by tumor type. The unadjusted incidence in the overall population was 10.9% with bevacizumab versus 9.8% with controls (odds ratio, 1.14; 95% CI, 0.96 to 1.35; P = .13); the rate per 100 patient-years was 18.5 for bevacizumab and 20.3 for controls (rate ratio, 0.91; 95% CI, 0.77 to 1.06; P =.23). Incidences of grade 3 to 5 events were similar in both groups. Several risk factors for VTEs were identified, including tumor type, older age, poorer performance status, VTE history, and baseline oral anticoagulant use. No interactions between bevacizumab treatment and these factors were observed. For patients who had a VTE and received full-dose anticoagulation therapy, the risk of severe bleeding was low (< 1%) and unaffected by bevacizumab treatment.

Conclusion

The addition of bevacizumab to chemotherapy did not statistically significantly increase the risk of VTEs versus chemotherapy alone. The risk for VTEs is driven predominantly by tumor and host factors.
Minimal Disseminated Disease in High-Risk Burkitt's Lymphoma Identifies Patients With Different Prognosis
Authors: Mussolin Lara , Pillon Marta , d'Amore Emanuele S.G. , Conter Valentino , Piglione Matilde , Nigro Luca Lo , Garaventa Alberto , Buffardi Salvatore , Aricò Maurizio , Rosolen Angelo
Published: March 2011

Purpose

To study minimal disseminated disease (MDD) in children with Burkitt's lymphoma (BL) and to determine its impact on prognosis.

Patients and Methods

We established a simplified long-distance polymerase chain reaction (LD-PCR) assay that can amplify up to 15 to 20 Kb of DNA sequence, making it possible to detect the t(8;14) at the genomic level with sensitivity of 10−4. We prospectively studied diagnostic biopsies and bone marrow aspirates from 134 patients affected by BL.

Results

A specific LD-PCR product was detected in 96 (72%) of 134 BL biopsies. Among 84 patients with t(8;14) positivity on tumor biopsy and bone marrow (BM), 26 (31%) had LD-PCR–positive BM, and 15 (18%) were positive at standard morphologic analysis. Twenty (85%) of 26 MDD-positive patients belonged to the R4 risk group, according to Berlin-Frankfurt-Munster definition. The 3-year progression-free survival was 68% (SE, 10%) in MDD-positive patients in R4 compared with 93% (SE, 5%) in MDD-negative patients in R4 (P = .03). By multivariate analysis (including MDD, sex, lactate dehydrogenase, CNS involvement), only MDD was predictive of higher risk of failure (hazard ratio, 4.7; P = .04).

Conclusion

MDD identifies a poor-prognosis subgroup among children with high-risk BL. To improve disease control in these patients, a more effective risk-adapted therapy, possibly including anti-CD20 monoclonal antibody, should be considered.
Cetuximab for the Treatment of Advanced Bronchioloalveolar Carcinoma (BAC): An Eastern Cooperative Oncology Group Phase II Study (ECOG 1504)
Authors: Ramalingam Suresh S. , Lee Ju-Whei , Belani Chandra P. , Aisner Seena C. , Kolesar Jill , Howe Craig , Velasco Mario R. , Schiller Joan H.
Published: March 2011

Purpose

Inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase have demonstrated modest anticancer activity in advanced bronchioloalveolar carcinoma (BAC). We conducted a phase II study to evaluate cetuximab for the treatment of advanced BAC.

Patients and Methods

Patients with advanced-stage pure BAC or adenocarcinoma with BAC features, fewer than two prior chemotherapy regimens, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 were eligible. Those with prior EGFR inhibitor therapy were excluded. Cetuximab was given as a weekly intravenous infusion at 250 mg/m2 after an initial loading dose of 400 mg/m2 in week 1. The primary end point was determination of response rate. EGFR and KRAS mutations were evaluated by pyrosequencing.

Results

Seventy-two patients were enrolled and 68 met eligibility requirements. Characteristics of patients included median age, 71 years; sex, 57% females; PS 0 or 1, 88% of patients; and smoking status, 19% never-smokers. Central pathology review confirmed the diagnosis in 45 of 49 available specimens. Approximately 50% of patients received more than two cycles of therapy (> 8 weeks). Skin rash was the most common toxicity (grade 3, 15%). The confirmed response rate was 7%, and stable disease was observed in 35%. The median survival and progression-free survival were 13 and 3.3 months, respectively. Only one of the six patients with an EGFR mutation and one of the seven patients with a KRAS mutation had a partial response.

Conclusion

Cetuximab was associated with modest efficacy in patients with advanced BAC, despite a low response rate. EGFR and KRAS mutations were not predictive of response to cetuximab.
Divergent mechanisms specify chordate motoneurons: evidence from ascidians
Authors: Hudson Clare , Ba Moly , Rouvière Christian , Yasuo Hitoyoshi
Published: March 2011

Ascidians are members of the vertebrate sister group Urochordata. Their larvae exhibit a chordate body plan, which forms by a highly accelerated embryonic strategy involving a fixed cell lineage and small cell numbers. We report a detailed analysis of the specification of three of the five pairs of motoneurons in the ascidian Ciona intestinalis and show that despite well-conserved gene expression patterns and embryological outcomes compared with vertebrates, key signalling molecules have adopted different roles. We employed a combination of cell ablation and gene manipulation to analyse the function of two signalling molecules with key roles in vertebrate motoneuron specification that are known to be expressed equivalently in ascidians: the inducer Sonic hedgehog, produced ventrally by the notochord and floorplate; and the inhibitory BMP2/4, produced on the lateral/dorsal side of the neural plate. Our surprising conclusion is that neither BMP2/4 signalling nor the ventral cell lineages expressing hedgehog play crucial roles in motoneuron formation in Ciona. Furthermore, BMP2/4 overexpression induced ectopic motoneurons, the opposite of its vertebrate role. We suggest that the specification of motoneurons has been modified during ascidian evolution, such that BMP2/4 has adopted a redundant inductive role rather than a repressive role and Nodal, expressed upstream of BMP2/4 in the dorsal neural tube precursors, acts as a motoneuron inducer during normal development. Thus, our results uncover significant differences in the mechanisms used for motoneuron specification within chordates and also highlight the dangers of interpreting equivalent expression patterns as indicative of conserved function in evo-devo studies.
Distinct cytoskeleton populations and extensive crosstalk control Ciona notochord tubulogenesis
Authors: Dong Bo , Deng Wei , Jiang Di
Published: March 2011

Cell elongation is a fundamental process that allows cells and tissues to adopt new shapes and functions. During notochord tubulogenesis in the ascidian Ciona intestinalis, a dramatic elongation of individual cells takes place that lengthens the notochord and, consequently, the entire embryo. We find a novel dynamic actin- and non-muscle myosin II-containing constriction midway along the anteroposterior aspect of each notochord cell during this process. Both actin polymerization and myosin II activity are required for the constriction and cell elongation. Discontinuous localization of myosin II in the constriction indicates that the actomyosin network produces local contractions along the circumference. This reveals basal constriction by the actomyosin network as a novel mechanism for cell elongation. Following elongation, the notochord cells undergo a mesenchymal-epithelial transition and form two apical domains at opposite ends. Extracellular lumens then form at the apical surfaces. We show that cortical actin and Ciona ezrin/radixin/moesin (ERM) are essential for lumen formation and that a polarized network of microtubules, which contributes to lumen development, forms in an actin-dependent manner at the apical cortex. Later in notochord tubulogenesis, when notochord cells initiate a bi-directional crawling movement on the notochordal sheath, the microtubule network rotates 90° and becomes organized as parallel bundles extending towards the leading edges of tractive lamellipodia. This process is required for the correct organization of actin-based protrusions and subsequent lumen coalescence. In summary, we establish the contribution of the actomyosin and microtubule networks to notochord tubulogenesis and reveal extensive crosstalk and regulation between these two cytoskeleton components.
Coordination of cell proliferation and anterior-posterior axis establishment in the mouse embryo
Authors: Stuckey Daniel W. , Clements Melanie , Di-Gregorio Aida , Senner Claire E. , Le Tissier Paul , Srinivas Shankar , Rodriguez Tristan A.
Published: March 2011

During development, the growth of the embryo must be coupled to its patterning to ensure correct and timely morphogenesis. In the mouse embryo, migration of the anterior visceral endoderm (AVE) to the prospective anterior establishes the anterior-posterior (A-P) axis. By analysing the distribution of cells in S phase, M phase and G2 from the time just prior to the migration of the AVE until 18 hours after its movement, we show that there is no evidence for differential proliferation along the A-P axis of the mouse embryo. Rather, we have identified that as AVE movements are being initiated, the epiblast proliferates at a much higher rate than the visceral endoderm. We show that these high levels of proliferation in the epiblast are dependent on Nodal signalling and are required for A-P establishment, as blocking cell division in the epiblast inhibits AVE migration. Interestingly, inhibition of migration by blocking proliferation can be rescued by Dkk1. This suggests that the high levels of epiblast proliferation function to move the prospective AVE away from signals that are inhibitory to its migration. The finding that initiation of AVE movements requires a certain level of proliferation in the epiblast provides a mechanism whereby A-P axis development is coordinated with embryonic growth.
Thinking about the Firm: A Review of Daniel Spulber's The Theory of the Firm
Authors: Hart Oliver
Published: March 2011

In this review, I describe how economists have moved beyond the firm as a black box to incorporate incentives, internal organization, and firm boundaries. I then turn to the way that the theory of the firm is treated in Daniel Spulber's book The Theory of the Firm: Microeconomics with Endogenous Entrepreneurs, Firms, Markets, and Organizations. Spulber's goal is to explain why firms exist, how they are established, and what they contribute to the economy. To accomplish this, Spulber defines a firm to be a transaction institution whose objectives differ from those of its owners. For Spulber, this separation is the key difference between the firm and direct exchange between consumers. I raise questions about whether this is a useful basis for a theory of the firm. (JEL D21)
Financial Regulation: Lessons from the Recent Financial Crises
Authors: Hoshi Takeo
Published: March 2011

The experiences of the financial crises in the United States recently and in Japan in the 1990s suggest two lessons for future financial regulations. First, the lack of an orderly resolution mechanism for large and complex financial institutions created serious problems. Second, it is important to distinguish between individual financial institutions' health and stability of the whole financial system. Policy recommendations in the Squam Lake Report address these issues well. The Dodd–Frank Act could provide an effective regulatory framework to implement these recommendations, but the success depends on the details of the regulations that have not been specified. (JEL E44, E52, G01, G21, G28, L51)
Top Incomes in the Long Run of History
Authors: Atkinson Anthony B , Piketty Thomas , Saez Emmanuel
Published: March 2011

A recent literature has constructed top income shares time series over the long run for more than twenty countries using income tax statistics. Top incomes represent a small share of the population but a very significant share of total income and total taxes paid. Hence, aggregate economic growth per capita and Gini inequality indexes are sensitive to excluding or including top incomes. We discuss the estimation methods and issues that arise when constructing top income share series, including income definition and comparability over time and across countries, tax avoidance, and tax evasion. We provide a summary of the key empirical findings. Most countries experience a dramatic drop in top income shares in the first part of the twentieth century in general due to shocks to top capital incomes during the wars and depression shocks. Top income shares do not recover in the immediate postwar decades. However, over the last thirty years, top income shares have increased substantially in English speaking countries and in India and China but not in continental European countries or Japan. This increase is due in part to an unprecedented surge in top wage incomes. As a result, wage income comprises a larger fraction of top incomes than in the past. Finally, we discuss the theoretical and empirical models that have been proposed to account for the facts and the main questions that remain open. (JEL D31, D63, H26, N30)
Frontiers of Real-Time Data Analysis
Authors: Croushore Dean
Published: March 2011

In the past ten years, researchers have explored the impact of data revisions in many different contexts. Researchers have examined the properties of data revisions, how structural modeling is affected by data revisions, how data revisions affect forecasting, the impact of data revisions on monetary policy analysis, and the use of real-time data in current analysis. This paper summarizes many of the questions for which real-time data analysis has provided answers. In addition, researchers and institutions have developed better real-time data sets around the world. Still, additional research is needed in key areas and research to date has uncovered even more fruitful areas worth exploring. (JEL C52, C53, C80, E01)
Assessment of the implementation and knowledge of the UK National Guidelines for HIV Testing (2008) in key conditions at a UK district general hospital
Authors: Gupta N D , Lechelt M
Published: March 2011

The objective of this study is to audit the implementation and knowledge of the British HIV Association (BHIVA) UK National guidelines for HIV testing (2008) in key conditions at Basildon & Thurrock University Hospital. Basildon Hospital is a district general hospital, serving over 400,000 patients in south-west Essex. A total of 348 patients were assessed through electronic to pathology data and patients' notes to investigate if they had been tested for HIV when diagnosed with the following conditions: tuberculosis (TB), hepatitis B and C, cervical intraepithelial neoplasia grade II/III, lymphoma, anal cancer, seminoma or Castleman's disease. The physicians involved were questioned as to their knowledge of the HIV testing guidelines. Of the 348 patients who were identified as having the above mentioned conditions, only 13.8% of those with any of the key conditions had received an HIV test. Only one non-HIV physician was aware of the guidelines. Knowledge of the 2008 BHIVA HIV testing guidelines is scanty among non-HIV-trained physicians. Health-care professionals in the field, irrespective of their role, should work harder to disseminate information and reduce prejudice that decreases testing of at-risk individuals.
Is it useful to perform a chest X-ray in asymptomatic patients with late latent syphilis?
Authors: Dabis R , Radcliffe K
Published: March 2011

According to the British Association for Sexual Health and HIV (BASHH) guidelines, a chest X-ray is recommended as part of the assessment of patients with late latent syphilis to exclude cardiovascular complications. The aims of this study were firstly to audit all cases of late latent syphilis seen at our centre since 1994 and to see whether a chest X-ray was requested and secondly to assess whether performing a chest X-ray was clinically useful. Of the 456 case notes audited, 298 chest X-rays were requested; 182 (61%) were reported as normal. Results were not available for 64 (21%) and 32 (11%) patients either declined or did not attend for follow-up. There were 20 (7%) chest X-rays that were reported as abnormal, yet none of these radiological findings were consistent with the cardiovascular complications of syphilis. In view of the lack of significant chest X-ray findings in asymptomatic patients with late latent syphilis, a chest X-ray should not be requested.
Prevalence and risk behaviours for Chlamydia trachomatis and Neisseria gonorrhoeae infection among female sex workers in an HIV/AIDS high-risk area
Authors: Jin X , Chan S , Ding G , Wang H , Xu J , Wang G , Chang D , Reilly K H , Wang N
Published: March 2011

The objectives of this study were to estimate the prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection among female sex workers (FSWs) in an HIV/AIDS high-risk area in China and to examine risk factors associated with CT or NG infection. A cross-sectional study of 568 FSWs was conducted in Kaiyuan City, Yunnan Province, PR China. The prevalence rates of HIV, CT and NG in the study participants were 11.1%, 17.4% and 8.3%, respectively. More than one-fifth (21.3%) of participants tested positive for either CT or NG. This study identifies a relatively high prevalence of CT or NG infection among FSWs in Kaiyuan. Notably, HIV infection was found to be associated with NG infection and study participants who tested positive for NG had a higher rate of CT infection. Further studies are warranted to examine the prevalence and spread of CT and NG in China, and their potential impact on the HIV epidemic.
Sexual risk behaviours and sexual health outcomes among heterosexual black Caribbeans: comparing sexually transmitted infection clinic attendees and national probability survey respondents
Authors: Gerver S M , Easterbrook P J , Anderson M , Solarin I , Elam G , Fenton K A , Garnett G , Mercer C H
Published: March 2011

We compared sociodemographic characteristics, sexual risk behaviours and sexual health experiences of 266 heterosexual black Caribbeans recruited at a London sexual health clinic between September 2005 and January 2006 with 402 heterosexual black Caribbeans interviewed for a British probability survey between May 1999 and August 2001. Male clinic attendees were more likely than men in the national survey to report: ≥10 sexual partners (lifetime; adjusted odds ratio [AOR]: 3.27, 95% confidence interval [CI]: 1.66–6.42), ≥2 partners (last year; AOR: 5.40, 95% CI: 2.64–11.0), concurrent partnerships (AOR: 3.26, 95% CI: 1.61–6.60), sex with partner(s) from the Caribbean (last 5 years; AOR: 7.97, 95% CI: 2.42–26.2) and previous sexually transmitted infection (STI) diagnosis/diagnoses (last 5 years; AOR: 16.2, 95% CI: 8.04–32.6). Similar patterns were observed for women clinic attendees, who also had increased odds of termination of pregnancy (AOR: 3.25, 95% CI: 1.87–5.66). These results highlight the substantially higher levels of several high-risk sexual behaviours among UK black Caribbeans attending a sexual health clinic compared with those in the general population. High-risk individuals are under-represented in probability samples, and it is therefore important that convenience samples of high-risk individuals are performed in conjunction with nationally representative surveys to fully understand the risk behaviours and sexual health-care needs of ethnic minority communities.
Human papillomavirus types in HIV seropositive men with penile warts in Johannesburg, South Africa
Authors: Firnhaber C , Sello M , Maskew M , Williams S , Schulze D , Williamson A-L , Allan B , Lewis D
Published: March 2011

Few data exist regarding the human papillomavirus (HPV) types in penile warts (PW) of HIV-infected men in Africa. Nurses collected penile swabs for HPV typing from 74 HIV-positive men with PW. HPV genotyping was performed using the Roche Linear Array Test. Analysis was performed on data relating to 74 samples. The mean age of the men was 36.0 years and 78.5% (51/65) were uncircumcised. Of the 73/74 validated results, all tested positive for HPV; 42.5% (31/73) and 32.9% (24/73) had HPV types 6 and 11, respectively. 84.9% of men tested positive for any oncogenic type: 20/73 (27.4%) were positive for type 16, 11/73 (15.1%) were positive for type 18 and 8/73 (11.0%) men had both types. Our study shows a high prevalence (68.5%) of HPV type 6 and/or 11 in this male population with PW. Given the poor availability of treatment, a quadrivalent vaccine for men may have significant benefit.
Self-reported history of sexually transmitted infection and chronic prostatitis symptoms: a cross-sectional study of a Nigerian undergraduate population
Authors: Ejike C E C C
Published: March 2011

The aetiology of chronic prostatitis is poorly understood. A cross-sectional study of a population of male undergraduates in Nigeria, using a questionnaire containing the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and some other relevant sex-related questions, was conducted. A total of 14.9% of the population had chronic prostatitis symptoms (CPSs) defined as a pain score of four or more on the NIH-CPSI pain subscale. Approximately 26 or 12% of the population had at least one, or ≥ 2 location(s) of pain, respectively. The presence of CPS was found to correlate with a self-reported history of sexually transmitted infection (STI) ( r = +0.237; P < 0.05) and 73% of those with a self-reported history of STI had CPS. Both voiding scores and quality-of-life scores were significantly higher in subjects with CPS, compared with those without CPS. Self-reported history of STI may be an important aetiological factor for chronic prostatitis/chronic pelvic pain symptoms.