Showing papers by "Shanghai Jiao Tong University published in 2009"

Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma

Abstract: METHODS In this phase 3, open-label study, we randomly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib (250 mg per day) (609 patients) or carboplatin (at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute) plus paclitaxel (200 mg per square meter of body-surface area) (608 patients). The primary end point was progression-free survival. RESULTS The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin–paclitaxel. The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority, as compared with carboplatin– paclitaxel, with respect to progression-free survival in the intention-to-treat population (hazard ratio for progression or death, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin–paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001), whereas in the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly longer among those who received carboplatin–paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 3.98; P<0.001). The most common adverse events were rash or acne (in 66.2% of patients) and diarrhea (46.6%) in the gefitinib group and neurotoxic effects (69.9%), neutropenia (67.1%), and alopecia (58.4%) in the carboplatin–paclitaxel group. CONCLUSIONS Gefitinib is superior to carboplatin–paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia. The presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib. (ClinicalTrials.gov number, NCT00322452.)

Observation of a large-gap topological-insulator class with a single Dirac cone on the surface

Abstract: Recent experiments and theories have suggested that strong spin–orbit coupling effects in certain band insulators can give rise to a new phase of quantum matter, the so-called topological insulator, which can show macroscopic quantum-entanglement effects. Such systems feature two-dimensional surface states whose electrodynamic properties are described not by the conventional Maxwell equations but rather by an attached axion field, originally proposed to describe interacting quarks. It has been proposed that a topological insulator with a single Dirac cone interfaced with a superconductor can form the most elementary unit for performing fault-tolerant quantum computation. Here we present an angle-resolved photoemission spectroscopy study that reveals the first observation of such a topological state of matter featuring a single surface Dirac cone realized in the naturally occurring Bi_2Se_3 class of materials. Our results, supported by our theoretical calculations, demonstrate that undoped Bi_2Se_3 can serve as the parent matrix compound for the long-sought topological device where in-plane carrier transport would have a purely quantum topological origin. Our study further suggests that the undoped compound reached via n-to-p doping should show topological transport phenomena even at room temperature.

Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer

Abstract: Pancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers in part because it is insensitive to many chemotherapeutic drugs. Studying a mouse model of PDA that is refractory to the clinically used drug gemcitabine, we found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA. We tested whether the delivery and efficacy of gemcitabine in the mice could be improved by coadministration of IPI-926, a drug that depletes tumor-associated stromal tissue by inhibition of the Hedgehog cellular signaling pathway. The combination therapy produced a transient increase in intratumoral vascular density and intratumoral concentration of gemcitabine, leading to transient stabilization of disease. Thus, inefficient drug delivery may be an important contributor to chemoresistance in pancreatic cancer.

A tunable topological insulator in the spin helical Dirac transport regime

Abstract: Helical Dirac fermions—charge carriers that behave as massless relativistic particles with an intrinsic angular momentum (spin) locked to its translational momentum—are proposed to be the key to realizing fundamentally new phenomena in condensed matter physics. Prominent examples include the anomalous quantization of magneto-electric coupling, half-fermion states that are their own antiparticle, and charge fractionalization in a Bose– Einstein condensate, all of which are not possible with conventional Dirac fermions of the graphene variety. Helical Dirac fermions have so far remained elusive owing to the lack of necessary spin-sensitive measurements and because such fermions are forbidden to exist in conventional materials harbouring relativistic electrons, such as graphene or bismuth. It has recently been proposed that helical Dirac fermions may exist at the edges of certain types of topologically ordered insulators—materials with a bulk insulating gap of spin–orbit origin and surface states protected against scattering by time-reversal symmetry—and that their peculiar properties may be accessed provided the insulator is tuned into the so-called topological transport regime. However, helical Dirac fermions have not been observed in existing topological insulators. Here we report the realization and characterization of a tunable topological insulator in a bismuthbased class of material by combining spin-imaging and momentum-resolved spectroscopies, bulk charge compensation, Hall transport measurements and surface quantum control. Our results reveal a spin-momentum locked Dirac cone carrying a nontrivial Berry’s phase that is nearly 100 per cent spin-polarized, which exhibits a tunable topological fermion density in the vicinity of the Kramers point and can be driven to the long-sought topological spin transport regime. The observed topological nodal state is shown to be protected even up to 300 K. Our demonstration of room-temperature topological order and non-trivial spintexture in stoichiometric Bi_2Se_3.M_x (M_x indicates surface doping or gating control) paves the way for future graphene-like studies of topological insulators, and applications of the observed spinpolarized edge channels in spintronic and computing technologies possibly at room temperature.

Dairy-manure derived biochar effectively sorbs lead and atrazine.

Abstract: Biochar (BC) produced from agricultural crop residues has proven effective in sorbing organic contaminants. This study evaluated the ability of dairy-manure derived biochar to sorb heavy metal Pb and organic contaminant atrazine. Two biochar samples were prepared by heating dairy manure at low temperature of 200 degrees C (BC200) and 350 degrees C (BC350). The untreated manure (BC25) and a commercial activated C (AC) were included as controls. Sorption of Pb by biochar followed a dual Langmuir-Langmuir model, attributing to Pb precipitation (84-87%) and surface sorption (13-16%). Chemical speciation, X-ray diffraction, and infrared spectroscopy indicated that Pb was precipitated as beta-Pb9(PO4)6 in BC25 and BC200 treatment, and as Pb3(CO3)2(OH)2 in BC350. Lead sorption by AC obeyed a single Langmuir model, attributing mainly to surface sorption probably via coordination of Pb d-electron to C==C (pi-electron) and --0--Pb bonds. The biochar was 6 times more effective in Pb sorption than AC, with BC200 being the most effective (up to 680 mmol Pb kg(-1)). The biochar also effectively sorbed atrazine where atrazine was partitioned into its organic phase, whereas atrazine uptake by AC occurred via surface sorption. When Pb and atrazine coexisted, little competition occurred between the two for sorption on biochar, while strong competition was observed on AC. Results from this study indicated that dairy manure can be converted into value-added biochar as effective sorbent for metal and/or organic contaminants.

A review on the forecasting of wind speed and generated power

Abstract: In the world, wind power is rapidly becoming a generation technology of significance. Unpredictability and variability of wind power generation is one of the fundamental difficulties faced by power system operators. Good forecasting tools are urgent needed under the relevant issues associated with the integration of wind energy into the power system. This paper gives a bibliographical survey on the general background of research and developments in the fields of wind speed and wind power forecasting. Based on the assessment of wind power forecasting models, further direction for additional research and application is proposed.

Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis

Abstract: Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.

Flocking of Multi-Agents With a Virtual Leader

Abstract: All agents being informed and the virtual leader traveling at a constant velocity are the two critical assumptions seen in the recent literature on flocking in multi-agent systems. Under these assumptions, Olfati-Saber in a recent IEEE Transactions on Automatic Control paper proposed a flocking algorithm which by incorporating a navigational feedback enables a group of agents to track a virtual leader. This paper revisits the problem of multi-agent flocking in the absence of the above two assumptions. We first show that, even when only a fraction of agents are informed, the Olfati-Saber flocking algorithm still enables all the informed agents to move with the desired constant velocity, and an uninformed agent to also move with the same desired velocity if it can be influenced by the informed agents from time to time during the evolution. Numerical simulation demonstrates that a very small group of the informed agents can cause most of the agents to move with the desired velocity and the larger the informed group is the bigger portion of agents will move with the desired velocity. In the situation where the virtual leader travels with a varying velocity, we propose modification to the Olfati-Saber algorithm and show that the resulting algorithm enables the asymptotic tracking of the virtual leader. That is, the position and velocity of the center of mass of all agents will converge exponentially to those of the virtual leader. The convergent rate is also given.

iPS cells produce viable mice through tetraploid complementation

Abstract: Since iPS (induced pluripotent stem) cells arrived on the scene in 2006, their properties have been measured against the yardstick of the true embryonic stem cells that they mimic. A clutch of recent papers, two of them published in this issue, reports the production of viable adult mice from iPS cells, a notable technical feat that shows that these cells are very close indeed to embryonic cells in their potential to produce cells for all tissues and all organs. Zhao et al. used a technique called tetraploid complementation, in which chimaeric mice are generated from injected pluripotent cells, and the embryonic tissue is derived solely from the injected cells. Boland et al. produced fertile adult mice derived entirely from iPS cells generated by inducible genetic reprogramming of mouse embryonic fibroblasts. The availability of these mice will provide a new resource for the study of iPS cell-derived tissues for both research and cell replacement therapy applications. Induced pluripotent stem (iPS) cells were first created by forced expression of four transcription factors in mouse fibroblasts, a technique that has since been widely used to generate embryonic stem (ES)-cell-like pluripotent cells from a variety of cell types in other species. The generation of several iPS cell lines in mice that are capable of generating viable, fertile live-born progeny by tetraploid complementation — a technique where chimaeric mice are generated using injected pluripotent cells — is now reported. Since the initial description of induced pluripotent stem (iPS) cells created by forced expression of four transcription factors in mouse fibroblasts, the technique has been used to generate embryonic stem (ES)-cell-like pluripotent cells from a variety of cell types in other species, including primates and rat1,2,3,4,5,6. It has become a popular means to reprogram somatic genomes into an embryonic-like pluripotent state, and a preferred alternative to somatic-cell nuclear transfer and somatic-cell fusion with ES cells7,8. However, iPS cell reprogramming remains slow and inefficient. Notably, no live animals have been produced by the most stringent tetraploid complementation assay, indicative of a failure to create fully pluripotent cells. Here we report the generation of several iPS cell lines that are capable of generating viable, fertile live-born progeny by tetraploid complementation. These iPS cells maintain a pluripotent potential that is very close to ES cells generated from in vivo or nuclear transfer embryos. We demonstrate the practicality of using iPS cells as useful tools for the characterization of cellular reprogramming and developmental potency, and confirm that iPS cells can attain true pluripotency that is similar to that of ES cells.

The Effect of Annual Report Readability on Analyst Following and the Properties of Their Earnings Forecasts

Abstract: This study examines the effect of the readability of firm written communication on the behavior of sell-side financial analysts. Using a measure of the readability of corporate 10-K filings, we document that analyst following, the amount of effort incurred to generate their reports, and the informativeness of their reports are greater for firms with less readable 10-Ks. Additionally, we find that less readable 10-Ks are associated with greater dispersion, lower accuracy, and greater overall uncertainty in analyst earnings forecasts. Overall, our results are consistent with the prediction of an increasing demand for analyst services for firms with less readable communication and a greater collective effort by analysts for firms with less readable disclosures. Our results contribute to the understanding of the role of analysts as information intermediaries for investors and the effect of the complexity of written financial communication on the usefulness of this information.

Compressive data gathering for large-scale wireless sensor networks

Abstract: This paper presents the first complete design to apply compressive sampling theory to sensor data gathering for large-scale wireless sensor networks. The successful scheme developed in this research is expected to offer fresh frame of mind for research in both compressive sampling applications and large-scale wireless sensor networks. We consider the scenario in which a large number of sensor nodes are densely deployed and sensor readings are spatially correlated. The proposed compressive data gathering is able to reduce global scale communication cost without introducing intensive computation or complicated transmission control. The load balancing characteristic is capable of extending the lifetime of the entire sensor network as well as individual sensors. Furthermore, the proposed scheme can cope with abnormal sensor readings gracefully. We also carry out the analysis of the network capacity of the proposed compressive data gathering and validate the analysis through ns-2 simulations. More importantly, this novel compressive data gathering has been tested on real sensor data and the results show the efficiency and robustness of the proposed scheme.

Sclerostin Mediates Bone Response to Mechanical Unloading Through Antagonizing Wnt/β‐Catenin Signaling

Abstract: Reduced mechanical stress leads to bone loss, as evidenced by disuse osteoporosis in bedridden patients and astronauts. Osteocytes have been identified as major cells responsible for mechanotransduction; however, the mechanism underlying the response of bone to mechanical unloading remains poorly understood. In this study, we found that mechanical unloading of wildtype mice caused decrease of Wnt/beta-catenin signaling activity accompanied by upregulation of Sost. To further analyze the causal relationship among these events, Sost gene targeting mice were generated. We showed that sclerostin selectively inhibited Wnt/beta-catenin in vivo, and sclerostin suppressed the activity of osteoblast and viability of osteoblasts and osteocytes. Interestingly, Sost(-/-) mice were resistant to mechanical unloading-induced bone loss. Reduction in bone formation in response to unloading was also abrogated in the mutant mice. Moreover, in contrast to wildtype mice, Wnt/beta-catenin signaling was not altered by unloading in Sost(-/-) mice. Those data implied that sclerostin played an essential role in mediating bone response to mechanical unloading, likely through Wnt/beta-catenin signaling. Our findings also indicated sclerostin is a promising target for preventing disuse osteoporosis.

Does the type of ownership control matter? Evidence from China's listed companies

Abstract: By tracing the identity of large shareholders, we group China’s listed companies into those controlled by state asset management bureaus (SAMBs), state owned enterprises (SOEs) affiliated to the central government (SOECGs), SOEs affiliated to the local government (SOELGs), and Private investors. We argue that these distinct types of owners have different objectives and motivations and this will affect how they exercise their control rights over the firms they invest in. In particular, we contend that private ownership of listed firms in China is not necessarily superior to certain types of state ownership. To test our arguments we investigate the relative efficiency of state versus private ownership of listed firms and the efficiency of various forms of state ownership. The empirical results indicate that the operating efficiency of Chinese listed companies varies across the type of controlling shareholder. SOECG controlled firms perform best and SAMB and Private controlled firms perform worst. SOELG controlled firms are in the middle. The results are consistent with our predictions.

Production of offspring from a germline stem cell line derived from neonatal ovaries

Abstract: 6. However, the existence of female germline stem cells (FGSCs) in postnatal mammalian ovaries still remains a controversial issue among reproductive biologists and stem cell researchers 6–10 . We have now established a neonatal mouse FGSC line, with normal karyotype and high telomerase activity, by immunomagnetic isolation and culture for more than 15 months. FGSCs from adult mice were isolated and cultured for more than 6 months. These FGSCs were infected with GFP virus and transplanted into ovaries of infertile mice. Transplanted cells underwent oogenesis and the mice produced offspring that had the GFP transgene. These findings contribute to basic research into oogenesis and stem cell self-renewal and open up new possibilities for use of FGSCs in biotechnology and medicine.

Second Asia-Pacific Consensus Guidelines for Helicobacter Pylori Infection

Abstract: The Asia-Pacific Consensus Conference was convened to review and synthesize the most current information on Helicobacter pylori management so as to update the previously published regional guidelines. The group recognized that in addition to long-established indications, such as peptic ulcer disease, early mucosa-associated lymphoid tissue (MALT) type lymphoma and family history of gastric cancer, H. pylori eradication was also indicated for H. pylori infected patients with functional dyspepsia, in those receiving long-term maintenance proton pump inhibitor (PPI) for gastroesophageal reflux disease, and in cases of unexplained iron deficiency anemia or idiopathic thrombocytopenic purpura. In addition, a population 'test and treat' strategy for H. pylori infection in communities with high incidence of gastric cancer was considered to be an effective strategy for gastric cancer prevention. It was recommended that H. pylori infection should be tested for and eradicated prior to long-term aspirin or non-steroidal anti-inflammatory drug therapy in patients at high risk for ulcers and ulcer-related complications. In Asia, the currently recommended first-line therapy for H. pylori infection is PPI-based triple therapy with amoxicillin/metronidazole and clarithromycin for 7 days, while bismuth-based quadruple therapy is an effective alternative. There appears to be an increasing rate of resistance to clarithromycin and metronidazole in parts of Asia, leading to reduced efficacy of PPI-based triple therapy. There are insufficient data to recommend sequential therapy as an alternative first-line therapy in Asia. Salvage therapies that can be used include: (i) standard triple therapy that has not been previously used; (ii) bismuth-based quadruple therapy; (iii) levofloxacin-based triple therapy; and (iv) rifabutin-based triple therapy. Both CYP2C19 genetic polymorphisms and cigarette smoking can influence future H. pylori eradication rates.

Functionally Graded Materials: Nonlinear Analysis of Plates and Shells

Abstract: Modeling of Functionally Graded Materials and Structures Effective Material Properties of FGMs Reddy's Higher Order Shear Deformation Plate Theory Generalized Karman-Type Nonlinear Equations Nonlinear Bending of Shear Deformable FGM Plates Nonlinear Bending of FGM Plates under Mechanical Loads in Thermal Environments Nonlinear Thermal Bending of FGM Plates due to Heat Conduction Postbuckling of Shear Deformable FGM Plates Postbuckling of FGM Plates with Piezoelectric Actuators under Thermoelectromechanical Loads Thermal Postbuckling Behavior of FGM Plates with Piezoelectric Actuators Postbuckling of Sandwich Plates with FGM Face Sheets in Thermal Environments Nonlinear Vibration of Shear Deformable FGM Plates Nonlinear Vibration of FGM Plates in Thermal Environments Nonlinear Vibration of FGM Plates with Piezoelectric Actuators in Thermal Environments Vibration of Postbuckled Sandwich Plates with FGM Face Sheets in Thermal Environments Postbuckling of Shear Deformable FGM Shells Boundary Layer Theory for the Buckling of FGM Cylindrical Shells Postbuckling Behavior of FGM Cylindrical Shells under Axial Compression Postbuckling Behavior of FGM Cylindrical Shells under External Pressure Postbuckling Behavior of FGM Cylindrical Shells under Torsion Thermal Postbuckling Behavior of FGM Cylindrical Shells Appendices

Recurrence of endometriosis and its control

Abstract: BACKGROUND Although surgery is currently the treatment of choice for managing endometriosis, recurrence poses a formidable challenge. To delay or to eliminate the recurrence is presently an unmet medical need in the management of endometriosis. To this end, proposals to investigate patterns of recurrence, to develop biomarkers for recurrence and to carry out biomarker-based intervention have been made. METHODS Publications pertaining to the recurrence of endometriosis and its related yet unaddressed issues were identified through MEDLINE. The reported recurrence rates, risk factors for recurrence, the effects of post-operative medication and causes of recurrence were reviewed and synthesized. In addition, several poorly explored issues such as time hazard function and mechanisms of recurrence were reviewed. Approaches to the development of biomarkers for recurrence and future intervention are discussed. RESULTS The reported recurrence rate was high, estimated as 21.5% at 2 years and 40-50% at 5 years. Few risk factors for recurrence have been consistently identified, and the evidence on the efficacy of the post-operative use of medication was scanty. The investigation on the patterns of recurrence may provide us with new insight into the possible mechanisms of recurrence and its control. The attempt to identify biomarkers for recurrence has started only very recently. CONCLUSIONS Much research is needed to better understand the patterns of recurrence and risk factors, and to develop biomarkers. One top priority is to develop biomarkers for recurrence, which may provide much needed clues to the possible mechanisms underlying recurrence and would allow the identification of patients with high recurrence risk, and permit for targeted intervention.

Species Variation in the Mechanisms of Mesenchymal Stem Cell‐Mediated Immunosuppression

Abstract: Bone marrow-derived mesenchymal stem cells (MSCs) hold great promise for treating immune disorders because of their immunoregulatory capacity, but the mechanism remains controversial. As we show here, the mechanism of MSC-mediated immunosuppression varies among different species. Immunosuppression by human- or monkey-derived MSCs is mediated by indoleamine 2,3-dioxygenase (IDO), whereas mouse MSCs utilize nitric oxide, under the same culture conditions. When the expression of IDO and inducible nitric oxide synthase (iNOS) were examined in human and mouse MSCs after stimulation with their respective inflammatory cytokines, we found that human MSCs expressed extremely high levels of IDO, and very low levels of iNOS, whereas mouse MSCs expressed abundant iNOS and very little IDO. Immunosuppression by human MSCs was not intrinsic, but was induced by inflammatory cytokines and was chemokine-dependent, as it is in mouse. These findings provide critical information about the immunosuppression of MSCs and for better application of MSCs in treating immune disorders.

Amplified trace gas removal in the troposphere.

Abstract: The degradation of trace gases and pollutants in the troposphere is dominated by their reaction with hydroxyl radicals (OH). The importance of OH rests on its high reactivity, its ubiquitous photochemical production in the sunlit atmosphere, and most importantly on its regeneration in the oxidation chain of the trace gases. In the current understanding, the recycling of OH proceeds through HO2 reacting with NO, thereby forming ozone. A recent field campaign in the Pearl River Delta, China, quantified tropospheric OH and HO2 concentrations and turnover rates by direct measurements. We report that concentrations of OH were three to five times greater than expected, and we propose the existence of a pathway for the regeneration of OH independent of NO, which amplifies the degradation of pollutants without producing ozone.

Biofilm formation and food safety in food industries

Abstract: Biofilms are a self-protection growth pattern of bacteria, which are different from planktonic cells. They have been of considerable interest in food hygiene since biofilms may contain spoilage and pathogenic bacteria which increases post-processing contamination and risk to public health. In addition, biofilm cells are more resistant to cleaning and disinfection processes in the food industry. Biofilm formation is a complex process in which genetic mechanisms and numerous factors such as the properties of substratum and bacterial cell surfaces are involved. In order to further understand the intricate mechanisms behind biofilm formation, various techniques including physical, chemical and molecular methods have been used to establish the possible model of biofilm formation in food industry. Therefore, the importance of bacterial biofilms in food safety control and biofilm formation mechanisms will be discussed in this paper. The objective of all efforts is to provide new insights for developing biofilm-free food-processing systems.

Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21

Abstract: We report the first large genome-wide association study (GWAS) in a Chinese population to identify susceptibility variants for psoriasis using a two-stage case-control design. In the first stage, we carried out a genome-wide association analysis in 1,139 cases and 1,132 controls of Chinese Han ancestry using Illumina Human 610-Quad BeadChips. In the second stage, we took top SNPs forward for replication in two independent samples of 5,182 cases and 6,516 controls of Chinese Han ancestry, and 539 cases and 824 controls of Chinese Uygur ancestry. In addition to the strong replication for two known susceptibility loci MHC (rs1265181, P = 1.93 x 10(-208), OR = 22.62) and IL12B (rs3213094, P(combined) = 2.58 x 10(-26), OR = 0.78), we identified a new susceptibility locus within the LCE gene cluster on 1q21 (rs4085613, P(combined) = 6.69 x 10(-30), OR = 0.76).