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1.  Blood leukocyte Alu and LINE-1 methylation and gastric cancer risk in the Shanghai Women's Health Study 
British Journal of Cancer  2011;106(3):585-591.
Background:
Recent data suggest a link between blood leukocyte DNA methylation, and cancer risk. However, reports on DNA methylation from a prospective study are unavailable for gastric cancer.
Methods:
We explored the association between methylation in pre-diagnostic blood leukocyte DNA and gastric cancer risk in a case–control study nested in the prospective Shanghai Women's Health Study cohort. Incident gastric cancer cases (n=192) and matched controls (n=384) were included in the study. Methylation of Alu and long interspersed nucleotide elements (LINE)-1 were evaluated using bisulphite pyrosequencing. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated from logistic regression adjusting for potential confounders.
Results:
Alu methylation was inversely associated with gastric cancer risk, mainly among cases diagnosed one or more years after blood collection. After excluding cases diagnosed during the first year of follow-up, the ORs for the third, second, and first quartiles of Alu methylation compared with the highest quartile were 2.43 (1.43–4.13), 1.47(0.85–2.57), and 2.22 (1.28–3.84), respectively. This association appeared to be modified by dietary intake, particularly isoflavone. In contrast, LINE-1 methylation levels were not associated with gastric cancer risk.
Conclusion:
Evidence from this prospective study is consistent with the hypothesis that DNA hypomethylation in blood leukocytes may be related to cancer risk, including risk of gastric cancer.
doi:10.1038/bjc.2011.562
PMCID: PMC3273339  PMID: 22173668
gastric cancer; DNA methylation; leukocyte
2.  Prognostic characteristics of duodenal gastrointestinal stromal tumours 
The British Journal of Surgery  2015;102(8):959-964.
Background
This study evaluated the clinical characteristics, surgical procedures and prognosis of duodenal gastrointestinal stromal tumours (GISTs).
Methods
Patients with a diagnosis of primary duodenal GIST treated between January 2000 and December 2012 were analysed. Patients with gastric and small intestinal GISTs were chosen as control groups according to the following parameters: age, tumour size, mitotic index and adjuvant imatinib therapy. Operative procedures for patients with duodenal GIST included pancreaticoduodenectomy or limited resection. Disease-free survival (DFS) was calculated using Kaplan–Meier analysis.
Results
Some 71 patients with duodenal, 71 with gastric and 70 with small intestinal GISTs were included in the study. DFS of patients with duodenal GIST was shorter than that of patients with gastric GIST (3-year DFS 84 versus 94 per cent; hazard ratio (HR) 3.67, 95 per cent c.i. 1.21 to 11.16; P = 0.014), but was similar to that of patients with small intestinal GIST (3-year DFS 84 versus 81 per cent; HR 0.75, 0.37 to 1.51; P = 0.491). Patients who underwent pancreaticoduodenectomy were older, and had larger tumours and a higher mitotic index than patients who had limited resection. The 3-year DFS was 93 per cent among patients who had limited resection compared with 64 per cent for those who underwent PD (HR 0.18, 0.06 to 0.59; P = 0.001).
Conclusion
The prognosis of duodenal GISTs is similar to that of small intestinal GISTs.
Prognosis no different than for small bowel gastrointestinal stromal tumours
doi:10.1002/bjs.9831
PMCID: PMC4682471  PMID: 25980461
3.  Treatment of patients with diabetic peripheral neuropathic pain in China: a double-blind randomised trial of duloxetine vs. placebo 
Background
Duloxetine has been approved in the United States, European Union and some Asian countries for the treatment of diabetic peripheral neuropathic pain (DPNP). We assessed the efficacy and safety of duloxetine (60 mg once daily) compared with placebo in Chinese patients suffering from DPNP.
Methods
This was a phase 3, multicenter, randomised, double-blind, parallel, placebo-controlled, 12-week trial of the treatment of DPNP with duloxetine. Subjects were male and female outpatients ≥ 18 years of age with DPNP, as assessed by the Michigan Neuropathy Screening Instrument, and had a rating of ≥ 4 on the Brief Pain Inventory-Modified Short Form-Severity weekly average pain item. The primary efficacy measure was the reduction in pain severity from baseline to 12 weeks, as measured by the weekly mean of 24-h average pain ratings recorded in the patient’s diary. Mean changes from baseline in efficacy measures were analysed by a restricted maximum likelihood-based, mixed-effects model repeated measures approach and by analysis of covariance.
Results
Of the 405 patients randomised, 203 patients were assigned to duloxetine 60 mg once daily and 202 patients were assigned to placebo. Duloxetine-treated patients showed significantly greater pain relief on 24-h average pain ratings compared with placebo-treated patients each week of the 12-week study period [week 12: least squares (LS) mean change duloxetine: −2.40, placebo: −1.97; LS mean change difference (95% confidence interval) = −0.43 (−0.82, −0.04), p = 0.030]. Compared with placebo, patients treated with duloxetine experienced higher rates of nausea (p = 0.010), somnolence (p < 0.001) and asthenia (p = 0.002).
Conclusions
Duloxetine-treated patients showed significantly greater pain relief compared with placebo-treated patients over the 12-week study period. Duloxetine was shown in Chinese patients to have a safety profile similar to that found in previous duloxetine trials.
doi:10.1111/ijcp.12641
PMCID: PMC4682474  PMID: 25939897
4.  An unusual odontogenic myxoma in mandible and submandibular region: a rare case report 
Dentomaxillofacial Radiology  2014;43(8):20140087.
An otherwise healthy 14-year-old male was referred to our hospital for the evaluation of a mass that was noticed 2 months previously. The mass was located in the left submandibular area. Comprehensive imaging examinations including panoramic radiography, CT and positron emission tomography-CT were performed. Appropriate surgical management and histopathological examination were taken for the patient. Histopathological examination demonstrated an odontogenic myxoma.
doi:10.1259/dmfr.20140087
PMCID: PMC4240259  PMID: 25270061
myxoma; odontogenic tumour; manifestation; radiology
5.  Relationship between Leukopenia and Intercellular Adhesion Molecules in Graves' Disease 
The West Indian Medical Journal  2015;63(6):601-604.
ABSTRACT
Objective:
Changes in soluble intercellular adhesion molecule-1 (sICAM-1) and E-selectin levels as well as leukocyte count were examined in this study to explore the relationship between leukopenia and ICAMs in Graves' disease (GD).
Methods:
Fasting blood samples were obtained from 37 GD patients with normal leukocytes and 32 GD patients with leukopenia. Enzyme-linked immunosorbent assay (ELISA) was performed to determine serum sICAM-1 and E-selectin levels for comparison. The same analyses were repeated for the GD patients with leukopenia after glucocorticoid treatment (15 mg/day to 30 mg/day prednisone).
Results:
The ELISA results showed that E-selectin levels were higher in GD patients with leukopenia than those with normal leukocytes (p < 0.05), but these levels decreased after glucocorticoid (prednisone) treatment (p < 0.05). No significant change in sICAM-1 levels was observed (p = 0.12). Correlation analysis showed that leukocyte count and E-selectin were negatively correlated (r = −0.778; p < 0.05).
Conclusion:
E-selectin may have an important function in GD with leukopenia, and glucocorticoids (prednisone) could decrease E-selectin level, which may be a new therapy target for GD with leukopenia.
doi:10.7727/wimj.2013.113
PMCID: PMC4663960  PMID: 25803374
Graves' disease; hyperthyroidism; intercellular adhesion molecule; leukopenia
6.  Platelet factor 4 protects bone marrow mesenchymal stem cells from acute radiation injury 
The British Journal of Radiology  2014;87(1040):20140184.
Objective:
The aim of this study was to find a new radiation protector, platelet factor 4 (PF4) and to identify its effect on haemopoietic microenvironment in vitro and in vivo.
Methods:
Radiation damage on bone marrow mesenchymal stem cells ex and in vitro was set up as models. Growth curve analysis, clonogenic survival assay, FACSCalibur™ (BD Immunocytometry Systems, San Jose, CA), 5-ethynyl-2′-deoxyuridine immunofluorescence staining and quantitative reverse transcription–polymerase chain reaction were employed to assess the characterization of bone marrow mesenchymal stem cells (BMSCs), proliferation, apoptosis, cell cycle and gene expression.
Results:
A dose- and time-dependent enhancement of cell viability and survival was observed for PF4 treatment along with 500 cGy γ-radiation in vitro. The same phenomena were noted in vivo, including enhancement of adherence and proliferation ability while inhibition of cell apoptosis, which were associated with a short-term decrease in the G0/G1 ratio owing to S phase arrest. These were accompanied with enhanced Bcl-2 expression and p53/p21 loss.
Conclusion:
These results uncover that PF4 might be a novel therapeutic approach, which could reduce DNA damage and increase survival of BMSCs, in part, by inhibiting p53/p21 axis and facilitating DNA damage repair.
Advances in knowledge:
This study explores the feasibility of a new radioprotector and hence may be clinically important.
doi:10.1259/bjr.20140184
PMCID: PMC4112396  PMID: 24922360
7.  Measurement of the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta _c(1S)$$\end{document}ηc(1S) production cross-section in proton–proton collisions via the decay \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\eta _c(1S)\,{\rightarrow } \,{{{ p}}} \overline{{{{ p}}}}} $$\end{document}ηc(1S)→pp¯ 
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V. | Göbel, C. | Golubkov, D. | Golutvin, A. | Gomes, A. | Gotti, C. | Grabalosa Gándara, M. | Graciani Diaz, R. | Granado Cardoso, L. A. | Graugés, E. | Graziani, G. | Grecu, A. | Greening, E. | Gregson, S. | Griffith, P. | Grillo, L. | Grünberg, O. | Gui, B. | Gushchin, E. | Guz, Yu. | Gys, T. | Hadjivasiliou, C. | Haefeli, G. | Haen, C. | Haines, S. C. | Hall, S. | Hamilton, B. | Hampson, T. | Han, X. | Hansmann-Menzemer, S. | Harnew, N. | Harnew, S. T. | Harrison, J. | He, J. | Head, T. | Heijne, V. | Hennessy, K. | Henrard, P. | Henry, L. | Hernando Morata, J. A. | van Herwijnen, E. | Heß, M. | Hicheur, A. | Hill, D. | Hoballah, M. | Hombach, C. | Hulsbergen, W. | Hunt, P. | Hussain, N. | Hutchcroft, D. | Hynds, D. | Idzik, M. | Ilten, P. | Jacobsson, R. | Jaeger, A. | Jalocha, J. | Jans, E. | Jaton, P. | Jawahery, A. | Jing, F. | John, M. | Johnson, D. | Jones, C. R. | Joram, C. | Jost, B. | Jurik, N. | Kaballo, M. | Kandybei, S. | Kanso, W. | Karacson, M. | Karbach, T. 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The production of the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta _c (1S)$$\end{document}ηc(1S) state in proton-proton collisions is probed via its decay to the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p\overline{p}$$\end{document}pp¯ final state with the LHCb detector, in the rapidity range \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.0 < y < 4.5$$\end{document}2.0 6.5 \mathrm{{\,GeV/}{ c}} $$\end{document}pT>6.5GeV/c. The cross-section for prompt production of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta _c (1S)$$\end{document}ηc(1S) mesons relative to the prompt \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{ J}}/{\psi } $$\end{document}J/ψ cross-section is measured, for the first time, to be \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sigma _{\eta _c (1S)}/\sigma _{{{{ J}}/{\psi }}} = 1.74\, \pm \,0.29\, \pm \, 0.28\, \pm \,0.18 _{{\mathcal{B}}}$$\end{document}σηc(1S)/σJ/ψ=1.74±0.29±0.28±0.18B at a centre-of-mass energy \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\sqrt{s}} = 7 {~\mathrm{TeV}}$$\end{document}s=7TeV using data corresponding to an integrated luminosity of 0.7 fb\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-1}$$\end{document}-1, and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sigma _{\eta _c (1S)}/\sigma _{{{{ J}}/{\psi }}} = 1.60 \pm 0.29 \pm 0.25 \pm 0.17 _{{\mathcal{B}}}$$\end{document}σηc(1S)/σJ/ψ=1.60±0.29±0.25±0.17B at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\sqrt{s}} = 8 {~\mathrm{TeV}}$$\end{document}s=8TeV using 2.0 fb\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-1}$$\end{document}-1. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta _c (1S)$$\end{document}ηc(1S) and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{ J}}/{\psi } $$\end{document}J/ψ decays to the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p\overline{p}$$\end{document}pp¯ final state. In addition, the inclusive branching fraction of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${b} $$\end{document}b-hadron decays into \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta _c (1S)$$\end{document}ηc(1S) mesons is measured, for the first time, to be \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathcal{B}}( b {\rightarrow } \eta _c X ) = (4.88\, \pm \,0.64\, \pm \,0.29\, \pm \, 0.67 _{{\mathcal{B}}}) \times 10^{-3}$$\end{document}B(b→ηcX)=(4.88±0.64±0.29±0.67B)×10-3, where the third uncertainty includes also the uncertainty on the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{ J}}/{\psi } $$\end{document}J/ψ inclusive branching fraction from \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${b} $$\end{document}b-hadron decays. The difference between the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{ J}}/{\psi } $$\end{document}J/ψ and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta _c (1S)$$\end{document}ηc(1S) meson masses is determined to be \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$114.7 \pm 1.5 \pm 0.1 {\mathrm {\,MeV\!/}c^2} $$\end{document}114.7±1.5±0.1MeV/c2.
doi:10.1140/epjc/s10052-015-3502-x
PMCID: PMC4498677  PMID: 26190939
8.  Averaging improves strain images of the biceps brachii using quasi-static ultrasound elastography 
The British Journal of Radiology  2014;87(1039):20130624.
Objective:
Quasi-static ultrasound elastography is a technique for measuring tissue deformation (strain) under externally applied loading and can be used to identify the presence of abnormalities. The objective of this study was to demonstrate the efficacy of averaging strain images from repeated compression cycles in mitigating user-induced error using quasi-static ultrasound elastography.
Methods:
Freehand compressions were performed with an ultrasound transducer on the biceps brachii of nine participants (five males and four females), as well as with a custom automated compression system. Sets of strain images from the freehand techniques were averaged to create single representative images and compared against strain images from the automated compressions using both qualitative and quantitative metrics.
Results:
Significant improvements in intra-operator repeatability and interoperator reproducibility can be achieved by averaging strain images from four to eight repeated compressions. The resulting strain images did not lose significant image data compared with strain images from single automated compressions.
Conclusion:
Averaging is introduced as a feasible and appropriate technique to improve strain image quality without sacrificing important image data.
Advances in knowledge:
Simple averaging of multiple freehand elastography measures can achieve a similar degree of accuracy, repeatability and reproducibility as that of more awkward and expensive automated methods. The resulting elastograms can be used to obtain a more accurate and complete diagnosis without additional cost to the doctor or the patient.
doi:10.1259/bjr.20130624
PMCID: PMC4075574  PMID: 24758309
9.  Search for long-lived particles decaying to jet pairs 
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A search is presented for long-lived particles with a mass between 25 and 50 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathrm{GeV}/\mathrm{c}^{2}$$\end{document}GeV/c2 and a lifetime between 1 and 200\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathrm{\,ps}$$\end{document}ps in a sample of proton–proton collisions at a centre-of-mass energy of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}=7$$\end{document}s=7 TeV, corresponding to an integrated luminosity of 0.62 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\text{ fb }^{-1}$$\end{document}fb-1, collected by the LHCb detector. The particles are assumed to be pair-produced by the decay of a standard model-like Higgs boson. The experimental signature of the long-lived particle is a displaced vertex with two associated jets. No excess above the background is observed and limits are set on the production cross-section as a function of the long-lived particle mass and lifetime.
doi:10.1140/epjc/s10052-015-3344-6
PMCID: PMC4423877  PMID: 25983649
10.  Vaginal deployment and tenofovir delivery by microbicide gels 
Gels are one of the soft material platforms being evaluated to deliver topically acting anti-HIV drugs (microbicides) to the vaginal environment. For each drug, its loaded concentration, gel properties and applied volume, and frequency of dosing can be designed to optimize PK and, thence, PD. These factors also impact user sensory perceptions and acceptability. Deterministic compartmental modeling of vaginal deployment and drug delivery achieved by test gels can help delineate how multiple parameters characterizing drug, vehicle, vaginal environment, and dosing govern details of PK and PD and also gel leakage from the canal. Such microbicide delivery is a transport process combining convection, e.g., from gel spreading along the vaginal canal, with drug diffusion in multiple compartments, including gel, mucosal epithelium, and stroma. The present work builds upon prior models of gel coating flows and drug diffusion (without convection) in the vaginal environment. It combines and extends these initial approaches in several key ways, including: (1) linking convective drug transport due to gel spreading with drug diffusion and (2) accounting for natural variations in dimensions of the canal and the site of gel placement therein. Results are obtained for a leading microbicide drug, tenofovir, delivered by three prototype microbicide gels, with a range of rheological properties. The model includes phosphorylation of tenofovir to tenofovir diphosphate (which manifests reverse transcriptase activity in host cells), the stromal concentration distributions of which are related to reference prophylactic values against HIV. This yields a computed summary measure related to gel protection (“percent protected”). Analyses illustrate tradeoffs amongst gel properties, drug loading, volume and site of placement, and vaginal dimensions, in the time and space history of gel distribution and tenofovir transport to sites of its anti-HIV action and concentrations and potential prophylactic actions of tenofovir diphosphate therein.
Electronic supplementary material
The online version of this article (doi:10.1007/s13346-015-0227-1) contains supplementary material, which is available to authorized users.
doi:10.1007/s13346-015-0227-1
PMCID: PMC4420798  PMID: 25874971
Microbicide; Compartmental model; Pharmacokinetics; Pharmacodynamics; Gel; Vagina; Tenofovir
11.  Tempo and mode of recurrent polyploidization in the Carassius auratus species complex (Cypriniformes, Cyprinidae) 
Heredity  2014;112(4):415-427.
Polyploidization is an evolutionarily rare but important mechanism in both plants and animals because it increases genetic diversity. Goldfish of the Carassius auratus species complex can be tetraploids, hexaploids and octaploids. Polyploidization events have occurred repeatedly in goldfish, yet the extent of this phenomenon and its phyletic history are poorly understood. We explore the origin, tempo and frequency of polyploidization in Chinese and Japanese goldfish using both mitochondrial (mtDNA) and nuclear DNA sequences from up to 1202 individuals including the outgroup taxon, Cyprinus carpio. Analyses of de novo nuclear gene data resolve two clusters of alleles and the pattern supports the prior hypothesis of an ancient allotetraploidization for Carassius. Alleles shared by tetraploid and hexaploid individuals indicate recent autoploidizations within the C. auratus complex. Sympatric tetraploids and hexaploids share mtDNA haplotypes and these frequently occur independently within six well-supported lineages and sublineages on a small spatial scale. Gene flow estimates (Fst values) indicate that hexaploids differ only slightly from sympatric tetraploids, if at all. In contrast, allopatric populations of tetraploids and hexaploids differ from one another to a far greater extent. Gene flow between sampled localities appears to be limited. Coalescence-based time estimations for hexaploids reveal that the oldest lineage within any sampled locality is around one million years old, which is very young. Sympatric, recurrent autoploidization occurs in all sampled populations of the C. auratus complex. Goldfish experience polyploidization events more frequently than any other vertebrate.
doi:10.1038/hdy.2013.121
PMCID: PMC3966126  PMID: 24398883
goldfish; autopolyploidization; tetraploid; hexaploid
12.  Film size-dependent voltage-modulated magnetism in multiferroic heterostructures 
The electric-voltage-modulated magnetism in multiferroic heterostructures, also known as the converse magnetoelectric (ME) coupling, has drawn increasing research interest recently owing to its great potential applications in future low-power, high-speed electronic and/or spintronic devices, such as magnetic memory and computer logic. In this article, based on combined theoretical analysis and experimental demonstration, we investigate the film size dependence of such converse ME coupling in multiferroic magnetic/ferroelectric heterostructures, as well as exploring the interaction between two relating coupling mechanisms that are the interfacial strain and possibly the charge effects. We also briefly discuss some issues for the next step and describe new device prototypes that can be enabled by this technology.
doi:10.1098/rsta.2012.0444
PMCID: PMC3895976  PMID: 24421375
multiferroic heterostructures; size dependence; magnetoelectric; magneto-optical Kerr effect; domain dynamics
13.  FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium 
Agarwal, D | Pineda, S | Michailidou, K | Herranz, J | Pita, G | Moreno, L T | Alonso, M R | Dennis, J | Wang, Q | Bolla, M K | Meyer, K B | Menéndez-Rodríguez, P | Hardisson, D | Mendiola, M | González-Neira, A | Lindblom, A | Margolin, S | Swerdlow, A | Ashworth, A | Orr, N | Jones, M | Matsuo, K | Ito, H | Iwata, H | Kondo, N | Hartman, M | Hui, M | Lim, W Y | T-C Iau, P | Sawyer, E | Tomlinson, I | Kerin, M | Miller, N | Kang, D | Choi, J-Y | Park, S K | Noh, D-Y | Hopper, J L | Schmidt, D F | Makalic, E | Southey, M C | Teo, S H | Yip, C H | Sivanandan, K | Tay, W-T | Brauch, H | Brüning, T | Hamann, U | Dunning, A M | Shah, M | Andrulis, I L | Knight, J A | Glendon, G | Tchatchou, S | Schmidt, M K | Broeks, A | Rosenberg, E H | van't Veer, L J | Fasching, P A | Renner, S P | Ekici, A B | Beckmann, M W | Shen, C-Y | Hsiung, C-N | Yu, J-C | Hou, M-F | Blot, W | Cai, Q | Wu, A H | Tseng, C-C | Van Den Berg, D | Stram, D O | Cox, A | Brock, I W | Reed, M W R | Muir, K | Lophatananon, A | Stewart-Brown, S | Siriwanarangsan, P | Zheng, W | Deming-Halverson, S | Shrubsole, M J | Long, J | Shu, X-O | Lu, W | Gao, Y-T | Zhang, B | Radice, P | Peterlongo, P | Manoukian, S | Mariette, F | Sangrajrang, S | McKay, J | Couch, F J | Toland, A E | Yannoukakos, D | Fletcher, O | Johnson, N | Silva, I dos Santos | Peto, J | Marme, F | Burwinkel, B | Guénel, P | Truong, T | Sanchez, M | Mulot, C | Bojesen, S E | Nordestgaard, B G | Flyer, H | Brenner, H | Dieffenbach, A K | Arndt, V | Stegmaier, C | Mannermaa, A | Kataja, V | Kosma, V-M | Hartikainen, J M | Lambrechts, D | Yesilyurt, B T | Floris, G | Leunen, K | Chang-Claude, J | Rudolph, A | Seibold, P | Flesch-Janys, D | Wang, X | Olson, J E | Vachon, C | Purrington, K | Giles, G G | Severi, G | Baglietto, L | Haiman, C A | Henderson, B E | Schumacher, F | Le Marchand, L | Simard, J | Dumont, M | Goldberg, M S | Labrèche, F | Winqvist, R | Pylkäs, K | Jukkola-Vuorinen, A | Grip, M | Devilee, P | Tollenaar, R A E M | Seynaeve, C | García-Closas, M | Chanock, S J | Lissowska, J | Figueroa, J D | Czene, K | Eriksson, M | Humphreys, K | Darabi, H | Hooning, M J | Kriege, M | Collée, J M | Tilanus-Linthorst, M | Li, J | Jakubowska, A | Lubinski, J | Jaworska-Bieniek, K | Durda, K | Nevanlinna, H | Muranen, T A | Aittomäki, K | Blomqvist, C | Bogdanova, N | Dörk, T | Hall, P | Chenevix-Trench, G | Easton, D F | Pharoah, P D P | Arias-Perez, J I | Zamora, P | Benítez, J | Milne, R L
British Journal of Cancer  2014;110(4):1088-1100.
Background:
Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium.
Methods:
Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression.
Results:
Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02–1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2.
Conclusion:
Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.
doi:10.1038/bjc.2013.769
PMCID: PMC3929867  PMID: 24548884
breast cancer; SNP; FGF receptors; susceptibility; disease subtypes
14.  Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case–Control Consortium (PanC4) 
Annals of Oncology  2013;24(11):2903-2910.
Background
Peptic ulcer and its treatments have been associated to pancreatic cancer risk, although the evidence is inconsistent.
Methods
We pooled 10 case–control studies within the Pancreatic Cancer Case–control Consortium (PanC4), including 4717 pancreatic cancer cases and 9374 controls, and estimated summary odds ratios (OR) using multivariable logistic regression models.
Results
The OR for pancreatic cancer was 1.10 [95% confidence interval (CI) 0.98–1.23] for history of ulcer (OR = 1.08 for gastric and 0.97 for duodenal ulcer). The association was stronger for a diagnosis within 2 years before cancer diagnosis (OR = 2.43 for peptic, 1.75 for gastric, and 1.98 for duodenal ulcer). The OR was 1.53 (95% CI 1.15–2.03) for history of gastrectomy; however, the excess risk was limited to a gastrectomy within 2 years before cancer diagnosis (OR = 6.18, 95% CI 1.82–20.96), while no significant increased risk was observed for longer time since gastrectomy. No associations were observed for pharmacological treatments for ulcer, such as antacids, H2-receptor antagonists, or proton-pump inhibitors.
Conclusions
This uniquely large collaborative study does not support the hypothesis that peptic ulcer and its treatment materially affect pancreatic cancer risk. The increased risk for short-term history of ulcer and gastrectomy suggests that any such association is due to increased cancer surveillance.
doi:10.1093/annonc/mdt336
PMCID: PMC3811904  PMID: 23970016
anti-ulcer drugs; case–control study; gastrectomy; pancreatic cancer; peptic ulcer; pooled analysis
15.  Anthropometric measures and epithelial ovarian cancer risk among Chinese women: results from the Shanghai Women's Health Study 
British Journal of Cancer  2013;109(3):751-755.
Background:
Studies of anthropometric measures and ovarian cancer risk have predominantly included women of European descent with mixed findings.
Methods:
Data from the prospective Shanghai Women's Health Study (SWHS) were used to evaluate associations between anthropometric measures and risk of epithelial ovarian cancer (EOC). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression.
Results:
A total of 152 EOC cases occurred among 70 258 women. Increasing quartiles of weight, hip circumference, and weight gain during adulthood were associated with significantly increased EOC risks. Body mass index (BMI) was also associated; overweight (25⩽BMI<29.99) and obese women (BMI⩾30.0) had significantly increased risks (HR: 1.49, 95% CI: 1.05, 2.13, and HR: 2.42, 95% CI: 1.37, 4.28, respectively). No significant associations were observed for height, waist circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHER).
Conclusion:
Results from this large prospective study of Chinese women support the hypothesis that general adiposity contributes to the aetiology of ovarian cancer.
doi:10.1038/bjc.2013.384
PMCID: PMC3738128  PMID: 23860524
adiposity; obesity; body mass index; ovarian cancer; prospective cohort
16.  Aplasia cutis congenita of eyelid: case report 
Eye  2013;27(8):992-994.
doi:10.1038/eye.2013.104
PMCID: PMC3740306  PMID: 23703630
17.  Cruciferous vegetables consumption and the risk of female lung cancer: a prospective study and a meta-analysis 
Annals of Oncology  2013;24(7):1918-1924.
Background
Epidemiological studies evaluating the association between cruciferous vegetables (CVs) intake and female lung cancer risk have produced inconsistent results.
Patients and methods
This study followed 74 914 Chinese women aged 40–70 years who participated in the Shanghai Women's Health Study. CV intake was assessed through a validated food-frequency questionnaire (FFQ) at baseline and reassessed during follow-up. Hazard ratios (HRs) and 95% confidence interval (CIs) were estimated by using Cox proportional hazards models. Furthermore, we carried out a meta-analysis of all observational studies until December 2011.
Results
After excluding the first 2 years of follow-up, 417 women developed lung cancer over a mean of 11.1 years of follow-up. An inverse association of borderline statistical significance was observed between CV consumption and female lung cancer risk, with HR for the highest compared with the lowest quartiles of 0.73 (95% CI 0.54–1.00, P trend = 0.1607). The association was strengthened in analyses restricting to never smokers, with the corresponding HR of 0.59 (95% CI 0.40–0.87, P trend = 0.0510). The finding of an inverse association between CV intake and lung cancer risk in women was supported by our meta-analysis of 10 included studies.
Conclusions
Our study suggests that CV consumption may reduce the risk of lung cancer in women, particularly among never smokers.
doi:10.1093/annonc/mdt119
PMCID: PMC3690909  PMID: 23553059
cruciferous vegetable; lung cancer; meta-analysis; prospective study; women
18.  Prospective evaluation of type 2 diabetes mellitus on the risk of primary liver cancer in Chinese men and women 
Annals of Oncology  2013;24(6):1679-1685.
Background
No prospective study has investigated the relationship between type 2 diabetes mellitus (T2DM) and the risk of primary liver cancer (PLC) in mainland China, and little is known about the effect of diabetes duration on PLC risk.
Design
Data from two population-based cohorts (the Shanghai Men's Health Study, SMHS, 2002–2006 and the Shanghai Women's Health Study, SWHS, 1996–2000) were thus used to assess the associations among T2DM, diabetes duration and PLC risk in Chinese population.
Results
During follow-up through 2009, 344 incident PLC cases were identified among 60 183 men and 73 105 women. T2DM is significantly associated with the increased risk of PLC in both men [hazard ratio (HR) = 1.63, 95% confidence interval (CI) 1.06–2.51] and women (HR = 1.64, 95% CI 1.03–2.61). The highest risk of incident liver cancer was observed in the first 5 years after diabetes diagnosis, and decreased substantially with the prolonged diabetes duration (Ptrend < 0.001). No synergistic interaction in the development of PLC was found between diabetes and other known risk factors.
Conclusions
T2DM is associated with the increased risk of subsequent liver cancer within 5 years after diagnosis in Chinese population, suggesting that hyperinsulinaemia rather than hyperglycaemia is more likely to be a primary mediator for this association.
doi:10.1093/annonc/mdt017
PMCID: PMC3660077  PMID: 23406734
China; cohort study; primary liver cancer; type 2 diabetes
19.  LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis 
Hou, P | Zhao, Y | Li, Z | Yao, R | Ma, M | Gao, Y | Zhao, L | Zhang, Y | Huang, B | Lu, J
Cell Death & Disease  2014;5(6):e1287-.
LncRNAs have critical roles in various biological processes ranging from embryonic development to human diseases, including cancer progression, although their detailed mechanistic functions remain illusive. The lncRNA linc-ROR has been shown to contribute to the maintenance of induced pluripotent stem cells and embryonic stem cells. In this study, we discovered that linc-ROR was upregulated in breast tumor samples, and ectopic overexpression of linc-ROR in immortalized human mammary epithelial cells induced an epithelial-to-mesenchymal transition (EMT) program. Moreover, we showed that linc-ROR enhanced breast cancer cell migration and invasion, which was accompanied by generation of stem cell properties. Contrarily, silencing of linc-ROR repressed breast tumor growth and lung metastasis in vivo. Mechanistically, our data revealed that linc-ROR was associated with miRNPs and functioned as a competing endogenous RNA to mi-205. Specifically, linc-ROR prevented the degradation of mir-205 target genes, including the EMT inducer ZEB2. Thus our results indicate that linc-ROR functions as an important regulator of EMT and can promote breast cancer progression and metastasis through regulation of miRNAs. Potentially, the findings of this study implicate the relevance of linc-ROR as a possible therapeutic target for aggressive and metastatic breast cancers.
doi:10.1038/cddis.2014.249
PMCID: PMC4611722  PMID: 24922071
20.  Measurement of charged particle multiplicities and densities in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$pp$$\end{document}pp collisions at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}=7\;$$\end{document}s=7TeV in the forward region 
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Charged particle multiplicities are studied in proton–proton collisions in the forward region at a centre-of-mass energy of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s} = 7\;$$\end{document}s=7TeV with data collected by the LHCb detector. The forward spectrometer allows access to a kinematic range of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2.0<\eta <4.8$$\end{document}2.0<η<4.8 in pseudorapidity, momenta greater than \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2\;\text{ GeV/ }c$$\end{document}2GeV/c and transverse momenta greater than \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$0.2\;\text{ GeV/ }c$$\end{document}0.2GeV/c. The measurements are performed using events with at least one charged particle in the kinematic acceptance. The results are presented as functions of pseudorapidity and transverse momentum and are compared to predictions from several Monte Carlo event generators.
doi:10.1140/epjc/s10052-014-2888-1
PMCID: PMC4371048  PMID: 25814891
21.  Measurement of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\psi {(2S)} $$\end{document}ψ(2S) polarisation in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$pp$$\end{document}pp collisions at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}$$\end{document}s = 7 TeV 
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The polarisation of prompt \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\psi {(2S)} $$\end{document}ψ(2S) mesons is measured by performing an angular analysis of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\psi {(2S)} \!\rightarrow \mu ^+\mu ^- $$\end{document}ψ(2S)→μ+μ- decays using proton-proton collision data, corresponding to an integrated luminosity of 1.0\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\,\text{ fb }^{-1} $$\end{document}fb-1, collected by the LHCb detector at a centre-of-mass energy of 7 TeV. The polarisation is measured in bins of transverse momentum \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p_\mathrm{T} $$\end{document}pT and rapidity \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$y$$\end{document}y in the kinematic region \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$3.5< p_\mathrm{T} <15{\mathrm {\,GeV\!/}c} $$\end{document}3.5
doi:10.1140/epjc/s10052-014-2872-9
PMCID: PMC4370868  PMID: 25814889
Lu, D | Joshi, A | Li, H | Zhang, N | Ren, M M | Gao, Y | Wada, R | Jin, J Y
Model-based meta-analysis of dose response is a sophisticated method to guide dose and regimen selection. In this report, the effects of paclitaxel dose and regimen (weekly or every 3 weeks) on the efficacy and safety in cancer patients were quantified by model-based meta-analysis of 29 monotherapy trials. Logistic regression models were developed to assess the relationship between dose and objective response rate or neutropenia rate. Survival models were developed to assess the relationship between dose and overall survival or progression-free survival. Paclitaxel efficacy (e.g., objective response rate, median overall survival, and progression-free survival) is correlated with average dose per week (mg/m2/week), whereas safety (e.g., neutropenia rate) is correlated with dose per administration (mg/m2). Weekly paclitaxel regimen at 65–80 mg/m2 is supported to have comparable to better efficacy and lower neutropenia incidence than an every-3-week regimen at 175 mg/m2.
doi:10.1038/psp.2014.14
PMCID: PMC4055787  PMID: 24850445
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The lifetime of the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${B} _{c} ^+$$\end{document}Bc+ meson is measured using semileptonic decays having a \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$J/\psi $$\end{document}J/ψ meson and a muon in the final state. The data, corresponding to an integrated luminosity of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2 \text{ fb }^{-1} $$\end{document}2fb-1, are collected by the LHCb detector in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$pp$$\end{document}pp collisions at a centre-of-mass energy of 8 TeV. The measured lifetime is \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\begin{aligned} \tau = 509\pm 8\pm 12\mathrm {~fs}, \end{aligned}$$\end{document}τ=509±8±12fs,where the first uncertainty is statistical and the second is systematic.
doi:10.1140/epjc/s10052-014-2839-x
PMCID: PMC4370795  PMID: 25814888
Human Reproduction (Oxford, England)  2013;28(4):1135-1143.
STUDY QUESTION
Do genetic polymorphisms which influence age at menarche in women of European ancestry also influence women of Chinese ancestry?
SUMMARY ANSWER
Many genetic variants influencing age at menarche in European populations appear to impact Chinese populations in a similar manner.
WHAT IS KNOWN AND WHAT THIS PAPER ADDS
Prior genome-wide association studies have uncovered 42 SNPs associated with age at menarche in European populations. This study is the first to demonstrate that many of the genetic determinants of age at menarche are shared between European and Chinese women.
PARTICIPANTS AND SETTING
We evaluated 37 of 42 SNPs identified as associated with age at menarche from a recent, large meta-analysis, consisting primarily of women of European ancestry, in a population of 6929 Chinese women from Shanghai, China. We also constructed weighted genetic risk scores (GRSs) combining the number of effect variants for all 37 SNPs, or only the SNPs associated with age at menarche among our study population, to evaluate their joint influence on age at menarche.
MAIN RESULTS
For 32 of the 37 evaluated variants, the direction of the allele associations were the same between women of European ancestry and women of Chinese ancestry (P = 3.71 × 10−6, binomial sign test); 9 of these were statistically significant. Subjects in the highest quintile of GRSs began menarche ∼5 months later than those in the lowest quintile.
BIAS, LIMITATIONS AND GENERALIZABILITY TO OTHER POPULATIONS
Age at menarche was obtained by self-report, which can be subject to recall errors. The current analysis was restricted to loci which met or approached GWAS significance thresholds and did not evaluate loci which may act predominantly or exclusively in the Chinese population. The smaller sample size for our meta-analysis compared with meta-analyses conducted in European populations reduced the power to detect significant results.
STUDY FUNDING/COMPETING INTERESTS
This study was supported, in part, by grants from US National Institutes of Health (grants R01CA124558, R01CA090899, R01CA070867; R01CA064277 and R01CA092585 and UL1 RR024975), Ingram professorship funds and Allen Foundation funds. There are no competing interests to declare.
doi:10.1093/humrep/det011
PMCID: PMC3600840  PMID: 23406970
menarche; genome-wide association study; genetics; reproductive endocrinology
Neuropharmacology  2012;65:90-100.
High-fat feeding or CNS leptin overexpression in chow-fed rats results in a region-specific cellular leptin resistance in medial basal hypothalamic regions and the ventral tegmental area (VTA). The present investigation examined the effects of targeted chronic leptin overexpression in the VTA as compared with the medial basal hypothalamus on long-term body weight homeostasis. The study also examined if this targeted intervention conserves regional leptin sensitivity or results in localized leptin resistance. Cellular leptin resistance was assessed by leptin-stimulated phosphorylation of signal transducers and activators of transcription 3 (STAT3). Tyrosine hydroxylase was measured in hypothalamus and VTA along with brown adipose tissue uncoupling protein 1. Leptin overexpression in VTA tempered HF-induced obesity, but to a slightly lesser extent than that with leptin overexpression in the hypothalamus. Moreover, the overexpression of leptin in the VTA stimulated cellular STAT3 phosphorylation in several regions of the medial basal hypothalamus, whereas verexpression in the hypothalamus did not activate STAT3 signaling in the VTA. This unidirectional trans-stimulation did not appear to involve migration of either the vector or the gene product. Long-term leptin overexpression in either the medial basal hypothalamus or VTA caused desensitization of leptin signaling in the treated region and cross-desensitization of leptin signaling in the untreated region. These results demonstrate a role of leptin receptors in the VTA in long-term body weight regulation, but the trans-activation of the hypothalamus following VTA leptin stimulation suggests that an integrative response involving both brain regions may account for the observed physiological outcomes.
doi:10.1016/j.neuropharm.2012.09.005
PMCID: PMC3521099  PMID: 22982569

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