The occurrence of 14 phthalate metabolites was found in human urine samples collected from seven Asian countries: China, India, Japan, Korea, Kuwait, Malaysia, and Vietnam. Phthalate metabolites were found in all samples, indicating widespread exposure of humans to phthalates in these Asian countries. The highest total (the sum of 14 phthalates) phthalate metabolite concentrations were found in samples collected from Kuwait (median: 1050 ng/mL), followed in decreasing order by samples from India (389 ng/mL), China (234 ng/mL), Vietnam (133 ng/mL), Japan (120 ng/mL), Korea (117 ng/mL), and Malaysia (94.9 ng/mL). The creatinine-adjusted median concentrations of total phthalates for urine samples from Kuwait, India, China, Vietnam, Japan, Korea, and Malaysia were 692, 506, 289, 119, 103, 104, and 169 μg/g creatinine, respectively. Monomethyl phthalate (mMP), monoethyl phthalate (mEP), mono (2-isobutyl phthalate) (miBP), mono-n-butyl phthalate (mBP), and metabolites of di-(2-ethylhexyl) phthalate (DEHP) were the dominant compounds, collectively accounting for >95% of the total concentrations in the samples from the seven countries. The profiles of urinary phthalate metabolite concentrations varied among the samples collected from the seven countries. Urine samples from Kuwait contained the highest concentrations of mEP (median: 391 ng/mL), mBP (94.1 ng/mL), and the metabolites of DEHP (202 ng/mL), whereas samples from China and Japan contained the highest concentrations of miBP (50.8 ng/mL) and mMP (17.5 ng/mL), respectively. mEP was the predominant metabolite in urine samples from India and Kuwait (accounting for 49% of the total), mBP and miBP were the predominant compounds in samples from China (52%), and DEHP metabolites were the predominant compounds in samples from Korea (46%) and Vietnam (52%). Based on the urinary concentrations of mEP, mBP, miBP, and DEHP metabolites of the samples from the seven Asian countries, we estimated daily intake rates of diethyl phthalate (DEP), dibutyl phthalate (DBP), and DEHP. The results indicated that people in the seven Asian countries are exposed to DEP, DBP, and DEHP at levels well below the reference doses (RfD) suggested as unsafe by the U.S. Environmental Protection Agency (EPA). The estimated exposure doses to DEHP in Kuwait, however, were above the RfD recommended by the EPA.
The prevalence of atrial fibrillation (AF) is high in both community- and hospital-based studies in the Far East and South East Asia. Hypertension is the most common risk factor, but coronary heart disease and diabetes mellitus are other important co-morbidities in these countries. Anticoagulant therapy use was low, being 0.5%-28% in Malaysia, Singapore, and China. The reported rate of stroke related to AF was 13.0%-15.4% based on community studies in those countries, and was 3.1%-24.2% of stroke rate in hospital-based cohorts. Better assessment of thromboembolic and bleeding risks is important. International guidelines now recommend the use of the CHA2DS2-VASc score to identify the ''truly low-risk'' AF patients, who do not need antithrombotic therapy, whilst those with ≥ 1 stroke risk factors can be offered oral anticoagulation. Aspirin is ineffective and may not be any safer than oral anticoagulants, especially in the elderly. It is anticipated that the availability of the new oral anticoagulant drugs would improve our efforts for stroke prevention in the Far East and South East Asia, especially where anticoagulation monitoring for warfarin is suboptimal.
Concentrations of 12 hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were determined in 306 urine samples collected from seven Asian countries (China, India, Japan, Korea, Kuwait, Malaysia, and Vietnam) by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The total concentrations of OH-PAHs found in the seven Asian countries were in the following increasing order: Malaysia (median: 2260 pg/mL) < Japan (4030 pg/mL) < China (5770 pg/mL) < India (6750 pg/mL) < Vietnam (8560 pg/mL) < Korea (9340 pg/mL) < Kuwait (10170 pg/mL). The measured urinary concentrations of 1-hydroxypyrene (1-PYR) in samples from Malaysia, Korea, and Japan (∼ 100 pg/mL) were similar to those reported for North America and Western Europe. The concentrations of 1-PYR in urine samples from China, India, and Vietnam were 4-10 times higher than those reported for other countries, thus far. Among the 12 OH-PAH compounds analyzed, hydroxynaphthalene (NAP: sum of 1-hydroxynaphthalene and 2-hydroxynaphthalene) was the dominant compound (accounting for 60-90% of total OH-PAHs), followed by hydroxyphenanthrene (PHEN: sum of 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene, and 9-hydroxyphenanthrene [3-16%]), 2-hydroxyfluorene (3-20%), and 1-PYR (2-8%). The total daily intakes (DIs) of PAHs were estimated based on the urinary concentrations of their metabolites. The DIs of naphthalene were found to be higher for populations in Korea, Kuwait, and Vietnam (> 10 μg/day) than those of the other countries studied (∼ 5 μg/day). The DIs of phenanthrene and pyrene (> 10 μg/day) in the populations of China, India, and Vietnam were higher than those estimated for the populations in the other countries studied (∼ 5 μg/day).
Head and neck cancer (HNC) is a disease of the upper aerodigestive tract and is one of the most frequently diagnosed cancers worldwide. A high rate of cancers involving the head and neck are reported across the Asian region, with notable variations between countries. Disease prognosis is largely dependent on tumor stage and site. Patients with early stage disease have a 60-95% chance of cure with local therapy. Early diagnosis and appropriate treatment are important to increase the likelihood of cure and survival. However, the majority of patients present with locally advanced disease and require multimodality treatment. This necessitates, a multidisciplinary approach which is essential to make appropriate treatment decisions, particularly with regards to tolerability, costs, available infrastructure and quality of life issues. Unfortunately, majority of the studies that dictate current practice have been developed in the west where diseases biology, patient population and available infrastructure are very different from those in the Asian continent. With this in mind an expert panel of Head and Neck Oncologists was convened in May 2012 to review the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) clinical practice guidelines and develop practical recommendations on the applicability of these guidelines on the management of head and neck cancer for Asian patients. The objective of this review and consensus meeting was to suggest revisions, to account for potential differences in demographics and resources, to the NCCN and ESMO guidelines, to better reflect current clinical management of head and neck cancer within the Asian region for health care providers. These recommendations, which reflect best clinical practice within Asia, are expected to benefit practitioners when making decisions regarding optimal treatment strategies for their patients.
Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top quark (the top squark) and the Higgs boson (Higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 fb-1 of proton-proton collision data at s=8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the top squark mass below 360 to 410 GeV, depending on the Higgsino mass.
Measurements are reported of the WZ and ZZ production cross sections in proton-proton collisions at [Formula: see text][Formula: see text] in final states where one Z boson decays to b-tagged jets. The other gauge boson, either W or Z, is detected through its leptonic decay (either [Formula: see text], [Formula: see text] or [Formula: see text], [Formula: see text], or [Formula: see text]). The results are based on data corresponding to an integrated luminosity of 18.9 fb[Formula: see text] collected with the CMS detector at the Large Hadron Collider. The measured cross sections, [Formula: see text] and [Formula: see text], are consistent with next-to-leading order quantum chromodynamics calculations.
The normalised differential top quark-antiquark production cross section is measured as a function of the jet multiplicity in proton-proton collisions at a centre-of-mass energy of 7[Formula: see text] at the LHC with the CMS detector. The measurement is performed in both the dilepton and lepton+jets decay channels using data corresponding to an integrated luminosity of 5.0[Formula: see text]. Using a procedure to associate jets to decay products of the top quarks, the differential cross section of the [Formula: see text] production is determined as a function of the additional jet multiplicity in the lepton+jets channel. Furthermore, the fraction of events with no additional jets is measured in the dilepton channel, as a function of the threshold on the jet transverse momentum. The measurements are compared with predictions from perturbative quantum chromodynamics and no significant deviations are observed.
A measurement of the cross section for the production of top quark-antiquark pairs ([Formula: see text]) in association with a vector boson V (W or Z) in proton-proton collisions at [Formula: see text][Formula: see text] is presented. The results are based on a dataset corresponding to an integrated luminosity of 19.5 fb[Formula: see text] recorded with the CMS detector at the LHC. The measurement is performed in three leptonic (e and [Formula: see text]) channels: a same-sign dilepton analysis targeting [Formula: see text] events, and trilepton and four-lepton analyses designed for [Formula: see text] events. In the same-sign dilepton channel, the [Formula: see text] cross section is measured as [Formula: see text], corresponding to a significance of 1.6 standard deviations over the background-only hypothesis. Combining the trilepton and four-lepton channels, a direct measurement of the [Formula: see text] cross section, [Formula: see text], is obtained with a significance of 3.1 standard deviations. The measured cross sections are compatible with standard model predictions within their experimental uncertainties. The inclusive [Formula: see text] process is observed with a significance of 3.7 standard deviations from the combination of all three leptonic channels.
Searches for the direct electroweak production of supersymmetric charginos, neutralinos, and sleptons in a variety of signatures with leptons and [Formula: see text], [Formula: see text], and Higgs bosons are presented. Results are based on a sample of proton-proton collision data collected at center-of-mass energy [Formula: see text] with the CMS detector in 2012, corresponding to an integrated luminosity of 19.5 [Formula: see text]. The observed event rates are in agreement with expectations from the standard model. These results probe charginos and neutralinos with masses up to 720 [Formula: see text], and sleptons up to 260 [Formula: see text], depending on the model details.
A measurement of differential cross sections for the production of a pair of isolated photons in proton-proton collisions at [Formula: see text] is presented. The data sample corresponds to an integrated luminosity of 5.0[Formula: see text] collected with the CMS detector. A data-driven isolation template method is used to extract the prompt diphoton yield. The measured cross section for two isolated photons, with transverse energy above 40 and 25[Formula: see text] respectively, in the pseudorapidity range [Formula: see text], [Formula: see text] and with an angular separation [Formula: see text], is [Formula: see text][Formula: see text]. Differential cross sections are measured as a function of the diphoton invariant mass, the diphoton transverse momentum, the azimuthal angle difference between the two photons, and the cosine of the polar angle in the Collins-Soper reference frame of the diphoton system. The results are compared to theoretical predictions at leading, next-to-leading, and next-to-next-to-leading order in quantum chromodynamics.
BACKGROUND: Dengue fever (DF) is one of the most important emerging arboviral human diseases. Globally, DF incidence has increased by 30-fold over the last fifty years, and the geographic range of the virus and its vectors has expanded. The disease is now endemic in more than 120 countries in tropical and subtropical parts of the world. This study examines the spatiotemporal trends of DF transmission in the Asia-Pacific region over a 50-year period, and identified the disease's cluster areas.
METHODOLOGY AND FINDINGS: The World Health Organization's DengueNet provided the annual number of DF cases in 16 countries in the Asia-Pacific region for the period 1955 to 2004. This fifty-year dataset was divided into five ten-year periods as the basis for the investigation of DF transmission trends. Space-time cluster analyses were conducted using scan statistics to detect the disease clusters. This study shows an increasing trend in the spatiotemporal distribution of DF in the Asia-Pacific region over the study period. Thailand, Vietnam, Laos, Singapore and Malaysia are identified as the most likely clusters (relative risk = 13.02) of DF transmission in this region in the period studied (1995 to 2004). The study also indicates that, for the most part, DF transmission has expanded southwards in the region.
CONCLUSIONS: This information will lead to the improvement of DF prevention and control strategies in the Asia-Pacific region by prioritizing control efforts and directing them where they are most needed.
A search for invisible decays of Higgs bosons is performed using the vector boson fusion and associated ZH production modes. In the ZH mode, the Z boson is required to decay to a pair of charged leptons or a [Formula: see text] quark pair. The searches use the 8 [Formula: see text] pp collision dataset collected by the CMS detector at the LHC, corresponding to an integrated luminosity of up to 19.7 [Formula: see text]. Certain channels include data from 7 [Formula: see text] collisions corresponding to an integrated luminosity of 4.9 [Formula: see text]. The searches are sensitive to non-standard-model invisible decays of the recently observed Higgs boson, as well as additional Higgs bosons with similar production modes and large invisible branching fractions. In all channels, the observed data are consistent with the expected standard model backgrounds. Limits are set on the production cross section times invisible branching fraction, as a function of the Higgs boson mass, for the vector boson fusion and ZH production modes. By combining all channels, and assuming standard model Higgs boson cross sections and acceptances, the observed (expected) upper limit on the invisible branching fraction at [Formula: see text] [Formula: see text] is found to be 0.58 (0.44) at 95 % confidence level. We interpret this limit in terms of a Higgs-portal model of dark matter interactions.
Observation of the diphoton decay mode of the recently discovered Higgs boson and measurement of some of its properties are reported. The analysis uses the entire dataset collected by the CMS experiment in proton-proton collisions during the 2011 and 2012 LHC running periods. The data samples correspond to integrated luminosities of 5.1[Formula: see text]at [Formula: see text] and 19.7[Formula: see text]at 8[Formula: see text] . A clear signal is observed in the diphoton channel at a mass close to 125[Formula: see text] with a local significance of [Formula: see text], where a significance of [Formula: see text] is expected for the standard model Higgs boson. The mass is measured to be [Formula: see text] , and the best-fit signal strength relative to the standard model prediction is [Formula: see text][Formula: see text][Formula: see text]. Additional measurements include the signal strength modifiers associated with different production mechanisms, and hypothesis tests between spin-0 and spin-2 models.
A search for heavy, right-handed neutrinos, [Formula: see text] ([Formula: see text]), and right-handed [Formula: see text] bosons, which arise in the left-right symmetric extensions of the standard model, has been performed by the CMS experiment. The search was based on a sample of two lepton plus two jet events collected in proton-proton collisions at a center-of-mass energy of 8[Formula: see text] corresponding to an integrated luminosity of 19.7 [Formula: see text]. For models with strict left-right symmetry, and assuming only one [Formula: see text] flavor contributes significantly to the [Formula: see text] decay width, the region in the two-dimensional [Formula: see text] mass plane excluded at a 95 % confidence level extends to approximately [Formula: see text] and covers a large range of neutrino masses below the [Formula: see text] boson mass, depending on the value of [Formula: see text]. This search significantly extends the [Formula: see text] exclusion region beyond previous results.
The purely electroweak (EW) cross section for the production of two jets in association with a Z boson, in proton-proton collisions at [Formula: see text], is measured using data recorded by the CMS experiment at the CERN LHC, corresponding to an integrated luminosity of 19.7[Formula: see text]. The electroweak cross section for the [Formula: see text] final state (with [Formula: see text] or [Formula: see text] and j representing the quarks produced in the hard interaction) in the kinematic region defined by [Formula: see text][Formula: see text], [Formula: see text][Formula: see text], transverse momentum [Formula: see text][Formula: see text], and pseudorapidity [Formula: see text], is found to be [Formula: see text], in agreement with the standard model prediction. The associated jet activity of the selected events is studied, in particular in a signal-enriched region of phase space, and the measurements are found to be in agreement with QCD predictions.
Results are presented from a search for particle dark matter (DM), extra dimensions, and unparticles using events containing a jet and an imbalance in transverse momentum. The data were collected by the CMS detector in proton-proton collisions at the LHC and correspond to an integrated luminosity of 19.7[Formula: see text]at a centre-of-mass energy of 8[Formula: see text]. The number of observed events is found to be consistent with the standard model prediction. Limits are placed on the DM-nucleon scattering cross section as a function of the DM particle mass for spin-dependent and spin-independent interactions. Limits are also placed on the scale parameter [Formula: see text] in the Arkani-Hamed, Dimopoulos, and Dvali (ADD) model of large extra dimensions, and on the unparticle model parameter [Formula: see text]. The constraints on ADD models and unparticles are the most stringent limits in this channel and those on the DM-nucleon scattering cross section are an improvement over previous collider results.
Cancer stem-like cells (CSC) are thought to drive tumor initiation, metastasis, relapse and therapeutic resistance, but their specific pathogenic characters in many cancers including non-small cell lung cancer (NSCLC) have yet to be well defined. Here we develop findings that the growth factor HGF promotes CSC sphere formation in NSCLC cell populations. In patient-derived sphere-forming assays (PD-SFA) with HGF, CD49f and CD104 were defined as novel markers of lung CSC (LCSC). In particular, we isolated a subpopulation of CD166(+)CD49f(hi)CD104(-)Lin(-) LCSC present in all human specimens of NSCLC examined, regardless of their histological subtypes or genetic driver mutations. This specific cell population was tumorigenic and capable of self-renewal, giving rise to tumor spheres in vitro and orthotopic lung tumors in immune-compromised mice. Mechanistic investigations established that NOTCH1 was preferentially expressed in this cell subpopulation and required for self-renewal via the transcription factor HES1. Through a distinct HES1-independent pathway, NOTCH1 also protected LCSCs from cisplatin-induced cell death. Notably, treatment with a γ-secretase inhibitor that blunts NOTCH1 function ablated self-renewing LCSC activity and restored platinum sensitivity in vitro and in vivo Overall, our results define the pathogenic characters of a cancer stem-like subpopulation in lung cancer, the targeting of which may relieve platinum resistance in this disease.
OBJECTIVE: We evaluate the efficacy of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) for the treatment of lupus nephritis (LN). Previous reports showed hUC-MSC could have dramatic treatment effect.
METHODS: Eighteen patients with WHO class III or IV LN were randomly assigned to hUC-MSC (dose 2×108 cells) or placebo. All patients received standard immunosuppressive treatment, which consisted of intravenous methylprednisolone and cyclophosphamide, followed by maintenance oral prednisolone and mycophenolate mofetil.
RESULTS: Remission occurred in 9 of 12 patients (75%) in the hUC-MSC group and 5 of 6 patients (83%) in the placebo group. Remission was defined as stabilisation or improvement in renal function, reduction in urinary red cells and protein. A similar proportion of patients on hUC-MSC and placebo achieved complete remission. Improvements in serum albumin, complement, renal function, Systemic Lupus Erythematosus Disease Activity Index and British Isles Lupus Assessment Group scores were similar in both groups. One patient on placebo had a stroke and another had ascites. One patient on hUC-MSC had leucopenia, pneumonia and subcutaneous abscess and another died of severe pneumonia. The trial was abandoned after 18 patients were enrolled when it had become obvious it would not demonstrate a positive treatment effect.
CONCLUSION: hUC-MSC has no apparent additional effect over and above standard immunosuppression.
The usability and tunability of the essential InP-InGaAs material combination in nanowire-based quantum wells (QWs) are assessed. The wurtzite phase core-multi-shell InP-InGaAs-InP nanowire QWs are characterised using cross-section transmission electron microscopy and photoluminescence measurements. The InP-InGaAs direct interface is found to be sharp while the InGaAs-InP inverted interface is more diffused, in agreement with their planar counterpart. Bright emission is observed from the single nanowires containing the QWs at room temperature, with no emission from the InP core or outer barrier. The tunability of the QW emission wavelength in the 1.3-1.55 μm communication wavelength range is demonstrated by varying the QW thickness and in the 1.3 μm range by varying the composition. The experiments are supported by simulation of the emission wavelength of the wurtzite phase InP-InGaAs QWs in the thickness range considered. The radial heterostructure is further extended to design multiple QWs with bright emission, therefore establishing the capability of this material system for nanowire based optical devices for communication applications.