The outbreak of SARS at Tan Tock Seng Hospital--relating epidemiology to control.

INTRODUCTION: The outbreak of severe acute respiratory syndrome (SARS) began after the index case was admitted on 1 March 2003. We profile the cases suspected to have acquired the infection in Tan Tock Seng Hospital (TTSH), focussing on major transmission foci, and also describe and discuss the impact of our outbreak control measures. MATERIALS AND METHODS: Using the World Health Organization (WHO) case definitions for probable SARS adapted to the local context, we studied all cases documented to have passed through TTSH less than 10 days prior to the onset of fever. Key data were collected in liaison with clinicians and through a team of onsite epidemiologists. RESULTS: There were 105 secondary cases in TTSH. Healthcare staff (57.1%) formed the majority, followed by visitors (30.5%) and inpatients (12.4%). The earliest case had onset of fever on 4 March 2003, and the last case, on 5 April 2003. Eighty-nine per cent had exposures to 7 wards which had cases of SARS that were not isolated on admission. In 3 of these wards, major outbreaks resulted, each with more than 20 secondary cases. Attack rates amongst ward-based staff ranged from 0% to 32.5%. Of 13 inpatients infected, only 4 (30.8%) had been in the same room or cubicle as the index case for the ward. CONCLUSIONS: The outbreak of SARS at TTSH showed the challenges of dealing with an emerging infectious disease with efficient nosocomial spread. Super-spreading events and initial delays in outbreak response led to widespread dissemination of the outbreak to multiple wards

Identification of chemerin receptor (ChemR23) in human endothelial cells: chemerin-induced endothelial angiogenesis

Chemerin acting via its distinct G protein-coupled receptor CMKLR1 (ChemR23), is a novel adipokine, circulating levels of which are raised in inflammatory states. Chemerin shows strong correlation with various facets of the metabolic syndrome; these states are associated with an increased incidence of cardiovascular disease (CVD) and dysregulated angiogenesis. We therefore, investigated the regulation of ChemR23 by pro-inflammatory cytokines and assessed the angiogenic potential of chemerin in human endothelial cells (EC). We have demonstrated the novel presence of ChemR23 in human ECs and its significant up-regulation (P < 0.001) by pro-inflammatory cytokines, TNF-α, IL-1β and IL-6. More importantly, chemerin was potently angiogenic, as assessed by conducting functional in-vitro angiogenic assays; chemerin also dose-dependently induced gelatinolytic (MMP-2 & MMP-9) activity of ECs (P < 0.001). Furthermore, chemerin dose-dependently activated PI3K/Akt and MAPKs pathways (P < 0.01), key angiogenic and cell survival cascades. Our data provide the first evidence of chemerin-induced endothelial angiogenesis and MMP production and activity

Firm-level evidence on productivity differentials, turnover, and exports in Taiwanese manufacturing

Recent dynamic models of firm entry and exit emphasise the relationship between a firm's productivity and the decision to enter or exit. If firm turnover is driven by productivity differentials then the reallocation of resources across firms at the micro level can have important implications for aggregate or industry-level productivity change. Using comprehensive firm-level panel data from the Taiwanese Census of Manufactures for the years 1981, 1986, and 1991, this paper documents the extent of firm turnover in both the domestic and export markets, uses index numbers to measure differences in total factor productivity between entering, exiting, and continuing firms, and quantifies the contribution of firm turnover to industry productivity improvements. We find significant differences in productivity across manufacturing firms and these differences are reflected in turnover patterns. Cohorts of new firms have lower average productivity than incumbents but are themselves a heterogeneous group. The more productive members of the group survive and, in many cases, their productivity converges to the productivity level of incumbents. Exiting firms are also less productive than survivors. Differences in productivity are also reflected in movements of firms in and out of the export market. Firms that remain exporters over multiple years have the highest productivity while beginning exporters, whether they are new firms or older firms, follow behind them. All are more productive on average than firms that exit the export market who, in turn, are more productive than firms that never exported. These patterns are consistent with the view that both the domestic and export market sort out high productivity from low productivity firms and that the export market is a tougher screen. Unlike the findings for most other countries, the differential productivity between entering and exiting firms is an important source of industry-level productivity improvements in the Taiwan manufacturing sector

In vivo and ex vivo regulation of visfatin production by leptin in human and murine adipose tissue : role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways

Visfatin is an adipogenic adipokine with increased levels in obesity, properties common to leptin. Thus, leptin may modulate visfatin production in adipose tissue (AT). Therefore, we investigated the effects of leptin on visfatin levels in 3T3-L1 adipocytes and human/murine AT, with or without a leptin antagonist. The potential signaling pathways and mechanisms regulating visfatin production in AT was also studied. Real-time RT-PCR and Western blotting were used to assess the relative mRNA and protein expression of visfatin. ELISA was performed to measure visfatin levels in conditioned media of AT explants, and small interfering RNA technology was used to reduce leptin receptor expression. Leptin significantly (P < 0.01) increased visfatin levels in human and murine AT with a maximal response at leptin 10–9 M, returning to baseline at leptin 10–7 M. Importantly, ip leptin administration to C57BL/6 ob/ob mice further supported leptin-induced visfatin protein production in omental AT (P < 0.05). Additionally, soluble leptin receptor levels rose with concentration dependency to a maximal response at leptin 10–7 M (P < 0.01). The use of a leptin antagonist negated the induction of visfatin and soluble leptin receptor by leptin. Furthermore, leptin-induced visfatin production was significantly decreased in the presence of MAPK and phosphatidylinositol 3-kinase inhibitors. Also, when the leptin receptor gene was knocked down using small interfering RNA, leptin-induced visfatin expression was significantly decreased. Thus, leptin increases visfatin production in AT in vivo and ex vivo via pathways involving MAPK and phosphatidylinositol 3-kinase signaling. The pleiotropic effects of leptin may be partially mediated by visfatin

Parents’ educational level and second-hand tobacco smoke exposure at home in a sample of Portuguese children

Second-hand tobacco smoke (SHS) exposure is a major and entirely avoidable health risk for children’s health, well-being and development. The main objective of the current study was to investigate the association between parents’ educational level and children’s SHS home exposure. A self-administered questionnaire was conducted within a sample of 949 students in 4th grade (mean age 9.56 ± 0.75, 53.4% male). The sample was randomly selected from all schools located at Lisbon District, Portugal. The current study confirmed that Portuguese children are exposed to unacceptable high levels of SHS at home, mainly by their parents’ smoke. Prevalence of smokers was higher amongst parents with low educational level. Children of parents with low educational level were more likely to suffer SHS exposure at home. These results confirmed the social inequalities associated with smoking, support the relevance of more research on this subject and stress the need for more interventions to control this problem. Some interventions should be specifically aimed at less educated parents, particularly at less educated mothers.CIEC – Research Centre on Child Studies, IE, UMinho (FCT R&D unit 317), Portugal; National Funds through the FCT (Foundation for Science and Technology) and co-financed by European Regional Development Funds (FEDER) through the Competitiveness and Internationalization Operational Program (POCI) through CIEC (Research Centre on Child Studies, of the University of Minho) with the reference POCI-01-0145-FEDER-007562info:eu-repo/semantics/publishedVersio

Lower cerebrospinal fluid/plasma fibroblast growth factor 21 (FGF21) ratios and placental FGF21 production in gestational diabetes

Objectives: Circulating Fibroblast Growth Factor 21 (FGF21) levels are increased in insulin resistant states such as obesity, type 2 diabetes mellitus and gestational diabetes mellitus (GDM). In addition, GDM is associated with serious maternal and fetal complications. We sought to study human cerebrospinal fluid (CSF) and corresponding circulating FGF21 levels in women with gestational diabetes mellitus (GDM) and in age and BMI matched control subjects. We also assessed FGF21 secretion from GDM and control human placental explants. Design: CSF and corresponding plasma FGF21 levels of 24 women were measured by ELISA [12 GDM (age: 26–47 years, BMI: 24.3–36.3 kg/m2) and 12 controls (age: 22–40 years, BMI: 30.1–37.0 kg/m2)]. FGF21 levels in conditioned media were secretion from GDM and control human placental explants were also measured by ELISA. Results: Glucose, HOMA-IR and circulating NEFA levels were significantly higher in women with GDM compared to control subjects. Plasma FGF21 levels were significantly higher in women with GDM compared to control subjects [234.3 (150.2–352.7) vs. 115.5 (60.5–188.7) pg/ml; P<0.05]. However, there was no significant difference in CSF FGF21 levels in women with GDM compared to control subjects. Interestingly, CSF/Plasma FGF21 ratio was significantly lower in women with GDM compared to control subjects [0.4 (0.3–0.6) vs. 0.8 (0.5–1.6); P<0.05]. FGF21 secretion into conditioned media was significantly lower in human placental explants from women with GDM compared to control subjects (P<0.05). Conclusions: The central actions of FGF21 in GDM subjects maybe pivotal in the pathogenesis of insulin resistance in GDM subjects. The significance of FGF21 produced by the placenta remains uncharted and maybe crucial in our understanding of the patho-physiology of GDM and its associated maternal and fetal complications. Future research should seek to elucidate these points

Functional cardiac orexin receptors : role of orexin-B/orexin 2 receptor in myocardial protection

Orexins/hypocretins exert cardiovascular effects which are centrally mediated. In this study we tested whether orexins and their receptors may also act in an autocrine/paracrine manner in the heart exerting direct effects. Quantitative RT-PCR, immunohistochemical and Western blot analyses revealed that the rat heart expresses orexins and orexin receptors. In isolated rat cardiomyocytes, only orexin-B (OR-B) caused an increase in contractile shortening, independent of diastolic or systolic calcium levels. A specific orexin receptor-2 (OX2R) agonist ([Ala11, D-Leu15]-Orexin B) exerted similar effects as OR-B, whereas a specific OX1R antagonist (SB-408124) did not alter the responsiveness of OR-B. Treatment of the same model with OR-B resulted in a dose-dependent increase of myosin light chain and troponin-I phosphorylation. Following ischaemia/reperfusion in the isolated Langendorff perfused rat heart model, OR-B, but not OR-A, exerts a cardioprotective effect; mirrored in an in vivo model as well. Unlike OR-A, OR-B was also able to induce ERK1/2 and Akt phosphorylation in rat myocardial tissue and ERK1/2 phosphorylation in human heart samples. These findings were further corroborated in an in vivo rat model. In human subjects with heart failure, there is a significant negative correlation between the expression of OX2R and the severity of the disease clinical symptoms, as assessed by the New York Heart Association (NYHA) functional classification. Collectively, we provide evidence of a distinct orexin system in the heart that exerts a cardioprotective role via an OR-B/OX2R pathway

Analysis of eBook Lending: A Game-Theory Approach

Retailers have seen a steady and continuous increase in eBooks sales in recent years. A new strategy to further promote eBook sales is to provide eBook lending option. For example, Amazon.com allows Kindle eBook buyers to lend their eBooks for 14 days. The free eBook lending option will add additional utility to eBook buyers such as exchanging for other eBooks or reducing uncertainties of purchasing new books. However, such strategy might cannibalize the retailers\u27 sales of print books. Using a game theory model, we explore whether the retailer will be better off to introduce the lending program. We derive the equilibrium price and identify the conditions under which the retailer can offer eBook lending option and generate more revenue

Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts

Aims: Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia. Methods and Results: FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased. Conclusion: In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry