Serum S-100B as a Potential Biomarker for Meningitis in Febrile Infants: An Interim Analysis

The purpose of this study is to identify the utility of serum S-100B levels as a marker for meningitis in febrile infants younger than 3 months of age. All infants younger than 3 months of age who presented to the Pediatric Emergency Department (PED) of Yale-New Haven Children\u27s Hospital and required both a lumbar puncture and venipuncture due to either a confirmed rectal temperature ≥38.0°C or an overall presentation that concerned the responsible physician for possible meningitis and required a lumbar puncture as part of their PED evaluation, were prospectively enrolled. A total of 111 patients participated after a 1.5-year recruitment period or about 40% of the 260 subjects calculated a priori to be required over 3 years in order to achieve 80% power. After informed written consent, approximately 1 mL of blood was obtained for the analysis of the serum level of S-100B, in addition to the volume normally drawn for standard laboratory analysis. Patients with confirmed meningitis as defined by a positive viral or bacterial culture, a positive polymerase chain reaction (PCR) for enterovirus or herpes simplex virus, and/or cerebrospinal fluid (CSF) pleocytosis, were compared with those subjects without meningitis. S-100B levels for 101 subjects were available for interim analysis, of which 27 (26.7%)met the criteria for meningitis and 74 (73.3%) did not. The median S-100B level in infants with meningitis was 247.0 ng/L (95% CI: 103.5, 804), as compared to 199.1 ng/L (142.5, 384.0) in those without meningitis (p\u3e0.05). Receiver operating characteristic analysis revealed an area under the curve of 0.4917 (0.3940, 0.5863). Ad hoc power calculations demonstrated a 57% probability of detecting a difference of 390 ng/L between the two groups when using this sample size. At this time, this interim analysis of this ongoing study suggests that a larger sample size will still be required to determine if serum S-100B is a useful marker for meningitis in febrile young infants. Because CSF fluid analysis and the associated risks of lumbar puncture remain the only means by which to identify infants with meningitis, the search for a simple serum test for to determine the likelihood of meningitis will continue to be worthwhile

The Effects of Increased Provision of Thoracic Surgical Specialists on the Variation in Lung Cancer Resection Rate in England

Introduction:There is a wide variation in the lung cancer resection rate in England. We assessed the effect of the regional provision of thoracic surgery service on the variation in lung cancer resection rate.Methods:A retrospective observational study correlating National Lung Cancer Audit data with thoracic surgery workforce data was performed to review the lung cancer resection rate in England in 2008 and 2009.Results:In 2008, there was a sixfold variation in resection rate, with a higher resection rate in hospitals where surgeons were based (base hospitals) than in peripheral hospitals (20.0% versus 11.6%, p < 0.001). The resection rate was also higher in cancer networks, which were served by two or more specialist thoracic surgeons (14.6% versus 12.7%, p = 0.028), and where surgeons were present in more than two-thirds of the lung cancer multidisciplinary team meetings (14.4% versus 12.0%, p = 0.046). In 2009, the overall resection rate increased from 14.5% to 18.4%. Four units increased their number of specialist thoracic surgeons and had a significantly higher increase in resection rate than units without expansion (relative rise 66.3% versus 19.2%; p = 0.022).Conclusions:The large variation in the resection rate seems, in part, to be related to the local availability of specialist thoracic surgeons. The greatest improvement in the resection rate was in units with expansion of specialist thoracic surgeons. We suggest the expansion of specialist thoracic surgeons will improve the resection rate and thereby the overall survival of lung cancer in England. This has significant implications for the future of training in cardiothoracic surgery and organization of cancer services

Vibroacoustic stimulation for fetal assessment in labour in the presence of a nonreassuring fetal heart rate trace (Review)

Background: Fetal vibroacoustic stimulation (VAS) is a simple, non-invasive technique where a device is placed on the maternal abdomen over the region of the fetal head and sound is emitted at a predetermined level for several seconds. It is hypothesised that the resultant startle reflex in the fetus and subsequent fetal heart rate (FHR) acceleration or transient tachycardia following VAS provide reassurance of fetal well-being. This technique has been proposed as a tool to assess fetal well-being in the presence of a nonreassuring cardiotocographic (CTG) trace during the first and second stages of labour. Objectives: To evaluate the clinical effectiveness and safety of VAS in the assessment of fetal well-being during labour, compared with mock or no stimulation for women with a singleton pregnancy exhibiting a nonreassuring FHR pattern. Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 September 2012) and reference lists of all retrieved articles. We sought unpublished trials and abstracts submitted to major international congresses and contacted expert informants. Selection criteria: All published and unpublished randomised trials that compared maternal and fetal/neonatal/infant outcomes when VAS was used to evaluate fetal status in the presence of a nonreassuring CTG trace during labour, compared with mock or no stimulation. Data collection and analysis: Two review authors independently sought to assess for inclusion all the potential studies we identified as a result of the search strategy. We planned to resolve any disagreement through discussion or, if required, to consult a third person. Where there was uncertainty about a particular study, we attempted to contact study authors for additional information. However, these attempts were unsuccessful. Main results: The search strategies yielded six studies for consideration of inclusion. However, none of these studies fulfilled the requirements for inclusion in this review. Authors' conclusions: There are currently no randomised controlled trials that address the safety and efficacy of VAS used to assess fetal well-being in labour in the presence of a nonreassuring CTG trace. Although VAS has been proposed as a simple, non-invasive tool for assessment of fetal well-being, there is insufficient evidence from randomised trials on which to base recommendations for use of VAS in the evaluation of fetal well-being in labour in the presence of a nonreassuring CTG trace

Transgenic Adipose-specific Expression of the Nuclear Receptor RORα Drives a Striking Shift in Fat Distribution and Impairs Glycemic Control.

RORα is a member of the nuclear receptor (NR) superfamily and analysis of the (global) RORα-deficient mouse model revealed this NR has a role in glycemic control and fat deposition. Therefore, we generated an adipose-specific RORα 'gain of function' mouse model under the control of the fatty acid binding protein 4 (FABP4) promoter to elucidate the function of RORα in adipose tissue. The Tg-FABP4-RORα4 mice demonstrated a shift in fat distribution to non-adipose tissues when challenged with a high fat diet (HFD). Specifically, we observed a subcutaneous lipodystrophy, accompanied by hepatomegaly (fatty liver/mild portal fibrosis) and splenomegaly; in a background of decreased weight gain and total body fat after HFD. Moreover, we observed significantly higher fasting blood glucose and impaired clearance of glucose in Tg-FABP4-RORα4 mice. Genome wide expression and qPCR profiling analysis identified: (i) subcutaneous adipose specific decreases in the expression of genes involved in fatty acid biosynthesis, lipid droplet expansion and glycemic control, and (ii) the fibrosis pathway as the most significant pathway [including dysregulation of the collagen/extracellular matrix (ECM) pathways] in subcutaneous adipose and liver. The pathology presented in the Tg-FABP4-RORα4 mice is reminiscent of human metabolic disease (associated with aberrant ECM expression) highlighting the therapeutic potential of this NR

Age composition and survival of public housing stock in Hong Kong

Emerging notably in more developed regions, building stock ageing which is characterised by shrinking new completions and falling “mortality” has been posing challenges to various stakeholders in built environment. To find way out of this transition, we need to know how long buildings will last these days and the factors leading to their “mortality”. By using data from 1950s till to date, a comprehensive investigation is conducted to analyse the age composition and life expectancy of public housing stock in Hong Kong. What comes after are survival analysis and empirical analysis of those demolished to identify the key factors leading to demolition. Presented in this paper are the preliminary findings as well as the research agenda on the theme to model age composition and survival of both private and public building stocks in Hong Kong and other similar cities in Asia Pacific Rim such as Adelaide and Singapore, together with research activities to formulate policies for sustainable urban management

RORα and 25-Hydroxycholesterol Crosstalk Regulates Lipid Droplet Homeostasis in Macrophages.

Nuclear hormone receptors have important roles in the regulation of metabolic and inflammatory pathways. The retinoid-related orphan receptor alpha (Rorα)-deficient staggerer (sg/sg) mice display several phenotypes indicative of aberrant lipid metabolism, including dyslipidemia, and increased susceptibility to atherosclerosis. In this study we demonstrate that macrophages from sg/sg mice have increased ability to accumulate lipids and accordingly exhibit larger lipid droplets (LD). We have previously shown that BMMs from sg/sg mice have significantly decreased expression of cholesterol 25-hydroxylase (Ch25h) mRNA, the enzyme that produces the oxysterol, 25-hydroxycholesterol (25HC), and now confirm this at the protein level. 25HC functions as an inverse agonist for RORα. siRNA knockdown of Ch25h in macrophages up-regulates Vldlr mRNA expression and causes increased accumulation of LDs. Treatment with physiological concentrations of 25HC in sg/sg macrophages restored lipid accumulation back to normal levels. Thus, 25HC and RORα signify a new pathway involved in the regulation of lipid homeostasis in macrophages, potentially via increased uptake of lipid which is suggested by mRNA expression changes in Vldlr and other related genes