Randomised controlled trial and economic evaluation of a chest pain observation unit compared with routine care

Objectives To measure the effectiveness and cost effectiveness of providing care in a chest pain observation unit compared with routine care for patients with acute, undifferentiated chest pain. Design Cluster randomised controlled trial, with 442 days randomised to the chest pain observation unit or routine care, and cost effectiveness analysis from a health service costing perspective. Setting The emergency department at the Northern General Hospital, Sheffield, United Kingdom. Participants 972 patients with acute, undifferentiated chest pain (479 attending on days when care was delivered in the chest pain observation unit, 493 on days of routine care) followed up until six months after initial attendance. Main outcome measures The proportion of participants admitted to hospital, the proportion with acute coronary syndrome sent home inappropriately, major adverse cardiac events over six months, health utility, hospital reattendance and readmission, and costs per patient to the health service. Results Use of a chest pain observation unit reduced the proportion of patients admitted from 54% to 37% (difference 17%, odds ratio 0.50, 95% confidence interval 0.39 to 0.65, P < 0.001) and the proportion discharged with acute coronary syndrome from 14% to 6% (8%, –7% to 23%, P = 0.264). Rates of cardiac event were unchanged. Care in the chest pain observation unit was associated with improved health utility during follow up (0.0137 quality adjusted life years gained, 95% confidence interval 0.0030 to 0.0254, P = 0.022) and a saving of £78 per patient (–£56 to £210, P = 0.252). Conclusions Care in a chest pain observation unit can improve outcomes and may reduce costs to the health service. It seems to be more effective and more cost effective than routine care

The influence of oral health status on speech intelligibility, articulation and quality of life of older community-dwelling people

Objective: To investigate the impact of the oral health status on speech intelligibility, articulation and quality of life of older community-dwelling people. Background To our knowledge, there have been no studies on this topic in patients aged 75 years or older. Material and methods: Thirty outpatients of a university dental clinic (median [IQR] age of 77.00 [75-82] years) participated. The OHIP-14, a dental examination, a speech intelligibility study and an articulation examination were conducted. Results: Distortions of rhotacisms and sigmatisms were most common, followed by distortions of labiodentals and apicoalveolars. Seven participants (23%) required dental treatment. Distortions of rhotacisms were lowest in participants with loss of teeth in the posterior part of the maxilla and equal in participants with edentulous maxilla and loss of teeth in the anterior part of the maxilla (P = 0.014). Labiodental distortions were lowest in participants with loss of teeth in the posterior part of the maxilla, but were higher in participants with loss of teeth in the anterior part of the maxilla and highest in participants with an edentulous maxilla (P = 0.035). People with normal mouth opening had lower percentage of labiodental distortions than people with a reduced mouth opening (P = 0.05). The proportion of participants with inadequate denture hygiene and distortions of bilabials was 71.4% compared to 10.5% for participants with adequate denture hygiene (P = 0.005). Conclusion: Dentists must consider the impact of a denture on speech, but also should be aware of other oral health factors that influence the speech and quality of life of elders

Expression of Epstein–Barr Virus–Encoded Small RNA (by the EBER-1 Gene) in Liver Specimens from Transplant Recipients with Post-Transplantation Lymphoproliferative Disease

Epstein-Barr virus (EBV)—associated post-transplantation lymphoproliferative disease (PTLD) develops in 1 to 10 percent of transplant recipients, in whom it can be treated by a reduction in the level of immunosuppression. We postulated that the tissue expression of the small RNA transcribed by the EBER-1 gene during latent EBV infection would identify patients at risk for PTLD. We studied EBER-1 gene expression in liver specimens obtained from 24 patients 2 days to 22 months before the development of PTLD, using in situ hybridization with an oligonucleotide probe. Control specimens were obtained from 20 recipients of allografts with signs of injury due to organ retrieval, acute graft rejection, or viral hepatitis in whom PTLD had not developed 9 to 71 months after the biopsy. Of the 24 patients with PTLD, 17 (71 percent) had specimens in which 1 to 40 percent of mononuclear cells were positive for the EBER-1 gene. In addition, 10 of these 17 patients (59 percent) had specimens with histopathological changes suggestive of EBV hepatitis. In every case, EBER-1—positive cells were found within the lymphoproliferative lesions identified at autopsy. Only 2 of the 20 controls (10 percent) had specimens with EBER-1—positive cells (P<0.001), and such cells were rare. EBER-1 gene expression in liver tissue precedes the occurrence of clinical and histologic PTLD. The possibility of identifying patients at risk by the method we describe here and preventing the occurrence of PTLD by a timely reduction of immunosuppression needs to be addressed by future prospective studies. (N Engl J Med 1992;327:1710–4.), POST-TRANSPLANTATION lymphoproliferative disease (PTLD), either polyclonal or monoclonal, complicates the clinical course of 1 to 10 percent of organ-transplant recipients.123 Immunohistochemical studies have demonstrated that the lymphoid cells within the lesions of PTLD almost invariably contain Epstein–Barr virus (EBV), primarily in a state of latent infection.4,5 The EBER-1 gene is expressed early during latent EBV infection and codes for a small messenger RNA (mRNA) expressed at up to 107 copies per cell.6 We and others have previously demonstrated the value of the detection of EBER-1 RNA for identifying EBV-infected cells in formalin-fixed paraffin-embedded tissues.7,8 In the current investigation, we used… © 1992, Massachusetts Medical Society. All rights reserved

Why is low waist-to-chest ratio attractive in males? The mediating roles of perceived dominance, fitness, and protection ability

Past research suggests that a lower waist-to-chest ratio (WCR) in men (i.e., narrower waist and broader chest) is viewed as attractive by women. However, little work has directly examined why low WCRs are preferred. The current work merged insights from theory and past research to develop a model examining perceived dominance, fitness, and protection ability as mediators of to WCR-attractiveness relationship. These mediators and their link to both short-term (sexual) and long-term (relational) attractiveness were simultaneously tested by having 151 women rate one of 15 avatars, created from 3D body scans. Men with lower WCR were perceived as more physically dominant, physically fit, and better able to protect loved ones; these characteristics differentially mediated the effect of WCR on short-term, long-term, and general attractiveness ratings. Greater understanding of the judgments women form regarding WCR may yield insights into motivations by men to manipulate their body image

Design and evaluation of the immunogenicity and efficacy of a biomimetic particulate formulation of viral antigens

Subunit viral vaccines are typically not as efficient as live attenuated or inactivated vaccines at inducing protective immune responses. This paper describes an alternative 'biomimetic' technology; whereby viral antigens were formulated around a polymeric shell in a rationally arranged fashion with a surface glycoprotein coated on to the surface and non-structural antigen and adjuvant encapsulated. We evaluated this model using BVDV E2 and NS3 proteins formulated in poly-(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with polyinosinic:polycytidylic acid (poly(I:C) as an adjuvant (Vaccine-NP). This Vaccine-NP was compared to ovalbumin and poly(I:C) formulated in a similar manner (Control-NP) and a commercial adjuvanted inactivated BVDV vaccine (IAV), all inoculated subcutaneously and boosted prior to BVDV-1 challenge. Significant virus-neutralizing activity, and E2 and NS3 specific antibodies were observed in both Vaccine-NP and IAV groups following the booster immunisation. IFN-γ responses were observed in ex vivo PBMC stimulated with E2 and NS3 proteins in both vaccinated groups. We observed that the protection afforded by the particulate vaccine was comparable to the licenced IAV formulation. In conclusion, the biomimetic particulates showed a promising immunogenicity and efficacy profile that may be improved by virtue of being a customisable mode of delivery

Modal Analysis and Coupling in Metal-Insulator-Metal Waveguides

This paper shows how to analyze plasmonic metal-insulator-metal waveguides using the full modal structure of these guides. The analysis applies to all frequencies, particularly including the near infrared and visible spectrum, and to a wide range of sizes, including nanometallic structures. We use the approach here specifically to analyze waveguide junctions. We show that the full modal structure of the metal-insulator-metal (MIM) waveguides--which consists of real and complex discrete eigenvalue spectra, as well as the continuous spectrum--forms a complete basis set. We provide the derivation of these modes using the techniques developed for Sturm-Liouville and generalized eigenvalue equations. We demonstrate the need to include all parts of the spectrum to have a complete set of basis vectors to describe scattering within MIM waveguides with the mode-matching technique. We numerically compare the mode-matching formulation with finite-difference frequency-domain analysis and find very good agreement between the two for modal scattering at symmetric MIM waveguide junctions. We touch upon the similarities between the underlying mathematical structure of the MIM waveguide and the PT symmetric quantum mechanical pseudo-Hermitian Hamiltonians. The rich set of modes that the MIM waveguide supports forms a canonical example against which other more complicated geometries can be compared. Our work here encompasses the microwave results, but extends also to waveguides with real metals even at infrared and optical frequencies.Comment: 17 pages, 13 figures, 2 tables, references expanded, typos fixed, figures slightly modifie

HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

What is the value of orthodontic treatment?

Orthodontic treatment is as popular as ever. Orthodontists frequently have long lists of people wanting treatment and the cost to the NHS in England was £258m in 2010-2011 (approximately 10% of the NHS annual spend on dentistry). It is important that clinicians and healthcare commissioners constantly question the contribution of interventions towards improving the health of the population. In this article, the authors outline some of the evidence for and against the claims that people with a malocclusion are at a disadvantage compared with those without a malocclusion and that orthodontic treatment has significant health benefits. The authors would like to point out that this is not a comprehensive and systematic review of the entire scientific literature. Rather the evidence is presented in order to stimulate discussion and debate