A user's guide to CEPXS/ONELD Version 1. 1

This is the user's guide to CEPXS/ONELD Version 1.1, a code package for coupled electron-photon transport in one-dimensional slab geometry. The code package consists of the multigroup cross-section generating code, CEPXS; the preprocessor code, PRE1D; the discrete ordinates code, ONELD; and the postprocessor code, POST1D. In Version 1.1, new features have been implemented through several new keywords. Since Version 1.0 keywords are still applicable, this document should be considered as an addendum to the Version 1.0 User's Guide. 5 refs

Oncolytic Viruses: Do They Have a Role in Anti-Cancer Therapy?

Oncolytic viruses are replication competent, tumor selective and lyse cancer cells. Their potential for anti-cancer therapy is based upon the concept that selective intratumoral replication will produce a potent anti-tumor effect and possibly bystander or remote cell killing, whilst minimizing normal tissue toxicity. Viruses may be naturally oncolytic or be engineered for oncolytic activity, and possess a host of different mechanisms to provide tumor selectivity. Clinical use of live replicating viruses is associated with a unique set of safety issues. Clinical experience has so far provided evidence of limited efficacy and a favourable toxicity profile. The interaction with the host immune system is complex. An anti-viral immune response may limit efficacy by rapidly clearing the virus. However, virally-induced cell lysis releases tumor associated antigens in a ‘dangerous’ context, and limited evidence suggests that this can lead to the generation of a specific anti-tumor immune response. Combination therapy with chemotherapy or radiotherapy represents a promising avenue for ongoing translation of oncolytic viruses into clinical practice. Obstacles to therapy include highly effective non-specific host mechanisms to clear virus following systemic delivery, immune-mediated clearance, and intratumoral barriers limiting virus spread. A number of novel strategies are now under investigation to overcome these barriers. This review provides an overview of the potential role of oncolytic viruses, highlighting recent progress towards developing effective therapy and asks if they are a realistic therapeutic option at this stage

Do coder characteristics influence validity of ICD-10 hospital discharge data?

<p>Abstract</p> <p>Background</p> <p>Administrative data are widely used to study health systems and make important health policy decisions. Yet little is known about the influence of coder characteristics on administrative data validity in these studies. Our goal was to describe the relationship between several measures of validity in coded hospital discharge data and 1) coders' volume of coding (≥13,000 vs. <13,000 records), 2) coders' employment status (full- vs. part-time), and 3) hospital type.</p> <p>Methods</p> <p>This descriptive study examined 6 indicators of face validity in ICD-10 coded discharge records from 4 hospitals in Calgary, Canada between April 2002 and March 2007. Specifically, mean number of coded diagnoses, procedures, complications, Z-codes, and codes ending in 8 or 9 were compared by coding volume and employment status, as well as hospital type. The mean number of diagnoses was also compared across coder characteristics for 6 major conditions of varying complexity. Next, kappa statistics were computed to assess agreement between discharge data and linked chart data reabstracted by nursing chart reviewers. Kappas were compared across coder characteristics.</p> <p>Results</p> <p>422,618 discharge records were coded by 59 coders during the study period. The mean number of diagnoses per record decreased from 5.2 in 2002/2003 to 3.9 in 2006/2007, while the number of records coded annually increased from 69,613 to 102,842. Coders at the tertiary hospital coded the most diagnoses (5.0 compared with 3.9 and 3.8 at other sites). There was no variation by coder or site characteristics for any other face validity indicator. The mean number of diagnoses increased from 1.5 to 7.9 with increasing complexity of the major diagnosis, but did not vary with coder characteristics. Agreement (kappa) between coded data and chart review did not show any consistent pattern with respect to coder characteristics.</p> <p>Conclusions</p> <p>This large study suggests that coder characteristics do not influence the validity of hospital discharge data. Other jurisdictions might benefit from implementing similar employment programs to ours, e.g.: a requirement for a 2-year college training program, a single management structure across sites, and rotation of coders between sites. Limitations include few coder characteristics available for study due to privacy concerns.</p

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

Experimental Infection of Mice with Avian Paramyxovirus Serotypes 1 to 9

The nine serotypes of avian paramyxoviruses (APMVs) are frequently isolated from domestic and wild birds worldwide. APMV-1, also called Newcastle disease virus, was shown to be attenuated in non-avian species and is being developed as a potential vector for human vaccines. In the present study, we extended this evaluation to the other eight serotypes by evaluating infection in BALB/c mice. Mice were inoculated intranasally with a prototype strain of each of the nine serotypes and monitored for clinical disease, gross pathology, histopathology, virus replication and viral antigen distribution, and seroconversion. On the basis of multiple criteria, each of the APMV serotypes except serotype 5 was found to replicate in mice. Five of the serotypes produced clinical disease and significant weight loss in the following order of severity: 1, 2>6, 9>7. However, disease was short-lived. The other serotypes produced no evident clinical disease. Replication of all of the APMVs except APMV-5 in the nasal turbinates and lungs was confirmed by the recovery of infectious virus and by substantial expression of viral antigen in the epithelial lining detected by immunohistochemistry. Trace levels of infectious APMV-4 and -9 were detected in the brain of some animals; otherwise, no virus was detected in the brain, small intestine, kidney, or spleen. Histologically, infection with the APMVs resulted in lung lesions consistent with broncho-interstitial pneumonia of varying severity that were completely resolved at 14 days post infection. All of the mice infected with the APMVs except APMV-5 produced serotype-specific HI serum antibodies, confirming a lack of replication of APMV-5. Taken together, these results demonstrate that all APMV serotypes except APMV-5 are capable of replicating in mice with minimal disease and pathology

Assessment of the quality and variability of health information on chronic pain websites using the DISCERN instrument

<p>Abstract</p> <p>Background</p> <p>The Internet is used increasingly by providers as a tool for disseminating pain-related health information and by patients as a resource about health conditions and treatment options. However, health information on the Internet remains unregulated and varies in quality, accuracy and readability. The objective of this study was to determine the quality of pain websites, and explain variability in quality and readability between pain websites.</p> <p>Methods</p> <p>Five key terms (pain, chronic pain, back pain, arthritis, and fibromyalgia) were entered into the Google, Yahoo and MSN search engines. Websites were assessed using the DISCERN instrument as a quality index. Grade level readability ratings were assessed using the Flesch-Kincaid Readability Algorithm. Univariate (using alpha = 0.20) and multivariable regression (using alpha = 0.05) analyses were used to explain the variability in DISCERN scores and grade level readability using potential for commercial gain, health related seals of approval, language(s) and multimedia features as independent variables.</p> <p>Results</p> <p>A total of 300 websites were assessed, 21 excluded in accordance with the exclusion criteria and 110 duplicate websites, leaving 161 unique sites. About 6.8% (11/161 websites) of the websites offered patients' commercial products for their pain condition, 36.0% (58/161 websites) had a health related seal of approval, 75.8% (122/161 websites) presented information in English only and 40.4% (65/161 websites) offered an interactive multimedia experience. In assessing the quality of the unique websites, of a maximum score of 80, the overall average DISCERN Score was 55.9 (13.6) and readability (grade level) of 10.9 (3.9). The multivariable regressions demonstrated that website seals of approval (<it>P </it>= 0.015) and potential for commercial gain (<it>P </it>= 0.189) were contributing factors to higher DISCERN scores, while seals of approval (<it>P </it>= 0.168) and interactive multimedia (<it>P </it>= 0.244) contributed to lower grade level readability, as indicated by estimates of the beta coefficients.</p> <p>Conclusion</p> <p>The overall quality of pain websites is moderate, with some shortcomings. Websites that scored high using the DISCERN questionnaire contained health related seals of approval and provided commercial solutions for pain related conditions while those with low readability levels offered interactive multimedia options and have been endorsed by health seals.</p

Single Assay for Simultaneous Detection and Differential Identification of Human and Avian Influenza Virus Types, Subtypes, and Emergent Variants

For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence, host-range, and resistance to antiviral agents

Health information seeking on the Internet: a double divide? Results from a representative survey in the Paris metropolitan area, France, 2005–2006

<p>Abstract</p> <p>Background</p> <p>The Internet is a major source of information for professionals and the general public, especially in the field of health. However, despite ever-increasing connection rates, a digital divide persists in the industrialised countries. The objective of this study was to assess the determinants involved in: 1) having or not having Internet access; and 2) using or not using the Internet to obtain health information.</p> <p>Methods</p> <p>A cross-sectional survey of a representative random sample was conducted in the Paris metropolitan area, France, in the fall of 2005 (n = 3023).</p> <p>Results</p> <p>Close to 70% of the adult population had Internet access, and 49% of Internet users had previously searched for medical information. Economic and social disparities observed in online health information seeking are reinforced by the economic and social disparities in Internet access, hence a double divide. While individuals who reported having a recent health problem were less likely to have Internet access (odds ratio (OR): 0.72, 95% confidence interval (CI): 0.53–0.98), it is they who, when they have Internet access, are the most likely to search for health information (OR = 1.44, 95% CI = 1.11–1.87).</p> <p>Conclusion</p> <p>In the French context of universal health insurance, access to the Internet varies according to social and socioeconomic status and health status, and its use for health information seeking varies also with health beliefs, but not to health insurance coverage or health-care utilisation. Certain economic and social inequalities seem to impact cumulatively on Internet access and on the use of the Internet for health information seeking. It is not obvious that the Internet is a special information tool for primary prevention in people who are the furthest removed from health concerns. However, the Internet appears to be a useful complement for secondary prevention, especially for better understanding health problems or enhancing therapeutic compliance.</p

Ascorbate Biosynthesis during Early Fruit Development Is the Main Reason for Its Accumulation in Kiwi

Background: Ascorbic acid (AsA) is a unique antioxidant as well as an enzyme cofactor. Although it has multiple roles in plants, it is unclear how its accumulation is controlled at the expression level, especially in sink tissues. Kiwifruit (Actinidia) is well-known for its high ascorbate content. Our objective was to determine whether AsA accumulates in the fruits primarily through biosynthesis or because it is imported from the foliage. Methodology/Principal Findings: We systematically investigated AsA levels, biosynthetic capacity, and mRNA expression of genes involved in AsA biosynthesis in kiwi (A. deliciosa cv. Qinmei). Recycling and AsA localization were also monitored during fruit development and among different tissue types. Over time, the amount of AsA, with its capacity for higher biosynthesis and lower recycling, peaked at 30 days after anthesis (DAA), and then decreased markedly up to 60 DAA before declining more slowly. Expression of key genes showed similar patterns of change, except for L-galactono-1,4-lactone dehydrogenase and L-galactose-1-phosphate phosphatase (GPP). However, GPP had good correlation with the rate of AsA accumulation. The expression of these genes could be detected in phloem of stem as well as petiole of leaf and fruit. Additionally, fruit petioles had greater ascorbate amounts, although that was the site of lowest expression by most genes. Fruit microtubule tissues also had higher AsA. However, exogenous applications of AsA to those petioles did not lead to its transport into fruits, and distribution of ascorbate was cell-specific in the fruits, with more accumulation occurring in large