Sequence variation of Epstein-Barr virus: viral types, geography, codon usage and diseases

138 new Epstein-Barr virus (EBV) genome sequences have been determined. 125 of these and 116 from previous reports were combined to produce a multiple sequence alignment of 241 EBV genomes, which we have used to analyze variation within the viral genome. The type 1/type2 classification of EBV remains the major form of variation and is defined mostly by EBNA2 and EBNA3, but the type 2 SNPs at the EBNA3 locus extend into the adjacent gp350 and gp42 genes, whose products mediate infection of B cells by EBV. A small insertion within the BART miRNA region of the genome was present in 21 EBV strains. EBV from saliva of USA patients with chronic active EBV infection aligned with the wild type EBV genome, with no evidence of WZhet rearrangements. The V3 polymorphism in the Zp promoter for BZLF1 was found to be frequent in nasopharyngeal carcinoma cases both from Hong Kong and Indonesia. Codon usage was found to differ between latent and lytic cycle EBV genes and the main forms of variation of the EBNA1 protein have been identified.IMPORTANCE Epstein-Barr virus causes most cases of infectious mononucleosis and post-transplant lymphoproliferative disease. It contributes to several types of cancer including Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B cell lymphoma, nasopharyngeal carcinoma and gastric carcinoma. EBV genome variation is important because some of the diseases associated with EBV have very different incidences in different populations and geographic regions - differences in the EBV genome might contribute to these diseases. Some specific EBV genome alterations that appear to be significant in EBV associated cancers are already known and current efforts to make an EBV vaccine and antiviral drugs should also take account of sequence differences in the proteins used as targets

Wegner on Hallucinations, Inconsistency, and the Illusion of Free Will. Some Critical Remarks

Wegner's argument on the illusory nature of conscious will, as developed in The Illusion of Conscious Will (2002) and other publications, has had major impact. Based on empirical data, he develops a theory of apparent mental causation in order to explain the occurrence of the illusion of conscious will. Part of the evidence for his argument is derived from a specific interpretation of the phenomenon of auditory verbal hallucinations as they may occur in schizophrenia. The aim of this paper is to evaluate the validity of the evidence on auditory verbal hallucinations as employed by Wegner. I conclude that auditory hallucinations do not provide solid evidence for Wegner's theory. Moreover, the phenomena in schizophrenia provide, in fact, an argument against part of Wegner's theory of apparent mental causation. © 2010 The Author(s)

Stereotactic body radiotherapy in the treatment of Pancreatic Adenocarcinoma in elderly patients

Background: Treatment of pancreatic adenocarcinoma in the elderly is often complicated by comorbidities that preclude surgery, chemotherapy and/or conventional external beam radiation therapy (EBRT). Stereotactic body radiotherapy (SBRT) has thus garnered interest in this setting.Methods: A retrospective review of 26 patients of age ≥ 80 with pancreatic adenocarcinoma treated with definitive SBRT+/-chemotherapy from 2007-2011 was performed. Twenty-seven percent of patients were stage I, 38% were stage II, 27% were stage III and 8% were stage IV. Patients most commonly received 24 Gy/1 fraction or 30-36 Gy/3 fractions. Kaplan-Meier was used to estimate overall survival (OS), local control (LC), cause specific survival (CSS) and freedom-from-metastatic disease (FFMD).Results: The median age was 86 (range 80-91), and median follow-up was 11.6 months (3.5-24.6). The median planning target volume was 21.48 cm3 (6.1-85.09). Median OS was 7.6 months with 6/12 month OS rates of 65.4%/34.6%, respectively. Median LC was 11.5 months, 6-month and 12-month actuarial LC rates were 60.1% and 41.2%, respectively. There were no independent predictors for LC, but there was a trend for improved LC with prescription dose greater than 20 Gy (p = 0.063). Median CSS was 6.3 months, and 6-month and 12-month actuarial CSS were 53.8% and 23.1%, respectively. Median FFMD was 8.4 months, and 6-month and 12-month actuarial rates were 62.0% and 41.4%, respectively. Nine patients (47%) had local failures, 11 (58%) had distant metastasis, and 7 (37%) had both. There were no acute or late grade 3+ toxicities.Conclusions: Definitive SBRT is feasible, safe and effective in elderly patients who have unresectable disease, have comorbidities precluding surgery or decline surgery. © 2013 Kim et al.; licensee BioMed Central Ltd

Bats Use Magnetite to Detect the Earth's Magnetic Field

While the role of magnetic cues for compass orientation has been confirmed in numerous animals, the mechanism of detection is still debated. Two hypotheses have been proposed, one based on a light dependent mechanism, apparently used by birds and another based on a “compass organelle” containing the iron oxide particles magnetite (Fe3O4). Bats have recently been shown to use magnetic cues for compass orientation but the method by which they detect the Earth's magnetic field remains unknown. Here we use the classic “Kalmijn-Blakemore” pulse re-magnetization experiment, whereby the polarity of cellular magnetite is reversed. The results demonstrate that the big brown bat Eptesicus fuscus uses single domain magnetite to detect the Earths magnetic field and the response indicates a polarity based receptor. Polarity detection is a prerequisite for the use of magnetite as a compass and suggests that big brown bats use magnetite to detect the magnetic field as a compass. Our results indicate the possibility that sensory cells in bats contain freely rotating magnetite particles, which appears not to be the case in birds. It is crucial that the ultrastructure of the magnetite containing magnetoreceptors is described for our understanding of magnetoreception in animals

Timed daily exercise remodels circadian rhythms in mice

Regular exercise is important for physical and mental health. An underexplored and intriguing property of exercise is its actions on the body’s 24 h or circadian rhythms. Molecular clock cells in the brain’s suprachiasmatic nuclei (SCN) use electrical and chemical signals to orchestrate their activity and convey time of day information to the rest of the brain and body. To date, the long-lasting effects of regular physical exercise on SCN clock cell coordination and communication remain unresolved. Utilizing mouse models in which SCN intercellular neuropeptide signaling is impaired as well as those with intact SCN neurochemical signaling, we examined how daily scheduled voluntary exercise (SVE) influenced behavioral rhythms and SCN molecular and neuronal activities. We show that in mice with disrupted neuropeptide signaling, SVE promotes SCN clock cell synchrony and robust 24 h rhythms in behavior. Interestingly, in both intact and neuropeptide signaling deficient animals, SVE reduces SCN neural activity and alters GABAergic signaling. These findings illustrate the potential utility of regular exercise as a long-lasting and effective non-invasive intervention in the elderly or mentally ill where circadian rhythms can be blunted and poorly aligned to the external world

Pathologic response with neoadjuvant chemotherapy and stereotactic body radiotherapy for borderline resectable and locally-advanced pancreatic cancer

Background: Neoadjuvant stereotactic body radiotherapy (SBRT) has potential applicability in the management of borderline resectable and locally-advanced pancreatic adenocarcinoma. In this series, we report the pathologic outcomes in the subset of patients who underwent surgery after neoadjuvant SBRT. Methods: Patients with borderline resectable or locally-advanced pancreatic adenocarcinoma who were treated with SBRT followed by resection were included. Chemotherapy was to the discretion of the medical oncologist and preceded SBRT for most patients. Results: Twelve patients met inclusion criteria. Most (92%) received neoadjuvant chemotherapy, and gemcitabine/capecitabine was most frequently utilized (n = 7). Most were treated with fractionated SBRT to 36 Gy/3 fractions (n = 7) and the remainder with single fraction to 24 Gy (n = 5). No grade 3+ acute toxicities attributable to SBRT were found. Two patients developed post-surgical vascular complications and one died secondary to this. The mean time to surgery after SBRT was 3.3 months. An R0 resection was performed in 92% of patients (n = 11/12). In 25% (n = 3/12) of patients, a complete pathologic response was achieved, and an additional 16.7% (n = 2/12) demonstrated <10% viable tumor cells. Kaplan-Meier estimated median progression free survival is 27.4 months. Overall survival is 92%, 64% and 51% at 1-, 2-, and 3-years. Conclusions: This study reports the pathologic response in patients treated with neoadjuvant chemotherapy and SBRT for borderline resectable and locally-advanced pancreatic cancer. In our experience, 92% achieved an R0 resection and 41.7% of patients demonstrated either complete or extensive pathologic response to treatment. The results of a phase II study of this novel approach will be forthcoming. © 2013 Rajagopalan et al.; licensee BioMed Central Ltd

Unconscious Thinking, Feeling and Behavior Towards Products and Brands: Introduction to a Journal of Brand Management Special Issue

This introduction reviews the motivating forces behind this issue, exploring the role of nonconscious consumer behavior in branding environments. The article establishes a foundation of unconscious research in psychology and consumer behavior, and then provides an introduction to the four articles that follow. The article concludes with a call to adopt an inclusive interpretive-positivistic stance to the study of unconscious consumer-brand behavior, attitudes and beliefs

Health-related quality of life and long-term prognosis in chronic hypercapnic respiratory failure: a prospective survival analysis

<p>Abstract</p> <p>Background</p> <p>Health-related quality of life (HRQL) is considered as an important outcome parameter in patients with chronic diseases. This study aimed to assess the role of disease-specific HRQL for long-term survival in patients of different diagnoses with chronic hypercapnic respiratory failure (CHRF).</p> <p>Methods</p> <p>In a cohort of 231 stable patients (chronic obstructive pulmonary disease (COPD), n = 98; non-COPD (obesity-hypoventilation syndrome, restrictive disorders, neuromuscular disorders), n = 133) with CHRF and current home mechanical ventilation (HMV), HRQL was assessed by the disease-specific Severe Respiratory Insufficiency (SRI) questionnaire and its prognostic value was prospectively evaluated during a follow-up of 2–4 years, using univariate and multivariate regression analysis.</p> <p>Results</p> <p>HRQL was more impaired in COPD (mean ± SD SRI-summary score (SRI-SS) 52.5 ± 15.6) than non-COPD patients (67.6 ± 16.4; p < 0.001). Overall mortality during 28.9 ± 8.8 months of follow-up was 19.1% (31.6% in COPD, 9.8% in non-COPD). To identify the overall role of SRI, we first evaluated the total study population. SRI-SS and its subdomains (except attendance symptoms and sleep), as well as body mass index (BMI), leukocyte number and spirometric indices were associated with long-term survival (p < 0.01 each). Of these, SRI-SS, leukocytes and forced expiratory volume in 1 s (FEV₁) turned out to be independent predictors (p < 0.05 each). More specifically, in non-COPD patients SRI-SS and most of its subdomains, as well as leukocyte number, were related to survival (p < 0.05), whereas in patients with COPD only BMI and lung function but not SRI were predictive.</p> <p>Conclusion</p> <p>In patients with CHRF and HMV, the disease-specific SRI was an overall predictor of long-term survival in addition to established risk factors. However, the SRI predominantly beared information regarding long-term survival in non-COPD patients, while in COPD patients objective measures of the disease state were superior. This on one hand highlights the significance of HRQL in the long-term course of patients with CHRF, on the other hand it suggests that the predictive value of HRQL depends on the underlying disease.</p

Fine-scale spatial variability of heat-related mortality in Philadelphia County, USA, from 1983-2008: a case-series analysis

<p>Abstract</p> <p>Background</p> <p>High temperature and humidity conditions are associated with short-term elevations in the mortality rate in many United States cities. Previous research has quantified this relationship in an aggregate manner over large metropolitan areas, but within these areas the response may differ based on local-scale variability in climate, population characteristics, and socio-economic factors.</p> <p>Methods</p> <p>We compared the mortality response for 48 Zip Code Tabulation Areas (ZCTAs) comprising Philadelphia County, PA to determine if certain areas are associated with elevated risk during high heat stress conditions. A randomization test was used to identify mortality exceedances for various apparent temperature thresholds at both the city and local scale. We then sought to identify the environmental, demographic, and social factors associated with high-risk areas via principal components regression.</p> <p>Results</p> <p>Citywide mortality increases by 9.3% on days following those with apparent temperatures over 34°C observed at 7:00 p.m. local time. During these conditions, elevated mortality rates were found for 10 of the 48 ZCTAs concentrated in the west-central portion of the County. Factors related to high heat mortality risk included proximity to locally high surface temperatures, low socioeconomic status, high density residential zoning, and age.</p> <p>Conclusions</p> <p>Within the larger Philadelphia metropolitan area, there exists statistically significant fine-scale spatial variability in the mortality response to high apparent temperatures. Future heat warning systems and mitigation and intervention measures could target these high risk areas to reduce the burden of extreme weather on summertime morbidity and mortality.</p

Regrets Associated with Providing Healthcare: Qualitative Study of Experiences of Hospital-Based Physicians and Nurses

Regret is an unavoidable corollary of clinical practice. Physicians and nurses perform countless clinical decisions and actions, in a context characterised by time pressure, information overload, complexity and uncertainty