Phenomenological Consequences of sub-leading Terms in See-Saw Formulas

Several aspects of next-to-leading (NLO) order corrections to see-saw formulas are discussed and phenomenologically relevant situations are identified. We generalize the formalism to calculate the NLO terms developed for the type I see-saw to variants like the inverse, double or linear see-saw, i.e., to cases in which more than two mass scales are present. In the standard type I case with very heavy fermion singlets the sub-leading terms are negligible. However, effects in the percent regime are possible when sub-matrices of the complete neutral fermion mass matrix obey a moderate hierarchy, e.g. weak scale and TeV scale. Examples are cancellations of large terms leading to small neutrino masses, or inverse see-saw scenarios. We furthermore identify situations in which no NLO corrections to certain observables arise, namely for mu-tau symmetry and cases with a vanishing neutrino mass. Finally, we emphasize that the unavoidable unitarity violation in see-saw scenarios with extra fermions can be calculated with the formalism in a straightforward manner.Comment: 22 pages, matches published versio

A knowledge management tool for public health: health-evidence.ca

<p>Abstract</p> <p>Background</p> <p>The ultimate goal of knowledge translation and exchange (KTE) activities is to facilitate incorporation of research knowledge into program and policy development decision making. Evidence-informed decision making involves translation of the best available evidence from a systematically collected, appraised, and analyzed body of knowledge. Knowledge management (KM) is emerging as a key factor contributing to the realization of evidence-informed public health decision making. The goal of health-evidence.ca is to promote evidence-informed public health decision making through facilitation of decision maker access to, retrieval, and use of the best available synthesized research evidence evaluating the effectiveness of public health interventions.</p> <p>Methods</p> <p>The systematic reviews that populate health evidence.ca are identified through an extensive search (1985-present) of 7 electronic databases: MEDLINE, EMBASE, CINAHL, PsycINFO, Sociological Abstracts, BIOSIS, and SportDiscus; handsearching of over 20 journals; and reference list searches of all relevant reviews. Reviews are assessed for relevance and quality by two independent reviewers. Commonly-used public health terms are used to assign key words to each review, and project staff members compose short summaries highlighting results and implications for policy and practice.</p> <p>Results</p> <p>As of June 2010, there are 1913 reviews in the health-evidence.ca registry in 21 public health and health promotion topic areas. Of these, 78% have been assessed as being of strong or moderate methodological quality. Health-evidence.ca receives approximately 35,000 visits per year, 20,596 of which are unique visitors, representing approximately 100 visits per day. Just under half of all visitors return to the site, with the average user spending six minutes and visiting seven pages per visit. Public health nurses, program managers, health promotion workers, researchers, and program coordinators are among the largest groups of registered users, followed by librarians, dieticians, medical officers of health, and nutritionists. The majority of users (67%) access the website from direct traffic (e.g., have the health-evidence.ca webpage bookmarked, or type it directly into their browser).</p> <p>Conclusions</p> <p>Consistent use of health-evidence.ca and particularly the searching for reviews that correspond with current public health priorities illustrates that health-evidence.ca may be playing an important role in achieving evidence-informed public health decision making.</p

Adiponectin Haploinsufficiency Promotes Mammary Tumor Development in MMTV-PyVT Mice by Modulation of Phosphatase and Tensin Homolog Activities

Background: Adiponectin is an adipokine possessing beneficial effects on obesity-related medical complications. A negative association of adiponectin levels with breast cancer development has been demonstrated. However, the precise role of adiponectin deficiency in mammary carcinogenesis remains elusive. Methodology/Principal Findings: In the present study, MMTV-polyomavirus middle T antigen (MMTV-PyVT) transgenic mice with reduced adiponectin expressions were established and the stromal effects of adiponectin haploinsufficiency on mammary tumor development evaluated. In mice from both FVB/N and C57BL/6J backgrounds, insufficient adiponectin production promoted mammary tumor onset and development. A distinctive basal-like subtype of tumors, with a more aggressive phenotype, was derived from adiponectin haplodeficient MMTV-PyVT mice. Comparing with those from control MMTV-PyVT mice, the isolated mammary tumor cells showed enhanced tumor progression in re-implanted nude mice, accelerated proliferation in primary cultures, and hyperactivated phosphatidylinositol-3-kinase (PI3K)/Akt/beta-catenin signaling, which at least partly attributed to the decreased phosphatase and tensin homolog (PTEN) activities. Further analysis revealed that PTEN was inactivated by a redox-regulated mechanism. Increased association of PTEN-thioredoxin complexes was detected in tumors derived from mice with reduced adiponectin levels. The activities of thioredoxin (Trx1) and thioredoxin reductase (TrxR1) were significantly elevated, whereas treatment with either curcumin, an irreversible inhibitor of TrxR1, or adiponectin largely attenuated their activities and resulted in the re-activation of PTEN in these tumor cells. Moreover, adiponectin could inhibit TrxR1 promoter-mediated transcription and restore the mRNA expressions of TrxR1. Conclusion: Adiponectin haploinsufficiency facilitated mammary tumorigenesis by down-regulation of PTEN activity and activation of PI3K/ Akt signalling pathway through a mechanism involving Trx1/TrxR1 redox regulations. © 2009 Lam et al.published_or_final_versio

A Conserved Role for Syndecan Family Members in the Regulation of Whole-Body Energy Metabolism

Syndecans are a family of type-I transmembrane proteins that are involved in cell-matrix adhesion, migration, neuronal development, and inflammation. Previous quantitative genetic studies pinpointed Drosophila Syndecan (dSdc) as a positional candidate gene affecting variation in fat storage between two Drosophila melanogaster strains. Here, we first used quantitative complementation tests with dSdc mutants to confirm that natural variation in this gene affects variability in Drosophila fat storage. Next, we examined the effects of a viable dSdc mutant on Drosophila whole-body energy metabolism and associated traits. We observed that young flies homozygous for the dSdc mutation had reduced fat storage and slept longer than homozygous wild-type flies. They also displayed significantly reduced metabolic rate, lower expression of spargel (the Drosophila homologue of PGC-1), and reduced mitochondrial respiration. Compared to control flies, dSdc mutants had lower expression of brain insulin-like peptides, were less fecund, more sensitive to starvation, and had reduced life span. Finally, we tested for association between single nucleotide polymorphisms (SNPs) in the human SDC4 gene and variation in body composition, metabolism, glucose homeostasis, and sleep traits in a cohort of healthy early pubertal children. We found that SNP rs4599 was significantly associated with resting energy expenditure (P = 0.001 after Bonferroni correction) and nominally associated with fasting glucose levels (P = 0.01) and sleep duration (P = 0.044). On average, children homozygous for the minor allele had lower levels of glucose, higher resting energy expenditure, and slept shorter than children homozygous for the common allele. We also observed that SNP rs1981429 was nominally associated with lean tissue mass (P = 0.035) and intra-abdominal fat (P = 0.049), and SNP rs2267871 with insulin sensitivity (P = 0.037). Collectively, our results in Drosophila and humans argue that syndecan family members play a key role in the regulation of body metabolism

Hepatitis C virus therapy is associated with lower health care costs not only in noncirrhotic patients but also in patients with end‐stage liver disease

BackgroundThe effect of anti-viral treatment on downstream costs for hepatitis C virus (HCV)-infected patients is unknown.AimTo evaluate follow-up costs in patients with chronic HCV, stratified by liver disease severity.MethodsUsing a US private insurance database, mean all-cause per-patient-per-month (PPPM) US (2010) medical costs were calculated for HCV-infected persons who did and did not receive anti-HCV treatment between January 2002 and August 2010. Analysis was stratified by liver disease severity [noncirrhotic disease (NCD), compensated cirrhosis (CC) or end-stage liver disease (ESLD)] defined by ICD-9 and CPT codes.ResultsA total of 33 309 patients were included (78% NCD, 7% CC and 15% ESLD); 4111 individuals (12%) received anti-HCV treatment during the 2-year baseline period. Mean PPPM follow-up health care costs were significantly lower among treated patients with NCD ($900 vs.$1378 in untreated patients, P &lt; 0.001) and ESLD ($3634 vs.$5071, P &lt; 0.001) groups but not in the CC group ($1404 vs.$1795, P &lt; 0.071; t-test). In a multivariable model adjusted for demographic characteristics, comorbidities, index date and geographical region, incremental cost ratios for total health care costs differed significantly (P &lt; 0.001) between treated and untreated patients in the NCD and ESLD groups but not in the CC group. From this model, mean PPPM total health care costs between treated and untreated patients were $885 and$1370 in the NCD, $1369 and$1802 in the CC, and $3547 and$5137 in the ESLD groups, respectively.ConclusionsAnti-HCV therapy was associated with lower follow-up US health care costs, and these savings were independent of baseline patient comorbidities and stage of disease