Bounds for Lepton Flavor Violation and the Pseudoscalar Higgs in the General Two Higgs Doublet Model using g−2g-2 muon factor

Current experimental data from the $g-2$ muon factor, seems to show the necessity of physics beyond the Standard Model (SM), since the difference between SM and experimental predictions is 2.6$\sigma$. In the framework of the General Two Higgs Doublet Model (2HDM), we calculate the muon anomalous magnetic moment to get lower and upper bounds for the Flavour Changing (FC) Yukawa couplings in the leptonic sector. We also obtain lower bounds for the mass of the pseudoscalar Higgs ($m_{A^0}$) as a function of the parameters of the model.Comment: 12 pages, RevTex4, 5 figures. Improved presentation, updated experimental data, amplified analysis, new figures added. Subbmited to Phys. Rev.

Factor Structure of Urdu Version of the Flourishing Scale

Background: A great deal of research has been carried out on the assessment of the eudaimonic perspective of psychological well-being and the hedonic perspective of subjective well-being. The Flourishing Scale (FS) has been extensively used in research and practice, as it assesses the fundamental aspects of social psychological functioning. Nevertheless, the psychometric properties of Urdu versions of eudaimonic measures, such as the FS, have not yet been ascertained. The translation and validation of the FS in the Urdu language was not available, and hence this study was planned with the aim to validate the Urdu version of the FS.Methods: We assessed the psychometric properties of the FS in a sample of adults aged 18 years and above in Pakistan (N = 130) using exploratory factor analysis based on principal component analysis with varimax rotation and confirmatory factor analysis.Results: The exploratory factor analysis confirmed the unidimensional nature of the 8-item FS. We assessed that the Urdu version of the FS showed a high internal consistency reliability (α = 0.914) with a significant intraclass correlation coefficient (ICC), p < 0.001). In our study, the Kaiser–Mayer–Olkin value was 0.915 with a chi-square test value (χ2) of 637.687, and Bartlett's test of sphericity was significant (df = 28, p < 0.001). The intraclass correlation coefficients (ICCs) at test–retest for all domains were statistically significant (p < 0.001) and showed excellent agreement for all the items. The revised confirmatory factor analysis revealed a good-fit model, but with item 8—“People respect me”—removed due to its lower factor loading.Conclusions: The findings suggest that the FS is a psychometrically sound instrument for assessing social psychological functioning among adults in Pakistan. Therefore, the validated Urdu version of the FS may be used in future studies of well-being in clinical psychology and positive psychology

The systematic guideline review: method, rationale, and test on chronic heart failure

Background: Evidence-based guidelines have the potential to improve healthcare. However, their de-novo-development requires substantial resources-especially for complex conditions, and adaptation may be biased by contextually influenced recommendations in source guidelines. In this paper we describe a new approach to guideline development-the systematic guideline review method (SGR), and its application in the development of an evidence-based guideline for family physicians on chronic heart failure (CHF). Methods: A systematic search for guidelines was carried out. Evidence-based guidelines on CHF management in adults in ambulatory care published in English or German between the years 2000 and 2004 were included. Guidelines on acute or right heart failure were excluded. Eligibility was assessed by two reviewers, methodological quality of selected guidelines was appraised using the AGREE instrument, and a framework of relevant clinical questions for diagnostics and treatment was derived. Data were extracted into evidence tables, systematically compared by means of a consistency analysis and synthesized in a preliminary draft. Most relevant primary sources were re-assessed to verify the cited evidence. Evidence and recommendations were summarized in a draft guideline. Results: Of 16 included guidelines five were of good quality. A total of 35 recommendations were systematically compared: 25/35 were consistent, 9/35 inconsistent, and 1/35 un-rateable (derived from a single guideline). Of the 25 consistencies, 14 were based on consensus, seven on evidence and four differed in grading. Major inconsistencies were found in 3/9 of the inconsistent recommendations. We re-evaluated the evidence for 17 recommendations (evidence-based, differing evidence levels and minor inconsistencies) - the majority was congruent. Incongruity was found where the stated evidence could not be verified in the cited primary sources, or where the evaluation in the source guidelines focused on treatment benefits and underestimated the risks. The draft guideline was completed in 8.5 man-months. The main limitation to this study was the lack of a second reviewer. Conclusion: The systematic guideline review including framework development, consistency analysis and validation is an effective, valid, and resource saving-approach to the development of evidence-based guidelines

Early exposure to secondhand tobacco smoke and the development of allergic diseases in 4 year old children in Malmö, Sweden

<p>Abstract</p> <p>Background</p> <p>Earlier studies have shown an association between secondhand tobacco smoke and allergy development in children. Furthermore, there is an increased risk of developing an allergy if the parents have an allergy. However, there are only few studies investigating the potential synergistic effect of secondhand tobacco smoke and allergic heredity on the development of an allergy.</p> <p>Methods</p> <p>The study was population-based cross-sectional with retrospective information on presence of secondhand tobacco smoke during early life. The study population consisted of children who visited the Child Health Care (CHC) centres in Malmö for their 4-year health checkup during 2006-2008 and whose parents answered a self-administered questionnaire (n = 4,278 children). The questionnaire was distributed to parents of children registered with the CHC and invited for the 4-year checkup during the study period.</p> <p>Results</p> <p>There was a two to four times increased odds of the child having an allergy or having sought medical care due to allergic symptoms if at least one parent had an allergy, while there were rather small increased odds related to presence of secondhand smoke during the child's first month in life or at the age of 8 months. However, children with heredity for allergies and with presence of secondhand tobacco smoke during their first year in life had highly increased odds of developing an allergy and having sought medical care due to allergic symptoms at 4 years of age. Thus, there was a synergistic effect enhancing the independent effects of heredity and exposure to secondhand tobacco smoke on allergy development.</p> <p>Conclusions</p> <p>Children with a family history of allergies and early exposure to secondhand tobacco smoke is a risk group that prevention and intervention should pay extra attention to. The tobacco smoke effect on children is an essential and urgent question considering it not being self chosen, possibly giving life lasting negative health effects and being possible to reduce.</p

Management of patients with biliary sphincter of Oddi disorder without sphincter of Oddi manometry

<p>Abstract</p> <p>Background</p> <p>The paucity of controlled data for the treatment of most biliary sphincter of Oddi disorder (SOD) types and the incomplete response to therapy seen in clinical practice and several trials has generated controversy as to the best course of management of these patients. In this observational study we aimed to assess the outcome of patients with biliary SOD managed without sphincter of Oddi manometry.</p> <p>Methods</p> <p>Fifty-nine patients with biliary SOD (14% type I, 51% type II, 35% type III) were prospectively enrolled. All patients with a dilated common bile duct were offered endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy whereas all others were offered medical treatment alone. Patients were followed up for a median of 15 months and were assessed clinically for response to treatment.</p> <p>Results</p> <p>At follow-up 15.3% of patients reported complete symptom resolution, 59.3% improvement, 22% unchanged symptoms, and 3.4% deterioration. Fifty-one percent experienced symptom resolution/improvement on medical treatment only, 12% after sphincterotomy, and 10% after both medical treatment/sphincterotomy. Twenty percent experienced at least one recurrence of symptoms after initial response to medical and/or endoscopic treatment. Fifty ERCP procedures were performed in 24 patients with an 18% complication rate (16% post-ERCP pancreatitis). The majority of complications occurred in the first ERCP these patients had. Most complications were mild and treated conservatively. Age, gender, comorbidity, SOD type, dilated common bile duct, presence of intact gallbladder, or opiate use were not related to the effect of treatment at the end of follow-up (p > 0.05 for all).</p> <p>Conclusions</p> <p>Patients with biliary SOD may be managed with a combination of endoscopic sphincterotomy (performed in those with dilated common bile duct) and medical therapy without manometry. The results of this approach with regards to symptomatic relief and ERCP complication rate are comparable to those previously published in the literature in cohorts of patients assessed by manometry.</p

Endotoxemia Is Associated with Altered Innate and Adaptive Immune Responses in Untreated HIV-1 Infected Individuals

BACKGROUND: Microbial translocation may contribute to the immunopathogenesis in HIV infection. We investigated if microbial translocation and inflammation were associated with innate and adaptive immune responses in adults with HIV. METHODOLOGY/PRINCIPAL FINDINGS: This was an observational cohort study. Sera from HIV-infected and HIV-uninfected individuals were analyzed for microbial translocation (soluble CD14, lipopolysaccharides [LPS], endotoxin core antibody, and anti-α-galactosyl antibodies) and inflammatory markers (high sensitivity C-reactive protein, IL-6, IL-1 receptor antagonist, soluble tumor necrosis factor receptor II, and IL-10) with enzyme-linked immunosorbent assays. Peripheral blood mononuclear cells (PBMC) from HIV-infected persons and healthy controls (primed with single-stranded HIV-1-derived RNA) were stimulated with LPS, and cytokine production was measured. Finally, HIV-infected patients were immunized with Prevnar 7vPnC±CpG 7909 followed by Pneumo Novum PPV-23. Effects of microbial translocation and inflammation on immunization were analyzed in a predictive regression model. We included 96 HIV-infected individuals, 76 on highly active antiretroviral therapy (HAART), 20 HAART-naive, and 50 healthy controls. Microbial translocation and inflammatory markers were higher among HIV-infected persons than controls. Cytokine levels following LPS stimulation were increased in PBMCs from HAART-naive compared to HAART-treated HIV-infected persons. Further, RNA-priming of PBMCs from controls acted synergistically with LPS to augment cytokine responses. Finally, high serum LPS levels predicted poor vaccine responses among HAART-naive, but not among HAART-treated HIV-infected individuals. CONCLUSIONS/SIGNIFICANCE: LPS acts synergistically with HIV RNA to stimulate innate immune responses in vitro and increasing serum LPS levels seem to predict poor antibody responses after vaccination among HAART-naive HIV-infected persons. Thus, our results suggest that microbial translocation may be associated with innate and adaptive immune dysfunction in untreated HIV infection

The International Law of Secession and the Protection of the Human Rights of Oppressed Sub-State Groups: Yesterday, Today and Tomorrow

This paper focuses on significant patterns/features in the historical development of the international law of secession and its contribution over time (or the lack thereof) to the struggle to afford greater protection to oppressed sub-state groups the world over. It was Crawford Young who once observed that “the state as an analytical quarry is an elusive and complex prey.” With the necessary modifications, this observation applies with almost equal force to the international law of secession. Complexity and confusion loom too large in this area of international law. For example, there is, at best, little clarity in the literature of the discipline of international law and in related fields of study regarding the existence or otherwise of an international legal entitlement to secession in favor of even the most highly oppressed and subjugated sub-state groups

Conflict of Interest in Clinical Practice Guideline Development: A Systematic Review

Background: There is an emerging literature on the existence and effect of industry relationships on physician and researcher behavior. Much less is known, however, about the effects of these relationships and other conflicts of interest (COI) on clinical practice guideline (CPG) development and recommendations. We performed a systematic review of the prevalence of COI and its effect on CPG recommendations. Methodology/Principal Findings: We searched Medline (1980 to March, 2011) for studies that examined the effect of COI on CPG development and/or recommendations. Data synthesis was qualitative. Twelve studies fulfilled inclusion criteria; 9 were conducted in the US. All studies reported on financial relationships of CPG authors with the pharmaceutical industry; 1 study also examined relationships with diagnostic testing and insurance companies. The majority of guidelines had authors with industry affiliations, including consultancies (authors with relationship, range 6–80%); research support (4–78%); equity/stock ownership (2–17%); or any COI (56–87%). Four studies reported multiple types of financial interactions for individual authors (number of types per author: range 2 to 10 or more). Data on the effect of COI on CPG recommendations were confined to case studies wherein authors with specific financial ties appeared to benefit from the related CPG recommendations. In a single study, few authors believed that their relationships influenced their recommendations. No studies reported on intellectual COI in CPGs

Estimating Genetic Ancestry Proportions from Faces

Ethnicity can be a means by which people identify themselves and others. This type of identification mediates many kinds of social interactions and may reflect adaptations to a long history of group living in humans. Recent admixture in the US between groups from different continents, and the historically strong emphasis on phenotypic differences between members of these groups, presents an opportunity to examine the degree of concordance between estimates of group membership based on genetic markers and on visually-based estimates of facial features. We first measured the degree of Native American, European, African and East Asian genetic admixture in a sample of 14 self-identified Hispanic individuals, chosen to cover a broad range of Native American and European genetic admixture proportions. We showed frontal and side-view photographs of the 14 individuals to 241 subjects living in New Mexico, and asked them to estimate the degree of NA admixture for each individual. We assess the overall concordance for each observer based on an aggregated measure of the difference between the observer and the genetic estimates. We find that observers reach a significantly higher degree of concordance than expected by chance, and that the degree of concordance as well as the direction of the discrepancy in estimates differs based on the ethnicity of the observer, but not on the observers' age or sex. This study highlights the potentially high degree of discordance between physical appearance and genetic measures of ethnicity, as well as how perceptions of ethnic affiliation are context-specific. We compare our findings to those of previous studies and discuss their implications

Relation of DNA Methylation of 5′-CpG Island of ACSL3 to Transplacental Exposure to Airborne Polycyclic Aromatic Hydrocarbons and Childhood Asthma

In a longitudinal cohort of ∼700 children in New York City, the prevalence of asthma (>25%) is among the highest in the US. This high risk may in part be caused by transplacental exposure to traffic-related polycyclic aromatic hydrocarbons (PAHs) but biomarkers informative of PAH-asthma relationships is lacking. We here hypothesized that epigenetic marks associated with transplacental PAH exposure and/or childhood asthma risk could be identified in fetal tissues. Mothers completed personal prenatal air monitoring for PAH exposure determination. Methylation sensitive restriction fingerprinting was used to analyze umbilical cord white blood cell (UCWBC) DNA of 20 cohort children. Over 30 DNA sequences were identified whose methylation status was dependent on the level of maternal PAH exposure. Six sequences were found to be homologous to known genes having one or more 5′-CpG island(s) (5′-CGI). Of these, acyl-CoA synthetase long-chain family member 3 (ACSL3) exhibited the highest concordance between the extent of methylation of its 5′-CGI in UCWBCs and the level of gene expression in matched fetal placental tissues in the initial 20 cohort children. ACSL3 was therefore chosen for further investigation in a larger sample of 56 cohort children. Methylation of the ACSL3 5′-CGI was found to be significantly associated with maternal airborne PAH exposure exceeding 2.41 ng/m3 (OR = 13.8; p<0.001; sensitivity = 75%; specificity = 82%) and with a parental report of asthma symptoms in children prior to age 5 (OR = 3.9; p<0.05). Thus, if validated, methylated ACSL3 5′CGI in UCWBC DNA may be a surrogate endpoint for transplacental PAH exposure and/or a potential biomarker for environmentally-related asthma. This exploratory report provides a new blueprint for the discovery of epigenetic biomarkers relevant to other exposure assessments and/or investigations of exposure-disease relationships in birth cohorts. The results support the emerging theory of early origins of later life disease development