The relationship between area poverty rate and site-specific cancer incidence in the United States

BACKGROUND The relationship between socioeconomic status and cancer incidence in the United States has not traditionally been a focus of population-based cancer surveillance systems. METHODS Nearly 3 million tumors diagnosed between 2005 and 2009 from 16 states plus Los Angeles were assigned into 1 of 4 groupings based on the poverty rate of the residential census tract at time of diagnosis. The sex-specific risk ratio of the highest-to-lowest poverty category was measured using Poisson regression, adjusting for age and race, for 39 cancer sites. RESULTS For all sites combined, there was a negligible association between cancer incidence and poverty; however, 32 of 39 cancer sites showed a significant association with poverty (14 positively associated and 18 negatively associated). Nineteen of these sites had monotonic increases or decreases in risk across all 4 poverty categories. The sites most strongly associated with higher poverty were Kaposi sarcoma, larynx, cervix, penis, and liver; those most strongly associated with lower poverty were melanoma, thyroid, other nonepithelial skin, and testis. Sites associated with higher poverty had lower incidence and higher mortality than those associated with lower poverty. CONCLUSIONS These findings demonstrate the importance and relevance of including a measure of socioeconomic status in national cancer surveillanc

Long-term efficacy and safety of dichlorphenamide for treatment of primary periodic paralysis

Introduction/Aim: Long-term efficacy and safety of dichlorphenamide (DCP) were characterized in patients with primary periodic paralysis (PPP). Methods: Patients with PPP in a double-blind, placebo-controlled study were randomly assigned to receive DCP 50 mg twice daily or placebo for 9 weeks, followed by a 52-week open-label DCP treatment phase (DCP/DCP and placebo/DCP populations). Efficacy (attack rate, severity-weighted attack rate) and safety were assessed in patients completing the study (61 weeks). In this post hoc analysis, efficacy and safety data were pooled from hyperkalemic and hypokalemic substudies. Results: Sixty-three adults (age, 19-76 years) completed the double-blind phase; 47 (74.6%) of these patients completed 61 weeks. There were median decreases in weekly attack and severity-weighted attack rates from baseline to week 61 (DCP/DCP [n = 25], −1.00 [P < .0001]; placebo/DCP [n = 20], −0.63 [P = .01] and DCP/DCP, −2.25 [P < .0001]; placebo/DCP, −1.69 [P = .01]). Relatively smaller median decreases in weekly attack and severity-weighted attack rates occurred from weeks 9 to 61 among patients receiving DCP continuously (n = 26; −0.14 [P = .1] and −0.24 [P = .09]) than among those switching from placebo to DCP after 9 weeks (n = 16; −1.04 [P = .049] and −2.72 [P = .08]). Common adverse events (AEs) were paresthesia and cognition-related events, which typically first occurred within 1 month of blinded treatment initiation and in rare cases led to treatment discontinuation. Dose reductions were frequently associated with common AE resolution. Discussion: One-year open-label DCP treatment after a 9-week randomized, controlled study confirmed long-term DCP remains safe and effective for chronic use. Tolerability issues (paresthesia, cognition-related AEs) were manageable in most patients

Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1

Pitfalls of using the risk ratio in meta‐analysis

For meta-analysis of studies that report outcomes as binomial proportions, the most popular measure of effect is the odds ratio (OR), usually analyzed as log(OR). Many meta-analyses use the risk ratio (RR) and its logarithm, because of its simpler interpretation. Although log(OR) and log(RR) are both unbounded, use of log(RR) must ensure that estimates are compatible with study-level event rates in the interval (0, 1). These complications pose a particular challenge for random-effects models, both in applications and in generating data for simulations. As background we review the conventional random-effects model and then binomial generalized linear mixed models (GLMMs) with the logit link function, which do not have these complications. We then focus on log-binomial models and explore implications of using them; theoretical calculations and simulation show evidence of biases. The main competitors to the binomial GLMMs use the beta-binomial (BB) distribution, either in BB regression or by maximizing a BB likelihood; a simulation produces mixed results. Two examples and an examination of Cochrane meta-analyses that used RR suggest bias in the results from the conventional inverse-variance-weighted approach. Finally, we comment on other measures of effect that have range restrictions, including risk difference, and outline further research

Sporormiella as a tool for detecting the presence of large herbivores in the Neotropics

The reliability of using the abundance of Sporormiella spores as a proxy for the presence and abundance of megaherbivores was tested in southern Brazil. Mud-water interface samples from nine lakes, in which cattle-use was categorized as high, medium, or low, were assayed for Sporormiella representation. The sampling design allowed an analysis of both the influence of the number of animals using the shoreline and the distance of the sampling site from the nearest shoreline. Sporormiella was found to be a reliable proxy for the presence of large livestock. The concentration and abundance of spores declined from the edge of the lake toward the center, with the strongest response being in sites with high livestock use. Consistent with prior studies in temperate regions, we find that Sporormiella spores are a useful proxy to study the extinction of Pleistocene megafauna or the arrival of European livestock in Neotropical landscapes

Elective Modernism and the Politics of (Bio) Ethical Expertise

In this essay I consider whether the political perspective of third wave science studies – ‘elective modernism’ – offers a suitable framework for understanding the policy-making contributions that (bio)ethical experts might make. The question arises as a consequence of the fact that I have taken inspiration from the third wave in order to develop an account of (bio)ethical expertise. I offer a précis of this work and a brief summary of elective modernism before considering their relation. The view I set out suggests that elective modernism is a political philosophy and that although its use in relation to the use of scientific expertise in political and policy-making process has implications for the role of (bio)ethical expertise it does not, in the final analysis, provide an account that is appropriate for this latter form of specialist expertise. Nevertheless, it is an informative perspective, and one that can help us make sense of the political uses of (bio)ethical expertise

Distinct Binding and Immunogenic Properties of the Gonococcal Homologue of Meningococcal Factor H Binding Protein

Neisseria meningitidis is a leading cause of sepsis and meningitis. The bacterium recruits factor H (fH), a negative regulator of the complement system, to its surface via fH binding protein (fHbp), providing a mechanism to avoid complement-mediated killing. fHbp is an important antigen that elicits protective immunity against the meningococcus and has been divided into three different variant groups, V1, V2 and V3, or families A and B. However, immunisation with fHbp V1 does not result in cross-protection against V2 and V3 and vice versa. Furthermore, high affinity binding of fH could impair immune responses against fHbp. Here, we investigate a homologue of fHbp in Neisseria gonorrhoeae, designated as Gonococcal homologue of fHbp (Ghfp) which we show is a promising vaccine candidate for N. meningitidis. We demonstrate that Gfhp is not expressed on the surface of the gonococcus and, despite its high level of identity with fHbp, does not bind fH. Substitution of only two amino acids in Ghfp is sufficient to confer fH binding, while the corresponding residues in V3 fHbp are essential for high affinity fH binding. Furthermore, immune responses against Ghfp recognise V1, V2 and V3 fHbps expressed by a range of clinical isolates, and have serum bactericidal activity against N. meningitidis expressing fHbps from all variant groups

Psychosocial Factors Associated with Patterns of Smoking Surrounding Pregnancy in Fragile Families

Although research has documented factors associated with maternal smoking, we need a more in-depth understanding of the risk factors associated with changes in smoking behaviors during the postpartum period. We investigate smoking patterns during pregnancy and 1 year postpartum as a function of relevant psychosocial factors. We use data on 3,522 postpartum mothers from the Fragile Families and Child Wellbeing Study to analyze the predictors of smoking among mothers who did not smoke during pregnancy but smoked at 1 year postpartum, mothers who smoked both during pregnancy and postpartum, and mothers who did not smoke during either period. Our covariates are grouped into four categories of risk factors for smoking: socioeconomic status, health care, life course and health, and partner and social support. Postpartum mothers in our sample were more likely to smoke throughout or after their pregnancies if they had only a high school education or less, had a household income three or more times below the poverty line, had public or no health insurance, breastfed for less than 5 months, were not married to the infant’s father, if the infant’s father currently smoked, and if they attended religious services less than once a week. Mental health problems were consistently associated with an increased risk of constant and postpartum smoking relative to non-smoking. Psychosocial factors play a role in postpartum smoking, but they have a stronger effect in predicting smoking that persists throughout pregnancy and the first year postpartum