A meta-analysis of pharmacotherapy for social anxiety disorder: an examination of efficacy, moderators, and mediators

INTRODUCTION: Social anxiety disorder (SAD) is among the most prevalent mental disorders, associated with impaired functioning and poor quality of life. Pharmacotherapy is the most widely utilized treatment option. The current study provides an updated meta-analytic review of the efficacy of pharmacotherapy and examines moderators and mediators of treatment efficacy. Areas Covered: A comprehensive search of the current literature yielded 52 randomized, pill placebo-controlled trials of pharmacotherapy for adults diagnosed with SAD. Data on potential mediators of treatment outcome were collected, as well as data necessary to calculate pooled correlation matrices to compute indirect effects. Expert Opinion: The overall effect size of pharmacotherapy for SAD is small to medium (Hedges' g = 0.41). Effect sizes were not moderated by age, sex, length of treatment, initial severity, risk of study bias, or publication year. Furthermore, reductions in symptoms mediated pharmacotherapy's effect on quality of life. Support was found for reverse mediation. Future directions may include sustained efforts to examine treatment mechanisms of pharmacotherapy using rigorous longitudinal methodology to better establish temporal precedence

Phylogenomics: Gene Duplication, Unrecognized Paralogy and Outgroup Choice

Comparative genomics has revealed the ubiquity of gene and genome duplication and subsequent gene loss. In the case of gene duplication and subsequent loss, gene trees can differ from species trees, thus frequent gene duplication poses a challenge for reconstruction of species relationships. Here I address the case of multi-gene sets of putative orthologs that include some unrecognized paralogs due to ancestral gene duplication, and ask how outgroups should best be chosen to reduce the degree of non-species tree (NST) signal. Consideration of expected internal branch lengths supports several conclusions: (i) when a single outgroup is used, the degree of NST signal arising from gene duplication is either independent of outgroup choice, or is minimized by use of a maximally closely related post-duplication (MCRPD) outgroup; (ii) when two outgroups are used, NST signal is minimized by using one MCRPD outgroup, while the position of the second outgroup is of lesser importance; and (iii) when two outgroups are used, the ability to detect gene trees that are inconsistent with known aspects of the species tree is maximized by use of one MCRPD, and is either independent of the position of the second outgroup, or is maximized for a more distantly related second outgroup. Overall, these results generalize the utility of closely-related outgroups for phylogenetic analysis

Survivability Is More Fundamental Than Evolvability

For a lineage to survive over long time periods, it must sometimes change. This has given rise to the term evolvability, meaning the tendency to produce adaptive variation. One lineage may be superior to another in terms of its current standing variation, or it may tend to produce more adaptive variation. However, evolutionary outcomes depend on more than standing variation and produced adaptive variation: deleterious variation also matters. Evolvability, as most commonly interpreted, is not predictive of evolutionary outcomes. Here, we define a predictive measure of the evolutionary success of a lineage that we call the k-survivability, defined as the probability that the lineage avoids extinction for k generations. We estimate the k-survivability using multiple experimental replicates. Because we measure evolutionary outcomes, the initial standing variation, the full spectrum of generated variation, and the heritability of that variation are all incorporated. Survivability also accounts for the decreased joint likelihood of extinction of sub-lineages when they 1) disperse in space, or 2) diversify in lifestyle. We illustrate measurement of survivability with in silico models, and suggest that it may also be measured in vivo using multiple longitudinal replicates. The k-survivability is a metric that enables the quantitative study of, for example, the evolution of 1) mutation rates, 2) dispersal mechanisms, 3) the genotype-phenotype map, and 4) sexual reproduction, in temporally and spatially fluctuating environments. Although these disparate phenomena evolve by well-understood microevolutionary rules, they are also subject to the macroevolutionary constraint of long-term survivability

Strategies to prevent HIV transmission among heterosexual African-American men

BACKGROUND: As part of qualitative research for developing a culturally sensitive and developmentally appropriate videotape-based HIV prevention intervention for heterosexual African- American men, six focus groups were conducted with thirty African-American men to determine their perceptions of AIDS as a threat to the African-American community, characteristics of past situations that have placed African Americans at risk for HIV infection, their personal high risk behaviors, and suggestions on how HIV intervention videotapes could be produced to achieve maximum levels of interest among African-American men in HIV training programs. METHODS: The groups took place at a low-income housing project in Houston, Texas, a major epicenter for HIV/AIDS. Each group was audiotaped, transcribed, and analyzed using theme and domain analysis. RESULTS: The results revealed that low-income African-American men perceive HIV/AIDS as a threat to their community and they have placed themselves at risk of HIV infection based on unsafe sex practices, substance abuse, and lack of knowledge. They also cite lack of income to purchase condoms as a barrier to safe sex practice. They believe that HIV training programs should address these risk factors and that videotapes developed for prevention should offer a sensationalized look at the effects of HIV/AIDS on affected persons. They further believe that programs should be held in African-American communities and should include condoms to facilitate reduction of risk behaviors. CONCLUSIONS: The results indicate that the respondents taking part in this study believe that HIV and AIDS are continued threats to the African-American community because of sexual risk taking behavior, that is, failure to use condoms. Further, African-American men are having sex without condoms when having sex with women often when they are under the influence of alcohol or other mind-altering substances and they are having sex with men while incarcerated and become infected and once released resume unprotected sexual relations with women. According to the men, substance abuse is an important part of the problem of HIV in the African-American community. This is in keeping with research that shows that drug use, especially crack cocaine, is linked to sexual risk taking among African Americans and to increased likelihood of becoming infected with other sexually transmitted diseases (STDs) including HIV. Thus, interventions for men should address condom use, condom availability, skills for using condoms, eroticizing condoms and substance abuse prevention. Men in the present study also strongly recommended that HIV/AIDS videotaped messages should include footage of the sensational effects of the disease

Tetraploid Wheat Landraces in the Mediterranean Basin: Taxonomy, Evolution and Genetic Diversity

The geographic distribution of genetic diversity and the population structure of tetraploid wheat landraces in the Mediterranean basin has received relatively little attention. This is complicated by the lack of consensus concerning the taxonomy of tetraploid wheats and by unresolved questions regarding the domestication and spread of naked wheats. These knowledge gaps hinder crop diversity conservation efforts and plant breeding programmes. We investigated genetic diversity and population structure in tetraploid wheats (wild emmer, emmer, rivet and durum) using nuclear and chloroplast simple sequence repeats, functional variations and insertion site-based polymorphisms. Emmer and wild emmer constitute a genetically distinct population from durum and rivet, the latter seeming to share a common gene pool. Our population structure and genetic diversity data suggest a dynamic history of introduction and extinction of genotypes in the Mediterranean fields

Geographic and Racial Variation in Premature Mortality in the U.S.: Analyzing the Disparities

Life expectancy at birth, estimated from United States period life tables, has been shown to vary systematically and widely by region and race. We use the same tables to estimate the probability of survival from birth to age 70 (S70), a measure of mortality more sensitive to disparities and more reliably calculated for small populations, to describe the variation and identify its sources in greater detail to assess the patterns of this variation. Examination of the unadjusted probability of S70 for each US county with a sufficient population of whites and blacks reveals large geographic differences for each race-sex group. For example, white males born in the ten percent healthiest counties have a 77 percent probability of survival to age 70, but only a 61 percent chance if born in the ten percent least healthy counties. Similar geographical disparities face white women and blacks of each sex. Moreover, within each county, large differences in S70 prevail between blacks and whites, on average 17 percentage points for men and 12 percentage points for women. In linear regressions for each race-sex group, nearly all of the geographic variation is accounted for by a common set of 22 socio-economic and environmental variables, selected for previously suspected impact on mortality; R2 ranges from 0.86 for white males to 0.72 for black females. Analysis of black-white survival chances within each county reveals that the same variables account for most of the race gap in S70 as well. When actual white male values for each explanatory variable are substituted for black in the black male prediction equation to assess the role explanatory variables play in the black-white survival difference, residual black-white differences at the county level shrink markedly to a mean of −2.4% (+/−2.4); for women the mean difference is −3.7% (+/−2.3)

Mutations in Radial Spoke Head Genes and Ultrastructural Cilia Defects in East-European Cohort of Primary Ciliary Dyskinesia Patients

Primary ciliary dyskinesia (PCD) is a rare (1/20,000), multisystem disease with a complex phenotype caused by the impaired motility of cilia/flagella, usually related to ultrastructural defects of these organelles. Mutations in genes encoding radial spoke head (RSPH) proteins, elements of the ciliary ultrastructure, have been recently described. However, the relative involvement of RSPH genes in PCD pathogenesis remained unknown, due to a small number of PCD families examined for mutations in these genes. The purpose of this study was to estimate the involvement of RSPH4A and RSPH9 in PCD pathogenesis among East Europeans (West Slavs), and to shed more light on ultrastructural ciliary defects caused by mutations in these genes. The coding sequences of RSPH4A and RSPH9 were screened in PCD patients from 184 families, using single strand conformational polymorphism analysis and sequencing. Two previously described (Q109X; R490X) and two new RSPH4A mutations (W356X; IVS3_2–5del), in/around exons 1 and 3, were identified; no mutations were found in RSPH9. We estimate that mutations in RSPH4A, but not in RSPH9, are responsible for 2–3% of cases in the East European PCD population (4% in PCD families without situs inversus; 11% in families preselected for microtubular defects). Analysis of the SNP-haplotype background provided insight into the ancestry of repetitively found mutations (Q109X; R490X; IVS3_2–5del), but further studies involving other PCD cohorts are required to elucidate whether these mutations are specific for Slavic people or spread among other European populations. Ultrastructural defects associated with the mutations were analyzed in the transmission electron microscope images; almost half of the ciliary cross-sections examined in patients with RSPH4A mutations had the microtubule transposition phenotype (9+0 and 8+1 pattern). While microtubule transposition was a prevalent ultrastructural defect in cilia from patients with RSPH4A mutations, similar defects were also observed in PCD patients with mutations in other genes