Fluctuating selection models and Mcdonald-Kreitman type analyses

It is likely that the strength of selection acting upon a mutation varies through time due to changes in the environment. However, most population genetic theory assumes that the strength of selection remains constant. Here we investigate the consequences of fluctuating selection pressures on the quantification of adaptive evolution using McDonald-Kreitman (MK) style approaches. In agreement with previous work, we show that fluctuating selection can generate evidence of adaptive evolution even when the expected strength of selection on a mutation is zero. However, we also find that the mutations, which contribute to both polymorphism and divergence tend, on average, to be positively selected during their lifetime, under fluctuating selection models. This is because mutations that fluctuate, by chance, to positive selected values, tend to reach higher frequencies in the population than those that fluctuate towards negative values. Hence the evidence of positive adaptive evolution detected under a fluctuating selection model by MK type approaches is genuine since fixed mutations tend to be advantageous on average during their lifetime. Never-the-less we show that methods tend to underestimate the rate of adaptive evolution when selection fluctuates

Sickle cell trait and priapism: a case report and review of the literature

Background A 32 year-old African-American man presented to our institution after attempting suicide via ingestion with quetiapine. He had reported a history of several days of substance abuse with alcohol, cocaine and marijuana related to a partying binge. Following this, his partner removed him from his residence resulting in a suicide attempt. During hospitalization the patient developed priapism, a condition he had not experienced before. Case presentation Given this was his first time with priapism, an extensive work-up revealed the patient had previously undiagnosed sickle cell trait, which we postulate to have been a significant factor in his development of acute priapism. Sickle cell trait is considered to be a generally benign condition except for a few rare complications under more demanding physical conditions. However, upon reviewing the literature on the association of sickle cell trait with priapism, we believe this may not be the case. Case reports and small series that appeared in the 1960s and 1970s indicated an association between priapism and sickle trait. Little has been reported recently, and the general teaching regarding sickle cell trait does not include this information. However, one case was reported with the use of phosphodiesterase-5 (PDE-5) inhibitors and the development of priapism in a patient with sickle cell trait. These medications are now first line treatment in erectile dysfunction. They act by enhancing nitric oxide (NO) production leading to relaxation of smooth muscle in the corpora cavernosa and penile arteries. Conclusion Priapism was not reported in the initial studies of these medications. Further review of the literature indicates this may be a complex relationship. Interestingly, PDE5 inhibitors also have been postulated to be protective in sickle cell disease and perhaps also sickle cell trait because priapism might be caused by reduced NO availability. In this article, we examine the evidence linking sickle cell trait to priapism, explore the implications of PDE5 use, particularly in the setting of sickle cell trait, and propose that teaching about sickle cell trait include a discussion of priapism risk

Trace-gas metabolic versatility of the facultative methanotroph Methylocella silvestris

The climate-active gas methane is generated both by biological processes and by thermogenic decomposition of fossil organic material, which forms methane and short-chain alkanes, principally ethane, propane and butane1, 2. In addition to natural sources, environments are exposed to anthropogenic inputs of all these gases from oil and gas extraction and distribution. The gases provide carbon and/or energy for a diverse range of microorganisms that can metabolize them in both anoxic3 and oxic zones. Aerobic methanotrophs, which can assimilate methane, have been considered to be entirely distinct from utilizers of short-chain alkanes, and studies of environments exposed to mixtures of methane and multi-carbon alkanes have assumed that disparate groups of microorganisms are responsible for the metabolism of these gases. Here we describe the mechanism by which a single bacterial strain, Methylocella silvestris, can use methane or propane as a carbon and energy source, documenting a methanotroph that can utilize a short-chain alkane as an alternative to methane. Furthermore, during growth on a mixture of these gases, efficient consumption of both gases occurred at the same time. Two soluble di-iron centre monooxygenase (SDIMO) gene clusters were identified and were found to be differentially expressed during bacterial growth on these gases, although both were required for efficient propane utilization. This report of a methanotroph expressing an additional SDIMO that seems to be uniquely involved in short-chain alkane metabolism suggests that such metabolic flexibility may be important in many environments where methane and short-chain alkanes co-occur

Furthering patient adherence: A position paper of the international expert forum on patient adherence based on an internet forum discussion

<p>Abstract</p> <p>Background</p> <p>As the problem of patient non-adherence persists and a solution appears hard to be found, it continues to be important to look for new ways to further the issue. We recently conducted a meta-review of adherence intervention studies which yielded a preliminary agenda for future research, practice and theory development in patient adherence. The objective of the present project was to find out to what extent adherence experts consider this agenda relevant and feasible.</p> <p>Methods</p> <p>The thirty-five corresponding authors of the review studies included in the meta-review were invited to join the International Expert Forum on Patient Adherence and to participate in a four-week web-based focus group discussion. The discussion was triggered by the points on the preliminary agenda presented as propositions to which forum members could react. Two researchers analysed the transcripts and selected relevant phrases.</p> <p>Results</p> <p>Twenty adherence experts participated. Various ideas and viewpoints were raised. After the closure of the web-site, the expert forum was asked to authorize the synthesis of the discussion, to list the propositions in order of priority and to answer a few questions on the use of the web-based focus group as a tool to obtain expert opinions. Their ranking showed that the development of simple interventions is the most promising step to take in fostering patient adherence, preferably within a multidisciplinary setting of medical, pharmaceutical, social and technical science and, not in the least, by incorporating patients' perspectives.</p> <p>Conclusion</p> <p>For enhancing adherence, the development of simple interventions originating from a multidisciplinary perspective including patients' input, appears most promising. Disclosing patients' perspectives requires open communication about patients' expectations, needs and experiences in taking medication and about what might help them to become and remain adherent.</p

Development of an international survey attitude scale: measurement equivalence, reliability, and predictive validity

Declining response rates worldwide have stimulated interest in understanding what may be influencing this decline and how it varies across countries and survey populations. In this paper, we describe the development and validation of a short 9-item survey attitude scale that measures three important constructs, thought by many scholars to be related to decisions to participate in surveys, that is, survey enjoyment, survey value, and survey burden. The survey attitude scale is based on a literature review of earlier work by multiple authors. Our overarching goal with this study is to develop and validate a concise and effective measure of how individuals feel about responding to surveys that can be implemented in surveys and panels to understand the willingness to participate in surveys and improve survey effectiveness. The research questions relate to factor structure, measurement equivalence, reliability, and predictive validity of the survey attitude scale. The data came from three probability-based panels: the German GESIS and PPSM panels and the Dutch LISS panel. The survey attitude scale proved to have a replicable three-dimensional factor structure (survey enjoyment, survey value, and survey burden). Partial scalar measurement equivalence was established across three panels that employed two languages (German and Dutch) and three measurement modes (web, telephone, and paper mail). For all three dimensions of the survey attitude scale, the reliability of the corresponding subscales (enjoyment, value, and burden) was satisfactory. Furthermore, the scales correlated with survey response in the expected directions, indicating predictive validity

Influence of Prior Influenza Vaccination on Antibody and B-Cell Responses

Currently two vaccines, trivalent inactivated influenza vaccine (TIV) and live attenuated influenza vaccine (LAIV), are licensed in the USA. Despite previous studies on immune responses induced by these two vaccines, a comparative study of the influence of prior influenza vaccination on serum antibody and B-cell responses to new LAIV or TIV vaccination has not been reported. During the 2005/6 influenza season, we quantified the serum antibody and B-cell responses to LAIV or TIV in adults with differing influenza vaccination histories in the prior year: LAIV, TIV, or neither. Blood samples were collected on days 0, 7–9 and 21–35 after immunization and used for serum HAI assay and B-cell assays. Total and influenza-specific circulating IgG and IgA antibody secreting cells (ASC) in PBMC were detected by direct ELISPOT assay. Memory B cells were also tested by ELISPOT after polyclonal stimulation of PBMC in vitro. Serum antibody, effector, and memory B-cell responses were greater in TIV recipients than LAIV recipients. Prior year TIV recipients had significantly higher baseline HAI titers, but lower HAI response after vaccination with either TIV or LAIV, and lower IgA ASC response after vaccination with TIV than prior year LAIV or no vaccination recipients. Lower levels of baseline HAI titer were associated with a greater fold-increase of HAI titer and ASC number after vaccination, which also differed by type of vaccine. Our findings suggest that the type of vaccine received in the prior year affects the serum antibody and the B-cell responses to subsequent vaccination. In particular, prior year TIV vaccination is associated with sustained higher HAI titer one year later but lower antibody response to new LAIV or TIV vaccination, and a lower effector B-cell response to new TIV but not LAIV vaccination

Baseline Levels of Influenza-Specific CD4 Memory T-Cells Affect T-Cell Responses to Influenza Vaccines

BACKGROUND: Factors affecting immune responses to influenza vaccines have not been studied systematically. We hypothesized that T-cell and antibody responses to the vaccines are functions of pre-existing host immunity against influenza antigens. METHODOLOGY/PRINCIPAL FINDINGS: During the 2004 and 2005 influenza seasons, we have collected data on cellular and humoral immune reactivity to influenza virus in blood samples collected before and after immunization with inactivated or live attenuated influenza vaccines in healthy children and adults. We first used cross-validated lasso regression on the 2004 dataset to identify a group of candidate baseline correlates with T-cell and antibody responses to vaccines, defined as fold-increase in influenza-specific T-cells and serum HAI titer after vaccination. The following baseline parameters were examined: percentages of influenza-reactive IFN-gamma(+) cells in T and NK cell subsets, percentages of influenza-specific memory B-cells, HAI titer, age, and type of vaccine. The candidate baseline correlates were then tested with the independent 2005 dataset. Baseline percentage of influenza-specific IFN-gamma(+) CD4 T-cells was identified as a significant correlate of CD4 and CD8 T-cell responses, with lower baseline levels associated with larger T-cell responses. Baseline HAI titer and vaccine type were identified as significant correlates for HAI response, with lower baseline levels and the inactivated vaccine associated with larger HAI responses. Previously we reported that baseline levels of CD56(dim) NK reactivity against influenza virus inversely correlated with the immediate T-cell response to vaccination, and that NK reactivity induced by influenza virus depended on IL-2 produced by influenza-specific memory T-cells. Taken together these results suggest a novel mechanism for the homeostasis of virus-specific T-cells, which involves interaction between memory helper T-cells, CD56(dim) NK and DC. SIGNIFICANCE: These results demonstrate that assessment of baseline biomarkers may predict immunologic outcome of influenza vaccination and may reveal some of the mechanisms responsible for variable immune responses following vaccination and natural infection

Field Application of a Subunit Vaccine against an Enteric Protozoan Disease

Background: Coccidiosis is a major global veterinary health problem in intensively reared chickens. It is caused by apicomplexan parasites of the genus Eimeria. Principal Findings: A subunit vaccine composed of purified antigens from the gametocytes of Eimeria maxima was used to stimulate the production and transfer of maternal antibodies between breeding hens and their hatchlings. The vaccine was injected into hens twice before they began laying eggs. Immunization had no adverse affects on egg laying or health of the hens and resulted in high antibody levels throughout the life of the hens. Progeny of immunized hens excreted significantly less oocysts of various species of Eimeria in their faeces than chicks from unvaccinated hens. Furthermore, the offspring of vaccinated hens developed stronger natural immunity to Eimeria, so that they were resistant to challenge infection even at 8 weeks of age, well after all maternal antibodies had left their circulation. Field trials were conducted in South Africa, Brazil and Thailand, involving at least 1 million progeny of vaccinated hens and at least 1 million positive control birds (raised on feed containing anticoccidial drugs or immunized with a live vaccine) in each country. Additionally, trials were carried out in Israel involving 60 million progeny of vaccinated hens and 112 million positive control birds. There were no significant differences in growth rate, feed conversion ratios or mortality in the offspring of vaccinated hens compared with the positive control chickens in any of these countries regardless of different management practices, different breeds of chickens or climate. Conclusions: These results demonstrate that a vaccine composed of antigens purified from the gametocytes of Eimeria can be used safely and effectively to prevent the deleterious effects of coccidiosis. It is the first subunit vaccine against any protozoan parasite to be successfully applied on a commercial scale. © 2008 Wallach et al

Effectiveness of Air Filters and Air Cleaners in Allergic Respiratory Diseases: A Review of the Recent Literature

Air filtration is frequently recommended as a component of environmental control measures for patients with allergic respiratory disease. Residential air filtration can be provided by whole house filtration via the home’s heating, ventilation, or air conditioning system, by portable room air cleaners, or a combination of the two. Appliances to filter the sleep breathing zone also have been developed. High-efficiency whole house filtration, high-efficiency particulate air sleep zone air filtration, and high-efficiency particulate air room air cleaners all appear to provide various degrees of benefit. Recent studies of various types of filtration, used alone or as part of more comprehensive environmental control measures, are reviewed