Time-based measurement of personal mite allergen bioaerosol exposure over 24 hour periods

© 2016 Tovey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Allergic diseases such as asthma and rhinitis are common in many countries. Globally the most common allergen associated with symptoms is produced by house dust mites. Although the bed has often been cited as the main site of exposure to mite allergens, surprisingly this has not yet been directly established by measurement due to a lack of suitable methods. Here we report on the development of novel methods to determine the pattern of personal exposure to mite allergen bioaerosols over 24-hour periods and applied this in a small field study using 10 normal adults. Air was sampled using a miniature time-based air-sampler of in-house design located close to the breathing zone of the participants, colocated with a miniature time-lapse camera. Airborne particles, drawn into the sampler at 2L/min via a narrow slot, were impacted onto the peripheral surface of a disk mounted on the hour-hand of either a 12 or 24 hour clock motor. The impaction surface was either an electret cloth, or an adhesive film; both novel for these purposes. Following a review of the time-lapse images, disks were post-hoc cut into subsamples corresponding to eight predetermined categories of indoor or outdoor location, extracted and analysed for mite allergen Der p 1 by an amplified ELISA. Allergen was detected in 57.2% of the total of 353 subsamples collected during 20 days of sampling. Exposure patterns varied over time. Higher concentrations of airborne mite allergen were typically measured in samples collected from domestic locations in the day and evening. Indoor domestic Der p 1 exposures accounted for 59.5% of total exposure, whereas total in-bed-asleep exposure, which varied 80 fold between individuals, accounted overall for 9.85% of total exposure, suggesting beds are not often the main site of exposure. This study establishes the feasibility of novel methods for determining the time-geography of personal exposure to many bioaerosols and identifies new areas for future technical development and clinical applications

The effects of an enhanced simulation programme on medical students' confidence responding to clinical deterioration

BACKGROUND: Clinical deterioration in adult hospital patients is an identified issue in healthcare practice globally. Teaching medical students to recognise and respond to the deteriorating patient is crucial if we are to address the issue in an effective way. The aim of this study was to evaluate the effects of an enhanced simulation exercise known as RADAR (Recognising Acute Deterioration: Active Response), on medical students’ confidence. METHODS: A questionnaire survey was conducted; the instrument contained three sections. Section 1 focused on students’ perceptions of the learning experience; section 2 investigated confidence. Both sections employed Likert-type scales. A third section invited open responses. Questionnaires were distributed to a cohort of third-year medical students (n = 158) in the North East of Scotland 130 (82 %) were returned for analysis, employing IBM SPSS v18 and ANOVA techniques. RESULTS: Students’ responses pointed to many benefits of the sessions. In the first section, students responded positively to the educational underpinning of the sessions, with all scores above 4.00 on a 5-point scale. There were clear learning outcomes; the sessions were active and engaging for students with an appropriate level of challenge and stress; they helped to integrate theory and practice; and effective feedback on their performance allowed students to reflect and learn from the experience. In section 2, the key finding was that scores for students’ confidence to recognise deterioration increased significantly (p. < .001) as a result of the sessions. Effect sizes (Eta(2)) were high, (0.68–0.75). In the open-ended questions, students pointed to many benefits of the RADAR course, including the opportunity to employ learned procedures in realistic scenarios. CONCLUSIONS: The use of this enhanced form of simulation with simulated patients and the judicious use of moulage is an effective method of increasing realism for medical students. Importantly, it gives them greater confidence in recognising and responding to clinical deterioration in adult patients. We recommend the use of RADAR as a safe and cost-effective approach in the area of clinical deterioration and suggest that there is a need to investigate its use with different patient groups

A hypothetico-deductive approach to assessing the social function of chemical signalling in a non-territorial solitary carnivore

The function of chemical signalling in non-territorial solitary carnivores is still relatively unclear. Studies on territorial solitary and social carnivores have highlighted odour capability and utility, however the social function of chemical signalling in wild carnivore populations operating dominance hierarchy social systems has received little attention. We monitored scent marking and investigatory behaviour of wild brown bears Ursus arctos, to test multiple hypotheses relating to the social function of chemical signalling. Camera traps were stationed facing bear ‘marking trees’ to document behaviour by different age sex classes in different seasons. We found evidence to support the hypothesis that adult males utilise chemical signalling to communicate dominance to other males throughout the non-denning period. Adult females did not appear to utilise marking trees to advertise oestrous state during the breeding season. The function of marking by subadult bears is somewhat unclear, but may be related to the behaviour of adult males. Subadults investigated trees more often than they scent marked during the breeding season, which could be a result of an increased risk from adult males. Females with young showed an increase in marking and investigation of trees outside of the breeding season. We propose the hypothesis that females engage their dependent young with marking trees from a young age, at a relatively ‘safe’ time of year. Memory, experience, and learning at a young age, may all contribute towards odour capabilities in adult bears

The effects of caffeinated and decaffeinated coffee on sex hormone-binding globulin and endogenous sex hormone levels: A randomized controlled trial

10.1186/1475-2891-11-86Nutrition Journal111

Assisted evolution enables HIV-1 to overcome a high trim5α-imposed genetic barrier to rhesus macaque tropism

Diversification of antiretroviral factors during host evolution has erected formidable barriers to cross-species retrovirus transmission. This phenomenon likely protects humans from infection by many modern retroviruses, but it has also impaired the development of primate models of HIV-1 infection. Indeed, rhesus macaques are resistant to HIV-1, in part due to restriction imposed by the TRIM5α protein (rhTRIM5α). Initially, we attempted to derive rhTRIM5α-resistant HIV-1 strains using two strategies. First, HIV-1 was passaged in engineered human cells expressing rhTRIM5α. Second, a library of randomly mutagenized capsid protein (CA) sequences was screened for mutations that reduced rhTRIM5α sensitivity. Both approaches identified several individual mutations in CA that reduced rhTRIM5α sensitivity. However, neither approach yielded mutants that were fully resistant, perhaps because the locations of the mutations suggested that TRIM5α recognizes multiple determinants on the capsid surface. Moreover, even though additive effects of various CA mutations on HIV-1 resistance to rhTRIM5α were observed, combinations that gave full resistance were highly detrimental to fitness. Therefore, we employed an 'assisted evolution' approach in which individual CA mutations that reduced rhTRIM5α sensitivity without fitness penalties were randomly assorted in a library of viral clones containing synthetic CA sequences. Subsequent passage of the viral library in rhTRIM5α-expressing cells resulted in the selection of individual viral species that were fully fit and resistant to rhTRIM5α. These viruses encoded combinations of five mutations in CA that conferred complete or near complete resistance to the disruptive effects of rhTRIM5α on incoming viral cores, by abolishing recognition of the viral capsid. Importantly, HIV-1 variants encoding these CA substitutions and SIVmac239 Vif replicated efficiently in primary rhesus macaque lymphocytes. These findings demonstrate that rhTRIM5α is difficult to but not impossible to evade, and doing so should facilitate the development of primate models of HIV-1 infection

Health and life insurance as an alternative to malpractice tort law

<p>Abstract</p> <p>Background</p> <p>Tort law has legitimate social purposes of deterrence, punishment and compensation, but medical tort law does none of these well. Tort law could be counterproductive in medicine, encouraging costly defensive practices that harm some patients, restricting access to care in some settings and discouraging innovation.</p> <p>Discussion</p> <p>Patients might be better served by purchasing combined health and life insurance policies and waiving their right to pursue malpractice claims. The combined policy should encourage the insurer to profit by inexpensively delaying policyholders' deaths. A health and life insurer would attempt to minimize mortal risks to policyholders from any cause, including medical mistakes and could therefore pursue systematic quality improvement efforts. If policyholders trust the insurer to seek, develop and reward genuinely effective care; identify, deter and remediate poor care; and compensate survivors through the no-fault process of paying life insurance benefits, then tort law is largely redundant and the right to sue may be waived. If expensive defensive medicine can be avoided, that savings alone could pay for fairly large life insurance policies.</p> <p>Summary</p> <p>Insurers are maligned largely because of their logical response to incentives that are misaligned with the interests of patients and physicians in the United States. Patient, provider and insurer incentives could be realigned by combining health and life insurance, allowing the insurer to use its considerable information access and analytic power to improve patient care. This arrangement would address the social goals of malpractice torts, so that policyholders could rationally waive their right to sue.</p

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Evidence for Restriction of Ancient Primate Gammaretroviruses by APOBEC3 but Not TRIM5α Proteins

Because of evolutionary pressures imposed through episodic colonization by retroviruses, many mammals express factors, such as TRIM5α and APOBEC3 proteins, that directly restrict retroviral replication. TRIM5 and APOBEC restriction factors are most often studied in the context of modern primate lentiviruses, but it is likely that ancient retroviruses imposed the selective pressure that is evident in primate TRIM5 and APOBEC3 genes. Moreover, these antiretroviral factors have been shown to act against a variety of retroviruses, including gammaretroviruses. Endogenous retroviruses can provide a ‘fossil record’ of extinct retroviruses and perhaps evidence of ancient TRIM5 and APOBEC3 antiviral activity. Here, we investigate whether TRIM5 and APOBEC3 proteins restricted the replication of two groups of gammaretroviruses that were endogenized in the past few million years. These endogenous retroviruses appear quite widespread in the genomes of old world primates but failed to colonize the human germline. Our analyses suggest that TRIM5α proteins did not pose a major barrier to the cross-species transmission of these two families of gammaretroviruses, and did not contribute to their extinction. However, we uncovered extensive evidence for inactivation of ancient gammaretroviruses through the action of APOBEC3 cytidine deaminases. Interestingly, the identities of the cytidine deaminases responsible for inactivation appear to have varied in both a virus and host species–dependent manner. Overall, sequence analyses and reconstitution of ancient retroviruses from remnants that have been preserved in the genomes of modern organisms offer the opportunity to probe and potentially explain the evolutionary history of host defenses against retroviruses

Mediators of the Link Between Autistic Traits and Relationship Satisfaction in a Non-Clinical Sample

People with ASD have deficits in their social skills and may therefore experience lower relationship satisfaction. This study investigated possible mechanisms to explain whether and how autistic traits, measured with the AQ, influence relationship satisfaction in a non-clinical sample of 195 married couples. More autistic traits were associated with lower relationship satisfaction for husbands but not for wives. Multiple mediation analyses revealed that husbands’ responsiveness towards their wives, trust, and intimacy mediated this link between autistic traits and relationship satisfaction. These findings suggest that autistic traits may hamper men’s relationship satisfaction because they impede relationship-specific feelings and behavior. There was no partner-effect of autistic traits, indicating that more autistic traits do not necessarily influence the partner’s perceptions of relationship satisfaction