Understanding heterogeneities in mosquito-bite exposure and infection distributions for the elimination of lymphatic filariasis

It is well known that individuals in the same community can be exposed to a highly variable number of mosquito bites. This heterogeneity in bite exposure has consequences for the control of vector-borne diseases because a few people may be contributing significantly to transmission. However, very few studies measure sources of heterogeneity in a way which is relevant to decision-making. We investigate the relationship between two classic measures of heterogeneity, spatial and individual, within the context of lymphatic filariasis, a parasitic mosquito-borne disease. Using infection and mosquito-bite data for five villages in Papua New Guinea, we measure biting characteristics to model what impact bed-nets have had on control of the disease. We combine this analysis with geospatial modelling to understand the spatial relationship between disease indicators and nightly mosquito bites. We found a weak association between biting and infection heterogeneity within villages. The introduction of bed-nets increased biting heterogeneity, but the reduction in mean biting more than compensated for this, by reducing prevalence closer to elimination thresholds. Nightly biting was explained by a spatial heterogeneity model, while parasite load was better explained by an individual heterogeneity model. Spatial and individual heterogeneity are qualitatively different with profoundly different policy implications

The labor market regimes of Denmark and Norway – one Nordic model?

The literature on the Danish and Norwegian labor market systems emphasizes the commonalities of the two systems. We challenge this perception by investigating how employers in multinational companies in Denmark and Norway communicate with employees on staffing changes. We argue that the development of ‘flexicurity’ in Denmark grants Danish employers considerably greater latitude in engaging in staffing changes than its Nordic counterpart, Norway. Institutional theory leads us to suppose that large firms located in the Danish setting will be less likely to engage in employer–employee communication on staffing plans than their Norwegian counterparts. In addition, we argue that in the Danish context indigenous firms will have a better insight into the normative and cognitive aspects to flexicurity than foreign-owned firms, meaning that they are more likely to engage in institutional entrepreneurialism than their foreign owned counterparts. We supplement institutional theory with an actor perspective in order to take into account the role of labor unions. Our analysis is based on a survey of 203 firms in Norway and Denmark which are either indigenous multinational companies or the subsidiaries of foreign multinational companies. The differences we observe cause us to conclude that the notion of a common Nordic model is problematic

Transplanting the leafy liverwort Herbertus hutchinsiae : A suitable conservation tool to maintain oceanic-montane liverwort-rich heath?

Thanks to the relevant landowners and managers for permission to carry out the experiments, Chris Preston for helping to obtain the liverwort distribution records and the distribution map, Gordon Rothero and Dave Horsfield for advice on choosing experimental sites and Alex Douglas for statistical advice. Juliane Geyer’s help with fieldwork was greatly appreciated. This study was made possible by a NERC PhD studentship and financial support from the Royal Botanic Garden Edinburgh and Scottish Natural Heritage.Peer reviewedPostprin

Stroma: the forgotten cells of innate immune memory

All organisms are exposed constantly to a variety of infectious and injurious stimuli. These induce inflammatory responses tailored to the threat posed. While the innate immune system is the front line of response to each stimulant, it has been considered traditionally to lack memory, acting in a generic fashion until the adaptive immune arm can take over. This outmoded simplification of the roles of innate and acquired arms of the immune system has been challenged by evidence of myeloid cells altering their response to subsequent encounters based on earlier exposure. This concept of ‘innate immune memory’ has been known for nearly a century, and is accepted among myeloid biologists. In recent years other innate immune cells, such as natural killer cells, have been shown to display memory, suggesting that innate immune memory is a trait common to several cell types. During the last 30 years, evidence has slowly accumulated in favour of not only haematopoietic cells, but also stromal cells, being imbued with memory following inflammatory episodes. A recent publication showing this also to be true in epithelial cells suggests innate immune memory to be widespread, if under‐appreciated, in non‐haematopoietic cells. In this review, we will examine the evidence supporting the existence of innate immune memory in stromal cells. We will also discuss the ramifications of memory in long‐lived tissue‐resident cells. Finally, we will pose questions we feel to be important in the understanding of these forgotten cells in the field of innate memory

Evaluating LINE-1 methylation in cleft lip tissues and its association with early pregnancy exposures

Aim: To pilot investigation of methylation of long interspersed nucleotide element-1 in lip tissues from infants with nonsyndromic cleft lip, and its association with maternal periconceptional exposures. Methods: The lateral and medial sides of the cleft lips of 23 affected infants were analyzed for long interspersed nucleotide element-1 methylation by bisulfite conversion and pyrosequencing. Results: The medial side showed 1.8% higher methylation compared with the lateral side; p = 0.031, particularly in male infants (2.7% difference; p = 0.011) or when the mothers did not take folic acid during periconceptional period (2.4% difference; p = 0.011). These results were not statistically significant when Bonferroni adjustment was used. Conclusion: The observed differences in DNA methylation, although nonsignificant after correction for multiple comparisons, suggest that differential regulation of the two sides may impact lip fusion and warrant larger-scale replication

Antenatal risk factors for peanut allergy in children

<p>Abstract</p> <p>Background</p> <p>Prenatal factors may contribute to the development of peanut allergy. We evaluated the risk of childhood peanut allergy in association with pregnancy exposure to Rh immune globulin, folic acid and ingestion of peanut-containing foods.</p> <p>Methods</p> <p>We conducted a web-based case-control survey using the Anaphylaxis Canada Registry, a pre-existing database of persons with a history of anaphylaxis. A total of 1300 case children with reported peanut allergy were compared to 113 control children with shellfish allergy. All were evaluated for maternal exposure in pregnancy to Rh immune globulin and folic acid tablet supplements, as well as maternal avoidance of dietary peanut intake in pregnancy.</p> <p>Results</p> <p>Receipt of Rh immune globulin in pregnancy was not associated with a higher risk of peanut allergy (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.51 to 1.45), nor was initiation of folic acid tablet supplements before or after conception (OR 0.53, 95% CI 0.19 to 1.48). Complete avoidance of peanut-containing products in pregnancy was associated with a non-significantly lower risk of peanut allergy (OR 0.53, 95% CI 0.27 to 1.03).</p> <p>Conclusion</p> <p>The risk of childhood peanut allergy was not modified by the following common maternal exposures in pregnancy: Rh immune globulin, folic acid or peanut-containing foods.</p> <p>Clinical implications</p> <p>Rh immune globulin, folic acid supplement use and peanut avoidance in pregnancy have yet to be proven to modulate the risk of childhood anaphylaxis to peanuts.</p> <p>Capsule Summary</p> <p>Identification of prenatal factors that contribute to peanut allergy might allow for prevention of this life-threatening condition. This article explores the role of three such factors.</p

Phylogenetic Approach Reveals That Virus Genotype Largely Determines HIV Set-Point Viral Load

HIV virulence, i.e. the time of progression to AIDS, varies greatly among patients. As for other rapidly evolving pathogens of humans, it is difficult to know if this variance is controlled by the genotype of the host or that of the virus because the transmission chain is usually unknown. We apply the phylogenetic comparative approach (PCA) to estimate the heritability of a trait from one infection to the next, which indicates the control of the virus genotype over this trait. The idea is to use viral RNA sequences obtained from patients infected by HIV-1 subtype B to build a phylogeny, which approximately reflects the transmission chain. Heritability is measured statistically as the propensity for patients close in the phylogeny to exhibit similar infection trait values. The approach reveals that up to half of the variance in set-point viral load, a trait associated with virulence, can be heritable. Our estimate is significant and robust to noise in the phylogeny. We also check for the consistency of our approach by showing that a trait related to drug resistance is almost entirely heritable. Finally, we show the importance of taking into account the transmission chain when estimating correlations between infection traits. The fact that HIV virulence is, at least partially, heritable from one infection to the next has clinical and epidemiological implications. The difference between earlier studies and ours comes from the quality of our dataset and from the power of the PCA, which can be applied to large datasets and accounts for within-host evolution. The PCA opens new perspectives for approaches linking clinical data and evolutionary biology because it can be extended to study other traits or other infectious diseases

Sex differences in the impact of ozone on survival and alveolar macrophage function of mice after Klebsiella pneumoniae infection

<p>Abstract</p> <p>Background</p> <p>Sex differences have been described in a number of pulmonary diseases. However, the impact of ozone exposure followed by pneumonia infection on sex-related survival and macrophage function have not been reported. The purpose of this study was to determine whether ozone exposure differentially affects: 1) survival of male and female mice infected with <it>Klebsiella pneumoniae</it>, and 2) the phagocytic ability of macrophages from these mice.</p> <p>Methods</p> <p>Male and female C57BL/6 mice were exposed to O₃or to filtered air (FA) (control) and then infected intratracheally with <it>K. pneumoniae </it>bacteria. Survival was monitored over a 14-day period, and the ability of alveolar macrophages to phagocytize the pathogen <it>in vivo </it>was investigated after 1 h.</p> <p>Results</p> <p>1) Both male and female mice exposed to O₃are significantly more susceptible to <it>K. pneumoniae </it>infection than mice treated with FA; 2) although females appeared to be more resistant to <it>K. pneumoniae </it>than males, O₃exposure significantly increased the susceptibility of females to <it>K. pneumoniae </it>infection to a greater degree than males; 3) alveolar macrophages from O₃-exposed male and female mice have impaired phagocytic ability compared to macrophages from FA-exposed mice; and 4) the O₃-dependent reduction in phagocytic ability is greater in female mice.</p> <p>Conclusion</p> <p>O₃exposure reduces the ability of mice to survive <it>K. pneumoniae </it>infection and the reduced phagocytic ability of alveolar macrophages may be one of the contributing factors. Both events are significantly more pronounced in female mice following exposure to the environmental pollutant, ozone.</p

Resolution of LPS-induced airway inflammation and goblet cell hyperplasia is independent of IL-18

BACKGROUND: The resolution of inflammatory responses in the lung has not been described in detail and the role of specific cytokines influencing the resolution process is largely unknown. METHODS: The present study was designed to describe the resolution of inflammation from 3 h through 90 d following an acute injury by a single intratracheal instillation of F344/N rats with LPS. We documented the inflammatory cell types and cytokines found in the bronchoalveolar lavage fluid (BALF), and epithelial changes in the axial airway and investigated whether IL-18 may play a role in the resolution process by reducing its levels with anti-IL-18 antibodies. RESULTS: Three major stages of inflammation and resolution were observed in the BALF during the resolution. The first stage was characterized by PMNs that increased over 3 h to 1 d and decreased to background levels by d 6–8. The second stage of inflammation was characterized by macrophage influx reaching maximum numbers at d 6 and decreasing to background levels by d 40. A third stage of inflammation was observed for lymphocytes which were elevated over d 3–6. Interestingly, IL-18 and IL-9 levels in the BALF showed a cyclic pattern with peak levels at d 4, 8, and 16 while decreasing to background levels at d 1–2, 6, and 12. Depletion of IL-18 caused decreased PMN numbers at d 2, but no changes in inflammatory cell number or type at later time points. CONCLUSION: These data suggest that IL-18 plays a role in enhancing the LPS-induced neutrophilic inflammation of the lung, but does not affect the resolution of inflammation

Involvement of ubiquitin-editing protein A20 in modulating in-flammation in rat cochlea associated with silver nanoparti-cles-induced CD68 up-regulation and TLR4 activation

The manuscript was just accepted for publication on Nanoscale Research Letters