The Importance of Noise Colour in Simulations of Evolutionary Systems.

Simulations of evolutionary dynamics often employ white noise as a model of stochastic environmental variation. Whilst white noise has the advantages of being simply generated and analytically tractable, empirical analyses demonstrate that most real environmental time series have power spectral densities consistent with pink or red noise, in which lower frequencies contribute proportionally greater amplitudes than higher frequencies. Simulated white noise environments may therefore fail to capture key components of real environmental time series, leading to erroneous results. To explore the effects of different noise colours on evolving populations, a simple evolutionary model of the interaction between life-history and the specialism-generalism axis was developed. Simulations were conducted using a range of noise colours as the environments to which agents adapted. Results demonstrate complex interactions between noise colour, reproductive rate, and the degree of evolved generalism; importantly, contradictory conclusions arise from simulations using white as opposed to red noise, suggesting that noise colour plays a fundamental role in generating adaptive responses. These results are discussed in the context of previous research on evolutionary responses to fluctuating environments, and it is suggested that Artificial Life as a field should embrace a wider spectrum of coloured noise models to ensure that results are truly representative of environmental and evolutionary dynamics

Vaccine-associated enhanced disease : case definition and guidelines for data collection, analysis, and presentation of immunization safety data

This is a Brighton Collaboration Case Definition of the term & ldquo;Vaccine Associated Enhanced Disease & rdquo; to be utilized in the evaluation of adverse events following immunization. The Case Definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2 vaccines and other emerging pathogens. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected Expert Reviewers prior to submission. (c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Prevalence, Causes and Socio-Economic Determinants of Vision Loss in Cape Town, South Africa

PURPOSE: To estimate the prevalence and causes of blindness and visual impairment in Cape Town, South Africa and to explore socio-economic and demographic predictors of vision loss in this setting. METHODS: A cross sectional population-based survey was conducted in Cape Town. Eighty-two clusters were selected using probability proportionate to size sampling. Within each cluster 35 or 40 people aged 50 years and above were selected using compact segment sampling. Visual acuity of participants was assessed and eyes with a visual acuity less than 6/18 were examined by an ophthalmologist to determine the cause of vision loss. Demographic data (age, gender and education) were collected and a socio-economic status (SES) index was created using principal components analysis. RESULTS: Out of 3100 eligible people, 2750 (89%) were examined. The sample prevalence of bilateral blindness (presenting visual acuity <3/60) was 1.4% (95% CI 0.9-1.8). Posterior segment diseases accounted for 65% of blindness and cataract was responsible for 27%. The prevalence of vision loss was highest among people over 80 years (odds ratio (OR) 6.9 95% CI 4.6-10.6), those in the poorest SES group (OR 3.9 95% CI 2.2-6.7) and people with no formal education (OR 5.4 95% CI 1.7-16.6). Cataract surgical coverage was 68% in the poorest SES tertile (68%) compared to 93% in the medium and 100% in the highest tertile. CONCLUSIONS: The prevalence of blindness among people ≥50 years in Cape Town was lower than expected and the contribution of posterior segment diseases higher than previously reported in South Africa and Sub Saharan Africa. There were clear socio-economic disparities in prevalence of vision loss and cataract surgical coverage in this setting which need to be addressed in blindness prevention programs

The Burden of Trachoma in Ayod County of Southern Sudan

Trachoma, a neglected tropical disease, is the leading cause of infectious blindness and is targeted for global elimination by the year 2020. We conducted a survey in Ayod County of Jonglei State, Southern Sudan, to determine whether blinding trachoma was a public health problem and to plan interventions to control this disease. We found the burden of trachoma in Ayod to be one of the most severe ever documented. Not only were adults affected by the advanced manifestations of the disease as is typical for older age groups, but young children were also affected. At least one person with clinical signs of trachoma was found in nearly every household, and 1 in 3 households had a person with severe blinding trachoma. Characteristics previously identified as risk factors were ubiquitous among surveyed households, but we were unable to identify why trachoma is so severe in this location. Surgical interventions are needed urgently to improve vision and prevent irreversible blindness in children and adults. Mass antibiotic distribution may alleviate current infections and transmission of trachoma may be reduced if communities adopt the behavior of face washing and safe disposal of human waste. Increasing access to improved water sources may not only improve hygiene but also reduce the spread of guinea worm and other water-borne diseases

Nonrandom Distribution of Vector Ticks (Dermacentor variabilis) Infected by Francisella tularensis

The island of Martha's Vineyard, Massachusetts, is the site of a sustained outbreak of tularemia due to Francisella tularensis tularensis. Dog ticks, Dermacentor variabilis, appear to be critical in the perpetuation of the agent there. Tularemia has long been characterized as an agent of natural focality, stably persisting in characteristic sites of transmission, but this suggestion has never been rigorously tested. Accordingly, we sought to identify a natural focus of transmission of the agent of tularemia by mapping the distribution of PCR-positive ticks. From 2004 to 2007, questing D. variabilis were collected from 85 individual waypoints along a 1.5 km transect in a field site on Martha's Vineyard. The positions of PCR-positive ticks were then mapped using ArcGIS. Cluster analysis identified an area approximately 290 meters in diameter, 9 waypoints, that was significantly more likely to yield PCR-positive ticks (relative risk 3.3, P = 0.001) than the rest of the field site. Genotyping of F. tularensis using variable number tandem repeat (VNTR) analysis on PCR-positive ticks yielded 13 different haplotypes, the vast majority of which was one dominant haplotype. Positive ticks collected in the cluster were 3.4 times (relative risk = 3.4, P<0.0001) more likely to have an uncommon haplotype than those collected elsewhere from the transect. We conclude that we have identified a microfocus where the agent of tularemia stably perpetuates and that this area is where genetic diversity is generated

Access to Water Source, Latrine Facilities and Other Risk Factors of Active Trachoma in Ankober, Ethiopia

Objective: This study aims to determine the prevalence and correlates of active trachoma in Ankober, Ethiopia. Methods: A cross-sectional community-based study was conducted during July 2007. A total of 507 children (ages 1–9 years), from 232 households were included in the study. All children were examined for trachoma by ophthalmic nurses using the WHO simplified clinical grading system. Interviews and observations were used to assess risk factors. Logistic regression procedures were used to determine associations between potential risk factors and signs of active trachoma. Results: Overall, the prevalence of active trachoma was found to be 53.9 % (95%CI 49.6%–58.2%). Presence of fly-eye (fly contact with the eyelid margin during eye examination) (Odds Ratio (OR) = 4.03 95 % CI 1.40–11.59), absence of facial cleanliness (OR = 7.59; 95%CI 4.60–12.52), an illiterate mother (OR = 5.88; 95%CI 2.10–15.95), lack of access to piped water (OR = 2.19; 95%CI 1.14–6.08), and lack of access to latrine facilities (OR = 4.36; 95%CI 1.49–12.74) were statistically significantly associated with increased risk of active trachoma. Conclusion: Active trachoma among children 1–9 years of age in Ankober is highly prevalent and significantly associated with a number of risk factors including access to water and latrine facilities. Trachoma prevention programs that include improved access to water and sanitation, active fly control, and hygiene education are recommended to lower the burde

A Novel Inactivated Intranasal Respiratory Syncytial Virus Vaccine Promotes Viral Clearance without Th2 Associated Vaccine-Enhanced Disease

Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneumonia in young children worldwide, and no vaccine is currently available. Inactivated RSV vaccines tested in the 1960's led to vaccine-enhanced disease upon viral challenge, which has undermined RSV vaccine development. RSV infection is increasingly being recognized as an important pathogen in the elderly, as well as other individuals with compromised pulmonary immunity. A safe and effective inactivated RSV vaccine would be of tremendous therapeutic benefit to many of these populations.In these preclinical studies, a mouse model was utilized to assess the efficacy of a novel, nanoemulsion-adjuvanted, inactivated mucosal RSV vaccine. Our results demonstrate that NE-RSV immunization induced durable, RSV-specific humoral responses, both systemically and in the lungs. Vaccinated mice exhibited increased protection against subsequent live viral challenge, which was associated with an enhanced Th1/Th17 response. In these studies, NE-RSV vaccinated mice displayed no evidence of Th2 mediated immunopotentiation, as has been previously described for other inactivated RSV vaccines.These studies indicate that nanoemulsion-based inactivated RSV vaccination can augment viral-specific immunity, decrease mucus production and increase viral clearance, without evidence of Th2 immune mediated pathology

Alum Adjuvant Enhances Protection against Respiratory Syncytial Virus but Exacerbates Pulmonary Inflammation by Modulating Multiple Innate and Adaptive Immune Cells

Respiratory syncytial virus (RSV) is well-known for inducing vaccine-enhanced respiratory disease after vaccination of young children with formalin-inactivated RSV (FI-RSV) in alum formulation. Here, we investigated alum adjuvant effects on protection and disease after FIRSV immunization with or without alum in comparison with live RSV reinfections. Despite viral clearance, live RSV reinfections caused weight loss and substantial pulmonary inflammation probably due to high levels of RSV specific IFN-γ+IL4-, IFN-γ-TNF-α+, IFN-γ+ TNF-α- effector CD4 and CD8 T cells. Alum adjuvant significantly improved protection as evidenced by effective viral clearance compared to unadjuvanted FI-RSV. However, in contrast to unadjuvanted FI-RSV, alum-adjuvanted FI-RSV (FI-RSV-A) induced severe vaccine- enhanced RSV disease including weight loss, eosinophilia, and lung histopathology. Alum adjuvant in the FI-RSV-A was found to be mainly responsible for inducing high levels of RSV-specific IFN-γ-IL4+, IFN-γ-TNF-α+ CD4+ T cells, and proinflammatory cytokines IL-6 and IL-4 as well as B220+ plasmacytoid and CD4+ dendritic cells, and inhibiting the induction of IFN-γ+CD8 T cells. This study suggests that alum adjuvant in FI-RSV vaccines increases immunogenicity and viral clearance but also induces atypical T helper CD4+ T cells and multiple inflammatory dendritic cell subsets responsible for vaccine-enhanced severe RSV disease

An Epstein-Barr Virus Anti-Apoptotic Protein Constitutively Expressed in Transformed Cells and Implicated in Burkitt Lymphomagenesis: The Wp/BHRF1 Link

Two factors contribute to Burkitt lymphoma (BL) pathogenesis, a chromosomal translocation leading to c-myc oncogene deregulation and infection with Epstein-Barr virus (EBV). Although the virus has B cell growth–transforming ability, this may not relate to its role in BL since many of the transforming proteins are not expressed in the tumor. Mounting evidence supports an alternative role, whereby EBV counteracts the high apoptotic sensitivity inherent to the c-myc–driven growth program. In that regard, a subset of BLs carry virus mutants in a novel form of latent infection that provides unusually strong resistance to apoptosis. Uniquely, these virus mutants use Wp (a viral promoter normally activated early in B cell transformation) and express a broader-than-usual range of latent antigens. Here, using an inducible system to express the candidate antigens, we show that this marked apoptosis resistance is mediated not by one of the extended range of EBNAs seen in Wp-restricted latency but by Wp-driven expression of the viral bcl2 homologue, BHRF1, a protein usually associated with the virus lytic cycle. Interestingly, this Wp/BHRF1 connection is not confined to Wp-restricted BLs but appears integral to normal B cell transformation by EBV. We find that the BHRF1 gene expression recently reported in newly infected B cells is temporally linked to Wp activation and the presence of W/BHRF1-spliced transcripts. Furthermore, just as Wp activity is never completely eclipsed in in vitro–transformed lines, low-level BHRF1 transcripts remain detectable in these cells long-term. Most importantly, recognition by BHRF1-specific T cells confirms that such lines continue to express the protein independently of any lytic cycle entry. This work therefore provides the first evidence that BHRF1, the EBV bcl2 homologue, is constitutively expressed as a latent protein in growth-transformed cells in vitro and, in the context of Wp-restricted BL, may contribute to virus-associated lymphomagenesis in vivo

Characterization of K-Complexes and Slow Wave Activity in a Neural Mass Model

NREM sleep is characterized by two hallmarks, namely K-complexes (KCs) during sleep stage N2 and cortical slow oscillations (SOs) during sleep stage N3. While the underlying dynamics on the neuronal level is well known and can be easily measured, the resulting behavior on the macroscopic population level remains unclear. On the basis of an extended neural mass model of the cortex, we suggest a new interpretation of the mechanisms responsible for the generation of KCs and SOs. As the cortex transitions from wake to deep sleep, in our model it approaches an oscillatory regime via a Hopf bifurcation. Importantly, there is a canard phenomenon arising from a homoclinic bifurcation, whose orbit determines the shape of large amplitude SOs. A KC corresponds to a single excursion along the homoclinic orbit, while SOs are noise-driven oscillations around a stable focus. The model generates both time series and spectra that strikingly resemble real electroencephalogram data and points out possible differences between the different stages of natural sleep