Extending backcalculation to analyse BSE data.

We review the origins of backcalculation (or back projection) methods developed for the analysis of AIDS (acquired immunodeficiency syndrome) incidence data. These techniques have been used extensively for >15 years to deconvolute clinical case incidence, given knowledge of the incubation period distribution, to obtain estimates of past HIV (human immunodeficiency virus) infection incidence and short-term predictions of future AIDS incidence. Adaptations required for the analysis of bovine spongiform encephalopathy (BSE) incidence included: stratification of BSE incidence by age as well as birth cohort; allowance for incomplete survival between infection and the onset of clinical signs of disease; and decomposition of the age- and time-related infection incidence into a time-dependent feed risk component and an age-dependent exposure/susceptibility function. The most recent methodological developments focus on the incorporation of data from clinically unaffected cattle screened using recently developed tests for preclinical BSE infection. Backcalculation-based predictions of future BSE incidence obtained since 1996 are examined. Finally, future directions of epidemiological analysis of BSE epidemics are discussed taking into account ongoing developments in the science of BSE and possible changes in BSE-related policies

A review of epidemiological parameters from Ebola outbreaks to inform early public health decision-making.

The unprecedented scale of the Ebola outbreak in West Africa has, as of 29 April 2015, resulted in more than 10,884 deaths among 26,277 cases. Prior to the ongoing outbreak, Ebola virus disease (EVD) caused relatively small outbreaks (maximum outbreak size 425 in Gulu, Uganda) in isolated populations in central Africa. Here, we have compiled a comprehensive database of estimates of epidemiological parameters based on data from past outbreaks, including the incubation period distribution, case fatality rate, basic reproduction number (R 0), effective reproduction number (R t) and delay distributions. We have compared these to parameter estimates from the ongoing outbreak in West Africa. The ongoing outbreak, because of its size, provides a unique opportunity to better understand transmission patterns of EVD. We have not performed a meta-analysis of the data, but rather summarize the estimates by virus from comprehensive investigations of EVD and Marburg outbreaks over the past 40 years. These estimates can be used to parameterize transmission models to improve understanding of initial spread of EVD outbreaks and to inform surveillance and control guidelines

Violent video games and morality: a meta-ethical approach

This paper considers what it is about violent video games that leads one reasonably minded person to declare "That is immoral" while another denies it. Three interpretations of video game content a re discussed: reductionist, narrow, and broad. It is argued that a broad interpretation is required for a moral objection to be justified. It is further argued that understanding the meaning of moral utterances – like "x is immoral" – is important to an understanding of why there is a lack of moral consensus when it comes to the content of violent video games. Constructive ecumenical expressivism is presented as a means of explaining what it is that we are doing when we make moral pronouncements and why, when it comes to video game content, differing moral attitudes abound. Constructive ecumenical expressivism is also presented as a means of illuminating what would be required for moral consensus to be achieved

Correlates of video games playing among adolescents in an Islamic country

<p>Abstract</p> <p>Background</p> <p>No study has ever explored the prevalence and correlates of video game playing among children in the Islamic Republic of Iran. This study describes patterns and correlates of excessive video game use in a random sample of middle-school students in Iran. Specifically, we examine the relationship between video game playing and psychological well-being, aggressive behaviors, and adolescents' perceived threat of video-computer game playing.</p> <p>Methods</p> <p>This cross-sectional study was performed with a random sample of 444 adolescents recruited from eight middle schools. A self-administered, anonymous questionnaire covered socio-demographics, video gaming behaviors, mental health status, self-reported aggressive behaviors, and perceived side effects of video game playing.</p> <p>Results</p> <p>Overall, participants spent an average of 6.3 hours per week playing video games. Moreover, 47% of participants reported that they had played one or more intensely violent games. Non-gamers reported suffering poorer mental health compared to excessive gamers. Both non-gamers and excessive gamers overall reported suffering poorer mental health compared to low or moderate players. Participants who initiated gaming at younger ages were more likely to score poorer in mental health measures. Participants' self-reported aggressive behaviors were associated with length of gaming. Boys, but not girls, who reported playing video games excessively showed more aggressive behaviors. A multiple binary logistic regression shows that when controlling for other variables, older students, those who perceived less serious side effects of video gaming, and those who have personal computers, were more likely to report that they had played video games excessively.</p> <p>Conclusion</p> <p>Our data show a curvilinear relationship between video game playing and mental health outcomes, with "moderate" gamers faring best and "excessive" gamers showing mild increases in problematic behaviors. Interestingly, "non-gamers" clearly show the worst outcomes. Therefore, both children and parents of non-game players should be updated about the positive impact of moderate video gaming. Educational interventions should also be designed to educate adolescents and their parents of the possible harmful impact of excessive video game playing on their health and psychosocial functioning.</p

Cluster randomized test-negative design (CR-TND) trials: a novel and efficient method to assess the efficacy of community level dengue interventions

Cluster randomized trials are the gold standard for assessing efficacy of community-level interventions, such as vector control strategies against dengue. We describe a novel cluster randomized trial methodology with a test-negative design, which offers advantages over traditional approaches. It utilizes outcome-based sampling of patients presenting with a syndrome consistent with the disease of interest, who are subsequently classified as test-positive cases or test-negative controls on the basis of diagnostic testing. We use simulations of a cluster trial to demonstrate validity of efficacy estimates under the test-negative approach. This demonstrates that, provided study arms are balanced for both test-negative and test-positive illness at baseline and that other test-negative design assumptions are met, the efficacy estimates closely match true efficacy. We also briefly discuss analytical considerations for an odds ratio-based effect estimate arising from clustered data, and outline potential approaches to analysis. We conclude that application of the test-negative design to certain cluster randomized trials could increase their efficiency and ease of implementation

Stellar Disk Truncations: Where do we stand ?

In the light of several recent developments we revisit the phenomenon of galactic stellar disk truncations. Even 25 years since the first paper on outer breaks in the radial light profiles of spiral galaxies, their origin is still unclear. The two most promising explanations are that these 'outer edges' either trace the maximum angular momentum during the galaxy formation epoch, or are associated with global star formation thresholds. Depending on their true physical nature, these outer edges may represent an improved size characteristic (e.g., as compared to D_25) and might contain fossil evidence imprinted by the galaxy formation and evolutionary history. We will address several observational aspects of disk truncations: their existence, not only in normal HSB galaxies, but also in LSB and even dwarf galaxies; their detailed shape, not sharp cut-offs as thought before, but in fact demarcating the start of a region with a steeper exponential distribution of starlight; their possible association with bars; as well as problems related to the line-of-sight integration for edge-on galaxies (the main targets for truncation searches so far). Taken together, these observations currently favour the star-formation threshold model, but more work is necessary to implement the truncations as adequate parameters characterising galactic disks.Comment: LaTeX, 10 pages, 6 figures, presented at the "Penetrating Bars through Masks of Cosmic Dust" conference in South Africa, proceedings published by Kluwer, and edited by Block, D.L., Freeman, K.C., Puerari, I., & Groess, R; v3 to match published versio

Does the revised cardiac risk index predict cardiac complications following elective lung resection?

Background: Revised Cardiac Risk Index (RCRI) score and Thoracic Revised Cardiac Risk Index (ThRCRI) score were developed to predict the risks of postoperative major cardiac complications in generic surgical population and thoracic surgery respectively. This study aims to determine the accuracy of these scores in predicting the risk of developing cardiac complications including atrial arrhythmias after lung resection surgery in adults. Methods: We studied 703 patients undergoing lung resection surgery in a tertiary thoracic surgery centre. Observed outcome measures of postoperative cardiac morbidity and mortality were compared against those predicted by risk. Results: Postoperative major cardiac complications and supraventricular arrhythmias occurred in 4.8% of patients. Both index scores had poor discriminative ability for predicting postoperative cardiac complications with an area under receiver operating characteristic (ROC) curve of 0.59 (95% CI 0.51-0.67) for the RCRI score and 0.57 (95% CI 0.49-0.66) for the ThRCRI score. Conclusions: In our cohort, RCRI and ThRCRI scores failed to accurately predict the risk of cardiac complications in patients undergoing elective resection of lung cancer. The British Thoracic Society (BTS) recommendation to seek a cardiology referral for all asymptomatic pre-operative lung resection patients with > 3 RCRI risk factors is thus unlikely to be of clinical benefit

Understanding disease control: influence of epidemiological and economic factors

We present a local spread model of disease transmission on a regular network and compare different control options ranging from treating the whole population to local control in a well-defined neighborhood of an infectious individual. Comparison is based on a total cost of epidemic, including cost of palliative treatment of ill individuals and preventive cost aimed at vaccination or culling of susceptible individuals. Disease is characterized by pre- symptomatic phase which makes detection and control difficult. Three general strategies emerge, global preventive treatment, local treatment within a neighborhood of certain size and only palliative treatment with no prevention. The choice between the strategies depends on relative costs of palliative and preventive treatment. The details of the local strategy and in particular the size of the optimal treatment neighborhood weakly depends on disease infectivity but strongly depends on other epidemiological factors. The required extend of prevention is proportional to the size of the infection neighborhood, but this relationship depends on time till detection and time till treatment in a non-nonlinear (power) law. In addition, we show that the optimal size of control neighborhood is highly sensitive to the relative cost, particularly for inefficient detection and control application. These results have important consequences for design of prevention strategies aiming at emerging diseases for which parameters are not known in advance

Predicting Phenotypic Diversity and the Underlying Quantitative Molecular Transitions

During development, signaling networks control the formation of multicellular patterns. To what extent quantitative fluctuations in these complex networks may affect multicellular phenotype remains unclear. Here, we describe a computational approach to predict and analyze the phenotypic diversity that is accessible to a developmental signaling network. Applying this framework to vulval development in C. elegans, we demonstrate that quantitative changes in the regulatory network can render ~500 multicellular phenotypes. This phenotypic capacity is an order-of-magnitude below the theoretical upper limit for this system but yet is large enough to demonstrate that the system is not restricted to a select few outcomes. Using metrics to gauge the robustness of these phenotypes to parameter perturbations, we identify a select subset of novel phenotypes that are the most promising for experimental validation. In addition, our model calculations provide a layout of these phenotypes in network parameter space. Analyzing this landscape of multicellular phenotypes yielded two significant insights. First, we show that experimentally well-established mutant phenotypes may be rendered using non-canonical network perturbations. Second, we show that the predicted multicellular patterns include not only those observed in C. elegans, but also those occurring exclusively in other species of the Caenorhabditis genus. This result demonstrates that quantitative diversification of a common regulatory network is indeed demonstrably sufficient to generate the phenotypic differences observed across three major species within the Caenorhabditis genus. Using our computational framework, we systematically identify the quantitative changes that may have occurred in the regulatory network during the evolution of these species. Our model predictions show that significant phenotypic diversity may be sampled through quantitative variations in the regulatory network without overhauling the core network architecture. Furthermore, by comparing the predicted landscape of phenotypes to multicellular patterns that have been experimentally observed across multiple species, we systematically trace the quantitative regulatory changes that may have occurred during the evolution of the Caenorhabditis genus