How to Make Epidemiological Training Infectious

In this fun, interactive exercise, students simulate an infectious disease outbreak among themselves that conceptually integrates two historically distinct fields in epidemiology

Effect of temperature anisotropy on various modes and instabilities for a magnetized non-relativistic bi-Maxwellian plasma

Using kinetic theory for homogeneous collisionless magnetized plasmas, we present an extended review of the plasma waves and instabilities and discuss the anisotropic response of generalized relativistic dielectric tensor and Onsager symmetry properties for arbitrary distribution functions. In general, we observe that for such plasmas only those electromagnetic modes whose magnetic field perturbations are perpendicular to the ambient magneticeld, i.e.,B1 \perp B0, are effected by the anisotropy. However, in oblique propagation all modes do show such anisotropic effects. Considering the non-relativistic bi-Maxwellian distribution and studying the relevant components of the general dielectric tensor under appropriate conditions, we derive the dispersion relations for various modes and instabilities. We show that only the electromagnetic R- and L- waves, those derived from them and the O-mode are affected by thermal anisotropies, since they satisfy the required condition B1\perpB0. By contrast, the perpendicularly propagating X-mode and the modes derived from it (the pure transverse X-mode and Bernstein mode) show no such effect. In general, we note that the thermal anisotropy modifies the parallel propagating modes via the parallel acoustic effect, while it modifies the perpendicular propagating modes via the Larmor-radius effect. In oblique propagation for kinetic Alfven waves, the thermal anisotropy affects the kinetic regime more than it affects the inertial regime. The generalized fast mode exhibits two distinct acoustic effects, one in the direction parallel to the ambient magnetic field and the other in the direction perpendicular to it. In the fast-mode instability, the magneto-sonic wave causes suppression of the firehose instability. We discuss all these propagation characteristics and present graphic illustrations

Diverse Hematological Malignancies Including Hodgkin-Like Lymphomas Develop in Chimeric MHC Class II Transgenic Mice

A chimeric HLA-DR4-H2-E (DR4) homozygous transgenic mouse line spontaneously develops diverse hematological malignancies with high frequency (70%). The majority of malignancies were distributed equally between T and B cell neoplasms and included lymphoblastic T cell lymphoma (LTCL), lymphoblastic B cell lymphoma (LBCL), diffuse large B cell lymphoma (DLBCL), the histiocyte/T cell rich variant of DLBCL (DLBCL-HA/T cell rich DLBCL), splenic marginal zone lymphoma (SMZL), follicular B cell lymphoma (FBL) and plasmacytoma (PCT). Most of these neoplasms were highly similar to human diseases. Also, some non-lymphoid malignancies such as acute myeloid leukemia (AML) and histiocytic sarcoma were found. Interestingly, composite lymphomas, including Hodgkin-like lymphomas, were also detected that had CD30+ Hodgkin/Reed-Sternberg (H/RS)-like cells, representing a tumor type not previously described in mice. Analysis of microdissected H/RS-like cells revealed their origin as germinal center B cells bearing somatic hypermutations and, in some instances, crippled mutations, as described for human Hodgkin lymphoma (HL). Transgene integration in an oncogene was excluded as an exclusive driving force of tumorigenesis and age-related lymphoma development suggests a multi-step process. Thus, this DR4 line is a useful model to investigate common molecular mechanisms that may contribute to important neoplastic diseases in man

HIV-1 Tat mimetic of VEGF correlates with increased microvessels density in AIDS-related diffuse large B-cell and Burkitt lymphomas

Angiogenic switch marks the beginning of tumor’s strategy to acquire independent blood supply. In some subtypes of non-Hodgkin’s lymphomas, higher local vascular endothelial growth factor (VEGF) expression correlates with increased microvessel density. However, this local VEGF expression is higher only in tumors with elevated expression of the receptors of the growth factor, suggesting an autocrine growth-promoting feedback loop. Several studies have indicated that VEGF receptors are also targeted by Tat protein from the HIV-1-infected cells. Given the similarity of the basic region of Tat to the angiogenic factors (basic fibroblast growth factor, VEGF), Tat mimics these proteins and binds to their receptors. We evaluated the role of HIV-1 Tat in regulating the level of VEGF expression and microvessel density in the AIDS-related diffuse large B-cell (DLBCL) and Burkitt lymphomas (BL). By luciferase assay, we showed that VEGF promoter activity was downregulated in vitro in cells transfected with Tat. Reduced VEGF protein expression in primary HIV-1 positive BL and DLBCL, compared to the negative cases, supported the findings of promoter downregulation from the cell lines. Microvascular density assessed by CD34 expression was, however, higher in HIV-1 positive than in HIV-1 negative tumors. These results suggest that Tat has a wider angiogenic role, besides the regulation of VEGF expression. Thus, targeting Tat protein itself and stabilizing transient silencing of VEGF expression or use of monoclonal antibodies against their receptors in the AIDS-associated tumors will open a window for future explorable pathways in the management of angiogenic phenotypes in the AIDS-associated non-Hodgkin’s lymphomas

Quantifying the effects of temperature on mosquito and parasite traits that determine the transmission potential of human malaria

Malaria transmission is known to be strongly impacted by temperature. The current understanding of how temperature affects mosquito and parasite life history traits derives from a limited number of empirical studies. These studies, some dating back to the early part of last century, are often poorly controlled, have limited replication, explore a narrow range of temperatures, and use a mixture of parasite and mosquito species. Here, we use a single pairing of the Asian mosquito vector, An. stephensi and the human malaria parasite, P. falciparum to conduct a comprehensive evaluation of the thermal performance curves of a range of mosquito and parasite traits relevant to transmission. We show that biting rate, adult mortality rate, parasite development rate, and vector competence are temperature sensitive. Importantly, we find qualitative and quantitative differences to the assumed temperature-dependent relationships. To explore the overall implications of temperature for transmission, we first use a standard model of relative vectorial capacity. This approach suggests a temperature optimum for transmission of 29°C, with minimum and maximum temperatures of 12°C and 38°C, respectively. However, the robustness of the vectorial capacity approach is challenged by the fact that the empirical data violate several of the model's simplifying assumptions. Accordingly, we present an alternative model of relative force of infection that better captures the observed biology of the vector-parasite interaction. This model suggests a temperature optimum for transmission of 26°C, with a minimum and maximum of 17°C and 35°C, respectively. The differences between the models lead to potentially divergent predictions for the potential impacts of current and future climate change on malaria transmission. The study provides a framework for more detailed, system-specific studies that are essential to develop an improved understanding on the effects of temperature on malaria transmission

Altered visual feedback from an embodied avatar unconsciously influences movement amplitude and muscle activity

Evidence suggests that the sense of the position of our body parts can be surreptitiously deceived, for instance through illusory visual inputs. However, whether altered visual feedback during limb movement can induce substantial unconscious motor and muscular adjustments is not known. To address this question, we covertly manipulated virtual body movements in immersive virtual reality. Participants were instructed to flex their elbow to 90° while tensing an elastic band, as their virtual arm reproduced the same, a reduced (75°), or an amplified (105°) movement. We recorded muscle activity using electromyography, and assessed body ownership, agency and proprioception of the arm. Our results not only show that participants compensated for the avatar’s manipulated arm movement while being completely unaware of it, but also that it is possible to induce unconscious motor adaptations requiring significant changes in muscular activity. Altered visual feedback through body ownership illusions can influence motor performance in a process that bypasses awareness

Sea Urchins Predation Facilitates Coral Invasion in a Marine Reserve

Macroalgae is the dominant trophic group on Mediterranean infralittoral rocky bottoms, whereas zooxanthellate corals are extremely rare. However, in recent years, the invasive coral Oculina patagonica appears to be increasing its abundance through unknown means. Here we examine the pattern of variation of this species at a marine reserve between 2002 and 2010 and contribute to the understanding of the mechanisms that allow its current increase. Because indirect interactions between species can play a relevant role in the establishment of species, a parallel assessment of the sea urchin Paracentrotus lividus, the main herbivorous invertebrate in this habitat and thus a key species, was conducted. O. patagonica has shown a 3-fold increase in abundance over the last 8 years and has become the most abundant invertebrate in the shallow waters of the marine reserve, matching some dominant erect macroalgae in abundance. High recruitment played an important role in this increasing coral abundance. The results from this study provide compelling evidence that the increase in sea urchin abundance may be one of the main drivers of the observed increase in coral abundance. Sea urchins overgraze macroalgae and create barren patches in the space-limited macroalgal community that subsequently facilitate coral recruitment. This study indicates that trophic interactions contributed to the success of an invasive coral in the Mediterranean because sea urchins grazing activity indirectly facilitated expansion of the coral. Current coral abundance at the marine reserve has ended the monopolization of algae in rocky infralittoral assemblages, an event that could greatly modify both the underwater seascape and the sources of primary production in the ecosystem

The Biodiversity of the Mediterranean Sea: Estimates, Patterns, and Threats

The Mediterranean Sea is a marine biodiversity hot spot. Here we combined an extensive literature analysis with expert opinions to update publicly available estimates of major taxa in this marine ecosystem and to revise and update several species lists. We also assessed overall spatial and temporal patterns of species diversity and identified major changes and threats. Our results listed approximately 17,000 marine species occurring in the Mediterranean Sea. However, our estimates of marine diversity are still incomplete as yet—undescribed species will be added in the future. Diversity for microbes is substantially underestimated, and the deep-sea areas and portions of the southern and eastern region are still poorly known. In addition, the invasion of alien species is a crucial factor that will continue to change the biodiversity of the Mediterranean, mainly in its eastern basin that can spread rapidly northwards and westwards due to the warming of the Mediterranean Sea. Spatial patterns showed a general decrease in biodiversity from northwestern to southeastern regions following a gradient of production, with some exceptions and caution due to gaps in our knowledge of the biota along the southern and eastern rims. Biodiversity was also generally higher in coastal areas and continental shelves, and decreases with depth. Temporal trends indicated that overexploitation and habitat loss have been the main human drivers of historical changes in biodiversity. At present, habitat loss and degradation, followed by fishing impacts, pollution, climate change, eutrophication, and the establishment of alien species are the most important threats and affect the greatest number of taxonomic groups. All these impacts are expected to grow in importance in the future, especially climate change and habitat degradation. The spatial identification of hot spots highlighted the ecological importance of most of the western Mediterranean shelves (and in particular, the Strait of Gibraltar and the adjacent Alboran Sea), western African coast, the Adriatic, and the Aegean Sea, which show high concentrations of endangered, threatened, or vulnerable species. The Levantine Basin, severely impacted by the invasion of species, is endangered as well

Statistical power and validity of Ebola vaccine trials in Sierra Leone: a simulation study of trial design and analysis.

BackgroundSafe and effective vaccines could help to end the ongoing Ebola virus disease epidemic in parts of west Africa, and mitigate future outbreaks of the virus. We assess the statistical validity and power of randomised controlled trial (RCT) and stepped-wedge cluster trial (SWCT) designs in Sierra Leone, where the incidence of Ebola virus disease is spatiotemporally heterogeneous, and is decreasing rapidly.MethodsWe projected district-level Ebola virus disease incidence for the next 6 months, using a stochastic model fitted to data from Sierra Leone. We then simulated RCT and SWCT designs in trial populations comprising geographically distinct clusters at high risk, taking into account realistic logistical constraints, and both individual-level and cluster-level variations in risk. We assessed false-positive rates and power for parametric and non-parametric analyses of simulated trial data, across a range of vaccine efficacies and trial start dates.FindingsFor an SWCT, regional variation in Ebola virus disease incidence trends produced increased false-positive rates (up to 0·15 at α=0·05) under standard statistical models, but not when analysed by a permutation test, whereas analyses of RCTs remained statistically valid under all models. With the assumption of a 6-month trial starting on Feb 18, 2015, we estimate the power to detect a 90% effective vaccine to be between 49% and 89% for an RCT, and between 6% and 26% for an SWCT, depending on the Ebola virus disease incidence within the trial population. We estimate that a 1-month delay in trial initiation will reduce the power of the RCT by 20% and that of the SWCT by 49%.InterpretationSpatiotemporal variation in infection risk undermines the statistical power of the SWCT. This variation also undercuts the SWCT's expected ethical advantages over the RCT, because an RCT, but not an SWCT, can prioritise vaccination of high-risk clusters.FundingUS National Institutes of Health, US National Science Foundation, and Canadian Institutes of Health Research