Quantifying trends in disease impact to produce a consistent and reproducible definition of an emerging infectious disease.

The proper allocation of public health resources for research and control requires quantification of both a disease's current burden and the trend in its impact. Infectious diseases that have been labeled as "emerging infectious diseases" (EIDs) have received heightened scientific and public attention and resources. However, the label 'emerging' is rarely backed by quantitative analysis and is often used subjectively. This can lead to over-allocation of resources to diseases that are incorrectly labelled "emerging," and insufficient allocation of resources to diseases for which evidence of an increasing or high sustained impact is strong. We suggest a simple quantitative approach, segmented regression, to characterize the trends and emergence of diseases. Segmented regression identifies one or more trends in a time series and determines the most statistically parsimonious split(s) (or joinpoints) in the time series. These joinpoints in the time series indicate time points when a change in trend occurred and may identify periods in which drivers of disease impact change. We illustrate the method by analyzing temporal patterns in incidence data for twelve diseases. This approach provides a way to classify a disease as currently emerging, re-emerging, receding, or stable based on temporal trends, as well as to pinpoint the time when the change in these trends happened. We argue that quantitative approaches to defining emergence based on the trend in impact of a disease can, with appropriate context, be used to prioritize resources for research and control. Implementing this more rigorous definition of an EID will require buy-in and enforcement from scientists, policy makers, peer reviewers and journal editors, but has the potential to improve resource allocation for global health

Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats

Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses

Moving Beyond Too Little, Too Late: Managing Emerging Infectious Diseases in Wild Populations Requires International Policy and Partnerships

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Mathematical practices and mathematical modes of enquiry: Same or different?

Background: In this paper, I share a case study of a teacher’s work on mathematics tasks in the context of a ‘mathematics for teaching’ course aiming to develop mathematical content understandings and mathematical practices among primary teachers in one South African province. The course was developed in a national context of concerns about the nature and levels of primary teachers’ mathematical knowledge. Theories viewing mathematical practices as fundamental, contrasted with those that view mathematical practices and mathematical content in more separate and ‘to be integrated’ ways, are used to frame the analysis and ritically reflect on the findings. Results: Data from this teacher’s pre-test and selected course assessments and interactions suggest that while he was able to develop some aspects of the mathematical practices described in the literature, his overall orientation remained attuned to memorization and recall. Findings also pointed to an ongoing reliance on external validation of the ‘correctness’ of his answers. Conclusions: The data suggest that the presence of elements of mathematical practices cannot be viewed as equivalent to the presence of mathematical modes of enquiry. The analysis presented in this paper suggests that while elements of mathematical practices can be developed, moving towards an encompassing orientation to mathematical modes of enquiry may require more central focus on problem-solving approaches to achieve a change in orientation

Comprehensive Primer Design for Analysis of Population Genetics in Non-Sequenced Organisms

Nuclear sequence markers are useful tool for the study of the history of populations and adaptation. However, it is not easy to obtain multiple nuclear primers for organisms with poor or no genomic sequence information. Here we used the genomes of organisms that have been fully sequenced to design comprehensive sets of primers to amplify polymorphic genomic fragments of multiple nuclear genes in non-sequenced organisms. First, we identified a large number of candidate polymorphic regions that were flanked on each side by conserved regions in the reference genomes. We then designed primers based on these conserved sequences and examined whether the primers could be used to amplify sequences in target species, montane brown frog (Rana ornativentris), anole lizard (Anolis sagrei), guppy (Poecilia reticulata), and fruit fly (Drosophila melanogaster), for population genetic analysis. We successfully obtained polymorphic markers for all target species studied. In addition, we found that sequence identities of the regions between the primer sites in the reference genomes affected the experimental success of DNA amplification and identification of polymorphic loci in the target genomes, and that exonic primers had a higher success rate than intronic primers in amplifying readable sequences. We conclude that this comparative genomic approach is a time- and cost-effective way to obtain polymorphic markers for non-sequenced organisms, and that it will contribute to the further development of evolutionary ecology and population genetics for non-sequenced organisms, aiding in the understanding of the genetic basis of adaptation

Integrative Taxonomy for Continental-Scale Terrestrial Insect Observations

Although 21st century ecology uses unprecedented technology at the largest spatio-temporal scales in history, the data remain reliant on sound taxonomic practices that derive from 18th century science. The importance of accurate species identifications has been assessed repeatedly and in instances where inappropriate assignments have been made there have been costly consequences. The National Ecological Observatory Network (NEON) will use a standardized system based upon an integrative taxonomic foundation to conduct observations of the focal terrestrial insect taxa, ground beetles and mosquitoes, at the continental scale for a 30 year monitoring program. The use of molecular data for continental-scale, multi-decadal research conducted by a geographically widely distributed set of researchers has not been evaluated until this point. The current paper addresses the development of a reference library for verifying species identifications at NEON and the key ways in which this resource will enhance a variety of user communities

PLEKHA7 Is an Adherens Junction Protein with a Tissue Distribution and Subcellular Localization Distinct from ZO-1 and E-Cadherin

The pleckstrin-homology-domain-containing protein PLEKHA7 was recently identified as a protein linking the E-cadherin-p120 ctn complex to the microtubule cytoskeleton. Here we characterize the expression, tissue distribution and subcellular localization of PLEKHA7 by immunoblotting, immunofluorescence microscopy, immunoelectron microscopy, and northern blotting in mammalian tissues. Anti-PLEKHA7 antibodies label the junctional regions of cultured kidney epithelial cells by immunofluorescence microscopy, and major polypeptides of Mr ∼135 kDa and ∼145 kDa by immunoblotting of lysates of cells and tissues. Two PLEKHA7 transcripts (∼5.5 kb and ∼6.5 kb) are detected in epithelial tissues. PLEKHA7 is detected at epithelial junctions in sections of kidney, liver, pancreas, intestine, retina, and cornea, and its tissue distribution and subcellular localization are distinct from ZO-1. For example, PLEKHA7 is not detected within kidney glomeruli. Similarly to E-cadherin, p120 ctn, β-catenin and α-catenin, PLEKHA7 is concentrated in the apical junctional belt, but unlike these adherens junction markers, and similarly to afadin, PLEKHA7 is not localized along the lateral region of polarized epithelial cells. Immunoelectron microscopy definitively establishes that PLEKHA7 is localized at the adherens junctions in colonic epithelial cells, at a mean distance of 28 nm from the plasma membrane. In summary, we show that PLEKHA7 is a cytoplasmic component of the epithelial adherens junction belt, with a subcellular localization and tissue distribution that is distinct from that of ZO-1 and most AJ proteins, and we provide the first description of its distribution and localization in several tissues

High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with acidic stores (lysosomes) in the heart

Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) stimulates calcium release from acidic stores such as lysosomes and is a highly potent calcium-mobilising second messenger. NAADP plays an important role in calcium signalling in the heart under basal conditions and following β-adrenergic stress. Nevertheless, the spatial interaction of acidic stores with other parts of the calcium signalling apparatus in cardiac myocytes is unknown. We present evidence that lysosomes are intimately associated with the sarcoplasmic reticulum (SR) in ventricular myocytes; a median separation of 20 nm in 2D electron microscopy and 3.3 nm in 3D electron tomography indicates a genuine signalling microdomain between these organelles. Fourier analysis of immunolabelled lysosomes suggests a sarcomeric pattern (dominant wavelength 1.80 μm). Furthermore, we show that lysosomes form close associations with mitochondria (median separation 6.2 nm in 3D studies) which may provide a basis for the recently-discovered role of NAADP in reperfusion-induced cell death. The trigger hypothesis for NAADP action proposes that calcium release from acidic stores subsequently acts to enhance calcium release from the SR. This work provides structural evidence in cardiac myocytes to indicate the formation of microdomains between acidic and SR calcium stores, supporting emerging interpretations of NAADP physiology and pharmacology in heart

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

A DESGW Search for the Electromagnetic Counterpart to the LIGO/Virgo Gravitational-wave Binary Neutron Star Merger Candidate S190510g

We present the results from a search for the electromagnetic counterpart of the LIGO/Virgo event S190510g using the Dark Energy Camera (DECam). S190510g is a binary neutron star (BNS) merger candidate of moderate significance detected at a distance of 227 ± 92 Mpc and localized within an area of 31 (1166) square degrees at 50% (90%) confidence. While this event was later classified as likely nonastrophysical in nature within 30 hours of the event, our short latency search and discovery pipeline identified 11 counterpart candidates, all of which appear consistent with supernovae following offline analysis and spectroscopy by other instruments. Later reprocessing of the images enabled the recovery of six more candidates. Additionally, we implement our candidate selection procedure on simulated kilonovae and supernovae under DECam observing conditions (e.g., seeing and exposure time) with the intent of quantifying our search efficiency and making informed decisions on observing strategy for future similar events. This is the first BNS counterpart search to employ a comprehensive simulation-based efficiency study. We find that using the current follow-up strategy, there would need to be 19 events similar to S190510g for us to have a 99% chance of detecting an optical counterpart, assuming a GW170817-like kilonova. We further conclude that optimization of observing plans, which should include preference for deeper images over multiple color information, could result in up to a factor of 1.5 reduction in the total number of follow-ups needed for discovery