Global seasonal influenza mortality estimates:a comparison of three different approaches

Prior to updating global influenza-associated mortality estimates, the World Health Organization convened a consultation in July 2017 to understand differences in methodology and implications for results of 3 influenza mortality projects from the US Centers for Disease Control and Prevention (CDC), the Netherlands Institute for Health Service Research’s Global Pandemic Mortality Project II (GLaMOR), and the Institute for Health Metrics and Evaluation (IHME). The expert panel reviewed estimates and discussed differences in data sources, analysis, and modeling assumptions. We performed a comparison analysis of the estimates. Influenza-associated respiratory death counts were comparable between CDC and GLaMOR; the IHME estimate was considerably lower. The greatest country-specific influenza-associated fold differences in mortality rate between CDC and IHME estimates and between GLaMOR and IHME estimates were among countries in Southeast Asia and the Eastern Mediterranean region. The data envelope used for the calculation was one of the major differences (CDC and GLaMOR: all respiratory deaths; IHME: lower-respiratory infection deaths). With the assumption that there is only one cause of death for each death, IHME estimates a fraction of the full influenza-associated respiratory mortality that is measured by the other 2 groups. Wide variability of parameters was observed. Continued coordination between groups could assist with better understanding of methodological differences and new approaches to estimating influenza deaths globally

Quantifying the three-dimensional facial morphology of the laboratory rat with a focus on the vibrissae

<div><p>The morphology of an animal’s face will have large effects on the sensory information it can acquire. Here we quantify the arrangement of cranial sensory structures of the rat, with special emphasis on the mystacial vibrissae (whiskers). Nearly all mammals have vibrissae, which are generally arranged in rows and columns across the face. The vibrissae serve a wide variety of important behavioral functions, including navigation, climbing, wake following, anemotaxis, and social interactions. To date, however, there are few studies that compare the morphology of vibrissal arrays across species, or that describe the arrangement of the vibrissae relative to other facial sensory structures. The few studies that do exist have exploited the whiskers’ grid-like arrangement to quantify array morphology in terms of row and column identity. However, relying on whisker identity poses a challenge for comparative research because different species have different numbers and arrangements of whiskers. The present work introduces an approach to quantify vibrissal array morphology regardless of the number of rows and columns, and to quantify the array’s location relative to other sensory structures. We use the three-dimensional locations of the whisker basepoints as fundamental parameters to generate equations describing the length, curvature, and orientation of each whisker. Results show that in the rat, whisker length varies exponentially across the array, and that a hard limit on intrinsic curvature constrains the whisker height-to-length ratio. Whiskers are oriented to “fan out” approximately equally in dorsal-ventral and rostral-caudal directions. Quantifying positions of the other sensory structures relative to the whisker basepoints shows remarkable alignment to the somatosensory cortical homunculus, an alignment that would not occur for other choices of coordinate systems (e.g., centered on the midpoint of the eyes). We anticipate that the quantification of facial sensory structures, including the vibrissae, will ultimately enable cross-species comparisons of multi-modal sensing volumes.</p></div

Relationship between whisker angles of emergence and basepoint parameters.

<p>(A) θ_w is a linear function of θ_bp and φ_bp. Mean ± standard error (SE) by whisker identity is shown in red. (B) Relatively uniform dispersion of actual vs. predicted values for θ_w about the identity line indicates selection of the correct model choice for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194981#pone.0194981.e008" target="_blank">Eq 7</a>. (C) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194981#pone.0194981.e008" target="_blank">Eq 7</a> is plotted as a colormap to show the variation of θ_w across the array. (D) φ_w can be described as a linear function of φ_bp. Mean ± SE by whisker identity is shown in red. (E) Relatively uniform dispersion of actual vs. predicted values for φ_w about the identity line indicates selection of the correct model for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194981#pone.0194981.e009" target="_blank">Eq 8</a>. (F) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194981#pone.0194981.e009" target="_blank">Eq 8</a> is plotted as a colormap to show the variation of φ_w across the array. (G) ζ_w can be described as a polynomial function linear in φ_bp and linear in θ_bp. Mean ± SE by whisker identity is shown in red. (H) Relatively uniform dispersion of actual vs. predicted values for ζ_w about the identity line indicates selection of the correct model for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194981#pone.0194981.e010" target="_blank">Eq 9</a>. (I) A colormap shows how <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194981#pone.0194981.e010" target="_blank">Eq 9</a> varies across the array.</p

Standardized whisker nomenclature to enable cross-species comparisons.

<p>(A) Close-up of the whisker basepoints on the mystacial pad, showing the traditional nomenclature. Greek letters are assigned to the whiskers of the caudal-most arc and more rostral arcs are assigned the numbers 1–6. (B) Close-up of the whiskers of the mystacial pad, showing a nomenclature more suited for cross-species comparisons, with columns assigned values from 1–7.</p

Proportion of angular area of facial features corresponds with proportion of cortical area.

<p>The ratunculus (grey outline, adapted from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194981#pone.0194981.ref062" target="_blank">62</a>]) is rotated and scaled to approximately align the barrel representations (grey circles) with the angular locations of the basepoints from the present study (black circles connected by black grid lines). Blue points represent angular locations of the rostral and caudal points of the eye, and the dorsal corner of the pinna. When these are translated and rotated (but not scaled) they align with the features on the ratunculus (light blue circles). Similarly, the green points, representing the rostral and caudal corners of the mouth and the incisors, align with those features after repositioning (but not scaling). The nose shows a similar pattern but is not shown for visual clarity.</p

Relationship between 2D whisker geometry and basepoint parameters.

<p>(A) Whisker arc length (S) can be described as a decaying exponential function of θ_bp, decreasing from caudal to rostral. The black line represents <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194981#pone.0194981.e004" target="_blank">Eq 4a</a>. Mean ± standard error (SE) by whisker identity is shown in red. (B) Relatively uniform dispersion of actual vs. predicted values for S about the identity line indicates correct model choice for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194981#pone.0194981.e004" target="_blank">Eq 4a</a>. (C) When grouped by whisker identity, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194981#pone.0194981.e004" target="_blank">Eq 4a</a> predicts that arc length decreases with column position. (D) Intrinsic curvature coefficient (A) can be described as a linearly increasing function of θ_bp from caudal to rostral. The black line represents <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194981#pone.0194981.e006" target="_blank">Eq 5</a>. Mean ± SE by whisker identity is shown in red. (E) Plotting A vs. S highlights that shorter whiskers have higher variability in curvature. This relationship is bound by the curve given by <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194981#pone.0194981.e007" target="_blank">Eq 6</a>. Inset: The upper bound on A constrains the “height” (H) of a whisker. (F) The height (H) of the whisker tip does not typically exceed more than 53.3% of the whisker’s arc length (S).</p

Schematics illustrating four possible choices of horizontal plane and the consequences of varying head pitch on the mathematical description of basepoint coordinates and whisker orientation.

<p>(A) The average whisker row plane is found by averaging the planes of best fit for each individual whisker row across left and right sides of the face. This plane is defined as “horizontal” in the present work. (B) Connecting the eye corners and nose yields an ~+12° offset from the average whisker row plane, tilting the rat head slightly upward. (C) The bregma-lambda plane is offset from the average whisker row plane by ~-8°, pitching the rat head slightly downward. (D) The semi-circular canal plane is offset by ~-38.5°, tilting the rat head substantially downward. (E) The left panel shows the angular basepoint coordinates (θ_bp, φ_bp) of two example whiskers (B2, D6) when the average row plane is defined as the horizontal x-y plane. The coordinate for B2 is (-21.5°, 22.3°) and the coordinate for D6 is (27.6°, -15.9°). The pale purple horizontal line at φ_bp = 0° represents the average row plane. The x-axis is also colored purple to highlight that it is parallel with the average row plane. The right panel shows the angular coordinates (θ_bp, φ_bp) of the same two whiskers (B2, D6) when the semi-circular canal plane is defined as horizontal. The coordinate for the B2 whisker is now (-2.2°, 30.2°) and the D6 whisker coordinate is now (13.1°, -29.5°). The pale green horizontal line indicates the semi-circular canal plane. The x-axis is also shown in green to highlight that it is now parallel to the semi-circular canal plane. Values in image have been truncated for visual clarity. (F) The left panel shows the angles of emergence for the C3 whisker, projected into the x-y plane (blue) and the x-z plane (red). These projection angles are denoted as θ_proj and φ_proj. In this panel, the average whisker row plane is defined as the horizontal plane, and the blue and red vectors represent projections of the proximal (approximately linear) portion of the whisker. The right panel illustrates the same angles of emergence when the semi-circular canal plane is defined as the horizontal plane. The redefined x-y plane is shown in green and the x-z plane in orange. New projection angles for the proximal, approximately linear portion of the whisker, are illustrated by the green and orange vectors. Again, although the relative orientation of the whisker with respect to all other facial features remains constant, the projection angles describing the orientation of that whisker are affected by choice of head pitch.</p

This figure shows the result of a template-matching classification method using the broad-band local field potentials.

<p>Using a cross-validation approach for each neuron, the training data (consisting of the raw microelectrode recording filtered between 1 and 10000 Hz) was used to estimate a template for each experimental condition. The test data were then compared to each template and the log likelihood calculated. To make classification asynchronous, the template was tested at different lags and the lowest error selected for that condition. The experimental condition with the lowest difference was used to classify the test data. Panel A shows the template waveforms for an example recording site. The templates are very distinct, with the standard deviation showing a relatively low trial-to-trial variability. Panel B shows the average confusion matrix for the template classification. The numbers in Panel B are the per-condition probability of correct classification.</p