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/Title (Climate change and influenza: the likelihood of early and severe influenza seasons following warmer than average winters � PLOS Currents Influenza)
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BT 15.000 718.042 Td /F2 21.0 Tf  [(Climate change and influenza: the likelihood of early and )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(severe influenza seasons following warmer than average winters)] TJ ET
Q
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BT 15.000 675.088 Td /F3 9.8 Tf  [(January 28, 2013)] TJ ET
BT 88.388 675.088 Td /F3 9.8 Tf  [(�)] TJ ET
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BT 93.263 675.088 Td /F3 9.8 Tf  [(Epidemiology)] TJ ET
BT 26.250 663.247 Td /F1 9.8 Tf  [(Sherry Towers)] TJ ET
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BT 89.635 667.135 Td /F1 8.7 Tf  [(1)] TJ ET
BT 94.453 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 99.874 663.247 Td /F1 9.8 Tf  [(Gerardo Chowell)] TJ ET
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BT 173.019 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 178.440 663.247 Td /F1 9.8 Tf  [(Rasheed Hameed)] TJ ET
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BT 261.834 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 267.255 663.247 Td /F1 9.8 Tf  [(Matthew Jastrebski)] TJ ET
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BT 360.935 663.247 Td /F1 9.8 Tf  [(Maryam Khan)] TJ ET
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BT 426.438 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 431.859 663.247 Td /F1 9.8 Tf  [(Jonathan Meeks)] TJ ET
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BT 503.394 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 508.815 663.247 Td /F1 9.8 Tf  [(Anuj Mubayi)] TJ ET
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BT 567.279 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 26.250 651.342 Td /F1 9.8 Tf  [(George Harris)] TJ ET
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BT 87.470 655.231 Td /F1 8.7 Tf  [(2)] TJ ET
BT 26.250 640.170 Td /F4 9.0 Tf  [(1)] TJ ET
BT 31.254 640.170 Td /F1 9.0 Tf  [( Arizona State University, )] TJ ET
BT 134.790 640.170 Td /F4 9.0 Tf  [(2)] TJ ET
BT 139.794 640.170 Td /F1 9.0 Tf  [( Northeastern Illinois University)] TJ ET
BT 26.250 628.449 Td /F1 9.8 Tf  [(Towers S, Chowell G, Hameed R, Jastrebski M, Khan M, Meeks J, Mubayi A, Harris G. Climate change and influenza: the )] TJ ET
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BT 26.250 604.639 Td /F1 9.8 Tf  [(. Edition 1. doi: 10.1371/currents.flu.3679b56a3a5313dc7c043fb944c6f138.)] TJ ET
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BT 26.250 575.537 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 555.582 Td /F1 9.8 Tf  [(The 2012-13 influenza season had an unusually early and severe start in the US, succeeding the record mild 2011-12 influenza )] TJ ET
BT 26.250 543.678 Td /F1 9.8 Tf  [(season, which occurred during the fourth warmest winter on record. Our analysis of climate and past US influenza epidemic )] TJ ET
BT 26.250 531.773 Td /F1 9.8 Tf  [(seasons between 1997-98 to present indicates that warm winters tend to be followed by severe epidemics with early onset, and )] TJ ET
BT 26.250 519.868 Td /F1 9.8 Tf  [(that these patterns are seen for both influenza A and B. We posit that fewer people are infected with influenza during warm )] TJ ET
BT 26.250 507.963 Td /F1 9.8 Tf  [(winters, thereby leaving an unnaturally large fraction of susceptible individuals in the population going into the next season, )] TJ ET
BT 26.250 496.059 Td /F1 9.8 Tf  [(which can lead to early and severe epidemics.)] TJ ET
BT 26.250 476.654 Td /F1 9.8 Tf  [(In the event of continued global warming, warm winters such as that of 2011-12 are expected to occur more frequently. Our )] TJ ET
BT 26.250 464.749 Td /F1 9.8 Tf  [(results thus suggest that expedited manufacture and distribution of influenza vaccines after mild winters has the potential to )] TJ ET
BT 26.250 452.844 Td /F1 9.8 Tf  [(mitigate the severity of future influenza epidemics.)] TJ ET
BT 26.250 416.242 Td /F4 12.0 Tf  [(Funding Statement)] TJ ET
BT 26.250 396.288 Td /F1 9.8 Tf  [(This research was partially supported by MISMS \(Multinational Influenza Seasonal Mortality Study\), an ongoing international )] TJ ET
BT 26.250 384.383 Td /F1 9.8 Tf  [(collaborative effort to understand influenza epidemiological and evolutionary patterns, led by the Fogarty International Center, )] TJ ET
BT 26.250 372.478 Td /F1 9.8 Tf  [(National Institutes of Health \(http://www.origem.info/misms/index.php\). AM acknowledges the partial support of grants NSF )] TJ ET
BT 26.250 360.573 Td /F1 9.8 Tf  [(DMS-1020880 and NIH AI097262-01.)] TJ ET
BT 26.250 331.471 Td /F4 12.0 Tf  [(Introduction)] TJ ET
BT 26.250 311.517 Td /F1 9.8 Tf  [(The 2011-12 influenza season was unusually late and mild, and set a new record for the season with the lowest and latest peak )] TJ ET
BT 26.250 299.612 Td /F1 9.8 Tf  [(of influenza-like illness \(ILI\) since surveillance efforts began )] TJ ET
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BT 285.805 301.119 Td /F4 8.7 Tf  [(1)] TJ ET
0.271 0.267 0.267 rg
BT 290.623 299.612 Td /F1 9.8 Tf  [(. While the underlying causative dynamics of the severity and )] TJ ET
BT 26.250 287.707 Td /F1 9.8 Tf  [(timing of influenza epidemics are multi-faceted, a primary contributing factor to the mildness of the 2011-12 season was likely )] TJ ET
BT 26.250 275.802 Td /F1 9.8 Tf  [(the fact that the national meteorological winter of 2011-12 was the fourth warmest on record )] TJ ET
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BT 424.567 277.310 Td /F4 8.7 Tf  [(2)] TJ ET
0.271 0.267 0.267 rg
BT 429.385 275.802 Td /F1 9.8 Tf  [(; several prior studies have shown )] TJ ET
BT 26.250 263.898 Td /F1 9.8 Tf  [(that influenza transmissibility sharply decreases in warmer temperatures and/or high humidity \(e.g., )] TJ ET
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BT 480.036 265.405 Td /F4 8.7 Tf  [(8)] TJ ET
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BT 484.854 263.898 Td /F1 9.8 Tf  [(\).)] TJ ET
BT 26.250 244.493 Td /F1 9.8 Tf  [(In contrast to the 2011-12 season, the ongoing 2012-13 season is off to an unusually early and severe start, despite the fact )] TJ ET
BT 26.250 232.588 Td /F1 9.8 Tf  [(that the national climate this past autumn was close to the seasonal average. Here we analyzed the weekly time series of )] TJ ET
BT 26.250 220.683 Td /F1 9.8 Tf  [(confirmed influenza cases in the US from the 1997-98 influenza season to present. Our findings indicate that influenza epidemic )] TJ ET
BT 26.250 208.779 Td /F1 9.8 Tf  [(severity and time of onset is significantly associated with the average winter temperature during the previous season, with )] TJ ET
BT 26.250 196.874 Td /F1 9.8 Tf  [(severe and early influenza seasons being much more likely following a mild winter.)] TJ ET
BT 26.250 177.469 Td /F1 9.8 Tf  [(In the event of continued global warming, warmer than average winters are expected to occur more frequently, but variability in )] TJ ET
BT 26.250 165.564 Td /F1 9.8 Tf  [(seasonal temperatures will of course remain, and average winters will still occur with regularity for some time to come. Our work )] TJ ET
BT 26.250 153.660 Td /F1 9.8 Tf  [(suggests that mild influenza seasons during unusually warm winters are a harbinger of the likelihood of an unusually severe )] TJ ET
BT 26.250 141.755 Td /F1 9.8 Tf  [(season to come. Hence, these findings could guide improved prevention efforts, including progressive vaccination programs )] TJ ET
BT 26.250 129.850 Td /F1 9.8 Tf  [(after a mild winter to achieve high vaccination coverage well in advance of the next influenza season.)] TJ ET
BT 26.250 93.248 Td /F4 12.0 Tf  [(Methods and Materials)] TJ ET
BT 26.250 73.293 Td /F4 9.8 Tf  [(Sources of data:)] TJ ET
BT 102.641 73.293 Td /F1 9.8 Tf  [( From the CDC website we obtained the weekly time series of laboratory-confirmed influenza incidence )] TJ ET
BT 26.250 61.389 Td /F1 9.8 Tf  [(recorded across ten US geographic regions between the 1997-98 to 2012-13 influenza seasons \(the time period over which )] TJ ET
BT 26.250 49.484 Td /F1 9.8 Tf  [(data was available\) )] TJ ET
0.267 0.267 0.267 rg
BT 112.411 50.991 Td /F4 8.7 Tf  [(9)] TJ ET
0.271 0.267 0.267 rg
BT 117.229 49.484 Td /F1 9.8 Tf  [(. In addition, we obtained the antigenic characterization of the dominant strains of each influenza season )] TJ ET
BT 26.250 37.579 Td /F1 9.8 Tf  [(and the percentage of isolates that matched the components of the influenza vaccine for that season )] TJ ET
0.267 0.267 0.267 rg
BT 462.543 39.086 Td /F4 8.7 Tf  [(9)] TJ ET
0.271 0.267 0.267 rg
BT 467.362 37.579 Td /F1 9.8 Tf  [(. We also obtained the )] TJ ET
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BT 15.000 718.042 Td /F2 21.0 Tf  [(Climate change and influenza: the likelihood of early and )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(severe influenza seasons following warmer than average winters)] TJ ET
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BT 15.000 675.088 Td /F3 9.8 Tf  [(January 28, 2013)] TJ ET
BT 88.388 675.088 Td /F3 9.8 Tf  [(�)] TJ ET
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BT 93.263 675.088 Td /F3 9.8 Tf  [(Epidemiology)] TJ ET
BT 26.250 663.247 Td /F1 9.8 Tf  [(Sherry Towers)] TJ ET
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BT 89.635 667.135 Td /F1 8.7 Tf  [(1)] TJ ET
BT 94.453 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 99.874 663.247 Td /F1 9.8 Tf  [(Gerardo Chowell)] TJ ET
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BT 173.019 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 178.440 663.247 Td /F1 9.8 Tf  [(Rasheed Hameed)] TJ ET
0.271 0.267 0.267 rg
BT 257.015 667.135 Td /F1 8.7 Tf  [(2)] TJ ET
BT 261.834 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 267.255 663.247 Td /F1 9.8 Tf  [(Matthew Jastrebski)] TJ ET
0.271 0.267 0.267 rg
BT 350.695 667.135 Td /F1 8.7 Tf  [(2)] TJ ET
BT 355.514 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 360.935 663.247 Td /F1 9.8 Tf  [(Maryam Khan)] TJ ET
0.271 0.267 0.267 rg
BT 421.619 667.135 Td /F1 8.7 Tf  [(2)] TJ ET
BT 426.438 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 431.859 663.247 Td /F1 9.8 Tf  [(Jonathan Meeks)] TJ ET
0.271 0.267 0.267 rg
BT 503.394 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 508.815 663.247 Td /F1 9.8 Tf  [(Anuj Mubayi)] TJ ET
0.271 0.267 0.267 rg
BT 562.460 667.135 Td /F1 8.7 Tf  [(2)] TJ ET
BT 567.279 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 26.250 651.342 Td /F1 9.8 Tf  [(George Harris)] TJ ET
0.271 0.267 0.267 rg
BT 87.470 655.231 Td /F1 8.7 Tf  [(2)] TJ ET
BT 26.250 640.170 Td /F4 9.0 Tf  [(1)] TJ ET
BT 31.254 640.170 Td /F1 9.0 Tf  [( Arizona State University, )] TJ ET
BT 134.790 640.170 Td /F4 9.0 Tf  [(2)] TJ ET
BT 139.794 640.170 Td /F1 9.0 Tf  [( Northeastern Illinois University)] TJ ET
BT 26.250 628.449 Td /F1 9.8 Tf  [(Towers S, Chowell G, Hameed R, Jastrebski M, Khan M, Meeks J, Mubayi A, Harris G. Climate change and influenza: the )] TJ ET
BT 26.250 616.544 Td /F1 9.8 Tf  [(likelihood of early and severe influenza seasons following warmer than average winters. PLOS Currents Influenza. 2013 Jan 28 )] TJ ET
BT 26.250 604.639 Td /F1 9.8 Tf  [(. Edition 1. doi: 10.1371/currents.flu.3679b56a3a5313dc7c043fb944c6f138.)] TJ ET
q
15.000 23.293 577.500 578.965 re W n
0.271 0.267 0.267 rg
BT 26.250 575.537 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 555.582 Td /F1 9.8 Tf  [(The 2012-13 influenza season had an unusually early and severe start in the US, succeeding the record mild 2011-12 influenza )] TJ ET
BT 26.250 543.678 Td /F1 9.8 Tf  [(season, which occurred during the fourth warmest winter on record. Our analysis of climate and past US influenza epidemic )] TJ ET
BT 26.250 531.773 Td /F1 9.8 Tf  [(seasons between 1997-98 to present indicates that warm winters tend to be followed by severe epidemics with early onset, and )] TJ ET
BT 26.250 519.868 Td /F1 9.8 Tf  [(that these patterns are seen for both influenza A and B. We posit that fewer people are infected with influenza during warm )] TJ ET
BT 26.250 507.963 Td /F1 9.8 Tf  [(winters, thereby leaving an unnaturally large fraction of susceptible individuals in the population going into the next season, )] TJ ET
BT 26.250 496.059 Td /F1 9.8 Tf  [(which can lead to early and severe epidemics.)] TJ ET
BT 26.250 476.654 Td /F1 9.8 Tf  [(In the event of continued global warming, warm winters such as that of 2011-12 are expected to occur more frequently. Our )] TJ ET
BT 26.250 464.749 Td /F1 9.8 Tf  [(results thus suggest that expedited manufacture and distribution of influenza vaccines after mild winters has the potential to )] TJ ET
BT 26.250 452.844 Td /F1 9.8 Tf  [(mitigate the severity of future influenza epidemics.)] TJ ET
BT 26.250 416.242 Td /F4 12.0 Tf  [(Funding Statement)] TJ ET
BT 26.250 396.288 Td /F1 9.8 Tf  [(This research was partially supported by MISMS \(Multinational Influenza Seasonal Mortality Study\), an ongoing international )] TJ ET
BT 26.250 384.383 Td /F1 9.8 Tf  [(collaborative effort to understand influenza epidemiological and evolutionary patterns, led by the Fogarty International Center, )] TJ ET
BT 26.250 372.478 Td /F1 9.8 Tf  [(National Institutes of Health \(http://www.origem.info/misms/index.php\). AM acknowledges the partial support of grants NSF )] TJ ET
BT 26.250 360.573 Td /F1 9.8 Tf  [(DMS-1020880 and NIH AI097262-01.)] TJ ET
BT 26.250 331.471 Td /F4 12.0 Tf  [(Introduction)] TJ ET
BT 26.250 311.517 Td /F1 9.8 Tf  [(The 2011-12 influenza season was unusually late and mild, and set a new record for the season with the lowest and latest peak )] TJ ET
BT 26.250 299.612 Td /F1 9.8 Tf  [(of influenza-like illness \(ILI\) since surveillance efforts began )] TJ ET
0.267 0.267 0.267 rg
BT 285.805 301.119 Td /F4 8.7 Tf  [(1)] TJ ET
0.271 0.267 0.267 rg
BT 290.623 299.612 Td /F1 9.8 Tf  [(. While the underlying causative dynamics of the severity and )] TJ ET
BT 26.250 287.707 Td /F1 9.8 Tf  [(timing of influenza epidemics are multi-faceted, a primary contributing factor to the mildness of the 2011-12 season was likely )] TJ ET
BT 26.250 275.802 Td /F1 9.8 Tf  [(the fact that the national meteorological winter of 2011-12 was the fourth warmest on record )] TJ ET
0.267 0.267 0.267 rg
BT 424.567 277.310 Td /F4 8.7 Tf  [(2)] TJ ET
0.271 0.267 0.267 rg
BT 429.385 275.802 Td /F1 9.8 Tf  [(; several prior studies have shown )] TJ ET
BT 26.250 263.898 Td /F1 9.8 Tf  [(that influenza transmissibility sharply decreases in warmer temperatures and/or high humidity \(e.g., )] TJ ET
0.267 0.267 0.267 rg
BT 455.942 265.405 Td /F4 8.7 Tf  [(3)] TJ ET
BT 460.761 265.405 Td /F4 8.7 Tf  [(4)] TJ ET
BT 465.580 265.405 Td /F4 8.7 Tf  [(5)] TJ ET
BT 470.398 265.405 Td /F4 8.7 Tf  [(6)] TJ ET
BT 475.217 265.405 Td /F4 8.7 Tf  [(7)] TJ ET
BT 480.036 265.405 Td /F4 8.7 Tf  [(8)] TJ ET
0.271 0.267 0.267 rg
BT 484.854 263.898 Td /F1 9.8 Tf  [(\).)] TJ ET
BT 26.250 244.493 Td /F1 9.8 Tf  [(In contrast to the 2011-12 season, the ongoing 2012-13 season is off to an unusually early and severe start, despite the fact )] TJ ET
BT 26.250 232.588 Td /F1 9.8 Tf  [(that the national climate this past autumn was close to the seasonal average. Here we analyzed the weekly time series of )] TJ ET
BT 26.250 220.683 Td /F1 9.8 Tf  [(confirmed influenza cases in the US from the 1997-98 influenza season to present. Our findings indicate that influenza epidemic )] TJ ET
BT 26.250 208.779 Td /F1 9.8 Tf  [(severity and time of onset is significantly associated with the average winter temperature during the previous season, with )] TJ ET
BT 26.250 196.874 Td /F1 9.8 Tf  [(severe and early influenza seasons being much more likely following a mild winter.)] TJ ET
BT 26.250 177.469 Td /F1 9.8 Tf  [(In the event of continued global warming, warmer than average winters are expected to occur more frequently, but variability in )] TJ ET
BT 26.250 165.564 Td /F1 9.8 Tf  [(seasonal temperatures will of course remain, and average winters will still occur with regularity for some time to come. Our work )] TJ ET
BT 26.250 153.660 Td /F1 9.8 Tf  [(suggests that mild influenza seasons during unusually warm winters are a harbinger of the likelihood of an unusually severe )] TJ ET
BT 26.250 141.755 Td /F1 9.8 Tf  [(season to come. Hence, these findings could guide improved prevention efforts, including progressive vaccination programs )] TJ ET
BT 26.250 129.850 Td /F1 9.8 Tf  [(after a mild winter to achieve high vaccination coverage well in advance of the next influenza season.)] TJ ET
BT 26.250 93.248 Td /F4 12.0 Tf  [(Methods and Materials)] TJ ET
BT 26.250 73.293 Td /F4 9.8 Tf  [(Sources of data:)] TJ ET
BT 102.641 73.293 Td /F1 9.8 Tf  [( From the CDC website we obtained the weekly time series of laboratory-confirmed influenza incidence )] TJ ET
BT 26.250 61.389 Td /F1 9.8 Tf  [(recorded across ten US geographic regions between the 1997-98 to 2012-13 influenza seasons \(the time period over which )] TJ ET
BT 26.250 49.484 Td /F1 9.8 Tf  [(data was available\) )] TJ ET
0.267 0.267 0.267 rg
BT 112.411 50.991 Td /F4 8.7 Tf  [(9)] TJ ET
0.271 0.267 0.267 rg
BT 117.229 49.484 Td /F1 9.8 Tf  [(. In addition, we obtained the antigenic characterization of the dominant strains of each influenza season )] TJ ET
BT 26.250 37.579 Td /F1 9.8 Tf  [(and the percentage of isolates that matched the components of the influenza vaccine for that season )] TJ ET
0.267 0.267 0.267 rg
BT 462.543 39.086 Td /F4 8.7 Tf  [(9)] TJ ET
0.271 0.267 0.267 rg
BT 467.362 37.579 Td /F1 9.8 Tf  [(. We also obtained the )] TJ ET
Q
q
15.000 684.354 577.500 53.646 re W n
0.267 0.267 0.267 rg
BT 15.000 718.042 Td /F2 21.0 Tf  [(Climate change and influenza: the likelihood of early and )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(severe influenza seasons following warmer than average winters)] TJ ET
Q
0.271 0.267 0.267 rg
BT 15.000 675.088 Td /F3 9.8 Tf  [(January 28, 2013)] TJ ET
BT 88.388 675.088 Td /F3 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
BT 93.263 675.088 Td /F3 9.8 Tf  [(Epidemiology)] TJ ET
BT 26.250 663.247 Td /F1 9.8 Tf  [(Sherry Towers)] TJ ET
0.271 0.267 0.267 rg
BT 89.635 667.135 Td /F1 8.7 Tf  [(1)] TJ ET
BT 94.453 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 99.874 663.247 Td /F1 9.8 Tf  [(Gerardo Chowell)] TJ ET
0.271 0.267 0.267 rg
BT 173.019 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 178.440 663.247 Td /F1 9.8 Tf  [(Rasheed Hameed)] TJ ET
0.271 0.267 0.267 rg
BT 257.015 667.135 Td /F1 8.7 Tf  [(2)] TJ ET
BT 261.834 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 267.255 663.247 Td /F1 9.8 Tf  [(Matthew Jastrebski)] TJ ET
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BT 360.935 663.247 Td /F1 9.8 Tf  [(Maryam Khan)] TJ ET
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BT 431.859 663.247 Td /F1 9.8 Tf  [(Jonathan Meeks)] TJ ET
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BT 508.815 663.247 Td /F1 9.8 Tf  [(Anuj Mubayi)] TJ ET
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BT 31.254 640.170 Td /F1 9.0 Tf  [( Arizona State University, )] TJ ET
BT 134.790 640.170 Td /F4 9.0 Tf  [(2)] TJ ET
BT 139.794 640.170 Td /F1 9.0 Tf  [( Northeastern Illinois University)] TJ ET
BT 26.250 628.449 Td /F1 9.8 Tf  [(Towers S, Chowell G, Hameed R, Jastrebski M, Khan M, Meeks J, Mubayi A, Harris G. Climate change and influenza: the )] TJ ET
BT 26.250 616.544 Td /F1 9.8 Tf  [(likelihood of early and severe influenza seasons following warmer than average winters. PLOS Currents Influenza. 2013 Jan 28 )] TJ ET
BT 26.250 604.639 Td /F1 9.8 Tf  [(. Edition 1. doi: 10.1371/currents.flu.3679b56a3a5313dc7c043fb944c6f138.)] TJ ET
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BT 26.250 575.537 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 555.582 Td /F1 9.8 Tf  [(The 2012-13 influenza season had an unusually early and severe start in the US, succeeding the record mild 2011-12 influenza )] TJ ET
BT 26.250 543.678 Td /F1 9.8 Tf  [(season, which occurred during the fourth warmest winter on record. Our analysis of climate and past US influenza epidemic )] TJ ET
BT 26.250 531.773 Td /F1 9.8 Tf  [(seasons between 1997-98 to present indicates that warm winters tend to be followed by severe epidemics with early onset, and )] TJ ET
BT 26.250 519.868 Td /F1 9.8 Tf  [(that these patterns are seen for both influenza A and B. We posit that fewer people are infected with influenza during warm )] TJ ET
BT 26.250 507.963 Td /F1 9.8 Tf  [(winters, thereby leaving an unnaturally large fraction of susceptible individuals in the population going into the next season, )] TJ ET
BT 26.250 496.059 Td /F1 9.8 Tf  [(which can lead to early and severe epidemics.)] TJ ET
BT 26.250 476.654 Td /F1 9.8 Tf  [(In the event of continued global warming, warm winters such as that of 2011-12 are expected to occur more frequently. Our )] TJ ET
BT 26.250 464.749 Td /F1 9.8 Tf  [(results thus suggest that expedited manufacture and distribution of influenza vaccines after mild winters has the potential to )] TJ ET
BT 26.250 452.844 Td /F1 9.8 Tf  [(mitigate the severity of future influenza epidemics.)] TJ ET
BT 26.250 416.242 Td /F4 12.0 Tf  [(Funding Statement)] TJ ET
BT 26.250 396.288 Td /F1 9.8 Tf  [(This research was partially supported by MISMS \(Multinational Influenza Seasonal Mortality Study\), an ongoing international )] TJ ET
BT 26.250 384.383 Td /F1 9.8 Tf  [(collaborative effort to understand influenza epidemiological and evolutionary patterns, led by the Fogarty International Center, )] TJ ET
BT 26.250 372.478 Td /F1 9.8 Tf  [(National Institutes of Health \(http://www.origem.info/misms/index.php\). AM acknowledges the partial support of grants NSF )] TJ ET
BT 26.250 360.573 Td /F1 9.8 Tf  [(DMS-1020880 and NIH AI097262-01.)] TJ ET
BT 26.250 331.471 Td /F4 12.0 Tf  [(Introduction)] TJ ET
BT 26.250 311.517 Td /F1 9.8 Tf  [(The 2011-12 influenza season was unusually late and mild, and set a new record for the season with the lowest and latest peak )] TJ ET
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BT 26.250 244.493 Td /F1 9.8 Tf  [(In contrast to the 2011-12 season, the ongoing 2012-13 season is off to an unusually early and severe start, despite the fact )] TJ ET
BT 26.250 232.588 Td /F1 9.8 Tf  [(that the national climate this past autumn was close to the seasonal average. Here we analyzed the weekly time series of )] TJ ET
BT 26.250 220.683 Td /F1 9.8 Tf  [(confirmed influenza cases in the US from the 1997-98 influenza season to present. Our findings indicate that influenza epidemic )] TJ ET
BT 26.250 208.779 Td /F1 9.8 Tf  [(severity and time of onset is significantly associated with the average winter temperature during the previous season, with )] TJ ET
BT 26.250 196.874 Td /F1 9.8 Tf  [(severe and early influenza seasons being much more likely following a mild winter.)] TJ ET
BT 26.250 177.469 Td /F1 9.8 Tf  [(In the event of continued global warming, warmer than average winters are expected to occur more frequently, but variability in )] TJ ET
BT 26.250 165.564 Td /F1 9.8 Tf  [(seasonal temperatures will of course remain, and average winters will still occur with regularity for some time to come. Our work )] TJ ET
BT 26.250 153.660 Td /F1 9.8 Tf  [(suggests that mild influenza seasons during unusually warm winters are a harbinger of the likelihood of an unusually severe )] TJ ET
BT 26.250 141.755 Td /F1 9.8 Tf  [(season to come. Hence, these findings could guide improved prevention efforts, including progressive vaccination programs )] TJ ET
BT 26.250 129.850 Td /F1 9.8 Tf  [(after a mild winter to achieve high vaccination coverage well in advance of the next influenza season.)] TJ ET
BT 26.250 93.248 Td /F4 12.0 Tf  [(Methods and Materials)] TJ ET
BT 26.250 73.293 Td /F4 9.8 Tf  [(Sources of data:)] TJ ET
BT 102.641 73.293 Td /F1 9.8 Tf  [( From the CDC website we obtained the weekly time series of laboratory-confirmed influenza incidence )] TJ ET
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0.271 0.267 0.267 rg
BT 35.250 552.798 Td /F4 9.8 Tf  [(Fig. 1: The time series of US weekly confirmed cases of influenza between 1997 to present.)] TJ ET
BT 35.250 533.428 Td /F1 9.8 Tf  [(The data for each season is shown relative to Jan 1st of that season. The extraordinarily early rise in cases of influenza )] TJ ET
BT 35.250 519.691 Td /F1 9.8 Tf  [(A\(H3N2\) and influenza B this season is made even more unusual by the fact that the simultaneous early epidemic rise of )] TJ ET
BT 35.250 505.955 Td /F1 9.8 Tf  [(two strains has not hitherto been observed, and the vaccine composition is a good match to the circulating strains.)] TJ ET
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BT 26.250 467.434 Td /F1 9.8 Tf  [(To calculate the population weighted average climate across US regions, the population and geospatial location information for )] TJ ET
BT 26.250 455.529 Td /F1 9.8 Tf  [(all urban centers in the US with population greater than 50,000 were obtained from the US Census Bureau \(comprising almost )] TJ ET
BT 26.250 443.625 Td /F1 9.8 Tf  [(500 population centers, and over 75% of the population of the US\) )] TJ ET
0.267 0.267 0.267 rg
BT 314.587 445.132 Td /F4 8.7 Tf  [(11)] TJ ET
0.271 0.267 0.267 rg
BT 324.224 443.625 Td /F1 9.8 Tf  [(. The corresponding weather stations in the vicinity of each )] TJ ET
BT 26.250 431.720 Td /F1 9.8 Tf  [(population center were identified, and daily climate data from 1997 to 2012 obtained from the National Climate Data Center )] TJ ET
BT 26.250 419.815 Td /F1 9.8 Tf  [(\(NCDC\) of the National Oceanic and Atmospheric Administration \(NOAA\) )] TJ ET
0.267 0.267 0.267 rg
BT 344.841 421.322 Td /F4 8.7 Tf  [(12)] TJ ET
0.271 0.267 0.267 rg
BT 354.478 419.815 Td /F1 9.8 Tf  [(. For each season, we calculated the average )] TJ ET
BT 26.250 407.910 Td /F1 9.8 Tf  [(temperature over the time period corresponding to the central 90% of the epidemic curve, �T_bef�. For seasons during which the )] TJ ET
BT 26.250 396.006 Td /F1 9.8 Tf  [(epidemic was suppressed, we calculated T_bef as the average temperature between the start of October to the end of March )] TJ ET
BT 26.250 384.101 Td /F1 9.8 Tf  [(\(the conclusions of this study were not sensitive to the exact date range used to define the epidemic period\).)] TJ ET
BT 26.250 364.696 Td /F1 9.8 Tf  [(In Figure 2 we show the US population weighted average temperature during winter \(January-March\) and autumn \(September-)] TJ ET
BT 26.250 352.791 Td /F1 9.8 Tf  [(December\) from 1997 to 2012. The winter of early 2012 was unusually warm, whereas temperature in autumn of 2012 was )] TJ ET
BT 26.250 340.887 Td /F1 9.8 Tf  [(close to the seasonal average of the study period\).)] TJ ET
0.965 0.965 0.965 rg
26.250 138.628 555.000 192.377 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
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0.271 0.267 0.267 rg
BT 35.250 193.232 Td /F4 9.8 Tf  [(Fig. 2: US population weighted average winter and autumn temperatures.)] TJ ET
BT 35.250 173.862 Td /F1 9.8 Tf  [(The temperature in early 2012 was significantly higher than average, whereas the temperature during autumn 2012 was )] TJ ET
BT 35.250 160.126 Td /F1 9.8 Tf  [(consistent with the average.)] TJ ET
Q
BT 26.250 121.605 Td /F4 9.8 Tf  [(Epidemic growth rate as a measure of epidemic severity:)] TJ ET
BT 289.598 121.605 Td /F1 9.8 Tf  [( In the early stages of an influenza epidemic, the temporal )] TJ ET
BT 26.250 109.700 Td /F1 9.8 Tf  [(evolution of incident cases grows exponentially as the effect of increasing incidence on the depletion of the susceptible )] TJ ET
BT 26.250 97.795 Td /F1 9.8 Tf  [(population remains small )] TJ ET
0.267 0.267 0.267 rg
BT 136.786 99.302 Td /F4 8.7 Tf  [(13)] TJ ET
BT 146.423 99.302 Td /F4 8.7 Tf  [(14)] TJ ET
BT 156.060 99.302 Td /F4 8.7 Tf  [(15)] TJ ET
0.271 0.267 0.267 rg
BT 165.698 97.795 Td /F1 9.8 Tf  [(. Here we assume that influenza testing rates are relatively constant within each epidemic )] TJ ET
BT 26.250 85.890 Td /F1 9.8 Tf  [(period, and identify the exponential epidemic phase as the initial portion of the influenza epidemics up to 4 weeks before the )] TJ ET
BT 26.250 73.986 Td /F1 9.8 Tf  [(time of the peak in incidence)] TJ ET
0.267 0.267 0.267 rg
BT 149.812 75.493 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 159.449 73.986 Td /F1 9.8 Tf  [( . Maximum likelihood methods are used to fit an exponential curve to that initial epidemic data to )] TJ ET
BT 26.250 62.081 Td /F1 9.8 Tf  [(determine the initial exponential growth rate, �r� )] TJ ET
0.267 0.267 0.267 rg
BT 232.706 63.588 Td /F4 8.7 Tf  [(16)] TJ ET
0.271 0.267 0.267 rg
BT 242.344 62.081 Td /F1 9.8 Tf  [(. We note that the initial growth rate could not be measured in seasons where )] TJ ET
BT 26.250 50.176 Td /F1 9.8 Tf  [(the spread of an influenza strain was entirely \(or almost entirely\) suppressed, and hence we assume in those cases that r=0.)] TJ ET
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q
15.000 40.295 577.500 736.705 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(overall influenza-related mortality during each season using data obtained from the CDC 122 Cities Mortality Reporting system )] TJ ET
0.267 0.267 0.267 rg
BT 26.250 757.079 Td /F4 8.7 Tf  [(10)] TJ ET
0.271 0.267 0.267 rg
BT 35.887 755.571 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Time series of influenza B, A\(H1N1\) and A\(H3N2\) for annual seasons between 1997-98 to 2012-13 are shown in Figure 1. Both )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(influenza B and A\(H3N2\) epidemics are off to an extraordinarily early start this season, made even more remarkable for the fact )] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(that the vaccine this season is a reasonably good match to the circulating strains, and also that early epidemic seasons in all )] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(previous years of surveillance data were due to the spread of one subtype only.)] TJ ET
0.965 0.965 0.965 rg
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0.267 0.267 0.267 RG
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35.250 495.708 537.000 66.614 re W n
0.271 0.267 0.267 rg
BT 35.250 552.798 Td /F4 9.8 Tf  [(Fig. 1: The time series of US weekly confirmed cases of influenza between 1997 to present.)] TJ ET
BT 35.250 533.428 Td /F1 9.8 Tf  [(The data for each season is shown relative to Jan 1st of that season. The extraordinarily early rise in cases of influenza )] TJ ET
BT 35.250 519.691 Td /F1 9.8 Tf  [(A\(H3N2\) and influenza B this season is made even more unusual by the fact that the simultaneous early epidemic rise of )] TJ ET
BT 35.250 505.955 Td /F1 9.8 Tf  [(two strains has not hitherto been observed, and the vaccine composition is a good match to the circulating strains.)] TJ ET
Q
BT 26.250 467.434 Td /F1 9.8 Tf  [(To calculate the population weighted average climate across US regions, the population and geospatial location information for )] TJ ET
BT 26.250 455.529 Td /F1 9.8 Tf  [(all urban centers in the US with population greater than 50,000 were obtained from the US Census Bureau \(comprising almost )] TJ ET
BT 26.250 443.625 Td /F1 9.8 Tf  [(500 population centers, and over 75% of the population of the US\) )] TJ ET
0.267 0.267 0.267 rg
BT 314.587 445.132 Td /F4 8.7 Tf  [(11)] TJ ET
0.271 0.267 0.267 rg
BT 324.224 443.625 Td /F1 9.8 Tf  [(. The corresponding weather stations in the vicinity of each )] TJ ET
BT 26.250 431.720 Td /F1 9.8 Tf  [(population center were identified, and daily climate data from 1997 to 2012 obtained from the National Climate Data Center )] TJ ET
BT 26.250 419.815 Td /F1 9.8 Tf  [(\(NCDC\) of the National Oceanic and Atmospheric Administration \(NOAA\) )] TJ ET
0.267 0.267 0.267 rg
BT 344.841 421.322 Td /F4 8.7 Tf  [(12)] TJ ET
0.271 0.267 0.267 rg
BT 354.478 419.815 Td /F1 9.8 Tf  [(. For each season, we calculated the average )] TJ ET
BT 26.250 407.910 Td /F1 9.8 Tf  [(temperature over the time period corresponding to the central 90% of the epidemic curve, �T_bef�. For seasons during which the )] TJ ET
BT 26.250 396.006 Td /F1 9.8 Tf  [(epidemic was suppressed, we calculated T_bef as the average temperature between the start of October to the end of March )] TJ ET
BT 26.250 384.101 Td /F1 9.8 Tf  [(\(the conclusions of this study were not sensitive to the exact date range used to define the epidemic period\).)] TJ ET
BT 26.250 364.696 Td /F1 9.8 Tf  [(In Figure 2 we show the US population weighted average temperature during winter \(January-March\) and autumn \(September-)] TJ ET
BT 26.250 352.791 Td /F1 9.8 Tf  [(December\) from 1997 to 2012. The winter of early 2012 was unusually warm, whereas temperature in autumn of 2012 was )] TJ ET
BT 26.250 340.887 Td /F1 9.8 Tf  [(close to the seasonal average of the study period\).)] TJ ET
0.965 0.965 0.965 rg
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0.271 0.267 0.267 rg
BT 35.250 193.232 Td /F4 9.8 Tf  [(Fig. 2: US population weighted average winter and autumn temperatures.)] TJ ET
BT 35.250 173.862 Td /F1 9.8 Tf  [(The temperature in early 2012 was significantly higher than average, whereas the temperature during autumn 2012 was )] TJ ET
BT 35.250 160.126 Td /F1 9.8 Tf  [(consistent with the average.)] TJ ET
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BT 26.250 121.605 Td /F4 9.8 Tf  [(Epidemic growth rate as a measure of epidemic severity:)] TJ ET
BT 289.598 121.605 Td /F1 9.8 Tf  [( In the early stages of an influenza epidemic, the temporal )] TJ ET
BT 26.250 109.700 Td /F1 9.8 Tf  [(evolution of incident cases grows exponentially as the effect of increasing incidence on the depletion of the susceptible )] TJ ET
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0.271 0.267 0.267 rg
BT 165.698 97.795 Td /F1 9.8 Tf  [(. Here we assume that influenza testing rates are relatively constant within each epidemic )] TJ ET
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BT 26.250 73.986 Td /F1 9.8 Tf  [(time of the peak in incidence)] TJ ET
0.267 0.267 0.267 rg
BT 149.812 75.493 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 159.449 73.986 Td /F1 9.8 Tf  [( . Maximum likelihood methods are used to fit an exponential curve to that initial epidemic data to )] TJ ET
BT 26.250 62.081 Td /F1 9.8 Tf  [(determine the initial exponential growth rate, �r� )] TJ ET
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BT 26.250 454.729 Td /F1 9.8 Tf  [(growth rate when compared to the temperature and growth rate the season before, with very similar patterns seen for both )] TJ ET
BT 26.250 442.824 Td /F1 9.8 Tf  [(influenza A and influenza B. In particular, mild winters were found to be significantly associated with early and severe epidemics )] TJ ET
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BT 26.250 198.991 Td /F1 9.8 Tf  [(We posit that warm winters are more likely to be succeeded by early and severe influenza seasons due to fewer people being )] TJ ET
BT 26.250 187.086 Td /F1 9.8 Tf  [(infected due to the warm weather, thereby leaving an unnaturally large fraction of susceptible individuals in the population going )] TJ ET
BT 26.250 175.182 Td /F1 9.8 Tf  [(into the next season. The severity of the next season could potentially be exacerbated by the early onset, if the onset occurs )] TJ ET
BT 26.250 163.277 Td /F1 9.8 Tf  [(before most of the population has had the opportunity to be vaccinated.)] TJ ET
BT 26.250 143.872 Td /F1 9.8 Tf  [(Our observation that climate patterns can have a profound impact on influenza epidemics beyond just the time frame of the )] TJ ET
BT 26.250 131.967 Td /F1 9.8 Tf  [(current season will likely open up interesting avenues of further research.)] TJ ET
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q
15.000 100.850 577.500 676.150 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(For seasons where the influenza epidemic was not suppressed, we use the NCDC climate data to estimate the average )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(temperature, �T�, over the time period comprising the initial epidemic growth phase.)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(For each influenza season from 1997-98 to 2012-13, we assessed the rate of exponential rise of the influenza epidemic for all )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(strains, and total ILI mortality during the epidemic. We excluded A\(H1N1\) data from the 2009-10 pandemic season due to the )] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(very unusual dual wave nature of the epidemic curve \(although it should be noted that the conclusions of the study remained )] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(unchanged even when those data were included\).)] TJ ET
BT 26.250 681.048 Td /F1 9.8 Tf  [(We found the initial growth rate to be significantly correlated with ILI mortality across seasons \(r=45%, p=0.04\). In this analysis )] TJ ET
BT 26.250 669.143 Td /F1 9.8 Tf  [(we thus used the initial growth rate for influenza seasons as an indicator of epidemic severity.)] TJ ET
BT 26.250 649.738 Td /F4 9.8 Tf  [(Partial correlations:)] TJ ET
BT 117.822 649.738 Td /F1 9.8 Tf  [( In this analysis we examine correlations between epidemic initial growth rate and other potentially related )] TJ ET
BT 26.250 637.833 Td /F1 9.8 Tf  [(variables, including temperature during the initial growth period, and the temperature and growth rate of the season before. In )] TJ ET
BT 26.250 625.929 Td /F1 9.8 Tf  [(assessing the correlations, we control for other potentially confounding variables via the use of partial correlations. For instance, )] TJ ET
BT 26.250 614.024 Td /F1 9.8 Tf  [(the partial correlation of variables A and B, controlling for variable C, is obtained by first regressing both A and B on C, then )] TJ ET
BT 26.250 602.119 Td /F1 9.8 Tf  [(assessing the correlation of the residuals from the two regression fits. Multiple variables can be controlled for by regressing both )] TJ ET
BT 26.250 590.214 Td /F1 9.8 Tf  [(A and B on a linear combination of those variables.)] TJ ET
BT 26.250 553.612 Td /F4 12.0 Tf  [(Results and Discussion)] TJ ET
BT 26.250 533.658 Td /F1 9.8 Tf  [(The initial growth rates we estimated for influenza A epidemics are on average 15% higher compared to those we estimated for )] TJ ET
BT 26.250 521.753 Td /F1 9.8 Tf  [(influenza B epidemics \(Student�s t-test p=0.03\), which is in agreement with results of previous studies )] TJ ET
0.267 0.267 0.267 rg
BT 465.995 523.260 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 475.632 521.753 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 502.348 Td /F1 9.8 Tf  [(In Figure 3 we show the initial growth rate \(r\) and epidemic peak timing \(t_peak\) as a function of the growth rate of the season )] TJ ET
BT 26.250 490.443 Td /F1 9.8 Tf  [(before \(r_bef\) and the average temperature the season before \(T_bef\). Significant associations are seen. In Table 1 we show )] TJ ET
BT 26.250 478.539 Td /F1 9.8 Tf  [(the partial correlations between the growth rate and time of the peak to the other variables, after adjustment for the accuracy of )] TJ ET
BT 26.250 466.634 Td /F1 9.8 Tf  [(the vaccine match to the circulating strain \(v\). We found a significant association between epidemic peak timing and epidemic )] TJ ET
BT 26.250 454.729 Td /F1 9.8 Tf  [(growth rate when compared to the temperature and growth rate the season before, with very similar patterns seen for both )] TJ ET
BT 26.250 442.824 Td /F1 9.8 Tf  [(influenza A and influenza B. In particular, mild winters were found to be significantly associated with early and severe epidemics )] TJ ET
BT 26.250 430.920 Td /F1 9.8 Tf  [(the next season, even after taking into account the epidemic growth rate during that mild winter and the temperature during the )] TJ ET
BT 26.250 419.015 Td /F1 9.8 Tf  [(next season; we found that when a winter was mild, on average 72% of the time the next epidemic was more severe than )] TJ ET
BT 26.250 407.110 Td /F1 9.8 Tf  [(average, with epidemic growth rate 40% higher than average, and a peak timing occurring 11 days earlier than average. In )] TJ ET
BT 26.250 395.205 Td /F1 9.8 Tf  [(addition, the relative likelihood of the following epidemic peaking before January 1)] TJ ET
BT 379.044 399.094 Td /F1 8.7 Tf  [(st)] TJ ET
BT 385.787 395.205 Td /F1 9.8 Tf  [( was over 80% higher.)] TJ ET
0.965 0.965 0.965 rg
26.250 216.015 555.000 169.310 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 385.325 m 581.250 385.325 l 581.250 384.575 l 26.250 384.575 l  f
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112.500 0 0 112.500 35.250 263.075 cm /I5 Do
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q
35.250 227.265 537.000 29.810 re W n
0.271 0.267 0.267 rg
BT 35.250 247.551 Td /F4 9.8 Tf  [(Fig. 3: Dependence of the peak timing and growth rate of influenza epidemics on the growth rate and average )] TJ ET
BT 35.250 235.646 Td /F4 9.8 Tf  [(temperature of the prior season.)] TJ ET
Q
BT 26.250 198.991 Td /F1 9.8 Tf  [(We posit that warm winters are more likely to be succeeded by early and severe influenza seasons due to fewer people being )] TJ ET
BT 26.250 187.086 Td /F1 9.8 Tf  [(infected due to the warm weather, thereby leaving an unnaturally large fraction of susceptible individuals in the population going )] TJ ET
BT 26.250 175.182 Td /F1 9.8 Tf  [(into the next season. The severity of the next season could potentially be exacerbated by the early onset, if the onset occurs )] TJ ET
BT 26.250 163.277 Td /F1 9.8 Tf  [(before most of the population has had the opportunity to be vaccinated.)] TJ ET
BT 26.250 143.872 Td /F1 9.8 Tf  [(Our observation that climate patterns can have a profound impact on influenza epidemics beyond just the time frame of the )] TJ ET
BT 26.250 131.967 Td /F1 9.8 Tf  [(current season will likely open up interesting avenues of further research.)] TJ ET
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BT 291.710 19.825 Td /F1 11.0 Tf  [(3)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Influenza)] TJ ET

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580.125 642.631 0.750 16.631 re f
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26.625 626.749 0.750 16.631 re f
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580.125 594.987 0.750 16.631 re f
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BT 26.250 507.009 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 487.055 Td /F1 9.8 Tf  [(ST is grateful to the organizers and funding agents of the recent Workshop on Mathematical and Statistical Modeling with )] TJ ET
BT 26.250 475.150 Td /F1 9.8 Tf  [(Applications in Epidemiology and Finance at Northeastern Illinois University; stimulating workshop discussions prompted the )] TJ ET
BT 26.250 463.245 Td /F1 9.8 Tf  [(initiation of these studies.)] TJ ET
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BT 26.250 406.689 Td /F1 9.8 Tf  [(1.)] TJ ET
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0.271 0.267 0.267 rg
BT 26.250 125.819 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 125.819 Td /F1 9.8 Tf  [(Centers for Disease Control and Prevention. Data from the CDC 122 Cities Mortality Reporting System as printed in Table )] TJ ET
BT 26.250 113.914 Td /F1 9.8 Tf  [(III of the MMWR each week.)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 105.428 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 86.878 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 86.878 Td /F1 9.8 Tf  [(United States Census Bureau.)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 78.392 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 59.842 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 59.842 Td /F1 9.8 Tf  [(National Climate Data Center. National Oceanic and Atmospheric Administration. )] TJ ET
0.267 0.267 0.267 rg
BT 26.250 51.356 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
Q
q
15.000 42.330 577.500 734.670 re W n
q
26.250 763.264 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 766.011 Td /F1 9.8 Tf  [(Table 1)] TJ ET
Q
0.965 0.965 0.965 rg
26.250 695.726 555.000 60.037 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 755.764 m 581.250 755.764 l 580.500 755.014 l 27.000 755.014 l  f
581.250 755.764 m 581.250 695.726 l 580.500 695.726 l 580.500 755.014 l  f
26.250 755.764 m 26.250 695.726 l 27.000 695.726 l 27.000 755.014 l  f
0.271 0.267 0.267 rg
BT 33.000 741.688 Td /F1 9.0 Tf  [(Correlation of the exponential growth rate \(r\) and epidemic peak timing \(t_peak\), to the growth rate and average temperature during the )] TJ ET
BT 33.000 732.530 Td /F1 9.0 Tf  [(season before, \(r_bef\) and \(T_bef\), respectively. The calculation of the correlations takes into account the temperature during the initial )] TJ ET
BT 33.000 723.373 Td /F1 9.0 Tf  [(epidemic period \(T\) and the accuracy of the vaccine match \(v\) for each season under consideration. The numbers in square brackets )] TJ ET
BT 33.000 714.215 Td /F1 9.0 Tf  [(indicate the 95% CI. The correlations in the influenza A column are the aggregated results of influenza A\(H3N2\) and A\(H1N1\) )] TJ ET
BT 33.000 705.058 Td /F1 9.0 Tf  [(epidemics.)] TJ ET
1.000 1.000 1.000 rg
26.250 578.731 555.000 116.995 re f
0.965 0.965 0.965 rg
27.000 658.887 186.715 36.089 re f
0.267 0.267 0.267 rg
26.625 694.601 187.090 0.750 re f
26.625 658.512 0.750 36.839 re f
0.271 0.267 0.267 rg
BT 31.500 685.452 Td /F4 9.8 Tf  [(Spearman)] TJ ET
BT 31.500 673.548 Td /F4 9.8 Tf  [(partial)] TJ ET
BT 31.500 661.643 Td /F4 9.8 Tf  [(correlations)] TJ ET
0.965 0.965 0.965 rg
213.715 658.887 122.262 36.089 re f
0.267 0.267 0.267 rg
213.715 694.601 122.262 0.750 re f
0.271 0.267 0.267 rg
BT 218.215 685.452 Td /F4 9.8 Tf  [(Influenza A)] TJ ET
BT 218.215 673.548 Td /F4 9.8 Tf  [(N=280)] TJ ET
0.965 0.965 0.965 rg
335.977 658.887 122.262 36.089 re f
0.267 0.267 0.267 rg
335.977 694.601 122.262 0.750 re f
0.271 0.267 0.267 rg
BT 340.477 685.452 Td /F4 9.8 Tf  [(Influenza B)] TJ ET
BT 340.477 673.548 Td /F4 9.8 Tf  [(N=150)] TJ ET
0.965 0.965 0.965 rg
458.238 658.887 122.262 36.089 re f
0.267 0.267 0.267 rg
458.238 694.601 122.637 0.750 re f
580.125 658.512 0.750 36.839 re f
0.271 0.267 0.267 rg
BT 462.738 685.452 Td /F4 9.8 Tf  [(All Influenza)] TJ ET
BT 462.738 673.548 Td /F4 9.8 Tf  [(N=430)] TJ ET
0.267 0.267 0.267 rg
26.625 658.512 187.465 0.750 re f
26.625 642.631 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 648.657 Td /F1 9.8 Tf  [(?\(r,T|r_bef,T_bef,v\))] TJ ET
0.267 0.267 0.267 rg
213.340 658.512 123.012 0.750 re f
213.340 642.631 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 218.590 648.657 Td /F1 9.8 Tf  [(-0.28[-0.38,-0.18])] TJ ET
0.267 0.267 0.267 rg
335.602 658.512 123.012 0.750 re f
335.602 642.631 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 340.852 648.657 Td /F1 9.8 Tf  [(-0.39[-0.50,-0.26])] TJ ET
0.267 0.267 0.267 rg
457.863 658.512 123.012 0.750 re f
457.863 642.631 0.750 16.631 re f
580.125 642.631 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 463.113 648.657 Td /F1 9.8 Tf  [(-0.35[-0.43,-0.28])] TJ ET
0.267 0.267 0.267 rg
26.625 642.631 187.465 0.750 re f
26.625 626.749 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 632.776 Td /F1 9.8 Tf  [(?\(r,r_bef|T,T_bef,v\))] TJ ET
0.267 0.267 0.267 rg
213.340 642.631 123.012 0.750 re f
213.340 626.749 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 218.590 632.776 Td /F1 9.8 Tf  [(-0.06[-0.16,0.05])] TJ ET
0.267 0.267 0.267 rg
335.602 642.631 123.012 0.750 re f
335.602 626.749 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 340.852 632.776 Td /F1 9.8 Tf  [(-0.11[-0.24,0.03])] TJ ET
0.267 0.267 0.267 rg
457.863 642.631 123.012 0.750 re f
457.863 626.749 0.750 16.631 re f
580.125 626.749 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 463.113 632.776 Td /F1 9.8 Tf  [(-0.06[-0.15,0.02])] TJ ET
0.267 0.267 0.267 rg
26.625 626.749 187.465 0.750 re f
26.625 610.868 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 616.894 Td /F1 9.8 Tf  [(?\(t_peak,r_bef|T,T_bef,v\))] TJ ET
0.267 0.267 0.267 rg
213.340 626.749 123.012 0.750 re f
213.340 610.868 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 218.590 616.894 Td /F1 9.8 Tf  [(-0.07[-0.19,0.06])] TJ ET
0.267 0.267 0.267 rg
335.602 626.749 123.012 0.750 re f
335.602 610.868 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 340.852 616.894 Td /F1 9.8 Tf  [(0.09[-0.06,0.24])] TJ ET
0.267 0.267 0.267 rg
457.863 626.749 123.012 0.750 re f
457.863 610.868 0.750 16.631 re f
580.125 610.868 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 463.113 616.894 Td /F1 9.8 Tf  [(-0.06[-0.16,0.04])] TJ ET
0.267 0.267 0.267 rg
26.625 610.868 187.465 0.750 re f
26.625 594.987 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 601.013 Td /F1 9.8 Tf  [(?\(r,T_bef|T,r_bef,v\))] TJ ET
0.267 0.267 0.267 rg
213.340 610.868 123.012 0.750 re f
213.340 594.987 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 218.590 601.013 Td /F1 9.8 Tf  [(0.15[0.04,0.25])] TJ ET
0.267 0.267 0.267 rg
335.602 610.868 123.012 0.750 re f
335.602 594.987 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 340.852 601.013 Td /F1 9.8 Tf  [(0.28[0.15,0.40])] TJ ET
0.267 0.267 0.267 rg
457.863 610.868 123.012 0.750 re f
457.863 594.987 0.750 16.631 re f
580.125 594.987 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 463.113 601.013 Td /F1 9.8 Tf  [(0.17[0.09,0.25])] TJ ET
0.267 0.267 0.267 rg
26.625 594.987 187.465 0.750 re f
26.625 579.106 187.465 0.750 re f
26.625 579.106 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 585.132 Td /F1 9.8 Tf  [(?\(t_peak,T_bef|T,r_bef,v\))] TJ ET
0.267 0.267 0.267 rg
213.340 594.987 123.012 0.750 re f
213.340 579.106 123.012 0.750 re f
213.340 579.106 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 218.590 585.132 Td /F1 9.8 Tf  [(-0.18[-0.30,-0.05])] TJ ET
0.267 0.267 0.267 rg
335.602 594.987 123.012 0.750 re f
335.602 579.106 123.012 0.750 re f
335.602 579.106 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 340.852 585.132 Td /F1 9.8 Tf  [(-0.31[-0.44,-0.17])] TJ ET
0.267 0.267 0.267 rg
457.863 594.987 123.012 0.750 re f
457.863 579.106 123.012 0.750 re f
457.863 579.106 0.750 16.631 re f
580.125 579.106 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 463.113 585.132 Td /F1 9.8 Tf  [(-0.11[-0.20,-0.01])] TJ ET
BT 26.250 507.009 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 487.055 Td /F1 9.8 Tf  [(ST is grateful to the organizers and funding agents of the recent Workshop on Mathematical and Statistical Modeling with )] TJ ET
BT 26.250 475.150 Td /F1 9.8 Tf  [(Applications in Epidemiology and Finance at Northeastern Illinois University; stimulating workshop discussions prompted the )] TJ ET
BT 26.250 463.245 Td /F1 9.8 Tf  [(initiation of these studies.)] TJ ET
BT 26.250 434.143 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 406.689 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 406.689 Td /F1 9.8 Tf  [(Centers for Disease Control and Prevention. Seasonal Flu: 2011-2012 Flu Season Draws to a Close.)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 398.203 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 379.653 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 379.653 Td /F1 9.8 Tf  [(State of the Climate. National Oceanic and Atmospheric Administration)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 371.167 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 352.617 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 352.617 Td /F1 9.8 Tf  [(Lowen AC, Mubareka S, Steel J, Palese P. Influenza virus transmission is dependent on relative humidity and temperature. )] TJ ET
BT 26.250 340.712 Td /F1 9.8 Tf  [(PLoS Pathog. 2007 Oct 19;3\(10\):1470-6.)] TJ ET
BT 26.250 321.307 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 321.307 Td /F1 9.8 Tf  [(Steel J, Palese P, Lowen AC. Transmission of a 2009 pandemic influenza virus shows a sensitivity to temperature and )] TJ ET
BT 26.250 309.402 Td /F1 9.8 Tf  [(humidity similar to that of an H3N2 seasonal strain. J Virol. 2011 Feb;85\(3\):1400-2.)] TJ ET
BT 26.250 289.998 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 289.998 Td /F1 9.8 Tf  [(Lowen AC, Steel J, Mubareka S, Palese P. High temperature \(30 degrees C\) blocks aerosol but not contact transmission of )] TJ ET
BT 26.250 278.093 Td /F1 9.8 Tf  [(influenza virus. J Virol. 2008 Jun;82\(11\):5650-2.)] TJ ET
BT 26.250 258.688 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 258.688 Td /F1 9.8 Tf  [(Mubareka S, Lowen AC, Steel J, Coates AL, Garcia-Sastre A, Palese P. Transmission of influenza virus via aerosols and )] TJ ET
BT 26.250 246.783 Td /F1 9.8 Tf  [(fomites in the guinea pig model. J Infect Dis. 2009 Mar 15;199\(6\):858-65.)] TJ ET
BT 26.250 227.379 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 227.379 Td /F1 9.8 Tf  [(Shaman J, Kohn M. Absolute humidity modulates influenza survival, transmission, and seasonality. Proc Natl Acad Sci U S )] TJ ET
BT 26.250 215.474 Td /F1 9.8 Tf  [(A. 2009 Mar 3;106\(9\):3243-8.)] TJ ET
BT 26.250 196.069 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 196.069 Td /F1 9.8 Tf  [(Shaman, J., Pitzer, V. E., Viboud, C., Grenfell, B. T., & Lipsitch, M. \(2010\). Absolute humidity and the seasonal onset of )] TJ ET
BT 26.250 184.164 Td /F1 9.8 Tf  [(influenza in the continental United States. PLoS biology, 8\(2\), e1000316.)] TJ ET
BT 26.250 164.760 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 164.760 Td /F1 9.8 Tf  [(Centers for Disease Control and Prevention. Seasonal Flu: FluView. 2012-2013 Influenza Season Week 1 ending January 5, )] TJ ET
BT 26.250 152.855 Td /F1 9.8 Tf  [(2013.)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 144.369 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 125.819 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 125.819 Td /F1 9.8 Tf  [(Centers for Disease Control and Prevention. Data from the CDC 122 Cities Mortality Reporting System as printed in Table )] TJ ET
BT 26.250 113.914 Td /F1 9.8 Tf  [(III of the MMWR each week.)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 105.428 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 86.878 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 86.878 Td /F1 9.8 Tf  [(United States Census Bureau.)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 78.392 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 59.842 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 59.842 Td /F1 9.8 Tf  [(National Climate Data Center. National Oceanic and Atmospheric Administration. )] TJ ET
0.267 0.267 0.267 rg
BT 26.250 51.356 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
Q
q
15.000 42.330 577.500 734.670 re W n
q
26.250 763.264 555.000 13.736 re W n
0.271 0.267 0.267 rg
BT 26.250 766.011 Td /F1 9.8 Tf  [(Table 1)] TJ ET
Q
0.965 0.965 0.965 rg
26.250 695.726 555.000 60.037 re f
0.267 0.267 0.267 rg
0.267 0.267 0.267 RG
26.250 755.764 m 581.250 755.764 l 580.500 755.014 l 27.000 755.014 l  f
581.250 755.764 m 581.250 695.726 l 580.500 695.726 l 580.500 755.014 l  f
26.250 755.764 m 26.250 695.726 l 27.000 695.726 l 27.000 755.014 l  f
0.271 0.267 0.267 rg
BT 33.000 741.688 Td /F1 9.0 Tf  [(Correlation of the exponential growth rate \(r\) and epidemic peak timing \(t_peak\), to the growth rate and average temperature during the )] TJ ET
BT 33.000 732.530 Td /F1 9.0 Tf  [(season before, \(r_bef\) and \(T_bef\), respectively. The calculation of the correlations takes into account the temperature during the initial )] TJ ET
BT 33.000 723.373 Td /F1 9.0 Tf  [(epidemic period \(T\) and the accuracy of the vaccine match \(v\) for each season under consideration. The numbers in square brackets )] TJ ET
BT 33.000 714.215 Td /F1 9.0 Tf  [(indicate the 95% CI. The correlations in the influenza A column are the aggregated results of influenza A\(H3N2\) and A\(H1N1\) )] TJ ET
BT 33.000 705.058 Td /F1 9.0 Tf  [(epidemics.)] TJ ET
1.000 1.000 1.000 rg
26.250 578.731 555.000 116.995 re f
0.965 0.965 0.965 rg
27.000 658.887 186.715 36.089 re f
0.267 0.267 0.267 rg
26.625 694.601 187.090 0.750 re f
26.625 658.512 0.750 36.839 re f
0.271 0.267 0.267 rg
BT 31.500 685.452 Td /F4 9.8 Tf  [(Spearman)] TJ ET
BT 31.500 673.548 Td /F4 9.8 Tf  [(partial)] TJ ET
BT 31.500 661.643 Td /F4 9.8 Tf  [(correlations)] TJ ET
0.965 0.965 0.965 rg
213.715 658.887 122.262 36.089 re f
0.267 0.267 0.267 rg
213.715 694.601 122.262 0.750 re f
0.271 0.267 0.267 rg
BT 218.215 685.452 Td /F4 9.8 Tf  [(Influenza A)] TJ ET
BT 218.215 673.548 Td /F4 9.8 Tf  [(N=280)] TJ ET
0.965 0.965 0.965 rg
335.977 658.887 122.262 36.089 re f
0.267 0.267 0.267 rg
335.977 694.601 122.262 0.750 re f
0.271 0.267 0.267 rg
BT 340.477 685.452 Td /F4 9.8 Tf  [(Influenza B)] TJ ET
BT 340.477 673.548 Td /F4 9.8 Tf  [(N=150)] TJ ET
0.965 0.965 0.965 rg
458.238 658.887 122.262 36.089 re f
0.267 0.267 0.267 rg
458.238 694.601 122.637 0.750 re f
580.125 658.512 0.750 36.839 re f
0.271 0.267 0.267 rg
BT 462.738 685.452 Td /F4 9.8 Tf  [(All Influenza)] TJ ET
BT 462.738 673.548 Td /F4 9.8 Tf  [(N=430)] TJ ET
0.267 0.267 0.267 rg
26.625 658.512 187.465 0.750 re f
26.625 642.631 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 648.657 Td /F1 9.8 Tf  [(?\(r,T|r_bef,T_bef,v\))] TJ ET
0.267 0.267 0.267 rg
213.340 658.512 123.012 0.750 re f
213.340 642.631 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 218.590 648.657 Td /F1 9.8 Tf  [(-0.28[-0.38,-0.18])] TJ ET
0.267 0.267 0.267 rg
335.602 658.512 123.012 0.750 re f
335.602 642.631 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 340.852 648.657 Td /F1 9.8 Tf  [(-0.39[-0.50,-0.26])] TJ ET
0.267 0.267 0.267 rg
457.863 658.512 123.012 0.750 re f
457.863 642.631 0.750 16.631 re f
580.125 642.631 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 463.113 648.657 Td /F1 9.8 Tf  [(-0.35[-0.43,-0.28])] TJ ET
0.267 0.267 0.267 rg
26.625 642.631 187.465 0.750 re f
26.625 626.749 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 632.776 Td /F1 9.8 Tf  [(?\(r,r_bef|T,T_bef,v\))] TJ ET
0.267 0.267 0.267 rg
213.340 642.631 123.012 0.750 re f
213.340 626.749 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 218.590 632.776 Td /F1 9.8 Tf  [(-0.06[-0.16,0.05])] TJ ET
0.267 0.267 0.267 rg
335.602 642.631 123.012 0.750 re f
335.602 626.749 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 340.852 632.776 Td /F1 9.8 Tf  [(-0.11[-0.24,0.03])] TJ ET
0.267 0.267 0.267 rg
457.863 642.631 123.012 0.750 re f
457.863 626.749 0.750 16.631 re f
580.125 626.749 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 463.113 632.776 Td /F1 9.8 Tf  [(-0.06[-0.15,0.02])] TJ ET
0.267 0.267 0.267 rg
26.625 626.749 187.465 0.750 re f
26.625 610.868 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 616.894 Td /F1 9.8 Tf  [(?\(t_peak,r_bef|T,T_bef,v\))] TJ ET
0.267 0.267 0.267 rg
213.340 626.749 123.012 0.750 re f
213.340 610.868 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 218.590 616.894 Td /F1 9.8 Tf  [(-0.07[-0.19,0.06])] TJ ET
0.267 0.267 0.267 rg
335.602 626.749 123.012 0.750 re f
335.602 610.868 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 340.852 616.894 Td /F1 9.8 Tf  [(0.09[-0.06,0.24])] TJ ET
0.267 0.267 0.267 rg
457.863 626.749 123.012 0.750 re f
457.863 610.868 0.750 16.631 re f
580.125 610.868 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 463.113 616.894 Td /F1 9.8 Tf  [(-0.06[-0.16,0.04])] TJ ET
0.267 0.267 0.267 rg
26.625 610.868 187.465 0.750 re f
26.625 594.987 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 31.875 601.013 Td /F1 9.8 Tf  [(?\(r,T_bef|T,r_bef,v\))] TJ ET
0.267 0.267 0.267 rg
213.340 610.868 123.012 0.750 re f
213.340 594.987 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 218.590 601.013 Td /F1 9.8 Tf  [(0.15[0.04,0.25])] TJ ET
0.267 0.267 0.267 rg
335.602 610.868 123.012 0.750 re f
335.602 594.987 0.750 16.631 re f
0.271 0.267 0.267 rg
BT 340.852 601.013 Td /F1 9.8 Tf  [(0.28[0.15,0.40])] TJ ET
0.267 0.267 0.267 rg
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