05 The Cochran–Armitage trend test was performed using SAS 9 2 (

05. The Cochran–Armitage trend test was performed using SAS 9.2 (SAS Institute Inc., USA). A temporal

cluster analysis of the HFRS epidemic between 1971 and 2011 was performed using the annual incidence data to detect the time periods of high HFRS risk. The procedure involves gradual scanning of a data window across time and noting the number of observed and expected observations inside each of the windows. For each scanning window of varying time, position and size, the risk of HFRS within and outside the window was tested by the Screening Library high throughput likelihood ratio (LLR) test, with the null hypothesis being equal risk. The expression of LLR was calculated as follows: LLR=cE(c)c×C−cC−E(c)C−c×I( )where C is the total number of cases, c is the observed number of cases within the window, and E(c) is the covariate adjusted expected number of cases within the window under the null-hypothesis. I() is an indicator function, which is equal to 1 when the window has more cases than expected under

the null-hypothesis, and 0 otherwise [25]. The window having the maximum LLR was indicative of the most likely cluster and considered TGF-beta pathway the time period with the highest HFRS risk. In this study, a maximum temporal cluster size of 20%, 30%, 40% and 50% of the study period were specified in the temporal cluster analysis in order to detect the time period with the highest risk of HFRS in different temporal scales. The relative risk of HFRS within and outside the window and the average incidence

inside the window were calculated to evaluate the degree of HFRS risk. This analysis was performed using SatScan 7.0.3 (Information Management Services Inc., Boston, MA, USA). It is reported that vaccines can effectively protect from HFRS infection for up to four or five years after the initial vaccination [26]. Therefore, the cross correlation analysis was conducted to detect the correlation between the annual HFRS incidence and vaccination compliance Dipeptidyl peptidase in Hu with a lag time of five years. The cross correlation could be identified if the cross correlation coefficient (CCF) was greater than two times the standard error (SE). This analysis was performed using SPSS 16.0 (SPSS Inc., Chicago, IL, USA). Wavelet analysis was employed to detect the shift of the periodic mode of the HFRS epidemic in Hu and the effect of the vaccination compliance on this shift. The Morlet wavelet was taken as the basis function for wavelet transforms, since it is able to decompose a signal using functions that narrow when high-frequency features are present and widen with low-frequency structures [27]. The series of HFRS cases were first filtered and then normalized. The local wavelet power spectrum (LWPS) was obtained by computing wavelet transforms and was subsequently color-coded from blue to red to denote increasing power. The global wavelet spectrum (GWS) was estimated by averaging the LWPS across time and the lower limit of significance was denoted by a dotted line.

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