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1.  Gout and subsequent increased risk of cardiovascular mortality in non-diabetics aged 50 and above: a population-based cohort study in Taiwan 
Background
Limited data are available on the risk ratios for fatal cardiovascular disease (CVD) outcome from gout and chronic kidney disease (CKD) in non-diabetic individuals.
Methods
Nationwide population-based retrospective prospective study with a 5-year follow-up to investigate the association between physician-diagnosed gout and CKD in non-diabetics aged 50 and above who had no pre-existing serious CVD and the subsequent risk of death from CVD. Hazard ratios (HR) of CVD mortality were adjusted for gender, age, smoking- and alcoholism-related diagnoses, hypertension, hyperlipidemia, atrial fibrillation and Charlson’s comorbidity index score.
Results
A case cohort (n=164,463) having gout and a control cohort (n= 3,694,377) having no gout were formed. The prevalence of gout in this study was 4.26% whereas that of gout plus CKD was 8.17%. Male to female ratio among the individuals with gout was 3.2:1. The relative risk (RR) of subsequent cardiovascular mortality between the case and control cohort was 1.71 (95% confidence interval (CI), 1.66-1.75). The presence of CKD in nondiabetic subjects with no gout (control group) has a RR of CVD mortality at 3.05 (95% CI, 2.94-3.15). The presence of gout has protective effect on subjects with CKD with a RR of 1.84 (95% CI, 1.71-1.98). As compared with individuals with no gout, the adjusted HR (aHR) for CVD mortality among the individuals with gout was 1.10 (95% CI 1.07-1.13). In a Cox model, when compared with subjects having neither gout nor CKD, the aHR in subjects with no gout but with CKD is 1.76 (95% CI, 1.70-1.82); in subjects with gout but without CKD, 1.10 (1.07-1.13); interestingly, the aHR is attenuated in subjects with concomitant gout plus CKD which is 1.38 (1.29-1.48).
Conclusions
Among non-diabetic individuals aged 50 years or above who had no preceding serious CVD, those with gout were 1.1 times more likely to die from CVD as were individuals without gout. The presence of gout appears to attenuate the risk of subsequent CV mortality in subjects with CKD. Further studies should focus on finding an explanation for the protective effect of gout on CV mortality in patients with CKD.
doi:10.1186/1471-2261-12-108
PMCID: PMC3556493  PMID: 23170782
2.  Assessment of performance of survival prediction models for cancer prognosis 
Background
Cancer survival studies are commonly analyzed using survival-time prediction models for cancer prognosis. A number of different performance metrics are used to ascertain the concordance between the predicted risk score of each patient and the actual survival time, but these metrics can sometimes conflict. Alternatively, patients are sometimes divided into two classes according to a survival-time threshold, and binary classifiers are applied to predict each patient’s class. Although this approach has several drawbacks, it does provide natural performance metrics such as positive and negative predictive values to enable unambiguous assessments.
Methods
We compare the survival-time prediction and survival-time threshold approaches to analyzing cancer survival studies. We review and compare common performance metrics for the two approaches. We present new randomization tests and cross-validation methods to enable unambiguous statistical inferences for several performance metrics used with the survival-time prediction approach. We consider five survival prediction models consisting of one clinical model, two gene expression models, and two models from combinations of clinical and gene expression models.
Results
A public breast cancer dataset was used to compare several performance metrics using five prediction models. 1) For some prediction models, the hazard ratio from fitting a Cox proportional hazards model was significant, but the two-group comparison was insignificant, and vice versa. 2) The randomization test and cross-validation were generally consistent with the p-values obtained from the standard performance metrics. 3) Binary classifiers highly depended on how the risk groups were defined; a slight change of the survival threshold for assignment of classes led to very different prediction results.
Conclusions
1) Different performance metrics for evaluation of a survival prediction model may give different conclusions in its discriminatory ability. 2) Evaluation using a high-risk versus low-risk group comparison depends on the selected risk-score threshold; a plot of p-values from all possible thresholds can show the sensitivity of the threshold selection. 3) A randomization test of the significance of Somers’ rank correlation can be used for further evaluation of performance of a prediction model. 4) The cross-validated power of survival prediction models decreases as the training and test sets become less balanced.
doi:10.1186/1471-2288-12-102
PMCID: PMC3410808  PMID: 22824262
3.  Transmissibility and temporal changes of 2009 pH1N1 pandemic during summer and fall/winter waves 
BMC Infectious Diseases  2011;11:332.
Background
In order to compare the transmissibility of the 2009 pH1N1 pandemic during successive waves of infections in summer and fall/winter in the Northern Hemisphere, and to assess the temporal changes during the course of the outbreak in relation to the intervention measures implemented, we analyze the epidemiological patterns of the epidemic in Taiwan during July 2009-March 2010.
Methods
We utilize the multi-phase Richards model to fit the weekly cumulative pH1N1 epidemiological data (numbers of confirmed cases and hospitalizations) as well as the daily number of classes suspended under a unique "325" partial school closing policy in Taiwan, in order to pinpoint the turning points of the summer and fall/winter waves, and to estimate the reproduction numbers R for each wave.
Results
Our analysis indicates that the summer wave had slowed down by early September when schools reopened for fall. However, a second fall/winter wave began in late September, approximately 4 weeks after the school reopened, peaking at about 2-3 weeks after the start of the mass immunization campaign in November. R is estimated to be in the range of 1.04-1.27 for the first wave, and between 1.01-1.05 for the second wave.
Conclusions
Transmissibility of the summer wave in Taiwan during July-early September, as measured by R, was lower than that of the earlier spring outbreak in North America and Europe, as well as that of the winter outbreak in Southern Hemisphere. Furthermore, transmissibility during fall/winter in Taiwan was noticeably lower than that of the summer, which is attributable to population-level immunity acquired from the earlier summer wave and also to the intervention measures that were implemented prior to and during the fall/winter wave.
doi:10.1186/1471-2334-11-332
PMCID: PMC3247203  PMID: 22136530
4.  Correction: Serological Evidence of Subclinical Transmission of the 2009 Pandemic H1N1 Influenza Virus Outside of Mexico 
PLoS ONE  2011;6(5):10.1371/annotation/edeb5a9c-04b2-4d09-ae2b-6d527bf27c81.
doi:10.1371/annotation/edeb5a9c-04b2-4d09-ae2b-6d527bf27c81
PMCID: PMC3103590
5.  Serological Evidence of Subclinical Transmission of the 2009 Pandemic H1N1 Influenza Virus Outside of Mexico 
PLoS ONE  2011;6(1):e14555.
Background
Relying on surveillance of clinical cases limits the ability to understand the full impact and severity of an epidemic, especially when subclinical cases are more likely to be present in the early stages. Little is known of the infection and transmissibility of the 2009 H1N1 pandemic influenza (pH1N1) virus outside of Mexico prior to clinical cases being reported, and of the knowledge pertaining to immunity and incidence of infection during April–June, which is essential for understanding the nature of viral transmissibility as well as for planning surveillance and intervention of future pandemics.
Methodology/Principal Findings
Starting in the fall of 2008, 306 persons from households with schoolchildren in central Taiwan were followed sequentially and serum samples were taken in three sampling periods for haemagglutination inhibition (HI) assay. Age-specific incidence rates were calculated based on seroconversion of antibodies to the pH1N1 virus with an HI titre of 1∶40 or more during two periods: April–June and September–October in 2009. The earliest time period with HI titer greater than 40, as well as a four-fold increase of the neutralization titer, was during April 26–May 3. The incidence rates during the pre-epidemic phase (April–June) and the first wave (July–October) of the pandemic were 14.1% and 29.7%, respectively. The transmissibility of the pH1N1 virus during the early phase of the epidemic, as measured by the effective reproductive number R0, was 1.16 (95% confidence interval (CI): 0.98–1.34).
Conclusions
Approximately one in every ten persons was infected with the 2009 pH1N1 virus during the pre-epidemic phase in April–June. The lack of age-pattern in seropositivity is unexpected, perhaps highlighting the importance of children as asymptomatic transmitters of influenza in households. Although without virological confirmation, our data raise the question of whether there was substantial pH1N1 transmission in Taiwan before June, when clinical cases were first detected by the surveillance network.
doi:10.1371/journal.pone.0014555
PMCID: PMC3022590  PMID: 21267441
6.  A Novel Preprocessing Method Using Hilbert Huang Transform for MALDI-TOF and SELDI-TOF Mass Spectrometry Data 
PLoS ONE  2010;5(8):e12493.
Motivation
Mass spectrometry is a high throughput, fast, and accurate method of protein analysis. Using the peaks detected in spectra, we can compare a normal group with a disease group. However, the spectrum is complicated by scale shifting and is also full of noise. Such shifting makes the spectra non-stationary and need to align before comparison. Consequently, the preprocessing of the mass data plays an important role during the analysis process. Noises in mass spectrometry data come in lots of different aspects and frequencies. A powerful data preprocessing method is needed for removing large amount of noises in mass spectrometry data.
Results
Hilbert-Huang Transformation is a non-stationary transformation used in signal processing. We provide a novel algorithm for preprocessing that can deal with MALDI and SELDI spectra. We use the Hilbert-Huang Transformation to decompose the spectrum and filter-out the very high frequencies and very low frequencies signal. We think the noise in mass spectrometry comes from many sources and some of the noises can be removed by analysis of signal frequence domain. Since the protein in the spectrum is expected to be a unique peak, its frequence domain should be in the middle part of frequence domain and will not be removed. The results show that HHT, when used for preprocessing, is generally better than other preprocessing methods. The approach not only is able to detect peaks successfully, but HHT has the advantage of denoising spectra efficiently, especially when the data is complex. The drawback of HHT is that this approach takes much longer for the processing than the wavlet and traditional methods. However, the processing time is still manageable and is worth the wait to obtain high quality data.
doi:10.1371/journal.pone.0012493
PMCID: PMC2930864  PMID: 20824164

Results 1-6 (6)