1.A case of human infection with highly pathogenic avian influenza A (H7N9) virus through poultry processing without protection measure.
Y MA ; Z B ZHANG ; L CAO ; J Y LU ; K B LI ; W Z SU ; T G LI ; Z C YANG ; M WANG
Chinese Journal of Epidemiology 2018;39(6):799-804
Objective: To investigate the infection pattern and etiological characteristics of a case of human infection with highly pathogenic avian influenza A (H7N9) virus and provide evidence for the prevention and control of human infection with highly pathogenic avian influenza virus. Methods: Epidemiological investigation was conducted to explore the case's exposure history, infection route and disease progression. Samples collected from the patient, environments and poultry were tested by using real time reverse transcriptase-polymerase chain reaction (RT-PCR). Virus isolation, genome sequencing and phylogenetic analysis were conducted for positive samples. Results: The case had no live poultry contact history, but had a history of pulled chicken processing without taking protection measure in an unventilated kitchen before the onset. Samples collected from the patient's lower respiratory tract, the remaining frozen chicken meat and the live poultry market were all influenza A (H7N9) virus positive. The isolated viruses from these positive samples were highly homogenous. An insertion which lead to the addition of multiple basic amino acid residues (PEVPKRKRTAR/GL) was found at the HA cleavage site, suggesting that this virus might be highly pathogenic. Conclusions: Live poultry processing without protection measure is an important infection mode of "poultry to human" transmission of avian influenza viruses. Due to the limitation of protection measures in live poultry markets in Guangzhou, it is necessary to promote the standardized large scale poultry farming, the complete restriction of live poultry sales and centralized poultry slaughtering as well as ice fresh sale.
Animals
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Chickens
;
China
;
Commerce
;
Humans
;
Influenza A Virus, H7N9 Subtype/pathogenicity*
;
Influenza in Birds/virology*
;
Influenza, Human/virology*
;
Phylogeny
;
Poultry/virology*
;
Real-Time Polymerase Chain Reaction
;
Zoonoses
2.Prevalence, awareness, treatment and control of hypertension in population older than 15 years of age in Beijing, 2013-2014.
C X WANG ; X G WU ; H J LIU ; S C GUAN ; C B HOU ; H H LI ; X GU ; Z Y ZHANG ; X H FANG
Chinese Journal of Epidemiology 2018;39(2):179-183
Objective: To investigate the rates on prevalence, awareness, treatment and control of hypertension in population older than 15 years of age in Beijing, 2013-2014. Methods: A cross-sectional survey was conducted in Beijing between 2013-2014. Stratified multistage random sampling method was used to select representative sample of 13 057 Chinese individuals aged over 15 years, from the general population. Blood pressure was measured for three readings at sitting position after resting for at least five minutes with an average reading recorded. A standardized structured questionnaire was developed to collect history of hypertension and antihypertensive treatment. Results: A total of 4 663 community residents aged over 15 years were hypertensive among the 13 057 individuals, with the standardized prevalence rate as 32.7%, in Beijing area. The age-standardized prevalence rates of hypertension appeared 34.6% in men and 30.8% in women. The age-and sexstandardized prevalence of hypertension rates were 33.3% in urban and 24.6% in rural areas. The prevalence of hypertension increased with age and appeared higher in men than in women, in urban than in rural residents. Among the hypertensive patients, rates of awareness, treatment and control were 66.8%, 64.6% and 31.6%, respectively. Conclusion: High prevalence of hypertension with low rates on awareness and treatment and control, appeared in the general population of Beijing. Related strategies should be developed regarding prevention, control and management of hypertension, to reduce the burden of this disease.
Adolescent
;
Adult
;
Age Distribution
;
Aged
;
Antihypertensive Agents/therapeutic use*
;
Asian People/statistics & numerical data*
;
Awareness
;
Blood Pressure
;
Blood Pressure Determination
;
China/epidemiology*
;
Cross-Sectional Studies
;
Female
;
Health Knowledge, Attitudes, Practice
;
Humans
;
Hypertension/epidemiology*
;
Male
;
Middle Aged
;
Prevalence
;
Rural Population
;
Sex Distribution
;
Surveys and Questionnaires
;
Urban Population
;
Young Adult
3.Interaction between abnormal expression of fragile histidine triad and methyl-CpG-binding protein 2 on cervical cancerization.
Q YANG ; Y LI ; L WANG ; Z C SONG ; M J FENG ; L DING ; J T WANG
Chinese Journal of Epidemiology 2018;39(5):689-693
Objective: To explore the relationship between abnormal expression of fragile histidine triad (FHIT) gene and methyl-CpG-binding protein 2 (MeCP2) as well as their interaction on cervical cancerization. Methods: A total of 73 patients with cervical squamous cell carcinoma (SCC), 113 patients with cervical intraepithelial neoplasia (CIN Ⅰ, n=45; CINⅡ/Ⅲ, n=68) and 60 women with normal cervix (NC) were included in the study. Real time PCR and Western blot were performed to detect the expression levels of mRNA and protein about FHIT and MeCP2, respectively. The methylation status of FHIT gene CpG island was tested by methylation-specifc PCR (MSP). Kruskal-Wallis H test, χ(2) test, trend χ(2) test and Spearman correlation analysis were conducted with software SPSS 20.0. The interaction was evaluated by generalized multifactor dimensionality reduction (GMDR) model. Results: With the deterioration of cervical lesion, the methylation rates of FHIT gene CpG island (χ(2)=18.64, P<0.001; trend χ(2)=18.08, P<0.001) increased gradually, while the expression levels of FHIT mRNA (H=27.32, P<0.001; trend χ(2)=12.65, P<0.001) and protein (H=47.10, P<0.001; trend χ(2)=29.79, P<0.001) decreased gradually. There was a negative correlation between the methylation rates of FHIT gene CpG island and the expression level of FHIT protein (r=-0.226, P<0.001). The levels of MeCP2 mRNA (H=26.19, P<0.001; trend χ(2)=11.81, P=0.001) and protein (H=69.02, P<0.001; trend χ(2)=47.44, P<0.001) increased gradually with the aggravation of cervical lesions. There was a positive correlation between the expression level of MeCP2 protein and the FHIT mRNA Ct ratio (r=0.254, P<0.001). Expression of proteins were negatively correlated between MeCP2 and FHIT (r=-0.213, P=0.001). The results analyzed by GMDR model showed that there were interactions among high MeCP2 protein expression, the CpG island methylation of FHIT and mRNA and protein expression in CINⅡ/Ⅲ group, and among high MeCP2 mRNA and protein expression, the CpG island methylation of FHIT and low mRNA and protein expression in SCC group. Conclusion: High expression of MeCP2 mRNA and protein, the CpG island methylation and low mRNA and protein expression of FHIT could increase the risk of cervical carcinogenesis, and there might be a synergistic effect on cervical carcinogenesis.
Acid Anhydride Hydrolases/metabolism*
;
Carcinoma, Squamous Cell/pathology*
;
DNA Methylation
;
Female
;
Gene Expression Regulation, Neoplastic
;
Humans
;
Methyl-CpG-Binding Protein 2/metabolism*
;
Neoplasm Proteins/metabolism*
;
Polymerase Chain Reaction/methods*
;
RNA, Messenger
;
Uterine Cervical Neoplasms/pathology*
;
Uterine Cervical Dysplasia/pathology*
4.Analysis on long-term trends of cervical cancer mortality and years of life lost in Tianjin, 1999-2015.
W L ZHENG ; H ZHANG ; D Z WANG ; S ZHANG ; S PANG ; C K LI ; G H JIANG
Chinese Journal of Epidemiology 2019;40(1):64-69
Objective: To analyze the mortality and years of life lost (YLL) trends of cervical cancer in Tianjin, and provide references for the research and prevention programs of cervical cancer. Methods: Mortality rate, standard mortality rate, cumulative rate (0-74 years-old) and truncated rate (35-64 years-old) of cervical cancer from 1999 to 2015 were calculated. The annual percentage change of the mortality rate and YLL rate were analyzed by using Joinpoint regression analysis, and the trend in different age-groups were analyzed. Results: From 1999 to 2015, 1 741 cases died of cervical cancer in Tianjin, the average crude mortality rate was 2.15/100 000. The average age-standardized rate of (ASR) China and ASR world were 1.47/100 000 and 1.50/100 000 respectively. The average YLL was 3 347.97 person-years. Deaths occurred in those aged 0-34 years, 35-64 years and 65 years and over accounted for 3.10%, 57.84% and 39.06% of the total, respectively. The mortality rate of cervical cancer in urban area was higher than that in rural area, with a ratio of 1.37∶1 between urban area and rural area. The age-specific mortality rate of cervical cancer during 1999-2015 increased with age. Two peaks of mortality rate were observed in those aged 50 years and aged 75 years, during 2014-2015. From 1999 to 2011, the mortality rate of cervical cancer was stable (APC=-0.2%, P=0.80), but there was a rapid increase from 2011 to 2015 (APC=21.6%, P<0.01). But group aged 20-49 years, it showed an upward trend from 1999 to 2015 (APC=6.9%, P<0.01). For group aged 50-69 years, it showed a downward trend from 1999 to 2007 (APC=-9.2%, P<0.01), and an upward trend from 2007 to 2015 (APC=14.5%, P<0.01). For group aged 70 years and over, it showed a downward trend from 1999 to 2009 (APC=-10.2%, P<0.01), but the difference in the mortality were not significant from 2009 to 2015 (APC=7.8%, P=0.10). Since 2008, the YLL rate of cervical cancer in group aged 50-70 years had exceeded that in group aged >70 years and the gap gradually widened. Conclusions: There had been a rapid increase trend of cervical cancer mortality since 2011 in Tianjin. Women aged 50-70 years were the main group of life loss.
Adolescent
;
Adult
;
Aged
;
China/epidemiology*
;
Female
;
Humans
;
Incidence
;
Middle Aged
;
Mortality/trends*
;
Regression Analysis
;
Residence Characteristics
;
Survival Rate/trends*
;
Uterine Cervical Neoplasms/mortality*
;
Young Adult
5.Effect of hnRNP K and its interaction with HPV16 on cervical intraepithelial neoplasia.
L DING ; M J FENG ; C L LIU ; L WANG ; Z C SONG ; Q YANG ; X X LI ; L SONG ; W GAO ; J T WANG
Chinese Journal of Epidemiology 2018;39(12):1630-1635
Objective: To investigate the effect of heterogeneous nuclear ribonucleoprotein K (hnRNP K) and its interaction with human papillomavirus 16 (HPV16) on cervical intraepithelial neoplasia (CIN). Methods: The participants included 67 women with normal cervix (NC), 69 women with CINⅠ and 68 women with CINⅡ/Ⅲ in a community cohort of pathologically diagnosed women established in Jiexiu of Shanxi province, from June 2014 to June 2015. A structured questionnaire was used to collect the demographic data of the subjects and the related factors of cervical lesions. Cervical exfoliated cells and cervical tissues from biopsy or surgery were selected. The infection status of HPV16 was detected by flow-through hybridization. The protein expression levels of hnRNP K were evaluated by Western blot. SPSS 23.0 software was used to collate and analyze the data. To study the differences in demographic characteristics, related factors, hnRNP K protein and HPV16 infection among NC, CINⅠand CINⅡ/Ⅲgroups, χ(2) test, trend χ(2) test, and Kruskal-Wallis H test were conducted. Multiple comparisons of hnRNP K protein in three groups were completed by using the Bonferroni method. The OR and its 95%CI of hnRNP K, HPV16 and CIN were calculated by using the unconditional logistic regression models. Two-way interactions between hnRNP K protein and HPV16 infection on CIN were analyzed by using additive model and related indicators. Results: HPV16 infection rates were 10.4% in women with normal cervix, 14.5% in women with CINⅠ and 41.2% in women with CINⅡ/Ⅲ, respectively. The differences among three groups were significant (P<0.001). Moreover, the infection rates of HPV16 gradually increased with the increasing severity of CIN (trend χ(2)=18.512, P<0.001). The differences in protein expression of hnRNP K among three groups were significant (H=48.138, P<0.001) and the expressionincreased with the development of cervical lesionss (trend χ(2)=21.765, P<0.001). Results from the interaction analysis indicated that there were additive effects between high expression of hnRNP K protein and HPV16 in CINⅡ/Ⅲ group compared with normal group (API=0.639, 95%CI: 0.083-1.196). In contrast, no such additive effect was found in CINⅠ group. Conclusions: HPV16 infection and over-expression of hnRNP K protein were associated with the increased risk of cervical intraepithelial neoplasia. There might be interaction between hnRNP K protein overexpression and HPV16 infection existed on the progress of CINⅡ/Ⅲ.
Case-Control Studies
;
Disease Progression
;
Female
;
Gene Expression Regulation, Neoplastic
;
Heterogeneous-Nuclear Ribonucleoprotein K/metabolism*
;
Human papillomavirus 16
;
Humans
;
Papillomavirus Infections
;
Uterine Cervical Neoplasms/virology*
;
Uterine Cervical Dysplasia/virology*
6.Impact of novel P2Y12 receptor inhibitors on platelet reactivity in acute coronary syndrome patients undergoing percutaneous coronary intervention.
T J Chong TOU ; P M LIU ; J F WANG ; Z C Sio CHAM ; Y F O U ; Z W Lei SIO ; P Z Lei PUT ; S M Lei SOK ; S X ZHOU ; W WU
Chinese Journal of Cardiology 2016;44(2):138-143
OBJECTIVETo investigate the impact of novel P2Y(12) receptor inhibitors including prasugrel or ticagrelor on platelet reactivity in patients with acute coronary syndrome (ACS) receiving percutaneous coronary intervention (PCI), and provide clinical data for novel oral P2Y(12) receptor inhibitors use among Chinese patients.
METHODSBetween October 2011 to February 2014, 174 consecutive patients (135 males; (67.8±11.8) years old) with ACS undergoing PCI in Kiang Wu Hospital, Macau were prospectively enrolled in this study. Oral aspirin and one P2Y(12) receptor inhibitor were administered for 5 days or above after PCI, patients were divided into clopidogrel, prasugrel and ticagrelor groups in accordance with the agent administered. Platelet reactivity of the patients was detected by VerifyNow P2Y(12) reaction unit (PRU); and the high on-treatment platelet reactivity (HPR) and non-HPR were defined as PRU≥208 and PRU<208 respectively. Patients with HPR during clopidogrel therapy were switched either to prasugrel or ticagrelor, or continued the same treatment; and then the platelet reactivity was monitored again.
RESULTSThere were 113 clopidogrel cases (64.9%), 20 prasugrel cases (11.5%) and 41 ticagrelor cases (23.6%). Fifty-seven cases (32.8%) were defined as HPR post P2Y(12) receptor inhibitor use, in which 55 cases (55/113, 48.7%) were treated with clopidogrel. The degree of inhibition of platelet reactivity was significantly different in patients on clopidogrel, prasugrel and ticagrelor therapy, percent inhibition assayed by the VerifyNow P2Y(12) system was 28.2%±23.5%, 61.4%±26.7% and 81.3%±19.8% respectively (P<0.05). Different degree of platelet reactivity was achieved by the 3 P2Y(12) receptor inhibitors at multiple time points. The among-group differences in platelet reactivity became apparent at the early treatment stage (P<0.05). Platelet aggregation decreased significantly in patients switched from clopidogrel to prasugrel or ticagrelor (P<0.05).
CONCLUSIONNovel oral P2Y(12) receptor inhibitors are more effective in inhibiting platelet reactivity in ACS patients, and our results show that novel oral P2Y(12) receptor inhibitors provide a new option for ACS patients with HPR post clopidogrel or high-risk features of ischemic complications, including stent thrombosis and post-PCI ischemic events.
Acute Coronary Syndrome ; Adenosine ; analogs & derivatives ; Aged ; Aspirin ; Blood Platelets ; Female ; Humans ; Male ; Percutaneous Coronary Intervention ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; Platelet Function Tests ; Prasugrel Hydrochloride ; Prospective Studies ; Ticlopidine ; analogs & derivatives
7.Interaction between polycyclic aromatic hydrocarbons and high risk human papillomavirus infection on cervical intraepithelial neoplasia.
M WANG ; L DING ; X Z LIU ; C L LIU ; L LI ; Y J LYU ; J T WANG
Chinese Journal of Epidemiology 2018;39(5):673-677
Objective: To evaluate the effects of polycyclic aromatic hydrocarbons (PAHs) and high risk human papillomavirus (HR-HPV) infection and their interaction on the progression of cervical intraepithelial neoplasia. Methods: A total of 486 patients, including 208 women with normal cervix (NC), 154 patients with low-grade cervical intraepithelial neoplasm (CINⅠ), 124 patients with high-grade cervical intraepithelial neoplasm (CINⅡ/Ⅲ), were selected from the cervical lesions cohort from June to December, 2014. HR-HPV was detected by using flow-through hybridization technology and the urine concentration of 1-hydroxypyrene (1-OHP) was detected with high performance liquid chromatography. By using software SPSS 22.0, the χ(2) test, trend χ(2) test, Kruskal-Wallis H test, Nemenyi rank test and Spearman rank correlation analysis were performed. And the interaction effects were evaluated by additive model. Results: The HR-HPV infection rates in NC, CINⅠ and CINⅡ/Ⅲ groups were 27.9%, 37.0% and 58.9%, respectively. The urine concentrations of 1-OHP (μmol/molCr) were 0.07±0.09, 0.11±0.10 and 0.17±0.15, respectively. With increasing severity of the cervical lesions, the HR-HPV infection rate gradually increased (trend χ(2)=29.89, P<0.001) and the high exposure rate of PAHs gradually increased (trend χ(2)=27.94, P<0.001). HR-HPV infection was positively correlated with 1-OHP exposure (r=0.680, P<0.001). There was a positive additive interaction between HPV infection and PAHs exposure in CIN Ⅱ/Ⅲ group, but it was not found in CIN Ⅰ group. Conclusion: Both HR-HPV infection and high exposure of PAHs might increase the risk of cervical intraepithelial neoplasm, and might have a synergistic effect on the progression of high-grade cervical intraepithelial neoplasia.
Case-Control Studies
;
Cohort Studies
;
Disease Progression
;
Female
;
Humans
;
Papillomaviridae/isolation & purification*
;
Papillomavirus Infections/virology*
;
Polycyclic Aromatic Hydrocarbons/pharmacology*
;
Pyrenes/urine*
;
Severity of Illness Index
;
Uterine Cervical Dysplasia/virology*
;
Uterine Cervical Neoplasms/virology*
8.Polymorphisms of four STRs and their associations with IDDM in Chinese Han population.
Z A ; S ZHANG ; C XIAO ; W LI ; Y HOU ; J ZHU ; J WANG
Chinese Journal of Medical Genetics 2000;17(4):248-251
OBJECTIVETo obtain the polymorphic data of short tandem repeat(STR) loci of D15S657, D11S1369, D6S2420 and D6S503 in Chinese Han population and to study the association of these four STR loci with insulin-dependent diabetes mellitus(IDDM).
METHODSThe polymorphisms of the four STRs were studied by polymerase chain reaction-polyacrylamide gel electrophoresis(PCR-PAGE) followed by direct sequencing of PCR products in 105 normal Chinese Hans and 48 patients with IDDM.
RESULTSSeven alleles at D15S657 locus, 5 alleles at D11S1369 locus, 7 alleles at D6S2420 locus and 4 alleles at D6S503 locus were found. No deviation from Hardy-Weinberg equilibrium was observed. The heterozygosities of these loci were 0. 7524, 0.6000, 0.6286, 0.6571 and the polymorphic information contents(PIC) 0.7616, 0.4430, 0.5345 and 0.5932, respectively. The allele frequencies of allele A(5) at D15S657 locus, allele A(5) at D11S1369 locus and allele A(4) at D6S2420 locus were increased significantly in patients with IDDM, compared to those in the control group.
CONCLUSIONThe four STRs, used as genetic markers, were suitable for case-control study, forensic medicine identification and population genetic study. There is an association between the polymorphisms of D15S657, D11S1369, D6S2420 and IDDM.
Adult ; Aged ; China ; ethnology ; Diabetes Mellitus, Type 1 ; genetics ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Tandem Repeat Sequences
9.Factors associated with illicit drug use intention in secondary vocational school students based on theory of triadic influence.
Y C WANG ; J C YU ; J Y CHEN ; Z Z WANG
Chinese Journal of Epidemiology 2018;39(7):925-930
Objective: To explore the factors associated with illicit drug use (IDU) intention in secondary vocational school students based on theory of triadic influence (TTI), and provide theoretical foundation for IDU prevention education. Methods: A total of 8 870 students were selected from secondary vocational schools in 5 cities in China through multistage cluster sampling. A self-administered questionnaire was used to collect the information about students' sensation seeking (SS), parental monitoring (PM), perceived availability of drug (PAD), social benefit expectancies(SBE), refusal efficacy (RE) and social norms and IDU intention. Based on the TTI, the logistic regression model was used to analyze the factors associated with IDU. Results: Among the intrapersonal stream of influence, the higher levels of SS was the risk factor associated with IDU (OR=1.71, 95%CI: 1.22-2.41, P<0.01), medium RE level (OR=0.18, 95%CI: 0.14-0.23, P<0.001) and high RE level (OR=0.17, 95%CI: 0.13-0.22, P<0.001) were the protective factors for IDU intention. Among the interpersonal stream of influence, medium PM level (OR=0.46, 95%CI: 0.37- 0.56, P<0.001) and high PM level (OR=0.33, 95%CI: 0.24-0.46, P<0.001) were the protective factors for IDU intention, perceived others' drug use as well as perceived others' approval of substance use were risk factors for IDU intentions (P<0.001); Among sociocultural environmental stream of influence, perceived easy availability of drugs (OR=3.47, 95%CI: 2.69-4.48, P<0.001) and perceived SBE of drugs (OR=2.04, 95%CI: 1.69-2.46, P<0.001) were risk factors for IDU intentions (P<0.001). Conclusions: High levels of SS and SBE, perceived easier availability of substance, perceived others' substance use and perceived others' approval of substance use positively predict the students' intention of IDU. IDU prevention education for adolescents should be focused on the above factors, and parental supervision and students' refuse skills should be improved.
Adolescent
;
China
;
Female
;
Humans
;
Illicit Drugs/adverse effects*
;
Intention
;
Male
;
Students/statistics & numerical data*
10.A Meta-analysis on the relations between short-term exposure to PM(2.5) and both mortality and related emergency visits in China.
M LI ; Y WU ; Y H TIAN ; G Y CAO ; S S YAO ; P AI ; Z HUANG ; C HUANG ; X W WANG ; Y Y CAO ; X XIANG ; J JUAN ; Y H HU
Chinese Journal of Epidemiology 2018;39(10):1394-1401
Objective: To carry out a quantitative estimate that related to the effects of short-term exposure to PM(2.5) on all-cause mortality and emergency visits in China by using the systematic review and Meta-analysis. Methods: We selected all the studies published before March 2018 from China National Knowledge Infrastructure, Wanfang database, PubMed and EMBASE and data on relative risk (RR), excess risk (ER) and their 95%CIs: appeared in these papers were extracted. According to the differences in the size or direction (heterogeneity) of the results, we computed summary estimates of the effect values using a random-effect or fixed effect model. We also conducted the subgroup analysis and Meta-analysis to have assessed the selected studies for the evidence of study bias. Results: A total of 33 original studies, indexed in databases, were identified. Among those studies, 39 sets of data on mortality and 4 sets of data on emergency were valid to show that within the daily concentration range from 47.7 to 176.7 μg/m(3), for 10 μg/m(3) increases in PM(2.5) concentrations, it would increase the daily numbers of deaths by 0.49% (95%CI: 0.39%-0.59%) and 0.30% (95%CI: 0.10%-0.51%) for all-cause deaths and all-cause emergency-room visits, respectively. For subgroup analysis, the combined effect of PM(2.5) in causing short-term all-cause deaths in the northern areas (ER=0.42%, 95%CI: 0.30%-0.54%) seemed lower than that in the southern areas (ER=0.63%, 95%CI: 0.44%-0.82%). The combined effect of PM(2.5) concentration below 75 μg/m(3) (ER=0.50%, 95%CI: 0.37%-0.62%) was higher than that of PM(2.5) concentration ≥75 μg/m(3) (ER=0.39%, 95%CI: 0.26%-0.52%). Conclusion: Within the concentration range from 47.7 to 176.7 μg/m(3), short-term exposure to current level of PM(2.5) might increase both the all-cause daily mortality and daily emergency visits in China.
Air Pollutants
;
Air Pollution/statistics & numerical data*
;
China
;
Databases, Factual
;
Emergency Service, Hospital/statistics & numerical data*
;
Environmental Exposure/statistics & numerical data*
;
Female
;
Humans
;
Male
;
Particulate Matter/toxicity*
;
Time Factors