1.A cohort study on the influence of the chronic diseases on activities of daily living of the elderly aged 65 years and over in China.
Z Y LI ; J L WU ; J J LI ; L J PEI
Chinese Journal of Epidemiology 2019;40(1):33-40
Objective: To understand the influence of chronic diseases on the risk of impaired activities of daily living (ADL) of the elderly. Methods: Baseline data of 10 501 elderly individuals recruited by the Chinese Longitudinal Healthy Longevity Survey in 2002 were used, and follow up for this population was conducted until 2014. Cox Proportional Hazard Model was used to estimate the hazards ratios (HR) for the associations between five kinds of chronic diseases, the number of chronic diseases and the risk of ADL impairment in different age groups of the elderly. Results: Hypertension increased the risk of ADL impairment in the elderly of all age groups, which increased the ADL impaired risk by 43% (HR=1.43, 95%CI: 1.14-1.79) in group aged 65-74 years, 21% (HR=1.21, 95%CI: 1.02-1.43) in group aged 75-89 years and 20% (HR=1.20, 95%CI: 1.02-1.43) in group aged 90-105 years, respectively. Diabetes and cerebrovascular disease increased the ADL impaired risk by 102%(HR=2.02, 95%CI: 1.29-3.17), and 79% (HR=1.79, 95%CI: 1.24-2.58) in group aged 65-74 years, respectively. 'Suffering from one chronic disease' increased the ADL impaired risk by 13% (HR=1.13, 95%CI: 1.02-1.25), and suffering from two or more chronic diseases increased the ADL impaired risk by 25% (HR=1.25, 95%CI: 1.13-1.40) in all the age groups. Suffering from two or more chronic diseases increased the ADL impaired risk by 50% (HR=1.50, 95%CI: 1.21-1.87) in group aged 65-74 years and 17% (HR=1.17, 95%CI: 1.01-1.38) in groups aged 75-89 years. Conclusions: Hypertension was one of the most important risk factors for the impaired ADL in the elderly population in all age groups. Hypertension, diabetes, cerebrovascular disease or comorbidity increased the risk of impaired ADL in group aged 65-74 years.
Activities of Daily Living
;
Aged
;
Aged, 80 and over
;
China
;
Chronic Disease
;
Cohort Studies
;
Humans
;
Longitudinal Studies
;
Risk Factors
2.Associations between maternal exposure to chemical fertilizers during pregnancy and the risk of offspring's low birth weights.
N WANG ; J L WU ; Y ZHANG ; S Q LIN ; R Y QIAO ; R J FAN ; L J PEI
Chinese Journal of Epidemiology 2018;39(10):1324-1328
Objective: To explore the association between the consumption of chemical fertilizers and the risk of low birth weight (LBW), to provide references for prevention programs on LBW and to improve the birth outcomes. Methods: Stratified multivariate logistic regression method was used in this study involving 153 preterm LBW infants, 179 term LBW infants and 204 normal control infants that were randomly selected from the birth monitoring data between October 2007 and September 2012 in Pingding county, Shanxi province. Associations between the risk of LBW and maternal exposure to chemical fertilizers during pregnancy were identified. A normal control group was set up to compare results between preterm and term LBW groups. Results: Totally, 18 749 infants were born between 2007 and 2012, with the total incidence rates of LBW as 48.5‰, preterm LBW as 19.4‰, and term LBW as 29.1‰. Concerning the case control study on preterm LBW, after adjustment for confounding factors, the risk of preterm LBW appeared 2.51 (95%CI: 1.05-5.99) times higher in villages with annual consumption of chemical fertilizer ≥100 tons than those villages that using chemical fertilizer less than 50 tons. No significant statistical associations were found between the amounts of household chemical fertilizer consumption and the risks of preterm LBW. Regarding the case control study on term LBW, after adjustment for confounding factors, in villages with ≥100 tons annual consumption of chemical fertilizers, the risk of term LBW was 4.03 (95%CI: 1.63-9.92) times of the risk in villages where the annal use of chemical fertilizers was less than 50 tons. There was no significant association between household consumption of chemical fertilizers and the risk of term LBW. Conclusions: Maternal exposure to chemical fertilizers during pregnancy was associated with the risk of LBW. Our findings suggested that the amount of chemical fertilizer consumption in rural areas seemed also associated with the risks of other adverse pregnancy outcomes. Women should avoid the chance of exposure to chemical fertilizers during pregnancy and the consumption of chemical fertilizers should be carefully managed.
Adult
;
Case-Control Studies
;
Environmental Exposure/adverse effects*
;
Female
;
Fertilizers/adverse effects*
;
Humans
;
Infant
;
Infant, Low Birth Weight
;
Infant, Newborn
;
Maternal Exposure
;
Pregnancy
;
Premature Birth/epidemiology*
;
Random Allocation
;
Risk Factors
3.Pharmacological applications of a novel neoepitope antibody to a modified amyloid precursor protein-derived beta-secretase product.
Guoxin WU ; Sethu SANKARANARAYANAN ; Donna L MONTGOMERY ; Adam J SIMON ; Zhiqiang AN ; Mary J SAVAGE
Protein & Cell 2011;2(7):573-584
We have previously described a novel artificial NFEV β-secretase (BACE1) cleavage site, which when introduced into the amyloid-β precursor protein (APP), significantly enhances APP cleavage by BACE1 in in vitro and cellular assays. In this study, we describe the identification and characterization of a single chain fragment of variable region (scFv), specific to the EV neo-epitope derived from BACE1 cleavage of the NFEV-containing peptide, and its conversion to IgG1. Both the scFv displayed on phage and EV-IgG1 show exquisite specificity for binding to the EV neoepitope without cross-reactivity to other NFEV containing peptides or WT-APP KMDA cleavage products. EV-IgG1 can detect as little as 0.3 nmol/L of the EV peptide. EV-IgG1 antibody was purified, conjugated with alkaline phosphatase and utilized in various biological assays. In the BACE1 enzymatic assay using NFEV substrate, a BACE1 inhibitor MRK-3 inhibited cleavage with an IC(50) of 2.4 nmol/L with excellent reproducibility. In an APP_NFEV stable SH-SY5Y cellular assay, the EC(50) for inhibition of EV-Aβ peptide secretion with MRK-3 was 236 nmol/L, consistent with values derived using an EV polyclonal antibody. In an APP_NFEV knock-in mouse model, both Aβ_EV40 and Aβ_EV42 peptides in brain homogenate showed excellent gene dosage dependence. In conclusion, the EV neoepitope specific monoclonal antibody is a novel reagent for BACE1 inhibitor discovery for both in vitro, cellular screening assays and in vivo biochemical studies. The methods described herein are generally applicable to novel synthetic substrates and enzyme targets to enable robust screening platforms for enzyme inhibitors.
Amino Acid Sequence
;
Amyloid Precursor Protein Secretases
;
antagonists & inhibitors
;
chemistry
;
genetics
;
Amyloid beta-Protein Precursor
;
Animals
;
Antibodies
;
pharmacology
;
Brain Chemistry
;
drug effects
;
Disease Models, Animal
;
Enzyme Inhibitors
;
pharmacology
;
Enzyme-Linked Immunosorbent Assay
;
Gene Knock-In Techniques
;
Humans
;
Inhibitory Concentration 50
;
Mice
;
Molecular Sequence Data
;
Single-Chain Antibodies
;
pharmacology
4.Characteristics of newly reported HIV/AIDS cases with non-marital but non-commercial heterosexual transmission in Hangzhou, 2015-2017.
J F CHEN ; H WU ; X L ZHANG ; Y LUO ; J M DING
Chinese Journal of Epidemiology 2018;39(12):1602-1606
Objective: To describe the characteristics of newly reported HIV/AIDS cases via non-marital or non-commercial heterosexual transmission and to find out the relative factors in Hangzhou, from 2015 to 2017. Methods: Data were collected through the national HIV/AIDS comprehensive control and prevention data system. Study subjects would include those reported HIV/AIDS cases who were residents of Hangzhou and were infected via non-marital heterosexual transmission, between January 1, 2015 and December 31, 2017. Demographic characteristics and behavioral information were collected. χ(2) test was used to compare different characteristics of the non-married heterosexual transmission subjects. Logistic regression was used to assess factors that associated with non-marital but non-commercial HIV heterosexual transmission with SPSS. 20 software used to analyze statistically. Results: Non-marital HIV heterosexual transmission accounted for 38.03% (1 393/3 663) of the total new reported HIV/AIDS cases in 2015-2017. Out of the 1 393 HIV/AIDS cases, those infected through non-marital but non-commercial heterosexual transmission accounted for 50.83% (708/1 393), and those through non-martial commercial transmission was accounted for 49.17% (685/1 393). Male to female ratio was 3.51 ∶ 1 (1 084/309). Male HIV cases reported that their major way of infection was via non-marital commercial transmission (670/1 084, 61.81%), while female patients reported the way was via non-marital non-commercial (294/309, 95.1%). Results from multivariate logistic analysis showed that the related risk factors and ORs for non-marital but non-commercial transmission appeared as: female (aOR=48.25, 95%CI: 26.94- 88.44),<30 year olds (aOR=2.43, 95%CI: 1.31-4.51), 30-39 year olds (aOR=1.92, 95%CI: 1.11- 3.33), 40-49 year olds (aOR=1.80, 95%CI: 1.08-3.00), married or unmarried (vs. divorced or widowed, aOR=1.57, 95%CI: 1.10-2.24; aOR=1.78, 95%CI: 1.15-2.78), high school and above of education level (vs. primary school and under of education level, aOR=1.82, 95%CI: 1.18-2.80), administrative officers or employee (vs. farmers, aOR=2.03, 95%CI: 1.04-1.91). Number of non- marital partners less than 5 (vs. number of non-marital partners more than 5, aOR=10.65, 95%CI: 6.41-17.42). Conclusions: HIV/AIDS cases with non-marital heterosexual transmission accounted for considerable proportion regarding the HIV transmission in Hangzhou from 2015 to 2017. Differences were found in the following factors as non-marital and non-commercial heterosexual transmission with diverse gender, age, marital status, educational level and occupation among of the HIV/AIDS patients.
Female
;
HIV
;
HIV Infections/transmission*
;
Heterosexuality
;
Humans
;
Male
;
Risk Factors
;
Sexual Behavior/psychology*
;
Sexual Partners
;
Single Person
5.A large scale cohort study on the immunization effect of hepatitis B vaccine in Fujian province.
D J ZHANG ; R T HONG ; L F HUANG ; R H WU
Chinese Journal of Epidemiology 2018;39(8):1091-1095
Objective: To evaluate the effectiveness of hepatitis B vaccination in Fujian province. Methods: Based on the hepatitis B immunization strategy of China, a cohort study was designed, involving the population in Fujian province. The population under study was divided into natural exposure birth cohort before 1992 and the immunization birth cohort after 1992 (including voluntary vaccination cohort and standardized vaccination cohort). By cleaning the database of hepatitis B cases which directly reported through network and looked into the incidence and related death outcomes of acute hepatitis B from 2004 to 2017, the incidence levels of hepatitis B and immunization effects were analyzed and evaluated among different birth cohorts. Results: During the observation period, the overall prevalence of hepatitis B in Fujian province was 44.594 per 100 000, with mortality rate as 0.010 per 100 000. The incidence of natural exposure cohort of birth was 56.885 per 100 000. The incidence of voluntary vaccination cohort of birth was 14.502 per 100 000. Compared with the voluntary vaccination cohort, the risk of hepatitis B increased significantly in the natural exposed cohort (RR=3.923), and the difference was statistically significant (P=0.000 7), with attributable risk as 42.383 per 100 000. The attributable risk ratio was 74.507. The population attributable risk ratio was 70.967%. The population attributable risk was 35.448 per 100 000. The attributable rate in standardized vaccination cohorts born after 2002 was 2.336 per 100 000. Compared with the cohorts born before 1992, the RR was 24.347 (P=0.000 0), the attributable risk was 54.549 per 100 000, and the attributable risk ratio was 95.893%, the population attributable risk ratio was 95.300%, the population attributable risk was 47.371 per 100 000, comparing to the natural exposed population. Conclusions: The effectiveness of hepatitis B immunization program had been remarkable in Fujian province since 1992. However, further studies on the persistency of hepatitis B vaccine immunization and its public health significance still needed to be carried out.
China/epidemiology*
;
Cohort Studies
;
Hepatitis B/prevention & control*
;
Hepatitis B Vaccines/administration & dosage*
;
Humans
;
Immunization
;
Incidence
;
Odds Ratio
;
Prevalence
;
Risk Factors
;
Vaccination/statistics & numerical data*
6.Effect of sugammadex on postoperative nausea and vomiting after surgery for intracranial aneurysm.
J CUI ; L YAO ; J L WU ; C Y LU ; Y ZHAO ; Y L ZHAO
Chinese Journal of Surgery 2023;61(8):700-706
Objective: To investigate the effect of sugammadex on postoperative nausea and vomiting(PONV) after intracranial aneurysm surgery. Methods: Data from intracranial aneurysms patients who met the inclusion and exclusion criteria and underwent interventional surgery in the Department of Neurosurgery, Peking University International Hospital from January 2020 to March 2021 were prospectively included. According to the random number table method, the patients were divided by 1∶1 into the neostigmine+atropine group (group N) and the sugammadex group (group S). Use an acceleration muscle relaxation monitor for muscle relaxation monitoring, and administer neostigmine+atropine and sugammadex to block residual muscle relaxation drugs after surgery. The incidence rates of PONV and severity, the appearance of anesthesia, and the correlation between PONV and postoperative complications were recorded in both groups during five periods after surgery: 0-0.5 hours (T1),>0.5-2.0 hours(T2),>2.0-6.0 hours (T3),>6.0-12.0 hours (T4) and >12.0-24.0 hours (T5). Group comparisons of quantitative data were performed by the independent sample t-test, and categorical data was performed by the χ2 or rank sum test. Results: A total of 66 patients were included in the study, including 37 males and 29 female, aged (59.3±15.4) years (range: 18 to 77 years). The incidence rates of PONV of 33 patients in group S at different time periods of T1, T2, T3, T4, and T5 after surgery were respectively 27.3%(9/33),30.3%(10/33),12.1%(4/33),3.0%(1/33),0(0/33),and the incidence rates of PONV of 33 patients in the group N at different time periods of T1, T2, T3, T4 and T5 after surgery were respectively 36.4%(12/33),36.4%(12/33),33.3%(11/33),6.1%(2/33) and 0(0/33).The incidence of PONV was lower in the group S only in the T3 period after reversal than in the group N (χ2=4.227, P=0.040).However, there was no statistically significant difference in the incidence of PONV between the two groups of patients in other periods (all P>0.05). The recovery time for spontaneous breathing in patients in group S was (7.7±1.4) minutes, the extubation time was (12.4±5.3) minutes, and the safe exit time for anesthesia recovery was (12.3±3.4) minutes; the N groups were (13.9±2.0) minutes, (18.2±6.0) minutes, and (18.6±5.2) minutes, respectively; three time periods in group S were shorter than those in group N, and the differences were statistically significant (all P<0.05). The results regarding the occurrence of complications in patients with different levels of PONV at different time intervals after surgery in the two groups were as follows: in the T3 time period of group N, a significant difference was observed only in the occurrence of postoperative complications among patients with different levels of PONV (χ2=24.786, P<0.01). However, in the T4 time period, significant differences were found in the occurrence of postoperative complications among both the same level and different level PONV patients (χ2=15.435, 15.435, both P<0.01). Significant differences were also observed in the occurrence of postoperative complications among the same level and different level PONV patients in both the T3 and T4 time periods of group S (all P<0.01). Conclusion: Sugammadex can be used to reverse muscle relaxation in patients undergoing intracranial aneurysm intervention surgery,and it does not have a significant impact on the incidence of PONV, it can also optimize the quality of anesthesia recovery and reduce the incidence of complications after intracranial aneurysm embolization surgery.
Male
;
Humans
;
Female
;
Sugammadex
;
Postoperative Nausea and Vomiting/chemically induced*
;
Neostigmine/adverse effects*
;
Intracranial Aneurysm/surgery*
;
gamma-Cyclodextrins/adverse effects*
;
Atropine
7.Study on the super-antigen genes of group A Streptococcus pyogenes strains isolated from patients with scarlet fever and pharyngeal infection, in Beijing, 2015-2017.
C N MA ; X M PENG ; S S WU ; D T ZHANG ; J C ZHAO ; G L LU ; Y PAN ; S J CUI ; Y M LIU ; W X SHI ; M ZHANG ; Q Y WANG ; P YANG
Chinese Journal of Epidemiology 2018;39(10):1375-1380
Objective: To analyze the characteristics of super-antigen (SAg) of group A Streptococcus pyogenes (GAS), isolated from patients with scarlet fever or pharyngeal infections in Beijing between 2015-2017. Methods: Throat swab specimens from patients with scarlet fever or pharyngeal infections were collected and tested for GAS. Eleven currently known SAg genes including SpeA, speC, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa were tested by real-time PCR while M protein genes (emm genes) were amplified and sequenced by PCR. Results: A total of 377 GAS were isolated from 6 801 throat swab specimens, with the positive rate as 5.5%. There were obvious changes noticed among speC, speG, speH and speK in three years. A total of 45 SAg genes profiles were observed, according to the SAgs inclusion. There were significant differences appeared in the frequencies among two of the highest SAg genes profiles between emm1 and emm12 strains (χ(2)=38.196, P<0.001; χ(2)=72.310, P<0.001). There also appeared significant differences in the frequencies of speA, speH, speI and speJ between emm1 and emm12 strains (χ(2)=146.154, P<0.001; χ(2)=52.31, P<0.001; χ(2)=58.43, P<0.001; χ(2)=144.70, P<0.001). Conclusions: Obvious changes were noticed among SAg genes including speC, speG, speH and speK from patients with scarlet fever or pharyngeal infections in Beijing between 2015-2017. SAg genes including speA, speH, speI and speJ appeared to be associated with the emm 1 and emm 12 strains. More kinds of SAg genes profiles were isolated form GAS but with no significant differences seen in the main SAg genes profiles, during the epidemic period.
Antigens, Bacterial/genetics*
;
Bacterial Outer Membrane Proteins
;
Bacterial Proteins
;
Beijing/epidemiology*
;
China/epidemiology*
;
Exotoxins
;
Female
;
Humans
;
Membrane Proteins
;
Pharyngitis/microbiology*
;
Pharynx/microbiology*
;
Pregnancy
;
Pregnancy Complications, Infectious/microbiology*
;
Real-Time Polymerase Chain Reaction
;
Scarlet Fever/microbiology*
;
Streptococcal Infections
;
Streptococcus pyogenes/isolation & purification*
;
Superantigens/genetics*
9.Clinicopathological study of epithelioid and spindle cell rhabdomysarcoma with EWSR1/FUS-TFCP2 fusion.
H L LI ; C H MO ; L XIE ; Y X WU ; M ZENG ; R J MAO
Chinese Journal of Pathology 2024;53(1):58-63
Objective: To investigate the clinicopathological and genetic features of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion. Methods: The clinical, morphological and immunohistochemical features of 14 cases of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion diagnosed from January 2019 to December 2022 in the Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed. The cases were all subject to FISH or next generation sequencing for analysis of molecular genetic features. The literature was reviewed. Results: There were 5 males and 9 females, with the age at presentation ranging from 6 to 36 years (mean, 22 years). Tumors occurred in the head and neck (9 cases), pelvic region (2 cases), bladder (one case), right humerus (one case), and the abdominal wall, humerus and pubic at the same time (one case). Presenting symptoms varied by location but often included pain or discomfort. Most of the patients showed aggressive radiographic features with soft tissue extension. The tumors had a median size of 6.6 cm (range, 2-23 cm). The tumors were poorly defined and irregularly shaped. Microscopic examination showed diffuse proliferation of spindle or epithelioid cells. While morphologically high-grade tumors displayed obvious cytological atypia, a high mitotic count and tumor necrosis, low-grade tumors grew in sheets and fascicles composed of spindle, epithelioid cells with moderate or abundant amounts of eosinophilic cytoplasm, without pronounced cytological atypia. The tumor cells expressed Desmin, MyoD1, and Myogenin, as well as ALK, EMA, and CKpan. EWSR1/FUS-TFCP2 gene fusion was detected in 14 cases with next generation sequencing and confirmed by FISH. Six cases had EWSR1-TFCP2 fusions and 8 cases showed FUS-TFCP2 fusions. Follow-up information was available in 13 patients, ranged from 5 to 37 months. At the end of follow-up period, 7 patients died of the disease. Six patients were alive:two cases had local recurrences and metastases, two cases of recurrences, one case of metastasis and one case without recurrences and metastasis. Conclusions: Epithelioid and spindle cell rhabdomysarcomas with EWSR1-TFCP2 or FUS-TFCP2 fusion show a very aggressive clinical course, and more commonly occur in the head and neck. Their genetic hallmark is the presence of EWSR1/FUS-TFCP2 fusions. Familiarity with its clinicopathological characteristics is helpful in avoiding misdiagnoses.
Male
;
Female
;
Humans
;
Child
;
Adolescent
;
Young Adult
;
Adult
;
Retrospective Studies
;
Transcription Factors/genetics*
;
Rhabdomyosarcoma
;
RNA-Binding Protein EWS/genetics*
;
China
;
Biomarkers, Tumor/genetics*
;
DNA-Binding Proteins/genetics*
;
RNA-Binding Protein FUS/genetics*
10.Validation of Self-administrated Questionnaire for Psychiatric Disorders in Patients with Functional Dyspepsia.
Ada W Y TSE ; Larry H LAI ; C C LEE ; Kelvin K F TSOI ; Vincent W S WONG ; Yawen CHAN ; Joseph J Y SUNG ; Francis K L CHAN ; Justin C Y WU
Journal of Neurogastroenterology and Motility 2010;16(1):52-60
INTRODUCTION: Psychiatric comorbidity is common in patients with functional dyspepsia (FD) but a good screening tool for psychiatric disorders in gastrointestinal clinical practice is lacking. Aims: 1) Evaluate the performance and optimal cut-off of 12-item General Health Questionnaire (GHQ-12) as a screening tool for psychiatric disorders in FD patients; 2) Compare health-related quality of life (HRQoL) in FD patients with and without psychiatric comorbidities. METHODS: Consecutive patients fulfilling Rome III criteria for FD without medical co-morbidities and gastroesophageal reflux disease were recruited in a gastroenterology clinic. The followings were conducted at 4 weeks after index oesophagogastroduodenoscopy: self-administrated questionnaires on socio-demographics, dyspeptic symptom severity (4-point Likert scale), GHQ-12, and 36-item short-form health survey (SF-36). Psychiatric disorders were diagnosed with Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) by a trained psychiatrist, which served as reference standard. RESULTS: 55 patients underwent psychiatrist-conducted interview and questionnaire assessment. 27 (49.1%) had current psychiatric disorders as determined by SCID (anxiety disorders: 38.2%, depressive disorders: 16.4%). Receiver operating characteristic curve analysis of GHQ-12 revealed an area under curve of 0.825 (95%CI: 0.698-0.914). Cut-off of GHQ-12 at > or =3 gave a sensitivity of 63.0% (95%CI = 42.4-80.6%) and specificity of 92.9% (95%CI = 76.5%-98.9%). Subjects with co-existing psychiatric disorders scored significantly lower in multiple domains of SF-36 (mental component summary, general health, vitality and mental health). By multivariate linear regression analysis, current psychiatric morbidities (Beta = -0.396, p = 0.002) and family history of psychiatric illness (Beta = -0.299, p = 0.015) were independent risk factors for poorer mental component summary in SF-36, while dyspepsia severity was the only independent risk factor for poorer physical component summary (Beta = -0.332, p = 0.027). CONCLUSIONS: Concomitant psychiatric disorders adversely affect HRQoL in FD patients. The use of GHQ-12 as a reliable screening tool for psychiatric disorders allows early intervention and may improve clinical outcomes of these patients.
Area Under Curve
;
Axis, Cervical Vertebra
;
Comorbidity
;
Diagnostic and Statistical Manual of Mental Disorders
;
Dyspepsia
;
Early Intervention (Education)
;
Gastroenterology
;
Gastroesophageal Reflux
;
Health Surveys
;
Humans
;
Linear Models
;
Mass Screening
;
Mental Disorders
;
Psychiatry
;
Quality of Life
;
Surveys and Questionnaires
;
Risk Factors
;
ROC Curve
;
Rome
;
Sensitivity and Specificity