a b s t r a c t

Objectives: Guidelines recommend the use of risk scoring in patients with chest pain. In this study, we aimed to compare the thrombolysis in myocardial infarction risk index (TIMI) score with the Troponin Only Manchester Acute Coronary Syndrome Score (T-MACS) score and to investigate the usability of the T-MACS score in the emergency department.

Methods: In our study; The TIMI and T-MACS scores of 310 patients with suspected NSTEMI who applied to the emergency department with chest pain and met the inclusion and exclusion criteria were prospectively evaluated. The primary outcome was MACE at 30 days including acute coronary syndromes, need for revascular- ization and deaths. Descriptive data and TIMI and T-MACS scores for predicting MACE and ACS was evaluated by calculating sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). ROC (Receiver Operating Characteristic) analysis was also performed to determine TIMI and T-MACS risk class.

Results: In our study, the mean age of the patients was 49.7 +- 19.4 years, the 1-month mortality rate was 1.3%, major adverse cardiac event rate was 6.5%, and acute coronary syndrome (ACS) rate was 5.5%. T-MACS risk class for predicting MACE sensitivity 100%, selectivity 51.72, PPV 12.5% (for Very low risk), NPV was calculated as 100%; sensitivity for TIMI risk class low risk 35%, selectivity 88.97%, PPV was calculated as 17.9%, NPV was calculated as 95.2%. T-MACS high risk class for predicting MACE; sensitivity was 60%, selectivity 99.66%, PPV 92.3% and NPV was 97.3%; TIMI high risk class for predicting MACE; sensitivity was 10%, selectivity was 97.93%, PPV was 25% and NPV was 94%.

Conclusions: The findings obtained in this study suggest that the T-MACS score is more successful than the TIMI score in determining the low risk (very low risk for T-MACS score), high risk, and estimated 1-month MACE risk in cases who presented to the emergency department with chest pain.

(C) 2022

1. Introduction

Ischemic heart diseases are among the most significant causes of death, along with many known risk factors worldwide [1]. We are faced with two separate challenges in patients presenting with Ischemic symptoms, such as quickly making the diagnosis of acute coronary syndrome (ACS) and detecting those without ACS and thus reducing the assemblage in the emergency department. Since 1980, deaths due to ischemic heart disease have gradually declined due to studies on risk factors in developed countries and treatment for ischemic heart dis- ease [2,3]. Newly developed anticoagulants, early PCI and Reperfusion strategy, fibrinolysis, and 6-month mortality due to the appropriate

* Corresponding author at: University of Health Sciences, Haydarpasa Numune Training and Research Hospital, Department of Emergency Medicine, 34660 Istanbul, Turkey.

E-mail addresses: [email protected], [email protected] (B.G. Yavuz).

use of recommended drugs were strongly associated with reduced mortality [4]. Although short-term mortality in patients diagnosed with NSTEMI is lower than in patients diagnosed with STEMI, their long-term mortality is higher due to the burden of coronary artery dis- ease, comorbidities and increased risk factors [5].

The diagnosis of STEMI can be easily made in patients presenting with chest pain by single or serial ECG assessments [6]. In the diagnosis of NSTEMI, challenges arise, such as the variety of the patient’s symptoms at presentation and the inability to diagnose with ECG [7]. Therefore, to improve NSTEMI recognition and management, it is rec- ommended to use scoring systems, such as thrombolysis in myocardial infarction risk index (TIMI) and HEART [8-10].

The TIMI score was devised by Elliott M. Antman et al. in 2000 to es- timate the risk of death and developing a cardiac ischemic event, based on information obtained from the initial medical evaluation of patients with UA/NSTEMI [11]. Troponin Only Manchester Acute Coronary

https://doi.org/10.1016/j.ajem.2022.07.017

0735-6757/(C) 2022

Syndrome Score (T-MACS) is a scoring system designed to exclude acute coronary syndrome with a single High-sensitivity troponin value without serial troponin follow-ups in patients presenting in the emergency department with chest pain [12].

In this study, we aimed to prospectively compare the use and effectiveness of TIMI and T-MACS scores, which are chest pain scores, in patients admitted to the emergency department with NSTEMI symp- toms, to identify high-risk patients and identify low-risk patients among them and discharge them safely.

1. Methods
   1. Study design

This prospective cross-sectional study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Com- mittee of the Faculty of Medicine, University of Health Sciences, Haydarpasa Numune Training and Research Hospital (approval number 170-1805). Our study was conducted in Haydarpasa Numune Training and Research Hospital emergency room between December 2019 and July 2020, and consent was obtained from the patients participating in this study, and the management of the patients was carried out by cer- tified ED physicians. Every year, approximately 250,000 patients visit the ED, where the study was conducted.

To improve NSTEMI recognition and management, it is recom- mended to use scoring systems. Our primary outcome was MACE at 30 days including acute coronary syndromes, need for revascularization and deaths. In our study, the efficacy of TIMI and T-MACS scores in predicting NSTEMI was compared by following the patients’ outcomes for MACE, acute coronary syndrome, revascularization and death within 30 days. We aimed to find a more effective scoring system to identify high-risk patients and low-risk patients to safely discharge patients. Weak points of our study is that it is single-centered. Multicenter pro- spective studies with more case numbers will help the clinician in the prediction of ACS and MACE and risk estimation.

• 1. Study setting and population

A study group was formed with patients aged 18 years and older admitted to our emergency department with symptoms of ischemic chest pain and were examined with a prediagnosis of NSTEMI and ac- cepted to participate in the study. Among these patients, those whose control ECG was compatible with STEMI in the emergency department, pregnant women and patients with cardiogenic shock and cardiac arrest were not included in this study.

Vital parameters, medical histories, family histories, smoking and demographic data of the patients were recorded. Physical examination was administered, a High-sensitive cardiac troponin-T (hs-cTnT) test was requested and ECGs were taken. The blood samples taken were studied in the Health Sciences University Haydarpasa Numune Health Application and Research Center Biochemistry Laboratory within one and a half hours. All this information was noted on the previously pre- pared case form.

To determine adequate sample size G*Power 3.1.9 used [13]. Based on the Ruangsomboon et al. study, the effect size was determined as d = 0.690 [14]. With the 95% power and 0.05 alpha, the minimum

Table 1

The general characteristics of the 310 patients.

n

Age 49.7 +- 19.4(18-92)

Gender

Female 168(54.2)

Male 142(45.8)

MACE

Yes 290(93.5)

No 20(6.5)

ACS

Yes 293(94.5)

No 17(5.5)

T-MACS risk class

Very-low 150(48.4)

Low 72(23.2)

Medium 75(24.2)

High 13(4.2)

TIMI risk class

Low 271(87.4)

Medium 31(10)

High 8(2.6)

Results are shown as mean +- SD (min-max), median (min-max) or n (%) values. MACE: Major adverse cardiac events, ACS: Acute Coronary Syn- drome, T-MACS: Troponin-only Manchester Acute Coronary Syndromes, TIMI: Thrombolysis in Myocardial Infarction.

in the last seven days, newly developed ST change, elevated cardiac troponins. In the presence of each parameter, the patient gets 1 point. It is classified as 0-2 low risk, 2-4 medium risk and 5-7 high risk [15]. T-MACS score parameters are: ECG ischemia, worsening (or increasing) angina, pain radiating to the right arm or shoulder, pain associated with vomiting, sweating detected by a physician, blood pressure which is lower than 100 mmHg on admission to the emergency department, Hc-TropoinT value measured at the patient’s arrival. In clinical practice, the T-MACS score calculation is designed to be calculated based on a computer, tablet or smartphone [12].

After the patients were discharged, major adverse cardiac event and one-month mortality information were obtained by calling phone numbers and learning through the death notification system. In our study, MACE included acute coronary syndromes, deaths and the need for revascularization.

1. Statistical analysis

While evaluating the data obtained in this study, the analyses were made using the IBM SPSS 23.0 package program (IBM Corp., Armonk, NY). Descriptive statistics were presented with n (%), mean +- standard deviation and median (min-max) values. Pearson chi-square test and Fisher’s exact test were used to analyze the relationships between categorical variables. The Shapiro-Wilks test was used in the analysis of the assumption of normality. In the analysis of the difference between the measurement values of the two groups, the Mann-Whitney U test was used when it did not comply with the normal distribution, and

Table 2

Comparison of the parameters of T-MACS and TIMI scores according to risk class.

T-MACS TIMI

sample size to be included in the study was calculated as n = 112.

2.3. Risk score calculation

MACE

Very low risk (n:150)

High risk (n:13)

Low risk (n:271)

High risk (n:8)

The TIMI and T-MACS scores of the patients were calculated using the information recorded on the case form. While calculating the scores, the standards set in previous studies were adhered to [12,15].

TIMI score parameters used in calculations are: Age > 65, > 3 risk factors for coronary artery disease, two or more anginal attacks in the last 24 h, known coronary artery stenosis of 50% or more, use of aspirin

Yes 150(100) 1(7.7) 258(95.2) 6(75)

No 0(0) 12(92.3) 13(4.8) 2(25) ACS

Yes	150(100)	1(7.7)	261(96.3)	6(75)
No	0(0)	12(92.3)	10(3.7)	2(25)

Results are presented with n (%) values. T-MACS: Troponin-only Manchester Acute Coro- nary Syndromes, TIMI: Thrombolysis in Myocardial Infarction, MACE: Major Adverse Car- diac Events, ACS: Acute Coronary Syndrome.

Table 3

Sensitivity, selectivity, PPV, NPV values for T-MACS and TIMI risk class in predicting MACE.

	Sensitivity	95% CI	Selectivity	95% CI	PPV	95% CI	NPV	95% CI
TIMI	35	15.4-59.2	88.97	84.8-92.3	17.9	10-30.2	95.2	93.5-96.5
T-MACS	100	83.2-100	51.72	45.8-57.6	12.5	11.3-13.9	100

CI: Confidence Interval, PPV: Positive predictive value, NPV: Negative Predictive Value, T-MACS: Troponin-only Manchester Acute Coronary Syndromes, TIMI: Thrombolysis in Myocardial Infarction.

Table 4

Sensitivity, selectivity, PPV, NPV values for T-MACS and TIMI risk class in predicting ACS.

Cut-off Point	Sensitivity	95% CI	Selectivity	95% CI	PPV	95% CI	NPV	95% CI
TIMI	41.18	18.4-67.1	89.08	84.9-92.4	17.9	10.2-29.6	96.3	94.6-97.5
T-MACS	100	80.5-100	51.19	45.3-57.1	10.6	9.6-11.8	100

CI: Confidence Interval, PPV: Positive predictive value, NPV: Negative Predictive Value.

the Student’s t-test was used when it did. ROC (Receiver Operating Characteristic) analysis was performed to distinguish patients according to TIMI and T-MACS risk class and to determine the cut-off point in determining 1-month mortality, ACS and MACE. Results are presented by Area Under the Curve (AUC), cut-off points, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). p-values <0.05 were considered statistically significant.

1. Results

In our study, 370 cases with suspected NSTEMI and meeting the in- clusion criteria were examined. STEMI was detected in 23 of these patients and they were excluded from this study. Sixteen patients left the study group because they were suspected of pregnancy, and 21 pa- tients stated that they wanted to withdraw from this study. A study group was formed with 310 patients. Of the patients participating in the present study, 54.2% were female and 45.8% were male, with a mean age of 49.7 +- 19.4 years (min:18, max:92). The 1-month mortal- ity rate of the patients was 1.3%, the MACE rate was 6.5%, and the ACS rate was 5.5%. When the T-MACS risk class distribution of the patients was examined, it was seen that 150 (48.4%) patients were in the very low-risk class, 72 (23.2%) in the low-risk class, 75 (24.2%) in the me- dium and 13 (4.2%) in the high-risk class. When the TIMI risk class distribution was examined, 271 patients (87.4%) were in the low-risk class, 31 (10%) were in the medium-risk class, and 8 (2.6%) were in the high-risk class. The general characteristics of the 310 patients in- cluded in this study are shown in Table 1.

A comparison of T-MACS and TIMI according to the study risk class is given in Table 2. According to the T-MACS rule-out criteria, 150 patients were included in the very low-risk class, and MACE and ACS were not detected among them. According to the TIMI rule-out criteria, 271 patients were classified as low risk and 10 ACS were seen among them. T-MACS correctly identified low-risk patients in 100% and TIMI in 96.3%. While ACS was detected in 92.3% of the patients in the high-risk class in the T-MACS score, ACS was detected in 25% of the pa- tients in the TIMI. As seen in Table 3, when the TIMI and T-MACS test characteristics were examined among patients who did not meet the rule-out criteria in predicting MACE, the selectivity detected higher in the TIMI score (88.97 vs. 51.72, respectively), but the sensitivity was low in TIMI (35 vs. 100, respectively). As can be seen in Table 4, when the test characteristics were compared between patients who did not meet the TIMI and T-MACS rule-out criteria in predicting ACS, the selectivity was higher in TIMI (51.19 vs. 89.08, respectively), but the sensitivity was lower (41.18 vs. 100, respectively).

While the area under the curve (AUC) was calculated as 0.622 (95% CI: 0.565-0.676) for the TIMI risk class and 0.926 (95% CI: 0.891-0.953)

for the T-MACS risk class, the findings showed that the T-MACS risk class was statistically more significant in differentiating MACE (p <

0.001). The ROC curve for TIMI and T-MACS risk class to predict MACE is shown in Fig. 1.

While the area under the curve (AUC) was calculated as 0.653 (95% CI: 0.598-0.706) for the TIMI risk class and 0.948 (95% CI: 0.917-0.970)

for the T-MACS risk class, the findings showed that the T-MACS risk class was statistically stronger in differentiating ACS (p < 0.001). The ROC curve created for TIMI and T-MACS risk class in predicting ACS is presented in Fig. 2.

1. Discussion

In this prospective study, we have shown that the T-MACS score is superior to TIMI in risk assessment and 1-month MACE estimation of patients who were followed up in the emergency department with a pre-diagnosis of the acute coronary syndrome but who did not have STEMI at the time of their admission to the emergency department.

When we look at the literature, in the study conducted by Stephen et al. in which the modified TIMI score and TIMI score were compared, the incidence of 30-day MACE in patients with TIMI low risk (<3 points) was 7.3%, while we found this rate to be 4.8% in low-risk patients in our study [16]. In a study by Henry Wamala et al., in which they compared nine Coronary risk scores, ischemic chest pain was present in 11% of pa- tients with TIMI low risk. In our study, we found chest pain of ischemic origin in 3.7% of low-risk patients [17]. In the study conducted by Body et al. in which they compared the four scoring systEMS used to decide on ACS in the emergency department, the incidence of ACS in high-risk pa- tients was 80.4% for T-MACS, 51.9% for TIMI, 92.3% for T-MACS and 25%

Fig. 1. ROC curve for TIMI and T-MACS risk class in predicting MACE.

ROC: Receiver operating characteristic, TIMI: Thrombolysis in Myocardial Infarction, T- MACS: Troponin-only Manchester Acute Coronary Syndromes, MACE: Major Adverse Car- diac Events.

Fig. 2. ROC curve for TIMI and T-MACS risk class in predicting ACS.

ROC: Receiver operating characteristic, TIMI: Thrombolysis in Myocardial Infarction, T- MACS: Troponin-only Manchester Acute Coronary Syndromes, ACS: Acute Coronary Syn- drome.

for TIMI [12]. While the high success of T-MACS in predicting ACS is consistent with the literature, we think that the low TIMI score is due to various reasons, such as having more anamnesis, patient incompati- bility and inability to give adequate anamnesis in emergency room conditions.

In the study conducted by Richard Body et al., NPV for ACS in very low-risk patients was 99.3% (95% CI 98.3% to 99.8%), and ACS was seen in <1% of patients in the very low-risk group. Also, ACS was excluded in 40.4% of patients [12]. In a study conducted by Body et al., in which four ACS risk scores were compared, ACS was excluded in 46.5% of patients presenting with chest pain with a sensitivity of 99.2% (95% CI 95.7% to 100.0%). In our study, a sensitivity of 100% (95% CI 80.5%-100%) was compatible with the literature, with 100% NPV excluding ACS in 48.3% of the patients [12].

While MACE was detected in 76.1% of high-risk cases in the confir- mation study of T-MACS and MACS score by Jaimi H Greenslade et al., MACE was found in 88.7% in high-risk patients in the study performed by Van Den Berg et al. [18,19]. In the validation study conducted by Body et al. 91.3% MACE was detected [12]. In our study, we found MACE in 92.3% of the cases in the high-risk class, which is consistent with the literature.

In the study conducted by Stephen PJ Macdonald et al., while the area under the ROC curve (AUC) for TIMI 1-month MACE was calculated as 0.71 (0.67 to 0.74), it was 0.78 (95% CI 0.74 to 0.81) in the study of Peter DW Reaney et al. [16,20]. In our study, the AUC for TIMI in predicting MACE was calculated as 0.622 (95% CI: 0.565-0.676). In the study of Body et al., in which they compared four ACS scores, the area under the ROC curve in ACS recognition for TIMI was 0.69 (95% CI 0.64 to 0.74), while it was 0.96 (95% CI 0.94 to 0.98) for T-MACS. In our study, the area under the ROC curve for ACS was 0.653 (95% CI: 0.598-0.706) for TIMI and 0.948 (95% CI: 0.917-0.970) for T-MACS. In

our study, we found T-MACS to be statistically more significant than TIMI in differentiating MACE and ACS (p < 0.001). The most important limitation of our study is that it is single-centered. Multicenter prospec- tive studies with more case numbers will help the clinician in the prediction of ACS and MACE and risk estimation.

1. Conclusion

In our study, we found that the T-MACS score was superior to TIMI in predicting ACS and predicting low risk (very low risk for T-MACS), high

risk and 1-month MACE in patients presenting to the emergency department with chest pain. Due to the advantages, for example, T-MACS can be easily calculated in emergency room conditions, T-MACS is statistically stronger in both ACS detection and MACE predic- tion than AUC values in ROC analysis (p < 0.001), T-MACS is more sensitive than TIMI in detecting risky patients in low-risk patients and has a higher NPV value, the findings suggest that the use of T-MACS is more appropriate than TIMI in risk scoring of NSTEMI cases in emergency services. In addition, the use of T-MACS is more appropriate than TIMI in risk scoring of NSTEMI cases since it is important for pa- tients to provide an accurate anamnesis for a clear evaluation of TIMI, and this is not always possible in emergency services.

Competing interests

Authors declare no conflict of interest.

Author contributions

Mucahit Kesgun performed methodology, formal analysis, data curation and writing original draft. Burcu Genc Yavuz performed methodology, formal analysis, data curation, conceptualization, writing original draft, review and editing. Dilay Satilmis performed methodol- ogy, formal analysis, conceptualization, data curation and resources. Sahin Colak performed methodology, formal analysis, data curation, resources, supervision, writing review and editing.

Acknowledgment funding

The authors did not apply for a specific grant for this research from any funding agency in the public, commercial or non-profit sectors.

Credit authorship contribution statement

Mucahit Kesgun: Methodology, Formal analysis, Data curation, Writing - original draft. Burcu Genc Yavuz: Methodology, Formal analysis, Data curation, Conceptualization, Writing - original draft, Writing - review & editing. Dilay Satilmis: Methodology, Formal analysis, Conceptualization, Data curation, Resources. Sahin Colak: Methodology, Formal analysis, Data curation, Resources, Supervision, Writing - review & editing.

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