A preliminary study of interactive questioning methods to assess and improve understanding of informed consent among patients with schizophrenia

Growing recognition of the inadequacy of traditional methods of providing informed consent, especially for individuals vulnerable to impaired decisional capacity, has spurred recent interest in how to assess and improve components of consent-related decision making. In this preliminary study, we aimed to compare different methods of interactive questioning during presentation of research consent information among patients with schizophrenia. Patients were randomized to receive either standard administration (SA) of a consent form or one of two interactive questioning methods: Corrective Feedback (CF), in which the correct answer was provided following the participant's response, or Errorless Learning (EL), in which correct answers were provided just prior to the question. The MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) was used to measure understanding, appreciation, reasoning, and expression of a choice following presentation of the consent form. There was no significant effect of condition (SA vs. EL vs. CF) on any of the components of decisional capacity. Understanding scores measured during the consent process were higher than those measured afterward, but the two scores were highly correlated. Thus, the results of this randomized study suggest that interactive questioning neither helped nor harmed understanding, appreciation, or reasoning among patients with schizophrenia. Other considerations, however, may favor use of such methods in the consenting process.     

Relationship of individual cognitive abilities to specific components of decisional capacity among middle-aged and older patients with schizophrenia

Prior empirical studies suggest that cognitive impairment is the strongest predictor of capacity to consent to research among persons with schizophrenia. Yet, despite the frequency and importance of cognitive deficits and impaired decisional capacity in schizophrenia, the scope of neuropsychological testing in most published reports in this area has been relatively narrow. In the present study of 70 people with schizophrenia aged 40 to 70 years we evaluated decisional capacity with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). Participants were also evaluated with standardized rating scales of psychopathology and level of insight and with a comprehensive neuropsychological test battery that permitted evaluation of 7 specific cognitive abilities. Results showed that the strongest correlates of capacity (particularly, understanding and appreciation of disclosed information) were cognitive test scores, but there was little evidence of differential relationships between individual cognitive abilities and specific dimensions of capacity. Understanding was also correlated with severity of negative symptoms and of general psychopathology, but not with age, education, severity of positive or depressive symptoms, or level of insight. Understanding improved over successive presentations of consent-relevant information. The results suggest that age and diagnosis should not be viewed as determinants of decisional capacity; investigators should be alert to the presence of cognitive deficits, as well as negative symptoms. Also, an interactive dialogue between patient and investigator with repeated presentation of information is likely to aid understanding of disclosed information among patients with schizophrenia.     

Prevalence and correlates of adequate performance on a measure of abilities related to decisional capacity: differences among three standards for the MacCAT-CR in patients with schizophrenia

Despite the availability of structured decision-making capacity assessment tools, insufficient guidance exists for applying their results. Investigators often use cutpoints on these instruments to identify potential subjects in need of further assessment or education. Yet, information is lacking regarding the effects of different cutpoints on the proportion and characteristics of individuals categorized as possessing adequate or impaired decisional abilities for consent to research. To demonstrate the potential impact of different standards, we informed 91 individuals, aged 50 or older with a diagnosis of schizophrenia or schizoaffective disorder, about a hypothetical clinical trial, and assessed their decisional abilities with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). Three published MacCAT-CR-based standards were applied to participants' scores to examine the rates and correlates of categorical determinations of adequate performance. The three standards ranged in stringency: the most stringent incorporated cutpoints on all three of the major MacCAT-CR subscales (Understanding, Appreciation, and Reasoning); the other two standards required threshold performance only on the Understanding subscale. The most stringent standard resulted in a 57% rate of impaired performance; the intermediate standard, 19%; and the least stringent standard, 8%. Nearly half of the participants (n=45) were classified as having performed adequately by the least stringent standard yet inadequately by the most stringent. The majority of these 45 were impaired on the Appreciation subscale (n=9), Reasoning (n=15), or both (n=18). Cognitive functioning was correlated with performance status for the more stringent standards. These findings underscore the need for refinement of capacity assessment procedures and for improvements in the use of capacity assessment tools for screening purposes and to assist in categorical capacity determinations.     

A new brief instrument for assessing decisional capacity for clinical research

CONTEXT: There is a critical need for practical measures for screening and documenting decisional capacity in people participating in different types of clinical research. However, there are few reliable and validated brief tools that could be used routinely to evaluate individuals' capacity to consent to a research protocol. OBJECTIVE: To describe the development, testing, and proposed use of a new practical instrument to assess decision-making capacity: the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC). The UBACC is intended to help investigators identify research participants who warrant more thorough decisional capacity assessment and/or remediation efforts prior to enrollment. DESIGN, SETTING, AND PARTICIPANTS: We developed the UBACC as a 10-item scale that included questions focusing on understanding and appreciation of the information concerning a research protocol. It was developed and tested among middle-aged and older outpatients with schizophrenia and healthy comparison subjects participating in research on informed consent. In an investigation of reliability and validity, we studied 127 outpatients with schizophrenia or schizoaffective disorder and 30 healthy comparison subjects who received information about a simulated clinical drug trial. Internal consistency, interrater reliability, and concurrent (criterion) validity (including correlations with an established instrument as well as sensitivity and specificity relative to 2 potential "gold standard" criteria) were measured. MAIN OUTCOME MEASURES: Reliability and validity of the UBACC. RESULTS: The UBACC was found to have good internal consistency, interrater reliability, concurrent validity, high sensitivity, and acceptable specificity. It typically took less than 5 minutes to administer, was easy to use and reliably score, and could be used to identify subjects with questionable capacity to consent to the specific research project. CONCLUSION: The UBACC is a potentially useful instrument for screening large numbers of subjects to identify those needing more comprehensive decisional capacity assessment and/or remediation efforts.     

Decision-making capacity for research participation among individuals in the CATIE schizophrenia trial

OBJECTIVE: Uncertainty regarding the degree to which persons with schizophrenia may lack decision-making capacity, and what the predictors of capacity may be led us to examine the relationship between psychopathology, neurocognitive functioning, and decision-making capacity in a large sample of persons with schizophrenia at entry into a clinical trial. METHOD: In the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial, a clinical trial sponsored by the National Institute of Mental Health designed to compare the effectiveness of antipsychotic drugs, subjects were administered the MacArthur Competence Assessment Tool-Clinical Research (MacCAT-CR) and had to demonstrate adequate decision-making capacity before randomization. The MacCAT-CR, the Positive and Negative Syndrome Scale (PANSS), and an extensive neurocognitive battery were completed for 1447 study participants. RESULTS: The neurocognitive composite score and all 5 neurocognitive subscores (verbal memory, vigilance, processing speed, reasoning, and working memory) were positive correlates of the MacCAT-CR understanding, appreciation, and reasoning scales at baseline. Higher levels of negative symptoms, but not positive symptoms, were inversely correlated with these three MacCAT-CR scales. Linear regression models of all three MacCAT-CR scales identified working memory as a predictor; negative symptoms made a small contribution to the understanding and appreciation scores. CONCLUSIONS: Negative symptoms and aspects of neurocognitive functioning were correlated with decision-making capacity in this large sample of moderately ill subjects with schizophrenia. In multiple regression models predicting performance on the MacCAT-CR scales, working memory was the only consistent predictor of the components of decision-making capacity. Individuals with schizophrenia who have prominent cognitive dysfunction, especially memory impairment, may warrant particular attention when participating in research.     

Competence to consent to research among long-stay inpatients with chronic schizophrenia

OBJECTIVE: Questions have been posed about the competence of persons with serious mental illness to consent to participate in clinical research. This study compared competence-related abilities of hospitalized persons with schizophrenia with those of a comparison sample of persons from the community who had never had a psychiatric hospitalization. METHODS: The study participants were administered the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), a structured instrument designed to aid in the assessment of competence to consent to clinical research. The scores of 27 persons who met DSM-IV criteria for schizophrenia who were long-stay patients on a state hospital research ward were compared with those of 24 individuals from the community who were of similar age, gender, race, and socioeconomic status. RESULTS: Significant differences were found between the patients and the community sample on three measures of competence-related abilities: understanding, reasoning, and appreciation. Degree of psychopathology and cognitive functioning were significantly negatively correlated with understanding and appreciation among the patients with schizophrenia. Length of hospitalization was significantly negatively correlated with all measures of decision-making capacities. CONCLUSIONS: The generally poor performance of the long-stay patients with chronic schizophrenia highlights the difficulties this group is likely to encounter in providing consent to research. However, variation across the sample points to the need for individualized assessment and for validated techniques for facilitating decision making in the face of decisional impairments.     

Decisional capacity for informed consent in schizophrenia research

BACKGROUND: The adequacy of subjects' informed consent to research is the focus of an important public and professional debate. The potential impairment of decisional capacity in persons with schizophrenia is central to the discussions. This study ascertains the decisional capacity for informed consent in schizophrenic research subjects, to determine if reduced capacity relates to specific aspects of psychopathologic features and to test the hypothesis that reduced capacity can be remediated with an educational informed consent process. METHODS: Decisional capacity was assessed for 30 research subjects with schizophrenia and 24 nonill (normal) comparison subjects. Measures of psychopathologic features and cognition were obtained for the subjects with schizophrenia. Subjects who performed poorly on the decisional capacity measure received an educational intervention designed to improve their ability to provide informed consent and were then retested. RESULTS: The patient group did not perform as well as the controls on initial decisional capacity assessment. Poor performance was modestly related to the extent of symptoms but robustly related to cognitive impairments. Following the educational intervention, the performance of subjects with schizophrenia was equal to that of the nonill comparison group. CONCLUSIONS: Many persons with schizophrenia may be challenged by the cognitive demands of an informed consent process for research participation. In many cases, their reduced capacity can be compensated by a more intensive educational intervention as part of the informed consent process.     

Assessment of capacity to consent to research among older persons with schizophrenia, Alzheimer disease, or diabetes mellitus: comparison of a 3-item questionnaire with a comprehensive standardized capacity instrument

CONTEXT: Considerable discussion surrounds issues related to the capacities of neuropsychiatric patients to consent to research, yet few empirical investigations have directly compared decisional capacity among patients with a serious mental illness with that among patients with neurologic or medical conditions. Also, as requirements for formal assessment of decisional capacity are becoming more common, there is a clear need to identify efficient screening methods. OBJECTIVES: To compare decisional capacity among 3 diagnostic groups, and to examine the degree to which impaired understanding can be detected with a brief set of screening questions. SETTING: Outpatient veterans hospital clinic and university-based neuropsychiatric research centers. DESIGN/ PARTICIPANTS: Cross-sectional comparison of decisional capacity among older (>/=60 years) outpatients with schizophrenia (n = 35), mild to moderate Alzheimer disease (n = 30), and type 2 diabetes mellitus (n = 36), and determination of sensitivity and specificity of a screening measure. MAIN OUTCOME MEASURES: Three-item decisional capacity questionnaire and the MacArthur Competence Assessment Tool for Clinical Research. RESULTS: Patients with diabetes mellitus performed the best on the capacity instruments, patients with Alzheimer disease had the worst performance, and patients with schizophrenia were intermediate. However, there was considerable heterogeneity within each group. Even within diagnostic groups, the level of cognitive functioning (measured with the Mini-Mental State Examination) was generally the best predictor of decisional capacity (particularly in the understanding component). The 3-item questionnaire was sensitive to impaired understanding as measured with the MacArthur Competence Assessment Tool for Clinical Research understanding subscale. CONCLUSIONS: Decisional capacity differed among the 3 groups; there was considerable heterogeneity even within each diagnostic group, so individualized consideration of capacity may be warranted. The level of cognitive deficits is 1 potential marker of which participants should receive comprehensive capacity evaluations, but sensitive brief questionnaires targeting key aspects of disclosed information may also provide an effective means of screening for participants warranting comprehensive capacity evaluations.     

A direct comparison of research decision-making capacity: schizophrenia/schizoaffective, medically ill, and non-ill subjects

To characterize predictors of impairment in research decision-making capacity, we undertook a direct comparison of schizophrenia/schizoaffective (n=52), medically ill (diabetic; n=51), and non-ill (n=57) subjects. Scores on the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) were correlated with demographic variables and scores on the Positive and Negative Syndrome Scale (PANSS), Mini-Mental State Examination (MMSE), and Short-Form-36 (SF-36). Across diagnoses, cognitive capacity, physical functioning, and a diagnosis of mental illness had the greatest impact on decision-making capacity, with level of education also having an impact. 69-89% of schizophrenia/schizoaffective subjects attained MacCAT-CR subscale scores achieved by almost all comparison (98-100%) and medically ill (94-100%) subjects. Positive, negative, and general psychotic symptoms correlated with poorer scores. Prior research experience, number of queries used during interview, and emotional functioning also predicted MacCAT-CR scores. These data suggest that investigators and IRBs should consider a number of variables, many of which reach across diagnoses, as they decide which populations and individual subjects may require more intensive screening for decisional impairment or educational interventions to improve their abilities to make capable decisions about research participation.     

Capacity to provide informed consent for participation in schizophrenia and HIV research

OBJECTIVE: The degree to which people with psychiatric symptoms and cognitive dysfunction can provide informed consent to participate in research is a controversial issue. This study was designed to examine the capacity of subjects with schizophrenia and subjects with HIV to provide informed consent for research participation and to determine the relationships among cognitive dysfunction, psychiatric symptoms, and decisional capacity. METHOD: Twenty-five men and women with a DSM-IV diagnosis of schizophrenia and 25 men and women with HIV were recruited. The groups were compared in terms of neuropsychological functioning, psychiatric symptoms, and ability to provide informed consent to a hypothetical drug trial. RESULTS: Eighty percent of the subjects with schizophrenia and 96% of the HIV-positive subjects demonstrated adequate capacity to consent to the hypothetical drug trial, but subjects in the schizophrenia group had significantly lower scores on two of the four aspects of decisional capacity. For the subjects with schizophrenia, neuropsychological functioning and psychiatric symptoms (e.g., apathy and avolition), but not psychotic symptoms (e.g., hallucinations and delusions), were significantly associated with decisional capacity. CONCLUSIONS: The majority of subjects who are recruited and willing to participate in schizophrenia or HIV research will have adequate capacity to provide consent. Cognitive dysfunction and the symptoms shown to be associated with impaired decisional capacity are not unique to schizophrenia and may occur with many other forms of illness. These findings underscore the importance of considering how decisional capacity will be assessed in all types of research, regardless of the specific condition being studied.     

Validation of Chinese version of the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) in patients with schizophrenia spectrum disorders

There is a lack of validated instruments assessing the decision-making capacity to consent to clinical research of patients with schizophrenia spectrum disorders who speak Chinese. This study aimed to determine the validity and reliability of the Chinese version of MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). The MacCAT-CR using a hypothetical study, the Positive and Negative Syndrome Scale (PANSS), the Mini-Mental State Examination (MMSE) assessed 139 patients with schizophrenia or schizoaffective disorder. The Cronbach's alpha coefficient was 0.74. The intra-class coefficients for understanding, appreciation, and reasoning scores ranged from 0.53 to 0.81. Regarding validity, the understanding, appreciation and reasoning scores were negatively correlated with the PANSS (r ranged from −0.27 to −0.33), and the negative subscale score (r ranged from −0.31 to −0.37) as well as positively correlated with the MMSE (r ranged from 0.26 to 0.43). All pvalues were less than 0.01. The factor analysis explained 57.6 % of the total variance; specifically, Components 1 and 2 contributed 44.5% and 13.1 % of the variance respectively. These findings indicate that the Chinese version of the MacCAT-CR is a reliable and valid instrument to assess the decision-making capacity to consent to clinical research of patients with schizophrenia spectrum disorders.     

Sense and nonsense: an essay on schizophrenia research ethics

In this essay, the authors select topics from the current debate on the ethics of schizophrenia research. Accepting competent and voluntary informed consent as essential for most projects, the authors discuss the relation of diagnosis to decisional capacity, the respective roles of psychosis and cognitive impairments in decisional capacity, and whether impairments in capacity can be remediated. The roles of investigator, external agent, patient subject, and family or surrogate in the informed consent process are reviewed. A lack of understanding of the treatment of persons with schizophrenia has distorted and inflamed public discussion of issues such as 'withholding treatment'. A standard, based in common sense, is proposed: for viewing protocols; for allowing autonomy and altruism despite diagnostic class; and, for a meaningful discussion of what is meant by and what should be done about 'risk without direct benefit' protocols.     

Using a brief intervention to improve decisional capacity in schizophrenia research

Studies have shown that individuals with psychiatric or general medical illness can benefit from interventions designed to enhance decisional capacity for research informed consent. In some cases, interventions have been rather lengthy or complex. The current study was designed to determine whether a brief intervention could improve decisional capacity in people with schizophrenia. Thirty individuals with schizophrenia and 30 healthy comparison participants were presented with a hypothetical research scenario. Decisional capacity was assessed with the MacArthur Competence Assessment Tool-Clinical Research version. Those with schizophrenia received a brief intervention aimed at improving understanding of the research protocol, after which decisional capacity was reassessed. A neuropsychological battery and symptom rating scales were also administered. At baseline, the schizophrenia group earned significantly lower scores than the comparison group on 2 aspects of decisional capacity (understanding, appreciation). At follow-up, the schizophrenia group had improved significantly on understanding and was no longer significantly different from the comparison group on any of the 4 dimensions of decisional capacity. Follow-up analyses also showed a significant effect of the intervention on a subset of the schizophrenia group who had performed most poorly at baseline. Participants with schizophrenia earned significantly lower scores than those in the comparison group across multiple neuropsychological domains. These findings add to the existing literature indicating that brief interventions can improve decisional capacity in individuals with schizophrenia, despite the fact that the illness typically causes significant cognitive dysfunction. The use of such interventions will enable a larger number of people with schizophrenia to make informed decisions regarding research participation.     

Decisional capacity of depressed elderly to consent to electroconvulsive therapy

The purpose of this article is to determine the abilities of severely depressed elderly to consent to electroconvulsive therapy (ECT) and to investigate the impact of educational intervention on their capacity. Forty severely depressed adults referred for ECT, with Mini-Mental State Examination scores greater than 20, were recruited. Using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), decisional capacities were assessed at baseline and reassessed after education. Between the 2 assessments, all subjects received standard education, and half of the group was subsequently randomized to receive further education. At baseline, the geriatric group scored lower on understanding, reasoning, and choice and higher on appreciation. After education, all MacCAT-T scores increased for both age groups. Depressed elderly in the sample, as a group, had adequate decisional capacities to consent to ECT. They showed greater improvement in decisional capacity with education. The findings highlight the importance of providing education to the elderly to optimize their ability to give informed consent.     

Improving understanding of research consent in middle-aged and elderly patients with psychotic disorders.

Individuals with schizophrenia may show impaired capacity to make decisions about participating in research, yet these patients also show considerable heterogeneity in decisional abilities. Problems with procedures contribute to patients' difficulties in understanding consent forms. Few studies have focused on improving comprehension of research consent in older patients with psychotic disorders. In this study, 80 middle-aged and elderly outpatients with schizophrenia or related psychotic disorders and 19 normal comparison subjects were randomized to receive a routine consent (RC) or enhanced consent (EC) procedure. The EC procedure consisted of a computerized slide show incorporating more structure and review of important information. A comprehension test was administered after the consent procedure; subjects were given up to three trials of the post-test to answer all of the questions correctly. Overall, the normal comparison subjects obtained a higher score on the post-consent comprehension test than the patients. Within each of these two groups, those who received EC had better comprehension than those who received RC. Interestingly, EC patients did not differ significantly from RC normal comparison subjects in their post-test scores. Among the patients, comprehension test scores correlated with level of education and cognitive performance.     

Informed consent and neuroanatomic correlates of intentionality and voluntariness among psychiatric patients

The authors examine the less-studied components of patients' autonomous decision making, or decisional autonomy, in the light of current research in psychiatry and neuropsychology and developments in the construct of informed consent. The three components of decisional autonomy-understanding, intentionality, and noncontrol or voluntariness-are related to clinical constructs in psychiatry and neuropsychology, in particular to executive control functions. The authors review studies that examine deficits in prefrontal cerebral function in schizophrenia, depression, and some anxiety disorders that are related to intentionality and voluntariness. Assessment of decisional autonomy should encompass evaluation of impaired intentionality and voluntariness, not simply impaired understanding. The main response to finding such impairments should be to provide treatment to ameliorate them. New strategies for psychiatric care should be developed to address the clinical challenges of an increasingly complex view of decisional autonomy.     

Current state of research on decision-making competence of cognitively impaired elderly persons.

As the number of cognitively impaired elderly persons increases, the need for evidence-based assessments of their capacity to consent to medical treatment and research participation will grow. The authors conducted an electronic and manual literature search for all English-language articles examining the decision-making capacity of elderly persons with dementia or cognitive impairment, reviewing articles in relation to key areas of methodological, clinical, and policy importance. The 32 relevant studies identified were highly heterogeneous, even in their definitions and measurements of decisional capacity. Although incapacity is common, many persons with dementia are capable of making their own medical and research decisions. In Alzheimer disease, memory and executive-function deficits predict decisional impairment. Still, at least in early stages of dementia, interventions may improve decisional abilities. Short and simple cognitive screening may be useful by identifying persons in need of more intensive evaluations. The use of expert judgment-based methods may mitigate the problem of a lack of a criterion standard for competence. Research into the decision-making competence of cognitively impaired elderly persons is a growing field. It is beginning to yield findings with practical implications for preserving the autonomy and welfare of this group of vulnerable elderly patients.     

Decisional capacity of severely depressed patients requiring electroconvulsive therapy

OBJECTIVE: The decisional capacity of severely depressed people frequently comes into question. The ability to improve this decisional capacity through educational efforts alone is not known. Our study aimed to determine the decisional capacity of severely depressed people requiring electroconvulsive therapy (ECT), and whether educational interventions improve their ability to provide informed consent for ECT. MATERIALS AND METHODS: Forty subjects with severe depression were recruited. Using the MacArthur Competence Assessment Tool for Treatment instrument, decisional capacity was assessed at baseline and reassessed after education. All of the subjects received standard education. Additionally, half were blindly randomized to receive an experimental educational intervention. RESULT: SAt baseline, there was no statistical difference in the decisional capacity between the standard and experimental intervention groups. After educational interventions, all four areas of decisional capacity improved for both groups (understanding p < 0.001, reasoning p < 0.001, appreciation p = 0.031, choice p = 0.006). However, there was no measurable additional improvement in scores for those randomized to receive additional education. CONCLUSION: Our findings indicate that this group of severely depressed people had good decisional capacities to give informed consent. Education improved their decisional capacity. There is an endpoint beyond which additional educational intervention does not result in measurable improvement in decisional capacity.     

Diminished capacity to make treatment decision for COVID-19 vaccination in schizophrenia

Recent evidence suggests that people with schizophrenia are at high risk for severe COVID-19 and should be prioritized for vaccination. However, impaired decision-making capacities could negatively affect the uptake of COVID-19 vaccination in this population. Capacity to consent to COVID-19 vaccination was assessed in 80 outpatients with schizophrenia. Using the MacArthur Competence Assessment Tool for Treatment, 56.3% of the sample were classified as having diminished capacity to consent to the vaccination. Diminished capacity to consent to COVID-19 vaccination was associated with lower vaccination rates, poorer cognition and higher level of psychotic symptoms. Developing interventions for enhancing informed consent for vaccination is urgent within this population.

     

Decisional capacity of patients with schizophrenia to consent to research: taking stock

With the growth in recent years of studies of decisional capacity for research among people with schizophrenia, this is an opportune time to ask three questions: What have we learned from these studies? What remains to be learned? And what normative issues still need to be resolved? Among the things learned are that patients with schizophrenia, as a group, have lower scores on measures of decisional capacity than normals, but higher performance than patients with dementia. However, performance is highly variable within the group, correlates most strongly with neuropsychological impairment, and seems susceptible in many patients to successful remediation. The issues that remain in need of exploration include the development of a brief screening instrument for decisional capacity that can be used routinely, and the identification of those patients most likely to benefit from more intensive informational procedures. Finally, among the normative issues still in need of resolution are the degree of capacity needed to consent to research participation, how to deal with fluctuating capacity during research projects, and the legitimate extent of surrogate consent for participation of incompetent patients in research.