Background
Disorders of language, spatial perception, attention, memory, calculation and praxis are a frequent consequence of acquired brain damage (in particular, stroke and traumatic brain injury (TBI)) and a major determinant of long-term disability. The possibility to effectively rehabilitate aphasia and other cognitive disorders can thus be expected to have a considerable impact on the burden of neurological disease. Many different ment approaches have been suggested. While the early treat-ments were developed on a purely empirical basis, in recent years there has been an effort to propose rehabilitation proce-dures based on the limited available knowledge of the neuro-science of recovery and on models of learning. Evidence about the effectiveness of cognitive rehabilitation is limited, with only a small number of randomized controlled trials (RCTs) which are generally of low quality. There is a need for adequately designed studies in this area, which should take into account specific problems such as patient heterogeneity, and the diffi-culties in the standardization of treatment techniques.
Framing clinical questions and general
inaccessible after brain damage. The treatment approach is centred on language comprehension, in particular in the auditory modality, and aphasia is considered as a unitary dis-order, with individual patients differing in term of the severity of impairment, rather than on the specific features of linguis-tic breakdown. Behavioural modification emphasizes the behavioural approach to the learning process, and is an appli-cation to aphasia treatment of programmed instruction based on operant conditioning. The techniques include shaping and fading, and other principles of behaviour modification, which are incorporated in many other treatment approaches. Neo-associationism includes several treatment programs, which focus on a detailed psycholinguistic and neurological descrip-tion of the classic aphasic syndromes [9], and comprise very heterogeneous approaches, such as Melodic Intonation Ther-apy and Treatment of Aphasic Perseveration. The neurolin-guistic-cognitive approach originates from the early attempts to apply linguistic theory to aphasia in the sixties and seven-ties, and flourished with the development of cognitive neu-ropsychology. The emphasis is on detailed assessment of language in single cases, and analysis of the pattern of linguis-tic dysfunction on the basis of a model of normal processing, resulting in a ‘functional’ diagnosis. The assumption is that a precise identification of the locus of functional damage pro-vides the grounds for a rational intervention [10]. Finally, pragmatic approaches aim at improving the patient’s ability to communicate, regardless of the linguistic or non-linguistic strategies. In the most widely known programme, Promoting Aphasics’ Communicative Effectiveness (PACE) [11], thera-pist and patient are engaged in situations in which they exchange ‘real’ information. Pragmatic principles are now incorporated in many eclectic treatment programmes, with a particular indication for severe aphasia.
The need to establish the effectiveness of aphasia rehabilita-tion has stimulated a number of investigarehabilita-tions that are based on a variety of methodologies. There is one systematic review of studies limited to post-stroke aphasia that addresses the effectiveness of language rehabilitation and covers articles about speech and language rehabilitation up to January 1999 [12]. The conclusion of the review is that ‘speech and lan-guage therapy treatment for people with aphasia after a stroke has not been shown either to be clearly effective or clearly ineffective within an RCT. Decisions about the management of patients must therefore be based on other forms of evidence.
Further research is required to find out if speech and lan-guage therapy for aphasic patients is effective. If researchers choose to do a trial, this must be large enough to have adequate statistical power, and be clearly reported.’ This con-clusion is based on 12 studies all of which were considered of poor quality.
Including lower classes of evidence has led other authors to different conclusions [13,14]. The findings of three large stud-ies all indicate significant benefits of treatment [15,16,17].
Single case studies have also shown large treatment effects
in aphasic patients [18]. Some of the RCT comparing therapy with unstructured stimulation were based on a very limited number of treatment sessions. A recent meta-analysis [19]
found a significant treatment effect if treatment was frequent and intensive over a short period of time (8.8 h of therapy per week for 11.2 weeks), compared to less frequent and inten-sive treatment over a long period of time (approximately 2 h per week for 22.9 weeks). Total length of therapy was signifi-cantly inversely correlated with mean change in Porch Index of Communicative Abilities (PICA) scores. The num-ber of hours of therapy provided in a week was significantly correlated to greater improvement on the PICA and the Token Test. These results indicate that an intense therapy programme provided over a short period of time can improve outcomes of speech and language therapy for stroke patients with aphasia.
2. Rehabilitation of ULN
Among patients with unilateral spatial neglect due to stroke how does the visual or visuo-spatial training improve attentional skill or general disability?
ULN is a frequent manifestation of damage to the right hemi-sphere. In the Copenhagen study, ULN was present in 23% of stroke patients in the acute stage [20]. The presence of ULN beyond the acute stage has been associated with poor outcome in terms of independence [21] and considerable effort has therefore been devoted to its rehabilitation. Several recent reviews are available [22,23,24], including the Cochrane Systematic Review [25]. The latter analysed 15 studies and found evidence that ULN rehabilitation resulted in significant and persisting improvements in performance on impairment level assessments. There was, however, insufficient evidence to confirm or exclude an effect of cognitive rehabilitation at the level of disability or return to home following discharge from hospital. Several different approaches are currently used for neglect rehabilitation. Visual scanning training was shown to improve significantly neglect in one class I study [26].
Spatiomotor or visuospatiomotor cueing improved neglect sig-nificantly in another class I study [27]. There is less evidence for the effectiveness of combined training of visual scanning, reading, copying and figure description, visual cueing with kinetic stimuli, video feedback and visuomotor feedback, train-ing of sustained attention, increastrain-ing of alertness or cuetrain-ing of spatial attention.
Several studies investigated effects that aimed at influencing multisensory representations. Generally, these studies demon-strated transient effects, lasting little longer than the end of the appropriate stimulation. The methods include vestibular stimu-lation by cold-water infusion into the left outer ear canal [28], galvanic vestibular stimulation, transcutaneous electrical stimulation of the left neck muscles, neck muscle vibration and changes in trunk orientation. The use of prism goggles deviating by 10 degrees to the right, introduced relatively 80 Part 2: Neurological symptoms/problems
recently, was shown to improve significantly, in a transient fashion, neglect symptoms [29,30]. Computer training was note effective in one class I study [31]. A more recent class II study showed statistically significant improvement in wheel chair mobility [32].
In conclusion, there is evidence for the effectiveness of visual scanning training and of visuo-spatio-motor training in ULN. Lower levels of evidence are available for the combined training of visual scanning, reading, copying and figure description, trunk orientation, neck vibration and forced use of left eye. Other treatments need to be tested in further studies such as the use of prism goggles, video feedback, training of sustained attention and alertness, chaloric or galvanic vestibu-lar stimulations as well as transcutaneous electrical stimulation of neck muscles. Visual cueing with kinetic stimuli and the use of computers in neglect rehabilitation remain controversial.
3. Rehabilitation of attention disorders
Among patient with attention disorders due to acute or sub-acute TBI or stroke, how does attentional training improve concentration and alertness or reduce general disability?
Attention deficits follow many types of brain damage, including stroke and TBI [33]. The Cochrane Review [34]
identified two studies [35] showing that attention training improved sustained attention in stroke. A very important distinction is between studies conducted in the acute and post-acute stage. In the acute stage, one class I study [36] com-pared the effectiveness of focused treatment consisting of sequential, hierarchical interventions directed at specific atten-tion mechanisms versus unstructured intervenatten-tion consisting of non-sequential, non-hierarchical activities requiring mem-ory or reasoning skills. Both groups improved to a similar degree and the observed improvements are probably due to spontaneous recovery. One class II study [37] used a multiple baseline design across subjects and evaluated a programme for the remediation of processing speed deficits in patients with severe TBI. Although the authors reported no benefit or generalization of effects of attention training there was improvement in some patients when practice on attention training tasks was combined with therapist feedback and praise. In another class II study [38], subjects with lateralized stroke showed beneficial effects of attention training on five of 14 outcome measures, especially on measures of perceptual speed and selective attention in left hemisphere lesions. Three class I studies assessed the attention treatment effectiveness during the post-acute period of rehabilitation [39,40,42]. In one study [39] patients with attention dysfunction showed marked improvement immediately after training on two measures of attention; however, when premorbid intelligence score and time since injury were added as covariates, the treatment effect was no longer significant. At 6-month fol-low-up, the treatment group showed continued improve-ment and superior performance compared to the control group
on tests involving auditory-verbal working memory. The authors suggested that the improvement, continuing over the follow-up period, was consistent with a strategy-training model, as it becomes increasingly automated and integrated into a wider range of behaviours. Another post-acute class I study [40] dealt with community dwelling patients with moderate to severe brain injury. The experimental attention training group improved significantly more than the alterna-tive (memory) treatment group on four attention measures administered throughout the treatment period, although the effects did not generalize to the second set of neuropsy-chological measures. Two other studies using a crossover design [41,42] reported superiority of ‘attention process train-ing’ compared to therapeutic support. In addition, the ‘time pressure management’ programme demonstrated greater improvement compared to a generic ‘concentration’ pro-gramme. Several attempts were made to establish the differen-tial role for effectiveness of training of specific components of attention. A Class II study [43] on TBI investigated four differ-ent sub-processes of attdiffer-ention: cognitive flexibility, speed of processing, interference and working memory. The findings support the view that there are different sub-processes of attention that can be trained specifically and this may have implications for neuropsychological assessment and rehabil-itation and may have implications for neuropsychological assessment and rehabilitation. Improvements in speed of processing appear to be less robust than improvements on non-speeded tasks [37]. Moreover, several studies suggest greater benefits of attention training on more complex tasks requiring selective or divided attention than on basic tasks of reaction time or vigilance [38,39].
In conclusion, there is class I evidence for attention training in the post-acute phase after TBI. On the other hand, there is insufficient evidence to distinguish the effects of specific atten-tion training from spontaneous recovery or more general cog-nitive interventions during the acute period of recovery and inpatient rehabilitation for patients with moderate-to-severe TBI and stroke.
4. Rehabilitation of memory
Among patients with memory problems due to TBI or stroke how does memory rehabilitation (internal and external memory aids) improve memory function or general disability?
In the US, the prevalence of TBI is 5.3 million and there is an incidence of over 1.7 million cases per year. However, informa-tion on the prevalence of memory impairment after TBI is scarce. One study reported that nearly a fourth (25%) of those having sustained TBI suffer from memory problems [44]. The prevalence of stroke in the US is 4.5 million and there is an incidence of 600,000 cases per year. On an international basis, the prevalence of stroke is over 35 million with an incidence of over 6 million cases annually. Although memory problems are commonly reported after TBI they are often neglected in stroke Chapter 10: Cognitive rehabilitation of non-progressive neuropsychological disorders 81
patients although a comprehensive assessment frequently shows memory problems also after stroke. Reliable statistics for stroke patients, however, is virtually non-existent, and even less is known about the efficacy of intervention of memory problems in these patients. Overall, clinical observation shows that some degree of spontaneous recovery or improvement of memory usually occurs but not much is known about the interaction between spontaneous recovery and intervention.
The need to establish the effectiveness of memory rehabilita-tion has stimulated a wide range of studies. Unfortunately, however, only few of these studies meet the critical standards for evaluating scientifically proven measures of prevention and treatment of neurological diseases and disability. Gener-ally, approaches to memory rehabilitation either target to restore or optimize damaged or residual functions, or they are directed towards compensating for lost or deficient func-tions (for a summary see Ref. [45]). Evidence-based studies have most frequently investigated techniques in memory rehabilitation that include the use of internal and external memory aids, assistive electronic technologies and pharma-cological agents. In what follows a summary of the findings of memory rehabilitation techniques reported in controlled studies is provided. The summary is based on two recom-mendations [1,13] and two systematic reviews [14–46]. It should be noted that the criteria according to which authors have included studies in their reviews and the recommenda-tions based on the reviews differ.
The use of internal memory aids
For patients with mild memory impairment compensatory memory training has been recommended [1,13,14]. It seems, however, unlikely that this pertains to all patient groups and types of memory impairment. For example, there is only one controlled study investigating the effectiveness of training compensatory memory strategies in a few (six) stroke patients, and this study did not report positive effects [47]. Although for TBI patients there are more evidence-based reports on the use of memory strategies, the findings are controversial pos-sibly due to the difference in the training techniques used and the heterogeneity of the groups investigated. For example, one randomized-controlled study reported positive effects of visual imagery training on memory functioning in TBI patients [48]. The interpretability of this study is, however, severely hampered by the small sample size (12 patients in each experimental group with 3 dropouts) and the little or no control over external variables such as patient distribution over seven different rehabilitation centres and patients being either in- or outpatients. Another technique that has shown some beneficial effects is the errorless learning technique. In this technique people are prevented from making errors and this is compared to errorful learning where people are allowed to make mistakes (e.g. trial-and-error learning) (for a summary see Ref. [49]). It seems, however, that the benefit of errorless learning depends on the type of task used, the way in which
memory is tested and on the severity of the memory impair-ment. Finally, the spacing-of-repetitions procedure has also shown some efficacy in improving learning in TBI patients [50,51]. This technique is based on the spacing effect, which has been shown to improve learning and memory when repeated trials are distributed over time (spaced repetitions).
The use of external memory aids
Controlled studies generally support the efficacy of external non-electronic memory aids such as calendars, lists, note-books and diaries (for a summary see Ref. [1]). The effective-ness of these memory aids seems to be boosted by combining them with internal memory strategy training. However, there is some indication that not all aids or strategies are similarly beneficial [52].
The use of assistive electronic technologies
Computers, paging systems, voice organizers and virtual environments have all been used to enhance memory per-formance. A few well controlled studies have demonstrated the efficacy of paging systems and voice organizers to enhance learning and improve activities of daily living (ADL) particu-larly in patients with moderate to severe memory impair-ments (for a summary see Ref. [1,13,14]). Despite the generally reported success of using memory assisted computer training and virtual environments, it is currently not clear whether they are superior to conventional methods as a comparison with conventional methods is still missing.
5. Rehabilitation of apraxia
Among patients with apraxia due to acquired brain damage, how does behavioural training programmes or teaching compensatory strategies improve praxis or reduce general disability?
Although apraxia occurs frequently after acquired brain damage [53], the literature on recovery and treatment is minimal. Several reasons for this lack of evidence can be identified [54]. First, patients with apraxia often seem to be unaware of their deficit and rarely complain. Second, many researchers believe that recovery from apraxia is spontaneous and treatment is not necessary. Finally, some authors believe that apraxia only occurs when performance is requested of patients in testing situations, and that correct behaviour is dis-played in natural settings. There is agreement that apraxia hinders ADL independence [55,56,57].
There are two recent RCTs on the rehabilitation of apraxia. One study [58] found that a behavioural training programme with gesture-production exercises led to a sig-nificant improvement of limb apraxia with better perform-ance and a reduction of errors in both ideational and ideomotor apraxia tests. Another study [59] assessed the effectiveness of strategy training in left hemisphere stroke patients with apraxia. After 8 weeks of treatment, patients who received strategy training improved significantly more 82 Part 2: Neurological symptoms/problems
than patients in the usual treatment group on standardized ADL observations and the Barthel ADL index. However, at follow-up 5 months later no beneficial effects of strategy training were found. A some what less well-controlled study investigated a therapy programme for teaching patients strate-gies to compensate for the presence of apraxia [60]. Large improvements in ADL functioning were reported in all meas-ures and small improvements on the apraxia test and motor functioning test.
In sum, there is evidence that behavioural training pro-grammes improve limb apraxia and the teaching of compensa-tory strategies enables apraxic patients to function more independently. The evidence supports the view that treatment of apraxia should be part of the overall neuro-rehabilitation programme after brain damage.
6. Rehabilitation of acalculia
Among patients with acalculia due to acquired brain damage, how does a re-teaching approach, or exploiting of residual resources improve calculation abilities?
Though often unnoticed, many neurological disorders are associated with impairments of number processing and cal-culation (INPC). Depending on the underlying disease and on lesion location, the frequency of calculation disorders in patients with neurological disorders has been estimated to range between 10% and 90% [61]. Furthermore, no group studies exist which have compared different treatment strat-egies in larger patient samples. Studies are mostly ‘quasi-experimental’ using a single-case or small-group approach guided by the principles of cognitive neuropsychology [62–65]
and single-subject research [66,67]. Two main types of ration-ales have been applied to improve INPC. The ‘reconstitution’
or ‘reteaching’ approach consists of extensive lost or dam-aged abilities by way of extensive practice. The indirect approach promotes the use of ‘back-up’ strategies based on the patient’s residual resources. In this case, the treatment would not merely point to restore the functionality of the impaired component but rather to exploit the preserved abil-ities to compensate for the deficit. Both types of remediation employ step-by-step training consisting in presentation of problems of increasing difficulty, facilitation cues and other types of assistance which are eventually faded with progressive recovery; in all cases direct feedback is provided to the patient on his/her accuracy and errors. Outcome measures typically entail a comparison of the individual’s pre- and post-treatment performance in transcoding tasks, simple and complex calcu-lation. The amount of functional disability on daily life is rarely assessed or estimated in this corpus of studies. Rehabilitation of INPC may be grouped into several areas of intervention [68]. Rehabilitation of transcoding ability (the ability to translate numerical stimuli between different formats) has been successfully performed in several studies (see, e.g.
[69,70]), mostly by re-teaching the patient the required set of
rules. Impairments of arithmetical facts (simple multiplication, addition, subtraction or division solved directly from memory) were the target of several rehabilitation studies (see, e.g.
[68,71,72]). In all studies, extensive practice with the defec-tive domain of knowledge (i.e. multiplication tables deter-mined significant improvement). A positive outcome was reached also by a rehabilitation programme based on the strategic use of the patient’s residual knowledge of arithmetic [73]. This specific case suggests that the integration of declar-ative, procedural and conceptual knowledge critically medi-ates the re-acquisition process. Deficient arithmetical problem solving (the ability to provide a solution for complex, multi-step arithmetical text problems) has also been treated in one study [74]. The study was rated as partly successful by the authors, as patients benefited from the cueing procedure engaged and generated a higher number of correct solution steps, but did not show a prominent effect on the actual exe-cution process. Overall, the available evidence suggests that rehabilitation procedures used to treat selected variants of INPC were successful at the single-subject or small group level.
Notably, significant improvements were observed even in severely impaired and chronic patients. Several caveats need to be mentioned in this context. At present, little is known about the prognosis and spontaneous recovery of INPC, thus, the effects of different interventions in the early stages of numerical disorders may be difficult to evaluate. Moreover, different underlying neurological disorders (e.g. stroke, demen-tia and trauma) have only partly been compared as to their spe-cific effects on INPC. Furthermore, it has not been studied in detail how impairments of attention or executive functions influence the rehabilitation process of INPC.
Conclusion
The evidence findings (systematic reviews, randomized-clinical trials) are summarized in Table 10.1. These results clearly indicate that many methodological issues remain to be solved. The prevalence and relevance of cognitive disorders in terms of functional outcome after stroke and TBI dictates the need to establish recommendations for good practice of cogni-tive rehabilitation. This need was formally recognized by a sub-committee of the Brain Injury-Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine.
The initial recommendations of the Committee were published in 1992 as the Guidelines for Cognitive Rehabilitation [75]
and were based on expert opinions that did not consider evi-dence-based empirical support of the effectiveness of cognitive rehabilitation. In 2000, an evidence-based review of the sci-entific literature for cognitive rehabilitation was published by the same group [13], and an update from 1998 to 2002 has appeared recently [14]. The update process will result in regular publications (K.D. Cicerone, personal communica-tion). There are other systematic reviews that address only TBI patients. The NIH Consensus Development Panel [76]
Chapter 10: Cognitive rehabilitation of non-progressive neuropsychological disorders 83
Part 2: Neurological symptoms/problems Table 10.1 Systematic reviews (SR) and randomized controlled trials (RCTs) on cognitive rehabilitation.
Type of Impairment Number of Intervention Outcome Main findings Comment
study patients participants
(reference) (number of trials)
SR [12] Aphasia stroke 950 (12) Treatment (professional) Aphasia tests Absence of evidence
versus no treatment disability (non-professional)
SR [19] Aphasia stroke 864 (10) Intensive treatment versus Aphasia tests Intensive treatment better less intensive treatment
SR [25] Neglect stroke 400 (15) Visual scanning and visuo- Neglect tests Improvement of neglect spatial motor training versus disability No evidence of impact
standard rehabilitation on disability
SR [34] Attention stroke 56 (2) Attention task versus Concentration Improvement
standard rehabilitation and alertness No evidence of impact on disability disability
RCT [39] Attention 31 (1) Attentional training versus Attention tests ‘Minor’ effects
post acute TBI no specific treatment
RCT [40] Attention 29 (1) Attention training versus Attention tests Improvement Multiple baseline design;
post acute TBI memory training no evidence of generalization
RCT cross Attention 22 (1) Time pressure management Attention and Improvement
over [42] acute TBI versus generic concentration memory tests
training
SR [14] Memory 132 (6) Internal memory aids Memory tests Improvement only in
‘mild’ patients
SR [49] Memory 147 (11) Errorless learning Memory tests Large effect size for errorless Quantitative systematic review learning treatment; no
significant effect of vanishing cues
SR [46] Memory stroke 12 (1) Internal and external aids Memory tests Absence of evidence
disability
RCT [58] Apraxia 13 (1) Apraxia training Apraxia tests Improvement
RCT [59] Apraxia stroke 113 (1) Apraxia training versus Disability Short-term (no long-term)
standard rehabilitation improvement
SR [77] TBI ? (32) Cognitive rehabilitation Disability Absence of evidence
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reviewed studies published from January 1988 through August 1998 (including 11 RCTs), and concluded that data on the effectiveness of cognitive rehabilitation programmes were limited by the heterogeneity of subjects, interventions and outcomes studied. Another review published by the Evidence-based Practice Center at Oregon Health Sciences University [77] concluded that the durability and clinical relevance of the reported rehabilitation effects was not established.
Although the situation has changed since the first recom-mendations for cognitive rehabilitation were published, we strongly agree with the view that the current status of stud-ies on the effectiveness of cognitive rehabilitation is unsatisfac-tory. As pointed out previously, many RCTs in neurological rehabilitation are of poor methodological quality: the sample size is often insufficient, a control condition is frequently miss-ing, and/or there is a failure to assess the outcome at the dis-ability level. There is definitely a need for large-scale RCTs evaluating well-defined methodologies of intervention in common clinical conditions (e.g. the assessment of the efficacy of an intervention for ULN after right hemispheric stroke on long-term motor disability). The question of the efficacy of cognitive rehabilitation ‘in general’ is clearly ill-posed for a number of reasons. First, we are dealing with heterogeneous clinical manifestations of different diseases. For example, it is questionable whether the same standardized aphasia treat-ment would be similarly effective for a patient with a fluent neologistic jargon due to closed head injury and for a patient with agrammatic nonfluent production associated with a fronto-parietal infarction. Asking whether aphasia therapy is
‘generally’ effective is like organizing a RCT to assess the effectiveness of a given treatment of skin rashes. At the same time the attempt to assess the effectiveness of a treatment only in patients with a complete genome screening, in which a spe-cific mutation associated with the precise type of skin rash has been identified, would not be realistic. Research in neuro-psychology has focused on the assessment of specific, theoreti-cally driven treatments on well-defined areas of impairment, usually by means of single-case methodology (e.g. the effect of a linguistically driven intervention compared with simple stimulation of the ability to retrieve lexical items belonging to a defined class). It must be underlined that the randomization procedure per se does not guarantee the adequacy of the study unless the sample is large enough to control for the effect of known or unknown confounding variables [78]. When target-ing a large sample size of patients, a realistic level of description should be chosen. It is conceivable that despite a careful clin-ical specification of the target group there is still a residual heterogeneity. In such a case clinical labels such as agramma-tism or anomia may represent an acceptable compromise. The second problem concerns the standardization of the treat-ment. In the case of a behavioural intervention, it is clear that a number of factors, such as dosage, frequency of interven-tion, etc. are more difficult to standardize than in the case of a
pharmacological treatment. Moreover, given the length and complexity of the interaction between treatment provider and client, personality factors and, in general, interpersonal dynam-ics can be expected to interfere. Again, a large sample size rather than an attempt to control beyond a reasonable degree may solve this problem. Computer-based approaches seem to simplify this problem; however, the evidence about their use-fulness in the absence of constant human (therapist) inter-vention is not encouraging. Finally, we are facing the problem of feasibility of a true placebo double-blind con-trolled intervention. It is often difficult if not impossible to conceal the intervention condition from the therapist and the patient. Furthermore, ethically it is usually not justified to withhold treatment from a patient group (the ‘placebo’
condition). However, such a situation is easily solved by cross-over designs.
In sum, high standards for performing well-controlled studies, as they are obligatory in pharmacological and surgi-cal intervention, also need to be developed for and applied to intervention studies in neurological rehabilitation. In par-ticular, it is necessary to show that rehabilitation is effective not only in modifying the impairment but also in having sustained effects at the disability level.