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PubMed2004

Cognitive deterioration in Alzheimer's disease: is the early course predictive of the later stages?

This study investigated the predictive value of the early progression rate of Alzheimer's disease on that of the later stages. We retrospectively evaluated 91 patients affected by possible Alzheimer's disease; the patients had been examined twice with the Milan overall dementia assessment (MODA) scale at an interval of 12 months (53 patients) or 24 months (38 patients). At the first assessment, speed of progression was calculated for each patient dividing the MODA difference from the normality threshold by the time elapsed from the cognitive decline onset. The second assessment of speed of progression was calculated dividing the difference between the two MODA scores by the time elapsed from the first examination. Patients with a slow progression rate in the early stage were unlikely to show a subsequent fast progression rate, and vice versa for patients with a fast early progression. A tool is provided for predicting the speed of cognitive decline of patients from a single MODA assessment. We suggest that, in future clinical trials on Alzheimer's disease, a stratification of participants based on the early rate of cognitive deterioration may be considered.

Age of Onset↗
PubMed2005

Telling truth from lie in individual subjects with fast event-related fMRI.

Deception is a clinically important behavior with poorly understood neurobiological correlates. Published functional MRI (fMRI) data on the brain activity during deception indicates that, on a multisubject group level, lie is distinguished from truth by increased prefrontal and parietal activity. These findings are theoretically important; however, their applied value will be determined by the accuracy of the discrimination between single deceptive and truthful responses in individual subjects. This study presents the first quantitative estimate of the accuracy of fMRI in conjunction with a formal forced-choice paradigm in detecting deception in individual subjects. We used a paradigm balancing the salience of the target cues to elicit deceptive and truthful responses and determined the accuracy of this model in the classification of single lie and truth events. The relative salience of the task cues affected the net activation associated with lie in the superior medial and inferolateral prefrontal cortices. Lie was discriminated from truth on a single-event level with an accuracy of 78%, while the predictive ability expressed as the area under the curve (AUC) of the receiver operator characteristic curve (ROC) was 85%. Our findings confirm that fMRI, in conjunction with a carefully controlled query procedure, could be used to detect deception in individual subjects. Salience of the task cues is a potential confounding factor in the fMRI pattern attributed to deception in forced choice deception paradigms.

Adolescent↗
PubMed1994

High risk of sensitization to latex in children with spina bifida.

The risk of per-operative anaphylactic shock in response to latex is established in children with spina bifida. This study focuses on 30 children with spina bifida and aims at evaluating the value of predictive tests (skin tests and RAST). No patient had shown a preoperative accident. Hypersensitivity to latex, sometimes suspected by questioning of the patient, was detected 12 times out of 30 (40%). 10 children of the 12 were atopic (83%). The incidence of atopy is significantly higher than that of the general pediatric population (14 out of 30; 46%). This study demonstrates the frequency of the latent hypersensitivity to latex and the subsequent potential risk of per-operative anaphylactic shock. This sensitization can be partly explained by multiple contacts with latex; urinary catheterization several times a day, daily use of latex gloves for routine care, repetitive surgery (more than 8 operations per child). However, atopy increases the risk of sensitization to latex. The authors underline the importance of taking preventive measures for these children such as the use of PVC, silicone or polyurethane catheters and of synthetic rubber. Hypoallergenic gloves are under investigation. A questionnaire and systematic preventive cutaneous assessment before each operation are strongly advised.

Anaphylaxis↗
PubMed1989

Serological differentiation of acute and chronic schistosomiasis mansoni by antibody responses to keyhole limpet hemocyanin.

The existence of a shared epitope between the hemocyanin of the marine mollusk Megathura crenulata, better known as the keyhole limpet, and schistosomula has been reported. This epitope has been shown to be a major immunogen in human infection. In this study, keyhole limpet hemocyanin (KLH) was used to measure antibodies recognizing the cross-reacting epitopes in sera from patients with acute and chronic schistosomiasis using an enzyme-linked immunosorbent assay (ELISA). Marked differences in IgG and IgM antibody response were noted between acutely and chronically infected patients at a reciprocal serum dilution of up to 2,560. The acute sera had a mean +/- SD OD490 nm values for IgG and IgM of 1.0 +/- 0.44 and 1.34 +/- 0.6 compared to mean +/- SD IgG and IgM absorbance for the chronic sera of 0.22 +/- 0.10 and 0.22 +/- 0.11 respectively. Setting our lowest positive limit at greater than 2 SD above the mean of the chronic sera, 28 of the 30 patients previously diagnosed as having acute schistosomiasis were correctly identified by their IgG and IgM response. Of 5 patients studied longitudinally, IgG persisted at the same levels 10-13 weeks after treatment. IgM levels, on the other hand, showed a tendency to decrease but remained above the established cut-off level. This study provides further evidence for the association of schistosomulum surface carbohydrate antibody with acute infection and demonstrates the ability of a simple non-competitive ELISA using microtiter plates coated with minute quantities of KLH to differentiate serologically between cases of acute and chronic schistosomiasis.

Acute Disease↗
PubMedDate not supplied

[Evaluation of the Spanish version of the Memory Impairment Screen].

INTRODUCTION: Screening tests for detecting dementias are usually long, sometimes difficult to apply, and require a certain amount of instruction prior to using them. The Memory Impairment Screen (MIS) is a fast (3-4 minutes), easy-to-apply screening test that evaluates short-term verbal memory. AIM: To evaluate the value of the MIS for screening for dementia in our population. SUBJECTS AND METHODS: We evaluated 101 subjects who were divided into two groups, one consisting of 49 individuals with dementia according to DMS-IV criteria and the other made up of 52 subjects with no cognitive impairment. Demographic variables (sex, age, schooling) were studied together with the results from the Global Deterioration Scale, the Folstein Mini-Mental State Examination (MMSE), the MIS, the Semantic Verbal Fluency (SVF) and the Command-Condition Clock Test (CCCT). STATISTICAL ANALYSIS: demographic variables and the results from the tests for the two groups (with and without dementia) were compared, and the parameters for diagnostic usefulness and the areas under the ROC (aROC) were determined. RESULTS: No significant differences were found between the sociodemographic variables except for a higher mean age in the group with dementia. The MIS showed a sensitivity of 83.7% (95% CI: 71-97.9), which was higher than the SVF and the CCCT, and a specificity of 94.2% (95% CI: 84.4-98), which was higher than the MMSE and the SVF. The aROC of the MIS was 0.935 (95% CI: 0.954-1.006). CONCLUSIONS: These findings show that the MIS is a good test for screening for dementia, and its simplicity and quick application could make it suitable for use in our population.

Aged↗
PubMed2000

The atopy patch test (APT)-- a useful tool for the diagnosis of food allergy in children with atopic dermatitis.

BACKGROUND: While immediate-type clinical reactions to food can quite easily be identified by history or measurement of specific IgE in combination with positive oral food challenges, the evaluation of food allergy in the absence of immediate clinical reactions still presents diagnostic difficulties--particularly in children with atopic dermatitis. The objective of this study was to evaluate the diagnostic value of the atopy patch test (APT) with regard to late-phase reactions observed in double-blind, placebo-controlled food challenges with cow's milk, hen's egg, wheat, and soybean. METHODS: We investigated 75 children (median age 2.1 years) with suspected food allergy by double-blind, placebo-controlled food challenges, specific IgE in serum, skin prick test, and APT. Of the subjects, 69/75 suffered from atopic dermatitis. RESULTS: Of 209 oral challenges, 133 were performed with allergen and 76 with placebo. We assessed 77/133 allergen and 2/76 placebo challenges as positive. In 66 of 77 (86%) positive oral challenges, specific IgE in serum to the corresponding allergen was positive; in 64/77 (83%) the skin prick test, and in 42/77 (55%) the APT was positive. While immediate-type reactions were associated with positive skin prick test and proof of specific IgE in serum, late-phase clinical reactions were associated with a positive APT (sensitivity 76%, specificity 95%). CONCLUSIONS: The APT seems to be a valuable additional tool in the diagnostic work-up of food allergy in children with atopic dermatitis - especially with regard to late-phase clinical reactions. The APT may help to prevent unnecessary restrictive diets which may be the consequence of misjudging late reactions by clinical assessment alone.

Animals↗
PubMed1995

Natural history of Alzheimer's disease: prognostic value of plateaux.

The aim of this 7-year inception cohort study was to determine the prognostic value of plateaux in cognitive decline in the course of Alzheimer's disease (AD) as well as their impact on the rate of progression of cognitive impairment. From a consecutive sample of 106 outpatients participating in a longitudinal study on AD, we selected 31 with a mild degree of mental deficit at presentation and a disease duration of at least 3 years when included into the study. All underwent extensive clinico-neuropsychological testing about every 6 months and there were no drop-outs. Mean period of follow-up lasted 6.8 (SD 2.9) years. Nineteen patients displayed a plateau, where a plateau refers to a patient's remaining on a mild level of cognitive decline for more than two years. Survival curves (Kaplan-Meier method) showed that patients with plateaux reached several end-points--very severe functional or cognitive impairment, urinary incontinence, death--significantly later than patients without (p < 0.04). Patients with plateaux showed a smaller cognitive loss (p < 0.01) in terms of the mean annual rate of progression of mental decline. In conclusion plateaux in an early stage of Alzheimer's Disease served to identify patients with a more favourable course.

Aged↗
PubMed2005

Prediction value of radiosensitivity of hepatocarcinoma cells for apoptosis and micronucleus assay.

AIM: To investigate the prediction value of radiosensitivity of hepatocarcinoma cells for apoptosis and micronucleus assay. METHODS: Clonogenic assay, flow cytometry, and CB micronuclei assay were used to survey the cell survival rate, radiation-induced apoptosis and micronucleus frequency of hepatocarcinoma cell lines SMMC-7721, HL-7702, and HepG2 after being irradiated by X-ray at the dosage ranging 0-8 Gy. RESULTS: After irradiation, there was a dose-effect relationship between micronucleus frequency and radiation dosage among the three cell lines (P<0.05). A positive relationship was observed between apoptosis and radiation dosage among the three cell lines. The HepG2 cells had a significant correlation (P<0.05) but apoptosis incidence had a negative relationship with micronucleus frequency. There was a positive relationship between apoptosis and radiation dosage and the correlation between SMMC-7721 and HL-7702 cell lines had a significant difference (P<0.01). After irradiation, a negative relationship between cell survival rate and radiation dosages was found among the three cell lines (P<0.01). There was a positive relationship between cell survival rate and micronucleus frequency (P<0.01). No correlation was observed between apoptosis and cell survival rate. CONCLUSION: The radiosensitivity of hepatocarcinoma cells can be reflected by apoptosis and micronuclei. Detection of apoptosis and micronuclei could enhance the accuracy for predicting radiosensitivity.

Apoptosis↗
PubMed1989

Value of the Cand-Tec Candida antigen assay in the diagnosis and therapy of systemic candidiasis in high-risk patients.

A total of 911 sera from 171 patients at risk for systemic candidiasis and 24 sera from 24 non-hospitalized control subjects were analyzed for the presence of candida antigen using a commercially available latex agglutination test (Cand-Tec). Thirty-seven (22%) patients had systemic candidiasis documented by positive blood cultures, deep biopsy culture and histopathology or autopsy. Six patients had transient candidemia, 20 patients had candiduria, 53 patients had mucous membrane colonization, 21 patients were not colonized but received empiric amphotericin B, and 34 patients were not colonized and not treated with amphotericin B. The intraobserver reproducibility was 90% for the exact titer and 100% for a deviation of one dilution. The sensitivity and specificity of the candida antigen test in detection of systemic candidiasis was 95% and 50% (greater than or equal to 1:2), 73% and 72% (greater than or equal to 1:4), and 46% and 80% (greater than or equal to 1:8) respectively. Despite the poor specificity, serial antigen determinations in patients with documented systemic candidiasis demonstrated both an early diagnostic and prognostic role for the candida antigen test. Seventy-one percent of patients whose antigen titer increased during the course of amphotericin B therapy of documented infection died versus only 13% of those whose titer decreased while on therapy (p = 0.01). The candida antigen test has a limited yet potentially useful role in the diagnosis and management of systemic candidiasis in high-risk patients.

Amphotericin B↗
PubMed2004

Clinical utility of serum holotranscobalamin as a marker of cobalamin status in elderly patients with neuropsychiatric symptoms.

Early diagnosis of cobalamin deficiency is crucial, owing to the latent nature of this disorder and the resulting possible irreversible neurological damage. A normal serum cobalamin concentration does not reliably rule out a functional cobalamin deficiency and there does not at present seem to be any single diagnostic approach to achieve this diagnosis. A new marker for cobalamin status is the serum concentration of cobalamin bound to transcobalamin II (holoTC). Because methods suitable for routine use have been unavailable until recently, the clinical value of low holoTC is still uncertain. Furthermore, there is at the moment no gold standard or true reference method to diagnose subtle cobalamin deficiency, which makes evaluation of the clinical usefulness of holoTC and the estimation of sensitivity and specificity problematic. In this study, we aimed to assess whether low holoTC concentrations are congruent with other biochemical signs of cobalamin deficiency in a group of psychogeriatric patients. The findings in the present study show that holoTC is strongly related to serum cobalamin (0.68; p<0.001 in both patients and controls). Distribution of the different markers for cobalamin/folate status in the 33 patients with low levels of serum holoTC (below 40 pmol/l) showed that 17 patients had normal levels of the other markers for cobalamin status. This may indicate poor specificity of low holoTC for cobalamin deficiency. In 23 out of 176 patients with normal levels of holoTC we observed pathological levels of other markers for cobalamin deficiency. The use of holoTC in the present study group did not give significant additional information other than that given by serum cobalamin and therefore cannot be recommended in this clinical setting.

Age Factors↗
PubMed2001

C-reactive protein in ischemic stroke: an independent prognostic factor.

BACKGROUND AND PURPOSE: There is growing evidence of the prognostic importance of C-reactive protein (CRP) in ischemic stroke. However, the independent value of CRP at different stages after stroke has not been established. Therefore, we assessed the prognostic values of CRP in ischemic stroke. We also compared the relation of CRP at admission and discharge with 1-year outcome. METHODS: One hundred ninety-three patients were included in a derivation set (n=128) and a validation set (n=65). Serum CRP was measured, within 24 hours after index ischemic stroke, within 48 to 72 hours, and at hospital discharge. We examined the association between the level of CRP at different stages after stroke and outcome. We adjusted for the possible confounding effect using a multivariate Cox proportional hazard model. RESULTS: A cutoff point of 1.5 mg/dL for CRP at discharge provided optimum sensitivity and specificity for adverse outcome, based on the receiver operator curves. CRP at admission (hazard ratio [HR] 2.78, 95% CI 1.45 to 5.33; P=0.0021) and discharge (HR 9.42, 95% CI 4.27 to 19.05; P<0.0001) were predictors of the combined end point of new vascular events or death at 1 year. CRP at hospital discharge was the strongest independent marker of adverse outcome (HR 7.42, 95% CI 2.75 to 20.03; P=0.0001). These results were confirmed in the validation set (HR 15.66, 95% CI 3.36 to 72.97; P=0.0005). CONCLUSIONS: CRP is a marker of increased 1-year risk in ischemic stroke. CRP at discharge is better related to later outcome and could be of greater utility for risk stratification. These findings are consistent with the hypothesis that elevated CRP may predict future cardiovascular events or death.

Aged↗
PubMed2000

Predictive value of neonatal neurological tests for developmental outcome of preterm infants.

BACKGROUND: There is a need to identify, as early as possible, infants who are at risk for long-term neurological morbidity. METHODS: To predict neurodevelopment outcome of preterm infants <30 weeks' gestation in a population of 100 infants, we used several neonatal and neurobehavioral tests, including cranial ultrasonography, the Prechtl neurological test, quality of spontaneous general movements, and quality of sleep-wake organization. RESULTS: The Prechtl test at corrected term age and findings on cranial sonograms both had high specificity, but the Prechtl test had better overall positive predictive power for normal neurological and developmental outcomes at 2 years' corrected age. Developmental changes in sleep and the amount of indeterminate sleep did not correlate with outcome. Scoring general movement quality did not predict outcome and did not augment the positive predictive power of the Prechtl test. CONCLUSIONS: The Prechtl test at corrected term age (independent of the other tests) is the best positive predictor of normal neurological outcome and Bayley test results at 2 years' corrected age.

Developmental Disabilities↗
PubMed2002

Risk factors for airway remodeling in asthma manifested by a low postbronchodilator FEV1/vital capacity ratio: a longitudinal population study from childhood to adulthood.

Airway remodeling may lead to irreversible loss of lung function in asthma. The impact of childhood asthma, airway responsiveness, atopy, and smoking on airway remodeling was investigated in a birth cohort studied longitudinally to age 26. A low postbronchodilator ratio of forced exhaled volume in 1 second (FEV1) to vital capacity (VC) at age 18 or 26 was used as a marker of airway remodeling. "Normal" study members with no history of asthma ever, no wheezing in the last year, and no smoking ever were used to determine sex- and age-specific reference values for this ratio. The lower limit of normal was defined as the mean ratio minus 1.96 standard deviation, delimiting the 2.5% of the normal population with the lowest FEV1/VC ratio. A low postbronchodilator FEV1/VC ratio was found in 7.4% and 6.4% of study members at ages 18 and age 26 and 4.6% at both assessments. Lung function was low throughout childhood in those with a consistently low postbronchodilator FEV1/VC ratio at both ages. Those with consistently low postbronchodilator ratios also showed a greater decline in the prebronchodilator FEV1/VC ratio from ages 9 to 26 compared with those with normal postbronchodilator ratios at both ages (males, -12% versus -6%, p < 0.0001; females, -10.5% versus -5.5%, p < 0.01). Asthma, male sex, airway hyperresponsiveness, and low lung function in childhood were each independently associated with a low postbronchodilator FEV1/VC ratio, which in turn was associated with an accelerated decline in lung function and decreased reversibility. These data suggest that airway remodeling in asthma, as manifested by impaired lung function, begins in childhood and continues into adult life.

Adolescent↗
PubMed1995

Value of wet mount and cervical cultures at the time of cervical cytology in asymptomatic women.

OBJECTIVE: To correlate Papanicolaou smear findings with the wet mount and cervical culture results in asymptomatic patients, and to review the value of doing wet mount and/or cervical cultures in these patients at the time of Papanicolaou smear. METHODS: Asymptomatic women presenting for routine Papanicolaou smears at Sinai Samaritan Medical Center, Milwaukee, Wisconsin, between January 1991 and January 1994 were studied by preparing wet mount (saline and potassium hydroxide preparations) and cervical cultures for Chlamydia trachomatis and Neisseria gonorrhoeae at the same visit. Fisher exact test and Pearson chi 2 statistics were applied. RESULTS: Nine hundred sixty-three patients were studied. Nearly 50% of our asymptomatic young urban women had a vaginal and/or cervical infection. Papanicolaou smears with inflammation were associated with bacterial vaginosis (P < .0001), excess white blood cells (P < .0001), trichomoniasis (P < .0001), abnormal wet mounts in general (P < .0001), and positive cervical cultures for C trachomatis and/or N gonorrhoeae (P < .001). Papanicolaou smears showing atypical cells of undetermined significance were associated with bacterial vaginosis (P < .001) and abnormal wet mounts in general (P < .03). Seventy-five percent of patients with positive cervical cultures had abnormal wet mounts. Eighty-three percent of the patients whose initial Papanicolaou smear showed inflammation and whose initial wet mount was abnormal had a normal Papanicolaou smear when the wet mount became normal. CONCLUSION: Preparing wet mounts at the time of Papanicolaou smear in asymptomatic young urban women will help in the interpretation of minimally abnormal smears and will probably decrease the need for repeat smears and colposcopy. Simultaneous cervical cultures would not add much information for such interpretation.

Adolescent↗
PubMed2005

Motor signs predict poor outcomes in Alzheimer disease.

OBJECTIVE: To examine whether the presence of motor signs has predictive value for important outcomes in Alzheimer disease (AD). METHODS: A total of 533 patients with AD at early stages (mean Folstein Mini-Mental State Examination [MMSE] 21/30 at entry) were recruited and followed semiannually for up to 13.1 years (mean 3) in five University-based AD centers in the United States and European Union. Four outcomes, assessed every 6 months, were used in Cox models: cognitive endpoint (Columbia Mini-Mental State Examination < or = 20/57 [ approximately MMSE < or = 10/30]), functional endpoint (Blessed Dementia Rating Scale > or = 10), institutionalization equivalent index, and death. Using a standardized portion of the Unified PD Rating Scale (administered every 6 months for a total of 3,149 visit-assessments, average 5.9 per patient), the presence of motor signs, as well as of individual motor sign domains, was examined as time-dependent predictor. The models controlled for cohort, recruitment center, sex, age, education, a comorbidity index, and baseline cognitive and functional performance. RESULTS: A total of 39% of the patients reached the cognitive, 41% the functional, 54% the institutionalization, and 47% the mortality endpoint. Motor signs were noted for 14% of patients at baseline and for 45% at any evaluation. Their presence was associated with increased risk for cognitive decline (RR, 1.72; 95% CI, 1.24 to 2.38), functional decline (1.80 [1.33 to 2.45]), institutionalization (1.68 [1.26 to 2.25]), and death (1.38 [1.05 to 1.82]). Tremor was associated with increased risk for reaching the cognitive and bradykinesia for reaching the functional endpoints. Postural-gait abnormalities carried increased risk for institutionalization and mortality. Faster rates of motor sign accumulation were associated with increased risk for all outcomes. CONCLUSIONS: Motor signs predict cognitive and functional decline, institutionalization, and mortality in Alzheimer disease. Different motor sign domains predict different outcomes.

Aged↗
PubMed2005

Delusions and hallucinations are associated with worse outcome in Alzheimer disease.

BACKGROUND: Delusions and hallucinations are common in Alzheimer disease (AD) and there are conflicting reports regarding their ability to predict cognitive decline, functional decline, and institutionalization. According to all previous literature, they are not associated with mortality. OBJECTIVE: To examine whether the presence of delusions or hallucinations has predictive value for important outcomes in AD. DESIGN, SETTING, AND PARTICIPANTS: A total of 456 patients with AD at early stages (mean Folstein Mini-Mental State Examination [MMSE] score of 21 of 30 at entry) were recruited and followed up semiannually for up to 14 years (mean, 4.5 years) in 5 university-based AD centers in the United States and Europe. Using the Columbia University Scale for Psychopathology in AD (administered every 6 months, for a total of 3266 visit-assessments, average of 7.2 per patient), the presence of delusions and hallucinations was extracted and examined as time-dependent predictors in Cox models. The models controlled for cohort effect, recruitment center, informant status, sex, age, education, a comorbidity index, baseline cognitive and baseline functional performance, behavioral symptoms, and use of neuroleptics and cholinesterase inhibitors. MAIN OUTCOME MEASURES: Cognitive (Columbia MMSE score of < or =20/57 [approximate Folstein MMSE score of < or =10/30]), functional (Blessed Dementia Rating Scale [parts I and II] score of > or =10), institutionalization equivalent index, and death. RESULTS: During the full course of follow-up, 38% of patients reached the cognitive, 41% the functional, 54% the institutionalization, and 49% the mortality end point. Delusions were noted for 34% of patients at baseline and 70% at any evaluation. Their presence was associated with increased risk for cognitive (risk ratio [RR], 1.50; 95% confidence interval [CI], 1.07-2.08) and functional decline (RR, 1.41; 95% CI, 1.02-1.94). Hallucinations were present in 7% of patients at initial visit and in 33% at any visit. Their presence was associated with increased risk for cognitive decline (RR, 1.62; 95% CI, 1.06-2.47), functional decline (RR, 2.25; 95% CI, 1.54-2.27), institutionalization (RR, 1.60; 95% CI, 1.13-2.28), and death (RR, 1.49; 95% CI, 1.03-2.14). CONCLUSIONS: Delusions and hallucinations are very common in AD and predict cognitive and functional decline. Presence of hallucinations is also associated with institutionalization and mortality.

Aged↗
PubMed1999

A diagnostic test for apraxia in stroke patients: internal consistency and diagnostic value.

The internal consistency and the diagnostic value of a test for apraxia in patients having had a stroke are presented. Results indicate that the items of the test form a strong and consistent scale: Cronbach's alpha as well as the results of a Mokken scale analysis present good reliability and good scalability. The diagnostic value of the test was determined by comparison of test results in three groups of patients: 44 stroke patients with apraxia (patients), 35 stroke patients without apraxia (patient controls), and 50 healthy nursing home residents with no history of stroke (normal controls). The diagnostic value is expressed by means of the sensitivity and specificity and the predictive value of the test. In addition, Receiver Operator Characteristics (ROC) curves are presented. The sensitivity and specificity of the apraxia test appear to be good: all values are higher than 80%. The test also has high predictive value. The ROC curves illustrate that the test is sufficiently discriminative to allow a differentiation between persons with apraxia and persons without apraxia.

Adult↗