Wilcoxon-Mann-Whitney odds ratio: A statistical measure for ordinal outcomes such as EDSS.

BACKGROUND: In many clinical situations, ordinal scales afford the primary method of semi-quantifying patient outcomes. In the field of multiple sclerosis, the primary ordinal scale is the Expanded Disability Status Scale. Predominant methods of ordinal scale statistical analysis provide a p-value without effect size or rely heavily on the assumption of proportionality of odds, subjecting them to lack of power and error. The Wilcoxon-Manny-Whitney Odds is a statistical method which provides significant information such as p-value, effect size, number needed to treat, confidence intervals, and is largely assumption-free. However, its utility has not been demonstrated in the field of multiple sclerosis. METHODS: Three clinical studies in the field of multiple sclerosis were selected which utilized ordinal scale outcomes at group or individual levels. Data from these studies was extracted using WebPlotDigitizer, and a custom Wilxocon-Mann-Whitney Odds software was applied to each dataset to re-analyze the main outcomes of the studies. RESULTS: Re-analysis of the manuscript by Muraro et al., 2017 demonstrated that autologous stem cell transplantation for relapsing remitting multiple sclerosis resulted in a 65% chance of improving from any Expanded Disability Status Scale category, although not significant. Re-analysis of the manuscript by Songthammawat et al., 2019 demonstrated chance of improvement with intravenous methylprednisolone and concurrent plasma exchange was 185% versus 32% in intravenous methylprednisolone with add-on plasma exchange, although not significant. Re-analysis of Kister et al., 2012 demonstrated the chances of mobility or cognition scores generally favored decline at every 5-year increment of study, and although statistically significant, these were smaller effect sizes ranging from an 11% chance of improvement to a 66% chance of decline over a 5-year interval. DISCUSSION: The Wilcoxon-Mann-Whitney Odds simplifies ordinal data analysis with its robust largely assumption-free nature. In the place of numerous statistical tests, this single test provides effect size estimate, number needed to treat, p-values, and confidence intervals. Importantly, the Wilcoxon-Mann-Whitney Odds effect size calculation is intuitively applicable to both individual and population-levels. Further, the Wilcoxon-Mann-Whitney Odds allows intuitive description of the progression of large cohorts over time, and we were able to clearly convey the odds of mobility and cognitive decline over 30 years in a large multiple sclerosis cohort. Overall, the Wilcoxon-Mann-Whitney Odds is a powerful and robust statistical test with significant promise within the field of multiple sclerosis.

Comparison of Multiple Sclerosis Cortical Lesion Types Detected by Multicontrast 3T and 7T MRI.

BACKGROUND AND PURPOSE: Our aims were the following: 1) to compare multicontrast cortical lesion detection using 3T and 7T MR imaging, 2) to compare cortical lesion type frequency in relapsing-remitting and secondary-progressive MS, and 3) to assess whether detectability is related to the magnetization transfer ratio, an imaging marker sensitive to myelin content. MATERIALS AND METHODS: Multicontrast 3T and 7T MR images from 10 participants with relapsing-remitting MS and 10 with secondary-progressive MS. We used the following 3T contrast sequences: 3D-T1-weighted, quantitative T1, FLAIR, magnetization-transfer, and 2D proton-density- and T2-weighted. We used the following 7T contrast sequences: 3D-T1-weighted, quantitative T1, and 2D-T2*-weighted. RESULTS: Cortical lesion counts at 7T were the following: 720 total cortical lesions, 420 leukocortical lesions (58%), 27 intracortical lesions (4%), and 273 subpial lesions (38%). Cortical lesion counts at 3T were the following: 424 total cortical, 393 leukocortical (93%), zero intracortical, and 31 subpial (7%) lesions. Total, intracortical, and subpial 3T lesion counts were significantly lower than the 7T counts (P < .002). Leukocortical lesion counts were not significantly different between scanners. Total and leukocortical lesion counts were significantly higher in secondary-progressive MS, at 3T and 7T (P ≤ .02). Subpial lesions were significantly higher in secondary-progressive MS at 7T (P = .006). The magnetization transfer ratio values of leukocortical lesions visible on both scanners were significantly lower than the magnetization transfer ratio values of leukocortical lesions visible only at 3T. No significant difference was found in magnetization transfer ratio values between subpial lesions visible only at 7T and subpial lesions visible on both 3T and 7T. CONCLUSIONS: Detection of leukocortical lesions at 3T is comparable with that at 7T MR imaging. Imaging at 3T is less sensitive to intracortical and subpial lesions. Leukocortical lesions not visible on 7T T2*-weighted MRI may be associated with less demyelination than those that are visible. Detectability of subpial lesions does not appear to be related to the degree of demyelination.

Ambroxol as a novel disease-modifying treatment for Parkinson's disease dementia: protocol for a single-centre, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Currently there are no disease-modifying treatments for Parkinson's disease dementia (PDD), a condition linked to aggregation of the protein α-synuclein in subcortical and cortical brain areas. One of the leading genetic risk factors for Parkinson's disease is being a carrier in the gene for ß-Glucocerebrosidase (GCase; gene name GBA1). Studies in cell culture and animal models have shown that raising the levels of GCase can decrease levels of α-synuclein. Ambroxol is a pharmacological chaperone for GCase and is able to raise the levels of GCase and could therefore be a disease-modifying treatment for PDD. The aims of this trial are to determine if Ambroxol is safe and well-tolerated by individuals with PDD and if Ambroxol affects cognitive, biochemical, and neuroimaging measures. METHODS: This is a phase II, single-centre, double-blind, randomized placebo-controlled trial involving 75 individuals with mild to moderate PDD. Participants will be randomized into Ambroxol high-dose (1050 mg/day), low-dose (525 mg/day), or placebo treatment arms. Assessments will be undertaken at baseline, 6-months, and 12-months follow up times. Primary outcome measures will be the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-Cog) and the ADCS Clinician's Global Impression of Change (CGIC). Secondary measures will include the Parkinson's disease Cognitive Rating Scale, Clinical Dementia Rating, Trail Making Test, Stroop Test, Unified Parkinson's disease Rating Scale, Purdue Pegboard, Timed Up and Go, and gait kinematics. Markers of neurodegeneration will include MRI and CSF measures. Pharmacokinetics and pharmacodynamics of Ambroxol will be examined through plasma levels during dose titration phase and evaluation of GCase activity in lymphocytes. DISCUSSION: If found effective and safe, Ambroxol will be one of the first disease-modifying treatments for PDD. TRIAL REGISTRATION: ClinicalTrials.gov NCT02914366, 26 Sep 2016/retrospectively registered.

The influence of small for gestational age status on outpatient bronchopulmonary dysplasia outcomes.

OBJECTIVE: To describe the characteristics of small for gestational age (SGA) and non-SGA infants with bronchopulmonary dysplasia (BPD) and to ascertain whether respiratory outcomes and health-care utilization patterns in these two populations differ. STUDY DESIGN: Three hundred and twenty-five infants with BPD born at <32 weeks gestation were recruited in the outpatient setting. Sociodemographic data and indicators of respiratory morbidity were collected via questionnaire and retrospective chart review. RESULT: SGA infants were on average 1 month older than non-SGA infants at discharge from the neonatal intensive care unit and were more likely to have a weight less than 10th percentile at first clinic visit. History of SGA was associated with increased risk of emergency department visits as well as with caregiver perception of poor weight gain. CONCLUSION: SGA status in infants with BPD is associated with increased health-care utilization, including length of initial hospitalization and emergency department visits.

MS incidence and prevalence in Africa, Asia, Australia and New Zealand: A systematic review.

OBJECTIVES: Studies of multiple sclerosis (MS) incidence and prevalence from Africa, Asia, Australia and New Zealand are relatively scarce. We systematically reviewed MS incidence and prevalence in these regions including a standardized evaluation of study quality. METHODS: We searched MEDLINE and EMBASE databases for studies of MS prevalence or incidence in Africa, Asia, Australia and New Zealand published in English or French between January 1, 1985 and January 31, 2011. Study quality was assessed using a standardized tool. All steps of the review were performed in duplicate. RESULTS: Of 3925 citations identified, 28 studies met inclusion criteria and 21 of these were from Asia. Quality scores ranged from 1/8 to 8/8; the lowest scores were observed in studies from Asia (median 4/8, IQR 3,6). Prevalence was lowest in South African Blacks (0.22/100,000) and highest amongst Australian-born individuals in Australia (125/100,000). Prevalence increased over time in many countries. MS prevalence increased with increasing latitude only in some regions, and prevalence varied significantly with ethnicity. Eight studies reported incidence, which ranged from 0.67/100,000/year in Taiwan to 3.67/100,00/year in Australia. CONCLUSIONS: This comprehensive study provides an update of MS epidemiology in Africa, Asia, Australia, and New Zealand. Incidence and prevalence were lowest in Africa and Asia and highest in Australia, but many Asian studies were of poor quality. Use of consistent case ascertainment methods, standardized data collection tools, and similar outcomes would all improve study quality and comparability. The underlying basis of observed ethnic differences is an important area for future study.

Health-care utilization and respiratory morbidities in preterm infants with pulmonary hypertension.

OBJECTIVE: To assess health-care utilization and risk of respiratory morbidities in preterm infants with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). STUDY DESIGN: Retrospective data were obtained from subjects (n=109) attending a BPD clinic. Subjects were stratified by the presence or absence of PH before and after 2 months of age. Analytic methods included t-tests, χ(2) tests and regression. RESULT: Subjects with BPD and PH present after 2 months of age were hospitalized for 2.2 months longer than those without PH (P=0.02). These subjects were 4.5 times more likely to receive home supplemental oxygen or mechanical ventilation (P=0.03). No difference in the risk of respiratory morbidities after initial hospital discharge was seen with PH. CONCLUSION: PH in preterm infants is associated with longer initial hospitalizations and a higher likelihood of requiring home respiratory support. This has implications for counseling families and reducing the medical, psychosocial, and economic burden of BPD and PH.

Effects of acute relapses on neuropsychological status in multiple sclerosis patients.

Little is known about neuropsychological status changes in multiple sclerosis (MS) patients experiencing a relapse. The Symbol Digit Modalities Test (SDMT) and MS Neuropsychological Screening Questionnaire (MSNQ) are brief measures of cognitive performance and self-reported status, respectively. We retrospectively identified relapses in subjects participating in the 48-week open-label, safety-extension study of natalizumab (STRATA) to determine if changes in cognitive ability occurred during acute relapses. SDMT and MSNQ were administered prior to infusions. We analyzed SDMT and MSNQ scores pre- and post-relapse in 53 MS patients with relapses (cases) and 115 MS patients without relapses (controls) matched on age, gender, baseline SDMT and time from study initiation. ANOVA and GLM were used to compare cases versus controls overall, and stratified by EDSS cerebral functional status (cFS) scores. SDMT change pre- to post-relapse in cases was significantly lower than difference between similar time points in controls (p = 0.003). When comparing visit 2 (two visits pre-relapse) to visit 1 (first visit post-relapse), MSNQ change was significantly different between cases and controls (p = 0.012). For cFS ≤ 1, the change in SDMT was significantly different between cases and controls but not for cFS ≥ 2. These results confirm the involvement of cognitive function during some MS relapses suggesting the SDMT or MSNQ can be used to identify transitory neuropsychological status changes and cognitive relapses.

Evaluation of the symbol digit modalities test (SDMT) and MS neuropsychological screening questionnaire (MSNQ) in natalizumab-treated MS patients over 48 weeks.

BACKGROUND AND OBJECTIVES: Brief cognitive tests to monitor cognitive impairment in patients with multiple sclerosis (MS) are needed. METHODS: Performance on monthly administrations of the Symbol Digit Modalities Test (SDMT) and the MS Neuropsychological Questionnaire (MSNQ) was assessed in 660 patients with MS in 21 countries (109 sites) for 48 weeks in an open-label, safety-extension study of natalizumab. RESULTS: At baseline, the cohort's mean age was 40.1 years, 67.6% were female and the median Expanded Disability Status Scale score was 2.5. Test-retest correlations were high for both SDMT (range 0.89 for weeks 0-4 to 0.96 for weeks 44-48) and MSNQ (0.82 for weeks 0-4 to 0.93 for weeks 44-48). There were no statistically significant effects of geographic region. While SDMT scores improved by 15 points over 48 weeks (p < 0.0001), incremental monthly changes were small (effect size d < 0.3). Similar results were obtained on the MSNQ except that scores moved downward, suggesting fewer cognitive complaints over 48 weeks (p < 0.0001), but again the incremental monthly changes were small (d <-0.2). CONCLUSIONS: These results replicate earlier work in a smaller cohort treated with conventional disease-modifying therapy, and support the reliability of the SDMT and MSNQ as potential screening for monitoring tools for cognition over time.

Psychometrics and normative data for the Multiple Sclerosis Functional Composite: replacing the PASAT with the Symbol Digit Modalities Test.

The MS Functional Composite (MSFC) is a continuous scale of neurological disability for patients with multiple sclerosis (MS). Cognition is represented by the Paced Auditory Serial Addition Test (PASAT), although the Symbol Digit Modalities Test (SDMT) has been proposed as a promising alternative. MSFC scores were calculated using either the PASAT or the SDMT with the following reference populations: National Multiple Sclerosis Society (NMSS) Task Force, 400 MS patients, and 100 normal controls. A subgroup of 115 patients was followed longitudinally, with a test-retest interval of 2.3 +/- 1.2 years. Pearson correlations were calculated and analyses of variance (ANOVAs) were used to assess relationships among the MSFC components and composite scores, and differences in performance between patients and controls. Longitudinal changes were also assessed. Logistic regression was performed to determine which MSFC scores are most predictive of diagnosis, course, and work disability. All MSFCs had similar test-retest reliability and correlations with other measures including neurological disability, depression, and fatigue. The SDMT showed slightly better validity with respect to predicting diagnosis, course, and work disability, although the amount of variance accounted for was similar for each version of the MSFC. Our data, derived from a large sample of MS patients and normal controls, supports the validity of both PASAT and SDMT versions of the MSFC. Because the SDMT has slightly better predictive validity and has a relatively easier administration procedure, some clinicians and researchers may wish to replace the PASAT with the SDMT in future calculations of the MSFC using the calculation methods provided in this manuscript.

Subjective fatigue is not associated with cognitive impairment in multiple sclerosis: cross-sectional and longitudinal analysis.

BACKGROUND: Studies in multiple sclerosis (MS) report conflicting conclusions regarding fatigue and cognition, which may partly be due to the use of small sample sizes and frequent reliance on a cross-sectional approach. OBJECTIVE: The ability to distinguish between these two disabling symptoms is necessary in order to properly assess and treat MS patients. METHODS: In a retrospective analysis, we assessed the correlation between fatigue and neuropsychological (NP) testing using a cross-sectional (n = 465) and longitudinal approach (n = 69). Cognition was measured using a comprehensive battery called the Minimal Assessment of Cognitive Function in MS (MACFIMS), and fatigue was measured with the Fatigue Severity Scale (FSS). FSS scores were categorized as normal (or=5.0). Repeat assessments (n = 69) were categorized as improved or worsened by a change in FSS of either 0.5 or 1.0. RESULTS: MS patients had significantly higher FSS scores than normal controls (P < 0.001). No correlation was found between FSS and NP scores in either cross-sectional or longitudinal analyses. Fatigue was moderately correlated with depression, assessed using the Beck Depression Inventory Fast Screen (BDIFS) (r = 0.44, P < 0.001). Longitudinally, there was a medium correlation between change in FSS and BDIFS (r = 0.34, P = 0.001), but no significant differences on NP scores using either definition of change. CONCLUSION: We conclude that self-reported fatigue, while correlated with self-reported depression, is not significantly related to cognitive capacity in MS.

High dose oral steroids commonly used to treat relapses in Canadian MS clinics.

BACKGROUND: Glucocorticoid treatment improves the speed of functional recovery of acute multiple sclerosis (MS) relapses but has not been shown to provide any long-term functional benefit. There is currently no convincing evidence that the clinical benefit is influenced by the route of administration or the dosage of glucocorticoid, or the particular glucocorticoid prescribed. Recent studies support similarities in the bioequivalence and in the clinical effect of high dose oral corticosteroids for MS relapses. OBJECTIVE: This survey aimed to determine the relapse treatment preferences of clinicians in Canadian MS clinics. METHODS: Members of the Canadian Network of MS Clinics are linked by an email server. A one page survey was distributed to the group to determine and report use of corticosteroids to manage MS relapses amongst Canadian MS specialists. RESULTS: Fifty-one clinicians from 17 MS clinics were surveyed. 32 (63%) surveys were returned representing 16 clinics. Five doses are most commonly prescribed, usually without a taper. Three or four doses and the use of a corticosteroid taper, however, are not uncommon. Gastric cytoprotection and sedatives are often prescribed for use as needed. CONCLUSION: This survey illustrates that when Canadian clinicians with expertise in managing MS treat MS relapses they choose high dose corticosteroids, either oral or i.v. The results therefore represent Canadian practice as these clinicians provide direct patient care and influence care by community neurologists. Until evidence clearly identifies a superior practice all options should be available to clinicians and their patients.

The bioavailability of IV methylprednisolone and oral prednisone in multiple sclerosis.

Oral prednisone (1)might be a convenient, inexpensive alternative to IV methylprednisolone (IVMP) if the bioequivalent dose was known. We compared the total amount of steroid absorbed after 1250 mg oral prednisone vs 1 gram IVMP in 16 patients with multiple sclerosis (MS). At 24 hours, the mean area under the concentration-time curve (AUC), the main component of bioavailability, did not differ between groups (p = 0.122). This suggests that the amount of absorbed corticosteroid is similar after either steroid at these doses.

Apoptosis in neonatal murine lung exposed to hyperoxia.

Exposure to high concentrations of oxygen in the neonatal period may impair lung growth and is a major contributing factor to the development of bronchopulmonary dysplasia. Cell death from hyperoxic injury may occur through either an apoptotic or nonapoptotic pathway, and we were interested in determining the type of cell death that occurs in the lung of neonatal mice exposed to hyperoxia. We found increased levels of Bax messenger RNA, a gene associated with apoptosis, in the lungs of neonatal mice born and raised in 92% hyperoxia. We next determined the extent of apoptosis taking place in the lungs of neonatal mice exposed to hyperoxia using terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling in 3.5-, 4.5-, and 5.5-d-old neonatal lung. The number of apoptotic cells in peripheral lung was significantly higher in the 3.5-, 4.5-, and 5.5-d-old mice treated with oxygen compared with that in the room-air control mice. Further, the number of apoptotic cells in the lung increased with longer exposure duration. In murine lung bronchus cells exposed to hyperoxia, growth arrest occurred after 48 h of oxygen exposure. Using annexin V binding, necrotic cell death was found to be the major form of cell death in these cells after 72 h of hyperoxic exposure. We conclude that 92% hyperoxia causes significant lung injury in neonatal mice exposed to hyperoxia, and that the number of apoptotic cells in the lung increases the longer the duration of exposure. The increase in apoptosis from hyperoxic exposure during a critical period of lung development may be an important factor in the impaired lung growth and remodeling that occur in animals exposed to high oxygen concentrations. Finally, it appears that hyperoxic injured cells in neonatal lung undergo both apoptotic and nonapoptotic cell death.

Growth arrest in A549 cells during hyperoxic stress is associated with decreased cyclin B1 and increased p21(Waf1/Cip1/Sdi1) levels.

Exposure to high concentrations of oxygen has previously been shown to cause growth arrest in A549 cells, a distal lung epithelial cell line. We found that when A549 cells were exposed to 95% oxygen they underwent substantial growth inhibition. This was associated with induction of p21(Waf1/Cip1/Sdi1) protein and a decrease in cyclin B1 protein. Flow cytometry revealed that A549 cells exposed to hyperoxia had a significant decrease in the percentage of cells in G(1) and a modest but significant increase in the percentage of cells in S phase and G(2)/M, consistent with cells entering S phase. A549 cells in room air and hyperoxia were then treated with nocodazole, a mitotic inhibitor. Room air A549 cells treated with nocodazole showed a marked increase in G(2)/M consistent with mitotic arrest. In contrast, hyperoxic treated cells had a modest but significant decrease in G(1) but only a minimal increase in G(2)/M consistent with partial G(1)/S arrest and growth inhibition in S phase. To further investigate the role of p21(Waf1/Cip1/Sdi1) as a checkpoint regulator during hyperoxic growth inhibition, HCT116 cells with wild-type and null p21(Waf1/Cip1/Sdi1) were exposed to hyperoxia. Both wild-type p21(+/+) cells and null p21(-/-) cells underwent growth inhibition when exposed to hyperoxia. At 48 h the hyperoxic treated HCT116 p21(+/+) had a similar cell cycle distribution as the hyperoxic treated HCT116 p21(-/-) cells, suggesting that p21(Waf1/Cip1/Sdi1) may not be essential for growth arrest during hyperoxia. These findings suggest that hyperoxia causes partial growth arrest at different phases of the cell cycle but primarily in S phase, that hyperoxic growth arrest is associated with a decrease in cyclin B1 protein and that p21 induction may not be essential for hyperoxic growth arrest.

G(1) Phase growth arrest and induction of p21(Waf1/Cip1/Sdi1) in IB3-1 cells treated with 4-sodium phenylbutyrate.

4-Sodium phenylbutyrate (4-PBA) has been used for many years in the treatment of urea cycle defects and has recently been studied as a chemotherapeutic agent for certain malignancies. 4-PBA has been shown to cause growth arrest, cellular differentiation, and apoptosis in certain malignant cells. Recently, it was shown that IB3-1 cells (a cystic fibrosis cell line, Delta508/W128X) treated with 4-PBA demonstrated a partial correction of the cystic fibrosis chloride channel defect. We were interested in evaluating the effect of 4-PBA on cell growth and cell cycle regulation in IB3-1 cells treated with 2 to 10 mM concentrations. We found that cells treated with 2 mM concentrations of 4-PBA for 96 h underwent a significant decrease in cell growth (P <.007). Using flow cytometry, we were able to demonstrate that growth arrest occurred at the G(1) phase of the cell cycle. This was detected as early as 24 h in IB3-1 cells treated with 5 mM 4-PBA (P <.03). Furthermore, the percentage of IB3-1 cells with less than a 2N DNA content increased with higher concentrations of 4-PBA, although this was not associated with an increase in apoptosis. Finally, p21(Waf1/Cip1/Sdi1) protein levels were induced in IB3-1 cells receiving 2 and 5 mM concentrations of 4-PBA as early as 24 h of exposure, suggesting that G(1) phase growth arrest in IB3-1 cells treated with 4-PBA is regulated through the p21(Waf1/Cip1/Sdi1) pathway.

CIC-2: a developmentally dependent chloride channel expressed in the fetal lung and downregulated after birth.

Growth and differentiation of the fetal lung are dependent on chloride and fluid secretion, yet the specific molecular identities of fetal chloride channels have not been fully determined. In this study, we demonstrate mRNA expression of the volume-activated chloride channel, CIC-2, in fetal rat lung using reverse-transcriptase polymerase chain reaction (RT-PCR) and ribonuclease (RNase) protection assay. By RNase protection assay, CIC-2 mRNA expression is most abundant in fetal lung and diminishes after birth until it is almost undetectable in adult rat lung. To confirm this result at the protein level, a C-terminal fragment of CIC-2 cDNA derived from 19-day fetal rat lung was cloned into an expression plasmid. The truncated 33-kD CIC-2 protein was expressed in Escherichia coli and purified by column chromatography. Polyclonal antibodies to this antigen were raised in chickens, and the antisera detected a 94-kD protein in fetal rat lung homogenates by Western blotting. Protein expression of CIC-2 was most abundant in mid and late gestation and decreased significantly shortly after birth, as would be predicted by the RNase protection data. CIC-2 protein was localized along the apical surface of fetal airway epithelium by immunocytochemistry. The abundant fetal expression of CIC-2 RNA and protein supports the hypothesis that CIC-2 is important to fetal lung development, and its apical location suggests that it may be involved in fluid secretion during normal lung morphogenesis.

The effectiveness of three sets of school-based instructional materials and community training on the acquisition and generalization of community laundry skills by students with severe handicaps.

This study examined the effectiveness of three sets of school-based instructional materials and community training on acquisition and generalization of a community laundry skill by nine students with severe handicaps. School-based instruction involved artificial materials (pictures), simulated materials (cardboard replica of a community washing machine), and natural materials (modified home model washing machine). Generalization assessments were conducted at two different community laundromats, on two machines represented fully by the school-based instructional materials and two machines not represented fully by these materials. After three phases of school-based instruction, the students were provided ten community training trials in one laundromat setting and a final assessment was conducted in both the trained and untrained community settings. A multiple probe design across students was used to evaluate the effectiveness of the three types of school instruction and community training. After systematic training, most of the students increased their laundry performance with all three sets of school-based materials; however, generalization of these acquired skills was limited in the two community settings. Direct training in one of the community settings resulted in more efficient acquisition of the laundry skills and enhanced generalization to the untrained laundromat setting for most of the students. Results of this study are discussed in regard to the issue of school versus community-based instruction and recommendations are made for future research in this area.