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BACKGROUND: Body mass index (BMI) above ≥ 25 kg/m2 is associated with increased risk for cancer-related morbidity and mortality. Achieving recommended amounts of physical activity (PA), sedentary time (ST), and sleep can help cancer survivors (CS) attain a healthy BMI. This cross-sectional study examined the potential role of reallocating time between moderate and light PA, ST, and sleep on BMI in CS. METHOD: A sample of CS (N = 73, Mage = 53.7 ± 12.9) wore an activPAL and Actiwatch accelerometer for 7 days, 24 h per day to measure PA intensity and sleep, respectively. Self-reported height and weight or scale/stadiometer were used to calculate BMI. Isotemporal substitution models were used to reallocate time, averaged over the 7-day period, from one activity of interest to another and examine the associations with BMI. Statistical significance was set at p < .05. RESULTS: The following reallocations of 30 min were significantly associated with BMI: sleep to ST (+ 0.80 kg/m2, p = 0.02) and ST to light PA (- 0.53 kg/m2, p = 0.008). No significant associations with BMI were observed for reallocating time to or away from moderate-vigorous PA. CONCLUSION: The results of this study suggest that sleep and light PA may have important implications for achieving a healthy BMI in CS. Therefore, future research should include interventions which target light PA and sleep to determine if they can improve BMI in CS.
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Supervivientes de Cáncer , Neoplasias , Humanos , Adulto , Persona de Mediana Edad , Anciano , Índice de Masa Corporal , Estudios Transversales , Ejercicio Físico , Sueño , AcelerometríaRESUMEN
OBJECTIVE: While the incidence and type of blood malignancies are well documented amid primary Sjögren's syndrome patients (pSS), data focusing on solid neoplasms are more conflicting. We aimed to describe clinical, pathological, and immunological characteristics of pSS patients with cancers, along with the chronological interplay between the two conditions. METHODS: Outcomes concerning both pSS and cancer were retrospectively collected from Montpellier University Hospital (tertiary center) between 2019 and 2020. pSS characteristics were compared to a control group of pSS patients without cancer. RESULTS: A total of 165 patients with pSS were included: 55 patients with cancer (52 female, mean age 58.4 ± 10.4 years at pSS diagnosis; mean follow-up 10.5 ± 10.1 years, 12 patients had multiple cancers) and 110 controls without cancer. Characteristics of pSS patients with cancers were different from controls mostly for lymphoma prognosis factors. Among the 70 cancers, we recorded 55 solid neoplasms (whom 27 breast cancers and 8 lung cancers, and 82% of adenocarcinomas), with no evidence of disease at the end of follow-up in 85% of them. Among the 15 recorded blood malignancies, ten were lymphomas with an excellent prognosis. Regarding chronological interplay between cancer and pSS, most cancers (43%) were diagnosed close (± 5 years) to pSS diagnosis. Breast cancers were diagnosed before or close to pSS diagnosis (mean delay - 1.8 ± 13.0 years), at an early stage, with only two relapses (no cancer-related death), while lung cancers were diagnosed late after. CONCLUSIONS: The tight chronological interplay between breast cancer and pSS and the intriguing pathological and immunological pattern of pSS in these patients suggest a hypothesis of immune control of cancer.
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Neoplasias Pulmonares , Linfoma , Síndrome de Sjögren , Humanos , Femenino , Persona de Mediana Edad , Anciano , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Linfoma/terapiaRESUMEN
OBJECTIVES: To describe the epidemiology, characteristics, response to initial treatment, and outcomes of Adult-Onset Still's disease (AOSD) in the Afro-Caribbean population of Martinique with free and easy access to specialised care. METHODS: We conducted a retrospective study from 2004 to 2022 in the island of Martinique, French West-Indies which total population was 354 800 in 2021. Patients were identified from multiple sources including standardised databases. To be included, patients had to be residents of the island and fulfilled Yamaguchi and/or Fautrel's criteria for AOSD, or have a compatible disease course, without a diagnosis of cancer, auto-immune disease or another auto-inflammatory disorder. Date of diagnosis, clinical and biological characteristics, treatments, and outcomes were collected. RESULTS: The prevalence was 7.6/100 000 inhabitants in 2021. The mean incidence was 0.4/100 000 during study period. Thirty-three patients (70.6% females) with a median follow-up of 35 months [7.5 to 119] were included. Twenty-six patients (78.8%) had a systemic pattern. Patients with a systemic monocyclic pattern had significantly more polyarticular involvement than patients with systemic polycyclic pattern (p = 0.016). Pulmonary involvement occurred in 51.5% of patients at diagnosis and systemic Pouchot score has been identified as an independent predictive factor for pulmonary involvement; OR of 3.29 [CI 95% 1.20; 9.01]. At first flare, all patients but one received oral glucocorticoids, 11 patients (32.4%) received intravenous glucocorticoids pulse and 12 patients (33%) received anti-IL1 therapy. Nineteen patients (57%) relapsed in a median time of 9 months [6 to 12] Three patients (9%) developed hemophagocytosis lymphohistiocytosis, fatal in 1 case. All deceased patients (n = 4, 11.76%) belonged to the systemic polycyclic pattern, with an event-free survival of 13.6 months [IQR 5.7; 29.5] CONCLUSION: AOSD in the Afro-Caribbean population of Martinique shares some similarities with other ethnic groups, but exhibit differences, such as a high proportion of lung involvement. Comparative studies are needed to confirm these results.
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Enfermedad de Still del Adulto , Adulto , Femenino , Humanos , Masculino , Pueblos Caribeños/estadística & datos numéricos , Etnicidad , Glucocorticoides/uso terapéutico , Martinica/epidemiología , Estudios Retrospectivos , Enfermedad de Still del Adulto/diagnóstico , Enfermedad de Still del Adulto/tratamiento farmacológico , Enfermedad de Still del Adulto/epidemiología , Enfermedad de Still del Adulto/etnología , Indias Occidentales/epidemiologíaRESUMEN
BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease with increased risk of infections. Here, we assessed whether pSS patients were at higher risk of hospitalization for community and opportunistic infections. METHODS: We selected newly hospitalized pSS patients between 2011 and 2018, through a nationwide population-based retrospective study using the French Health insurance database. We compared the incidence of hospitalization for several types of infections (according to International Classification for Disease codes, ICD-10) between pSS patients and an age- and sex-matched (1:10) hospitalized control group. We calculated adjusted Hazard Ratios (aHR, 95% CI) adjusted on socio-economic status, past cardiovascular or lung diseases and blood malignancies factors. RESULTS: We compared 25 661 pSS patients with 252 543 matched patients. The incidence of hospitalizations for a first community infection was increased in pSS patients [aHR of 1.29 (1.22-1.31), p < .001]. The incidence of hospitalization for bronchopulmonary infections was increased in pSS patients [aHR of 1.50 (1.34-1.69), p < .001, for pneumonia]. Hospitalizations for pyelonephritis and intestinal infections were increased [aHR of 1.55 (1.29-1.87), p < .001 and 1.18 (1.08-1.29), p < .001, respectively]. Among opportunistic infections, only zoster, and mycobacteria infections (tuberculosis and non-tuberculous) were at increased risk of hospitalization [aHR of 3.32 (1.78-6.18), p < .001; 4.35 (1.41-13.5), p = .011 and 2.54 (1.27-5.06), p = .008, respectively]. CONCLUSIONS: pSS patients are at higher risk of hospitalization for infections. The increased risk of hospitalization for mycobacterial infections illustrates the potential bilateral relationship between the two conditions. Vaccination against respiratory pathogens and herpes zoster virus may help prevent some hospitalizations in pSS patients.KEY MESSAGESPrimary Sjögren's syndrome (pSS) increases hospitalization risk for community infections: bronchopulmonary, skin, dental, ear-nose-throat, intestinal infections and pyelonephritis.Hospitalizations for zoster and mycobacterial infections are also increased in this population.Dedicated preventive measures and vaccination campaigns could decrease the burden of infections in pSS patients.
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Herpes Zóster , Infecciones Oportunistas , Pielonefritis , Síndrome de Sjögren , Estudios de Cohortes , Herpes Zóster/epidemiología , Hospitalización , Humanos , Estudios Retrospectivos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/epidemiologíaRESUMEN
Lupus nephritis (LN) has been described as having worse survival and renal outcomes in African-descent patients than Caucasians. We aimed to provide long-term population-based data in an Afro-descendant cohort of LN with high income and easy and free access to specialized healthcare. STUDY DESIGN: We performed a retrospective population-based analysis using data from 2002-2015 of 1140 renal biopsies at the University Hospital of Martinique (French West Indies). All systemic lupus erythematosus patients with a diagnosis of LN followed for at least 12 months in Martinique or who died during this period were included. RESULTS: A total of 89 patients were included, of whom 68 (76.4%) had proliferative (class III or IV), 17 (19.1%) had membranous (class V), and 4 (4.5%) had class I or II lupus nephritis according to the ISN/RPS classification. At a mean follow-up of 118.3 months, 51.7% of patients were still in remission. The rates of end-stage renal disease were 13.5%, 19.1%, and 21.3% at 10, 15, and 20 years of follow-up, respectively, and mortality rates were 4.5%, 5.6%, and 7.9% at 10, 15, and 20 years of follow-up, respectively. CONCLUSIONS: The good survival of our Afro-descendant LN patients, similar to that observed in Caucasians, shades the burden of ethnicity but rather emphasizes and reinforces the importance of optimizing all modifiable factors associated with poor outcome, especially socioeconomics.
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PURPOSE: Quality of life (QOL) is an important psychosocial outcome in cancer survivors (CS). Physical activity (PA), reducing sedentary time (ST), and sleep can help CS improve QOL; however, these behaviors are commonly studied in isolation, despite their interdependence during the 24-h day (i.e., time in one activity cannot increase without time decreasing in another activity). This study examined the effects of reallocating time between moderate to vigorous PA (MVPA), light PA, ST, and sleep on QOL in a mixed sample of CS. METHODS: A cross-sectional sample of CS (N = 73) diagnosed with breast (29.7%), colorectal (33.8%), or other (36.5%) cancer. MVPA, light PA, and ST were measured using the activPAL™ accelerometer, and sleep duration using the Actiwatch™ accelerometer. Both were worn for 7 days, 24 h per day. QOL was self-reported using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. Isotemporal substitution models were used to reallocate 30 min between activities. Statistical significance was set at p < .05. RESULTS: Participants accumulated, M = 24.0 ± 18.9 min/day of MVPA, 291.7 ± 100.4 min/day of light PA, 593.1 ± 108.3 min/day of ST, and 486.6 ± 57.6 min/night of sleep. Isotemporal substitution effects for reallocating time between MVPA, light PA, ST, and sleep were not significantly associated with QOL. CONCLUSIONS: Findings from this study suggest that among CS who are achieving adequate levels of PA and sleep, changes in 30 min of these activities may not impact QOL. Future studies should aim to recruit a larger, more representative sample and explore the role of bouted activity time.
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Supervivientes de Cáncer , Neoplasias , Supervivientes de Cáncer/psicología , Estudios Transversales , Ejercicio Físico , Humanos , Calidad de Vida , SueñoRESUMEN
X-linked adrenoleukodystrophy (ALD) caused by the ABCD1 mutation, is the most common inherited peroxisomal disease. Previously, we generated an ALD patient-derived SCHi001-A iPSC model. In this study, we have performed the first genome editing of ALD patient-derived SCHi001-A iPSCs using homology-directed repair (HDR). The mutation site, c.1534G > A [GenBank: NM_000033.4], was corrected by introducing ssODN and the CRISPR/Cas9 system. The cell line exhibited normal iPSC plulipotency marker expression following genome editing. Mutation-corrected iPSCs from SCHi001-A iPSC line can be used in research into the pathophysiology of and therapeutics for ALD.
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Advances in sequencing technologies have facilitated the discovery of previously unknown genetic variants in both inherited and acquired disorders, and tools to correct these pathogenic variants are rapidly evolving. Since the first introduction of CRISPR-Cas9 in 2012, the field of CRISPR-based genome editing has progressed immensely, giving hope to many patients suffering from genetic disorders that lack effective treatment. In this review, we will examine the basic principles of CRISPR-based genome editing, explain the mechanisms of new genome editors, including base editors and prime editors, and evaluate the therapeutic possibilities of CRISPR-based genome editing by focusing on recently published clinical trials and animal studies. Although efficacy and safety issues remain a large concern, we cannot deny that CRISPR-based genome editing will soon be prevalent in clinical practice.
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BACKGROUND: Cutaneous Leishmaniasis (CL) is endemic in French Guiana but cases are usually sporadic. An outbreak signal was issued on May 15th 2020 with 15 suspected cases after a military training course in the rainforest. An outbreak investigation was carried out. METHODOLOGY/PRINCIPAL FINDINGS: Thirty cases were confirmed. Leishmania guyanensis was the most frequent species (90%). The most frequent presentation was ulcerative (90%). Lesions on the face and hands were frequent (40% each). Eight cases (26%) presented a poor outcome after treatment with pentamidine and required a second line with amphotericin B. Three of them required further treatments with meglumine antimoniate or miltefosine. Two spots within the training area were deemed as likely sites of contamination, due to illegal logging. The isolated Leishmania strains did not form a separate cluster. Participation in Week 13 of year 2020 was associated with infection (OR = 4.59 [1.10-19.83]; p = 0.016) while undergoing only the "Fighting" exercise was protective (OR = 0.1 [0-0.74]; p = 0.021). There was no association between infection and other risk factors at the individual level. The attack rate of Regiment B (14/105 = 13.3%) was significantly higher (OR = 4.22 [1.84-9.53], p = 0.0001) compared to Regiment A (16/507 = 3.2%). The attack rate during this training course (30/858 = 3.5%) was significantly higher (OR 2.29 [1.28-4.13]; p = 0.002) than for other missions in French Guiana during the same period (22/1427 = 1.5%). CONCLUSIONS: This outbreak could be explained by a combination of factors: climatic conditions around week 13, at-risk activities including night trainings, absence of impregnation, a lesser experience of rainforest duties in Regiment B and illegal logging attracting sandflies on military training grounds.
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Leishmania/aislamiento & purificación , Leishmaniasis Cutánea/epidemiología , Leishmaniasis Cutánea/parasitología , Personal Militar/estadística & datos numéricos , Filogenia , Adulto , Antiprotozoarios/administración & dosificación , Brotes de Enfermedades , Femenino , Guyana Francesa/epidemiología , Humanos , Leishmania/efectos de los fármacos , Leishmania/genética , Leishmania/fisiología , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pentamidina/administración & dosificación , Adulto JovenRESUMEN
OBJECTIVE: Characterize firefighters' acute stress and tiredness by duty status (ie, "off night/day," "on night/day"). METHODS: Thirty nine career firefighters completed three, eight-day smartphone-based ecological momentary assessment periods with seven surveys per day assessing stress and tiredness. Mixed-effects location scale models examined duty status effects on stress and tiredness. RESULTS: Firefighters' lowest stress and tiredness levels were when off-duty (ßâ=â16.27 and ßâ=â24.71, respectively) and their highest levels were when on-duty (ßâ=â24.47 and ßâ=â32.18, respectively). Within-subject effects of duty status accounted for a larger proportion of variability in stress and tiredness for all duty types, except for stress when "on-duty night/off-duty day." CONCLUSIONS: Firefighters had more similar stress and tiredness outcomes when they were on-duty and less similar outcomes when off-duty. This could be due to firefighters having more similar experiences when they are on- versus off-duty.
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Fatiga/epidemiología , Bomberos , Estrés Laboral/epidemiología , Evaluación Ecológica Momentánea , Humanos , Proyectos PilotoRESUMEN
Evidence suggests that physical activity and alcohol use are positively related among young adults. Two studies have examined daily relations, and results have shown conflicting findings. We examined relations between physical activity and alcohol use at both within- and between-individual levels and investigated moderators of the relation at both levels. 269 college students wore accelerometers to collect physical activity data over a 2-week period. At the end of each day, they indicated whether or not they drank alcohol. Multilevel logistic regression indicated neither within- nor between-subject relations were statistically significant. Positive affect, negative affect, and drinking motives moderated these relations at the between-subject level. Contrary to previous research, we did not observe a relation between physical activity and alcohol use at the daily level. Unique features of the current study suggest next steps for future research examining the perplexing PA-alcohol relation in this population.
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Consumo de Bebidas Alcohólicas/epidemiología , Ejercicio Físico , Adaptación Psicológica , Adolescente , Consumo de Bebidas Alcohólicas/psicología , Femenino , Humanos , Masculino , Motivación , Estudiantes , Universidades , Adulto JovenRESUMEN
Older adults constitute an increasingly large share of the workforce. Older workers often contribute positively to organizational outcomes through characteristics such as deep organizational knowledge and long-standing client relationships. Thus, it is important to understand how to maintain or increase older workers' job satisfaction, a variable that has been linked to positive work outcomes. In this study, several hypotheses regarding job satisfaction and age were derived from Carstensen's socioemotional selectivity theory and were tested using longitudinal analysis of a cross-sequential sample. Supporting socioemotional selectivity theory, results showed that autonomy became increasingly important to job satisfaction as workers age. Contrary to the theory, annual income also became increasingly important to job satisfaction. We discuss the importance of our findings for theory, research, and practice.
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Envejecimiento/psicología , Satisfacción en el Trabajo , Autonomía Profesional , Trabajo/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Empleo , Femenino , Humanos , Renta , Entrevistas como Asunto , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Parkinson's disease (PD) is neurodegenerative movement disorder characterized by degeneration of midbrain-type dopamine (mDA) neurons in the substantia nigra (SN). The RNA-binding protein Lin28 plays a role in neuronal stem cell development and neuronal differentiation. In this study, we reveal that Lin28 conditional knockout (cKO) mice show degeneration of mDA neurons in the SN, as well as PD-related behavioral deficits. We identify a loss-of-function variant of LIN28A (R192G substitution) in two early-onset PD patients. Using an isogenic human embryonic stem cell (hESC)/human induced pluripotent stem cell (hiPSC)-based disease model, we find that the Lin28 R192G variant leads to developmental defects and PD-related phenotypes in mDA neuronal cells that can be rescued by expression of wild-type Lin28A. Cell transplantation experiments in PD model rats show that correction of the LIN28A variant in the donor patient (pt)-hiPSCs leads to improved behavioral phenotypes. Our data link LIN28A to PD pathogenesis and suggest future personalized medicine targeting this variant in patients.
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Enfermedad de Parkinson/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/fisiología , Sustancia Negra/metabolismo , Animales , Conducta Animal , Trasplante de Células , Modelos Animales de Enfermedad , Dopamina/metabolismo , Neuronas Dopaminérgicas/fisiología , Células Madre Embrionarias/fisiología , Edición Génica , Predisposición Genética a la Enfermedad , Humanos , Células Madre Pluripotentes Inducidas/fisiología , Células Madre Pluripotentes Inducidas/trasplante , Ratones , Ratones Noqueados , Mutación , Células-Madre Neurales/fisiología , Células-Madre Neurales/trasplante , Enfermedad de Parkinson/genética , Ratas , Trasplante de Células MadreRESUMEN
Risk factors for melanoma, the deadliest form of skin cancer, include lifetime sun exposure and a history of sunburns. However, a minority of adolescents report consistent engagement in sun protective behaviors. The few sun protection interventions that have targeted adolescents have had little effect on behavior change, which suggests that a better understanding of the issue, especially from the adolescents' perspective, is needed. Although efforts to qualitatively examine adolescent sun protection have been carried out in a handful of countries, no studies to date have focused on U.S. adolescents. We conducted focus groups with 44 6th-8th grade students in Colorado to explore their sun protection knowledge, attitudes and behaviors. Results supported previous findings that adolescents do not engage in regular skin protection but have experienced the negative consequences of sun exposure (e.g., severe sun burns, and blistering). In addition, participants demonstrated limited and sometimes inaccurate knowledge about the long-term risks of sun exposure, as well as effective methods of sun protection. Barriers to engaging in sun protective behaviors included a desire to tan, inconvenience, and physical discomfort. Facilitators included peer and family encouragement, previous experience with sunburns and/or skin cancer, and knowledge of potential consequences. These findings provide valuable insights that can inform future intervention and research related to sun protection among U.S. adolescents.
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Conocimientos, Actitudes y Práctica en Salud , Quemadura Solar/prevención & control , Adolescente , Actitud Frente a la Salud , Femenino , Grupos Focales , Humanos , Masculino , Psicología del Adolescente , Neoplasias Cutáneas/prevención & control , Neoplasias Cutáneas/psicología , Quemadura Solar/psicología , Protectores SolaresRESUMEN
BACKGROUND: The purpose of this study was to evaluate the efficacy of corticosteroid injection and determine the duration of symptom-free period after treatment with a single ultrasound-guided injection for a painful Morton's neuroma. MATERIALS AND METHODS: From May 2002 to November 2003, 35 consecutive patients (7 males, 28 females) (mean age, 54; age range, 29 to 77 years) underwent a single ultrasound guided corticosteroid injection. Thirty-nine injections were performed as 4 patients had bilateral Morton's neuromas. The injection of 1.0 cc Celestone Chronodose (5.7 mg/ml) with 0.5 cc of 1% lidocaine was performed into the symptomatic intermetatarsal web-space. The efficacy of the injection was determined by the Johnson grading scale, and modified lower extremity functional scale. RESULTS: On the Johnson scale, 15 of 39 (38%) neuromas showed complete satisfaction 9 months after treatment and 11 of 39 (28%) were satisfied with minor reservations. A total of 26 of 39 (66%) neuromas had a positive outcome 9 months after the injection. On the functional daily activity (FDA) scale, 20 of 39 (51%) neuromas showed no difficulty and 4 of 39 (10%) indicated minor difficulties, which was considered a positive outcome 9 months after injection. Complete pain relief was achieved in 11 of 39 (28%) neuromas 9 months after treatment. Twelve of 39 (31%) neuromas did not respond to conservative treatment and required surgery. The results of treatment suggested improvement in efficacy if injection was used early. The size of the lesion measured on ultrasound showed no correlation with pain relief after injection. CONCLUSION: A single corticosteroid injection can offer short-term pain relief in the conservative management of Morton's neuroma.
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Betametasona/análogos & derivados , Antepié Humano/inervación , Glucocorticoides/administración & dosificación , Neuroma/tratamiento farmacológico , Neoplasias del Sistema Nervioso Periférico/tratamiento farmacológico , Adulto , Anciano , Betametasona/administración & dosificación , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Inyecciones Intralesiones , Masculino , Persona de Mediana Edad , Neuroma/complicaciones , Neuroma/diagnóstico por imagen , Dolor/etiología , Dolor/prevención & control , Neoplasias del Sistema Nervioso Periférico/complicaciones , Neoplasias del Sistema Nervioso Periférico/diagnóstico por imagen , Resultado del Tratamiento , UltrasonografíaRESUMEN
The results of a functional analysis of problem behavior and a paired-choice assessment were compared to determine whether the same social reinforcers were identified for problem behavior and an appropriate response (time allocation). The two assessments were conducted in classroom settings with 4 adolescents with mental retardation who engaged in severe problem behavior. Each student's classroom teacher served as the therapist for all phases of assessment. The two assessment procedures identified the same social reinforcers for problem and appropriate behavior for 3 of 4 participants.