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Survival often depends on behavior that can adapt to rapid changes in contingencies, which should be particularly well suited to a contingency-sensitive and data-based discipline such as applied behavior analysis (ABA). The speed and scale with which contingencies shifted in early March 2020 due to the effects of COVID-19 represent a textbook case for rapid adaptation with a direct impact on the survival of many types of enterprises. We describe here the impact, changes, and outcomes achieved by a large, multifaceted ABA clinical program that has (a) ongoing data that forecasted and tracked changes, (b) staff well practiced with data-based shifts in operations (behavior), and (c) up-to-date information (data) on policy and regulations. The results showed rapid shifts in client and staff behavior on a daily basis, shifts in services from in-person services to telehealth, and increases in volumes, revenue, and margins. We detail regulations and provide actionable steps that clinical organizations can take pertinent to this shift now and in the future. The challenges of the COVID-19 pandemic underscore the importance of maintaining robust coordination and communication across our field in order to address crises that affect our field.

Robust fermentation performance of microbial cell factories is critical for the successful scaling of a biotechnological process. From shake flask cultivations to industrial-scale bioreactors, consistent strain behavior is fundamental to achieve the production targets. To assert the importance of this feature, we evaluated the impact of the yeast strain design and construction method on process scalability -from shake flasks to bench-scale fed-batch fermentations- using two recombinant Saccharomyces cerevisiae strains capable of producing β-carotene; SM14 and βcar1.2 strains. SM14 strain, obtained previously from adaptive evolution experiments, was capable to accumulate up to 21 mg/gDCW of β-carotene in 72 h shake flask cultures; while the βcar1.2, constructed by overexpression of carotenogenic genes, only accumulated 5.8 mg/gDCW of carotene. Surprisingly, fed-batch cultivation of these strains in 1L bioreactors resulted in opposite performances. βcar1.2 strain reached much higher biomass and β-carotene productivities (1.57 g/L/h and 10.9 mg/L/h, respectively) than SM14 strain (0.48 g/L/h and 3.1 mg/L/h, respectively). Final β-carotene titers were 210 and 750 mg/L after 80 h cultivation for SM14 and βcar1.2 strains, respectively. Our results indicate that these substantial differences in fermentation parameters are mainly a consequence of the exacerbated Crabtree effect of the SM14 strain. We also found that the strategy used to integrate the carotenogenic genes into the chromosomes affected the genetic stability of strains, although the impact was significantly minor. Overall, our results indicate that shake flasks fermentation parameters are poor predictors of the fermentation performance under industrial-like conditions, and that appropriate construction designs and performance tests must be conducted to properly assess the scalability of the strain and the bioprocess.

Self-injurious behavior (SIB) is a chronic disorder that often begins in early childhood; however, few studies have examined the onset of SIB in young children. This preliminary study reports on the identification, assessment and observation of SIB in 32 children who had begun to engage in SIB within the previous 6 months. Participants were ages birth to 5 years and presented with or were at risk for intellectual and/or developmental disabilities. Assessment measures included parental interviews, developmental and language measures, standardized measures of problem behavior, and direct observations conducted in the home. Results indicated that for most children, SIB emerged prior to age 1 year, and multiple topographies of SIB and other problem behaviors developed in most children. Multiple measures were useful in identifying SIB and in characterizing the behavior by topography, frequency, and severity. Findings from the examination of child communication in relation to SIB were inconclusive. Results are discussed in relation to theories of SIB emergence, and previous observational studies of young children with SIB.

Many forms of psychopathology and substance abuse problems are characterized by chronic ritualized forms of avoidance and escape behavior that are designed to control or modify external or internal (i.e., thoughts, emotions, bodily sensations) threats. In this functional magnetic resonance imaging investigation, we examined amygdala reactivity to threatening cues when avoidance responding consistently prevented contact with an upcoming aversive event (money loss). In addition, we examined escape responding that terminated immediate escalating money loss and approach responding that produced a future money gain. Results showed cues prompting avoidance, escape and approach behavior recruited a similar fronto-striatal-parietal network. Within the amygdala, bilateral activation was observed to threatening avoidance and escape cues, even though money loss was consistently avoided, as well as to the reward cue. The magnitude of amygdala responses within subjects was relatively similar to avoidance, escape and approach cues, but considerable between-subject differences were found. The heightened amygdala response to avoidance and escape cues observed within a subset of subjects suggests threat-related responses can be maintained even when aversive events are consistently avoided, which may account for the persistence of avoidance-coping in various clinical disorders. Further assessment of the relation between amygdala reactivity and avoidance-escape behavior may prove useful in identifying individuals with or at risk for neuropsychiatric disorders.

Active avoidance involving controlling and modifying threatening situations characterizes many forms of clinical pathology, particularly childhood anxiety. Presently our understanding of the neural systems supporting human avoidance is largely based on nonhuman research. Establishing the generality of nonhuman findings to healthy children is a needed first step towards advancing developmental affective neuroscience research on avoidance in childhood anxiety. Accordingly, this investigation examined brain activation patterns to threatening cues that prompted avoidance in healthy youths. During functional magnetic resonance imaging, fifteen youths (ages 9-13) completed a task that alternately required approach or avoidance behaviors. On each trial either a threatening 'Snake' cue or a 'Reward' cue advanced towards a bank containing earned points. Directional buttons enabled subjects to move cues away from (Avoidance) or towards the bank (Approach). Avoidance cues elicited activation in regions hypothesized to support avoidance in nonhumans (amygdala, insula, striatum and thalamus). Results also highlighted that avoidance response rates were positively correlated with amygdala activation and negatively correlated with insula and anterior cingulate activation. Moreover, increased amygdala activity was associated with decreased insula and anterior cingulate activity. Our results suggest that nonhuman neurophysiological research findings on avoidance may generalize to neural systems associated with avoidance in childhood. Perhaps most importantly, the amygdala/insula activation observed suggests that threat-related responses can be maintained even when aversive events are consistently avoided, which may account for the persistence of avoidance-coping in childhood anxiety. The present approach may offer developmental affective neuroscience a conceptual and methodological framework for investigating avoidance in childhood anxiety.

UNLABELLED A 73-year-old man with lung squamous-cell carcinoma simultaneously developed a factor VIII:C inhibitor and a transient positive direct Coombs' test. The factor VIII:C inhibitor was characterized as a mixture of IgG1, IgG2, IgG4 with kappa and lambda light chains. The Coombs' test was IgM-specific. TREATMENT blood transfusions (packed red cells), cyclophosphamide and prednisone. Bleeding subsided without factor VIII-replacement therapy. Before death, in spite of the tumour-mass progression, factor VIII:C was normal.

Summary Approximately six hours of biofeedback training was given to eight fecally incontinent children with myelomeningocele in order to establish bowel control. Their ages ranged from five to 15 years. The patients were shown a polygraph tracing of the external anal sphincter while they were being encouraged voluntarily to contract the sphincter when the rectum was distended with progressively larger volumes of air in a balloon. Seven of the eight patients showed normal sensation for rectal distension. Following this training period, five of the children had no incontinent periods, and two of these had discontinued enemas or suppositories. A sixth patient had an 80 per cent reduction in the frequency of incontinence. The remaining two did not benefit. At follow-up between 13 and 24 months later, four children were incontinent once a month or less often; two others were incontinent once per day, a considerable decrease from the pre-training period. The two children who failed to learn were still incontinent at follow-up. These results show that fecally incontinent patients with myelomeningocele can learn to evacuate normally or to reduce soiling after a relatively short period of biofeedback training. RESUME Approximativement six heures dcae;apprentissage en biofeedback ont ete donnees a huit enfants incontinents fecaux, porteurs de myelomeningocele, pour obtenir un controle rectal. Les âges allaient de cinq a 15 ans. Les malades pouvaient observer un trace polygraphique du sphincter anal externe pendant quils etaient encourages volontairement a contracter ce sphincter et que le rectum etait progressivement distendu par le gonflement progressif d'un balloon. Sept enfants sur huit resentirent une sensation normale a la distension rectale. A la suite de cette periode d'apprentissage, cinq des six enfants ne presenteent plus de periode d'incontinence et deux d'entre eux purent abandonner lavements et suppositoires. Un sixieme malade presenta une reduction de 80 pour cent de son incontinence. It n'y eut aucun benefice pour les deux cas restants. Lors d'un controle entre 13 et 24 mois plus tard, quatre enfants etaient incontinents une fois par mois ou moins, deux une fois par jour, ce qui traduisait une diminution considerable par rapport a la periode de pre-apprentissage. Les deux enfants qui n'avaient pu beneficier d'un apprentissage etaient toujours incontinents au moment du controTle. Ces resultats montrent que des malades porteurs de myelomeningocele et incontinents fecaux peuvent acquerir une evacuation rectale normale ou reduire leur incontinence apres une periode relativement courte dcar;apprentissage en biofeedback. ZUSAMMENFASSUNG Acht Kinder mit Stuhlinkontinenz bei Myelomeningocele erhielten etwa sechs Stunden ein Biofeedback Training, durch das eine Darmkontrolle aufgebaut werden sollte. Das Alter der Patienten lag zwischen funf und 15 Jahren. Man forderte die Patienten auf, den Sphincter ani externus willkurlich zu kontrahieren, wahrend das Rectum durch ein zunehmend groβeres Luftvolumen in einem Ballon gedehnt wurde und zeigte ihnen gleichzeitig polygraphische Aufzeichnungen vom Sphincter. Sieben der acht Patienten hatten eine normale Empfindung fur die Dehnung des Rectums. Nach dieser Trainingsperiode hatten funf der Kinder keine Inkontinez mehr und zwei davon konnten Klistiere oder Suppositorien absetzen. Bei einer sechsten Patienten war die Inkontinenzhaufigkeit um 80 Prozent reduziert. Die restlichen zwei hatten keinen Erfolg. Eine Kontrolle nach 13 und 24 Monaten: vier Kinder waren einmal im Monat oder seltener inkontinent; zwei andere waren einmal am Tag inkontinent; insgesamt war das eine betrachtliche Verbesserung zu dem Zustand vor dem Training. Die beiden Kinder, die keinen Lernerfolg hatten, waren auch bei den Kontrollen weiterhin inkontinent. Diese Ergebnisse zeigen, daβ stuhlinkontinente Patienten mit Myelomengocele es eriernen konnen, den Stuhl normal zu entleeren oder das Einkoten zu reduzieren, nachdem sie fur eine relativ kurze Zeit ein Biofeedback Training gemacht haben. RESUMEN Se aplico aproximadamente seis horas de aprendizaje de biofeedback a ocho nibos con incontinencia fecal por mielomeningocele, con el objeto de establecer un control intestinal. Sus edades oscilaban entre cinco y 15 anos. A los pacientes se les mostro un trazado poligrafico del esfinter anal externo, al mismo tiempo que se les incitaba a contraer voluntariamente el esfinter cuando el recto estaba distendido por volumenes de aire progresivamente mas grandes gracias a un baton aereo. Siete de los ocho pacientes mostraron una sensation normal de distension rectal. Siguiendo este periodo de entrenamiento, cinco de los ninos no tuvieron periodos de incontinencia y dos de ellos nee esitaron de una forma discontinua de enemas o supositorios. Un sexto paciente tuvo un 80 por ciento de reduction en la frecuencia de la incontinencia. Los otros dos no obtuvieron ningun beneficio. Vistos posteriormente a los 13 y 24 meses, cuatro ninos eran incontinentes una vez al mes o incluso con menor frecuencia, otros dos eran incontinentes una vez al dia, lo que representaba una disminucion considerable en comparacion con el periodo anterior al del entrenamiento. Los dos ninos que habian fallado en el aprendizaje continuaban todavia incontinentes. Estos resultados muestran que los pacientes con incontinencia fecal con meningocele pueden aprender a evacuar normalmente o a reducir la incontinencia depues de un periodo relativamente corto de entrenamiento por biofeedback.

Functional magnetic resonance imaging (fMRI) is used to study brain function during behavioral tasks. The participation of pediatric subjects is problematic because reliable task performance and control of head movement are simultaneously required. Differential reinforcement decreased head motion and improved vigilance task performance in 4 children (2 with behavioral disorders) undergoing simulated fMRI scans. Results show that behavior analysis techniques can improve child cooperation during fMRI procedures.

We describe a Master's program in Applied Behavior Analysis that involves collaboration between an academic graduate program in psychology and the departments of an institution dedicated to the delivery of behavioral services: in this instance, the University of Maryland, Baltimore County, and the Kennedy Krieger Institute of the Johns Hopkins University School of Medicine. The launching of a new program and its subsequent maintenance involves a variety of contingencies, both academic and professional. This paper discusses a few of them, and demonstrates how quickly and effectively progress can be made when compatible and reciprocal contingencies of support are identified for all of the various participants in a program. As we enter the Decade of Behavior, we hope this program will provide a source of more practitioners of applied behavior analysis, so sorely needed to meet the growing demand for our demonstrably successful interventions. ********** One hallmark of behavior analysis and one source of its success in interventions is its recognition of multiple causation in the determination of complex behavior. Multiple causation operates, for example, in verbal behavior, as when the order that someone places at a fast food restaurant is simultaneously determined by many different variables: the person behind the counter as an audience, the menu as an occasion for textual behavior, the food visible in pictures and on the trays of other customers as an occasion for tacting, the overheard orders of other customers as an occasion for echoic behavior, the factors that make the food to be ordered reinforcing as establishing operations, and so on. When many variables that each occasion the same verbal response come together at one time, the verbal behavior that follows may be virtually inevitable. It is no surprise that many causes also enter into institutional behavior, and because much of our own activity as behavior analysts occurs in institutional settings, it may be useful to explore the multiple causation that may be involved in the creation and maintenance of behavior analytic programs. History It is difficult to pinpoint just when discussions began about a possible collaborative program involving the Department of Psychology at the University of Maryland, Baltimore County (UMBC) and the Kennedy Krieger Institute of the Johns Hopkins University School of Medicine (KKI); they may go back two decades or more. Some of the more recent and key administrative discussions (within the past five years) involved A. Charles Catania at UMBC, the chair of the Department of Behavioral Psychology at KKI, Michael F. Cataldo, and the chair of the UMBC Department of Psychology, Carlo DiClemente. Once agreement had been reached about the desirability and feasibility of the program and the nature of its administration, Wayne W. Fisher and A. Charles Catania undertook the implementation of the program, with special attention to design of courses and professional training. The mutual interests of all participants quickly became evident. They included but were not limited to the following: The growing field of applied behavior analysis called for more well-trained practitioners; the UMBC administration wanted to expand the enrollment of graduate students, especially at the Master's level; and, the behavior analysts at KKI needed more qualified people to staff inpatient treatment units and wanted more opportunities to interact with students of behavior analysis. The collaborative program was approved by the UMBC Department of Psychology during the 1997-1998 academic year, and the call for applications went out late in Spring 1998 with a July 1 deadline. Under those circumstances, the numbers were of course too small to really constitute a class, and a couple of students who were unable to complete applications in time were provisionally admitted to course work as special students. More standardized application procedures brought in four more students in the 1999-2000 academic year (including one student from Iceland) and six more in the current (2000-2001) academic year. …

Use of animal models can increase scientific understanding of and clinical/educational intervention possibilities for persons with mental retardation. Information gathered through such models has provided an important foundation for both theory and practice. Progress in understanding and ameliorating intellectual disability through animal modeling will be enhanced by efforts to increase the validity of the models. That is, the models must capture not merely important behavioral/cognitive processes per se, but also processes that may be especially impaired in intellectual disability. The authors reviewed criteria for determining that a given individual has an intellectual disability, selected examples of research on animal behavior that have contributed to effective prevention and treatment approaches, and successful approaches for modeling behavioral retardation. Animal models using behavioral measures based on characteristics that discriminate human mental retardation may prove to provide the most valid and clinically relevant approach. © 1997 Wiley-Liss, Inc.

Background: Previous studies have reported an association between sun exposure and improved cutaneous melanoma (CM) survival. We analysed the association of UV exposure with prognostic factors and outcome in a large melanoma cohort. Methods: A questionnaire was given to 289 (42%) CM patients at diagnosis (Group 1) and to 402 CM patients (58%) during follow-up (Group 2). Analyses were carried out to investigate the associations between sun exposure and melanoma prognostic factors and survival. Results: Holidays in the sun two years before CM diagnosis were significantly associated with lower Breslow thickness (p=0.003), after multiple adjustment. Number of weeks of sunny holidays was also significantly and inversely associated with thickness in a dose-dependent manner (p=0.007). However when stratifying by gender this association was found only among women (p=0.0004) the risk of CM recurrence in both sexes was significantly lower in patients (n=271) who had holidays in the sun after diagnosis, after multiple adjustment including education: HR=0.30 (95%CI:0.10-0.87; p=0.03) conclusions: Holidays in the sun were associated with thinner melanomas in women and reduced rates of relapse in both sexes. However, these results do not prove a direct causal effect of sun exposure on survival since other confounding factors, such as vitamin D serum levels and socio-economic status, may play a role. Other factors in sun seeking individuals may also possibly affect these results.

In this investigation, 20 clients with mental retardation and destructive behavior disorders were treated with psychotropic medication based on symptoms associated with a psychiatric disorder. For each patient, single-case design and direct observation procedures were utilized to evaluate outcome. Three clients (15%) showed at least a 50% reduction in destructive behavior; seven (35%) experienced a 50% or greater increase in destructive behavior; 10 (50%) experienced no change in their destructive behavior. The best response was to stimulant medications prescribed on the basis of pervasive hyperactivity and distractibility. The worst response was to lithium prescribed on the basis of manic-like symptoms (e.g., psychomotor agitation) or cyclical behavior disturbance. The low response rate was hypothesized to be a function of the unique underlying brain dysfunction in severely to profoundly retarded individuals with destructive behavior disorders, and the difficulties with applying psychiatric diagnoses in the population. Given the individual variability of response among clients and the prevalence of behavior dysfunction of the population, single-case methodology may have a useful role in the assessment of psychopharmacotherapy with individuals with severe to profound mental retardation and destructive behavior disorders.

Attention-deficit/Hyperactivity Disorder (ADHD) is a developmental disorder which, by current definition, has onset prior to age 7 years. MRI studies have provided some insight into brain differences associated with ADHD, but thus far have almost exclusively focused on children ages 7 years and older. To better understand the neurobiological development of ADHD, cortical and subcortical brain development should be systematically examined in younger children presenting with symptoms of the disorder. High resolution anatomical (MPRAGE) images, acquired on a 3.0T scanner, were analyzed in a total of 26 preschoolers, ages 4–5 years (13 with ADHD, 13 controls, matched on age and sex). The ADHD sample was diagnosed using DSM-IV criteria, and screened for language disorders. Cortical regions were delineated and measured using automated methods in Freesurfer; basal ganglia structures were manually delineated. Children with ADHD showed significantly reduced caudate volumes bilaterally; in contrast, there were no significant group differences in cortical volume or thickness in this age range. After controlling for age and total cerebral volume, left caudate volume was a significant predictor of hyperactive/impulsive, but not inattentive symptom severity. Anomalous basal ganglia, particularly caudate, development appears to play an important role among children presenting with early onset symptoms of ADHD.

Factors related to the amount of health care used by 5- to 11-year-old children in a health maintenance organization (HMO) were investigated using a comprehensive multivariate model that assessed the contribution of child health need, mental health, and social functioning; maternal mental health, social support and health care utilization; and family functioning and life events. Mothers reported on the 450 participating children. Health care visits for a two-year retrospective period were obtained from the computerized encounter system. Child health need and maternal patterns of health care use were powerful predictors of the overall amount of health care used, and these factors discriminated high users from low users of care. Family conflict was associated with a higher volume of care, while children's depressive symptoms and non-white race were related to lower use. Maternal social support, mental health, and life events were not predictive of use in either full multivariate model. Enabling factors were held relatively constant by participation of all families in a prepaid HMO. The multiple regression model explained 33% of the variance in use, slightly more than in previous studies of children's health care use. When included in a comprehensive analysis, child and family psychosocial characteristics help to explain children's health care use beyond what is possible using simple health and illness variables. The implications of these findings in the development of further research and to the practice of routine pediatric care are discussed.

Continued problematic behavior in children and adolescents after brain trauma is a major barrier to medical care, rehabilitation, and eventual independent living. The present study demonstrates the application of already well-developed behavior analysis techniques to the early posttrauma expression of behavior problems during hospital recovery. To satisfy concerns regarding both cost and individualized treatment, interventions were carried out primarily by regular hospital staff (nurses and therapists), medical record data were used to document gains, and time series, within subject designs were used to show experimental control. Four patients (three male and one female) ranging in age from 10 to 16 years, received intervention based on behavior analysis techniques, which reduced disruption and increased cooperation with therapy and medical care. Behavior analysis techniques will be relevant to future rehabilitation research to the extent that the posttrauma patient's behavior is effected by environmental consequences as demonstrated here.

Immunogenicity of tumour cells, immunomodulation and direct targeting of signalling pathways are promising avenues and matter of dated and innovative research in melanoma. Unfortunately, tumour cells are considered to be antigenic, but not immunogenic, either due to presentation of weakly recognized antigens or to the inability of the immune system to recognize them. However, spontaneous complete remission can be rarely observed in patients affected by melanoma, which are mainly attributed to the immune response against the tumour. Also, an elevated frequency of spontaneous humoral immune responses against tumour antigens was occasionally found in patients. These data confirm the existence of an interaction of the immune system with the tumour which can be used as a promising pathway for intervention and incorporates all portions of the immune system. The cancer immunotherapy approach is based on artificial activation of the immune system against the tumour and groups several types of treatments including immunization/vaccination but also modulation of immunity by cytokines or antibodies. Immunization approaches could either be based on undefined tumour antigens (e.g. whole tumour cells, tumour cell lysates, or tumour-antigen enriched fractions) or aimed at eliciting T-cell responses against specific tumour antigens. Novel and contemporary antigen-targeted therapy strategies, mainly directed to Cancer Testis and Heat Shock Proteins, leading to a possible active immunization against melanoma through T-cell specific activation, are discussed in this review.

Injury is the third leading cause of death in the United States and the leading cause for children, adolescents, and young adults. Injury results from multiple factors and so may its prevention. The first and simplest approach toward preventing injuries has been to innovatively and aggressively apply a traditional public health model. Strategically, the goal has been to remove harmful agents of injury and to make the environment safer. Tactics such as public information, product regulation, legislative action, and the like have been credited with reductions in mortality and morbidity. To expand our understanding and our prevention strategies across multiple injuries, other scientific knowledge bases and intervention models from fields such as psychology and child development are being used to study childhood injury. These approaches show that in addition to environmental determinants, psychosocial factors involving both the care giver and the child are related to injury. The research programs described here illustrate the advantage of investigating psychosocial factors at both molar and molecular levels. General characteristics of mothers and children related to injury help define families at risk, as well as suggesting vehicles for intervention. Behavioral factors influencing risk perception highlight the etiology of increased risk in adolescence. Injury episodes, even slight, as well as "near injuries" and dangerous and risky behavior can be quantified and analyzed by retrospective ("postmortem") approaches yielding data on commonly occurring consequences (and the lack thereof) for minor injury. Finally, approaches that simulate dangerous situations can identify interaction patterns that result in childhood injury. Based on such research, we are coming to view injuries as the result of patterns of behaviors that develop and persist over time, and as such these patterns can be detected and, one hopes, altered before a serious medical event occurs. The role of the pediatrician after injury occurs is clear. With regard to prevention of injuries, pediatricians' roles are being defined by those individuals who have begun to investigate causes, educate families, and advocate for regulation and prevention. However, like the causes and methods for prevention, the disciplines involved in the study and prevention of injury are multiple. Such a multidisciplinary approach that considers multiple factors, theories, models, and interventions to prevent injury may be the approach that is as simple as possible.

Compared the behavior of parents and their previously injured children with parents and their uninjured children in unstructured play and distracted parent conditions. Injured children were more disruptive, more active, and had more contacts with hazards, whereas uninjured children had more appropriate behavior. Parents of injured children had lower rates of play activities. Observable classes of parent and child behaviors amenable to change were associated with a history of child injury. Further study is needed to assess the use of safe and unsafe behavior as proxy measures for injuries and to identify functional classes of safe and unsafe behavior for which active strategies can be developed to prevent children's injuries. Language: en

We evaluated the effects of introducing and discontinuing an intervention designed to improve adherence with scheduled appointments in a pediatric allergy clinic. Five nonadherent and three adherent patients received reminders and incentives for keeping their scheduled appointments. Adherence with appointments increased for three of the five nonadherent children, who had an average increase of 13%, and adherent patients continued to keep appointments during the intervention condition. After 10 scheduled allergy clinic appointments had been kept, incentives were discontinued while reminders continued. Improvements in adherence were not maintained after incentives were discontinued and two children showed reductions in adherence to below-baseline levels. Incentive programs increase appointment keeping, but discontinuing incentives abruptly may result in the return of nonadherence, even when reminders are provided as a maintenance strategy. Future pediatric psychology research and practice should investigate both the benefits and limitations of strategies designed to improve adherence.

Background Many human neuroimaging investigations on recognition memory employ verbal instructions to direct subject's attention to a stimulus attribute. But do the same or a similar neurophysiological process occur during nonverbal experiences, such as those involving contingency-shaped responses? Establishing the spatially distributed neural network underlying recognition memory for instructed stimuli and operant, contingency-shaped (i.e., discriminative) stimuli would extend the generality of contemporary domain-general views of recognition memory and clarify the involvement of declarative memory processes in human operant behavior. Methods Fifteen healthy adults received equivalent amounts of exposure to three different stimulus sets prior to neuroimaging. Encoding of one stimulus set was prompted using instructions that emphasized memorizing stimuli (Instructed). In contrast, encoding of two additional stimulus sets was prompted using a GO/NO-GO operant task, in which contingencies shaped appropriate GO and NO-GO responding. During BOLD functional MRI, subjects completed two recognition tasks. One required passive viewing of stimuli. The second task required recognizing whether a presented stimulus was a GO/NO-GO stimulus, an Instructed stimulus, or novel (NEW) stimulus. Retrieval success related to recognition memory was isolated by contrasting activation from each stimulus set to a novel stimulus (i.e., an OLD > NEW contrast). To explore differences potentially related to source memory, separate contrasts were performed between stimulus sets. Results No regions reached supralevel thresholds during the passive viewing task. However, a relatively similar set of regions was activated during active recognition regardless of the methods and included dorsolateral and ventrolateral prefrontal cortex, right inferior and posterior parietal regions and the occipitoparietal region, precuneus, lingual, fusiform gyri and cerebellum. Results also showed the magnitude of the functional response in the occipitoparietal region was inversely correlated with reaction times (RTs), such that the largest functional response and slowest RTs occurred to Instructed stimuli and the smallest functional response and fastest RTs occurred to GO stimuli, with effects to NO-GO stimuli intermediate. The inverse relation was also present bilaterally in the parahippocampus and hippocampus. Comparisons between stimulus sets also revealed regional differences potentially related to source memory. Conclusion Recognition of stimuli previously associated with instructions and operant contingencies (i.e., discriminative stimuli) generally recruited similar inferior frontal and occipitoparietal regions and right posterior parietal cortex, with the right occipitoparietal region showing the largest effect. These findings suggest domain-general views of recognition memory may be applicable to understanding the neural correlates of control exerted by discriminative stimuli and suggest declarative memory processes are involved in human operant behavior.

Results of numerous human imaging studies and nonhuman neurophysiological studies on "reward" highlight a role for frontal, striatal, and thalamic regions in operant learning. By integrating operant and functional neuroimaging methodologies, the present investigation examined brain activation to two types of discriminative stimuli correlated with different contingencies. Prior to neuroimaging, 10 adult human subjects completed operant discrimination training in which money was delivered following button pressing (press-money contingency) in the presence of one set of discriminative stimuli, and termination of trials followed not responding (no response-next trial contingency) in the presence of a second set of discriminative stimuli. After operant training, subjects were instructed to memorize a third set of control stimuli unassociated with contingencies. Several hours after training, functional magnetic resonance imaging was performed while subjects viewed discriminative and control stimuli that were presented individually for 1,500 ms per trial, with stimulus presentations occurring, on average, every 6 s. Activation was found in frontal and striatal brain regions to both sets of discriminative stimuli relative to control stimuli. In addition, exploratory analyses highlighted activation differences between discriminative stimuli. The results demonstrate the utility of coupling operant and imaging technologies for investigating the neural substrates of operant learning in humans.

A "quick" prevalence study of intractable diarrhoea (defined as diarrhoea lasting more than 3 weeks and dependent on parenteral nutrition [PN] for more than 50% of daily caloric intake) was conducted by FAX. All 35 paediatric gastroenterology services which had been contacted answered questionnaire sent by FAX. 20 cases of intractable diarrhoea were identified in 9 centres. In 12 cases PN was administered at home, the other 8 cases being treated as inpatients for an average duration of 9.5 months. A diagnosis had been established in 11 out of 20 cases. Auto-immune enteropathy was the most frequent diagnosis (5 cases); congenital microvillous atrophy (3 cases); chronic pseudo-obstruction (2 cases) and multiple food intolerance (1 case). Undefined 9/20 cases presented atrophy of intestinal mucosa. The age of the beginning of diarrhoea varied from 2 days to 12 years, but was more than 16 months only in some cases with auto-immune enteropathy. CONCLUSION: Intractable diarrhoea has a low prevalence in Italy and remains a rare but very intricating problem. Long-term PN is recommended in most cases: autoimmune enteropathy is the most frequent cause but in about half of the cases the aetiopathogenetic diagnosis is still not defined.

e20042 Background: Elettrochemotherapy (ECT) is a consolidated treatment in Europe for the treatment of cutaneous and non-cutaneous cancers. The aim of this study was to analyse the effects of ECT ...

e19036 Background: Vulvar melanoma (VM) represents 3-7% of melanoma in women. The 5-year survival rate ranges from 8 to 55%. Surgical excision represents the best definitive therapy but surgical radicality does not impact on recurrence or survival. Methods: Thirty women with histologically confirmed VM diagnosed between 1993 and 2009 were selected for this monocentric retrospective study. One patient with metastases at time of diagnosis was excluded from the statistical analysis. Clinical, pathological and follow-up data were collected. Cumulative incidences of events were calculated and compared across subgroups by means of the Gray test. Results: Average age at diagnosis was 62 years. Average Breslow thickness was 4.91 mm. Ulceration was present in 11 cases and was unknown in 5. One case of VM was multifocal at presentation. Eleven patients underwent a wide local excision, 11 a hemivulvectomy and 7 a radical vulvectomy Sentinel node biopsy was performed in 23 patients and at least one positive sentinel node was found in 8 cases. Eight patients received adjuvant therapy. Ten patients had a second tumor (other than melanoma); of these, a breast cancer was recorded in 5 cases. Four patients had a second primary melanoma: of the vulva (n=2), vagina (n=1), and urethra (n=1). Median follow-up among ongoing survivors was 79 months and median overall survival was 69 months. The 5-year overall survival was 55.4%. Median event free survival 34 months. Positive lymph nodal status was associated with an increased risk of loco-regional recurrences (P=0.04). Positive lymph nodal status (P=0.06), Breslow thickness > 2mm (P=0.05) and number of mitoses > 10/mm2 (P=0.04) increased the risk of distant metastases. Age, ulceration and type of surgery were not significantly associated with any type of event. Conclusions: Lymph node involvement, elevated depth of invasion and a high number of mitoses were the most important prognostic factors for locoregional recurrence and distant metastases. The same trends were observed for the overall survival, but results were not statistically significant. Conservative surgery in the form of wide local excision with adequate margins may replace vulvectomy. Sentinel node biopsy is feasible and its role in VM should be further investigated.

Background Anxiety is relatively common in depression and capable of modifying the severity and course of depression. Yet our understanding of how anxiety modulates frontal and limbic activation in depression is limited. Methods We used functional magnetic resonance imaging and two emotional information processing tasks to examine frontal and limbic activation in ten patients with major depression and comorbid with preceding generalized anxiety (MDD/GAD) and ten non-depressed controls. Results Consistent with prior studies on depression, MDD/GAD patients showed hypoactivation in medial and middle frontal regions, as well as in the anterior cingulate, cingulate and insula. However, heightened anxiety in MDD/GAD patients was associated with increased activation in middle frontal regions and the insula and the effects varied with the type of emotional information presented. Conclusions Our findings highlight frontal and limbic hypoactivation in patients with depression and comorbid anxiety and indicate that anxiety level may modulate frontal and limbic activation depending upon the emotional context. One implication of this finding is that divergent findings reported in the imaging literature on depression could reflect modulation of activation by anxiety level in response to different types of emotional information.

Background: Advanced MM pts’ prognosis remains poor and is not improved by the neither DTIC nor IL-2 [median survival-time B-Raf is a MAPK tyrosin-kinase mutated in about 62% of cutaneous melanomas. c-Kit is a RTK mainly mutated in mucosal (39%), acral (36%) and sun damaged cutaneous (28%) melanomas. MGMT is a gene encoding for 06-metylguanine-DNA-metyltransferase, which is mutated in about 15% of melanomas. Using available tissue samples from a phase 2 study on advanced melanoma pts treated with DTIC + B combination, we looked at these molecular markers on tissues samples, in order to test whether any of them could correlate with therapy response. Patients & Methods: Between July 2006-May 2010, 40 CTh-naïve advanced MM pts underwent CTh with DTIC (800mg/mq q4w) + B (10mg/kg q2w), being disease evaluated at each access by physical examination and every 3 cycles by whole-body (wb) CT-scan, according to RECIST criteria. Response rate and median TTP were analyzed. Secondly we tried to explore any combination between the molecular markers and therapy response. Results: 36/40 pts were evaluated at the analysis-time, with 4 screening failures (3 pts: brain metastasis detection at the pre-study wb CT-scan; 1pts: bleeding risk). Male/Female=23/13; median age was 57yr. PS 0/1 = 32/4. 3 pts (8.3%) developed complete response, 4 pts (11.1%) partial response (PR), 11 (30.5%) stable disease (SD ≫24w = 6 pts, 16.6%); 17 (50%) progressive disease (PD; 8pts: RECIST-criteria PD at the first CT-scan evaluation; 9 pts: early clinical PD). On the available tissue samples from the patients in the study, B-Raf and c-Kit mutation analysis as well as methylation analysis for MGMT were performed. Secondly, VEGF-A and VEGFR were tested on the same tissues by immune-staining. Median TTP was 6 mo (Interquartile range: 2.5-10). Exploratory data analysis interestingly shows 50% clinical benefit (defined as CR+PR+SD≫24w) and 16.5 mo (95% CI 12.7-31.5) median survival. Conclusions: Data analysis is ongoing; furthermore, to state a correlation between molecular markers expressions and response to therapy or survival the most pts enrolled in the study are retrieving material from previous surgery and from the primary tumour. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 288. doi:10.1158/1538-7445.AM2011-288

Magnetic resonance imaging is a promising technological advance used for research and diagnosis of disease. The procedure has no risks, except when uncooperative patients require sedation. Four normal children participated in simulated scans to study the effects of (a) antecedent changes in the imaging environment and (b) operant conditioning of movement inhibition. Changing the environment can decrease movement, but operant contingencies were necessary to decrease movement to a level that, in most cases, would allow the procedure to occur without sedation.

8536 Background: Advanced MM pts' poor prognosis is not improved by the neither of the 2 FDA approved agents, DTIC and IL-2 (median survival-time < 9 month [mo]; 5-yr survival-rate < 5%). Single-agent DTIC has average response-rate of 10% and median response-duration of 5-6 mo, being poly-CTh never proven to be superior. To improve such sober results, different DTIC- combinations have been proposed. MM in vitro models showed VEGF transcription up-regulation by DTIC, suggesting DTIC/anti-VEGF combination as an intriguing exploiting path. Methods: Between July 2006-September 2009, at IEO, Milan, 40 CTh-naive advanced MM pts underwent CTh with DTIC (800 mg/mq q4w) + B (10 mg/kg q2w), being disease evaluated at each access by physical examination and every 3 cycles by whole-body (wb) CT-scan, according to RECIST criteria. Response rate, median TTP and safety were analyzed. Results: 36/40 pts were evaluated at the analysis-time, with 4 screening failures (3 pts: brain metastasis detection at the pre-study wb C...

8589 Background: A new, promising application of bleomycin was discovered and developed by Mir in 1991, combining the drug with electroporation. This new technique was called electrochemotherapy (ECT). The new treatment is based on the increased bleomycin delivery into tumor cells after cell membrane permeabilization by electric pulses administered locally at the site of superficial tumor localizations. Since 1991 more than 300 articles were published on the argument and experiences from many institutes in Europe seems to be very promising. Actually ECT is used for the treatment of cutaneous and subcutaneous tumoral lesions from different tumoral types. Favorable results in treating superficial metastatic lesions have been published with a complete response rate for treated nodules raging from 70% to 90%. Methods: In our Institute we treated 75 consecutive patients from 2006 to 2009 for superficial cancer lesions, especially metastatic melanomas (58 patients) and squamous or large basal cell carcinomas (1...

Evaluated the impact of psychological treatment for 93 children (ages 1-15) with common behavior, toilet, school, and psychosomatic problems. Children and parents, who were members of a health maintenance organization, had 1-6 visits to a primary care-based psychological consultation service. Individualized treatment was guided by problem-specific behavioral protocols. Parent outcome and behavior checklist ratings indicated improvement or resolution for 74% of children and high satisfaction with the psychological service. Children's use of medical services, especially acute primary care visits, was reduced during the year after treatment; a matched comparison group's use was unchanged. Addressing children's unmet mental health needs reduces medical care utilization. A primary health care model of psychological services provides an integrated system for serving the health and mental health needs of children.

Pediatric feeding disorders are estimated to occur in as many as one in every four infants and children, and when serious can require numerous, costly and sustained interventions. For over a decade research has cumulated evidence on the contributions of Behavior Analysis in understanding and remediating some types of pediatric feeding disorders. The systematic use of this body of evidence in conjunction with other approaches (medical, nutrition, occupational therapy, physical therapy, and so forth) is being carried out on an inpatient treatment unit at the Kennedy Krieger Institute. Key aspects are described here, including direct observation behavior assessment, approaches for increasing and decreasing feeding behavior, skill acquisition, transfer of treatment gains, and parent training. The results based on case studies and overall program evaluation indicate that medically complicated, severe feeding disorders can be treated successfully in a few months with a multidisciplinary approach which incorporates behavioral procedures.

Children with recurrent abdominal pain (RAP) are frequent users of medical care services, often seeking care for a variety of illnesses and symptoms. In a clinical replication series, we treated 16 children with RAP who were referred to a primary care-based pediatric psychology service. They received a multi-component targeted therapy, which included self-monitoring, limited parent attention, relaxation training, increased dietary fiber, and required school attendance. After treatment, improvement or resolution of pain symptoms was reported for 13 (81%) children, and school absences were significantly decreased. Medical care utilization significantly decreased after treatment, whereas a comparison group of untreated children with RAP showed no change in medical care visits over time. Brief targeted therapy delivered in a primary health care setting appeared to be effective in reducing a range of problems associated with RAP. A primary care service is an ideal setting for integrating behavioral medicine services into the health care system.

The popularity and reported success of biofeedback treatment for neuromuscular disorders has occurred despite a lack of research identifying the critical variables responsible for therapeutic gain. In this study, we assessed the degree to which severe neurological dysfunction could be improved by using one of the components present in all biofeedback treatment, contingency management. Three cases of orofacial dysfunction were treated by reinforcing specific improvements reliably detectable without the use of biofeedback equipment. The results showed that contingency management procedures alone were sufficient to improve overt motor responses but, unlike biofeedback treatment, did not produce decreases in the hypertonic muscle groups associated with the trained motor behavior. The findings suggest that sophisticated, expensive biofeedback equipment may not be necessary in treating some neuromuscular disorders and that important clinical gains may be achieved by redesigning the patient's daily environment to be contingently therapeutic, rather than only accommodating the disabilities of the physically handicapped.

This paper reviews 33 individual case or group studies describing the application of behavior therapy techniques to the management of 41 electively mute children. Management strategies included stimulus fading, reinforcement, stimulus fading plus reinforcement, and escape or avoidance procedures. Reinforcement procedures proved most effective when a minimum operant level of speech existed in the treatment setting. In the absence of baseline speech, stimulus fading procedures were successful in transferring speech stimulus fading procedures were successful in transferring speech from settings in which the child spoke comfortably, to new individuals and situations. Response cost contingencies improved the efficacy of both reinforcement and stimulus fading plus reinforcement procedures. Among the 37 cases reporting individual observations at treatment termination, 57% (21) spoke spontaneously and 43% (16) responded to prompts or questions. Follow-up observations on 32 individual cases over intervals ranging ...

A combination of a reversal design and a multiple-baseline design across settings and tic behaviors was employed to determine the effectiveness of a treatment package consisting of self-monitoring, external reinforcement, and timeout in the control of a hyperactive child's multiple tic behaviors. In the clinic the treatment package was applied only to facial tics, with three other tics (shoulder shrugging, rump protrusion, and a vocal tic) observed but never treated. At home facial tics were initially treated, and then vocal tics. Shoulder shrugging, rump protrusion, and “other tics” were never directly treated. Treatment was effective in decreasing the occurrence of facial tics in the clinic to zero. Even though no intervention was placed on the other tics, they also decreased in frequency concomitant with the facial tics. The home data also demonstrated a decrease to zero when the treatment package was sequentially applied to facial and vocal tics, with a concomitant decrease in the untreated tic behaviors. A 32-week follow-up showed maintenance of the treatment effects.

Lead poisoning, a serious problem that can result in permanent neurological damage, often results from the ingestion of inedible substances that contain lead. The behavior of ingesting nonedible substances in termed pica. In this study, behavior modification procedures were used to eliminate pica in three young children with lead poisoning. Three kinds of procedures were used: (1) discriminate training, in which the subject was taught to recognize that paint and several objects were not edible; (2) reinforcement for the absence of pica; and (3) overcorrection for the occurence of pica. Pica was eliminated in all three subjects. While it was not always clear which component of the treatment was responsible for the decrease, the sequence used had the advantage of an effictive clinical technique proceeding from least to progressively more restrictive procedures.

Scientific and public interest in the effects of diet on behavior disorders has recently increased. This paper argues that (1) the experimental analysis of behavior offers an effective scientific methodology for assessing the effects of dietary substances on behavior problems, and that (2) such analysis permits behavioral consequences to be considered as an alternative treatment to dietary control. A case study of a 9-year-old retarded boy with autistic behaviors is presented. Suspected dietary substances were demonstrated not to be effective influences on the child's behavior, whereas a simple behavior modification program improved his problem behaviors. Also discussed are issues and problems which arise in research on dietary effects on behavior and in selection of effective and ethical treatments.

Two studies were conducted to analyze behaviors of staff and patients on a Pediatric Intensive Care Unit (PICU). In the first study, behavioral observation procedures were employed to assess patient state, physical position, affect, verbal behaviors, visual attention and activity engagement, and staff verbal behavior. On the average, one-third of the patients were judged to be conscious and alert but markedly nonengaged with their environment. In the second study, a member of the hospital staff provided alert patients with individual activities to determine whether a simple environmental manipulation could positively affect behavior of children in intensive care. Employing a reversal design, the activity intervention was found to increase attention and engagement and positive affect, and to decrease inappropriate behavior. Both studies demonstrate that behavioral assessment procedures can provide an empirical basis for designing PICU routines affecting children's psychosocial status, and, thus, complement current procedures designed to provide quality medical care.

Epilepsy represents a serious medical and social problem. In the majority of cases, seizures are successfully managed by a variety of anticonvulsant medications, even though these drugs may potentiate significant physical and developmental side effects. A small group of studies to date have offered evidence that behavioral procedures can successfully manage some seizure disorders and are particularly desirable treatment choices when seizure disorders are intractable to drug management or when drug side effects are to be avoided. The present case adds to this small but growing group of studies in that it demonstrates the use of behavioral procedures in the analysis and treatment of high-rate myoclonic seizures. Seizures were evaluated on a hospital ward and in a controlled experimental setting. The data indicated a variable rate of seizures across days and activities and a reduction of seizure frequency in the controlled setting when time-out was made contingent on seizures. A program of “contingent rest” was then applied on the hospital ward that demonstrated a reduction in myoclonic seizure frequency and the apparent prevention of several grand mal episodes. An observer calibration procedure showed high correspondence between behaviorally and physiologically recorded seizures. A discussion of issues in behavioral medicine research follows.

Analyses of response relationships offer the potential for designing treatment procedures that are more economical and entail less risk for misuse than many we currently employ. The present study investigated whether previous results indicating the reduction of problem behaviors by reinforcing compliance in fact occurred because of the contingent relationship between compliance and the presumed reinforcing events. A clinic analogue procedure consisting of a standard set of adult requests was employed in a multiple baseline design across subjects with three children receiving three conditions — no reinforcement, noncontingent reinforcement, and reinforcement contingent on compliance — and a fourth child receiving the first and third conditions to assess possible order effects. The data indicated that: (1) compliance covaried inversely with some, but not all, of the problem behaviors measured; (2) sustained covariation occurred only when reinforcement was contingent on compliance; (3) substantially large but transient increases in compliance and decreases in problem behavior during noncontingent reinforcement occurred for those children who initially demonstrated high compliance and low levels of aberrant behavior during baseline; and (4) the problem behaviors that inversely covaried with compliance were idiosyncratic across children. The results suggest that treatment procedures based on response relationship strategies should consider that children's individual learning histories may determine which behaviors covary and the likelihood that large, initial changes can occur with noncontingent reinforcement.

The successful use of operant procedures to alter behaviors associated with various medical conditions suggests that such behaviors may be learned and that the principles of learning may be applied not only to treatment but also to the study of the pathogenesis of illness behavior. The present study, conducted within an ongoing neuromuscular research project, assessed the covariation of behaviors associated with chronic pain within and across behavioral and drug approaches to treatment. Problems of screaming and five other behaviors (including self-reports of pain) were measured across conditions of varying behavioral contingencies (noncontingent reinforcement vs the removal of reinforcement contingent upon screaming) and varying administration (time since medication and dosage) of Parsidol during attempts to treat the muscle pain of a 24-year-old male with a severe, chronic neuromuscular disorder diagnosed as dystonia musculorum deformans (DMD). Results indicated that: (a) pain behaviors covaried during behavioral and drug conditions even though the behavioral intervention only targeted screaming; (b) effects were greater on nontargeted behaviors during periods that followed rather than preceded drug administration; (c) in contrast to behavioral observation data, physiological measures of neuromuscular activity (EMG) did not differ across conditions. These results suggest that functional response-response relationships exist in patients as the result of their illness experience.

Since 1975, behavioral science solutions for important problems of pediatric practice have been well established. Analysis of current research trends in behavioral science indicates that this interdisciplinary collaboration is likely to expand greatly in three areas: the use of behavioral procedures to remediate routine behavior and developmental problems; the analysis of the medical setting and its effect on children; and the direct modification of biological conditions by behavioral means.

A reversal design was utilized in which differential vs non-differential adult attention was made contingent upon the delusional speech of an 11-yr-old boy. Within this design, effects of verbalizing the contingency and the use of a pharmacological treatment were also studied. The results indicated that differential adult attention only to appropriate task related statements increased such statements while decreasing delusional speech, whereas non-differential attention to any type of statement resulted in a predominance of delusional speech. A trial of methylphenidate showed no difference relative to non-differential attention. Additionally, the results suggest that verbalizing the differential attention contingency may be an effective tactic for rapid behavior change. The results are discussed in relation to the necessity for comparing possible courses of treatment as a strategy for insuring effective treatment.