Individual Repertoires Research Articles

Content and contingencies: Considerations regarding curriculum development for young children with autism.

Early intensive behavioral intervention (EIBI) for children with autism is a non-linear, multi-component endeavor concerned with complex instructional contingencies and curriculum content. It might be useful to think of EIBI in terms of three general elements: curriculum protocol, analysis, and implementation and program structuring. These elements are interdependent and when discussing clinical field of EIBI all three elements must be considered. Curriculum content and instructional contingencies interact in complex ways as numerous skill domains are addressed in a systematic and incremental manner. In directing this process of cumulative hierarchical learning, a strong focus on maintaining intrinsic program coherence is imperative. The present paper discusses some important aspects of intricacies of EIBI. ********** From a behavior analytic perspective autism is not viewed as a central deficit but rather condition is conceptualized as a constellation of many individual deficits to be treated separately (Lovaas & Smith, 1989). This pragmatic stance is shaped by extensive research that shows that improvement in one domain does not necessarily facilitate improvement in another. For instance, acquisition of prepositions does not necessarily facilitate acquisition of pronouns (Lovaas & Smith, 1989). No aspect of skill development can be taken for granted and intervention must proceed in incremental steps addressing multiple skill domains simultaneously. Continuous time analysis of typically developing children shows that language development proceeds in incremental steps with an abundance of structured and fine-tuned environmental support. Acquisition of any complex skill requires many levels of accomplishment and higher skill levels can be acquired effectively only after lower levels have been mastered (Moerk, 1992). As such, learning is cumulative and hierarchical (Staats, 1981, 1994). These facts are amplified dramatically with respect to young children with autism. Children with autism require considerable time, numerous levels of accomplishment, incremental steps and highly attuned environmental support (i.e., contingency arrangements) in order to acquire even basic skills. This poses significant conceptual and analytical challenges when designing effective intervention. Staats (1994) has pointed out that applied behaviorists, acquainted only with principles of reinforcement, are limited in their ability to analyze many problems of human behavior, thus shortchanging value of behavioral approach (p. 105). The clinical field of early intensive behavioral intervention (EIBI) transcends basic principles of behavior analysis (i.e., basic conceptual calculus and learning principles) and must strive to establish concepts and principles that are effective in dealing with tremendous behavioral complexity and development. Whereas learning is concerned with formation of new response patterns and response functions, development is concerned with the emergence of new kinds of behavioral organization as outcome of transformational sequences from previous conditions (Ribes, 1996, p. 42). A NON-LINEAR ENDEAVOR The skill building process is not a linear endeavor in which individual repertoires comprise isolated and unrelated units independently controlled by environmental variables. Rather, skill building is encompassed by a complex and dynamic system in which behavioral units and repertoires are related and interdependent. Complex behavior is not a matter of straight that can be adequately accounted for in terms of linear logic. Rather, there are snags and snarls and multiple lines of progression characterized by confluence, overlapping and convergence. Furthermore, there are complex hierarchies (e.g., category structure) and dynamic networks to consider. According to concept of cumulative and hierarchical learning, one repertoire provides basis for learning another repertoire, etc. …

Nestling growth and song repertoire size in great reed warblers: evidence for song learning as an indicator mechanism in mate choice.

Females of many songbird species show a preference for mating with males that have larger song repertoires, but the advantages associated with this preference are uncertain. We tested the hypothesis that song complexity can serve as an indicator of male quality because the development of the brain regions underlying song learning and production occurs when young birds typically face nutritional and other stresses, so that song reflects how well a male fared during post-hatch development. A key prediction of this hypothesis is that variation in nestling condition should correspond to variation in the adult song repertoires of individuals. We used data from a long-term study of the great reed warbler (Acrocephalus arundinaceus) to test this prediction, correlating two measures of nestling development with subsequent repertoire size of males. We found that the length of the innermost primary feather, a standard measure of development, significantly predicted first-year repertoire size. The relationship between repertoire size and body mass was nearly significant, in spite of the large variance inherent in this measure. These data support the idea that song may provide females with information about a male's response to developmental stress, which in turn is expected to correlate with indirect or direct benefits she might receive.

The television of abundance arrives: cable choices and interest maximization

Utility theory offers some suggestions for how people react as the so-called “television of abundance” reaches the point where audiences can maximize their interests. Contrasting the interest maximization outlook with the media substitution hypothesis, this study explores cable channel repertoire patterns. A random survey of 319 cable subscribers in a major metropolitan area measured exposure to several dozen channel categories. Utilizing factor analysis, pattern repertoires were developed, comparing social category groupings. Overall, the findings support an interest maximization perspective, with individual category pattern repertoires providing insight into the use of abundant cable offerings to serve specialized needs.

Music memory provides access to verbal knowledge in a patient with global amnesia

We report on the patient CH, who showed marked impairment of declarative memory in everyday life and standardized memory tests subsequent to herpes simplex encephalltis. However, there was anecdotal evidence for preserved learning capacity for verbal material (song titles) in connection with playing accordion music. Our experiments, tallored to CH's individual accordion repertoire, confirmed strong associations between language (song titles) and music (accordion melodies): CH performed 100% of the melodies correctly after being presented with the respective song titles. Presented with melodies, she recognized 90% of the titles out of several distractors. This good verbal memory success is conspicuous in the light of her otherwise severe memory impairments. To elucidate the phenomenon, we examined additionally the semantic knowledge concerning music-associated verbal material in CH by definition, categorization, reading and naming tasks. If music-associated words belonged to an actually better preserved or relearned vocabulary, we would have expected CH to perform better with music-associated concepts than with comparable, non-music-associated concepts. However, that was not the case. CH's good verbal memory in a musical context may be explained in terms of a material-specific, semantically empty priming effect.

LAPAROSCOPIC HERNIA REPAIRS: The Importance of Cost as an Outcome Measurement at the Century's End

At the dawn of this new millennium, surgeons not only must be masters of their craft but also are responsible for identifying and learning new techniques that are being introduced at an ever-increasing rate. Surgeons must overcome the instinctual mistrust of "the new" and, at the same time, avoid over enthusiastic, uncritical adoption of unproven procedures. Today's surgeons must also carefully assess and select the procedures and technologies that they will have time to learn and that will complement their practices and interests. More new things are coming along than any single individual can learn and practice with expertise, which makes general surgery a specialty with relative, as opposed to specifically, defined boundaries. Surgeons also should participate in the process of measuring the outcomes effective and to offer some advantages over open repair, namely less pain and a more rapid recovery period. On the other hand, this surgery has been shown to be difficult to learn and more costly. In a situation such as this, one can delete the procedure from the individual or institutional repertoire or use the modern tools of medical management to attempt to address the "outlier" issues and preserve the good. Laparoscopic hernia repair is a good procedure that can be done in a cost-effective manner if cost-conscious practice guidelines are initiated. It is not yet, however, a technique for all surgeons because of its difficulty to learn and advanced skills needed to perform it well.

Cytotoxic T cell immunity against telomerase reverse transcriptase in humans.

Telomerase is a ribonucleoprotein enzyme which has been linked to malignant transformation in human cells. Telomerase activity is increased in the vast majority of human tumors, making its gene product the first molecule common to all human tumors. The generation of endogenously processed telomerase peptides bound to Class I MHC molecules could therefore target cytotoxic T lymphocytes (CTL) to tumors of different origins. This could advance vaccine therapy against cancer provided that precursor CTL recognizing telomerase peptides in normal adults and cancer patients can be expanded through immunization. We demonstrate here that the majority of normal individuals and patients with prostate cancer immunized in vitro against two HLA-A2.1 restricted peptides from telomerase reverse transcriptase (hTRT) develop hTRT-specific CTL. This suggests the existence of precursor CTL for hTRT in the repertoire of normal individuals and in cancer patients. Most importantly, the CTL of cancer patients specifically lysed a variety of HLA-A2(+) cancer cell lines, demonstrating immunological recognition of endogenously processed hTRT peptides. Moreover, in vivo immunization of HLA-A2.1 transgenic mice generated a specific CTL response against both hTRT peptides. Based on the induction of CTL responses in vitro and in vivo, and the susceptibility to lysis of tumor cells of various origins by hTRT CTL, we suggest that hTRT could serve as a universal cancer vaccine for humans.

Systemic activation and antigen-driven oligoclonal expansion of T cells in a mouse model of colitis

Transfer of CD4+CD45RBhigh T cells into immunodeficient mice results in both the expansion of the transferred T cells and colitis. Here we show that colitis pathogenesis requires expression of MHC class II molecules by the immune-deficient host. Analysis of the TCRβ repertoire of the cells found in the large intestine of diseased mice revealed a population with restricted TCR diversity. Furthermore, nucleotide sequence analysis demonstrated the selection for particular CDR3β amino acid sequence motifs. Collectively, these data indicate that the expansion of T cells in the intestine and colitis pathogenesis are likely to require the activation of Ag-specific T cells, as opposed to nonspecific or superantigen-mediated events. There is relatively little overlap, however, when the TCR repertoires of different individuals are compared, suggesting that a number of Ags can contribute to T cell expansion and the generation of a T cell population in the intestine. Surprisingly, many of the expanded clones found in the large intestine also were found in the spleen and elsewhere, although inflammation is localized to the colon. Additionally, donor-derived T cells appear to be activated in both the intestine and the spleen at early time points after cell transfer. Together, these results strongly suggest that disease induction in this model involves either the early and systemic activation of antigen-specific T cells or the rapid dispersal of T cells activated at a particular site.

Systemic activation and antigen-driven oligoclonal expansion of T cells in a mouse model of colitis.

Transfer of CD4+CD45RBhigh T cells into immunodeficient mice results in both the expansion of the transferred T cells and colitis. Here we show that colitis pathogenesis requires expression of MHC class II molecules by the immune-deficient host. Analysis of the TCRbeta repertoire of the cells found in the large intestine of diseased mice revealed a population with restricted TCR diversity. Furthermore, nucleotide sequence analysis demonstrated the selection for particular CDR3beta amino acid sequence motifs. Collectively, these data indicate that the expansion of T cells in the intestine and colitis pathogenesis are likely to require the activation of Ag-specific T cells, as opposed to nonspecific or superantigen-mediated events. There is relatively little overlap, however, when the TCR repertoires of different individuals are compared, suggesting that a number of Ags can contribute to T cell expansion and the generation of a T cell population in the intestine. Surprisingly, many of the expanded clones found in the large intestine also were found in the spleen and elsewhere, although inflammation is localized to the colon. Additionally, donor-derived T cells appear to be activated in both the intestine and the spleen at early time points after cell transfer. Together, these results strongly suggest that disease induction in this model involves either the early and systemic activation of antigen-specific T cells or the rapid dispersal of T cells activated at a particular site.

Exploring the Efficacy of Self-Regulatory Training as a Possible Alternative to Social Skills Training

This article describes an intervention study based on an alternative model of social skills instruction using a multiple-baseline design across three boys with severe behavioral disorders. The treatment model does not assume a social skill deficit, but rather a deficit in self-regulatory behavior leading to inappropriate use of behaviors already in the individual's repertoire. Self-monitoring procedures were used to cue participants to use their social skills, were effective in altering participants' social behaviors, and created maintained positive change. Data highlight the promise of the activation model as both a theoretical and a treatment methodology warranting further study. Directions for further research are presented.

Polysaccharide vaccines as probes of antibody repertoires in man.

Antibodies specific for capsular polysaccharide epitopes mediate immunity to encapsulated bacterial pathogens, and accordingly, vaccine development has focused upon the induction of these specificities. Efficacious vaccines, consisting of either polysaccharide alone or polysaccharide coupled to protein carriers, have been developed for a number of pathogens. Their clinical importance notwithstanding, these vaccines serve as model antigens to study the genetic and somatic forces molding adaptive immunity in man. In this article we review progress aimed at delineating the structure and dynamics of the human antibody repertoire to the Haemophilus influenzae type b polysaccharide (Hib PS), a system which has been studied from infancy to old age. Collectively, the data reveal a repertoire which is encoded by a relatively large number of germline variable (V) region gene segments, but which is typically expressed within individuals as a markedly restricted, oligoclonal population. One particular V domain has attained canonical status because of its high penetrance at the population level and its predominance in individual repertoires. Although this combining site is assembled in early infancy and retains its prominence throughout life, its frequency of expression, affinity and protective function are dictated by the molecular form of the Hib PS immunogen (vaccine). The determinants of Hib PS binding affinity can include both germline and somatically-acquired V region polymorphisms. We discuss how these properties of the Hib PS repertoire could impact immunity to Hib, and we consider the implications of these findings towards understanding the evolution of immunoglobulin germline V genes.

Whistle Convergence among Allied Male Bottlenose Dolphins (Delphinidae, Tursiops sp.)

Dolphins are adept at learning new vocalizations (whistles) throughout life, an ability thus far demonstrated in few nonhuman mammals. In dolphins, this ability is well documented in captivity but poorly studied in the wild, and little is known of its role in natural social behavior. This study documents the previously unknown phenomenon of whistle convergence among habituated free‐living male bottlenose dolphins (Tursiops sp.). Over a 4 yr study period, three male subjects formed an alliance, spending most of their time together and cooperating to herd females. Within individuals, whistle repertoires were more variable than expected based on previous studies, mostly performed with captive dolphins, but became less so during the course of the study. Among individuals, the distinctiveness of individual repertoires decreased such that the three males were virtually indistinguishable by the end of the study. Initially, some whistle types were shared. By the end of the study, the three males had formed a close alliance, and had all converged on one particular shared whistle form which they had rarely produced before forming the alliance. The results are discussed in terms of their implications for the prevailing ‘signature whistle’ hypothesis, as well as possible mechanisms and functional significance of whistle convergence among cooperating males.

Black-capped chickadee call dialects along a continuous habitat corridor

The gargle call, a vocalization used in agonistic encounters by black-capped chickadees, Poecile atricapillus , was examined for evidence of geographical variation along a corridor of continuous riparian habitat in northern Colorado. We captured birds from three different sites during the nonbreeding season and brought them into the laboratory, where their gargle calls were recorded. We sorted sonagrams produced from these vocalizations visually into distinct gargle types having similar compositions of individual units, or syllables. This allowed us to characterize both individual and population repertoires. The majority (88.7%) of gargle types analysed were found to be unique to individual populations rather than shared among or between populations. Examination of individual repertoires showed that chickadees shared a higher proportion of gargle types with birds from their own sites compared with birds from either of the two other sites. Thus, gargle dialects occurred among these chickadee populations despite the absence of geographical barriers to blending of vocal traditions. As the birds studied were obtained from sites along an uninterrupted dispersal corridor, the results of this study suggest that behavioural mechanisms are responsible for maintenance of dialects in this aggressive call.

Restricted and individual usage of T-cell receptor beta-gene variables in nickel-induced CD4+ and CD8+ cells.

Nickel allergy is manifested as contact allergic eczema elicited by delayed-type hypersensitivity, the reaction being mediated by T lymphocytes. We examined the T-cell receptor (TCR) beta-chain variable gene segment (Vbeta) use of nickel-induced CD4+ and CD8+ T cells in the peripheral blood of nickel-sensitive and nonsensitized subjects. The results show that each patient had an individual Vbeta repertoire overexpressed, these being in CD4+ cells Vbeta10 and Vbeta13 (in subject A); Vbeta1, Vbeta2, Vbeta13 and Vbeta21 (subject B); Vbeta1 and Vbeta10 (subject C); Vbeta9 and Vbeta19 (subject D). Thus, no single Vbeta gene dominated in a majority of the CD4+ samples. The Vbeta genes overexpressed in patient CD8+ nickel-induced T cells were Vbeta1 (in subject A), Vbeta1 (subject B), Vbeta1 and Vbeta2 (subject C) and Vbeta7 (subject D), domination of Vbeta1 being seen in most of the CD8+ samples (75%). No specific overexpression of any Vbeta genes in the nickel-allergic subjects was found in comparison with the non-sensitized subjects. In conclusion, an individual pattern of restricted Vbeta genes was induced with nickel in CD4+ and CD8+ T cells in each nickel allergy patient.

Peptide-mediated regulation of allergen-specific immune responses

The exposure of susceptible individuals to environmental allergens induces enhanced levels of specific IgE antibodies, which bind to high affinity receptors on mast cells and basophils. Cross linking of receptor-bound IgE occurs, mediators are released and the immediate allergic reactions develop. Increased vascular permeability and the production of cytokines and chemokines cause polymorphonuclear granulocytes and lymphocytes to migrate into the site of allergic reactions and the late phase reaction is established. This illustrates that the cellular and cytokine networks activated in the pathogenesis of allergic inflammation are complex and involve many different cell types. However, the regulation of allergic immune responses in atopic individuals is mediated by cytokines characteristic of the Th2 functional phenotype (IL-4, IL-5, IL-10 and IL-13).1–5 In non-atopic individuals Thl cells, which produce IL-2 and IFN-γ, but not IL-4 or IL-5, are activated and regulate immune responses to allergens.6,7 However, from clonal analysis it is evident that Th0 cells, which have the potential to produce both Thl and Th2 cytokines, form a major component of the allergen specific repertoire in atopic individuals. Therefore, the ability to modify qualitative aspects of immune responses to allergens in atopic individuals by inhibiting the release of Th2 cytokines, and/or promoting the production of Thl cytokines may alter the clinical phenotype of some patients. The approach of immunotherapy mediated by peptides and designed to target allergen reactive CD4+ T cells are discussed in this report.

Strategy Choice in Sociocultural Context

Historically, research on strategy development has focused on charting changes in modal strategy use associated with age and experience. In recent years, however, researchers have begun to document the variety of strategies children have in their repertoires at different ages and with different degrees of experience on tasks. Of growing importance is understanding the processes by which children choose among available approaches. In this paper, I review evidence that sociocultural influences play a powerful role in shaping both the repertoires of strategies individuals have available to solve problems, and the choices they make among those strategies.

The repertoire of HLA-Cw-specific NK cell receptors CD158 a/b (EB6 and GL183) in individuals with different HLA phenotypes.

Over the last few years, natural killer (NK) cells have been shown to express major histocompatibility complex (MHC) molecules recognizing receptors that are thought to function primarily as negative signalling receptors. Much attention has been focused on the NK cell receptors CD158a (EB6) and CD158b (GI 183), which recognize two alternative epitopes on the HLA-Cw locus. In order to investigate whether HLA type affects the CD158a/b repertoire, expressed as percentage positive cells for a particular receptor and mean expression on this population of NK cells, peripheral blood lymphocytes of 47 HLA-typed donors were examined. Peripheral blood samples were examined by flow cytometric analysis to investigate the expression of CD158a and CD158b receptors on the surface of NK cells. In parallel, we determined each individual's HLA phenotype. There was a great heterogeneity in CD158 expression; nevertheless all individuals had NK cells belonging either to the CD158 a+b-, a-b+ or a-b- populations. No positive or inverse correlations could be shown between either receptor expression intensity or proportion of positive cells, and presence of the appropriate ligand. Thus no association between an individual's NK receptor repertoire and HLA serotype could be demonstrated. It is concluded that CD158 is expressed on NK cells in a highly redundant fashion. Our data do not support either a positive selection mechanism or the receptor calibration model.

Analysis of TCRAV and TCRBV Repertoires in Healthy Individuals by Microplate Hybridization Assay

ABSTRACT: We have developed an adaptor ligation PCR-based microplate hybridization assay (MHA) for analysis of T cell receptor α chain variable region (TCRAV) and T cell receptor β chain variable region (TCRBV) repertoires. Forty three TCRAV and thirty eight TCRBV-specific probes were immobilized onto microplate wells in water-soluble carbodiimide. After hybridization of 5′-biotinylated PCR products, quantitative ELISA was carried out and followed by automated colorimetric reading. The conditions for immobilization and hybridization were optimized using representative TCRBV-specific probes. The sensitivity of MHA allows us to detect as low as 40 pg of biotinylated PCR products. The frequencies of individual V segments obtained by MHA were consistent with those obtained by FACS analysis and reverse dot blot assays. Analysis of the entire TCRAV and TCRBV repertoires could be done using a single 96-well plate, and completed in less than 6 h. Simplicity and reproducibility of this method make it suitable for routine laboratory use. The expression of TCRAV and TCRBV segments was next studied in peripheral blood mononuclear cells (PBMC) of 14 healthy donors using the newly developed MHA method. TCRAV8S1, TCRAV23S1, TCRBV2S1, TCRBV3S1, TCRBV4S1, and TCRBV6S5 were highly expressed in PBMC. Further, the TCRAV repertoires among individuals were less variable compared to the TCRBV repertoires. Interestingly, considerable variations in the expression levels of BV3S1, BV4S1, and BV17S1 were observed among individuals. One polymorphic site was found at the coding region of BV4S1, and there were two alleles. These results suggest that variable expression among individuals may be associated with unknown allelic polymorphism in coding and/or regulatory regions of these TCRBV segments, or with disparity in HLA genes.

Variation in the use of discourse markers in a language contact situation

ABSTRACTUse of discourse markers by 17 speakers of Anglophone Montreal French (AMF) showed great variation in individual repertoires and frequency of use. Only five subjects manifested rates of usage comparable to those of native speakers or to their own LI usage in English. In decreasing order of frequency, the speakers usedtu sais‘y'know’;là‘there’ (the most frequent among L1 Montreal French speakers);bon‘good’,alors‘so’,comme‘like’, andbien‘well’; and the local discourse conjunctionfait que‘so’. The subjects occasionally made use of the English markersyou know, so, like, andwell. Québécois French markers with no English equivalent were used by the speakers who had been exposed to French in their early childhood environment. The one marker that showed influence from English wascomme, apparently calqued on Englishlike. Overall, frequent use of discourse markers correlated only with the speakers' knowledge of French grammar – evidence that a higher frequency of discourse marker use is the hallmark of the fluent speaker. As a feature that is not explicitly taught in school, mastery of the appropriate use of discourse markers is thus particularly revealing of the speakers' integration into the local speech community.

The TCR-delta repertoire in human intestine undergoes characteristic changes during fetal to adult development.

The TCR-delta repertoire in adult human intestine is oligoclonal and unique in each individual. In the present study, changes in the junctional regions of TCR-delta transcripts in human intestine that occur during development from fetal to adult life were used to characterize fundamental changes in the TCR-delta repertoire in the human intestinal tract during ontogeny. At mid-gestation, the fetal repertoire was polyclonal, but limited, in its junctional diversity by the relative lack of N region nucleotide additions and by the frequent formation of coding region joins at regions of short sequence homology. In addition, identical TCRDV2 transcripts that resemble canonical TCR-delta sequences in mice were present in the intestine of different fetuses. In the early period after birth, the intestinal TCR-delta repertoire was polyclonal, and more diverse than the fetal repertoire, with junctional regions that contained extensive N nucleotide additions and frequently were as complex as those of adults. The intestinal TCR-delta repertoire showed increasing restriction with age and, by 14 to 17 yr, the repertoire was oligoclonal and resembled the repertoire of individuals in the sixth to seventh decade. Moreover, the adult TCR-delta repertoire was almost identical at multiple sites throughout the intestine, suggesting a model in which gammadelta T cell clones, selected by ligands in the intestinal tract, undergo expansion and recirculation before lodging throughout the small intestine or colon.

Immune Network at the Edge of Chaos

Some time ago Jerne proposed a new theory to explain the basis of the behaviour of the immune system. He suggested the existence of a functional connected network, based on pattern recognition of the idiotypes carried by the lymphocytes, which is responsible for the self regulation of the immune system. Only 15–20% of the lymphocytes available in the immune repertoire will participate in this functional network, while the rest of the lymphocytes will be free to respond to any foreign antigen. Each individual immune repertoire will be different depending on the lymphocytes that participate in the connected network.Using a very simple cellular automata model of the immune repertoire dynamics we show that, although the usual regimes (stable and chaotic) attained by this automata, are not interesting from the biological point of view, the transition region, at the edge of chaos, is very appropriate to describe such dynamics. In this region we have obtained a functional connected network involving 10–20% of the lymphocytes available in the repertoire, as suggested by Jerne and others. The model also reproduces the immune system signature, the ensemble of different lymphocytes that each individual expresses in his immune repertoire, which varies from one individual to another. We show how the immune memory comes out as a consequence of the dynamics of the system. From our results we confirm and present evidence that the chaotic regime corresponds to a sort of non-healthy state, as has been suggested previously.