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Molecular cloning of a T cell-specific adapter protein (TSAd) containing an Src homology (SH) 2 domain and putative SH3 and phosphotyrosine binding sites.

Adapter proteins link catalytic signaling proteins to cell surface receptors or downstream effector proteins. In this paper, we present the cDNA sequence F2771, isolated from an activated CD8+ T cell cDNA library. The F2771 cDNA encodes a novel putative adapter protein. The predicted amino acid sequence includes an SH2 domain as well as putative SH3 and phosphotyrosine binding interaction motifs, but lacks any known catalytic domains. The expression of the gene is limited to tissues of the immune system and, in particular, activated T cells. The protein expressed by F2771 cDNA in transfected COS cells is localized in the cytoplasm. A polyclonal antiserum raised against an F2771-encoded peptide reacts with a tyrosine-phosphorylated 52-kDa protein expressed in phytohemagglutinin-stimulated peripheral blood mononuclear cells. The gene is localized to chromosome 1q21, a region often found to be aberrant in lymphomas. The T cell-specific expression and the rapid induction of mRNA expression upon receptor binding, as well as the lack of catalytic domains in the presence of protein interaction domains, indicate that the F2771 gene encodes a novel T cell-specific adapter protein (TSAd) involved in the control of T cell activation.

Adaptor Proteins, Signal Transducing↗

Branchial osmoregulatory response to salinity in the gilthead sea bream, Sparus auratus.

The branchial osmoregulatory response of gilthead sea bream (Sparus auratus L.) to short-term (2-192 hr) and long-term (2 weeks) exposure to different environmental salinities (5 per thousand, 15 per thousand, 25 per thousand, 38 per thousand and 60 per thousand) was investigated. A "U-shaped" relationship was observed between environmental salinity and gill Na+,K+ -ATPase activity in both long- and short-term exposure to altered salinity, with the increase in activity occurring between 24 and 96 hr after the onset of exposure. Plasma osmolality and plasma ions (sodium, chloride, calcium and potassium) showed a tendency to increase in parallel with salinity. These variables only differed significantly (P<0.05) in fish adapted to 60 per thousand salinity with respect to fish adapted to full-strength sea-water (SW). Plasma glucose remained unchanged whereas plasma lactate was elevated at 5 per thousand and 60 per thousand. Muscle water content (MWC) was significantly lower in fish adapted to 60 per thousand. Chloride cells (CC) were only present on the surface of the gill filaments and absent from the secondary lamellae. CC distribution was not altered by external salinity. However, the number and size of CC were significantly increased at salinity extremes (5 per thousand and 60 per thousand), whereas fish exposed to intermediate salinities (15 per thousand and 25 per thousand) had fewer and smaller cells. Furthermore, the CC of fish exposed to diluted SW became rounder whereas they were more elongated in fish in full-strength and hypersaline SW. This is consistent with previous reports indicating the existence of two CC types in euryhaline fish. At likely environmental salinities, gilthead sea bream show minor changes in plasma variables and the effective regulation of gill Na+,K+ -ATPase. However, at very low salinities both haemodilution and up-regulation of gill Na+,K+ -ATPase predict a poor adaptation most likely related to deficiency or absence of specific components of the CC important for ion xuptake.

Analysis of Variance↗

Introduction to Bayesian methods III: use and interpretation of Bayesian tools in design and analysis.

The Bayesian approach and several of its advantages in drug and medical device development are described. One advantage from the perspective of analysis is that it provides a methodology for synthesizing information. However, taking a Bayesian approach to designing clinical trials is potentially more valuable than using this approach in analyzing trial results. Bayesian methodology provides a mechanism for updating what is known as results accumulate during a trial. Such updating can be incorporated completely explicitly and prospectively. An important way in which the Bayesian approach can be used is in calculating the predictive probability distribution of future results on the basis of current results. I show how to exploit predictive distributions in adapting to results that accumulate during the course of a trial. Possible adaptations including decreasing or increasing sample size, dropping treatment arms, and modifying the randomization proportions to the various arms depending on the interim results. Consequences of taking a Bayesian approach to clinical trial design are efficiency, better treatment of patients in the trial, and greater precision regarding the primary endpoints. An example of the last of these is Bayesian modeling of the relationship between early and longer term endpoints. Such modeling also enables earlier decision making. Case studies 2 and 3 deal with trials that were shorter and smaller, respectively, because of such modeling.

Bayes Theorem↗

The adaptive immune system and long-term outcome in patients with stable coronary disease. Predictive value of routine laboratory measurements.

Components of the adaptive immune system, in particular lymphocytes and immunoglobulin, play a major role in advanced atherosclerotic lesions. We sought to determine whether routine, measurements of the relative number of circulating lymphocytes (%L) and gamma-globulin (%G) reflecting immunoglobulin are related to event-free survival in patients with stable coronary artery disease (CAD). We prospectively studied the combined endpoint all-cause mortality, myocardial infarction and coronary revascularization procedures in 141 patients after successful percutaneous coronary intervention during a median follow-up time of 13.2 years. Using Cox regression, we found a significant influence of %L on event-free survival (P=0.007) with a relative risk of 2.21 comparing third to first tertile. Subjects with higher %G values likewise had a shorter event-free survival (P=0.008) with a relative risk of 1.67 comparing third to first tertile. The predictive value of %L and %G remained significant after adjustment for demographic data, cardiovascular risk factors, extent of CAD and other inflammatory markers. We conclude that the fraction of gamma-globulin and in particular the relative lymphocyte cell count may serve as readily available and reliable prognostic tools for the long-term outcome in patients with stable CAD.

Arteriosclerosis↗

Modeling for neuromonitoring depth of anesthesia.

This article reviews the various modeling techniques for neuromonitoring depth of anesthesia (DOA). Traditional techniques such as parametric, predictive, optimal, and adaptive modeling, proportional, integral, derivative (PID) modeling, together with modern techniques such as bispectral-based, artificial neural-network-based, fuzzy logic, and neuro-fuzzy modeling, bring us to the current state of the art in DOA neuromonitoring. This article reviews historical information about each of the modern techniques and provides an example demonstrating its implementation; reviews drug pharmacokinetic/pharmacodynamic (PK/PD) and drug interaction PK/PD modeling techniques for a balanced total intravenous anesthesia (TIVA) administration; and discusses the existing technical problems and clinical challenges, suggesting new techniques necessary for the future development of a DOA monitoring and control system.

Anesthesia↗

Personality profiles in eating disorders: rethinking the distinction between axis I and axis II.

OBJECTIVE: Like other DSM-IV axis I syndromes, eating disorders are diagnosed without respect to personality, which is coded on axis II. The authors assessed the utility of segregating eating disorders and personality pathology and examined the extent to which personality patterns account for meaningful variation within axis I eating disorder diagnoses. METHOD: One hundred three experienced psychiatrists and psychologists used a Q-sort procedure (the Shedler-Westen Assessment Procedure-200) that assesses personality and personality pathology to describe a patient they were currently treating for bulimia or anorexia. Data were subjected to a cluster-analytic procedure (Q-analysis) to determine whether patients clustered into coherent groupings on the basis of their personality profiles. Categorical and dimensional personality diagnoses were then used to predict measures relevant to adaptation and etiology, controlling for axis I diagnosis. RESULTS: Three categories of patients emerged: a high-functioning/perfectionistic group, a constricted/overcontrolled group, and an emotionally dysregulated/undercontrolled group. This categorization demonstrated substantial incremental validity beyond axis I diagnosis in predicting eating disorder symptoms, adaptive functioning (Global Assessment of Functioning scores and history of psychiatric hospitalization), and etiological variables (sexual abuse history). CONCLUSIONS: Axis I symptoms are a useful component, but only one component, in the accurate diagnosis of eating disorders. Classifying patients with eating disorders by eating symptoms alone groups together patients with anorexic symptoms who are high functioning and self-critical with those who are highly disturbed, constricted, and avoidant, and groups together patients with bulimic symptoms who are high functioning and self-critical with those who are highly disturbed, impulsive, and emotionally dysregulated. These distinctions may be relevant to etiology, prognosis, and treatment.

Adult↗

Stochastic prediction in pursuit tracking: an experimental test of adaptive model theory.

In this paper we test the proposition that in pursuit tracking, subjects compute stochastic (statistical) models of the temporal variations in position of the target and use these models to forecast target position for at least a response time interval into the future. A computer simulation of a human operator employing stochastic model prediction of target position is used to generate a synthetic pursuit tracking response signal. Actual pursuit tracking response signals are measured from 10 normal subjects using the same stimulus signal. Cross correlation and spectral analysis are employed to compute gain and phase frequency response characteristics for both synthetic and actual tracking data. The similarity of the gain and phase curves for synthetic and actual data provides compelling evidence in support of the proposition.

Adult↗

Chromosome fragility and psychopathology in obligate female carriers of the fragile X chromosome.

The relationship between fragility (the percentage of cells exhibiting the fragile X chromosome abnormality) and psychopathological conditions was investigated in a sample of 40 obligate female carriers of the fragile X chromosome. Subjects were categorized by those with positive fragility greater than 0% (n = 19) and those with 0% fragility (n = 21). Compared with women with 0% fragility, it was expected that women with positive fragility would have a higher likelihood of manifesting a spectrum of social and psychological disability previously shown to be associated with fragile X syndrome in women. It was also expected that within the group with positive fragility, degree of fragility would be related to severity of symptoms. Results partially supported the hypotheses: women with fragility over 0% were more likely to be assigned a diagnosis of schizotypal features, were rated higher on symptoms associated with the schizophrenia spectrum, and scored lower on IQ, level of healthiest functioning, education, and socioeconomic status than women with 0% fragility. Subsequent comparisons with a control group indicated that the group with 0% fragility and normal controls did not differ on these variables. Within the group with positive fragility, increasing fragility was related to greater severity of symptoms and lower IQ, education, socioeconomic status, and levels of adaptive functioning, as predicted. Contrary to expectations, positive fragility was not associated with proportion of affective disorder diagnoses or ratings on affective disorder symptoms. The results of the study provide evidence that degree of fragility is a potentially important predictor of psychopathology among women with normal IQ who are carriers of the fragile X chromosome abnormality.

Adult↗

Death without warning? A clinical postmortem study of suicide in 43 Israeli adolescent males.

Forty-three consecutive Israeli male suicides, 18 to 21 years of age, that occurred during compulsory military service were studied using preinduction assessment data, service records, and extensive postmortem interviews with family and peers. At preinduction, subjects, as a group, appeared above average in intelligence, physical fitness, and measures predictive of successful adaptation to military service. Active duty performance was generally satisfactory. Ascertained post mortem, 53.5% met formal criteria for major depressive disorder; most cases, however, appeared recent and reactive. Narcissistic and/or schizoid traits were common. Substance abuse was absent and antisocial personality disorder was rare (4.7%). Furthermore, in eight patients (18.6%) no Axis I diagnosis could be made; half of these also lacked any significant Axis II pathology. These findings, at partial variance with US studies, suggest a complex relationship between suicide and mental disorder. The striking failure of intensive screening and preventive measures to prevent these suicides highlights unresolved questions of etiology and intervention.

Adaptation, Psychological↗

The concept of an evolved adaptation.

A Darwinian adaptation is an organism's feature that was functionally designed by the process of evolution by selection acting in nature in the past. Functional design rules out explanations of drift, incidental effect, phylogenetic legacy and mutation. Elucidation of the functional design of an adaptation entails an implicit reconstruction of the selection that made the adaptation. Darwinian adaptations and other individual traits may be currently adaptive, maladaptive or neutral. One relatively recent meaning of adaptation is inconsistent with the Darwinian conception of adaptation. The inconsistent meaning characterizes much research on humans and non-human species in behavioural ecology. Its focus is on equating Darwinian adaptation with current adaptiveness. Current adaptiveness is not an actual scientific prediction of a hypothesis about Darwinian adaptation. Some aspects of the discussion in the evolutionary literature surrounding the current adaptiveness view of adaptation are evaluated. Contrary to claims by some who advocate current adaptiveness, the environment of evolutionary adaptedness of humans and other organisms is scientifically knowable through discovery of the functional design of Darwinian adaptations.

Adaptation, Psychological↗

Collection efficiencies of MNC subpopulations during autologous CD34+ peripheral blood progenitor cell (PBPC) harvests in small children and adolescents.

There is increasing demand for mononuclear cell (MNC) harvests not only for PBPC but also for immune therapies using dendritic cells and donor lymphocytes. We determined the collection efficiencies (CE) of various MNC subpopulations during CD34+ cell harvests using a Fenwal CS 3000 Plus Omnix system in small children and adolescents. The cell content of 140 leukapheresis products (LP) was prospectively evaluated in 45 pretreated patients with solid tumors and hematological malignancies. The median age was 12 years (range 0.8-22), and the median body weight (BW) 43 kg (range 9-92). Depending upon the BW of the patients, the media used for priming were saline (SP) in 86, human albumin (HA, HAP) in 10, and packed red blood cells (BP) in 44 apheresis procedures. The major nucleated cell (NC) fractions collected were monocytes (52% of NC) and CD3+ T cells (26%). The median cell yield for monocytes was 174 * 10(6)/kg (range 24-613) representing a CE of 55%. The median number of CD3(+) T cells was 84 * 10(6)/kg (range 5.6-380; CE = 74%). CD34+ cells represented a very small cell fraction of the LP (1.3% of NC), with a median yield of 4.2 * 10(6)/kg (range 0.2-87) and a CE of 63%. The cell yield of various MNCs was significantly correlated with the cell count in the peripheral blood (PB) and with the blood volume processed (ANOVA, P < 0.0001). No influence on the CE was observed for the priming procedure, the patients' age or sex, or the other adaptations used in the harvesting protocol. In conclusion, the Fenwal CS 3000 Plus OMNIX system with the CD34+ cell program and the described adaptations, is also predictably useful for harvest of monocytes or lymphocytes in pediatric patients. We present regression equations that predict the cell yield of various MNC subpopulations in apheresis products.

Adolescent↗

Field experiments on duration and precision of grey and red squirrel spatial memory

Field experiments on squirrel spatial memory under naturalistic conditions showed that grey squirrels, Sciurus carolinensisare capable of relocating precise spatial goals using short range visual cues. These goals were in the form of buried food, similar to natural cache sites, and were relocated to within 5 cm in 62.5% of all attempts after a retention interval of 20 days. Some recall could be demonstrated after more protracted retention intervals (43 and 62 days). These results suggest that grey squirrels' spatial memory is accurate enough to support a successful retrieval strategy. Application of one of the same methods to a population of red squirrels, Sciurus vulgariswhich is not as reliant on stored food, suggested that their spatial memory is less long lasting as predicted by the adaptive specialization hypothesis of cognitive function.Copyright 1997 The Association for the Study of Animal Behaviour1997The Association for the Study of Animal Behaviour

Journal Article↗

No relationship between territory size and the risk of cuckoldry in birds.

It has been suggested that male birds adjust their territory size in order to prevent potential intruders from gaining extra-pair copulations. The risk of cuckoldry is supposed to be highest when the distance between a female and the neighbouring males is shortest. This paper describes the variation in territory size of the chiffchaff, Phylloscopus collybita, in relation to the breeding cycle. Contrary to the risk of cuckoldry hypothesis, chiffchaff territories were larger prior to the fertile period of the females and at a minimal size during the fertile period. A review of the literature shows little, if any, evidence of a peak in territory size during the fertile period of the females for most species studied. It is suggested that territoriality is in need of an operational definition. Without such a definition, it is difficult to make and test predictions about the adaptive basis of variation in territory size. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

Application of the Surface Complex Formation Model to Ion Exchange Equilibria

The surface complexation model as previously applied to pure anion and pure cation exchange equilibria has been extended to the description of the amphotheric sorption of inorganic ions onto activated alumina. Logarithmic equilibrium parameters (generalized separation factors) can be calculated from equilibrium concentrations in simple systems for the sorption of anions and cations. Both separation factors are functions of the oxide loading composition. Plotting the separation factors vs the loading compositions yields a set of two sorption constants for each kind of ion. The major advantage of the theoretical approach is that these constants can be applied without any adaptation to the prediction of multicomponent systems. Evaluation of experiments with two commercially available activated alumina products demonstrate the validity of the approach. The equilibrium of multicomponent systems can be predicted with excellent accuracy by means of the parameters for the uptake of chloride, nitrate, sulfate, sodium, and potassium ions. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗

Adolescent pregnancy: an intervention challenge.

Even in the best of circumstances, pregnancy is a time of emotional upheaval. This is especially true for pregnant adolescents who are also attempting to adjust to pubertal status and to establish an identity independent from their family. Although research has focused on the etiology of teenage pregnancy, relatively few interventions consider the developmental obstacles encountered when treating pregnant teenagers. In particular, adolescents are cognitively unprepared to predict long-term outcomes, a skill essential for confronting the challenges of pregnancy. One new intervention, known as previewing, seeks to overcome this deficit. Previewing encourages expectant teenage mothers to represent future scenarios with the infant as a means of predicting and rehearsing adaptive outcomes.

Adolescent↗

The prediction of EEG signals using a feedback-structured adaptive rational function filter.

In this article, we present a feedback-structured adaptive rational function filter based on a recursive modified Gram-Schmidt algorithm and apply it to the prediction of an EEG signal that has nonlinear and nonstationary characteristics. For the evaluation of the prediction performance, the proposed filter is compared with other methods, where a single-step prediction and a multi-step prediction are considered for a short-term prediction, and the prediction performance is assessed in normalized mean square error. The experimental results show that the proposed filter shows better performance than other methods considered for the short-term prediction of EEG signals.

Algorithms↗

What is improved if a mental rotation task is repeated--the efficiency of memory access, or the speed of a transformation routine?

The present study contrasts 3 theories which provide explanations for performance improvement in mental rotation tasks. Wallace and Hofelich conjectured that the process as such may be executed more rapidly after training, while Bethell-Fox and Shepard attributed practice effects to the fact that images may be transformed first elementwise, but later as a Gestalt. In contrast, Tarr and Pinker assumed that a transformation of an image will no longer be computed after training but simply be retrieved from memory. Thirty-seven subjects participated in 3 test sessions in which they had to decide on the parity of 3-D block figures presented from different perspectives. Experimental group subjects underwent 4 additional practice sessions in which a subset of the figures and a subset of perspective views were used. Tests adapted to the predictions of the 3 theories revealed specific learning effects but no transfer, neither to old objects presented in new perspectives nor to new objects. This supports an instance-based explanation of practice effects which states that objects are represented in multiple perspective views.

Adult↗

The role of blood gas and acid-base assessment in the diagnosis of intrapartum fetal asphyxia.

The diagnosis of fetal asphyxia requires a blood gas and acid-base assessment demonstrating a significant metabolic acidosis. However, the fetus may tolerate an asphyxial insult without central nervous system injury because of the fetal cardiovascular adaptation to hypoxemia. Prediction of the significance of an asphyxial insult to the fetus requires a measure of both the duration and degree of the asphyxia as well as an expression of the fetal compensatory response to the asphyxia.

Acid-Base Equilibrium↗