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PubMed2025

Prematurity and Genetic Liability for Autism Spectrum Disorder.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by diverse presentations and a strong genetic component. Environmental factors, such as prematurity, have also been linked to increased liability for ASD, though the interaction between genetic predisposition and prematurity remains unclear. This study aims to investigate the impact of genetic liability and preterm birth on ASD conditions. METHODS: We analyzed phenotype and genetic data from two large ASD cohorts, the Simons Foundation Powering Autism Research for Knowledge (SPARK) and Simons Simplex Collection (SSC), encompassing 78,559 individuals for phenotype analysis, 12,519 individuals with genome sequencing data, and 8,104 individuals with exome sequencing data. Statistical significance of differences in clinical measures was evaluated between individuals with different ASD and preterm status. We assessed the rare variants burden using generalized estimating equations (GEE) models and polygenic load using ASD-associated polygenic risk score (PRS). Furthermore, we developed a machine learning model to predict ASD in preterm children using phenotype and genetic features available at birth. RESULTS: Individuals with both preterm birth and ASD exhibit more severe phenotypic outcomes despite similar levels of genetic liability for ASD across the term and preterm groups. Notably, preterm ASD individuals showed an elevated rate of de novo variants identified in exome sequencing (GEE model, p=0.005) in comparison to the non-ASD preterm group. Additionally, a GEE model showed that a higher ASD PRS, preterm birth, and male sex were positively associated with a higher predicted probability for ASD, reaching a probability close to 90% in SPARK. Lastly, we developed a machine learning model using phenotype and genetic features available at birth with limited predictive power (AUROC = 0.65). CONCLUSIONS: Preterm birth may exacerbate the multimorbidity present in ASD, which was not due to the ASD genetic factors. However, increased genetic factors may elevate the likelihood of a preterm child being diagnosed with ASD. Additionally, a polygenic load of ASD-associated variants had an additive role with preterm birth in the predicted probability for ASD, especially for boys. We propose that incorporating genetic assessment into neonatal care could benefit early ASD identification and intervention for preterm infants.

Autism Spectrum Disorder↗
PubMed2004

[Clinical reasoning and decision making in practice. A 23 year old woman with malaise, anorexia, fever and behavior changes].

A 23-year-old woman presented with a history of some months of malaise, anorexia, fever and behavioural changes. She had been examined by a general physician on repeated occasions before coming to the hospital. After physical examination and laboratory investigations, she was sent home. She returned to the hospital the same day with increased drowsiness and headache. Additional diagnostic procedures were performed. An echocardiography showed vegetations on the mitral valve. A CT scan of the brain showed a left frontotemporal haemorrhage. Infective endocarditis with septic embolisation to the brain, which resulted in a cerebral haemorrhage, was diagnosed. The patient was admitted and intravenous antibiotics were administered. Because of haemodynamic instability, a mitral valve replacement was performed on the fifth day of admission. The patient recovered well postoperatively. Four weeks later, she was found in a comatose condition. She died as a result of a second intracerebral haemorrhage, which was probably caused by a mycotic aneurysm. An important lesson to be learned from this case is that endocarditis should be considered in patients with a long history of anorexia, weight loss, malaise and fever, especially when a heart murmur is present. Secondly, if intracranial haemorrhage has occurred in patients with infective endocarditis, therapeutic options should always be discussed with a neurosurgeon, even in those cases where the probability of a mycotic aneurysm is low.

Adult↗
PubMed1980

Controlled neuropsychological investigation of patients with neurotic excoriations.

On the basis of preliminary empirical findings and the pertinent neuropsychological literature the following hypothese are put forward: (1) Because of a certain amount of abreaction (scratching), patients with neurotic excoriations will obtain higher scores in tests of verbal learning and long-term memory than "common' neurotics but probably lower scores in such tests than a group of "normal' subjects. (2) Visual long-term memory is relatively impaired both in patients with neurotic excoriations and in "common' neurotics compared to a "normal' group. (3) Performances IQ for both patient groups mentioned will be relatively low compared to verbal IQ. - The first and second of these suppositions were confirmed but not the third.

Adult↗
PubMed2005

Prosthodontics 1966-2042: changes in prosthodontic education, past and future.

Past changes in prosthodontic education have been influenced by educators" understanding of learning, the physical plants in which they teach and the evolution of the profession (both clinically and politically). A 1968 survey illustrates an emphasis on materials and techniques, and the literature of the day respected "expert" opinion. Although the need for prosthodontics was expected to decline with the promotion of preventive measures, it is actually increasing with the aging population. Organizational support for defining the specialty of prosthodontics to encompass a broad spectrum of dental restorations and related care helped develop commitment to improved research and education. Instrumental in these improvements were faculty with advanced education in the discipline, better physical plants in which to work and an understanding of the theories of teaching and learning. Faculty will continue to be innovative and adopt new approaches such as evidence-based dentistry and problem-based learning. However, the lure of research funding and institutional expectations will probably influence how faculty spend their time and energy. Prosthodontic education will continue to evolve, but it will be influenced by its institutional and professional environments.

Canada↗
PubMed2000

Learning cortical topography from spatiotemporal stimuli.

Stimulus representation is a functional interpretation of early sensory cortices. Early sensory cortices are subject to stimulus-induced modifications. Common models for stimulus-induced learning within topographic representations are based on the stimuli's spatial structure and probability distribution. Furthermore, we argue that average temporal stimulus distances reflect the stimuli's relatedness. As topographic representations reflect the stimuli's relatedness, the temporal structure of incoming stimuli is important for the learning in cortical maps. Motivated by recent neurobiological findings, we present an approach of cortical self-organization that additionally takes temporal stimulus aspects into account. The proposed model transforms average interstimulus intervals into representational distances. Thereby, neural topography is related to stimulus dynamics. This offers a new time-based interpretation of cortical maps. Our approach is based on a wave-like spread of cortical activity. Interactions between dynamics and feedforward activations lead to shifts of neural activity. The psychophysical saltation phenomenon may represent an analogue to the shifts proposed here. With regard to cortical plasticity, we offer an explanation for neurobiological findings that other models cannot explain. Moreover, we predict cortical reorganizations under new experimental, spatiotemporal conditions. With regard to psychophysics, we relate the saltation phenomenon to dynamics and interaction in early sensory cortices and predict further effects in the perception of spatiotemporal stimuli.

Animals↗
PubMed1995

Sudden death in epilepsy: a study of incidence in a young cohort with epilepsy and learning difficulty.

Sudden death, often seizure related, may occur in patients with epilepsy. Population-based incidence is probably on the order of 1:1,000/year. The incidence is much higher in selected groups, however. We wished to establish the incidence of sudden unexpected death (SUD) in a young cohort with severe epilepsy and learning difficulties. The study cohort included 310 pupils with epilepsy enrolled at a special residential school between April 1970 and April 1993. The follow-up period totaling 4,135 person-years included a period of residence at the school as well as time after leaving. Age and sex standardized overall mortality ratio was 15.9 [95% confidence interval (CI) 10.6-23.0], with 20 of 28 deaths considered epilepsy related. An incidence of sudden death cases of 1:295/year was noted. All 14 sudden deaths occurred when the pupils were not under the close supervision of the school and most were unwitnessed, which has implications for prevention.

Adolescent↗
PubMed2002

Contrast agents provide a faster learning curve in dipyridamole stress echocardiography.

AIM: Interobserver variability is an important limitation of the stress echocardiography and depends on the echocardiographer training. Our aim was to evaluate if the use of contrast agents during dipyridamole stress echocardiography would improve the agreement between an experienced and a non-experienced observer in stress echo and therefore if contrast would affect the learning period of dypyridamole stress echo. METHODS AND RESULTS: Two independent observers without knowledge of any patient data interpreted all stress studies. One observer was an experienced one and the other had experience in echocardiography but not in stress echo. Two observers analysed 87 non-selected and consecutive studies. Out of the 87 studies, 46 were performed without contrast administration, whereas i.v. contrast (2.5 g Levovist by two bolus at rest and at peak stress) was administered in 41. In all cases, second harmonic imaging and stress digitalisation pack was used. The agreement between observers showed a kappa index of 0.58 and 0.83 without and with contrast administration, respectively. CONCLUSIONS: The use of contrast agents provides a better agreement in the evaluation of stress echo between an experienced and a non-experienced observer in stress echo. Adding routinely contrast agents could probably reduce the number of exams required for the necessary learning curve in stress echocardiography.

Clinical Competence↗
PubMed1976

Token economies in institutional settings. Historical, political, deprivation, ethical, and generalization issues.

The use of the token economy in institutional settings is examined in light of historical, political, deprivation, ethical, and generalization issues. The major points may be summarized as follows. a) The token economy may be viewed as a palliative measure to prevent the incredibly regressive effects of institutionalization. b) To achieve control in token programs in many "total institutions," an artificial state of deprivation must be achieved. c) Generalization of behaviors into the natural environment following the patient's stay in a token economy program should not be taken for granted. d) What the patient learns in a token economic system may not be what the token economy's program director probably intends.

Behavior Therapy↗
PubMed1993

Adolescents with learning disabilities: a comparative life-stream interpretation.

The subjective experiences of adolescents with learning disabilities (LD) were compared to those of their low-achieving and normally achieving peers. Three groups of juniors and seniors from one suburban high school district, 18 students with learning disabilities (15 males, 3 females), 17 low-achieving students (12 males, 5 females), and 20 average-achieving students (12 males, 8 females), were given electronic pagers and booklets for 1 week. They were signaled every 40 minutes during school hours, and every 2 hours after school. As soon as possible after receiving a signal, they responded to questions in their booklets. The questions provided subjective measures on levels of affect, activation, cognitive efficiency self-esteem, motivation, and feedback from others. The students with learning disabilities reported feeling more positive and active than either of the other groups during school hours, while after school there were no differences on any of the subjective measures for the three groups. Specific LD school practices are high-lighted for their probable impact on the heightened affect and activation of the students with learning disabilities.

Adolescent↗
PubMed1991

Effects of NMDA receptor antagonists and sigma ligands on the acquisition of conditioned fear in mice.

Recent studies have shown that several compounds known to act as competitive or non-competitive antagonists of NMDA receptors can disrupt learning in rodents. The present study was carried out to investigate the effects of a range of NMDA antagonists, acting at several sites in the NMDA receptor complex, on the acquisition of learned fear in mice. Dose-related disruptions of learning were produced by the non-competitive antagonists phencyclidine, dizocilpine, dextromethorphan and (+) and (-)N-allylnormetazocine. The (+) enantiomer of N-allylnormetazocine was approximately twice as potent as the (-) enantiomer. The competitive NMDA receptor antagonist, CGS 19755, also blocked the acquisition of learned fear as did the non-specific glutamate antagonist riluzole. In contrast, the anti-ischaemic drugs ifenprodil and SL 82.0715, which probably act as NMDA antagonists through an effect on the polyamine site, had no effect on learning up to doses which substantially reduced locomotion. The sigma receptor ligand DTG was also inactive. These results confirm that both competitive and non-competitive NMDA antagonists disrupt learning but indicate that the extent to which such an effect is observed may depend on the site at which the compounds act within the receptor complex. Activity at sigma receptors is unrelated to the effect on learning.

Animals↗
PubMed1997

Interactions of physical training and heat acclimation. The thermophysiology of exercising in a hot climate.

Physical training and heat acclimation are both commonly adopted tactics to improve performance and/or tolerance times when individuals must compete or work in the heat. Potential benefits include: (i) improved aerobic fitness and thus a greater cardiovascular reserve (probably seen mainly after training); (ii) a lower resting body temperature that allows greater heat storage (probably seen mainly after acclimation); (iii) a decreased energy cost of a given intensity of exercise (seen after acclimation and also as the learning component of training); (iv) an enhanced sweating response at a given percentage of maximal effort (probably developed by both treatments); (v) a slower increase in body temperature owing to (iii) and/or (iv) [seen after both treatments]; (vi) a reduced cardiovascular stress because of changes in the autonomic nervous system (probably realised mainly by training), expansion of blood volume (seen after both treatments) and/or a decreased peripheral pooling of blood (probably found after both treatments); and (vii) improved subjective tolerance reflecting a decrease in the relative intensity of a given activity (probably seen mainly after training), a reduction in the physiological strain (found after both treatments) and/or habituation to heat-exercise stress (probably developed by both treatments). Factors affecting improvements in physiological and psychological responses to a given set of conditions include: (i) the individual's initial fitness and acclimatisation to heat; (ii) age, gender, hydration, sleep deprivation, circadian rhythms and in women the menstrual cycle: (iii) use of ergogenic aids such as fluid ingestion, carbohydrate and/or electrolyte replacement and blood doping; (iv) event or test conditions such as the mode of exercise, the severity of environmental heat stress and the type of clothing worn; and (v) treatment conditions such as the intensity, duration and frequency of exercise and/or heat exposure, the length of any rest intervals and cumulative depletion of body water and minerals.

Acclimatization↗
PubMed2006

Selective learning and memory impairments in mice deficient for polysialylated NCAM in adulthood.

The neural cell adhesion molecule (NCAM) has been implicated in regulating synaptic plasticity mechanisms as well as memory consolidation processes. Attachment of polysialic acid to NCAM (PSA-NCAM) has been reported to down-regulate its adhesive forces, a process hypothesized to be implicated in synapse selection after learning experiences. PSA-NCAM has been critically implicated in hippocampus-related synaptic plasticity and memory storage, but information about its functional role in other brain areas remains scarce. Here, we studied mice deficient for polysialyltransferase-1 (ST8SialV/PST-1), an enzyme which attaches PSA to NCAM during postnatal development and adulthood, and whose deficiency results in a drastic reduction of PSA-NCAM expression throughout the brain in adulthood. Mice were tested for their performance in the water maze and auditory fear conditioning (AFC). We report that ST8SiaIV knockout mice were impaired in spatial as well as reversal learning in the water maze. On the other hand, AFC was intact and ST8SiaIV mice exhibited no impairments in the acquisition or retention of cued fear memories. Spatial orientation learning and reversal learning require complex integration of spatial information and response selection involving the hippocampus and prefrontal cortex, whereas cued fear conditioning is an associative type of emotional memory that highly depends on amygdala function. Therefore, our results indicate that PSA-NCAM contributes differentially to learning processes that differ in the nature of the neural computations involved, which probably reflects a differential role of this molecule in different brain regions.

Amygdala↗
PubMed1994

Wizards and scientists: the pharmacologic experience in the Middle Ages.

During the Dark ages, Greco-Roman science survived in the eastern Roman Empire and the most important advances in pharmacology and pharmacy were made in Byzantium. As the Arab empires spread in the 7th and 8th centuries, they incorporated earlier learning, and the most important contribution of Arabic medical writers was probably the introduction of formularies to aid in the preparation of medicines. In turn, the later spread of Arabic knowledge to the West introduced little-known plants and fostered an interest in collecting and cultivating them, and also introduced the palatable dose forms preferred by the Arabic doctors. In the West, however, the Christian Church taught a doctrine of unquestioning faith, and despite the centers of learning, e.g. at Salerno, most ordinary people depended on the healing power of faith, religious relics and traditional folk medicine. Hydrology was also well developed in the Middle Ages. The formularia that survive describe many indigenous plants, but with few illustrations. Their gathering and preparation is generally guided by magic ceremonies and ritual, and plants often took their properties from their habitat, e.g. the wayside plantain was thought good for tired or wounded feet. Concepts of therapeutic plants were also influenced by alchemy and were linked to related metals and planets.

Byzantium↗
PubMed2000

Estimating functions of independent component analysis for temporally correlated signals.

This article studies a general theory of estimating functions of independent component analysis when the independent source signals are temporarily correlated. Estimating functions are used for deriving both batch and on-line learning algorithms, and they are applicable to blind cases where spatial and temporal probability structures of the sources are unknown. Most algorithms proposed so far can be analyzed in the framework of estimating functions. An admissible class of estimating functions is derived, and related efficient on-line learning algorithms are introduced. We analyze dynamical stability and statistical efficiency of these algorithms. Different from the independently and identically distributed case, the algorithms work even when only the second-order moments are used. The method of simultaneous diagonalization of cross-covariance matrices is also studied from the point of view of estimating functions.

Algorithms↗
PubMed2002

Generalizing a neuropsychological model of visual categorization to auditory categorization of vowels.

Twelve male listeners categorized 54 synthetic vowel stimuli that varied in second and third formant frequency on a Bark scale into the American English vowel categories [see text]. A neuropsychologically plausible model of categorization in the visual domain, the Striatal Pattern Classifier (SPC; Ashby & Waldron, 1999), is generalized to the auditory domain and applied separately to the data from each observer. Performance of the SPC is compared with that of the successful Normal A Posteriori Probability model (NAPP; Nearey, 1990; Nearey & Hogan, 1986) of auditory categorization. A version of the SPC that assumed piece-wise linear response region partitions provided a better account of the data than the SPC that assumed linear partitions, and was indistinguishable from a version that assumed quadratic response region partitions. A version of the NAPP model that assumed nonlinear response regions was superior to the NAPP model with linear partitions. The best fitting SPC provided a good account of each observer's data but was outperformed by the best fitting NAPP model. Implications for bridging the gap between the domains of visual and auditory categorization are discussed.

Adolescent↗
PubMed1999

Interruptions to foraging and learning in a changing environment.

Many resources are both stochastic and variable in their average profitability. Animals have to sample them to track their current states, but whether it is economic to attempt this depends on many factors. Furthermore, there are many interruptions and distractions from foraging (e.g. escape from predators, bad weather, displacement by competitors) which interfere with the acquisition of information. We present a dynamic model of foraging in a stochastic and varying environment, under the constant threat of interruption, to investigate this very general problem. A forager faces two foraging options, one of which provides a known and constant reward, the other providing a reward that is not only stochastic, but whose mean payoff varies in time. The forager has to learn which option has the highest current payoff by sampling. However, interruptions to foraging can occur at any time, the timing and duration of which are beyond the animal's control. When there is a small probability of foraging being interrupted, the forager should forage extensively on the unknown option, but as the probability of interruptions is increased, there is a sudden transition to foraging only on the known option. This occurs because interruptions affect both the level of information required to make exploitation of the unknown option profitable, and the ability to acquire and maintain that information. At what probability of being interrupted this threshold emerges is affected by the value of learning about the unknown option and the duration of interruptions. We discuss the generality of our results with reference to the pervasive problem of updating information in the face of different types of interruption. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed2005

Social isolation stress impairs passive avoidance learning in senescence-accelerated mouse (SAM).

Despite cumulative evidence showing the detrimental effect of psychosocial stress on the learning/memory functions in dementia diseases, the precise neurobiological mechanisms behind such an effect remain unclear. Mice of the senescence-accelerated mice prone 10 (SAMP10) strain, a neurodegenerative dementia model, were chronically exposed to social isolation stress from the age of 5 weeks. At the age of 12 weeks, conditioning memory and spatial memory were evaluated by one-trial passive avoidance and Y-maze tests, respectively. Chronic social isolation stress significantly reduced conditioning memory but did not affect spatial memory. Although further behavioral tasks using an elevated plus maze and a pain threshold test exhibited stress-induced analgesia, an analysis of covariance excluded the possibility that such analgesia might contribute to the stress-induced impairment of conditioning memory. In addition, endocrinological and immunohistochemical analysis revealed that isolation stress elevated the serum corticosterone levels and inhibited the increase in c-Fos expression in the central amygdaloidal nucleus (CeA) that is required for conditioning memory during passive avoidance learning. In conclusion, chronic social isolation stress exacerbated conditioning memory in SAM mice, probably through a glucocorticoid-mediated decrease in neural activation in the CeA.

Aging↗