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Transforming schools into communities of thinking and learning about serious matters.

In this article, a program of research known as Fostering Communities of Learners is described. This program is in place in several schools and classrooms serving inner-city students from 6 to 12 years of age. Based on theoretical advances in cognitive and developmental psychology, the program is successful at improving both literacy skills and domain-area subject matter knowledge (e.g., environmental science and biology). Building on young children's emergent strategic and metacognitive knowledge, together with their skeletal biological theories, the program leads children to discover the deep principles of the domain and to develop flexible learning and inquiry strategies of wide applicability.

Child↗

Tutorial software for clinical chemistry incorporating interactive multimedia clinical cases.

We have developed computer-based clinical case histories incorporating multimedia elements to aid the learning of medicine in a problem-based manner. Topics have been developed in the specialty of Clinical Biochemistry but the approach used is suitable for any branch of clinical medicine. Each topic has material aimed at medical students and also postgraduate candidates for professional examinations. A browser program is also incorporated. Emphasis is made on interaction through the case and modeling of real-life decisions in diagnosis and treatment. Advantages of the program are self-paced learning, assessment of understanding, feedback, and emphasis on deep understanding of the basic physiological and biochemical processes underlying clinical problems.

Chemistry, Clinical↗

Memory and aphasia.

Sixty-one acute and 17 chronic vascular left-hemisphere damaged patients were tested with five memory tasks that investigated verbal short-term (digit span) and long-term (paired-associate and story learning) memory, and spatial short- and long-term memory (Corsi's span and learning). Both brain-damaged groups were significantly impaired in all memory tasks (except for chronic patients in the story learning task) compared to normal controls. The presence of aphasia and locus of lesion (anterior, posterior and deep) had no effect on the memory impairment, with only one exception of paired-associate learning that was better performed by non-aphasic than aphasic patients. Eleven subjects were better at paired-associate learning than story recall, the reverse dissociation was never found. Finally, chronic patients performed significantly better than acute patients only in the Corsi's learning task.

Acute Disease↗

A Rasch measurement model analysis of the Revised Approaches to Studying Inventory.

BACKGROUND: The Revised Approaches to Studying Inventory (Entwistle & Tait, 1994) comprises 38 self-report items designed to measure student approaches to learning in a higher education context. The items have been conceptualised and designed from five learning orientations, corresponding to five subscales of the Inventory: 'a deep approach', 'a surface approach', 'a strategic approach', 'a lack of direction' and 'academic self-confidence'. AIMS: The study aims to create an interval level scale for the Inventory and analyse its psychometric properties using a modern measurement model, the Extended Logistic Model of Rasch (Andrich, 1988a, 1988b; Rasch, 1980), and investigate the conceptual design of the Inventory. SAMPLE: The sample was 346 students (170 females, 176 males, 212 less than 23 years and 134 older than 23), studying in first year Faculty of Business, at a university in Perth, Western Australia. METHOD: A scale was created for the Inventory and analysed for reliability, fit to the model, meaning and validity. The Inventory was analysed separately for each of four subgroups (females, males, younger and older students) to test the invariance of the scale. The five subscales were analysed separately to test the conceptual design and meaning of the Inventory. RESULTS: The Inventory has satisfactory psychometric properties, when items 20 and 33 are deleted. Easier and harder items need to be added to better target the student measures. Its conceptual design from the five learning orientations is confirmed. Only 15 items have satisfactory invariance across the four subgroups. The psychometric properties of three subscales (deep approach, surface approach and strategic approach) are only moderately satisfactory and the item separabilities of the other two (lack of direction and academic self-confidence) are unsatisfactory. CONCLUSIONS: The Extended Logistic Model of Rasch was found to be useful in creating an interval level scale for the Inventory, and for analysing its psychometric properties and conceptual design. It is suggested that the Inventory can be improved conceptually by adding more items relating to attitudes, intentions and behaviour and by adding harder and easier items to target the student measures better.

Adult↗

Adaptations to high hydrostatic pressure.

The importance of adaptation to high pressure has long been implicit in the findings of studies in which 1 atm-adapted species were subjected to elevated pressures. Recent comparative studies have shown that pressure sensitivities of enzymes, structural proteins, and membrane-based systems differ markedly between shallow- and deep-living species. These studies allow operational definition of what constitutes high pressures for different biological structures and processes. These are the habitat (adaptation) pressures at which a given type of system first exhibits reduced perturbation by pressure. These threshold pressures vary among physiological systems, but are similar for a given system among different species. Dehydrogenase enzymes and adenylyl cyclases exhibit threshold perturbation pressures of only 50-100 atm; the Na(+)-K(+)-ATPase of teleost gills appears to have a pressure perturbation threshold near 200 atm, and a similar threshold was found for actin self-assembly. Even this limited sample of physiological processes indicates that the terms deep and high pressure begin to apply at depths of only 500 m or less--and processes yet to be examined in comparative analysis may yield even lower pressure thresholds. The differences in sensitivity to pressure of homologous systems in shallow- and deep-living organisms have implications at several levels of biological organization. The vertical distribution patterns of species in aquatic habitats may be established, in part, by interspecific differences in resistance to pressure. High pressures may restrict the depths to which shallow-living species can penetrate, and the obligately barophilic systems found in deep-living organisms may limit their upper distribution limits. The similarities noted among the adaptations of deep-sea species with different shallow-water ancestors reflect a high degree of convergent evolution in pressure adaptation. It will be interesting to learn if the similarities in pressure-resistance of function among diverse deep-sea species are the result of similar or identical changes at the molecular level, e.g. in protein sequence. Acclimation to pressure may be of widespread occurrence among species that undergo large changes in depth, e.g. during ontogeny. Pressure acclimation may require pressure-regulation of gene expression. Lastly, comparisons of species from the cold deep sea with those from hydrothermal vents have shown that adaptations to both temperature and pressure play critical roles in determining the distribution patterns of deep-living species.

Adaptation, Physiological↗

Epinephrine-induced learning under anesthesia: retention performance at several training-testing intervals.

While under deep barbiturate anesthesia, rats received a series of 10 classical conditioning trials in which white noise was paired with intramuscular shock. The anesthetized animals received either saline or epinephrine injections prior to the training trials. Independent sets of animals were tested for retention performance 2, 7, or 15 days after training. In these test trials, a conditioned suppression measure was used in which the white noise was turned on while the animals were drinking. The results indicated that the animals that had received saline while trained under anesthesia exhibited no evidence of later retention. Animals that had received epinephrine injections prior to training under anesthesia suppressed their drinking in the presence of the white noise when tested 2 or 7, but not 15, days later. Thus, the results indicate that epinephrine can enable learning under anesthesia and, in addition, forgetting occurs within 15 days.

Anesthesia↗

Effect of intermittent deep hypothermic circulatory arrest on brain metabolism.

The effect of intermittent systemic reperfusion during deep hypothermic circulatory arrest was investigated in dogs to learn how the total arrest period may be prolonged. The animals were cooled on cardiopulmonary bypass to 18 degrees C and divided into the following three experimental groups: group I (n = 7), 60 minutes of uninterrupted circulatory arrest; group II (n = 7), 120 minutes of circulatory arrest with 10 minutes of intermittent systemic perfusion every 30 minutes during the arrest period; group III (n = 7), 120 minutes of circulatory arrest with 10 minutes of intermittent systemic perfusion every 20 minutes during the arrest period. Cerebral oxygen extraction rate increased significantly during the arrest periods (p < 0.05) and returned to normal after each 10-minute period of systemic reperfusion in every group. During circulatory arrest, cerebral excess lactate increased in a time-dependent manner after 20 minutes (r = 0.78; p < 0.001). Anaerobic metabolism did not increase throughout the circulatory arrest period in group III, although it increased significantly in groups I and II (p < 0.05). The present data demonstrate that cerebral energy metabolism becomes predominantly anaerobic within the first 20 minutes of deep hypothermic circulatory arrest. The present findings suggest that intermittent systemic recirculation for brief 10-minute periods every 20 minutes during circulatory arrest should prevent cerebral anaerobic metabolism during long periods of arrest that are required to complete complicated surgical repairs.

Animals↗

Deep venous thrombosis associated with heterotopic ossification.

The differential diagnosis of the swollen lower extremity in the patient with spinal cord injury includes deep venous thrombosis, fracture, cellulitis, joint sepsis, heterotopic ossification, hematoma formation, and neoplasm. A patient with an asymmetrically swollen limb who was found to have concurrent ipsilateral acute deep venous thrombosis and active heterotopic ossification is described. The diagnostic workup included various laboratory and radiologic studies. Therapy included anticoagulation with heparin and warfarin. To treat the heterotopic ossification, indomethacin, etidronate, and graded range of motion were used. We learned from this patient and several similar cases that acute deep-venous thrombosis and active heterotopic ossification may occur concurrently, and therapeutic anticoagulation did not lead to bleeding within or around the area of active heterotopic ossification. The possibility of a relationship between heterotopic ossification and deep venous thrombosis is presently being studied at our institution.

Diagnosis, Differential↗

Hypothermia causes adult-like retention deficits of prior learning in infant mice.

Nine-day-old S-W mice receiving deep body hypothermia or hyperthermia immediately after escape training were retested 1 or 24 hr later. Results indicated that hypothermia impaired 24-hr retention but had no effect upon 1-hr memory. Hyperthermia had no effect, with the mice demonstrating retention of the escape response at both retest intervals. In Experiment 2, administration of hypothermia or hyperthermia 23 hr after original training had no effect upon memory nor did either treatment produce motoric deficits upon retest 1 hr following thermal exposure. Experiment 3 indicated that hypothermia administered immediately after training produced retention deficits directly related to amount of body temperature reduction following hypothermia. These data are similar to those obtained with adult mice and suggest that memory processes occurring in 9-day-old mice may represent the onset of functioning of processes underlying adult long-term memory.

Age Factors↗

Purkinje cell synapses target physiologically unique brainstem neurons.

The cerebellum controls motor learning via Purkinje cell synapses onto discrete populations of neurons in the deep cerebellar nuclei and brainstem vestibular nuclei. In the circuitry that subserves the vestibulo-ocular reflex, the postsynaptic targets of Purkinje cells, termed flocculus target neurons (FTNs), are thought to be a critical site of learning. Little is known, however, about the intrinsic cellular properties of FTNs, which are sparsely distributed in the medial vestibular nucleus. To identify these neurons, we used the L7 promoter to express a tau-green fluorescent protein fusion protein selectively in Purkinje cells. Fluorescent Purkinje cell axons and terminal boutons surrounded the somata and proximal dendrites of a small subset of neurons, presumed FTNs, in the medial vestibular nucleus. Targeted intracellular recordings revealed that FTNs fired spontaneously at high rates in brain slices (mean, 47 spikes/sec) and exhibited dramatic postinhibitory rebound firing after the offset of membrane hyperpolarization. These intrinsic firing properties were exceptional among brainstem vestibular nucleus neurons but strikingly similar to neurons in the deep cerebellar nuclei, indicating a common role for intrinsic firing mechanisms in cerebellar control of diverse behaviors.

Action Potentials↗

Influence of context and preferred learning environments: approaches to studying physiology.

One hundred and twenty-eight medical students who had experienced a traditional-style preclinical curriculum completed three self-report questionnaires. Using factor analysis of students' responses this study explores interactions between study orientation, preferences for different kinds of learning environment, and evaluations of the physiology course. Such interactions can provide insight into the reasons why students fail to adopt effective learning strategies. Although many students had the intention to understand, they did not adopt a deep approach. Achievement motivation was strong, test anxiety high, and the course was perceived to be competitive. The meaning orientation merged with the achieving orientation; students were thus performance rather than task oriented. These students perceived the course to have been challenging, as did students within the reproducing orientation and who had 'surface' preferences. Students within the non-academic orientation had difficulty coping with the course. The findings suggest that conventional teaching and assessment methods are preventing students from developing appropriate criteria and internal standards for evaluating performance. An illusion of comprehension may prevent students from seeing the need to adopt more effective learning strategies and cause 'good' students with the ability to adopt a deep approach to abort the pursuit of deep understanding. Students' preferences and evaluations of teaching and assessment indicate that students within the different learning orientations have different educational needs. The implications for instruction and evaluation are discussed.

Attitude of Health Personnel↗

Integration of single cell multiomics data by deep transfer hypergraph neural network.

Multi-omics characterization of individual cells offers remarkable potential for analyzing the dynamics and relationships of gene regulatory states across millions of cells. How to integrate multimodal data is an open problem, existing integration methods struggle with accuracy and modality-specific biological variation retention. In this paper, we present scHyper (scalable, interpretable machine learning for single cell integration), a low-code and data-efficient deep transfer model designed for integrating paired and unpaired single-cell multimodal data. We benchmark scHyper against datasets from different multimodal data. ScHyper learns a low-dimensional representation and aligns the covariance matrices of the measured modalities, achieving high accuracy even with large scale atlas-level datasets with low memory and computational time across different cell lines, shedding light on regulatory relationships between different types of omics. Altogether, we show that scHyper is a versatile and robust tool for cell-type label transfer and integration from multimodal single-cell datasets.

Single-Cell Analysis↗

Collateral sensitivity-harnessing microbial vulnerabilities as a solution to antimicrobial resistance.

Bacteria exhibit an evolutionary trade-off through their development of collateral sensitivity (CS) which allows them to resist one antibiotic while becoming more vulnerable to another. This vulnerability offers a compelling therapeutic opportunity by selecting against resistant isolates. Laboratory evolution studies, genome sequencing, deep mutagenesis and use of artificial intelligence and machine learning can design the bespoke strategy against multi-drug-resistant bacteria. This review discusses about recent studies that are rationally designed to harness this evolutionary trade-off for the development of alternative antimicrobial strategies. The translational barriers to the clinical implementation of CS are addressed and evidence-based design principles for optimization of CS-guided therapy are discussed.

Bacteria↗

A comparison of the muscarinic response and morphological properties of identified cells in the guinea-pig olfactory cortex in vitro.

The electrophysiological and morphological characteristics of neurons in the guinea-pig olfactory cortex brain slice were investigated using a combined intracellular recording and neurobiotin-dye filling technique, in an attempt to show whether a clear relation existed between cell morphology and excitatory muscarinic response profile. Out of 46 sampled neurons, 25 (termed type 1), responded to bath-application of the muscarinic agonist oxotremorine-M (10 microM, 2-3 min) with a strong and persistent excitation coupled with the appearance of a slow depolarizing afterpotential (10-20 mV amplitude) following a large depolarizing stimulus. These neurons were identified as deep pyramidal cells located in cortical layer III, with characteristic pyramidal/ovoid shaped cell bodies, prominent apical dendrites with branches extending to the surface, and extensive basal dendritic trees. The cells showed a regular spiking pattern in response to injected depolarizing current, with no evidence of bursting behaviour. Nine cells (termed type 2), were strongly excited by oxotremorine-M, but only generated a weak depolarizing afterpotential (< 5 mV) following stimulation. These neurons (located in layer III or at layer II-III border) had a variable, non-pyramidal morphology with either a fusiform/tripolar, stellate/multipolar or bipolar/bi-tufted appearance, respectively. Apart from a more prominent post-spike afterhyperpolarization observed in some type 2 cells, their resting membrane properties and firing patterns were indistinguishable from those of type 1 responding cells. Twelve cells (termed type 3) showed little or no excitatory response to oxotremorine-M, and never generated a post-stimulus slow afterdepolarization. These cells (within compact layer II) had the morphological features of superficial pyramidal cells, typified by their short apical trunks and well-developed apical dendritic trees. They could be distinguished electrophysiologically by their ability to show spike fractionation during injection of large depolarizing current pulses. The morphology and laminar position of neurobiotin-filled cells was also compared with those of cells stained by the Golgi-Cox method. Some factors that may have contributed to the observed differences in muscarinic response profile are discussed. It is proposed that the selective muscarinic induction of the slow depolarizing afterpotential phenomenon in deep pyramidal cells may be important in olfactory cortical learning and memory processes.

Animals↗

Syndromes of acquired dyslexia and patterns of recovery: a 6- to 10-year follow-up study of seven brain-injured people.

Seven subjects who were neurologically impaired following encephalitis (n = 2), head injury (n = 3), and stroke (n = 2) were referred several years previously because of acquired dyslexia. Two were almost totally alexic, 2 were surface dyslexic, 2 were deep dyslexic and 1 was a letter-by-letter reader. Following a period of rehabilitation, the 2 with alexia became surface dyslexic and letter-by-letter readers; 1 of the deep dyslexics showed some improvements but remained a deep dyslexic; and the letter-by-letter reader learned to read more quickly. At follow-up, 6 to 10 years later, there had been little significant change. The 2 subjects whose alexia resolved into surface dyslexia with letter-by-letter reading had increased their reading ages but remained surface dyslexic and letter-by-letter readers. The subject who had been a letter-by-letter reader was faster at easier and more frequently used words but slower at harder, less frequently used words. Changes in the other 4 subjects were negligible. Implications for rehabilitation are discussed.

Adolescent↗

Teaching of pharmacology in Universiti Malaya and the other medical schools in Malaysia -- a historical perspective.

Traditional pharmacology teaching has focused more on drug instead of therapeutics, such that although pharmacological knowledge is acquired, practical skills in prescribing remain weak. In Malaysia many new medical schools (both public and private) have been set up in the last 12 years due to a change in government policy, resulting in a wide spectrum of medical curricula. Universiti Malaya (UM) being the oldest medical school in Malaysia was deep set in its traditional way of teaching-learning, since its inception in 1962, until a visit from the General Medical Council of the United Kingdom in 1984 triggered off a change of tide. Since then the medical curriculum in UM has undergone two major revisions. The first revised curriculum (1988) aimed to inject more clinical relevance into basic science teaching, through introducing clinical lectures and skills in the paraclinical year. Professional behaviour was also addressed. The second revised curriculum (1998) sought to improve further the integration of knowledge as well as to produce a holistic doctor, viewing the patient as a person instead of a clinical entity. The teaching-learning of pharmacology has gradually moved from factual regurgitation to more clinical reasoning, from lab-based to more patient-oriented approach. As more new medical schools are being set up in Malaysia, exchange of experience in this area of learning will hopefully help us find a happy medium between "the old is best" and "the new is better" type approach so that a pedagogically sound and yet logistically practical curriculum can be found in our local setting, to help produce doctors with good prescribing practice.

Curriculum↗

Development of the approaches to work and workplace climate questionnaires for physicians.

Two questionnaires were developed to investigate the workplace learning of physicians. The Approaches to Work Questionnaire for Physicians and the Workplace Climate Questionnaire for Physicians were adapted from general measures developed by Kirby, Knapper, Evans, Carty, and Gadula. These questionnaires were administered to a random sample of Ontario physicians. Consistent with the results of Kirby et al., three dimensions of approaches to work were observed: Deep. Surface-Rational, and Surface-Disorganized. Three dimensions of workplace climate were also found, Supportive-Receptive, Choice-Independence, and Workload. Results indicate that physicians adopt primarily a Deep approach to work, but that there is a smaller tendency toward Surface-Disorganized learning, one that is strongly correlated with perceptions of heavy workload. The Deep approach was associated with work environments perceived to be Supportive-Receptive and offer Choice-Independence. The use of these questionnaires in research and practice is discussed.

Adult↗

Identification of variants and dual promoters of murine serine/threonine kinase KKIAMRE.

KKIAMRE is a serine/threonine protein kinase whose transcripts increase in the deep cerebellar nuclei of the rabbit after eyeblink conditioning, a model of associative learning and memory. We here characterized the expression, isoforms, and promoters of murine KKIAMRE gene. The expression of KKIAMRE was detected, by in situ hybridization and immunohistochemistry, in neurons in various brain regions including deep cerebellar nuclei. The gene spans approximately 40 kb and consists of 15 exons. Analysis of cDNA clones revealed multiple variants, having diversity in the putative carboxy-terminal regulatory domain, generated by alternative splicing and intraexonal termination. Furthermore, they had alternative 5' noncoding sequences. Primer extension, RNase protection, and transient expression assays revealed that two alternative promoters linked to distinct noncoding exons direct the expression of KKIAMRE. The gene was mapped on chromosomes 5 and 4 in mouse and human, respectively.

Amino Acid Sequence↗