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Hepatobiliary surgery: lessons learned from live donor hepatectomy.

The liver is unique in the rapid tissue regeneration occurs after resection or injury, and affords the surgeon the opportunity to safely remove up to 60% to 70% of the liver volume for treatment of cancer or for use as a live donor graft for transplantation. The complex development of the liver and biliary system in utero results in multiple and complicated anatomic variations. The hepatobiliary surgeon of today must be able to integrate a broadening array of radiologic and liver resection techniques that may improve patient safety and surgical outcome. Equally important is the ability to quickly recognize postoperative complications so that prompt intervention can be instituted. Successful outcome requires a balance between sound judgement, technical acumen, and attention to detail. Herein, we provide lessons learned from live donor liver transplantation that are directly applicable to any patient undergoing major hepatic resection.

Hepatectomy↗

Neural activity in the primate prefrontal cortex during associative learning.

The prefrontal (PF) cortex has been implicated in the remarkable ability of primates to form and rearrange arbitrary associations rapidly. This ability was studied in two monkeys, using a task that required them to learn to make specific saccades in response to particular cues and then repeatedly reverse these responses. We found that the activity of individual PF neurons represented both the cues and the associated responses, perhaps providing a neural substrate for their association. Furthermore, during learning, neural activity conveyed the direction of the animals' impending responses progressively earlier within each successive trial. The final level of activity just before the response, however, was unaffected by learning. These results suggest a role for the PF cortex in learning arbitrary cue-response associations, an ability critical for complex behavior.

Animals↗

Bifurcating neuron: computation and learning.

The ability of bifurcating processing units and their networks to rapidly switch between different dynamic modes has been used in recent research efforts to model new computational properties of neural systems. In this spirit, we devise a bifurcating neuron based on control of chaos collapsing to a period-3 orbit in the dynamics of a quadratic logistic map (QLM). Proposed QLM3 neuron is constructed with the third iterate of QLM and uses an external input, which governs its dynamics. The input shifts the neuron's dynamics from chaos to one of the stable fixed points. This way the inputs from certain ranges (clusters) are mapped to stable fixed points, while the rest of the inputs is mapped to chaotic or periodic output dynamics. It has been shown that QLM3 neuron is able to learn a specific mapping by adaptively adjusting its bifurcation parameter, the idea of which is based on the principles of parametric control of logistic maps [Proceedings of the International Symposium on Nonlinear Theory and its Applications (NOLTA'97), Honolulu, HI, 1997; Proceedings of SPIE, 2000]. Learning algorithm for the bifurcation parameter is proposed, which employs the error gradient descent method.

Learning↗

Learning words and rules: abstract knowledge of word order in early sentence comprehension.

Children quickly acquire basic grammatical facts about their native language. Does this early syntactic knowledge involve knowledge of words or rules? According to lexical accounts of acquisition, abstract syntactic and semantic categories are not primitive to the language-acquisition system; thus, early language comprehension and production are based on verb-specific knowledge. The present experiments challenge this account: We probed the abstractness of young children's knowledge of syntax by testing whether 25- and 21-month-olds extend their knowledge of English word order to new verbs. In four experiments, children used word order appropriately to interpret transitive sentences containing novel verbs. These findings demonstrate that although toddlers have much to learn about their native languages, they represent language experience in terms of an abstract mental vocabulary. These abstract representations allow children to rapidly detect general patterns in their native language, and thus to learn rules as well as words from the start.

Child Language↗

Rapid adaptation of saccadic amplitude in humans and monkeys.

To study adaptive motor learning in the saccadic system we have used a psychophysical procedure that introduces a "visuomotor mismatch" between the retinal error signal (retinal distance between fovea and target image) and the motor error signal (movement required to accurately foveate the target). The saccadic system responds to this visuomotor mismatch by rapidly modifying the amplitude of the saccade. We will refer to this procedure as induced saccadic dysmetria. In our paradigm, the saccadic dysmetria is produced by electronically adding or subtracting a fraction of the eye position signal to adjust the target's position. Thus the original visual error signal that initiates the saccade no longer elicits an appropriately sized saccade; there is a mismatch between target step and saccade amplitude. We find that the human and nonhuman primate saccadic systems respond to this error by rapidly and adaptively adjusting the amplitude of saccades. Such adaptive adjustments are not the result of changes in saccade strategy but represent a genuine recalibration. We conclude that induced saccadic dysmetria provides us with a tool for the study of adaptive motor learning in the oculomotor system. It is hypothesized that the adaptive mechanism may use either or both of two signals: a visual error signal representing the retinal distance of the target from the fovea after the initial saccade and/or a motor error signal represented by the amplitude of the corrective saccade.

Adaptation, Ocular↗

The potential of open learning in animal breeding.

Animal breeding education is presently facing many challenges. These include rapid changes in breeding knowledge and technology, resource and funding restrictions, and altering demographics of the learner and the animal breeding industry. These challenges can be met via an open learning educational format. This nontraditional approach is based on the needs of individual learners, not the interests of the teacher or the institution. An important feature of open learning is its appropriateness for the professional development audience. Delivery methods include interactive distance courses on the Web, computer-assisted learning, and team-based study. The Canadian dairy breeding industry has expressed the need for ongoing professional development to understand and adopt new animal breeding technologies. The University of Guelph responded by delivering a series of animal breeding short courses (Executive Certificate Program in Animal Breeding) to industry decision makers in 1997. A version modified specifically for farmers and breeding industry personnel was offered in 1998. Through the collaboration of experts from various agricultural institutions and the use of a learner-centered format, this professional development initiative was a pedagogical and financial success. This paper describes how the open learning approach differs from traditional university teaching. Using the University of Guelph example in animal breeding professional development, the framework for a successful open learning program will be examined. The best practices for effective adult education will also be identified and discussed within this case study.

Adult↗

Hindsight bias, outcome knowledge and adaptive learning.

The ubiquitous nature of hindsight bias is a cause for concern for those engaged in investigations and retrospective analysis of medical error. Hindsight does not equal foresight. Investigations that are anchored to outcome knowledge run the risk of not capturing the complexities and uncertainties facing sharp end personnel and why their actions made sense at the time. Important lessons go unlearned if the exercise is simply to back track someone else's decision landmarks. Outcome knowledge can also bias our thinking on the quality of the processes that led to the outcome. This paper examines the influence of outcome knowledge in relation to reconstructive memory and legal testimony, ways for reducing the impact of outcome knowledge, and an adaptive learning framework that places hindsight bias in a broader context of rapid updating of knowledge.

Adaptation, Psychological↗

Intravenous l-DOPA plus carbidopa in depressed patients: average evoked response, learning, and behavioral changes.

The peripheral decarboxylase inhibitor carbidopa (L-alphamethyl-dopa-hydrazine) allowed safe intravenous administration of L-DOPA in amounts sufficient to alter cortical average evoked response (AER) and learning function in 13 depressed patients. The apparently rapid conversion of L-DOPA to dopamine, as reported from studies in animals, is consistent with the 20-30 min onset of effects seen in our study. Unipolar and bipolar depressed patients responded differently to the alterations in brain biogenic amines and also to the nonspecific stress of the experiment. Intravenous L-DOPA given acutely had effects on the AER that were similar to those documented with oral dopa given chronically--an augmentation of amplitude--intensity slopes in unipolar patients and a relative reduction of slopes in bipolar patients. In contrast, intravenous L-DOPA did not enhance verbal learning as did chronic oral treatment, but rather was associated with reduced learning compared with placebo infusions. Different neurochemical changes following L-DOPA given in single intravenous doses may be responsible for the different learning and behavioral changes form those found previously with oral dopa administered chronically.

Administration, Oral↗

Acute and chronic effects of MDMA on molecular mechanisms implicated in memory formation in rat hippocampus: surface expression of CaMKII and NMDA receptor subunits.

Acute 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") treatment induces learning deficits in different animal models. In a passive avoidance learning task in rats, previous studies suggested a role for Ca2+/calmodulin-dependent protein kinase II (CaMKII) and N-methyl-D-aspartate (NMDA) receptors in the acute learning impairment. As cognitive deficits by "ecstasy" in humans have been only reported in frequent recreational users, we examined whether a repeated MDMA treatment could induce in rats lasting molecular changes related to memory consolidation of passive avoidance. In rats with a pronounced 5-HT depletion by MDMA, the effect of another drug challenge was also examined. The surface expression in the hippocampus of NMDA receptor subunits, the scaffolding postsynaptic density protein PSD-95, phosphorylated CaMKII and protein phosphatase 1 (PP1) was measured. In rats repeatedly treated with MDMA (10 mg/kg) twice daily for 4 consecutive days, hippocampal 5-HT levels were markedly reduced 1 week later. At this time, neither learning performance was affected nor changes in membrane levels of NMDA receptor subunits, PSD-95, CaMKII and PP1 were found. In these rats, however, another drug challenge produced a rapid reduction in PSD-95 immunoreactivity and prevented the learning-specific increase in the NMDA receptor NR1 subunit and phosphorylated CaMKII. The results show no lasting change in learning-associated molecular events after a neurotoxic MDMA treatment. This drug only produces transient effects on early molecular events involved in memory consolidation, which do not appear to depend on endogenous 5-HT levels.

Animals↗

Single-trial learning of novel stimuli by individual neurons of the human hippocampus-amygdala complex.

The ability to distinguish novel from familiar stimuli allows nervous systems to rapidly encode significant events following even a single exposure to a stimulus. This detection of novelty is necessary for many types of learning. Neurons in the medial temporal lobe (MTL) are critically involved in the acquisition of long-term declarative memories. During a learning task, we recorded from individual MTL neurons in vivo using microwire electrodes implanted in human epilepsy surgery patients. We report here the discovery of two classes of neurons in the hippocampus and amygdala that exhibit single-trial learning: novelty and familiarity detectors, which show a selective increase in firing for new and old stimuli, respectively. The neurons retain memory for the stimulus for 24 hr. Thus, neurons in the MTL contain information sufficient for reliable novelty-familiarity discrimination and also show rapid plasticity as a result of single-trial learning.

Action Potentials↗

Duration of knowledge in general thoracic surgery.

BACKGROUND: Medical knowledge changes rapidly, so current medical education approaches emphasize the development of life-long learning skills ("teaching the learner to learn") as opposed to the simple acquisition of contemporary medical knowledge. Because there are no data on the rapidity of change of general thoracic surgical knowledge, we do not know whether this trend in medical education is appropriate for thoracic surgical trainees. We undertook a study to assess the duration of knowledge in general thoracic surgery. METHODS: The first general thoracic surgery article from each issue of The Annals of Thoracic Surgery between 1965 and 1997 was abstracted into a summary statement. A form, made up of 360 summary statements in random order, was assessed by 6 general thoracic surgeons. They assessed statement validity on a 5-point scale (1 = statement false; 5 = statement true). Average statement validity scores for 30 time intervals were calculated. The relationship between time of publication and statement validity was analyzed. RESULTS: Average validity scores ranged from 2.24 (represents 1965 to 1966) to 4.32 (represents 1969 to 1970). Validity scores increased with time (y = 3.46 + 0.017x, where y is validity score and x is time), and this was significant (r = 0.40; p = 0.027). However, the absolute change in average validity scores over the 33-year study period was only 0.52 or 13.1% of the "modern" era scores. CONCLUSIONS: The assumption that medical knowledge changes quickly may not be true in general thoracic surgery. Although life-long learning skills are important, general thoracic surgery training programs should continue to emphasize fundamental knowledge in the specialty.

Clinical Competence↗

Effect of cerebellar granule cell depletion on learning of the equilibrium behaviour: study in postnatally X-irradiated rats.

To assess the role of the mossy fibre-granule cell pathway in learning, the cerebellum of young DA/HAN strain rats was irradiated to make the cortex completely or partially agranular. The X-rays were delivered according to two different schedules, between 5-14 postnatal days (early group) and between 10-14 postnatal days (late group). Histological controls at 35 days showed a mean loss of granule cells of 96 +/- 1% in the early group and of 61 +/- 3% in the late group. The irradiated animals were subjected, from day 23 to day 35, to daily sensorimotor training on a rotorod. The scores and the strategy used (walking or hanging) by the rats were noted. The results demonstrate that a partial loss of granule cells due to a late X-irradiation schedule induced mild motor disabilities but no learning deficit, the only problem being difficulty in elaborating rapidly an efficient strategy to solve a novel problem. A sub-total loss of the granule cells, due to an early X-irradiation schedule, induced gross motor disabilities and the animals used hanging > 90% of the time. Due to the discrepancy between the learning abilities, which were preserved at least in part, and the gross motor impairments, the animals elaborated a novel strategy (jumping from the beam), allowing them to escape the experimental situation. This avoidance behaviour may be due to a decrease of anxiety, a lack of behavioural inhibition and/or attentional deficits that have been already observed in several other examples of cerebellar abnormalities.

Aging↗

[Improved alternative electro-stimulus Y-maze for evaluating the spatial memory of rats].

OBJECTIVE: To establish an effective model for evaluating the spatial memory of rats. METHODS: The adjacent left or right arm in Y-maze was defined as an initial arm or an objective one alternatively, and electro-stimulus to vola was used as a reinforcement. Meanwhile, the reliability of the model was validated by measuring the memory deficits induced by intraperitoneal (i.p.) injection of scopolamine (0.5 mg/kg) or bilaterally intrahippocampal (i.h.) microinjection of MK-801(0.2 microg/site). RESULTS: The normal, sham-operated or saline-treated rats learned the left-right alternative memory model rapidly while injection of either scopolamine or MK-801 caused spatial memory deficits in Y-maze, including deficits in working and reference memory. Moreover,there was no appreciable difference in electricity intensity between the treated group and the control group. CONCLUSION: The alternative Y-maze with electro-stimulus is a comparatively objective model which can evaluate the spatial memory in rats effectively.T

Animals↗

Building breakthrough businesses within established organizations.

Many companies assume that once they've launched a major innovation, growth will soon follow. It's not that simple. High-potential new businesses within established companies face stiff headwinds well after their inception. That's why a company's emphasis must shift: from ideas to execution and from leadership excellence to organizational excellence. The authors spent five years chronicling new businesses at the New York Times Company, Analog Devices, Corning, Hasbro, and other organizations. They found that a breakthrough new business (referred to as NewCo) rarely coexists gracefully with the established business in the company (called CoreCo). The unnatural combination creates three specific challenges--forgetting, borrowing, and learning--that NewCo must meet in order to survive and grow. NewCo must first forget some of what made CoreCo successful. NewCo and CoreCo have elemental differences, so NewCo must leave behind CoreCo's notions about what skills and competencies are most valuable. NewCo must also borrow some of CoreCo's assets--usually in one or two key areas that will give NewCo a crucial competitive advantage. Incremental cost reductions, for example, are never a sufficient justification for borrowing. Finally, NewCo must be prepared to learn some things from scratch. Because strategic experiments are highly uncertain endeavors, NewCo will face several critical unknowns. The more rapidly it can resolve those unknowns--that is, the faster it can learn--the sooner it will zero in on a winning business model or exit a hopeless situation. Managers can accelerate this learning by planning more simply and more often and by comparing predicted and actual trends.

Capital Financing↗

Sleep stages, memory and learning.

Learning and memory can be impaired by sleep loss during specific vulnerable "windows" for several days after new tasks have been learned. Different types of tasks are differentially vulnerable to the loss of different stages of sleep. Memory required to perform cognitive procedural tasks is affected by the loss of rapid-eye-movement (REM) sleep on the first night after learning occurs and again on the third night after learning. REM-sleep deprivation on the second night after learning does not produce memory deficits. Declarative memory, which is used for the recall of specific facts, is not similarly affected by REM-sleep loss. The learning of procedural motor tasks, including those required in many sports, is impaired by the loss of stage 2 sleep, which occurs primarily in the early hours of the morning. These findings have implications for the academic and athletic performance of students and for anyone whose work involves ongoing learning and demands high standards of performance.

Humans↗

The effects of paradoxical sleep deprivation and valine on spatial learning and brain 5-HT metabolism.

We have previously reported that rapid eye movement sleep deprivation (REMSD), induced by the flower pot technique, causes a deficit in reference spatial memory and increases rates of serotonin (5-HT) metabolism in the brain. In this study we used increased concentrations of dietary valine to inhibit tryptophan (TRP) transport across the blood-brain barrier in an attempt to modify the REMSD-induced increase of 5-HT metabolism. Rats were fed either a control diet or the same diet supplemented to 2% by weight valine, and were allocated to one of three experimental groups: cage control (CC), stress tank control (TC), or REMSD. Reference and working spatial memory of all rats was tested in a Morris water maze on Days 2, 3, and 4. REMSD produced a significant decrement in reference memory on Days 2 and 4, independent of dietary condition. The valine diet had a detrimental effect on the reference memory of TC rats on Day 2 but not Day 4. Measurements made on Day 4 indicated that the valine diet decreased brain TRP only in the CC rats. In contrast, the valine diet did not prevent increases in brain TRP or 5-HT metabolism in REMSD rats, and increased hypothalamic and brain stem TRP concentrations and the hippocampal 5-HIAA/5-HT ratio in TC rats. These results indicate that dietary valine does not prevent REMSD-induced changes in spatial memory or serotonin metabolism, although it does reduce brain TRP in nonstressed rats.

Animals↗

The WEBD project: a research of new methodologies for a distant-learning 3D system prototype.

OBJECTIVES: To create and to spread a new interactive multimedia instrument, based upon virtual reality technologies, that allows both the running simulation of machines and equipment and the reproduction via Web of complex three-dimensional (3D) anatomical models such as the skull. METHODS: There were two main aspects of the project, one of design engineering and the other biomedical engineering, for the creation of "artificial" and anatomical objects. The former were made with 3D Studio Max R4 by Autodesk, San Rafael, CA, while the latter were created starting from real bones scanned with a CT system or a surface scanner and elaborated with different programs (3D Studio Max R4, Scenebuilder by Viewpoint, New York, NY and Spinfire by Actify, San Francisco, CA). The 3D models were to be integrated into web modules and had to respect file limits while preserving a sufficient definition. Two systems of evaluation were used, a questionnaire on a selected sample and an external evaluation by a different university. RESULTS: The Viewpoint format offers the best interactivity and size reduction (up to 96% from the original 3D model). The created modules included production of radiological images, rapid prototyping, and anatomy. The complete "3D Distant Learning Prototype" is available at www.webd.etsii.upm.es. CONCLUSIONS: The software currently available permits the construction of interactive modules. The verification on the selected sample and the evaluation by the University of Naples show that the structure is well organized and that the integration of the 3D models meets the requirements.

Computer Graphics↗

Suppression of active sleep by chronic treatment with chlorimipramine during early postnatal development: effects upon adult sleep and behavior in the rat.

In an attempt to study the possible role of active sleep in brain development, male rats were injected twice daily with chlorimipramine, a potent monoamine reuptake blocker, from 1 week to 3 weeks of postnatal age. AS was reduced to less than 10% of total sleep time, the level found in mature rats. Most of the AS reduction was compensated for by quiet sleep but a slight increase in wakefulness also occurred, owing to brief interruptions of sleep at times when AS was expected. In adulthood, the AS-deprived rats showed a higher percentage of AS than did the controls, due to an increase in frequency and duration of AS epochs. Moreover, many of the epochs contained abnormally frequent and strong jerky body movements and rapid-eye-movements, reminiscent of neonatal AS patterns. In addition, the amplitude of hippocampal theta waves during AS was greater than in control rats. The chlorimipramine-treated rats also showed behavioral abnormalities in later life. On the open field test exploratory behavior was much reduced, while increased rearing and defecation occurred. Masculine sexual performance was severely deficient, primarily due to the low level of intromissions and ejaculations. Experimental animals performed less efficiently than controls on a temporal learning task (differential reinforcement of low response rate) and responded more rapidly on a spatial task (left-right alternation learning). These results demonstrate that early interference with the functioning of monoaminergic systems can have long-lasting physiological and behavioral consequences. Furthermore, they are consistent with the hypothesis that AS is an important factor in normal brain development.

Aggression↗