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PubMed2000

Attractor dynamics in word recognition: converging evidence from errors by normal subjects, dyslexic patients and a connectionist model.

People make both semantic and visual errors when trying to recognise the meaning of degraded words. This result mirrors the finding that deep dyslexic patients make both semantic and visual errors when reading aloud. We link the results with the demonstration that a recurrent connectionist network which produces the meaning of words in response to their spelling pattern produces this distinctive combination of errors both when its input is degraded and when it is lesioned. The reason why the network can simulate the errors of both normal subjects and patients lies in the nature of the attractors which it develops as it learns to map orthography to semantics. The key role of attractor structure in the successful simulation suggests that the normal adult semantic reading route may involve attractor dynamics.

Adult↗

PubMed2000

Brain localization and behavioral impact of the G-protein-gated K+ channel subunit GIRK4.

Neuronal G-protein-gated potassium (K(G)) channels are activated by several neurotransmitters and constitute an important mode of synaptic inhibition in the mammalian nervous system. K(G) channels are composed of combinations of four subunits termed G protein-gated inwardly rectifying K(+) channels (GIRK). All four GIRK subunits are expressed in the brain, and there is a general consensus concerning the expression patterns of GIRK1, GIRK2, and GIRK3. The localization pattern of GIRK4, however, remains controversial. In this study, we exploit the negative background of mice lacking a functional GIRK4 gene to identify neuronal populations that contain GIRK4 mRNA. GIRK4 mRNA was detected in only a few regions of the mouse brain, including the deep cortical pyramidal neurons, the endopiriform nucleus and claustrum of the insular cortex, the globus pallidus, the ventromedial hypothalamic nucleus, parafascicular and paraventricular thalamic nuclei, and a few brainstem nuclei (e.g., the inferior olive and vestibular nuclei). Mice lacking GIRK4 were viable and appeared normal and did not display gross deficiencies in locomotor activity, visual tasks, and pain perception. Furthermore, GIRK4-deficient mice performed similarly to wild-type controls in the passive avoidance paradigm, a test of aversive learning. GIRK4 knock-out mice did, however, exhibit impaired performance in the Morris water maze, a test of spatial learning and memory.

Animals↗

PubMed2006

Ten commonly asked computer questions ... and answers. Part 1.

I hope that you have learned something from this article that will help you get through your next computer crisis. Remember that most computer problems are not your fault and they are not the end of the world. It stinks when your car breaks down, and it stinks when your PC crashes, but you will get through it. If your PC does crash, write down what you were doing when it crashed, any changes that were made, any software that was installed, and take a deep breath. You will be able to help get the problem solved quicker if you stay relaxed. Part 2 of this article, to be published in a future issue of Dentistry Today, will answer the next 5 commonly asked computer questions.

Computer Systems↗

PubMed1981

The role of anaerobes in human infections.

Anaerobic bacteria have been shown to play a role in infection of all types in humans. Certain infections are notable for the prominent role played by anaerobes; included are brain abscess, chronic sinusitis and otitis media, oral and dental infections, neck space infections, bite infections, lung abscess, aspiration pneumonia, empyema, intra-abdominal infections of all types (notably peritonitis, intra-abdominal abscess, and liver abscess), abdominal surgical wound infections, female genital tract infections of all types, various superficial and deep soft tissue infections, and osteomyelitis. In recent years, two new anaerobic infections have been appreciated-infant botulism and pseudomembranous colitis due to Clostridium difficile. Considerable progress has been made recently in delineating factors predisposing to anaerobic infections, virulence factors in anaerobes, and host defense mechanisms vs. these organisms. Taxonomic schemes for anaerobes have been improved and simplified considerably, as have techniques for growing and identifying anaerobic bacteria. Rapid procedures are coming into the picture. Finally, much has been learned about therapy of these infections. Although there has been some problem of increased resistance of anaerobes to antimicrobial agents, several promising new drugs are now available to offset this.

Anaerobiosis↗

PubMed1995

[Sleep disorders in childhood].

Sleep disorders in childhood are frequent and usually harmless. They rarely point to a serious disease. Difficulty in falling asleep and nightly awakenings are age-dependent and transitory. While the largely harmless somnambulism and pavor nocturnus occur in the deep sleep of the first third of the night, the anxiety dreams of REM sleep appear preferentially in the second half of the night. Other disorders such as nocturnal enuresis and talking in sleep may occur during the whole night. It is very important to inform the parents because this helps to counter fears and false expectations. Consistent sleep hygiene needs to be developed with avoidance of irregular sleep rhythm and an unrestful sleep environment. Sometimes it is necessary to learn new behaviour patterns with the child. Only exceptionally is drug therapy indicated. However, nocturnal breathing disorders and nocturnal epilepsy do have a pathological significance and need specific therapy. In order to clarify the reasons for sleep disorders, it is necessary to keep a sleep diary, to undertake specific examinations (e.g. psychological, pneumological, neurological, urological, otorhinolaryngological and possibly using diagnostic equipment such as video-polysomnography).

Cataplexy↗

PubMed1996

Balancing the clinical outcomes and economics associated with thromboembolic prophylaxis.

The approach to the treatment of patients is being influenced by the movement towards integrating health care services. This trend presents several challenges to health care professionals as patients move through the cycles of wellness, prevention, acute treatment, and after-care. Consequently, the development of treatment guidelines based upon clinical and economic parameters is critical. Preventing thromboembolic complications is receiving a great deal of attention due to the tremendous medical and economic consequences of deep venous thrombosis and pulmonary embolism. The early discharge of patients from acute surgical and medical facilities is increasing the need to consider outpatient prophylaxis. Pharmacoeconomic modeling demonstrates that enoxaparin may be more cost-effective than warfarin for outpatient prophylaxis when used for 3 weeks or less. The requirement of a subcutaneous injection of enoxaparin is not a detraction to this recommendation. Patient self-medication is a common practice and is growing in prevalence. Patients are eager to learn about their illnesses and treatment options as a result of their attitudes regarding empowerment and responsibility for their own health care.

Cost of Illness↗

PubMed2005

Muscle fiber differentiation in fish embryos as shown by in situ hybridization of a large repertoire of muscle-specific transcripts.

Skeletal muscles are composed of different fiber types, largely defined by differential expression of protein isoforms involved in myofibrillogenesis or metabolism. To learn more about the gene activations that underlie the differentiation and the diversification of embryonic fish myotomal fibers, we investigated the developmental expression of 25 muscle genes in trout embryos by in situ hybridization of muscle-specific transcripts. The earliest event of muscle differentiation, at approximately the 25-somite stage, was the expression of a variety of muscle-specific genes, including slow-twitch and fast-twitch muscle isoforms. The activation of these muscle genes started in the deep somitic domain, where the slow muscle precursors (the adaxial cells) were initially located, and progressively spread laterally throughout the width of the myotome. This mediolateral progression of gene expression was coordinated with the lateral migration of slow adaxial cells, which specifically expressed the slow myosin light chain 1 and the SLIM1/FHL1 genes. Subsequently, the fast and slow skeletal muscle isoforms precociously expressed in the course of the mediolateral wave of muscle gene activation became down-regulated in the superficial slow fibers and the deep fast fibers, respectively. Finally, several muscle-specific genes, including troponins, a slow myosin-binding protein C, tropomodulins, and parvalbumin started their transcription only in late embryos. Taken together, these findings show in fish embryos that a common myogenic program is triggered in a mediolateral progression in all muscle cells. The acquisition of the slow phenotype involves the additional activation of several slow-specific genes in migrating adaxial muscle cells. These events are followed by sequential gene activations and repressions in fast and slow muscle cells.

Animals↗

PubMed1989

Proposed mechanisms for cerebellar coordination, stabilization and monitoring of movements and posture.

In this paper cerebellar mechanisms have been proposed for the coordination of all movements, for the learning effect of training on movements, for the effect of mental set on posture and voluntary movements, for the detection of velocity and acceleration, and for the stabilization of movements and posture. Coordination of agonist, antagonist, fixation and synergistic muscles during a movement could occur via a cerebellar matrix which connects agonist efferent feedback from the Motor Cortex to the appropriate antagonist motor cortical neurons. Improved efficiency through repetition (learning) occurs through suggested changes at the molecular and synaptic levels. The Inferior O-live-Climbing Fibre System is seen as a dynamic oscillator; indicating when a movement begins, its velocity and acceleration, and its stability. According to this view, the cerebellum stabilizes movements, and adds the effect of mental set on posture and voluntary movements, by inducing changes in the gain of stretch reflexes. Inhibitory interneurons add versatility to movements, while excitatory collaterals from cerebellar afferents directly to cerebellar deep nuclei improve sensitivity of the system. These mechanisms work for all movements whether active, passive, or reflexive.

Action Potentials↗

PubMed1997

Spinal cord injury rehabilitation. 2. Medical complications.

This self-directed learning module highlights new advances in understanding medical complications of spinal cord injury through the lifespan. It is part of the chapter on spinal cord injury rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article covers reasons for transferring patients to specialized spinal cord injury centers once they have been stabilized, and the management of common medical problems, including fever, autonomic dysreflexia, urinary tract infection, acute and chronic abdominal complications, deep vein thrombosis, pulmonary complications, and heterotopic ossification. Formulation of an educational program for prevention of late complications is also discussed, including late renal complications, syringomyelia, myelomalacia, burns, pathologic fractures, pressure ulcers, and cardiovascular disease. New advances covered in this section include new information on old problems, and a discussion of exercise tolerance in persons with tetraplegia, the pathophysiology of late neurologic deterioration after spinal cord injury, and a view of the care of these patients across the lifespan.

Adolescent↗

PubMed1979

Memory retraining in brain-damaged patients: the airplane list.

Recall failures can be traced to inadequate encoding and unfocussed retrieval search. A method is given for encouraging deep and elaborate encoding of a list of words, and two brain-damaged patients who were unable to recall the list at first, were shown to retrieve many of the words when retrieval cues were given by the examiner.

Brain Damage, Chronic↗

PubMed2006

Profound hypothermia is superior to ultraprofound hypothermia in improving survival in a swine model of lethal injuries.

BACKGROUND: Rapid induction of profound hypothermia can improve survival from uncontrolled lethal hemorrhage. However, the optimal depth of hypothermia in this setting remains unknown. This experiment was designed to compare the impact of deep (15 degrees C), profound (10 degrees C), and ultraprofound (5 degrees C) hypothermia on survival and organ functions. METHODS: Uncontrolled lethal hemorrhage was induced in 32 swine (80-120 lb) by creating an iliac artery and vein injury, followed 30 minutes later by laceration of the descending thoracic aorta. Hypothermia was induced rapidly (2 degrees C/min) by infusing cold organ preservation solution into the aorta through a thoracotomy. The experimental groups were (n = 8 per group): a normothermic control, and 3 hypothermic groups in which the core temperature was reduced to 15 degrees C, 10 degrees C, and 5 degrees C. Vascular injuries were repaired during 60 minutes of hypothermia. Animals were then rewarmed (0.5 degrees C/min) and resuscitated on cardiopulmonary bypass, and monitored for 6 weeks for neurologic deficits, cognitive function, and organ dysfunction. RESULTS: All normothermic animals died, whereas 6-week survival rates for the 15 degrees C, 10 degrees C, and 5 degrees C groups were 62.5%, 87.5%, and 25%, respectively (P < .05: normothermic vs 15 degrees C and 10 degrees C; 10 degrees C vs 5 degrees C). The surviving animals from the 15 degrees C and 10 degrees C groups were neurologically intact, displayed normal learning capacity, and had no long-term organ dysfunction. The survivors from the 5 degrees C group displayed slower recovery and impaired cognitive functions. CONCLUSIONS: In a model of lethal injuries, rapid induction of profound hypothermia can prevent death. The depth of hypothermia influences survival, with a better outcome associated with a core temperature of 10 degrees C compared with 5 degrees C.

Animals↗

PubMed2005

The effect of extracorporeal life support on the brain: cardiopulmonary bypass.

This article reviews the mechanisms of brain injury associated with cardiopulmonary bypass. These include embolic injury of both a gaseous and particulate nature as well as global hypoxic ischemic injury. Ischemic injury can result from problems associated with venous drainage or with arterial inflow including a steal secondary to systemic to pulmonary collateral vessels. Modifications in the technique of cardiopulmonary bypass have reduced the risk of global hypoxic/ischemic injury. Laboratory and clinical studies have demonstrated that perfusion hematocrit should be maintained above 25% and preferably above 30%. Perfusion pH is also critically important, particularly when hypothermia is employed. An alkaline pH can limit cerebral oxygen delivery by inducing cerebral vasoconstriction as well as shifting oxyhemoglobin dissociation leftwards. If deep hypothermia is employed, it is critically important to add carbon dioxide using the so-called "pH stat" strategy. Oxygen management during cardiopulmonary bypass is also important. Although there is currently enthusiasm for using air rather than pure oxygen, ie, adding nitrogen, this does introduce a greater risk of gaseous nitrogen emboli since nitrogen is much less soluble than oxygen. The use of pure oxygen in conjunction with CO2 to apply the pH stat strategy is recommended. Many of the lessons learned from studies focusing on brain protection during cardiopulmonary bypass can be applied to the patient being supported with extracorporeal membrane oxygenation.

Brain↗

PubMed2006

Cerebral blood flow during cardiopulmonary bypass in pediatric cardiac surgery: the role of transcranial Doppler--a systematic review of the literature.

BACKGROUND: Transcranial Doppler Ultrasound (TCD) is a sensitive, real time tool for monitoring cerebral blood flow velocity (CBFV). This technique is fast, accurate, reproducible and noninvasive. In the setting of congenital heart surgery, TCD finds application in the evaluation of cerebral blood flow variations during cardiopulmonary bypass (CPB). METHODOLOGY: We performed a search on human studies published on the MEDLINE using the keyword "trans cranial Doppler" crossed with "pediatric cardiac surgery" AND "cardio pulmonary by pass", OR deep hypothermic cardiac arrest", OR "neurological monitoring". DISCUSSION: Current scientific evidence suggests a good correlation between changes in cbral blood flow and mean cerebral artery (MCA) blood flow velocity. The introduction of Doppler technology has allowed an accurate monitorization of cerebral blood flow (CBF) during circulatory arrest and low-flow CPB. TCD has also been utilized in detecting cerebral emboli, improper cannulation or cross clamping of aortic arch vessels. Limitations of TCD routine utilization are represented by the need of a learning curve and some experience by the operators, as well as the need of implementing CBF informations with, for example, data on brain tissue oxygen delivery and consumption. CONCLUSION: In this light, TCD plays an essential role in multimodal neurological monitorization during CPB (Near Infrared Spectroscopy, TCD, processed electro encephalography) that, according to recent studies, can help to significantly improve neurological outcome after cardiac surgery in neonates and pediatric patients.

Aorta, Thoracic↗

PubMed2001

Matching identities of familiar and unfamiliar faces caught on CCTV images.

People can be inaccurate at matching unfamiliar faces shown in high-quality video images, even when viewpoint and facial expressions are closely matched. However, identification of highly familiar faces appears good, even when video quality is poor. Experiment 1 reported a direct comparison between familiar and unfamiliar faces. Participants who were personally familiar with target items appearing on video were highly accurate at a verification task. Unfamiliar participants doing the same task performed very inaccurately. Familiarity affected discriminability, but not bias. Experiments 2 and 3 showed that brief periods of familiarization have little beneficial effect unless "deep" or "social" processing is encouraged. The results show that video evidence can be used effectively as a probe to identity when the faces shown are highly familiar to observers, but caution should be used where images of unfamiliar people are being compared.

Adult↗

PubMed1999

Learned movements elicited by direct stimulation of cerebellar mossy fiber afferents.

Definitive evidence is presented that the conditioned stimulus (CS) in classical conditioning reaches the cerebellum via the mossy fiber system. Decerebrate ferrets received paired forelimb and periocular stimulation until they responded with blinks to the forelimb stimulus. When direct mossy fiber stimulation was then given, the animals responded with conditioned blinks immediately, that is, without ever having been trained to the mossy fiber stimulation. Antidromic activation was prevented by blocking mossy fibers with lignocaine ventral to the stimulation site. It could be excluded that cerebellar output functioned as the CS. Analysis of latencies suggests that conditioned responses (CRs) are not generated by mossy fiber collaterals to the deep nuclei. Hence, the memory trace is probably located in the cerebellar cortex.

Afferent Pathways↗

PubMed2026

Deep DNA and protein level feature integration for robust clinical variant interpretation using probabilistic gradient boosting.

A major challenge in clinical genomics is to classify genetic variations correctly, since it directly affects disease diagnosis and personal care. The existing methods tend to be based on the combination of different factors, such as protein structure, population frequencies, phenotypic annotations, and sequence conservation. Nevertheless, these methods often cannot be used to achieve the necessary interpretability, quantify uncertainty, and address rare cases. This paper presents a probabilistic gradient boosting model on variant pathogenicity prediction. The suggested framework applies biological characteristics at both level of DNA and protein levels while also scaling the level of uncertainty in clinical decision making. Our machine learning aims to solve the issues of variant interpretation by managing the features and through probability-based pathogenicity prediction. The framework formulation is aimed at generalizing over various datasets and minimizing overfitting. At the same time, it can ensure reasonable performance to facilitate clinical experiments. The model has also been tested on three standard datasets and demonstrated to be more predictive of the pathogenic effect of variants, in comparison with a variety of existing tools. The probabilistic gradient boosting model proposed had ROC AUC values of 0.9293, 0.9610, and 0.9646 on ClinVar variants, GRCh37, and GRCh38 human genome respectively. Furthermore, the dataset was ensured to include both exonic and intronic variants, and Variants of Uncertain Significance were also taken into consideration for Performance Testing. Through this it also aims to provide better clinical significance which will lead to a good interpretable tool for priority of variants for a large variety of disease conditions.

ClinVar↗

PubMed1998

A pelvic muscle precontraction can reduce cough-related urine loss in selected women with mild SUI.

OBJECTIVES: To test the hypothesis that selected older women with mild-to-moderate stress urinary incontinence (SUI) can learn to demonstrate significantly reduced urine loss in 1 week by intentionally contracting the pelvic floor muscles before and during a cough (a skill we have termed "The Knack"). DESIGN: A prospective, randomized, single-blind interventional study. SETTING: The Older American Independence Center, a federally sponsored research program affiliated with the University of Michigan in Ann Arbor, Michigan. PARTICIPANTS: Twenty-seven women with a mean (SD) age of 68.0 (5.5) years, self-reported SUI, and demonstrable urine loss during a deep cough. INTERVENTION: Women were randomized to an immediate intervention group (Group I: n=13) who were taught the Knack after their first clinic visit, or a wait-listed control group (Group II: n=14) who were taught the Knack after 1 month. MEASUREMENTS: At 1 week after instruction, we tested the efficacy of the Knack in a standing stress test by (1) comparing the volumes of cough-related urine loss leaked by all subjects, with and without use of the Knack, and (2) comparing the volumes of cough-related urine loss leaked by Group I, using the Knack, with Group II, which had not yet been taught the Knack. RESULTS: Intra-individual results showed that at 1-week follow-up, the Knack was used to reduce urine loss resulting from a medium cough by an average of 98.2%, compared with that of a similar cough performed 1 minute before without the Knack (P=.009); likewise urine loss was reduced by an average of 73.3% (P=.003) in a deep cough. Reduction in urine loss was not significantly correlated with a digital measure of pelvic floor muscle strength. CONCLUSION: Within 1 week, selected older women with mild-to-moderate SUI can acquire the skill of using a properly-timed pelvic floor muscle contraction to significantly reduce urine leakage during a cough.

Aged↗

PubMedDate not supplied

Automatic structuring of radiology free-text reports.

A natural language processor was developed that automatically structures the important medical information (eg, the existence, properties, location, and diagnostic interpretation of findings) contained in a radiology free-text document as a formal information model that can be interpreted by a computer program. The input to the system is a free-text report from a radiologic study. The system requires no reporting style changes on the part of the radiologist. Statistical and machine learning methods are used extensively throughout the system. A graphical user interface has been developed that allows the creation of hand-tagged training examples. Various aspects of the difficult problem of implementing an automated structured reporting system have been addressed, and the relevant technology is progressing well. Extensible Markup Language is emerging as the preferred syntactic standard for representing and distributing these structured reports within a clinical environment. Early successes hold out hope that similar statistically based models of language will allow deep understanding of textual reports. The success of these statistical methods will depend on the availability of large numbers of high-quality training examples for each radiologic subdomain. The acceptability of automated structured reporting systems will ultimately depend on the results of comprehensive evaluations.

Humans↗