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PubMed2005

Human evolution and the development of spondylolysis.

STUDY DESIGN: We propose that chronic spondylolytic defects at L5 are influenced by insufficient differential mediolateral distances between inferior articular facets of L4 and the superior facets of S1, which results in these structures impinging on adjacent sides of the par interarticularis during hyperlordosis. Individuals with adequate increase in interfacet distances from L4 through S1 are less likely to develop or maintain defects. OBJECTIVES: We test the above hypothesis by comparing the transverse interfacet dimensions throughout the lumbar columns of normal and spondylolytic individuals. SUMMARY OF BACKGROUND DATA: Spondylolysis is a common condition, yet its etiology is poorly understood. It is generally considered to be the result of a vaguely defined fatigue fracture through the pars interarticularis. The cause(s) of spondylolysis, however, have not been clearly identified. METHODS: Lumbar vertebrae from the Hamann-Todd osteological collection at the Cleveland Museum of Natural History were examined. Thirty individuals with bilateral spondylolysis at L5 were compared with 30 age- and sex-matched controls. Differences in transverse distances between articular facets and in transverse breadths of vertebral bodies were compared using two-tailed t tests. RESULTS: Results show that normal individuals have a significantly greater increase in interfacet dimensions progressing down the spine from L4 to S1 than do those with spondylolysis. These differences are not the result of normal individuals having increasingly large vertebrae, as results are significant even when standardized for vertebral body breadth. Vertebral body size itself does not differ systematically between groups. CONCLUSIONS: Spondylolysis is the direct result of contact pressures on both sides of the pars interarticularis resulting from inadequate separation between the inferior articular processes of L4 and the superior articular facets of S1. Individuals lacking sufficient increase in transverse interfacet dimensions in their lumbar columns are at greater risk of developing and maintaining spondylolytic defects.

Adult↗

PubMed1999

Sources of artifact and systematic error in quantitative snapshot of FLASH imaging and methods for their elimination.

Snapshot FLASH preceded by a preparation sequence is used to measure NMR parameters. Some preparation information is lost during snapshot FLASH acquisition as the magnetization evolves towards the steady state. This problem is often addressed by assuming that image intensity is proportional to the central k-space line, which may be sampled immediately after preparation using a centric-reordered scheme. Although some limitations of this assumption have been discussed, they are often ignored in parameter measurement. In this study, magnetization evolution effects in snapshot FLASH were investigated by computer simulation and phantom experiments in the context of T2 measurement. It was found that the standard analysis may lead to significant error in parameter measurement. Some improvement may be obtained using a more sophisticated analysis to take account of magnetization evolution. However, at the expense of a 50% reduction in signal intensity, accurate values may be obtained by a novel method that uses crusher gradients to eliminate evolved magnetization.

Artifacts↗

PubMed1995

Systematics of cetaceans using restriction site mapping of mitochondrial DNA.

Phylogenetic analysis of 14 cetacean species, including members from two baleen whale families and three toothed whale families, was undertaken using restriction site mapping of mitochondrial DNA and using cladistic and distance measures to infer phylogenies. The amount of between-taxa sequence divergence inferred from the data was lower than expected from the standard interpretation of the fossil record, but more consistent with some recent estimates of sequence divergence in cetacean mitochondrial DNA or nuclear DNA. This implies either that the rate of molecular evolution of cetacean DNA is much lower than that of other mammalian orders or that the fossil record of cetaceans requires reinterpretation. The incompleteness of the cetacean fossil record precludes resolution of the paradox at the present time. However, this discrepancy could in part be attributed to the sampling error inherent in the restriction site mapping technique, as comparative studies using the complete mtDNA genome and restriction site data of the blue and fin whales (genus Balaenoptera) indicate that the restriction site maps underestimate sequence divergence by about 40%. In contrast to a recent study suggesting that toothed whales were paraphyletic, with the sperm whales being more closely related to the rorquals than to the other toothed whales, the restriction data tend to support the monophyly of the baleen and the toothed whales, a finding which is consistent with a recent molecular-based study and with morphological and paleontological data. Topologies of the subfamily and generic levels are generally consistent with morphologically based schemes.

Animals↗

PubMed1984

Methods of systematic analysis: the relative superiority of phylogenetic systematics.

The superiority of cladistic methods to both synthetic and phenetic methods is briefly advanced and reviewed. Cladistics creates testable hypotheses of phylogeny that also give a highly informative summary of available data. Thus it best fits the criteria for a method for determining the general reference classification in biology. For protistologists in particular, cladistics is especially useful. Inundated by an abundance of ultrastructural, biochemical, and cell biological information, protistologists could be greatly helped by the informative way in which cladistics orders and summarizes the data. In addition to classifying protist taxa, hypotheses about the evolution of cell organelles and cellular could be scientifically formulated and tested by cladistics . Because cladistic classifications best summarize the data, they would also be best for making predictions about taxa and characters. They would, for the same reason, be the most stable. Widespread adoption of cladistic methods would serve to stabilize the now fluid state of protist taxonomy. It is for all of these reasons that such methods best suit the needs of the evolutionary protistologist .

Animals↗

PubMed2003

Excitatory amino acid antagonists for acute stroke.

BACKGROUND: Focal cerebral ischaemia causes release of excitatory amino acid (EAA) neurotransmitters, principally glutamate, with resultant over-stimulation of EAA receptors and downstream pathways. Excess glutamate release is a pivotal event in the evolution of irreversible ischaemic damage in animal models of ischaemia, and drugs that modulate glutamate action either by inhibiting its release, or blocking post-synaptic receptors, are potent neuroprotective agents. Many clinical trials with EAA modulating drugs have been conducted, none individually demonstrating efficacy. OBJECTIVES: To synthesise all the available data on all different classes of EAA modulators and to evaluate evidence of effects on outcome systematically. SEARCH STRATEGY: Relevant trials were identified in the Specialised Register of Controlled Trials (last searched May 2001). In addition, MEDLINE and EMBASE online searches for the terms "neuroprotection" (and its variants), "neuroprotective agent", for all individual drugs and drug classes included in the review, hand searches of conference proceedings from European, International, American Heart Association and Princeton conferences on Stroke, American Neurological Association and American Academy of Neurology meetings from 1992-2001, and direct contact with individual investigators and pharmaceutical companies. SELECTION CRITERIA: Trials were included if they were randomised, controlled studies giving agents with pharmacological properties that included modification of release of EAAs, or blockade of EAA receptors, in stroke within 24h of onset. Efficacy analysis was restricted to trials with a parallel group design: dose escalation studies were excluded. Intention-to-treat analyses were performed on all data. Outcome had to be reported in terms of death or dependence 1-12 months after the acute event. DATA COLLECTION AND ANALYSIS: Data were available for 36 of 41 relevant trials identified, involving 11,209 subjects. Data were unavailable for 632 participants (517 in trials fulfilling criteria for efficacy analysis). Seven trials did not report disability data, which were available for 29 trials involving 10,802 subjects. Twenty one of these trials, involving 10,342 subjects, were parallel group studies included in the primary efficacy analysis. Efficacy analysis included data derived from 9 trials not primarily designed to assess efficacy (1022 subjects). The primary (efficacy) end-point was the proportion of patients dead or disabled at final follow-up (defined by Barthel Index<60 at 3 months by preference). Mortality was a secondary end-point. Drugs were considered as individual agents, and also grouped principally into categories of ion channel modulators (glutamate release inhibition) and NMDA antagonists. MAIN RESULTS: There was no significant heterogeneity of outcome amongst individual drugs, or of drug classes either for the primary efficacy analysis (death or dependence) or for mortality at final follow-up. For the primary efficacy analysis, odds of death or dependence were 1.03 [95% confidence interval 0.96-1.12], and for mortality 1.02 [0.92-1.12]. Neither ion channel modulators (death or dependence 1.02 [0.90-1.16]) nor NMDA antagonists (death or dependence 1.05 [0.95-1.16]) differed from the principal analysis including all compounds. Trends for increased mortality with three NMDA antagonists were seen - selfotel (OR 1.19 [0.81-1.74]), aptiganel (OR 1.32 [0.91-1.93]) and gavestinel (OR 1.12 [0.95-1.32]) - but this did not achieve significance for the NMDA antagonists considered as a class (1.09 [0.96-1.23]). Aptiganel was also associated with a trend towards worse functional outcome (OR 1.20 [0.88-1.65]) although this was not the case for either of the other two compounds. No statistically significant detriment of psychotomimetic NMDA antagonists was found, although a trend towards higher mortality in this sub-group was seen (OR 1.25 [0.96-1.64]). REVIEWER'S CONCLUSIONS: There was no evidence of significant benefit or harm from drugs modulating excitatory amino acid action. Reductio]). REVIEWER'S CONCLUSIONS: There was no evidence of significant benefit or harm from drugs modulating excitatory amino acid action. Reduction of death or dependence by 8% or more has been excluded for gavestinel and lubeluzole, which contribute most of the data for this review. However, mechanistic understanding of neuroprotection is too poor to extrapolate from these two failed development plans to all glutamate modulators. Further clinical trials of neuroprotective agents remain justified, since confidence limits around estimates of effect remain wide for most agents, and cannot reliably exclude benefit. Although numbers of patients are too small to confirm or refute a trend towards increased mortality with some NMDA antagonists, further commercial development of these agents is exceedingly unlikely.

Acute Disease↗

PubMed2003

Prognostication and intensive care unit outcome: the evolving role of scoring systems.

Prognostic scoring systems remain important in clinical practice. They enable us to characterize our patient populations with robust measures for predicted mortality. This allows us to audit our own experience in the context of institutional quality control measures and facilitates, albeit imperfectly, comparisons across units and patient populations. Practically, they provide an objective means to characterize case-mix and this helps to quantify resource needs when negotiating with hospital administrators for funding. Prognostic scores also help to stratify patient populations for research purposes. To be used accurately and effectively, one must have a good understanding of the limitations that are intrinsic to these prognostic systems. It is important to understand the details of their derivation and validation. The population of patients that is used to develop the models may not be relevant to your patient population. The model may have been derived several years before and may no longer reflect current practice patterns and treatment. These models may become obsolete over time. As with all scoring systems, there are potential problems with misclassification and more serious, systematic error, in data collection. One needs to rigorously adhere to guidelines about how these data are to be collected and processed; the persons who collect the data require regular updates and ongoing training. In their current form, the systems should not be used to prognosticate in individual patients, nor should they be used to define medical futility. The prognostic models should be viewed as being in evolution. Many patient and ICU characteristics that seem to have an important impact on mortality have yet to be incorporated into any of the current models. As an example, these may include the genetic characteristics of the patients and the ICU's organizational structure and process of care [51, 52]. Because the organ dysfunction measures are able to be obtained daily they give a much more complete understanding of the patient's entire ICU course as opposed to the initial 24-hour period. Daily scores also help to capture the intensity of resource use and may help us gain a better understanding of what is truly ICU-acquired organ dysfunction. These measures may also be used for research to better characterize the natural history and course of a certain disease group or population. Also, they may be used in innovative ways to predict ICU mortality and post-ICU long-term morbidity. These current and developing applications will help us to further understand the link between ICU severity of illness and long-term morbidity as we move beyond survival as the sole measure of ICU outcome.

APACHE↗

PubMed2005

Time is brain--quantified.

BACKGROUND AND PURPOSE: The phrase "time is brain" emphasizes that human nervous tissue is rapidly lost as stroke progresses and emergent evaluation and therapy are required. Recent advances in quantitative neurostereology and stroke neuroimaging permit calculation of just how much brain is lost per unit time in acute ischemic stroke. METHODS: Systematic literature-review identified consensus estimates of number of neurons, synapses, and myelinated fibers in the human forebrain; volume of large vessel, supratentorial ischemic stroke; and interval from onset to completion of large vessel, supratentorial ischemic stroke. RESULTS: The typical final volume of large vessel, supratentorial ischemic stroke is 54 mL (varied in sensitivity analysis from 19 to 100 mL). The average duration of nonlacunar stroke evolution is 10 hours (range 6 to 18 hours), and the average number of neurons in the human forebrain is 22 billion. In patients experiencing a typical large vessel acute ischemic stroke, 120 million neurons, 830 billion synapses, and 714 km (447 miles) of myelinated fibers are lost each hour. In each minute, 1.9 million neurons, 14 billion synapses, and 12 km (7.5 miles) of myelinated fibers are destroyed. Compared with the normal rate of neuron loss in brain aging, the ischemic brain ages 3.6 years each hour without treatment. Altering single input variables in sensitivity analyses modestly affected the estimated point values but not order of magnitude. CONCLUSIONS: Quantitative estimates of the pace of neural circuitry loss in human ischemic stroke emphasize the time urgency of stroke care. The typical patient loses 1.9 million neurons each minute in which stroke is untreated.

Brain↗

PubMed1999

[Contribution of John Hughlings Jackson to the understanding of epilepsy].

The figure of J.H. Jackson is one of the most relevant in the history of neurology. His longest period not only during his training but also during his professional plenitude took place in the National Hospital. Jackson was a great clinician, wrote many articles and gave a lot of lectures, but never wrote either a treatise or a monograph about his special field. He did not carry out animal experiments. He introduced in Britain the use of the ophthalmoscope in the neurological exploration and founded the journal Brain. He was specially interested in language disorders, paralysis, vertigo, mental disorders, cerebral tumours and above all epilepsy. He systematized what we today know as complex partial crisis, establishing the link between the function of the temporal lobe and the sensorial auras, automatism's, déjà-vu and jamais vu phenomena. He described the uncinate crisis, the topographic progression of the motor partial crisis and its posterior generalisation, establishing the motor pattern of cerebral cortex. The clinical observations of epileptic phenomena, with the influence of the evolutive ideas from Spencer, were the seeds for the elaboration of the evolutive development of the function of the nervous system. His theory about evolution and dissolution of the neurological functions was the starting point for Freud's clinical investigation. The Jacksonian set of ideas were experimentally proved by the neurophysiological work of Sherrington.

England↗

PubMedDate not supplied

[Implementation of the nursing process in a radiotherapy unit: development of a medical record].

The goal of our service is to systematize the nursing care provided to the clients with gynecological and mammary cancer who underwent radiation therapy, using the nursing process, the North American Nursing Diagnosis Association (NANDA) taxonomy and collaborative problems in the diagnoses phase. Therefore, we created a record card in which we briefly reported the relevant data to nursing care, containing: anamnesis, general explanations about treatment, main collaborative problems, nursing diagnoses, interventions, outcomes and evolution. This card was tested in service and evaluated by the group that had created it regarding content and design, enabling the elaboration of its last version that is presented in the article.

Attitude of Health Personnel↗

PubMed1983

[Perinatal mortality in the Grand Duchy of Luxembourg. The trend from 1969 to 1979].

A systematic survey on perinatal mortality has been carried out in Grand Duchy of Luxembourg for eleven years: a 40 to 100 reduction of the rate is noticed, decreasing from 20.6 p. 1 000 in 1969 to 11.9 p. 1 000 in 1978 with a more distinct reduction of the early neonatal component. Important differences are observed in various geographical places both in the rates and in the evolution during the studied period. Differences associated with socioeconomic factors, maternal age and civil status at birth seem to fade out. During the whole period, perinatal mortality rates are lower in foreigners and more particularly in recent immigrants than in Luxembourg people. The chronological aspect of the evolution suggests that these facts are correlated with the adoption of preventive measures in perinatality. This program seems to be efficient not only by globally reducing perinatal mortality but also by decreasing social inequalities in perinatality.

Birth Rate↗

PubMed2025

Genome-wide phylogeny reshapes our understanding of the evolution of deep-sea dragonfishes, bristlemouths, viperfishes, and allies (Stomiiformes).

BACKGROUND: The evolutionary relationships within Stomiiformes, a diverse order of deep-sea fishes dominating the mesopelagic and bathypelagic zones, remain contentious due to conflicting morphological and molecular evidence. These fishes, comprising 464 species across four traditionally recognized families (Gonostomatidae, Sternoptychidae, Phosichthyidae, and Stomiidae), exhibit remarkable adaptations such as bioluminescence, ultra-black pigmentation, and extreme jaw morphologies. Their global abundance and ecological significance, including contributions to the biological carbon pump, underscores the need to resolve their phylogeny amid escalating threats from climate change and human activities. RESULTS: We conducted the most comprehensive phylogenomic analysis of Stomiiformes to date, integrating 936 nuclear loci from 60 species and an expanded dataset of 135 species with mitochondrial sequences from publicly available repositories such as the Barcode of Life Data Systems (BOLD) database. We used maximum likelihood and coalescent-based approaches to assess family monophyly and relationships, including extensive quality control to address contamination in public databases. Our analyses reveal unstable tree topologies and complex evolutionary histories that challenge traditional classifications, while our quality control analyses identified 29% of BOLD sequences as misidentified or contaminated, emphasizing rigorous curation for deep-sea taxa. Congruent with a recent taxonomic treatment of Stomiiformes, the families Phosichthyidae and Gonostomatidae exhibit polyphyly and paraphyly, respectively, while subfamilies within Stomiidae are extensively non-monophyletic, leading us to recommend their abandonment. We propose the recognition of eight monophyletic families: Vinciguerriidae, Diplophidae, Gonostomatidae, Yarrellidae, Ichthyococcidae, Phosichthyidae, Sternoptychidae, and Stomiidae, supported by robust molecular and morphological evidence. CONCLUSIONS: This revised classification reflects the morphological and ecological diversity of Stomiiformes, aligning with their evolutionary diversification in the deep sea. Our phylogenomic framework resolves longstanding systematic uncertainties and highlights the power of genome-wide data in tackling taxonomically challenging clades. These findings provide a foundation for understanding deep-sea fish diversification and assessing the potential ecological drivers for their evolutionary diversity.

Animals↗

PubMed2006

Similarity-based gene detection: using COGs to find evolutionarily-conserved ORFs.

BACKGROUND: Experimental verification of gene products has not kept pace with the rapid growth of microbial sequence information. However, existing annotations of gene locations contain sufficient information to screen for probable errors. Furthermore, comparisons among genomes become more informative as more genomes are examined. We studied all open reading frames (ORFs) of at least 30 codons from the genomes of 27 sequenced bacterial strains. We grouped the potential peptide sequences encoded from the ORFs by forming Clusters of Orthologous Groups (COGs). We used this grouping in order to find homologous relationships that would not be distinguishable from noise when using simple BLAST searches. Although COG analysis was initially developed to group annotated genes, we applied it to the task of grouping anonymous DNA sequences that may encode proteins. RESULTS: "Mixed COGs" of ORFs (clusters in which some sequences correspond to annotated genes and some do not) are attractive targets when seeking errors of gene prediction. Examination of mixed COGs reveals some situations in which genes appear to have been missed in current annotations and a smaller number of regions that appear to have been annotated as gene loci erroneously. This technique can also be used to detect potential pseudogenes or sequencing errors. Our method uses an adjustable parameter for degree of conservation among the studied genomes (stringency). We detail results for one level of stringency at which we found 83 potential genes which had not previously been identified, 60 potential pseudogenes, and 7 sequences with existing gene annotations that are probably incorrect. CONCLUSION: Systematic study of sequence conservation offers a way to improve existing annotations by identifying potentially homologous regions where the annotation of the presence or absence of a gene is inconsistent among genomes.

Algorithms↗

PubMed1998

Microbial diversity of soda lakes.

Soda lakes are highly alkaline extreme environments that form in closed drainage basins exposed to high evaporation rates. Because of the scarcity of Mg2+ and Ca2+ in the water chemistry, the lakes become enriched in CO3(2-) and Cl-, with pHs in the range 8 to > 12. Although there is a clear difference in prokaryotic communities between the hypersaline lakes where NaCl concentrations are > 15% w/v and more dilute waters, i.e., NaCl concentrations about 5% w/v, photosynthetic primary production appears to be the basis of all nutrient recycling. In both the aerobic and anaerobic microbial communities the major trophic groups responsible for cycling of carbon and sulfur have in general been identified. Systematic studies have shown that the microbes are alkaliphilic and many represent separate lineages within accepted taxa, while others show no strong relationship to known prokaryotes. Although alkaliphiles are widespread it seems probable that these organisms, especially those unique to the hypersaline lakes, evolved separately within an alkaline environment. Although present-day soda lakes are geologically quite recent, they have probably existed since archaean times, permitting the evolution of independent communities of alkaliphiles since an early period in the Earth's history.

Archaea↗

PubMed2002

Towards high-resolution solid-state NMR on large uniformly 15N- and [13C,15N]-labeled membrane proteins in oriented lipid bilayers.

Based on exact numerical simulations, taking into account isotropic and conformation-dependent anisotropic nuclear spin interactions, we systematically analyse the prospects for high-resolution solid-state NMR on large isotope-labeled membrane proteins macroscopically oriented in phospholipid bilayers. Using the known X-ray structures of rhodopsin and porin as models for large membrane proteins with typical alpha-helical and beta-barrel structural motifs, the analysis considers all possible one- to six-dimensional spectra comprised of frequency dimensions with evolution under any combination of amide 1H, amide 15N, and carbonyl 13C chemical shifts as well as 1H-15N dipole-dipole couplings. Under consideration of typical nuclear spin interaction and experimental line-shape parameters, the analysis provides new insight into the resolution capability and orientation-dependent transfer efficiency of existing experiments as well as guidelines as to improved experimental approaches for the study of large uniformly 15N- and [13C,15N]-labeled membrane proteins. On basis of these results and numerical optimizations of coherence-transfer efficiencies, we propose several new high-resolution experiments for sequential protein backbone assignment and structure determination.

Amino Acid Motifs↗

PubMed1999

The DNA sequence of human chromosome 22.

Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.

Animals↗

PubMed2004

Structural and electronic properties of TaSi(n) (n=1-13) clusters: a relativistic density functional investigation.

The TaSi(n) (n=1-13) clusters with doublet, quartet, and sextet spin configurations have been systematically investigated by a relativistic density functional theory with the generalized gradient approximation available in Amsterdam density functional program. The total bonding energies, equilibrium geometries, Mulliken populations as well as Hirshfeld charges of TaSi(n) (n=1-13) clusters are calculated and presented. The emphasis on the stabilities and electronic properties is discussed. The most stable structures of the small TaSi(n) (n=1-6) clusters and the evolutional rule of low-lying geometries of the larger TaSi(n) (n=7-13) clusters are obtained. Theoretical results indicate that the most stable structure of TaSi(n) (n=1-6) clusters keeps the similar framework as the most stable structure of Si(n+1) clusters except for TaSi(3) cluster. The Ta atom in the lowest-energy TaSi(n) (n=1-13) isomers occupies a gradual sinking site, and the site moves from convex, to flatness, and to concave with the number of Si atom varying from 1 to 13. When n=12, the Ta atom in TaSi(12) cluster completely falls into the center of the Si frame, and a cagelike TaSi(12) geometry is formed. Meanwhile, the net Mulliken and Hirsheld populations of the Ta atom in the TaSi(n) (n=1-13) clusters vary from positive to negative, manifesting that the charges in TaSi(n) (n>/=12) clusters transfer from Si atoms to Ta atom. Additionally, the contribution of Si-Si and Si-Ta interactions to the stability of TaSi(n) clusters is briefly discussed. Furthermore, the investigations on atomic averaged binding energies and fragmentation energies show that the TaSi(n) (n=2,3,5,7,10,11,12) clusters have enhanced stabilities. Compared with pure silicon clusters, a universal narrowing of highest occupied molecular orbital-lowest unoccupied molecular orbital gap in TaSi(n) clusters is found.

Journal Article↗

PubMed2003

Neocortical pyramidal cells respond as integrate-and-fire neurons to in vivo-like input currents.

In the intact brain neurons are constantly exposed to intense synaptic activity. This heavy barrage of excitatory and inhibitory inputs was recreated in vitro by injecting a noisy current, generated as an Ornstein-Uhlenbeck process, into the soma of rat neocortical pyramidal cells. The response to such in vivo-like currents was studied systematically by analyzing the time development of the instantaneous spike frequency, and when possible, the stationary mean spike frequency as a function of both the mean and the variance of the input current. All cells responded with an in vivo-like action potential activity with stationary statistics that could be sustained throughout long stimulation intervals (tens of seconds), provided the frequencies were not too high. The temporal evolution of the response revealed the presence of mechanisms of fast and slow spike frequency adaptation, and a medium duration mechanism of facilitation. For strong input currents, the slow adaptation mechanism made the spike frequency response nonstationary. The minimal frequencies that caused strong slow adaptation (a decrease in the spike rate by more than 1 Hz/s), were in the range 30-80 Hz and depended on the pipette solution used. The stationary response function has been fitted by two simple models of integrate-and-fire neurons endowed with a frequency-dependent modification of the input current. This accounts for all the fast and slow mechanisms of adaptation and facilitation that determine the stationary response, and proved necessary to fit the model to the experimental data. The coefficient of variability of the interspike interval was also in part captured by the model neurons, by tuning the parameters of the model to match the mean spike frequencies only. We conclude that the integrate-and-fire model with spike-frequency-dependent adaptation/facilitation is an adequate model reduction of cortical cells when the mean spike-frequency response to in vivo-like currents with stationary statistics is considered.

Action Potentials↗

PubMed1993

Evolution of a quality-based compensation model: the third generation.

U.S. Healthcare (USHC) contracts for care with primary care physicians who are compensated through capitation (i.e., a fixed payment at specific intervals per member for all care provided, irrespective of the number of services). The amount of capitation is dependent upon their quality assessment rating and their ability to manage the cost of care effectively. In January of 1992 USHC implemented its current, third-generation incentive model and significantly altered its Quality Care Compensation System. The evolution of this model is presented to demonstrate that this third-generation Quality Care Compensation Model is a fair and effective means of measuring and valuing the delivery of health care to a population. It rewards physicians who expend the extra effort to manage both quality and cost. The experience of USHC continues to demonstrate that it is possible to develop and monitor incentive mechanisms in a systematic fashion with quality improvement as the outcome.

Adult↗