High cefepime plasma concentrations and neurological toxicity in febrile neutropenic patients with mild impairment of renal function.

High-dose cefepime therapy is recommended for febrile neutropenia. Safety issues have been raised in a recent meta-analysis reporting an increased risk of mortality during cefepime therapy. Cefepime-related neurological toxicity has been associated with overdosing due to severe renal dysfunction. This study aimed to investigate the association between cefepime plasma concentrations and neurological toxicity in febrile neutropenic patients. Cefepime trough concentrations (by high-performance liquid chromatography) were retrospectively analyzed for 30 adult febrile neutropenic patients receiving the recommended high-dose regimen (6 g/day for a glomerular filtration rate [GFR] of >50 ml/min). The dose adjustment to renal function was evaluated by the ratio of the cefepime daily dose per 100 ml/min of glomerular filtration. The association between cefepime plasma concentrations and neurological toxicity was assessed on the basis of consistent neurological symptoms and/or signs (by NCI criteria). The median cefepime concentration was 8.7 mg/liter (range, 2.1 to 38 mg/liter) at a median of 4 days (range, 2 to 15 days) after the start of therapy. Neurological toxicity (altered mental status, hallucinations, or myoclonia) was attributed to cefepime in 6/30 (20%) patients (median GFR, 45 ml/min; range, 41 to 65 ml/min) receiving a median dose of 13.2 g/day per 100 ml/min GFR (range, 9.2 to 14.3 g/day per 100 ml/min GFR). Cefepime discontinuation resulted in complete neurological recovery for five patients and improvement for one patient. A multivariate logistic regression model confirmed high cefepime concentrations as an independent predictor of neurological toxicity, with a 50% probability threshold at ≥22 mg/liter (P = 0.05). High cefepime plasma concentrations are associated with neurological toxicity in febrile neutropenic patients with mild renal dysfunction. Careful adherence to normalized dosing per 100 ml/min GFR is crucial. Monitoring of plasma concentrations may contribute to preventing neurological toxicity of high-dose therapy for this life-threatening condition.

Aitchison Geometry for Probability and Likelihood as a new approach to mathematical statistics

The Aitchison vector space structure for the simplex is generalized to a Hilbert space structure A2(P) for distributions and likelihoods on arbitrary spaces. Centralnotations of statistics, such as Information or Likelihood, can be identified in the algebraical structure of A2(P) and their corresponding notions in compositional data analysis, such as Aitchison distance or centered log ratio transform.In this way very elaborated aspects of mathematical statistics can be understoodeasily in the light of a simple vector space structure and of compositional data analysis. E.g. combination of statistical information such as Bayesian updating,combination of likelihood and robust M-estimation functions are simple additions/perturbations in A2(Pprior). Weighting observations corresponds to a weightedaddition of the corresponding evidence.Likelihood based statistics for general exponential families turns out to have aparticularly easy interpretation in terms of A2(P). Regular exponential families formfinite dimensional linear subspaces of A2(P) and they correspond to finite dimensionalsubspaces formed by their posterior in the dual information space A2(Pprior).The Aitchison norm can identified with mean Fisher information. The closing constant itself is identified with a generalization of the cummulant function and shown to be Kullback Leiblers directed information. Fisher information is the local geometry of the manifold induced by the A2(P) derivative of the Kullback Leibler information and the space A2(P) can therefore be seen as the tangential geometry of statistical inference at the distribution P.The discussion of A2(P) valued random variables, such as estimation functionsor likelihoods, give a further interpretation of Fisher information as the expected squared norm of evidence and a scale free understanding of unbiased reasoning

Running versus strength-based warm-up : acute effects on isometric knee extension function

This study investigated the influence of two warm-up protocols on neural and contractile parameters of knee extensors. A series of neuromuscular tests including voluntary and electrically evoked contractions were performed before and after running- (R (WU); slow running, athletic drills, and sprints) and strength-based (S (WU); bilateral 90 degrees back squats, Olympic lifting movements and reactivity exercises) warm ups (duration ~40 min) in ten-trained subjects. The estimated overall mechanical work was comparable between protocols. Maximal voluntary contraction torque (+15.6%; P < 0.01 and +10.9%; P < 0.05) and muscle activation (+10.9 and +12.9%; P < 0.05) increased to the same extent after R (WU) and S (WU), respectively. Both protocols caused a significant shortening of time to contract (-12.8 and -11.8% after R (WU) and S (WU); P < 0.05), while the other twitch parameters did not change significantly. Running- and strength-based warm ups induce similar increase in knee extensors force-generating capacity by improving the muscle activation. Both protocols have similar effects on M-wave and isometric twitch characteristics.

The influence of environmental conditions on immune responses, morphology and recapture probability of nestling house martins (Delichon urbica)

Nestling birds produced later in the season are hypothesized to be of poor quality with a low probability of survival and recruitment. In a Spanish population of house martins (Delichon urbica), we first compared reproductive success, immune responses and morphological traits between the first and the second broods. Second, we investigated the effects of an ectoparasite treatment and breeding date on the recapture rate the following year. Due probably to a reverse situation in weather conditions during the experiment, with more rain during rearing of the first brood, nestlings reared during the second brood were in better condition and had stronger immune responses compared with nestlings from the first brood. Contrary to other findings on house martins, we found a similar recapture rate for chicks reared during the first and the second brood. Furthermore, ectoparasitic house martin bugs had no significant effect on the recapture rate. Recaptured birds had similar morphology but higher immunoglobulin levels when nestlings compared with non-recaptured birds. This result implies that a measure of immune function is a better predictor of survival than body condition per se.

Cognition and brain function in schizotypy : a selective review

Schizotypy refers to a set of personality traits thought to reflect the subclinical expression of the signs and symptoms of schizophrenia. Here, we review the cognitive and brain functional profile associated with high questionnaire scores in schizotypy. We discuss empirical evidence from the domains of perception, attention, memory, imagery and representation, language, and motor control. Perceptual deficits occur early and across various modalities. Whilst the neural mechanisms underlying visual impairments may be linked to magnocellular dysfunction, further effects may be seen downstream in higher cognitive functions. Cognitive deficits are observed in inhibitory control, selective and sustained attention, incidental learning and memory. In concordance with the cognitive nature of many of the aberrations of schizotypy, higher levels of schizotypy are associated with enhanced vividness and better performance on tasks of mental rotation. Language deficits seem most pronounced in higher-level processes. Finally, higher levels of schizotypy are associated with reduced performance on oculomotor tasks, resembling the impairments seen in schizophrenia. Some of these deficits are accompanied by reduced brain activation, akin to the pattern of hypoactivations in schizophrenia spectrum individuals. We conclude that schizotypy is a construct with apparent phenomenological overlap with schizophrenia and stable inter-individual differences that covary with performance on a wide range of perceptual, cognitive and motor tasks known to be impaired in schizophrenia. The importance of these findings lies not only in providing a fine-grained neurocognitive characterisation of a personality constellation known to be associated with real-life impairments, but also in generating hypotheses concerning the aetiology of schizophrenia.

Free inertial processes driven by Gaussian noise: Probability distributions, anomalous diffusion and fractal behavior

We study the motion of an unbound particle under the influence of a random force modeled as Gaussian colored noise with an arbitrary correlation function. We derive exact equations for the joint and marginal probability density functions and find the associated solutions. We analyze in detail anomalous diffusion behaviors along with the fractal structure of the trajectories of the particle and explore possible connections between dynamical exponents of the variance and the fractal dimension of the trajectories.

The contact region between three domains of the extracellular loop of ASIC1a is critical for channel function.

Acid-sensing ion channels are members of the epithelial Na(+) channel/degenerin family. They are neuronal nonvoltage-gated Na(+) channels that are activated by extracellular acidification. In this study, we investigated the role of a highly conserved region of the extracellular part of ASIC1a that forms the contact between the finger domain, the adjacent beta-ball, and the upper palm domain in ASIC1a. The finger domain contributes to the pH-dependent gating and is linked via this contact zone to the rest of the protein. We found that mutation to Cys of residues in this region led to decreased channel expression and current amplitudes. Exposure of the engineered Cys residues to Cd(2+) or to charged methane thiosulfonate sulfhydryl reagents further reduced current amplitudes. This current inhibition was not due to changes in acid-sensing ion channel pH dependence or unitary conductance and was likely due to a decrease of the probability of channel opening. For some mutants, the effect of sulfhydryl reagents depended on the pH of exposure in the range 7.4 to 6.8, suggesting that this zone undergoes conformational changes during inactivation. Our study identifies a region in ASIC1a whose integrity is required for normal channel function.

Circadian regulation of renal function and potential role in hypertension.

PURPOSE OF REVIEW: Previous studies have shown that a variety of specific renal functions exhibit circadian oscillations. This review aims to provide an update on the molecular mechanisms underlying circadian rhythms in the kidney, and to discuss how dysregulation of circadian rhythms can interfere with kidney function. RECENT FINDINGS: The molecular mechanism responsible for generating and maintaining circadian rhythms has been unraveled in great detail. This mechanism, known as the circadian clock, drives circadian oscillation in expression levels of a large number of renal mRNA transcripts. Several proteins critically involved in renal homeostatic functions have been shown to exhibit significant circadian oscillation in their expression levels or in their posttranslational modifications. In transgenic mouse models, disruption of circadian clock activity results in dramatic changes in the circadian pattern of urinary sodium and potassium excretion and causes significant changes in arterial blood pressure. A growing amount of evidence suggests that dysregulation of circadian rhythms is associated with the development of hypertension and accelerated progression of chronic kidney disease and cardiovascular disease in humans. Chronotherapy studies have shown that the efficacy of antihypertensive medication is greatly dependent on the circadian time of drug administration. SUMMARY: Recent research points to the major role of circadian rhythms in renal function and in control of blood pressure.

Prediction of Childhood Asthma Using Conditional Probability and Discrete Event Simulation

Abstract: Asthma prevalence in children and adolescents in Spain is 10-17%. It is the most common chronic illness during childhood. Prevalence has been increasing over the last 40 years and there is considerable evidence that, among other factors, continued exposure to cigarette smoke results in asthma in children. No statistical or simulation model exist to forecast the evolution of childhood asthma in Europe. Such a model needs to incorporate the main risk factors that can be managed by medical authorities, such as tobacco (OR = 1.44), to establish how they affect the present generation of children. A simulation model using conditional probability and discrete event simulation for childhood asthma was developed and validated by simulating realistic scenario. The parameters used for the model (input data) were those found in the bibliography, especially those related to the incidence of smoking in Spain. We also used data from a panel of experts from the Hospital del Mar (Barcelona) related to actual evolution and asthma phenotypes. The results obtained from the simulation established a threshold of a 15-20% smoking population for a reduction in the prevalence of asthma. This is still far from the current level in Spain, where 24% of people smoke. We conclude that more effort must be made to combat smoking and other childhood asthma risk factors, in order to significantly reduce the number of cases. Once completed, this simulation methodology can realistically be used to forecast the evolution of childhood asthma as a function of variation in different risk factors.

Nonlinear prediction based on score function

The linear prediction coding of speech is based in the assumption that the generation model is autoregresive. In this paper we propose a structure to cope with the nonlinear effects presents in the generation of the speech signal. This structure will consist of two stages, the first one will be a classical linear prediction filter, and the second one will model the residual signal by means of two nonlinearities between a linear filter. The coefficients of this filter are computed by means of a gradient search on the score function. This is done in order to deal with the fact that the probability distribution of the residual signal still is not gaussian. This fact is taken into account when the coefficients are computed by a ML estimate. The algorithm based on the minimization of a high-order statistics criterion, uses on-line estimation of the residue statistics and is based on blind deconvolution of Wiener systems [1]. Improvements in the experimental results with speech signals emphasize on the interest of this approach.

The molecular mechanisms and evolutionary significance of plumage colour variation in pied flycatchers (Ficedula hypoleuca)

A common feature of natural populations is that individuals differ in morphology, physiologyand behavior (i.e .phenotype). A thorough understanding of the molecular mechanisms and evolutionary forces behind this phenotypic variation is a prerequisite for understanding evolution.This thesis examines the molecular mechanism and the roles of the different evolutionary forces in plumage colour variation in pied flycatchers (Ficedulahypoleuca). Malepied flycatchers exhibit marked variation in both pigmentary and structural plumage colourand the trait has repeatedly been suggested to be of adaptive significance. An examination of plumage colour variation on reproductive output trevealed that structural colouration, and more specifically the degree of ultraviolet (UV) reflectance had an effect on number of young sired. Paternity analyses of breeding males revealed that males that had been cuckolded by their social mate tended to be less UV reflectant than males that had not been cuckolded.Neither pigment-based norstructural colouration was found to affect the probability of siring young in other nests. Phenotypic differentiation was found to be markedly greater than differentiation at neutralgenetic markers across the pied flycatcher breeding range. Furthermore patterns of differentiationin phenotypes and selectively neutral genes were not uniform. Outlier tests searching for genomic footprints of selection revealed elevated levels of genetic divergence in a gene associated with feather development (and thus potentially structural colouration) and ultraviolet vision. Th eobserved differentiation in allelic frequencies was particularly pronounced in the Spanish piedflycatcher populations. Examining gene expression during feather development indicated that the TYRP1 gene (known to be involved in the production of black pigment) may be relevant in generating phenotypic variation in pied flycatcher plumage. Also, energy homeostasis related genesfeatured prominently among the genes found to be expressed in one extreme phenotype but not the other. This is of particular interest in light of what is known about the pleiotropy ofthe melanocortin system which underlies brown-black pigment production. The melanocortinsystem is also associated with energy homeostasis (among a number of other physiological functions) and thus the results could be pointing to the signalling function of brown-blackplumage. Plumage colour variation in pied flycatchers, both structural and pigmentary, can thus beconcluded to be exhibiting signals of non-neutral evolution. Structural colouration was found to play a role in sexual selection and putative signals of selection were further detected in acandidate gene for this trait. Evidence for non-neutral evolution of pigmentary colouration was also detected. These findings, together with the fact that preliminary evidence for an energy balance associated signalling function for plumage was found, present good starting points for further investigations into the meaning and mechanisms of plumage colour variation in piedflycatchers.

Energetic efficiency of an agricultural tractor in function of tire inflation pressure

The tire inflation pressure, among other factors, determines the efficiency in which a tractor can exert traction. It was studied the effect of using two tire inflation pressures, 110.4 kPa in the front and rear wheels, 124.2 kPa in the front wheel and 138 kPa in the rear wheels, the energetic efficiency of an agricultural tractor of 147 kW of engine power, in the displacement speed of 6.0 km.h-1, on track with firm surface, with the tractor engine speed of 2000 rpm. For each condition of the tire pressure, the tested tractor was subjected to constant forces in the drawbar of 45 kN and 50 kN, covering 30 meters. It was used a randomized complete block with a 2x2 factorial arrangement (tire pressure and drawbar power) with four replications, totaling 16 experimental units. Data were subjected to analysis of variance, using the Tukey test at 5% probability for comparison averages. The lowest hourly and specific fuel consumption, the lowest slippage of the wheelsets and the highest efficiency in the drawbar was obtained with the tire inflation pressure of 110.4 kPa in the front and rear tires of the tractor, highlighting that lower pressures improve energetic and operational performance of the tractor.

Generating competitive advantage through competitor information systems

This pro gradu –thesis discusses generating competitive advantage through competitor information systems. The structure of this thesis follows the structure of the WCA model by Alter (1996). In the WCA model, business process is influenced by three separate but connected elements: information, technology, and process participants. The main research question is how competitor information can be incorporated into or made into a tool creating competitive advantage. Research subquestions are: How does competitor information act as a part of the business process creating competitive advantage? How is a good competitor information system situated and structured in an organisation? How can management help information generate competitive advantage in the business process with participants, information, and technology? This thesis discusses each of the elements separate, but the elements are connected to each other and to competitive advantage. Information is discussed by delving into competitor information and competitor analysis. Competitive intelligence and competitor analysis requires commitment throughout the organisation, including top management, the desire to perform competitive intelligence and the desire to use the end products of that competitive intelligence. In order to be successful, systematic competitive intelligence and competitor analysis require vision, willingness to strive for the goals set, and clear strategies to proceed. Technology is discussed by taking a look into the function of the competitor information systems play and the place they occupy within an organization. In addition, there is discussion about the basic infrastructure of competitor information systems, and the problems competitor information systems can have plaguing them. In order for competitor information systems to be useful and worthy of the resources it takes to develop and maintain them, competitor information systems require on-going resource allocation and high quality information. In order for competitor information systems justify their existence business process participants need to maintain and utilize competitor information systems on all levels. Business process participants are discussed through management practices. This thesis discusses way to manage information, technology, and process participants, when the goal is to generate competitive advantage through competitor information systems. This is possible when information is treated as a resource with value, technology requires strategy in order to be successful within an organization, and process participants are an important resource. Generating competitive advantage through competitor information systems is possible when the elements of information, technology, and business process participants all align advantageously.

The modulation of simple reaction time by the spatial probability of a visual stimulus

Simple reaction time (SRT) in response to visual stimuli can be influenced by many stimulus features. The speed and accuracy with which observers respond to a visual stimulus may be improved by prior knowledge about the stimulus location, which can be obtained by manipulating the spatial probability of the stimulus. However, when higher spatial probability is achieved by holding constant the stimulus location throughout successive trials, the resulting improvement in performance can also be due to local sensory facilitation caused by the recurrent spatial location of a visual target (position priming). The main objective of the present investigation was to quantitatively evaluate the modulation of SRT by the spatial probability structure of a visual stimulus. In two experiments the volunteers had to respond as quickly as possible to the visual target presented on a computer screen by pressing an optic key with the index finger of the dominant hand. Experiment 1 (N = 14) investigated how SRT changed as a function of both the different levels of spatial probability and the subject's explicit knowledge about the precise probability structure of visual stimulation. We found a gradual decrease in SRT with increasing spatial probability of a visual target regardless of the observer's previous knowledge concerning the spatial probability of the stimulus. Error rates, below 2%, were independent of the spatial probability structure of the visual stimulus, suggesting the absence of a speed-accuracy trade-off. Experiment 2 (N = 12) examined whether changes in SRT in response to a spatially recurrent visual target might be accounted for simply by sensory and temporally local facilitation. The findings indicated that the decrease in SRT brought about by a spatially recurrent target was associated with its spatial predictability, and could not be accounted for solely in terms of sensory priming.

An analysis of decoupling procedures in generating thermal Green's functions of O([lambda]â ´) by the Zubarev equation of motion method

The Zubarev equation of motion method has been applied to an anharmonic crystal of O( ,,4). All possible decoupling schemes have been interpreted in order to determine finite temperature expressions for the one phonon Green's function (and self energy) to 0()\4) for a crystal in which every atom is on a site of inversion symmetry. In order to provide a check of these results, the Helmholtz free energy expressions derived from the self energy expressions, have been shown to agree in the high temperature limit with the results obtained from the diagrammatic method. Expressions for the correlation functions that are related to the mean square displacement have been derived to 0(1\4) in the high temperature limit.