Respiratory variability in mechanically ventilated patients. Critical Care 2011

Introduction: Increased respiratory pattern variability is associated with improved oxygenation. Pressure support (PS) is a widely used partial-assist mechanical ventilation (MV) mode, in which each breathing cycle is initiated by flow or pressure variation at the airway due to patient inspiratory effort. Neurally adjusted ventilatory assist (NAVA) is relatively new and uses the electrical activity of the diaphragm (Eadi) to deliver ventilatory support proportional to the patient's inspiratory demand. We hypothesize that respiratory variability should be greater with NAVA compared with PS.Methods: Twenty-two patients underwent 20 minutes of PS followed by 20 minutes of NAVA. Flow and Eadi curves were used to obtain tidal volume (Vt) and ∫Eadi for 300 to 400 breaths in each patient. Patient-specific cumulative distribution functions (CDF) show the percentage Vt and ∫Eadi within a clinically defined (±10%) variability band for each patient. Values are normalized to patient-specific medians for direct comparison. Variability in Vt (outcome) is thus expressed in terms of variability in ∫Eadi (demand) on the same plot.Results: Variability in Vt relative to variability in ∫Eadi is significantly greater for NAVA than PS (P = 0.00012). Hence, greater variability in outcome Vt is obtained for a given demand in ∫Eadi, under NAVA, as illustrated in Figure 1 for a typical patient. A Fisher 2 × 2 contingency analysis showed that 45% of patients under NAVA had a Vt variability in equal proportion to ∫Eadi variability, versus 0% for PS (P < 0.05).Conclusions: NAVA yields greater variability in tidal volume, relative to ∫Eadi demand, and a better match between Vt and ∫Eadi. These results indicate that NAVA could achieve improved oxygenation compared with PS when sufficient underlying variability in ∫Eadi is present, due to its ability to achieve higher tidal volume variability from a given variability in ∫Eadi.

Partitioning of genetic (Rapd) variability among sexes and populations of the Barn Owl (Tyto alba) in Europe

The white Barn Owl subspecies (Tyto alba alba) is found in southern Europe and the reddish-brown subspecies (T a. guttata) in northern and eastern Europe. In central Europe, the two subspecies interbreed producing a large range of phenotypic variants. Because of the different ratios of the subspecies in different geographic regions, we predict that genetic variation should be greater in Switzerland than in Hungary. We tested this hypothesis by measuring genetic variation with the RAPD method. As predicted, the genetic differentiation within a Swiss population of Barn Owls was significantly greater than the variation within a Hungarian population. This suggests that gene flow is greater in central Europe than at the eastern limit of the Barn Owl distribution in Hungary. In both countries genetic variation was more pronounced in females than in males. As in other birds, this is probably because female Barn Owls are less philopatric than males. The number of migrants between Hungary and Switzerland is ca. 1 individual per generation; if calculated separately for the sexes, then 0.525 for males and ca. I for females (Nm values). The difference in the number of migrants between genders again is likely a consequence of higher male philopatry. The sexual differentiation is greater in the Swiss population than in the Hungarian and the genetic substructuring of the populations of the species is substantial. The reason for the considerable population substructuring could be the nonmigratory behavior and socially monogamous pairing of the species, as well as the geographical barriers (Alps) between the populations examined.

Altered brain-derived neurotrophic factor blood levels and gene variability are associated with anorexia and bulimia

Murine models and association studies in eating disorder (ED) patients have shown a role for the brain-derived neurotrophic factor (BDNF) in eating behavior. Some studies have shown association of BDNF -270C/T single-nucleotide polymorphism (SNP) with bulimia nervosa (BN), while BDNF Val66Met variant has been shown to be associated with both BN and anorexia nervosa (AN). To further test the role of this neurotrophin in humans, we screened 36 SNPs in the BDNF gene and tested for their association with ED and plasma BDNF levels as a quantitative trait. We performed a family-based association study in 106 ED nuclear families and analyzed BDNF blood levels in 110 ED patients and in 50 sib pairs discordant for ED. The rs7124442T/rs11030102C/rs11030119G haplotype was found associated with high BDNF levels (mean BDNF TCG haplotype carriers = 43.6 ng/ml vs. mean others 23.0 ng/ml, P = 0.016) and BN (Z = 2.64; P recessive = 0.008), and the rs7934165A/270T haplotype was associated with AN (Z =-2.64; P additive = 0.008). The comparison of BDNF levels in 50 ED discordant sib pairs showed elevated plasma BDNF levels for the ED group (mean controls = 41.0 vs. mean ED = 52.7; P = 0.004). Our data strongly suggest that altered BDNF levels modulated by BDNF gene variability are associated with the susceptibility to ED, providing physiological evidence that BDNF plays a role in the development of AN and BN, and strongly arguing for its involvement in eating behavior and body weight regulation.

A comparison of random sequence reads versus 16S rDNA sequences for estimating the biodiversity of a metagenomic library

The construction of metagenomic libraries has permitted the study of microorganisms resistant to isolation and the analysis of 16S rDNA sequences has been used for over two decades to examine bacterial biodiversity. Here, we show that the analysis of random sequence reads (RSRs) instead of 16S is a suitable shortcut to estimate the biodiversity of a bacterial community from metagenomic libraries. We generated 10,010 RSRs from a metagenomic library of microorganisms found in human faecal samples. Then searched them using the program BLASTN against a prokaryotic sequence database to assign a taxon to each RSR. The results were compared with those obtained by screening and analysing the clones containing 16S rDNA sequences in the whole library. We found that the biodiversity observed by RSR analysis is consistent with that obtained by 16S rDNA. We also show that RSRs are suitable to compare the biodiversity between different metagenomic libraries. RSRs can thus provide a good estimate of the biodiversity of a metagenomic library and, as an alternative to 16S, this approach is both faster and cheaper.

U.S. Farm Policy and the Variability of Commodity Prices and Farm Revenues, February 2000

A dynamic, three-commodity rational-expectations storage model is used to compare the impact of the Federal Agricultural Improvement and Reform (FAIR) Act of 1996 with a freemarket policy and with the agricultural policies that preceded the FAIR Act. Results support the hypothesis that the changes made when FAIR was enacted did not lead to permanent significant increases in the volatility of farm prices or revenues. An important finding is that the main economic impacts of the Pre-FAIR scenario, relative to the free-market regime were to transfer income to farmers and to substitute government storage for private storage in a way that did little to support prices or to stabilize farm incomes.

Multiple target tracking using random sets

This paper presents several algorithms for joint estimation of the target number and state in a time-varying scenario. Building on the results presented in [1], which considers estimation of the target number only, we assume that not only the target number, but also their state evolution must be estimated. In this context, we extend to this new scenario the Rao-Blackwellization procedure of [1] to compute Bayes recursions, thus defining reduced-complexity solutions for the multi-target set estimator. A performance assessmentis finally given both in terms of Circular Position Error Probability - aimed at evaluating the accuracy of the estimated track - and in terms of Cardinality Error Probability, aimed at evaluating the reliability of the target number estimates.

Variability of voriconazole plasma levels measured by new high-performance liquid chromatography and bioassay methods.

Voriconazole (VRC) is a broad-spectrum antifungal triazole with nonlinear pharmacokinetics. The utility of measurement of voriconazole blood levels for optimizing therapy is a matter of debate. Available high-performance liquid chromatography (HPLC) and bioassay methods are technically complex, time-consuming, or have a narrow analytical range. Objectives of the present study were to develop new, simple analytical methods and to assess variability of voriconazole blood levels in patients with invasive mycoses. Acetonitrile precipitation, reverse-phase separation, and UV detection were used for HPLC. A voriconazole-hypersusceptible Candida albicans mutant lacking multidrug efflux transporters (cdr1Delta/cdr1Delta, cdr2Delta/cdr2Delta, flu1Delta/flu1Delta, and mdr1Delta/mdr1Delta) and calcineurin subunit A (cnaDelta/cnaDelta) was used for bioassay. Mean intra-/interrun accuracies over the VRC concentration range from 0.25 to 16 mg/liter were 93.7% +/- 5.0%/96.5% +/- 2.4% (HPLC) and 94.9% +/- 6.1%/94.7% +/- 3.3% (bioassay). Mean intra-/interrun coefficients of variation were 5.2% +/- 1.5%/5.4% +/- 0.9% and 6.5% +/- 2.5%/4.0% +/- 1.6% for HPLC and bioassay, respectively. The coefficient of concordance between HPLC and bioassay was 0.96. Sequential measurements in 10 patients with invasive mycoses showed important inter- and intraindividual variations of estimated voriconazole area under the concentration-time curve (AUC): median, 43.9 mg x h/liter (range, 12.9 to 71.1) on the first and 27.4 mg x h/liter (range, 2.9 to 93.1) on the last day of therapy. During therapy, AUC decreased in five patients, increased in three, and remained unchanged in two. A toxic encephalopathy probably related to the increase of the VRC AUC (from 71.1 to 93.1 mg x h/liter) was observed. The VRC AUC decreased (from 12.9 to 2.9 mg x h/liter) in a patient with persistent signs of invasive aspergillosis. These preliminary observations suggest that voriconazole over- or underexposure resulting from variability of blood levels might have clinical implications. Simple HPLC and bioassay methods offer new tools for monitoring voriconazole therapy.

Interobserver and intraobserver variability of the apparent diffusion coefficient in treated malignant hepatic lesions on a 3.0T machine: measurements in the whole lesion versus in the area with the most restricted diffusion.

PURPOSE: To assess the inter/intraobserver variability of apparent diffusion coefficient (ADC) measurements in treated hepatic lesions and to compare ADC measurements in the whole lesion and in the area with the most restricted diffusion (MRDA). MATERIALS AND METHODS: Twenty-five patients with treated malignant liver lesions were examined on a 3.0T machine. After agreeing on the best ADC image, two readers independently measured the ADC values in the whole lesion and in the MRDA. These measurements were repeated 1 month later. The Bland-Altman method, Spearman correlation coefficients, and the Wilcoxon signed-rank test were used to evaluate the measurements. RESULTS: Interobserver variability for ADC measurements in the whole lesion and in the MRDA was 0.17 x 10(-3) mm(2)/s [-0.17, +0.17] and 0.43 x 10(-3) mm(2)/s [-0.45, +0.41], respectively. Intraobserver limits of agreement could be as low as [-0.10, +0.12] 10(-3) mm(2)/s and [-0.20, +0.33] 10(-3) mm(2)/s for measurements in the whole lesion and in the MRDA, respectively. CONCLUSION: A limited variability in ADC measurements does exist, and it should be considered when interpreting ADC values of hepatic malignancies. This is especially true for the measurements of the minimal ADC.

The dermatophyte species Arthroderma benhamiae: intraspecies variability and mating behaviour.

Arthroderma benhamiae is a zoophilic dermatophyte belonging to the Trichophyton mentagrophytes species complex. Here, a population of A. benhamiae wild strains from the same geographical area (Switzerland) was studied by comparing their morphology, assessing their molecular variability using internal transcribed spacer (ITS) and 28S rRNA gene sequencing, and evaluating their interfertility. Sequencing of the ITS region and of part of the 28S rRNA gene revealed the existence of two infraspecific groups with markedly different colony phenotypes: white (group I) and yellow (group II), respectively. For all strains, the results of mating type identification by PCR, using HMG (high-mobility group) and α-box genes in the mating type locus as targets, were in total accordance with the results of mating type identification by strain confrontation experiments. White-phenotype strains were of mating type + (mt+) or mating type - (mt-), whilst yellow-phenotype strains were all mt-. White and yellow strains were found to produce fertile cleistothecia after mating with A. benhamiae reference tester strains, which belonged to a third group intermediate between groups I and II. However, no interfertility was observed between yellow strains and white strains of mt+. A significant result was that white strains of mt- were able to mate and produce fertile cleistothecia with the white A. benhamiae strain CBS 112371 (mt+), the genome of which has recently been sequenced and annotated. This finding should offer new tools for investigating the biology and genetics of dermatophytes using wild-type strains.

Non-random fertilization in mice correlates with the MHC and something else

One evolutionary explanation for the success of sexual reproduction assumes that sex is an advantage in the coevolutionary arms race between pathogens and hosts. Accordingly, an important criterion in mate choice and maternal selection thereafter could be the allelic specificity at polymorphic loci involved in parasite-host interactions, e.g. the MHC (major histocompatibility complex). The MHC has been found to influence mate choice and selective abortions in mice and humans. However, it could also influence the fertilization process itself, i.e. (i) the oocyte's choice for the fertilizing sperm, and (ii) the outcome of the second meiotic division after the sperm has entered the egg. We tested both hypotheses in an in vitro fertilization experiment with two inbred mouse strains congenic for their MHC. The genotypes of the resulting blastocysts were determined by polymerase chain reaction. We found nonrandom MHC combinations in the blastocysts which may result from both possible choice mechanisms. The outcome changed significantly over time, indicating that a choice for MHC combinations during fertilization may be influenced by one or several external factors.

The variability of peridotite composition across a mantle shear zone (Lanzo massif, Italy): interplay of melt focusing and deformation

In this paper we present new data on the spatial variability of peridotite composition across a kilometer-scale mantle shear zone within the Lanzo massif (Western Alps, Italy). The shear zone separates the central from the northern part of the massif. Plagioclase peridotite shows gradually increasing deformation towards the shear zone, from porphyroclastic to mylonitic textures in the central body, while the northern body is composed of porphyroclastic rocks. The peridotite displays a large range of compositions, from fertile peridotite to refractory harzburgite and dunite. Deformed peridotites (proto-mylonite and mylonites) tend to be compositionally more homogeneous and fertile than weakly deformed peridotites. The composition of most plagioclase peridotites show rather high and constant (Ce/Yb) (N) ratios, and Yb (N) that cannot be explained by any simple melting model. Instead, refertilization modeling, consisting of melt increments from spinel peridotite sources, particularly with E-MORB melt, reasonably reproduces the plagioclase peridotite whole rock composition. Combined with constraints from Ce-Nb and Ce-Th systematics, we speculate that peridotites such as those from Lanzo record pervasive refertilization processes in the thermal boundary layer. In this scenario, mantle shear zones might act as important areas of melt focusing in the upper mantle that separates the thermal boundary layer from the conductively cooled mantle.

Variability of radioiodine measurements in the thyroid.

Monte Carlo simulations were carried out to study the response of a thyroid monitor for measuring intake activities of (125)I and (131)I. The aim of the study was 3-fold: to cross-validate the Monte Carlo simulation programs, to study the response of the detector using different phantoms and to study the effects of anatomical variations. Simulations were performed using the Swiss reference phantom and several voxelised phantoms. Determining the position of the thyroid is crucial for an accurate determination of radiological risks. The detector response using the Swiss reference phantom was in fairly good agreement with the response obtained using adult voxelised phantoms for (131)I, but should be revised for a better calibration for (125)I and for any measurements taken on paediatric patients.

Coordination pattern variability provides functional adaptations to constraints in swimming performance.

In a biophysical approach to the study of swimming performance (blending biomechanics and bioenergetics), inter-limb coordination is typically considered and analysed to improve propulsion and propelling efficiency. In this approach, 'opposition' or 'continuous' patterns of inter-limb coordination, where continuity between propulsive actions occurs, are promoted in the acquisition of expertise. Indeed a 'continuous' pattern theoretically minimizes intra-cyclic speed variations of the centre of mass. Consequently, it may also minimize the energy cost of locomotion. However, in skilled swimming performance there is a need to strike a delicate balance between inter-limb coordination pattern stability and variability, suggesting the absence of an 'ideal' pattern of coordination toward which all swimmers must converge or seek to imitate. Instead, an ecological dynamics framework advocates that there is an intertwined relationship between the specific intentions, perceptions and actions of individual swimmers, which constrains this relationship between coordination pattern stability and variability. This perspective explains how behaviours emerge from a set of interacting constraints, which each swimmer has to satisfy in order to achieve specific task performance goals and produce particular task outcomes. This overview updates understanding on inter-limb coordination in swimming to analyse the relationship between coordination variability and stability in relation to interacting constraints (related to task, environment and organism) that swimmers may encounter during training and performance.