Medical appropriateness of hospital utilization: an overview of the Swiss experience.

We present here the principal results of four concurrent hospital utilization reviews conducted in Switzerland in 1990 and 1991, based on an adapted Appropriateness Evaluation Protocol. The studies were performed on all the hospital days from a sample of patients admitted over a 6 month period. The level of inappropriate use ranged between 8 and 15% in terms of days and was consistently higher in medicine than in surgery. In comparison with other published studies, the low proportion of observed inappropriate days is probably due, at least partly, to differences in study design.

Reactivation of protein aggregates by mortalin and Tid1-the human mitochondrial Hsp70 chaperone system.

The mitochondrial 70-kDa heat shock protein (mtHsp70), also known in humans as mortalin, is a central component of the mitochondrial protein import motor and plays a key role in the folding of matrix-localized mitochondrial proteins. MtHsp70 is assisted by a member of the 40-kDa heat shock protein co-chaperone family named Tid1 and a nucleotide exchange factor. Whereas, yeast mtHsp70 has been extensively studied in the context of protein import in the mitochondria, and the bacterial 70-kDa heat shock protein was recently shown to act as an ATP-fuelled unfolding enzyme capable of detoxifying stably misfolded polypeptides into harmless natively refolded proteins, little is known about the molecular functions of the human mortalin in protein homeostasis. Here, we developed novel and efficient purification protocols for mortalin and the two spliced versions of Tid1, Tid1-S, and Tid1-L and showed that mortalin can mediate the in vitro ATP-dependent reactivation of stable-preformed heat-denatured model aggregates, with the assistance of Mge1 and either Tid1-L or Tid1-S co-chaperones or yeast Mdj1. Thus, in addition of being a central component of the protein import machinery, human mortalin together with Tid1, may serve as a protein disaggregating machine which, for lack of Hsp100/ClpB disaggregating co-chaperones, may carry alone the scavenging of toxic protein aggregates in stressed, diseased, or aging human mitochondria.

Role of Protein Ubiquitination in NFH-LacZ mice

In neurodegenerative diseases, one can observe deposits of degradation products that represent hallmark structures. Actually, the underlying mechanisms are not well understood, but some hypotheses claim that the ubiquitin-proteasome system is perturbed in neurodegenerative diseases. Some of the influencing factors are aging, oxidation and the formation of free radicals, as well as genetic mutations which affect the function of proteins and result in an accumulation and formation of aggresomes. The amyotrophic lateral sclerosis, in which a malfunction of the sodium dismutase perturbs the redox system, is characterized by the accumulation of elements of the cytoskeleton in motor neurons and a progressive neuronal death. We suppose that in these diseases the ubiquitin- proteasome system is deregulated and try to demonstrate this hypothesis by comparing the ubiquitination of different neurofilaments in brain and spinal cord of transgenic and control mice. These NFH-LacZ mice with a truncated NF-H protein and a ß-galactosidase marker protein induce an accumulation of NF-proteins and neurofilaments are no longer transported into axons or dendrites. The accumulation of such aggregates resembles the phenotype of amyotrophic lateral sclerosis. Beside the ubiquitination the neurofilament expression and phosphorylation state was investigated. The results cannot demonstrate a perturbation of the ubiquitin-proteasome system of neurofilaments in transgenic mice. In contrast, in accordance with the mechanism of the NFH-LacZ mice a decrease of high and medium density neurofilaments and a hypophosphorylation were found. In conclusion, to elicit the pathological mechanism of amyotrophic lateral sclerosis and to develop focused treatments, we have to review the pathological mechanism of the transgenic mice and repeat the experiments with other animal models or with human material. Other possibilities would be to focus on other degradation mechanisms, such as the endosome/lysosome system, and to define their role in the amyotrophic lateral sclerosis more clearly.

Regulation of protein transport from the Golgi complex to the endoplasmic reticulum by CDC42 and N-WASP.

Actin is involved in the organization of the Golgi complex and Golgi-to-ER protein transport in mammalian cells. Little, however, is known about the regulation of the Golgi-associated actin cytoskeleton. We provide evidence that Cdc42, a small GTPase that regulates actin dynamics, controls Golgi-to-ER protein transport. We located GFP-Cdc42 in the lateral portions of Golgi cisternae and in COPI-coated and noncoated Golgi-associated transport intermediates. Overexpression of Cdc42 and its activated form Cdc42V12 inhibited the retrograde transport of Shiga toxin from the Golgi complex to the ER, the redistribution of the KDEL receptor, and the ER accumulation of Golgi-resident proteins induced by the active GTP-bound mutant of Sar1 (Sar1[H79G]). Coexpression of wild-type or activated Cdc42 and N-WASP also inhibited Golgito-ER transport, but this was not the case in cells expressing Cdc42V12 and N-WASP(AWA), a mutant form of N-WASP that lacks Arp2/3 binding. Furthermore, Cdc42V12 recruited GFP-NWASP to the Golgi complex. We therefore conclude that Cdc42 regulates Golgi-to-ER protein transport in an N-WASP¿dependent manner.

On the efficiency of recursive evaluations with applications to risk theory

On the efficiency of recursive evaluations with applications to risk theoryCette thèse est composée de trois essais qui portent sur l'efficacité des évaluations récursives de la distribution du montant total des sinistres d'un portefeuille de polices d'assurance au cours d'un période donnée. Le calcul de sa fonction de probabilité ou de quantités liées à cette distribution apparaît fréquemment dans la plupart des domaines de la pratique actuarielle.C'est le cas notamment pour le calcul du capital de solvabilité en Suisse ou pour modéliser la perte d'une assurance vie au cours d'une année. Le principal problème des évaluations récursives est que la propagation des erreurs provenant de la représentation des nombres réels par l'ordinateur peut être désastreuse. Mais, le gain de temps qu'elles procurent en réduisant le nombre d'opérations arithmétiques est substantiel par rapport à d'autres méthodes.Dans le premier essai, nous utilisons certaines propriétés d'un outil informatique performant afin d'optimiser le temps de calcul tout en garantissant une certaine qualité dans les résultats par rapport à la propagation de ces erreurs au cours de l'évaluation.Dans le second essai, nous dérivons des expressions exactes et des bornes pour les erreurs qui se produisent dans les fonctions de distribution cumulatives d'un ordre donné lorsque celles-ci sont évaluées récursivement à partir d'une approximation de la transformée de De Pril associée. Ces fonctions cumulatives permettent de calculer directement certaines quantités essentielles comme les primes stop-loss.Finalement, dans le troisième essai, nous étudions la stabilité des évaluations récursives de ces fonctions cumulatives par rapport à la propagation des erreurs citées ci-dessus et déterminons la précision nécessaire dans la représentation des nombres réels afin de garantir des résultats satisfaisants. Cette précision dépend en grande partie de la transformée de De Pril associée.

Citizens' control and the efficiency of local public services

Està àmpliament acceptat que la descentralització fiscal incrementa el control dels ciutadans sobre els polítics, fomenta el rendiment de comptes i augmenta l¿eficiència. Aquest treball té per objectiu identificar les característiques socio-econòmiques dels ciutadans (votants potencials) que generen un major control sobre els responsables polítics locals provocant, així, un major nivell d'eficiència en un context descentralitzat.També s'analitzen les característiques fiscals dels governs locals que fomenten aquest control i eficiència. L'estudi s'ha aplicat a una mostra de municipis catalans seguint la metodologia convencional basada en l'estimació en dues etapes. A la primera etapa s'estima l'eficiència en que operen els municipis mitjançant la tècnica DEA. La novetat rau en el càlcul d'una nova versió d'indicador global d¿output municipal. En la segona etapa, a través d¿una estimació tipus Tobit (models censurats) i de mètodes bootstrap, es mostra com els factors abans comentats poden influir sobre l¿eficiència. Els resultats suggereixen que la forta presencia de comerciants, jubilats i persones amb dret a vot afavoreixen el control dels ciutadans, el rendiment de comptes i l¿eficiència. Un factor que facilita aquest control, i per tant una major eficiència, és la presència de baixos costos d'oportunitat d'obtenir informació sobre la gestió local dels serveis públics.

Citizens' control and the efficiency of local public services

Està àmpliament acceptat que la descentralització fiscal incrementa el control dels ciutadans sobre els polítics, fomenta el rendiment de comptes i augmenta l¿eficiència. Aquest treball té per objectiu identificar les característiques socio-econòmiques dels ciutadans (votants potencials) que generen un major control sobre els responsables polítics locals provocant, així, un major nivell d'eficiència en un context descentralitzat.També s'analitzen les característiques fiscals dels governs locals que fomenten aquest control i eficiència. L'estudi s'ha aplicat a una mostra de municipis catalans seguint la metodologia convencional basada en l'estimació en dues etapes. A la primera etapa s'estima l'eficiència en que operen els municipis mitjançant la tècnica DEA. La novetat rau en el càlcul d'una nova versió d'indicador global d¿output municipal. En la segona etapa, a través d¿una estimació tipus Tobit (models censurats) i de mètodes bootstrap, es mostra com els factors abans comentats poden influir sobre l¿eficiència. Els resultats suggereixen que la forta presencia de comerciants, jubilats i persones amb dret a vot afavoreixen el control dels ciutadans, el rendiment de comptes i l¿eficiència. Un factor que facilita aquest control, i per tant una major eficiència, és la presència de baixos costos d'oportunitat d'obtenir informació sobre la gestió local dels serveis públics.

The adjustment of energy expenditure and oxidation to energy intake: the role of carbohydrate and fat balance.

Evidence is accumulating that total body mass and its relative composition influence the rate of fat utilization in man. This effect can be explained by two factors operating in concert: (i) the effect of the size of the tissue mass and (ii) the nature of the fuel mix oxidized, i.e. the proportion of energy derived from fat vs. carbohydrate. In a cross-sectional study of 307 women with increasing degrees of obesity, we observed that the respiratory quotient (RQ) in post-absorptive conditions became progressively lower with increased body fatness, indicating a shift in substrate utilization. However, the RQ is known to be also influenced by the diet commonly ingested by the subjects. A short-term mixed diet overfeeding in lean and obese women has also demonstrated the high sensitivity of RQ to changes in energy balance. Following a one-day overfeeding (2500 kcal/day in excess of the previous 24 h energy expenditure), the magnitude of increase in RQ was identical in lean and obese subjects and the net efficiency of substrate utilization and storage was not influenced by the state of obesity.

What energy level is required to avoid nutrient depletion after surgery in oropharyngeal cancer?

The rate of energy expenditure was repeatedly measured by indirect calorimetry both in the basal state (BMR) and in the resting fed state (RMR) in 8 middle-aged male patients operated for oropharyngeal cancer. In the postsurgical phase, two sequential energy levels were administered by nasogastric tube: (1) a 'maintenance' level (days 3-5) at 1.4 X measured presurgery BMR; (2) a 'supramaintenance' level (days 6-9) at 1.7 X measured BMR on day 6. Before surgery the patients had a BMR averaging (23.7 +/- 1.0 kcal/kg.day). After surgery BMR increased to 27.6 +/- 2.7 kcal/kg.day (day 6), then it decreased to 24.4 +/- 1.4 kcal/kg.day (day 10). The difference between RMR and BMR yielded a nutrient-induced thermogenesis averaging 5 +/- 1 and 8.5 +/- 2% (p less than 0.05) on levels 1 and 2, respectively. It is concluded that an energy level corresponding to 1.4 X presurgery BMR is sufficient to maintain energy and substrate equilibrium in nondepleted patients, whereas 1.7 X BMR induces positive protein and fat balances concomitant to a decrease efficiency of energy utilization.

Diversity and efficiency of bradyrhizobium strains isolated from soil samples collected from around sesbania virgata roots using cowpea as trap species

The genetic diversity of ten Bradyrhizobium strains was evaluated for tolerance to high temperatures, to different salinity levels and for the efficiency of symbiosis with cowpea plants (Vigna unguiculata (L.) Walp.). Eight of these strains were isolated from nodules that appeared on cowpea after inoculation with suspensions of soil sampled from around the root system of Sesbania virgata (wand riverhemp) in ecosystems of South Minas Gerais. The other two strains used in our analyses as references, were from the Amazon and are currently recommended as cowpea inoculants. Genetic diversity was analyzed by amplifying repetitive DNA elements with the BOX primer, revealing high genetic diversity with each strain presenting a unique band profile. Leonard jar assays showed that the strains UFLA 03-30 and UFLA 03-38 had the highest N2-fixing potentials in symbiosis with cowpea. These strains had more shoot and nodule dry matter, more shoot N accumulation, and a higher relative efficiency than the strains recommended as inoculants. All strains grew in media of pH levels ranging from 4.0 to 9.0. The strains with the highest N2-fixing efficiencies in symbiosis with cowpea were also tolerant to the greatest number of antibiotics. However, these strains also had the lowest tolerance to high salt concentrations. All strains, with the exceptions of UFLA 03-84 and UFLA 03-37, tolerated temperatures of up to 40 ºC. The genetic and phenotypic characteristics of the eight strains isolated from soils of the same region were highly variable, as well as their symbiotic efficiencies, despite their common origin. This variability highlights the importance of including these tests in the selection of cowpea inoculant strains.

Role of the GNOM gene in Arabidopsis apical-basal patterning--From mutant phenotype to cellular mechanism of protein action.

How the apical-basal axis of polarity is established in embryogenesis is still a mystery in plant development. This axis appeared specifically compromised by mutations in the Arabidopsis GNOM gene. Surprisingly, GNOM encodes an ARF guanine-nucleotide exchange factor (ARF-GEF) that regulates the formation of vesicles in membrane trafficking. In-depth functional analysis of GNOM and its closest relative, GNOM-LIKE 1 (GNL1), has provided a mechanistic explanation for the development-specific role of a seemingly mundane trafficking regulator. The current model proposes that GNOM is specifically involved in the endosomal recycling of the auxin-efflux carrier PIN1 to the basal plasma membrane in provascular cells, which in turn is required for the accumulation of the plant hormone auxin at the future root pole through polar auxin transport. Thus, the analysis of GNOM highlights the importance of cell-biological processes for a mechanistic understanding of development.

Nutrition, dry matter accumulation and partitioning and phosphorus use efficiency of potato grown at different phosphorus levels in nutrient solution

High rates of phosphate fertilizers are applied to potato (Solanum tuberosum L.), which may cause antagonistic interactions with other nutrients and limit crop yields when over-supplied. The purpose of this study was to evaluate the influence of phosphorus (P) levels in nutrient solution on P use efficiency, nutritional status and dry matter (DM) accumulation and partitioning of potato plants cv. Ágata. The experiment was carried out in a greenhouse, arranged in a completely randomized block design with four replications. Treatments consisted of seven P levels in nutrient solution (0, 2, 4, 8, 16, 31, and 48 mg L-1). Plants were harvested after 28 days of growth in nutrient solution, and separated in roots, stems and leaves for evaluations. The treatment effects were analyzed by regression analysis. Phosphorus levels of up to 8 mg L-1 increased the root and shoot DM accumulation, but drastically decreased the root/shoot ratio of potato cv. Ágata. Higher P availability increased P concentration, accumulation and absorption efficiency, but decreased P use efficiency. Higher P levels increased the N, P, Mg, Fe, and Mn concentrations in roots considerably and decreased K, S, Cu, and Zn concentrations. In shoot biomass, N, P, K, and Ca concentrations were significantly increased by P applied in solution, unlike Mg and Cu concentrations. Although higher P levels (> 8 mg L-1) in nutrient solution increased P concentration, accumulation and absorption efficiency, the DM accumulation and partitioning of potato cv. Ágata were not affected.

The efficiency of different estimation methods of hydro-physical limits

The soil water available to crops is defined by specific values of water potential limits. Underlying the estimation of hydro-physical limits, identified as permanent wilting point (PWP) and field capacity (FC), is the selection of a suitable method based on a multi-criteria analysis that is not always clear and defined. In this kind of analysis, the time required for measurements must be taken into consideration as well as other external measurement factors, e.g., the reliability and suitability of the study area, measurement uncertainty, cost, effort and labour invested. In this paper, the efficiency of different methods for determining hydro-physical limits is evaluated by using indices that allow for the calculation of efficiency in terms of effort and cost. The analysis evaluates both direct determination methods (pressure plate - PP and water activity meter - WAM) and indirect estimation methods (pedotransfer functions - PTFs). The PTFs must be validated for the area of interest before use, but the time and cost associated with this validation are not included in the cost of analysis. Compared to the other methods, the combined use of PP and WAM to determine hydro-physical limits differs significantly in time and cost required and quality of information. For direct methods, increasing sample size significantly reduces cost and time. This paper assesses the effectiveness of combining a general analysis based on efficiency indices and more specific analyses based on the different influencing factors, which were considered separately so as not to mask potential benefits or drawbacks that are not evidenced in efficiency estimation.

Efficiency of nitrogen fertilizer applied at corn sowing in contrasting growing seasons in Paraguay

In order to select soil management practices that increase the nitrogen-use efficiency (NUE) in agro-ecosystems, the different indices of agronomic fertilizer efficiency must be evaluated under varied weather conditions. This study assessed the NUE indices in no-till corn in southern Paraguay. Nitrogen fertilizer rates from 0 to 180 kg ha-1 were applied in a single application at corn sowing and the crop response investigated in two growing seasons (2010 and 2011). The experimental design was a randomized block with three replications. Based on the data of grain yield, dry matter, and N uptake, the following fertilizer indices were assessed: agronomic N-use efficiency (ANE), apparent N recovery efficiency (NRE), N physiological efficiency (NPE), partial factor productivity (PFP), and partial nutrient balance (PNB). The weather conditions varied largely during the experimental period; the rainfall distribution was favorable for crop growth in the first season and unfavorable in the second. The PFP and ANE indices, as expected, decreased with increasing N fertilizer rates. A general analysis of the N fertilizer indices in the first season showed that the maximum rate (180 kg ha-1) obtained the highest corn yield and also optimized the efficiency of NPE, NRE and ANE. In the second season, under water stress, the most efficient N fertilizer rate (60 kg ha-1) was three times lower than in the first season, indicating a strong influence of weather conditions on NUE. Considering that weather instability is typical for southern Paraguay, anticipated full N fertilization at corn sowing is not recommended due the temporal variability of the optimum N fertilizer rate needed to achieve high ANE.

Plasticity of protein expression during culture of fetal skin cells.

In order to gain insight into the biology of fetal skin during culture, cellular proteins were studied during four culture passages (P00, P01, P04 as well as P10) using high-resolution two-dimensional (2-D) gel electrophoresis and mass spectrometry (MS). Bioinformatic analyses were focused on a region of each gel corresponding to pI between 4 and 8 and M(r) from 8000 to 35 000. In this area, 373 +/- 42 spots were detected (N = 18). Twenty-six spots presented an integrated intensity that increased in the higher passages, whereas five spots showed a progressively lower intensity in subsequent passaging. MS analysis was performed on spots that were unambiguously identified on preparative 2-D gels. Among the 26 spots showing an increased size between P00 and P10, 9 were identified, and corresponded to 3 proteins: (i) peptidyl-prolyl cis-trans isomerase A (P05092; cyclophilin A or cyclosporin A-binding protein), (ii) triosephosphate isomerase (P00938), and (iii) enoyl-CoA hydratase (P30084). Among these nine identified spots, three were absent at P00, but were present at P10. They corresponded to isoforms of peptidyl-prolyl cis-trans isomerase and triosephosphate isomerase, respectively. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses of the acidic isoforms of triosephosphate isomerase showed modifications of cysteine residues to cysteic acid. All these isoforms were clearly present in the skin cells of a 4-year-old child, as well as in skin cells from a 80-year-old man, at P00. These observations probably reflect either an oxidative stress related to cell culture, or, alternatively, maturation, differentiation and the aging of the cells.