Do Intensive Care Data on Respiratory Infections Reflect Influenza Epidemics?

Objectives

Severe influenza can lead to Intensive Care Unit (ICU) admission. We explored whether ICU data reflect influenza like illness (ILI) activity in the general population, and whether ICU respiratory infections can predict influenza epidemics.

Methods

We calculated the time lag and correlation between ILI incidence (from ILI sentinel surveillance, based on general practitioners (GP) consultations) and percentages of ICU admissions with a respiratory infection (from the Dutch National Intensive Care Registry) over the years 2003–2011. In addition, ICU data of the first three years was used to build three regression models to predict the start and end of influenza epidemics in the years thereafter, one to three weeks ahead. The predicted start and end of influenza epidemics were compared with observed start and end of such epidemics according to the incidence of ILI.

Results

Peaks in respiratory ICU admissions lasted longer than peaks in ILI incidence rates. Increases in ICU admissions occurred on average two days earlier compared to ILI. Predicting influenza epidemics one, two, or three weeks ahead yielded positive predictive values ranging from 0.52 to 0.78, and sensitivities from 0.34 to 0.51.

Conclusions

ICU data was associated with ILI activity, with increases in ICU data often occurring earlier and for a longer time period. However, in the Netherlands, predicting influenza epidemics in the general population using ICU data was imprecise, with low positive predictive values and sensitivities.     

Proline-rich Akt substrate of 40-kDa contains a nuclear export signal

The proline-rich Akt substrate of 40-kDa (PRAS40) has been linked to the regulation of the activity of the mammalian target of rapamycin complex 1 as well as insulin action. Despite these cytosolic functions, PRAS40 was originally identified as nuclear phosphoprotein in Hela cells. This study aimed to detail mechanisms and consequences of the nucleocytosolic trafficking of PRAS40. Sequence analysis identified a potential leucine-rich nuclear export signal (NES) within PRAS40. Incubation of A14 fibroblasts overexpressing human PRAS40 (hPRAS40) resulted in nuclear accumulation of the protein. Furthermore, mutation of the NES mimicked the effects of leptomycin B, a specific inhibitor of nuclear export, on the subcellular localization of hPRAS40. Finally, A14 cells expressing the NES-mutant showed impaired activation of components of the Akt-pathway as well as of the mTORC1 substrate p70 S6 kinase after insulin stimulation. This impaired insulin signaling could be ascribed to reduced protein levels of insulin receptor substrate 1 in cells expressing mutant NES. In conclusion, PRAS40 contains a functional nuclear export signal. Furthermore, enforced nuclear accumulation of PRAS40 impairs insulin action, thereby substantiating the function of this protein in the regulation of insulin sensitivity.     

Functional response of Anodonta anatina feeding on a green alga and four strains of cyanobacteria, differing in shape, size and toxicity

We studied the functional response of the freshwater unionid bivalve Anodonta anatina, feeding on five phytoplankton strains differing in food quality: the small green alga Scenedesmus obliquus, a toxic and a non-toxic strain of the filamentous cyanobacterium Planktothrix agardhii and a toxic and a non-toxic strain of the coccoid cyanobacterium Microcystis aeruginosa. On S. obliquus, A. anatina had a type II functional response with a maximum mass-specific ingestion rate (IR_max) of 5.24 mg C g DW⁻¹ h⁻¹ and a maximum mass-specific clearance rate (CR_max) of 492 (±38) ml g DW⁻¹ h⁻¹, the highest values for all the phytoplankton strains that were investigated. On toxic and non-toxic P. agardhii filaments, A. anatina also had a type II functional response, but IR_max and CR_max were considerably lower (IR_max 1.90 and 1.56 mg C g DW⁻¹ h⁻¹; CR_max 387 (±97) and 429 (±71) ml g DW⁻¹ h⁻¹, respectively) than on S. obliquus. Toxicity of P. agardhii had no effect on the filtration rate of the mussels. On the non-toxic M. aeruginosa (small coccoid cells), we also observed a type II functional response, although a type I functional response fitted almost as good to these data. For the colonial and toxic M. aeruginosa, a type I functional response fitted best to the data: IR increased linearly with food concentration and CR remained constant. CR_max and IR_max values for the (colonial) toxic M. aeruginosa (383 (±40) ml g DW⁻¹ h⁻¹; 3.7 mg C g DW⁻¹ h⁻¹) demonstrated that A. anatina filtered and ingested this cyanobacterium as good as the other cyanobacterial strains. However, on the non-toxic M. aeruginosa we observed the lowest CR_max of all phytoplankters (246 (±23) ml g DW⁻¹ h⁻¹, whereas IR_max was similar to that on toxic M. aeruginosa. The high maximum ingestion rates on S. obliquus and M. aeruginosa indicate a short handling time of these phytoplankton species. The high clearance rates on S. obliquus, toxic M. aeruginosa and P. agardhii reflect a high effort of the mussels to filter these particles out of the water column at low concentrations. The low clearance rates on non-toxic M. aeruginosa may be explained by the small size and coccoid form of this cyanobacterium, which may have impaired A. anatina to efficiently capture the cells. Although A. anatina had relatively high maximum clearance rates on non-toxic and toxic P. agardhii, this cyanobacterium does not seem to be a good food source, because of the observed high rates of pseudofaeces production and hence low ingestion rates.     

Modeling and optimal control of an energy-storing prosthetic knee

Advanced prosthetic knees for transfemoral amputees are currently based on controlled damper mechanisms. Such devices require little energy to operate, but can only produce negative or zero joint power, while normal knee joint function requires alternative phases of positive and negative work. The inability to generate positive work may limit the user's functional capabilities, may cause undesirable adaptive behavior, and may contribute to excessive metabolic energy cost for locomotion. In order to overcome these problems, we present a novel concept for an energy-storing prosthetic knee, consisting of a rotary hydraulic actuator, two valves, and a spring-loaded hydraulic accumulator. In this paper, performance of the proposed device will be assessed by computational modeling and by simulation of functional activities. A computational model of the hydraulic system was developed, with methods to obtain optimal valve control patterns for any given activity. The objective function for optimal control was based on tracking of joint angles, tracking of joint moments, and the energy cost of operating the valves. Optimal control solutions were obtained, based on data collected from three subjects during walking, running, and a sit-stand-sit cycle. Optimal control simulations showed that the proposed device allows near-normal knee function during all three activities, provided that the accumulator stiffness was tuned to each activity. When the energy storage mechanism was turned off in the simulations, the system functioned as a controlled damper device and optimal control results were similar to literature data on human performance with such devices. When the accumulator stiffness was tuned to walking, simulated performance for the other activities was sub-optimal but still better than with a controlled damper. We conclude that the energy-storing knee concept is valid for the three activities studied, that modeling and optimal control can assist the design process, and that further studies using human subjects are justified.     

The equine herpesvirus 1 UL20 product interacts with glycoprotein K and promotes egress of mature particles

The aim of the present study was to identify and functionally characterize the equine herpesvirus 1 (EHV-1) UL20 protein (UL20p). Using a specific antiserum, UL20p was shown to be associated with membranes of infected cells, as well as with envelopes of purified virions. By Western blot analysis, UL20p was detected in two main forms exhibiting M(r)s of 25,000 and 75,000. Both moieties did not enter the separating gel after heating of protein samples to 99 degrees C. The slower-migrating form of UL20p contains N-linked carbohydrates, and its presence is dependent of that of other viral proteins. Infection of cells that either constitutively express UL20p or a gK-green fluorescent protein (GFP) fusion protein with various EHV-1 deletion mutants revealed a relatively stable hetero-oligomer containing gK and UL20p with an apparent M(r) of 75,000. As demonstrated by confocal microscopy, UL20p distribution in Rk13 cells changed from a diffuse granular or netlike appearance to a pattern confined to the Golgi network when gK was coexpressed. Analysis of a UL20 deletion mutant of EHV-1 strain RacL11 indicated an involvement of UL20p in cell-to-cell spread, as well as in very late events in virus egress. Based on these and electron microscopic studies we suggest that the EHV-1 UL20 protein might be necessary to avoid fusion of mature virions with membranes of their transport vesicles.     

Distinct cellular and molecular mechanisms mediate initial axon development and adult-stage axon regeneration in C. elegans

The molecular and cellular mechanisms that allow adult-stage neurons to regenerate following damage are poorly understood. Recently, axons of motoneurons and mechanosensory neurons in adult C. elegans were found to regrow after being snipped by femtosecond laser ablation. Here, we explore the molecular determinants of adult-stage axon regeneration using the AVM mechanosensory neurons. The first step in AVM axon development is a pioneer axonal projection from the cell body to the ventral nerve cord. We show that regeneration of the AVM axon to the ventral nerve cord lacks the deterministic precision of initial axon development, requiring competition and pruning of unwanted axon branches. Nevertheless, axons of injured AVM neurons regrow to the ventral nerve cord with over 60% reliability in adult animals. In addition, in contrast to initial development, axon guidance during regeneration becomes heavily dependent on cytoplasmic protein MIG-10/Lamellipodin but independent of UNC-129/TGF-beta repellent and UNC-40/DCC receptor, and axon growth during regeneration becomes heavily dependent on UNC-34/Ena and CED-10/Rac actin regulators. Thus, C. elegans may be used as a genetic system to characterize novel cellular and molecular mechanisms underlying adult-stage nervous system regeneration.     

Does “supersaturated coexistence” resolve the “paradox of the plankton”?

In contradiction with field observations, theory predicts that the number of coexisting plankton species at equilibrium cannot exceed the number of limiting resources, which is called the "paradox of the plankton". Recently, Huisman & Weissing (1999 , 2000 ) showed, in a model study, that the number of coexisting species may exceed the number of limiting resources when internal system feedback induces oscillations or chaos. In this paper, we use the term "supersaturated coexistence" for this phenomenon. On the basis of these findings, they claimed that the paradox of the plankton is solved. We investigated the prerequisites for supersaturated coexistence in the same model. Our results indicate that supersaturated coexistence is a rare phenomenon in parameter space, requires a very precise parameterization of the community members and is sensitive to the introduction of new species and the removal of the present species. This raises the question of whether supersaturated coexistence is likely to occur in nature. We conclude that the claim by Huisman & Weissing (1999 , 2000 ) is premature.     

Distribution of assimilated carbon in plants and rhizosphere soil of basket willow (Salix viminalis L.)

Willow is often used in bio-energy plantations for its potential to function as a renewable energy source, but knowledge about its effect on soil carbon dynamics is limited. Therefore, we investigated the temporal variation in carbon dynamics in willow, focusing on below-ground allocation and sequestration to soil carbon pools. Basket willow plants (Salix viminalis L.) in their second year of growth were grown in pots in a greenhouse. At five times during the plants growth, namely 0, 1, 2, 3 and 4 months after breaking winter dormancy, a subset of the plants were continuously labelled with ¹⁴CO₂ in an ESPAS growth chamber for 28 days. After the labelling, the plants were harvested and separated into leaves, first and second year stems and roots. The soil was analysed for total C and ¹⁴C content as well as soil microbial biomass. Immediately after breaking dormancy, carbon stored in the first year stems was relocated to developing roots and leaves. Almost half the newly assimilated C was used for leaf development the first month of growth, dropping to below 15% in the older plants. Within the second month of growth, secondary growth of the stem became the largest carbon sink in the system, and remained so for the older age classes. Between 31 and 41% of the recovered ¹⁴C was allocated to below-ground pools. While the fraction of assimilated ¹⁴C in roots and root+soil respiration did not vary with plant age, the amount allocated to soil and soil microbial biomass increased in the older plants, indicating an increasing rhizodeposition. The total amount of soil microbial biomass was 30% larger in the oldest age class than in an unplanted control soil. The results demonstrate a close linkage between photosynthesis and below-ground carbon dynamics. Up to 13% of the microbial biomass consisted of carbon assimilated by the willows within the past 4 weeks, up to 11% of the recovered ¹⁴C was found as soil organic matter.     

Kinetic and structural characterization of adsorption-induced unfolding of bovine alpha -lactalbumin.

Conformational changes of bovine alpha-lactalbumin induced by adsorption on a hydrophobic interface are studied by fluorescence and circular dichroism spectroscopy. Adsorption of bovine alpha-lactalbumin on hydrophobic polystyrene nanospheres induces a non-native state of the protein, which is characterized by preserved secondary structure, lost tertiary structure, and release of calcium. This partially denatured state therefore resembles a molten globule state, which is an intermediate in the folding of bovine alpha-lactalbumin. Stopped-flow fluorescence spectroscopy reveals two kinetic phases during adsorption with rate constants k(1) approximately 50 s(-1) and k(2) approximately 8 s(-1). The rate of partial unfolding is remarkably fast and even faster than unfolding induced by the addition of 5.4 m guanidinium hydrochloride to native alpha-lactalbumin. The large unfolding rates exclude the possibility that unfolding of bovine alpha-lactalbumin to the intermediate state occurs before adsorption takes place. Stopped-flow fluorescence anisotropy experiments show that adsorption of bovine alpha-lactalbumin on polystyrene nanospheres occurs within the dead time (15 ms) of the experiment. This shows that the kinetic processes as determined by stopped-flow fluorescence spectroscopy are not affected by diffusion or association processes but are solely caused by unfolding of bovine alpha-lactalbumin induced by adsorption on the polystyrene surface. A scheme is presented that incorporates the results obtained and describes the adsorption of bovine alpha-lactalbumin.