Red blood cell lifespan, erythropoiesis and hemoglobin control

Erythropoietin (EPO) and iron deficiency as causes of anemia in patients with limited renal function or end-stage renal disease are well addressed. The concomitant impairment of red blood cell (RBC) survival has been largely neglected. Properties of the uremic environment like inflammation, increased oxidative stress and uremic toxins seem to be responsible for the premature changes in RBC membrane and cytoskeleton. The exposure of antigenic sites and breakdown of the phosphatidylserine asymmetry promote RBC phagocytosis. While the individual response to treatment with EPO-stimulating agents (ESA) depends on both the RBC's lifespan and the production rate, uniform dosing algorithms do not meet that demand. The clinical use of mathematical models predicting ESA-induced changes in hematocrit might be greatly improved once independent estimates of RBC production rate and/or lifespan become available, thus making the concomitant estimation of both parameters unnecessary. Since heme breakdown by the hemoxygenase pathway results in carbon monoxide (CO) which is exhaled, a simple CO breath test has been used to calculate hemoglobin turnover and therefore RBC survival and lifespan. Future research will have to be done to validate and implement this method in patients with kidney failure. This will result in new insights into RBC kinetics in renal patients. Eventually, these findings are expected to improve our understanding of the hemoglobin variability in response to ESA.

Climate-induced interannual variability of marine primary and export production in three global coupled climate carbon cycle models

Fully coupled climate carbon cycle models are sophisticated tools that are used to predict future climate change and its impact on the land and ocean carbon cycles. These models should be able to adequately represent natural variability, requiring model validation by observations. The present study focuses on the ocean carbon cycle component, in particular the spatial and temporal variability in net primary productivity (PP) and export production (EP) of particulate organic carbon (POC). Results from three coupled climate carbon cycle models (IPSL, MPIM, NCAR) are compared with observation-based estimates derived from satellite measurements of ocean colour and results from inverse modelling (data assimilation). Satellite observations of ocean colour have shown that temporal variability of PP on the global scale is largely dominated by the permanently stratified, low-latitude ocean (Behrenfeld et al., 2006) with stronger stratification (higher sea surface temperature; SST) being associated with negative PP anomalies. Results from all three coupled models confirm the role of the low-latitude, permanently stratified ocean for anomalies in globally integrated PP, but only one model (IPSL) also reproduces the inverse relationship between stratification (SST) and PP. An adequate representation of iron and macronutrient co-limitation of phytoplankton growth in the tropical ocean has shown to be the crucial mechanism determining the capability of the models to reproduce observed interactions between climate and PP.

Does organic grassland farming benefit plant and arthropod diversity at the expense of yield and soil fertility?

Organic management is one of the most popular strategies to reduce negative environmental impacts of intensive agriculture. However, little is known about benefits for biodiversity and potential worsening of yield under organic grasslands management across different grassland types, i.e. meadow, pasture and mown pasture. Therefore, we studied the diversity of vascular plants and foliage-living arthropods (Coleoptera, Araneae, Heteroptera, Auchenorrhyncha), yield, fodder quality, soil phosphorus concentrations and land-use intensity of organic and conventional grasslands across three study regions in Germany. Furthermore, all variables were related to the time since conversion to organic management in order to assess temporal developments reaching up to 18 years. Arthropod diversity was significantly higher under organic than conventional management, although this was not the case for Araneae, Heteroptera and Auchenorrhyncha when analyzed separately. On the contrary, arthropod abundance, vascular plant diversity and also yield and fodder quality did not considerably differ between organic and conventional grasslands. Analyses did not reveal differences in the effect of organic management among grassland types. None of the recorded abiotic and biotic parameters showed a significant trend with time since transition to organic management, except soil organic phosphorus concentrations which decreased with time. This implies that permanent grasslands respond slower and probably weaker to organic management than crop fields do. However, as land-use intensity and inorganic soil phosphorus concentrations were significantly lower in organic grasslands, overcoming seed and dispersal limitation by re-introducing plant species might be needed to exploit the full ecological potential of organic grassland management. We conclude that although organic management did not automatically increase the diversity of all studied taxa, it is a reasonable and useful way to support agro-biodiversity.

Diagnostic delay in Crohn's disease is associated with a complicated disease course and increased operation rate

OBJECTIVES The impact of diagnostic delay (a period from appearance of first symptoms to diagnosis) on the clinical course of Crohn's disease (CD) is unknown. We examined whether length of diagnostic delay affects disease outcomes. METHODS Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (68%), regional hospitals (14%), and private practices (18%). The frequencies of occurrence of bowel stenoses, internal fistulas, perianal fistulas, and CD-related surgery (intestinal and perianal) were analyzed. RESULTS A total of 905 CD patients (53.4% female, median age at diagnosis 26 (20-36) years) were stratified into four groups according to the quartiles of diagnostic delay (0-3, 4-9, 10-24, and ≥25 months, respectively). Median diagnostic delay was 9 (3-24) months. The frequency of immunomodulator and/or antitumor necrosis factor drug use did not differ among the four groups. The length of diagnostic delay was positively correlated with the occurrence of bowel stenosis (odds ratio (OR) 1.76, P=0.011 for delay of ≥25 months) and intestinal surgery (OR 1.76, P=0.014 for delay of 10-24 months and OR 2.03, P=0.003 for delay of ≥25 months). Disease duration was positively associated and non-ileal disease location was negatively associated with bowel stenosis (OR 1.07, P<0.001, and OR 0.41, P=0.005, respectively) and intestinal surgery (OR 1.14, P<0.001, and OR 0.23, P<0.001, respectively). CONCLUSIONS The length of diagnostic delay is correlated with an increased risk of bowel stenosis and CD-related intestinal surgery. Efforts should be undertaken to shorten the diagnostic delay.

A continuous-time MILP model for short-term scheduling of make-and-pack production processes

In process industries, make-and-pack production is used to produce food and beverages, chemicals, and metal products, among others. This type of production process allows the fabrication of a wide range of products in relatively small amounts using the same equipment. In this article, we consider a real-world production process (cf. Honkomp et al. 2000. The curse of reality – why process scheduling optimization problems are diffcult in practice. Computers & Chemical Engineering, 24, 323–328.) comprising sequence-dependent changeover times, multipurpose storage units with limited capacities, quarantine times, batch splitting, partial equipment connectivity, and transfer times. The planning problem consists of computing a production schedule such that a given demand of packed products is fulfilled, all technological constraints are satisfied, and the production makespan is minimised. None of the models in the literature covers all of the technological constraints that occur in such make-and-pack production processes. To close this gap, we develop an efficient mixed-integer linear programming model that is based on a continuous time domain and general-precedence variables. We propose novel types of symmetry-breaking constraints and a preprocessing procedure to improve the model performance. In an experimental analysis, we show that small- and moderate-sized instances can be solved to optimality within short CPU times.