Toward an Information Tool for Integrated Product Policy: Requirements for Data and Computation

Integrated product policy, according to the European Union, requires reliable data on the impact of consumer products along their life cycles. We argue that this necessarily requires the development of an information tool for hybrid analysis, combining aspects of life-cycle assessment and input-output analysis. A number of requirements in the development of such a hybrid information tool are identified, mainly concerning data and computational structure. For the former, some important points of attention are discussed, whereas for the latter, operational formulas are developed.     

Very Preterm Infants Failing CPAP Show Signs of Fatigue Immediately after Birth

Objective

To investigate the differences in breathing pattern and effort in infants at birth who failed or succeeded on continuous positive airway pressure (CPAP) during the first 48 hours after birth.

Methods

Respiratory function recordings of 32 preterm infants were reviewed of which 15 infants with a gestational age of 28.6 (0.7) weeks failed CPAP and 17 infants with a GA of 30.1 (0.4) weeks did not fail CPAP. Frequency, duration and tidal volumes (VT) of expiratory holds (EHs), peak inspiratory flows, CPAP-level and FiO₂-levels were analysed.

Results

EH incidence increased <6 minutes after birth and remained stable thereafter. EH peak inspiratory flows and VT were similar between CPAP-fail and CPAP-success infants. At 9-12 minutes, CPAP-fail infants more frequently used smaller VTs, 0-9 ml/kg and required higher peak inspiratory flows. However, CPAP-success infants often used large VTs (>9 ml/kg) with higher peak inspiratory flows than CPAP-fail infants (71.8 ± 15.8 vs. 15.5 ± 5.2 ml/kg.s, p <0.05). CPAP-fail infants required higher FiO₂ (0.31 ± 0.03 vs. 0.21 ± 0.01), higher CPAP pressures (6.62 ± 0.3 vs. 5.67 ± 0.26 cmH₂O) and more positive pressure-delivered breaths (45 ± 12 vs. 19 ± 9%) (p <0.05)

Conclusion

At 9-12 minutes after birth, CPAP-fail infants more commonly used lower VTs and required higher peak inspiratory flow rates while receiving greater respiratory support. VT was less variable and larger VT was infrequently used reflecting early signs of fatigue.     

Quantifying the Displacement of Mismatches in Multiple Sequence Alignment Benchmarks

Multiple Sequence Alignment (MSA) methods are typically benchmarked on sets of reference alignments. The quality of the alignment can then be represented by the sum-of-pairs (SP) or column (CS) scores, which measure the agreement between a reference and corresponding query alignment. Both the SP and CS scores treat mismatches between a query and reference alignment as equally bad, and do not take the separation into account between two amino acids in the query alignment, that should have been matched according to the reference alignment. This is significant since the magnitude of alignment shifts is often of relevance in biological analyses, including homology modeling and MSA refinement/manual alignment editing. In this study we develop a new alignment benchmark scoring scheme, SPdist, that takes the degree of discordance of mismatches into account by measuring the sequence distance between mismatched residue pairs in the query alignment. Using this new score along with the standard SP score, we investigate the discriminatory behavior of the new score by assessing how well six different MSA methods perform with respect to BAliBASE reference alignments. The SP score and the SPdist score yield very similar outcomes when the reference and query alignments are close. However, for more divergent reference alignments the SPdist score is able to distinguish between methods that keep alignments approximately close to the reference and those exhibiting larger shifts. We observed that by using SPdist together with SP scoring we were able to better delineate the alignment quality difference between alternative MSA methods. With a case study we exemplify why it is important, from a biological perspective, to consider the separation of mismatches. The SPdist scoring scheme has been implemented in the VerAlign web server (http://www.ibi.vu.nl/programs/veralignwww/). The code for calculating SPdist score is also available upon request.     

Application of bacteria as self-healing agent for the development of sustainable concrete

The application of concrete is rapidly increasing worldwide and therefore the development of sustainable concrete is urgently needed for environmental reasons. As presently about 7% of the total anthropogenic atmospheric CO₂ emission is due to cement production, mechanisms that would contribute to a longer service life of concrete structures would make the material not only more durable but also more sustainable. One such mechanism that receives increasing attention in recent years is the ability for self-repair, i.e. the autonomous healing of cracks in concrete. In this study we investigated the potential of bacteria to act as self-healing agent in concrete, i.e. their ability to repair occurring cracks. A specific group of alkali-resistant spore-forming bacteria related to the genus Bacillus was selected for this purpose. Bacterial spores directly added to the cement paste mixture remained viable for a period up to 4 months. A continuous decrease in pore size diameter during cement stone setting probably limited life span of spores as pore widths decreased below 1 μm, the typical size of Bacillus spores. However, as bacterial cement stone specimens appeared to produce substantially more crack-plugging minerals than control specimens, the potential application of bacterial spores as self-healing agent appears promising.     

PCR-Denaturing Gradient Gel Electrophoresis of Complex Microbial Communities: A Two-Step Approach to Address the Effect of Gel-to-Gel Variation and Allow Valid Comparisons Across a Large Dataset

Denaturing gradient gel electrophoresis (DGGE) is widely used in microbial ecology to profile complex microbial communities over time and in response to different stimuli. However, inherent gel-to-gel variability has always been a barrier toward meaningful interpretation of DGGE profiles obtained from multiple gels. To address this problem, we developed a two-step methodology to align DGGE profiles across a large dataset. The use of appropriate inter-gel standards was of vital importance since they provided the basis for efficient within- and between-gel alignment and a reliable means to evaluate the final outcome of the process. Pretreatment of DGGE profiles by a commercially available image analysis software package (TL120 v2006, Phoretix 1D Advanced) followed by a simple interpolation step in Matlab minimized the effect of gel-to-gel variation, allowing for comparisons between large numbers of samples with a high degree of confidence. At the same time, data were obtained in the form of whole densitometric curves, rather than as band presence/absence or intensity information, and could be readily analyzed by a collection of well-established multivariate methods. This work clearly demonstrates that there is still room for significant improvements as to the way large DGGE datasets are processed and statistically interrogated.     

Investigation into the role of macrophages in the formation and degradation of beta2-microglobulin amyloid fibrils

Dialysis related amyloidosis is a serious complication of long-term hemodialysis in which beta(2)-microglobulin (beta(2)m) forms amyloid fibrils that deposit predominantly in cartilaginous tissues. How these fibrils form in vivo, however, is poorly understood. Here we perform a systematic investigation into the role of macrophages in the formation and degradation of beta(2)m amyloid fibrils, building on observations that macrophages are found in association with beta(2)m amyloid deposits in vivo and that these cells contain intra-lysosomal beta(2)m amyloid. In live cell imaging experiments we demonstrate that macrophages internalize monomeric beta(2)m, whereupon it is sorted to lysosomes. At lysosomal pH beta(2)m self-associates in vitro to form amyloid-like fibrils with an array of morphologies as visualized by atomic force microscopy. Cleavage of the monomeric protein by both macrophages and lysosomal proteases isolated from these cells results in the rapid degradation of the monomeric protein, preventing amyloid formation. Incubation of macrophages with preformed fibrils revealed that macrophages internalize amyloid-like fibrils formed extracellularly, but in marked contrast with the monomeric protein, the fibrils were not degraded within macrophage lysosomes. Correspondingly beta(2)m fibrils were highly resistant to degradation by high concentrations of lysosomal proteases isolated from macrophages. Despite their enormous degradative capacity, therefore, macrophage lysosomes cannot ameliorate dialysis-related amyloidosis by degrading pre-existing amyloid fibrils, but lysosomal proteases may play a protective role by eliminating amyloid precursors before beta(2)m fibrils can accumulate in what may represent an otherwise fibrillogenic environment.     

Rheumatoid arthritis–associated autoantibodies in non–rheumatoid arthritis patients with mucosal inflammation: a case–control study

IntroductionRheumatoid arthritis–associated autoantibodies (RA-AAB) can be present in serum years before clinical onset of rheumatoid arthritis (RA). It has been hypothesized that initiation of RA-AAB generation occurs at inflamed mucosal surfaces, such as in the oral cavity or lungs. The aim of this study was to assess systemic presence of RA-AAB in patients without RA who had oral or lung mucosal inflammation.MethodsThe presence of RA-AAB (immunoglobulin A [IgA] and IgG anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), IgM and IgA rheumatoid factor (RF), IgG anti-carbamylated protein antibodies and IgG and IgA anti-citrullinated peptide antibodies against fibrinogen, vimentin and enolase) were determined in sera of non-RA patients with periodontitis (PD, n = 114), bronchiectasis (BR, n = 80) or cystic fibrosis (CF, n = 41). Serum RA-AAB levels were compared with those of periodontally healthy controls (n = 36). Patients with established RA (n = 86) served as a reference group. Association of the diseases with RA-AAB seropositivity was assessed with a logistic regression model, adjusted for age, sex and smoking.ResultsLogistic regression analysis revealed that IgG anti-CCP seropositivity was associated with BR and RA, whereas the association with PD was borderline significant. IgA anti-CCP seropositivity was associated with CF and RA. IgM RF seropositivity was associated with RA, whereas the association with BR was borderline significant. IgA RF seropositivity was associated with CF and RA. Apart from an influence of smoking on IgA RF in patients with RA, there was no influence of age, sex or smoking on the association of RA-AAB seropositivity with the diseases. Anti-CarP levels were increased only in patients with RA. The same held for IgG reactivity against all investigated citrullinated peptides.ConclusionAlthough overall levels were low, RA-AAB seropositivity was associated with lung mucosal inflammation (BR and CF) and may be associated with oral mucosal inflammation (PD). To further determine whether mucosal inflammation functions as a site for induction of RA-AAB and precedes RA, longitudinal studies are necessary in which RA-AAB of specifically the IgA isotype should be assessed in inflamed mucosal tissues and/or in their inflammatory exudates.