Performance optimization of a leagility inspired supply chain model: a CFGTSA algorithm based approach

Lean and agile principles have attracted considerable interest in the past few decades. Industrial sectors throughout the world are upgrading to these principles to enhance their performance, since they have been proven to be efficient in handling supply chains. However, the present market trend demands a more robust strategy incorporating the salient features of both lean and agile principles. Inspired by these, the leagility principle has emerged, encapsulating both lean and agile features. The present work proposes a leagile supply chain based model for manufacturing industries. The paper emphasizes the various aspects of leagile supply chain modeling and implementation and proposes a new Hybrid Chaos-based Fast Genetic Tabu Simulated Annealing (CFGTSA) algorithm to solve the complex scheduling problem prevailing in the leagile environment. The proposed CFGTSA algorithm is compared with the GA, SA, TS and Hybrid Tabu SA algorithms to demonstrate its efficacy in handling complex scheduling problems

Integration of new and revised chronological data to constrain the terrace evolution of the Danube River (Gerecse Hills, Pannonian Basin)

Terrace ages deduced from diverse geochronological records yielded inconsistent data in the Danube valley in Hungary. The problem of discrepancies in the different chronological datasets has to be resolved before the Quaternary tectonic and climatic processes leading to valley incision and terrace formation may be properly evaluated. To establish a more robust chronology of the Danube valley in Hungary, new cosmogenic nuclide- (⁠10Be depth profiles, ⁠26Al/⁠10Be burial durations and burial depth profile) and luminescence-based (pIRIR⁠290) terrace ages were acquired and compared to revised paleontological and published U/Th and magnetostratigraphic data. All the applied geo-chronometers led to concordant terrace ages, with the exception of the U/Th method applied on travertine deposits covering terraces. U/Th ages predating the last interglacial manifest a bias towards younger ages, and so they were ignored in relation to the quantification of terrace ages. As a result, terrace ages from the Late Pliocene to Late Pleistocene were settled. With regard to data from the Middle Pleistocene onwards, the combination of diverse methodologies led to a tighter bracketing of terrace ages than would be possible using a single dating method. The modelling of cosmogenic ⁠26Al and ⁠10Be concentrations enabled to derive surface denudation rates and their combination with paleontological data also allowed us to decide between diverse landscape evolution scenarios

Growth, cell division and sporulation in mycobacteria

Bacteria have the ability to adapt to different growth conditions and to survive in various environments. They have also the capacity to enter into dormant states and some bacteria form spores when exposed to stresses such as starvation and oxygen deprivation. Sporulation has been demonstrated in a number of different bacteria but Mycobacterium spp. have been considered to be non-sporulating bacteria. We recently provided evidence that Mycobacterium marinum and likely also Mycobacterium bovis bacillus Calmette–Guérin can form spores. Mycobacterial spores were detected in old cultures and our findings suggest that sporulation might be an adaptation of lifestyle for mycobacteria under stress. Here we will discuss our current understanding of growth, cell division, and sporulation in mycobacteria

A balanced view of scale in spatial statistical analysis

Concepts of spatial scale, such as extent, grain, resolution, range, footprint, support and cartographic ratio are not interchangeable. Because of the potential confusion among the definitions of these terms, we suggest that authors avoid the term "scale" and instead refer to specific concepts. In particular, we are careful to discriminate between observation scales, scales of ecological phenomena and scales used in spatial statistical analysis. When scales of observation or analysis change, that is, when the unit size, shape, spacing or extent are altered, statistical results are expected to change. The kinds of results that may change include estimates of the population mean and variance, the strength and character of spatial autocorrelation and spatial anisotropy, patch and gap sizes and multivariate relationships, The First three of these results (precision of the mean, variance and spatial autocorrelation) can sometimes be estimated using geostatistical support-effect models. We present four case studies of organism abundance and cover illustrating some of these changes and how conclusions about ecological phenomena (process and structure) may be affected. We identify the influence of observational scale on statistical results as a subset of what geographers call the Modifiable Area Unit Problem (MAUP). The way to avoid the MAUP is by careful construction of sampling design and analysis. We recommend a set of considerations for sampling design to allow useful tests for specific scales of a phenomenon under study. We further recommend that ecological studies completely report all components of observation and analysis scales to increase the possibility of cross-study comparisons

Medicines informal market in Congo, Burundi and Angola: counterfeit and sub-standard antimalarials

BACKGROUND: The presence of counterfeits and sub-standards in African medicines market is a dramatic problem that causes many deaths each year. The increase of the phenomenon of pharmaceutical counterfeiting is due to the rise of the illegal market and to the impossibility to purchase branded high cost medicines. METHODS: In this paper the results of a quality control on antimalarial tablet samples purchased in the informal market in Congo, Burundi and Angola are reported. The quality control consisted in the assay of active substance by means of validated liquid chromatographic methods, uniformity of mass determination, disintegration and dissolution tests. Moreover, a general evaluation on label and packaging characteristics was performed. RESULTS: The results obtained on thirty antimalarial tablet samples containing chloroquine, quinine, mefloquine, sulphadoxine and pyrimethamine showed the presence of different kinds of problems: a general problem concerning the packaging (loose tablets, packaging without Producer name, Producer Country and sometimes without expiry date); low content of active substance (in one sample); different, non-declared, active substance (in one sample); sub-standard technological properties and very low dissolution profiles (in about 50% of samples). This last property could affect the bioavailability and bioequivalence in comparison with branded products and could be related to the use of different excipients in formulation or bad storage conditions. CONCLUSION: This paper evidences that the most common quality problem in the analysed samples appears to be the low dissolution profile. Here it is remarked that the presence of the right active substance in the right quantity is not a sufficient condition for a good quality drug. Dissolution test is not less important in a quality control and often evidences in vitro possible differences in therapeutic efficacy among drugs with the same active content. Dissolution profile can be dramatically affected by the choice of excipients in the oral solid formulation and, in many cases, is out of specifications due to the absence of formulation studies by producers of developing countries

Biomarkers of Therapeutic Response in the IL-23 Pathway in Inflammatory Bowel Disease

OBJECTIVES: Interleukin-23 (IL-23) has emerged as a new therapeutic target for the treatment of inflammatory bowel disease (IBD). As biomarkers of disease state and treatment efficacy are becoming increasingly important in drug development, we sought to identify efficacy biomarkers for anti-IL-23 therapy in Crohn's disease (CD). METHODS: Candidate IL-23 biomarkers, downstream of IL-23 signaling, were identified using shotgun proteomic analysis of feces and colon lavages obtained from a short-term mouse IBD model (anti-CD40 Rag2(-/-)) treated preventively with monoclonal antibodies (mAbs) to the IL-23 receptor (IL-23R). The biomarkers were then measured in an IBD T-cell transfer model treated therapeutically with a mAb to IL-23 (p19), confirming their association with IBD. To assess the clinical relevance of these markers, we assessed their concentrations in clinical serum, colon tissue, and feces from CD patients. RESULTS: We identified 57 proteins up or downregulated in diseased animals that returned to control values when the mice were treated with mAbs to IL-23R. Among those, S100A8, S100A9, regenerating protein 3β (REG), REG3γ, lipocalin 2 (LCN2), deleted in malignant tumor 1 (DMBT1), and macrophage migration inhibitory factor (MIF) mRNA levels correlated with disease score and dose titration of mAbs to IL-23R or IL-23(p19). All biomarkers, except DMBT1, were also downregulated after therapeutic administration of mAbs to IL-23(p19) in a T-cell transfer IBD mouse model. In sera from CD patients, we confirmed a significant upregulation of S100A8/A9 (43%), MIF (138%), pancreatitis-associated protein (PAP, human homolog of REG3β/γ; 49%), LCN2 (520%), and CCL20 (1280%), compared with control samples, as well as a significant upregulation of S100A8/A9 (887%), PAP (401%), and LCN2 (783%) in human feces from CD patients compared with normal controls. CONCLUSIONS: These studies identify multiple protein biomarkers downstream of IL-23 that could be valuable tools to assess the efficacy of this new therapeutic agent.Clinical and Translational Gastroenterology (2012) 3, e10; doi:10.1038/ctg.2012.2; published online 16 February 2012