Evolutionary multiobjective optimization of the multi-location transshipment problem

We consider a multi-location inventory system where inventory choices at each location are centrally coordinated. Lateral transshipments are allowed as recourse actions within the same echelon in the inventory system to reduce costs and improve service level. However, this transshipment process usually causes undesirable lead times. In this paper, we propose a multiobjective model of the multi-location transshipment problem which addresses optimizing three conflicting objectives: (1) minimizing the aggregate expected cost, (2) maximizing the expected fill rate, and (3) minimizing the expected transshipment lead times. We apply an evolutionary multiobjective optimization approach using the strength Pareto evolutionary algorithm (SPEA2), to approximate the optimal Pareto front. Simulation with a wide choice of model parameters shows the different trades-off between the conflicting objectives

IL12/23 blockade for refractory immune-mediated colitis: 2 center experience

BACKGROUND AND AIMS: Immune checkpoint inhibitor mediated colitis (IMC) is commonly managed with steroids and biologics. We evaluated the efficacy of ustekinumab (UST) in treating IMC refractory to steroids plus infliximab and/or vedolizumab. RESULTS: Nineteen patients were treated with UST for IMC refractory to steroids plus infliximab (57.9%) and/or vedolizumab (94.7%). Most had grade ≥3 diarrhea (84.2%) and colitis with ulceration was present in 42.1%. Thirteen patients (68.4%) attained clinical remission with UST and mean fecal calprotectin levels dropped significantly after treatment (629±101.5 mcg/mg to 92.0±21.7 mcg/mg, p=0.0004). CONCLUSIONS: UST is a promising therapy for treatment of refractory IMC

Investigation of Changing Pore Topology and Porosity during Matrix Acidizing using Different Chelating Agents

Core flooding acidizing experiments on sandstone/carbonate formation are usually performed in the laboratory to observe different physical phenomena and to design acidizing stimulation jobs for the field. During the tests, some key parameters are analyzed such as pore volume required for breakthrough as well as pressure. Hydrochloric acid (HCl) is commonly used in the carbonate matrix acidizing while Mud acid (HF: HCl) is usually applied during the sandstone acidizing to remove damage around the well bore. However, many problems are associated with the application of these acids, such as fast reaction, corrosion and incompatibility of HCl with some minerals (illite). To overcome these problems, chelating agents (HEDTA, EDTA and GLDA) were used in this research. Colton tight sandstone and Guelph Dolomite core samples were used in this study. The experiments usually are defined in terms of porosity, permeability, dissolution and pore topology. Effluent samples were analyzed to determine dissolved iron, sodium, potassium, calcium and other positive ions using Inductively Coupled Plasma (ICP). Meanwhile Nuclear Magnetic Resonance (NMR) was employed to determine porosity and pore structure of the core sample. Core flood experiments on Berea sandstone cores and dolomite samples with dimensions of 1.5 in × 3 in were conducted at a flow rate of 1 cc/min under 150oF temperature. NMR and porosity analysis concluded that applied chemicals are effective in creating fresh pore spaces. ICP analysis concluded that HEDTA showed good ability to chelate calcium, sodium, magnesium, potassium and iron. It can be established from the analysis that HEDTA can increase more amount of permeability as compared to other chelates

The actin-binding ERM protein Moesin binds to and stabilizes microtubules at the cell cortex

Ezrin, Radixin, and Moesin (ERM) proteins play important roles in many cellular processes including cell division. Recent studies have highlighted the implications of their metastatic potential in cancers. ERM’s role in these processes is largely attributed to their ability to link actin filaments to the plasma membrane. In this paper, we show that the ERM protein Moesin directly binds to microtubules in vitro and stabilizes microtubules at the cell cortex in vivo. We identified two evolutionarily conserved residues in the FERM (4.1 protein and ERM) domains of ERMs that mediated the association with microtubules. This ERM–microtubule interaction was required for regulating spindle organization in metaphase and cell shape transformation after anaphase onset but was dispensable for bridging actin filaments to the metaphase cortex. These findings provide a molecular framework for understanding the complex functional interplay between the microtubule and actin cytoskeletons mediated by ERM proteins in mitosis and have broad implications in both physiological and pathological processes that require ERMs

Heavy burden of non-communicable diseases at early age and gender disparities in an adult population of Burkina Faso: world health survey

<p>Abstract</p> <p>Background</p> <p>WHO estimates suggest that age-specific death rates from non-communicable diseases are higher in sub-Saharan Africa than in high-income countries. The objectives of this study were to examine, in Burkina Faso, the prevalence of non-communicable disease symptoms by age, gender, socioeconomic group and setting (rural/urban), and to assess gender and socioeconomic inequalities in the prevalence of these symptoms.</p> <p>Methods</p> <p>We obtained data from the Burkina Faso World Health Survey, which was conducted in an adult population (18 years and over) with a high response rate (4822/4880 selected individuals). The survey used a multi-stage stratified random cluster sampling strategy to identify participants. The survey collected information on socio-demographic and economic characteristics, as well as data on symptoms of a variety of health conditions. Our study focused on joint disease, back pain, angina pectoris, and asthma. We estimated prevalence correcting for the sampling design. We used multiple Poisson regression to estimate associations between non-communicable disease symptoms, gender, socioeconomic status and setting.</p> <p>Results</p> <p>The overall crude prevalence and 95% confidence intervals (CI) were: 16.2% [13.5; 19.2] for joint disease, 24% [21.5; 26.6] for back pain, 17.9% [15.8; 20.2] for angina pectoris, and 11.6% [9.5; 14.2] for asthma. Consistent relationships between age and the prevalence of non-communicable disease symptoms were observed in both men and women from rural and urban settings. There was markedly high prevalence in all conditions studied, starting with young adults. Women presented higher prevalence rates of symptoms than men for all conditions: prevalence ratios and 95% CIs were 1.20 [1.01; 1.43] for joint disease, 1.42 [1.21; 1.66] for back pain, 1.68 [1.39; 2.04] for angina pectoris, and 1.28 [0.99; 1.65] for asthma. Housewives and unemployed women had the highest prevalence rates of non-communicable disease symptoms.</p> <p>Conclusions</p> <p>Our work suggests that social inequality extends into the distribution of non-communicable diseases among social groups and supports the thesis of a differential vulnerability in Burkinabè women. It raises the possibility of an abnormally high rate of premature morbidity that could manifest as a form of premature aging in the adult population. Increased prevention, screening and treatment are needed in Burkina Faso to address high prevalence and gender inequalities in non-communicable diseases.</p

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes1, with epidemiological association with other autoimmune diseases2. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment

Measuring the predictability of life outcomes with a scientific mass collaboration.

How predictable are life trajectories? We investigated this question with a scientific mass collaboration using the common task method; 160 teams built predictive models for six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. Despite using a rich dataset and applying machine-learning methods optimized for prediction, the best predictions were not very accurate and were only slightly better than those from a simple benchmark model. Within each outcome, prediction error was strongly associated with the family being predicted and weakly associated with the technique used to generate the prediction. Overall, these results suggest practical limits to the predictability of life outcomes in some settings and illustrate the value of mass collaborations in the social sciences