Usulan Konseptual Sistem Distribusi Cross Docking untuk Meminimumkan Biaya Distribusi pada Industri Retail

For retail industry, the distribution system is the main challenge that must be faced by the company. Choosing the right strategy will save unnecessary costs and reduce distribution time. The distribution time is needed to get products to the warehouse and to get them ready for shipping at the distribution centre. If the distribution time is felt to be too long, it might add costs. The objective of the study was to design a conceptual cross docking distribution system to minimize distribution costs and reduce distribution time by focusing on the product distribution inside the distribution center until the products are delivered to each outlet. Designing a conceptual cross docking distribution system consists of transportation costs, retain costs, the amoun to truck necessities, truck schedules, and the safety stock planning. Results from our calculation showed that the company's distribution costs werereduced. That is, the distribution costs were down by 62% compared to the current distribution costs. Based on the result, it is concluded that the conceptual cross docking distribution system designed in the present research successfully answered the existing problems. Kata kunci : Cross Docking, Truck Scheduling, Simulatio

Patient-centred pharmaceutical design to improve acceptability of medicines : similarities and differences in paediatric and geriatric populations

Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Patient acceptability of a medicinal product is a key aspect in the development and prescribing of medicines. Children and older adults differ in many aspects from the other age subsets of population and require particular considerations in medication acceptability. This review highlights the similarities and differences in these two age groups in relation to factors affecting acceptability of medicines. New and conventional formulations of medicines are considered regarding their appropriateness for use in children and older people. Aspects of a formulation that impact acceptability in these patient groups are discussed, including, for example, taste/smell/viscosity of a liquid and size/shape of a tablet. A better understanding of the acceptability of existing formulations highlights opportunities for the development of new and more acceptable medicines and facilitates safe and effective prescribing for the young and older populationsPeer reviewedFinal Published versio

In vivo passage of Salmonella Typhimurium results in minor mutations in the bacterial genome and increases in vitro invasiveness

International audienceAbstractEggs and raw or undercooked egg-containing food items are frequently identified as the bacterial source during epidemiolocal investigation of Salmonella outbreaks. Multi-locus variable number of tandem repeats analysis (MLVA) is a widely used Salmonella typing method enabling the study of diversity within populations of the same serotype. In vivo passage, however, has been linked with changes in MLVA type and more broadly the Salmonella genome. We sought to investigate whether in vivo passage through layer hens had an effect on MLVA type as well as the bacterial genome and whether any mutations affected bacterial virulence. Layer hens were infected with either Salmonella Typhimurium DT9 (03-24-11-11-523) as part of a single infection or were co-infected with an equal amount of Salmonella Mbandaka. Salmonella shedding in both single and co-infected birds was variable over the course of the 16-week experiment. Salmonella Typhimurium and Salmonella Mbandaka were identified in feces of co-infected birds. Salmonella colonies isolated from fecal samples were subtyped using MLVA. A single change in SSTR-6 was observed in Salmonella Typhimurium strains isolated from co-infected birds. Isolates of Salmonella Typhimurium of both the parent (03-24-11-11-523) and modified (03-24-12-11-523) MLVA type were sequenced and compared with the genome of the parent strain. Sequence analysis revealed that in vivo passaging resulted in minor mutation events. Passaged isolates exhibited significantly higher invasiveness in cultured human intestinal epithelial cells than the parent strain. The microevolution observed in this study suggests that changes in MLVA may arise more commonly and may have clinical significance

Differing Alterations of Odor Volatiles among Pathogenic Stimuli

Alterations of the volatile metabolome (the collection of volatiles present in secretions and other emanations) that occur in response to inflammation can be detected by conspecifics and chemometric analyses. Using a model system where mouse urinary metabolites are altered by treatment with lipopolysaccharide (found in the outer cell membrane of gram-negative bacteria), we hypothesized that alteration of body odor volatiles will vary according to the pathogen responsible for inducing the inflammation. We tested this hypothesis by treating mice with different immunogens that engage different immune signaling pathways. Results suggest that alterations of body odor volatiles resulting from inflammation do contain detailed information about the type of pathogen that instigated the inflammation and these differences are not merely dependent on the severity of the inflammatory event. These results are encouraging for the future of differential medical diagnosis of febrile diseases by analysis of the volatile metabolome. In particular, our data support the possibility that bacterial infections can be differentiated from viral infections such that antibiotic drug stewardship could be drastically improved by reducing unneeded treatments with antibiotics

Cytokine contributions to alterations of the volatile metabolome induced by inflammation

Several studies demonstrate that inflammation affects body odor. Volatile signals associated with inflammation induced by pyrogens like LPS are detectable both by conspecifics and chemical analyses. However, little is known about the mechanisms which translate detection of a foreign molecule or pathogen into a unique body odor, or even how unique that odor may be. Here, we utilized C57BL/6J trained mice to identify the odor of LPS-treated conspecifics to investigate potential pathways between LPS-induced inflammation and changes in body odor, as represented by changes in urine odor. We hypothesized that the change in volatile metabolites could be caused directly by the pro-inflammatory cytokine response mediated by TNF or IL-1b, or by the compensatory anti-inflammatory response mediated by IL-10. We found that trained biosensors generalized learned LPS-associated odors to TNF-induced odors, but not to IL-1b or IL-10-induced odors. Analyses of urine volatiles using headspace gas chromatography revealed distinct profiles of volatile compounds for each treatment. Instrumental discrimination relied on a mixture of compounds, including 2-sec-butyl-4,5-dihydrothiazole, cedrol, nonanal, benzaldehyde, acetic acid, 2- ethyl-1-hexanol, and dehydro-exo-brevicomin. Although interpretation of LDA modeling differed from behavioral testing, it does suggest that treatment with TNF, IL-1b, and LPS can be distinguished by their resultant volatile profiles. These findings indicate there is information found in body odors on the presence of specific cytokines. This result is encouraging for the future of disease diagnosis via analysis of volatiles

Sharing an environment with sick conspecifics alters odors of healthy animals

Body odors change with health status and the odors of sick animals can induce avoidance behaviors in healthy conspecifics. Exposure to sickness odors might also alter the physiology of healthy conspecifics and modify the odors they produce. We hypothesized that exposure to odors of sick (but non-infectious) animals would alter the odors of healthy cagemates. To induce sickness, we injected mice with a bacterial endotoxin, lipopolysaccharide. We used behavioral odor discrimination assays and analytical chemistry techniques followed by predictive classification modeling to ask about differences in volatile odorants produced by two types of healthy mice: those cohoused with healthy conspecifics and those cohoused with sick conspecifics. Mice trained in Y-maze behavioral assays to discriminate between the odors of healthy versus sick mice also discriminated between the odors of healthy mice cohoused with sick conspecifics and odors of healthy mice cohoused with healthy conspecifics. Chemical analyses paired with statistical modeling revealed a parallel phenomenon. Urine volatiles of healthy mice cohoused with sick partners were more likely to be classified as those of sick rather than healthy mice based on discriminant model predictions. Sickness-related odors could have cascading effects on neuroendocrine or immune responses of healthy conspecifics, and could affect individual behaviors, social dynamics, and pathogen spread

The SPRED1 Variants Repository for Legius Syndrome

Legius syndrome (LS) is an autosomal dominant disorder caused by germline loss-of-function mutations in the sprouty-related, EVH1 domain containing 1 (SPRED1) gene. The phenotype of LS is multiple café au lait macules (CALM) with other commonly reported manifestations, including intertriginous freckling, lipomas, macrocephaly, and learning disabilities including ADHD and developmental delays. Since the earliest signs of LS and neurofibromatosis type 1 (NF1) syndrome are pigmentary findings, the two are indistinguishable and individuals with LS may meet the National Institutes of Health diagnostic criteria for NF1 syndrome. However, individuals are not known to have an increased risk for developing tumors (compared with NF1 patients). It is therefore important to fully characterize the phenotype differences between NF1 and LS because the prognoses of these two disorders differ greatly. We have developed a mutation database that characterizes the known variants in the SPRED1 gene in an effort to facilitate this process for testing and interpreting results. This database is free to the public and will be updated quarterly

Lower objectively measured physical activity is linked with perceived risk of hypoglycemia in type 1 diabetes

Aims Compare physical activity (PA) levels in adults with and without type 1 diabetes and identify diabetes-specific barriers to PA. Methods Forty-four individuals with type 1 diabetes and 77 non-diabetic controls in the Coronary Artery Calcification in Type 1 Diabetes study wore an accelerometer for 2 weeks. Moderate-to-vigorous physical activity (MVPA) was compared by diabetes status using multiple linear regression. The Barriers to Physical Activity in Type 1 Diabetes questionnaire measured diabetes-specific barriers to PA, and the Clarke hypoglycemia awareness questionnaire measured hypoglycemia frequency. Results Individuals with type 1 diabetes engaged in less MVPA, fewer bouts of MVPA, and spent less time in MVPA bouts per week than individuals without diabetes (all p  0.05). The most common diabetes-specific barrier to PA was risk of hypoglycemia. Individuals with diabetes reporting barriers spent less time in MVPA bouts per week than those not reporting barriers (p = 0.047). Conclusions Individuals with type 1 diabetes engage in less MVPA than those without diabetes despite similar self-reported levels, with the main barrier being perceived risk of hypoglycemia. Adults with type 1 diabetes require guidance to meet current PA guidelines and reduce cardiovascular risk

Constraining Lyman-alpha spatial offsets at 3<z<5.53<z<5.5 from VANDELS slit spectroscopy

We constrain the distribution of spatially offset Lyman-alpha emission (Ly$\alpha$) relative to rest-frame ultraviolet emission in $\sim300$ high redshift ($3<z<5.5$) Lyman-break galaxies (LBGs) exhibiting Ly$\alpha$ emission from VANDELS, a VLT/VIMOS slit-spectroscopic survey of the CANDELS Ultra Deep Survey and Chandra Deep Field South fields (${\simeq0.2}~\mathrm{deg}^2$ total). Because slit spectroscopy compresses two-dimensional spatial information into one spatial dimension, we use Bayesian inference to recover the underlying Ly$\alpha$ spatial offset distribution. We model the distribution using a 2D circular Gaussian, defined by a single parameter $\sigma_{r,\mathrm{Ly}\alpha}$, the standard deviation expressed in polar coordinates. Over the entire redshift range of our sample ($3<z<5.5$), we find $\sigma_{r,\mathrm{Ly}\alpha}=1.70^{+0.09}_{-0.08}$ kpc ($68\%$ conf.), corresponding to $\sim0.25$ arcsec at $\langle z\rangle=4.5$. We also find that $\sigma_{r,\mathrm{Ly}\alpha}$ decreases significantly with redshift. Because Ly$\alpha$ spatial offsets can cause slit-losses, the decrease in $\sigma_{r,\mathrm{Ly}\alpha}$ with redshift can partially explain the increase in the fraction of Ly$\alpha$ emitters observed in the literature over this same interval, although uncertainties are still too large to reach a strong conclusion. If $\sigma_{r,\mathrm{Ly}\alpha}$ continues to decrease into the reionization epoch, then the decrease in Ly$\alpha$ transmission from galaxies observed during this epoch might require an even higher neutral hydrogen fraction than what is currently inferred. Conversely, if spatial offsets increase with the increasing opacity of the IGM, slit losses may explain some of the drop in Ly$\alpha$ transmission observed at $z>6$. Spatially resolved observations of Ly$\alpha$ and UV continuum at $6<z<8$ are needed to settle the issue.Comment: Submitted to MNRA