Modelling Pricing Policy Based on Shelf-Life of Non Homogeneous Available-To-Promise in Fruit Supply Chains

[EN] Fruit Supply Chains (SCs) are influenced by uncontrollable natural factors causing heterogeneity in their products, as regards certain attributes that are relevant to customers and vary over time because of the shelf-life. As a consequence customers should be served not only with the required quantity and due date as usual, but also with the quality, freshness and homogeneity specified in their orders. The order promising process (OPP) is based on the uncommitted availability of homogeneous product quantities in planned lots (ATP) that are uncertain. Therefore, there is a risk of not being reliable in the commitments because of discrepancies between the real and planned homogeneous quantities. Furthermore, due to the shelf-life (SL), serving customers with the freshest product introduce the risk of increasing waste because of the aging process. To efficiently manage these risks, this work proposes a mathematical model for handling the heterogeneous ATP in fruit SCs and a pricing policy based on the product SL in the moment of delivery. In order to illustrate the application of the modelling approach, a short numerical example is introduced. The example evidences a conflictive situation when optimizing the assignation of homogeneous ATP between serving orders with fresh and more valuable product, what could lead to increase the risk of having waste because of expiration, and consequently, more costs and less profit.This research has been supported by the Ministry of Science, Technology and Telecommunications, government of Costa Rica (MICITT), through the program of innovation and human capital for competitiveness (PINN) (PED-019-2015-1).Grillo-Espinoza, H.; Alemany Díaz, MDM.; Ortiz Bas, Á. (2016). Modelling Pricing Policy Based on Shelf-Life of Non Homogeneous Available-To-Promise in Fruit Supply Chains. IFIP Advances in Information and Communication Technology. 480:608-617. https://doi.org/10.1007/978-3-319-45390-3_52S608617480Alarcon, F., Alemany, M.M.E., Lario, F.C., Oltra, R.F.: The lack of homogeneity in the product (LHP) in the ceramic tile industry and its impact on the reallocation of inventories. Boletin Soc. Espanola Ceram. Vidr. 50, 49–57 (2011). doi: 10.3989/cyv.072011Alemany, M.M.E., Grillo, H., Ortiz, A., Fuertes-Miquel, V.S.: A fuzzy model for shortage planning under uncertainty due to lack of homogeneity in planned production lots. Appl. Math. Model. (2015). doi: 10.1016/j.apm.2014.12.057Alemany, M.M.E., Lario, F.-C., Ortiz, A., Gomez, F.: Available-To-Promise modeling for multi-plant manufacturing characterized by lack of homogeneity in the product: an illustration of a ceramic case. Appl. Math. Model. 37, 3380–3398 (2013). doi: 10.1016/j.apm.2012.07.022Blanco, A.M., Masini, G., Petracci, N., Bandoni, J.A.: Operations management of a packaging plant in the fruit industry. J. Food Eng. 70, 299–307 (2005). doi: 10.1016/j.jfoodeng.2004.05.075Grillo, H., Alemany, M.M.E., Ortiz, A.: A review of mathematical models for supporting the order promising process under Lack of Homogeneity in Product and other sources of uncertainty. Comput. Ind. Eng. 91, 239–261 (2016)Kilic, O.A., van Donk, D.P., Wijngaard, J., Tarim, S.A.: Order acceptance in food processing systems with random raw material requirements. Spectrum 32, 905–925 (2010). doi: 10.1007/s00291-010-0213-4Lin, J.T., Hong, I.H., Wu, C.H., Wang, K.S.: A model for batch available-to-promise in order fulfillment processes for TFT-LCD production chains. Comput. Ind. Eng. 59, 720–729 (2010). doi: 10.1016/j.cie.2010.07.026Maihami, R., Karimi, B.: Optimizing the pricing and replenishment policy for non-instantaneous deteriorating items with stochastic demand and promotional efforts. Comput. Oper. Res. 51, 302–312 (2014). doi: 10.1016/j.cor.2014.05.022Mundi, M.I., Alemany, M.M.E., Poler, R., Fuertes-Miquel, V.S.: Fuzzy sets to model master production effectively in Make to Stock companies with Lack of Homogeneity in the Product. Fuzzy Sets Syst. 293, 95–112 (2016). http://dx.doi.org/10.1016/j.fss.2015.06.009Tsao, Y.-C., Sheen, G.-J.: Dynamic pricing, promotion and replenishment policies for a deteriorating item under permissible delay in payments. Part Spec. Issue Top. Real-Time Supply Chain Manag. 35, 3562–3580 (2008). doi: 10.1016/j.cor.2007.01.02

The impact of seasonal operating room closures on wait times for oral cancer surgery

Background Operating room slowdowns occur at specific intervals in the year as a cost-saving measure. We aim to investigate the impact of these slowdowns on the care of oral cavity cancer patients at a Canadian tertiary care centre. Methods A total of 585 oral cavity cancer patients seen between 1999 and 2015 at the London Health Science Centre (lhsc) Head and Neck Multidisciplinary Clinic were included in this study. Operating room hours and patient load from 2006 to 2014 were calculated. Our primary endpoint was the wait time from consultation to definitive surgery. Exposure variables were defined according to wait time intervals occurring during time periods with reduced operating room hours. Results Overall case volume rose significantly from 2006 to 2014 (p \u3c 0.001), while operating room hours remained stable (p = 0.555). Patient wait times for surgery increased from 16.3 days prior to 2003 to 25.5 days in 2015 (p = 0.008). Significant variability in operating room hours was observed by month, with lowest reported for July and August (p = 0.002). The greater the exposure to these months, the more likely patients were to wait longer than 28 days for surgery (odds ratio per day [or]: 1.07, 95% confidence interval [ci]: 1.05 to 1.10, p \u3c 0.001). Individuals seen in consultation preceding a month with below average operating room hours had a higher risk of disease recurrence and/or death (hazard ratio [hr]: 1.59, 95% ci: 1.10 to 2.30, p = 0.014). Conclusions Scheduled reductions in available operating room hours contribute to prolonged wait times and higher disease recurrence. Further work is needed to identify strategies maximizing efficient use of health care resources without negatively affecting patient outcomes

Review of mathematical models for production planning under uncertainty due to lack of homogeneity: proposal of a conceptual model

[EN] Lack of homogeneity in the product (LHP) appears in some production processes that confer heterogeneity in the characteristics of the products obtained. Supply chains with this issue have to classify the product in different homogeneous subsets, whose quantity is uncertain during the production planning process. This paper proposes a generic framework for reviewing in a unified way the literature about production planning models dealing with LHP uncertainty. This analysis allows the identification of similarities among sectors to transfer solutions between them and gaps existing in the literature for further research. The results of the review show: (1) sectors affected by LHP inherent uncertainty, (2) the inherent LHP uncertainty types modelled, and (3) the approaches for modelling LHP uncertainty most widely employed. Finally, we suggest a conceptual model reflecting the aspects to be considered when modelling the production planning in sectors with LHP in an uncertain environment.This research was initiated within the framework of the project funded by the Ministerio de Economía y Competitividad [Ref. DPI2011-23597] entitled ‘Methods and models for operations planning and order management in supply chains characterised by uncertainty in production due to the lack of product uniformity’ (PLANGES-FHP) already finished. After, the project leading to this application has received funding from the European Union’s research and innovation programme under the H2020 Marie Skłodowska-Curie Actions with the grant agreement No 691249, Project entitled ’Enhancing and implementing Knowledge based ICT solutions within high Riskand Uncertain Conditions for Agriculture Production Systems’ (RUC-APS).Mundi, I.; Alemany Díaz, MDM.; Poler, R.; Fuertes-Miquel, VS. (2019). 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González-Araya, M. C. Gripe, and S. V. Rodrıguez. 2014. “A Mixed Integer Linear Program for Operational Planning in a Meat Packing Plant.” Accessed January 15, 2015. http://www.researchgate.net/profile/Victor_Albornoz/publication/268687089_A_Mixed_Integer_Linear_Program_for_Operational_Planning_in_a_Meat_Packing_Plant/links/547382bf0cf29afed60f55c7.pdf.José Alem, D., & Morabito, R. (2012). Production planning in furniture settings via robust optimization. Computers & Operations Research, 39(2), 139-150. doi:10.1016/j.cor.2011.02.022Alemany, M. M. E., Lario, F.-C., Ortiz, A., & Gómez, F. (2013). Available-To-Promise modeling for multi-plant manufacturing characterized by lack of homogeneity in the product: An illustration of a ceramic case. Applied Mathematical Modelling, 37(5), 3380-3398. doi:10.1016/j.apm.2012.07.022Alemany, M., Ortiz, A., & Fuertes-Miquel, V. S. (2018). 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Home parenteral nutrition with an omega-3-fatty-acid-enriched MCT/LCT lipid emulsion in patients with chronic intestinal failure (the HOME study):study protocol for a randomized, controlled, multicenter, international clinical trial

BACKGROUND: Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited. METHODS/DESIGN: The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs. DISCUSSION: Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03282955. Registered on 14 September 2017

Mutational analysis of head and neck squamous cell carcinoma stratified by smoking status.

Smoking has historically been recognized as a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). This study aimed to assess the mutational differences between heavy smokers (\u3e20 pack years) and never smokers among the HNSCC patients within The Cancer Genome Atlas (TCGA). Single nucleotide variation and copy number aberration differences between heavy smokers and never smokers were compared within human papillomavirus-positive (HPV-positive) (n = 67) and HPV-negative (n = 431) TCGA cohorts with HNSCC, and the impact of these mutations on survival were assessed. No genes were differentially mutated between smoking and never-smoking patients with HPV-positive tumors. By contrast, in HPV-negative tumors, NSD1 and COL1A11 were found to be more frequently mutated in heavy smokers, while CASP8 was more frequently altered in never smokers. HPV-negative patients with NSD1 mutations experienced significantly improved overall survival compared with NSD1 WT patients. This improved prognosis was validated in an independent cohort of 77 oral cavity cancer patients and a meta-analysis that included 2 additional data sets (688 total patients, hazard ratio for death 0.44, 95% CI, 0.30-0.65). NSD1 mutations are more common in HPV-negative heavy smokers, define a cohort with favorable prognosis, and may represent a clinically useful biomarker to guide treatment deintensification for HPV-negative patients

A systematic molecular and pharmacologic evaluation of AKT inhibitors reveals new insight into their biological activity.

Background AKT, a critical effector of the phosphoinositide 3-kinase (PI3K) signalling cascade, is an intensely pursued therapeutic target in oncology. Two distinct classes of AKT inhibitors have been in clinical development, ATP-competitive and allosteric. Class-specific differences in drug activity are likely the result of differential structural and conformational requirements governing efficient target binding, which ultimately determine isoform-specific potency, selectivity profiles and activity against clinically relevant AKT mutant variants.Methods We have carried out a systematic evaluation of clinical AKT inhibitors using in vitro pharmacology, molecular profiling and biochemical assays together with structural modelling to better understand the context of drug-specific and drug-class-specific cell-killing activity.Results Our data demonstrate clear differences between ATP-competitive and allosteric AKT inhibitors, including differential effects on non-catalytic activity as measured by a novel functional readout. Surprisingly, we found that some mutations can cause drug resistance in an isoform-selective manner despite high structural conservation across AKT isoforms. Finally, we have derived drug-class-specific phosphoproteomic signatures and used them to identify effective drug combinations.Conclusions These findings illustrate the utility of individual AKT inhibitors, both as drugs and as chemical probes, and the benefit of AKT inhibitor pharmacological diversity in providing a repertoire of context-specific therapeutic options

Surgical preferences of patients at risk of hip fractures: hemiarthroplasty versus total hip arthroplasty

BACKGROUND: The optimal treatment of displaced femoral neck fractures in patients over 60 years is controversial. While much research has focused on the impact of total hip arthroplasty (THA) and hemiarthroplasty (HA) on surgical outcomes, little is known about patient preferences for either alternative. The purpose of this study was to elicit surgical preferences of patients at risk of sustaining hip fracture using a novel decision board. METHODS: We developed a decision board for the surgical management of displaced femoral neck fractures presenting risks and outcomes of HA and THA. The decision board was presented to 81 elderly patients at risk for developing femoral neck fractures identified from an osteoporosis clinic. The participants were faced with the scenario of sustaining a displaced femoral neck fracture and were asked to state their treatment option preference and rationale for operative procedure. RESULTS: Eighty-five percent (85%) of participants were between the age of 60 and 80 years; 89% were female; 88% were Caucasian; and 49% had some post-secondary education. Ninety-three percent (93%; 95% confidence interval [CI], 87-99%) of participants chose THA as their preferred operative choice. Participants identified several factors important to their decision, including the perception of greater walking distance (63%), less residual pain (29%), less reoperative risk (28%) and lower mortality risk (20%) with THA. Participants who preferred HA (7%; 95% CI, 1-13%) did so for perceived less invasiveness (50%), lower dislocation risk (33%), lower infection risk (33%), and shorter operative time (17%). CONCLUSION: The overwhelming majority of patients preferred THA to HA for the treatment of a displaced femoral neck fracture when confronted with risks and outcomes of both procedures on a decision board

Research trends in combinatorial optimization

Acknowledgments This work has been partially funded by the Spanish Ministry of Science, Innovation, and Universities through the project COGDRIVE (DPI2017-86915-C3-3-R). In this context, we would also like to thank the Karlsruhe Institute of Technology. Open access funding enabled and organized by Projekt DEAL.Peer reviewedPublisher PD

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons