An evaluation of vendor selection models from a Total Cost of Ownership perspective.

Many different vendor selection models have been published in the purchasing literature. However there has been no systematic approach to compare the relative efficiency of the systems. In this paper we propose to use the concept of Total Cost of Ownership as a basis for comparing vendor selection models. We illustrate the comparison with real life data set of the purchasing problem of ball bearings at Cockerill Sambre, a Belgian multinational company in the steel industry. Mathematical programming models outperform rating models and multiple item models generate better results than single item models from a Total Cost of Ownership perspective for this specific case study.Evaluation; Models; Selection;

Total cost of ownership purchasing of a service : the case of airline slection at Alcatel Bell.

The multiple objective problem of purchasing for business falls into two broad categories: the purchasing of components for manufacturing and the purchasing of services. Several supplier selection models have been suggested in the literature for the purchasing of production-related components. To our knowledge, no supplier selection model for the purchasing of services has been published. In this paper we elaborate on a mathematical programming model that selects suppliers of a multiple item service and simultaneously determines market shares of the suppliers selected. The methodology is based on the collection of Total Cost of Ownership (TCO) information, quantifying all the costs associated with the purchasing process throughout the entire value chain of the firm. We apply this methodology to the real life case study of selecting airlines for 56 destinations at Alcatel Bell and have obtained TCO savings of 19.5%.Purchasing; Selection; Manufacturing; Models; Mathematical programming; Suppliers;

Client Satisfaction with Tele-Community Based Rehabilitation Services for Low Resource Setting

Introduction. The COVID-19 pandemic forced a sudden shift in the delivery of community-based rehabilitation (CBR) services to online platforms such as tele-CBR. Feedback from community partners is important to determine if these services meet their expectations and to inform if adjustments may be needed for future implementation of CBR services using this mode of service delivery. The purpose of the study is to describe the level of client satisfaction of those who received tele-CBR from a university-led CBR program. Methods. This is a descriptive study using quantitative and qualitative approaches for collecting, analyzing, and integrating information on client satisfaction. Quantitative methods included the review of existing program monitoring forms with numerical ratings. Qualitative methods included key informant interviews of care providers and staff members of a partner organization. The interviews revealed their experiences, challenges, and possible factors affecting the level of satisfaction. Results. All respondents gave high satisfaction ratings with the services received through tele-CBR. Factors such as continuous access to therapy services, learning from an interdisciplinary team, and convenience reflect the usability and acceptability of tele-CBR. Challenges include lack of reliable internet signal, lack of child engagement, high distractibility, and limitation in socialization. Discussion. Study participants were positive about the usefulness of the tele-CBR sessions reinforcing better access to vital therapy interventions during the pandemic. The responses suggest the importance of choice in the mode of service delivery. To improve acceptability, respondents highlighted the need to continue engaging carers in both approaches as complementary services. Service recipients and representatives of the partner organization indicated that tele-CBR services were useful, viable, and acceptable. Tele-CBR has the potential to improve equity and access to therapy services

Immunosuppressive effects of new thiophene-based KV1.3 inhibitors

Voltage-gated potassium channel KV1.3 inhibitors have been shown to be effective in preventing T-cell proliferation and activation by affecting intracellular Ca2+ homeostasis. Here, we present the structure-activity relationship, KV1.3 inhibition, and immunosuppressive effects of new thiophene-based KV1.3 inhibitors with nanomolar potency on K+ current in T-lymphocytes and KV1.3 inhibition on Ltk- cells. The new KV1.3 inhibitor trans-18 inhibited KV1.3 -mediated current in phytohemagglutinin (PHA)-activated T-lymphocytes with an IC50 value of 26.1 nM and in mammalian Ltk- cells with an IC50 value of 230 nM. The KV1.3 inhibitor trans-18 also had nanomolar potency against KV1.3 in Xenopus laevis oocytes (IC50 = 136 nM). The novel thiophene-based KV1.3 inhibitors impaired intracellular Ca2+ signaling as well as T-cell activation, proliferation, and colony formation

Pleiotropic effects of levofloxacin, fluoroquinolone antibiotics, against influenza virus-induced lung injury

© 2015 Enoki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Reactive oxygen species (ROS) and nitric oxide (NO) are major pathogenic molecules produced during viral lung infections, including influenza. While fluoroquinolones are widely used as antimicrobial agents for treating a variety of bacterial infections, including secondary infections associated with the influenza virus, it has been reported that they also function as anti-oxidants against ROS and as a NO regulator. Therefore, we hypothesized that levofloxacin (LVFX), one of the most frequently used fluoroquinolone derivatives, may attenuate pulmonary injuries associated with influenza virus infections by inhibiting the production of ROS species such as hydroxyl radicals and neutrophil-derived NO that is produced during an influenza viral infection. The therapeutic impact of LVFX was examined in a PR8 (H1N1) influenza virus-induced lung injury mouse model. ESR spin-trapping experiments indicated that LVFX showed scavenging activity against neutrophil-derived hydroxyl radicals. LVFX markedly improved the survival rate of mice that were infected with the influenza virus in a dose-dependent manner. In addition, the LVFX treatment resulted in a dose-dependent decrease in the level of 8-hydroxy-2'-deoxyguanosine (a marker of oxidative stress) and nitrotyrosine (a nitrative marker) in the lungs of virus-infected mice, and the nitrite/nitrate ratio (NO metabolites) and IFN-? in BALF. These results indicate that LVFX may be of substantial benefit in the treatment of various acute inflammatory disorders such as influenza virus-induced pneumonia, by inhibiting inflammatory cell responses and suppressing the overproduction of NO in the lungs

Neutrophil Extracellular Traps in Breast Cancer and Beyond: Current Perspectives on NET Stimuli, Thrombosis and Metastasis, and Clinical Utility for Diagnosis and Treatment

Abstract The formation of neutrophil extracellular traps (NETs), known as NETosis, was first observed as a novel immune response to bacterial infection, but has since been found to occur abnormally in a variety of other inflammatory disease states including cancer. Breast cancer is the most commonly diagnosed malignancy in women. In breast cancer, NETosis has been linked to increased disease progression, metastasis, and complications such as venous thromboembolism. NET-targeted therapies have shown success in preclinical cancer models and may prove valuable clinical targets in slowing or halting tumor progression in breast cancer patients. We will briefly outline the mechanisms by which NETs may form in the tumor microenvironment and circulation, including the crosstalk between neutrophils, tumor cells, endothelial cells, and platelets as well as the role of cancer-associated extracellular vesicles in modulating neutrophil behavior and NET extrusion. The prognostic implications of cancer-associated NETosis will be explored in addition to development of novel therapeutics aimed at targeting NET interactions to improve outcomes in patients with breast cancer

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background: Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods: The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results: A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion: Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)