Downstream Coordination Research Articles

Green pharma supply chain: a review of existing practices and future directions

PurposeThe pharmaceutical industry is facing significant pressure to tackle antimicrobial resistance (AMR). Other ecological, societal and regulatory pressures are also driving the industry to “go green”. While such a (green) transition could be possible through appropriate green practices’ implementation, the present understanding about it is superficial and vague. A key reason is the lack of green practices’-related studies on pharmaceuticals, which are also insufficiently comprehensive. This knowledge gap is sought to be addressed.Design/methodology/approachA systematic literature review (SLR) was conducted with 73 carefully selected articles, then subjected to thematic content analyses for synthesising the relevant themes and sub-themes.FindingsAround 76 operational-level green practices covering all key stakeholders across the drug lifecycle were identified. It was revealed that designing drugs having accelerated environmental degradability is important to combat AMR. Also, redesigning existing drugs is environmentally more resource-intensive than developing new ones with significant cost-saving potential in solvent recycling and flexible manufacturing, both of which are not common at present. With regards to green-related barriers, stringent quality requirements on drugs (and therefore risks in making relevant green-oriented modifications) and time-consuming and costly regulatory approvals were found to be the key ones.Practical implicationsThe operational green practices’ framework developed for individual pharmaceutical supply chain stakeholders could help practitioners in benchmarking, modifying and ultimately, adopting green practices. The findings could also assist policymakers in reframing existing regulations, such as Good Manufacturing Practices or GMP-related, to promote greener drug development.Originality/valueThis work is the first systematic attempt to identify and categorise operational-level green supply chain practices across stakeholders in the pharmaceutical sector.Highlights•Biodegradability of drugs is more important than environmental degradability.•Flexible manufacturing process design (or quality by design) reduces resource wastage.•Ecopharmacovigilance is effective in combating PIE and AMR-related issues.•Upstream and downstream coordination is key to greening pharma operations.•Costly and time-consuming regulatory approval is a key barrier to greening pharma processes.

Prolonged use of a soft diet during early growth and development alters feeding behavior and chewing kinematics in a young animal model.

In infants and children with feeding and swallowing issues, modifying solid foods to form a liquid or puree is used to ensure adequate growth and nutrition. However, the behavioral and neurophysiological effects of prolonged use of this intervention during critical periods of postnatal oral skill development have not been systematically examined, although substantial anecdotal evidence suggests that it negatively impacts downstream feeding motor and coordination skills, possibly due to immature sensorimotor development. Using an established animal model for infant and juvenile feeding physiology, we leverage X-ray reconstruction of moving morphology to compare feeding behavior and kinematics between 12-week-old pigs reared on solid chow (control) and an age- and sex-matched cohort raised on the same chow softened to a liquid. When feeding on two novel foods, almond and apple, maintenance on a soft diet decreases gape cycle duration, resulting in a higher chewing frequency. When feeding on almonds, pigs in this group spent less time ingesting foods compared to controls, and chewing cycles were characterized by less jaw rotation about a dorsoventral axis (yaw) necessary for food reduction. There was also a reduced tendency to alternate chewing side with every chew during almond chewing, a behavioral pattern typical of pigs. These more pronounced impacts on behavior and kinematics during feeding on almonds, a tougher and stiffer food than apples, suggest that food properties mediate the behavioral and physiological impacts of early texture modificationand that the ability to adapt to different food properties may be underdeveloped. In contrast, the limited effects of food texture modification on apple chewing indicate that such intervention/treatment does not alter feeding behavior of less challenging foods. Observed differences cannot be attributed to morphology because texture modification over the treatment period had limited impact on craniodental growth. Short-term impacts of soft-texture modification during postweaning development on feeding dynamics should be considered as potential negative outcomes of this treatment strategy.

Muscles are barely required for the patterning and cell dynamics in axolotl limb regeneration.

Regeneration of a complex appendage structure such as limb requires upstream and downstream coordination of multiple types of cells. Given type of cell may sit at higher upstream position to control the activities of other cells. Muscles are one of the major cell masses in limbs. However, the subtle functional relationship between muscle and other cells in vertebrate complex tissue regeneration are still not well established. Here, we use Pax7 mutant axolotls, in which the limb muscle is developmentally lost, to investigate limb regeneration in the absence of skeletal muscle. We find that the pattern of regenerated limbs is relative normal in Pax7 mutants compared to the controls, but the joint is malformed in the Pax7 mutants. Lack of muscles do not affect the early regeneration responses, specifically the recruitment of macrophages to the wound, as well as the proliferation of fibroblasts, another major population in limbs. Furthermore, using single cell RNA-sequencing, we show that, other than muscle lineage that is mostly missing in Pax7 mutants, the composition and the status of other cell types in completely regenerated limbs of Pax7 mutants are similar to that in the controls. Our study reveals skeletal muscle is barely required for the guidance of other cells, as well the patterning in complex tissue regeneration in axolotls, and provides refined views of the roles of muscle cell in vertebrate appendage regeneration.

Selective Retrieval of Individual Cells from Microfluidic Arrays Combining Dielectrophoretic Force and Directed Hydrodynamic Flow.

Hydrodynamic-based microfluidic platforms enable single-cell arraying and analysis over time. Despite the advantages of established microfluidic systems, long-term analysis and proliferation of cells selected in such devices require off-chip recovery of cells as well as an investigation of on-chip analysis on cell phenotype, requirements still largely unmet. Here, we introduce a device for single-cell isolation, selective retrieval and off-chip recovery. To this end, singularly addressable three-dimensional electrodes are embedded within a microfluidic channel, allowing the selective release of single cells from their trapping site through application of a negative dielectrophoretic (DEP) force. Selective capture and release are carried out in standard culture medium and cells can be subsequently mitigated towards a recovery well using micro-engineered hybrid SU-8/PDMS pneumatic valves. Importantly, transcriptional analysis of recovered cells revealed only marginal alteration of their molecular profile upon DEP application, underscored by minor transcriptional changes induced upon injection into the microfluidic device. Therefore, the established microfluidic system combining targeted DEP manipulation with downstream hydrodynamic coordination of single cells provides a powerful means to handle and manipulate individual cells within one device.

Mount Merapi eruption

PurposeUneven distribution and mistarget beneficiaries are among problems encountered during post-disaster relief operations in 2010 Mount Merapi eruption. The purpose of this paper is to develop an empirically founded agent-based simulation model addressing the evacuation dynamics and to explore coordination mechanism and other promising strategies during last-mile relief delivery.Design/methodology/approachAn agent-based model which was specified and parameterized by empirical research (interviews and survey) was developed to understand the mechanism of individual decision making underlying the evacuation dynamics. A set of model testing was conducted to evaluate confidence level of the model in representing the evacuation dynamics during post-disaster of 2010 Mount Merapi eruption. Three scenarios of last-mile relief delivery at both strategic and operational levels were examined to evaluate quantitatively the effectiveness of the coordination mechanism and to explore other promising strategies.FindingsResults indicate that the empirically founded agent-based modeling was able to reproduce the general pattern of observable Internal Displaced Persons based on government records, both at micro and macro levels, with a statistically non-significant difference. Low hazard perception and leader-following behavior which refuses to evacuate are the two factors responsible for late evacuation. Unsurprisingly, coordination through information sharing results in better performance than without coordination. To deal with both uneven distribution and long-term demand fulfillment, coordination among volunteers during aid distribution (at downstream operation) is not sufficient. The downstream coordination should also be accompanied with coordination between aid centers at the upstream operation. Furthermore, the coordination which is combined with other operational strategies, such as clustering strategy, using small-sized trucks and pre-positioning strategy, seems to be promising. It appears that the combined strategy of coordination and clustering strategy performs best among other combined strategies.Practical implicationsThe significant role of early evacuation and self-evacuation behavior toward efficient evacuation indicates that human factor (i.e. hazard perception and cultural factor) should be considered in designing evacuation plan. Early warning system through both technology and community empowerment is necessary to support early evacuation. The early warning system should also be accompanied with at least 69 percent of the population performing self-evacuation behavior for the effective evacuation. As information sharing through coordination is necessary to avoid redundant efforts, uneven distribution and eventually to reduce unmet demand, the government can act as a coordinating actor to authorize the operation and mobilize the resources. The combination of coordination and another strategy reducing lead time such as clustering analysis, thus increasing responsiveness, is seemly strategy for efficient and effective last-mile relief distribution.Originality/valueLiterature on coordination is dominated by qualitative approach, which is difficult to evaluate its effectiveness quantitatively. Providing realistic setting of the evacuation dynamics in the course of the 2010 Mount Merapi eruption, the empirically founded agent-based model can be used to understand the factors influencing the evacuation dynamics and subsequently to quantitatively examine coordination mechanisms and other potential strategies toward efficient and effective last-mile relief distribution.

Inhibitory-κB Kinase (IKK) α and Nuclear Factor-κB (NFκB)-Inducing Kinase (NIK) as Anti-Cancer Drug Targets.

The cellular kinases inhibitory-κB kinase (IKK) α and Nuclear Factor-κB (NF-κB)-inducing kinase (NIK) are well recognised as key central regulators and drivers of the non-canonical NF-κB cascade and as such dictate the initiation and development of defined transcriptional responses associated with the liberation of p52-RelB and p52-p52 NF-κB dimer complexes. Whilst these kinases and downstream NF-κB complexes transduce pro-inflammatory and growth stimulating signals that contribute to major cellular processes, they also play a key role in the pathogenesis of a number of inflammatory-based conditions and diverse cancer types, which for the latter may be a result of background mutational status. IKKα and NIK, therefore, represent attractive targets for pharmacological intervention. Here, specifically in the cancer setting, we reflect on the potential pathophysiological role(s) of each of these kinases, their associated downstream signalling outcomes and the stimulatory and mutational mechanisms leading to their increased activation. We also consider the downstream coordination of transcriptional events and phenotypic outcomes illustrative of key cancer ‘Hallmarks’ that are now increasingly perceived to be due to the coordinated recruitment of both NF-κB-dependent as well as NF-κB–independent signalling. Furthermore, as these kinases regulate the transition from hormone-dependent to hormone-independent growth in defined tumour subsets, potential tumour reactivation and major cytokine and chemokine species that may have significant bearing upon tumour-stromal communication and tumour microenvironment it reiterates their potential to be drug targets. Therefore, with the emergence of small molecule kinase inhibitors targeting each of these kinases, we consider medicinal chemistry efforts to date and those evolving that may contribute to the development of viable pharmacological intervention strategies to target a variety of tumour types.

삼단계 공급사슬에서의 상류단계 및 하류단계 협력

It is well-known that coordination within a supply chain reduces an inefficiency due to double marginalization in a decentralized chain. We study the effect of coordination in a three-tier supply chain consisting of a supplier, a manufacturer, and a retailer. A manufacturer invests in quality improvement. In this supply chain, coordination may occur between a supplier and a manufacturer (upstream coordination), or between a manufacturer and a retailer (downstream coordination). Using differential games approach, we characterize the equilibrium strategies and profits in three models, i.e., a decentralized supply chain, upstream coordination, and downstream coordination, for a finite planning horizon. We show that, although either type of coordination improves supply chain efficiency, upstream coordination and downstream coordination have different impacts on the equilibrium pricing and quality strategies and the consequent profits.

An evaluation of silver-stage American Eel conspecific chemical cueing during outmigration

American Eel Anguilla rostrata abundance has declined in recent decades, in part because sexually maturing, silver-stage adults, outmigrating from freshwater to oceanic spawning grounds, encounter migratory blockades or perish when passing through active hydroelectric turbines. To help improve downstream passage effectiveness and increase survival rates, the role of silver-stage American Eel conspecific chemical cueing during outmigration was investigated using a new type of bioassay. Inside a laboratory flume, downstream-swimming eels were exposed to both live (putative attractant) and dead (putative repellent) conspecific washings to determine whether their trajectory of downstream movement, level of activity, or time spent inside targeted areas of the arena changed after exposure. Silver eels were not attracted to or repulsed by either odor, as none of five scoring metrics indicated a behavioral response. Results did not support the hypothesis that conspecific chemical cueing is a mechanism for downstream migration coordination or danger avoidance; however responses may not have been readily apparent in this type of assay. Fisheries managers may opt to focus future research on more feasible restoration efforts using alternate experimental designs to remedy this ecological issue.

The Impact of Cross-Unit Coordination and Process Improvement Efforts in Anatomic Pathology: A Systems Perspective.

The impact of coordination and problem solving on health care quality has become increasingly prevalent within the literature. However, few studies have empirically investigated the impact of these factors across organizational boundaries. This was an embedded, single-case study conducted within a large, academic Anatomic Pathology department. We surveyed 96 team members within 18 distinct processing or specialty units within the department and forward the Network Alignment Approach to measure coordination between units. In addition, we measure perceived safety culture and frequency of error in specimen documentation and preparation. Regression results suggest that downstream cross-unit coordination between units (clarity of customer requirements) significantly improves safety culture (P < .001). In addition, within-unit process improvement efforts improved safety culture (P < .001). These 2 factors alone accounted for 30% of the variation in the regression model, with safety culture as our dependent variable. Clarity of customer requirements and process improvement efforts significantly improve safety culture within the system. This approach to understanding and analyzing connections within complex systems provides insight into specific ways that leaders can begin to understand how each unit or department can improve as both a customer and a supplier within the larger system.

A methodology for analyzing shipyard supply chains and supplier selection

Purpose– The purpose of this paper is to focus on shipyard supply chains in order to identify the processes that take place and evaluate the risks associated with suppliers.Design/methodology/approach– For this analysis two methodologies are applied. The first is the understand, document, simplify, optimize, where the first two steps are used for analysing the processes and the documentation of the best practices, which take place in the daily operations. The second tool is Kraljic’s matrix, which is applied for the identification of supplier selection and associated risks.Findings– The analysis shows that strategic co-operations between shipyards suppliers are essential for improved supply chain performance since supplier improvement in terms of lead times and product quality are achieved. It is also seen that the shipyard supply chain performance can be improved by adjusting the best practices to the needs dictated each time by the project’s specifications.Practical implications– The findings provide valuable insights for practitioners, as well as academicians, policy makers and also integrate supplier selection under the supply chain. Managers can acquire reliable information about those suppliers who exhibit best practice.Originality/value– A number of key processes and best practices have been identified, which are essential for the upstream and downstream coordination of the shipyard supply chain. The present work is an approach to evaluating the risks associated with the shipyard’s suppliers and assists in benchmarking their risk profile.

A three-echelon supply chain with price-only contracts and sub-supply chain coordination

This paper studies coordination in a three-echelon supply chain and examines the impact of sub-supply chain coordination (sub-coordination). Our analysis is based on the price-only contracts that are commonly used in practice. The model is of the newsvendor type. We consider the following cases: no coordination between any members of the supply chain (decentralized), coordination between only two members (sub-supply chain coordination) and coordination of the whole supply chain as a benchmark. We explicitly analyze the order quantity and contracting decisions for a decentralized three-echelon supply chain. We compare supply chain efficiency when there is upstream coordination and when there is downstream coordination and show that the former is more efficient than or as efficient as the latter. In our setting, the difference between upstream and downstream sub-supply chain coordination is equivalent to the shortage cost transfer. We find that both the supplier and the retailer would prefer to act alone rather than to coordinate with the manufacturer when sub-supply chain coordination is suggested. This contradiction may partly explain the popularity of price-only contracts in practice. (C) 2012 Elsevier B.V. All rights reserved.

The Differential and Contingent Impact of Concurrency on New Product Development Project Performance: A Holistic Examination*

ABSTRACTThis article comprehensively examines how the four facets of new product development (NPD) concurrency, consisting of process and product concurrency groupings, influence NPD project performance under the five contextual conditions of (i) location of product in family stream, (ii) project size, (iii) stage in the product life cycle, (iv) innovativeness of the product, and (v) predictability of market demand. Using data from a large sample of NPD projects in multiple industries, there is support for this hypothesized four‐faceted structure of concurrency, consisting of process and product concurrency groupings, thereby contributing new knowledge to the concurrency literature. All four facets of concurrency display a contingent impact on NPD project performance, even though individual effects vary according to the specific contextual variable under consideration. In particular, the process concurrency facet of dynamic iterative routines was universally effective across all five contextual variables, while the product concurrency facet of cross‐functional coordination was effective in significantly influencing at least one NPD project measure. This article also reports similar, but less strong, contingency patterns, with respect to the process concurrency facet of the implementation of downstream coordination and the product concurrency facet of the use of computer‐based integrated design tools. Theoretical and practical implications of our results are also offered.

Capacity allocation, ordering, and pricing decisions in a supply chain with demand and supply uncertainties

This paper studies coordinated decisions in a decentralized supply chain that consists of one Original Equipment Manufacturer (OEM), one manufacturer, and one distributor, and possesses uncertainties at both demand and supply sides. These uncertainties emerge, respectively, from random demand the distributor faces and randomness of capacity with which the OEM processes the manufacturer’s outsourced quantity. Sharing supply and demand uncertainty information along the supply chain enables us to develop three models with different coordination efforts—the OEM and manufacturer coordination, the manufacturer and distributor coordination, and the OEM, manufacturer, and distributor coordination—and quantify the coordinated decisions in these three models. Our analysis of these coordination models suggests that coordinating with the OEM improves the manufacturer’s probability of meeting downstream demand and his expected profit, yet coordinating with the manufacturer is not necessarily beneficial to the OEM when downstream coordination is lacking.

A Novel Approach to Fast Eliminating the Characteristic Curves Crossing Problem of Relay Coordination in Radial Subtransmission Networks

A novel approach is presented to solve the coordination problem of overcurrent relays in radial subtransmission networks resulting from the intersection of characteristic curves. Based on the ANSI/IEEE standard characteristic curve equation of digital overcurrent relays, a slope adjustment equation for a selected point on the characteristic curve is derived and then used as the core of a dedicated software program developed to compute the corresponding relay setting with different tap value in order that, passed through the selected point, another curve with steeper slope is chosen and thus able to escape from the crossed position. Finally, with the assistance of the graphical capability of commercial package OneLiner in drawing the upstream and downstream relay coordination curves after adjustment, the curves intersection problem in protection coordination can be readily eliminated. In addition, an actual case of a radial subtransmission network with six buses in Taiwan Power Company is simulated to validate the feasibility of the approach.

Variable coordination of cotranscribed genes in Escherichia coli following antisense repression

BackgroundA majority of bacterial genes belong to tight clusters and operons, which complicates gene functional studies using conventional knock-out methods. Antisense agents can down-regulate the expression of genes without disrupting the genome because they bind mRNA and block its expression. However, it is unclear how antisense inhibition affects expression from genes that are cotranscribed with the target.ResultsTo examine the effects of antisense inhibition on cotranscribed genes, we constructed a plasmid expressing the two reporter genes gfp and DsRed as one transcriptional unit. Incubation with antisense peptide nucleic acid (PNA) targeted to the mRNA start codon region of either the upstream gfp or the downstream DsRed gene resulted in a complete expression discoordination from this artificial construct. The same approach was applied to the three cotranscribed genes in the endogenously expressed lac-operon (lacZ, Y and A) and partial downstream expression coordination was seen when the lacZ start codon was targeted with antisense PNA. Targeting the lacY mRNA start codon region showed no effect on the upstream lacZ gene expression whereas expression from the downstream lacA gene was affected as strongly as the lacY gene. Determination of lacZ and lacY mRNA levels revealed a pattern of reduction that was similar to the Lac-proteins, indicating a relation between translation inhibition and mRNA degradation as a response to antisense PNA treatment.ConclusionThe results show that antisense mediated repression of genes within operons affect cotranscribed genes to a variable degree. Target transcript stability appears to be closely related to inhibition of translation and presumably depends on translating ribosomes protecting the mRNA from intrinsic decay mechanisms. Therefore, for genes within operons and clusters it is likely that the nature of the target transcript will determine the inhibitory effects on cotranscribed genes. Consequently, no simple and specific methods for expression control of a single gene within polycistronic operons are available, and a thorough understanding of mRNA regulation and stability is required to understand the results from both knock-down and knock-out methods used in bacteria.