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This paper is based on observations that competing retailers have the option of either agreeing in advance to transship excess inventory to each other or seeing unsatisfied customers switch to the competitor for a substitute. A transshipment game and a substitution game between competing retailers is studied. After establishing the existence and uniqueness of a pure-strategy Nash equilibrium in retail prices and safety stocks for each game, it is shown that transshipment never leads to a lower retail price and a higher safety stock, so transshipment never leads to a situation that definitely benefits consumers. It is also shown that when the transshipment price is low and competition strong (perhaps because of low retailer differentiation), retailers should prefer consumers substituting. However, when the transshipment price is high and competition weak (with high retailer differentiation), then transshipment benefits them. Transshipment becomes less attractive as competition increases or retailer differentiation decreases. Competitive retailers serving the same market need to be cautious in agreeing to transship because they face larger opportunity costs than retailers serving independent markets. The results provide guidance for management as well as for public policy regarding transshipment in a competitive market. [Supplementary materials are available for this article. Go to the publisher's online edition of IIE Transactions for the following free supplemental resource: Appendix with proofs of statements in Transshipment Between Competing Retailers] [ABSTRACT FROM AUTHOR]

Replenishment and pricing decisions are of great importance to firms. Traditionally replenishment and pricing strategies are determined by separate units of a firm, the former by production and the latter by marketing. In determining these two strategies, firms frequently have to face two challenges. One stems from a lack of coordination between production and marketing, which leads to revenue loss or excess inventory. The other is caused by lack of information when making these two decisions. That is, firms usually have to make decisions when market information is poor. We consider the joint effects of coordination and information when market demand becomes more variable in the sense of a specific mean preserving transformation. We have three main findings. First, when these two strategies are coordinated by the Headquarters (HQ) of the firm, the HQ uses pricing and inventory as two instruments to manage uncertainty. How exactly increasing demand variability affects the decisions depends on the type of demand uncertainty faced. In particular, for additive demand uncertainty, both price and service level decrease in demand variability, whereas for multiplicative demand uncertainty, they both increase in demand variability. Second, the value of information increases with the level of demand variability, suggesting that it is more beneficial to have information when demand is more variable. The impact of demand variability on the value of coordination, however, is indeterminate. Furthermore, perfect information has more value than perfect coordination if and only if demand variability is high. Third, coordinating these two decisions reduces the value of obtaining the demand information and similarly coordination is more valuable when the demand information is unavailable than otherwise. [ABSTRACT FROM AUTHOR]

We have examined the quantity and composition of melanin in both photoprotected (volar upper arm) and chronically photoexposed (dorsal forearm) skin from a range of different ethnic skin types including African, Indian, Mexican, Chinese and European. The most lightly pigmented (European, Chinese and Mexican) skin types have approximately half as much epidermal melanin as the most darkly pigmented (African and Indian) skin types. However, the composition of melanin in these lighter skin types is comparatively more enriched with lightly coloured, alkali-soluble melanin components (up to three-fold). Regardless of ethnicity, epidermal melanin content is significantly greater in chronically photoexposed skin than it is in corresponding photoprotected skin (up to two-fold). However, by comparison there is only a modest enrichment of lightly coloured, alkali soluble melanin components in photoprotected skin (up to 1.3-fold). Analysis of melanosomes extracted from the epidermis in these subjects indicates that the proportion of spheroidal melanosomes is low in all skin types examined (<10%). This suggests that in human skin, pheomelanin is a very minor component of epidermal melanin, even in the lightest (European) skin types. Analysis of melanosome size revealed a significant and progressive variation in size with ethnicity: African skin having the largest melanosomes followed in turn by Indian, Mexican, Chinese and European. On the basis of these findings, we propose that variation in skin pigmentation is strongly influenced by both the amount and the composition (or colour) of the melanin in the epidermis. Variation in melanosome size may also play a significant role. However, the data also suggest that in human skin there are subtle differences in the mechanisms associated with the maintenance of constitutive pigmentation and facultative hyperpigmentation, respectively. [ABSTRACT FROM AUTHOR]

Objective measurements of human skin colour were made with a tristimulus (L *a *b *) chromameter in a range of different ethnic skin types. These were compared with biochemical measurements of melanin content, melanin composition and melanosome size in skin biopsies obtained from the same sites. L *, a * and b * values were found to vary significantly with ethnicity. In general, constitutively dark skin types have lower L * values, higher a * values and higher b * values than constitutively light skin types. Total epidermal melanin content appears to be the primary determinant of L * values in human skin (r =-0.88; P < 0.00001), whilst melanosome size also has a significant but more subtle influence on L * values (r =-0.73; P < 0.00001). There is also a strong positive contribution to a * values from epidermal melanin (r =0.66, P < 0.00001), which accounts for the ethnic variation in a * values observed in this study. Melanin is also a major contributor to b * values in lighter skin types (r =0.71, P < 0.00001). However, this relationship breaks down in darker skin types where b * values actually reach a maximum and then decrease as the concentration of melanin in the skin increases. This appears to be because of optical masking of yellow light by high concentrations of melanin in the epidermis. Analysis of the relationships between L *, a * and b * values in human skin indicate that they are very closely interrelated, and suggest that the optical properties of melanin in the epidermis are very similar to those of a dye on a fabric substrate. [ABSTRACT FROM AUTHOR]

Previous work by Armstrong and Atkins examined age replacement and spare ordering decisions for a system which contained one machine subject to random failure and with only one spare machine in stock or on order at any one time. In this technical note we consider several extensions to that work which generalize the cost terms and the order lead time while retaining the one-machine one-spare structure of the original paper. [ABSTRACT FROM AUTHOR]

A range of fibrous materials, including several types of asbestos and carbon fibres with nano scale diameters that had reported positive genotoxicity data (predominantly clastogenicity), were tested in the in vitro micronucleus test (OECD 487) in GLP-compliant studies in Chinese Hamster Ovary cells. Out of eight materials tested, only one (crocidolite, an asbestos fibre) gave a positive response either in the presence or absence of metabolic activation (S9) and at short (3 h) or extended (24 h) exposure times (p ≤ 0.001). Our data suggest that the commonly used tests for clastogenicity in mammalian cells require extensive modification before fibrous materials are detected as positive, raising questions about the validity of these tests for detecting clastogenic and aneugenic fibrous materials. [ABSTRACT FROM AUTHOR]

Abstract: Vesicles prepared from block copolymers have been mooted for the encapsulation of water-soluble molecules. This is because the membranes of polymer vesicles have been shown to be more stable than those in vesicles formed from lipids, with the membrane properties being tuned by the length and nature of the hydrophobic block in the polymer. The generally accepted mechanisms of vesicle formation involve either wrap-up of a lamellar sheet or formation via a sequence of micelle to worm to disks to vesicles. These should lead to efficient encapsulation. Alternatively, a method involving phase separation followed by re-structuring has been recently suggested. Here, we show that this final mechanism holds for vesicles formed from a PEO-b-PDEAMA copolymer by a pH switch and that this mechanism leads to highly inefficient encapsulation on vesicle formation. [Copyright &y& Elsevier]

PROTEOMEX, an approach which combines conventional proteome analysis with serological screening, is a powerful tool to separate proteins and identify immunogenic components in malignant diseases. By applying this approach, we characterized nine metabolic enzymes which were differentially expressed in renal cell carcinoma (RCC) cell lines and compared their expression profiles to that of normal kidney epithelium cells. Four of these proteins, superoxide dismutase (SODC), triosephosphatase isomerase (TPIS), thioredoxin (THIO) and ubiquitin carboxyl-terminal hydrolase (UBL1) were further analysed for both their constitutive and interferon (IFN)-γ inducible protein expression pattern in cell lines or tissue specimens derived from RCC or normal kidney epithelium using Western blot analysis and immunohistochemistry, respectively. With the exception of the RCC cell line MZ1940RC, which completely lacks the expression of UBL1, a heterogeneous and variable expression pattern of the different metabolic enzymes was detected in RCC and normal renal epithelium. The highest differences in the expression levels were found for THIO in the RCC cell lines, which was 2-fold upregulated when compared to autologous normal kidney epithelium. Moreover, IFN-γ treatment did not influence the constitutive expression of these metabolic enzymes. Thus, PROTEOMEX represents a valuable approach for the identification of metabolic enzymes which might be used as markers for the diagnosis of RCC. [Copyright &y& Elsevier]

Spinal cord injury (SCI) is a devastating event causing lifelong disability that results in a significant decrease in quality of life and immense cost to the health care system, individuals and their families. Providing specialized and timely care can improve recovery and reduce costs, but to make this a reality requires understanding of the current care delivery processes and the care journey. The objective of this focus issue is to examine the current state of health care delivery and discover opportunities to improve access and timing to specialized care for individuals with tSCI. This issue provides an overview of care throughout the SCI continuum and its impact on individuals with tSCI using pan-Canadian data. The issue also presents findings from the RHI Access to Care and Timing (ACT) Project, a multi-center research study involving a multi-disciplinary team of Canadian researchers and clinicians. The initial articles describe the current state of the tSCI care journey including a comparison of environmental barriers, health status, and quality-of-life outcomes between patients living in rural and urban settings. The issue concludes with an article describing the national knowledge translation efforts of using the evidence from the articles published here to inform practice and policy change. Overall, this focus issue will be an excellent reference to guide and optimize evidence informed decision-making in the care of those with tSCI. The evidence can be transferred to care in non-traumatic SCI and other conditions that benefit from timely access to specialized care such as stroke and traumatic brain injury. [ABSTRACT FROM AUTHOR]

Timely access and ongoing delivery of care and therapeutic interventions is needed to maximize recovery and function after traumatic spinal cord injury (tSCI). To ensure these decisions are evidence-based, access to consistent, reliable, and valid sources of clinical data is required. The Access to Care and Timing Model used data from the Rick Hansen SCI Registry (RHSCIR) to generate a simulation of healthcare delivery for persons after tSCI and to test scenarios aimed at improving outcomes and reducing the economic burden of SCI. Through model development, we identified knowledge gaps and challenges in the literature and current health outcomes data collection throughout the continuum of SCI care. The objectives of this article were to describe these gaps and to provide recommendations for bridging them. Accurate information on injury severity after tSCI was hindered by difficulties in conducting neurological assessments and classifications of SCI (e.g., timing), variations in reporting, and the lack of a validated SCI-specific measure of associated injuries. There was also limited availability of reliable data on patient factors such as multi-morbidity and patient-reported measures. Knowledge gaps related to structures (e.g., protocols) and processes (e.g., costs) at each phase of care have prevented comprehensive evaluation of system performance. Addressing these knowledge gaps will enhance comparative and cost-effectiveness evaluations to inform decision-making and standards of care. Recommendations to do so were: standardize data element collection and facilitate database linkages, validate and adopt more outcome measures for SCI, and increase opportunities for collaborations with stakeholders from diverse backgrounds. [ABSTRACT FROM AUTHOR]

Despite the relatively low incidence of traumatic spinal cord injury (tSCI), the management and care of persons with tSCI can be resource intensive and complex, spanning multiple phases of care and disciplines. Using a simulation model built with a system level view of the healthcare system allows for prediction of the impact of interventions on patient and system outcomes from injury through to community reintegration after tSCI. As has been previously described, the Access to Care and Timing (ACT) project developed a simulation model for tSCI care using techniques from operations research. The objective of this article is to briefly describe the methodology and the application of the ACT Model, as it was used in several of the articles in this focus issue. The approaches employed in this model provide a framework to look into the complexity of interactions both within and among the different SCI programs, sites, and phases of care. [ABSTRACT FROM AUTHOR]

Survivors of traumatic spinal cord injury (tSCI) have intense healthcare needs during acute and rehabilitation care and often through the rest of life. To prepare for a growing and aging population, simulation modeling was used to forecast the change in healthcare financial resources and long-term patient outcomes between 2012 and 2032. The model was developed with data from acute and rehabilitation care facilities across Canada participating in the Access to Care and Timing project. Future population and tSCI incidence for 2012 and 2032 were predicted with data from Statistics Canada and the Canadian Institute for Health Information. The projected tSCI incidence for 2012 was validated with actual data from the Rick Hansen SCI Registry of the participating facilities. Using a medium growth scenario, in 2032, the projected median age of persons with tSCI is 57 and persons 61 and older will account for 46% of injuries. Admissions to acute and rehabilitation facilities in 2032 were projected to increase by 31% and 25%, respectively. Because of the demographic shift to an older population, an increase in total population life expectancy with tSCI of 13% was observed despite a 22% increase in total life years lost to tSCI between 2012 and 2032. Care cost increased 54%, and rest of life cost increased 37% in 2032, translating to an additional CAD $16.4 million. With the demographics and management of tSCI changing with an aging population, accurate projections for the increased demand on resources will be critical for decision makers when planning the delivery of healthcare after tSCI. [ABSTRACT FROM AUTHOR]

Costs associated with initial hospitalization following spinal cord injury (SCI) are substantial, and a major driver of costs is the length of stay (LOS); that is, the time that the injured individual remains hospitalized prior to community reintegration. Our aim was to study the factors and variables that contribute to LOS following traumatic SCI. Modeling (process mapping of the SCI healthcare delivery system in Canada and discrete event simulation) and regression analysis using a national registry of individuals with acute traumatic SCI in Canada, existing databases, and peer-reviewed literature were used to examine the driver of LOS following traumatic SCI. In different jurisdictions, there is considerable variation in the definitions and methods used to determine LOS following SCI. System LOS can be subdivided into subcomponents, and progression through these is not unidirectional. Modeling reveals that healthcare organization and processes are important contributors to differences in LOS independent of patient demographics and injury characteristics. Future research is required to identify and improve understanding of contributors to LOS following traumatic SCI. This will help enhance system performance. Work in this area will be facilitated by the adoption of common terminology and definitions, as well as by the use of simulations and modeling. [ABSTRACT FROM AUTHOR]

Background: A patient’s journey through the health care system is influenced by clinical and system processes across the continuum of care. Methods: To inform optimized access to care and patient flow for individuals with traumatic spinal cord injury (tSCI), we developed a simulation model that can examine the full impact of therapeutic or systems interventions across the care continuum for patients with traumatic spinal cord injuries. The objective of this paper is to describe the detailed development of this simulation model for a major trauma and a rehabilitation centre in British Columbia (BC), Canada, as part of the Access to Care and Timing (ACT) project and is referred to as the BC ACT Model V1.0. Findings: To demonstrate the utility of the simulation model in clinical and administrative decision-making we present three typical scenarios that illustrate how an investigator can track the indirect impact(s) of medical and administrative interventions, both upstream and downstream along the continuum of care. For example, the model was used to estimate the theoretical impact of a practice that reduced the incidence of pressure ulcers by 70%. This led to a decrease in acute and rehabilitation length of stay of 4 and 2 days, respectively and a decrease in bed utilization of 9% and 3% in acute and rehabilitation. Conclusion: The scenario analysis using the BC ACT Model V1.0 demonstrates the flexibility and value of the simulation model as a decision-making tool by providing estimates of the effects of different interventions and allowing them to be objectively compared. Future work will involve developing a generalizable national Canadian ACT Model to examine differences in care delivery and identify the ideal attributes of SCI care delivery. [ABSTRACT FROM AUTHOR]

Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant diseases. Although there is a considerable variability in clinical expression, NF1 is almost fully penetrant in adult patients and may be associated with a variety of skeletal anomalies. Spinal deformities are the most common skeletal manifestation, with an incidence estimated from 10–25% in various studies. Some NF1 patients have a dystrophic form of scoliosis, which is characterized by early age at onset and rapid progression. Complications have been reported during spinal instrumentation of dystrophic curves due to soft, non-resistant vertebral bony tissue, suggesting that an alteration of bone quality may occur in NF1 patients. Recent studies have suggested that decreased bone mineral density (BMD) may occur among patients with NF1. We performed a cross-sectional study on 104 adults with NF1, using quantitative ultrasonometry (QUS) to investigate whether decreased BMD is a general phenomenon in NF1 patients. The data reveal that BMD, as measured by age- and gender- adjusted Z-scores, is significantly lower in NF1 patients than in the normal reference population. The decrease in BMD appears to be even more marked among NF1 patients with scoliosis that requires surgical treatment. The findings indicate that NF1 produces a generalized alteration of bone in addition to the focal osseous dysplasias of the vertebrae, tibia, and sphenoid wing that characterize this condition. The pathological mechanism underlying these bony changes remains to be elucidated. [ABSTRACT FROM AUTHOR]

The amino-terminal propeptide of procollagen type III (PIIINP) has been proposed as a marker for fibrogenesis in patients with different fibroproliferative disorders, e.g. liver and lung fibrosis. In this study, serum concentrations of PIIINP were measured by ELISA as a marker for excessive cicatrization in burned patients before and after scar correction. All patients were followed 6 months to determine a new fibrotic reaction during the wound healing process using the Burn Scar Index and to correlate pre- and post-operative concentrations of PIIINP in their sera with the risk to develop a new severe tissue fibrosis leading to pathological scar formation. Furthermore, PIIINP was determined in the excised scar tissue by immunohistochemistry. The study included 38 patients. Nineteen patients (8 female, 11 male, average age 48.3+/-18.9 years) had hypertrophic scars after major burn injury (TBSA, 21+/-12%; Burn Scar Index, 10.4+/-3.7 points) and underwent scar correction. Nineteen patients (12 female, 7 male, average age 42.3+/-25.5 years) who underwent elective plastic-surgical operations served as the control group. Blood samples were drawn immediately before operation, at the 1st, 3rd, 7th, and 14th post-operative days, as well as 1st, 3rd, and 6th months after operation.Pre-operatively, PIIINP was significantly elevated (P<0.05) in burned patients who underwent scar correction. There was a significant increase (P<0.05) of PIIINP in burned patients from 9.8+/-3.7ng/ml pre-operatively to 13.9+/-4.2ng/ml at the 7th post-operation day. Up to 3 months after operation, the 6 months after scar correction concentration remained at a significantly elevated level compared to pre-operative values. The burned patients had a Burn Scar Index of 7.8+/-3.6 points. Pre-operative PIIINP serum concentrations correlated with the Burn Scar Index (r(2)=0.7 and 0.68; P<0.05). Scar tissue stained intensively positive for PIIINP. There was a significant correlation between pre-operative serum values and degree of immunostaining (r(2)=0.45; P<0.05). The increased concentration of PIIINP seen in our burned patients' sera might serve as a marker for the extent of skin fibrosis and for the risk of developing new severe fibrotic reactions after scar correction. [ABSTRACT FROM AUTHOR]

The amino-terminal propeptide of procollagen type III (PIIINP) has been proposed as a marker for fibrogenesis in patients with different fibroproliferative disorders, e.g. liver and lung fibrosis. In this study, serum concentrations of PIIINP were measured by ELISA as a marker for excessive cicatrization in burned patients before and after scar correction. All patients were followed 6 months to determine a new fibrotic reaction during the wound healing process using the Burn Scar Index and to correlate pre- and post-operative concentrations of PIIINP in their sera with the risk to develop a new severe tissue fibrosis leading to pathological scar formation. Furthermore, PIIINP was determined in the excised scar tissue by immunohistochemistry.The study included 38 patients. Nineteen patients (8 female, 11 male, average age 48.3±18.9 years) had hypertrophic scars after major burn injury (TBSA, 21±12%; Burn Scar Index, 10.4±3.7 points) and underwent scar correction. Nineteen patients (12 female, 7 male, average age 42.3±25.5 years) who underwent elective plastic-surgical operations served as the control group. Blood samples were drawn immediately before operation, at the 1st, 3rd, 7th, and 14th post-operative days, as well as 1st, 3rd, and 6th months after operation.Pre-operatively, PIIINP was significantly elevated (P<0.05) in burned patients who underwent scar correction. There was a significant increase (P<0.05) of PIIINP in burned patients from 9.8±3.7 ng/ml pre-operatively to 13.9±4.2 ng/ml at the 7th post-operation day. Up to 3 months after operation, the 6 months after scar correction concentration remained at a significantly elevated level compared to pre-operative values. The burned patients had a Burn Scar Index of 7.8±3.6 points. Pre-operative PIIINP serum concentrations correlated with the Burn Scar Index (r2=0.7 and 0.68; P<0.05). Scar tissue stained intensively positive for PIIINP. There was a significant correlation between pre-operative serum values and degree of immunostaining (r2=0.45; P<0.05).The increased concentration of PIIINP seen in our burned patients’ sera might serve as a marker for the extent of skin fibrosis and for the risk of developing new severe fibrotic reactions after scar correction. [Copyright &y& Elsevier]

Explores the effect of chronic photoexposure on epidermal melanin content and composition in highly pigmented human skin in vivo. Techniques applied in the analysis of melanin content and composition in highly pigmented skin; Description of melanin; Analysis of melanosome morphology; Information on the determinant of human skin color and melanin production in normal human melanocytes.