Mitigating the Cost of Anarchy in Supply Chain Systems

In a decentralized two-stage supply chain where a supplier serves a retailer who, in turn, serves end customers, operations decisions based on local incentives often lead to suboptimal system performance. Operating decisions based on local incentives may in such cases lead to a degree of system disorder or anarchy, wherein one party's decisions put the other party and/or the system at a disadvantage. While models and mechanisms for such problem classes have been considered in the literature, little work to date has considered such problems under nonstationary demands and fixed replenishment order costs. This paper models such two-stage problems as a class of Stackelberg games where the supplier announces a set of time-phased ordering costs to the retailer over a discrete time horizon of finite length, and the retailer then creates an order plan, which then serves as the supplier's demand. We provide metrics for characterizing the degree of efficiency (and anarchy) associated with a solution, and provide a set of easily understood and implemented mechanisms that can increase this efficiency and reduce the negative impacts of anarchic decisions

A note on "The Economic Lot Sizing Problem with Inventory Bounds"

In a recent paper, Liu (2008) considers the lot-sizing problem with lower and upper bounds on the inventory levels. He proposes an O(n^2) algorithm for the general problem, and an O(n) algorithm for the special case with non-speculative motives. We show that neither of the algorithms provides an optimal solution in general. Furthermore, we propose a fix for the former algorithm that maintains the O(n^2) complexity

Prenatal diagnosis of isovaleric acidaemia by enzyme and metabolite assay in the first and second trimesters

Isovaleric acidaemia (IVA) is caused by a deficiency of isovaleryl CoA dehydrogenase. The diagnosis can be established biochemically by the demonstration of increased levels of isovalerylglycine (IVG) and 3-hydroxyisovaleric acid in urine and by the deficiency of incorporation of radiolabel from [14C]isovaleric acid in macromolecules in cultured fibroblasts. This paper reports a consecutive series of 24 prenatal diagnoses in pregnancies at high risk, using both methods-metabolite and indirect enzyme assay. Affected fetuses were diagnosed in four pregnancies: three in the second trimester and one recent case in the first trimester. The latter represents the first reported case of a first-trimester diagnosis of IVA by direct analysis of chorionic villi. We also report the first demonstration of strongly accumulated IVG in the amniotic fluid in the 12th week of an affected pregnancy

Early systemic microvascular damage in pigs with atherogenic diabetes mellitus coincides with renal angiopoietin dysbalance

Background: Diabetes mellitus (DM) is associated with a range of microvascular complications including diabetic nephropathy (DN). Microvascular abnormalities in the kidneys are common histopathologic findings in DN, which represent one manifestation of ongoing systemic microvascular damage. Recently, sidestream dark-field (SDF) imaging has emerged as a noninvasive tool that enables one to visualize the microcirculation. In this study, we investigated whether changes in the systemic microvasculature induced by DM and an atherogenic diet correlated spatiotemporally with renal damage. Methods: Atherosclerotic lesion development was triggered in streptozotocin-induced DM pigs (140 mg/kg body weight) by administering an atherogenic diet for approximately 11 months. Fifteen months following induction of DM, microvascular morphology was visualized in control pigs (n = 7), non-diabetic pigs fed an atherogenic diet (ATH, n = 5), and DM pigs fed an atherogenic diet (DM+ATH, n = 5) using SDF imaging of oral mucosal tissue. Subsequently, kidneys were harvested from anethesized pigs and the expression levels of well-established markers for microvascular integrity, such as Angiopoietin-1 (Angpt1) and Angiopoietin-2 (Angpt2) were determined immunohistochemically, while endothelial cell (EC) abundance was determined by immunostaining for von Willebrand factor (vWF). Results: Our study revealed an increase in the capillary tortuosity index in DM+ATH pigs (2.31±0.17) as compared to the control groups (Controls 0.89±0.08 and ATH 1.55±0.11; p<0.05). Kidney biopsies showed marked glomerular lesions consisting of mesangial expansion and podocyte lesions. Furthermore, we observed a disturbed Angpt2/ Angpt1balance in the cortex of the kidney, as evidenced by increased expression of Angpt2 in DM+ATH pigs as compared to Control pigs (p<0.05). Conclusion: In the setting of DM, atherogenesis leads to the augmentation of mucosal capillary tortuosity, indicative of systemic microvascular damage. Concomitantly, a dysbalance in renal angiopoietins was correlated with the development of diabetic nephropathy. As such, our studies strongly suggest that defects in the systemic microvasculature mirror the accumulation of microvascular damage in the kidney

The effect of bioresorbable vascular scaffold implantation on distal coronary endothelial function in dyslipidemic swine with and without diabetes

Background: We studied the effect of bioresorbable vascular scaffold (BVS) implantation on distal coronary endothelial function, in swine on a high fat diet without (HFD) or with diabetes (DM + HFD). Methods: Five DM + HFD and five HFD swine underwent BVS implantation on top of coronary plaques, and were studied six months later. Conduit artery segments >. 5. mm proximal and distal to the scaffold and corresponding control segments of non-scaffolded coronary arteries, as well as segments of small arteries within the flow-territories of scaffolded and non-scaffolded arteries were harvested for in vitro vasoreactivity studies. Results: Conduit segments proximal and distal to the BVS edges showed reduced endothelium-dependent vasodilation as compared to control vessels (p <. 0.01), with distal segments being most prominently affected (p <. 0.01). Endothelial dysfunction was only observed in DM + HFD swine and was principally due to a loss of NO. Endothelium-independent vasodilation and vasoconstriction were unaffected. Surprisingly, segments from the microcirculation distal to the BVS showed enhanced endothelium-dependent vasodilation (p <. 0.01), whereas endothelium-independent vasodilation and vasoconstriction were unaltered. This enhanced vasorelaxation was only observed in DM + HFD swine, and did not appear to be either NO- or EDHF-mediated. Conclusions: Six months of BVS implantation in DM + HFD swine causes NO-mediated endothelial dysfunction in nearby coronary segments, which is accompanied by a, possibly compensatory, increase in endothelial function of the distal microcirculation. Endothelial dysfunction extending into coronary conduit segments beyond the implantation-site, is in agreement with recent reports expressing concern for late scaffold thrombosis and of early BVS failure in diabetic patients

Risk Assessment After a Severe Hospital-Acquired Infection Associated With Carbapenemase-Producing Pseudomonas aeruginosa

__Importance:__ Resistance of gram-negative bacilli to carbapenems is rapidly emerging worldwide. In 2016, the World Health Organization defined the hospital-built environment as a core component of infection prevention and control programs. The hospital-built environment has recently been reported as a source for outbreaks and sporadic transmission events of carbapenemase-producing gram-negative bacilli from the environment to patients. __Objective:__ To assess risk after the identification of an unexpected, severe, and lethal hospital-acquired infection caused by carbapenemase-producing Pseudomonas aeruginosa in a carbapenemase-low endemic setting. __Design, Settings, and Participants:__ A case series study in which a risk assessment was performed on all 11 patients admitted to the combined cardiothoracic surg

Endothelial function rather than endothelial restoration is altered in paclitaxel- as compared to bare metal-, sirolimusand tacrolimus-eluting stents

Aims: Drug eluting stents (DES) are under scrutiny for late stent thrombosis. Impaired re-endothelialisation is proposed as an explanation but coronary and peripheral-artery models disagree. We assessed physical and functional endothelial restoration within bare (BMS), paclitaxel, sirolimus and tacrolimus eluting stents and the distal microvasculature in porcine coronary arteries. Methods and results: Endothelium within and distal to DES and BMS was assessed for stent-strut endothelial-restoration (five days) and endothelial-function (five, 28 days, by eNOS and vWF expression) and by in vitro microvascular function. There were no significant differences (P=0.3) in stent strut endothelial-restoration at five days between DES (76-90%) and BMS (95%). However, the microvasculature distal to PES showed a decreased NO bioavailability at five days, which improved at 28 days. Within the stent, however, PES still showed a reduced eNOS expression at 28 days (P≤0.002). Conclusions: DES in porcine coronary arteries show no significant early differences in re-endothelialisation as compared to BMS. However, PES did affect endothelial function both within and distal to stents. These results extend the concept of delayed healing in DES to include delayed restoration of function rather than endothelial presence as a possible explanation for late unwanted sequelae. Microvascular dysfunction does not predict in-stent delayed endothelialisation in this model