Stochastic Programming and Distributionally Robust Optimization Approaches for Location and Inventory Prepositioning of Disaster Relief Supplies

In this paper, we study the problem of disaster relief inventory prepositioning under uncertainty. Specifically, we aim to determine where to open warehouses and how much relief item inventory to preposition in each, pre-disaster. During the post-disaster phase, prepositioned items are distributed to demand nodes, and additional items are procured and distributed as needed. There is uncertainty in the (1) disaster level, (2) locations of affected areas, (3) demand of relief items, (4) usable fraction of prepositioned items post-disaster, (5) procurement quantity, and (6) arc capacity. We propose and analyze two-stage stochastic programming (SP) and distributionally robust optimization (DRO) models, assuming known and unknown uncertainty distributions, respectively. The first and second stages correspond to pre- and post-disaster phases, respectively. We propose a Monte Carlo Optimization procedure to solve the SP and a decomposition algorithm to solve the DRO model. To illustrate potential applications of our approaches, we conduct extensive experiments using a hurricane season and an earthquake as case studies. Our results demonstrate the (1) the robustness and superior post-disaster operational performance of the DRO decisions under various distributions compared to SP decisions, especially under misspecified distributions and high variability, (2) the trade-off between considering distributional ambiguity and following distributional belief, and (3) computational efficiency of our approaches

Effects of Geopolitical Strain on Global Pharmaceutical Supply Chain Design and Drug Shortages

Pharmaceutical supply chains are global and exhibit geographic and industrial concentration for some drugs. In this context, geopolitical risk and company decisions threaten drug availability, where countries with low manufacturing capacity are most at risk. We present the first supply chain design model that considers geopolitical strain, i.e., export bans and export ban-induced price increases, and the role of alliances in mitigating those risks. Uncertainty is also included in suppliers, production, and demand. The model takes the company's perspective as a decision-maker looking to locate plants and minimize costs by satisfying worldwide demand. The model is solved by integrating the Sample Average Approximation and L-shaped methods. Our case study is based on vincristine, a generic oncology drug. We find that geopolitical strain may reduce shortages in the short term and affect investment decisions and their outcomes. Bilateral alliances between nations result in minor improvements for the company and drug shortages. The results also reveal disparities in drug access. The global expected shortage at the base case is 21%. For high and upper-middle-income countries, expected shortages are 3.1% and 3.7%. However, expected shortages are 98.7% and 95.2% for low and lower-middle-income countries. New pricing policies may improve drug access

An Optimization Approach to Improve Equitable Access to Local Parks

Local parks are public resources that promote human and environmental welfare. Unfortunately, park inequities are commonplace as historically marginalized groups may have insufficient access. Platforms exist to identify the geographical areas that would benefit from future park improvements. However, these platforms do not include budget, infrastructure, and environmental considerations that are relevant to park location decisions. To support recreational and government agencies in addressing inequities in the distribution and quality of parks, we propose a mixed-integer program that minimizes insufficient access, defined as weighted deviations across multiple categories. We consider an equity-focused min-max objective and an overall objective to minimize total weighted deviations. We apply the model to a case study of Asheville, North Carolina. We conduct extensive data collection to parameterize the model. In policy analyses, we consider the effects of available budget, planning horizons, strategic demographic priorities, and thresholds of access. The model reflects user-defined criteria and goals, and the results suggest that the framework may be generalizable to other cities. This study serves as the first step in the development and incorporation of mathematical modeling to achieve social goals within the recreational setting

Gastric motor and sensory function in health assessed by magnetic resonance imaging: Establishment of reference intervals for the Nottingham test meal in healthy subjects

BACKGROUND Current investigations of gastric emptying rarely identify the cause of symptoms or provide a definitive diagnosis in patients with dyspepsia. This study assessed gastric function by magnetic resonance imaging (MRI) using the modular "Nottingham test meal" (NTM) in healthy volunteers (HVs). METHODS The NTM comprises (a) 400 mL liquid nutrient (0.75 kcal/mL) labeled with Gadolinium-DOTA and (b) an optional solid component (12 agar-beads [0 kcal]). Filling sensations were documented. MRI measurements of gastric volume, emptying, contraction wave frequency, and secretion were obtained using validated methods. KEY RESULTS Gastric function was measured in a population of 73 HVs stratified for age and sex. NTM induced moderate satiety and fullness. Labeled fluid was observed in the small bowel in all subjects after meal ingestion ("early-phase" GE). Secretion was rapid such that postprandial gastric content volume was often greater than meal volume (GCV0 > 400 mL), and there was increasing dilution of the meal during the study (P < 0.001). Gastric half-time was median 66-minutes (95% reference interval 35 to 161-minutes ["late-phase" GE]). The number of intact agar beads in the stomach was 7/12 (58%) at 60-minutes and 1/12 (8%) at 120-minutes. Age, bodyweight and sex had measurable effects on gastric function; however, these were small compared to inter-individual variation for most metrics. CONCLUSIONS AND INFERENCES Reference intervals are presented for MRI measurements of gastric function assessed for the mixed liquid/solid NTM. Studies in patients will determine which metrics are of clinical value and also whether the reference intervals presented here offer optimal diagnostic sensitivity and specificity

Developmental change in look durations predicts later effortful control in toddlers at familial risk for ASD

Background: Difficulties with Executive Functioning (EF) are common in individuals with a range of developmental disorders, including Autism Spectrum Disorder (ASD). Interventions that target underlying mechanisms of EF early in development could be broadly beneficial, but require infant markers of such mechanisms in order to be feasible. Prospective studies of infants at high familial risk (HR) for ASD have revealed a surprising tendency for HR toddlers to show longer epochs of attention to faces than low-risk (LR) controls. In typical development, decreases in look durations towards the end of the first year of life are driven by the development of executive attention – a foundational component of EF. Here, we test the hypothesis that prolonged attention to visual stimuli (including faces) in HR toddlers reflects early differences in the development of executive attention. Methods: In a longitudinal prospective study, we used eye-tracking to record HR and LR infants’ looking behaviour to social and non-social visual stimuli at ages 9 and 15 months. At age 3 years we assessed children with a battery of clinical research measures and collected parental report of Effortful Control (EC) – a temperament trait closely associated with EF and similarly contingent on executive attention. Results: Consistent with previous studies, we found an attenuated reduction in peak look durations to faces between 9 and 15 months for the HR group compared with the LR group, and lower EC amongst the HR-ASD group. In line with our hypothesis, change in peak look duration to faces between 9 and 15 months was negatively associated with EC at age 3. Conclusions: We suggest that for HR toddlers, disruption to the early development of executive attention results in an attenuated reduction in looking time to faces. Effects may be more apparent for faces due to early biases to orient towards them; further, attention difficulties may interact with earlier-emerging differences in social information processing. Our finding that prolonged attention to faces may be an early indicator of disruption to the executive attention system is of potential value in screening for infants at risk for later EF difficulties and for evaluation of intervention outcomes

Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of meier-gorlin syndrome

Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS), a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. These findings suggest that impaired DNA replication could underlie the developmental defects characteristic of these disorders. Here, we show that although origin licensing capacity is impaired in all patient cells with mutations in origin licensing component proteins, this does not correlate with the rate of progression through S phase. Thus, the replicative capacity in MGS patient cells does not correlate with clinical manifestation. However, ORC1-deficient cells from MGS patients and siRNA-mediated depletion of origin licensing proteins also have impaired centrosome and centriole copy number. As a novel and unexpected finding, we show that they also display a striking defect in the rate of formation of primary cilia. We demonstrate that this impacts sonic hedgehog signalling in ORC1-deficient primary fibroblasts. Additionally, reduced growth factor-dependent signaling via primary cilia affects the kinetics of cell cycle progression following cell cycle exit and re-entry, highlighting an unexpected mechanism whereby origin licensing components can influence cell cycle progression. Finally, using a cell-based model, we show that defects in cilia function impair chondroinduction. Our findings raise the possibility that a reduced efficiency in forming cilia could contribute to the clinical features of MGS, particularly the bone development abnormalities, and could provide a new dimension for considering developmental impacts of licensing deficiency

Life and expectations post-kidney transplant: a qualitative analysis of patient responses

Abstract Background The effect of a kidney transplant on a recipient extends beyond the restoration of kidney function. However, there is limited qualitative analysis of recipient perspectives on life following transplantation, particularly in the United States. To understand the full patient experience, it is necessary to understand recipient views on life adjustments after kidney transplantation, medical management, and quality of life. This could lead to improvements in recipient care and sense of well-being. Methods We conducted a paper-based survey from March 23 to October 1, 2015 of 476 kidney transplant recipients at the University of Michigan Health System in Ann Arbor, Michigan. We analyzed their open-ended responses using qualitative research methods. This is a companion analysis to a previous quantitative report on the closed-ended responses to that survey. Results Common themes relating to changes following transplantation included: improvements in quality of life, a return to normalcy, better health and more energy. Concerns included: duration of graft survival, fears about one day returning to dialysis or needing to undergo another kidney transplant, comorbidities, future quality of life, and the cost and quality of their healthcare. Many recipients were grateful for their transplant, but some were anxious about the burdens transplantation placed on their loved ones. Conclusions While most recipients reported meaningful improvements in health and lifestyle after kidney transplantation, a minority of participants experienced declines in energy or health status. Worries about how long the transplant will function, future health, and cost and quality of healthcare are prevalent. Future research could study the effects of providing additional information, programs, and interventions following transplantation that target these concerns. This may better prepare and support kidney recipients and lead to improvements in the patient experience.https://deepblue.lib.umich.edu/bitstream/2027.42/149149/1/12882_2019_Article_1368.pd

The challenges of transferring chronic illness patients to adult care: reflections from pediatric and adult rheumatology at a US academic center

<p>Abstract</p> <p>Background</p> <p>Little is known about the transfer of care process from pediatric to adult rheumatology for patients with chronic rheumatic disease. The purpose of this study is to examine changes in disease status, treatment and health care utilization among adolescents transferring to adult care at the University of California San Francisco (UCSF).</p> <p>Methods</p> <p>We identified 31 eligible subjects who transferred from pediatric to adult rheumatology care at UCSF between 1995–2005. Subject demographics, disease characteristics, disease activity and health care utilization were compared between the year prior to and the year following transfer of care.</p> <p>Results</p> <p>The mean age at the last pediatric rheumatology visit was 19.5 years (17.4–22.0). Subject diagnoses included systemic lupus erythematosus (52%), mixed connective tissue disease (16%), juvenile idiopathic arthritis (16%), antiphospholipid antibody syndrome (13%) and vasculitis (3%). Nearly 30% of subjects were hospitalized for disease treatment or management of flares in the year prior to transfer, and 58% had active disease at the time of transfer. In the post-transfer period, almost 30% of subjects had an increase in disease activity. One patient died in the post-transfer period. The median transfer time between the last pediatric and first adult rheumatology visit was 7.1 months (range 0.7–33.6 months). Missed appointments were common in the both the pre and post transfer period.</p> <p>Conclusion</p> <p>A significant percentage of patients who transfer from pediatric to adult rheumatology care at our center are likely to have active disease at the time of transfer, and disease flares are common during the transfer period. These findings highlight the importance of a seamless transfer of care between rheumatology providers.</p