Stimuli-Responsive Microneedle Arrays For On-Demand Drug Delivery

Pulsatile, or “on-demand”, delivery systems have the capability to deliver a therapeutic molecule at the right time/site of action and in the right amount (1). Pulsatile delivery systems present multiple benefits over conventional dosage forms and provide higher patient compliance. The combination of stimuli-responsive materials with the drug delivery capabilities of hydrogel-forming MN arrays (2) opens an interesting area of research. In the present work we describe, a stimuli-responsive hydrogel-forming microneedle (MN) array that enable delivery of a clinically-relevant model drug (ibuprofen) upon application of UV radiation (Figure 1A). MN arrays were prepared using a micromolding technique using a polymer prepared from 2-hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) (Figure 1B). The arrays were loaded with up to 5% (w/w) ibuprofen included in a light-responsible conjugate (3,5-dimethoxybenzoin conjugate) (2). The presence of the conjugate inside the MN arrays was confirmed by Raman spectroscopy measurements. MN arrays were tested in vitro showing that they were able to deliver up to three doses of 50 mg of ibuprofen after application of an optical trigger (wavelength of 365 nm) over a long period of time (up to 160 hours) (Figure 1C and 1D). The work presented here is a probe of concept and a modified version of the system should be used as UV radiation is shown to be the major etiologic agent in the development of skin cancers. Consequently, for future applications of this technology an alternative design should be developed. Based on the previous research dealing with hydrogel forming MN arrays a suitable strategy will be to use hydrogel-forming MN arrays containing a backing layer made with the material described in this work as the drug reservoir (2). Finally, a porous layer of a material that blocks UV radiation should be included between the MN array and the drug reservoir. Therefore radiation can be applied to the system without reaching the skin surface. Therefore after modification, the system described here interesting properties as “on-demand” release system for prolonged periods of time. This technology has potential for use in “on-demand” delivery of a wide range of drugs in a variety of applications relevant to enhanced patient care.

Apple Pollination: Demand Depends on Variety and Supply Depends on Pollinator Identity

Insect pollination underpins apple production but the extent to which different pollinator guilds supply this service, particularly across different apple varieties, is unknown. Such information is essential if appropriate orchard management practices are to be targeted and proportional to the potential benefits pollinator species may provide. Here we use a novel combination of pollinator effectiveness assays (floral visit effectiveness), orchard field surveys (flower visitation rate) and pollinator dependence manipulations (pollinator exclusion experiments) to quantify the supply of pollination services provided by four different pollinator guilds to the production of four commercial varieties of apple. We show that not all pollinators are equally effective at pollinating apples, with hoverflies being less effective than solitary bees and bumblebees, and the relative abundance of different pollinator guilds visiting apple flowers of different varieties varies significantly. Based on this, the taxa specific economic benefits to UK apple production have been established. The contribution of insect pollinators to the economic output in all varieties was estimated to be £92.1M across the UK, with contributions varying widely across taxa: solitary bees (£51.4M), honeybees (£21.4M), bumblebees (£18.6M) and hoverflies (£0.7M). This research highlights the differences in the economic benefits of four insect pollinator guilds to four major apple varieties in the UK. This information is essential to underpin appropriate investment in pollination services management and provides a model that can be used in other entomolophilous crops to improve our understanding of crop pollination ecology.

Responding to Fluctuating Demand for Healthcare Services

The level of demand for healthcare services can fluctuate quite strongly. Indeed, some parts of the healthcare service are renowned for having peaks of demand which challenge capacity. Dealing with fluctuations in demand is a common problem in many service industries. This article examines some of the strategies available for influencing the level of demand, including the use of price, communications and demand analysis. The article also outlines a wide variety of ways in which patients can be encouraged to be more tolerant of waiting to receive service from healthcare professionals. In particular, eight principles of waiting are discussed and illustrated in the context of healthcare services.

Using Information on Unconstrained Student Demand to Improve University Course Schedules

We examine how using information on unconstrained demand can improve operational decisions. Specifically, we examine the widespread problem of developing course schedules in not-for-profit university settings. We investigate the potential benefit of incorporating, into the scheduling process, information on the unconstrained demand of students for courses. Prior to this study, the status quo in our college, like that in a large proportion of university settings, was building the course schedule to avoid time conflicts between required courses and to minimize time conflicts between designated groups of courses, such as electives in a particular area. Compared to the status quo approach, we find that, based on three semester's worth of actual data, an approach that explicitly considers students’ course preferences improves a student-based metric of schedule quality on the order of over 4% (which is the equivalent, in our setting, of improving service for over 20% of students).

Job-demand for Learning, Job-related Learning and Need for Achievement

Individual learning is important, as it is both a precursor and an outcome of learning in organisations. Job-related learning is driven by external factors (e.g., the demands of the job) and internal factors (i.e., the personality of the individual). The study examined whether need for achievement moderates the relationship between job-demand for learning and job-related learning. Data were obtained from 153 full-time, white-collar employees from a range of industries. Hierarchical regression analysis using the product term revealed that need for achievement moderates the relationship between job-demand for learning and job-related learning. Specifically, although job-demand for learning is correlated positively to job-related learning for both the high and the low need for achievement groups, this correlation is stronger amongst the high group. The findings are discussed in terms of their implications for future research and practice.

Production planning, pricing and market coordination for news vendor problem with price dependent demand

Thesis (Ph.D.)--University of Washington, 2016-08

Job-demand for Learning and Job-related Learning: the Mediating Effect of Job Performance Improvement Initiatives

This study examined whether job-performance-improvementinitiatives mediate the relationship between individuals’ job-demand for learning and job-related learning. Data were obtained from 115 full-time employees in a diverse range of occupations. A partial least squares analysis revealed that job-performance-improvement-initiatives mediate partially the effects of job-demand for learning on job-related learning. Several implications for future research and policy are drawn from the findings.

A fuzzy clustering approach to a demand response model

This paper proposes a novel demand response model using a fuzzy subtractive cluster approach. The model development provides support to domestic consumer decisions on controllable loads management, considering consumers' consumption needs and the appropriate load shape or rescheduling in order to achieve possible economic benefits. The model based on fuzzy subtractive clustering method considers clusters of domestic consumption covering an adequate consumption range. Analysis of different scenarios is presented considering available electric power and electric energy prices. Simulation results are presented and conclusions of the proposed demand response model are discussed. (C) 2016 Elsevier Ltd. All rights reserved.

Do you want some cash-back?: assessing the demand for a no-claim rebate life-insurance product

Diseña e implementa un experimento de campo en el Perú rural, con el fin de examinar la sensibilidad de la demanda de los productos de microseguros de vida con la introducción de las devoluciones, que son reembolsos parciales de la prima del seguro cuando no se produce alguna eventualidad en el asegurado. Se encontró que las devoluciones crean mayores niveles de confianza entre el asegurador y el asegurado, lo que promete aumentar la demanda de seguros. Los resultados sugieren que las devoluciones pueden ser productos de innovación atractivos en los países en desarrollo.

THE PRICE SENSITIVITY OF DEMAND FOR HIGHER EDUCATION AMONG NON-TRADITIONAL STUDENTS

This dissertation examines the price sensitivity of demand for higher education among non-traditional students in the United States. Chapter 1 discusses the issues related to the demand for higher education. It presents the recent trends and reviews the literature addressing these issues. A major conclusion that emerges from this chapter is that the price sensitivity of demand for higher education appears to depend on the source of the variation in price and the characteristics of the students who face the price change. The baseline estimate for the price sensitivity of demand is that a $1,000 (in year 2000 dollars) decrease in tuition costs should result in a 4 percentage-point increase in enrollment for the traditional 18- to 24-year-old student. Chapter 2 examines the price sensitivity of demand for higher education for military spouses resulting from variation in tuition due to military-mandated moves across states. The data suggest that a $1,000 (in year 2000 dollars) decrease in the cost of 2-year schools is associated with a 1--1.5 percentage-point increase in the probability of attending college. This estimate is less than half the previous estimates due to in-state tuition price differences faced by the civilian 18- to 24-year-old population on a percentage-point basis. However, this represents a 7--10 percent increase for this population, and the magnitude of this metric is in line with previous estimates. This suggests tuition assistance can be an effective means of increasing enrollment for military spouses, but other barriers to education for this population may also need to be addressed. Chapter 3 examines the impact of a change in the tax treatment of savings set aside for higher education by those who decide to suspend their education and enter the workforce. The taxation of these funds appears to have increased the rate at which these funds are included in an employee's initial contract and the quantity of funds allocated. These results are counterintuitive if the tax preference was the primary reason for the savings plan. However, these results suggest the rationale for the savings plan was to offer targeted additional compensation to recruits with greater negotiating power. Taxation of funds previously set aside did not appear to have a statistically significant impact on their utilization. Point estimates of the price sensitivity of demand from changes in the out-of-pocket costs for higher education induced by the taxation of these funds were small and often not statistically significant. The results from this dissertation show responses to changes in the net cost of college that differ by the source of price variation and the population experiencing them. This is consistent with the previous literature. This dissertation contributes to the literature by providing estimates for the price sensitivity of demand for higher education to previously understudied non-traditional students.

The state and known impacts of fish species transferred to or within continental Africa

Fish introductions have been made from small fish ponds to the largest lakes in Africa. The primary intent of these introductions has been to sustain or increase fish production, although some introductions have been made to develop sport fisheries and to control unwanted organisms. Some of these introductions have fulfilled their objective in the short term, but several of these "successful" introductions have created uncertainties about their long term sustainability. Lates niloticus, Oreochromis niloticus, O. leucostictus, Tilapia melanopleura and T. zilli were introduced into lakes Victoria and Kyoga in 1950s and early 1960s. By the 1980s O. niloticus and O. niloticus dominated the fisheries of these lakes, virtually eliminating a number of endemic fish species. The loss of genetic diversity of the fish in the worlds second largest lake has also been accompanied by a loss of trophic diversity. The transformation of the fish community has, in Lake Victoria coincided with a profound eutrophication (algal blooms, fish kills, hypolimnetic anoxia) which might be related to alterations of the lake's food-web structure. In contrast, the introduction of a planktivore, Limnothrissa miodon into Lake Kivu and the Kariba reservoir has established highly successful fisheries with little documented effect on the pre-existing fish community or trophic ecology of the lakes. The highly endemised species-rich African Great lakes may be particularly sensitive to species introductions and require special consideration and caution when introductions are contemplated because species extinctions, introgressive hybridization and ecosystem alterations may occur following fish introductions.

Effects of Information and Time of Use Pricing on Irish Electricity Demand and Supply

In this dissertation I quantify residential behavior response to interventions designed to reduce electricity demand at different periods of the day. In the first chapter, I examine the effect of information provision coupled with bimonthly billing, monthly billing, and in-home displays, as well as a time-of-use (TOU) pricing scheme to measure consumption over each month of the Irish Consumer Behavior Trial. I find that time-of-use pricing with real time usage information reduces electricity usage up to 8.7 percent during peak times at the start of the trial but the effect decays over the first three months and after three months the in-home display group is indistinguishable from the monthly treatment group. Monthly and bi-monthly billing treatments are not found to be statistically different from another. These findings suggest that increasing billing reports to the monthly level may be more cost effective for electricity generators who wish to decrease expenses and consumption, rather than providing in-home displays. In the following chapter, I examine the response of residential households after exposure to time of use tariffs at different hours of the day. I find that these treatments reduce electricity consumption during peak hours by almost four percent, significantly lowering demand. Within the model, I find evidence of overall conservation in electricity used. In addition, weekday peak reductions appear to carry over to the weekend when peak pricing is not present, suggesting changes in consumer habit. The final chapter of my dissertation imposes a system wide time of use plan to analyze the potential reduction in carbon emissions from load shifting based on the Ireland and Northern Single Electricity Market. I find that CO2 emissions savings are highest during the winter months when load demand is highest and dirtier power plants are scheduled to meet peak demand. TOU pricing allows for shifting in usage from peak usage to off peak usage and this shift in load can be met with cleaner and cheaper generated electricity from imports, high efficiency gas units, and hydro units.

In situ characterization of sediment oxygen demand across the spectrum of non-resuspension to full resuspension with varying bed shear stress

Sediment oxygen demand (SOD) can be a significant oxygen sink in various types of water bodies, particularly slow-moving waters with substantial organic sediment accumulation. In most settings where SOD is a concern, the prevailing hydraulic conditions are such that the impact of sediment resuspension on SOD is not considered. However, in the case of Bubbly Creek in Chicago, Illinois, the prevailing slack water conditions are interrupted by infrequent intervals of very high flow rates associated with pumped combined sewer overflow (CSO) during intense hydrologic events. These events can cause resuspension of the highly organic, nutrient-rich bottom sediments, resulting in precipitous drawdown of dissolved oxygen (DO) in the water column. While many past studies have addressed the dependence of SOD on near-bed velocity and bed shear stress prior to the point of sediment resuspension, there has been limited research that has attempted to characterize the complex and dynamic phenomenon of resuspended-sediment oxygen demand. To address this issue, a new in situ experimental apparatus referred to as the U of I Hydrodynamic SOD Sampler was designed to achieve a broad range of velocities and associated bed shear stresses. This allowed SOD to be analyzed across the spectrum of no sediment resuspension associated with low velocity/ bed shear stress through full sediment resuspension associated with high velocity / bed shear stress. The current study split SOD into two separate components: (1) SODNR is the sediment oxygen demand associated with non-resuspension conditions and is a surface sink calculated using traditional methods to yield a value with units (g/m2/day); and (2) SODR is the oxygen demand associated with resuspension conditions, which is a volumetric sink most accurately characterized using non-traditional methods and units that reflect suspension in the water column (mg/L/day). In the case of resuspension, the suspended sediment concentration was analyzed as a function of bed shear stress, and a formulation was developed to characterize SODR as a function of suspended sediment concentration in a form similar to first-order biochemical oxygen demand (BOD) kinetics with Monod DO term. The results obtained are intended to be implemented into a numerical model containing hydrodynamic, sediment transport, and water quality components to yield oxygen demand varying in both space and time for specific flow events. Such implementation will allow evaluation of proposed Bubbly Creek water quality improvement alternatives which take into account the impact of SOD under various flow conditions. Although the findings were based on experiments specific to the conditions in Bubbly Creek, the techniques and formulations developed in this study should be applicable to similar sites.

Estimating the demand curve for sustainable use of pesticides from contingent-valuation data

Stated-preference valuation techniques are often used to assess consumers' willingness-to-pay for food items produced in farming systems that adopt a sustainable use of pesticides (SUP). We propose an innovative valuation methodology in which dichotomous-choice contingent valuation is used to estimate the demand curve (price-quantity relationship) for such food items where price means price premium for the SUP output, quantity is the probability of choosing SUP and the conventional food product is kept available in the market at the current market price. This methodology can be used to evaluate market differentiation as a policy option to promote the SUP. The methodology is tested with data from a sample of urban consumers of fruits and vegetables in Portugal. The estimated demand curve is used to define the price level maximizing the total premium revenue for the SUP sector as a whole. This optimal level of the price premium is €77.55 (or 163% of the value of the monthly basket of fruits and vegetables at current prices). Adopting the optimal price premium will decrease the number of consumers of SUP food by 54%. The reduction is even higher for low income consumers (80%) leaving them more exposed to the risks of pesticide use.