Quantifying uncertainty in cost effectiveness analyses

This study compared four alternative approaches (Taylor, Fieller, percentile bootstrap, and bias-corrected bootstrap methods) to estimating confidence intervals (CIs) around cost-effectiveness (CE) ratio. The study consisted of two components: (1) Monte Carlo simulation was conducted to identify characteristics of hypothetical cost-effectiveness data sets which might lead one CI estimation technique to outperform another. These results were matched to the characteristics of an (2) extant data set derived from the National AIDS Demonstration Research (NADR) project. The methods were used to calculate (CIs) for data set. These results were then compared. The main performance criterion in the simulation study was the percentage of times the estimated (CIs) contained the “true” CE. A secondary criterion was the average width of the confidence intervals. For the bootstrap methods, bias was estimated. ^ Simulation results for Taylor and Fieller methods indicated that the CIs estimated using the Taylor series method contained the true CE more often than did those obtained using the Fieller method, but the opposite was true when the correlation was positive and the CV of effectiveness was high for each value of CV of costs. Similarly, the CIs obtained by applying the Taylor series method to the NADR data set were wider than those obtained using the Fieller method for positive correlation values and for values for which the CV of effectiveness were not equal to 30% for each value of the CV of costs. ^ The general trend for the bootstrap methods was that the percentage of times the true CE ratio was contained in CIs was higher for the percentile method for higher values of the CV of effectiveness, given the correlation between average costs and effects and the CV of effectiveness. The results for the data set indicated that the bias corrected CIs were wider than the percentile method CIs. This result was in accordance with the prediction derived from the simulation experiment. ^ Generally, the bootstrap methods are more favorable for parameter specifications investigated in this study. However, the Taylor method is preferred for low CV of effect, and the percentile method is more favorable for higher CV of effect. ^

A serial scheme for minimizing the duration of resource-constrained projects within Microsoft Project

Microsoft Project is one of the most-widely used software packages for project management. For the scheduling of resource-constrained projects, the package applies a priority-based procedure using a specific schedule-generation scheme. This procedure performs relatively poorly when compared against other software packages or state-of-the-art methods for resource-constrained project scheduling. In Microsoft Project 2010, it is possible to work with schedules that are infeasible with respect to the precedence or the resource constraints. We propose a novel schedule-generation scheme that makes use of this possibility. Under this scheme, the project tasks are scheduled sequentially while taking into account all temporal and resource constraints that a user can define within Microsoft Project. The scheme can be implemented as a priority-rule based heuristic procedure. Our computational results for two real-world construction projects indicate that this procedure outperforms the built-in procedure of Microsoft Project

Genetic Engineering of Induced Pluripotent Stem Cells and Reprogramming to Motor Neurons to Elucidate Selective Motor Neuron Death in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease, fatal within 1 to 5 years after onset of symptoms. About 3 out of 100’000 persons are diagnosed with ALS and there is still no cure available [1, 2]. 95% of all cases occur sporadically and the aetiology remains largely unknown [XXXX]. However, up to now 16 genes were identified to play a role in the development of familial ALS. One of these genes is FUS that encodes for the protein fused in sarcoma/translocated in liposarcoma (FUS/TLS). Mutations in this gene are responsible for some cases of sporadic as well as of inherited ALS [3]. FUS belongs to the family of heterogeneous nuclear ribonucleoproteins and is predicted to be involved in several cellular functions like transcription regulation [4], RNA splicing [5, 6], mRNA transport in neurons [7] and microRNA processing [8]. Aberrant accumulation of mutated FUS has been found in the cytoplasm of motor neurons from ALS patients [9]. The mislocalization of FUS is based on a mutation in the nuclear localization signal of FUS [10]. However, it is still unclear if the cytoplasmic localization of FUS leads to a toxic gain of cytoplasmic function and/or a loss of nuclear function that might be crucial in the course of ALS. The goal of this project is to characterize the impact of ALS-associated FUS mutations on in vitro differentiated motor neurons. To this end, we edit the genome of induced pluripotent stem cells (iPSC) using transcription activator-like effector nucleases (TALENs) [11,12] to create three isogenic cell lines, each carrying an ALS-associated FUS mutation (G156E, R244C and P525L). These iPSC’s will then be differentiated to motor neurons according to a recently establishe protocol (Ref Wichterle) and serve to study alterations in the transcriptome, proteome and metabolome upon the expression of ALS-associated FUS. With this approach, we hope to unravel the molecular mechanism leading to FUS-associated ALS and to provide new insight into the emerging connection between misregulation of RNA metabolism and neurodegeneration, a connection that is currently implied in a variety of additional neurological diseases, including spinocerebellar ataxia 2 (SCA-2), spinal muscular atrophy (SMA), fragile X syndrome, and myotonic dystrophy.

Genetic Engineering of Induced Pluripotent Stem Cells and Reprogramming to Motor Neurons to Elucidate Selective Motor Neuron Death in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease, fatal within 1 to 5 years after onset of symptoms. About 3 out of 100’000 persons are diagnosed with ALS and there is still no cure available [1, 2]. 95% of all cases occur sporadically and the aetiology remains largely unknown [3]. However, up to now 16 genes were identified to play a role in the development of familial ALS. One of these genes is FUS that encodes for the protein fused in sarcoma (FUS). Mutations in this gene are responsible for some cases of sporadic as well as of inherited ALS [4]. FUS belongs to the family of heterogeneous nuclear ribonucleoproteins and is predicted to be involved in several cellular functions like transcription regulation, RNA splicing, mRNA transport in neurons and microRNA processing [5] Aberrant accumulation of mutated FUS has been found in the cytoplasm of motor neurons from ALS patients [6]. The mislocalization of FUS is based on a mutation in the nuclear localization signal of FUS [7]. However, it is still unclear if the cytoplasmic localization of FUS leads to a toxic gain of cytoplasmic function and/or a loss of nuclear function that might be crucial in the course of ALS. The goal of this project is to characterize the impact of ALS-associated FUS mutations on in vitro differentiated motor neurons. To this end, we edit the genome of induced pluripotent stem cells (iPSC) using transcription activator-like effector nucleases (TALENs) [8,9] to create three isogenic cell lines, each carrying an ALS-associated FUS mutation (G156E, R244C and P525L). These iPSC’s will then be differentiated to motor neurons according to a recently established protocol [10] and serve to study alterations in the transcriptome, proteome and metabolome upon the expression of ALS-associated FUS. With this approach, we hope to unravel the molecular mechanism leading to FUS-associated ALS and to provide new insight into the emerging connection between misregulation of RNA metabolism and neurodegeneration, a connection that is currently implied in a variety of additional neurological diseases, including spinocerebellar ataxia 2 (SCA-2), spinal muscular atrophy (SMA), fragile X syndrome, and myotonic dystrophy. [1] Cleveland, D.W. et al. (2001) Nat Rev Neurosci 2(11): 806-819 [2] Sathasivam, S. (2010) Singapore Med J 51(5): 367-372 [3] Schymick, J.C. et al. (2007) Hum Mol Genet Vol 16: 233-242 [4] Pratt, A.J. et al. (2012). Degener Neurol Neuromuscul Dis 2012(2): 1-14 [5] Lagier-Tourenne, C. Hum Mol Genet, 2010. 19(R1): p. R46-64 [6] Mochizuki, Y. et al. (2012) J Neurol Sci 323(1-2): 85-92 [7] Dormann, D. et al. (2010) EMBO J 29(16): 2841-2857 [8] Hockemeyer, D. et al. (2011) Nat Biotech 29(8): 731-734 [9] Joung, J.K. and J.D. Sander (2013) Nat Rev Mol Cell Biol 14(1): 49-55 [10]Amoroso, M.W. et al. (2013) J Neurosci 33(2): 574-586.

Land system science and sustainable development of the earth system: A global land project perspective

Land systems are the result of human interactions with the natural environment. Understanding the drivers, state, trends and impacts of different land systems on social and natural processes helps to reveal how changes in the land system affect the functioning of the socio-ecological system as a whole and the tradeoff these changes may represent. The Global Land Project has led advances by synthesizing land systems research across different scales and providing concepts to further understand the feedbacks between social-and environmental systems, between urban and rural environments and between distant world regions. Land system science has moved from a focus on observation of change and understanding the drivers of these changes to a focus on using this understanding to design sustainable transformations through stakeholder engagement and through the concept of land governance. As land use can be seen as the largest geo-engineering project in which mankind has engaged, land system science can act as a platform for integration of insights from different disciplines and for translation of knowledge into action.

On an Application of Microsoft Excel’s Evolutionary Solver to the Resource-Constrained Project Scheduling Problem RCPSP

The Solver Add-in of Microsoft Excel is widely used in courses on Operations Research and in industrial applications. Since the 2010 version of Microsoft Excel, the Solver Add-in comprises a so-called evolutionary solver. We analyze how this metaheuristic can be applied to the resource-constrained project scheduling problem (RCPSP). We present an implementation of a schedule-generation scheme in a spreadsheet, which combined with the evolutionary solver can be used for devising good feasible schedules. Our computational results indicate that using this approach, non-trivial instances of the RCPSP can be (approximately) solved to optimality.

Game Theoretic Bidding Strategies for Auctions in Green Electricity Markets

Electricity markets in the United States presently employ an auction mechanism to determine the dispatch of power generation units. In this market design, generators submit bid prices to a regulation agency for review, and the regulator conducts an auction selection in such a way that satisfies electricity demand. Most regulators currently use an auction selection method that minimizes total offer costs ["bid cost minimization" (BCM)] to determine electric dispatch. However, recent literature has shown that this method may not minimize consumer payments, and it has been shown that an alternative selection method that directly minimizes total consumer payments ["payment cost minimization" (PCM)] may benefit social welfare in the long term. The objective of this project is to further investigate the long term benefit of PCM implementation and determine whether it can provide lower costs to consumers. The two auction selection methods are expressed as linear constraint programs and are implemented in an optimization software package. Methodology for game theoretic bidding simulation is developed using EMCAS, a real-time market simulator. Results of a 30-day simulation showed that PCM reduced energy costs for consumers by 12%. However, this result will be cross-checked in the future with two other methods of bid simulation as proposed in this paper.

Adjustable Art Table Project

An adjustable art table was designed for the artists at Passion Works Studio to fulfill a need for a wheelchair-friendly art table. The client desired that the table be sturdy, not electronic and can be used by multiple users. In response, a mechanical approach was taken and various raising devices were explored. A mechanical height adjustment would make for a more stable table and would not require any electricity or motor to adjust. The table also was built with a large, smooth tabletop designed specifically for multiple users making art. The highlight feature is the height adjustment which allows the table to adjust between 29 and 42.5 inches. The table requires just one person to raise, and two people to lower. To raise the table, an individual only needs to unlock the legs and then press in a button to activate the gas springs, which raise the table. Once the table is set to the desired height, the table can lock into place securely. To lower the table, one person must activate the gas springs and push down simultaneously with another person pushing down on the other side of the table. There is enough room for three people, depending on the size of the wheelchairs. With no wheelchairs, as many as six people can use the table. Therefore, the specifications were met, since it raises and lowers within the desired range, and it provides a solid surface for multiple users to do art work.

Creating Useful Products From Connecticut's 2000 LIDAR Data Set JHR 08-314 Project 07-2

The State of Connecticut owns a LIght Detection and Ranging (LIDAR) data set that was collected in 2000 as part of the State’s periodic aerial reconnaissance missions. Although collected eight years ago, these data are just now becoming ready to be made available to the public. These data constitute a massive “point cloud”, being a long list of east-north-up triplets in the State Plane Coordinate System Zone 0600 (SPCS83 0600), orthometric heights (NAVD 88) in US Survey feet. Unfortunately, point clouds have no structure or organization, and consequently they are not as useful as Triangulated Irregular Networks (TINs), digital elevation models (DEMs), contour maps, slope and aspect layers, curvature layers, among others. The goal of this project was to provide the computational infrastructure to create a first cut of these products and to serve them to the public via the World Wide Web. The products are available at http://clear.uconn.edu/data/ct_lidar/index.htm.

The determinants of improvements in health outcomes and of cost reduction in hospital inpatient care

This study aims to address two research questions. First, ‘Can we identify factors that are determinants both of improved health outcomes and of reduced costs for hospitalized patients with one of six common diagnoses?’ Second, ‘Can we identify other factors that are determinants of improved health outcomes for such hospitalized patients but which are not associated with costs?’ The Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database from 2003 to 2006 was employed in this study. The total study sample consisted of hospitals which had at least 30 patients each year for the given diagnosis: 954 hospitals for acute myocardial infarction (AMI), 1552 hospitals for congestive heart failure (CHF), 1120 hospitals for stroke (STR), 1283 hospitals for gastrointestinal hemorrhage (GIH), 979 hospitals for hip fracture (HIP), and 1716 hospitals for pneumonia (PNE). This study used simultaneous equations models to investigate the determinants of improvement in health outcomes and of cost reduction in hospital inpatient care for these six common diagnoses. In addition, the study used instrumental variables and two-stage least squares random effect model for unbalanced panel data estimation. The study concluded that a few factors were determinants of high quality and low cost. Specifically, high specialty was the determinant of high quality and low costs for CHF patients; small hospital size was the determinant of high quality and low costs for AMI patients. Furthermore, CHF patients who were treated in Midwest, South, and West region hospitals had better health outcomes and lower hospital costs than patients who were treated in Northeast region hospitals. Gastrointestinal hemorrhage and pneumonia patients who were treated in South region hospitals also had better health outcomes and lower hospital costs than patients who were treated in Northeast region hospitals. This study found that six non-cost factors were related to health outcomes for a few diagnoses: hospital volume, percentage emergency room admissions for a given diagnosis, hospital competition, specialty, bed size, and hospital region.^

Concordance between medical records and personal interview in ascertaining breast cancer and diabetes status: Analysis of the south Texas women's health project

Accurate ascertainment of risk factors and disease status is vital in public health research for proper classification of research subjects. The two most common ways of obtaining this data is by self-report and review of medical records (MRs). South Texas Women’s Health Project was a case-control study looking at interrelationships between hormones, diet, and body size and breast cancer among Hispanic women 30-79 years of age. History of breast cancer, diabetes mellitus (DM) and use of DM medications was ascertained from a personal interview. At the time of interview, the subject identified her major health care providers and signed the medical records release form, which was sent to the designated providers. The MRs were reviewed to confirm information obtained from the interview.^ Aim of this study was to determine the sensitivity and specificity between MRs and personal interview in diagnosis of breast cancer, DM and DM treatment. We also wanted to assess how successful our low-cost approach was in obtaining pertinent MRs and what factors influenced the quality of MR or interview data. Study sample was 721 women with both self-report and MR data available by June 2007. Overall response rate for MR requests was 74.5%. MRs were 80.9% sensitive and 100% specific in confirming breast cancer status. Prevalence of DM was 22.7% from the interviews and 16% from MRs. MRs did not provide definite information about DM status of 53.6% subjects. Sensitivity and specificity of MRs for DM status was 88.9% and 90.4% respectively. Disagreement on DM status from the two sources was seen in 15.9% subjects. This discordance was more common among older subjects, those who were married and were predominantly Spanish speaking. Income and level of education did not have a statistically significantly association with this disagreement.^ Both self-report and MRs underestimate the prevalence of DM. Relying solely on MRs leads to greater misclassification than relying on self-report data. MRs have good to excellent specificity and thus serve as a good tool to confirm information obtained from self-report. Self-report and MRs should be used in a complementary manner for accurate assessment of DM and breast cancer status.^

Specialized managed care for children with cystic fibrosis: Resource use patterns and rate design for a high cost Medicaid population

Objective. This research study had two goals: (1) to describe resource consumption patterns for Medi-Cal children with cystic fibrosis, and (2) to explore the feasibility from a rate design perspective of developing specialized managed care plans for such a special needs population.^ Background. Children with special health care needs (CSHN) comprise about 2% of the California Medicaid pediatric population. CSHN have rare but serious health problems, such as cystic fibrosis. Medicaid programs, including Medi-Cal, are enrolling more and more beneficiaries in managed care to control costs. CSHN, however, do not fit the wellness model underlying most managed care plans. Child health advocates believe that both efficiency and quality will suffer if CSHN are removed from regionalized special care centers and scattered among general purpose plans. They believe that CSHN should be "carved out" from enrollment in general plans. One alternative is the Specialized Managed Care Plan, tailored for CSHN.^ Methods. The study population consisted of children under age 21 with CF who were eligible for Medi-Cal and California Children's Services program (CCS) during 1991. Health Care Financing Administration (HCFA) Medicaid Tape-to-Tape data were analyzed as part of a California Children's Hospital Association (CCHA) project.^ Results. Mean Medi-Cal expenditures per month enrolled were $2,302 for 457 CF children, compared to about \$1,270 for all 47,000 CCS special needs children and roughly $60 for almost 2.6 million ``regular needs'' children. For CF children, inpatient care (80\%) and outpatient drugs (9\%) were the major cost drivers, with {\it all\/} outpatient visits comprising only 2\% of expenditures. About one-third of CF children were eligible due to AFDC (Aid to Families with Dependent Children). Age group explained about 17\% of all expenditure variation. Regression analysis was used to select the best capitation rate structure (rate cells by age and eligibility group). Sensitivity analysis estimated moderate financial risk for a statewide plan (360 enrollees), but severe risk for single county implementation due to small numbers of children.^ Conclusions. Study results support the carve out of CSHN due to unique expenditure patterns. The Specialized Managed Care Plan concept appears feasible from a rate design perspective given sufficient enrollees. ^