Barrett's Esophagus and Associated Adenocarcinoma : studies on pathogenesis, clinical staging and cost-utility of cancer treatment

Esophageal and gastroesophageal junction (GEJ) adenocarcinoma is rapidly increasing disease with a pathophysiology connected to oxidative stress. Exact pre-treatment clinical staging is essential for optimal care of this lethal malignancy. The cost-effectiviness of treatment is increasingly important. We measured oxidative metabolism in the distal and proximal esophagus by myeloperoxidase activity (MPA), glutathione content (GSH), and superoxide dismutase (SOD) in 20 patients operated on with Nissen fundoplication and 9 controls during a 4-year follow-up. Further, we assessed the oxidative damage of DNA by 8-hydroxydeoxyguanosine (8-OHdG) in esophageal samples of subjects (13 Barrett s metaplasia, 6 Barrett s esophagus with high-grade dysplasia, 18 adenocarcinoma of the distal esophagus/GEJ, and 14 normal controls). We estimated the accuracy (42 patients) and preoperative prognostic value (55 patients) of PET compared with computed tomography (CT) and endoscopic ultrasound (EUS) in patients with adenocarcinoma of the esophagus/GEJ. Finally, we clarified the specialty-related costs and the utility of either radical (30 patients) or palliative (23 patients) treatment of esophageal/GEJ carcinoma by the 15 D health-related quality-of-life (HRQoL) questionnaire and the survival rate. The cost-utility of radical treatment of esophageal/GEJ carcinoma was investigated using a decision tree analysis model comparing radical, palliative, and hypothetical new treatment. We found elevated oxidative stress ( measured by MPA) and decreased antioxidant defense (measured by GSH) after antireflux surgery. This indicates that antireflux surgery is not a perfect solution for oxidative stress of the esophageal mucosa. Elevated oxidative stress in turn may partly explain why adenocarcinoma of the distal esophagus is found even after successful fundoplication. In GERD patients, proximal esophageal mucosal anti-oxidative defense seems to be defective before and even years after successful antireflux surgery. In addition, antireflux surgery apparently does not change the level of oxidative stress in the proximal esophagus, suggesting that defective mucosal anti-oxidative capacity plays a role in development of oxidative damage to the esophageal mucosa in GERD. In the malignant transformation of Barrett s esophagus an important component appears to be oxidative stress. DNA damage may be mediated by 8-OHdG, which we found to be increased in Barrett s epithelium and in high-grade dysplasia as well as in adenocarcinoma of the esophagus/GEJ compared with controls. The entire esophagus of Barrett s patients suffers from increased oxidative stress ( measured by 8-OhdG). PET is a useful tool in the staging and prognostication of adenocarcinoma of the esophagus/GEJ detecting organ metastases better than CT, although its accuracy in staging of paratumoral and distant lymph nodes is limited. Radical surgery for esophageal/GEJ carcinoma provides the greatest benefit in terms of survival, and its cost-utility appears to be the best of currently available treatments.

Costs and Benefits of a Shared Digital Long-Term Preservation System

This paper describes the cost-benefit analysis of digital long-term preservation (LTP) that was carried out in the context of the Finnish National Digital Library Project (NDL) in 2010. The analysis was based on the assumption that as many as 200 archives, libraries, and museums will share an LTP system. The term ‘system’ shall be understood as encompassing not only information technology, but also human resources, organizational structures, policies and funding mechanisms. The cost analysis shows that an LTP system will incur, over the first 12 years, cumulative costs of €42 million, i.e. an average of €3.5 million per annum. Human resources and investments in information technology are the major cost factors. After the initial stages, the analysis predicts annual costs of circa €4 million. The analysis compared scenarios with and without a shared LTP system. The results indicate that a shared system will have remarkable benefits. At the development and implementation stages, a shared system shows an advantage of €30 million against the alternative scenario consisting of five independent LTP solutions. During the later stages, the advantage is estimated at €10 million per annum. The cumulative cost benefit over the first 12 years would amount to circa €100 million.

A Low-Cost System for Measurement and Spectral Analysis of Motor Acoustic Noise

Workplace noise has become one of the major issues in industry not only because of workers’ health but also due to safety. Electric motors, particularly, inverter fed induction motors emit objectionably high levels of noise. This has led to the emergence of a research area, concerned with measurement and mitigation of the acoustic noise. This paper presents a lowcost option for measurement and spectral analysis of acoustic noise emitted by electric motors. The system consists of an electret microphone, amplifier and filter. It makes use of the windows sound card and associated software for data acquisition and analysis. The measurement system is calibrated using a professional sound level meter. Acoustic noise measurements are made on an induction motor drive using the proposed system as per relevant international standards. These measurements are seen to match closely with those of a professional meter.

U.S. Caribbean fish trap fishery costs and earnings study

Executive Summary: This study describes the socio-economic characteristics of the U.S. Caribbean trap fishery that encompasses the Commonwealth of Puerto Rico and Territory of the U.S. Virgin Islands. In-person interviews were administered to one hundred randomly selected trap fishermen, constituting nearly 25% of the estimated population. The sample was stratified by geographic area and trap tier. The number of traps owned or fished to qualify for a given tier varied by island. In Puerto Rico, tier I consisted of fishermen who had between 1-40 fish traps, tier II was made up of fishermen who possessed between 41 and 100 fish traps, and tier III consisted of fishermen who held in excess of 100 fish traps. In St. Thomas and St. John, tier I was composed of fishermen who held between 1 and 50 fish traps, tier II consisted of fishermen who had between 51-150 fish traps and tier III was made up of fishermen who had in excess of 150 fish traps. Lastly, in St. Croix, tier I was made up of fishermen who had less than 20 fish traps and tier II consisted of fishermen who had 20 or more fish traps. The survey elicited information on household demographics, annual catch and revenue, trap usage, capital investment on vessels and equipment, fixed and variable costs, behavioral response to a hypothetical trap reduction program and the spatial distribution of traps. The study found that 79% of the sampled population was 40 years or older. The typical Crucian trap fisherman was older than their Puerto Rican and St. Thomian and St. Johnian counterparts. Crucian fishermen’s average age was 57 years whereas Puerto Rican fishermen’s average age was 51 years, and St. Thomian and St. Johnian fishermen’s average age was 48 years. As a group, St. Thomian and St. Johnian fishermen had 25 years of fishing experience, and Puerto Rican and Crucian fishermen had 30, and 29 years, respectively. Overall, 90% of the households had at least one dependent. The average number of dependents across islands was even, ranging between 2.8 in the district of St. Thomas and St. John and 3.4 in the district of St. Croix. The percentage utilization of catch for personal or family use was relatively low. Regionally, percentage use of catch for personal or family uses ranged from 2.5% in St. Croix to 3.8% in the St. Thomas and St. John. About 47% of the respondents had a high school degree. The majority of the respondents were highly dependent on commercial fishing for their household income. In St. Croix, commercial fishing made up 83% of the fishermen’s total household income, whereas in St. Thomas and St. John and Puerto Rico it contributed 74% and 68%, respectively. The contribution of fish traps to commercial fishing income ranged from 51% in the lowest trap tier in St. Thomas and St. John to 99% in the highest trap tier in St. Croix. On an island basis, the contribution of fish traps to fishing income was 75% in St. Croix, 61% in St. Thomas and St. John, and 59% in Puerto Rico. The value of fully rigged vessels ranged from $400 to $250,000. Over half of the fleet was worth $10,000 or less. The St. Thomas and St. John fleet reported the highest mean value, averaging $58,518. The Crucian and Puerto Rican fleets were considerably less valuable, averaging $19,831 and $8,652, respectively. The length of the vessels ranged from 14 to 40 feet. Fifty-nine percent of the sampled vessels were at least 23 feet in length. The average length of the St. Thomas and St. John fleet was 28 feet, whereas the fleets based in St. Croix and Puerto Rico averaged 21 feet. The engine’s propulsion ranged from 8 to 400 horsepower (hp). The mean engine power was 208 hp in St. Thomas and St. John, 108 hp in St. Croix, and 77 hp in Puerto Rico. Mechanical trap haulers and depth recorders were the most commonly used on-board equipment. About 55% of the sampled population reported owning mechanical trap haulers. In St. Thomas and St. John, 100% of the respondents had trap haulers compared to 52% in Puerto Rico and 20% in St. Croix. Forty-seven percent of the fishermen surveyed stated having depth recorders. Depth recorders were most common in the St. Thomas and St. John fleet (80%) and least common in the Puerto Rican fleet (37%). The limited presence of emergency position indication radio beacons (EPIRBS) and radar was the norm among the fish trap fleet. Only 8% of the respondents had EPIRBS and only 1% had radar. Interviewees stated that they fished between 1 and 350 fish traps. Puerto Rican respondents fished on average 39 fish traps, in contrast to St. Thomian and St. Johnian and Crucian respondents, who fished 94 and 27 fish traps, respectively. On average, Puerto Rican respondents fished 11 lobster traps, and St. Thomian and St. Johnian respondents fished 46 lobster traps. None of the Crucian respondents fished lobster traps. The number of fish traps built or purchased ranged between 0 and 175, and the number of lobster traps built or bought ranged between 0 and 200. Puerto Rican fishermen on average built or purchased 30 fish traps and 14 lobster traps, and St. Thomian and St. Johnian fishermen built or bought 30 fish traps and 11 lobster traps. Crucian fishermen built or bought 25 fish traps and no lobster traps. As a group, fish trap average life ranged between 1.3 and 5 years, and lobster traps lasted slightly longer, between 1.5 and 6 years. The study found that the chevron or arrowhead style was the most common trap design. Puerto Rican fishermen owned an average of 20 arrowhead traps. St. Thomian and St. Johnian and Crucian fishermen owned an average of 44 and 15 arrowhead fish traps, respectively. The second most popular trap design was the square trap style. Puerto Rican fishermen had an average of 9 square traps, whereas St. Thomian and St. Johnian fishermen had 33 traps and Crucian fishermen had 2 traps. Antillean Z (or S) -traps, rectangular and star traps were also used. Although Z (or S) -traps are considered the most productive trap design, fishermen prefer the smaller-sized arrowhead and square traps because they are easier and less expensive to build, and larger numbers of them can be safely deployed. The cost of a fish trap, complete with rope and buoys, varied significantly due to the wide range of construction materials utilized. On average, arrowhead traps commanded $94 in Puerto Rico, $251 in St. Thomas and St. John, and $119 in St. Croix. The number of trips per week ranged between 1 and 6. However, 72% of the respondents mentioned that they took two trips per week. On average, Puerto Rican fishermen took 2.1 trips per week, St. Thomian and St. Johnian fishermen took 1.4 trips per week, and Crucian fishermen took 2.5 trips per week. Most fishing trips started at dawn and finished early in the afternoon. Over 82% of the trips lasted 8 hours or less. On average, Puerto Rican fishermen hauled 27 fish traps per trip whereas St. Thomian and St. Johnian fishermen and Crucian fishermen hauled 68 and 26 fish traps per trip, respectively. The number of traps per string and soak time varied considerably across islands. In St. Croix, 84% of the respondents had a single trap per line, whereas in St. Thomas and St. John only 10% of the respondents had a single trap per line. Approximately, 43% of Puerto Rican fishermen used a single trap line. St. Thomian and St. Johnian fishermen soaked their traps for 6.9 days while Puerto Rican and Crucian fishermen soaked their traps for 5.7 and 3.6 days, respectively. The heterogeneity of the industry was also evidenced by the various economic surpluses generated. The survey illustrated that higher gross revenues did not necessarily translate into higher net revenues. Our analysis also showed that, on average, vessels in the trap fishery were able to cover their cash outlays, resulting in positive vessel income (i.e., financial profits). In Puerto Rico, annual financial profits ranged from $4,760 in the lowest trap tier to $32,467 in the highest tier, whereas in St. Thomas and St. John annual financial profits ranged from $3,744 in the lowest tier to $13,652 in the highest tier. In St. Croix, annual financial profits ranged between $9,229 and $15,781. The survey also showed that economic profits varied significantly across tiers. Economic profits measure residual income after deducting the remuneration required to keep the various factors of production in their existing employment. In Puerto Rico, annual economic profits ranged from ($9,339) in the lowest trap tier to $ 8,711 in the highest trap tier. In St. Thomas and St. John, annual economic profits ranged from ($7,920) in the highest tier to ($18,486) in the second highest tier. In St. Croix, annual economic profits ranged between ($7,453) to $10,674. The presence of positive financial profits and negative economic profits suggests that higher economic returns could be earned from a societal perspective by redirecting some of these scarce capital and human resources elsewhere in the economy. Furthermore, the presence of negative economic earnings is evidence that the fishery is overcapitalized and that steps need to be taken to ensure the long-run economic viability of the industry. The presence of positive financial returns provides managers with a window of opportunity to adopt policies that will strengthen the biological and economic performance of the fishery while minimizing any adverse impacts on local fishing communities. Finally, the document concludes by detailing how the costs and earnings information could be used to develop economic models that evaluate management proposals. (PDF contains 147 pages)

Statistical and econometric analysis of the treatment of HIV/AIDS

The epidemic of HIV/AIDS in the United States is constantly changing and evolving, starting from patient zero to now an estimated 650,000 to 900,000 Americans infected. The nature and course of HIV changed dramatically with the introduction of antiretrovirals. This discourse examines many different facets of HIV from the beginning where there wasn't any treatment for HIV until the present era of highly active antiretroviral therapy (HAART). By utilizing statistical analysis of clinical data, this paper examines where we were, where we are and projections as to where treatment of HIV/AIDS is headed.

Chapter Two describes the datasets that were used for the analyses. The primary database utilized was collected by myself from an outpatient HIV clinic. The data included dates from 1984 until the present. The second database was from the Multicenter AIDS Cohort Study (MACS) public dataset. The data from the MACS cover the time between 1984 and October 1992. Comparisons are made between both datasets.

Chapter Three discusses where we were. Before the first anti-HIV drugs (called antiretrovirals) were approved, there was no treatment to slow the progression of HIV. The first generation of antiretrovirals, reverse transcriptase inhibitors such as AZT (zidovudine), DDI (didanosine), DDC (zalcitabine), and D4T (stavudine) provided the first treatment for HIV. The first clinical trials showed that these antiretrovirals had a significant impact on increasing patient survival. The trials also showed that patients on these drugs had increased CD4+ T cell counts. Chapter Three examines the distributions of CD4 T cell counts. The results show that the estimated distributions of CD4 T cell counts are distinctly non-Gaussian. Thus distributional assumptions regarding CD4 T cell counts must be taken, into account when performing analyses with this marker. The results also show the estimated CD4 T cell distributions for each disease stage: asymptomatic, symptomatic and AIDS are non-Gaussian. Interestingly, the distribution of CD4 T cell counts for the asymptomatic period is significantly below that of the CD4 T cell distribution for the uninfected population suggesting that even in patients with no outward symptoms of HIV infection, there exists high levels of immunosuppression.

Chapter Four discusses where we are at present. HIV quickly grew resistant to reverse transcriptase inhibitors which were given sequentially as mono or dual therapy. As resistance grew, the positive effects of the reverse transcriptase inhibitors on CD4 T cell counts and survival dissipated. As the old era faded a new era characterized by a new class of drugs and new technology changed the way that we treat HIV-infected patients. Viral load assays were able to quantify the levels of HIV RNA in the blood. By quantifying the viral load, one now had a faster, more direct way to test antiretroviral regimen efficacy. Protease inhibitors, which attacked a different region of HIV than reverse transcriptase inhibitors, when used in combination with other antiretroviral agents were found to dramatically and significantly reduce the HIV RNA levels in the blood. Patients also experienced significant increases in CD4 T cell counts. For the first time in the epidemic, there was hope. It was hypothesized that with HAART, viral levels could be kept so low that the immune system as measured by CD4 T cell counts would be able to recover. If these viral levels could be kept low enough, it would be possible for the immune system to eradicate the virus. The hypothesis of immune reconstitution, that is bringing CD4 T cell counts up to levels seen in uninfected patients, is tested in Chapter Four. It was found that for these patients, there was not enough of a CD4 T cell increase to be consistent with the hypothesis of immune reconstitution.

In Chapter Five, the effectiveness of long-term HAART is analyzed. Survival analysis was conducted on 213 patients on long-term HAART. The primary endpoint was presence of an AIDS defining illness. A high level of clinical failure, or progression to an endpoint, was found.

Chapter Six yields insights into where we are going. New technology such as viral genotypic testing, that looks at the genetic structure of HIV and determines where mutations have occurred, has shown that HIV is capable of producing resistance mutations that confer multiple drug resistance. This section looks at resistance issues and speculates, ceterus parabis, where the state of HIV is going. This section first addresses viral genotype and the correlates of viral load and disease progression. A second analysis looks at patients who have failed their primary attempts at HAART and subsequent salvage therapy. It was found that salvage regimens, efforts to control viral replication through the administration of different combinations of antiretrovirals, were not effective in 90 percent of the population in controlling viral replication. Thus, primary attempts at therapy offer the best change of viral suppression and delay of disease progression. Documentation of transmission of drug-resistant virus suggests that the public health crisis of HIV is far from over. Drug resistant HIV can sustain the epidemic and hamper our efforts to treat HIV infection. The data presented suggest that the decrease in the morbidity and mortality due to HIV/AIDS is transient. Deaths due to HIV will increase and public health officials must prepare for this eventuality unless new treatments become available. These results also underscore the importance of the vaccine effort.

The final chapter looks at the economic issues related to HIV. The direct and indirect costs of treating HIV/AIDS are very high. For the first time in the epidemic, there exists treatment that can actually slow disease progression. The direct costs for HAART are estimated. It is estimated that the direct lifetime costs for treating each HIV infected patient with HAART is between $353,000 to $598,000 depending on how long HAART prolongs life. If one looks at the incremental cost per year of life saved it is only $101,000. This is comparable with the incremental costs per year of life saved from coronary artery bypass surgery.

Policy makers need to be aware that although HAART can delay disease progression, it is not a cure and HIV is not over. The results presented here suggest that the decreases in the morbidity and mortality due to HIV are transient. Policymakers need to be prepared for the eventual increase in AIDS incidence and mortality. Costs associated with HIV/AIDS are also projected to increase. The cost savings seen recently have been from the dramatic decreases in the incidence of AIDS defining opportunistic infections. As patients who have been on HAART the longest start to progress to AIDS, policymakers and insurance companies will find that the cost of treating HIV/AIDS will increase.

Regional IAM: analysis of risk-adjusted costs and benefits of climate policies

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International transport costs and the margins of Intra-Latin American maritime trade.

This paper focuses on the analysis of the relationship between maritime trade and transport cost in Latin America. The analysis is based on disaggregated (SITC 5 digit level) trade data for intra Latin maritime trade routes over the period 1999-2004. The research contributes to the literature by disentangling the effects of transport costs on the range of traded goods (extensive margin) and the traded volumes of goods (intensive margin) of international trade in order to test some of the predictions of the trade theories that introduce firm heterogeneity in productivity, as well as fixed costs of exporting. Recent investigations show that spatial frictions (distance) reduce trade mainly by trimming the number of shipments and that most firms ship only to geographically proximate customers, instead of shipping to many destinations in quantities that decrease in distance. Our analyses confirm these findings and show that the opposite pattern is observed for ad-valorem freight rates that reduce aggregate trade values mainly by reducing the volume of imported goods (intensive margin).

A cluster randomised controlled trial evaluation and cost-effectiveness analysis of the Roots of Empathy schools-based programme for improving social and emotional wellbeing outcomes among 8-9 year olds in Northern Ireland

A substantial body of evidence suggest that well designed school based prevention programmes can be effective in improving a variety of social, health and academic outcomes for children and young people. This poster presents the methodology for evaluating the Roots of Empathy (ROE) programme. ROE is a universal programme delivered on a whole-class basis for one academic year. It consists of 27 lessons that run over a school year and is based around a monthly classroom visit by an infant and parent, typically recruited from the local community, whom the class 'adopts' at the start of the school year. The evaluation aims to evaluate the immediate and longer term impact of ROE on social and emotional wellbeing outcomes among 8-9 year old pupils, as well as evaluate the cost-effectiveness of the programme.