Ex vivo analysis of T-cell responses to Epstein-Barr virus-encoded oncogene latent membrane protein 1 reveals highly conserved epitope sequences in virus isolates from diverse geographic regions

Epstein-Barr virus (EBV)-encoded oncogene latent membrane protein (LMP) 1, which is consistently expressed in multiple EBV-associated malignancies, has been proposed as a potential target antigen for any future vaccine designed to control these malignancies. However, the high degree of genetic variation in the LMP1 sequence has been considered a major impediment for its use as a potential immunotherapeutic target for the treatment of EBV-associated malignancies. In the present study, we have employed a highly efficient strategy, based on ex vivo functional assays, to conduct an extensive sequence-wide analysis of LMP1-specific T-cell responses in a large panel of healthy virus carriers of diverse ethnic origin and nasopharyngeal carcinoma patients. By comparing the frequencies of T cells specific for overlapping peptides spanning LMP1, we mapped a number of novel HLA class I- and class II-restricted LMP1 T-cell epitopes, including an epitope with dual HLA class I restriction. More importantly, extensive sequence analysis of LMP1 revealed that the majority of the T-cell epitopes were highly conserved in EBV isolates from Caucasian, Papua New Guinean, African, and Southeast Asian populations, while unique geographically constrained genetic variation was observed within one HLA A2 supertype-restricted epitope. These findings indicate that conserved LMP1 epitopes should be considered in designing epitope-based immunotherapeutic strategies against EBV-associated malignancies in different ethnic populations.

On the economic analysis of response to preventive measures

There are many circumstances in which the effectiveness of preventive measures depends to a large extent on the compliance of the patient in changing his or her behavior or lifestyle. It is shown how economic techniques can be used (i) to describe the rationale of individuals and predict their behavior (Section 2); and (ii) to assess preventive measures that, by requiring a change of conduct, imply "costs" to the individual due to a decline in the quality of life (Appendix). Cigarette smoking and coronary heart disease are used as an illustration. While the analysis of Section 2 uses graphical techniques, a simple textbook-type of lifetime utility model with a mathematical emphasis is used in the Appendix. It is also shown that techniques often used to assess health care programs such as the QALYs (Quality-Adjusted Life Years) are inappropriate to the evaluation of preventive programs aiming at behavioral changes. Finally, topics that call for further research are indicated.

Exploratory analysis of OpenStreetMap for land use classification

In the last years, volunteers have been contributing massively to what we know nowadays as Volunteered Geographic Information. This huge amount of data might be hiding a vast geographical richness and therefore research needs to be conducted to explore their potential and use it in the solution of real world problems. In this study we conduct an exploratory analysis of data from the OpenStreetMap initiative. Using the Corine Land Cover database as reference and continental Portugal as the study area, we establish a possible correspondence between both classification nomenclatures, evaluate the quality of OpenStreetMap polygon features classification against Corine Land Cover classes from level 1 nomenclature, and analyze the spatial distribution of OpenStreetMap classes over continental Portugal. A global classification accuracy around 76% and interesting coverage areas’ values are remarkable and promising results that encourages us for future research on this topic.

Quality control and conduct of genome-wide association meta-analyses.

Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.

Data Envelopment Analysis (DEA) : A pedagogical guide for decision makers in the public sector

This guide introduces Data Envelopment Analysis (DEA), a performance measurement technique, in such a way as to be appropriate to decision makers with little or no background in economics and operational research. The use of mathematics is kept to a minimum. This guide therefore adopts a strong practical approach in order to allow decision makers to conduct their own efficiency analysis and to easily interpret results. DEA helps decision makers for the following reasons: - By calculating an efficiency score, it indicates if a firm is efficient or has capacity for improvement. - By setting target values for input and output, it calculates how much input must be decreased or output increased in order to become efficient. - By identifying the nature of returns to scale, it indicates if a firm has to decrease or increase its scale (or size) in order to minimize the average cost. - By identifying a set of benchmarks, it specifies which other firms' processes need to be analysed in order to improve its own practices.

A Sensitivity analysis of poverty definitions

We conduct a sensitivity analysis of several estimators related to household income, to explore how some details of the definitions of the variables concerned influence the values of the common estimates, such as the mean, median and (poverty) rates. The purpose of this study is to highlight that some of the operational definitions entail an element of arbitrariness which leaves an undesirable stamp on the inferences made. The analyses use both a cross-sectional and a longitudinal (panel) component of the EU-SILC database.

A correlation sensitivity analysis of non-life underwriting risk in solvency capital requirement estimation

This paper analyses the impact of using different correlation assumptions between lines of business when estimating the risk-based capital reserve, the Solvency Capital Requirement (SCR), under Solvency II regulations. A case study is presented and the SCR is calculated according to the Standard Model approach. Alternatively, the requirement is then calculated using an Internal Model based on a Monte Carlo simulation of the net underwriting result at a one-year horizon, with copulas being used to model the dependence between lines of business. To address the impact of these model assumptions on the SCR we conduct a sensitivity analysis. We examine changes in the correlation matrix between lines of business and address the choice of copulas. Drawing on aggregate historical data from the Spanish non-life insurance market between 2000 and 2009, we conclude that modifications of the correlation and dependence assumptions have a significant impact on SCR estimation.

Comment faire de la surveillance sanitaire? L'exemple de l'Observatoire Valaisan de la Santé en Suisse [How to conduct public health surveillance? The example of the Observatoire Valaisan de la Santé in Switzerland].

OBJECTIVE: To describe the goals and methods of contemporary public health surveillance and to present the activities of the Observatoire Valaisan de la Santé (OVS), a tool unique in Switzerland to conduct health surveillance for the population of a canton. METHODS: Narrative review and presentation of the OVS. RESULTS: Public health surveillance consists of systematic and continuous collection, analysis, interpretation and dissemination of health data necessary for public health planning. Surveillance is organized according to contemporary public health issues. Switzerland is currently in an era dominated by chronic diseases due to ageing of the population. This "new public health" era is also characterized by the growing importance of health technology, rational risk management, preventive medicine and health promotion, and the central role of the citizen/patient. Information technologies provide access to new health data, but public health surveillance methods need to be adapted. In Switzerland, health surveillance activities are conducted by several public and private bodies, at federal and cantonal levels. The Valais canton has set up the OVS, an integrative, regional, and reactive system to conduct surveillance. CONCLUSION: Public health surveillance provides information useful for public health decisions and actions. It constitutes a key element for public health planning.

Diagnostic performance of &supl;⁸F-fluorodeoxyglucose positron emission tomography in giant cell arteritis: a systematic review and meta-analysis.

PURPOSE: The aim of this study was to conduct a systematic review and perform a meta-analysis on the diagnostic performances of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) for giant cell arteritis (GCA), with or without polymyalgia rheumatica (PMR). METHODS: MEDLINE, Embase and the Cochrane Library were searched for articles in English that evaluated FDG PET in GCA or PMR. All complete studies were reviewed and qualitatively analysed. Studies that fulfilled the three following criteria were included in a meta-analysis: (1) FDG PET used as a diagnostic tool for GCA and PMR; (2) American College of Rheumatology and Healey criteria used as the reference standard for the diagnosis of GCA and PMR, respectively; and (3) the use of a control group. RESULTS: We found 14 complete articles. A smooth linear or long segmental pattern of FDG uptake in the aorta and its main branches seems to be a characteristic pattern of GCA. Vessel uptake that was superior to liver uptake was considered an efficient marker for vasculitis. The meta-analysis of six selected studies (101 vasculitis and 182 controls) provided the following results: sensitivity 0.80 [95% confidence interval (CI) 0.63-0.91], specificity 0.89 (95% CI 0.78-0.94), positive predictive value 0.85 (95% CI 0.62-0.95), negative predictive value 0.88 (95% CI 0.72-0.95), positive likelihood ratio 6.73 (95% CI 3.55-12.77), negative likelihood ratio 0.25 (95% CI 0.13-0.46) and accuracy 0.84 (95% CI 0.76-0.90). CONCLUSION: We found overall valuable diagnostic performances for FDG PET against reference criteria. Standardized FDG uptake criteria are needed to optimize these diagnostic performances.

Determinants of linear judgment: A meta-analysis of lens model studies

The mathematical representation of Brunswik s lens model has been usedextensively to study human judgment and provides a unique opportunity to conduct ameta-analysis of studies that covers roughly five decades. Specifically, we analyzestatistics of the lens model equation (Tucker, 1964) associated with 259 different taskenvironments obtained from 78 papers. In short, we find on average fairly high levelsof judgmental achievement and note that people can achieve similar levels of cognitiveperformance in both noisy and predictable environments. Although overall performancevaries little between laboratory and field studies, both differ in terms of components ofperformance and types of environments (numbers of cues and redundancy). An analysisof learning studies reveals that the most effective form of feedback is information aboutthe task. We also analyze empirically when bootstrapping is more likely to occur. Weconclude by indicating shortcomings of the kinds of studies conducted to date, limitationsin the lens model methodology, and possibilities for future research.

Introducing a first AIDS vaccine in Switzerland: a Policy Delphi analysis.

This preliminary exploration was limited by a number of factors. The format of the study has necessarily induced some form of selection bias of the panelists, because of the complexity of some questions, and the time required to complete the questionnaires. Several issues have not been addressed. One example could be the response to HIV infection occurring in a vaccinee. The study also did not address the difficulties related to the licensing of the vaccine. Indeed, the proposed scenario assumed that the vaccine had been registered as a starting point for the analysis. Finally, it has not been possible to conduct a sensitivity analysis, in order to evaluate how the responses would have been modified if some important characteristics of the vaccine had been modified.Very diverse evaluations were given in response to questions related with attitudes and perception of AIDS and AIDS vaccine. The possibility that vaccine availability or usage can be associated with an increased frequency in risky behaviors was spontaneously mentioned by half of the panelists. The estimation of the proportion of persons at highest risk who would choose to use this vaccine also indicated a high degree of uncertainty. This study offers important lessons. According to a broad and diverse panel of individuals, an incompletely effective AIDS vaccine would result in an additional level of complexity for the AIDS prevention strategy, rather than a simplification. The use of such a vaccine would have to be coupled with counselling. This implies a sustained emphasis on the recommendations which have been central to the STOP AIDS campaigns until now. In addition, consensual issues, as well as other issues more likely to be controversial have been identified. This should greatly help focusing the work of any committee designated to develop and implement a vaccination policy if an AIDS vaccine became available. Finally, our experience with the Policy Delphi indicates that this mode of structured communication could be usefully applied to other public health issues presenting a high visibility as well as a complex relationship with public perception.

The new Keynesian approach to monetary policy analysis: Lessons and new directions

I discuss several lessons regarding the design and conduct of monetary policy that have emerged out of the New Keynesian research program. Those lessons include the bene.ts of price stability, the gains from commitment about future policies, the importance of nat-ural variables as benchmarks for policy, and the bene.ts of a credible anti-inflationary stance. I also point to one challenge facing NK modelling efforts: the need to come up with relevant sources of policy tradeoffs. A potentially useful approach to meeting that challenge, based on the introduction of real imperfections, is presented.

TIME-21 Funding Analysis A report to the Iowa Legislature, per Section 26, Senate File 2420, 82nd General Assembly

The 82nd General Assembly of the Iowa legislature, in Section 26 of Senate File 2420, required the Iowa Department of Transportation (Iowa DOT) to conduct an analysis of TIME-21 funding. Specifically the legislation requires the following: “The department of transportation shall conduct an analysis of the additional revenues necessary to provide at least two hundred million dollars annually to the TIME-21 fund by FY 2011-2012. The analysis shall include but is not limited to the amount of excise tax levied on motor fuel and adjustments that might be made to various fees collected by the department in order to create an appropriate balance of taxes and fees paid by Iowa drivers and out-of-state drivers. The department shall submit a report to the governor and the general assembly on or before December 31, 2008, regarding its analysis.” As a starting point to this analysis, a reassessment of long-range needs and revenues (including the estimated $200 million most critical annual unmet needs) was made. This was done by assessing changing trends in roadway conditions, revenue and construction costs since the original Study of Iowa’s Current Road Use Tax Funds (RUTF) and Future Road Maintenance and Construction Needs was completed December 2006.

TIME-21 Funding Analysis A report to the Iowa Legislature, per Section 26, Senate File 2420, 82nd General Assembly

The 82nd General Assembly of the Iowa legislature, in Section 26 of Senate File 2420, required the Iowa Department of Transportation (Iowa DOT) to conduct an analysis of TIME-21 funding. Specifically the legislation requires the following: “The department of transportation shall conduct an analysis of the additional revenues necessary to provide at least two hundred million dollars annually to the TIME-21 fund by FY 2011-2012. The analysis shall include but is not limited to the amount of excise tax levied on motor fuel and adjustments that might be made to various fees collected by the department in order to create an appropriate balance of taxes and fees paid by Iowa drivers and out-of-state drivers. The department shall submit a report to the governor and the general assembly on or before December 31, 2008, regarding its analysis.” As a starting point to this analysis, a reassessment of long-range needs and revenues (including the estimated $200 million most critical annual unmet needs) was made. This was done by assessing changing trends in roadway conditions, revenue and construction costs since the original Study of Iowa’s Current Road Use Tax Funds (RUTF) and Future Road Maintenance and Construction Needs was completed December 2006.

Adenocarcinoma of the pancreas: Comparative single centre analysis between ductal and mucinous type.

1. Background¦Adenocarcinomas of the pancreas are exocrine tumors, originate from ductal system, including two morphologically distinct entities: the ductal adenocarcinoma and mucinous adenocarcinoma. Ductal adenocarcinoma is by far the most frequent malignant tumor in the pancreas, representing at least about 90% of all pancreas cancers. It is associated with very poor prognosis, due to the fact that actually there are no any biological markers or diagnostic tools for identification of the disease at an early stage. Most of the time the disease is extensive with vascular and nerves involvement or with metastatic spread at the time of diagnosis (1). The median survival is less than 5% at 5 years, placing it, at the fifth leading cause of death by cancer in the world (2). The mucinous form of pancreatic adenocarcinoma is less frequent, and seems to have a better prognosis with about 57% survival at 5 years (1)(3)(4).¦Each morphologic type of pancreatic adenocarcinoma is associated with particular preneoplastic lesions. Two types of preneoplastic lesions are described: firstly, pancreatic intra-epithelial neoplasia (PanIN) which affects the small and peripheral pancreatic ducts, and the intraductal papillary-mucinous neoplasm (IPMN) interested the main pancreatic ducts and its principal branches. Both of preneoplastic lesions lead by different mechanisms to the pancreatic adenocarcinoma (1)(2)(3)(4)(5)(6)(7)(8)(9)(10).¦The purpose of our study consists in a retrospective analysis of various clinical and histo-morphological parameters in order to assess a difference in survival between these two morphological types of pancreatic adenocarcinomas.¦1.2 Material and methods¦We conducted a retrospective analysis including 35 patients, (20 men and 15 women), beneficed the surgical treatment for pancreas adenocarcinoma at the Surgical Department of University Hospital in Lausanne. The patients involved in our study have been treated between 2003 and 2008, permitting at least 5-years mean follow up. For each patient the following parameters were analysed: age, gender, type of operation, type of preneoplastic lesions, TNM stage, histological grade of the tumor, vascular invasion, lymphatic and perineural invasion, resection margins, and adjuvant treatment.¦The results from these observations were included in a univariate and multivariate statistical analysis and compared with overall survival, as well as specific survival for each morphologic subtype of adenocarcinoma.¦As a low number of mucinous adenocarcinomas (n=5) was insufficient to conduct a pertinent statistical analysis, we compared the data obtained from adenocarcinomas developed on PanIN with adenocarcinomas developed on IPMN including both, ductal or mucinous types.¦1.3 Result¦Our results show that adenocarcinomas developed on pre-existing IPMN including both morphologic types (ductal and mucinous form) are associated with a better survival and prognosis than adenocarciomas developed on PanIN.¦1.4 Conclusion¦This study reflects that the most relevant parameter in survival in pancreatic adenocarcinoma seems to be the type of preneoplastic lesion. The significant difference in survival was noted between adenocarcinomas developing on PanIN as compared to adenocarcinomas developed on IPMN precursor lesions. Ductal adenocarcinomas developped on IPMN present significantly longer survival than those developed on PanIN lesions (P value= 0,01). Therefore we can suggest that the histological type of preneoplastic lesion rather than the histological type of adenocarcinoma should be the determinant prognosis factor in survival of pancreatic adenocarcinoma.