Demographic, socioeconomic and cultural changes in India have increased longevity, delayed childbearing, decreased parity and resulted in a more westernised lifestyle, contributing to the increasing burden of cancer, especially among women.We evaluated secular changes in the incidence of breast, cervical and ovarian cancer in Mumbai women aged 30–64 between 1976 and 2005. Age-standardised incidence rates were calculated and presented by site and calendar period. An age–period–cohort (APC) analysis quantified recent time trends and the significance of birth cohort and calendar period effects. The estimated annual percent change (EAPC) was obtained from the drift parameter, expressing the linear time trend common to both calendar period and birth cohort.Over the 30-year study period, the age-standardised rates significantly increased for breast cancer : 1.0, 1.3)), significantly decreased for cervical cancer ) and there was no statistically significant change for ovarian cancer ). For breast and cervical cancer, the best-fitting model was the APC model.The rates of breast, cervical and ovarian cancer remain low in comparison with western countries, and the divergent trends of breast (increasing) and cervical cancer (decreasing) in Mumbai were similar to those observed in several other Asian countries. The changing risk profile in successive generations – improved education, higher socioeconomic status, later age at marriage and at first child, and lower parity – may in combination partially explain the diverging generational changes in breast and cervical cancer in Mumbai in the last decades. The increasing incidence of cancer in India has mirrored trends in developed countries, although the rates for major sites, such as female breast cancer have remained comparatively low. Over the last two decades, the urbanisation and increasing modernisation of India has transformed education, lifestyle, health-care access and longevity, and has contributed to an increased risk profile for chronic diseases such as cancer . A higheThis study aims to quantify the recent time trends in the most commonly occurring female cancers in Mumbai women, with a view to better understanding the contribution of changing lifestyle. An age–period–cohort (APC) analysis of breast, ovarian and cervical cancer incidence trends was conducted, using the population-based cancer registry data in Mumbai, India over a 30-year period, 1976–2005.All incident cases of breast, ovarian and cervical cancer  diagnosed in 1976–2005 were extracted from the Mumbai Cancer Registry. Registry personnel conducted routine visits to 140 collaborating hospitals over a 603 square kilometre area of over 12 million residents to review pathology logs on new cancer diagnoses. Medical charts and pathology reports were reviewed for clinical information including date and method of diagnosis, histological grade and subtype, and stage of disease as well as demographic information such as age, gender, ethnicity and marital status. The Mumbai Registry data set has consistently met IARC's quality standards with respect to inclusion in consecutive volumes of their Cancer Incidence of Five Continents series  and the effects of period and cohort curvature, were obtained using the analysis of deviance of nested models, as suggested by A more formal assessment of the contribution of age, period and cohort effects involved the fitting of APC models to the trends , 1987b. a priori hypothesis that the increasing trends in breast and ovarian cancer, for example, are allied to generational influences; a changing prevalence and distribution of known and unknown lifestyle and environmental factors in the female population of Mumbai, should, given a sufficient time lag, result in changing cancer rates observed in successive birth cohorts. Stata  against a changing prevalence and distribution of risk factors, which may show up as changes in rates among successive generations (cohort effects).vs Asian countries  1992–93: Maharastra, India, 1995; National Family Health Survey India (NFHS-2): 1998–99 Maharastra, India, 2000). In a case series of 11780 tumours (The significant decline in cervical cancer, once the most common cancer of Mumbai women, is likely due to changes in marriage and family planning, supported by underlying improvements in education and socioeconomic status. Generational changes in age at marriage and first pregnancy  have resAlthough ovarian cancer rates in Mumbai were half those in the United States in 1976 , it rankThe APC models yielded significant non-linear cohort effects for underlying changes in breast and cervical cancer risk, which is consistent with the adoption of modern reproductive practices. Lifestyle patterns of Mumbai females changed considerably during the study period; women in Mumbai attained higher levels of education, postponed marriage, had their first child at an older age and had fewer pregnancies over time . Furthera priori epidemiological or biological knowledge – was beyond our present understanding of the trends, and instead we assumed a period slope of zero, allowing for the drift to be included in birth cohort. This method still allows non-linear effects for period to be visible (A graphical display of the APC parameters was included in this study, although a meaningful ‘solution’ – one that numerically allocates the drift to period and cohort on the basis of  visible . There mOverall, trends in breast cancer and cervical cancer incidence rates in Mumbai, India mirrored those observed in Western countries over the same 30-year time period. The changing risk profile among younger generations allied to a westernisation of lifestyle – improved education, higher socioeconomic status, later age at marriage and at first child, and lower parity – explain part of the generational changes that yielded significant changes for both cervical and breast cancer rates over time.


A joint effort by two of the original National Institute of Allergy and Infectious Diseases-funded BRCs, PATRIC provides researchers with an online resource that stores and integrates a variety of data types  and associated metadata. Datatypes are summarized for individual genomes and across taxonomic levels. All genomes in PATRIC, currently more than 10 000, are consistently annotated using RAST, the Rapid Annotations using Subsystems Technology. Summaries of different data types are also provided for individual genes, where comparisons of different annotations are available, and also include available transcriptomic data. PATRIC provides a variety of ways for researchers to find data of interest and a private workspace where they can store both genomic and gene associations, and their own private data. Both private and public data can be analyzed together using a suite of tools to perform comparative genomic or transcriptomic analysis. PATRIC also includes integrated information related to disease and PPIs. All the data and integrated analysis and visualization tools are freely available. This manuscript describes updates to the PATRIC since its initial report in the 2007 NAR Database Issue.The Pathosystems Resource Integration Center (PATRIC) is the all-bacterial Bioinformatics Resource Center (BRC) ( This initiative outlined the scope of biodefense research to understand the biology of these organisms and to develop new diagnostics, treatments and vaccines to treat them. In 2004, NIAID provided funding for eight Bioinformatics Resource Centers (BRCs) to provide scientists with genomics and related data on these organisms (http://www.patricbrc.org), providing researchers with thousands of consistently annotated bacterial genomes, integrating the related ‘omics data and providing a suite of analysis tools to support infectious disease research. Here, we give a detailed description of the new features added during the transformation of PATRIC from a resource that began with eight genomes and limited integration to its current capacity of more than 10 000 genomes, with a variety of other integrated data types and improved analysis capabilities.In 2002, the National Institute of Allergy and Infectious Diseases (NIAID) developed a strategic plan for Biodefense research that defined the ‘Priority Pathogens’ and developed a subsequent watch list of genera, categorized as A, B and C priority microbial pathogens , and also KBase (http://kbase.science.energy.gov/) to support inter-comparison of annotations and functional content. In addition, PATRIC also maintains the original annotations from GenBank to allow users to explore and compare differences. However, having every genome consistently annotated with the same technology and terminology makes PATRIC truly unique in that researchers can make comparisons across taxonomic boundaries without wondering if the differences they are observing are related to different annotation sources. As part of genome annotation, proteins are mapped to protein families called FIGfams, which enable comparative genomic analysis at PATRIC. FIGfams are isofunctional homologs, with each FIGfam containing a set of proteins that are ‘end-to-end homologous and share a common function’. (Every genome available at PATRIC is annotated using Rapid Annotations using Subsystems Technology (RAST) , an end-nction’.  They areMycobacterium’ taxon page includes only those genomes and features contained within that genus. Data are also summarized at the genome level, which identifies all the integrated data for an individual strain. A third summary of data occurs at the gene level , we have developed a system where new microarray gene datasets are collected from GEO every month. Platform annotations, data and metadata are automatically collected and then manually reviewed. This manual curation includes a review of the experiment description and the related publication to understand experimental design; combines data from replicates; and creates pair-wise comparisons or contrasts as described in the publication to identify differential gene expression, data normalization and log-transformation. Using the above process, 704 transcriptomic datasets across 65 bacterial genera  and more than 100 000 bacterial PPIs from a number of public repositories, including IntAct , BIND 1 and MINTCurrently, there are more than 33 000 experimentally solved bacterial protein structures available in various public data repositories such as the PDB  and NCBIBacterial typing methods based on phenotype  have traditionally been used for epidemiological studies and outbreak investigations . When thPATRIC integrates data across sources, data types, molecular entities and organisms. Data are collected and integrated from public repositories such as NCBI, the United States Department of Agriculture, the Centers for Disease Control (CDC) and other NIAID-funded projects, such as the System Biology for Infectious Disease centers, as well as from studies carried out by individual investigators. There are distinct procedures in place to work with different types of data providers, with data automatically collected from public repositories.Much of this integration centers on genomes and genes. Biological entities such as genes, RNAs, proteins, pathways and other data are readily linked to genomes. Genomes also provide an anchor for linking pathogens, hosts and vectors to molecular data. Metadata about genomes are used to allow users to search, filter and collect data of interest A. In addAs the number of genomes being sequenced increases, so does the difficulty in finding genomes of interest and pertinent associated data. Although PATRIC contains thousands of comparable genomes, there are mechanisms in place that allow researchers to find genomes of interest including single specific genomes, whole genome sets within certain taxa, sets of genomes that share common metadata, and even closely related sets of genomes based on phylogeny. Researchers can locate genomes of interest using a variety of means including a global search deployed from the main navigation bar, phylogenetic trees, genome/gene lists, genome/feature finder tools and metadata filters . Once seIn addition, both NCBI- and PATRIC-centric versions of BLAST allow users to find genes or genomes that match specific sequence criteria. In addition, PATRIC has an ID mapping tool that leverages UniProt’s ID mappings, which allows researchers to map identifiers from a variety of resources  to the corresponding PATRIC identifiers.Once researchers have found genomes or data of interest, they can create groups based upon their selections. These user-specified groups of genomes are an important precursor to many of PATRIC’s sophisticated analysis tools. To save these groups, PATRIC provides registered users with a private workspace, functioning as a digital laboratory notebook E. The woThe PATRIC database supports multiple ways to access data, accommodating the needs of both expert and computationally naive users. Researchers have the option of selecting datasets by browsing or searching the database through the website user interface that supports both ad hoc queries and directed navigation methods. Results may be saved to data files and downloaded as needed. In addition to APIs, PATRIC also provides an FTP service for bulk data downloads.PATRIC is designed primarily to allow experimental biologists to view and analyze data in an easy and efficient manner. The processes, tools and viewers used to find and analyze the data integrated within PATRIC are described below, as well as the process for researchers to upload and explore their private data with PATRIC.PATRIC’s compilation of all public bacterial genomes and their consistent annotation using RAST provides a powerful platform for comparative genomic analysis. The Protein Family Sorter tool at PATRIC allows users to select a set of genomes of interest (maximum up to 400 genomes) and examine distribution of protein families across the genomes A, commonAn integral part of genomic analysis is phylogeny, and PATRIC provides Order-level phylogenetic trees. The pipeline used was initially developed during the first incarnation of PATRIC  and usesPATRIC’s Comparative Pathway tool is also based on the RAST annotations. It allows researchers to identify a set of metabolic pathways based on taxonomy, EC number, pathway ID, pathway name and/or specific annotation type. The data are mapped to and summarized on pathway maps D from thPATRIC provides the ability to compare RAST and RefSeq annotations using the Genome Browser B built oPATRIC integrates transcriptomic and genomic data, allowing researchers to explore gene expression data across species, within a specific genome, or for a gene of interest. As of September 2013, 704 transcriptomic experiments across 27 bacterial genera have been incorporated with manually curated data and metadata. All datasets are listed and summarized on the appropriate taxon landing pages along with experiment metadata, such as organism, strain, gene mutations and experimental conditions. The available functionality includes a suite of integrated tools to explore, visualize and compare a large number of published transcriptomics datasets. PATRIC also allows researchers to upload and analyze their own gene expression data in their private workspace and compare it to existing data. Metadata-driven filtering allows users to search for experiments or comparisons of interest F. Interahttp://www.pathogenportal.org/), where users can upload their RNA-Seq or ChIP-Seq data, align it against a BRC provided genome and generate quantitative transcript profiles using BRC annotations. PATRIC has enabled end-to-end support for transcriptomic data analysis, allowing researchers to stream expression and annotation data from their RNA Rocket workspace to the PATRIC genome browser, as well as viewing differential expressions analysis data in the heat map viewer alongside other integrated transcriptomic experiments.An RNA-Seq analysis pipeline, called the RNA Rocket, was developed in a cross-BRC project in collaboration with the PATRIC, EuPathDB  and VectPATRIC provides Disease View, which provides easy access to integrated information related to hosts, pathogens, infectious diseases and outbreaks by a user-friendly web interface . This reThe Pathogen Interaction Gateway (PIG)  providesPlanned improvements in PATRIC include integrating additional data types, annotation enhancements to RAST annotations and expanding the Bring Your Own Data (BYOD) concept.By the end of 2013, PATRIC will incorporate all publicly available proteomics datasets that match certain criteria from PRIDE  and fromIn the longer term, PATRIC will continue to be driven by the needs of infectious disease researchers, especially for NIH priority pathogens. We are watching for technologies like metagenomics and metabolic modeling to become more prominent in research communities, and plan to include them when both the data and the associated analysis techniques are more standardized and stable. In addition, as emerging techniques and new types of data drive researchers toward integrated views of both the host or vector and pathogen, this will be used to drive requirements for additional data and capabilities at the website.Key improvements relating to annotation of virulence factors and antibiotic resistance genes will be incorporated into RAST and subsequently into PATRIC. Genera-specific annotation of specialty gene sets related to pathogenicity and antibiotic resistance will be carried out using information derived from external sources such as VFDB , MvirDB PATRIC will launch ‘Bring Your Own Genome’ in 2014 where registered users will be able upload their genomes into their private PATRIC workspace, annotate them using RAST and compare them with the publically available genomes at PATRIC using the comparative analysis tools. PATRIC will also add additional functionality currently available at RAST, including a sequence-based comparison tool. Future plans for BYOD also include support for uploading, validating, viewing and analyzing raw reads , assembled genome sequences and other ‘omics data types, such as proteomics data, transcriptomics data, metabolomics data and growth phenotype data.National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Service [Contract No. HHSN272200900040C].Funding for open access charge: Conflict of interest statement. None declared.


But these benefits can be offset by health threats posed by the emissions from fossil fuel–based electricity production—direct public health effects attributable to particulate matter, sulfur and nitrous oxides, volatile organic compounds, carbon monoxide, and ozone are estimated to account for more than 70% of the external costs of power generation . A multitiered analysis of the relationship between coal consumption, electricity use, and health outcomes uses three complementary data sets to compare positive and negative health effects of power generation The authors developed an autoregressive time-series model of infant mortality, life expectancy, electricity consumption, and coal consumption for 41 different countries over the period 1965–2005. They divided the countries into three groups depending on infant mortality and life expectancy rates as of 1965: countries with high infant mortality and low life expectancy, those with moderately high infant mortality and medium to high life expectancy, and those with low infant mortality and high life expectancy.Model predictions suggested infant mortality would decrease with increasing electricity consumption over time, but only in countries that started off with high infant mortality and low life expectancy, a group that included Algeria, Brazil, India, Indonesia, Pakistan, Peru, South Africa, and Turkey. Models did not predict a change in life expectancy with increased electricity use, but did predict a decrease in life expectancy with increased coal consumption in countries with moderate infant mortality and life expectancy in 1965. In addition, infant mortality was predicted to increase with increased coal consumption in those countries with low infant mortality and high life expectancy.The authors compared these results with estimates from two independent methods for modeling health effects of energy-related environmental exposures. The first method, the World Health Organization’s Environmental Burden of Disease model, estimates the burden of human disease related to outdoor air pollution, indoor air pollution, drinking water, and sanitation. The second method, the Greenhouse Gas and Air Pollution Interactions and Synergies model developed by the International Institute for Applied Systems Analysis, estimates potential life-shortening effects of pollutant emissions from coal-fired power plants. Estimates from both models were consistent with those derived from the authors’ autoregressive model.The study’s limitations include a lack of comprehensive data for variables such as education level, vaccination rates, and health care access and/or expenditures. However, the consistency of the results of the three analyses strongly supports the authors’ conclusions and highlights ways that human health impacts might be integrated into climate change mitigation and energy policy research.


Renal preservation therapy has been a promising concept for the treatment of localized renal cell carcinoma (RCC) for 20 years. Nowadays partial nephrectomy (PN) is well accepted to treat the localized RCC and the oncological control is proved to be the same as the radical nephrectomy (RN). Under the result of well oncological control, minimal invasive method gains more popularity than the open PN, like laparoscopic partial nephrectomy (LPN) and robot assisted laparoscopic partial nephrectomy (RPN). On the other hand, thermoablative therapy and cryoablation also play an important role in the renal preservation therapy to improve the patient procedural tolerance. Novel modalities, but limited to small number of patients, include high-intensity ultrasound (HIFU), radiosurgery, microwave therapy (MWT), laser interstitial thermal therapy (LITT), and pulsed cavitational ultrasound (PCU). Although initial results are encouraging, their real clinical roles are still under evaluation. On the other hand, active surveillance (AS) has also been advocated by some for patients who are unfit for surgery. It is reasonable to choose the best therapeutic method among varieties of treatment modalities according to patients' age, physical status, and financial aid to maximize the treatment effect among cancer control, patient morbidity, and preservation of renal function. With the improvement of the detection modalities , the cases of small renal mass (SRMs) increased. In imaging study, 20% highly suspected renal malignancy would be finally proved as benign pathology after operation. On the other hand, studies proved that the more remaining kidney tissue we have, the lower prevalence the chronic kidney disease (CKD) would happen. Thus treatment gradually focused on the renal preservation therapy. To treat the patients with SRMs, three factors should be balanced: patient morbidity, preservation of renal function, and cancer control. In surgical part, nephron-sparing surgery (NSS)/partial nephrectomy (PN) have evolved from the treatment option to the standard management for small renal masses, have been shown to have equivalent oncological efficacy as radical nephrectomy (RN), while reducing the prevalence of the subsequent renal insufficiency. With the same oncological control, the goal of current surgical intervention is to decrease the risk of CKD. Preservation of renal function may be associated with improved survival and avoided of the risk of cardiovascular death. In ablative therapy, radiofrequency ablation (RFA), and cryoablation (CA) remained the role for high-risk group to reduce interventional morbidity. Active surveillance also play an role for the elderly, or high-risk patients, who are unfit for further intervention.Urologists usually ask why AS for small renal tumors. The incidence of renal cancer increased, and they caused the medical fees expansion. Despite increasing surgeries were performed, the mortality rate for all renal tumors still increased . Two queAge and Charlson score (not treatment type) impacted overall survival on the study with multivariate analysis, and cardiovascular events were usually a leading cause of mortality, driven by chronic renal failure (CRF) . It shouActive surveillance is a reasonable option for patients with limited life expectancy or for those who are unfit for or do not desire intervention. In the future, it will be helpful to know more about the natural history of untreated small renal masses. Developing inclusion and termination criteria is important to decrease the calculated risk of the cancer progression.Though the partial nephrectomy is the standard treatment for SRMs, the overall complication rate is around 20%. Thus less invasive percutaneous or laparoscopic ablation therapy such as cryoablation (CA) and radiofrequency ablation (RFA) are developed to be an alternative of surgical resection. The American Urological Association (AUA) guidelines regard the thermal ablation as the choice for the surgical high-risk patients who still wants to receive active treatment and accepts the need for long-term radiographic surveillance . EuropeaBoth CA and RFA could be done by laparoscopic or percutaneous (Perc) method. CA causes irreversible cell death at −70°C and RFA makes cell death and tissue coagulation with heating over 60°C The ideal mass to ablate is solid/enhancing and peripheral/exophytic mass, and the challenging cases were endophytic, hilar, and upper pole mass. Renal biopsy should be taken irrespective of technique and technology and choice of technique should be based on the situation and morphology of renal mass and patient comorbidity. The ideal case for laparoscopic approach is tumor in the anterior valve, upper pole and medial tumor nearby the ureter; good candidate for percutaneous ablation is the tumor in posterior valve, endophytic central and hilar area. The trend is to perform percutaneous method if you could do both of them.In the current studies, cryoablation may have similar efficacy and complication rate as RFA . The surNovel modalities but limited to small number of patients include high-intensity ultrasound (HIFU), radiosurgery, microwave therapy (MWT), laser interstitial thermal therapy (LITT), and pulsed cavitational ultrasound (PCU). They are still under evaluation , 33–36.In recent years, the management of localized kidney tumors has changed, resulting in a shift away from radical nephrectomy (RN) toward a more frequent use of partial nephrectomy (PN). Open partial nephrectomy (OPN) has already become the standard of care in the treatment of renal masses smaller than 4 cm as well as select tumors up to 7 cm. The 5-year cancer-specific survival rate of partial nephrectomy had been proved more than 95%, almost the same as radical nephrectomy . In addiSurgery is still the gold standard in the management of SRMs. Nephron sparing surgery (NSS)/partial nephrectomy (PN) is the best option whenever it could be used. RFA/CA are reasonable options for those old and high-risk patients that till wish active treatment for SRMs. New modality like HIFU is still under evaluation. Active surveillance (AS) should be restricted to the patients with high-surgical risk, elderly, infirm or who refuses surgery. For NSS/PN, evolution is from open partial nephrectomy (OPN) to minimal invasive treatment . It is reasonable to choose the best therapeutic method among varieties of treatment modalities according to patients' age, physical status, and financial aid to maximize the treatment effect among cancer control, patient morbidity, and preservation of renal function.


Corruption is a serious threat to global health outcomes, leading to financial waste and adverse health consequences. Yet, forms of corruption impacting global health are endemic worldwide in public and private sectors, and in developed and resource-poor settings alike. Allegations of misuse of funds and fraud in global health initiatives also threaten future investment. Current domestic and sectorial-level responses are fragmented and have been criticized as ineffective. In order to address this issue, we propose a global health governance framework calling for international recognition of “global health corruption” and development of a treaty protocol to combat this crucial issue. The impact of globalization on health has been marked by new and daunting challenges. Though globalization has enabled advancements in trade, travel, and communications, it has also facilitated rapid global spread of infectious diseases such as SARS and H1N1/A, requiring a paradigm shift in global health governance. Yet, the next global pandemic is not the only challenge facing global health. A more immediate threat is systemic global healthcare corruption that adversely impacts both developed and resource-poor states.As reported by Transparency International, the scale and scope of corruption impacting health is immense. Exact numbers are elusive, but it is estimated billions of dollars are lost annually due to corruption and fraud in a global health market estimated to be worth 10% of global gross domestic product in 2009 . SystemaImportantly, health corruption not only leads to financial waste of scarce resources, but also has adverse impact on healthcare access, infrastructures, financing, and social determinants of health. In addition, health corruption can severely compromise quality and coverage of services, leading to price inflation for health service unit costs .Indeed, health corruption at the domestic level represents a severe impediment to global health efforts in resource-poor settings and transitional economies. Corruption can drain resources from already impoverished and fragile health systems, precluding access to life-saving treatment for vulnerable patient populations ,6. With Recent scandals that have plagued global multilateral health programs have also raised concerns regarding presence of corruption in global health. Allegations of corruption and fraud in the Global Fund to Fight AIDS, Tuberculosis and Malaria  represent a serious threat to continued funding and support of global health initiatives. This is particularly concerning given ongoing funding challenges arising from the recent global economic crisis .The confluence of domestic and international level health corruption impacting global populations points to a lack of an international framework specifically addressing the wide range of interrelated issues associated with health-related corruption. Improved global health governance is an important first step. Reform to detect and eliminate forms of corruption that impact health must be coordinated in order to ensure that health systems are protected and that global health interventions meet their full potential.Corruption is defined as the “misuse of entrusted power for private gain” . In the In combination with the reality that criminal activities can easily impact and move across geopolitical borders affecting multiple states/organizations, health corruption presents significant challenges for detection and enforcement. The broad infiltration of corruption, diversity of illicit acts, and multitude of stakeholders involved (often with limited or indirect accountability) adds to health system complexity, existing information asymmetry, and uncertainty in health markets, with developing countries particularly vulnerable ,10.Beyond developing countries, domestic corruption is also endemic in developed and emerging economies. For example, 5-10% of USA public sector health expenditures are lost to fraudulent overbilling . Recent The global drug supply chain also provides an illustration of how lack of regulatory harmonization can lead to forms of global health-related corruption ,15. HealNote that health corruption also extends to legitimate corporate entities. For example, corruption allegations against multinational pharmaceutical and medical device companies such as Johnson & Johnson, Merck, Eli Lilly, and Medtronic have surfaced involving bribery of physicians and health officials overseas. As pharmaceutical companies push to gain entry into emerging markets, competition gives rise to corrupt practices and have been prosecuted as potential violations under USA and UK foreign anti-bribery laws . ReflectThis broad spectrum of domestic level health corruption that has a global impact encompasses countries at all levels of development, spans various types of illicit activities, and includes both public and private actors.  and the UNODC. This can be accomplished through consultative meetings and development of a Global Health Corruption Treaty Protocol to the UNCAC, with ongoing and active participation of WHO to add provisions specifically addressing health. We believe an effective working definition of global health corruption could start as the: “misappropriation of authority, resources, trust or power for private or institutional gain that has adverse effects on regional, local, or international health systems and/or that negatively impacts individual patient and/or population health outcomes.” This definition should include the varying forms of corruption occurring both at the domestic and global program system level, as both forms of corruption can have an impact on global health.This standard definition can provide the basis for strategic efforts to coordinate cross-border, regional and international actors to detect and prosecute criminals in concert with existing or future domestic and regional laws that recognize the important differentiation of general corruption and corruption impacting health. This can result in individual countries enacting domestic laws that are harmonized internationally to allow law enforcement to coordinate global anti-corruption strategies for more effective prosecution. This can lead to development of best practices, with defined subsets of forms of global health corruption, identification of common vulnerabilities in health corruption, development of efficient financing mechanisms and judicial systems, and minimum requirements for transparency, enforcement and prosecution.To implement this governance system, a “model act” approach, similar to USA that allows adoption of model clauses and harmonization by individual states, may be an efficient strategy. This would allow WHO-UNODC to build on agreed upon global health corruption definitions but tailor them for cultural and infrastructural differences, allowing more effective adoption by individual countries sensitive to the local environment. Components could include model requirements for public and private sector policies on disclosure, auditing, procurement, drug supply, and payments to healthcare professionals.Developed country anti-bribery laws may also serve as potential enforcement tools that can be assessed for inclusion in a global health corruption framework. Laws such as the USA Foreign Corrupt Practices Act and UK Anti-Bribery Act prohibit corporations and individuals based in these countries from bribing public officials in other countries and engaging in other forms of corruption; they have been successful in at least some health sector prosecutions ,18.Other national laws, such as the USA Anti-kickback Statute and the False Claims Act, impose both civil and criminal fines for the submission of false claims and for providing forms of remuneration to healthcare professionals for referrals for services covered under national healthcare programs . These lFurther, domestic and regional efforts such as the UK’s National Health System anti-fraud unit and the European Healthcare Fraud and Corruption Network could also be considered. These represent models for tailored anti-global health corruption systems that may be scaled up for increased more regional/global coverage.As part of enhanced governance efforts, WHO-UNODC should utilize existing research and guidance on corruption in health, including methods, tools and good practices as developed by the United Nations Development Programme (“UNDP”) . These sRecognizing that there is no “one size fits all” approach in establishing a comprehensive framework to deal with all forms of global health corruption, careful attention should be given to programmatic differences between domestic versus global health systems. Hence, vertically integrated global health initiatives spanning the scope of multiple, international stakeholders focused on individual diseases need to be addressed uniquely within the context of susceptibility to corruption. Similarly closed national health systems that are not primarily funded by international health or development assistance and are primary-care focused need to be assessed differently from their global health system counterparts.Fortunately, global governance models are available for guidance. Using the UNCAC experience, global governance approaches to corruption can include WHO-UNODC member creation of formal and binding systems. This includes establishing a strategy for global health corruption protocol implementation, anti-corruption system financing, and overall health system strengthening. This can be accomplished by providing technical assistance to member states, developing model policies and tools for anti-corruption, identifying “at-risk” countries, exploring innovative financing mechanisms  and coordinating efforts with other multilateral and bilateral development, health, and enforcement agencies, civil society, and the private sector . These eAt a minimum, these governance systems should involve multiple interventions and include: (1) transparency and audit policies; (2) a common framework for corruption monitoring and evaluation of public health programs and funding; (3) Codes of Conduct for public and private sector actors; (4) minimum standards for member state laws to specifically prevent and prosecute health-based corruption; (5) health financing improvements to curtail the need for an informal health sector; (6) a centralized surveillance and data repository system to report and investigate global health corruption; (7) multilateral processes to freeze proceeds from corruption and aid in recovery of diverted assets; and (8) commitment to earmark portions of seized assets to fund and develop these anti-corruption systems among members.This dynamic and comprehensive “global health anti-corruption” framework can build on existing and future best practices, as well as examine previous corruption case studies to determine appropriate strategies that are sensitive to domestic or regional limitations. Though these policies may results in some additional costs and require administrative resources to implement, they are nevertheless crucial in protecting and obtaining the benefits from public health investments, enhancing health system strengthening, and maintaining public trust in global health interventions.The potential benefits of the proposed global health governance framework could be significant, starting with global recognition regarding the unique risks of global health corruption and its adverse impact on societies worldwide.Importantly, this strategy can assist in addressing corruption both on a global and domestic level. Beyond coordinating domestic and international law enforcement efforts, more focused strategies to prioritize rapid review of health projects and systems that are most susceptible to corruption and have the greatest potential negative impact on health outcomes should be addressed immediately . As an eIn addition, anti-corruption actions can be strategically targeted for diverse domestic populations by disseminating community-based monitoring tools addressing different forms of health corruption endemic in particular setting . As well, proactive regional risk assessment can allocate resources to populations most affected by global health corruption. Such a “top down/bottom up” approach can allow for flexibility of a dual global and domestic approach to combating global health corruption, ensuring better accountability, transparency, and importantly, effective use of anti-corruption investment.Global health corruption remains a serious, ongoing, and under recognized threat to global health progress. Unfortunately, the world’s most vulnerable shoulder much of this life-and-death burden. Further, recent global health program scandals serve to emphasize the need for progressive and global reform.Under Article 12 of the International Covenant on Economic, Social, and Cultural Rights, every human has a fundamental right to the highest attainable standard of health . Global The authors declare no potential conflicts of interest or competing interests associated with this manuscript.We note that with respect to author contributions, Tim Mackey (TM) and Bryan A. Liang (BAL) jointly conceived the study, TM and BAL jointly wrote the manuscript, TM, and BAL jointly edited the manuscript, and BAL supervised its legal and policy analysis. All authors read and approved the final manuscript.Tim K. Mackey, MAS: TKM is a Senior Research Associate, Institute of Health Law Studies, Ph.D Candidate in the Joint Doctoral Program in Global Health at University of California, San Diego-San Diego State University, and Clinical Instructor at University of California, San Diego. He holds a Masters Degree in Health Law, UCSD-California Western School of Law. He has a diverse professional background including public and private sector experience and completing an internship at the World Health Organization. He has co-authored over 60 publications and given numerous presentation on issues including counterfeit medicines, global health governance, health migration, biodiversity, eHealth, organized crime and corruption, and pandemic response.Bryan A. Liang, MD, JD, PhD: BAL is Executive Director and Shapiro Distinguished Professor, Institute of Health Law Studies, California Western School of Law; Director and Professor of Anesthesiology, San Diego Center for Patient Safety, UCSD School of Medicine. His work focuses upon the systemic impact of health policy and law on patient safety, broadly construed. He combines experience working in policy contexts in Asia, the European Union, and USA with legal, medical, and economics training to formulate rational social policy promoting patient safety. He received his BS from MIT; PhD from University of Chicago; MD from Columbia; JD from Harvard.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-698X/12/23/prepub


To accomplish its mission, DOE is characterizing and classifying potential geologic storage reservoirs in basins throughout the U.S. and Canada, and developing best practices for project developers, to help ensure the safety of future geologic storage projects. DOE’s Carbon Sequestration Program, Regional Carbon Sequestration Partnership (RCSP) Initiative, administered by the National Energy Technology Laboratory (NETL), is identifying, characterizing, and testing potential injection formations. The RCSP Initiative consists of collaborations among government, industry, universities, and international organizations. Through this collaborative effort, a series of integrated knowledge-based tools have been developed to help potential sequestration project developers. They are the Carbon Sequestration Atlas of the United States and Canada, National Carbon Sequestration Database and Geographic System (NATCARB), and best practice manuals for CCS including 2; Public Outreach and Education for Carbon Storage Projects; Monitoring, Verification, and Accounting of CO2Depositional Reservoir Classification for CO 2Stored in Deep Geologic Formation; Site Screening, Site Selection, and Initial Characterization of CO Storage in Deep Geologic Formations. DOE’s future research will help with refinement of these tools and additional best practice manuals (BPM) which focus on other technical aspects of project development.The United States Department of Energy (DOE) is the lead federal agency for the development and deployment of carbon sequestration technologies. Its mission includes promoting scientific and technological innovations and transfer of knowledge for safe and permanent storage of CO Anthropogenic CO2 emissions and resulting increases in CO2 atmospheric concentrations have been generally increasing since the start of the industrial age [2 are being emitted into the atmosphere annually [2 in the atmosphere is expected to increase at a rate of 1.3% annually between 2007 and 2035 [Our modern economy and our associated quality of life—lighting, transportation, communications, heat and air conditioning—rely fundamentally on the consumption of energy, of which approximately 85%, worldwide, comes from the combustion of fossil fuels. One of the byproducts of combustible fuels is carbon dioxide . DOE’s Office of Fossil Energy manages a Carbon Sequestration Program through NETL which focuses on research and development of CCS technologies to reduce CO2 emissions.While the specific links between increasing atmospheric CO2 that would otherwise be emitted to the atmosphere. Applied research is being conducted to develop and test different approaches to CCS. Technology testing and development through the Regional Carbon Sequestration Partnership (RCSP) Initiative and other entities will be instrumental to the commercial deployment of CCS. DOE’s vision is to fully understand the available CCS options, cost factors, environmental implications, and technological options.DOE’s Carbon Sequestration Program is focused on geologic storage of captured CO2.In 1997, DOE established the Carbon Sequestration Program (Program), which is administered by the Office of Fossil Energy and implemented through NETL to move CCS technologies toward commercialization. The Program encompasses all aspects of CCS and has engaged government and private sector partners that have expertise in CCS technology. The Program covers three key elements for technology development : core re2 capture with a less than 10% increase in the cost of energy services for pre-combustion carbon capture ready for wide scale deployment in the 2020 timeframe. In addition, the Program aims to achieve 99% storage permanence while validating storage potential within +/− 30%. Attaining these goals will require an integrated approach to address CCS challenges through R&D projects, participation in working groups, and the RCSP Initiative. Development of these technologies will help address future challenges to overcome a multitude of economic, social, and technical challenges, including cost-effective CO2 capture through successful integration with fossil fuel conversion systems; effective CO2 monitoring and verification; permanence of underground CO2 storage; and public acceptance.The Program strives to develop fossil fuel conversion systems that offer 90% CO2. Legal and social issues include developing a regulatory framework with regards to the permitting and treatment of CO2 once it is injected into a geologic reservoir, developing infrastructure such as pipelines, developing a workforce trained in CCS, and the legal framework for the liability and ownership of the pore space and injected CO2. Additionally, commercial deployment of CCS will require public education on the benefits of CCS. The Program is developing best practice manuals from lessons learned to help transfer knowledge gained to the private sector.The commercial deployment of CCS faces many challenges. Technical challenges include the development of lower cost capture technologies, accurate estimates of geologic storage potential, and evaluating the permanence of injected CO3.The RCSPs are public/private cooperative efforts tasked with developing guidelines and testing the most suitable technologies, regulations, and infrastructure needs for CCS in the United States and Canada. The seven RCSPs that form this initiative currently include more than 400 state agencies, universities, and private companies, spanning 43 states, and four Canadian provinces.http://www.netl.doe.gov/technologies/carbon_seq/refshelf/refshelf.html.The RCSPs’ initiative consists of three distinct phases of work: (1) Characterization Phase (2003–2005); (2) Validation Phase (2005–2011); and (3) Development Phase (2008–2018+). The Characterization Phase began in September 2003 with the seven RCSPs working to develop the necessary framework to validate and potentially deploy CCS technologies. At the end of the Characterization Phase, the RCSPs had succeeded in establishing a national network of companies and professionals working to support CCS deployments, creating a National Carbon Sequestration Database and Geographic Information System (NATCARB), and raising awareness and support for CCS as a green house gas (GHG) mitigation option. Fact sheets for some of the projects conducted by the RCSPs and NETL are available at 2 storage projects; (2) collect physical data to confirm CO2 storage potential and injectivity estimates; (3) demonstrate the effectiveness of monitoring, verification, and accounting (MVA) technologies; (4) develop guidelines for well completion, operations, and abandonment; and (5) develop strategies to optimize the CO2 storage potential of various geologic formations. The Validation Phase consists of 20 geologic injection tests.The Validation Phase focuses on validating the most promising regional opportunities to deploy CCS technologies by building upon the accomplishments of the Characterization Phase. Efforts are being conducted to (1) validate and refine current reservoir simulations for CO2 by each RCSP into regionally significant geologic formations. These large-volume injection tests are designed to demonstrate that CO2 storage sites have the potential to store regional volumes of CO2 emissions safely, permanently, and economically for hundreds of years. Development Phase tests will result in a better understanding of commercial scale CCS projects and of regulatory, liability, and ownerships issues associated with these projects. These projects will provide a firm foundation for commercialization of large-scale CCS.The Development Phase builds on the information generated in the Characterization and Validation Phases and involves the injection of 1 million tons or more of CO4.2 storage in five Midwestern states . With the implementation of the RCSP Initiative, the database was expanded to cover the entire U.S. and parts of Canada by linking the seven RCSPs and various public databases. NATCARB provides web-based data access to CO2 stationary sources, potential geologic CO2 storage data, infrastructure information, supporting analytical tools for CO2 storage resource estimation, and CCS cost estimation. NATCARB addresses the broad needs of all users, and includes not only geographical information systems (GIS) and database query tools for the high-end technical user, but also simplified displays for the general public, employing readily available web tools such as Google Earth™ and Google Maps™. Data are generated, maintained, and enhanced locally at the RCSP level, or at specialized data warehouses and public servers. They are assembled, accessed, and analyzed in real-time through a single geoportal. NATCARB is available through the NETL/DOE website at http://www.netl.doe.gov/technologies/carbon_seq/natcarb/index.html.DOE manages the development of a powerful, user-friendly database that supplies regions of the country with valuable information regarding CCS. The database, called the National Carbon Sequestration Database and Geographic Information System (NATCARB), was originally designed to assess the potential for geologic CO5.Geologic Storage Formation Classification: Understanding Its Importance and Impact on CCS Opportunities in the United States, to better understand the characteristics of potential geologic storage formations as a component of CCS. This desk reference is intended to:2 geologic storage in formations.Assist with an understanding of basic geological principles and terminology associated with potential CO2.Show the importance of geologic depositional systems in determining the internal architecture of such formations, thus making it possible to predict the general behavior of the injected CO2 in different depositional environments.Establish the importance of using the geologic depositional system to assess existing and future research, design, and demonstration needs related to storing COFocus the efforts of DOE on potential reservoirs in depositional environments that have not been previously investigated.Through NETL, DOE has recently released a comprehensive manual, titled 2 storage varies based on the necessary criteria of:Capacity, based on the porosity or openings within a rock, often called “pore space”.Injectivity, dependent on the permeability or the relative ease with which a fluid or gas can move within the pore space(s) of a rock.Integrity, the ability to confine a fluid or gas within a geologic unit, is of primary importance, because without impermeable seals, fluids will take the path of least resistance and move to a lower pressure area, including the surface.Three major rock types might be targeted by future developers of CCS projects for storage formations: igneous, metamorphic, and sedimentary. Each major type of rock was formed under different conditions, and their potential for COetc.) in order to build a conceptual model of a formation. The decision to select a particular geologic unit for geologic storage usually depends on a detailed understanding of the reservoir characteristics and the behavior and fate of the injected fluids and their impact on the geologic strata receiving the fluids. Critical factors include economic analysis of the location of the site, distance from the CO2 source to the site, depth of the reservoir (which influences drilling and injectivity of CO2), the volume of CO2 that the site can contain, the trapping mechanism and sealing capacity, and the ultimate fate of the stored CO2. Many of these issues will be affected by the different classes of reservoirs being targeted for injection.The answers to questions concerning capacity, injectivity, and integrity can be learned, in part, by reservoir characterization of the formations in the area of the proposed geologic storage site. Reservoir characterization is an evolving science that integrates many different scientific disciplines , where CO2 storage is in the pore space between grains, which are most often filled with undrinkable saline water. Igneous formations, which cover more of the Earth’s surface than sedimentary formations, offer potentially great geologic storage sites because of their total volume both on continents and under the oceans, but are mostly untested. Coal seams are considered both sedimentary and metamorphic and have their own unique properties. The most important storage mechanism for coal is its preferential ability to absorb CO2 directly on its surface. This situation differs from other sedimentary and igneous formations where the CO2 occupies the pore space.Most CO2 storage. This is being accomplished through the implementation of 28 CO2 injection field projects in collaboration with the RCSP Initiative and ten American Recovery and Reinvestment Act of 2009 (Recovery Act) projects focused on the characterization of geologic formations as sites for possible commercial CCS development. DOE proposes a geologic depositional classification system for CO2 storage to better understand how the field work being conducted fulfills the need to test these different classes of depositional systems and determine what future R&D projects are still needed.One major goal of the Program is to classify the depositional environments of various formations that are known to have excellent reservoir properties and are amenable to geologic CO2 storage, based on depositional environments, is presented as While geologic formations are infinitely variable in detail, they have been classified by geologists and engineers in the petroleum industry by their trapping mechanism, the hydrodynamic conditions , lithology , and more recently by their depositional environment (how they were formed). The depositional environment influences how formation fluids are held in place, how they move, and how they interact with other formation fluids and solids . For the purposes of geologic storage, the geologic formation/reservoir classification system has been expanded to include unconventional reservoirs, such as coal seams, and igneous formations, like stacked basalts. The reservoir classification scheme developed for CO2 in geologic storage would be anticipated to flow in the future. Although diagenesis has modified fluid flow paths in the intervening millions of years, the basic architectural framework created during deposition remains; geologic processes that exist today also existed when the sediments were initially deposited. Analysis of modern day depositional analogs and evaluation of core, outcrops, and well logs from ancient subsurface formations provide an indication of how formations were deposited and how fluid flow within the formation is anticipated to flow.For fluid flow in porous media, knowledge of how depositional systems formed and directional tendencies imposed by the depositional environment can influence how fluids flow within these systems and how CO2 injection tests.The DOE is gathering data and developing a database of regional reservoirs and associated properties for each type of depositional environment. This data could be utilized by site developers and property owners to develop risk assessments and business models for CCS and to better define costs for geologic storage and determine the type and quality of geologic reservoirs in a region. DOE’s goal is to characterize the different depositional environments with drilling, subsurface geophysics, chemical analysis, geomechanical analysis of the rocks, and conducting both small- and large-scale CO2) has not been completed for shelf clastic, reef, and coal environments. Small-scale injection tests have not been performed on fluvial deltaic, eolian, and turbidite sedimentary environments. Large-scale injection tests have not been performed on deltaic, strandplain, shelf carbonate, eolian, turbidite, basalt large igneous providences (LIP), and coal. Three highly experimental reservoirs  have not been evaluated. The evaluated projects are in various states of completion—some investigations are completed and some just started. Understanding the impacts of different reservoir classes on CO2 storage supports DOE’s efforts to develop the knowledge and tools necessary for commercialization of CCS technologies throughout the United States. Using lessons learned from the behavior of CO2 in reservoirs from these geologic investigations and their known depositional environments is important in developing an understanding for similar depositional environments being considered for storage  “Monitoring, Verification, and Accounting of CO2 Stored in Deep Geologic Formations.”Through the various projects in the Program, lessons learned have been documented in a series of best practice manuals (BPMs) that serve as the basis for the design and implementation of commercial CCS projects. As of August 2010, DOE has released three BPMs: (1) “Public Outreach and Education for Carbon Storage Projects,” (2) “Site Screening, Selection, and Characterization for Storage of CO2 storage projects. Although project developers are the primary audience for this document, other stakeholders may find the contents useful. Early CO2 storage projects have been highly visible, and their success will likely impact future CO2 storage projects.The objective of the Public Outreach and Education for Carbon Storage Projects Best Practices Manual is to communicate lessons learned and to recommend best practices emerging from the public outreach conducted by the seven RCSPs. The manual is intended to assist project developers in understanding and adopting best practices in outreach to support COThe primary lesson learned from the RCSPs’ experience is that public outreach should be an integrated component of project management. Conducting effective public outreach will not necessarily ensure project success, but underestimating its importance can contribute to delays, increased costs, and community ill will. Effective public outreach involves listening, sharing information, and addressing concerns through proactive community engagement. Public outreach begins at the onset of the project, continues through the close of the project, and involves each individual on the project team.2 storage in a community being considered for a project. Ideally, public outreach can lead to a mutually beneficial outcome where project developers move ahead with the support of well-informed stakeholders who are comfortable with the project benefits and potential risks and trust the project team. As described in this BPM and shown in The RCSPs’ concept of public outreach involves efforts to understand, anticipate, and address public perceptions and concerns about CO7.2 in Deep Geologic Formations,” which includes a series of process diagrams and guidelines for site screening, site selection, and initial characterization. This document is based on the lessons learned from the RCSPs through the Validation Phase and integrates the analyses into a proposed geologic storage framework. The proposed classification framework is divided into three phases: Exploration Phase, Site Characterization Phase, and Implementation Phase. The Exploration Phase classifies storage estimates for prospective storage and classifies the site based on the level of analyses conducted. The Exploration Phase has three project sub-classes: Potential Sub-Regions, Selected Areas, and Qualified Site(s). These sub-classes correspond to three stages of evaluation during the Exploration Phase: site screening, site selection, and initial characterization (2 and compliance with the Underground Injection Control (UIC) program requirements.Another in the series of BPMs developed is the “Site Screening, Site Selection, and Initial Characterization for Storage of COrization . The mosThe primary goal of the Exploration Phase is to pare down a large region into a select few sites as seen in The Site Screening process diagram in In order to assist future project developers, a set of guidelines  has beenhttp://www.netl.doe.gov/technologies/carbon_seq/refshelf/BPM-SiteScreening.pdf.Upon completion of the site screening process, a selected area will be further evaluated during the site selection process. During site selection, five components will be analyzed. Existing data and analyses from site screening will be augmented with proprietary or other purchased data to evaluate both technical and nontechnical components, subsurface geologic data, regulatory requirements, model data, site data, and social data. Completion of each analysis will lead to a decision gate. A “yes” response will result in a list of qualified sites that will then be evaluated based on an economic feasibility plan. A “no” response at any decision gate will result in an alternative selected area being selected, and the analysis will begin again. Once it successfully proceeds through the decision gates, the selected area will be included on a list of qualified sites to be prioritized based on criteria developed during project definition, and the highest priority qualified site will proceed to the next evaluation stage—initial characterization. Process maps and site selection guidelines can be found on the NETL/DOE website: The final stage of evaluation in the Exploration Phase is initial characterization. The distinction between the initial characterization stage within the Exploration Phase and within the Site Characterization Phase is based on the level of additional funding and detailed analyses needed for the site to prepare an evaluation for potential implementation. During initial characterization, sites identified in site selection will be evaluated using five technical and nontechnical elements, including (1) baseline data, (2) regulatory requirements, (3) model data, (4) social data, and (5) site development plan. The site would be evaluated according to the evaluation criteria and a determination would be made to either collect additional data and elevate the site to the Site Characterization Phase or leave it ranked as a qualified site. If the qualified site advances to the Site Characterization Phase, then the storage estimates would be considered contingent storage resource. Initial characterization process maps and guidelines can be found on the NETL/DOE website.The site screening, site selection, and initial characterization manual will be periodically updated based on new lessons learned from the Development Phase of DOE projects. The geologic storage classification framework will also be updated as definitions and project status guidelines are further developed and refined for the Site Characterization and Implementation Phases.8.2 geologic storage a safe, effective, and acceptable method for GHG control. MVA of geologic storage sites is expected to serve several purposes, including addressing safety and environmental concerns; inventory verification; project and national accounting of GHG emissions reductions at geologic storage sites; and evaluating potential regional, national, and international GHG reduction goals.Reliable and cost-effective MVA techniques are an important part of making COImprove understanding of storage processes and confirm their effectiveness.2 with formation of solids and fluids.Evaluate the interactions of COAssess environmental, safety, and health impacts in the event of a leak to the atmosphere.Evaluate and monitor any required remediation efforts should a leak occur.etc.).Provide a technical basis to assist in legal disputes resulting from any impact of sequestration technology . Only necessary monitoring equipment is retained.Post-Closure Phase: Period when ongoing monitoring is used to demonstrate that the storage project is performing as expected until it is safe to discontinue further monitoring. Once it is satisfactorily demonstrated that the site is stable, monitoring will no longer be required except in the unlikely event of release, regulatory requirements, or other matters that may require new information about the status of the storage project.The life cycle of a geologic storage project involves four phases. Monitoring activities will vary among these phases:2, near surface CO2, and subsurface CO2. The evaluated technologies were subdivided as primary technologies, secondary technologies, and potential additional MVA technologies.Primary technologies are considered proven technologies capable of satisfying the monitoring requirements under the United States Environmental Protection Agencies underground injection control (UIC) regulations for Class I (non-hazardous), Class II(enhanced oil recovery operations), and Class V  injection wells and meet a goal of 99 percent containment by 2015. These technologies have been utilized in the petroleum industry and for geologic characterization.Secondary technologies are technologies that show promise but would need to demonstrate that they are sufficiently precise and quantitative to detect, locate, and quantify emissions as part of a CCS monitoring program.2 in a broad portfolio of potential reservoirs types. This also includes improvements of existing technologies to allow for detailed monitoring of CO2 in GS.Potential additional MVA technologies are promising additional technologies being developed to better understand the long-term behavior of COThis BPM evaluated the different available technologies for use in MVA. The technologies were evaluated for their effectiveness of monitoring atmospheric concentrations of COet al. (2004) [2 storage can be assessed.Establishing baseline conditions from which the impacts of COAssessing the integrity of shut-in, plugged, or abandoned wells.Monitoring to ensure injection effectiveness.2 plume.Monitoring to detect the location of the injected COComparing model predictions to monitoring data.Detecting and quantifying leakage from the storage formation to other strata or the surface.Assessing health, safety, and environmental impacts of leakage.2 injection.Monitoring to detect micro-seismicity associated with COMonitoring to aid in the design and evaluation of remediation efforts, if needed.Evaluating interactions with, or impacts on, other geologic resources.3.Reassuring the public, where visibility and transparency are of prime importanceIn order to implement effective controls on injection well completion, injection rates, and well head and formation pressures, specific monitoring objectives were recommended by Benson . (2004) , includiDeveloping geologic models for the sequestration site that include the reservoir, the seals, and overlying geology, aquifer(s), vadose zone, and surface.2 injection.Performing reservoir simulations of the sequestration processes of interest, such as prediction of changes and the distribution of fluid phases resulting from COUsing the geologic model and results of reservoir simulations to perform numerical simulations to predict the response of candidate geophysical and geochemical monitoring techniques.The monitoring requirements may change through the different phases of the project. This is dependent on the project’s needs and site-specific conditions. The recommended steps in the BPM for selection of suitable geophysical techniques include:The goal of this BPM is to provide information to limit unnecessary burden on owners, operators, or permitting agencies and provide a strong foundation for national consistency in permitting and safe operation of geologic storage projects.2 storage projects and monitoring requirements under the Clean Air Act. DOE plans to update the MVA BPM to account for additional monitoring requirements once these rules become final (http://water.epa.gov/type/groundwater/uic/wells_sequestration.cfm).Recent regulatory developments through the U.S. EPA have focused on finalizing rules for a new Class of UIC injection well for CO9.Carbon Sequestration Atlas of the U.S. and Canada is updated and published every two years. The BPMs will be updated as results from the RCSP field tests are analyzed and published. It is also anticipated that these BPMs will be updated as the technology and information matures.Through NETL’s RCSP Initiative, informational tools are being developed to promote successful deployment of CCS technology as a GHG mitigation option. As part of this effort, the RCSPs provide information from their regional characterization efforts and field projects to support the development of NATCARB and the BPMs. NATCARB is updated in real-time as the RCSPs perform and obtain results from their field tests allow real time access to the most recent data that the RCSPs have available. The This document was developed from several different studies/documents that were sponsored by NETL and the RCSP Initiative. A list of the documents, in addition to the cited references, is included in


LifeMap Discovery is freely available to academic nonprofit institutions at http://discovery.lifemapsc.comLifeMap Discovery™ provides investigators with an integrated database of embryonic development, stem cell biology and regenerative medicine. The hand-curated reconstruction of cell ontology with stem cell biology; including molecular, cellular, anatomical and disease-related information, provides efficient and easy-to-use, searchable research tools. The database collates  More explicit strategies include in vitro differentiation of embryonic stem (ES) cells, and reprogramming of cells to produce induced pluripotent stem (iPS) cells, collectively referred to herein as pluripotent stem (PS) cells. Clearly, the knowledge that is essential in these strategies and methods spans traditionally distinct disciplines – developmental biology, stem cells biology and general cellular and molecular biology.Several strategies are being developed to achieve better control over the process of generating the desired target cells and tissues. These strategies utilize e.g. plasticity in vivo lineage tracing reports suggest that the field of regenerative medicine will continue to be challenged with the enormous complexity of unique cell types existing distinctly in the developing organism.The numerous stem cell types and second generation embryonic progenitor cells differentiation protocols, as well as innovative ways of managing the processes of differentiation, isolation and propagation of novel cells, and During the differentiation process of human PS cells leading to the hundreds of known derivatives, the cells transition and passage through intermediate progenitor cell phenotypes such as paraxial mesoderm, somatic mesoderm, migrating neural crest, and so on. However, very little is known about the molecular markers, cell culture requirements, specific protocols for differentiation, or replicative capacity of most of these intermediate embryonic progenitor cell types. In addition, first-generation hES cell-based therapeutic candidates are likely contaminated with various embryonic progenitors, the capacity of such contaminants to generate various types of derived cells and possible adverse effects is currently a matter of considerable debate.In vitro stem cell differentiation and in vivo differentiation during development are closely related, yet that relation is not trivial or simple to mimic. Nonetheless, formation of tissues and organs that occurs in vivo, such as in transgenic murine models of development may provide highly valuable clues about developmental paths, signaling and gene expression patterns. To provide the wide scope and essential level of detailed information needed for improving stem cell applied and basic research, LifeMap Discovery integrates embryonic development and stem cell biology with molecular, cellular, anatomical and disease-related information into an interlaced data model that allows integration of these distinct areas. The underlying postulate made by LifeMap Discovery, is that the gene expression patterns that occur in developing cells, and the signaling between cells that regulates cell differentiation, provides invaluable information for (i) biologically accurate identification and classification of differentiated stem and progenitor subtypes, and (ii) suggesting mechanisms and enable the researcher to deduce the best protocols for differentiating these cells to the desired target phenotype.In the stem cell field, very few publicly available databases currently exist; each of the existing databases targets certain elements of interest to stem cell research such as expression, regulation in vitro cells providing molecular and cellular information such as gene expression, culturing conditions, differentiation protocols and related cell-therapy applications about these entities. Additionally, the developmental in vivo data and the experimental in vitro data are manually inter-linked according to their relevance to provide users with the full array of relevant information for optimal stem cell and developmental biology-related research.LifeMap Discovery is designed to provide the research community with viable, scalable, and easy to manage data describing cellular and anatomical development, and presented in a useful framework model, and with various types of de novo assimilation of peer reviewed scientific data and data resources describing mouse and human development. LifeMap Discovery is based on systematic gathering, analysis and In vivo development – cellular and anatomical ontology of the mammalian body.Stem cell differentiation – describing cultured cells and differentiation protocols.Regenerative medicine – utilizing stem cells for development of therapeutic products.in vivo cells and anatomical compartments are linked to their most similar in vitro entities, based on gene expression analysis or manual assignments based on literature.These different parts are evaluated and inter-linked by computational and manually curated methods, most noteworthy, the Underlying LifeMap Discovery is the ontology of the cellular differentiation that occurs during mammalian embryonic development. Decades of efforts in experimental embryology have elucidated the majority of the cellular pathways of mammalian development; hence, substantial amounts of data can currently be summarized in a relational database connecting each developing cell to a specific, temporospatial anatomical compartment that composes the developing organ or tissue. To account for these complex relations, and how data is collected and recorded in scientific literature, embryonic development is presented in LifeMap Discovery on three concentric levels:Organ/Tissue: A low-resolution description of mammalian development, beginning at the zygote, proceeding to the three germ layers as well as extraembryonic tissues, and extending towards the derived organs and tissues that comprise the adult body . Anatomical compartments are constructed as a developmental tree, where each parent compartment gives rise to one or more compartments, i.e. the child has a “developed-from” relation to its parent. In addition, some anatomical compartments are sub-divided, or contain other anatomical compartments, i.e., a “part-of” entity relation.Cell: Cellular data is collected at specific developmental time points or embryonic stages (e.g. Theiler stage for mouse or Carnegie stages for human). Detailed developmental paths taken by cells directed toward specific fates, such as blood, endothelium, skeletal muscles, bone, cartilage etc. Somatic cells transverse a developmental path, which defines their cellular ontology from their first ancestor or ancestors (termed “primary progenitor”) to the fully differentiated cell type.Capturing the complete cell differentiation process into an ontology also requires the ability to address each of the cells and anatomical structures in a non-redundant fashion. LifeMap Discovery introduces a cell nomenclature system that takes advantage of this three-tier system and distinctly identifies the cell-anatomical relation in the developing embryo so that ambiguities are effectively eliminated. Each cell obtains a unique ID referred to as the Embryonic Index (EIndex). The EIndex is generated by combining indexes from the organ/tissue, anatomical compartment and cells. organ/tissue card contains an illustration of the organ and links to related organs, unique lineages , anatomical compartments and cells, differentiation protocols and cell therapy applications.The anatomical compartment card provides a brief description accompanied by illustrations describing development, structure and anatomy as well as links to cells that populate the specific anatomical compartment. In addition, the card provides lists of genes specifically expressed in the compartment of interest and its related cells, links to data which has been extracted from filtered in situ hybridizations, and relevant high throughput experiments. The card also lists diseases and cell therapy applications related to the specific anatomical compartments or to its populating cells.The cell card displays the relevant embryonic developmental stage, and provides a list of expressed genes which were gathered by manual curation and/or extracted from related microarray and/or in situ hybridization experiments. The cell card also provides information on signaling and signal transduction cascades which affect cell function and differentiation in vivo, as well as related diseases which affect or involve the given cell and can potentially lead to cell-based therapeutic application by related in vitro cells. A number of useful databases that host in vivo gene or protein expression data such as MGI The in vivo development, e.g. skeletal muscle development from paraxial mesoderm. In general, skeletal muscle development differs by the anatomical origin, i.e head or trunk (body) areas of the developing embryo. The described complexity is demonstrated by the highlighted entities in the high level-ontology tree, shown at th germ layer of the embryo, emerging early in mammalian development and dividing into head  and trunk populations. While the specialized paraxial mesoderm within this mesenchyme contribute to the development of head skeletal muscles , the NC will differentiate into multiple cell types including bone, cartilage, and peripheral nerves of the anterior aspects of the head , Tbx1, MyoR (Msc) as shown in Pax3, which was shown to be essential in trunk myogenesis (together with the muscle regulatory factor Myf5). Specific differentiation signals such as Wnt3A and Wnt1, specifically inhibit skeletal muscle progenitors' differentiation in the head region  cells thin BA1 . Finally disease .The database comprehends the biological complexity utilizing the three-level tier system in an attempt to accelerate researchers search for information. Here, the two different cells described in the examples  are located at the same anatomical compartment, HdM.BA1, yet contribute to different cellular developmental paths, with distinct progeny and unique molecular signatures.in vitro cells including embryonic stem cells (ES cells), induced pluripotent stem cells (iPSCs), embryonic progenitor cells, fetal and adult stem cells and primary cells. These cells are designated in the database as either (i) source cells, undergoing any number of differentiation protocols or cell therapy applications, or (ii) protocol derived cells (PDCs) that are generated by a single differentiation step, usually as part of a multistep differentiation protocol.LifeMap Discovery provides information for various types of The “stem cell” differentiation section includes two main levels of information discussed in detail below:Stem, progenitor and primary cells Differentiation protocols in vitro cells which may serve as source cells for differentiation protocols and cell therapy applications or as valuable in vitro cell data source containing high throughput data that is useful for classification purposes. Similar to in vivo cells, each In vitro cell is presented in a card including information about its growth conditions, gene expression, related cell-therapy applications, references and more. Source in vitro cells may be matched to one or more in vivo cells or anatomical compartments of the embryo or mature mammal. The matching is done either manually or computationally (see section below), and is primarily based on gene expression profiles, but can also be based on function and morphology observations described in the literature.This section provides information relating to the various The main cell types available in this section are:ES cells and iPS cells: Pluripotent cells from mouse or human origin, derived either from early stage embryos (ES cells) or from adult/fetal tissues by induction (iPS cells). Their ability to differentiate into mature cells derived from all three germ-layers makes them promising candidates to be used in regenerative medicine. Both cell types serve as source cells for differentiation protocols towards various mature cell types.Fetal/stem progenitor cells: These cells are isolated from adult or fetal tissues and have limited differentiation capacity relative to ES cells or iPS cells. However, the ability to isolate them directly from patients make these cells attractive candidates for personalized regenerative medicine approaches. In LifeMap Discovery, these cells are described as source cells for both differentiation protocols and cell therapy applications.Primary cells: These cells are isolated from adult tissues, have limited propagation capacity in vitro and do not possess differentiation potential. They are commonly used either as supportive cells for differentiation of stem cells, as source cells for cell replacement therapies or as a source of valuable data that may be useful in characterizing unknown cells. These cells are presented in LifeMap Discovery as sources of cell therapy applications. Their gene expression profiles are useful for identification of unknown differentiated cells.Embryonic progenitor cells: Cells corresponding to the proliferating progenitors derived from pluripotent stem cells, are designated “embryonic progenitors in LifeMap Discovery. Clonally-purified embryonic progenitors are commercially available as PureStem™ human embryonic progenitor (hEP) cells, which were derived in vitro from hES cells, using a “shotgun” strategy including; spontaneous differentiation of hES cells into embryoid bodies (EBs), single cell dissociation and proliferation of various clones using a matrix of time periods and growth conditions in vivo developmental lineages  supplemented with TGFβ3, and GDF5 for 14 days, leads to differentiation into chondrocytes-like cells, based on the acquired expression of chondrocytes selective gene markers such as: ACVR1, RUNX1, PTH1R, FGFR3, SOX9, MATN3, COL11A2, LECT1, ACAN, COL9A2, COL2A1.The card also shows different culturing conditions and protocols  used to in vivo cell entities in the database, as previously described.The stem cell differentiation protocols section provides a detailed flow of protocols used to induce differentiation of various pluripotent and multipotent stem and progenitor cells to clinically relevant target cells. Each protocol is displayed in a card that contains an informative and interactive viewer, outlining the protocol as a multistep process. The protocol card depicts the source and target cells of each step in the protocol and the details of the procedure required to obtain each target cell from its source cell. Each protocol is fully referenced (cited and linked to PubMed), and includes a concise description of each step. The main protocol section includes the “protocol derived cells”, in which a user can click on each intermediate cell type, and obtain all available information about the derived cell and the step details including description, duration, main growth factors, procedure, growth conditions and % efficiency. Genes expressed in the derived cell are shown, as well as the top differentially expressed genes, extracted from microarray experiments (when available) and linked to GEO PAX7. Upon induction, differentiated cells are sorted and proliferated to yield an expanded population of PAX7 cells, which express myogenic progenitor markers such as MYOG and MYH1. These progenitors may be subsequently used to differentiate into myotubes in vitro or form mature skeletal muscle cells in vivo. The protocol card includes the title, description and available data, followed by an interactive clickable viewer describing each step of the protocol along with its source and target cells. Each of the protocol derived cells (PDCs) is clickable and will open the relevant information about this cell and the conditions used to derive it. The derivation steps are also shown on the viewer, and include the main growth factors used in each step, the main procedure performed (e.g. FACS) and the step duration. In the example protocol described, the hES cell line H9 was used as a source cell along with two other iPS cell clones (not shown). The resulting PDCs “Expanded PAX7 cells” were matched to the in vivo myoblasts of the cervical-hypaxial-myotome To demonstrate the protocol section, we select a protocol differentiating human pluripotent cells (hES cells and iPS cells) into skeletal muscle-like progenitors in vivo cells and anatomical compartments  which are either related to development or represent potential targets for cell-based therapeutic approaches are also presented in LifeMap Discovery with links to the relevant entities, indicating whether a condition affects the presented entity or can potentially be treated by specific matched cultured cells. The full list of diseases related to in vivo entities is available at: http://discovery.lifemapsc.com/regenerative-medicine/diseases.LifeMap Discovery provides information relating to regenerative medicine and cell-based therapy strategies as well. Cell-based therapy for neurodegenerative disease, heart disease, eye disease, type I diabetes, osteoarthritis etc., via replacement of damaged cells or tissues, and/or stimulation of the natural repair mechanisms of the body, offer great promise for near-future treatment of these conditions. Diseases associated with in vivo cells or anatomical compartments, the cell therapy application also appears at the matched in vivo card and under its related organ, demonstrating the possibility to use specific cell- based treatment to cure diseases that affect the in vivo entities. Additional information, available in the cell-therapy application card includes the mode and regimen of cell delivery, mechanism of action, related animal models, pre-clinical and clinical information and related publications and links.Cell-based therapeutic products are described at different stages of development . Each card describes a unique potential cell-based treatment approach for a specific disease or a group of related diseases. The information has been manually curated from various publications and/or selectively drawn from clinical trials resources. Each card is linked to the relevant cultured cells which were used as the source cells for the application. Since cultured cells are usually matched to http://www.malacards.org), enabling rapid access to information on relevant diseases such as description, clinical features, drugs and therapeutics, disease related gene expression, publications and more.In addition, LifeMap Discovery provides specific links to MalaCards, the human disease database . Data is usually cited or deep linked directly to specialized data resources, e.g. links from available genes expressed in a specific location/time will be linked to the corresponding in vitro analogs. LifeMap Discovery offers the following searching, browsing and graphical navigational options:The basic database functionality includes the ability to navigate the multi-dimensional space which is composed of cells linked to each other in a developmental and anatomy context, and the various classifications to anatomy, disease relations and Textual search – finding organs, tissues, cells and protocols, disease and cell therapy applications within the database.Gene search – finding where one or several genes are expressed.Detailed, sortable listing of all entities in all sections, and the ability to filter them as desired.in vivo cell and anatomical compartment development.Interactive graphical developmental navigator of Interactive graphical display of stem cell differentiation protocols.in vivo cells and anatomical compartments that occur during mammalian development.We will focus on two useful features of data mining (i) gene search and (ii) matching of cultured stem and progenitor cells to in vivo levels, cells, anatomical compartments and organ/tissues, as well as for in vitro cells (resulting from differentiation protocols). Gene search is available at http://discovery.lifemapsc.com/gene-expression-signals/gene-search.Gene expression data is most valuable for understanding function and classification of cells and tissues in the complex developmental stages and anatomical regions. LifeMap Discovery provides gene expression information at each of the three Sox10, Pax7 and Sox9.in vitro cultured cells and external resources (which include data on genes from high throughput gene expression datasets). The gene search can also be limited to specific types of genes or gene expression patterns: positively expressed, cell and lineage selective markers and genes that are implicated in signaling pathways. In the results summary section, results are provided in a table listing the occurrences of any of the genes on the search list, sorted by the number of genes found in the location and developmental time . Columns are sortable and include the number of matched genes in each listed card, the card type: cell, anatomical compartment, in vitro cells and in external resources . In each database element, genes are scored based on overall or temporospatial abundance, available expression level or confidence. Genes are grouped or clustered based on similarity (unsupervised) or biological context (supervised). Each method and data type may yield a unique collection of sets of genes (geneset).Sample preparation: The experimental gene expression data of the in vitro cell to be matched (7PEND24 in our example) is prepared. Raw data is normalized and a proper reference set is chosen. Depending on the data type (e.g. microarray vendor) the data is treated according to established analysis protocols to remove bad probes or treat multiple probes and samples. The various analysis and differential expression extraction methods are beyond the scope of this paper and described elsewhere . One such method is using Gene Set Enrichment Analysis (GSEA) Consolidation: The resulting geneset scores often show a wide selection of matches from the tested phenotype to other entities which are not trivial to interpret. Reasons include inherent, biological, temporal and measurement noise. For instance, the underlying gene expression data assimilated in LifeMap Discovery contains qualitative and quantitative data, obtained by numerous different technologies and different references, thus, the obtained results are not directly comparable. The computational process strives to reduce the noise and rank the matching results by aggregation and filtering. Each result has an associated set of scores for normalized match, significance and error measurements. In addition, each result can be broken down to the matched genes, their relative contribution in terms of expression, and their rank in the geneset. Results are thus aggregated based on tags and ordered by score with links to the genes and their scores.Interpretation: Interpretation and assignment of matched cells is completed manually by reviewing the results and making sure they make biological sense.in vivo development into stem cell research and into clinical utility for future basic and applied research, including regenerative medicine applications. A deep understanding of the complex developmental paths, gene expression patterns in developing cells, and the signaling cascade that drives cellular differentiation, is invaluable for identification and classification of differentiated stem and progenitor cells, and for development of more accurate protocols for differentiating stem cells into desired target cells.LifeMap Discovery has been created to bring essential and relevant knowledge from The unique value provided to the research community by LifeMap Discovery originates from:de novo assembly, reconstruction, annotation and presentation of developmental paths and cell lineages, inferred from peer-reviewed literature.The ongoing Manual assembly of gene expression and signaling molecules at each temporospatial cell and anatomical compartment.Collection and direct linking of high-throughput and large scale gene expression data.in vitro cells at various states of differentiations to similar in vivo cells, thereby identifying, classifying and indicating possible targets for research and clinical applications.Computational analysis and matching of Clinical relevance, associated diseases and differentiation protocols, providing a rich platform for therapeutic discovery.in vitro and clinical data to accelerate stem and progenitor cell based therapeutics for the treatment of yet incurable conditions and diseases. The LifeMap Discovery platform offers information free of charge to academic institutions and will continue to grow and expand to related areas.LifeMap's long-term objective is the generation of the entire mammalian development atlas with cellular resolution. The goal is to bring to researchers high quality curated information on the cells, anatomical compartments and tissues/organs that comprise it, alongside