text:
Vol. 47, Issue No. 08, 25 Feb, 2012
Updated on 25 February 2012
Noppakun Thammatacharee
Rapeepong Suphanchaimat
Viroj Tangcharoensathien
Walaiporn Patcharanarumol
Thailand's Universal Health Coverage Scheme
Thailand achieved universal health coverage by 2002 with three public health insurance schemes covering the entire population. Of these, the Social Health Insurance scheme for private sector employees has been run on a capitation contract model since 1991. The Universal Coverage Scheme followed its example, with capitation payments for outpatient services and a global budget with diagnosis-related group-based payments for inpatient care. There are several arguments in favour of this closed-end payment system such as administrative simplicity, efficiency, prevention of supplier-induced demand and long-term cost containment.
Thailand's Universal Health Coverage Scheme
Viroj Tangcharoensathien, Rapeepong Suphanchaimat, Noppakun Thammatacharee, Walaiporn Patcharanarumol
was sustained over decades, particularly at district and provincial hospitals.[5] An independent external assessment of 10 years of UCS (2001-11) confirms that Thailand had pro-poor health policies before 2001 and that the UCS continues and fosters this.[6]
Financial risk protection has been
Thailand achieved universal health coverage by 2002 with three public health insurance schemes covering the entire population. Of these, the Social Health Insurance scheme for private sector employees has been run on a capitation contract model since 1991. The Universal Coverage Scheme followed its example, with capitation payments for outpatient services and a global budget with diagnosis-related group-based payments for inpatient care. There are several arguments in favour of this closed-end payment system such as administrative simplicity, efficiency, prevention of supplier-induced demand and long-term cost containment.
Viroj Tangcharoensathien (viroj@ihpp.thaigov. net), Rapeepong Suphanchaimat (rapeepong@ ihpp.thaigov.net) and Walaiporn Patcharanarumol (walaiporn@ihpp.thaigov. net) are with the International Health Policy Programme, Ministry of Public Health, and Noppakun Thammatacharee (noppakun@ hisro.or.th) is with the Health Insurance System Research Office.
fter 27 years of gradually extending health protections coverage to different groups of the population such as the poor, public and private sector employees and the informal sector, Thailand achieved universal health coverage in 2001 and passed the National Health Security Act in 2002.[1] There are now three public health insurance schemes covering the whole population – the Civil Servant Medical Benefit Scheme (CSMBS) for public sector employees and their dependents, the Social Health Insurance (SHI) scheme for private sector employees and the Universal C overage Scheme (UCS) for the rest of the population.
General tax revenue is used to finance the CSMBS and the UCS while tripartite payroll contributions fund the SHI. Compared to payroll contributions, general tax is more progressive as the rich pay a larger proportion of their income to health financing than the poor.[2] As a matter of fact, general tax is the most progressive source of health finance, with direct tax being more so than consumption tax.
Evidence shows that the poor in Thailand benefit in a substantial way from public health services. The health system in each district, comprising health centres and a district hospital, serves as the provider network for a registered population. Its geographical proximity to the rural population plays a crucial role in ensuring the poor utilise it.[3] The primary health care services available today are the result of the rural health service infrastructure being expanded between 1970 and 1990 until all subdistricts and districts were covered by health centres and district hospitals.[4] Government health spending favoured the poor much before the coming of the UCS in 2001, and the pro-poor trend
vol xlviI no 8
greatly improved by the UCS; with a minimal incidence of catastrophic health expenditure, assessed by whether household out-of-pocket payment for health services exceeded 10% of total consumption expenditure.[7] The incidence of medical impoverishment is very low and decreasing, as measured by the additional number of people falling below the national poverty line as a result of health payments. Between 2004 and 2009, the UCS is estimated to have prevented at least 3,00,000 households from becoming poor because of paying medical bills.
Closed-End Provider Payment
The UCS adopted a system of closed-end payments to healthcare providers right from its inception in 2001. According to this, age-adjusted capitation is used to pay for outpatient services provided by a network of contracting units. This network is the district health system, consisting of a district hospital and five to eight health centres serving a population of about 50,000. It is paid on the b asis of the number of people served and their age structure, and there is a slant in favour of the elderly and children, who have a higher chance of using the services. An examination of utilisation rates shows that they are higher among these sections than the rest of the population. In this system, the financial risk is transferred to the contractor provider network, capitation payments not being linked to the number of times services are provided.
A national global budget was set up annually to reimburse provincial and tertiary hospitals for inpatient services through diagnosis-related group (DRG)based payments, reflecting volumes and case-mix, and adjusted according to the relative weights pertaining to particular hospitals. Hospitals are thus reimbursed inpatient expenditure based on the casemix severity measured by the cost weight
(so-called relative weight). The more complex a case, the higher the resource use and the higher the reimbursement level. At the end of a typical year, the total expenditure on inpatient services will not exceed the global budget. For example, in 2011, the total global budget was set at THB 54,000 million and the total national relative weight was 6 million. Therefore reimbursement per relative weight was THB 9,000. It would have been THB 8,300 per weight if the total national relative weight was 6.5 million; or THB 9,500 per weight if the total national relative weight was 5.7 million.
Capitation payments for outpatient services and a global budget with DRG for inpatient care are de facto a "hard budget".[8] A fee-for-service system implicitly results in a "soft budget" that insurance funds have difficulty in controlling because total spending is driven by numbers and the cost of services rendered. The financial risk is here transferred to the insurance fund or met through co-payment or extra billing, which has to be paid by the beneficiaries. The deficit of the insurance fund will and country experiences with the purchasing design for health services.
2 Findings
Provider Payment Methods
Table 1 shows the different modes of paying healthcare providers and the effects they have on their behaviour.[10] When primary care providers are paid on a line item budgeting system, they have incentives to increase input factors such as beds and staff and tend to use up all the budget allocated to them. The a nnual budget allocation is not linked to service output and providers may not be accountable and responsive to patients. When providers are paid on the basis of each dispensed item, it sends a strong signal to boost the number of services per patient, resulting in cost increases, which are either shouldered by the i nsurance fund or met through co- payment by the beneficiaries.
Paying per admission day sends a strong signal to prolong the stay of p atients in hospitals to boost revenue. DRG, a closedend payment per case according to its complexity, sends signals that could encourage admitting more patients, readmitting them or early discharge. But hospitals have to manage expenditure within the ceiling if they receive a global budget. A combination of a global budget set by an insurance fund and paying individual hospitals by DRG improves the chances of patients receiving quality care.
Inefficiency and Cost Escalation
Fee-for-service arrangements are used to pay general practitioners (GPs) in several Organisation for Economic Co-operation and Development (OECD) countries and are even more widely used to compensate specialists working in ambulatory care. Fee levels are either negoti ated centrally, as in Japan, Germany and Canada, or set by the individual practitioners. Countries
Table 1: Overview on Provider Payment Methods and Related Incentives
Payment Method Provider Behaviour
Primary health care services
• Input-based line item budget Increase input factors (bed, staff, etc) and use full budget
be recouped by an increased budget of • Fee-for-service Increase number of services per patient
• Capitation adjusted by Treat patient within budget, or in worst case, provide substandard
premium contributions in subsequent
age and gender care and exclude high-risk patients; refer patients to specialists and
years. So, at the end, the burden is shift
other hospitals ed to taxpayers or members of the fund. • Capitation-fee-for-service mix Treat within budget and increase number of fee-based services
The three key functions of healthcare Hospital admission services financing are resource mobilisation, pool-• Input-based line item budget Increase number of staff, beds; reduce number of admissions; keep occupancy rate low but prolong patients' average lengths of stay, refer
ing and purchasing health services.[9]
high risk/intensity patients to other hospitals
E fficiency and long-term financial sustain
• Hospital day Increase number of admissions and prolong patients' average length ability are influenced by the way clinicians of stay (ALOS)
command health resources such as diagnostics, medicines and treatment. The more services they prescribe, the higher the cost to the insurance fund or the higher co-payment beneficiaries have to shoulder, and the overall effect is an escalation in cost. If clinicians are motivated by efficiency, the cost will be better contained. Their behaviour can be influenced by the way they are paid.
This paper briefly reviews the strengths and weaknesses of different methods of paying health providers for outpatient and hospitalisation services, with special attention on fee-for-service payment, capitation, a global budget and DRG. It also looks into how Thailand introduced capitation and a global budget with DRG for the UCS in 2001, drawing on International
• Diagnostic-related Increase number of admissions, shorten ALOS, select less severe patient groups (DRG) case-mix
• Global budget Provide care within a budget ceiling
In contrast, when providers are paid on a capitation basis (per person registered with them), they have to manage expenditure within the budget they r eceive for the population registered with them. In a worse-case scenario, when effective auditing by the insurance fund is absent, they could provide substandard care or limit necessary services. They could also refer patients to specialists or other hospitals if they are not liable to pay for such referrals (nongatekeeping primary care provider).
Likewise, paying for hospital admission (inpatient) services based on line item budgeting induces similar behaviour.
such as Australia and New Zealand allow "extra billing" by GPs on top of standard patient reimbursement rates.
Information asymmetry and fee-forservice mechanisms give physicians "full discretion" over the level and mix of services provided, referrals and other treatment options. However, doctors have incentives to expand the volume and prices of the services they provide. The risk of supply-induced demand is particularly strong with this type of payment system.
There is an extensive literature on the most effective and efficient payment mechanisms, but as a generalisation,
fee-for-service payment paid through health insurance is a recipe for rapidly rising costs that will eventually require many types of controls over provider (and even patient) behaviour.[11]
In the US, health spending reached nearly $2.5 trillion in 2009 (17.6% of gross domestic product, or GDP) and was projected to reach $2.7 trillion in 2011.[12] One of the drivers of expenditure there is fee-for-service payment.
Fee-for-service payment misaligns incentives;
it creates a big incentive for overutilisation.
Although most physicians are not income
maximisers, they know that it is better to be
paid to do something, and the higher the pay
ment the better. Paying for doing more adds a
strong financial motivation to what is often a
slim clinical rationale for an intervention.
Fee-for-service payment is one of the key sources of inefficiency in the health sector. It leads to an overuse of procedures, investigation and equipment, all generated by supplier-induced demand.[14] In China, for instance, the inappropriate incentives embedded in fee-for-service payment have been recognised as creating inefficiencies, waste and poor-quality healthcare, compromising the goal of ensuring access to affordable, quality healthcare to all.[15]
Pioneering SHI Scheme
Thailand introduced the SHI scheme for private sector employees with the promulgation of the Social Security Act in 1990. The law was published in the Royal Gazette on 1 September 1990, after which there were 180 days for organisational preparation. The SHI is a tripartite payroll tax contributory scheme, equally paid for by the employer, employee and the government. The scheme covers four benefits – non-work related sickness, maternity, invalidity and funeral grants. It was initially enforced in all firms having more than 20 employees, but after three years extended to all companies with more than 10 employees.[16] Over time, the scheme has been expanded to include three other social protection measures, a child allowance and pension and unemployment benefits, with extra contributions for these purposes.
The contribution rate specified by the law was 1.5% of payroll by the three
parties (4.5% of payroll in total) for the four benefits. This contribution estimate was based on the total resources required for these benefits. In the mid1980s, when knowledge of strategic purchasing and provider payment was not widespread in developing countries, International Labour Organisation (ILO) consultants had advised the Thailand's labour department that with this contribution rate, the benefit package would only cover inpatient services; an estimate that was based on the fee-for-service reimbursements paid by the Workmen Compensation Fund (for work-related illnesses, injuries and deaths). But the capitation contract model contributed significantly to the success of the SHI scheme's implementation, in particular with regard to cost containment and fi n ancial sustainability, and this persuaded the UCS to adopt the model in 2001.
Adoption of Capitation Contract Model
The preparatory team for the SHI scheme, using existing evidence, convinced the first secretary general of the Social Security Office (SSO) to accept capitation at a level of THB 700 (THB 25 was $1 at the time) per person. This was adopted by the SSO in 1991. (One of the authors, Viroj Tangcharoensathien, was a member of this team.) The contractor hospitals received THB 700 per SHI member registered with them. The more the number of persons registered with a hospital, the larger the revenue it received. This was not tied to the number of outpatient and inpatient services rendered.
We now take a look at the arguments that were made in favour of capitation. First, the capitation of THB 700 per member in 1991 allowed for the purchase of both outpatient and admission services. The capitation rate was based on a simple formula – three visits per capita per annum multiplied by a unit cost of THB 150 per visit, plus 0.1 admissions per capita per annum multiplied by a unit cost of THB 3,000 per admission. This actually gives a capitation rate of THB 750, but the SSO approved only THB
700. The total resources required using the capitation model were found to be
affordable because it matched the revenue collected from payroll contributions.[17]
Second, the formula allowed contractor providers some margin. There was a chance that the utilisation rate might not reach three visits per person per year and admission rates might also be lower than estimated because most private s ector employees were young adults who tended to be reasonably healthy.
Third, instead of only covering inpatient care using fee-for-service payment, the same amount of funds could purchase additional outpatient services, thus minimising the health expenditure burden of members. In the process, workers received better protection and the SSO gained social credit for delivering more benefits than promised.
Fourth, the reform-minded technocrats had direct experience of the cost escalation that took place in the feefor-service CSMBS, which was risky for the fund. It was also unlikely that it could be successfully reformed. Under fee-for-service payment, a ceiling must be introduced to safeguard the financial stability of the social security fund and co-payment becomes a burden on low-income wage earners. Co-payment was not allowed to figure in the capitation model.
Fifth, the administrative cost of managing the capitation system was modest. Only a monthly wire transfer of the capitation fee had to be made to the contractor hospital. This was in marked contrast to the huge workload a fee-for-service system would have entailed (three visits plus 0.1 admissions multiplied by 1.8 million members resulted in 5.6 million transactions). An exhausted claims review staff would have ended up rubber stamping claims all night long.
Sixth, capitation did come with registration as opposed to the free choice a fee-for-service system granted. However, a limited choice was available under the contract model – members could make an annual choice of which contractor they preferred. There were a sufficient number of competing public and private hospitals in urban areas the SSO could make contractual arrangements with and there was no need for it to construct its own hospitals.
Seventh, capitation ensured a smooth flow of income to contractor providers, which facilitated better business planning. This has been subsequently confirmed by key hospital informants.
After the capitation contract model was adopted, evidence showed that public and private contractor hospitals made good margins in the first four or five years as the utilisation rate was well b elow the estimate. The THB 700 capitation rate was maintained until the first revision in 1998, which was made in the wake of the 1997 Asian financial crisis.
UCS Adopts Capitation Model
Under the capitation contract model, the utilisation rate by SHI beneficiaries gradually increased as did the quality of service.[18] The model went through various adjustments to the Thai health system over a decade before the UCS was based on it, with some modifications. Instead of inclusive capitation for outpatient and inpatient services, as in the SHI scheme, the UCS applies capitation only for outpatients and a global budget with case-based payments, or DRG, for inpatients. This is to prevent the underprovision of inpatient services, which can occur with inclusive capitation – expensive admission could be dumped into ambulatory care to keep costs down. U nder the global budget and DRG payment system, hospitals are reimbursed on the basis of the relative weight of each DRG for inpatient cases.
The free-choice, fee-for-service model of the CSMBS was not pursued due to s erious cost escalation, supplier-induced demand[19] and systems inefficiency. Reformists perceived that the free consumer choice inherent in the fee-for-service system would not outweigh the cost of inefficiency.[20] In addition, free choice does not promote equity in access and use of health services by rural people if they have to pay to travel to provincial hospitals, bypassing primary health care in their home district. Free choice undermines the functioning of primary health care in district health systems and results in higher inequity in access and use of health services. At the same time, it provides less access to tertiary care for rural people.
It is important to note that the same group of health system and policy researchers and reformers who were involved in the design, monitoring and evaluation of the SHI scheme in the 1990s influenced the design of the UCS in 2001. The introduction of the capitation model in the UCS in 2001-02 met with no resistance from public or private providers because they were used to working within the SHI system since 1991. However, efforts to push the fee-for-service CSMBS towards a capitation model have consistently failed since 1995 due to benefits accruing to all entrenched parties.
A number of factors contributed to the success of the contract model in the SHI scheme and to its later extension to the UCS, again with favourable results.
After the Social Security Act was endorsed by Thailand's parliament in September 1990, there were only 180 days for organisational preparation, such as setting up a system for collecting premiums, registering employers and employees, and developing information systems. The secretary general of the SSO recognised the complexity of the fee-forservice reimbursement method, the high number of claims that would have to be handled and the need for strong auditing systems as in the Workmen Compensation Scheme. The new proposal based on the simplified management strategy of a capitation contract model was compelling, given the very short time there was before implementation.
In addition, while the fee-for-service model could only cover inpatient serv ices with 4.5% of payroll contribution, the capitation model could give cover both outpatient and inpatient services with the same amount – an argument in its f avour and a reason for it gaining political support. Later, the successful implementation of the capitation model in the SHI scheme nationwide since 1991 made every partner in the UCS confident about it.
Role of Evidence
The capitation formula allows for quite a favourable margin given the utilisation rate. In practice, employees covered by the SHI scheme were initially not fully aware of their rights and entitlements. So the utilisation rate in the first three to four years was lower than the estimate and this resulted in substantial profits to both public and private contractor hospitals.
In addition, the SHI scheme's capitation contract model had a good image right from the beginning and even with auditing and monitoring systems well in place, it resulted in adequate service provision.
Evidence on its own was not enough and it was very important to present the secretary general of the SSO with all the information he needed for the UCS as well as compelling arguments. The trust that existed between the decision-makers and the technical team members played a significant role. The reformers of the 1991 SHI and the 2001 UCSs were the same group of health system and policy researchers and entrepreneurs. Their values, experience and background in health systems ensured that they realised the importance of primary health care and that their attitude was pro-poor.
The formula to calculate capitation for the UCS was similar to the SHI but the
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february 25, 2012 vol xlviI no 8
information was more up to date. Thailand has key national representative household data sets with the health and welfare survey conducted regularly by National Statistical Office. Data on the utilisation rate of health schemes, health seeking and the unit cost of health care providers facilitated estimating the rate of capitation. The formula and data used were peer-reviewed by all the key partners through the financing subcommittee. All the partners, including the bureau of budget, politicians and healthcare providers, felt assured the capitation rate stood on a firm platform of evidence.
Thailand introduced capitation to the SHI scheme in 1991 and managed to successfully run it, dispensing quality healthcare and also satisfying providers in terms of their margins, particularly in the initial years. This ensured the SHI contract model served as an example for the UCS. It is now evident that capitation and case-based payments in the UCS have led to an increased use of generic 18.5 billion pesos",[23] which is what it spent that year on healthcare purchases.
In universal health coverage, the ways in which healthcare services are purchased and providers are paid are important factors determining long-term cost containment, systems efficiency and financial risk protection for beneficiaries. A fee-for-services system provides free choice to consumers, but its downside of supplier-induced demand, cost increases and inefficiency outweigh whatever benefits unfettered choice may have. Policymakers need to pay special attention to the purchasing design so that it realigns incentives for providers with the social goals of quality and efficiency. Closed-end payment offers better cost containment and provides a d ecent quantity and quality of care, as proved by 20 years of the SHI scheme and 10 years of the UCS in Thailand.
[7] Limwattananon, S, V Tangcharoensathien and P Prakongsai (2007): "Catastrophic and Poverty Impacts of Health Payments: Results from National Household Surveys in Thailand", Bulletin of the World Health Organisation, 85, pp 600-06.
[8] Rechel, B, S Thomson and E van Ginneken (2010): Health Systems in Transition: Template for Authors (Copenhagen: WHO).
[9] World Health Organisation (2010): The World Health Report 2010: Health Systems Financing
(Geneva: WHO).
[10] Schneider, P (2007): "Provider Payment Reforms: Lessons from Europe and America for South Eastern Europe", Policy Note (Washington DC: World Bank).
[11] Doetinchem, O, G Carrin and D Evans (2010): "Thinking of Introducing Social Health Insurance? Ten Questions", Background Paper No 26, World Health Report 2010 (Geneva: WHO).
[12] California Health Care Almanac, Health Care Costs 101, at http://www.chcf.org/~/media/ MEDIA%20LIBRARY%20Files/PDF/H/PDF%20 HealthCareCosts11.pdf, accessed on 7 February 2012.
[13] Emanuel, E J and V R Fuchs (2008): "The Perfect Storm of Overutilisation", Journal of the American Medical Association, 299, pp 278991; Fuchs, V R (2009): "Eliminating 'Waste' in Health Care", Journal of the American Medical Association, 302, pp 2481-82.
[14] Thomson Reuters (2009): "Where Can $700 Billion in Waste Be Cut Annually from the US Healthcare System?", White paper (Ann Arbor: Thomson Reuters), at http://thomsonreuters.com/content/press_room/healthcare/waste_US_healthcare_system, accessed on 5 February 2012.
[15] Yip, W, W Hsiao, Q Meng, W Chen and X Sun
medicines and an emphasis on proper diagnosis and treatment, resulting in cost containment and systems efficiency.
Once a payment system is entrenched, particularly where private, for-profit providers dominate the healthcare market, radical reform from a fee-for-service system to a capitation or case-based payment system will face united resistance from the medical profession, as seen in South Korea.[21] It is introducing the right purchasing strategies at an early stage that lays the foundation for the successful performance of social health insurance.
In the Philippines, the design of Phil-Health does not provide adequate financial protection to its members. Outpatient services are not covered; inpatient care is reimbursed on a fee-for-service basis, but only up to a maximum amount, with patients having to pay the rest from their pockets. This resulted in slightly more than a third of the total medical bill being paid by patients in 2008.[22] The PhilHealth annual report for 2008 stated, "PhilHealth must move away from fee-for-service towards provider payment schemes where it can easily leverage its purchasing power of more than
[1] Tangcharoensathien, V, P Prakongsai, S Limwattananon, W Patcharanarumol and P Jongudomsuk (2009): "From Targeting to Universality: Lessons from the Health System in Thailand" in Peter Townsend (ed.), Building Decent Societies: Rethinking the Role of Social Security in Development (Hampshire: Palgrave Macmillan), pp 310-22.
[2] Prakongsai, P, S Limwattananon and V Tangcharoensathien (2009): "The Equity Impact of the Universal Coverage Policy: Lessons from Thailand", Advances in Health Economics and Health Services Research, 21, pp 57-81.
[3] Prakongsai, P (2008): "The Impact of the Universal Coverage Policy on Equity of the Thai Health Care System", Doctoral thesis, London School of Hygiene and Tropical Medicine, University of London.
[4] Patcharanarumol, W, V Tangcharoensathien, S Limwattananon, W Panichkriangkrai, K Pachanee, W Poungkantha, L Gilson and A Mills (2011): "Why and How Did Thailand Achieve Good Health at Low Cost?" in D Balabanova, M McKee and A Mills (ed.), 'Good Health at Low Cost' 25 Years On – What Makes a Successful Health System? (London: London School of Hygiene and Tropical Medicine), pp 193-223.
[5] Limwattananon, S, V Tangcharoensathien, K Tisayathicom, T Boonyapaisarncharoen and P Prakongsai (2012): "Why Has the Universal Coverage Scheme in Thailand Achieved a Pro-Poor Public Subsidy for Health Care?", International Health Policy Programme, Nonthaburi, Ministry of Public Health.
[6] Evans, T, M Chowdhury, D Evans, A Fidler, M Lindelow, M Mills, X Scheil-Adlung and Thai Research Team (2012): "Thailand's Universal Coverage Scheme: Achievements and Challenges: An Independent Assessment of the First 10 Years (2001-2010)", Synthesis Report, Draft 3, Nonthaburi, Health Insurance Systems Research Office.
(2010): "Realignment of Incentives for Healthcare Providers in China", Lancet, 375, pp 1120-30.
[16] Social Security Office (1990): Social Security Act, at http://www.sso.go.th/cms/ spaw2/uploads/files/ssolaw/1.1web.htm, accessed on 3 March 2010.
[17] Tangcharoensathien, V and S Waleeithikul (1991): "Social Security Act: Who Gain, Who Lose?", Thai Medical Council Bulletin, 20, pp 215-22.
[18] Mills, A, S Bennett, P Siriwanarangsun and V Tangcharoensathien (2000): "The Response of Providers to Capitation Payment: A Case-Study from Thailand", Health Policy, 51, pp 163-80; Tangcharoensathien, V, A Supachutikul and J Lertiendumrong (1999): "The Social Security Scheme in Thailand: What Lessons Can Be Drawn?", Social Science and Medicine, 48, pp 913-23.
[19] Tangcharoensathien, V,	J Lertiendumrong and S Saranasathaporn (1999): "Report on Research for Reform of the Civil Servant Medical Benefit Scheme", Mimeograph in Thai (Bangkok: Health Systems Research Institute).
[20] Langenbrunner, J C, C Cashin and S O' Dougherty, ed. (2009): Designing and Implementing Health Care Provider Payment Systems How-To Manuals (Washington DC: International Bank for Reconstruction and Development/World Bank).
[21] Kwon, S (2003): "Payment System Reform for Health Care Providers in Korea", Health Policy Plan, 18, pp 84-92.
[22] Tangcharoensathien, V, W Patcharanarumol, P Ir, S M Aljunid, A G Mukti, K Akkhavong, E Banzon, D B Huong, H Thabrany and A Mills (2011): "Health-Financing Reforms in Southeast Asia: Challenges in Achieving Universal Coverage", Lancet, 377, pp 863-73.
[23] Philippines Health Insurance Corporation (2008): PhilHealth Annual Report, at http://www. philhealth.gov.ph/about_us/annual_report/ ar2008.pdf, accessed on 6 Feb 2012.
Read more about Thailand's Universal Health Coverage Scheme


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Identification and Analysis of Genes Associated with Epithelial Ovarian Cancer by Integrated Bioinformatics Methods
Ting Gui, Chenhe Yao, Binghan Jia, Keng Shen
Background: Though considerable efforts have been made to improve the treatment of epithelial ovarian cancer (EOC), the prognosis of patients has remained poor. Identifying differentially expressed genes (DEGs) involved in EOC progression and exploiting them as novel biomarkers or therapeutic targets for EOC is highly valuable.
Methods: Overlapping DEGs were screened out from three independent gene expression omnibus (GEO) datasets and subjected to Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. The protein-protein interactions (PPI) network of DEGs was constructed in the STRING database. The top 20 hub genes were selected using cytoHubba. The expression of hub genes was detected in GEPIA, Oncomine, and human protein atlas (HPA) databases. The relationship of hub genes with the pathological stage and the overall survival and progression-free survival in EOC patients was investigated using the cancer genome atlas data.
Results: A total of 306 DEGs were identified, including 265 up-regulated and 41 down-regulated. Through the PPI network analysis, the top 20 genes were screened out, among which 4 hub genes were selected after literature retrieval, including CDC45, CDCA5, KIF4A, ESPL1. The four genes were up-regulated in EOC tissues and the expression of these four genes decreased gradually with the continuous progression of EOC. Survival curves illustrated that patients with a lower level of CDCA5 and ESPL1 had better overall survival and progression-free survival.
Conclusions: Two hub genes, CDCA5 and ESPL1, identified as playing tumor-promotive roles, could be utilized as potential novel therapeutic targets for EOC treatment.
Sexual & Reproductive Medicine
epithelial ovarian cancer (EOC)
differentially expressed genes (DEGs)
biomarker
bioinformatical analysis
Ovarian cancer has the highest mortality in gynecologic cancers and most patients are diagnosed at advanced stages [1]. Many patients would still relapse even if they are treated with satisfied cytoreductive surgery (CRS) combined with standard platinum-based chemotherapy. The 5-year survival rate for patients with advanced ovarian cancer is about 30% [2]. Thus, investigating reliable and effective molecular markers and understanding essential genes involved in the biological process of ovarian cancer is urgently needed.
The Gene Expression Omnibus (GEO) database is a free online database that stores a multiple of high-throughput microarrays, chips, and next-generation sequence functional genomic data sets [3]. The GEO database could be utilized to screen out differentially expressed genes (DEGs), to explore molecular signals and correlations, and to analyze gene regulatory networks. However, due to high expenses and limited sample tissues, the analysis results of individual experiments may be biased and unreliable. Therefore, integrated analyses of multiple datasets may improve the accuracy and reliability of the analysis and hence produce a more comprehensive and well-rounded discovery of DEGs in a variety of cancers.
In this study, original data from microarray analysis conducted on epithelial ovarian cancer (EOC) samples were downloaded from the GEO database, and integrated analysis was implemented. A total of 20 overlapping DEGs were screened out by the intersection of three independent datasets. Then, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and protein-protein interactions (PPI) were performed to evaluate the underlying molecular mechanisms involved in carcinogenesis and tumor progression. The hub genes that may play essential roles in EOC were identified, and the relative expression level of hub genes and their relationship with EOC patient survival were validated in multiple online databases.
Microarrays and bioinformatics analysis
The original CEL files of three independent GEO datasets (GSE119056, GSE54388, GSE66957) were downloaded and analyzed using R language. We utilized the affy package to perform the background correction and data normalization, including conversion of raw data formats, imputation of missing values and background correction. Then, the samples were subjected to differential expression analysis using the Limma package. p < 0.05 and |log FC |>1 were set as the threshold, and the genes that met the criteria were screened out as DEGs. The intersection of DEGs from three datasets was performed using the VennDiagram package in R language.
Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis
KOBAS v 3.0 (http://lobas.cbi.pku.edu.cn) is a web server for gene/protein functional annotation and functional gene set enrichment [4]. The overlapping DEGs from three GEO datasets were subjected to GO and KEGG pathway analysis by this online tool. p < 0.05 was considered as statistically significant.
Identification of top modules and hub genes in a protein-protein interaction (PPI) network
Exploring the functional interactions between proteins is essential for understanding the molecular mechanisms of EOC. The Search Tool for the Retrieval of Interacting Genes (STRING v 11.0) is an online tool (http://string-db.org) designed to establish potential interactions among a good number of genes [5]. The overlapping DEGs were put into the software to construct the PPI network and were then visualized using Cytoscape software 3.7 (http://www.cytoscape.org) [6]. In addition, the Molecular Complex Detection (MCODE) in Cytoscape software (Cytoscape v 3.7.1) was applied to screen out top modules inside the PPI network with degree cut-off = 2, node score cut-off = 0.2, Max depth = 100 and k-score = 2. CytoHubba, a plugin in the Cytoscape software, was adopted to calculate the degree of each protein node. In our study, the top twenty genes were selected as hub genes.
Validation of hub gene expression levels in multiple database
To validate the mRNA level of hub genes in EOC, we examined the relative expression of these genes in two databases, namely, GEO and GEPIA. GEO (Gene Expression Omnibus; http://www.ncbi.nlm.nih.gov/geo/), an online platform providing microarray datasets and data-mining functions, could be applied to validate the expression of specific genes in multiple diseases including cancers, thereby facilitating the discovery of potential essential genes involved in disease development and progression [7]. GEPIA (Gene Expression Profiling Interactive Analysis; http://gepia.cancer-pku.cn/), a web-based tool based on the cancer genome atlas (TCGA) and GTEx data, could be utilized to conduct differential expression analysis, correlation analysis, patient survival analysis, similar gene detection and dimensionality reduction analysis [8]. In the current study, we detected the relative expression of three hub genes in these two databases with a threshold of p < 0.05 and a fold change of 2.
Survival analysis and tumor stage/grade analysis of hub genes
UCSC Xena v 1.0 (http://xenabrowser.net/) is an online database from which users could obtain functional genomic data sets to make correlations between genomic and/or phenotypic variables. In this study, we utilized this free online tool to detect whether the expression of hub genes was correlated with the overall survival and tumor stage/grade of EOC patients from TCGA samples. Patients were grouped into a relatively high expression group and a low expression group according to the median, and p < 0.05 was considered as statistically significant.
All the statistical analysis in this study was performed using SPSS 21.0 software. Comparisons between the two groups were performed using Student's two-tailed t test. Kaplan-Meier survival analysis was performed to compare EOC patient survival based on hub gene expression using log-rank test. p < 0.05 was considered statistically significant.
1. Identification of DEGs from GEO datasets analysis
Raw data from three independent datasets (GSE119056, GSE54388, GSE66957) were downloaded from GEO and then subjected to differential expression analysis using R language.. Genes screened from the criteria set as p < 0.05 plus |log FC |>1 were plotted using R language to visualize the distribution of DEGs between EOC and compared normal controls from three datasets. The volcano plot of each gene expression profile data was shown in Fig. 1a-c. Red or blue dots represent significantly up-regulated or down-regulated genes, respectively. Afterwards, three hundred and six overlapping DEGs in total, including 265 up-regulated genes and 41 down-regulated genes, were found in EOCs compared with adjacent ovarian tissues under the criteria (Fig. 1d-1e).
2. GO analysis and KEGG analysis of the overlapping DEGs
To gain a more in-depth understanding of the common DEGs from three datasets, GO analysis and KEGG pathway enrichment analysis were performed in KOBAS. The top 10 biological processes that these DEGs involved in was presented in Fig. 2a, among which cell division, cell proliferation, adhesion, and response to drug were closely associated with cancer progression. Regarding cellular component, GO analysis results showed that the overlapping DEGs were mainly enriched in cytoplasm, nucleus, cell membrane, and extracellular exosome (Fig. 2b). It was well-established that extracellular exosome could participate in the malignant progression of cancer including EOC. For molecular function classification, the DEGs were significantly enriched in the following functions: protein binding, ATP binding, poly A RNA binding, and chromatin binding (Fig. 2c). The results from KEGG analysis showed that these DEGs were particularly enriched in pathways in cancer, cell cycle, and carbon metabolism (Fig. 2d). The above findings consistently indicated that these DEGs might modulate EOC proliferation and metastasis through multiple signaling pathways.
3. PPI netwok of common DEGs and hub gene identification
To further explore the unerlying association between DEGs, a PPI network was constructed by using the STRING database (Fig. 3a). Then, the top two modules inside the PPI network were identified with the MCODE application in Cytoscape (Fig. 3b-c). Overall, the number of nodes was 306, the number of edges was 1105, the average node degree was 7.22, the average local clustering coefficient was 0.424, and the PPI enrichment p-value was < 1.0e-16. For details, module 1 consisted of 30 nodes and 416 edges. For module 2, 12 nodes and 46 edges existed. Furthermore, cytoHubba was applied to screen out hub genes, and the top 20 genes were selected by using the MCC method (Fig. 3d). The top 20 hub genes included BUB1, CDK1, CCNB2, TPX2, KIF11, CDC45, CENPF, DLGAP5, CDCA5, UBE2C, TOP2A, ASPM, MELK, KIF4A, SPAG5, MKI67, CEP55, ESPL1, KIF14, and NEK2.
4. Literature retrieval of DEGs in Pubmed
Literature retrieval of the 20 DEGs screened from the three datasets showed that there were 5 genes having only 1 or 2 research papers published in Pubmed until now, including CDC45, CDCA5, KIF4A, SPAG5, and ESPL1. Although there was only 1 research paper found focusing on the gene SPAG5, the correlation of SPAG5 with the ovarian cancer had been explored deeply in the paper. Thus, we selected the other four genes, CDC45, CDCA5, ESPL1, and KIF4A, as the hub genes in our subsequent research.
5. Validation of hub gene expression levels in multiple database
We determined the transcriptional expression differences of hub genes between EOC tissues and normal tissues in datasets of GEO and GEPIA. As shown in Fig. 4 (GEO) and Fig. 5 (GEPIA), mRNA levels of four hub genes, CDC45, CDCA 5, ESPL1, and KIF4A, were significantly up-regulated in EOC samples compared with normal ovarian tissues.
6. Clinical Stage Analysis Of The Hub Genes
The expression levels of the 4 hub genes at different stages were shown in Fig. 6. According to the result, it was easy to find that there were significant variations in the expression levels of CDC45 [Pr(> F) = 0.000554], CDCA5 [Pr(> F) = 0.00668], KIF4A [Pr(> F) = 0.0217], and ESPL1 [Pr(> F) = 0.00966]. The overall trends indicated that the expression of these four genes decreased gradually with the continuous progression of OC.
7. Survival analysis of DEGs expression in patients with EOCs
To further investigate the prognostic values of DEGs in EOC patients, we conducted a survival assay based on the TCGA data downloaded from the UCSC Xena database. As suggested in Fig. 7(a-d), the relatively higher expression of CDCA5 and ESPL1 was associated with poor prognosis of EOC patients, coherent with higher expression in EOC tissues vs. lower expression in normal ovarian tissues, while the other two genes, CDC45 and KIF4A, had no statistical influence on patients' overall survival.
Furthermore, we also detected whether these genes were related to the progression-free survival of EOC patients, and survival curves illustrated that CDCA5 and ESPL1 notably affected the progression-free survival time of EOC patients (Fig. 7(e-h)). Evidently, patients with a lower level of CDCA5 and ESPL1 had better progression-free survival compared to patients with higher CDCA5 and ESPL1 expression.
From the analysis above, we concluded that CDCA5 and ESPL1 might be closely correlated with EOC overall and progression-free survival, implying the essential roles that these two genes might play in EOC progression.
Despite significant advances in EOC treatment, including surgery, chemotherapy, radiotherapy, and novel targeted agents, EOC had remained an intractable cancer over the past several decades. Therefore, uncovering the etiological and molecular mechanisms underlying EOC is of vital importance for cancer therapy and prevention. For many years, bioinformatics analysis has been playing crucial roles in cancer study, and it facilitates the understanding of carcinogenesis by integrating data at the genome level with systematic bioinformatics methods. Among the multiple bioinformatics strategies, DNA microarray gene expression profiling has been widely applied to explore DEGs involved in tumorigenesis, diagnosis, and therapeutic approaches [9].
In this study, we first screened DEGs from three independent GEO datasets, and implemented GO-KEGG pathways enrichment analysis. A PPI network was constructed in the STRING database and the top 20 hub genes were selected in Cytoscape. We then implemented literature retrieval of the 20 genes in Pubmed. Five genes were found having only one or two research papers published previously, including CDC45, CDCA5, KIF4A, ESPL1, and SPAG5. Although there was only one research paper found focusing on the gene SPAG5, the correlation of this gene with the ovarian cancer had been explored deeply in the paper. Therefore, we focused on the other four hub genes in our subsequent research. The relative expression of the four genes, CDC45, CDCA5, KIF4A, and ESPL1, was detected in Oncomine and GEPIA databases, suggesting that all the four hub genes were up-regulated in EOC tissues with statistical significance. Clinical stage analysis indicated that the expression of these four genes decreased gradually with the continuous progression of OC. Survival curves illustrated that patients with a lower level of CDCA5 and ESPL1 had better overall survival and progression-free survival compared to patients with higher expression. Therefore, these two hub genes, CDCA5 and ESPL1, could be utilized as potential diagnostic indicators for EOC.
Cell-division cycle-associated 5 (CDCA5), also known as sororin, is thought to play a critical role in ensuring the accurate separation of sister chromatids during the S and G2/M phases of the cell cycle through interactions with cohesin and cdk1 [10, 11]. CDCA5 has also been shown to interact with ERK as well as cyclin E1, a critical regulator of the G1/Smitotic checkpoint [10–12]. Recent studies have correlated the expression of CDCA5 with tumorigenesis and tissue invasion in several cancers.
Regarding lung cancer, several researches confirmed that CDCA5, exhibiting high specificity and sensitivity to distinguish malignant lesions from non-malignant tissues and associated with poor survival, could be identified as predictive biomarkers for tumorigenesis and poor prognosis of lung adenocarcinomas [13, 14]. In study performed by Nguyen et al, suppression of CDCA5 expression inhibited the growth of lung cancer cells; concordantly, induction of exogenous expression of CDCA5 conferred growth-promoting activity in mammalian cells. Their data suggested that transactivation of CDCA5 and its phosphorylation at Ser209 by ERK played an important role in lung cancer proliferation, and that the selective suppression of the ERK-CDCA5 pathway could be a promising strategy for cancer therapy [12].
In researches of hepatocellular carcinoma (HCC), CDCA5 was also found to be up-regulated in HCC cells, and related to poor prognosis [15]. CDCA5 participated the promotion of HCC cells proliferation, migration, and invasion, palying a tumor-promotive role and being a potential therapeutic target for patients with HCC [16, 17]. Besides, CDCA5 was found to be transcribed by E2F1, and could promote oncogenesis by enhancing cell proliferation and inhibiting apoptosis via the AKT pathway in HCC [18]. Another research found that increased CDCA5 expression was associated with increased tumor diameter and microvascular invasion in HCC [19]. Furthermore, silencing of CDCA5 inhibited cell proliferation and induced G2/M cycle arrest in vitro, and CDCA5 down-regulation in xenograft model impeded HCC growth in vivo. CDCA5 depletion decreased the levels of ERK 1/2 and AKT phosphorylation in vitro and in vivo. Taken together, theses results indicated that CDCA5 might act as a novel prognostic biomarker and therapeutic target for HCC [20].
In addition, it has also been confirmed that CDCA5 was significantly upregulated in breast cancer, bladder cancer, oral squamous cell cancer, urinary tract carcinoma, head and neck squamous cell carcinoma, and esophageal squamous cell carcinoma, and the high expression of CDCA5 was closely related to pathological stages and poor prognosis of patients [21–26].
ESPL1, also known as extra spindle poles-like 1 protein or separin, plays a central role in chromosome segregation by cleaving the cohesin complex at the onset of anaphase [27], and altered ESPL1 activity is correlated with aneuploidy and cancer [28]. At present, the results on the roles of ESPL1 in cancers are conflicting.
ESPL1 expression has been found to be upregulated in a wide range of cancers and high expression of ESPL1 is associated with a loss of key tumor suppressor gene P53, which further contributes to the progression of mammary adenocarcinomas [29, 30]. The research conducted by Finetti et al reinforced that ESPL1 was a candidate oncogene in luminal B breast cancer, and the expression of ESPL1 might represent a promising therapeutic approach for the poor-prognosis tumors [31]. Genomic analysis of transitional cell carcinoma (TCC) by both whole-genome and whole-exome sequencing of 99 individuals with TCC found frequent alterations in ESPL1 [32]. Chen et al found that ESPL1 may be associated with bladder cancer development and recurrence [33]. In addition, Liu et al. identified 7 pivotal genes involved in endometrial cancer prognosis and constructed a prognostic gene signature, among which ESPL1 was one of the genes that were viewed as risky prognostic genes [34]. ESPL1 expression was found to be increased in endometrial cancer tissues, but the clinical significance and functional mechanism of ESPL1 in EC remains to be verified [34]. Nevertheless, it has also been reported that ESPL1 plays an opposite role in gastric adenocarcinoma. ESPL1 expression was negatively correlated with gastric adenocarcinoma pathologic stage progression, and the high expression of ESPL1 was significantly correlated with favorable outcomes [35]. Further work is required to resolve the conflicting roles of ESPL1 in cancer and determine its functions in cancers including the ovarian cancer.
There are several limitations in our study as follows. First, there is an urgent need for biological experiments to validate our results because our research is based on data analysis. Second, we lack the molecular mechanisms for these genes, and we will incorporate these for further exploration. In the future, we will further design experiments (including PCR, Western Blot, immunohistochemistry, etc.) based on specific mechanisms, conduct in-depth research, and improve the inadequacies.
Our study provided a comprehensive bioinformatics analysis of DEGs, which may have the potential to serve as reliable molecular biomarkers for the diagnosis and prognosis of EOC. Two genes, CDCA5 and ESPL1, were validated to be up-regulated in EOC samples, and high expression of these two genes were related with poor overall survival and progression-free survival. CDCA5 and ESPL1 may act as efficient biomarkers and potential therapy targets in EOC. Further studies are merited to explore the biological functions of these genes and to clarify the underlying molecular mechanisms involved in the pathogenesis of EOC.
cytoreductive surgery; GEO:Gene Expression Omnibus; DEGs:differentially expressed genes; EOC:epithelial ovarian cancer; GO:gene ontology; KEGG:Kyoto encyclopedia of genes and genomes; PPI:protein-protein interactions; STRING:Search Tool for the Retrieval of Interacting Genes; MCODE:Molecular Complex Detection; GEPIA:Gene Expression Profiling Interactive Analysis; TCGA:tool based on the cancer genome atlas.
Content for publication
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
This study was supported by National Natural Science Foundation of China (No. 81402140).
Conception and design: Ting Gui, Keng Shen
Acquisition of data: Ting Gui, Chenhe Yao
Analysis and interpretation of data: Ting Gui, Binghan Jia
Writing, review, and revision of the manuscript:Ting Gui, Keng Shen
We thank the GEO, TCGA, DAVID, KEGG, STRING, GEPIA2, STITCH, Kaplan-Meier plotter databases for providing their platforms and the contributors for their valuable data sets.
Ting Gui and Keng Shen:
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Chenhe Yao and Binghan Jia:
Department of R&D Technology Center, Beijing Zhicheng Biomedical Technology Co, Ltd, Beijing, China.
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redpajama_set_name: RedPajamaCommonCrawl


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Julie Tingley is an 8-year Tampa transplant who has found her way through numerous professional and parenting transitions by maintaining focus on her daily inspirations: Ella, 6, and Kate, 3. With a vision of a better future for her girls, she has introduced the KNOW Book + Tribe, a women's publication and community, to Tampa Bay.
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Neptune Entertainment is happy to announce the title of DJ Neptune's debut album G.R.E.A.T.N.E.S.Sand to commensurate the excitement, Neptune is releasing a brand new single off the yet to be released Album #GREATNESS, featuring rave of the moment and new Star Boy signee Mr Eazi who is currently taking Afrobeat to another level.
According Neptune: It's been a long journey of sleepless nights and hard work putting this master piece together and am more than happy I will be sharing it with you all very soon. Enjoy the new Anthem MARRY by DJ Neptune featuring Mr Eazi, produced by KIDDOMINANT.
You're d bomb. Thumbs up.


Looking for a cool new application for your mobile phone that can solve a problem for you? Check out the latest applications we've reviewed this month!
This fantastic new application for iPhone and Android allows you to take photos of your skin and moles and more easily track your spots changes. In recent times you would have to document the changes in your skin with pen and paper however this app allows you to keep a timeline and you can compare and contrast changes over time and consult easily with your GP.
Schedule a ride just by tapping the car icon on your phone and confirming your trip details! Then all you have to do is sit back and enjoy the ride.
Just finished a really good book and want to tell others about it or struggling to find something else to read? Discover and share your favourite books on the Goodreads app. Don't purchase a book solely based on its cover anymore, find out what others think first!


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Home » ACRO testifies about clinical trials in New Jersey
ACRO testifies about clinical trials in New Jersey
ACRO Executive Director Doug Peddicord, Ph.D., testified at a public hearing of the New Jersey Division of Consumer Affairs about a regulation that, if adopted, would have a devastating impact on the availability of clinical trials for patients in New Jersey and cripple the ability of New Jersey physicians to conduct industry-sponsored clinical trial research on investigational therapies.
The regulation, proposed by the Christie administration as a way to address the opioid crisis, would set a cap of $10,000 per year on payments by biopharmaceutical companies to physicians for services ranging from speaking at continuing education events to consulting on the development of new drugs and treatments. In his testimony Dr. Peddicord pointed out that this $10,000 cap would apply also to clinical trial grants, which typically include the fair-market costs of medical equipment and supplies, tests and laboratory services, and expense compensation to patients, as well as research staff salaries and the host of other activities required to produce accurate data for the FDA to evaluate the safety and effectiveness of a new drug.
"Because ACRO member companies often distribute clinical trial grants on behalf of manufacturers and understand the true costs of conducting a clinical trial, which might run from $10,000 to $20,000 per patient over the course of a months-long trial involving breast or prostate cancer, for instance, we thought it extremely important to request that New Jersey revise the proposed regulation to exclude such payments," said ACRO Chairman and President and CEO of Bioclinica, John Hubbard. "However well-intentioned, if this regulation does not exempt payments to doctors to run clinical trials it will be impossible to enroll a single patient in many trials and the state's position as a major hub of biomedical innovation will be destroyed."
Also testifying at the public hearing were representatives of the Pharmaceutical Research and Manufacturers of America (PhRMA), the Biotechnology Innovation Organization (BIO), Bio NJ, the Medical Society of New Jersey, the HealthCare Institute of New Jersey, and others, many of whom noted the extraordinary threat to medical research posed by the regulation as currently written. A decision on whether the proposed rule will be revised or withdrawn is expected before the end of the year.


text:
NBC's Alexander: Trump Calling on Conservative Media Prevented 'Real Questions'
'He blamed basically leaks, that he's called criminal acts'
ALEXANDER: "You are exactly right. What was striking, and I know this is sort of atmospherics, but it does matter in terms of substance which is important, as even Prime Minister Netanyahu said. President Trump, again, called on a series of more conservative leaning news organizations which didn't allow for any real questions, trying to zero in on this issue of Mike Flynn, the now former national security advisor. What is notable is that Donald Trump has said in some earlier tweets but now he said publicly, he basically blamed leaks that he's called criminal acts. He said this was an effort to distract from Hillary Clinton's terrible loss. And more broadly, he said that this was all a result of fake news that Mike Flynn, a wonderful man has been treated very unfairly."


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About Trevor Aaronson
"Powerful talk."
—Huffington Post "On the TED stage he made a strong case."
Trevor Aaronson as a Guest Speaker
Trevor Aaronson is an investigative journalist who writes about the intersection of national security and civil liberties. He is the author of The Terror Factory: Inside the FBI's Manufactured War on Terrorism.
He has been a guest and keynote speaker at universities, law schools, conferences, and public forums. Recent speaking engagements have included TED 2015, Columbia Law School, University of Miami School of Law, New York University School of Law, Dickinson College, and Young Presidents' Organization.
His TED Talk, "How this FBI strategy is actually creating US-based terrorists," has been viewed more than 1 million times.
Aaronson's topics include:
Are We Catching Terrorists Or Creating Them?: How the FBI and U.S. Department of Justice uses informants, many of them crooks and conmen, to lure hapless men into terrorism sting operations, raising questions about entrapment, ethnic and religious targeting, and civil liberties.
Privacy in an Age of Surveillance: Surveillance technology intended to prevent a terrorist attack is now being turned on law-abiding U.S. citizens, threatening the personal privacy of every American.
Ethnic and Religious Profiling: Since 9/11, the FBI has recruited a network of 15,000 informants. Many are tasked with infiltrating U.S. Muslim communities, and their widespread use has resulted in a minority community whose leaders believe it is constantly under siege.
Ethics and Standards in Investigative Reporting: Trevor Aaronson has won more than two dozen national and regional awards for his investigative journalism and co-founded the nonprofit Florida Center for Investigative Reporting, a leader in collaborative reporting.
Schedule a Speaking Event: To inquire about scheduling a talk, please email speaking@trevoraaronson.com or fill out this form.
TED 2015
© Copyright Trevor Aaronson


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The Copyright Symbol and Your Submissions
During the PAD Challenge, I noticed quite a few poets including either the word Copyright or the copyright symbol--a C inside a circle. While I understand the fear of someone stealing your work and may have even done that with my own fiction and poetry earlier on as a writer, I want you to know you don't need to include those markings, especially when you're submitting your poetry to journals and magazines to be published.
Reason #1: People don't tend to steal other people's poems. It's just not profitable AND if someone were so inclined, they would steal the poem whether you include the symbol or not. Once you set your writing down in fixed form, it is protected by copyright. But after more than 8 years working on Writer's Market, I have yet to hear of a case where an unknown poet has to take his or her poetry copyright case to court. (Of course, saying that, I do realize that there's a first for everything. For more info on copyright, go to http://www.copyright.gov/).
Reason #2: Adding the copyright symbol does not increase your chances of getting published. There is no editor who sees the copyright symbol attached and thinks, "Yay! We've got a copyright symbol; let's get this issue out now!" In fact, it often hurts your chances, because...
Reason #3: Adding the copyright symbol to your submission marks you as an amateur and as a poet who is paranoid that the editor will steal your work. While an editor would still accept exceptional work from a poet who includes the word Copyright or the copyright symbol, be aware that those markings will distract most editors from reading your work--even if just the tiniest bit.
So that's my practical advice about including the copyright symbol and/or the word Copyright. It doesn't decrease your chances of having your work stolen, but it does increase the chance your work won't be accepted. So, why do it?
Poetry Challenge 2008
Robert Lee Brewer is Senior Editor of Writer's Digest, which includes editing Writer's Market, Poet's Market, and Guide to Literary Agents. He's the author of Solving the World's Problems, Smash Poetry Journal, and The Complete Guide of Poetic Forms: 100+ Poetic Form Definitions and Examples for Poets. He loves blogging on a variety of writing and publishing topics, but he's most active with Poetic Asides and writes a column under the same name for Writer's Digest magazine. Follow him on Twitter @robertleebrewer.


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Q: Generate Provisioning Certificate for iOS on windows 7 I already have created a phonegap application. Now, i want to build Phonegap iOS on windows 7.
I have written code in Android in Eclipse on windows 7.
I already have generated .APK, .XAP, .IPK. Now, i want to create .IPA(iOS application).
Is it compulsory to have a MAC OS to just generate Phonegap iOS application?
Is it compulsory to have apple developer account to just generate Phonegap iOS application?
Can i generate a certificate and a provisioning profile for iOS on Windows 7?

A: Yes it is compulsory to have a Developer account, Because without developer you cannot generate Provisioning profile.
I don't know about the certificate, but you can generate Provisioning profile on Windows 7 because it is not dependent upon OS, it needs the certificate.
It is not necessary to have MAC OS for generating Phone iOS Application

A: Since PhoneGap Build uses Apple's standard development process to build applications, you will need to sign up for their developer program to build iOS applications on PhoneGap Build. You will also need a Mac to configure your certificate and provisioning profile.

A: Compulsory to have a mac and developer account to install software on an iphone or ipad.
You don't need a mac to develop the application

redpajama_set_name: RedPajamaStackExchange


When the supply of spareparts of the Vampire fighter from the United Kingdom was threatened, The Indian Air Force decided to evaluate and induct alternative sources of supply. The Ouragan was to be used by the IAF for nearly fifteen years.
Ouragan IC555 seen on a ferry from France to India during a stopover at Karachi's Mauripur airfield. The aircraft probably flown by Sqn Ldr Suranjan Das belonged to No.8 Squadron.
A box of four Toofanis in formation somewhere over North India.
A box formation somewhere over North India.
Toofanis at a forward airfield in 1963. There are atleast nine Toofanis that can be seen in this photo.


Zesty aromas galore from this textured 7.1% Rye IPA collaboration brew with Fjaderholmarnas Brewery in Sweden. A saturated mango explosion from the new harvest american Cryo hops Mosaic and Amarillo with a bitey finish from the rye. Tropical and refreshing.
The name derives from The Law of Jante, a nordic code of conduct that essentially encourages people not to think they are better than anyone else.


One specific series of events sent me spiraling off into some pretty unhealthy spaces. My family was there to help talk me through it, and the small things, like hugs from my children, meant the most. I also felt a need to reach out to other academics to get some feedback on how to proceed as it was related to my professional life.
In this situation, I was afraid, hurting, and looking for someone that would just listen without judgment. I didn't want an answer, or even a response, I just needed to vent. This was a new phenomenon to me as I've never spent much time understanding, or finding a need for anonymity online. I wasn't thinking about how reaching out to vent might impact my identity. The opportunity to freely share my story out online, without the judgement or retribution that would come with this sharing.
I see people openly share their foibles, flaws, and failures on social media, and (for the most part) others are there to comfort, reassure, and give some resolution. Most of this sharing I see occur on Facebook, where anonymity doesn't exist. I'm usually struck by the bravery of individuals as they share these narratives openly with others. I also (admittedly) judge some others depending on how frequently they use the social networks as a sounding board.
Ultimately, the situation resolved itself. I made a big situation out of nothing because others made a big situation out of it. But, I learned a lot from the situation about the pain, and the seeking for solace from others….while still shrouded by some of the cloak that online anonymity can provide. This led me to think a bit more about the power of anonymity in online spaces.
There are numerous reasons why an individual may seek to be anonymous while online, but this is a choice that people are increasingly making. There are also a variety of tools, practices, and habits that can be used to achieve anonymity online.
One of the best ways to understand anonymity online comes from social science. Morio & Buchholz (2009) separated this into three levels (visual anonymity, disassociation with real and online identities, and lack of identifiability.
Visual anonymity – When individuals communicate without seeing each other. A good example of that is using text-based chatting programs over the Internet. People's physical appearances are obscured in that scenario.
Dissociation of real and online identities – A single individual can create more than one online identity using more than one screen name & avatars. Individuals then have the ability to become more than one person with dissimilar personalities. They also have the ability to adopt new genders & races.
Lack of identifiability – This is the level closest to true anonymity online. When individuals cannot be identified, their behaviors are not distinguishable from others. An example would be an online forum in which people can post anonymous comments without attaching usernames to that post.
Examples of extreme abuse, ranging from bullying to harassment are some of the biggest arguments against anonymity online. These online interactions can include personal threats about kidnapping, sexual assault, hate speech, or threats to disclose personal/financial information.
Online anonymity also presents challenges as some people believe anything that they read, or they find in print. Being able to "write" anything online also makes it much easier to share, and as a result, any information can be freely shared with others globally. This provides challenges as individuals/groups can anonymously share false information online with the purpose of confusing or gaslighting others.
There are numerous benefits to online anonymity. These range from freedoms of speech and movement to issues of identity construction and personal safety.
Identity protection isn't something we think about until we've lost obscurity. In normal social settings, we can sit in a downtown area, and not have concerns that everyone will know us, and all of our information. In a sense, we relish this opportunity to fade into the background and "people watch." People that have global recognition, often have concerns about their privacy and security when everyone knows your face and name.
Online anonymity is also very important when we consider its role in freedom of expression. The Internet and social networks have been used to allow voices that are actively being silenced to speak without fear of retribution. This may include a whistleblower for a company, a citizen showing a video clip from their neighborhood, or an individual speaking up against a regime in their country. In any of these circumstances, the revelation of their identities may (and has) come with dangerous consequences.
The final major area where online anonymity holds enormous value is those that have questions about personal and/or health topics. Many individuals already do this as they "Google It" to find a remedy to a health ailment before (or instead of) speaking to their physician. We also see instances where individuals are struggling with their sexuality and they search online to find out more information, or ask questions in an online discussion board without revealing their identity and risking negative exposure.
Some people believe that if they have nothing to hide, they don't have to worry about online anonymity. The truth is that as our lives become more connected in digital spaces, we regularly leave behind a trail of digital residue that contains social updates, pictures, video, location data, and other information about our lives.
The situation I described at the start of this piece provided me with an important lens through which I could see (and feel) the need for online anonymity. My challenge is that most of my life is an open book. In terms of a continuum that I see existing between open and closed, I tend toward the open side of things in my digital identity. I blog about everything, share manuscripts, and freely share my work and ideas online. Perhaps it is due to my privilege, or perhaps I haven't felt the emotional impetus to reach out while remaining thinly protected.
With great power comes great responsibility. The Internet allows all individuals to share their voices and narratives online. This means that we'll see and hear from the best…and the worst…that is out there. I believe that we need to empower and advocate for all voices, while protecting everyone's right to share.
As our lives become more digital, we need to think about the privacy of our data and traffic. We also need to save these spaces for the voiceless, or those looking to be heard.


MamaOnABudget: Let's do some MATH – SAVE and Lower Our Expenses!
Making ends meet is the norm in many a household. For a single Mother it's even more intense when child support trickles in if that!
My hours were cut at work and am looking for a second job to help fill in the need. The need to cut expenses became a MUST and being the numbers lady that I am I did some Math.
Really hits you in the face doesn't in????!! Now the hard part is cutting these down as best we can.
I started with the Cable & Internet bill. I called the provider to see if they can offer me a better deal. Turned out I had the best they currently had so decided to go cold turkey on the cable. We rarely watch it and can find our favorite shows on Netflix and Hulu, which I already have accounts for. I opted to keep the Internet as I need it for work, home schooling and to find work!
Next was cutting out my lunch money for work. It was the BIGGEST "want" and it's nice to splurge maybe once a week for "Tamale Friday" with the gals at work. For the most part I stuck to my sack of rice, beans and chicken that I cook a pot at a time to take to work. I talked to my favorite Greek Restaurant and they sold me a pint of their AMAZING dressing so that I can make my chicken salad a TREAT! I stopped by "Cosco" and purchased my raw nuts by bulk to last me for the month as I eat them regularly as snacks and was spending way too much on the smaller containers at the Market.
The Cell Phone is a life line for my children and I. I can't cancel it but I was able to lower the plan and save myself another $20 on the bill. I may venture out and cancel my Data Plan and see how I fare, being the cyber media person that I am!
I said GOOD BYE to my acrylics. I love them dearly and will miss them immensely but I purchased a nail polish to keep them strong and help them grow. With a bit of TLC I may one day have my own claws once again. Even though I keep my Pedi's fresh I can't get the polished look and feel of a salon. I did find a lower priced location that did a 'decent' job for $10 less and can live with that until further notice.
The children are doing their part and look forward to having their own yard sales and lemonade stands. They're too sweet and gotta nourish their Entrepreneur spirits!
It's a good start and know I will find other ways to make that Dollar S-T-R-E-T-C-H! One day at a time and looking forward to quite an ADVENTURE!
Slapping on that Red Lipstick Smile and keeping that head held HIGH!!!!
Previous Post Review: "LiquidDream Foundation" from Pink Stiletto Cosmetics: Can I say WOW?!
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1. Kindly please notify us as soon as possible with the details so that we are aware of the issue.
2. Please advice your customer to contact their processing bank. Click here to view the list of the bank contact details.
Please take note that this is an issue between FPX and the banks. There is not much that we can do.


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Victoria residents see smoky skies, air quality at 'very high risk' Friday
Posted: Sep. 11, 2020 6:00PM | Last Updated: Sep. 11, 2020 6:26PM
WatchPeople all over the Island woke up to smoky skies and the smell of fire today. The smoke, coming from the U.S., triggered the B.C. government to issue an air quality alert for the Victoria area earlier Friday.
For the second time in a week, Vancouver Island residents woke up to very smoky skies and the smell of wood smoke.
Friday morning presented haziness and smokiness hovering over Victoria and other parts of Vancouver Island as a result of wildfires burning down in the United States.
"Earlier this week, we had essentially a 24-hour event from the smoke coming from eastern Washington state," said Armel Castellan, warning preparedness meteorologist with Environment Canada. "In this case, we are dealing with a flow that is bringing fire smoke from Oregon and Washington in western sides of the cascades as opposed to eastern Washington state."
The lingering smoke has triggered the B.C. government to issue an air quality alert for Victoria as a result of high concentrations of smoke particles.
B.C.'s Air Quality Health Index rates risks of a community on a scale of one to ten – with one being the cleanest air.
Victoria's rating was upgraded to a 10+ on Friday morning, which means there are "very high" health risks associated with the current air quality conditions. The West Shore is under the same rating.
"So really, the worst part of the scale that we can be in," said Castellan. "[It] really is affecting literally everybody, including healthy adults. We're recommending that they don't choose to recreate or exercise outside."
Castellan said the smoke will likely last well into Sunday and probably into Monday as well.
The advisory adds that children and the elderly should also avoid outdoor physical exertion.
Environment Canada has also issued a public alert for the Victoria area, suggesting that "inversions in mountain valleys can increase the likelihood of smoke being trapped" close to the ground.
"During a wildfire, smoke conditions can change quickly over short distances and can vary considerably hour-by-hour. Wildfire smoke is a natural part of our environment but it is important to be mindful that exposure to smoke may affect your health," reads a statement from Environment Canada.
"People with pre-existing health conditions, respiratory infections such as COVID-19, older adults, pregnant women and infants, children, and sensitive individuals are more likely to experience health effects from smoke exposure."
Although the Air Quality Health Index is only indicating "very high risk" in Victoria, Environment Canada has posted its smoky skies bulletin for the majority of Vancouver Island.
The west coast of the United States has been ablaze over the past week, with Washington, Oregon, and California all experiencing significant wildfires.
In their latest smoky skies bulletin, the Government of BC is anticipating that the smoke could last for the next 24-72 hours over Vancouver Island and other parts of the province.
CHEK News
Jasmine Bala
'It doesn't even ring': Island Health says fix coming for COVID-19 call centre
'It came out of nowhere': Man stabbed in Centennial Square told he may never work again


text:
using DataStructures
using Test
using Random
using Serialization

import DataStructures: IntSet

@test isempty(detect_ambiguities(Base, Core, DataStructures))

using Primes

tests = ["int_set",
         "deque",
         "circ_deque",
         "sorted_containers",
         "stack",
         "queue",
         "accumulator",
         "classified_collections",
         "disjoint_set",
         "binheap",
         "mutable_binheap",
         "default_dict",
         "ordered_dict",
         "ordered_set",
         "trie",
         "list",
         "multi_dict",
         "circular_buffer",
         "sorting",
         "priority_queue"
        ]

if length(ARGS) > 0
    tests = ARGS
end

@testset "DataStructures" begin

for t in tests
    fp = joinpath(dirname(@__FILE__), "test_$t.jl")
    println("$fp ...")
    include(fp)
end

end # @testset

redpajama_set_name: RedPajamaGithub


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