When carbon is removed from forests through harvest, a portion of the harvested carbon is stored in wood products, often for many decades. The United States Forest Service (USFS) and other agencies are interested in accurately accounting for carbon flux associated with harvested wood products (HWP) to meet greenhouse gas monitoring commitments and climate change adaptation and mitigation objectives. This paper uses the Intergovernmental Panel on Climate Change (IPCC) production accounting approach and the California Forest Project Protocol (CFPP) to estimate HWP carbon storage from 1906 to 2010 for the USFS Northern Region, which includes forests in northern Idaho, Montana, South Dakota, and eastern Washington.Global forests capture and store significant amounts of COBased on the IPCC approach, carbon stocks in the HWP pool were increasing at one million megagrams of carbon (MgC) per year in the mid 1960s, with peak cumulative storage of 28 million MgC occurring in 1995. Net positive flux into the HWP pool over this period is primarily attributable to high harvest levels in the mid twentieth century. Harvest levels declined after 1970, resulting in less carbon entering the HWP pool. Since 1995, emissions from HWP at solid waste disposal sites have exceeded additions from harvesting, resulting in a decline in the total amount of carbon stored in the HWP pool. The CFPP approach shows a similar trend, with 100-year average carbon storage for each annual Northern Region harvest peaking in 1969 at 937,900 MgC, and fluctuating between 84,000 and 150,000 MgC over the last decade.The Northern Region HWP pool is now in a period of negative net annual stock change because the decay of products harvested between 1906 and 2010 exceeds additions of carbon to the HWP pool through harvest. However, total forest carbon includes both HWP and ecosystem carbon, which may have increased over the study period. Though our emphasis is on the Northern Region, we provide a framework by which the IPCC and CFPP methods can be applied broadly at sub-national scales to other regions, land management units, or firms. The for-1 . Thus, UAbout 5 percent of total US forest sector carbon stocks and 6 percent of the annual flux is attributable to carbon in HWP . Though 2 concentrations and the resulting impacts on climate has focused attention on the ecosystem service of forest carbon storage, including storage in HWP. Forest management can affect the quantity of carbon stored in both ecosystems and forest products over time, and management activities in the US frequently include silvicultural treatments that produce HWP. Credible information on forest ecosystem and HWP carbon stocks and fluxes can inform forest managers and the public of the tradeoffs between carbon storage and other forest management objectives, and between short and long-term carbon consequences of alternative forest management strategies [Increasing social and managerial interest in mitigating rising atmospheric COrategies -6.As governments contemplate climate change mitigation and adaptation options, there is growing interest among forest managers in monitoring and managing forests for sequestration of carbon as an ecosystem service. For example, during 2010, the US Forest Service (USFS) developed a climate change scorecard that is to be completed annually for each of the 155 national forests and national grasslands managed by the agency . The scoHWP carbon monitoring systems have been implemented at the national level ,3,8, as There is a clear need for the means to monitor the contribution of HWP to carbon pools and greenhouse gas mitigation at sub-national scales. Currently, forest managers do not have the tools they need to accomplish monitoring goals that have been established at the national level. Developing these tools is an important step in facilitating carbon assessment and stewardship and in informing management actions on the ground. Our objectives with this study are to: 1) use established accounting approaches to make estimates of HWP carbon stocks and fluxes for the USFS Northern Region as a demonstration of sub-national HWP accounting, and 2) provide a framework with clear metrics and estimation methods that can be applied to other regions, land management units, or firms. We also provide guidance to managers concerning the differences between alternative approaches with regards to data and resource requirements. We do not develop a system for evaluating the future impacts of specific management actions, nor do we advocate any particular course of action to improve carbon stewardship.We use the IPCC production accounting approach, which has been adopted by the US EPA; hereafter referred to as the IPCC/EPA approach), and the California Forest Project Protocol  to estiIn the IPCC/EPA production accounting approach, the annual carbon stock change for the total forest sector (ΔS) is a function of carbon flow among the atmosphere, forest ecosystems, and HWP, and is calculated as:R1 is the annual change in carbon stored in HWP that were made from wood harvested from Northern Region forests  is the sum of the net change in carbon stored in products in use (ΔCIU R1) and the net change in carbon stored in products at solid waste disposal sites (ΔCSWDS R1). Figure R1) and emissions to the atmosphere from wood products harvested in the Northern Region that were exported outside the region (EEX R1). Exports (PEX) include wood and paper products, as well as roundwood, chips, residue, pulp and recovered (recycled) products from wood harvested in the Northern Region. Under the production accounting approach, imports from other regions (indicated with dotted lines around the right side portions for both boxes showing HWP in use or in SWDS are not included in Northern Region accounting because the emphasis is on the location of harvest (H). Emissions are further categorized as emitted with energy capture (e.g. fuelwood) and emitted without energy capture . The relevant metric for this accounting approach is annual stock change in the HWP carbon pool.In this approach, the annual change in carbon stored in HWP  and decreased during the Great Depression in the 1930's .All else being equal, higher harvest levels result in more carbon removed from the ecosystem pool and added to the HWP pool Figure . Figure 2, the CO2 equivalent annual emissions from 20 million passenger vehicles. Since 1995, carbon stocks in the HWP pool for the Northern Region have been in decline  and after a short lag, a much larger portion of discarded HWP goes into modern landfills where it is subject to lower rates of decay than in aerobic dumps or disposal by open burning, which were the dominant disposal methods prior to RCRA.Obtaining historical information may present a challenge for some regions and national forests. It may be particularly difficult to reconstruct harvest data prior to the mid-1940s, though regression of trends after the period might be appropriate for extrapolation to earlier periods. Alternatively, regions could base their carbon accounting on national level parameters, making the assumption that national-level numbers are adequate for regional and sub-regional analysis. If national level values represent the best available data, the IPCC/EPA method requires only harvest volume information from the user. Many regional and forest type-specific default dynamics and decay functions are supplied by national level work ,9. The sIf time series data are not available or are very costly to procure, focusing on annual data may be more productive. The CFPP 100-year average is an example of an approach that does not require reconstructing the historical harvest. In general, the CFPP has ease of use superior to the IPCC/EPA production approach but does not provide the same detailed information about the HWP carbon pool. The CFPP approach does not estimate temporal trends in this pool whereas the IPCC/EPA approach can show both total stock and annual stock change. In addition, our results show that the effects of uncertainty appear to be higher for the 100-year average than for the IPCC/EPA estimates, for this case study, as measured as a percentage difference from the expected value. As with the IPCC/EPA calculations, appropriate regional and forest type-specific variables may be found in published sources ,9,17.The choice about which protocol should be applied could focus on the tradeoff between the simplicity of data collection and ease of calculations compared to a need to address both total stocks and flux. Also, managers may need to be consistent in all using one protocol or another in order to make results comparable across regions and easily aggregated in analysis done at larger scales. The more resource intensive methods of the IPCC/EPA estimates are worthwhile only if the additional detail is useful or if this reporting format is mandated.We successfully applied the methods described by Skog  to estimThere are well-developed methods of life cycle assessment (LCA) that account for all carbon emissions associated with manufactured products and that facilitate the comparison of different levels of consumption and substitution of wood products for alternative products . NeitherThe IPCC/EPA and CFPP approaches instead focus on estimating physical stocks and fluxes of carbon in clearly defined forest carbon pools. This information can be used in an LCA, but does not address the same questions as an LCA. However, with some caution, these approaches can be used to estimate the effects of alternative past or future harvest levels on HWP carbon stocks and fluxes. For example, a hypothetical time series of harvest volumes can be used to predict what future product storage and emissions would look like under specific alternative forest management and harvest scenarios. But this is not an effective proxy for a consequential LCA, which might include harvesting, transportation and processing emissions, as well as product substitutions, and other trade components not included in the two approaches used here. For sub-national carbon accounting, IPCC/EPA and CFPP approaches have several benefits over LCA. They are relatively easy to apply and congruent with US national carbon accounting standards, which is particularly important in developing tools that can be used by USFS managers to meet carbon monitoring goals.Together with accounting and modeling methods that quantify ecosystem forest carbon, the approaches used in this study provide a powerful tool to monitor carbon stocks, stock change, and 100-year averages, as well as the ability to assess the possible outcomes of management actions intended to reduce the vulnerability of forest resources to climate change.HWP is an important carbon pool that should be considered in decision making associated with carbon monitoring and climate change adaptation and mitigation. In this analysis, we have found that when harvest and wood product production data exist, national and state level accounting protocols can be applied effectively at finer scales, such as regional, national forest, or individual landowner scales. The Northern Region HWP pool is now in a period of negative net annual stock change because the decay of products harvested between 1906 and 2010 exceeds additions of carbon to the HWP pool through harvest. However, total forest carbon is a function of both HWP and ecosystem carbon, which may have increased over the study period. We also demonstrate methods for quantifying uncertainty to describe the confidence we have in estimates of their carbon storage metrics. However, there are clear tradeoffs between alternative approaches to estimating HWP carbon stocks. The CFPP 100-year average uses harvest year data and is easier to apply, but it does not provide information about total carbon stocks or annual stock change. In comparison, the IPCC/EPA production accounting approach is more data intensive because it includes past harvest and product disposition data for each inventory year, but it provides estimates of total stocks and stock change, which makes it congruent with national accounting and reporting protocols. The IPCC/EPA approach could be used to predict changes to the HWP component of the forest sector carbon pool resulting from planned or potential change in the amount of wood harvested. We believe further research is necessary to help policy makers and managers better understand the implications of alternative forest management strategies on forest carbon stocks and stock change. An integrated approach might include consequential LCA that evaluates changes in harvest activity on carbon emissions including all sources of emissions and product substitutions.Northern Region harvesting activity since 1980 has been reported in detailed cut and sold reports. These reports include the value and volume of timber sold and harvested in the region, which are reported by both fiscal and calendar year . In addiRecords for annual harvest prior to 1980 are more difficult to obtain. Paper records are available in the Northern Region archives for fiscal years 1946 to 1979, but these do not report the harvest by timber product classes and vary in their reporting for individual national forests. The forestland included in the Northern Region and the administrative designations of specific forests has changed over time. Whenever possible, we used forest-specific data to standardize harvest totals from 1946 to 1979 to the modern boundary of the Northern Region. For example, the harvest for Colville National Forest, which was transferred to the Pacific Northwest Region in 1975, was removed from the harvest totals reported for the Northern Region from 1946 through 1974.Documents from the archives also report the annual harvest in mbf for fiscal years 1906 to 1920, calendar years 1921 to 1936, and fiscal years 1937 to 1945. In these records, the harvest is divided into three administrative designations for years 1914 to 1945, but data for individual forests and timber products are not reported for the period 1906 to 1945. Again, we adjusted annual harvest data in an attempt to standardize the harvest to the modern boundaries of the Northern Region. For years prior to 1946, the annual harvest reported for the Northern Region was reduced by 5.3 percent, which is the average proportion of the Northern Region annual harvest attributable to Colville National Forest from 1946 to 1971. The proportion of the harvest attributable to Colville National Forest stayed relatively constant over this period, ranging from a low of 2.4 percent in 1946 to a high of 7.2 percent in 1965.For the period 1906 through 1979, annual harvest totals for the Northern Region reported in mbf were converted to ccf using a conversion factor of 2.2 ccf per mbf Table . By stanFigure The recalcitrance of carbon in harvested wood products is highly dependent upon the end use of those products. For example, carbon in lumber used in new single family home construction has a longer duration of use than carbon in lumber used for shipping containers, which is released into the atmosphere more quickly through combustion and decay. For years 1950 through 2006, annual primary product output was distributed to specific end uses according to annual wood product consumption estimates in McKeever . Estimatt is the amount of carbon remaining in use in inventory year t, N0 is the amount of carbon in the end use category in the vintage year of harvest, t is the number of years since harvest, t1/2 is the half-life of carbon in that end use, and exp is notation for the exponential function. In our calculations, the starting amount  is adjusted downward by 8 percent to reflect a loss when placed in use, which is assumed to enter the discarded carbon category. This loss in use accounts for waste when primary products (e.g. softwood lumber) are put into specific end uses . Fuelwood products are assumed to have full emissions with energy capture in the year they were produced (Table where Ned Table .For carbon of a particular vintage in a given inventory year, the balance of carbon in HWP that is not in use and not emitted with energy capture is assumed to be in the discarded products category Figure . Carbon 2 equivalents, nor do we account for methane remediation that includes combustion and subsequent emissions with energy capture. All landfill and dump emissions are considered emissions without energy capture.Carbon from burned and composted discarded products is assumed to be emitted without energy capture. Carbon in the recovered category reenters the products in use category. Carbon in products discarded to landfills and dumps are subject to decay determined by their respective half-lives. The half-life value for discarded products in dumps and landfills expresses the decay rate at which carbon in these categories is emitted to the atmosphere. However, only a fraction of discarded products in landfills is considered to be subject to decay. Seventy-seven percent of solid wood carbon and 44 percent of paper carbon in landfills is identified as fixed carbon, not subject to decay . For a gIPCC/EPA methods were used to calculate HWP carbon stocks and stock change for inventory years 1906 through 2010. In addition, we present the 100-year average carbon storage for products in use, products in SWDS, and all HWP using the CFPP. In this approach, averages for each harvest year are determined based on storage factors for primary wood product classes as described previously. The amount of carbon delivered from a harvest to mills is determined by applying conversion factors by wood type. However, not all of the carbon that is delivered to the mill ends up in HWP. The amount of delivered carbon that ends up in HWP is determined by mill efficiency factors of 67.5 percent for softwood and 56.8 percent for hardwoods, with the balance of carbon assumed to be immediately emitted to the atmosphere. These mill efficiency factors determine the total carbon transferred into HWP in the year of harvest. For each harvest year, the average carbon stored over 100 years in wood products harvested in that year is calculated based on 100-year average storage factors applied to the HWP carbon in different wood product classes, with different factors applied for the in use and in landfills HWP carbon categories . The totIn our calculations the carbon in HWP to which the CFPP storage factors are applied is based on conversion, residue production, and product recovery factors incorporated into the production accounting approach, not on the conversion factors and generalized mill efficiency factors included in the CFPP. In other words, the results presented here apply the CFPP protocol to the same HWP carbon pool used in the production accounting approach, which is shown in Figure Interpretation of the results should be made in light of some constraints. Though we attempted to normalize annual harvests to the modern boundary of the Northern Region using forest-specific harvest data, in actuality the annual harvest is from a land base that is somewhat variable over time. The USFS has commonly engaged in land exchanges, divestments and acquisitions in the Northern Region since 1906, which means that the system boundary for this analysis is not consistent. In addition, conversion factors, the distribution of timber products to primary products, and the distribution of primary products to end uses have changed over time. Though we have used annual data whenever possible, there is some uncertainty associated with applying averages to annual harvests in the early years of this harvest series.Uncertainty is quantified using the methods described by Skog . We idenThe probability distributions of these random variables were developed based on estimates in Skog  and on pThe effect of uncertainty on the HWP stocks and 100-year average was evaluated using Monte Carlo simulation in @Risk software version 5.7 . The simThe authors declare that they have no competing interests.KDS built a team to carry out the project, entered historical harvest data, helped with estimation procedures and data management decisions, and compiled and edited the manuscript. NMA designed the spreadsheets to perform calculations, entered most of the data, prepared results, wrote the methods and results sections of the manuscript, and edited the manuscript. KES made substantive intellectual contributions by first steering the team to the existing EPA/IPCC and CFPP protocols, then by applying his and other's recently published work to this particular system, by directing the uncertainty analysis, and by reviewing manuscript drafts. SPH contributed intellectually by sharing recent ecosystem carbon estimation approaches, reviewing initial system design, and outlining sections of the manuscript. DRL and GJ contributed to study design, helped validate and adjust historically-based estimates, and participated in preparing the manuscript. JFM provided important information regarding the need for the project, drafted the background section of the manuscript and facilitated internal draft reviews. All authors read and approved the final manuscript.


The fundamental principle of the Malaysian healthcare system is that accessibility to health care should not be related to one’s ability to pay, especially when involving sickness . This isAdditional public services are provided by university affiliated and military hospitals. There are seven non-MOH Government Hospitals with 3,245 beds, 209 Private Hospitals with 11,689 beds, and 22,174 and 12,274 Private Maternity and Nursing Homes, respectively. The total number of doctors is 25,102 giving a doctor to population ratio of 1:1,105 but the distribution is skewed towards the urban areas. The Total Expenditure for both the public and private sectors on Health for 2008 was RM30,227,929,810.20  which translates to 4.7% of the Total Expenditure on Health as a Percentage of GDP of which approximately 45% was public expenditure. An admission to private hospitals was 1.6 times higher than the public hospitals.From what was largely a government-led and funded public service enterprise since independence, the Malaysian healthcare service has over the decades (since the 1980s), transformed into a vibrant dual-tiered parallel system, with a sizable and thriving private sector. Thus far we have not approached a unified system with a declared national healthcare policy of offering universal access to every citizen.The private sector has always attracted both general and family physicians operating individual clinics or by joining more established group practices. The specialists generally join the better-paying more personalised care practices in urban private medical centres. Private healthcare expansion began in earnest during the 1980s, where private hospital beds increased nearly 10-fold , and the private sector’s share of hospital beds increased from 3.9–5.8% to 23.4–26.7% [Interventional radiology had its origins with the advent of diagnostic angiography, which was first available at University Malaya Medical Centre  in 1968. Four rooms for specialised investigations were established for retrograde pyelography, neuroradiology, angiography and cardiac investigation laboratory. At the time of setting up, there was a critical shortage of radiologists and radiographers in the region, so there was no chance of recruiting trained staff in sufficient numbers to run this large department successfully. The late Professor Emeritus Danaraj initiated an academic staff training scheme, and under this the first radiologist to complete training in London, Dr. Mark Soo, returned to Malaysia in October 1967, followed by others at approximately yearly intervals. The first local Head of Department, Dr. Mark Soo Yoi Sun, was appointed in 1969. The Chair of Radiology was created in 1979 and Dr. Joginder Singh  was appointed the first Professor of Radiology.One of the early pioneers were Dr. Ah-Hoo Ang and Dr. Joginder Singh who did not have any formal training. The procedures that were being performed initially were pneumoencephalograms, percutaneous transhepatic cholangiograms (PTC), translumbar aortograms and once the Seldinger technique was developed, cardiac and other angiograms . Subtractions had to be done manually always with not so optimal results.Interestingly, there were a high number of patients with primary arteritis and Bergers’ disease in those days . Carotid angiographies using direct carotid punctures were started in 1971, the same year percutaneous transhepatic biliary drainage (PTBD) procedures were being performed. Nephrostomies were started in 1974/5 when embolisation of lower limb arteriovenous malformations (AVMs) was also being performed using gelfoam. The embolisation provided was only temporary and the patients were given appointments for repeat procedures. Overseas training in Australia taken by Dr. Joginder Singh in 1977, allowed the interventional service to be further expanded.Pre-shaped catheters were only available in 1978 when recycled catheters were shipped from the USA by some of the interventional radiologists there. Prior to this, the catheters had to be hand-shaped by using steam, which often did not perform the job satisfactorily. Coronary angiographies were started in the early 1980s by Dr. Joginder Singh and Dr. K.T. Singham (a cardiologist who returned from overseas training).The initial angiography system was donated by the Australian Government under the Colombo plan. This used roll film had to be viewed on a film roller. This was followed by a “puck-changer” angiography system in the late 1970s. With the advent of the CT scanner in 1980, the number of angiograms dropped tremendously. The resources were made available by the medical centre and it was the full complement of other specialists’ i.e. cardiothoracic surgeons, physicians, etc, which made growth possible. Dr. Ang migrated to Australia in 1976 while Dr. Joginder retired in 1995 following which Dr. Abdullah Daud took over.Dr. Samad Sajikan who was seconded to the Universiti Kebangsaan Malaysia (UKM) from the MOH, was responsible for taking the practice of interventional radiology to the next level from the mid-1990s. Eventually holding the position of Professor and Head of the Radiology Department in UKM, he was instrumental in making interventional radiology and interventional radiologists recognised as a vital component of medical practice not only in the Kuala Lumpur General Hospital (KLGH) and the Universiti Hospital UKM (which were sharing the same premises) but in the entire country. They were performing hepatobiliary, urological and pulmonary interventions. Inferior vena cava (IVC) filters were implanted in 1995. Funding was initially difficult and replacement of the aging equipment was also challenging. There was little neuro and peripheral vascular work at that time.Dr. Samad was the role model who inspired the younger radiologists with his passion, knowledge, skills and dedication. His network of international interventional radiologists in Japan, UK, USA, etc, was also one of his strengths. Dr. Samad was the nidus around which the next generation of interventional radiologists sprouted and grew. Dr. Samad is currently in private practice and he can be truly called the “father” of interventional radiology in Malaysia. His mantle in UHUKM was then taken over by Dr. Nafikuddin Hj. Mahmud while the KLGH services were taken over by Dr. Alex Tang .Interventional radiology in the University Hospital of the Science University of Malaysia (UHUSM) was pioneered by Dr. Nurul Azman Ahmad Alias who trained under Dr. Samad in UKM. He returned to Kota Bharu, Kelantan, and was fortunate to have a surgeon who was supportive both in terms of referring patients and also looking after the patients following the interventional procedures. The early days in UHUSM were troubled with old and, frequently, non-functioning equipment. The department then managed to secure funding from the university and they were able to move along. They were fortunate to have supportive interventional radiologists, both locally (e.g. Dr. Adam Pany) and regionally who were prepared to visit them regularly to help them learn the newer techniques. Today, they are busy doing a full range of interventional producers.It has only been in the last decade or so when the number of formally trained interventional radiologists has increased in Malaysia. This has been attributed to an increased awareness of the important role interventional radiology plays in medical practice by the leaders in radiology as well as the support shown by the early leaders in interventional radiology. The training has been performed overseas especially in the UK, Australia and Singapore.There are practicing interventional radiologists in all three sectors i.e. the public, private as well as the universities. The total number of trained interventional radiologists is currently approximately 20 with the majority within the universities, followed by the private hospital and the fewest within the MOH. There is a constant move of specialists from the MOH to the private sector and this has hampered the development of interventional radiology within the MOH. It is anticipated that this trend will persist. It is anticipated that it will be at least 5 years before any significant changes are seen.It is heartening to note that over the last decade the number of radiologists has increased significantly and this has enabled most public and private hospitals to build up their numbers and provide a higher level of service. It is believed that as these numbers increase, it will free some of them from the heavy diagnostic imaging workload so that those who are keen are able to take up interventional radiology.Partly because the workloads are still not sufficient, most departments in all sectors do not have separate units/divisions for interventional radiology. Additionally, interventional radiology is still very young, with the constant turnover and the need to be still a competent general radiologist for private practice; most do not wish to take the plunge. The interventional radiologists still spend a significant proportion of their time doing diagnostic work encompassing all the modalities. More importantly in the private sector, the compensation structure still favours diagnostic studies instead of the interventional procedures. It is not uncommon for these interventional radiologists to perform their procedures after completing the diagnostic work. Due to the lack of numbers and, more importantly, expertise, there is no separation between the neuro-interventionalists and body interventionalists, and most do both.Over the years, as the number of cardiologists has increased, so has their involvement in the peripheral vascular interventional work. Now, some perform aortic stent grafts and carotid interventions. In the recent past, the vascular surgeons have also started performing these procedures.Following the recent Asian-Pacific Congress of Cardiovascular and Interventional Radiology (APCCVIR), the Malaysian Society of Interventional Radiology was formed. The current President is Dr. Alex Tang. This society will hopefully further develop the number of interventional radiologists.Under the Medical Act 1971, all medical practitioners who practise in Malaysia must be registered with the Malaysian Medical Council. This register has defined criteria for registration which is based on their basic medical degrees, whether specialists or non-specialists. The Act, as it exists, has no provision for a specialist register.For specialists working in its hospitals and healthcare facilities of the MOH, the Government has its own gazettement exercise which is a requirement under the General Order under the Malaysian Public Services commission. This system has been operating well for the MOH. Unfortunately, this requirement does not apply legally to non-MOH organisations and the private sector. Different institutions may have individual processes and criteria and, therefore, differing standards. The universities have a similar but yet separate system where the criteria for appointment of specialists follow closely those of MOH. There is a special board under the management of each university, which has the power to approve confirmation as specialist and payment of specialist allowances. As for the private sector, there are no legal requirements beyond registering as a qualified practitioner. Each institution has its own privileging committee, which decides on the scope of practice of each specialist working in that institution. Thus, different institutions with their individual processes and criteria may result in differing standards.The MOH along with the Malaysian Medical Council (MMC) and the Academy of Medicine Malaysia has put in place the processes and structure for a National Specialist Register . SimilarUntil the new Medical Act is passed, credentialing of specialists will be performed by the National Credentialing Committee (NCC), established in the MOH under the chairmanship of the Director General of Health, Malaysia. The NCC consists of members from both the MOH and Academy of Medicine of Malaysia. Upon passage of the new Medical Act, the MMC will ensure that those admitted to the National Specialist Register (NSR) are competent and fit to practice. Thus far, there were more than 44 specialty subcommittees as listed in the NSR website. Radiology has been registered as a speciality under the current structure with no provision for any subspecialty as the numbers are too small and the subspecialty practices are still in their infancy.Training of interventional radiologists has also been fragmented with the different sectors following their own programme. The MOH has embarked on a 3-year programme of supervised clinical training in a local institution for 2 years and 9 months to a year abroad mostly in the UK or in Australia. Following this period of approved training, the MOH will then recognise them as subspecialists following additional requirements. Currently, there are three qualified interventional radiologists with four in training and an additional three who will be joining soon . The MOHThe universities, thus far, have been sending their interventional radiologists for fellowship programmes. These informal programmes are also for 1–2 years with a period of between 1 and 2 years in the UK, Singapore or Australia. There is still no formal system of recognition as subspecialists within the universities and neither is there a promotion or increased compensation . The praWith regards to the private sector, each hospital has its own credentialing body which accords the interventional radiologist practicing privileges. There has been a gradual trend for these hospitals to seek interventional radiologists preferentially when looking for radiologists. However, these radiologists still do a significant amount of diagnostic work in their practices.The future of healthcare poses challenges, which include a changing disease pattern, a well-informed and demanding public, rising costs, new medical technologies, globalisation and liberalisation. Access to healthcare and their effectiveness to meet the needs of the population is largely dependent on how healthcare is organised and delivered, and what type of medical technology is used to make the delivery more efficient. On both these counts, a comprehensive and integrated interventional radiology service built on appropriate imaging technologies will be able to play a pivotal role in solving some of these challenges. The MOH, thus far, does not have a national policy on the development of interventional radiology based on the country’s needs and, as such, the efforts have been piecemeal.Today, there are pockets of interventional services being provided in different institutions at different time points but there is distinct lack of a national framework for the development of the speciality. Even though careful planning and development efforts have enabled the country to progress through various phases of modernisation, in line with changing demographics, socio-economic and technological challenges, there is a lack of coherent national programme in the development of interventional radiology. This is a major limiting factor for the growth of interventional radiology. Thus, differences between the different stakeholders i.e. the MOH, universities and private institutions, have been allowed to perpetuate and have hampered the development of such a framework.The universities have a “local” perspective of interventional radiology and are looking at meeting their needs. One of the major shortcomings limiting the progress, not just of interventional radiology, is the distinct lack of “political” influence with the decision makers. It is, therefore, difficult for growth of the specialty. Differences in the view-points and, more importantly, personalities within the interventional community are also issues. The radiological community has their hands full with issues of manpower, turf, certification and continuing professional development, etc., that issues of the interventional community  are difficult to move forward.Full-time interventional radiology in the private sector is not sustainable unless there are specialised private centres e.g. neuro-intervention. Efforts are being made through the College of Radiology, Academy of Medicine of Malaysia, to change the compensation structure for interventional procedures to make the specialty more financially attractive to the younger practicing radiologist.The current generation of practicing doctors and future radiologists belong to a different generation, the so-called Generation-Y . These gIn an effort to overcome some of these confusing and differing views with regard to subspecialty training for interventional radiology, the University of Malaya through the Department of Biomedical Imaging, Faculty of Medicine, has offered a 4-semester program called an Advanced Master in Radiology in all the different specialties including interventional radiology. This is a structured programme, which consists of course work, clinical training and a research component. The programme is scheduled to start in 2010.In the background of increased accountability and cost-pressures, the introduction of newer treatment modalities, advent of lesser invasive treatment modalities e.g. FUS and an increasing number of other specialties interest in imaging guided intervention e.g. neuro, interventional radiology faces a tremendous pressure to hang on to its slim lead. There has been increasing involvement of cardiologists and vascular surgeons in performing peripheral vascular and aortic stenting. There have also been efforts by the neurosurgeons to want to perform neuro-intervention in major public hospitals. There is currently a halt to this.Unless all the players in this drama can come together and convince the MOH of the importance of interventional radiology in improving outcome and at the same time reducing costs of treatments, the future of interventional radiology in Malaysia does not look promising but only time will tell.


Gene expression analysis has been intensively researched for more than a decade. Recently, there has been elevated interest in the integration of microarray data analysis with other types of biological knowledge in a holistic analytical approach. We propose a methodology that can be facilitated for pathway based microarray data analysis, based on the observation that a substantial proportion of genes present in biochemical pathway databases are members of a number of distinct pathways. Our methodology aims towards establishing the state of individual pathways, by identifying those truly affected by the experimental conditions based on the behaviour of such genes. For that purpose it considers all the pathways in which a gene participates and the general census of gene expression per pathway.We utilise hill climbing, simulated annealing and a genetic algorithm to analyse the consistency of the produced results, through the application of fuzzy adjusted rand indexes and hamming distance. All algorithms produce highly consistent genes to pathways allocations, revealing the contribution of genes to pathway functionality, in agreement with current pathway state visualisation techniques, with the simulated annealing search proving slightly superior in terms of efficiency.We show that the expression values of genes, which are members of a number of biochemical pathways or modules, are the net effect of the contribution of each gene to these biochemical processes. We show that by manipulating the pathway and module contribution of such genes to follow underlying trends we can interpret microarray results centred on the behaviour of these genes. Pathway based microarray data analysis is an attempt to integrate microarray data analysis with biochemical pathway knowledge . Rather Biochemical pathway data is readily accessible in various public databases, such as KEGG , ReactomHowever, genes in a biochemical pathway often show quite variable behaviour in terms of RNA production and previous work in the field has already suggested that not all such genes are representative of the pathway's behaviour . To an eEscherichia coli K12 pathways, currently stored in KEGG database.We however, have suggested an additional cause for observing variation in the expression of genes, forming a biochemical pathway. According to the Kyoto encyclopaedia of genes and genomes database (KEGG), it is quite common for a gene to be a member of two or more biochemical pathways. We refer to such genes as multi-membership genes to distinct them from single-membership genes that are members of one and only pathway. Figure According to our hypothesis, differential expression of a multi-membership gene may be the effect of different regulation of that gene, by the biological system, at the level of transcription due to its involvement in the activity of more than one biochemical pathways. Consequentially, the observed expression of any such gene corresponds to the net effect of its regulation in order to contribute adequately to the activity of the biochemical pathways it is a member of. To our knowledge the multi-membership nature of genes and its impact on pathway based microarray analysis has not been extensively explored. This is an omission that can potentially lead to misleading conclusions, given that multi-membership genes may mask the true behaviour of individual pathways.We assume that an increase or a decrease in the activity of a biochemical pathway is accompanied by a respective trend for increase or decrease in the functionality of most of the genes forming the pathway, whose fluctuations in expression affect the given pathways' state. Thus, to the extent that gene functionality is adjusted at the level of transcription, we expect genes to be regulated by the living system in a way that follows the trend of expression in a particular pathway and to generally show consistent behaviour, with only few exceptions, such as repressor genes and alternative isoenzymes.We have proposed a methodology that takes into account the expression of all genes in a given organism, that are members of biochemical pathways, and the consensus of gene expression per pathway in order to identify the underlying pathway expression changes caused by the biological system through regulation of the expression of their constituent genes . Unlike Given the tendency of the hill climbing search to get trapped into local maxima, we proceeded further, applying a simulated annealing  and a geIn addition, we further developed the simulated annealing approach to work with modules, that is, shorter chains of biochemical events, which form part of KEGG pathways, applying the methodology to a number of microarray experiments.Escherichia coli genes out of a total of 4288 protein-coding genes, for the harmless laboratory strain K12  concatenates the lists A and B preserving order and sets C to be the result.Algorithm 3 describes the crossover process, while algorithm 4 the mutation process, called at steps 7 and 11 of the main genetic algorithm script, respectively. Within Algorithm 3 the operator C = 3. Set Crossover A = 4. Set Crossover B = 28]. All Overall, the algorithm has been able to allocate genes to pathways in a way that allows us to infer the state of individual pathways with increased certainty removing contradictions from the final results. Pathways are now mostly filled with genes of similar expression, which we consider to be the most indicative of a pathway's state.Escherichia coli K-12 data from [Escherichia coli cells were grown in tryptophan enriched medium, leading to increased activity of the tryptophan metabolism pathway. Most tryptophan metabolism genes show subtle to substantial up-regulation except from yqeF which shows significant down-regulation , allowing them to examine if a cluster is enriched with genes from a particular functional category to a greater extent than would be expected by chance. Clusters in which the majority of genes belong to a certain category produce low probability with p-values near 0.Similar approaches have been adopted to identify interesting groupings produced by cluster analysis of gene expression data. In  the authWe have applied a similar approach to a microarray dataset, consisting of experiments from GEO platform 17 , to compThe result of implementing the hill climbing, simulated annealing and genetic algorithm to a set of 46 microarray experiments from GEO platform GPL17 is shown on Figure Figure Figure As expected, the mean fitness value also shows an increase as the number of allocations of genes to pathways grows Figure , with hiOn the contrary, there is no significant correlation between the number of gene to pathways allocations and the mean hamming distance between allocations produced by subsequent runs of the three search algorithms, as shown on Figure The same is true for the FARI's Figure  where thThe minimum FARI observed is 0.902, and the values remain high regardless of the observed variation in hamming distance. For example the mean FARI for pairs of allocations of hamming distance above 1 standard deviation is 0.964, 0.962 and 0.963 for the hill climbing, simulated annealing and genetic algorithm respectively. Based on this observation we can assume with sufficient degree of confidence that in cases of pairs of allocations, exhibiting substantial hamming distance, groups of genes have still been allocated together, in the same pathway, thus the FARI values are high. However, the pathways have been swapped, explaining the higher hamming distance values.While the results discussed in the data processing with hill climbing section seem biologically meaningful, a certain issue arises that is worth consideration. In particular, it can be argued that since a gene can be assigned to any of its member pathways without removal from another, the allocation in the case of each individual pathway does not affect the rest. In that sense one can examine each pathway in isolation, considering the majority of genes, in terms of up- and down-regulation. In this case the maximisation problem is reduced to a few simpler maximisation problems whose solutions can then be combined.This approach, however, has its own drawbacks which need to be considered. Importantly, it is not possible to apply this rationale in cases where up and down-regulated genes are present in equal or even similar numbers in a pathway, such as the case of gluconeogenesis and the pentose phosphate pathway in the discussed diauxic shift experiment. In fact, examining the dataset from GPL17 discussed in the methods performance on pathways section we observed that this situation occurs in four pathways on average in each experiment. Furthermore, the condition that a gene cannot be removed from all its pathways cannot be met. By implementing the removal of the genes from each pathway that contradict the expression of the majority, we have observed that, on average, about 30 genes remain unassigned, corresponding to about 20% of all expressed multi-membership genes per experiment. Importantly, in algorithm 1, whenever this situation occurs the gene is reassigned to a pathway.Nevertheless, the initial argument bears merit, thus we proceeded further to refine the proposed algorithmic approach. In particular, we implemented a search working with KEGG modules rather than pathways, that is, sub-networks which represent chains of events, leading to gradual alteration of a substrate into a desired product. In essence a module is still a pathway, where we zoom in to look into a particular sequence of biochemical reactions, such as the case of KEGG module M00003, representing gluconeogenesis, which forms part of the KEGG Glycolysis/gluconeogenesis pathway.One clear advantage of working with modules is that here, in principal we expect proteins forming the module to show agreement in terms of activity, which when reflected on their respective gene expression should produce more consistent results in terms of up- or down-regulation than in the case of genes forming entire KEGG pathways.In addition, here we can disallow allocation of expressed genes to modules of opposing nature. For example, the Glycolysis KEGG module M00001 gradually breaks down glucose to pyruvate, producing energy. In contrast, the gluconeogenesis module M00003 is responsible for the synthesis of glucose from precursors such as pyruvate. While KEGG includes glycolysis and gluconeogenesis in a single pathway due to the large number of genes shared by both, they are not simply the reverse of each other. Moreover, the two modules act in opposing directions and are not activated together as this would lead to a futile cycle , as prevSaccharomyces cerevisiae applies to about 14% of multi-membership genes, to only one of these modules at any particular instance. For example whenever an up-regulated gene is assigned to glycolysis, it is removed from gluconeogenesis, as long as it is a member of both modules. We implement this at step 11) of Algorithm 1, opting for simulated annealing, previously discussed. In the following sections we present the results of implementing this approach, to which we shall refer as module algorithm, based on a number of microarray experiments. We have examined the performance of the search starting from random allocations and concentrate on results characterised by high fitness values for biological interpretation.Hence, we have modified the algorithm to allow allocation of expressed genes shared by modules of opposing nature, which in the case of The module algorithm, not allowing gene allocation to modules of opposing nature, was applied to 21 microarray experiments obtained from GEO, characterised by sufficient numbers of expressed genes and presence of genes of contradicting behaviour in the same modules. The datasets were also selected based on the experimental conditions, whose nature allows us to comment on the obtained results. Importantly, upon processing the presence of contradicting genes was reduced by 50% on average with standard deviation of about 7%. Following is a discussion of results produced by applying this approach to the aforementioned experiments, concentrating on modules where genes appear to contradict each other state of expression, especially where genes are subject to reallocation.In GSM1075, from , microarIn GSM845 yeast cells subjected to starvation, after 12 hours, exhibit activation of gluconeogenesis and suppression of glycolysis. As expected the search has removed genes from biosynthetic modules while degradation of amino acids appears activated in the case of lysine and leucine Figure .In GSM876 from the same dataset, RNA is examined 12 hours after nitrogen depletion. The researchers comment on the repressive effect of the conditions on the cluster of glycolytic genes. Indeed our algorithm has produced an allocation where Glycolysis is clearly supressed while gluconeogenesis seems in the process of activation, along with the glyoxylate cycle module Figure . NucleotIn another dataset that deals with the global response of yeast, in terms of gene expression, to glucose addition  in the growth medium, application of the search algorithm to data corresponding to 15min following the pulse, produces allocations where up-regulated genes have been assigned to glycolysis Figure . In contIn contrast in GSM 290980 where RNA extracted from cells with no glucose in the medium after 2 hours are compared to cells with glucose, the search adequately assigns up-regulated genes to gluconeogenesis while down-regulated genes are allocated to glycolysis. As Figure Naturally, it is worth examining the relative performance of the search based on modules, as in the case of the pathway search algorithms. Figure As previously observed the, the mean number of iterations required for the algorithm to converge exhibits significant correlation of 0.9419 to the number of possible gene allocations Figure , as doesThe same applies to the mean FARI's, where the correlation between the mean FARI per experiment and the number of possible multi-membership gene to module allocations is -0.3700 Figure . Once agWe have shown that our algorithms can effectively assign multi-membership genes to their constituent pathways and modules, increasing the level of agreement, in terms of the direction of expression in either case. Nevertheless, working with modules seems advantageous from both biological and analytical point of view. That is, genes in a module are expected to show more consistent behaviour, while the more detailed definition of biochemical processes forming modules allows us to identify modules of opposing nature. In such cases we restrict allocation of the same expressed genes to both processes.The methodology is of potential interest, in the effort to infer the state of individual pathways and modules  based on microarray data analysis. It suggests an interesting direction for future work, as the multi-membership nature of genes has not been extensively considered as such in relevant research.Interestingly, we have observed minimal variation in the performance of the three search approaches, namely the hill climbing, simulated annealing and genetic algorithm. All methods produce highly consistent results and reach roughly equal fitness values, although the simulated annealing approach does seem slightly superior. Furthermore, the consistency of the produced allocations in terms of Hamming distance and FARI values does not show any correlation to the size of the search space, as defined by the number of possible genes to pathways or modules allocations in each experiment.A related issue that may be resolved following this approach is the observed swapping of piles of genes between pathways, by subsequent runs of the search algorithms. As discussed in the preceding sections, certain groups of genes seem to be allocated to different biochemical processes, but still placed together by separate applications of the methods described here. There is room for further investigation in that respect.An issue that requires more thorough investigation is the presence of genes, e.g. repressors, for which it is expected to observe change in expression that contradicts the up- or down-regulated state of the pathway they are members of. While our methods can still produce meaningful results, since this is confined to individual cases, especially when modules are used for the analysis, we plan to tackle this issue by improving our fitness function, taking into account the behaviour of suppressors and facilitating a more detailed pathway categorisation, for example using the Reactome database.Escherichia coli and Saccharomyces cerevisiae which are relatively simple living forms. According to KEGG statistics, the number of protein genes found in Escherichia coli K-12 is 4149 with 1397 of them allocated to biochemical pathways. In contrast, a human cell encloses 25724 protein genes, 5283 of which have currently been allocated to 198 KEGG pathways. Due to the resulting larger search space the methodology discussed here is likely to generate greater reshuffling in the results produced upon processing of microarray data from such more sophisticated organisms.It is worth noting that the methodology has been applied to Finally, an appealing direction for future work would be the use of the proposed approach on a large dataset, consisting of thousands of microarray experiments to infer the state of individual pathways in terms of activation and subsequently apply association rules mining between biochemical processes in an effort to elucidate pathway regulation and interaction.The authors declare that they have no competing interests.All authors contributed to the development of the underlying concept; SP wrote the scripts and was the principal researcher; AP aided in interpretation; SS aided software development. All authors read and approved the final manuscript.


Existing studies are divided as to whether social inequalities in health widen or converge as people age. In part this is due to reliance on cross-sectional data, but also among longitudinal studies to differences in the measurement of both socioeconomic status (SES) and health and in the treatment of survival effects. The aim of this paper is to examine social inequalities in health as people age using longitudinal data from the West of Scotland Twenty-07 Study to investigate the effect of selective mortality, the timing of the SES measure and cohort on the inequality patterns.The Twenty-07 Study has followed three cohorts, born around 1932, 1952 and 1972, from 1987/8 to 2007/8; 4,510 respondents were interviewed at baseline and, at the most recent follow-up, 2,604 were interviewed and 674 had died. Hierarchical repeated-measures models were estimated for self-assessed health status, with and without mortality, with baseline or time-varying social class, sex and cohort.Social inequalities in health emerge around the age of 30 after which they widen until the early 60s and then begin to narrow, converging around the age of 75. This pattern is a result of those in manual classes reporting poor health at younger ages, with the gap narrowing as the health of those in non-manual classes declines at older ages. However, employing a more proximal measure of SES reduces inequalities in middle age so that convergence of inequalities is not apparent in old age. Including death in the health outcome steepens the health trajectories at older ages, especially for manual classes, eliminating the convergence in health inequalities, suggesting that healthy survival effects are important. Cohort effects do not appear to affect the pattern of inequalities in health as people age in this study.There is a general belief that social inequalities in health appear to narrow at older ages; however, taking account of selective mortality and employing more proximal measures of SES removes this convergence, suggesting inequalities in health continue into old age. Social inequalities in health have been demonstrated at most ages and across time -3, althoThe main explanation for widening inequalities in health is that they are the result of the accumulated effects of social disadvantage over time ,18 and tGiven the existing literature, it is difficult to conclude with certainty whether social inequalities in health widen or converge with age. This paper aims to investigate this question addressing some of the limitations in the literature by: including mortality-'the final health status'  - with sThe Twenty-07 Study  has follOver the last 12 months would you say that your health on the whole has been... excellent, good, fair, poor?, which has been modelled as a binary  and continuous (1 = excellent through 4 = poor) outcome. Using self-assessed health as a continuous variable allows the severity of health problems to be investigated, and has been shown to be a reasonable assumption [The self-assessed health question asked at waves 2 to 5 was: sumption ,28. If tSocial class based on occupation was coded according to the Registrar General's 1980 classification  for the Given the clustered nature of the data - both geographically and within individuals - hierarchical repeated-measures models were employed, which include incomplete cases up to the point at which they drop out and use likelihood estimators that adjust for non-response if the data are missing at random . Models Preliminary investigations comparing linear, quadratic and cubic age functions identified the latter as the best statistical fit so a cubic function was used for all analyses. Random slope models were used, with the linear coefficient for age allowed to vary between individuals, but this had little effect on the other coefficients and, for simplicity, details are not presented here. Each model was constructed for both the binary and continuous outcome variables. First the cubic health trajectories for people from manual and non-manual classes at baseline were estimated controlling for gender, age and cohort. Secondly, a time-varying measure of social class was explored to see if this changed the pattern of inequality. Next, the effect of survival bias was investigated by including death as part of the two outcome variables with both baseline and time-varying class.In all models, interactions for cohort and gender with all other covariates were tested; where significant these are discussed below. To investigate the relative importance of age, cohort and period effects, the cohort variable was replaced with period, as age, period, and cohort cannot be included in the same models but modelling pairs of these variables and comparing the results provides some insights about which are the important factors . The relThe distribution of respondents at each wave by key variables is shown in Table Table The final two columns show the data used in this paper (person-waves); the first column includes all waves in which respondents were alive, participated in the study and had valid data for all variables, whereas the final column includes extra person-waves for each wave in which a respondent had not participated because they had died.Figure Figure The effect of expanding the health outcomes to include death is shown in Figure Figure In this study of three age cohorts, covering 60 years of the lifecourse, social class inequalities in self-assessed health vary considerably as people age and are dependent on the measurement of health and class. Without including decedents or employing proximal measures of social class, those in manual households appear to become ill earlier than those in non-manual households, who have a low probability of reporting poor health until the age of 65 years when the probability of reporting poor health steepens making inequalities in health appear to narrow. However, including death as part of the health outcome changes the pattern. Convergence of inequalities is still evident when the outcome is a simple comparison between reporting excellent/good health and fair/poor health or death, but inequalities persist to 75 for the continuous measure, which ranges from 1 (excellent) to 5 (dead) and hence better captures severity. Replacing baseline social class with a time-varying measure shows smaller inequalities in health in late middle age, and taking account of this suggests that inequalities continue into old age without narrowing. We find only modest evidence of cohort effects on the prevalence of poor health but these do not explain the pattern of inequalities with age. We found only one statistically significant gender interaction with SES as people aged (from 16 models), which might suggest that inequalities in women's health widened more than men's. However, given the number of interactions tested for, this may be due to chance.A number of other studies also find that disadvantaged groups become ill at younger ages in relation to physical health , diseaseThis paper has extended the age range and time period over which the issue of widening or converging inequalities in health has been considered in a single study. It directly examined the shape of age-health trajectories and unlike much of the existing literature, which has used linear or quadratic functions, found a cubic shape performed best, consistent with the only other study that tested for this . EmployiWhile many studies have speculated about the effects of survival bias, only a few have investigated it directly. We go further by including the available data on people who died and investigating what the pattern of social inequalities in health would look like if decedents were not excluded from the analyses after their death. We also use a measure of time-varying SES. This is the first study to take both issues into account at the same time.There are a number of limitations to this analysis. First, while the Twenty-07 Study covers ages 15/6 to 75/6, it cannot investigate inequalities at very old ages; this is a limitation in much of the literature, reflecting the length and scope of many longitudinal studies. Secondly, the study was originally set in a predominantly urban area with a wide range of health experiences but generally poor health , and as There are two ways in which this analysis might underestimate the extent of social inequalities in health. First, it is based on self-assessed health, which has been shown to be a good predicator of mortality  and morbFurther research is required to investigate the trajectories for different socioeconomic and health measures and how inequalities in them change across the widest age ranges available in longitudinal data. Using more proximal measures of social class suggests that social mobility may be important and this also need further investigation. There was a suggestion that there may be gender differences in these associations which have also been found in cross-sectional research,  and thesSocial class, measured at the start of the Twenty-07 Study, has a lasting effect on the health of respondents over 20 years in three different cohorts, with inequalities not only in the presence of poor health but also in its severity. The persistence of inequalities throughout the lifecourse when time-varying class is employed suggests that current circumstances are also important for health. Policies to reduce inequalities therefore should address current circumstances as well as long term causes of inequalities in childhood.The authors declare that they have no competing interests.MB developed the research questions, which were refined in discussions between all authors, oversaw the analyses, drafted the paper and is guarantor. MJG carried out the analyses with statistical advice from AHL. Both MJG and AHL also contributed to drafts of the paper, and all authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/947/prepub


The European Project on OSteoArthritis (EPOSA), here presented for the first time, is a collaborative study involving five European cohort studies on aging. This project focuses on the personal and societal burden and its determinants of osteoarthritis (OA). The aim of the current report is to describe the purpose of the project, the post harmonization of the cross-national data and methodological challenges related to the harmonization processThe study includes data from cohort studies in five European countries  on older community-dwelling persons aged ≥ 59 years. The study design and main characteristics of the five cohort studies are described. Post harmonization algorithms are developed by finding a "common denominator" to merge the datasets and weights are calculated to adjust for differences in age and sex distribution across the datasets.A harmonized database was developed, consisting of merged data from all participating countries. In total, 10107 persons are included in the harmonized dataset with a mean age of 72.8 years (SD 6.1). The female/male ratio is 53.3/46.7%. Some variables were difficult to harmonize due to differences in wording and categories, differences in classifications and absence of data in some countries. The post harmonization algorithms are described in detail in harmonization guidelines attached to this paper.There was little evidence of agreement on the use of several core data collection instruments, in particular on the measurement of OA. The heterogeneity of OA definitions hampers comparing prevalence rates of OA, but other research questions can be investigated using high quality harmonized data. By publishing the harmonization guidelines, insight is given into (the interpretation of) all post harmonized data of the EPOSA study. Osteoarthritis (OA) is a process or condition affecting the joint cartilage and subchondral bone and is frequently accompanied by pain, stiffness, disability and radiographic changes . It is tThe European Project on Osteoarthritis (EPOSA) studies the personal and societal burden and its determinants of OA in the aging European population using data from five population-based cohort studies across Europe. These cohorts include not only persons with severe OA who receive treatment, but also persons with (mild) OA who have not sought care (so far). Emphasis lies on the personal consequences  and societal consequences  of OA. Population-based studies are important as they provide data on the burden of the disease in terms of prevalence and impact on quality of life and health status, thus offering insight into the need for health care and prevention strategies.The cohorts involved have not been set up in a standardized way and different sampling strategies have been used. The present paper provides a description of the cohorts included in the project, focuses on the post harmonization procedures to merge these cross-national data and describes the methodological challenges encountered in the process of harmonization. Our purpose is to document the degree to which these post harmonization efforts have succeeded. Furthermore, this paper describes to what extent common data collection instruments have been used and the important similarities and dissimilarities between these instruments. Post harmonization of OA, ADL limitations and social participation are described in detail to illustrate particular methodological challenges. The complete harmonization guidelines can be found in additional file The data of five existing longitudinal cohort studies are combined using post harmonization procedures. The five cohorts are population based, but vary in recruitment procedures and measurement instruments used. Table The EPOSA project involves five cohort studies performed in five different countries. While the methodology of each cohort is described in detail elsewhere, here a brief description of their main characteristics is provided.Germany is represented by the University of Ulm, Institute of Epidemiology and Medical Biometry and AGAPLESION Bethesda Clinic Ulm. The study on Activity and Function in the Elderly in Ulm (ActiFE-Ulm)  is embedItaly is represented by the Department of Medical and Surgical Sciences, University of Padova, and National Research Council (CNR), Aging Branch, Institute of Neuroscience, Padova. The Progetto Veneto Anziani (ProVA) study was originally designed to assess the effects of cardiovascular and osteoarticular diseases on disability . ParticiThe Netherlands is represented by the VU University Medical Center, EMGO Institute for Health and Care Research, Amsterdam. Data were used from the Longitudinal Aging Study Amsterdam (LASA) , an ongoSpain is represented by the Universidad Autónoma de Madrid Centro Universitario de Salud Pública. The study included is Ageing in Peñagrande . ParticiThe United Kingdom is represented by the University of Southampton, Southampton General Hospital, MRC Lifecourse Epidemiology Unit. The Hertfordshire Cohort Study (HCS) was designed to examine the relationship between growth in infancy and the subsequent risk of common adult diseases, including osteoporosis and osteoarthritis . PotentiWhen various samples are used to study one particular hypothesis, the problem of heterogeneity between samples emerges. To cope with these differences, two approaches are possible: centralized analyses, which include harmonization of the datasets to create one large dataset in which the analyses are done, or coordinated independent analyses, in which the analyses are done in each dataset and the results per dataset are pooled afterwards . In the Figure The involved partners sent all relevant data with variable and value labels in English to the coordinating center . The coordinating center then developed the harmonized dataset in cooperation with the partners. A code book (harmonization guidelines) was made explaining how the variables were harmonized  and by method . Each of these different approaches to OA case definitions was evident in the five cohorts, highlighting the lack of accepted standard case definitions in current European studies. As OA is believed to be a collection of disorders with shared features rather than a single disease entity, several definitions of OA may be the best strategy. Thus, it was decided not to develop one harmonized variable for OA, but rather develop several OA variables  which can be used according to specific research questions. Table In ProVA, persons were classified by physicians as having definite, possible or no OA in the knees, hips or hands. In the other countries, however, dichotomous definitions for clinical OA were used (yes/no). To test whether the possible-category in the ProVA data should be interpreted as either definite/yes or no, two statistical procedures were used: (1) optimal scaling technique, and (2) regression models with known OA-correlates. The optimal scaling technique used is called Princals, which is based on non-linear factor analysis . This teTable In all five cohorts, a variety of Activity of Daily Living (ADL) variables were assessed in structured interviews Table . First iAll five cohorts had some information on social participation. In the ActiFE study the Lubben Social Network Scale was used, which assesses social isolation in older adults by measuring perceived social support received by family and friends. Two examples of items of this questionnaire are "How many relatives do you see or hear from at least once a month?" and "How many relatives do you feel at ease with that you can talk about private matters?". If social participation is regarded as an objective measurement of social activity, it is not possible to include data from ActiFE, as the questionnaire measures self perceived social support rather than engagement in social activities. In ProVA, Peñagrande, LASA and HCS, the frequency of participation in social activities was measured. In HCS the social activity score was derived from the social health questionnaire which includes the participation and frequency of 13 activities, such as positions of office or visiting friends. In Peñagrande, only two questions were asked regarding the frequency of caring for sick persons and caring for children. In LASA, respondents were asked whether they were involved in social organizations such as a political party or sport club and how often they participated in activities or meetings of these organizations. Although the frequency of social activities was assessed in four cohorts, the response categories varied: e.g. in ProVA the number of weekly hours devoted to social activities was asked, while in HCS the response categories were "weekly", "monthly" or "less often". Thus, the number and types of activities and the response categories differ greatly across the cohorts. It was therefore concluded that the social participation variables from the different cohorts were too heterogeneous to be harmonized.As the percentage of older persons is increasing rapidly across the Western world, the prevalence of OA is expected to rise . So far,In this paper, the harmonization procedures are described that are used in the European Project on Osteoarthritis (EPOSA). This study combines data of existing cohort studies across five European countries varying in climate, socio-economic status, life style, and health care policies. Across the cohorts, different measurement instruments were used and post harmonization algorithms were needed to merge the datasets and enable statistical analyses that allow testing cross-country differences.Due to the lack in standardization of the definition of OA, it was impossible to harmonize OA into one variable of OA. However, OA is believed to be a collection of disorders with shared features rather than a single disease entity, suggesting that it is appropriate to use several definitions of OA. Different definitions were constructed, based on three sources of information, i.e. self-report, clinical diagnosis and radiography. Higher rates of knee, hand and hip OA were found, for self-reported definitions than for the clinical definitions and radiography. These findings suggest that the prevalence rates of OA are higher for less specific definitions (e.g. pain or self-report) than for more specific definitions . The only exception is the ProVA study, in which the self-reported prevalence rates were lower than the clinical prevalence rates. This may be explained by the fact that we interpreted "possible clinical OA" as having OA, which may have led to an overestimation. If the "possible" category is interpreted as not having OA, the prevalence rates for clinical OA are lower than for self-reported OA (data not shown). In contrast to our findings, a recent review study showed that prevalence rates were higher when radiographic OA definition was used compared to symptomatic or self-reported OA definitions . This study included population based studies as well as hospital based studies, which makes it difficult to compare these results with the results of our study. The study also showed the difficulty in drawing conclusions on pooled prevalence rates due to large differences in study design, definition of OA and measurement of OA.A limitation of this study might be the lack of radiographic OA data in most cohorts (only available in ProVA and HCS), as radiographic OA is still seen as the standard case definition of OA in many epidemiological studies . Also thDespite the harmonization efforts, important differences remain in the interpretation of the OA-definitions for each EPOSA cohort. The number of joints included in the non-specific OA definitions varied  and the source of information varied . These differences in definitions hamper cross-country comparisons of prevalence rates. The interpretation of the definitions between countries is too diverse and pre harmonization is needed to reliably study cross-national differences in prevalence rates of OA. In the literature, much effort has been devoted to developing a standard definition of OA for epidemiologic studies that includes symptoms, disability, and joint structural disease . A diffiRecently, recommendations for standardization of radiographic OA and symptomatic OA were given by researchers of the Translational Research in Europe Applied Technologies for Osteo-Arthritis (TREAT-OA) consortium, a large study on genetic and biochemical risk factors of OA . ConsensPost harmonization of other instruments other than OA measures was also problematic. Although a common ADL limitations measure was constructed, it has to be tested whether this measure is a valid and reliable instrument. Loss of information was especially great regarding social participation. Unfortunately, these data could not be harmonized because of heterogeneity of the social activity questionnaires across cohorts.The measurement instruments used in each of the cohorts and for all variables were carefully selected by each of the cohorts and validated instruments were used if available. However, it is unclear to what degree the harmonized variables are valid. Validating all constructed variables is not feasible. To compensate for this, we are publishing the harmonization guidelines to be transparent about the data harmonization. In future papers the effect of harmonization on the validity of the main variables used will be discussed in the concerning papers.Fortunately, many other variables were successfully harmonized and include presence of other chronic diseases, anthropometric measures, physical performance, grip strength, pain, self perceived health and hospitalization. Although the intention of the harmonization was to study the prevalence rates of OA across countries and to focus on personal and societal consequences of OA, we cannot pursue these research questions with the current harmonized OA data. On the other hand, it is very well possible to study risk factors and consequences of OA in a part of the cohorts (based on the research questions and OA definitions available in the cohorts) and to study other non-OA-related research questions using high quality harmonized EPOSA data.Post harmonization of epidemiologic studies has become more common in the past 20 years . It is oDespite these issues, the EPOSA dataset provides a unique opportunity to study various research questions in general populations of older persons across Europe. The cross-national nature of the study provides for a large number of older persons in the analyses and large variation across cohorts, resulting in sufficient power to draw conclusions with respect to associations between variables. The harmonized dataset allows for analysis on the individual level, and stratified analyses allow for studying cross-nation differences. In addition, direct replication of findings across countries is possible. Four of the cohorts participating in the EPOSA study provide follow-up data, enabling longitudinal data analyses.Despite the extensive harmonization procedure, some variables, including OA, may continue to be difficult to compare across countries, and interpretation of findings may require particular attention. These aspects will be considered carefully by all involved investigators, and potential biases in the cross-national comparisons will be discussed in each future article.This paper provides the harmonization procedures on OA and other selected variables of the EPOSA project. This paper shows the degree of success of the post harmonization attempts that have been made. Given the heterogeneity within the OA definitions, this dataset is less suitable to study prevalence rates of OA. However, the dataset is suitable for studying other research questions using high quality harmonized data. Furthermore, it is recommended that researchers reach agreement on data collection instruments in the design stage of cohort studies to facilitate successful pooling of data.The authors declare that they have no competing interests.GP and LS drafted the manuscript. All authors contributed to the conception and design of the study. All authors read and corrected draft versions of the manuscript and approved of the printed version.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/12/272/prepubHarmonization guidelines. This file provides all harmonized variables of the EPOSA study in detail.Click here for file


Only a limited proportion of patients with psychiatric disorders attend the healthcare facilities, and that too when the condition becomes severe. Treatment from unqualified medical practitioners and faith healers is a common practice, and is attributable to the delay in proper treatment.A cross-sectional study was conducted to understand the pathway of care adopted by psychiatric patients and its relationship with the socio-demographic determinants in the study population. The subjects were selected from urban specialty psychiatric hospitals and interviewed using a pre-tested, semi-structured interview schedule. The data was analyzed using SPSS v10.0 software. The Chi square test, T test, and Kruskall Wallis Test were used, as needed.A total of 295 patients  were included in this study. The majority of the patients (45%) were suffering from Bipolar affective disorders (45%), followed by schizophrenia (36%). The majority, 203 (68%), were from the rural area, with 94 patients being illiterate. The mean distance traveled for treatment was 249 km. The majority of these (69%) had first contacted faith healers and a qualified psychiatrist was the first contacted person for only 9.2% of the patients.A large proportion of psychiatric patients do not attend any health facility due to a lack of awareness about treatment services, the distance, and due to the fear of the stigma associated with treatment. The psychiatric patients first seek the help of various sources prior to attending a psychiatric health facility. The pathway adopted by these patients need to be kept in mind at the time of preparation of the mental health program. Mental illnesses are commonly linked with a higher disability and burden of disease, than many physical illnesses. The World Health Organization noted that one in every four people are affected by a mental disorder at some stage of life. Six neurThe pathway a patient adopts to reach the appropriate treatment center is termed as the pathway of care. Studying the pathway of care helps us in analyzing health services use, identification of the sources of delay in attending the right care, and to find out the possible remedies. These care pathways are not random; they are structured by the convergence of psychosocial and cultural factors and have sufficient integrity to be studied directly as unfolding processes.In recent times, the pathway of care by psychiatric patients has been studied across the world.–9 Howeve10This is a hospital-based study, conducted at the Outpatient Department of a specialty psychiatric hospital  in Gwalior, India. This is a well-known, referral hospital in central India, and is affiliated to the medical college in the city. The Psychiatry Department of the medical college was located at this hospital, at the time of this study. The study subjects were the patients with psychiatric illnesses, who made their first contact with the study center, during the study period of May 2003 to April 2004.Considering the time and resources available, it was decided that at least 250 patients would be included in this study. The data collection was based on the incidental sampling method, where suThe two prefixed days of the week (Tuesday and Friday) were selected for data collection . Only those subjects who had their first contact with the psychiatry outpatient clinic here were included in the study, after their informed consent. Those subjects who had been old cases at this facility or had attended any other specialty psychiatric health facility were not included, because such cases were not likely to have any recent contact with outside agencies and might have added to the recall bias. The data was collected by two  of the four authors of this study. The clinical information and the interview schedule were used for data collection by interviewing either the patient or the informant or both, as appropriate. . As the cases were worked up in detail; if at any stage of the study it was found that it was not the first contact with any psychiatric health facility, those subjects were not included in the final data analysis. The diagnosis was finally given, after complete history and examination, on the DSM-IV criteria, by one of the authors (SG), who is a qualified psychiatrist. The study protocol was approved by the institutional review board of the GMA and by the Medical College Hospital in Gwalior.P value of <0.05 was considered statistically significant.The data so collected was analyzed using the SPSS v10.0 software. The basiA total of 304 subjects were enrolled in this study; however, the final analysis was done for 295 subjects . P=<0.05). The per capita monthly family income for the female subjects was lower than that for male subjects, with a statistical significant difference. . On the analysis of the distance traveled by these patients for treatment, it was noted that the mean distance traveled by these patients was 249 km.Only 27 (9.2%) patients consulted a psychiatrist as the first helping agency, while 202 (68.5%) of the cases first consulted faith healers. Age group, gender, diagnosis, educational status, per capita income and distance from GMA, were the factors found to be statistically and significantly related to the first help sought Tables  and 2. TThe present study also found (data not in the tables) that 215 (73%) of these patients delayed health seeking due to the fear of stigma. One hundred and fifty-two (52%) were not aware of the place of appropriate treatment. Seventy-six (26%) thought that the symptom would resolve by itself. Fifty nine percent had shared their thoughts about the illness with their spouse. It was interesting to note that 35 (12%) of these patients had attended the clinic without the knowledge of family members.Some qualitative information was also collected. A number of patients from rural areas reported the fear of stigmatization and isolation from the community if the psychiatric illness was disclosed, as the reason for the delay in treatment. The urban participants preferred to go to private practitioners as they believed that confidentiality was not maintained at government facilities. Some thought the treatment would be expensive and delayed the treatment.The possible reasons for most of the subjects in this study being 16 to 45 years may be because this is the economically productive age group; therefore, these patients have been brought for the right care. Nevertheless, the presentation of psychotic disorders more in the relatively younger age group (<40 years) has also been reported by authors in the past.–11This distribution in this study is highly skewed toward males (69%), which might be attributed to the prevailing gender bias in Indian society, where the illness of a male member is taken more seriously than that of a female patient. The findings in the present study also support the fact that psychiatric hospital services are utilized more by male patients than by female patients. Other studies from India have made similar observations.16 The re16The majority of patients in our study belonged to the lower socio-economic status, with low level of literacy, and was with a rural background. The study also noted that patients belonging to families from the urban, literate, and higher socio-economic status, preferred to take treatment from private practitioners or general hospital psychiatric setups. This could be due to the perceived stigma associated with mental illnesses and with that of psychiatric hospitals.Patients having psychotic disorders) rather than for patients with any other psychiatric illness. Similar findings have been reported by other authors in India,[Predominance of psychotic illnesses  among these patients may indicate that patients with minor and more common mental illnesses do not seek treatment from a specialty psychiatric hospital, as there is a common myth that psychiatric hospitals are for mentally ill persons,  early diagnosis and treatment can significantly improve the outcome and prognosis, Gater et al have not al[et al and Bane al[et al have fouAnother important point noted in our study was that the previous patients and their relatives (included in category ‘others’) were the major referring agency for patients to go for psychiatric care followed by allopathic practitioners. A study in 1998, observedThe limitation of this study was that it was conducted at a mental hospital only; a study from a medical college hospital, where more representative population attends the OPDs or a multicentric study could have given different results. Secondly, prefixed days are usually attended by the same specialist always; therefore, attendance to such prefixed days may also depend upon the perceived expertise and professional reputation of the expert, among the general population. Third, the patient groups used in this study were heterogenous and the pathway of care may have affected them, according to the disorder.The study found that the majority of patients attending the mental hospital suffered from severe mental illnesses and belonged to the male gender, rural locality, lower socio-economic class, and was with a low educational status. Faith healers were the most commonly sought primary helping agency among the study subjects. Pathways involving faith healers and traditional healers took a longer time to reach the right psychiatric help. The need for incorporating an efficient and effective referral mechanism, the role of various service providers in the pathway of care, and availability of services should kept in mind when preparing any mental health program in India.The Psychiatrist in this study was the person who had completed three years of postgraduation studies in Psychiatric medicine from an institute recognized by the Medical Council of India.Allopathic Practitioner was anybody who had at least completed his graduation in Medicine and received the degree of MBBS from any medical college in India. However, this person would not have specialized in Psychiatric Medicine.Traditional practitioner was anybody who had qualified in any stream of medicine except Allopathic medicine. Government of India recognizes Ayurveda, Unani, Siddha, and Homeopathy as standard streams of medicine. The practitioners of any of these streams were considered as traditional practitioners in this study.Faith healers were the people who practiced witchcraft, and treated patients by using magico-religious practices. They did not have any medical qualification.Others were the relatives / friends of the study subjects. The previous patients with such illnesses were also included in this group, in the present study.