The achievement of the Millennium Development Goals (MDGs) depends on sufficient supply of health workforce in each country. Although country-level data support this contention, it has been difficult to evaluate health workforce supply and MDG outcomes at the country level. The purpose of the study was to examine the association between the health workforce, particularly the nursing workforce, and the achievement of the MDGs, taking into account other factors known to influence health status, such as socioeconomic indicators.A merged data set that includes country-level MDG outcomes, workforce statistics, and general socioeconomic indicators was utilized for the present study. Data were obtained from the Global Human Resources for Health Atlas 2004, the WHO Statistical Information System (WHOSIS) 2000, UN Fund for Development and Population Assistance (UNFDPA) 2000, the International Council of Nurses "Nursing in the World", and the WHO/UNAIDS database.The main factors in understanding HIV/AIDS prevalence rates are physician density followed by female literacy rates and nursing density in the country. Using general linear model approaches, increased physician and nurse density (number of physicians or nurses per population) was associated with lower adult HIV/AIDS prevalence rate, even when controlling for socioeconomic indicators.Increased nurse and physician density are associated with improved health outcomes, suggesting that countries aiming to attain the MDGs related to HIV/AIDS would do well to invest in their health workforce. Implications for international and country level policy are discussed. The socio-political impact of HIV/AIDS is increasingly being identified as a global crisis, rather than only a health crisis. There are estimates that generations of economic development and progress will be woefully reduced by the pandemic and that the socio-political fall-out due to HIV/AIDS has only started. Complacency in the developed world is risky because of the global nature of the world economic markets and the inter-dependencies for trade and manufacturing that are complex and multi-national. Nonetheless, data regarding mortality, especially infant mortality, and life expectancy indicate marked disparities between rich and poor countries .One of the United Nations Millennium Development Goals (MDGs) is to reverse the spread of HIV/AIDS by 2015. Providing safe and effective anti-retroviral medications to HIV positive patients in developing countries will help enhance positive health outcomes [The WHO, in addition to focusing on basic public health and epidemiology, also focuses on workforce development, making recommendations to Ministries of Health on health care workforce utilization and deployment. Indeed, for 2006, the World Health Day theme was workforce based: Working Together for Health. This is, in part, due to the serious implications of workforce migration from the developing to the developed world but also trying to match the numbers and types of health care workers (skill mix) to country level needs.Of particular focus in this paper is the contributions made by nursing professionals. The workforce migration issues are most acute in nursing, in part due to societal and economic conditions in many countries of the world. As most nurses in the world are female, gender politics, educational inequalities, and wage disparities are driving forces for migration to countries where wages are higher, there is more public respect for the profession, and nurses have the opportunity for professional advancement .There is widespread recognition that the factors associated with health are multifactorial and include not only health-related risk factors but also social determinants such as poverty, social status, education, employment and other social factors . Thus thData for the study were derived from a number of WHO and NGO sources. Human resources for health were derived from the Global Health Atlas of Health Workforce 2004 . Health The variables in the data set included the following : 1) number of nurses per 100 000 population; 2) number of midwives per 100 000 population; 3) number of nurses and midwives per 100 000 population; 3) number of physicians per 100 000 population; 4) the presence of nursing regulatory bodies at the national level; 5) the presence of a national nursing association; 6) whether there is regulation for nursing practice; 7) the presence of a WHO Collaborating Centre for nursing (WHO CC); 8) the years of schooling required to become a registered nurse; 9) government expenditure on health as a percentage of total expenditure on health; 10) governmental expenditure on health as a percentage of total general government expenditure; 11) out of pocket expenditure on health as a percentage of private expenditure on health; 12) per capita expenditure on health (USD); 13) per capita expenditure on health in international dollars; 14) private expenditure on health as percentage of total expenditure on health; 15) social security expenditure on health as percentage of general governmental expenditure on health; 16) total expenditure on health as percentage of gross domestic product; 17) total adult literacy rate in %; 18) male adult literacy rate in %; and 19) female adult literacy rate in %. The outcome variable was percentage of adults ages 15 to 49 living with HIV/AIDS, the prevalence rate.Two approaches were used for analysis: data mining using classification and regression trees (CART) and standard statistical analyses using ordinary least squares regression. We chose to use both approaches to help us determine, using the data mining approach, which variables were to be used in the standard regression approach. This was particularly important because many of the social and economic variables are multi-collinear. Furthermore, because there was not a specific theoretical model that guided our work , we did not want to exclude variables that may not generally meet the threshold for a stepwise regression approach.CART is a data mining approach which has been applied successfully in nursing and medical domains. CART can be used for prediction: as an example, CART can help predict levels of HIV/AIDS prevalence rates based on previously learnt data. CART can also be used for interpretative purposes. For example, it can be used to understand better patterns driving specific outcomes, such as HIV/AIDS prevalence rates. In this study, both interpretation and prediction were used.CART splits data and finds patterns (or sequences of variables explaining consistent outcomes) until all the terminal nodes reach optimum similarity. The selection of the variables is based on maximization of impurity reduction . The example shown in Figure In the first part of the results, authors present a partial description of the key variables that are associated with HIV/AIDS prevalence rates. All variables described under methods were used in developing the CART models. In the next section, authors predict key selected results based on CART to reveal patterns in the data. For this analysis, the CART-derived decision tree and findings show that physician density is the first key discriminator between high and low HIV/AIDS prevalence rates among the 194 countries for which data were collected.When analysing country profiles from 194 countries, 139 countries had a known level of HIV/AIDS prevalence rate  had a physician density > 29.5. These countries showed a lower HIV/AIDS prevalence rate compared to countries with physician density <29.5. When physician density was between 29.5 and 69, then nurse density emerged as the second most important criterion associated with lower levels of HIV/AIDS prevalence.The average HIV/AIDS rate was 1.36 (9 countries) when physician density was greater than 106, which indicated that a very high level of physician density alone is not a good predictor of lower levels of HIV/AIDS prevalence. Thus, a CART-based approach provides a statistically valid and logical explanation of complex predictions including many variables of different types, even qualitative.One of the advantages of using CART – similar to other benchmarking techniques – is the ability to predict outcomes on the basis of existing clusters or rules classifying the problem domain. For this research, we decided to use CART derived clusters to help identify which variable(s) can best explain HIV/AIDS prevalence rates in selected countries around the world. The four countries selected for this purpose were Botswana, Swaziland, Thailand, and Zimbabwe. These four countries were selected on the basis of 1) high levels of HIV/AIDS prevalence rates and 2) the presence of data for the potential explanatory variables. The selection of a different set of countries would not have likely affected the results. The first step was to eliminate them from the sample, one by one. The second step considered recalculating new cluster values. The third step assessed whether the nodes and their associated values had changed, and if so, by how much. In order to perform this analysis, authors compared each country profile in the new cluster tree and assessed the variation between predicted values and actual values of HIV/AIDS prevalence rates.CART produced very accurate (greater than 95% accuracy) outcomes using the methods described in Table 2 = .36). The workforce variables, when controlling for the per capita expenditure on health, were both significant: physician density with standardized regression coefficients (beta) of -0.52 and nurse density = -0.22. Most simply, this is the change in the log percentage of adults ages 15 to 49 with HIV for a unit change in the independent variable. The interpretation, therefore, is that even when controlling for per capita expenditures on health, both physician and nurse density make a contribution to HIV/AIDS prevalence rates for those between 15 to 49 years of age. When controlling for physician density, nurse density had an independent association with HIV/AIDS prevalence rates for the 15 to 49 age group. Of note, per capita expenditure on health in international dollars had less relative influence on prevalence rates than either of the workforce variables  . Because of non-normal distribution of HIV/AIDS prevalence rates, the log of the HIV/AIDS prevalence rates was used. The statistical assumptions for multiple regression were examined and met. Because there was multiple co-linearity for some of the independent variables, particularly the socio-economic ones, the final model contains two independent variables (physician density and nurse density) and one covariate . The final model was significant  with 36% explained variance (adj RThis paper describes how a data mining approach and standard statistical analyses were able to support the link between health workforce composition and HIV/AIDS prevalence rates in selected countries. In summary, nursing and physician density were both associated with HIV/AIDS prevalence rates. The other important variable was female literacy level. There were a number of variables that did not emerge in the data mining analysis that have been conventionally used to explain HIV/AIDS prevalence, in particular socioeconomic status variables, such as expenditures on health and gross domestic product.There are a number of explanations for our findings. Consistent with the emphasis on the social determinants of health, there is evidence that higher overall educational attainment for both genders was associated with lower prevalence rates of HIV/AIDS in Uganda . SimilarIn countries where HIV/AIDS over-stressed the health care system and where pharmaceutical treatments are not available or are not widely available, home-based care, organized and delivered by nurses, may be the only available form of health care. Thus an investment in home care nursing in these countries can reduce the spread of HIV/AIDS through community and public health nursing approaches .To lessen the impact of HIV/AIDS on health care systems globally will require a multi-faceted approach. It may not be sufficient to simply request more financial support without revising current approaches to train and retain nurses and physicians and to increase female literacy. Governments may want to consider programs specifically targeted to strengthen and alternatively distribute the nursing workforce given that our findings showed nurse density having an association with HIV/AIDS prevalence rates. Strengthening the nursing workforce may also require additional investments in education to prepare additional number of nurses where there is an absolute shortage of personnel. Any such programs will also need to consider improving the working conditions of nurses to ensure that they do not fall victims to the disease they help to prevent through occupational exposure. Concurrently, there will have to be multi-sectoral efforts to improve the status of women through education. A recent paper identified "economic, social, and political empowerment of women" as a key necessary driver behind new policies on HIV/AIDS . Our datThere are areas for further research which will have to be addressed. Data obtained for nurses in this study could not differentiate between the various educational background and practice of nurses worldwide. Had we been able to run a more detailed analysis aided by accurate description of the nursing workforce, results would have allowed for more precision concerning the impact on HIV/AIDS outcomes. Another limitation was the lack of ability to separate the number of midwives and their contributions to preventing HIV/AIDS from the nursing data. There are large variations in practice; in some countries midwives have their independent practice, in other countries nurses who receive midwifery training do both, while a third scenario is where all midwives must be trained nurses. We acknowledge that there is an increased need to have trained HIV/AIDS health care providers, especially in areas where resources are scarce . Yet we In addition, further country-level information on how nursing is integrated within the culture and within the health care system of that particular country may be informative in identifying best nursing workforce practices for health care structure, licensure/registration, scope of practice, education and support of nursing education, collaboration with physicians, and the use of traditional or community health care workers. New models are needed to assess HIV/AIDS testing, care, and treatment impact on patients and their communities, all of which are largely influenced by culture and setting.There are a number of limitations to our study. First, we were using country level data and there are some countries where prevalence reports are not made public. The inclusion of these countries would have benefited this research. Second, by the use of a reduced dataset, we risked over-simplifying complex political and health care system characteristics that could have modified results. Third, because HIV/AIDS is often associated with stigma in many parts of the world, we may have overlooked the effect of such factors in the absence of accurate data. Fourth, because nursing workforce educational levels widely varied, we could not distinguish the contributions made by the various levels of nurses. Fifth, the data sources were from different years and different sources of information, which may have resulted in missing some of the dynamic nature of the change in the variables used in the combined data base. Finally, our study variables indicate correlations and we are not implying cause-and-effect relationships.Looking at our outcomes, it is evident that nursing density has a significant association with HIV/AIDS outcomes in many countries. Investment in the nursing workforce by creating and supporting additional nursing education programs may have a positive impact on HIV/AIDS prevalence rates in many developing nations. In addition to the preparation of new nurses and midwives, increasing satisfaction of the currently employed and improving their working conditions may decrease nurse migration . Work byAttainment of the MDG for HIV/AIDS will not be achieved by opening up pharmaceutical treatment in the form of ARVs without a commensurate investment in the health care workforce which provides the necessary care for patients living with HIV/AIDS. Rightfully, much international attention is currently focused on the unequal access to pharmaceutical treatment for HIV/AIDS patients. But even if the drugs were widely available at low cost tomorrow, the current, insufficient number of health personnel would not be enough to match the millions of infected individuals waiting for the attention of health care worker.The authors have no competing financial interests. Dr Zrinyi was formerly employed by the WHO but has no current financial or other ties to the WHO.MZ developed the merged data set. OLC performed the data mining. EAM performed the multiple regression analysis. The generation of the idea and writing of the paper was a three way effort in drafting and revising the final copy. All three authors approved the final version.


The impact of the XVII International AIDS Conference (AIDS 2008) was reflected in a number of commitments from political and business leaders, who announced initiatives ranging from implementing comprehensive sexual education for young people in Latin America to reducing regulatory barriers and the price of drugs in the host country. The unprecedented media coverage brought attention and public awareness to the epidemic in Latin America.Several meetings and sessions at AIDS 2008 also addressed the potential for the International AIDS Conference to play an even stronger role in tracking progress towards universal access and in improving accountability in the global response to AIDS, particularly given some of the inherent weaknesses in the United Nations General Assembly Special Session (UNGASS) review process. The impact of AIDS 2008 was strongest in Mexico, the host country, and in Latin America. Highlights included the policy changes announced by President Calderon on pharmaceutical manufacturing to the focus on sex workers and gay and other MSM in marches, activism and the conference programme.The next two years will determine whether the successes reported in Mexico are sustained and whether there is progress in addressing the barriers that continue to hamper an evidence-based response to HIV/AIDS. The next International AIDS Conference is scheduled for the universal address deadline of 2010. In an effort to strengthen the role of the conference as an accountability mechanism, the AIDS 2008 Conference Coordinating Committee organized several sessions and meetings that focused on tracking progress on existing commitments and developing strategies for increased accountability among stakeholders. In a session reviewing progress on UNGASS targets, several speakers reminded participants that, while the UNGASS process has been essential to scale-up efforts, it is hampered by the fact that both the goals themselves and the reports on progress towards meeting the commitments are drafted by UN Member States, over which both multilateral institutions and civil society have limited influence . Kieran As a multidisciplinary meeting that brings together scientific, political and community leadership as equal partners in the global response, the conference has inherent advantages compared to UNGASS meetings, in which government officials from Member States ultimately determine the commitments and key messages. The current size and complexity of the conference programme, however, brings with it significant challenges to restructuring part or all of the conference to serve as a more formal accountability mechanism, with a more systematic monitoring component. If â€“ as some speakers suggested â€“ the conference is evolving into a broader health and development meeting, it will doubtless add additional complexity to such an effort.At a meeting of key stakeholders at the conference hosted by the IAS, there was strong support for a more strategic and structured approach to monitoring progress on universal access targets and Millennium Development Goals (MDGs), particularly at AIDS 2010, which coincides with the deadline for meeting UNGASS commitments. However, the suggestion that the conference issue report cards on a select group of countries using a set of core indicators, an approach similar to that proposed by AIDS Accountability International , raised Potential strategies for formalizing the role of the International AIDS Conference as an accountability mechanism include establishing a separate accountability track or restructuring the Leadership Programme to serve this purpose. The issue of securing the participation of senior political leaders in a forum where their commitments to most at risk populations, controversial prevention interventions (such as drug consumption rooms), or structural drivers of the epidemic will be scritinized, is an ongoing challenge for conference organizers . IAS ExeNot all accountability discussions focused on political leaders and government policymakers; one session included an innovative performance evaluation process established by civil society representatives on the UNITAID board to assess civil society accountability Figure  7,8].,8.7,8].The plethora of regional AIDS conferences and other scientific meetings is presenting donors and HIV professionals with increasingly difficult decisions about whether to fund and participate in these resource-intensive events. The IAS has devoted significant work and resources to regional partnerships over the last several years and is providing financial, organizational and technical support â€“ with support from the Bill & Melinda Gates Foundation â€“ to several regional conferences. The purpose of this approach is not only to strengthen knowledge transfer between these conferences and the larger International AIDS Conference â€“ through such mechanisms as the regional sessions organized for AIDS 2008 â€“ but to leverage donor investments in knowledge exchange and networking while ensuring that regional-specific issues are adequately addressed. The IAS has also expanded its own professional development activities, partnering with other agencies to strengthen learning opportunities  to remove homosexual acts from the criminal code.• Mexican President Felipe Calderon announced removal of the regulatory barrier which required pharmaceutical companies to have a manufacturing plant in Mexico in order to sell their drugs in the country, and to making low drug pricing a priority for his government.• Mexico City Mayor Marcello Ebrard spoke out against homophobia in his Closing Session speech and announced that local government will be distributing new text books on health that address sex education in public schools.• Indian Health Minister Anbumani Ramadoss publicly urged the Indian parliament to repeal section 377 of its criminal codes, which criminalizes 'unnatural acts' , reinforcing an earlier statement to that effect by India's High Court Judge, Bilal Nazki.• China announced that it would lift its ban prohibiting people living with HIV from entering the country.• The Coalition of First Ladies and Women Leaders of Latin America on HIV announced their commitment to eliminating MTCT and syphilis by 2015.• Representatives from 30 Ministries of Health and 25 Ministries of Education in Latin America announced they would prioritize HIV prevention education and sex education in schools as part of their regional strategy on HIV/AIDS.• Merck and Company announced it would cut its price of Stocrin (efavirenz) in Mexico by 40% from 777 pesos per patient monthly to 468 pesos (roughly from US $77.50 to US $46), and on Isentress  by 30% from 9.05 pesos to 6.85 pesos per patient monthly (approximately US $903 to US $683).• Spanish Vice President Maria Teresa Fernandez de la Vega announced her country's contribution of €10.2 million to UNAIDS, of which €3 million will support the activities of the International AIDS Vaccine Initiative and €1.5 million will go to the International Partnership for Microbicides.• The Spanish government announced the inclusion of lipoatrophy treatment to the list of services covered by the National Health System.Beyond the tangible policy and funding announcements, analysis of the news coverage revealed an unprecedented amount of media attention to stigma and discrimination, particularly related to the Opening Session keynote on this issue by UN Secretary-General Ban-Ki moon. Other topics that received considerable media attention internationally include the challenges faced globally by gay and other MSM, and the ongoing debate regarding whether AIDS receives a disproportionate amount of funding relative to other health and development issues. Coverage by Mexican and other Latin American media focused particularly on barriers to delivering prevention, care and treatment to gay and other MSM, an issue which emerged as a dominant theme of AIDS 2008.The need to address homophobia and the challenges faced by the gay and other MSM populations was underlined in a statement released by the Episcopal Social Pastoral Commission of the Mexican Catholic Church. The statement condemned the stigma and discrimination faced by PLHIV and pledged to work with other social actors in the response, particularly those targeting socially vulnerable communities, 'such as indigenous people, women, prisoners, young people, those excluded from the education and health systems, rural dwellers, migrants and their families, children and young homeless people.' Notably South African news coverage focused on conference sessions that addressed the dangers of criminalizing HIV, covering Justice Edwin Cameron's plenary speech on this topic, as well as the promising potential of task-shifting to address health system capacity issues in low and middle-income countries.As part of its ongoing strategy to expand the reach and impact of the conference through use of the Internet, the IAS relied on its online partners Clinical Care Options, which once again provided official online scientific coverage, and Kaisernetwork.org, which produced over 75 webcasts, daily news reports, and other news summaries to a global online audience. It also initiated a pilot project aimed at expanding the reach of the conference to those unable to attend via conference hubs Figure .AIDS 2008 addressed some of the most pressing issues facing the HIV field as it moves ever closer to the 2010 deadline for meeting universal access targets. Among the many tangible impacts of the conference, some of the most important are: recognition of the need for policymakers to take steps to move beyond rhetorical commitments to human rights for vulnerable populations to concrete legislative and policy changes that will have an impact on the environmental and structural drivers of the epidemic; new evidence that the health system-strengthening effects of HIV-specific funding can lead to greater synergies with other areas of the health care system and help deconstruct the polemic of vertical versus horizontal investments; a new consensus on the need for 'combination prevention', which integrates existing biomedical, behavioural and community based approaches with interventions that address the social and structural inequalities which continue to drive infections; new clinical evidence suggesting that ART should be initiated earlier and used aggressively to curb mortality and morbidity, and to maximize its potential impact on reducing transmission; the promise of PrEP as a potential new biomedical prevention tool on the horizon; and new basic science research that is exploring cellular dynamics in the inflammatory response to HIV that could lead to new therapeutic applications and - perhaps- new insights into viral eradication.The next two years will determine whether the advances reported at AIDS 2008 are sustained and how much progress will be made on the necessary policy and legislative changes to achieve universal access by 2010, the next year of the International AIDS Conference.Rodney Kort is an independent consultant contracted by the International AIDS Society for the purpose of preparing and editing the AIDS 2008 Impact Report for publication.Rodney Kort drafted this text and has approved the manuscript for publication.


The SIR for all non-AIDS-defining cancers was only just significantly increased in men with HIV-infection but not AIDS  and was nonsignificant in such women .This study used data from the Communicable Disease Surveillance Centre's national HIV database and the Thames Cancer Registry to assess the risk of cancer in HIV-infected people in southeast England. Among 26 080 HIV-infected men with 158 660 person-years follow-up, 1851 cancers, and among 7110 HIV-infected women (31 098 person-years), 171 cancers were identified. The standardised incidence ratio (SIR) for all non-AIDS-defining cancers was significantly increased in HIV-infected men  2.6–3.1) but was nonsignificant in HIV-infected women . Most of the cancers observed were in men ( The epidemic of HIV-infection is continuing with nearly 6000 new HIV-infections reported in 2002, the highest annual total since 1985, and over 50 000 people reported with HIV-infection or AIDS in the UK by the end of 2001 . People By the end of 2001, nearly 70% of people reported to the Communicable Disease Surveillance Centre (CDSC) with HIV-infection or AIDS in the UK were reported from London and the Southeast. This corresponds approximately to the catchment area of the Thames Cancer Registry (TCR). The aim of this study was to link data from the cohort of people reported with HIV-infection or AIDS with data from the TCR to assess the risk of different types of cancer in HIV-infected people, those with AIDS and those with HIV-infection but not AIDS. In addition, we aimed to assess the completeness both of cancer registration in HIV-infected people and of HIV-infection reporting in people with cancer.The CDSC collates information on the diagnosis of HIV-infection and AIDS in adults in England, Wales and Northern Ireland. Microbiologists and clinicians report demographic details and how the infection was probably acquired; the hospital trust from which the person was reported is also recorded. Names are not recorded but a soundex code is assigned to each record, comprising the first letter of the surname and three numbers based on the other letters. Soundex codes are not unique to one surname but can be used with other fields to detect duplicate entries. Deaths and AIDS diagnoses in previously reported people are also reported. The CDSC also receives information on HIV-infections and AIDS diagnoses in Scotland from the Scottish Centre for Infection and Environmental Health.The TCR collects details of cancers diagnosed in southeast England in a catchment population of about 14 million people in London, Surrey, Sussex, Kent, Hertfordshire and Essex; it also records demographic data, including name, address and postcode. Patients are flagged in the NHS Central Register, which provides dates and causes of death. Cancer registration in England and the HIV/AIDS reporting system are both approved under the section 60 regulations of the Health and Social Care Act. The current study was approved by the Public Health Laboratory Service Ethics Committee and the West Midlands Multi-centre Research Ethics Committee.The TCR data set in our study comprised the 224 199 cancers (ICD10 C00-97) that were diagnosed from 1985 to 2001 in people aged 15–59 years, who were resident in the TCR catchment area and had no cancer before 1985. The CDSC data set comprised the 50 182 HIV-infected people who were reported from the UK and diagnosed by the end of 2001. Both these data sets included date of birth, sex, soundex code, first initial and date of death. The TCR data also included second initial and details of the cancer. The CDSC data also included HIV-diagnosis date, whether the person had AIDS, AIDS-diagnosis date, when the person was last reported alive, and details of AIDS-defining cancers. A variable was created for whether the HIV-infection was first reported from a hospital in London, Southeast and Eastern regions, which includes the TCR catchment area. We then excluded people in the CDSC data whose first report was outside this area or who had no sex or date or birth, leaving cohorts of 27 054 men and 7510 women.The two data sets were matched at the CDSC, accepting matched records if the date of birth, sex and soundex code were all identical. We excluded matches if the TCR date of death was before the date when the CDSC last knew that the person was alive, the dates of death differed by more than 30 days, or the CDSC date of death was more than 30 days before the cancer diagnosis date. We also excluded matches if the CDSC first initial did not match the first or second initial from the TCR database. Whereas the CDSC database is person-based, the TCR database is tumour-based. A tumour record should only match to one person, and we selected the best match for four tumour records that had each matched to two different people by reviewing the full patient records. A person could legitimately match to more than one tumour record, but we excluded second or third tumours to facilitate the calculation of person-years. This left 2139 one-to-one matches. We added the cancer diagnosis date, ICD10 three-digit cancer diagnosis code and TCR date of death to the CDSC data for people who had matched to a TCR tumour record.To calculate person-years at risk, we created entry and exit dates for each person. For men and women with HIV-infection, we used whichever was later of the person's 15th birthday, their HIV-diagnosis date minus 30 days or 01/01/85, the start of the study period, as the entry date. For men and women with AIDS, we did the same but used the AIDS-diagnosis date minus 30 days. We backdated diagnosis dates so that cancers that may have initiated an HIV-diagnosis were included. We used the same exit date for men and women with HIV-infection and AIDS. We replaced 31/12/01, the end of the study period, with the CDSC date of death if this was present and before 31/12/01; with the TCR date of death if present and before 31/12/01; with the cancer diagnosis date if present; and with the person's 60th birthday if this was before the current exit date. We regarded the TCR dates of death as more accurate because they were supplied by the NHS Central Register.Before each analysis, we excluded people with exit dates before 01/01/85, entry dates after 31/12/01, exit dates before entry dates, or the same entry and exit dates. The observed numbers of each cancer, all cancers and all non-AIDS-defining cancers were then counted for each cohort during the study period. AIDS-defining cancers are Kaposi's sarcoma , non-Hodgkin's lymphoma  and cancer of the cervix uteri (ICD10 C53). For people with HIV-infection and AIDS, the person-years at risk in each sex and five-year age-band and period were multiplied by the incidence rate for each cancer site in southeast England during the same period. This gave an expected number of each cancer for each cohort during the study period. For the sexes separately, we subtracted the observed and expected numbers for each cancer in those with AIDS from the corresponding numbers for HIV-infected people to give the numbers for those with HIV-infection but not AIDS. The observed numbers of each cancer, all cancers and all non-AIDS-defining cancers were then divided by the expected number for each cohort and 95% confidence intervals (CI) calculated for the ratios.Kaposi's sarcoma is very rare in young people without HIV-infection. To assess completeness of reporting of people with HIV-infection, we reviewed the proportion of KS in the TCR data that matched to a person in the CDSC data reported from anywhere in the UK. To assess completeness of cancer registration in HIV-infected people, we reviewed the proportion of people from the CDSC data with both an AIDS-defining cancer and a first report from regions wholly or partly within the TCR catchment area who matched to a comparable tumour record from the TCR data. We compared presumptive or definitive KS and Burkitt's lymphoma or immunoblastic lymphoma from the CDSC data with, respectively, KS and NHL from the TCR data. Burkitt's lymphoma and immunoblastic lymphoma are classified as NHL by the TCR.After making the exclusions based on entry and exit dates, the analysis included 26 080 HIV-infected men who contributed 158 660 person-years and 1851 cancers. The SIR for all cancers was 11.5 (95% CI 10.9–12.0), and the SIR for non-AIDS-defining cancers was 2.8 (95% CI 2.6–3.1) . The SIRThe analysis included 7110 HIV-infected women who contributed 31 098 person-years and 171 cancers. The SIR for all cancers  was lower than in HIV-infected men, and the SIR for non-AIDS-defining cancers  was nonsignificant . There wn=1559) of the observed cancers in HIV-infected men were in men with AIDS. The SIR for all cancers was 42.3 (95% CI 40.2–44.5), and for non-AIDS-defining cancers 8.2 (95% CI 7.2–9.2)  . The SIRn=127) of the observed cancers in HIV-infected women were in women with AIDS. The SIR for all cancers  was lower than in men with AIDS, as was the SIR for non-AIDS-defining cancers   . There wMen with HIV-infection but not AIDS contributed 128 438 person-years and 292 cancers to the analysis. The SIR for all cancers was 2.3 (95% CI 2.1–2.6), but for non-AIDS-defining cancers the increase was only marginal  . The SIRWomen with HIV-infection but not AIDS contributed 26 370 person-years and 44 cancers. The SIR for all cancers was 1.5 and only just significantly increased (95% CI 1.1–2.1), and the SIR for non-AIDS-defining cancers was only 0.8 (95% CI 0.5–1.2) . The SIRn=954) were more likely than unmatched cases  to be in men. The matched group was also younger than the unmatched group: for example, 94% (n=960) of the matched group were aged under 50 years compared with 87% (n=203) of the unmatched group. Matched cases were also more likely to have died by the end of the study period  than unmatched cases .There were 1251 cases of KS in the TCR data and 1017 (81%) had a valid match to a person in the CDSC data reported from anywhere in the UK. This included 11 matches where KS was the second or third tumour. Matched cases  had a valid match to a KS record in the TCR data. This included six matches where the KS from the TCR data was the second or third tumour. There were 516 people from the CDSC data with Burkitt's lymphoma or immunoblastic lymphoma and a first report from a region located wholly or partly within the TCR catchment area, and 228 (44%) had a valid match to an NHL record from the TCR data. This included matches involving two cases of NHL from the TCR data that were second or third tumours.This study used data from the national database of HIV-infected people and a regional cancer registry to assess the risk of cancer in HIV-infected people in the TCR area, which has the highest number of people reported with HIV-infection in England. Despite including about 33 000 HIV-infected people, there were few cancers in women. Although much smaller than certain linkage studies of people with AIDS  of people from the CDSC data with Burkitt's lymphoma or immunoblastic lymphoma and a first report from a region located wholly or partly within the TCR catchment area to a TCR NHL record. The overall completeness of registrations 5 years after diagnosis has been estimated as 92% (During the overall analyses and the assessment of the completeness of cancer registration in HIV-infected people, we excluded people from the CDSC data whose first report was not from a region located wholly or partly within the TCR catchment area, that is not from London, Southeast and Eastern Regions. As the Southeast and Eastern Regions extend beyond the TCR catchment area, the cohorts will have included people from outside the TCR catchment area. Some of the apparent incompleteness of registration of KS and NHL from the CDSC data by the TCR may, therefore, be explained by their registration at other regional cancer registries. Overall, the inclusion of people from outside the TCR catchment area will have meant that person-years at risk and expected cancers were overestimated and SIRs were underestimated.To examine the robustness of our estimates, we created different entry and exit dates. The SIRs and profile of cancers with significantly increased or decreased SIRs were generally similar with entry dates created using the HIV- or AIDS-diagnosis date minus 30 days or the HIV- or AIDS-diagnosis date itself.Two other exit dates were created by using the CDSC last known alive date instead of the TCR and CDSC dates of death, and by omitting the steps involving the dates of death and only using the cancer diagnosis date and the person's 60th birthday. Observed cancers were the same for each exit date because the penultimate step was always to replace the current date with the cancer diagnosis date if present, but total person-years at risk and, therefore, expected cancers and SIRs varied. Expected cancers were generally highest and SIRs were generally lowest when exit dates were based only on cancer diagnosis dates and 60th birthdays. For HIV-infected men, expected cancers were not consistently lower for exit dates based on last known alive dates or dates of death. For HIV-infected women, expected cancers were generally lowest and SIRs were generally highest for exit dates based on last known alive dates. For men and women with AIDS, expected cancers were generally lowest and SIRs were generally highest for exit dates based on dates of death rather than last known alive dates. This was because a smaller proportion of people with AIDS than all HIV-infected people had a last known alive date. Although it seemed reasonable to use exit dates based on dates of death for this study, it may be more accurate to combine last known alive dates and dates of death in a single exit date in future analyses.Comparing our results with results from other studies is complicated by different methods and time periods used. Results from other studies were also usually presented for men and women combined. The introduction of highly active antiretroviral therapy in 1996 may also have altered the risk of some cancers. It has been suggested that people may cease to be at risk of KS once immune function has been improved by therapy . ConversStudies have been largely consistent for people with AIDS. We observed an increased risk of lung cancer, Hodgkin's disease and all non-AIDS-defining cancers in people with AIDS in southeast England compared with the general population. This was consistent with studies linking cancer registry data with data from people who were diagnosed with AIDS in the USA from 1978 to 1996 (Results for non-AIDS-defining cancers for HIV-infected people were not as consistent. Even so, we found an increased risk of liver cancer, lung cancer and all non-AIDS-defining cancers in HIV-infected people, which was consistent with a Scottish study linking cancer registry data with data from people with HIV-infection and/or AIDS from 1981 to 1996 (The increased risk of other skin cancer in HIV-infected people was higher in this study than other studies (We also assessed the risk of cancer in HIV-infected people who had not had an AIDS diagnosis reported. The excess of KS and NHL in these men and women is an artefact. If the matches were correct, the people involved should have been reported with AIDS and not included in this part of the analysis, although any other cancers in these people were excluded when we excluded second and third tumours. Most of the increased risk in HIV-infected people in this study was related to AIDS, which suggests that, so far, most cancers in HIV-infected people have been associated with AIDS-related immunosuppression. The risk only remained increased for anal cancer, liver cancer, other skin cancer, Hodgkin's disease, and other lymphoid haematopoietic cancer, and the risk of all non-AIDS-defining cancers was only just increased in HIV-infected men without AIDS. The increased risk of liver cancer may have been due to the comparison of cohorts of people with a high and low prevalence of hepatitis B infection. Chronic infection with hepatitis B causes liver cancer. Prevalence is much higher in Africa than Western Europe , and oveOther groups assessed the risk of cancer before AIDS by linking data from cancer registries and AIDS registers and examining periods from 5 years to 6 months before AIDS (This study has established the feasibility of assessing the risk of cancer in HIV-infected adults using data from the CDSC and a UK regional cancer registry. Factors that could have affected the estimates of observed and expected cancers have been identified and should be further explored in any future analyses. Future analyses could also involve stratification of the cohort by subgroups based on route of acquisition, ethnicity or country of birth as well as examine different periods to explore possible effects on cancer risk of highly active anti-retroviral therapy. This will also facilitate comparison with the results of studies from other time periods.


The 59 sessions included 12 plenary addresses by leaders from every area of HIV research. The conference was particularly rich in research that may affect the path of the epidemic in low- and middle-income countries, although policy- and practice-shaping developments from high-income countries were also present.Attracting more than 5800 participants from 123 countries, the 5http://www.iasociety.org as well as on the JIAS website at http://www.jiasociety.org/.Consistent with the focus of the pathogenesis conference series, this report aims not only to highlight particularly important original research and other developments from IAS 2009, but also to analyze their potential impact on policy and practice in the coming years for those working in HIV and related fields. The report includes abstract numbers of cited presentations linked to online files of slides, posters or abstracts, as available. A full abstract search of IAS 2009 and prior IAS conferences is available on the IAS website at New data presented at IAS 2009 is already having an impact on HIV policy and practice on a global scale.■ Results of several basic research studies provided the field with a better understanding of the elevated HIV infection risk among African women compared with women from the USA due to chronically activated T cells and higher levels of cytokines favouring HIV transmission in genital tract mucosa (likely a result of increased exposure to pathogens), how complex genetic variables may affect HIV acquisition and disease progression, and how early antiretroviral therapy (ART) can substantially reduce the size of latent HIV reservoirs, a significant clinical issue in chronic HIV infection.■ Data from a study demonstrating that pre-ART inflammation and coagulation markers predict death and related findings showing that HIV replication induces activation of tissue factor pathways, thrombosis and fibrinolysis  underscored the growing recognition of how HIV permits chronic inflammation as a paradigm shift in our understanding of HIV disease progression.■ Findings demonstrating that maternal triple-drug ART used throughout pregnancy and breastfeeding reduced vertical transmission to 1%  are expected to inform revised World Health Organization (WHO) and South African national guidelines on antiretroviral prophylaxis.■ Research delineating the impact of antiretroviral therapy on reducing coincident tuberculosis and malaria epidemics in HIV-prevalent regions argued for wider and earlier access to treatment. By the end of the conference, South African health authorities indicated they would consider providing ART to everyone co-infected with TB and HIV.■ In the biomedical prevention field, new work helped define the impact of pregnancy on HIV transmission in serodiscordant couples and the apparent lack of a direct effect of male circumcision on HIV acquisition in female partners.■ An updated presentation of a WHO modelling study, which suggests that universal voluntary testing and immediate ART could turn the tide of the epidemic, was bolstered by additional data from recent studies demonstrating the potential preventive impact of ART at a population level. The significant challenges of operationalizing such a strategy remain to be elaborated.3 was more cost effective than deferred ART intervention added to the growing scientific consensus that normative guidance should advise earlier ART initiation, particularly given the recently suspended Comprehensive International Program of Research on AIDS (CIPRA) HT 001 trial in Haiti, which found substantially higher rates of mortality and morbidity in the deferred versus early ART intervention arms.■ A study indicating that early ART intervention for everyone with a CD4+ count of less than 350 cells/mm■ Operations research presented at the conference provided important new insights into how integrating HIV with other health services and using a variety of service delivery approaches (including deploying trained community or lay workers) can exponentially expand health system capacity without compromising standards of care or treatment outcomes.■ Results from the five-year Development of Anti-Retroviral Therapy in Africa (DART) trial comparing laboratory CD4+ and viral load monitoring with clinical monitoring found minimal differences in virologic outcomes, but substantially higher costs associated with laboratory monitoring. These and other data from IAS 2009 suggest that CD4+ count monitoring is cost effective as a targeted, rather than routine, strategy.■ A provocative overview of AIDS financing suggested that much more could be done to get “less AIDS for the money” by ensuring that interventions are evaluated more consistently for efficacy and cost effectiveness, and strategically targeted for maximum benefit given the widely varying epidemics in different regions.The International AIDS Society (IAS) recruited writers with content expertise in the four conference tracks to draft a post-conference report. Throughout the conference and in the closing session, four teams of rapporteurs summarized all oral and many poster presentations, and discussed their relevance in the context of research and the provision of care, treatment and provision. This report is based on a review of all individual and summary rapporteur reports back, additional conference sessions and satellites worthy of note. It also draws upon important findings from additional studies in recently published scientific literature and, where relevant, media reports.th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention was released in October 2009 and is available online at http://www.iasociety.org. That report was revised to meet the author specifications for publication as a supplement of the Journal of the International AIDS Society, and peer reviewed prior to publication.Each writer then submitted reports on specific tracks which were reviewed, edited and combined into a draft report. The Impact Report: Summary of Key Research and Implications for Policy and Practice – 5As the first IAS conference to return to sub-Saharan Africa since the watershed XIII International AIDS Conference (AIDS 2000) in Durban, IAS 2009 served to highlight both the enormous progress in HIV treatment, prevention and care over the past decade, and the ongoing challenges of delivering HIV interventions in a resource-limited region that remains the epicentre of the global epidemic. This is the last conference of the pathogenesis series before the 2010 deadline for universal access, set by the G8 and subsequently by the international community at the World Summit in 2005.The research, discussions and debate at IAS 2009 demonstrated both the necessity of establishing that ambitious goal, and the growing concern that despite the extraordinary progress in sub-Saharan Africa and most other regions on country-level targets for 2010, it is unlikely that many countries will meet their 2010 goal of universal access to a package of care, treatment and support. This is due to a mix of shifting political priorities, inadequate resources, the refusal of some countries to implement evidence-based interventions, the recent global economic crisis, and the enormous challenges in delivering these interventions, based on fundamental human rights principles, in health care systems that are chronically under resourced.The focus in this supplement is on profiling the presentations, discussions and debates that are likely to have the most significant impact on the epidemic in advancing an evidence-based response to HIV/AIDS.Journal of the International AIDS Society supplement is to advance the response to AIDS by profiling important new research and emerging discussions and translating them into the evidence-based policies and programmes required to achieve universal access to HIV prevention, treatment, care and support.The purpose of the IAS 2009 Impact Report and this http://www.jiasociety.org/) or the IAS Abstract Database (http://www.iasociety.org).In any conference as large and diverse as IAS 2009, new findings and worthy research are presented on a wide range of topics. To ensure a manageable length for the report , we have limited the number of studies referenced in this report to those that demonstrated the most substantive potential impact on future research, policy development (including normative guidance) and related clinical and health care delivery interventions. A complete source of all conference abstracts is available online at either the JIAS Abstract Database (This supplement is divided into an Introduction and four subsequent sections (one covering each of the four conference tracks), each of which includes an analysis of the implications and potential impact of the major developments reported at IAS 2009 in the areas of research, programme development, policy and advocacy. The four subsequent sections are:2. Basic sciences: An analysis of new evidence presented in Track A, as well as in related sessions, activities and affiliated events.3. Clinical sciences: An analysis of new evidence presented in Track B, as well as in related sessions, activities and affiliated events.4. Biomedical prevention: An analysis of new evidence presented in Track C, as well as in related sessions, activities and affiliated events.5. Operations research: An analysis of new evidence presented in this inaugural track (Track D) of the pathogenesis conference, including related sessions, activities and affiliated events. A clear and widely accepted definition of operations research continues to evolve, but encompasses a wide range of disciplines using research  to inform the evaluation and delivery of HIV prevention, care and treatment interventions.One of the most important takeaway messages from the conference is the wealth of new data that is expected to inform upcoming WHO and national clinical guidance on ART treatment for adults, adolescents and paediatrics, and the significant impact this will have, not only on people living with HIV, but also for people at risk for or living with tuberculosis or malaria; these three diseases continue to be the world’s three largest causes of mortality.Research on the impact of ART on pregnancy outcomes is also likely to inform guidance for HIV-positive pregnant and lactating women. For example, WHO released update guidance in November 2009, recommending prolonged use of antiretrovirals (ARVs) to reduce the risk of mother to child transmission of HIV and, for the first time, that HIV-positive mothers or their infants take ARVs while breastfeeding to prevent HIV transmission. Also, data from IAS 2009 expanded our understanding of circumcision and its limits. A number of important studies in Track D will inform discussions of the (expanded) role of laboratory services, including the key role that simple, point-of-care tests could play in diagnosing and treating HIV early in disease progression, and also on the need to more frequently evaluate all HIV programmes and service delivery modalities for their effectiveness and to ensure that programmes are context specific, evidence based and designed to maximize their impact on local treatment, care and epidemiology.IAS 2009 will bring renewed evidence of the impact of HIV policies and programmes to political leaders in the lead up to the 2010 G8 Summit in Canada, AIDS 2010 in Vienna and the 2010 United Nations General Assembly Special Session (UNGASS) on HIV/AIDS in New York. It also brings with this evidence the caution that the success to date is fragile and underfunded, dependent on countries meeting their international and national commitments with the best available scientific evidence, and dependent on ensuring that the response to AIDS remains a global priority beyond 2010.The JIAS hopes that this supplement will be a useful resource for HIV professionals working in every sector of the response to AIDS, and that it will become a powerful evidence-based advocacy tool used to strengthen and expand the response to HIV/AIDS worldwide.Journal of the International AIDS Society.Rodney Kort is an independent consultant contracted by the International AIDS Society for the purpose of preparing the IAS 2009 Impact Report  and adapting the entire report for publication in the RK drafted this text and approved the manuscript for publication.


Little empirical research has examined how cultural factors influence psychosocial factors for heroin drug use. The objectives of the study were to investigate the levels of individualism and collectivism among young adolescents and how cultural differences were associated with the constructs of the Theory of Planned Behavior and other psychosocial factors for heroin drug use.A cross-sectional study was conducted among young adolescents in an HIV and heroin-stricken area in China. The Individualism-Collectivism Interpersonal Assessment Inventory (ICIAI) was used to measure cultural norms and values in the context of three social groups: family members, close friends, and classmates.A total of 220 boys and 241 girls were recruited and participated in an interview. Compared to boys, girls reported higher levels of the three specific-relationship ICIAIs, as well as higher levels of perceived behavioral control for heroin use, perceived peer control, and communication with parent about heroin use, but a lower level of favorable attitude towards heroin use. The levels of descriptive and subjective norms of heroin use were low in both girls and boys. Among boys, family ICIAI was positively associated with perceived behavioral control, and friend ICIAI was positively associated with perceived peer control and communication with parent. Among girls, family ICIAI was positively associated with perceived behavioral control and communication with parents about heroin use, but negatively with favorable attitudes to heroin use; friend ICIAI was positively associated with perceived peer control, and classmate ICIAI was negatively associated with favorable attitudes toward heroin use.This study documents that collectivistic aspects of Chinese culture may influence psychosocial factors for heroin use, although the patterns are varied by gender. Findings provide an empirical basis for the development of culturally competent intervention programs for heroin use intervention and prevention. Culture has been considered an ecological-level variable that may influence mental processes, human behaviors, and health . AlthougThe majority of the theoretical models of behavioral change have been developed and designed for assessing HIV-related risks among people in Western countries. One of the commonly-used models in HIV behavioral intervention is the theory of planned behavior (TPB) . The theIndividualism versus Collectivism (IC) is the most common dimension of culture operationalized at the individual level ,8. IndivMatsumoto and colleagues developed the Individualism-Collectivism Interpersonal Assessment Inventory (ICIAI) to measure IC at the individual level . ICIAI eThere are few studies examining whether the individualistic-oriented intervention theories are sensitive to the collectivistic-oriented culture and how cultural differences influence psychosocial factors for heroin use. We, thus, conducted a cross-sectional study among middle-school students in an HIV- and heroin-stricken area in China. The objectives of the study were to investigate the levels of individualism and collectivism among young adolescents and how cultural differences were associated with the constructs of the theory of planned behavior, communication with parents about heroin use, and perceived peer control for preventive practices. We expected that girls, compared to boys, had higher levels of collectivistic tendencies. This expectation was based on gender-preferences in China. Traditionally, males are socialized to be independent, self-reliant, and emotionally detached, whereas females are expected to be dependent, reliant and emotional . IllicitWe selected "H County" in Guangxi province as the study site. Guangxi is along a drug trafficking route, which originates from the "Golden Triangle", passes through northern provinces of Vietnam and Guangxi and finally into Hong Kong and the rest of the world . GuangxiSince the goal of the study was to investigate how individualism and collectivism influenced psychosocial factors for heroin use, we purposely selected middle schools located in the areas where prevalence of heroin injection use was high. There were 66 middle schools in H County. The following steps were taken to select schools: (1) ranked all rural towns based on the levels of heroin injection prevalence, using local surveillance data; (2) selected the top five towns in the ranking; (3) randomly selected one school from each town if there was more than one school; (4) randomly selected two schools out of five schools for qualitative studies and the remaining three schools for a cross-sectional study. Eligibility of participants included: (1) students in second and third grade  in the three selected middle schools, and (2) students who were able to obtain parental permission and to invite one of their parents or guardians to participate in the study.We first selected classes that had enough students in each of the three schools. If the number of students was not enough because students could not obtain their parental permission or could not invite one of their parents or guardians to participate in the study, students in other classes in the same grade were invited. All students who obtained parental permission and invited one of their parents or guardians participated in the study. The study protocol was approved by the Institutional Review Boards of Virginia Commonwealth University and Guangxi Medical University.Students used a self-administered questionnaire to answer questions in classrooms in each selected middle school. Only one student was permitted to sit at a desk to answer questions on the anonymous questionnaire . One or two trained interviewers presented in the classrooms and answered questions raised by students. All interviewers received training in interviewing techniques, developing rapport, ensuring confidentiality, and answering questions raised by subjects.Measurement items and scales were initially drafted in English and then translated into Chinese by three research members who were fluent in both languages. The Chinese version of measures was then distributed to research team members who reviewed and modified wording to make them appropriate for the Chinese context. Next, the self-administered questionnaire was piloted among students in a second-grade classroom in a middle school . After completion of the questionnaire, we asked students to make comments or suggestions, focusing on understanding and wording of the questions listed in the questionnaire. Some modifications were made based on the results of the pilot.Matsumoto's Individualism-Collectivism Interpersonal Assessment Inventory (ICIAI) was used to measure IC at the individual level . This inStudents were requested to rate how important each of the item as a value to them in a five5-point scale ranging from 1 'not important at all' to 5 'very important'. The score of each of the three relationship-specific ICIAI value scales  were created by averaging the items within each relationship group. Higher scores reflected more collectivism.Measurement scales of the following psychosocial constructs were adopted from reports by Rice et. al. , Orbel SFavorable attitude towards heroin use was measured by a seven-item scale . Response options for these items ranged from 0 (strongly disagree) to 3 (strongly agree). Perceived behavioral control was measured by a ten-item scale . Response choice to each item was from 0 (strongly disagree) to 3 (strongly agree). Descriptive norms refer to students' perceptions of other people's behaviors (heroin use) . Two thirds of the students were in the second grade and 37% in the third grade in the selected middle schools. Most of subjects were members of the Han majority  documented that the within-subject differences in the three relationship-specific ICIAIs were statistically significant among boys  and girls . Both boys and girls exhibited the highest values in the family ICIAI, high values in the friend ICIAI, and lower values in the classmate ICIAI , while girls are expected to be conforming and obedient to parents before marriage, to their husband after marriage, and to their son after the death of their husband. These parental expectations prevail to a greater degree in rural areas as more traditional and conservative cultural patterns are more common there compared to urban areas.As reflected by the different degree of the three relationship-specific ICIAIs, both boys and girls exhibited the highest values toward family members, and reported more collectivistic attitudes regarding close friends compared with classmates. This finding supports Matsumoto and colleagues' argument that if a culture fosters collectivistic tendencies within relationships between the self and in-groups , it is unlikely that those same tendencies would occur to the same degree in relationships with members of out-groups  . ChineseFindings of this study document that the relationship-specific ICIAIs were associated with several constructs of the theory of planned behavior, with variations by gender. Boys and girls who retained stronger collectivistic tendencies towards family members were more likely to perceive abilities to perform positive activities against heroin use. The perception may result from characteristics of collectivistic culture, i.e. collectivistic individuals preserve family values and believe that it is their responsibility, as a family member, to save the family's face and maintain the family's dignity. Avoidance of damage to their family values may motivate and enhance their ability to avoid heroin use. Perceived behavioral control is considered a key construct in the theory of planned behavior and acts as a moderator of the relationships of attitudes and norms with intention . InteresAs expected, perceived peer control for performance of acceptable practices and behaviors was positively associated with friend ICIAI among girls and boys. Triandis  has suggThere are limitations that should be noted in the study. Because the study participants were recruited from HIV and heroin-stricken rural areas in one county, the sample was not representative of all rural areas in China. Future large scale studies need to be done to verify findings from this study. Another limitation is that we could not examine relationships between the three determinants of the intention to use heroin because very few students (1%) reported such intention although heroin use is a serious problem in that area. The low level of intention may be due to the fact, according to available research, that most of Chinese heroin users started using it between the age of 16-24 years old often when they dropped out of middle schools .Taking the findings together, this study suggests how Chinese culture can be integrated with concepts from the theory of planned behavior and other risk and protective factors for drug use that have been developed in western countries. The findings indicate that interventions aimed at preventing heroin-use initiation among adolescents should target both adolescents and their parents. As values towards close friends also play an important role in the theory of planned behavior, interventions that include close peers such as the popular opinion leader intervention approach may be useful ,29. The IC: Individualism versus Collectivism; ICIAI: Individualism-Collectivism Interpersonal Assessment Inventory; IDU: injection drug use; PBC: perceived behavioral control; SD: standard deviation; TPB: the theory of planned behavior.Funding for this study was awarded to Hongjie Liu by NIH-NIDA Grant R03DA019397. The NIDA had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. All authors declare that they have no conflicts of interest.HL, ZL and WL designed the study and wrote the protocol. JL and ZZ managed the literature searches and summaries of previous related work. Authors HL and JL undertook the statistical analysis and wrote the manuscript. All authors contributed to and have approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/563/prepub


This indicates that BLM may increase the accessibility of the sensor proteins that recognize the lesion. Over the years evidence has accumulated that BLM is one of the earliest proteins that accumulates at the site of the lesion. Finally BLM also acts like a "molecular node" by integrating the upstream signals and acting as a bridge between the transducer and effector proteins (which again includes BLM itself), which in turn repair the DNA damage. Hence BLM seems to be a protein involved in multiple functions - all of which may together contribute to its reported role as a "caretaker tumor suppressor". In this review the recent literature documenting the upstream BLM functions has been elucidated and future directions indicated.Bloom Syndrome (BS) is an autosomal recessive disorder due to mutation in Bloom helicase (referred in literature either as BLM helicase or BLM). Patients with BS are predisposed to almost all forms of cancer. BS patients are even today diagnosed in the clinics by hyper-recombination phenotype that is manifested by high rates of Sister Chromatid Exchange. The function of BLM as a helicase and its role during the regulation of homologous recombination (HR) is well characterized. However in the last few years the role of BLM as a DNA damage sensor has been revealed. For example, it has been demonstrated that BLM can stimulate the ATPase and chromatin remodeling activities of RAD54  ATM-Rad3-related) [in vivo by exposure of cells to ionizing radiation (IR) or drugs like neocarzinostatin or bleomycin. Both stalled replication forks and DSBs lead to the generation of nuclear chromatinized foci called stalled replication foci and ionizing radiation-induced foci (IRIF), respectively. Replication arrest can also lead to the generation of DSBs [Signal transduction during DNA damage response is mediated by two proximal sensory kinases, ATM (ataxia telangiectasia-mutated) and ATR (related) ,2. ATM a of DSBs , thereby of DSBs .The protein that was initially demonstrated to accumulate at the site of IRIF was the phosphorylated form of histone variant H2AX (γH2AX)  Figure . HoweverOne such FHA-BRCT domain containing protein that accumulates at the sites of DNA damage is the mediator of DNA damage checkpoint 1 (MDC1) Figure . RecruitNBS1 , a key member of the MRN complex, accumulates at the IRIF due to its own phospho-peptide binding FHA-BRCT domain  Figure . MDC1 stThe localization of conjugated ubiquitin at the sites of DNA damage had been demonstrated quite sometime back ,20. SubsInterestingly around this time it was reported that the E3 ligase, Ring finger protein 8 (RNF8) assembles at the site of DSBs via the interaction of its FHA domain with the conserved Thr-Gln-any amino acid-Phe (TQXF) motif in MDC1. Phosphorylation of the MDC1 TQXF motifs by ATM and ATR is required for the interaction with RNF8 -28 Figu. Once reradiosensitivity, immunodeficiency, dysmorphic features and learning difficulties) was defective in the recruitment of 53BP1 and BRCA1 to the DSBs [motifs that interact with ubiquitin (MIU), is recruited to the to sites of DNA damage by binding to ubiquitinated H2A. The assembly of RNF168 at DSBs occurs in RNF8-dependent manner and leads to the amplification of RNF8-dependent substrate ubiquitylation  is an autosomal recessive disorder that is associated with predisposition to cancer . BS is cBLM give rise to BS. Though BS patients are rare, BLM heterozygotes that carry a BLM mutation may be faced with a higher probability of developing colorectal cancer [Ash mutation (a six nucleotide deletion and a seven nucleotide insertion at position 2281 of the cDNA) [BLM allele are cancer prone [The mean age of cancer diagnosis in BLM patients is 24 years and death is generally associated before the age of 30 ,37. Germl cancer . The exahe cDNA) . Transgeer prone . Based oThough the functions of BLM in the resolution of DNA damage are well characterized, the role of this helicase in the DNA damage response is yet to be fully deciphered. The response of BLM to DNA damage signal is a direct consequence of the changes in the intranuclear localization of the helicase. In asynchronous cells BLM is found to be in promyelocytic leukemia nuclear bodies (PML NBs) and nucleolus ,42. Expoin vitro [in vivo [in vitro [in vivo. Using Fluorescence Recovery After Photobleaching (FRAP) the residence time of BLM in the HU-induced foci is only 7.2 seconds, providing evidence about the transitory nature of BLM during the sensing and recognition of DNA damage.Multiple lines of evidence exist indicating that BLM may function very early in response to DNA damage Figure . BLM is in vitro -57 and i[in vivo . BLM stiin vitro , and is However it has been reported that BLM also accumulates at the site of stalled replication around 1 hour post-HU-treatment ,61. ThisHence BLM seems to have roles in multiple phases of the DNA damage response pathway. In the immediate early phase BLM acts independently in the pathway, not even requiring other known early sensors of DNA damage like γH2AX, MDC1 and 53BP1. In the intermediate phase BLM acts as a molecular node, physically and functionally interacting with multiple proteins already associated at the site of damage and acting either in hierarchical or combinatorial manner so that the downstream repair proteins can receive and process the DNA damage signal. It is in this last step, the repair phase Figure , BLM actin vitro biochemical role during HR had become the focus of intense research. Maybe due to the above reason and also possibly due to the non-availability of the desired tools and reagents, initial studies deciphering the in vivo cellular functions of BLM had been much fewer and less well characterized. However in the last half decade using a range of immortalized genetically engineered cell lines, specific antibodies that recognize endogenous BLM or its phosphorylated forms and with the widespread availability of robust microscopic techniques, the focus has shifted to towards deciphering how the helicase functions in a cellular context. This review had aimed to summarize all the important findings in this emerging field.BLM helicase has attracted much attention due to the hyper-recombinogenic phenotype of BS patients and their predisposition to almost all forms of cancers known to human. Since BLM was first discovered to be a helicase , its in Perhaps the most important message that emerges is that BLM helicase has a fascinating "double life" apart from its well-characterized role as a helicase functioning during HR. Hence the functions of BLM are not confined to its role during HR but much earlier when the cells are exposed to the deleterious lesions. Hence BLM acts as a sensor, transmitter and finally the effector at different steps during the entire DNA damage signaling cascade - effectively acting as the "caretaker tumor suppressor" . The facIt is perhaps important to point out the similarity of the proposed multiple functions of BLM with those of NBS1 and 53BP1. One of the first functions assigned to MRE11-RAD50-NBS1 (MRN) complex was a role in the repair of DNA double strand breaks . Initialin vivo substrate) but also with its stage specific protein partners, a few known but perhaps many unknown. The information available till date already indicates that the time has come for BLM helicase to bloom and show its true potential to the researchers.Finally the question arises - what are the future directions of research on BLM especially in relation to its role as a damage sensor. It remains to be firmly established whether BLM can actually act as the universal damage sensor and transmitter as most of the studies until now have been done on cells containing either stalled forks or DSBs. The study of BLM post-translational modifications (PTMs) individually and in combination, and how the PTMs affect BLM functions during signal recognition and transmission is bound to be of much interest to researchers. But perhaps in the genomics era, the time has come not to look at BLM functions in isolation. With the help of high throughput technologies it is imperative that BLM functions are analyzed on a "global" scale perhaps in conjunctions with the dynamicity of its interaction with its chromatin , France, he examined the functional interaction between the tumor suppressor p53 and the glucocorticoid receptor. Subsequently, in the Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, USA, SS studied the inter-regulatory roles of p53 and RecQ helicases. His ongoing research interests involve the study of the interactions between the members of the eukaryotic signal-transduction cascade and the DNA-repair and -recombination machinery. He joined the National Institute of Immunology, India, as a group leader in September 2004.