Synthetic Lethal (SL) genetic interactions play a key role in various types of biological research, ranging from understanding genotype-phenotype relationships to identifying drug-targets against cancer. Despite recent advances in empirical measuring SL interactions in human cells, the human genetic interaction map is far from complete. Here, we present a novel approach to predict this map by exploiting patterns in cancer genome evolution. First, we show that empirically determined SL interactions are reflected in various gene presence, absence, and duplication patterns in hundreds of cancer genomes. The most evident pattern that we discovered is that when one member of an SL interaction gene pair is lost, the other gene tends not to be lost, i.e. the absence of co-loss. This observation is in line with expectation, because the loss of an SL interacting pair will be lethal to the cancer cell. SL interactions are also reflected in gene expression profiles, such as an under representation of cases where the genes in an SL pair are both under expressed, and an over representation of cases where one gene of an SL pair is under expressed, while the other one is over expressed. We integrated the various previously unknown cancer genome patterns and the gene expression patterns into a computational model to identify SL pairs. This simple, genome-wide model achieves a high prediction power (AUC = 0.75) for known genetic interactions. It allows us to present for the first time a comprehensive genome-wide list of SL interactions with a high estimated prediction precision, covering up to 591,000 gene pairs. This unique list can potentially be used in various application areas ranging from biotechnology to medical genetics. A synthetic lethal (SL) genetic interaction is defined as a functional relationship between two genes where the loss of either gene is viable but the loss of both is lethal . A comprSaccharomyces cerevisiae and Caenorhabditis elegans[S.cerevisiae and Schizosaccharomyces pombe[Previous computational approaches have mostly been developed to predict SL interactions in model microorganisms, such as s elegans–18. Howeces pombe and the ces pombe to identces pombe. This raBy exploiting the availability of gene expression data for a large number of cancer samples and receWe retrieved the experimentally measured SL pairs and non-SL pairs from two studies, 24. We The CNV data is directly retrieved from the cBioPortal for Cancer Genomics. The CNVhttp://gdac.broadinstitute.org/runs/stddata__2014_03_16/data. For each cancer study, we first downloaded the files named as ‘_RSEM_genes_normalized_data.Level_3’, which contains the estimated expression levels for each gene in human genome from RNAseq data by using the RSEM package[The RNAseq data are obtained from the Broad Institute’s Genome Data Analysis Center (GDAC) Firehose. The linM package. In totaM package, 29 in R1 = nhomCL/nt, where nhomCL is the number of patients with the homozygous co-loss of A-B and nt is the total number of patients where A-B have a status as ,  or . We calculated the f1 of a gene pair without including samples that have homozygous deletions of more than 2000 genes , the co-loss event can be i) homCL: homozygous co-loss , ii) hetCL: heterozygous co-loss  or iii) mixCL: mixed co-loss . For each co-loss event, we defined a fraction that quantifies the likelihood of the co-loss event. For instance, for the homozygous co-loss event, we defined the fraction for a gene pair A-B as fondingly . It shouondingly .4 and f5  are under-expressed. f5 is used to quantify how likely gene pair A-B has the expression up-down events, i.e., A is over expressed and B is under expressed or vice versa.The variations in gene expression can be: -1 = under-expression, 0 = normal, and 1 = over-expression. Here, we defined two fractions, f4 and f5 . f4 quan1, f2, f3 and f4, we expected that SL pairs have smaller values for these fractions than non-SL pairs. However, for f5 we expected that SL pairs have larger values than non-SL pairs. To test these hypotheses, we compared the fractions in SL pairs with the fractions in non-SL pairs via one-sided Wilcoxon rank tests in R. We carried out four comparisons of homozygous deletion, heterozygous deletion, mixed deletion and co-underexpression to estimate the difference of co-loss tendency between SL and non-SL pairs. In the analysis of up-down compensation, we carried out two comparisons of expression up-down or genomic up-down. Bonferroni correction was used to correct for 4 multiple comparisons in the analysis of co-loss tendency and 2 multiple comparisons in the analysis of up-down compensation .Here, each defined fraction is a signal where SL pairs show difference from non-SL pairs. For f1, f2, f3 or f4 but a larger mean of f5 than SL pairs. To test the hypotheses, we counted the randomizations (n1) where the difference of mean between the random pairs and SL pairs is contradictory to the expectation. For each comparison, we conducted 1000 randomizations and calculated the P-value for each hypothesis test as P = (n1+1)/1001.To validate the robustness of the signals, we compared the fractions in SL pairs to the fractions in random pairs. In each randomization, we first generated 300 random pairs from all human genes for which gene expression and CNV were available and then compared the mean of the fractions in the random pairs with the mean in SL pairs. We expected that the random pairs have a smaller mean of fThe training set is significantly skewed with only 4.6% of the pairs belonging to the positive class (SL pairs) and the rest belonging to the negative class (non-SL pairs). Such a skewed training set can affect the performance of most standard classification algorithms. Thus, wpi(x) is the probability that x is predicted to be SL by classifier i. The probabilities pi(x) from all classifiers, except for RandomForest, are obtained from the ‘RWeka’ package[We adopted an ensemble-based model to integrate the aforementioned 5 signals for predicting whether a gene pair has an SL interaction or not. The balanced training set (described above) was used to train the ensemble-based prediction model that combines multiple classifiers, namely AdaBoost, J48, LogitBoost, RandomForest, Logit, JRip and PART. The combination rule is simply based on the mean function, ’ package. The Ran’ package.To quantify the performance of the ensemble-based model, we used a 10-fold cross-validation framework on all empirically measured 270 SL pairs and 5660 non-SL pairs. In each cross-validation, the ensemble-based model is trained on nine of the randomly constructed 10 fractions and predictions are made for the test samples in the remaining fraction. The performance of the model in each cross-validation is evaluated by a ROC curve, the corresponding AUC score and a precision-recall curve. Repeating this procedure 10 times, a mean ROC curve, a mean AUC score and a mean precision-recall curve are calculated as the evaluation for the performance of the ensemble-based prediction model.p(x)) threshold of 0.81, which achieved a precision of 67% at a recall of 10%.To predict SL interactions in human at a genome-wide scale, we first selected 15620 genes that are measured for both CNV and mRNA variations in cancer cells. As mentioned in the results section, due to the presence of arm-level copy number variations, gene pairs on the same chromosome are more likely to be co-lost regardless of the status of SL interaction. Thus, we applied our model to ~115 million genes pairs that are located on different chromosomes. To construct a highly accurate SL interaction map, we predicted a list of more than 591,000 SL interactions based on a probability score , i.e., i1/n2, where n1 is the number of tumor samples with a co-loss of both genes and n2 is the number of tumor samples in which at least one gene is lost . Secondly, given the limited genome coverage of the known SL and non-SL pairs available for our analysis, we also compared the likelihood of co-loss events of SL pairs with random pairs from the human genome. We found a significant difference in co-loss between SL pairs and random pairs , but this is not significant when we compared the SL pairs to random gene pairs.Previous studies , 35 haveIn total, we found five patterns in the CNVs and gene expression variations in cancer cells, all of which showed that synthetic lethal interactions are reflected in cancer genome evolution. These five patterns fall into two categories: i) genes in SL pairs are more likely to be over-expressed when their interaction partner is under-expressed and ii) genes in SL pairs are less likely to be co-lost either at the DNA level or at the gene expression level.We next asked whether these five genomic patterns are strong enough to reliably predict SL pairs in human on a genome-wide scale. To do that we developed an ensemble-based model that integrates the five patterns. It should be noted that we did not include the genomic up-down pattern found in CNVs since SL pairs are not significantly different from random pairs. An ensemble-based model is a classifier that combines the prediction results from multiple classifiers, such as decision trees and logistic regression. It is known that such an ensemble-based model can improve performance relative to a single classification procedure, especiaWe used the empirically measured 270 SL pairs and 5660 non-SL pairs as described in the previous analysis. To construct the prediction model, we first needed to handle the imbalance of sample size between the negative class, i.e. non-SL pairs, and the positive class, i.e. SL pairs. The skewed distribution of the classes can affect the performance of prediction models . To solvTo assess the performance of the ensemble-based prediction model, we used a 10-fold cross-validation on all the empirically measured 270 SL pairs and 5660 non-SL pairs. The plot of sensitivity  versus false positive rate of the ensemble-based model shows that our model achieves an area under ROC curve (AUC) of 0.75 [In this study we present a novel computational model that identifies SL interactions from cancer genomic data on a genome-wide scale. To develop such a model, we first systematically explored how SL interactions are reflected in cancer genomes and their gene expression levels. We found that compared with non-SL pairs, genes in SL pairs are significantly less likely to be co-lost in a cancer genome, both at the level of gene expression and at the level of copy number variation. Moreover, SL pairs are more likely to have an expression up-down pattern where one gene is over-expressed while the other one is under-expressed, which is consistent with another recent study. Based o elegans –18, or p elegans . A strat elegans . As SLs of 0.779). In contFuture work should focus on the following issues to improve the performance of the model. First, given the genomic and microenvironment heterogeneity among different types of tumors, 47, theTaken together, we systematically investigated and showed that SL interactions are reflected in genome evolution of cancer in various forms. Based on the unique patterns discovered in cancer genomics, we proposed a simple approach to identify SL, which strongly improves existing frameworks. We generated a unique SL interaction network in human at the genome-scale covering up to 591,000 pairs with a high estimated precision. In the light of medical genetics, this list is highly valuable in the search for anti-cancer drug targets and in understanding human diseases.S1 Dataset(TXT)Click here for additional data file.S1 File(DOCX)Click here for additional data file.S1 Table(XLSX)Click here for additional data file.S2 Table(XLSX)Click here for additional data file.


The paper investigates the determinants and the impact of HIV/AIDS on households in Adamawa State. 120 respondents affected with HIV/AIDS were selected for interview using simple random sampling techniques. Both primary and secondary data were used in its analysis to determine the impact of the disease on household’s income. The data collected were analyzed using descriptive analytical techniques and a logistic regression model was employed to estimate the likelihood that a household witnessed a fall in income as a result of the disease. The paper revealed that HIV/AIDS had an adverse impact on household’s productivity, income, saving and capital formation. The paper, therefore recommends an intensive Aids education programme and Government at all level as well as NGO’s should endeavor to provide adequate HIV testing kits, medication and free counseling services to enable the households determine their HIV status. The health status of the people in any country is a critical element in its economic growth as well as an important factor in the overall quality of household’s life and productivity. AIDS tend to selectively affect women, youths, which are the vulnerable groups; it influences a wide range of social and economic factors. In Adamawa State, agriculture is the dominant industry in the state, thus any serious infection of HIV could lead to low productivity of the industry. Recent studies have revealed that HIV/AIDS prevalence among women and youths is increasingly worrisome. The target is the most productive group of the population (15-49 groups). This is the age bracket involved in social and economic sectors as well as the civil service and education. Thus these sectors could suffer severely from labor supply, loss of time due to illness, funeral bills, orphans, street children, medical expenditure and other vices. The consequences could be disastrous if nothing is done to control the spreads.National prevalence has been steadily increasing from 1.8 percent in 1990 to 5.5 percent in 1999. The difference between HIV seroprevalence in urban and rural areas is not large, indicating that the AIDS problem in Nigeria is not strictly an urban one. This trend dictates labour participation rates both in the rural Nigeria; where the labour force is engaged in agricultural production, and in Urban Nigeria where most Nigerians migrate, find information to travel abroad for so called better life.Factors that determine the labour force participation are the size of the family, level of education, job opportunities and migration amongst others. These are the main demographic dynamics in Nigeria over the years. Demographic indicators show that the dynamics in the population are skewed towards low productivity and increased social problems – high population movements to cities (Urban), high HIV/AIDS infections, and porous borders of the study area (Adamawa State) with Cameroun and Niger resulting to increased congestions and the rate infections.Labour is total human efforts used in the productive process. It can also be defined as the strength expanded on the creation of goods and services. It includes number of hours worked and the physical strength. Labour can be services that have value and exchange. Economics is therefore concerned with efficiency – best use of productive resources and value. This is why policies for enhancing the labour force productivity is vital in achieving growth goals of the Nigerian economy, for instance the Vision 2020, which depended on the quality of the labour force, that will propel this economy to the desired growth by the year 2020.The main objective of this paper is to examine the effects of HIV/AIDS scourge on labour force productivity of Adamawa state households.The health status of the people in any country is a critical element in the growth of its economy as well as an important factor in the overall quality of life. AIDS tend to selectively affect women, youths, which are the vulnerable groups; it will influence a wide range of social and economic factors. In Adamawa State, agriculture is the dominant industry; high rate of infection could lead to the stagnation of the industry. Recent studies have revealed that HIV/AIDS prevalence among women and youths is increasingly worrisome. The target is the most productive group of the population (15-49 groups).Until the early 1990’s, the empirical economic growth literature focused exclusively on the role of capital and labour . Millions of children are orphaned by AIDS; and the number is growing. (b). Poverty is intensifying and deepening. (c). Productive capacity is being reduced in all sectors such that:-Food crises of 2003 in South Africa could be traced to HIV/AIDS infection.Depriving those economies scarce skills, and children of their parents. In addition, it is observed that HIV/AIDS could leave the Kenyan economy one-sixth smaller than it would be without a high prevalence by the year 2015. And in Southern Africa, by the year 2020, the level of GDP could be lowered by 17% due to HIV/AIDS while the level of per capita GDP could be lowered by 17%.An empirical study of this nature is therefore necessary in an attempt to determine the actual effect of HIV/AIDS on the household’s productivity, income and standard of living. The objectives of the paper are therefore to assess the impact of HIV/AIDS on household in Adamawa State.However, there is now significant evidence demonstrating the aggregate impact of health on growth and on level levels of real GDP per capita .Similar studies have been done in Asia by th century,  concluded that over half of the growth in full income up to 1950 was attributable to mortality decline.Moreover, studies that consider full income which assigns economic value to changes in life expectancy-suggest that falling mortality rates have a more substantial positive impact on economic development than is shown by GDP per capita data. For example, in a assessment of the growth of real income per capita on the United States over the 20Considering the effect of mortality rates on full income suggest that estimates of the impact of AIDS on economic performance are under stated.Health affects labour productivity. Healthier workers are more energetic, have better attendance records and are likely to have higher mental capacity and morale. In development countries in particular, manual work makes up a large production of output, and physical endurance and strength rely crucially on sound health. A major study by et al. 2000).Health improvements therefore spur the increase in savings which, by enabling greater investments in physical capital, spurs economic growth. East Asia’s dramatic savings boom between 1950 to 1990, which contributed greatly to its unprecedented economic growth  by Eammanuel and Naphthali Rebecca (2008) found that, “In spite of the persistent war against HIV/AIDS world all over, an amazing prevalence rate (14.2%) of the infection was still recorded in this part of the globe comprising of 1%, HIV-1, 0.51% HIV-2 and 1.6%, HIV-1+2 serotypes”. This shows the degree of devastation of the disease in the state and its consequent effects on productivity of the state, showing its impacts on the working population over time. This has been manifested in low agricultural productivity of the state compared to the productivity of the sector in the 1980s and early 1990s.Study Area: The study was conducted in Adamawa State. The state is located in the North Eastern region of Nigeria. The study area was chosen in the North-Eastern Geo-political zone and export to other parts of the country, Central Africa, Niger and Federal Republic of Cameroon. The state has a total human population of 3, 194, 781 . The state has a total land area of 38, 741. 12 square kilometers . Out of these, the lowland, the hills and mountain ranges and upland plains constitute 32. 58%, 26.56% and 40.58 respectively . The state has (21) local government areas. Geographically, Adamawa State lies between latitude 7° and 11° and longitudes 11° and 14° . It share boundary with Taraba State in the South and West, Gombe in the North West and Borno State to the North. The state has an international boundary with Cameroon Republic along its eastern state.The study was conducted between the periods of January 2010 to June 2010. The study covered six (6) local government areas out of 21 local government areas in the state. Two local governments were randomly selected from each of the three senatorial zones. And from each local government, four (4) villages were randomly selected, making a total of 24 villages sampled from the state. Five (5) respondents were also randomly picked from each village, making a total of one hundred and twenty (120) respondents to be randomly selected for the study. Data are obtained from both primary and secondary sources. While the former includes direct interviews with concerned individuals and families and the use of questionnaires, the latter encompasses hospitals and medical laboratories records from ten (10) major centres in the state. There are, however, series of HIV/AIDS related cases that were/are not recorded, for there is a very high tendency of several non-hospital HIV/AIDS issues, due to reasons peculiar to and inherent in rural communities.The paper adopts a descriptive analytical technique resulting in evaluating the impact of HIV/AIDS on the households in the state.A logistic regression model was employed to investigate the livelihood that household’s income level falls as a result of HIV/AIDS. The logistic regression model is as follows:P (Y=1) is the probability that a household’ income level falls as a result of the disease.Where X is vector of the determinants of the odds of income level. The regression equation was build up by including variables that were presumed to affect the household poverty status. Such as:(1)Sex of the household ,(2).Household size.(3).The sales of household assets which takes the value of 1 if the household sold the property and 0 if it did not.(4).Total amount of money spend on caring for AIDS patients; on funeral and on other mourning expenses.Majority of the HIV/AIDS patients interviewed were males (61.7%), while only 38.3% of the respondents were females as shown on It could be concluded that most of the HIV/AIDS patients in the study area are males. The study also shows that (58.3%) of the 120 respondents sampled were married, 10.5% were not married. And 14.2% and 16.7% of the respondents were divorcees and widows respectively.Most of the HIV/AIDS patients are married and within the ages of 30 – 39 years (51%). More so, most of the sampled respondents have 4 – 6 persons per household, 91% were with the disease from 1– 5 years and most of them (58.3%) did not attend formal education.On the average, unit price per man-hour in N150.00 and the value pulled man-hours for the respondents per months is N15, 062.05 and for those caring for them, the estimated value stood at N69, 462.5It can therefore be concluded that the man-hour and income lost to AIDS are tremendously. Hence, the income lost would have been saved or invested that in capable of improving the per capita income and standard of the hiring of the household in the state. The finding is in line with that of Mason (2004) who also confirmed that a lot of income has been lost away because of AIDS infectionThis finding also agrees with  who positioned that HIV/AIDS may result in absence from work, loss of income temporary and if the patient dies the temporary loss income becomes a permanent loss.The analysis in The result Also the result shows that female headed households are more likely to have fall in income due to AIDS infection since men may be have more access to productive resources such as land credits technology, job opportunities etc. than female headed. Another explanation is that widows may themselves be infected and lacking the physical strength to engage effectively in income generating activities and food production. The result also revealed that household sale of family assets to cope with HIV/AIDS tends to reduce income levels of households.Conclusively, from the analysis above, HIV/AIDS significantly reduces household income.HIV/AIDS scourge has serious adverse effects on the household productivity, savings and capital accumulation and investments in Adamawa State as confirmed by study. Findings of the study reveal that HIV/AIDS has made significant contributions in reducing household income especially for female headed households. Further, the results revealed that the scourge has been responsible for loss of income, increased household expenditure for medical, funeral related expenses and a greater fall of household savings and assets.An intensive HIV/AIDS education programme among the Nigeria populace is desirable and recommended. Government at all levels as well as NGO’s should provide adequate HIV/AIDS testing kits and free counseling services to enable every household to determine their status and consequently take necessary steps to prevent the spread and manage those already affected provision of affordable anti-retroviral drugs to the already affected households can go a long way in prolonging their lives as well as enhance their productivity.The government design and implement effective, appropriate policies and programmes for poverty alleviation, targeting HIV/AIDs victims.


The productivity of countries around the globe is adversely affected by the health-related problems of their labour force. This study examined the effect of the prevalence of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and life expectancy on the economic growth of 33 Sub-Saharan African (SSA) countries over a period of 11 years (2002–2012). The study employed a dynamic panel approach as opposed to the static traditional approach utilised in the literature. The dynamic approach became eminent because of the fact that HIV/AIDS is a dynamic variable as its prevalence today depends on the previous years. The result revealed that HIV/AIDS is negatively correlated with economic growth in the region, with a coefficient of 0.014, and significant at the 1% level. That is, a 10% increase in HIV/AIDS prevalence leads to a 0.14% decrease in the GDP of the region. Tackling HIV/AIDS is therefore imperative to the developing Sub-Saharan African region and all hands must be on deck to end the menace globally. The productivity of many countries around the globe is adversely affected by the health-related problems of their labour force; these include the prevalence of communicable diseases, such as HIV/AIDS. The United Nations (UN) Millennium Declaration in 2000 targeted 189 rich and poor countries (including African countries) to attain improvement in human development by the year 2015. This was followed by the formulation of the Millennium Development Goals (MDGSs), in which 8 targets were set: the eradication of extreme poverty and hunger, achieving universal primary education, promoting gender equality and empowering women, reducing child mortality rates, improving maternal health, combating HIV/AIDS, malaria, and other diseases, ensuring environmental sustainability, and developing a global partnership for development in these countries from 2005 to 2015.Whilst the countries in the West have attained the MDG goals, many countries in Africa, Asia, and Latin America are still lagging behind in achieving some of the stated goals. Objective one of the Millennium Development Goals is to eradicate extreme poverty and hunger by 2015. None of the African countries has achieved the set target; however, 10 countries are on track to achieve the target: Angola, Benin, Ghana, Liberia, Malawi, Mauritania, Mozambique, Rwanda, Swaziland, and Tanzania . The numOn average, the economic growth of Sub-Saharan Africa is low, and the factors responsible might be observed, while some are obviously unobserved. Some of the empirical literature that highlighted the effect of the prevalence of HIV/AIDS on growth concentrated more on single-country analysis. These studies include: Although numerous theories of economic growth exist in the economic literature, the macroeconomic approach to assessing the effect of health-related issues on economic growth mainly adopts the human capital approach. The stock of health of an individual remains a dominant strategy amongst many health–economic growth studies for measuring well-being, such as the work by t period. This relationship can best be explained in the equation below:This study adopts the renowned Solow’s growth model (1956), assuming a Cobb–Douglas production function with two important factor inputs, labour and capital, and their relationship with output. Labour augmenting technical progress is in the Letwhere Q is the total output produced in the given country; L is the total labour input used in the production process; K is the total capital input used in the production of Q; while A is the level of technology.Therefore, equation (i) can be augmented by incorporating human capital (H), where H is the stock of human capital and can also be affected by other factors, like education and health, among others.Equation (ii) can be transformed into a log-linear equation; hence, L represents the variable labour force productivity, K is the gross capital formation, and H represents the human capital.Other variables, such as the life expectancy rate, health, and education, can be used as a proxy for human capital to measure the quality of labour in the production process; introducing them into equation (iii) above, we have:where L is the labour force productivity, GCF represents gross capital formation, and LE stands for the life expectancy rate.where HIV/AIDS stands for human immunodeficiency virus/acquired immune deficiency syndrome and the prevalence of HIV/AIDS in labour aged 14 to 45 years.The African region remains the most heavily affected region in the global HIV/AIDS epidemic. In 2011, an estimated 23.5 million people living with the virus resided in Africa, which represents 60% of the global HIV burden . Different econometric methods and models have been employed by several authors and researchers to investigate the effect of the prevalence of HIV/AIDS on economic indicators, and the effect/impact of the former is not always in favour of the latter in the region. For example, The literature reviewed above indicated that the elasticity of the prevalence of HIV/AIDS is inelastic, implying that the percentage increase in HIV/AIDS is greater than the percentage decrease in economic growth due to the fact that the prevalence is increasing globally and diseases have no geographical boundary; as such, AIDS accounts for a greater fraction of the global distribution of communicable diseases. Africa is at the top of the list, with more than 16 million individual carriers of the disease, almost 3% of the population of the entire sub-continent . HoweverOn the other hand, the effects of life expectancy on economic growth have gained much attention in the economic literature in recent years. Economic theory suggests that the increasing life expectancy induces individuals to obtain more schooling and hence affects their income positively. CF is capital flight, H is the sum of the change in debt of a country; B is the net foreign direct investment; A is the current account surplus; and F is the change in reserves. Capital flight is introduced into the model as a variable to capture the fact that money that flees out of the economy affects growth negatively. The models are divided into two, with human immunodeficiency virus (HIV) and life expectancy (LE) considered as the dependent variables for each of the two models. This consideration is important to counteract the possible endogeneity problem between HIV and LE.This research applied the panel data method of analysis to 33 Sub-Saharan African countries to measure the effect of the prevalence of HIV/AIDS and life expectancy on economic growth. The difference GMM, as proposed by From equation (v) shown in section II, an econometric model can be written as:0 is an intercept of the model; ln HIV / AIDS is the human immunodeficiency virus, which refers to the percentage of people aged between 15 and 49 years; gross capital formation, denoted by ln GCF, consists of additional fixed assets possessed by a given country, such as plant, machinery, and equipment purchases and the construction of road networks, active railway lines, and other physical structures, such as schools, hospitals, private residential dwellings, and commercial and industrial buildings; ln LFT is the labour force productivity, defined as the working population aged from 15 to 64 years; life expectancy is denoted by ln LER, defined as the number of years an individual would live from the date of his/her birth to the date of his/her death; ln CF is the capital flight; and ε is the residual of the model. Hence, the panel data model can be written as:where RGDP is the percentage growth in the annual GDP per capita as the dependent variable; αEquation (vii) can further be transformed into an empirical GMM model by estimating the equation and capturing the effect of the prevalence of HIV/AIDS and life expectancy on economic growth, while internally controlling for the possible endogeneity of the variables using moment conditions. This choice of modelling is informed by the fact that labour force productivity and life expectancy are most likely to be influenced by the prevalence of diseases such as HIV/AIDS; for example, a higher income is associated with a better health condition of the workers and sickness may influence their income negatively, thus reversing the causality  for country at time t; θGit−1 stands for the lag of the dependent variable; and itr is the vector of independent variables used in the research, such as HIV/AIDS, gross capital formation, labour force productivity, and capital flight. Meanwhile, iλ represents the unobserved country-specific effects, such as the geographical location and institutional factors, and itε is the time-varying error term. Meanwhile, model 2 is specified as:where itG2 represents the dependent variable, which refers to the log percentage of GDP per capita (growth rate) for country i at time t; θG2it−1 stands for the lag of the dependent variable; and itr2 is the vector of independent variables (without HIV/AIDS), such as the life expectancy rate, gross capital formation, labour force productivity, and capital flight. Meanwhile, iλ represents the unobserved country-specific effects, such as the geographical location and institutional factors, and itε is the time-varying error term.where The models are estimated using the lagged difference dependent variables as an instrument to control the problem of autocorrelation of the first and second order and the lagged values of the explanatory variables as instruments to control for endogeneity in the regressors. Moreover, a two-step equation system is employed, which produces consistent estimates of the variance covariance matrix, which is robust to panel-specific heteroskedasticity and allows a robust test of instrument validity . TherefoThe elasticities of the two-step coefficients will be calculated by dividing the coefficient of the independent variables by one minus the coefficient of the lagged dependent variable, respectively, as follows:β0 / 1−α0, where β0 is the coefficient two-step independent variable and α0 is the coefficient of the lagged dependent variable, respectively.Elasticity = The variables adopted for this study include the percentage growth in the annual GDP per capita as a proxy for economic growth as the dependent variable, while HIV/AIDS, life expectancy (LE), gross capital formation (GCF), labour force productivity (LFT), and capital flight (CF) are the independent variables, respectively. The data are generated from the World Development Indicators (World Bank database). Based on the availability of data, we selected the most recent possible sample of 33 countries out of 48 Sub-Saharan African countries for a period of 11 years (2002–2012).To avoid the problem of endogeneity between our two hypothesis variables, that is, HIV/AIDS and the life expectancy rate, and to achieve more robust results, we divided them into two isolated models. The result is presented in Tables The coefficients of the lagged dependent variable, life expectancy, and gross capital formation produced a positive and significant result, whereas those of labour force productivity and capital flight indicated negative coefficients. Model 2 also passed the Arellano–Bond and Sargan tests for autocorrelation and over identification of restrictions, respectively.The elasticity of HIV/AIDS is inelastic such that the percentage increase in the prevalence of HIV/AIDS is greater than the percentage decrease in economic growth in Sub-Saharan Africa. This implies that a 10% increase in the prevalence of HIV/AIDS leads to a 0.14% decrease in the GDP of the region, and this finding is consistent with the theory and supported by previous studies  and This paper focused on the effect of the prevalence of HIV/AIDS and the life expectancy rate on economic growth in 33 Sub-Saharan African countries based on the availability of data over a period of 11 years. The generalised method of moments (GMM) was employed to achieve the objectives of the study. The result reveals that HIV/AIDS is statistically significant and negatively related to growth, consistent with theory and supported by many previous researchers , 2012. TBased on the findings of this research, the following recommendations are made. There is a need for future studies to determine the effect of HIV/AIDS and the life expectancy rate on economic growth in the region using a micro approach, because having contact with those involved would provide a true picture of their health status. Community effort in educating people, especially schoolchildren, about the danger of communicable diseases such as HIV/AIDS is strongly recommended. The family should spearhead the enlightenment of their wards from home to reduce or stop risky behaviours. Governments of SSA in partnership with NGOs should develop strategies for fighting the disease, such as making anti-retrovirus available and affordable in health service delivery centres, and funds generated from international donor agencies should be effectively and efficiently utilised in fighting HIV/AIDS and other related diseases in the region. The result of life expectancy shows a positive relationship with economic growth in the region. This is an indication that the factors influencing life expectancy, such as infant mortality, maternal health, and environmental factors, need to be given serious attention if sustainable development is to be achieved in the Sub-Saharan African region. Finally, the research was unable to capture social capital in its analysis as one of the important variables that determines the GDP and this can serve as a literature gap for future studies to fill.


Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees.We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner’s right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements.Publication agreements constraining academic authors’ independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol. In a document analysis of trial protocols and publications, Erik von Elm and colleagues investigate the potential impact of publication agreements between industry sponsors and academic investigators. Many randomized trials are designed and sponsored by for-profit companies that contract academic investigators to recruit and manage patients.Clinical research under these circumstances is a business transaction that bears the potential for conflicts of interest, in particular with respect to trial publication.Besides evidence from a small sample, it was unclear how often trial protocols included publication agreements between industry and academic investigators, whether these agreements constrained the investigators’ publication rights, and how consistent such agreements stated in trial protocols were with those reported in corresponding publications.We investigated publication agreements in 647 randomized trial protocols approved in 2000–2003 by six research ethics committees in Switzerland, Canada, and Germany, and in 388 corresponding journal publications.Seventy percent of protocols mentioned an agreement on publication rights between industry and academic investigators; in 86% of those agreements, industry retained the right to disapprove or at least review manuscripts before publication.Seventy-four percent of agreements documented in protocols were not mentioned in corresponding journal articles.Publication agreements constraining academic investigators’ independence are incompletely reported in publications; this may compromise the scientific evidence base established by randomized clinical trials.More transparency on publication constraints is warranted.Half of the included journal articles were published before 2008, leaving open the possibility that these findings do not reflect current reporting practice. Many randomized clinical trials (RCTs) are designed and sponsored by for-profit companies –3. CompaAcademic investigators’ careers depend on publication of research results in peer-reviewed journals. For-profit companies aim for approval of new products by regulating agencies or expansion of product indications . PublicaTo promote transparency in the arrangements between industry and academia, reporting guidelines recommend disclosure of potential conflicts of interest of authors and funders ,13. CompPrevious studies have documented constraints on the publication rights of academic investigators in industry-sponsored RCTs ,20. GøtzIn this article, we consider agreements on publication rights in a cohort of RCT protocols approved by six research ethics committees (RECs) between 13 January 2000 and 25 November 2003 in three countries and the reporting of these agreements in corresponding publications. We also investigate co-authorship by industry employees and the concordance of statements regarding publication rights between trial protocols and corresponding publications.The participating RECs approved the study or explicitly stated that no ethical approval was necessary.We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship of industry employees.Previous publications describe in detail the design of this retrospective cohort study ,22. In bIn the present analysis, we considered only RCT protocols that clearly documented industry involvement in the design, support, or conduct of the trial . We excluded protocols of studies that (i) compared different doses or routes of administration of the same drug (such as early dose-finding studies), (ii) enrolled only healthy volunteers, (iii) were never started, or (iv) were still ongoing as of April 27, 2013. With respect to multiple corresponding publications, we included only the primary full publication that reported the results from the randomized comparison, and excluded research letters, letters to the editor, and conference abstracts. In the case of more than one full publication, we considered the first publication that included results for the RCT’s primary outcomes.We defined documentation of publication rights as any statement about an agreement between an industry sponsor and the academic investigators regarding the publication of trial results. We classified eligible RCT protocols according to the sponsoring party (investigator or industry) that assumed formal responsibility for the conduct of the trial; the sponsoring party was identified from the following types of information in the protocol: a clearly named sponsor, a prominently displayed company or institution logo, the affiliations of protocol authors, statements about data ownership or publication rights, and statements about full funding by industry or public funding agencies. Disagreements were resolved by consensus or by involving a third investigator as arbitrator . Investigator-sponsored trials eligible for this study had at least some industry funding, provision of study drugs, or logistical support from industry; industry did not, however, entirely fund these trials.We recorded the presence or absence of any publication agreement between the academic investigators and industry documented in protocols and reported in publications. If reviewers identified such documentation, they assigned it to the most appropriate of the following four mutually exclusive categories: (i) The industry partner retains the right to disapprove any submission for publication . (ii) The industry partner retains the right to at least review and comment on any manuscript/abstract before publication . (iii) No constraints by the industry partner; in particular, no right to withhold the submission from publication. (iv) Reference to a separate publication agreement document between the industry partner and the investigator, with no further details. Prompted by a reviewer’s comment and considering the considerable ambiguity of original statements, we collapsed categories (i) and (ii) in the analyses herein and labelled the combined category as follows: the industry partner retains the right to disapprove or at least review any abstract or manuscript for publication. Examples of publication agreements in trial protocols are provided in Twelve investigators trained in clinical research methodology extracted data from the included trial protocols and correspondence between the RECs and local investigators at the respective centres. To increase consistency in data extraction, pairs of two reviewers extracted the initial 30% of data independently and compared results to achieve consensus; disagreements were resolved by discussion and consultation with an arbitrator  if necessary. If the available REC files provided no information about the publication status of a trial, we conducted comprehensive searches of electronic databases and surveyed investigators to find any corresponding publications as of April 27, 2013. Twenty-two investigators trained in clinical research methodology extracted data from all corresponding publications, independently and in duplicate; disagreements were resolved by discussion to achieve consensus or by consultation with an arbitrator . None of the reviewers among the teams extracted data from both a protocol and its corresponding publication.https://www.r-project.org/) for all analyses. Data are deposited in the Dryad Digital Repository: doi:10.5061/dryad.3s6j7 [We summarized binary data as frequencies and proportions and continuous data as medians and interquartile ranges. Publication agreements are described for protocols and corresponding publications separately. To explore differences regarding publication agreements, we stratified by industry versus investigator sponsorship. Prompted by reviewer comments, we additionally explored the differences regarding publication agreements stratified by the extent of industry funding, categorized as (i) provision of medication/device only, (ii) partially funded, beyond medication/device but not whole trial, and (iii) full funding of trial. When analyzing concordance between protocols and publications, we considered only those protocols in which the publication agreement was accessible to us. We used the statistical programme R version 3.1.2  had no industry involvement and were excluded. We included 647 (72.4%) protocols, of which 456 (70.5%) mentioned publication agreements . RCTs wiIn 393 of 456 (86.2%) protocols, the industry partner had the right to disapprove or at least to review publications proposed by academic investigators . PublicaOf 388 full journal publications, 98 (25.3%) mentioned an agreement regarding the publication of trial results and 290 (74.7%) did not. For 61 of the 98 (62.2%) trials that mentioned an agreement, authors reported that the industry partner had the right to disapprove or at least to review any publication. In 37 (37.8%) publications, the author statement suggested unrestricted publication rights  . The disIn 260 of 388 (67.0%) publications, at least one co-author was an industry employee . The median proportion of industry employees among all authors for journal publications was 25% ; it was 30% for industry-sponsored RCTs and 10% for investigator-sponsored RCTs. In 14 of the 37 (37.8%) publications in which there was a statement that suggested unrestricted publication rights, at least one co-author was an industry employee.Of 647 RCT protocols that were approved between 13 January 2000 and 25 November 2003 by six RECs in three countries and sponsored or supported by industry, 86% documented publication constraints reserving the right of the industry partner to review the manuscript or allowing the industry partner to disapprove the manuscript. Most agreements (74%) documented in protocols remained unreported in subsequent publications. In 18 instances, author statements in publications suggested no constraints by industry partners while protocols actually documented such constraints. Moreover, at least one co-author was an industry employee in two-thirds of journal publications and in one-third of publications in which statements suggested no publication constraints for academic authors. This suggests that, irrespective of the agreement in the protocol, the industry partner could influence publication content and submission decisions through co-authorship.Our data were collected as part of a large international cohort involving six RECs that allowed full access to trial protocols and filed correspondence between the local academic investigator and the REC in charge ,22; onlyOur study has limitations: First, separate agreement documents or legal contracts specifying publication rights were not available to us. However, only 5% of protocols that mentioned publication agreements referred to such separate documents. To the extent that protocols failed to refer to separate documents, we may have underestimated the overall prevalence of publication agreements. Second, we did not approach the local investigators submitting protocols to the REC to inquire whether their publication rights were actually constrained by the industry partner. Therefore, we cannot estimate to what extent the documented agreements impacted the content of publications or led to delays in publication or to non-publication of trial results. Third, the wording of the agreements in protocols was very heterogeneous. We extracted the original text only to provide examples but used our judgement to classify the statements according to four prespecified categories. Because of the considerable ambiguity of the original statements, we eventually collapsed two categories into one. Fourth, we used a convenience sample of six RECs that were—to our knowledge—not in any way particular. Five of them had authority for large university hospitals in their catchment areas, and one was responsible for a large teaching hospital. We cannot say whether these RECs are representative of other RECs in their own or other countries. Fifth, all included protocols were approved from 13 January 2000 and 25 November 2003, and half of the included publications were from the year 2007 or before, leaving the possibility that a substantial proportion of our sample no longer reflects current practices of reporting of publication agreements. In particular, the increasing demand for transparency in the reporting of clinical trials through guidelines and journal policies may have positively influenced current practice. Sixth, exploring the influence of industry co-authors in the writing process would require additional qualitative research, for example, interviews with author teams; however, this was not part of the present study. Seventh, we did not collect information regarding associated data-sharing agreements. The nature of such agreements might have influenced the interpretation of the publication agreements that were the focus of our study. Finally, we previously published the protocol of the overall project but not details about the present sub-study . TherefoGøtzsche et al. reported that 91% of 44 protocols from industry-sponsored trials approved by two RECs in 1994/1995 included constraints on publication rights, but none of the associated publications reported these constraints . In our Based on survey data from 108 US medical schools, Schulman et al. reported that academic institutions routinely engage in industry-sponsored research that fails to adhere to ICMJE guidelines regarding trial design, access to data, and publication rights . In anotPrevious publications have documented misleading presentations of evidence, sometimes referred to as “spin” . In induIndustry funding disclosed in trial manuscripts may represent a red flag for editors who are to decide about acceptance. If publication restrictions are acknowledged, this may be another. In turn, omission of such statements—or the presence of content that contradicts existing publication restrictions—deprives clinicians, guideline developers, and policy makers of such an alert, and may be deliberate.We acknowledge that there are instances, in which restricting the investigators’ right to publish is appropriate, e.g., separate publication of subsets of data from a multicentre trial could be confusing. Such restrictions should, however, be limited in time, e.g., until completion of the trial, including publication of its main results. Pending patent applications may be another justification for a time-limited delay of publication, but can certainly not excuse withholding it completely. We suggest that a general reference to confidentiality in the protocol without further explanation is not sufficient to justify restriction or delay of publication.Besides the issues of publication rights, co-authorship by industry employees on published trial reports allows the industry editorial influence. This issue also needs consideration in the context of possible reporting bias—in the light of our findings, journal editors should be aware of this issue.The cooperation between industry and academic investigators can be very fruitful and can lead to great improvements in medical care. RECs have a crucial role in ensuring the ethical conduct of clinical research and should therefore also consider whether commercial sponsors’ rights to disapprove publication of trial results hamper the scientific process and erode trust in clinical research. Additionally, mandatory documentation of publication agreements in protocols (as proposed recently ) and triPublication agreements are common in protocols of industry-sponsored RCTs. Journal publications of RCTs rarely provide readers with information about existing agreements, and when they do, statements can be discrepant with information in the corresponding trial protocols. Publication agreements constraining academic authors’ independence, and the incomplete reporting of such agreements in publications, may corrupt the scientific evidence base established by RCTs.S1 Fig(TIFF)Click here for additional data file.S1 TableAt the time of our study, the RECs in Basel and Lucerne were independent, but they have since been merged.(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S5 TableVariables collected from protocols and publications for the entire cohort.(PDF)Click here for additional data file.


Despite the dramatically improved survival due to combination antiretroviral therapies (cART), life expectancy of people with HIV/AIDS remains lower than that of the general population. This study aimed to estimate, at a population level, the survival experience of Italian people with AIDS (PWA) and to quantify the prognostic role of selected factors at diagnosis in the risk of early mortality .A population-based, retrospective-cohort study was conducted among Italian PWA diagnosed between 1999 and 2009 and recorded in the national AIDS registry. The vital status, up to December 2010, of 14,552 PWA was ascertained through a record linkage procedure with the Italian mortality database. Survival probabilities were estimated through Kaplan-Meier method. To identify risk factors for early mortality from any cause, odds ratios (ORs) and corresponding 95 % confidence intervals (CIs), adjusted for major confounders, were computed using multivariate logistic regression models.3 at AIDS diagnosis . Elevated ORs for early mortality also emerged for PWA diagnosed with primary brain lymphoma , or progressive multifocal leukoencephalopathy .Of the 5,706 deaths registered among the 14,552 PWA included in the study, 2,757 (18.9 %) occurred within six months from AIDS diagnosis. The probability of surviving six months increased from 81.2 % in PWA diagnosed in 1999–2000 to 82.9 % in 2009, while the 5-year survival augmented from 60.7 % in PWA diagnosed in 1999–2000 to 65.4 % for PWA diagnosed in 2005–2006. Elevated risks of early mortality were associated to older age , injecting drug use , and CD4 count <50 cells/mmOur study documented, among Italian PWA, the high - though slightly decreasing - frequency of early mortality in the full cART era. These findings indicate the need for enduring and ameliorating preventive actions aimed at timely HIV testing among all individuals at risk for HIV infection and/or those who present diseases known to be related with HIV infection. Development of combination antiretroviral therapies (cART) in the mid-1990s revolutionized the care of HIV-infected patients, leading to a marked decline in morbidity and mortality associated with HIV infection , at a po. In Italy, cART for HIV-infected individuals is free of charge and administered according to regularly updated standardized guidelines , year of diagnosis, CD4 cell count, use of cART before AIDS, date of first HIV-positive test, and AIDS-defining diseases. AIDS-defining diseases were classified into: i) infectious diseases ; ii) neoplasms ; and iii) other conditions . Individuals with more than one AIDS-defining disease were assigned to the condition with the worst prognosis [.A population-based, retrospective-cohort study was conducted among Italian PWA diagnosed between 1999 and 2009 and reported to the RNAIDS. In Italy, AIDS diagnoses  are comrognosis ., and it includes names and surnames. In agreement with the national law regulating the use of sensible data, we carried out a record linkage between the RNAIDS and the Italian mortality database following the inclusion, in 2012, of this study in the National Statistical Plan and the consequent authorization of the Italian Data Protection Authority. The record linkage was performed using an upgraded version of Software for Automated Linkage in Italy (SALI), a software application developed and validated in Italy to identify the same individuals in two different databases ensuring anonymity through a blinded procedure [.The vital status of PWA  was provided by the Italian National Institute of Statistics (ISTAT), where death certificates from the whole national territory are centrally collected and electronically stored in the Italian mortality database. Death certificate registration is mandatory (with completeness being around 100 %) and since January 1999, the ISTAT database of death certificates is managed according to European guidelines , and it rocedure , 12.Data regarding the 17,969 PWA reported to the RNAIDS from 1999 to 2009 were linked to data concerning the 6,895,720 deaths reported to the Italian mortality database between 1999 and 2010. The study period selected for the Italian mortality database was one-year longer than the RNAIDS one to allow for the detection of deaths for PWA diagnosed in 2009.N = 3,184); (2) PWA who at time of death resided or died in the provinces of Trento and Bolzano because names and surnames were not reported in death certificates (N = 167); 3) pediatric cases  (N = 48); 4) PWA with coincident dates of AIDS diagnosis and death (N = 18). Therefore, 14,552 adult Italian PWA constituted the study group.Specifically excluded from this analysis were: (1) PWA who were non-Italian citizens, to limit false-negative results of the linkage due to non-Italian names and surnames , we computed data also for one, three, and five years survival following AIDS diagnosis to document temporal changes in both short- and long-term mortality rates. The survival probability of PWA after AIDS diagnosis was estimated by means of the Kaplan–Meier method [.The main study outcome was death from any cause at six months following AIDS diagnosis , and it constituted the focus of this analysis. Two statistical approaches were used, a time-dependent, survival analysis and a logistic regression analysis. For the survival analysis, we considered failure events the deaths for any cause that occurred at 6 months, one, three, and five years after AIDS diagnosis. Survival time was computed as the time elapsed from the date of AIDS diagnosis to the date of death , to end of follow-up or to December 31, 2010  whichever came firstr method . To idenr method .Of the 14,552 PWA diagnosed between 1999 and 2009 included in this study, 5,706 were deceased as of December 31, 2010. Of these 5,706 deaths, 2,757  were early mortality deaths, i.e., they occurred within six months after AIDS diagnosis. Over time, the probability of surviving six months from AIDS diagnosis increased from 81.2 % for cases diagnosed in 1999–2000 to 82.9 % (+2.1 %) for those diagnosed in 2009. Improvements were also registered for three- and five-year survival  . Use of cART before AIDS was recorded in 36.2 % of these PWA .Table 3 was more frequently observed among PWA who acquired HIV infection through heterosexual intercourse (50.1 %), or homosexual male intercourse (42.3 %) than among injecting drug users (33.8 %)  , as compared to PWA who first tested HIV-positive seven or more months before AIDS   Fig. . PWA who01) Fig. .Fig. 2AIThe risk of early mortality was not affected by time elapsed between first HIV-positive test and AIDS, even after stratification for cART before AIDS  Table .Table 2DPneumocystis carinii pneumonia, for PWA diagnosed with non-Hodgkin lymphomas, particularly primary brain lymphoma , and progressive multifocal leukoencephalopathy (41.5 % of PWA with such disease died within six months from diagnosis) .The number of defining conditions diagnosed at time of AIDS was a strong, statistically significant, prognostic factor for early mortality. PWA with three or more AIDS-defining diseases showed a 1.97-fold higher risk of early mortality, compared to those with one disease Table . ElevateOur population-based investigation focused on early mortality of AIDS cases, and it showed that, over time, a slight amelioration in the proportion of PWA who died within six months from AIDS (from 81.2 % in PWA diagnosed in 1999–2000 to 82.9 % in 2009). Improvements were also documented in five-year survival, from 60.7 % in 1999–2002 to 65.4 % in 2005–2006. Our findings, together with the reduced risk of early mortality for PWA diagnosed in more recent years that emerged from the multivariate analysis, seemed to suggest a progress in the management of AIDS that has led to a slight, but clinically significant, improvement also in short term survival. This latter encouraging observation is consistent with findings reported elsewhere , and it , the results of this analysis strongly indicated that the largest part of one year post-AIDS mortality occurs within six months after diagnosis.Overall, the findings indicated that, 18.9 % of Italian PWA, diagnosed between 1999 and 2009, died within six months from AIDS diagnosis. This quantification of early mortality risk is particularly high when compared with findings from clinical trials . It shou.Approximately one fifth of Italian AIDS cases diagnosed between 1999 and 2009 were aged 50 years or older, and older age was confirmed to be a strong negative prognostic factor also for early mortality. In this study, the negative effect of older age on early mortality was clear overall, after adjusting by CD4 cell count, HIV transmission group, or other factors, or when stratifying by time elapsed from first HIV-positive test to AIDS. This finding is in agreement with the results of a recently published article showing that, in France, PWA aged 60 years or more were at a nearly 3-fold higher risk of late HIV presentation, and this event was strongly associated to an elevated risk of death in the first six months after AIDS diagnosis ., or life expectancy of HIV-infected people on cART [. It must be stressed that a strong HIV prevention effort has been addressed to women in recent years in Italy. National guidelines focusing on HIV testing in pregnancy have been issued to avoid mother-to-child transmission and, indirectly, to identify unaware HIV-infected women [.Overall, women with AIDS, who constitute about 22 % of Italian PWA included in this analysis, showed a risk of early mortality similar to men. This result seems in line with lack of gender difference reported in the proportion of HIV late presenters in Italy , or life on cART , 20. It ed women .Some of the characteristics herein investigated have been previously recognized as risk factors for mortality of PWA , namely . In line with the literature, our results suggest that cART-treated individuals benefit from a longer AIDS-free lifetime and that they develop a full-blown AIDS when the immune suppression is already at an advanced stage. Therefore, the risk of early mortality in the pre-AIDS treated group was related to the final depletion of the immune system and/or the presence of other life threatening conditions. Moreover, this finding may also be due to channelling bias  and/or to the presence of unmeasured confounding factors.In our study, the use of cART before AIDS was associated to a slight increased risk of early mortality (OR = 1.12). In Italy, cART is administered free of charge to every HIV-infected individual fitting standardized clinical and laboratory criteria . In lineThe type of AIDS-defining disease turned out to be a strong negative prognostic factor for early mortality. Among these, non-Hodgkin lymphomas and multifocal leukoencephalopathy were associated to more than 3-fold higher ORs, similarly to what reported in other population-based and clinical studies conducted in several high-income countries , 23.Finally, IDU showed the highest early mortality risk compared to PWA who acquired the infection through sexual contact; however, among IDU we observed the lowest proportion of individuals with a low CD4 cell count, suggesting that the elevated risk of early mortality was, in this group. mainly attributable to a longer duration of HV infection and/or to comorbidities, such as liver diseases or cancer, rather than to immune suppression.The main strengths of this population-based, retrospective-cohort study are the national coverage for both AIDS notifications data and death certificates; the quality of data, in terms of completeness and representativeness; the large size of the study population; and the long observation period. It is relevant to mention that the linkage between the two independent databases allowed the detection of all PWA who died for any reason, and not only for AIDS-related conditions, without the inconvenience of losses to follow-up that can occur in cohort studies based on a unique data source. However, we are aware that prospective cohort studies, in comparison with retrospective ones could provide a larger set of information and a more precise assessment of follow-up time for the survival analysis.Conversely, a major study limitation is the exclusion of non-Italian PWA from the analysis whose contribution to the AIDS epidemic in Italy is relevant. However, the linkage methodology used in this study –despite taking into account frequent spelling errors in names– could be less sensitive when matching foreign names and surnames due to a higher inaccuracy, in addition to a higher tendency of foreign citizens to migrate. Information on date of HIV-seroconversion is not collected by RNAIDS, as well as duration of adherence to treatment with cART; therefore, the duration of HIV infection of PWA and major parameters of treatment with cART could not be used for the aims of this investigation. Moreover, data on post-AIDS use of cART are not available at the RNAIDS, and this represents another important limitation that could have concealed the impact of cART on short term mortality.In the full cART era, population-based investigations focusing on the mortality of PWA and on prognostic factors represent valuable pieces of epidemiological evidence for clinicians and for researchers alike. These study results indicated that, in Italy, about one fifth of PWA died within six months after AIDS diagnosis, and this early mortality risk slightly decreased in the last decade. The main risk factors of early mortality were older age, use of injection drugs, a very low CD4 cell count and the presence of a number of life threatening conditions at AIDS diagnosis. These findings indicate the need for enduring and ameliorating preventive actions aimed at timely HIV testing among all individuals at risk for HIV infection and/or those who present diseases known to be related with HIV infection.


Developments in chemotherapy have led to changes in cancer care in Japan, with the government promoting a transition to outpatient chemotherapy. This requires patients and their families to participate more actively in treatment than in the past. However, it remains unclear how patients’ motivation for medical treatment affects clinical consultations with their physicians. To investigate this, we developed a psychological index called the Achievement Motive Index for Medical Treatment (AMI-MeT), which comprises self-derived achievement motivation (AMS) and achievement motivation derived from others (AMO). However, its factor structure has not yet been confirmed in populations other than healthy university students. Thus, the aims of this study were to confirm the factor structure of the AMI-MeT in other groups and to determine the convergent and divergent validity of the AMI-MeT.n = 414), apparently healthy workers (n = 154), and cancer patients (n = 51). Multi-group confirmatory factor analysis was conducted and the mean scores of the AMI-MeT were compared between the groups. Correlations between the AMI-MeT and the Self-Construal Scale, comprising independent self-construal (IndSC) and interdependent self-construal (InterSC) subscales, were investigated in another group of students (n = 335).The AMI-MeT was administered to university students (P < .01). The correlation analysis revealed that AMS scores were associated with IndSC scores  and AMO scores with InterSC scores .The multi-group confirmatory factor analysis supported a two-factor structure of the AMI-MeT: the weak invariance model was the best fit for the data. The mean scores of the AMI-MeT in apparently healthy workers and cancer patients were significantly higher than that in students  contains supplementary material, which is available to authorized users. Japan has a history of withholding cancer notification , but manAlthough many patients have been inclined to actively participate in treatment decision making in Japan , those wstrongly disagree) to 7 (strongly agree). In the previous pilot study, these two subscales had adequate reliability , and the construct validity of the AMI-MeT was confirmed through a comparison with Horino’s achievement motive scale . Th. Th25]. ve scale . The iteHowever, because the AMI-MeT was preliminarily developed in a rather small sample of university students, its reliability and validity remain insufficient. Specifically, the AMI-MeT was tested only using exploratory factor analysis in a single sample of university students; no confirmatory factor analysis has been performed in other populations. Additionally, the AMI-MeT has not yet been applied to the patient population—so far, it can only assess the motivation of university students, who do not have the same needs or interests as do patients. Finally, it remains unclear whether the subscales (AMS and AMO) are in fact based on dualistic concepts of the self, since they have been found to correlate only with achievement for self-fulfillment/competition . These iThe aims of this article are, in two studies, to demonstrate that the AMI-MeT data from university students, apparently healthy workers, and cancer patients fit the two-factor model; that AMI-MeT scores differ between the three groups; and that the AMI-MeT subscales correlate with dualistic concepts of the self.The questionnaire surveys were approved by the institutional review board at Kyoto University Graduate School of Medicine  and the Kyoto Industrial Health Association (April 2011).To confirm the factor structure of the AMI-MeT in more diverse groups and demonstrate that it accurately assesses motivation for medical treatment, we administered the AMI-MeT to several groups with varying needs for medical treatment: university students, apparently healthy workers, and cancer patients. It is likely that most university students, a young and comparatively healthy population, are less likely to need medicine or to go to the hospital, making them generally less motivated to do. In contrast, cancer patients who have already been diagnosed and informed of their diagnosis might feel a greater need for medical treatment—therefore, they are perhaps a relatively highly motivated population. Workers who had come to a medical institution for a health check were proposed to be a middle population in terms of motivation, somewhere between university students and cancer patients, as they would be potentially aware of the concerns or needs for medical treatment, but not to the same extent as would cancer patients. In other words, given that this group had voluntarily gone for a health screening, they were likely concerned about having undiagnosed diseases or perhaps realized the necessity of obtaining treatment. As such, we defined them as an “apparently healthy” group.SD = 5.4); we excluded any answer sheets that contained missing data. The second group comprised apparently healthy workers—that is, workers who had not yet been diagnosed with a disease but who had voluntarily undergone a health screening at a medical institution of the Kyoto Industrial Health Association between April 2011 and March 2012. Two hundred and thirty-three workers received the questionnaire after their health checks at the institution, and 164 completed it; of these, 154 valid responses were obtained . The third group comprised patients who had been diagnosed with breast or lung cancer and had come to start chemotherapy at Kyoto University Hospital between January and July 2009 or between April 2012 and January 2013. The questionnaire survey was administered to cancer patients who were part of the MORE-IC project. After the first author explained the aim of the MORE-IC project, 51 valid responses were obtained .The first group comprised university students from the Kansai region of Japan, who were asked to complete the questionnaire after a psychology class between October and November 2011. Of the 456 students given the questionnaire, 414 responded to all items of the questionnaire  with a multi-group procedure –28 and c2/df) and chi-square difference test (Δχ2) [To evaluate and compare these models, the chi-squared model test (χst (Δχ2)  were const (Δχ2) , and smast (Δχ2) . An RMSEst (Δχ2) . The const (Δχ2)  and the st (Δχ2) –36 were 2) was also calculated with Microsoft Excel.To demonstrate whether the AMI-MeT score (ten items) of cancer patients and workers are higher than are those of students, we performed a one-way analysis of variance (ANOVA with post hoc pairwise Bonferroni-adjusted comparisons) between the three groups. The statistical analysis was performed with SPSS 22.0. The effect size (ηMarkus and Kitayama (1991) proposed that Europeans and Americans construe the self as fundamentally individual and separate from others, and they labeled this the independent self-construal (IndSC)…. In contrast, Markus and Kitayama (1991) pointed out that the Japanese tend to construe the self as fundamentally connected to others and defined by relationships with others, which they labeled the interdependent self-construal (InterSC). ( p. 143)To determine the convergent and divergent validity of the AMI-MeT, we examined whether it correlates with another theoretically relevant psychological scale. In this case, we referred to the concept of self-construal , which iIn later works, InterSC was proposed to consist of two components: “relational component” and “group-oriented component” –39. AlthGiven this conceptual background, we assumed that AMS  would be correlated with IndSC; in other words, those who fundamentally construe themselves as individuals may take a more personal interest in medical decision making. We also supposed that AMO  would show a correlation with InterSC; that is, having a group-oriented awareness of medicine could affect the value individual respondents place on medical treatment that is based on social norms or expectations.SD = 2.9); we excluded any answer sheets that contained missing data.The questionnaire was distributed to university students in the Kansai region of Japan. They were asked to complete the questionnaire after a psychology class in May 2012. The data from Study 2 was part of another questionnaire survey. Notably, some of the respondents from Study 2 could have answered the questionnaire in Study 1. To avoid analyzing the same students twice, we made sure to treat them as separate groups while handing out the questionnaire. Of the 518 students given the questionnaire, 335 filled it in completely , participants indicated their level of agreement with 12 items assessing IndSC  and 12 statements assessing InterSC .Motivation for medical treatment was measured using the AMI-MeT. To validate the dualistic concepts of the AMI-MeT subscales, we administered the Self-Construal Scale (SCS) , which iTo demonstrate the convergent and divergent validity of the subscales of the AMI-MeT with the dualistic concepts of the self, we calculated the Pearson’s correlation coefficients between the AMI-MeT subscales and SCS subscales. This statistical analysis was performed with SPSS 22.0.2/df) and the chi-square difference test (Δχ2) showed that the weak invariance model was the best fit for the data  = 9.31, P < .01, η2 = .029; worker vs. student: P < .01; cancer patient vs. student: P < .01). The difference was also found for the mean scores of the AMO (five items); in contrast, AMS scores (five items) did not significantly differ between groups (Table The mean score of the AMI-MeT (ten items) was compared between the three groups. The score of workers and cancer patients were significantly higher than was that of students  than with the InterSC scores , and that the AMO scores were more related with the InterSC scores  than with the IndSC scores . Because there was a high correlation between AMS and AMO , a partial correlation analysis was also conducted. When we controlled for AMO in investigating the relationships between AMS and IndSC and between AMS and InterSC, we found partial correlations of r = .22 (P < .01) and r = .00 (n.s.), respectively. Furthermore, when we controlled for AMS in investigating the relationships between AMO and IndSC and between AMO and InterSC, we found partial correlations of r = -.03 (n.s.) and r = .24 (P < .01), respectively.Before examining the correlations, we calculated the Cronbach’s alphas of the subscales of both the AMI-MeT and the SCS, as follows: AMS and AMO, α = .79 and .75, respectively; IndSC and InterSC, α = .69 and .74, respectively. The correlation analysis revealed that the AMS scores were more related with the IndSC scores , and examined the concurrent validity of the AMI-MeT, as it exhibited significant differences in the mean score between groups . Additionally, we demonstrated the convergent and divergent validity of the subscales of the AMI-MeT using the SCS, as we believed that motivation for medical treatment would be theoretically linked with the concept of self-construal .As demonstrated in Analysis 1, the AMI-MeT has a two-factor structure (AMS and AMO). Notably, as shown in Analysis 2, the AMO scores of workers and cancer patients were significantly higher than were those of students, while the AMS scores did not differ among the groups. We expected both workers and cancer patients to recognize the need for medical treatment because they had actually come to the hospital, whereas university students might not recognize such a need—thus, the items of the AMO subscale may accurately reflect the value a respondent assigns on the basis of social norms or expectations, rather than personal interest. Accordingly, the AMO could be considered to have good concurrent validity. It must be noted that the concurrent validity of the AMS could not be discussed in the same manner as that of the AMO in this research setting, because the items of the AMS are not as reflective of visiting the hospital as are the items of the AMO.r = .25 and .30, respectively) were barely stronger than were those expected to be low . However, given that the conceptual similarity between AMS and AMO could result in their being highly correlated , we also conducted a partial correlation analysis to eliminate the potential confounds. As the partial correlation analysis indicated, there were weak but significant associations between AMS and IndSC and between AMO and InterSC , and no associations between AMS and InterSC and between AMO and IndSC . Thus, this partial correlation analysis while controlling for AMS and AMO supports the convergent and divergent validity of the subscales of the AMI-MeT.Regarding the convergent and divergent validity of the subscales of the AMI-MeT , the hypothesized strong associations  than in previous studies. Takahashi et al. (2009) reported Cronbach’s alphas of .48–.58 for the IndSC subscale and .86–.87 for the InterSC subscale ; overallFinally, our results cannot generalize to all cancer patients. We limited our sample to cancer patients who were diagnosed with breast or lung cancer and who were asked to answer the AMI-MeT before their clinical consultation for starting outpatient chemotherapy in a university hospital. Because individuals’ concerns about cancer treatment likely differ depending on their possible treatment options, disease stage, or social role, further investigation is required to explore how patients’ interests vary.We confirmed the validity and reliability of the two-factor model of the AMI-MeT and checked that the AMI-MeT could accurately measure motivation for medical treatment among different groups. In the future, when we investigate how shared decision making proceeds between Japanese physicians and patients or what occurs in their conversation process, the AMI-MeT will be useful tool for detecting patients with high and low motivation.