Contextual factors associated with cancer screening uptake: A systematic review of observational studies.

We conducted a systematic review of a wide range of contextual factors related to cancer screening uptake that have been studied so far. Studies were identified through PubMed and Web of Science databases. An operational definition of context was proposed, considering as contextual factors: social relations directly aimed at cancer screening, health care provider and facility characteristics, geographical/accessibility measures and aggregated measures at supra-individual level. We included 70 publications on breast, cervical and/or colorectal cancer screening from 42 countries, covering a data period of 24 years. A wide diversity of factors has been investigated in the literature so far. While several of them, as well as many interactions, were robustly associated with screening uptake (family, friends or provider recommendation, provider sex and experience, area-based socio-economic status…), others showed less consistency (ethnicity, urbanicity, travel time, healthcare density …). Screening inequities were not fully explained through adjustment for individual and contextual factors. Context, in its diversity, influences individual screening uptake and lots of contextual inequities in screening are commonly shared worldwide. However, there is a lack of frameworks, standards and definitions that are needed to better understand what context is, how it could modify individual behaviour and the ways of measuring and modifying it.

Water and Soil Pollution: Ecological Environmental Study Methodologies Useful for Public Health Projects. A Literature Review.

Health risks at population level may be investigated with different types of environmental studies depending on access to data and funds. Options include ecological studies, case-control studies with individual interviews and human sample analysis, risk assessment or cohort studies. Most public health projects use data and methodologies already available due to the cost of ad-hoc data collection. The aim of the article is to perform a literature review of environmental exposure and health outcomes with main focus on methodologies for assessing an association between water and/or soil pollutants and cancer. A systematic literature search was performed in May 2019 using PubMed. Articles were assessed by four independent reviewers. Forty articles were identified and divided into four groups, according to the data and methods they used, i.e.: (1) regression models with data by geographical area; (2) regression models with data at individual level; (3) exposure intensity threshold values for evaluating health outcome trends; (4) analyses of distance between source of pollutant and health outcome clusters. The issue of exposure assessment has been investigated for over 40 years and the most important innovations regard technologies developed to measure pollutants, statistical methodologies to assess exposure, and software development. Thanks to these changes, it has been possible to develop and apply geo-coding and statistical methods to reduce the ecological bias when considering the relationship between humans, geographic areas, pollutants, and health outcomes. The results of the present review may contribute to optimize the use of public health resources.

Recherche interventionnelle pour la réduction des inégalités sociales et territoriales de dépistage des cancers.

Social inequalities constitute a major obstacle to the social and economic cohesion of a country, particularly those affecting the health field. In the field of cancer screening, the current situation is that of a social gradient of participation and strong territorial inequalities. This paper reports on the results of two interventional investigations to add incentives to the existing device to provide screening tests for specific populations. A prospective trial with a collective randomization unit was set up from April 2011 to April 2013 in the 3 areas of Northern France (Aisne, Oise and Somme), to assess social workers' help with screening of colorectal cancer (Prado trial). A retrospective study was conducted on the experience of mammobile driving in the area of Orne for several years. The analysis of the results shows that each of these devices is capable of reducing or even erasing social and territorial inequalities at a reasonable cost to society. It also shows that in terms of screening, inequalities can only be reduced if additional devices dedicated to particular populations are added to the national system according to a principle of proportionate universalism.

Cost-Effectiveness Analysis of a Mobile Mammography Unit for Breast Cancer Screening to Reduce Geographic and Social Health Inequalities.

BACKGROUND: Breast cancer is the leading cancer in terms of incidence and mortality among women in France. Effective organized screening does exist, however, the participation rate is low, and negatively associated with a low socioeconomic status and remoteness. OBJECTIVES: To determine the cost-effectiveness of a mobile mammography (MM) program to increase participation in breast cancer screening and reduce geographic and social inequalities. METHODS: A cost-effectiveness analysis from retrospective data was conducted from the payer perspective, comparing an invitation to a mobile mammography unit (MMU) or to a radiologist's office (MM or RO group) with an invitation to a radiologist's office only (RO group) (n = 37 461). Medical and nonmedical direct costs were estimated. Outcome was screening participation. The mean incremental cost and effect, the incremental cost-effectiveness ratio, and the cost-effectiveness acceptability curve were estimated. RESULTS: The mean incremental cost for invitation to MM or RO was estimated to be €23.21 (95% CI, 22.64-23.78) compared with RO only, and with a point of participation gain of 3.8% (95% CI, 2.8-4.8), resulting in an incremental cost per additional screen of €610.69 (95% CI, 492.11-821.01). The gain of participation was more important in women living in deprived areas and for distances exceeding 15 km from an RO. CONCLUSION: Screening involving a MMU can increase participation in breast cancer screening and reduce geographic and social inequalities while being more cost-effective in remote areas and in deprived areas. Because of the retrospective design, further research is needed to provide more evidence of the effectiveness and cost-effectiveness of using a MMU for organized breast cancer screening and to determine the optimal conditions for implementing it.

[Intervention research for the reduction of social and local inequalities in matters relating to cancer screening] / Recherche interventionnelle pour la réduction des inégalités sociales et territoriales de dépistage des cancers.

Social inequalities constitute a major obstacle to the social and economic cohesion of a country, particularly those affecting the health field. In the field of cancer screening, the current situation is that of a social gradient of participation and strong territorial inequalities. This paper reports on the results of two interventional investigations to add incentives to the existing device to provide screening tests for specific populations. A prospective trial with a collective randomization unit was set up from April 2011 to April 2013 in the 3 areas of Northern France (Aisne, Oise and Somme), to assess social workers' help with screening of colorectal cancer (Prado trial). A retrospective study was conducted on the experience of mammobile driving in the area of Orne for several years. The analysis of the results shows that each of these devices is capable of reducing or even erasing social and territorial inequalities at a reasonable cost to society. It also shows that in terms of screening, inequalities can only be reduced if additional devices dedicated to particular populations are added to the national system according to a principle of proportionate universalism.

Longterm Risk of Solid Organ De Novo Malignancies After Liver Transplantation: A French National Study on 11,226 Patients.

De novo malignancies are one of the major late complications and causes of death after liver transplantation (LT). Using extensive data from the French national Agence de la Biomédecine database, the present study aimed to quantify the risk of solid organ de novo malignancies (excluding nonmelanoma skin cancers) after LT. The incidence of de novo malignancies among all LT patients between 1993 and 2012 was compared with that of the French population, standardized on age, sex, and calendar period (standardized incidence ratio; SIR). Among the 11,226 LT patients included in the study, 1200 de novo malignancies were diagnosed (10.7%). The risk of death was approximately 2 times higher in patients with de novo malignancy (48.8% versus 24.3%). The SIR for all de novo solid organ malignancies was 2.20 (95% confidence interval [CI], 2.08-2.33). The risk was higher in men (SIR = 2.23; 95% CI, 2.09-2.38) and in patients transplanted for alcoholic liver disease (ALD; SIR = 2.89; 95% CI, 2.68-3.11). The cancers with the highest excess risk were laryngeal (SIR = 7.57; 95% CI, 5.97-9.48), esophageal (SIR = 4.76; 95% CI, 3.56-6.24), lung (SIR = 2.56; 95% CI, 2.21-2.95), and lip-mouth-pharynx (SIR = 2.20; 95% CI, 1.72-2.77). In conclusion, LT recipients have an increased risk of de novo solid organ malignancies, and this is strongly related to ALD as a primary indication for LT.

Cost-Effectiveness Analysis of a Navigation Program for Colorectal Cancer Screening to Reduce Social Health Inequalities: A French Cluster Randomized Controlled Trial.

BACKGROUND: Patient navigation programs to increase colorectal cancer (CRC) screening adherence have become widespread in recent years, especially among deprived populations. OBJECTIVES: To evaluate the cost-effectiveness of the first patient navigation program in France. METHODS: A total of 16,250 participants were randomized to either the usual screening group (n = 8145) or the navigation group (n = 8105). Navigation consisted of personalized support provided by social workers. A cost-effectiveness analysis of navigation versus usual screening was conducted from the payer perspective in the Picardy region of northern France. We considered nonmedical direct costs in the analysis. RESULTS: Navigation was associated with a significant increase of 3.3% (24.4% vs. 21.1%; P = 0.003) in participation. The increase in participation was higher among affluent participants (+4.1%; P = 0.01) than among deprived ones (+2.6%; P = 0.07). The cost per additional individual screened by navigation compared with usual screening (incremental cost-effectiveness ratio) was €1212 globally and €1527 among deprived participants. Results were sensitive to navigator wages and to the intervention effectiveness whose variations had the greatest impact on the incremental cost-effectiveness ratio. CONCLUSIONS: Patient navigation aiming at increasing CRC screening participation is more efficient among affluent individuals. Nevertheless, when the intervention is implemented for the entire population, social inequalities in CRC screening adherence increase. To reduce social inequalities, patient navigation should therefore be restricted to deprived populations, despite not being the most cost-effective strategy, and accepted to bear a higher extra cost per additional individual screened.

Could mobile mammography reduce social and geographic inequalities in breast cancer screening participation?

Evaluation of mobile mammography for reducing social and geographic inequalities in breast cancer screening participation. We examined the responses to first invitations to undergo breast cancer screening from 2003 to 2012 in Orne, a French department. Half of the participants could choose between screening in a radiologist's office or a mobile mammography (MM) unit. We calculated the participation rate and individual participation model according to age group, deprivation quintile and distance. Among participants receiving an MM invitation, the preference was for MM. This was especially the case in the age group >70years and increased with deprivation quintile and remoteness. There were no significant participation trends with regard to deprivation or remoteness. In the general population, the influence of deprivation and remoteness was markedly diminished. After adjustment, MM invitation was associated with a significant increase in individual participation (odds ratio=2.9). MM can target underserved and remote communities, allowing greater participation and decreasing social and geographic inequalities in the general population. Proportionate universalism is an effective principle for public health policy in reducing health inequalities.

Patient navigation to reduce social inequalities in colorectal cancer screening participation: A cluster randomized controlled trial.

Despite free colorectal cancer screening in France, participation remains low and low socioeconomic status is associated with a low participation. Our aim was to assess the effect of a screening navigation program on participation and the reduction in social inequalities in a national-level organized mass screening program for colorectal cancer by fecal-occult blood test (FOBT). A multicenter (3 French departments) cluster randomized controlled trial was conducted over two years. The cluster was a small geographical unit stratified according to a deprivation index and the place of residence. A total of 14,556 subjects (72 clusters) were included in the control arm where the FOBT program involved the usual postal reminders, and 14,373 subjects (66 clusters) were included in the intervention arm. Intervention concerned only non-attended subjects with a phone number available defined as the navigable population. A screening navigator was added to the usual screening organization to identify and eliminate barriers to CRC screening with personalized contact. The participation rate by strata increased in the intervention arm. The increase was greater in affluent strata than in deprived ones. Multivariate analyses demonstrated that the intervention mainly with phone navigation increased individual participation (OR=1.19 [1.10, 1.29]) in the navigable population. For such interventions to reduce social inequalities in a country with a national level organized mass screening program, they should first be administered to deprived populations, in accordance with the principle of proportionate universalism. ClinicalTrials.gov Identifier: NCT01555450.

Area-based social inequalities in adult mortality: construction of French deprivation-specific life tables for the period 2016-2018.

Background: In order to tackle social inequalities in mortality, it is crucial to quantify them. We produced French deprivation-specific life tables for the period 2016-2018 to measure the social gradient in adult all-cause mortality. Methods: Data from the Permanent Demographic Sample (EDP) were used to provide population and death counts by age, sex and deprivation quintile. The European Deprivation Index (EDI), applied at a sub-municipal geographical level, was used as an ecological measure of deprivation. Smoothed mortality rates were calculated using a one-dimensional Poisson counts smoothing method with P-Splines. We calculated life expectancies by age, sex and deprivation quintile as well as interquartile mortality rate ratios (MRR). Results: At the age of 30, the difference in life expectancy between the most and least deprived groups amounted to 3.9 years in males and 2.2 years in females. In terms of relative mortality inequalities, the largest gaps between extreme deprivation groups were around age 55 for males (MRR = 2.22 [2.0; 2.46] at age 55), around age 50 in females (MRR = 1.77 [1.48; 2.1] at age 47), and there was a decrease or disappearance of the gaps in the very older adults. Conclusions: There is a strong social gradient in all-cause mortality in France for males and females. The methodology for building these deprivation-specific life tables is reproducible and could be used to monitor its development. The tables produced should contribute to improving studies on net survival inequalities for specific diseases by taking into account the pre-existing social gradient in all-cause mortality.

Can an Ecological Index of Deprivation Be Used at the Country Level? The Case of the French Version of the European Deprivation Index (F-EDI).

Most ecological indices of deprivation are constructed from census data at the national level, which raises questions about the relevance of their use, and their comparability across a country. We aimed to determine whether a national index can account for deprivation regardless of location characteristics. In Metropolitan France, 43,853 residential census block groups (IRIS) were divided into eight area types based on quality of life. We calculated score deprivation for each IRIS using the French version of the European Deprivation Index (F-EDI). We decomposed the score by calculating the contribution of each of its components by area type, and we assessed the impact of removing each component and recalculating the weights on the identification of deprived IRIS. The set of components most contributing to the score changed according to the area type, but the identification of deprived IRIS remained stable regardless of the component removed for recalculating the score. Not all components of the F-EDI are markers of deprivation according to location characteristics, but the multidimensional nature of the index ensures its robustness. Further research is needed to examine the limitations of using these indices depending on the purpose of the study, particularly in relation to the geographical grid used to calculate deprivation scores.

Toxicity and efficacy of stereotactic body radiotherapy for ultra-central lung tumours: a single institution real life experience.

OBJECTIVES: The use of stereotactic body radiotherapy (SBRT) to treat ultra-central lung tumours remains more controversial than for peripheral and central tumours. Our objective was to assess toxicities, local control (LC) rate and survival data in patients with ultra-central lung tumours treated with SBRT. METHODS: We conducted a retrospective and monocentric study about 74 patients with an ultra-central lung tumour, consecutively treated between 2012 and 2018. Ultra-central tumours were defined as tumours whose planning target volume overlapped one of the following organs at risk (OARs): the trachea, right and left main bronchi, intermediate bronchus, lobe bronchi, oesophagus, heart. RESULTS: Median follow-up was 25 months. Two patients (2.7%) showed Grade 3 toxicity. No Grade 4 or 5 toxicity was observed. 11% of patients experienced primary local relapse. LC rate was 96.7% at 1 year and 87.6% at 2 years. Median progression free survival was 12 months. Median overall survival was 31 months. CONCLUSION: SBRT for ultra-central tumours remains safe and effective as long as protecting organs at risk is treatment-planning priority. ADVANCES IN KNOWLEDGE: The present study is one of the rare to describe exclusively ultra-central tumours through real-life observational case reports. Globally, literature analysis reveals a large heterogeneity in ultra-central lung tumours definition, prescribed dose, number of fractions. In our study, patients treated with SBRT for ultra-central lung tumours experienced few Grade 3 toxicities (2.7%) and no Grade 4 or 5 toxicities, due to the highest compliance with dose constraints to OARs. LC remained efficient.

Evaluation of a mobile mammography unit: concepts and randomized cluster trial protocol of a population health intervention research to reduce breast cancer screening inequalities.

BACKGROUND: Breast cancer is the leading cancer in women in France both in incidence and mortality. Organized breast cancer screening (OBCS) has been implemented nationwide since 2004, but the participation rate remains low (48%) and inequalities in participation have been reported. Facilities such as mobile mammography units could be effective to increase participation in OBCS and reduce inequalities, especially areas underserved in screening. Our main objective is to evaluate the impact of a mobile unit and to establish how it could be used to tackle territorial inequalities in OBCS participation. METHODS: A collaborative project will be conducted as a randomized controlled cluster trial in 2022-2024 in remote areas of four French departments. Small geographic areas were constructed by clustering women eligible to OBCS, according to distance to the nearest radiology centre, until an expected sample of eligible women was attained, as determined by logistic and financial constraints. Intervention areas were then selected by randomization in parallel groups. The main intervention is to propose an appointment at the mobile unit in addition to current OBCS in these remote areas according to the principle of proportionate universalism. A few weeks before the intervention, OBCS will be promoted with a specific information campaign and corresponding tools, applying the principle of multilevel, intersectoral and community empowerment to tackle inequalities. DISCUSSION: This randomized controlled trial will provide a high level of evidence in assessing the effects of mobile unit on participation and inequalities. Contextual factors impacting the intervention will be a key focus in this evaluation. Quantitative analyses will be complemented by qualitative analyses to investigate the causal mechanisms affecting the effectiveness of the intervention and to establish how the findings can be applied at national level. TRIAL REGISTRATION: Registered on ClinicalTrials.gov, December 21, 2021: NCT05164874 .

Socio-Territorial Inequities in the French National Breast Cancer Screening Programme-A Cross-Sectional Multilevel Study.

BACKGROUND: France implemented in 2004 the French National Breast Cancer Screening Programme (FNBCSP). Despite national recommendations, this programme coexists with non-negligible opportunistic screening practices. AIM: Analyse socio-territorial inequities in the 2013-2014 FNBCSP campaign in a large sample of the eligible population. METHOD: Analyses were performed using three-level hierarchical generalized linear model. Level one was a 10% random sample of the eligible population in each département (n = 397,598). For each woman, age and travel time to the nearest accredited radiology centre were computed. These observations were nested within 22,250 residential areas called "Îlots Regroupés pour l'Information Statistique" (IRIS), for which the European Deprivation Index (EDI) is defined. IRIS were nested within 41 départements, for which opportunistic screening rates and gross domestic product based on purchasing power parity were available, deprivation and the number of radiology centres for 100,000 eligible women were computed. RESULTS: Organized screening uptake increased with age (OR1SD = 1.05 [1.04-1.06]) and decreased with travel time (OR1SD = 0.94 [0.93-0.95]) and EDI (OR1SD = 0.84 [0.83-0.85]). Between départements, organized screening uptake decreased with opportunistic screening rate (OR1SD = 0.84 [0.79-0.87]) and départements deprivation (OR1SD = 0.91 [0.88-0.96]). Association between EDI and organized screening uptake was weaker as opportunistic screening rates and as département deprivation increased. Heterogeneity in FNBCSP participation decreased between IRIS by 36% and between départements by 82%. CONCLUSION: FNBCSP does not erase socio-territorial inequities. The population the most at risk of dying from breast cancer is thus the less participating. More efforts are needed to improve equity.

Focus on the expected quality of reporting in SBRT/radiosurgery prospective studies: how far have we come in 30 years?

OBJECTIVES: We aimed at describing and assessing the quality of reporting in all published prospective trials about radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). METHODS: The Medline database was searched for. The reporting of study design, patients' and radiotherapy characteristics, previous and concurrent cancer treatments, acute and late toxicities and assessment of quality of life were collected. RESULTS: 114 articles - published between 1989 and 2019 - were analysed. 21 trials were randomised (18.4%). Randomisation information was unavailable in 59.6% of the publications. Data about randomisation, ITT analysis and whether the study was multicentre or not, had been significantly less reported during the 2010-2019 publication period than before (respectively 29.4% vs 57.4% (p < 0.001), 20.6% vs 57.4% (p < 0.001), 48.5% vs 68.1% (p < 0.001). 89.5% of the articles reported the number of included patients. Information about radiation total dose was available in 86% of cases and dose per fraction in 78.1%. Regarding the method of dose prescription, the prescription isodose was the most reported information (58.8%). The reporting of radiotherapy characteristics did not improve during the 2010 s-2019s. Acute and late high-grade toxicity was reported in 37.7 and 30.7%, respectively. Their reporting decreased in recent period, especially for all-grade late toxicities (p = 0.044). CONCLUSION: It seems necessary to meet stricter specifications to improve the quality of reporting. ADVANCES IN KNOWLEDGE: Our work results in one of the rare analyses of radiosurgery and SBRT publications. Literature must include necessary information to first, ensure treatments can be compared and reproduced and secondly, to permit to decide on new standards of care.

Local treatment in the setting of de novo metastatic rectal cancer: reappraisal of prognostic factors.

BACKGROUND: This retrospective study was conducted to: (1) provide more modern data on real-life local management of metastatic rectal cancer; (2) compare therapeutic strategies; and (3) identify prognostic factors of local failure, overall survival and progression-free survival. METHODS: Data about efficacy and acute toxicity were collected. Patients were diagnosed with metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. Local failure, overall survival and progression-free survival were correlated with patient, tumour and treatment characteristics using univariate and multivariate analyses. RESULTS: Data of 148 consecutive patients with metastatic rectal cancer were analysed. Median follow-up was 19 months. Median overall survival was 16 months. All patients received local radiotherapy, with a median equivalent 2 Gy per fraction dose of 47.7 Gy. Rectal surgery was performed in 97 patients (65.6%). The majority of patients (86/97, 88.7%) received pre-operative chemoradiation. In multivariate analysis, rectal surgery was found to be the only independent predictor of increased overall survival (24.6 vs 7.1 months, p <0.001). Of the patients undergoing surgical treatment, 22.8% presented with significant complications that required a delay of systemic treatment. Grade 3-4 acute radiation therapy-related toxicities were observed in 6.1% of patients, mainly gastrointestinal toxicities (5.4%). CONCLUSION: Rectal surgery was a key predictive factor of increased progression-free survival and overall survival in patients receiving at least local radiotherapy. In our series of real-life patients, local surgery and radiation seemed as well tolerated as reported in selected phase III non-metastatic rectal cancer patients. These data suggested that local management could be beneficial for metastatic rectal cancer patients.

Arabidopsis TFL2/LHP1 specifically associates with genes marked by trimethylation of histone H3 lysine 27.

TERMINAL FLOWER 2/LIKE HETEROCHROMATIN PROTEIN 1 (TFL2/LHP1) is the only Arabidopsis protein with overall sequence similarity to the HETEROCHROMATIN PROTEIN 1 (HP1) family of metazoans and S. pombe. TFL2/LHP1 represses transcription of numerous genes, including the flowering-time genes FLOWERING LOCUS T (FT) and FLOWERING LOCUS C (FLC), as well as the floral organ identity genes AGAMOUS (AG) and APETALA 3 (AP3). These genes are also regulated by proteins of the Polycomb repressive complex 2 (PRC2), and it has been proposed that TFL2/LHP1 represents a potential stabilizing factor of PRC2 activity. Here we show by chromatin immunoprecipitation and hybridization to an Arabidopsis Chromosome 4 tiling array (ChIP-chip) that TFL2/LHP1 associates with hundreds of small domains, almost all of which correspond to genes located within euchromatin. We investigated the chromatin marks to which TFL2/LHP1 binds and show that, in vitro, TFL2/LHP1 binds to histone H3 di- or tri-methylated at lysine 9 (H3K9me2 or H3K9me3), the marks recognized by HP1, and to histone H3 trimethylated at lysine 27 (H3K27me3), the mark deposited by PRC2. However, in vivo TFL2/LHP1 association with chromatin occurs almost exclusively and co-extensively with domains marked by H3K27me3, but not H3K9me2 or -3. Moreover, the distribution of H3K27me3 is unaffected in lhp1 mutant plants, indicating that unlike PRC2 components, TFL2/LHP1 is not involved in the deposition of this mark. Rather, our data suggest that TFL2/LHP1 recognizes specifically H3K27me3 in vivo as part of a mechanism that represses the expression of many genes targeted by PRC2.

[Radiotherapy and immune suppression: A short review]. / Radiothérapie et immunosuppression : synthèse de la littérature.

The management of patients undergoing immunosuppressive agents is really challenging. Based on precaution principle, it seems mandatory to stop immunosuppressive (or immunomodulating) agents during radiation. Yet, it is impossible in grafted patients. It is possible in patients with autoimmune disease, but in this case, the autoimmune disease might modify patient's radio-sensitivity. We provide a short review about the safety of radiotherapy in grafted/auto-immune patients. The literature is limited with data coming from outdated case-report or case-control studies. It seems that radiotherapy is feasible in grafted patients, but special dose-constraints limitations must probably be considered for the transplant and the other organs at risk. There is very little data about the safety of radiotherapy, when associated with immunomodulating agents. The most studied drug is the methotrexate but only its prescription as a chemotherapy (high doses for a short period of time) was reported. When used as an immunomodulator, it should probably be stopped 4 months before and after radiation. Apart from rheumatoid arthritis, it seems that collagen vascular diseases and especially systemic scleroderma and systemic lupus erythematous feature increased radio-sensitivity with increased severe late toxicities. Transplanted patients and collagen vascular disease patients should be informed that there is very little data about safety of radiation in their case.

A Plasmodium falciparum FcB1-schizont-EST collection providing clues to schizont specific gene structure and polymorphism.

BACKGROUND: The Plasmodium falciparum genome (3D7 strain) published in 2002, revealed ~5,400 genes, mostly based on in silico predictions. Experimental data is therefore required for structural and functional assessments of P. falciparum genes and expression, and polymorphic data are further necessary to exploit genomic information to further qualify therapeutic target candidates. Here, we undertook a large scale analysis of a P. falciparum FcB1-schizont-EST library previously constructed by suppression subtractive hybridization (SSH) to study genes expressed during merozoite morphogenesis, with the aim of: 1) obtaining an exhaustive collection of schizont specific ESTs, 2) experimentally validating or correcting P. falciparum gene models and 3) pinpointing genes displaying protein polymorphism between the FcB1 and 3D7 strains. RESULTS: A total of 22,125 clones randomly picked from the SSH library were sequenced, yielding 21,805 usable ESTs that were then clustered on the P. falciparum genome. This allowed identification of 243 protein coding genes, including 121 previously annotated as hypothetical. Statistical analysis of GO terms, when available, indicated significant enrichment in genes involved in "entry into host-cells" and "actin cytoskeleton". Although most ESTs do not span full-length gene reading frames, detailed sequence comparison of FcB1-ESTs versus 3D7 genomic sequences allowed the confirmation of exon/intron boundaries in 29 genes, the detection of new boundaries in 14 genes and identification of protein polymorphism for 21 genes. In addition, a large number of non-protein coding ESTs were identified, mainly matching with the two A-type rRNA units (on chromosomes 5 and 7) and to a lower extent, two atypical rRNA loci (on chromosomes 1 and 8), TARE subtelomeric regions (several chromosomes) and the recently described telomerase RNA gene (chromosome 9). CONCLUSION: This FcB1-schizont-EST analysis confirmed the actual expression of 243 protein coding genes, allowing the correction of structural annotations for a quarter of these sequences. In addition, this analysis demonstrated the actual transcription of several remarkable non-protein coding loci: 2 atypical rRNA, TARE region and telomerase RNA gene. Together with other collections of P. falciparum ESTs, usually generated from mixed parasite stages, this collection of FcB1-schizont-ESTs provides valuable data to gain further insight into the P. falciparum gene structure, polymorphism and expression.

The Portuguese version of the European Deprivation Index: Development and association with all-cause mortality.

Socioeconomic inequalities are major health determinants. To monitor and understand them at local level, ecological indexes of socioeconomic deprivation constitute essential tools. In this study, we describe the development of the updated version of the European Deprivation Index for Portuguese small-areas (EDI-PT), describe its spatial distribution and evaluate its association with a general health indicator-all-cause mortality in the period 2009-2012. Using data from the 2011 European Union-Statistics on Income and Living Conditions Survey (EU-SILC), we obtained an indicator of individual deprivation. After identifying variables that were common to both the EU-SILC and the census, we used the indicator of individual deprivation to test if these variables were associated with individual-level deprivation, and to compute weights. Accordingly, eight variables were included. The EDI-PT was produced for the smallest area unit possible (n = 18084 census block groups, mean/area = 584 inhabitants) and resulted from the weighted sum of the eight selected variables. It was then categorized into quintiles (Q1-least deprived to Q5-most deprived). To estimate the association with mortality we fitted Bayesian spatial models. The EDI-PT was unevenly distributed across Portugal-most deprived areas concentrated in the South and in the inner North and Centre of the country, and the least deprived in the coastal North and Centre. The EDI-PT was positively and significantly associated with overall mortality, and this relation followed a rather clear dose-response relation of increasing mortality as deprivation increases (Relative Risk Q2 = 1.012, 95% Credible Interval 0.991-1.033; Q3 = 1.026, 1.004-1.048; Q4 = 1.053, 1.029-1.077; Q5 = 1.068, 1.042-1.095). Summing up, we updated the index of socioeconomic deprivation for Portuguese small-areas, and we showed that the EDI-PT constitutes a sensitive measure to capture health inequalities, since it was consistently associated with a key measure of population health/development, all-cause mortality. We strongly believe this updated version will be widely employed by social and medical researchers and regional planners.