Future and potential spending on health 2015-40: Development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries

Background: The amount of resources, particularly prepaid resources, available for health can affect access to health care and health outcomes. Although health spending tends to increase with economic development, tremendous variation exists among health financing systems. Estimates of future spending can be beneficial for policy makers and planners, and can identify financing gaps. In this study, we estimate future gross domestic product (GDP), all-sector government spending, and health spending disaggregated by source, and we compare expected future spending to potential future spending. Methods: We extracted GDP, government spending in 184 countries from 1980-2015, and health spend data from 1995-2014. We used a series of ensemble models to estimate future GDP, all-sector government spending, development assistance for health, and government, out-of-pocket, and prepaid private health spending through 2040. We used frontier analyses to identify patterns exhibited by the countries that dedicate the most funding to health, and used these frontiers to estimate potential health spending for each low-income or middle-income country. All estimates are inflation and purchasing power adjusted. Findings: We estimated that global spending on health will increase from US$9.21 trillion in 2014 to$24.24 trillion (uncertainty interval [UI] 20.47-29.72) in 2040. We expect per capita health spending to increase fastest in upper-middle-income countries, at 5.3% (UI 4.1-6.8) per year. This growth is driven by continued growth in GDP, government spending, and government health spending. Lower-middle income countries are expected to grow at 4.2% (3.8-4.9). High-income countries are expected to grow at 2.1% (UI 1.8-2.4) and low-income countries are expected to grow at 1.8% (1.0-2.8). Despite this growth, health spending per capita in low-income countries is expected to remain low, at $154 (UI 133-181) per capita in 2030 and$195 (157-258) per capita in 2040. Increases in national health spending to reach the level of the countries who spend the most on health, relative to their level of economic development, would mean $321 (157-258) per capita was available for health in 2040 in low-income countries. Interpretation: Health spending is associated with economic development but past trends and relationships suggest that spending will remain variable, and low in some low-resource settings. Policy change could lead to increased health spending, although for the poorest countries external support might remain essential

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at √s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into diferent pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at √s = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, tt¯, and tb) or third-generation leptons (τν and τ τ ) are included in this kind of combination for the frst time. A simplifed model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confdence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion

Predictive clinical-radiological model for diagnosing active pulmonary tuberculosis

El objetivo de este estudio fue desarrollar un modelo predictivo sobre la presencia de tuberculosis pulmonar activa utilizando datos clínico-epidemiológicos y hallazgos de radiografía simple (Rx) y tomografía computadorizada (TC) de tórax. Material y métodos: Se realizó un estudio observacional, retrospectivo, descriptivo y analítico, que recopiló 22 variables clínico-epidemiológicas, 11 hallazgos radiológicos en Rx de tórax y 23 en la TC, que se realizaron en pacientes con sospecha clínica de tuberculosis pulmonar durante un período de 10 años. Se aplicó un modelo de regresión logística multivariado a los predictores potenciales de cultivo positivo, obteniendo un modelo predictivo. Resultados: Se recogieron 1.540 pacientes con sospecha clínica de tuberculosis a los que se les realizó Rx y TC torácico. El cultivo fue positivo en 101 casos. Se utilizó un proceso de eliminación hacia atrás para obtener el mejor conjunto de variables predictivas. Se obtuvieron 24 variables que fueron significativas (6 clínicas, 5 de Rx y 13 de TC) y se les asignó una puntuación. A la suma de estas puntuaciones se restó la edad en años multiplicada por 0,03. El modelo sugiere el diagnóstico de tuberculosis pulmonar activa en pacientes con una puntuación superior a 1,845. Obtuvo una sensibilidad de 85,1%, especificidad de 83,6%, valor predictivo positivo de 26,6%, y valor predictivo negativo de 98,7%. El área bajo la curva ROC fue de 0,9163. Conclusión: Este sistema de puntuación basado en criterios clínico-epidemiológicos y hallazgos radiológicos puede ayudar a diagnosticar tuberculosis pulmonar activa en casos de sospecha diagnóstica.The objective of this study was to develop a predictive model on the presence of active pulmonary tuberculosis using clinical-epidemiological data and findings of chest radiography and thoracic computed tomography (CT). Material and methods: An observational, retrospective, descriptive and analytical study was conducted, which collected 22 clinical and epidemiological variables, 11 radiological findings on chest x-ray and 23 on CT that were performed in patients with clinical suspicion of pulmonary tuberculosis during a period of 10 years. A multivariate logistic regression model was applied to the potential predictors of positive culture, obtaining a predictive model. Results: We collected 1,540 patients with clinical suspicion of tuberculosis who underwent radiography and thoracic CT. The culture was positive in 101 cases. A backward elimination process was used to obtain the best set of predictive variables. We obtained 24 variables that were significant (6 clinical, 5 of chest plain films and 13 of CT) and were assigned a score. The sum of these scores was subtracted from the age in years and multiplied by 0.03. The model suggests the diagnosis of active pulmonary tuberculosis in patients with a score higher than 1.845. The model obtained a sensitivity of 85.1%, specificity of 83.6%, positive predictive value of 26.6, and negative predictive value of 98.7%. The area under the ROC curve was 0.9163. Conclusion: This scoring system based on clinical-epidemiological criteria and radiological findings can help rule out active pulmonary tuberculosis in cases of diagnostic suspicion

Estudio de costo-efectividad de la biopsia mamaria asistida por vacío versus biopsia con aguja gruesa o arpón

Objectives To determine the cost effectiveness of breast biopsy by 9 G vacuum-assisted guided by vertical stereotaxy or ultrasonography in comparison with breast biopsy by 14 G core-needle biopsy and surgical biopsy. Material and methods We analyzed a total of 997 biopsies (181 vacuum-assisted, 626 core, and 190 surgical biopsies). We calculated the total costs (indirect and direct) of the three types of biopsy. We did not calculate intangible costs. We measured the percentage of correct diagnoses obtained with each technique. To identify the most cost-effective option, we calculated the mean ratios for the three types of biopsies. Results Total costs amounted to €225.09 for core biopsy, €638.90 for vacuum-assisted biopsy, and €1780.01 for surgical biopsy. The overall percentage of correct diagnoses was 91.81 per cent for core biopsy, 94.03 per cent for vacuum-assisted biopsy, and 100 per cent for surgical biopsy; however, these differences did not reach statistical significance (P = 0.3485). For microcalcifications, the percentage of correct diagnoses was 50 per cent for core biopsy and 96.77 per cent for vacuum-assisted biopsy (P < 0.0001). For nodules, there were no significant differences among techniques. The mean cost-effectiveness ratio considering all lesions was 2.45 for core biopsy, 6.79 for vacuum-assisted biopsy, and 17.80 for surgical biopsy. Conclusion Core biopsy was the dominant option for the diagnosis of suspicious breast lesions in general. However, in cases with microcalcifications, the low percentage of correct diagnoses achieved by core biopsy (50 per cent) advises against its use in this context, where vacuum-assisted biopsy would be the technique of choice because it is more cost-effective than surgical biopsy, the other technique indicated for biopsying microcalcifications.Objetivo Realizar estudio de costo-efectividad de la biopsia por aspiración al vacío (BAV) (9 G) guiada por estereotaxia vertical o ecografía comparada con biopsia con aguja gruesa (BAG) (14 G) y biopsia con arpón. Material y métodos Analizamos 997 biopsias mamarias (181 BAV, 626 BAG y 190 arpones). Calculamos costes totales (directos e indirectos) de los tres tipos de biopsia. No calculamos costes intangibles. El efecto a medir fue el “porcentaje de diagnósticos correctos” obtenidos con cada una de las técnicas. Calculamos los ratios medios de los tres tipos de biopsias e identificamos la opción dominante más costo-efectiva. Resultados Costes totales de BAG 225,09 €, de BAV 638,90 € y de biopsia con arpón 1780,01 €. Porcentaje de diagnósticos correctos globales con BAG 91,81%, BAV 94,03% y biopsia con arpón 100%, sin diferencias significativas (p = 0,3485). En microcalcificaciones, los porcentajes de diagnósticos correctos fueron con BAG 50% y con BAV 96,77%, p < 0,0001. En nódulos tampoco hubo diferencias significativas. El ratio medio costo-efectividad considerando todas las lesiones en conjunto, fue para BAG 2,45, BAV 6,79 y arpón 17,80. Conclusión La BAG fue la opción dominante para el diagnóstico de lesiones mamarias sospechosas de malignidad en general. En el caso de las microcalcificaciones, el bajo porcentaje de diagnósticos de la BAG (50%) desaconsejan su uso y colocan a la BAV como técnica de elección; la BAV es, además, más costo-efectiva que el arpón, que es la otra técnica indicada para biopsiar microcalcificaciones

An Interdisciplinary Study on the Parana Delta of Argentina

With combined efforts from water management, architectural and hydraulic engineering students, an interdisciplinary and resilient design is set up for the Paraná Delta. The design relates to all the current environmental, architectural and flood risk challenges - among others, as well as the potential issues in the future since the Paraná Delta is a highly dynamic environment.Multidiscipinary Projec

Considerations on diagnosis and surveillance measures of PTEN hamartoma tumor syndrome : clinical and genetic study in a series of Spanish patients

Altres ajuts: European Regional Development Fund; Federación Española de Enfermedades Raras (FEDER); European Social Fund (ESF).Background: The limited knowledge about the PTEN hamartoma tumor syndrome (PHTS) makes its diagnosis a challenging task. We aimed to define the clinical and genetic characteristics of this syndrome in the Spanish population and to identify new genes potentially associated with the disease. Results: We reviewed the clinical data collected through a specific questionnaire in a series of 145 Spanish patients with a phenotypic features compatible with PHTS and performed molecular characterization through several approaches including next generation sequencing and whole exome sequencing (WES). Macrocephaly, mucocutaneous lesions, gastrointestinal polyposis and obesity are prevalent phenotypic features in PHTS and help predict the presence of a PTEN germline variant in our population. We also find that PHTS patients are at risk to develop cancer in childhood or adolescence. Furthermore, we observe a high frequency of variants in exon 1 of PTEN, which are associated with renal cancer and overexpression of KLLN and PTEN. Moreover, WES revealed variants in genes like NEDD4 that merit further research. Conclusions: This study expands previously reported findings in other PHTS population studies and makes new contributions regarding clinical and molecular aspects of PHTS, which are useful for translation to the clinic and for new research lines