Models for engaging public-private partnerships in civil infrastructure projects: A case of ‘having your cake and eating it too’?

Session 4Bpublished_or_final_versio

GOPHER, an HPC framework for large scale graph exploration and inference

Biological ontologies, such as the Human Phenotype Ontology (HPO) and the Gene Ontology (GO), are extensively used in biomedical research to investigate the complex relationship that exists between the phenome and the genome. The interpretation of the encoded information requires methods that efficiently interoperate between multiple ontologies providing molecular details of disease-related features. To this aim, we present GenOtype PHenotype ExplOrer (GOPHER), a framework to infer associations between HPO and GO terms harnessing machine learning and large-scale parallelism and scalability in High-Performance Computing. The method enables to map genotypic features to phenotypic features thus providing a valid tool for bridging functional and pathological annotations. GOPHER can improve the interpretation of molecular processes involved in pathological conditions, displaying a vast range of applications in biomedicine.This work has been developed with the support of the Severo Ochoa Program (SEV-2015-0493); the Spanish Ministry of Science and Innovation (TIN2015- 65316-P); and the Joint Study Agreement no. W156463 under the IBM/BSC Deep Learning Center agreement.Peer ReviewedPostprint (author's final draft

Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations.

Background Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. Methods Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. Results Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. Conclusions The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance

The economic burden of musculoskeletal disease in Korea: A cross sectional study

<p>Abstract</p> <p>Background</p> <p>Musculoskeletal diseases are becoming increasingly important due to population aging. However, studies on the economic burden of musculoskeletal disease in Korea are scarce. Therefore, we conducted a population-based study to measure the economic burden of musculoskeletal disease in Korea using nationally representative data.</p> <p>Methods</p> <p>This study used a variety of data sources such as national health insurance statistics, the Korea Health Panel study and cause of death reports generated by the Korea National Statistical Office to estimate the economic burden of musculoskeletal disease. The total cost of musculoskeletal disease was estimated as the sum of direct medical care costs, direct non-medical care costs, and indirect costs. Direct medical care costs are composed of the costs paid by the insurer and patients, over the counter drugs costs, and other costs such as medical equipment costs. Direct non-medical costs are composed of transportation and caregiver costs. Indirect costs are the sum of the costs associated with premature death and the costs due to productivity loss. Age, sex, and disease specific costs were estimated.</p> <p>Results</p> <p>Among the musculoskeletal diseases, the highest costs are associated with other dorsopathies, followed by disc disorder and arthrosis. The direct medical and direct non-medical costs of all musculoskeletal diseases were $4.18 billion and$338 million in 2008, respectively. Among the indirect costs, those due to productivity loss were $2.28 billion and costs due to premature death were$79 million. The proportions of the total costs incurred by male and female patients were 33.8% and 66.2%, respectively, and the cost due to the female adult aged 20-64 years old was highest. The total economic cost of musculoskeletal disease was $6.89 billion, which represents 0.7% of the Korean gross domestic product.</p> <p>Conclusions</p> <p>The economic burden of musculoskeletal disease in Korea is substantial. As the Korean population continues to age, the economic burden of musculoskeletal disease will continue to increase. Policy measures aimed at controlling the cost of musculoskeletal disease are therefore required.</p

Genome wide analysis of gene expression changes in skin from patients with type 2 diabetes

Non-healing chronic ulcers are a serious complication of diabetes and are a major healthcare problem. While a host of treatments have been explored to heal or prevent these ulcers from forming, these treatments have not been found to be consistently effective in clinical trials. An understanding of the changes in gene expression in the skin of diabetic patients may provide insight into the processes and mechanisms that precede the formation of non-healing ulcers. In this study, we investigated genome wide changes in gene expression in skin between patients with type 2 diabetes and non-diabetic patients using next generation sequencing. We compared the gene expression in skin samples taken from 27 patients (13 with type 2 diabetes and 14 non-diabetic). This information may be useful in identifying the causal factors and potential therapeutic targets for the prevention and treatment of diabetic related diseases

Clinical significance of hypoalbuminemia in outcome of patients with scrub typhus

<p>Abstract</p> <p>Background</p> <p>This study was designed to investigate the clinical significance of hypoalbuminemia as a marker of severity and mortality in patients with Scrub typhus.</p> <p>Methods</p> <p>The patients with scrub typhus were divided into two groups based on the serum albumin levels; Group I (serum albumin <3.0 g/dL) and Group II (serum albumin ≥3.0 g/dL). The outcome of patients with hypoalbuminemia was compared with that of normoalbuminemia.</p> <p>Results</p> <p>Of the total 246 patients who underwent the study, 84 patients (34.1%) were categorized as Group I and 162 patients were (65.9%) as Group II. Group I showed significantly higher incidence of confusion (24.6% vs. 5.3%, <it>p </it>< 0.001), pulmonary edema (15.8% vs. 3.2%, <it>p </it>= 0.002), pleural effusion (22.8% vs. 11.1%, <it>p </it>= 0.03), arrhythmia (12.3% vs. 2.6%, <it>p </it>= 0.008) and non-oliguric acute renal failure (40.4% vs. 11.1%, <it>p </it>< 0.001) compared to group II. Hypoalbuminemic group had a higher APACHE II score (11.37 ± 5.0 vs. 6.94 ± 4.2, <it>p </it>< 0.001), longer hospital stay (19.9 ± 42.1 days vs 7.5 ± 13.8 days, <it>p </it>= 0.012), and higher hospital cost compared to Group II.</p> <p>Conclusions</p> <p>This study showed hypoalbuminemia in scrub typhus was closely related to the frequency of various complication, longer hospital stay, consequently the higher medical cost, necessitating more efficient management of patients, including medical resources.</p

Comparison of placental growth factor and fetal flow Doppler ultrasonography to identify fetal adverse outcomes in women with hypertensive disorders of pregnancy: an observational study.

BACKGROUND: Hypertensive disorders of pregnancy and intrauterine growth restriction (IUGR) are leading causes of maternal and perinatal morbidity and mortality. Failure to detect intrauterine growth restriction in women at high risk has been highlighted as a significant avoidable cause of serious fetal outcome. In this observational study we compare fetal flow using Doppler ultrasonography with a new test for placental growth factor (PlGF) to predict fetal adverse events. METHODS: Eighty-nine women with hypertensive disorders of pregnancy (24 with chronic hypertension, 17 with gestational hypertension, 12 with HELLP syndrome, 19 with preeclampsia and 17 with superimposed preeclampsia) were enrolled. A single maternal blood sample to measure free PlGF (Alere Triage) taken before 35 weeks of pregnancy was compared to the last Doppler ultrasound measurement of fetal flow before delivery. PlGF was classified as normal (PlGF>/=100 pg/ml), low (12<PlGF<100) or very low (PlGF</=12 pg/ml). A positive test for abnormal fetal flow was defined as either signs of centralisation of the fetal circulation or diastolic block or reverse flow in the umbilical artery or descending aorta; this was a criterion for delivery. Fetal outcomes were intrauterine growth restriction and birth before 37 weeks of pregnancy. RESULTS: In total 61/89 women had a preterm birth and 22 infants had IUGR. Of those who delivered preterm, 20/20 women with abnormal fetal flow and 36/41 (87.8%) women with normal fetal flow had low or very low PlGF. Of those infants with IUGR, 22/22 had low or very low maternal PlGF and 10/22 had abnormal fetal flow. CONCLUSIONS: PlGF may provide useful information before 35th gestational week to identify fetuses requiring urgent delivery, and those at risk of later adverse outcomes not identified by fetal flow Doppler ultrasonography

The blind men and the AML elephant:can we feel the progress?

The pharmacological therapy of non-promyelocytic acute myeloid leukemia (AML) has remained unchanged for over 40 years with an anthracycline–cytarabine combination forming the backbone of induction treatments. Nevertheless, the survival of younger patients has increased due to improved management of the toxicity of therapies including stem cell transplantation. Older patients and those with infirmity that precludes treatment-intensification have, however, not benefited from improvements in supportive care and continue to experience poor outcomes. An increased understanding of the genomic heterogeneity of AML raises the possibility of treatment-stratification to improve prognosis. Thus, efforts to identify agents with non-conventional anti-leukemic effects have paralleled those aiming to optimize leukemia cell-kill with conventional chemotherapy, resulting in a number of randomized controlled trials (RCT). In the last 18 months, RCTs investigating the effects of vosaroxin, azacitidine and gemtuzumab ozogamycin and daunorubicin dose have been reported with some studies indicating a statistically significant survival benefit with the investigational agent compared with standard therapy and potentially, a new era in AML therapeutics. Given the increasing costs of cancer care, a review of these studies, with particular attention to the magnitude of clinical benefit with the newer agents would be useful, especially for physicians treating patients in single-payer health systems

Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy

Background: This study was aimed 1) to investigate the predictive value of FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) for histopathologic response and 2) to explore the results of FDG PET/CT by molecular phenotypes of breast cancer patients who received neoadjuvant chemotherapy. Methods: Seventy-eight stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for evaluating early metabolic response. Results: The mean pre- and post-chemotherapy standard uptake value (SUV) were 7.5 and 3.9, respectively. The early metabolic response provided by FDG PET/CT after one cycle of neoadjuvant chemotherapy was correlated with the histopathologic response after completion of neoadjuvant chemotherapy (P = 0.002). Sensitivity and negative predictive value were 85.7% and 95.1%, respectively. The estrogen receptor negative phenotype had a higher pre-chemotherapy SUV (8.6 vs. 6.4, P = 0.047) and percent change in SUV (48% vs. 30%, P = 0.038). In triple negative breast cancer (TNBC), the pre-chemotherapy SUV was higher than in non-TNBC (9.8 vs. 6.4, P = 0.008). Conclusions: The early metabolic response using FDG PET/CT could have a predictive value for the assessment of histopathologic non-response of stage II/III breast cancer treated with neoadjuvant chemotherapy. Our findings suggest that the initial SUV and the decline in SUV differed based on the molecular phenotype