Accelerated placental aging in early onset preeclampsia pregnancies identified by DNA methylation.

Aim: To determine whether dynamic DNA methylation changes in the human placenta can be used to predict gestational age. Materials & methods: Publicly available placental DNA methylation data from 12 studies, together with our own dataset, using Illumina Infinium Human Methylation BeadChip arrays. Results & conclusion: We developed an accurate tool for predicting gestational age of placentas using 62 CpG sites. There was a higher predicted gestational age for placentas from early onset preeclampsia cases, but not term preeclampsia, compared with their chronological age. Therefore, early onset preeclampsia is associated with placental aging. Gestational age acceleration prediction from DNA methylation array data may provide insight into the molecular mechanisms of pregnancy disorders.Benjamin T Mayne, Shalem Y Leemaqz, Alicia K Smith, James Breen, Claire T Roberts, Tina Bianco-Miott

Treatment of Hepatitis C virus genotype 3 infection with direct-acting antiviral agents

Hepatitis C virus (HCV) genotype 3 is responsible for 30.1% of chronic hepatitis C infection cases worldwide. In the era of directacting antivirals, these patients have become one of the most challenging to treat, due to fewer effective drug options, higher risk of developing cirrhosis and hepatocellular carcinoma and lower sustained virological response (SVR) rates. Currently there are 4 recommended drugs for the treatment of HCV genotype 3: pegylated interferon (PegIFN), sofosbuvir (SOF), daclatasvir (DCV) and ribavirin (RBV). Treatment with PegIFN, SOF and RBV for 12 weeks has an overall SVR rate of 83-100%, without significant differences among cirrhotic and non-cirrhotic patients. However, this therapeutic regimen has several contra-indications and can cause significant adverse events, which can reduce adherence and impair SVR rates. SOF plus RBV for 24 weeks is another treatment option, with SVR rates of 82-96% among patients without cirrhosis and 62-92% among those with cirrhosis. Finally, SOF plus DCV provides 94-97% SVR rates in non-cirrhotic patients, but 59-69% in those with cirrhosis. The addition of RBV to the regimen of SOF plus DCV increases the SVR rates in cirrhotic patients above 80%, and extending treatment to 24 weeks raises SVR to 90%. The ideal duration of therapy is still under investigation. For cirrhotic patients, the optimal duration, or even the best regimen, is still uncertain. Further studies are necessary to clarify the best regimen to treat HCV genotype 3 infection491

Value of various PSA parameters for diagnosing prostate cancer in men with normal digital rectal examination

OBJECTIVES: The risks of identifying prostate cancer (PCa) in patients with serum total PSA (tPSA) between 4 and 10 ng/dl are between 25 and 35%. There are no data in Brazil showing the incidence of disease when all variables for PSA assessment are considered altogether, specifically tPSA, free fraction, PSA velocity and PSA stratified by age. The objective in this work was to define the incidence of disease in a population of men with abnormal values of PSA variables and normal digital rectal examination. MATERIALS AND METHODS: Between 1998 and 2003, 273 prostate biopsies were performed by the same radiologist and analyzed by the same pathologist. All patients had a normal digital rectal examination and biopsy had been indicated due to tPSA above 4 ng/dl or free-to-total PSA ratio (F/T PSA) below 15% or PSA velocity higher than 25% per year or a PSA level regarded as high for the age range. The relationship between these parameters and the positivity for prostate caner was determined. RESULTS: Patients' mean age was 63.8 years, and PCa was identified in 135 cases (49.5%). The incidence of PCa, related to unitary variations in tPSA, ranged from the limits of 33 to 80%, respectively, in tPSA < 3 and PSA between 15.1 to 20. When the other PSA parameters were assessed (free PSA, PSA according to age, rise velocity) PCa was detected in more than 25.3% of cases. CONCLUSION: When patients with normal digital rectal examination are selected for prostate biopsy due to tPSA levels above 4 or F/T PSA ratio lower than 15% or PSA velocity higher than 25% per year or high PSA for the age range, the incidence of PCa is quite higher than that observed in a population selected exclusively with basis on total PSA value.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Division of UrologyUNIFESP, EPM, Division of UrologySciEL

Preserving Differential Privacy in Convolutional Deep Belief Networks

The remarkable development of deep learning in medicine and healthcare domain presents obvious privacy issues, when deep neural networks are built on users' personal and highly sensitive data, e.g., clinical records, user profiles, biomedical images, etc. However, only a few scientific studies on preserving privacy in deep learning have been conducted. In this paper, we focus on developing a private convolutional deep belief network (pCDBN), which essentially is a convolutional deep belief network (CDBN) under differential privacy. Our main idea of enforcing epsilon-differential privacy is to leverage the functional mechanism to perturb the energy-based objective functions of traditional CDBNs, rather than their results. One key contribution of this work is that we propose the use of Chebyshev expansion to derive the approximate polynomial representation of objective functions. Our theoretical analysis shows that we can further derive the sensitivity and error bounds of the approximate polynomial representation. As a result, preserving differential privacy in CDBNs is feasible. We applied our model in a health social network, i.e., YesiWell data, and in a handwriting digit dataset, i.e., MNIST data, for human behavior prediction, human behavior classification, and handwriting digit recognition tasks. Theoretical analysis and rigorous experimental evaluations show that the pCDBN is highly effective. It significantly outperforms existing solutions

ALTERNATIVE DESIGN AND ECONOMIC FEASIBILITY OF AN EXPERIMENTAL WHR FOR INTAKE AIR CONDITIONING OF A LARGE INTERNAL COMBUSTION ENGINE

This work presents an alternative design for an experimental waste heat recovery thermal system to be coupled to a large turbocharged internal combustion engine for combustion air conditioning. The goal is to carry out a design of a new thermal system under restricted economic requirements for one of the generators set of Luiz Oscar Rodrigues de Melo Thermoelectric Power Plant. Thereby, a comparison with the original proposal from previous works is also developed in order to demonstrate the differences in terms of thermo-economic design parameters. The waste recovery thermal system produces sufficient chilled water through a single-effect absorption chiller, powered by hot water which is produced by recovering the exhaust gases residual heat to supply cooling applications on the combustion air. The results showed a significant reduction for the chiller capacity demand, from 550 to 185 RT, that would be enough to provide chilled water for 98.72% of the analyzed operation historical period. The economic feasibility indicators reveal the proposal for the alternative waste heat recovery system as the best financial option, presenting a lower investment cost (US$316,793.27 of savings) and a time for capital recovery of 2.14 years, 1.61 years shorter when compared with the initial WHR system

Conservation and Diversity of Influenza A H1N1 HLA-Restricted T Cell Epitope Candidates for Epitope-Based Vaccines

Background: The immune-related evolution of influenza viruses is exceedingly complex and current vaccines against influenza must be reformulated for each influenza season because of the high degree of antigenic drift among circulating influenza strains. Delay in vaccine production is a serious problem in responding to a pandemic situation, such as that of the current H1N1 strain. Immune escape is generally attributed to reduced antibody recognition of the viral hemagglutinin and neuraminidase proteins whose rate of mutation is much greater than that of the internal non-structural proteins. As a possible alternative, vaccines directed at T cell epitope domains of internal influenza proteins, that are less susceptible to antigenic variation, have been investigated. Methodology/Principal Findings: HLA transgenic mouse strains expressing HLA class I A*0201, A*2402, and B*0702, and class II DRB1*1501, DRB1*0301 and DRB1*0401 were immunized with 196 influenza H1N1 peptides that contained residues of highly conserved proteome sequences of the human H1N1, H3N2, H1N2, H5N1, and avian influenza A strains. Fifty-four (54) peptides that elicited 63 HLA-restricted peptide-specific T cell epitope responses were identified by IFN-γ ELISpot assay. The 54 peptides were compared to the 2007-2009 human H1N1 sequences for selection of sequences in the design of a new candidate H1N1 vaccine, specifically targeted to highly-conserved HLA-restricted T cell epitopes. Conclusions/Significance: Seventeen (17) T cell epitopes in PB1, PB2, and M1 were selected as vaccine targets based on sequence conservation over the past 30 years, high functional avidity, non-identity to human peptides, clustered localization, and promiscuity to multiple HLA alleles. These candidate vaccine antigen sequences may be applicable to any avian or human influenza A virus. © 2010 Tan et al