Nasa desalting kit development, phase ii first progress report

NASA desalting kit development - container and processor desig

Reconciling Utility with Privacy in Genomics

Direct-to-consumer genetic testing makes it possible for everyone to learn their genome sequences. In order to contribute to medical research, a growing number of people publish their genomic data on the Web, sometimes under their real identities. However, this is at odds not only with their own privacy but also with the privacy of their relatives. The genomes of relatives being highly correlated, some family members might be opposed to revealing any of the family's genomic data. In this paper, we study the trade-off between utility and privacy in genomics. We focus on the most relevant kind of variants, namely single nucleotide polymorphisms (SNPs). We take into account the fact that the SNPs of an individual contain information about the SNPs of his family members and that SNPs are correlated with each other. Furthermore, we assume that SNPs can have different utilities in medical research and different levels of sensitivity for individuals. We propose an obfuscation mechanism that enables the genomic data to be publicly available for research, while protecting the genomic privacy of the individuals in a family. Our genomic-privacy preserving mechanism relies upon combinatorial optimization and graphical models to optimize utility and meet privacy requirements. We also present an extension of the optimization algorithm to cope with the non-linear constraints induced by the correlations between SNPs. Our results on real data show that our proposed technique maximizes the utility for genomic research and satisfies family members' privacy constraints

Expression of CXCL10 is associated with response to radiotherapy and overall survival in squamous cell carcinoma of the tongue

Five-year survival for patients with oral cancer has been disappointingly stable during the last decades, creating a demand for new biomarkers and treatment targets. Lately, much focus has been set on immunomodulation as a possible treatment or an adjuvant increasing sensitivity to conventional treatments. The objective of this study was to evaluate the prognostic importance of response to radiotherapy in tongue carcinoma patients as well as the expression of the CXC-chemokines in correlation to radiation response in the same group of tumours. Thirty-eight patients with tongue carcinoma that had received radiotherapy followed by surgery were included. The prognostic impact of pathological response to radiotherapy, N-status, T-stage, age and gender was evaluated using Cox's regression models, Kaplan-Meier survival curves and chi-square test. The expression of 23 CXC-chemokine ligands and their receptors were evaluated in all patients using microarray and qPCR and correlated with response to treatment using logistic regression. Pathological response to radiotherapy was independently associated to overall survival with a 2-year survival probability of 81 % for patients showing a complete pathological response, while patients with a non-complete response only had a probability of 42 % to survive for 2 years (p = 0.016). The expression of one CXC-chemokine, CXCL10, was significantly associated with response to radiotherapy and the group of patients with the highest CXCL10 expression responded, especially poorly (p = 0.01). CXCL10 is a potential marker for response to radiotherapy and overall survival in patients with squamous cell carcinoma of the tongue

Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials

Temporal blastemal cell gene expression analysis in the kidney reveals new Wnt and related signaling pathway genes to be essential for Wilms' tumor onset

Wilms' tumors (WTs) originate from metanephric blastema cells that are unable to complete differentiation, resulting in triphasic tumors composed of epithelial, stromal and blastemal cells, with the latter harboring molecular characteristics similar to those of the earliest kidney development stages. Precise regulation of Wnt and related signaling pathways has been shown to be crucial for correct kidney differentiation. In this study, the gene expression profile of Wnt and related pathways was assessed in laser-microdissected blastemal cells in WTs and differentiated kidneys, in human and in four temporal kidney differentiation stages (i.e. E15.5, E17.5, P1.5 and P7.5) in mice, using an orthologous cDNA microarray platform. A signaling pathway-based gene signature was shared between cells of WT and of earliest kidney differentiation stages, revealing genes involved in the interruption of blastemal cell differentiation in WT. Reverse transcription-quantitative PCR showed high robustness of the microarray data demonstrating 75 and 56% agreement in the initial and independent sample sets, respectively. The protein expression of CRABP2, IGF2, GRK7, TESK1, HDGF, WNT5B, FZD2 and TIMP3 was characterized in WTs and in a panel of human fetal kidneys displaying remarkable aspects of differentiation, which was recapitulated in the tumor. Taken together, this study reveals new genes candidate for triggering WT onset and for therapeutic treatment targets

Gastric bypass versus best medical treatment for diabetic kidney disease: 5 years follow up of a single-centre open label randomised controlled trial

BACKGROUND: We compared the albuminuria-lowering effects of Roux-en-Y gastric bypass (RYGB) to best medical treatment in patients with diabetic kidney disease and obesity to determine which treatment is better. METHODS: A 5 year, open-label, single-centre, randomised trial studied patients with diabetic kidney disease and class I obesity after 1:1 randomization to best medical treatment (n = 49) or RYGB (n = 51). The primary outcome was the proportion of patients achieving remission of microalbuminuria after 5 years. Secondary outcomes included improvements in diabetic kidney disease, glycemic control, quality of life, and safety. For efficacy outcomes, we performed an intention-to-treat (ITT) analysis. This study was registered with ClinicalTrials.gov, NCT01821508. FINDINGS: 88% of patients (44 per arm) completed 5-year follow-up. Remission of albuminuria occurred in 59.6% (95% CI = 45.5–73.8) after best medical treatment and 69.7% (95% CI = 59.6–79.8) after RYGB (risk difference: 10%, 95% CI, −7 to 27, P = 0.25). Patients after RYGB were twice as likely to achieve an HbA1c ≤ 6.5% (60.2% versus 25.4%, risk difference, 34.9%; 95% CI = 15.8–53.9, P < 0.001). Quality of life after five years measured by the 36-Item Short Form Survey questionnaire (standardized to a 0-to-100 scale) was higher in the RYGB group than in the best medical treatment group for several domains. The mean differences were 13.5 (95% CI, 5.5–21.6, P = 0.001) for general health, 19.7 (95% CI, 9.1–30.3, P < 0.001) for pain, 6.1 (95% CI, −4.8 to 17.0, P = 0.27) for social functioning, 8.3 (95% CI, 0.23 to 16.3, P = 0.04) for emotional well-being, 12.2 (95% CI, 3.9–20.4, P = 0.004) for vitality, 16.8 (95% CI, −0.75 to 34.4, P = 0.06) for mental health, 21.8 (95% CI, 4.8–38.7, P = 0.01) for physical health and 11.1 (95% CI, 2.24–19.9, P = 0.01) for physical functioning. Serious adverse events were experienced in 7/46 (15.2%) after best medical treatment and 11/46 patients (24%) after RYGB (P = 0.80). INTERPRETATION: Albuminuria remission was not statistically different between best medical treatment and RYGB after 5 years in participants with diabetic kidney disease and class 1 obesity, with 6–7 in ten patients achieving remission of microalbuminuria (uACR <30 mg/g) in both groups. RYGB was superior in improving glycemia, diastolic blood pressure, lipids, body weight, and quality of life. FUNDING: The study was supported by research grants from Johnson & Johnson Brasil, Oswaldo Cruz German Hospital, and by grant 12/YI/B2480 from Science Foundation Ireland (Dr le Roux) and grant 2015-02733 from the Swedish Medical Research Council (Dr le Roux). Dr Pereira was funded by the Chevening Scholarship Programme (Foreign and Commonwealth Office, UK)

Elastic Wave Scattering from a Rough Strip-Like Crack

Ultrasonic nondestructive testing is a widely used method for searching for defects, e.g. cracks, in the nuclear power industry. Even though the method can be considered as wellestablished the theoretical understanding is far from complete, especially when more complicated situations are considered. Consequently, it is advantageous to have access to a good mathematical model of the testing procedure. Such a model can, for instance, be used to perform parametric studies, to develop testing procedures, for qualification purposes, and for education. Furthermore, systematic use of a well tested and validated simulation program will most likely result in a better physical understanding of the process. It should also be emphasized that experimental work is a very expensive alternative to mathematical modeling

Role of DNA methylation in head and neck cancer

Head and neck cancer (HNC) is a heterogenous and complex entity including diverse anatomical sites and a variety of tumor types displaying unique characteristics and different etilogies. Both environmental and genetic factors play a role in the development of the disease, but the underlying mechanism is still far from clear. Previous studies suggest that alterations in the genes acting in cellular signal pathways may contribute to head and neck carcinogenesis. In cancer, DNA methylation patterns display specific aberrations even in the early and precancerous stages and may confer susceptibility to further genetic or epigenetic changes. Silencing of the genes by hypermethylation or induction of oncogenes by promoter hypomethylation are frequent mechanisms in different types of cancer and achieve increasing diagnostic and therapeutic importance since the changes are reversible. Therefore, methylation analysis may provide promising clinical applications, including the development of new biomarkers and prediction of the therapeutic response or prognosis. In this review, we aimed to analyze the available information indicating a role for the epigenetic changes in HNC

Impact of the COVID-19 pandemic on total, sex- and age-specific all-cause mortality in 20 countries worldwide during 2020: results from the C-MOR project

Background To understand the impact of the COVID-19 pandemic on mortality, this study investigates overall, sex- and age-specific excess all-cause mortality in 20 countries, during 2020. Methods Total, sex- and age-specific weekly all-cause mortality for 2015–2020 was collected from national vital statistics databases. Excess mortality for 2020 was calculated by comparing weekly 2020 observed mortality against expected mortality, estimated from historical data (2015–2019) accounting for seasonality, long- and short-term trends. Crude and age-standardized rates were analysed for total and sex-specific mortality. Results Austria, Brazil, Cyprus, England and Wales, France, Georgia, Israel, Italy, Northern Ireland, Peru, Scotland, Slovenia, Sweden, and the USA displayed substantial excess age-standardized mortality of varying duration during 2020, while Australia, Denmark, Estonia, Mauritius, Norway, and Ukraine did not. In sex-specific analyses, excess mortality was higher in males than females, except for Slovenia (higher in females) and Cyprus (similar in both sexes). Lastly, for most countries substantial excess mortality was only detectable (Austria, Cyprus, Israel, and Slovenia) or was higher (Brazil, England and Wales, France, Georgia, Italy, Northern Ireland, Sweden, Peru and the USA) in the oldest age group investigated. Peru demonstrated substantial excess mortality even in the <45 age group. Conclusions This study highlights that excess all-cause mortality during 2020 is context dependent, with specific countries, sex- and age-groups being most affected. As the pandemic continues, tracking excess mortality is important to accurately estimate the true toll of COVID-19, while at the same time investigating the effects of changing contexts, different variants, testing, quarantine, and vaccination strategies