Integrative analysis of the inter-tumoral heterogeneity of triple-negative breast cancer.

Triple-negative breast cancers (TNBC) lack estrogen and progesterone receptors and HER2 amplification, and are resistant to therapies that target these receptors. Tumors from TNBC patients are heterogeneous based on genetic variations, tumor histology, and clinical outcomes. We used high throughput genomic data for TNBC patients (n = 137) from TCGA to characterize inter-tumor heterogeneity. Similarity network fusion (SNF)-based integrative clustering combining gene expression, miRNA expression, and copy number variation, revealed three distinct patient clusters. Integrating multiple types of data resulted in more distinct clusters than analyses with a single datatype. Whereas most TNBCs are classified by PAM50 as basal subtype, one of the clusters was enriched in the non-basal PAM50 subtypes, exhibited more aggressive clinical features and had a distinctive signature of oncogenic mutations, miRNAs and expressed genes. Our analyses provide a new classification scheme for TNBC based on multiple omics datasets and provide insight into molecular features that underlie TNBC heterogeneity

Correlation of ciprofloxacin resistance with the AdeABC efflux system in Acinetobacter baumannii clinical isolates

Background: Acinetobacter baumannii is one of the most important pathogens capable of colonization in burn patients, leading to drug-resistant wound infections. This study evaluated the distribution of the AdeABC efflux system genes and their relationship to ciprofloxacin resistance in A. baumannii isolates collected from burn patients. Methods: A total of 68 A. baumannii clinical strains were isolated from patients hospitalized in Motahari Burns Center in Tehran, Iran. Ciprofloxacin susceptibility was tested by the disk diffusion and agar dilution methods. PCR amplification of the adeRS-adeB drug efflux genes was performed for all resistant and susceptible isolates. To assess the role of the drug efflux pump in ciprofloxacin susceptibility, carbonyl cyanide 3-chlorophenylhydrazone (CCCP) was used as an efflux pump inhibitor (EPI). Results: Approximately 95.6% of the Acinetobacter isolates were resistant to ciprofloxacin, with minimum inhibitory concentration (MIC) values ranging from 4 to ≥128 μg/mL. The susceptibility of 86.1% of the resistant isolates increased by factors of 2 to 64 in the presence of CCCP. All resistant isolates were positive for the adeRS-adeB genes, and 73.2% of them had mutations in the AdeRS regulatory system. Conclusions: The results showed that AdeABC genes are common in A. baumannii, which might be associated with ciprofloxacin non-susceptibility, as indicated by the observed linkage to the presence of the genes essential for the activity of the AdeABC, several single mutations occurring in the adeRS regulatory system, and an increase of ciprofloxacin susceptibility in the presence of a CCCP EPI. © The Korean Society for Laboratory Medicin

Return to work after trauma: A survival analysis

Purpose To evaluate the return to work (RTW) rate, time and predictors among trauma patients using survival analysis. Methods This cohort study was conducted with a three-month follow-up on 300 trauma patients hospitalized in Shahid Beheshti Hospital, Kashan, Iran in 2014. The data were collected through conducting interviews and referring to patients' medical records during their hospital stay and follow-up information at one & three months after discharge from hospital. Final analysis was conducted on the data retrieved from 273 patients. Data were analyzed by chi-square test, Mann–Whitney U test and survival analysis method. Results The rate of RTW at the end of the first and the third follow-up months was respectively 21.6% and 61.2%. Survival analysis showed that the RTW time (Time between admission to first return to work) was significantly longer among patients with illiteracy, drug abuse, hospitalization history in the intensive care unit, low socioeconomic status, non-insurance coverage, longer hospital stay, multiple and severe injuries as well as severe disability. Conclusion Our findings indicated that trauma has profound effects on the rate and time of RTW. Besides disability, many personal and clinical factors can affect the outcome of RTW

Need for redefining needs

Defining needs is difficult due to the inherent complexity of the concept of 'need', so it is not surprising that numerous definitions have been proposed. 'Health' consists of a wide range of characteristics so 'health needs' ought to include personal and social care, health care, accommodation, finance, education, employment and leisure, transport and access.Target-driven standards in areas of health care with a high political profile appear to be replacing the concept of universal provision and clinical need; this major change in clinical care warrants a re-evaluation of health care outcomes. Identifying who might benefit from this new approach to health care is equally important if scarce resources are to be fully and appropriately utilised. If the goal of care is 'optimal health', the key marker of success ought to be to ascertain individual patients' health care needs (HCN) and tailor services accordingly. Wide variation in the description of 'needs' directly affects policies and services intended to meet a population's health care needs. Consequently, the definition of 'needs' has important implications for healthcare provision- the more constrained the definition, the less healthcare will be made available and vice versa. This paper describes some common definitions of needs and discusses their respective benefits and disadvantages in terms of health care provision and their potential impact on health polic

Is quality of life measurement likely to be a proxy for health needs assessment in patients with coronary artery disease?

BACKGROUND: The identification of patients' health needs is pivotal in optimising the quality of health care, increasing patient satisfaction and directing resource allocation. Health needs are complex and not so easily evaluated as health-related quality of life (HRQL), which is becoming increasingly accepted as a means of providing a more global, patient-orientated assessment of the outcome of health care interventions than the simple medical model. The potential of HRQL as a surrogate measure of healthcare needs has not been evaluated. OBJECTIVES AND METHOD: A generic (Short Form-12; SF-12) and a disease-specific questionnaire (Seattle Angina Questionnaire; SAQ) were tested for their potential to predict health needs in patients with acute coronary disease. A wide range of healthcare needs were determined using a questionnaire specifically developed for this purpose. RESULTS: With the exception of information needs, healthcare needs were highly correlated with health-related quality of life. Patients with limited enjoyment of personal interests, weak financial situation, greater dependency on others to access health services, and dissatisfaction with accommodation reported poorer HRQL (SF-12: p < 0.001; SAQ: p < 0.01). Difficulties with mobility, aids to daily living and activities requiring assistance from someone else were strongly associated with both generic and disease-specific questionnaires (SF-12: r = 0.46-0.55, p < 0.01; SAQ: r = 0.53-0.65, p < 0.001). Variables relating to quality of care and health services were more highly correlated with SAQ components (r = 0.33-0.59) than with SF-12 (r = 0.07-0.33). Overall, the disease-specific Seattle Angina Questionnaire was superior to the generic Short Form-12 in detecting healthcare needs in patients with coronary disease. Receiver-operator curves supported the sensitivity of HRQL tools in detecting health needs. CONCLUSION: Healthcare needs are complex and developing suitable questionnaires to measure these is difficult and time-consuming. Without a satisfactory means of measuring these needs, the extent to which disease impacts on health will continue to be underestimated. Further investigation on larger populations is warranted but HRQL tools appear to be a reasonable proxy for healthcare needs, as they identify the majority of needs in patients with coronary disease, an observation not previously reported in this patient grou

The obscured X-ray source population in the HELLAS2XMM survey: the Spitzer view

Recent X-ray surveys have provided a large number of high-luminosity, obscured Active Galactic Nuclei (AGN), the so-called Type 2 quasars. Despite the large amount of multi-wavelength supporting data, the main parameters related to the black holes harbored in such AGN are still poorly known. Here we present the results obtained for a sample of eight Type 2 quasars in the redshift range 0.9-2.1 selected from the HELLAS2XMM survey, for which we used Ks-band, Spitzer IRAC and MIPS data at 24 micron to estimate bolometric corrections, black hole masses, and Eddington ratios.Comment: 6 pages, to appear in "The Multicoloured Landscape of Compact Objects and their Explosive Progenitors: Theory vs Observations" (Cefalu, Sicily, June 2006). Eds. L. Burderi et al. (New York: AIP

Asymptotic solutions for turbulent mass transfer at high Schmidt number

International audienceThis paper introduces a new methodology for the complexity analysis of higher-order functional programs, which is based on three ingredients: a powerful type system for size analysis and a sound type inference procedure for it, a ticking monadic transformation, and constraint solving. Noticeably, the presented methodology can be fully automated, and is able to analyse a series of examples which cannot be handled by most competitor methodologies. This is possible due to the choice of adopting an abstract index language and index polymorphism at higher ranks. A prototype implementation is available

Adaptation of the MacNew quality of life questionnaire after myocardial infarction in an Iranian population

BACKGROUND: Health-related quality of life (HRQL) assessment is an important measure of the impact of a wide range of disease process on an individual. To date, no HRQL tool has been evaluated in an Iranian population with cardiovascular disorders, specifically myocardial infarction, a major cause of mortality and morbidity. The MacNew Heart Disease Health-related Quality of Life instrument is a disease-specific HRQL questionnaire with satisfactory validity and reliability when applied cross-culturally. METHOD: A Persian version of MacNew was prepared by both forward and backward translation by bilinguals after which a feasibility test was performed. Consecutive patients (n = 51) admitted to a coronary care unit with acute myocardial infarction were recruited for measurement of their HRQL with retest one month after discharge in the follow-up clinic. Principal components analysis, intra-class correlation reliability, internal consistency, and test-retest reliability were assessed. RESULTS: Trivial rates of missing data confirmed the acceptability of the tool. Principal component analysis revealed that the three domains, emotional, social and physical, performed as well as in the original studies. Internal consistency was high and comparable to other studies, ranging from 0.92 for the emotional and physical domains, to 0.94 for the social domain, and to 0.95 for the Global score. Domain means of 5, 5.3 and 4.9 for emotional, physical and social respectively indicate that our Iranian population has similar emotional and physical but worse social HRQL scores. Test-retest analysis showed significant correlation in emotional and physical domains (P < 0.05). CONCLUSION: The Persian version of the MacNew questionnaire is comparable to the English version. It has high internal consistency and reasonable reproducibility, making it an appropriate specific quality of life tool for population-based studies and clinical practice in Iran in patients who have survived an acute myocardial infraction. Further studies are needed to confirm its validity in larger populations with cardiovascular diseas

Asymptotic solutions for turbulent mass transfer at high Schmidt number

We present closed-form solutions for high Schmidt number mass transfer in a hydrodynamically fully developed turbulent flow. Governing equations for the near- and far-field are developed for a large class of boundary conditions (BCs) for which the mass flux is a function of the concentration at the wall. We show that for this class of BCs, which includes nonlinear wall reactions, the mass transfer coefficient is independent of the BC and the Sherwood correlation is therefore universal. For Dirichlet, Neumann and Robin BCs, the far-field solutions are in good correspondence with the method of separating variables and near-field solutions are in good agreement with numerical simulations. However, in contrast with the far-field solutions, the Sherwood correlation in the near-field depends on the specific BC. As an example of nonlinear BCs, solutions for a second-order wall reaction are derived which are compared with numerical simulations and found to be in excellent agreement.</jats:p