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There are currently over 2.5 million breast cancer survivors in the United States and, according to the American Cancer Society, 10 to 20 percent of these women will develop recurrent breast cancer. Early detection of recurrence can avoid unnecessary radical treatment. However, self-examination or mammography screening may not discover a recurring cancer if the number of surviving cancer cells is small, while biopsy is too invasive and cannot be frequently repeated. It is therefore important to identify non-invasive biomarkers that can detect early recurrence. The present paper develops a mathematical model of cancer recurrence. The model, based on a system of partial differential equations, focuses on tissue biomarkers that include the plasminogen system. Among them, only uPAR is known to have significant correlation to its concentration in serum and could therefore be a good candidate for serum biomarker. The model includes uPAR and other associated cytokines and cells. It is assumed that the residual cancer cells that survived primary cancer therapy are concentrated in the same location within a region with a very small diameter. Model simulations establish a quantitative relation between the diameter of the growing cancer and the total uPAR mass in the cancer. This relation is used to identify uPAR as a potential serum biomarker for breast cancer recurrence. [ABSTRACT FROM AUTHOR]

Background: We investigated the correlation between pancreatic ductal adenocarcinoma patient prognosis and the presence of tumour infiltrating lymphocytes and expression of 521 immune system genes. Methods: Intratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochemistry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenectomy. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA). Results: Twenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like receptor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell development); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NFκB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37. Discussion: Tumour infiltrating lymphocytes were present at higher levels in samples from patients with better prognosis. Our findings indicate that tumour infiltrating lymphocyte levels and expression level of the immune system genes listed above influence pancreatic ductal adenocarcinoma prognosis. This information could be used to improve selection of best responders to immune inhibitors. [ABSTRACT FROM AUTHOR]

Background: The possibility of incorporating generics into combination antiretroviral therapy and breaking apart once-daily single-tablet regimens (STRs), may result in less efficacious medications and/or more complex regimens with the expectation of marked monetary savings. A modeling approach that assesses the merits of such policies in terms of lifelong costs and health outcomes using adherence and effectiveness data from real-world U.S. settings. Methods: A comprehensive computer-based microsimulation model was developed to assess the lifetime health (life expectancy and quality adjusted life-years—QALYs) and economic outcomes in HIV-1 infected patients initiating STRs compared with multiple-table regimens including generic medications where possible (gMTRs). The STRs considered included tenofovir disoproxil fumarate/emtricitabine and efavirenz or rilpivirine or elvitegravir/cobicistat. gMTRs substitutions included each counterpart to STRs, including generic lamivudine for emtricitabine and generic versus branded efavirenz. Results: Life expectancy is estimated to be 1.301 years higher (discounted 0.619 QALY gain) in HIV-1 patients initiating a single-tablet regimen in comparison to a generic-based multiple-table regimen. STRs were associated with an average increment of $26,547.43 per patient in medication and $1,824.09 in other medical costs due to longer survival which were partially offset by higher inpatients costs ($12,035.61) with gMTRs treatment. Overall, STRs presented incremental lifetime costs of $16,335.91 compared with gMTRs, resulting in an incremental cost-effectiveness ratio of $26,383.82 per QALY gained. Conclusions: STRs continue to represent good value for money under contemporary cost-effectiveness thresholds despite substantial price reductions of generic medications in the U. S. [ABSTRACT FROM AUTHOR]

Medically implanted devices are becoming increasingly important in medical practice. Over 4 million people in the United States have long-term biomedical implants. However, many medical implants have to be removed because of infection or because their protein coating causes excessive inflammation and decrease in the immune system response. In this work, a discrete twodimensional model of blood cells and bacteria interactions on the surface of a medical implant is transformed into a discrete one-dimensional model. This one dimensional model is then upscaled into a partial differential equation model. The results from the discrete two-dimensional model and the continuous one-dimensional model are then compared for different protein coating mixtures. Two medical treatment alternatives are also explored and the two models are compared again. [ABSTRACT FROM AUTHOR]

Background: Benzene is a common industrial chemical known to induce leukemia and other blood disorders, as well as aneuploidy, in both human blood cells and sperm at exposures > 10 ppm. Recent reports have identified health effects at exposure levels < 1 ppm, the permissible exposure limit (PEL; 8 hr) set by the U.S. Occupational Safety and Health Administration. Objective: We investigated whether occupational exposures to benzene near 1 ppm induce aneuploidy in sperm. Methods: We used multicolor fluorescence in situ hybridization to measure the incidence of sperm with numerical abnormalities of chromosomes X, Y, and 21 among 33 benzene-exposed men and 33 unexposed men from Chinese factories. Individual exposures were assessed using personal air monitoring and urinary concentrations of benzene and trans,trans-muconic acid (E,E-MA). Air benzene concentrations were not detectable in unexposed men; in exposed men, concentrations ranged from below the detection limit to 24 ppm (median, 2.9 ppm), with 27% of exposed men (n = 9) having concentrations of ≥ 1 ppm. Exposed men were categorized into low and high groups based on urinary E,E-MA (median concentrations of 1.9 and 14.4 mg/L, respectively; median air benzene of 1 and 7.7 ppm, respectively), and aneuploidy frequencies were compared with those of unexposed men. Results: Sperm aneuploidy increased across low- and high-exposed groups for disomy X [incidence rate ratio (IRR) = 2.0; 95% confidence interval (CI), 1.1-3.4; and IRR = 2.8; 95% CI, 1.5-4.9, respectively], and for overall hyperhaploidy for the three chromosomes investigated (IRR = 1.6; 95% CI, 1.0-2.4; and IRR = 2.3; 95% CI, 1.5-3.6, respectively). We also found elevated disomy X and hyperhaploidy in the nine men exposed to ≥ 1 ppm benzene compared with unexposed men (IRR = 1.8; 95% CI, 1.1-3.0; and IRR = 2.0; 95% CI, 1.1-3.9, respectively). Conclusions: Benzene appeared to increase the frequencies of aneuploid sperm for chromosomes associated with chromosomal abnormality syndromes in human offspring, even in men whose air benzene exposure was at or below the U.S. permissible exposure limit. [ABSTRACT FROM AUTHOR]

Background and Objectives Exploitation of economies of scale is often argued in favour of blood-bank consolidation into large regional centres, despite a lack of adequate empirical support. This study was aimed at testing the economies of scale hypothesis in a sample of blood centres in the USA. Materials and Methods An input-orientated data envelopment analysis (DEA) was used to calculate the technical efficiency scores of blood centres, and to determine whether they were operating under increasing returns to scale (IRS), constant returns to scale (CRS) or decreasing returns to scale (DRS). Correlation between the blood-centre efficiency score and the demographic and socioeconomic characteristics of the service area was further investigated. Results Seventy-one blood centres were included in the analysis. The scale of operations ranged from 7270 to 275 500 red blood cell (RBC) units per year. Six (8%) centres operated under CRS, 29 (55%) under IRS, and most of their technical inefficiency was scale-independent, and 26 (37%) operated under DRS, and most of their technical inefficiency was size-related. Efficiency scores were unrelated to any demographic or socioeconomic characteristics of the blood centre service area. Conclusions Within the size range of blood centres included in this study, expanding the level of operations beyond a certain point leads to DRS. [ABSTRACT FROM AUTHOR]

Platelets are a heterogeneous small anucleate blood cell population with a central role both in physiological haemostasis and in pathological states, spanning from thrombosis to inflammation, and cancer. Recent advances in proteomic studies provided additional important information concerning the platelet biology and the response of platelets to several pathophysiological pathways. Platelets circulate systemically and can be easily isolated from human samples, making proteomic application very interesting for characterizing the complexity of platelet functions in health and disease as well as for identifying and quantifying potential platelet proteins as biomarkers and novel antiplatelet therapeutic targets. To date, the highly dynamic protein content of platelets has been studied in resting and activated platelets, and several subproteomes have been characterized including platelet-derived microparticles, platelet granules, platelet releasates, platelet membrane proteins, and specific platelet post-translational modifications. In this review, a critical overview is provided on principal platelet proteomic studies focused on platelet biology from signaling to granules content, platelet proteome changes in several diseases, and the impact of drugs on platelet functions. Moreover, recent advances in quantitative platelet proteomics are discussed, emphasizing the importance of targeted quantification methods for more precise, robust and accurate quantification of selected proteins, which might be used as biomarkers for disease diagnosis, prognosis and therapy, and their strong clinical impact in the near future. [ABSTRACT FROM AUTHOR]

Focuses on the identification of a white particulate matter in red blood cell components by the researchers in Atlanta, Georgia. Influence of massive transfusion on causing pulmonary insufficiency; Development of precautionary measures emphasizing the importance of visual inspection of blood and blood components; Analogy with the argument that the decision makers waited for scientific proof before making steps to reduce HIV in the blood supply.