Risk-Adjusted Control Charts: Theory,Methods, and Applications in Health

Control charts, the most popular tool of statistical process control, appeared in the literature to ensure that an industrial process is operating only with natural variability, i.e., under statistical control. In the last decades, control charts have been also widely used to assess the quality of non-industrial processes, such as medicine and public health. Mainly in the last two decades, a modification of standard and advanced control charts appeared in the bibliography to improve the monitoring mainly of medical processes. This is the risk-adjusted control charts which take into consideration the varying health conditions of the patients. These charts are used to monitor certain medical processes such as surgeries, mortality, and doctors’ experience. In this paper, we have tried to present all the risk-adjusted control charts presented in the literature appropriately categorized. The risk-adjusted charts have been grouped into three categories: control charts for continuous variables, control charts for attributes (non-continuous variables), time-weighted control charts. The application of risk-adjusted control charts in practical medical processes is also discussed. This review paper highlights the value of the risk-adjusted control charts.

     

Dissecting the nonlinear response of maize yield to high temperature stress with model‐data integration

Evidence suggests that global maize yield declines with a warming climate, particularly with extreme heat events. However, the degree to which important maize processes such as biomass growth rate, growing season length (GSL) and grain formation are impacted by an increase in temperature is uncertain. Such knowledge is necessary to understand yield responses and develop crop adaptation strategies under warmer climate. Here crop models, satellite observations, survey, and field data were integrated to investigate how high temperature stress influences maize yield in the U.S. Midwest. We showed that both observational evidence and crop model ensemble mean (MEM) suggests the nonlinear sensitivity in yield was driven by the intensified sensitivity of harvest index (HI), but MEM underestimated the warming effects through HI and overstated the effects through GSL. Further analysis showed that the intensified sensitivity in HI mainly results from a greater sensitivity of yield to high temperature stress during the grain filling period, which explained more than half of the yield reduction. When warming effects were decomposed into direct heat stress and indirect water stress (WS), observational data suggest that yield is more reduced by direct heat stress (?4.6 ± 1.0%/°C) than by WS (?1.7 ± 0.65%/°C), whereas MEM gives opposite results. This discrepancy implies that yield reduction by heat stress is underestimated, whereas the yield benefit of increasing atmospheric CO₂ might be overestimated in crop models, because elevated CO₂ brings yield benefit through water conservation effect but produces limited benefit over heat stress. Our analysis through integrating data and crop models suggests that future adaptation strategies should be targeted at the heat stress during grain formation and changes in agricultural management need to be better accounted for to adequately estimate the effects of heat stress.     

Circulating microparticles carry oxidation-specific epitopes and are recognized by natural IgM antibodies

Oxidation-specific epitopes (OSEs) present on apoptotic cells and oxidized low density lipoprotein (OxLDL) represent danger-associated molecular patterns that are recognized by different arcs of innate immunity, including natural IgM antibodies. Here, we investigated whether circulating microparticles (MPs), which are small membrane vesicles released by apoptotic or activated cells, are physiological carriers of OSEs. OSEs on circulating MPs isolated from healthy donors and patients with ST-segment elevation myocardial infarction (STE-MI) were characterized by flow cytometry using a panel of OSE-specific monoclonal antibodies. We found that a subset of MPs carry OSEs on their surface, predominantly malondialdehyde (MDA) epitopes. Consistent with this, a majority of IgM antibodies bound on the surface of circulating MPs were found to have specificity for MDA-modified LDL. Moreover, we show that MPs can stimulate THP-1 (human acute monocytic leukemia cell line) and human primary monocytes to produce interleukin 8, which can be inhibited by a monoclonal IgM with specificity for MDA epitopes. Finally, we show that MDA⁺ MPs are elevated at the culprit lesion site of patients with STE-MI. Our results identify a subset of OSE⁺ MPs that are bound by OxLDL-specific IgM. These findings demonstrate a novel mechanism by which anti-OxLDL IgM antibodies could mediate protective functions in CVD.     

The in vivo preventive and therapeutic properties of curcumin in bile reflux‐related oncogenesis of the hypopharynx

Bile at strongly acidic pH exerts a carcinogenic effect on the hypopharynx, based upon recent pre‐clinical studies that support its role as an independent risk factor. We recently demonstrated in vitro that curcumin can prevent oncogenic profile of bile in human hypopharyngeal cells, by inhibiting NF‐κB. We hypothesize that topically applied curcumin to the hypopharynx can similarly block early oncogenic molecular events of bile, by inhibiting NF‐κB and consequently altering the expression of genes with oncogenic function. Using Mus musculus (C57Bl/6J), we topically applied curcumin (250 μmol/L; three times per day; 10 days) to the hypopharynx, 15 minutes before, 15 minutes after or in combination with bile acids (pH 3.0). Immunohistochemical analysis and qPCR revealed that topically applied curcumin either before, after or in combination with acidic bile exposure significantly suppressed its induced NF‐κB activation in regenerating epithelial cells, and overexpression of Rela, Bcl2, Egfr, Stat3, Wnt5a, Tnf, Il6, Ptgs2. Akt1 was particularly inhibited by curcumin when applied simultaneously with bile. We provide novel evidence into the preventive and therapeutic properties of topically applied curcumin in acidic bile‐induced early oncogenic molecular events in hypopharyngeal mucosa, by inhibiting NF‐κB, and shaping future translational development of effective targeted therapies using topical non‐pharmacologic inhibitors of NF‐κB.     

Body composition determinants of metabolic phenotypes of obesity in nonobese and obese postmenopausal women

Objective : Although obesity is typically associated with increased cardiovascular risk, a subset of obese individuals display a normal metabolic profile (“metabolically healthy obese,” MHO) and conversely, a subset of nonobese subjects present with obesity‐associated cardiometabolic abnormalities (“metabolically obese nonobese,” MONO). The aim of this cross‐sectional study was to identify the most important body composition determinants of metabolic phenotypes of obesity in nonobese and obese healthy postmenopausal women. Design and Methods : We studied a total of 150 postmenopausal women (age 54 ± 7 years, mean ± 1 SD). Based on a cardiometabolic risk score, nonobese (body mass index [BMI] ≤ 27) and obese women (BMI > 27) were classified into “metabolically healthy” and “unhealthy” phenotypes. Total and regional body composition was assessed with dual‐energy X‐ray absorptiometry (DXA). Results : In both obese and nonobese groups, the “unhealthy” phenotypes were characterized by frequent bodyweight fluctuations, higher biochemical markers of insulin resistance, hepatic steatosis and inflammation, and higher anthropometric and DXA‐derived indices of central adiposity, compared with “healthy” phenotypes. Indices of total adiposity, peripheral fat distribution and lean body mass were not significantly different between “healthy” and “unhealthy” phenotypes. Despite having increased fat mass, MHO women exhibited comparable cardiometabolic parameters with healthy nonobese, and better glucose and lipid levels than MONO. Two DXA‐derived indices, trunk‐to‐legs and abdominal‐to‐gluteofemoral fat ratio were the major independent determinants of the “unhealthy” phenotypes in our cohort. Conclusions : The “metabolically obese phenotype” is associated with bodyweight variability, multiple cardiometabolic abnormalities and an excess of central relative to peripheral fat in postmenopausal women. DXA‐derived centrality ratios can discriminate effectively between metabolic subtypes of obesity in menopause.     

Evaluation of Plasma Trace Elements in Different Stages of Nonalcoholic Fatty Liver Disease

Biological Trace Element Research - Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome. Its global prevalence is estimated between 25 and 45%,...     

Highly Infectious CJD Particles Lack Prion Protein but Contain Many Viral‐Linked Peptides by LC‐MS/MS

It is widely believed that host prion protein (PrP), without nucleic acid, converts itself into an infectious form (PrP‐res) that causes transmissible encephalopathies (TSEs), such as human sporadic CJD (sCJD), endemic sheep scrapie, and epidemic BSE. There are many detailed investigations of PrP, but proteomic studies of other proteins in verified infectious TSE particles have not been pursued, even though brain homogenates without PrP retain their complete infectious titer. To define proteins that may be integral to, process, or protect an agent genome, we developed a streamlined, high‐yield purification of infectious FU‐CJD mouse brain particles with minimal PrP. Proteinase K (PK) abolished all residual particle PrP, but did not reduce infectivity, and viral‐size particles lacking PrP were ～70S (vs. 90–120S without PK). Furthermore, over 1,500 non‐PrP proteins were still present and positively identified in high titer FU‐CJD particles without detectable PrP by mass spectrometry (LC‐MS/MS); 114 of these peptides were linked to viral motifs in the environmental–viral database, and not evident in parallel uninfected controls. Host components were also identified in both PK and non‐PK treated particles from FU‐CJD mouse brain and human sCJD brain. This abundant cellular data had several surprises, including finding Huntingtin in the sCJD but not normal human brain samples. Similarly, the neural Wiskott–Aldrich sequence and multivesicular and endosome components associated with retromer APP (Alzheimer amyloid) processing were only in sCJD. These cellular findings suggest that new therapies directed at retromer–vesicular trafficking in other neurodegenerative diseases may also counteract late‐onset sCJD PrP amyloid pathology. J. Cell. Biochem. 115: 2012–2021, 2014. © 2014 Wiley Periodicals, Inc.