Ralph B. D'Agostino

Bio: Ralph B. D'Agostino is an academic researcher from Wake Forest University. The author has contributed to research in topics: Framingham Heart Study & Framingham Risk Score. The author has an hindex of 226, co-authored 1287 publications receiving 229636 citations. Previous affiliations of Ralph B. D'Agostino include VA Boston Healthcare System & University of Illinois at Urbana–Champaign.

Dietary Patterns of Women Are Associated with Incident Abdominal Obesity but Not Metabolic Syndrome

Abstract: Data on the relationship between empirical dietary patterns and metabolic syndrome (MetS) and its components in prospective study designs are limited. In addition, demographic and lifestyle determinants of MetS may modify the association between dietary patterns and the syndrome. We prospectively examined the relationship between empirically derived patterns and MetS and MetS components among 1146 women in the Framingham Offspring/Spouse cohort. They were aged 25–77 y with BMI ≥18.5 kg/m2 and free of cardiovascular disease, diabetes, cancer, and MetS at baseline, and followed for a mean of 7 y. Five dietary patterns, Heart Healthier, Lighter Eating, Wine and Moderate Eating, Higher Fat, and Empty Calorie, were previously identified using cluster analysis from food intake collected using a FFQ. After adjusting for potential confounders, we observed lower odds for abdominal obesity for Higher Fat [OR = 0.48 (95% CI: 0.25, 0.91)] and Wine and Moderate Eating clusters [OR = 0.28 (95% CI: 0.11, 0.72)] compared with the Empty Calorie cluster. Additional adjustment for BMI somewhat attenuated these OR [Higher Fat OR = 0.52 (95% CI: 0.27, 1.00); Wine and Moderate Eating OR = 0.34 (95% CI: 0.13, 0.89)]. None of the clusters was associated with MetS or other MetS components. Baseline smoking status and age did not modify the relation between dietary patterns and MetS. The Higher Fat and Wine and Moderate Eating patterns showed an inverse association with abdominal obesity; certain foods might be targeted in these habitual patterns to achieve optimal dietary patterns for MetS prevention.

Increase in Prevalence of Diabetic Ketoacidosis at Diagnosis Among Youth With Type 1 Diabetes: The SEARCH for Diabetes in Youth Study.

Abstract: OBJECTIVE We previously reported a high (˜30%) but stable prevalence of diabetic ketoacidosis (DKA) at youth-onset diagnosis of type 1 diabetes (2002 and 2010). Given the changing demographics of youth-onset type 1 diabetes, we sought to evaluate temporal trends in the prevalence of DKA at diagnosis of type 1 diabetes from 2010 to 2016 among youth <20 years of age and evaluate whether any change observed was associated with changes in sociodemographic distribution of those recently diagnosed. RESEARCH DESIGN AND METHODS We calculated prevalence of DKA within 1 month of type 1 diabetes diagnosis by year and evaluated trends over time (2010-2016) (n = 7,612 incident diabetes cases; mean [SD] age 10.1 [4.5] at diagnosis). To assess whether trends observed were attributable to the changing distribution of sociodemographic factors among youth with incident type 1 diabetes, we estimated an adjusted relative risk (RR) of DKA in relation to calendar year, adjusting for age, sex, race/ethnicity, income, education, health insurance status, language, season of diagnosis, and SEARCH for Diabetes in Youth Study site. RESULTS DKA prevalence increased from 35.3% (95% CI 32.2, 38.4) in 2010 to 40.6% (95% CI 37.8, 43.4) in 2016 (Ptrend = 0.01). Adjustment for sociodemographic factors did not substantively change the observed trends. We observed a 2% annual increase in prevalence of DKA at or near diagnosis of type 1 diabetes (crude RR 1.02 [95% CI 1.01, 1.04] and adjusted RR 1.02 [95% CI 1.01, 1.04]; P = 0.01 for both). CONCLUSIONS Prevalence of DKA at or near type 1 diabetes diagnosis has increased from 2010 to 2016, following the high but stable prevalence observed from 2002 to 2010. This increase does not seem to be attributable to the changes in distribution of sociodemographic factors over time.

Development of health risk appraisal functions in the presence of multiple indicators: the Framingham Study nursing home institutionalization model.

Abstract: A health risk appraisal function is a mathematical model designed to estimate the risk or probability of a person's mortality or morbidity for various diseases based upon risk factors such as age, medical history and smoking behaviour. The Framingham Study has contributed substantially to the development and use of these for endpoints such as mortality and incidence of coronary heart disease and other cardiovascular diseases. This paper discusses a methodology for the development of health risk appraisal functions when the number of potential risk factors is large and illustrates it with sex specific functions for nursing home institutionalization. The methodology involves grouping variables substantively into sets, applying principal component factor analysis and variable clustering to obtain substantively meaningful composite scores, ranking these in order of substantive importance, and then entering these with a hierarchical ordering into a Cox proportional hazard regression.

Interferon Beta and Interferon Alpha 2a Differentially Protect Head and Neck Cancer Cells from Vesicular Stomatitis Virus-Induced Oncolysis

Abstract: Oncolytic viruses (OV) preferentially kill cancer cells due in part to defects in their antiviral responses upon exposure to type I interferons (IFNs). However, IFN responsiveness of some tumor cells confers resistance to OV treatment. The human type I IFNs include one IFN-β and multiple IFN-α subtypes that share the same receptor but are capable of differentially inducing biological responses. The role of individual IFN subtypes in promoting tumor cell resistance to OV is addressed here. Two human IFNs which have been produced for clinical use, IFN-α2a and IFN-β, were compared for activity in protecting human head and neck squamous cell carcinoma (HNSCC) lines from oncolysis by vesicular stomatitis virus (VSV). Susceptibility of HNSCC lines to killing by VSV varied. VSV infection induced increased production of IFN-β in resistant HNSCC cells. When added exogenously, IFN-β was significantly more effective at protecting HNSCC cells from VSV oncolysis than was IFN-α2a. In contrast, normal keratinocytes and endothelial cells were protected equivalently by both IFN subtypes. Differential responsiveness of tumor cells to IFN-α and -β was further supported by the finding that autocrine IFN-β but not IFN-α promoted survival of HNSCC cells during persistent VSV infection. Therefore, IFN-α and -β differentially affect VSV oncolysis, justifying the evaluation and comparison of IFN subtypes for use in combination with VSV therapy. Pairing VSV with IFN-α2a may enhance selectivity of oncolytic VSV therapy for HNSCC by inhibiting VSV replication in normal cells without a corresponding inhibition in cancer cells. IMPORTANCE There has been a great deal of progress in the development of oncolytic viruses. However, a major problem is that individual cancers vary in their sensitivity to oncolytic viruses. In many cases this is due to differences in their production and response to interferons (IFNs). The experiments described here compared the responses of head and neck squamous cell carcinoma cell lines to two IFN subtypes, IFN-α2a and IFN-β, in protection from oncolytic vesicular stomatitis virus. We found that IFN-α2a was significantly less protective for cancer cells than was IFN-β, whereas normal cells were equivalently protected by both IFNs. These results suggest that from a therapeutic standpoint, selectivity for cancer versus normal cells may be enhanced by pairing VSV with IFN-α2a.

Antibiotic treatment and survival of nursing home patients with lower respiratory tract infection: a cross-national analysis

Abstract: PURPOSE Although lower respiratory tract infections are a leading cause of death in frail elderly patients, few studies have compared treatments and outcomes. We assessed the effects of different antibiotic treatment strategies on survival of elderly nursing home residents with lower respiratory tract infections in the United States and the Netherlands, where treatment approaches are quite different. METHODS We combined data from 2 prospective cohort studies of lower respira- tory tract infections conducted in 36 nursing homes in the United States and 61 in the Netherlands. We included residents whose infections were treated with anti- biotics: 806 in the United States and 415 in the Netherlands. Outcome measures were 1-month and 3-month mortality. We used logistic regression to adjust for differing illness severity. RESULTS Dutch residents had higher mortality than US residents (28.1% vs 15.1% at 1 month, respectively; P <.001). After adjusting for illness severity with logistic regression, the differences between the Dutch and US populations were not signifi - cant (odds ratio 1.34; 95% confi dence interval, 0.94-1.90). Predicted mortality was overestimated for more severely ill US residents at 1 month but not at 3 months. No antibiotic regimen was consistently associated with increased or decreased mortality. CONCLUSION Despite differences in illness severity and treatment, adjusted mortality did not differ between the 2 countries. Although we cannot exclude a short-term survival benefi t from more aggressive treatment in the United States, differences in baseline health appear prognostically more important than the type of antibiotic treatment.

G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences

Abstract: G*Power (Erdfelder, Faul, & Buchner, 1996) was designed as a general stand-alone power analysis program for statistical tests commonly used in social and behavioral research. G*Power 3 is a major extension of, and improvement over, the previous versions. It runs on widely used computer platforms (i.e., Windows XP, Windows Vista, and Mac OS X 10.4) and covers many different statistical tests of thet, F, and χ2 test families. In addition, it includes power analyses forz tests and some exact tests. G*Power 3 provides improved effect size calculators and graphic options, supports both distribution-based and design-based input modes, and offers all types of power analyses in which users might be interested. Like its predecessors, G*Power 3 is free.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.