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991.
992.
Oliver Pain Alexandra C. Gillett Jehannine C. Austin Lasse Folkersen Cathryn M. Lewis 《European journal of human genetics : EJHG》2022,30(3):339
There is growing interest in the clinical application of polygenic scores as their predictive utility increases for a range of health-related phenotypes. However, providing polygenic score predictions on the absolute scale is an important step for their safe interpretation. We have developed a method to convert polygenic scores to the absolute scale for binary and normally distributed phenotypes. This method uses summary statistics, requiring only the area-under-the-ROC curve (AUC) or variance explained (R2) by the polygenic score, and the prevalence of binary phenotypes, or mean and standard deviation of normally distributed phenotypes. Polygenic scores are converted using normal distribution theory. We also evaluate methods for estimating polygenic score AUC/R2 from genome-wide association study (GWAS) summary statistics alone. We validate the absolute risk conversion and AUC/R2 estimation using data for eight binary and three continuous phenotypes in the UK Biobank sample. When the AUC/R2 of the polygenic score is known, the observed and estimated absolute values were highly concordant. Estimates of AUC/R2 from the lassosum pseudovalidation method were most similar to the observed AUC/R2 values, though estimated values deviated substantially from the observed for autoimmune disorders. This study enables accurate interpretation of polygenic scores using only summary statistics, providing a useful tool for educational and clinical purposes. Furthermore, we have created interactive webtools implementing the conversion to the absolute (https://opain.github.io/GenoPred/PRS_to_Abs_tool.html). Several further barriers must be addressed before clinical implementation of polygenic scores, such as ensuring target individuals are well represented by the GWAS sample.Subject terms: Personalized medicine, Medical genomics 相似文献
993.
A group of women (n = 38) who met the DSM-III critieria for bulimia and a group of normal control women (n = 26) between the ages of 18–34 were administered the revised version of the Bem Sex Role Inventory (1981) to test the hypothesis that bulimic women are “hyperfeminine” in their sex-role orientation. Both the original and the median split method of scoring the data were employed. The hypothesis was not supported: normal controls scored higher than bulimics on the femininity scale. The findings from both scoring methods reflect a tendency for the bulimic women to systematically score lower than the controls on all sex-typed items resulting in significantly more bulimics in the “undifferentiated” category. This scoring pattern can be understood as an indication of low self-esteem or as a less well-defined sense of self. It was hypothesized that both possibilities would increase these young women's susceptibility to developing bulimic symptoms. 相似文献
994.
Illnesses associated with Escherichia coli O157:H7 infections. A broad clinical spectrum 总被引:29,自引:0,他引:29
P M Griffin S M Ostroff R V Tauxe K D Greene J G Wells J H Lewis P A Blake 《Annals of internal medicine》1988,109(9):705-712
STUDY OBJECTIVE: To describe the spectrum of illnesses associated with Escherichia coli O157:H7 infections. DESIGN: Described an outbreak that showed the broad spectrum of these infections. Reviewed the clinical findings in the other eight major outbreaks reported between 1982 and 1986. Also reviewed reports of sporadic cases. SETTING: Outbreaks in communities, nursing homes, a day care center, and a kindergarten. CASES: Persons identified in outbreaks of E. coli O157:H7 infections. RESULTS: Escherichia coli O157:H7 infection causes bloody diarrhea (hemorrhagic colitis), nonbloody diarrhea, the hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Infection can be asymptomatic, can involve extraintestinal sites, and can be fatal. Bloody diarrhea is the commonest symptom. Most patients have severe abdominal cramps; fever is documented in less than half. Findings from fecal leukocyte examinations often suggest a noninfectious cause. Results of radiologic and colonoscopic examinations can be consistent with a diagnosis of inflammatory bowel disease or ischemic colitis. Patients at the extremes of age are at increased risk for E. coli O157:H7-associated diarrhea, the hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and death. Antimicrobial agents have not been shown to modify the illness, but there are few data on individual agents. CONCLUSION: Infection with E. coli O157:H7 should be considered in all patients with bloody diarrhea, the hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura because the infection can masquerade as gastrointestinal bleeding of noninfectious cause, the antecedent diarrhea may be resolved and forgotten by the time the hemolytic uremic syndrome or thrombotic thrombocytopenic purpura is diagnosed, and the detection of E. coli O157:H7 requires specific stool culture techniques. 相似文献
995.
Left ventricular false tendons in children: Prevalence as detected by 2-dimensional echocardiography and clinical significance 总被引:5,自引:0,他引:5
Lowell W. Perry MD Roger N. Ruckman MD Stephen R. Shapiro MD Karen S. Kuehl MD Frank M. Galioto Jr. MD Lewis P. Scott III MD 《The American journal of cardiology》1983,52(10):1264-1266
During a 28-month period, consecutive 2-dimensional echocardiograms were reviewed to determine the prevalence of left ventricular (LV) false tendons, their associated anomalies and clinical significance. LV false tendons were found in 31 (0.8%) of 3,847 consecutive 2-dimensional echocardiograms. Of 31 LV false tendons, 30 passed longitudinally from papillary muscle to septum and 1 went from free wall to free wall. The 31 patients were aged 1 day to 15 years. Associated heart disease, most often ventricular septal defect, bicuspid aortic valve and coarctation of the aorta, was present in 48%, of whom 73% were girls. Of those without heart disease, 69% were boys. In patients with heart disease, precordial murmurs were due to the underlying cardiac anomaly. Of those without heart disease, 15 of 16 (94%) had a precordial murmur, usually of the Still's type over the lower left sternal border. Four of 31 (13%), 1 with and 3 without heart disease, had unifocal premature ventricular contractions that were rate-dependent in the 2 patients undergoing stress testing. LV false tendons appear to occur in 0.8 % of pediatric patients and usually are accompanied by a Still's type innocent murmur if unassociated with heart disease. Some LV false tendons are associated with rate-dependent premature ventricular contractions. 相似文献
996.
M Kriwisky P Froom M Gross J Ribak B S Lewis 《The American journal of cardiology》1987,59(12):1149-1151
Mitral leaflet motion during systole was studied by echocardiography in 102 healthy young men. Mean posterior maximal leaflet motion was 2 +/- 1 mm behind the CD line on 2-dimensionally (2-D) directed M-mode examination. On the apical 4-chamber cross-sectional view a mean area of 0.34 +/- 0.24 mm2 was contained by the mitral leaflets above the plane of the mitral anulus. Elevated values on the M-mode view (greater than or equal to 4 mm) compared with the 2-D 4-chamber view (greater than or equal to 0.70 mm2) were discordant, with 90% (18 of 20) of the elevated values found in 1 view only. Thus, there is a wide spectrum of mitral leaflet motion in asymptomatic young men. The value of the echocardiogram in diagnosis of mitral valve prolapse is questionable because any cutoff point between normal and abnormal is arbitrary and the degree of motion has not been shown to correlate with morbidity or mortality. 相似文献
997.
To determine whether patients with systemic lupus erythematosus undergoing long-term peritoneal dialysis have persistent clinical and serologic remissions, the clinical courses of eight patients with end-stage renal disease in whom peritoneal dialysis was begun at Rush-Presbyterian-St. Luke's Medical Center between 1981 and 1986 were analyzed. Patients were followed for a mean of 90.1 +/- 28.8 months before dialysis and 20.8 +/- 4.7 months after the initiation of dialysis. Disease activity was quantified for each individual in terms of "flares" per year before and after the initiation of peritoneal dialysis, the means of which were 0.66 +/- 0.46 and 0.94 +/- 0.28, respectively. Comparison of these rates showed no statistical difference. Seven of the eight patients had at least one flare while receiving peritoneal dialysis, all of which required prednisone therapy (mean 31.3 mg per day). The clinical manifestations included fever, rash, myalgias, anemia, leukopenia, serositis, and cerebritis. Eighty-eight percent of these flares had associated worsening of serologic results. Prednisone was discontinued in only one patient at any time during peritoneal dialysis. This experience reveals that patients with lupus continue to show clinical and serologic disease activity and require maintenance prednisone therapy while receiving long-term peritoneal dialysis. 相似文献
998.
J F Lewis A B Hodsman A A Driedger R T Thompson R G McFadden 《The American journal of medicine》1987,83(6):1139-1143
Hypophosphatemia has been shown to cause acute respiratory failure. The mechanism is believed to be due to decreased high-energy substrate availability at the cellular level leading to respiratory muscle dysfunction. However, direct measurement of these substrates has not been previously studied. A patient with hypophosphatemic respiratory failure is described in whom phosphocreatine and pH were continuously monitored using nuclear magnetic resonance spectroscopy. This revealed a defect in muscle metabolism that required several weeks to recover despite prompt correction of the serum phosphate level. 相似文献
999.
1000.
Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP 下载免费PDF全文
Czar MJ Kersh EN Mijares LA Lanier G Lewis J Yap G Chen A Sher A Duckett CS Ahmed R Schwartzberg PL 《Proceedings of the National Academy of Sciences of the United States of America》2001,98(13):7449-7454
We have introduced a targeted mutation in SH2D1A/DSHP/SAP, the gene responsible for the human genetic disorder X-linked lymphoproliferative disease (XLP). SLAM-associated protein (SAP)-deficient mice had normal lymphocyte development, but on challenge with infectious agents, recapitulated features of XLP. Infection of SAP- mice with lymphocyte choriomeningitis virus (LCMV) or Toxoplasma gondii was associated with increased T cell activation and IFN-gamma production, as well as a reduction of Ig-secreting cells. Anti-CD3-stimulated splenocytes from uninfected SAP- mice produced increased IFN-gamma and decreased IL-4, findings supported by decreased serum IgE levels in vivo. The Th1 skewing of these animals suggests that cytokine misregulation may contribute to phenotypes associated with mutation of SH2D1A/SAP. 相似文献