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- Lang, T. F., et al.
(författare)
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Age-related loss of proximal femoral strength in elderly men and women: The Age Gene/Environment Susceptibility Study - Reykjavik
- 2012
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 50:3, s. 743-748
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Tidskriftsartikel (refereegranskat)abstract
- The risk of hip fracture rises rapidly with age, and is particularly high in women. This increase in fracture risk reflects both the age-related change in the risk of falling and decrements in the strength of the proximal femur. To better understand the extent to which proximal femoral density, structure and strength change with age as a function of gender, we have carried out a longitudinal analysis of proximal femoral volumetric quantitative computed tomographic (vQCT) images in men and women, analyzing changes in trabecular and cortical bone properties, and using subject-specific finite element modeling (FEM) to estimate changes in bone strength. In the AGES-Reykjavik Study vQCT scans of the hip were performed at a baseline visit in 2002-2006 and at a second visit 5.05 +/- 0.25 years later. From these, 223 subjects (111 men, 112 women, aged 68-87 years) were randomly selected. The subjects were evaluated for longitudinal changes in three bone variables assessed in a region similar to the total femur region quantified by DXA: areal bone mineral density (aBMD), trabecular volumetric bone mineral density (tBMD) and the ratio of cortical to total tissue volume (cvol/ivol). They were also evaluated for changes in bone strength using FEM models of the left proximal femur. Models were analyzed under single-limb stance loading (F-Stance), which approximates normal physiologic loading of the hip, as well as a load approximating a fall onto the posterolateral aspect of the greater trochanter (F-Fall). We computed five-year absolute and percentage changes in aBmD, tBMD, cvol/ivol, F-Fall and F-Stance. The Mann-Whitney Test was employed to compare changes in bone variables between genders and the Wilcoxon Signed Rank Test was used to compare changes in bone strength between loading conditions. Multiple (linear) regression was employed to determine the association of changes in F-Fall and F-Stance with baseline age and five-year weight loss. Both men and women showed declines in indices of proximal femoral density and structure (aBMD: men -3.9 +/- 6.0%, women -6.1 +/- 6.2%; tBMD: men -14.8 +/- 20.3%, women -23.9 +/- 26.8%; cvol/ivol: men -2.6 +/- 4.6%, women -4.7 +/- 4.8%, gender difference: p<0.001). Both men and women lost bone strength in each loading condition (F-Stance: men -4.2 +/- 9.9%, women -8.3 +/- 8.5%; F-Fall: men -7.0 +/- 15.7%, women -12.8 +/- 13.2%; all changes from baseline p<0.0001). The gender difference in bone strength loss was statistically significant in both loading conditions (p<0.001 for F-Stance and P<0.01 for F-Fall) and F-Fall, was lost at a higher rate than F-Stance in men (p<0.01) and women (p<0.0001). The gender difference in strength loss was statistically significant after adjustment for baseline age and weight loss in both loading conditions (p<0.01). In these multi-linear models, men showed increasing rates of bone loss with increasing age (F-Fall: p=0.002; F-Stance; p=0.03), and women showed increasing bone strength loss with higher degrees of weight loss (F-Stance: p=0.003). The higher loss of F-Fall compared to F-Stance supports previous findings in animal and human studies that the sub-volumes of bone stressed under normal physiologic loading are relatively better protected in aging. The gender difference in hip bone strength loss is consistent with the higher incidence of hip fractureamong elderly women. (C) 2011 Elsevier Inc. All rights reserved.
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- Li, W, et al.
(författare)
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Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL
- 2020
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1, s. 63-
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Tidskriftsartikel (refereegranskat)abstract
- Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype.
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- Keyak, J. H., et al.
(författare)
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Effect of finite element model loading condition on fracture risk assessment in men and women: The AGES-Reykjavik study
- 2013
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 57:1, s. 18-29
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Tidskriftsartikel (refereegranskat)abstract
- Proximal femoral (hip) strength computed by subject-specific CT scan-based finite element (FE) models has been explored as an improved measure for identifying subjects at risk of hip fracture. However, to our knowledge, no published study has reported the effect of loading condition on the association between incident hip fracture and hip strength. In the present study, we performed a nested age- and sex-matched case-control study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort Baseline (pre-fracture) quantitative CT (QCT) scans of 5500 older male and female subjects were obtained. During 4-7 years follow-up, 51 men and 77 women sustained hip fractures. Ninety-seven men and 152 women were randomly selected as controls from a pool of age- and sex-matched subjects. From the QCT data, FE models employing nonlinear material properties computed FE-strength of the left hip of each subject in loading from a fall onto the posterolateral (F-PL), posterior (F-P) and lateral (F-L) aspects of the greater trochanter (patent pending). For comparison, FE strength in stance loading (F-Stance) and total femur areal bone mineral density (aBMD) were also computed. For all loading conditions, the reductions in strength associated with fracture in men were more than twice those in women (p <= 0.01). For fall loading specifically, posterolateral loading in men and posterior loading in women were most strongly associated with incident hip fracture. After adjusting for aBMD, the association between F-P and fracture in women fell short of statistical significance (p = 0.08), indicating that FE strength provides little advantage over aBMD for identifying female hip fracture subjects. However, in men, after controlling for aBMD, F-PL was 424 N (11%) less in subjects with fractures than in controls (p = 0.003). Thus, in men, FE models of posterolateral loading include information about incident hip fracture beyond that in aBMD. (c) 2013 Elsevier Inc. All rights reserved.
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| 8. |
- Keyak, J. H., et al.
(författare)
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Male-female differences in the association between incident hip fracture and proximal femoral strength: A finite element analysis study
- 2011
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 48:6, s. 1239-1245
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Tidskriftsartikel (refereegranskat)abstract
- Hip fracture risk is usually evaluated using dual energy X-ray absorptiometry (DXA) or quantitative computed tomography (QCT) which provide surrogate measures for proximal femoral strength. However, proximal femoral strength can best be estimated explicitly by combining QCT with finite element (FE) analysis. To evaluate this technique for predicting hip fracture in older men and women, we performed a nested age- and sex-matched case-control study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort. Baseline (pre-fracture) QCT scans of 5500 subjects were obtained. During 4-7 years follow-up, 51 men and 77 women sustained hip fractures. Ninety-seven men and 152 women were randomly selected as age- and sex-matched controls. FE-strength of the left hip of each subject for stance (F-Stance) and posterolateral fall (F-Fall) loading, and total femur areal bone mineral density (aBMD) were computed from the QCT data. F-Stance and F-Fall in incident hip fracture subjects were 13%-25% less than in control subjects (p <= 0.006) after controlling for demographic parameters. The difference between FE strengths of fracture and control subjects was disproportionately greater ill men (stance, 22%; fall, 25%) than in women (stance, 13%; fall, 18%) (p <= 0.033), considering that Fstar,ce and FFall in fracture subjects were greater in men than in women ( p < 0.001). For men, F-Stance was associated with hip fracture after accounting for aBMD (p = 0.013). These data indicate that F-Stance provides information about fracture risk that is beyond that provided by aBMD (p = 0.013). These findings support further exploration of possible sex differences in the predictors of hip fracture and of sex-specific strategies for using FE analysis to manage osteoporosis. (C) 2011 Elsevier Inc. All rights reserved.
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| 10. |
- Insel, P. S., et al.
(författare)
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Biomarkers and cognitive endpoints to optimize trials in Alzheimer's disease
- 2015
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 2:5, s. 534-547
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To find the combination of candidate biomarkers and cognitive endpoints to maximize statistical power and minimize cost of clinical trials of healthy elders at risk for cognitive decline due to Alzheimer's disease. Methods: Four-hundred and twelve cognitively normal participants were followed over 7 years. Nonlinear methods were used to estimate the longitudinal trajectories of several cognitive outcomes including delayed memory recall, executive function, processing speed, and several cognitive composites by subgroups selected on the basis of biomarkers, including APOE-epsilon 4 allele carriers, cerebrospinal fluid biomarkers (A beta(42), total tau, and phosphorylated tau), and those with small hippocampi. Results: Derived cognitive composites combining Alzheimer's Disease Assessment Scale (ADAS)-cog scores with additional delayed memory recall and executive function components captured decline more robustly across biomarker groups than any measure of a single cognitive domain or ADAS-cog alone. Substantial increases in power resulted when including only participants positive for three or more biomarkers in simulations of clinical trials. Interpretation: Clinical trial power may be improved by selecting participants on the basis of amyloid and neurodegeneration biomarkers and carefully tailoring primary cognitive endpoints to reflect the expected decline specific to these individuals.
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