6,332 publications from this institution
Additional file 3: Table S2A-D. Associations between DNA methylation and BMI in the main meta-analyses. Results for CpGs with p-values < 1x10-4 are shown.
The origin of unsteady glacier motions, an area to which Robert M. McMeeking contributed significantly [1,2], is of interest for assessing stability of major ice sheets (Greenland, Antarctica). Meltwater and its pressure p at the bed of glaciers are known to have major influence on flow. Our work [3,4] focuses on outburst under-flooding of an ice sheet, as a means of delivering highly pressurized water to its bed, transiently with p > o (= ice overburden pressure). The process is viewed as a turbulently driven hydraulic fracture along the ice/bed interface. Such can result [5] when the glacier dams a rising lake, or from geothermal heating of a sub-glacial lake. The particular scenario we address is, instead, rapid drainage into the ice of a large surficial meltwater lake, like recently documented in Greenland [6] during mid-summer. This first involves Weertman gravitationally driven hydraulic cracking from the lake to the bed, and then rapid spreading of water along the bed, initially as a high-p sheet flow. We compare modeling to results of the Greenland study [6], for which a 0.043 km 3 lake disappeared into the ice, mostly within 1.5 hr. The lake drainage rate in that case, and the ~3 km length, parallel to the glacier surface, of a crevasse/moulin system along which drainage apparently occurred, suggest that in the rapid early phases of the underflooding the Reynolds number (based on basal fracture opening h and thickness-averaged flow speed U along it) was of order 10 6 . Accordingly, we adopted a Manning-Strickler-Nikuradse description of wall shear stress in the rough turbulent range to relate U(x,t), h(x,t), p(x,t), and the wall roughness scale k, where x is the coordinate in the direction of fracture propagation. We further assumed linear elastic response of ice and bed, and (for the large fracture propagation lengths of interest) negligible KIc . By extending studies like in [7,8] to that rough turbulent flow range, we have thus solved approximately the plane strain version of the hydraulic fracture problem when the basal crack length 2L is modest compared to ice sheet thickness H (i.e., for a crack in an unbounded body, subject to crack face pressure p o ). We outline those results here and will, in the presentation, report some preliminary improvements on them in current work to account for the range L/H of order 1 and larger, often a practically interesting one [4-6], by explicitly accounting for a nearby free surface. That adopts the approach of [9] to numerically relate the h(x,t) and p(x, t ) o distributions. To fully solve the problem for the rate of fracture propagation, and volume storage of meltwater within the fracture, the distributions must also be constrained to satisfy the governing fluid equations (analogously to [10], but for turbulent rather than laminar flow). Those fluid equations, to be solved on – L(t) 0) (hU )
A work-hardening elastic-plastic stress analysis is presented for a sharp notch or, as a limiting case, a crack perturbing a remotely applied uniform stress field. Mathematical complexities are reduced through considering the kinematically simple case of antiplane longitudinal shear deformations and by employing a deformation plasticity theory rather than the more appropriate incremental theory. Consequently, a general solution is available valid for any relation between stress and strain in the work-hardening range, so long as the remotely applied stress does not exceed the initial yield stress. When a power law relates stress to a strain in the work-hardening range, the deformation theory solution is also the correct incremental solution at low applied stress levels causing yielding on a scale small compared to notch depth. For cracks, the near crack tip strain field is shown to depend on loads and geometry only through the elastic stress intensity factor when yielding is on a small scale, and the elastic-plastic boundary and lines of constant strain magnitude are circles. Extensive numerical results are tabulated for a crack, 45 deg V-notch, and 90 deg V-notch in power-law-hardening materials, and exhibited graphically for a crack.
Flaw-induced delamination of orthotropic laminates subject to through-thickness temperature gradients is analyzed. A crack-like flaw impedes heat flow through the laminate, producing thermal stresses and crack tip stress intensities. The focus is on delamination cracks which propagate under steady-state conditions. The steady-state analysis becomes accurate for a crack whose length is about one laminate thickness. Moreover, the analysis provides realistic fail-safe criteria for excluding delamination.
Fully plastic plane stress solutions are given for a center-cracked strip in tension and an edge-cracked strip in pure bending. In the fully plastic formulation the material is characterized by a pure power hardening stress-strain relation which reduces at one limit to linear elasticity and at the other to rigid/perfect plasticity. Simple formulas are given for estimating the J-integral, the load-point displacement and the crack opening displacement in terms of the applied load for strain hardening materials characterized by the Ramberg-Osgood stress-strain relation in tension. The formulas make use of the linear elastic solution and the fully plastic solution to interpolate over the entire range of small and large scale yielding. The accuracy of the formulas is assessed using finite element calculations for some specific configurations.
Prediabetes refers to impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), the stage preceding the development of clinical diabetes. IGT is defined as 2-h post-load glucose 140mg/dl (7.8mmol/l) and <200mg/dl (11.1mmol/l); IFG as fasting plasma glucose 110mg/dl (6.1mmol/l) and <126mg/dl (7.0mmol/l). More recently, HbA1c of 5.7–6.4% was added as another criterion for defining prediabetes. According to the Third National Health and Nutrition Examination Survey, 1988–1994, the prevalence of IFG in the US population 20 years of age was 6.9% and that of IGT in those 40–74 years of age was 15.8%. No matter how it is defined, prediabetes is associated with a substantially elevated risk of cardiovascular disease (CVD). This finding provides support for the ‘ticking clock’ hypothesis, which postulates that ‘the clock for coronary heart disease starts ticking before the onset of clinical diabetes.’ The evidence is also compatible with the ‘common soil’ hypothesis, which posits that diabetes and cardiovascular disease share common pathophysiological and environmental antecedents, i.e., ‘they spring from a common soil.’ In the Nurses’ Health Study cohort, participants who converted from prediabetes to type 2 diabetes during follow-up had a more atherogenic risk profile (e.g., higher BMI values and greater prevalence of hypertension and hypercholesterolemia) and increased incidence of CVD than those who did not convert. However, individuals with preexisting diabetes at baseline had the most adverse CVD risk profiles and the highest incidence of CVD during follow-up. Therefore, prediabetes, diabetes, and cardiovascular disease constitute a continuum of cardiometabolic risk. As a consequence, early management of prediabetes through lifestyle interventions or pharmacological means is not only critical to reduce the progression from prediabetes to diabetes, but also to decrease the long-term risk of CVD. In this issue of European Journal of Cardiovascular Prevention and Rehabilitation, Hopper et al. reported a meta-analysis of prospective, randomized controlled trials (RCTs) that evaluated the effects of lifestyle intervention or pharmacological treatment on diabetes prevention among individuals with IGT and/or IFG. Ten RCTs with 23,152 patients were included in the metaanalysis. The average duration of the trials was 3.75 years. Overall, the interventions reduced the risk of diabetes by 17% (95%CI 14–20%), with lifestyle interventions more effective than drug-based ones (RR1⁄4 0.52, 0.46–0.58 vs 0.70, 0.58–0.85, p< 0.05). No significant benefit in either total or cardiovascular mortality was observed for either intervention. This meta-analysis confirms earlier data showing the superiority of lifestyle interventions over drug-based treatment for diabetes prevention among prediabetic individuals. In the Diabetes Prevention Program (DPP), the lifestyle intervention group experienced a 58% decrease in the risk of diabetes over a 3-year period compared to controls. This effect was considerably greater than that in the metformin group (31%). Findings were similar for incidence of the metabolic syndrome, with the lifestyle group experiencing 41% risk reduction, and the metformin group 17% risk reduction, compared with placebo. The strong relationship between diabetes and CVD outcomes suggests that interventions that are effective in preventing diabetes would also reduce risk of CVD. However, this meta-analysis found no benefits of lifestyle or pharmacological interventions on total or CVD death. Lack of power is a major limitation of this metaanalysis as the vast majority of trials were not designed to examine CVD outcomes. Of the 10 RCTs combined, there were only 274 CVD deaths in the intervention groups and 85 in the control groups. Some trials had no CVD deaths in either group. Besides relatively small
