Battery electric vehicles (BEVs) offer significant potential to reduce the nation's consumption of petroleum based products and the production of greenhouse gases however, their widespread adoption ...is limited largely by the cost and performance limitations of modern batteries. With recent growth in efforts to accelerate BEV adoption (e.g. the Department of Energy's (DOE) EV Everywhere Grand Challenge) and the age of existing BEV battery technology targets, there is sufficient motivation to re-evaluate the industry's technology targets for battery performance and cost. Herein we document the analysis process that supported the selection of the United States Advanced Battery Consortium's (USABC) updated BEV battery technology targets. Our technology agnostic approach identifies the necessary battery performance characteristics that will enable the vehicle level performance required for a commercially successful, mass market full BEV, as guided by the workgroup's OEM members. The result is an aggressive target, implying that batteries need to advance considerably before BEVs can be both cost and with existing petroleum powered vehicles.
Summary Background Patients and clinicians share concerns that generic drug substitution might lead to loss of efficacy or emergence of adverse events. In this trial, we assessed US Food and Drug ...Administration (FDA) bioequivalence standards by studying the effects of switching between two disparate generic immediate-release lamotrigine products in patients with epilepsy. Methods The Equivalence among Generic Antiepileptic Drugs (EQUIGEN) chronic-dose study was a randomised, double-blind, crossover study that enrolled adults (aged ≥18 years) with epilepsy from six epilepsy centres at academic institutions across the USA who were receiving immediate-release lamotrigine dosed at 100 mg, 200 mg, 300 mg, or 400 mg twice daily. Eligible patients were randomly allocated (1:1) to one of two treatment sequences (sequence 1 or sequence 2), comprising four study periods of 14 days each. During each 14-day treatment period, patients received balanced doses of an oral generic lamotrigine product every 12 h (200–800 mg total, identical to lamotrigine dose prior to study enrolment); after each 14-day period, patients were crossed over to receive the other generic product. Computer-based randomisation was done using random permuted blocks of size two or four for each site to prevent sequence predictability. Both patients and study personnel were masked to the generic products selected, their predicted exposure (ie, “high” vs “low”), and their group allocation. The primary outcome of this trial was bioequivalence between the generic products, which was assessed at the end of the study through a comparison of maximum plasma concentration (Cmax ) and area under the concentration–time curve (AUC) for each product in the analysis population (all patients who completed all four treatment periods). Bioequivalence was established if the 90% CIs of the ratios of these two parameters for the two products were within equivalence limits (80–125%) in the analysis population. This study is registered with ClinicalTrials.gov \, number NCT01713777. Findings Between April 25, 2013, and Aug 12, 2014, 35 eligible patients were enrolled and randomly assigned to treatment sequence 1 (n=15) or treatment sequence 2 (n=20). 33 patients completed all four treatment periods and were included in the primary outcome analysis. The 90% CIs of the ratios of both Cmax and AUC were within equivalence limits (AUC 90% CI 98–103, Cmax 90% CI 99–105), showing that lamotrigine exposures were equivalent between the generic products. No significant changes in seizure frequency or adverse events were recorded. No deaths, study-related serious adverse events, or changes in clinical laboratory values or vital signs occurred during this study. Interpretation Disparate generic lamotrigine products in patients with epilepsy showed bioequivalence with no detectable difference in clinical effects, confirming that US Food and Drug Administration bioequivalence standards are appropriate. Funding American Epilepsy Society, Epilepsy Foundation, and US Food and Drug Administration.
Objective To identify pathophysiologic changes that lead to the onset of type 2 diabetes (T2DM) in adolescents. Study design Obese adolescents with normal glucose tolerance (n = 41) were studied ...longitudinally over the course of 4 years with serial measure of the acute insulin response to glucose (AIRg ) as well as proinsulin (PI) concentrations. Insulin resistance was estimated with the homeostatic model assessment of insulin resistance (HOMA-IR), the disposition index (DI) computed as AIRg × 1/HOMA-IR, and intravenous glucose tolerance estimated as the glucose disappearance constant. Results Four adolescents developed diabetes mellitus (DM) during the study, and the rest of the cohort remained nondiabetic. Baseline PI exceeded the IQR of the nondiabetic group in 3 of 4 subjects with DM, and all had >85% reduction from baseline AIRg , and DI, within 6 months of diagnosis. All the subjects with DM gained weight over the course of the study, but these changes paralleled those for the nondiabetic group. HOMA-IR increased substantially in 1 of the subjects with DM at the time of diagnosis but was comparable with baseline in the other 3. The DI and glucose disappearance constant of the subjects with DM was less than the 10th percentile of the nondiabetic group before and after diagnosis. Conclusion Conversion from normal glucose tolerance to T2DM in adolescents can occur rapidly, and the onset of T2DM is heralded by a substantial decrease in AIRg and DI, as well as increased release of PI. These results support loss of β-cell function as the proximate step in the development of T2DM in this age group.
Prior approaches to line segment detection typically involve perceptual grouping in the image domain or global accumulation in the Hough domain. Here we propose a probabilistic algorithm that merges ...the advantages of both approaches. In a first stage lines are detected using a global probabilistic Hough approach. In the second stage each detected line is analyzed in the image domain to localize the line segments that generated the peak in the Hough map. By limiting search to a line, the distribution of segments over the sequence of points on the line can be modeled as a Markov chain, and a probabilistically optimal labelling can be computed exactly using a standard dynamic programming algorithm, in linear time. The Markov assumption also leads to an intuitive ranking method that uses the local marginal posterior probabilities to estimate the expected number of correctly labelled points on a segment. To assess the resulting Markov Chain Marginal Line Segment Detector (MCMLSD) we develop and apply a novel quantitative evaluation methodology that controls for under-and over-segmentation. Evaluation on the YorkUrbanDB dataset shows that the proposed MCMLSD method outperforms the state-of-the-art by a substantial margin.
The incretin effect reflects the actions of enteral stimuli to promote prandial insulin secretion. Impairment of this measure has been proposed as an early marker of β-cell dysfunction and described ...in T2D, IGT, and even obesity without IGT. We sought to determine the effects of obesity and diabetes on the incretin effect in young subjects with short exposures to metabolic abnormalities and a few other confounding medical conditions. Subjects with T2D (n = 10; 18.0 ± 0.4 yr) or NGT, either obese (n = 11; 17.7 ± 0.4 yr) or lean (n = 8; 26.5 ± 2.3 yr), had OGTT and iso-iv. The incretin effect was calculated as the difference in insulin secretion during these tests and was decreased ∼50% in both the NGT-Ob and T2D subjects relative to the NGT-Ln group. The T2D group had impaired glucose tolerance and insulin secretion during the OGTT, whereas the lean and obese NGT subjects had comparable glucose excursions and β-cell function. During the iso-iv test, the NGT-Ob subjects had significantly greater insulin secretion than the NGT-Ln and T2D groups. These findings demonstrate that in young subjects with early, well-controlled T2D the incretin effect is reduced, similar to what has been described in diabetic adults. The lower incretin effect calculated for the obese subjects with NGT is driven by a disproportionately greater insulin response to iv glucose and does not affect postprandial glucose regulation. These findings confirm that the incretin effect is an early marker of impaired insulin secretion in persons with abnormal glucose tolerance but suggest that in obese subjects with NGT the incretin effect calculation can be confounded by exaggerated insulin secretion to iv glucose.
OBJECTIVES
To evaluate the effect of hospitalizations on patterns of sedentary and physical activity time in mobility‐limited older adults randomized to structured physical activity or health ...education.
DESIGN
Secondary analysis of investigator‐blinded, parallel‐group, randomized trial conducted at 8 U.S. centers between February 2010 and December 2013.
PARTICIPANTS
Sedentary men and women aged 70 to 89 at baseline who wore a hip‐fitted accelerometer 7 consecutive days at baseline and 6, 12, and 24 months after randomization (N=1,341).
MEASUREMENTS
Participants were randomized to a physical activity (PA; n = 669) intervention that included aerobic, resistance, and flexibility training or to a health education (HE; n = 672) intervention that consisted of workshops on older adult health and light upper‐extremity stretching. Accelerometer patterns were characterized as bouts of sedentary (<100 counts/min; ≥1, ≥10, ≥30, ≥60 minute lengths) and activity (≥100 counts/min; ≥1, ≥2, ≥5, ≥10 minute lengths) time. Each participant was categorized as having 0, 1 to 3, or 4 or more cumulative hospital days before each accelerometer assessment.
RESULTS
Hospitalization increased sedentary time similarly in both intervention groups (8 min/d for 1–3 cumulative hospital days and 16 min/d for ≥4 cumulative hospital days). Hospitalization was also associated with less physical activity time across all bouts of less than 10 minutes (≥1: −7 min/d for 1–3 cumulative hospital days, –16 min/d for ≥4 cumulative hospital days; ≥2: −5 min/d for 1–3 cumulative hospital days, −11 min/d for ≥4 cumulative hospital days; ≥5: −3 min/d for 1–3 cumulative hospital days, −4 min/d for ≥4 cumulative hospital days). There was no evidence of recovery to prehospitalization levels (time effect p >.41). PA participants had less sedentary time in bouts of less than 30 minutes than HE participants (−8 to −10 min/d) and more total activity (+3 to +6 min/d), although hospital‐related changes were similar between the intervention groups (interaction effect p >.26).
CONCLUSION
Participating in a PA intervention before hospitalization had expected benefits, but participants remained susceptible to hospitalization's detrimental effects on their daily activity levels. There was no evidence of better activity recovery after hospitalization. J Am Geriatr Soc 67:261–268, 2019.
OBJECTIVES
Our aim was to examine the impacts of baseline fatigue on the effectiveness of a physical activity (PA) intervention to prevent major mobility disability (MMD) and persistent major ...mobility disability (PMMD) in participants from the Lifestyle Interventions and Independence for Elders (LIFE) study.
DESIGN
Prospective cohort of individuals aged 65 years or older undergoing structured PA intervention or health education (HE) for a mean of 2.6 years.
SETTING
LIFE was a multicenter eight‐site randomized trial that compared the efficacy of a structured PA intervention with an HE program in reducing the incidence of MMD.
PARTICIPANTS
Study participants (N = 1591) at baseline were 78.9 ± 5.2 years of age, with low PA and at risk for mobility impairment.
MEASUREMENTS
Self‐reported fatigue was assessed using the modified trait version of the Exercise‐Induced Feelings Inventory, a six‐question scale rating energy levels in the past week. Responses ranged from 0 (none of the time) to 5 (all of the time). Total score was calculated by averaging across questions; baseline fatigue was based on the median split: 2 or higher = more fatigue (N = 856) and lower than 2 = less fatigue (N = 735). Participants performed a usual‐paced 400‐m walk every 6 months. We defined incident MMD as the inability to walk 400‐m at follow‐up visits; PMMD was defined as two consecutive walk failures. Cox proportional hazard models quantified the risk of MMD and PMMD in PA vs HE stratified by baseline fatigue adjusted for covariates.
RESULTS
Among those with higher baseline fatigue, PA participants had a 29% and 40% lower risk of MMD and PMMD, respectively, over the trial compared with HE (hazard ratio HR for MMD = .71; 95% confidence interval CI = .57‐.90; P = .004) and PMMD (HR = .60; 95% CI = .44‐.82; P = .001). For those with lower baseline fatigue, no group differences in MMD (P = .36) or PMMD (P = .82) were found. Results of baseline fatigue by intervention interaction was MMD (P = .18) and PMMD (P = .05).
CONCLUSION
A long‐term moderate intensity PA intervention was particularly effective at preserving mobility in older adults with higher levels of baseline fatigue. J Am Geriatr Soc 68:619–624, 2020
Objective— To compare biomechanical properties of 3 new generation polyethylene sutures (FiberTape FT, FiberWire FW, and OrthoFiber OF) with nylon leader line (NL) for use during extraarticular ...fixation of cranial cruciate deficient stifles.
Study Design— In vitro biomechanical testing of suture loops under monotonic tensile and cyclical loading until failure.
Sample Population— Constructs of FT, FW, OF, and NL.
Methods— Twenty loops of each of 12 combinations of fixation and suture had monotonic tensile and cyclical loading. Two knotting techniques (square knot SQ, slip knot SL) and a crimp clamp (CR) system were evaluated. Elongation, stiffness, and strength of constructs was tested. The main effects of group, loop material, and their interaction were evaluated.
Results— Knotted FT, FW, and OF had less elongation than knotted NL under monotonic tensile and cyclical loading. Under monotonic tensile loading, knotted FT and OF were stiffer than knotted NL. CR FT, CR FW, and CR OF were stiffer than CR NL and CR FT, CR FW, and CR OF were stiffer than knotted FT, FW, and OF. FW and OF knotted loops were weaker than knotted NL. CR FT was stronger than CR NL. CR FT and CR OF were weaker than knotted FT and OF.
Conclusions— Polyethylene sutures are stronger, stiffer and elongate less than nylon leader. Crimping suture alters the biomechanical properties of the loop.
Clinical Relevance— FW, FT, and OF may perform better in reconstructive procedures, where increased strength and stiffness are considered to be beneficial.
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