3D and 2D finite element analysis in soft tissue cutting for haptic display

Paper presented at the 2005 International Conference on Advanced Robotics, ICAR '05, Seattle, WA.Real-time medical simulation for robotic surgery planning and surgery training requires realistic yet computationally fast models of the mechanical behavior of soft tissue. This paper presents a study to develop such a model to enable fast haptics display in simulation of softtissue cutting. An apparatus was developed and experiments were conducted to generate force-displacement data for cutting of soft tissue such as pig liver. The forcedisplacement curve of cutting pig liver revealed a characteristic pattern: the overall curve is formed by repeating units consisting of a local deformation segment followed by a local crack-growth segment. The modeling effort reported here focused on characterizing the tissue in the local deformation segment in a way suitable for fast haptic display. The deformation resistance of the tissue was quantified in terms of the local effective modulus (LEM) consistent with experimental force-displacement data. An algorithm was developed to determine LEM by solving an inverse problem with iterative finite element models. To enable faster simulation of cutting of a three-dimensional (3D) liver specimen of naturally varying thickness, three levels of model order reduction were studied. Firstly, a 3D quadratic-element model reduced to uniform thickness but otherwise haptics-equivalent (have identical forcedisplacement feedback) to a 3D model with varying thickness matching that of the liver was used. Next, hapticsequivalent 2D quadratic-element models were used. Finally, haptics-equivalent 2D linear-element models were used. These three models had a model reduction in the ratio of 1.0:0.3:0.04 but all preserved the same input-output (displacement, force) behavior measured in the experiments. The values of the LEM determined using the three levels of model reduction are close to one another. Additionally, the variation of the LEM with cutting speed was determined. The values of LEM decreased as the cutting speed increased

Determining fracture characteristics in scalpel cutting of soft tissue

Paper presented at the First IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics, BioRob 2006, Pisa, Italy.This paper addresses the characteristic response of soft tissue to the growth of a cut (cracking) with a scalpel blade. We present our experimental equipment, experiments, and the results for scalpel cutting of soft tissue. The experimentally measured cut-force versus cut-length data was used to determine the soft tissue’s resistance to fracture (resistance to crack extension) in scalpel cutting. The resistance to fracture (the toughness) of the soft tissue is quantified by the measure R defined as the amount of mechanical work needed to cause a cut (crack) to extend for a unit length in a soft-tissue sample of unit thickness. The equipment, method, and model are applicable for all soft tissue. We used pig liver as soft-tissue samples for our experiments

Precision extruding deposition and characterization of cellular poly-e -caprolactone tissue scaffolds

Rapid Prototyping Journal, Vol. 10, Issue 1, 2004. pp. 42-49. Retrieved April 2006 from http://www.pages.drexel.edu/~sunwei/WSUN-Papers/RPJ-2004-PCL.pdfSuccesses in scaffold guided tissue engineering require scaffolds to have specific macroscopic geometries and internal architectures to provide the needed biological and biophysical functions. Freeform fabrication provides an effective process tool to manufacture many advanced scaffolds with designed properties. This paper reports our recent study on using a novel precision extruding deposition (PED) process technique to directly fabricate cellular poly-ecaprolactone (PCL) scaffolds. Scaffolds with a controlled pore size of 250 mm and designed structural orientations were fabricated

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

A genomewide analysis provides evidence for novel linkages in inflammatory bowel disease in a large European cohort.

Inflammatory bowel disease (IBD) is characterized by a chronic relapsing intestinal inflammation, typically starting in early adulthood. IBD is subdivided into two subtypes, on the basis of clinical and histologic features: Crohn disease and ulcerative colitis (UC). Previous genomewide searches identified regions harboring susceptibility loci on chromosomes 1, 3, 4, 7, 12, and 16. To expand our understanding of the genetic risk profile, we performed a 9-cM genomewide search for susceptibility loci in 268 families containing 353 affected sibling pairs. Previous linkages on chromosomes 12 and 16 were replicated, and the chromosome 4 linkage was extended in this sample. New suggestive evidence for autosomal linkages was observed on chromosomes 1, 6, 10, and 22, with LOD scores of 2.08, 2.07, 2.30, and 1.52, respectively. A maximum LOD score of 1.76 was observed on the X chromosome, for UC, which is consistent with the clinical association of IBD with Ullrich-Turner syndrome. The linkage finding on chromosome 6p is of interest, given the possible contribution of human leukocyte antigen and tumor necrosis-factor genes in IBD. This genomewide linkage scan, done with a large family cohort, has confirmed three previous IBD linkages and has provided evidence for five additional regions that may harbor IBD predisposition genes

Extending thrombolysis to 4·5–9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data

Background: Stroke thrombolysis with alteplase is currently recommended 0–4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis. Methods: In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0–1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. Findings: We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15–2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23–76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81–2·96, p=0·66). Interpretation: Patients with ischaemic stroke 4·5–9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis