Mechanism of joint formation and characteristics of interface in ultrasonic welding: Literature review

The study of ultrasonic welding has been going on for more than 50 years. The mechanism of joint formation and characterization of the interface in ultrasonically made joints between metal sheets and wires have been the most thought-provoking area for the researchers. The study of post-welding microstructure, the formation of any intermetallic compound at the interface and their effect on the joint strength, the presence of heat affected zone in the ultrasonically joined sheets has been explored but still, arguably the least understood. Interface characteristics are different in similar and dissimilar combinations of metals. This work presents a comprehensive review of literature regarding the studies on the microstructural analysis at the interface of the joints made by Ultrasonic Welding on different combinations of metal sheets. Additionally, this paper provides an analysis of the observations made by different scientists that promote the future scope of research in this area. The study has been confined to Ultrasonic metal welding only

A new ghost cell/level set method for moving boundary problems:application to tumor growth

In this paper, we present a ghost cell/level set method for the evolution of interfaces whose normal velocity depend upon the solutions of linear and nonlinear quasi-steady reaction-diffusion equations with curvature-dependent boundary conditions. Our technique includes a ghost cell method that accurately discretizes normal derivative jump boundary conditions without smearing jumps in the tangential derivative; a new iterative method for solving linear and nonlinear quasi-steady reaction-diffusion equations; an adaptive discretization to compute the curvature and normal vectors; and a new discrete approximation to the Heaviside function. We present numerical examples that demonstrate better than 1.5-order convergence for problems where traditional ghost cell methods either fail to converge or attain at best sub-linear accuracy. We apply our techniques to a model of tumor growth in complex, heterogeneous tissues that consists of a nonlinear nutrient equation and a pressure equation with geometry-dependent jump boundary conditions. We simulate the growth of glioblastoma (an aggressive brain tumor) into a large, 1 cm square of brain tissue that includes heterogeneous nutrient delivery and varied biomechanical characteristics (white matter, gray matter, cerebrospinal fluid, and bone), and we observe growth morphologies that are highly dependent upon the variations of the tissue characteristics—an effect observed in real tumor growth

Predicting drug pharmacokinetics and effect in vascularized tumors using computer simulation

In this paper, we investigate the pharmacokinetics and effect of doxorubicin and cisplatin in vascularized tumors through two-dimensional simulations. We take into account especially vascular and morphological heterogeneity as well as cellular and lesion-level pharmacokinetic determinants like P-glycoprotein (Pgp) efflux and cell density. To do this we construct a multi-compartment PKPD model calibrated from published experimental data and simulate 2-h bolus administrations followed by 18-h drug washout. Our results show that lesion-scale drug and nutrient distribution may significantly impact therapeutic efficacy and should be considered as carefully as genetic determinants modulating, for example, the production of multidrug-resistance protein or topoisomerase II. We visualize and rigorously quantify distributions of nutrient, drug, and resulting cell inhibition. A main result is the existence of significant heterogeneity in all three, yielding poor inhibition in a large fraction of the lesion, and commensurately increased serum drug concentration necessary for an average 50% inhibition throughout the lesion (the IC50 concentration). For doxorubicin the effect of hypoxia and hypoglycemia (“nutrient effect”) is isolated and shown to further increase cell inhibition heterogeneity and double the IC50, both undesirable. We also show how the therapeutic effectiveness of doxorubicin penetration therapy depends upon other determinants affecting drug distribution, such as cellular efflux and density, offering some insight into the conditions under which otherwise promising therapies may fail and, more importantly, when they will succeed. Cisplatin is used as a contrast to doxorubicin since both published experimental data and our simulations indicate its lesion distribution is more uniform than that of doxorubicin. Because of this some of the complexity in predicting its therapeutic efficacy is mitigated. Using this advantage, we show results suggesting that in vitro monolayer assays using this drug may more accurately predict in vivo performance than for drugs like doxorubicin. The nonlinear interaction among various determinants representing cell and lesion phenotype as well as therapeutic strategies is a unifying theme of our results. Throughout it can be appreciated that macroscopic environmental conditions, notably drug and nutrient distributions, give rise to considerable variation in lesion response, hence clinical resistance. Moreover, the synergy or antagonism of combined therapeutic strategies depends heavily upon this environment

Perioperative serum albumin as a predictor of adverse outcomes in abdominal surgery: prospective cohort hospital based study in Northern Tanzania

BACKGROUND: Albumin is an important protein that transports hormones, fatty acids, and exogenous drugs; it also maintains plasma oncotic pressure. Albumin is considered a negative active phase protein because it decreases during injuries and sepsis. In spite of other factors predicting surgical outcomes, the effect of pre and postoperative serum albumin to surgical complications can be assessed by calculating the percentage decrease in albumin (delta albumin). This study aimed to explore perioperative serum albumin as a predictor of adverse outcomes in major abdominal surgeries. METHODS: All eligible adult participants from Kilimanjaro Christian Medical Centre Surgical Department were enrolled in a convenient manner. Data were collected using a study questionnaire. Full Blood Count (FBP), serum albumin levels preoperatively and on postoperative day 1 were measured in accordance with Laboratory Standard Operating Procedures (SOP). Data was entered and analyzed using STATA version 14. Association and extent of decrease in albumin levels as a predictor of surgical site infection (SSI), delayed wound healing and death within 30 days of surgery was determined using ordinal logistic regression models. In determining the diagnostic accuracy, a Non-parametric Receiver Operating Curve (ROC) model was used. We adjusted for ASA classification, which had a negative confounding effect on the predictive power of the percent drop in albumin to adverse outcomes. RESULTS: Sixty one participants were studied; the mean age was 51.6 (SD16.3), the majorities were males 40 (65.6%) and post-operative adverse outcomes were experienced by 28 (45.9%) participants. In preoperative serum albumin values, 40 (67.8%) had lower than 3.4 g/l while 51 (91%) had postoperative albumin values lower than 3.4 g/l. Only 15 (27.3%) had high delta albumin with the median percentage value of 14.77%. Delta albumin was an independent significant factor associated with adverse outcome (OR: 6.68; 95% CI: 1.59, 28.09); with a good predictive power and area under ROC curve (AUC) of 0.72 (95% CI 0.55 0.89). The best cutoff value was 11.61% with a sensitivity of 76.92% and specificity of 51.72%. CONCLUSION: Early perioperative decreases in serum albumin levels may be a good, simple and cost effective tool to predict adverse outcomes in major abdominal surgeries

Selective inhibition of tropomyosin-receptor-kinase A (TrkA) reduces pain and joint damage in two rat models of inflammatory arthritis

Background: Inflammation is an essential component of arthritis pain. Nerve growth factor (NGF) plays a key role in acute and chronic pain states especially those associated with inflammation. NGF acts through tropomyosin-receptor-kinase A (TrkA). NGF blockade has reduced arthritis pain in clinical trials. We explored the mechanisms within the joint which may contribute to the analgesic effects of NGF by selectively inhibiting TrkA in carrageenan-induced or collagen-induced joint pain behaviour. The goal of the current study was to elucidate whether inflammation is central to the efficacy for NGF blockade. Methods: Rats were injected in their left knees with 2 % carrageenan or saline. Collagen-induced arthritis (CIA) was induced by intradermal injections of a mixture of bovine type II collagen (0.2 mg) and incomplete Freund’s adjuvant (0.2 mg). Oral doses (30 mg/kg) of AR786 or vehicle control were given twice daily after arthritis induction. Ibuprofen-treated (35 mg/kg, orally, once daily) rats with CIA were used as positive analgesic controls. Pain behaviour was measured as hind-limb weight-bearing asymmetry and hind-paw withdrawal thresholds to von Frey hair stimulation (carrageenan synovitis), or withdrawal to joint compression using a Randall Selitto device (CIA). Inflammation was measured as increased knee joint diameter and by histopathological analysis. Results: Intra-articular injections of carrageenan or induction of CIA was each associated with pain behaviour and synovial inflammation. Systemic administration of the TrkA inhibitor AR786 reduced carrageenan-induced or CIA-induced pain behaviour to control values, and inhibited joint swelling and histological evidence of synovial inflammation and joint damage. Conclusions: By using two models of varying inflammation we demonstrate for the first time that selective inhibition of TrkA may reduce carrageenan-induced or CIA-induced pain behaviour in rats, in part through potentially inhibiting synovial inflammation, although direct effects on sensory nerves are also likely. Our observations suggest that inflammatory arthritis causes pain and the presence of inflammation is fundamental to the beneficial effects (reduction in pain and pathology) of NGF blockade. Further research should determine whether TrkA inhibition may ameliorate human inflammatory arthritis