A Comparative Study of Machine Learning and Algorithmic Approaches to Automatically Identify the Yield Point in Normal and Aneurysmal Human Aortic Tissues.

The stress-strain curve of biological soft tissues helps characterize their mechanical behavior. The yield point on this curve is when a specimen breaches its elastic range due to irreversible microstructural damage. The yield point is easily found using the offset yield method in traditional engineering materials. However, correctly identifying the yield point in soft tissues can be subjective due to its nonlinear material behavior. The typical method for yield point identification is visual inspection, which is investigator-dependent and does not lend itself to automation of the analysis pipeline. An automated algorithm to identify the yield point objectively assesses soft tissues' biomechanical properties. This study aimed to analyze data from uniaxial extension testing on biological soft tissue specimens and create a machine learning (ML) model to determine a tissue sample's yield point. We present a trained machine learning model from 279 uniaxial extension curves from testing aneurysmal/nonaneurysmal and longitudinal/circumferential oriented tissue specimens that multiple experts labeled through an adjudication process. The ML model showed a median error of 5% in its estimated yield stress compared to the expert picks. The study found that an ML model could accurately identify the yield point (as defined) in various aortic tissues. Future studies will be performed to validate this approach by visually inspecting when damage occurs and adjusting the model using the ML-based approach.

Ultrasonic investigation of materials-An avenue for project-based learning.

Project-based learning (PBL) provides an effective practical application to the learners. Further, PBL develops problem-solving, critical thinking, etc., in the learner. This paper describes a type of project offered to the students at the collegiate level to enhance the students' ability to work in a team, manage a project, and present their results. These projects use acoustic waves in the ultrasound frequency range that can be used as a powerful nondestructive tool for the characterization of the materials. In situ measurement of the ultrasonic longitudinal velocity and evaluation of the elastic constants carried out on the materials in solid pellet form over a wide range of temperatures at a fundamental frequency of 5 MHz enables the study of various phase transitions, such as metal to insulator, ferromagnetic to paramagnetic, and even structural phase transitions that occur in the materials. Here, the investigation is elaborated on using ultrasonic waves on some materials in pellet form and the results obtained are presented.

Flow Monitoring of ECMO Circuit for Detecting Oxygenator Obstructions.

Oxygenator thrombosis during extracorporeal membrane oxygenation (ECMO), is a complication that necessitates component replacement. ECMO centers monitor clot burden by intermittent measurement of pressure drop across the oxygenator. An increase in pressure drop at a preset flow rate suggests an increase in resistance/clot formation within the oxygenator. This monitoring method comes with inherent disadvantages such as monitoring gaps, and increased risk of air embolism and infection. We explored utilizing flow measurement, which avoids such risks, as an indicator of ECMO circuit obstructions. The hypothesis that flow rate through a shunt tube in the circuit will increase as distal resistances in the circuit increases was tested. We experimentally simulated controlled levels of oxygenator obstructions using glass microspheres in an ex vivo veno-venous ECMO circuit and measured the change in shunt flow rate using over the tube ultra-sound flow probes. A mathematical model was also used to study the effect of distal resistances in the ECMO circuit on shunt flow. Results of both the mathematical model and the experiments showed a clear and measurable increase in shunt flow with increasing levels of oxygenator obstruction. Therefore, flow monitoring appears to be an effective non-contact and continuous method to monitor for obstruction during ECMO.

Electrochemical Approach to Measure Physiological Fluid Flow Rates.

In vivo measurement of the flow rate of physiological fluids such as the blood flow rate in the heart is vital in critically ill patients and for those undergoing surgical procedures. The reliability of these measurements is therefore quite crucial. However, current methods in practice for measuring flow rates of physiological fluids suffer from poor repeatability and reliability. Here, we assessed the feasibility of a flow rate measurement method that leverages time transient electrochemical behavior of a tracer that is injected directly into a medium (the electrochemical signal caused due to the tracer injectate will be diluted by the continued flow of the medium and the time response of the current-the electrodilution curve-will depend on the flow rate of the medium). In an experimental flow loop apparatus equipped with an electrochemical cell, we used the AC voltammetry technique and tested the feasibility of electrodilution-based measurement of the flow rate using two mediums-pure water and anticoagulated blood-with 0.9 wt% saline as the injectate. The electrodilution curve was quantified using three metrics-change in current amplitude, total time, and change in the total charge for a range of AC voltammetry settings (peak voltages and frequencies). All three metrics showed an inverse relationship with the flow rate of water and blood, with the strongest negative correlation obtained for change in current amplitude. The findings are a proof of concept for the electrodilution method of the flow rate measurement and offer the potential for physiological fluid flow rate measurement in vivo.

Failure properties of abdominal aortic aneurysm tissue are orientation dependent.

INTRODUCTION: Biomechanical rupture risk assessment of abdominal aortic aneurysm (AAA) requires information about failure properties of aneurysmal tissue. There are large differences between reported values. Among others, studies vary in using either axially or circumferentially oriented samples. This study investigates the effect of sample orientation on failure properties. METHODS: Aneurysmal tissues from 45 patients (11 females) were harvested during open AAA repair, cut into uniaxial samples (90) and tested mechanically within 3 h. If possible, the samples were cut in both axial (49 samples) and circumferential (41 samples) directions. Wall thickness, First Piola-Kirchhoff strength Pult and ultimate tension Tult were recorded. Influence of sample orientation and other clinical parameters were investigated using non parametric tests. RESULTS: Medians of Pult (values 1100 kPa for circumferential vs. 715 kPa for axial direction, p < 10-4) and Tult (17.4 N/cm in circumferential vs. 11.2 N/cm in axial direction, p < 10-4) were significantly higher in circumferential direction. For paired data, the median of difference was 411 kPa (p < 10-3) in Pult and 7.4 N/cm (p < 10-4) in Tult in favor of circumferential direction. CONCLUSIONS: In this first study of anisotropy in AAA wall failure properties using paired comparisons, the strength in circumferential orientation was found to be higher than in axial orientation.

Molecular characterisation of parvoviruses from domestic cats reveals emergence of newer variants in India.

Objectives The present study was undertaken to characterise the viral polypeptide 2 (VP2) gene of parvovirus from domestic cats in India. Methods The faecal samples from diarrhoeic/healthy domestic cats were collected from different geographical regions of India for screening by PCR assay followed by sequence analysis of the VP2 gene. Results Canine parvovirus (CPV)/feline panleukopenia virus (FPV) infections were found in 12 (11.3%) of 106 faecal samples tested. Two new CPV-2a (297Ala and Asn426) and three FPV strains were identified by VP2 gene analysis. Several unique and existing amino acid mutations were found, suggesting continuous evolution and emergence of newer variants. The phylogenetic analysis of the CPV sequences revealed that the two new CPV-2a strains from Mumbai (MC8) and Puducherry (P15) were clustered together in a single clade but had evolved independently and were ancestrally related to Chinese CPV-2a isolates. The FPV sequences (T-C-6 and T-C-1) from Thrissur, Kerala, formed a different clade (FPV clade) and were closely related to each other and had an ancestral relationship with an FPV isolate from the USA. Another FPV isolate from Goa (GC1) was positioned in the same clade but had evolved independently. Conclusions and relevance Detection of CPV in both diarrhoeic/healthy cats and the occurrence of FPV infection in a vaccinated cat provide new insights into parvovirus infections in cats in India.

Spotlight on platelets: summary of BBTS combined special interest group autumn meeting, November 2015.

This conference first addressed aspects of component quality, highlighting the role of pathogen inactivation, the role of PAS or plasma in prolonging platelet viability and acceptable storage deviations. A series of talks on the medical use of platelets covered the role of platelet transfusion in preventing intracranial haemorrhage, platelet prophylaxis in haematological patients and the new trial of the HLA Matchmaker programme to provide epitope-matched platelets. The session on the surgical use of platelets considered the role of platelet transfusions in patients on anti-platelet agents, major trauma and interventional procedures and also the scope for tests of platelet function to direct therapy. The conference concluded with a panel discussion highlighting key areas of general interest, including the clinical use of platelets and near patient platelet function tests.

Post-transplant T cell chimerism predicts graft versus host disease but not disease relapse in patients undergoing an alemtuzumab based reduced intensity conditioned allogeneic transplant.

In this multicentre retrospective study we have studied the impact of T cell chimerism on the outcome of 133 patients undergoing an alemtuzumab based reduced intensity conditioning allograft (RIC). The median age of the patients was 50 years (range 42-55 years). 77 patients were transplanted using an HLA identical sibling donor while 56 patients received a fully matched volunteer unrelated donor graft. 64 patients had a lymphoid malignancy and 69 were transplanted for a myeloid malignancy. 38 patients (29%) relapsed with no significant difference in risk of relapse between patients developing full donor and mixed donor chimerism in the T-cell compartment on D+90 and D+180 post transplant. Day 90 full donor T cell chimerism correlated with an increased incidence of acute GVHD according to NIH criteria (p=0.0004) and the subsequent development of chronic GVHD. Consistent with previous observations, our results confirmed a correlation between the establishment of T cell full donor chimerism and acute GVHD in T deplete RIC allografts. However our study failed to identify any correlation between T cell chimerism and relapse risk and challenge the use of pre-emptive donor lymphocyte infusions (DLI) in patients with mixed T cell chimerism transplanted using an alemtuzumab based RIC regimen.

Azacitidine fails to eradicate leukemic stem/progenitor cell populations in patients with acute myeloid leukemia and myelodysplasia.

Epigenetic therapies demonstrate significant clinical activity in acute myeloid leukemia (AML) and myelodysplasia (MDS) and constitute an important new class of therapeutic agents. However hematological responses are not durable and disease relapse appears inevitable. Experimentally, leukemic stem/progenitor cells (LSC) propagate disease in animal models of AML and it has been postulated that their relative chemo-resistance contributes to disease relapse. We serially measured LSC numbers in patients with high-risk AML and MDS treated with 5'-azacitidine and sodium valproate (VAL-AZA). Fifteen out of seventy-nine patients achieved a complete remission (CR) or complete remission with incomplete blood count recovery (CRi) with VAL-AZA therapy. There was no significant reduction in the size of the LSC-containing population in non-responders. While the LSC-containing population was substantially reduced in all patients achieving a CR/CRi it was never eradicated and expansion of this population antedated morphological relapse. Similar studies were performed in seven patients with newly diagnosed AML treated with induction chemotherapy. Eradication of the LSC-containing population was observed in three patients all of whom achieved a durable CR in contrast to patients with resistant disease where LSC persistence was observed. LSC quantitation provides a novel biomarker of disease response and relapse in patients with AML treated with epigenetic therapies. New drugs that target this cellular population in vivo are required.

Increasing the enrolment of rural applicants to the faculty of medicine and addressing diversity by using a priority matrix approach to assign values to rural attributes.

In an external review of the admissions process for the Faculty of Medicine, University of Manitoba, Canada, it was suggested that admissions policies be modified to increase the enrolment of students more likely to practise in rural locations, by selecting a cohort of students with attributes reflecting potential for rural practice. A broad-based Working Group devised a framework for scoring personal attributes reflecting a potential for living and working in rural areas. This framework, based on established characteristics reported in the literature, valued applicants who had rural connections, a history of rural employment, a history of rural community service, or a combination of these attributes. Relative weights for the attributes were determined using a priority matrix approach. Historic admissions data, comprising applicants' rural origin (defined only by location of high school graduation), composite scores, and ranking, were reanalyzed to identify the magnitude of numerical constants that, when applied to composite scores, enhanced the relative ranking of eligible rural-origin applicants. This resulted in a hypothetical 29%-33% increase in the number of rural-origin students in incoming classes in those years. In the inaugural year of implementation of the policy and methodology, 60 admission offers (44.1%) were made to applicants with one or more rural attributes. Without adjustments, only 49 applicants with rural attributes (36%) would have been offered admission. This methodology resulted in a 22.4% increase in admission offers to applicants with rural attributes, and ushered in an incoming class that was more representative of the province's rural-urban demographics than in previous years. This methodology, although focused on rurality, could be equally applicable to any attribute, and to achieve greater diversity and equity among medical school applicants.

Evolution of bubble clouds induced by pulsed cavitational ultrasound therapy - histotripsy.

Mechanical tissue fractionation can be achieved using successive, high-intensity ultrasound pulses in a process termed histotripsy. Histotripsy has many potential clinical applications where noninvasive tissue removal is desired. The primary mechanism for histotripsy is believed to be cavitation. Using fast-gated imaging, this paper studies the evolution of a cavitating bubble cloud induced by a histotripsy pulse (10 and 14 cycles) at peak negative pressures exceeding 21MPa. Bubble clouds are generated inside a gelatin phantom and at a tissue-water interface, representing two situations encountered clinically. In both environments, the imaging results show that the bubble clouds share the same evolutionary trend. The bubble cloud and individual bubbles in the cloud were generated by the first cycle of the pulse, grew with each cycle during the pulse, and continued to grow and collapsed several hundred microseconds after the pulse. For example, the bubbles started under 10 microm, grew to 50 microm during the pulse, and continued to grow 100 microm after the pulse. The results also suggest that the bubble clouds generated in the two environments differ in growth and collapse duration, void fraction, shape, and size. This study furthers our understanding of the dynamics of bubble clouds induced by histotripsy.

Genome-wide detection of recurring sites of uniparental disomy in follicular and transformed follicular lymphoma.

Single-nucleotide polymorphism (SNP) array analysis was performed using the 10K GeneChip array on a series of 26 paired follicular lymphoma (FL) and transformed-FL (t-FL) biopsies and the lymphoma cell lines SCI-1, DoHH2 and RL2261. Regions of acquired homozygosity were detected in 43/52 (83%) primary specimens with a mean of 1.7 and 3.0 aberrations in the FL and t-FL, respectively. A notable feature was the occurrence of recurring sites of acquired uniparental disomy (aUDP) on 6p, 9p, 12q and 17p in cell lines and primary samples. Homozygosity of 9p and 17p arose predominantly in t-FL and in three cases rendered the cell homozygous for a pre-existing mutation of either CDKN2A or TP53. These data suggest that mutation precedes mitotic recombination, which leads to the removal of the remaining wild-type allele. In all, 18 cases exhibited abnormalities in both FL and t-FL samples. In 10 cases blocks of homozygosity were detected in FL that were absent in the subsequent t-FL sample. These differences support the notion that FL and t-FL may arise in a proportion of patients by divergence from a common malignant ancestor cell rather than by clonal evolution from an antecedent FL.

Non-invasive determination of zero-pressure geometry of arterial aneurysms.

Arterial aneurysms are in a pre-deformed state in vivo under non-zero pressure. The ability to determine their zero pressure geometry may help in improving accuracy of determination of stress distribution and reverse estimation of material properties from dynamic imaging data. An approximate method to recover the zero pressure geometry of the AAA is proposed. This method is motivated by the observation that the patterns in displacement field for a given AAA are strikingly consistent in an AAA under all physiological pressures. The basic principle is to leverage this observation to iteratively identify the geometry that when subjected to the in vivo pressure, will recover the geometry reconstructed from in vivo imaging. The methodology is demonstrated and validated using patient-specific AAA models.

Three-dimensional finite element analysis of residual stress in arteries.

Calculation of residual stress in arteries, using the analytical approach has been quite valuable in our understanding of its critical role in vascular mechanics. Stresses are calculated at the central section of an infinitely long tube by imposing a constant axial stretch while deforming the artery from the stress-free state to its unloaded state. However, segments used to perform opening-angle measurements have finite lengths. Further, the stress-free artery configuration is assumed to be circular. Experiments show that they are slightly noncircular. The numerical approach to residual stress calculation can allow us to study both these issues. Using 3D cylindrical geometries and an isotropic material model, we investigated how segment length can affect residual stress calculations and identified the appropriate segment length for experiments. Further, we recorded and used the true noncircular stress-free state of an artery segment, computed the residual stress distribution, and compared it to that from a similar, but circular segment. Our findings suggest that segment length must be ten times the wall thickness for it to be "long" enough. We also found that the circularity assumption may be a reasonable approximation for typical arteries.

Prediction of rupture risk in abdominal aortic aneurysm during observation: wall stress versus diameter.

OBJECTIVES: We previously showed that peak abdominal aortic aneurysm (AAA) wall stress calculated for aneurysms in vivo is higher at rupture than at elective repair. The purpose of this study was to analyze rupture risk over time in patients under observation. METHODS: Computed tomography (CT) scans were analyzed for patients with AAA when observation was planned for at least 6 months. AAA wall stress distribution was computationally determined in vivo with CT data, three-dimensional computer modeling, finite element analysis (nonlinear hyperelastic model depicting aneurysm wall behavior), and blood pressure during observation. RESULTS: Analysis included 103 patients and 159 CT scans (mean follow-up, 14 +/- 2 months per CT). Forty-two patients were observed with no intervention for at least 1 year (mean follow-up, 28 +/- 3 months). Elective repair was performed within 1 year in 39 patients, and emergent repair was performed in 22 patients (mean, 6 +/- 1 month after CT) for rupture (n = 14) or acute severe pain. Significant differences were found for initial diameter (observation, 4.9 +/-.1 cm; elective repair, 5.9 +/-.1 cm; emergent repair, 6.1 +/-.2 cm; P <.0001) and initial peak wall stress (38 +/- 1 N/cm(2), 42 +/- 2 n/cm(2), 58 +/- 4 N/cm(2), respectively; P <.0001), but peak wall stress appeared to better differentiate patients who later required emergent repair (elective vs emergent repair: diameter, 3% difference, P =.5; stress, 38% difference, P <.0001). Receiver operating characteristic (ROC) curves for predicting rupture were better for peak wall stress (sensitivity, 94%; specificity,81%; accuracy, 85% [with 44 N/cm(2) threshold]) than for diameter (81%, 70%, 73%, respectively [with optimal 5.5 cm threshold). With proportional hazards analysis, peak wall stress (relative risk, 25x) and gender (relative risk, 3x) were the only significant independent predictors of rupture. CONCLUSIONS: For AAAs under observation, peak AAA wall stress seems superior to diameter in differentiating patients who will experience catastrophic outcome. Elevated wall stress associated with rupture is not simply an acute event near the time of rupture.

Microbiologically influenced corrosion in petroleum product pipelines--a review.

Microbiologically influenced corrosion is responsible for most of the internal corrosion problems in oil transportation pipelines and storage tanks. One problematic area in treating gas lines is the occurrence of the stratification of water in the line. Under these conditions, corrosion inhibitors do not come into contact properly and oil and inhibitors undergo degradation. The role of bacteria on oil degradation, the consequences of oil degradation in fuel systems and its influence on corrosion have been explained in detail. Besides, factors influencing on degradation of oil and corrosion inhibitors have also been discussed. Mechanism of microbiologically influenced corrosion in oil pipeline has been explained. Many of the misapplication of biocides/inhibitors occur mainly because the characteristics of biocides/inhibitors are not considered before use in pipeline industry. List of biocides and monitoring programme have been collected from literature and presented.

In vivo analysis of mechanical wall stress and abdominal aortic aneurysm rupture risk.

OBJECTIVE: The purpose of this study was to calculate abdominal aortic aneurysm (AAA) wall stresses in vivo for ruptured, symptomatic, and electively repaired AAAs with three-dimensional computer modeling techniques, computed tomographic scan data, and blood pressure and to compare wall stress with current clinical indices related to rupture risk. METHODS: CT scans were analyzed for 48 patients with AAAs: 18 AAAs that ruptured (n = 10) or were urgently repaired for symptoms (n = 8) and 30 AAAs large enough to merit elective repair within 12 weeks of the CT scan. Three-dimensional computer models of AAAs were reconstructed from CT scan data. The stress distribution on the AAA as a result of geometry and blood pressure was computationally determined with finite element analysis with a hyperelastic nonlinear model that depicted the mechanical behavior of the AAA wall. RESULTS: Peak wall stress (maximal stress on the AAA surface) was significantly different between groups (ruptured, 47.7 +/- 6 N/cm(2); emergent symptomatic, 47.5 +/- 4 N/cm(2); elective repair, 36.9 +/- 2 N/cm(2); P =.03), with no significant difference in blood pressure (P =.2) or AAA diameter (P =.1). Because of trends toward differences in diameter, comparison was made only with diameter-matched subjects. Even with identical mean diameters, ruptured/symptomatic AAAs had a significantly higher peak wall stress (46.8 +/- 4.5 N/cm(2) versus 38.1 +/- 1.3 N/cm(2); P =.05). Maximal wall stress predicted risk of rupture better than the LaPlace equation (20.7 +/- 5.7 N/cm(2) versus 18.8 +/- 2.9 N/cm(2); P =.2) or other proposed indices of rupture risk. The smallest ruptured AAA was 4.8 cm, but this aneurysm had a stress equivalent to the average electively repaired 6.3-cm AAA. CONCLUSION: Peak wall stresses calculated in vivo for AAAs near the time of rupture were significantly higher than peak stresses for electively repaired AAAs, even when matched for maximal diameter. Calculation of wall stress with computer modeling of three-dimensional AAA geometry appears to assess rupture risk more accurately than AAA diameter or other previously proposed clinical indices. Stress analysis is practical and feasible and may become an important clinical tool for evaluation of AAA rupture risk.

An N-terminal domain of herpes simplex virus type Ig E is capable of forming stable complexes with gI.

Using limited proteolytic analyses, we show that gE present in soluble herpes simplex virus type 1 gE-gI complexes is cleaved into a C-terminal (CgE) and an N-terminal (NgE) domain. The domain boundary is in the vicinity of residue 188 of mature gE. NgE, but not CgE, forms a stable complex with soluble gI.

Use of chimeric proteins to investigate the role of transporter associated with antigen processing (TAP) structural domains in peptide binding and translocation.

The transporter associated with antigen processing (TAP) comprises two subunits, TAP1 and TAP2, each containing a hydrophobic membrane-spanning region (MSR) and a nucleotide binding domain (NBD). The TAP1/TAP2 complex is required for peptide translocation across the endoplasmic reticulum membrane. To understand the role of each structural unit of the TAP1/TAP2 complex, we generated two chimeras containing TAP1 MSR and TAP2 NBD (T1MT2C) or TAP2 MSR and TAP1 NBD (T2MT1C). We show that TAP1/T2MT1C, TAP2/T1MT2C, and T1MT2C/T2MT1C complexes bind peptide with an affinity comparable to wild-type complexes. By contrast, TAP1/T1MT2C and TAP2/T2MT1C complexes, although observed, are impaired for peptide binding. Thus, the MSRs of both TAP1 and TAP2 are required for binding peptide. However, neither NBD contains unique determinants required for peptide binding. The NBD-switched complexes, T1MT2C/T2MT1C, TAP1/T2MT1C, and TAP2/T1MT2C, all translocate peptides, but with progressively reduced efficiencies relative to the TAP1/TAP2 complex. These results indicate that both nucleotide binding sites are catalytically active and support an alternating catalytic sites model for the TAP transport cycle, similar to that proposed for P-glycoprotein. The enhanced translocation efficiency of TAP1/T2MT1C relative to TAP2/T1MT2C complexes correlates with enhanced binding of the TAP1 NBD-containing constructs to ATP-agarose beads. Preferential ATP interaction with TAP1, if occurring in vivo, might polarize the transport cycle such that ATP binding to TAP1 initiates the cycle. However, our observations that TAP complexes containing two identical TAP NBDs can mediate translocation indicate that distinct properties of the nucleotide binding site per se are not essential for the TAP catalytic cycle.