CFD Analysis of Flow Pattern in Electrochemical Machining for L-Shaped Tool

Electrochemical machining is a non-conventional machining process worked with a principle of Faraday’s law. Due to improper tool design of complicated shapes, there are chances of passivation and boiling of electrolyte in ECM process that causes poor machining. Predicting the flow pattern is also important to prevent boiling tendency of electrolyte is due to overheating of electrolyte. This project work is for optimizing the design of L-shaped tool and to study the flow pattern, current density distribution, velocity profile, temperature pattern, turbulence and final shape change of workpiece top surface. Four models with different shaped grooves for supplying electrolyte are evaluated. ANSYS-CFX software was used for simulating this CFD problem. Geometrical model consists of a circular workpiece made with Iron, 20% brine solution as electrolyte and Lshaped copper tool with different kind of grooves. This problem is considered as a steadystate problem with turbulence model. A potential difference of 10V is applied in between the IEG. The models were simulated for various inlet velocities and the major findings are stated below. The maximum temperature in IEG for all models has a decreasing tendency with respect to the increase in inlet velocities. The maximum current density has increasing tendency with respect to increase in inlet velocities. MRR and turbulence also increase in inlet velocities. Tendency of passivation is decreasing in case of all models with increasing velocity. Model 3 is the best tool design from among the four models evaluated

Peak expiratory flow rate nomogram in relation to anthropometric determinants of South Indian school children

Background: The predictive normal value of peak expiratory flow rate (PEFR), used in monitoring of healthy andasthmatic children, is correlated with height, but it may vary with other anthropometric measurements and ethnicdifferences. Purpose: To study the correlation of PEFR with age, sex, body mass index (BMI), chest circumference(CC), and MUAC and to formulate PEFR nomograms in relation to these anthropometric variables in a ruralschool going children of age group 6-12 years in southern India. Methods: A descriptive cross-sectional studywas conducted in 2000 children consist of 993 boys and 1007 girls who fulfilled the selection criteria from eightrandomly selected government schools from a rural area. PEFR was measured age wise using Mini-Wright peakflow meter and the highest among the three values was taken. PEFR nomograms were formulated, and its correlationwith BMI, height, weight, CC, and MUAC were estimated using linear regression analysis. Results: PEFR hasstrong (p < 0.001) positive correlation with age, height, weight, MUAC, and CC, but it has poor correlation withBMI (p = 0.985) which showed flat regression line with narrow 95% confidence limits. Conclusion: In this study,PEFR has nonsignificant correlation with BMI but has strong positive correlation with other anthropometricmeasurements. This underlines the need of a local reference nomogram as anthropometric measurements affect thePEFR reference values

Brucellosis in Wayanad Tribal Goat Population: A Preliminary Serological Survey

Caprine brucellosis is an endemic disease and is present in many countries. It causes heavy losses in goats and is transmissible to man. The study aimed at determining the seroprevalence of caprine brucellosis for the first time by serological tests in Wayanad district of Kerala, where goat rearing is the main occupation among tribal women. A total of 24 sera were positive by the RBPT with a seroprevalence of 5.7%. Upon STAT testing of all the 420 sera, 18 out of 24 samples (4.3%) showed presence of Brucella antibodies. Considering sensitivity, specificity and ease in performing the test, it is suggested that a combination of RBPT and STAT can be used in the diagnosis of caprine brucellosis in order to control and eradicate the disease

Integration of Liquid Biopsy and Pharmacogenomics for Precision Therapy of EGFR Mutant and Resistant Lung Cancers

The advent of molecular profiling has revolutionized the treatment of lung cancer by comprehensively delineating the genomic landscape of the epidermal growth factor receptor (EGFR) gene. Drug resistance caused by EGFR mutations and genetic polymorphisms of drug metabolizing enzymes and transporters impedes effective treatment of EGFR mutant and resistant lung cancer. This review appraises current literature, opportunities, and challenges associated with liquid biopsy and pharmacogenomic (PGx) testing as precision therapy tools in the management of EGFR mutant and resistant lung cancers. Liquid biopsy could play a potential role in selection of precise tyrosine kinase inhibitor (TKI) therapies during different phases of lung cancer treatment. This selection will be based on the driver EGFR mutational status, as well as monitoring the development of potential EGFR mutations arising during or after TKIs treatment, since some of these new mutations may be druggable targets for alternative TKIs. Several studies have identified the utility of liquid biopsy in the identification of EGFR driver and acquired resistance with good sensitivities for various blood-based biomarkers. With a plethora of sequencing technologies and platforms available currently, further evaluations using randomized controlled trials (RCTs) in multicentric, multiethnic and larger patient cohorts could enable optimization of liquid-based assays for the detection of EGFR mutations, and support testing of CYP450 enzymes and drug transporter polymorphisms to guide precise dosing of EGFR TKIs

A critical review on polyvinylidene fluoride (PVDF)/zinc oxide (ZnO) based piezoelectric and triboelectric nanogenerators

In the recent era of energy crisis, piezoelectric and triboelectric effects are surfacing out of several research topics. Polyvinylidene fluoride (PVDF) and its copolymers are well known piezoelectric polymers due to their high piezoelectricity and widely used in flexible devices. PVDF is greatly utilized in preparation of triboelectric layer also due to its higher electronegative nature amongst common polymers. On the other hand, zinc oxide (ZnO) has been studied widely to investigate its multifunctional properties including piezoelectricity, pyroelectricity and antibacterial activity. This versatile material can be prepared, using low cost and environmental friendly routes, in various morphologies. Various research is already performed to capture the synergistic effect of reinforcing ZnO within PVDF polymeric matrix. This work firstly describes the basic principles of piezoelectric and triboelectric effects. Thereafter, piezoelectric and triboelectric performances of PVDF and ZnO based materials are briefly depicted based on their structures. Finally, challenges and future scopes, associated with the mechanical energy harvesting from such materials, are highlighted

Transcriptomic profile of adverse neurodevelopmental outcomes after neonatal encephalopathy

A rapid and early diagnostic test to identify the encephalopathic babies at risk of adverse outcome may accelerate the development of neuroprotectants. We examined if a whole blood transcriptomic signature measured soon after birth,predicts adverse neurodevelopmental outcomeeighteenmonths after neonatal encephalopathy.We performed next generation sequencing on whole blood ribonucleic acid obtained within sixhours of birth from the first 47encephalopathic babies recruited to the Hypothermia for Encephalopathy in Low and middle-income countries (HELIX)trial. Two infants with blood culture positive sepsis were excluded, and the data from remaining 45 were analysed. A total of 855genes were significantly differentially expressed between the good and adverse outcome groups, of which RGS1and SMC4 werethe most significant. Biological pathway analysis adjusted for gender, trial randomisation allocation (cooling therapy versus usual care) and estimated blood leukocyte proportions revealed over-representation of genes from pathways related to melatoninand polo-like kinase in babieswith adverse outcome. These preliminary data suggest that transcriptomic profiling may be a promising tool for rapid risk stratification in neonatal encephalopathy. It may provide insights into biological mechanismsand identify novel therapeutic targetsfor neuroprotection

Explaining the Atypical Reaction Profiles of Heme Enzymes with a Novel Mechanistic Hypothesis and Kinetic Treatment

Many heme enzymes show remarkable versatility and atypical kinetics. The fungal extracellular enzyme chloroperoxidase (CPO) characterizes a variety of one and two electron redox reactions in the presence of hydroperoxides. A structural counterpart, found in mammalian microsomal cytochrome P450 (CYP), uses molecular oxygen plus NADPH for the oxidative metabolism (predominantly hydroxylation) of substrate in conjunction with a redox partner enzyme, cytochrome P450 reductase. In this study, we employ the two above-mentioned heme-thiolate proteins to probe the reaction kinetics and mechanism of heme enzymes. Hitherto, a substrate inhibition model based upon non-productive binding of substrate (two-site model) was used to account for the inhibition of reaction at higher substrate concentrations for the CYP reaction systems. Herein, the observation of substrate inhibition is shown for both peroxide and final substrate in CPO catalyzed peroxidations. Further, analogy is drawn in the “steady state kinetics” of CPO and CYP reaction systems. New experimental observations and analyses indicate that a scheme of competing reactions (involving primary product with enzyme or other reaction components/intermediates) is relevant in such complex reaction mixtures. The presence of non-selective reactive intermediate(s) affords alternate reaction routes at various substrate/product concentrations, thereby leading to a lowered detectable concentration of “the product of interest” in the reaction milieu. Occam's razor favors the new hypothesis. With the new hypothesis as foundation, a new biphasic treatment to analyze the kinetics is put forth. We also introduce a key concept of “substrate concentration at maximum observed rate”. The new treatment affords a more acceptable fit for observable experimental kinetic data of heme redox enzymes

Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh

Background: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia. Methods: We did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18–22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02387385. Findings: We screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87–1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention. Interpretation: Therapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available. Funding: National Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation. Translations: For the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes