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Penetrating injuries of the neck involving major vessels are associated with high morbidity and mortality. A traumatic arteriovenous (AV) fistula can provide a protective effect by decompressing the injured arterial structure and prevent massive blood loss and airway compression. We present a novel description of CCA (common carotid artery) transection with associated protective AV fistula. Protective AV fistulae have been uncommonly described, and to our knowledge, this is the first case involving carotid transection with associated protective AV fistula ultimately allowing lifesaving operative repair.

Objectives This report aims to review the management and outcomes of Brucella-associated mycotic aortic aneurysms. Methods This is a retrospective chart review at a tertiary-level healthcare system. IRB approval was waived per policy. Results We describe a case of Brucella aortitis acquired from habitual contact with wild hogs. Clinical presentation included lower back pain and elevated white blood cell count. Diagnosis was confirmed with imaging showing an infrarenal abdominal aortic aneurysm and serology revealing elevated Brucella antibodies titers. The patient was initially managed with endovascular aortic repair and combined oral and intravenous antibiotics therapy. He then underwent explanation and extra-anatomical bypass due to symptomatic periaortic infection and interval development of type I endoleak. The patient was asymptomatic after his final operation at 24 months of follow-up and remained on suppressive oral antibiotic therapy. Conclusions An aortic aneurysm secondary to Brucella is a rare entity. A detailed history of long-term exposure to animals may be a clue to obtain serologic testing. Operative debridement and re-establishing of reliable blood flow combined with long-term antibiotic suppression are the mainstay of treatment.

This is a report of an iatrogenic inferior vena cava (IVC) segmental resection and reconstruction utilizing bovine pericardium. A 48-year-old female patient presented for a planned right nephrectomy by the urology service secondary to xanthogranulomatous pyelonephritis. This was complicated by inadvertent resection of an 8 cm segment of the infrarenal IVC. Postoperatively, the patient did not tolerate IVC ligation due to severe lower extremity edema. She then underwent reconstruction with a bovine pericardium conduit as an interposition graft. The post-operative course was complicated by pulmonary embolism requiring percutaneous intervention. This report addresses the utility of bovine pericardium for IVC reconstruction in an infected field.

The purpose of this paper is to explore the emerging themes within the discipline of retail design. The advent of multiple channels within the physical retail channel (showrooms, kiosks) and digital retail (mobile applications, e-commerce marketplace) pose challenges in the form of consistency of communication of brand identity and values. The research is a combination of thematic maps and qualitative interview techniques. Purposive sampling was considered for the selection of participants. In total 45 interviews have been taken of the various stakeholders – retailers, retail designers, communication designers and customers. Three broad themes emerged from the analysis- Technology, Design Elements and Communication, each having a number of sub-themes. 1. The themes that have emerged are based on views of minor representative of each category 2. Interviews from the social media and ecommerce marketplaces could have been taken. This can be the future research area. 1. The effects of deployment of AR/VR, 3D on the consumer decision-making is still not fully realized by the designers. 2. The consistency in brand imagery across channels can act as market differentiator. 3. The marketing communication managers should seek to enhance brand salience 4. The integration of customer data across various touchpoints (Big data) will be a distinguishing feature in near future. 5. Not all social media platforms are equal in creating and sustaining brandstorm and e-wom (word of mouth). This study is an attempt to make contribution in the area of retail design in the multichannel retail ecosystem. The themes that emerge out of the study are expected to assist in developing the framework wherein the brand image can be communicated consistently across channels.

Voltage-gated sodium channel NaV1.7 is a genetically validated target for pain. Identification of NaV1.7 inhibitors with all of the desired properties to develop as an oral therapeutic for pain has been a major challenge. Herein, we report systematic structure-activity relationship (SAR) studies carried out to identify novel sulfonamide derivatives as potent, selective, and state-dependent NaV1.7 inhibitors for pain. Scaffold hopping from benzoxazine to chroman and indane bicyclic system followed by thiazole replacement on sulfonamide led to identification of lead molecules with significant improvement in solubility, selectivity over NaV1.5, and CYP2C9 inhibition. The lead molecules 13, 29, 32, 43, and 51 showed a favorable pharmacokinetics (PK) profile across different species and robust efficacy in veratridine and formalin-induced inflammatory pain models in mice. Compound 51 also showed significant effects on the CCI-induced neuropathic pain model. The profile of 51 indicated that it has the potential for further evaluation as a therapeutic for pain.

Prostaglandin D2 (PGD2) released from immune cells or other cell types activates its receptors, D prostanoid receptor (DP)1 and 2 (DP1 and DP2), to promote inflammatory responses in allergic and lung diseases. Prostaglandin-mediated inflammation may also contribute to vascular diseases such as abdominal aortic aneurysm (AAA). However, the role of DP receptors in the pathogenesis of AAA has not been systematically investigated. In the present study, DP1-deficient mice and pharmacological inhibitors of either DP1 or DP2 were tested in two distinct mouse models of AAA formation: angiotensin II (AngII) infusion and calcium chloride (CaCl2) application. DP1-deficient mice [both heterozygous (DP1+/−) and homozygous (DP1−/−)] were protected against CaCl2-induced AAA formation, in conjunction with decreased matrix metallopeptidase (MMP) activity and adventitial inflammatory cell infiltration. In the AngII infusion model, DP1+/− mice, but not DP1−/− mice, exhibited reduced AAA formation. Interestingly, compensatory up-regulation of the DP2 receptor was detected in DP1−/− mice in response to AngII infusion, suggesting a potential role for DP2 receptors in AAA. Treatment with selective antagonists of DP1 (laropiprant) or DP2 (fevipiprant) protected against AAA formation, in conjunction with reduced elastin degradation and aortic inflammatory responses. In conclusion, PGD2 signaling contributes to AAA formation in mice, suggesting that antagonists of DP receptors, which have been extensively tested in allergic and lung diseases, may be promising candidates to ameliorate AAA.

The identification of a novel class of potent pan-genotypic NS5A inhibitors with good pharmacokinetic profile suitable for potential use in treating HCV infections is disclosed here. The present series of compounds are with less complex tricyclic central core, identified through a systematic SAR study carried out on biphenyl moiety. The SAR outcome has confirmed the requirement of near planar and linear conformation of the molecule to achieve the best pan-genotypic activity. In addition, SAR with substituted imidazoles on improvement of antiviral activity is disclosed. The newly identified compounds 12, 16, 19-21 have shown desirable pharmacokinetic profiles with a favorable uptake of compounds in liver and maintained a significant concentration for up to 8 h in the liver. In addition, compounds 20 and 21 have shown superior pan-genotypic anti-HCV activity compared to ledipasvir and daclatasvir. Additional characterization and preliminary safety assessment resulted in the identification of compound 20 as a potential clinical candidate.

Aims Chronic adventitial and medial infiltration of immune cells play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). Nicotinic acid (niacin) was shown to inhibit atherosclerosis by activating the anti-inflammatory G protein-coupled receptor GPR109A [also known as hydroxycarboxylic acid receptor 2 (HCA2)] expressed on immune cells, blunting immune activation and adventitial inflammatory cell infiltration. Here, we investigated the role of niacin and GPR109A in regulating AAA formation. Methods and results Mice were supplemented with niacin or nicotinamide, and AAA was induced by angiotensin II (AngII) infusion or calcium chloride (CaCl2) application. Niacin markedly reduced AAA formation in both AngII and CaCl2 models, diminishing adventitial immune cell infiltration, concomitant inflammatory responses, and matrix degradation. Unexpectedly, GPR109A gene deletion did not abrogate the protective effects of niacin against AAA formation, suggesting GPR109A-independent mechanisms. Interestingly, nicotinamide, which does not activate GPR109A, also inhibited AAA formation and phenocopied the effects of niacin. Mechanistically, both niacin and nicotinamide supplementation increased nicotinamide adenine dinucleotide (NAD+) levels and NAD+-dependent Sirt1 activity, which were reduced in AAA tissues. Furthermore, pharmacological inhibition of Sirt1 abrogated the protective effect of nicotinamide against AAA formation. Conclusion Niacin protects against AAA formation independent of GPR109A, most likely by serving as an NAD+ precursor. Supplementation of NAD+ using nicotinamide-related biomolecules may represent an effective and well-tolerated approach to preventing or treating AAA.

The formation of White (WEL) and Brown Etching Layers (BEL) on rail raceways during service causes the initiation of microcracks which finally leads to failure. Detailed characterization of the WEL and the BEL in a pearlitic rail steel is carried out from micrometer to atomic scale to understand their microstructural evolution. A microstructural gradient is observed along the rail depth including martensite, austenite and partially dissolved parent cementite in the WEL and tempered martensite, ultrafine/nanocrystalline martensite/austenite, carbon saturated ferrite and partially dissolved parent cementite in the BEL. Plastic deformation in combination with a temperature rise during wheel-rail contact was found to be responsible for the initial formation and further microstructural evolution of these layers. The presence of austenite in the WEL/BEL proves experimentally that temperatures rise into the austenite range during wheel-rail contact. This is in agreement with finite element modelling results. Each wheel-rail contact must be considered as an individual short but intense deformation and heat treatment cycle that cumulatively forms the final microstructure, as shown by diffusion length calculations of C and Mn. The presence of secondary carbides in the BEL indicates that the temperature in the BEL during individual loading cycles reaches levels where martensite tempering occurs. Partially fragmented primary cementite laths, enriched in Mn, depleted in Si, and surrounded by a C-gradient and dislocations were found in the BEL. The initial step in the formation of BEL and WEL is the defect- and diffusion-assisted decomposition of the original microstructure.

Climate change requires us to extract hundreds of gigatonnes of CO2 from the atmosphere over the next few decades. This requires we develop and scale up viable technologies to sequester CO2 from the highly dilute atmospheric concentrations. CO2 gas freezes at −78.5 °C and thus, in principle, can be separated from air, the nitrogen in which begins to freeze at −210 °C. Vortex tubes were investigated as a potential method of carbon capture through a series of geometrical and procedural optimisations. Ambient air is compressed and then separated by temperature due to the action of the Vortex Tube. These optimisations determined an increase in system pressure and length at cold mass fraction of 40% led to increased cooling. The heat profile of pipes suggested radiative cooling as the vortex propagated. An optimised single tube reached a maximum cooling of 39.9±2 °C. Vortex tubes thus present a method of separating and capturing components of the atmosphere. With further work, such as the successful combination of tubes in series, it is hoped that vortex tubes may prove to be a scalable solution capable of contributing to the reduction in atmospheric CO2 using the solar cyclone tower to provide the energy and air flows required for this task.

Voltage-gated sodium channel Na

BACKGROUND: In spite of general decline worldwide, off-pump coronary artery bypass grafting (CABG) surgery is performed in more than 60% of patients undergoing CABG in India; mainly because of shorter operative time and reduced procedure cost. However, paucity of data exists in literature about early outcomes following off-pump CABG from India. METHODOLOGY: We conducted a prospective observational study of 800 consecutive cases that underwent off-pump CABG (OPCAB) from August 2015 to October 2017. Primary end point of the study was the 30-day/in-hospital mortality from any cause. RESULTS: On multivariate analysis, emergency surgery (OR 9.72; CI 1.96–48.21, p value 0.005), severe left ventricular dysfunction (OR 2.28; CI 1.25–4.76, p value 0.026), postoperative atrial fibrillation (OR 9.95; CI 3.12–32.01, p value 0.05), and dialysis-dependent renal failure (OR 29.7, CI 10.02–87.99, p value 0.006) were the factors associated with mortality. The observed mortality was 1.6%, and the expected mortality by EuroSCORE II was 2.6%. The median EuroSCORE II of expired patients was 3.03 and of entire cohort was 1.54 (p value 0.001). Stroke rate was 0.9%. Deep sternal wound infection occurred in 0.9%, and 3.8% patients were readmitted to the hospital after discharge. CONCLUSION: Early outcome of off-pump CABG was excellent in this study. Increased incidence of deep sternal wound infection remains a concern. Multicenter study with a larger sample size is required for a dependable evaluation of the efficacy of off-pump CABG in Indian population.

Sufficient liquid feeding under constrained solidification conditions like, those experienced in welding and casting, is vital to avoid solidification cracking. We present the results of unique in-situ experimental observations of liquid feeding in a solidifying steel melt pool. Liquid feeding was observed in the inter-cellular regions during the terminal stage of solidification. An average liquid flow speed of 450–500 μm s−1 was found. A pressure difference of the order of 104 Pa is calculated to cause the liquid flow. The rate of solidification shrinkage and the rate of deformation were found to be less than the rate of liquid feeding.

Coil migration into the colon is an extremely rare complication of aneurysm embolization and only three cases have been reported. Two of these cases were managed with resection of the involved colon and the remaining case was managed with serial imaging. We present a 70-year-old man who developed hematochezia two years after coil embolization of a ruptured left hypogastric artery aneurysm. The patient was successfully treated with diverting colostomy and endoscopic closure of the sigmoid colon defect. We present the only case report of the use of advanced endoscopy to treat endovascular coil migration.

Hot cracking during laser welding of Transformation Induce Plasticity (TRIP) steel at the edges of steel flanges can be a problem. In this study, modified hot cracking tests were performed by welding on a single-side clamped specimen at various distances from the free edge, while the heat input and external constraints remained constant. In situ temperature and strain measurements were carried out using pre-attached thermocouples and digital image correlation, respectively. A thermal-mechanical finite element (FE) model was constructed and validated with the temporal and spatial data measured. From the validated FE model, the temperature and strain evolution in the weld mushy zone were studied. A critical strain for the onset of hot cracking in the TRIP steel examined was found to be in the range of 3.2 to 3.6%. This threshold was further evaluated and experimentally confirmed by welding with different heat inputs.

Hot cracking during laser welding of advanced high-strength steels is reported to be a serious problem by automotive manufacturers. In this work, hot cracking susceptibilities of transformation-induced plasticity (TRIP) and dual-phase (DP) steels are studied based on a multi-scale modelling approach. Transient temperatures measured from welding experiments are used to validate a finite element (FE) model. The temperature, thermal gradient and cooling rate in the weld fusion zone are extracted from the FE model and pre-defined as boundary conditions to a phase field model. The welding-induced microstructural evolution is simulated considering thermodynamic and mobility data. Results show that, compared to the DP steel, the TRIP steel has a broader solidification range, a greater pressure drop at the inter-dendritic regions, and an increased phosphorus segregation at the grain boundaries; all these make this steel more susceptible for hot cracking.

We report a case of mycotic thoracic aortic aneurysm managed by staged hybrid repair. A 30-year-old male patient with polysubstance abuse presented with chest pain and elevated white blood cell count. CTA performed showed a rapidly developing mycotic thoracic aortic pseudoaneurysm. He underwent emergent thoracic endovascular aortic repair followed 24 hours later by surgical debridement of the posterior mediastinum. Cultures grew Methicillin-resistant Staphylococcus aureus and patient was placed on long term antibiotics. The patient was asymptomatic on follow up one year after his final operation with complete exclusion of pseudoaneurysm with no endoleak.

Solidification cracking susceptibility during laser welding was studied experimentally and numerically in advanced high strength steel sheets, namely transformation-induced plasticity (TRIP) and dual phase (DP) steel. Using the same heat input, laser bead-on-plate welding was carried out on single sided clamped specimens at various starting distances from the free edge. It was observed that TRIP steel with high phosphorus is susceptible to cracking while in DP steel with low phosphorus, solidification cracking was not observed. The metallurgical factors affecting the solidification cracking were studied and it was found that solidification morphology, phosphorus segregation at the prior austenite grain boundaries, inclusions, interface growth rate and interdendritic liquid feeding have a prominent effect on the strength of the mushy zone. These results are discussed pertaining to the cracking mechanism. For the same welding parameters, a difference in the weld pool shape was observed in both the steels, which is attributed to the high temperature thermophysical properties. Weld pool shape affects the strain distribution in the mushy region and thus the cracking behaviour. The cracking phenomenon is further described using hot ductility curves. Keywords: Solidification cracking, Weld pool shape, Advanced high strength steels, Automotive, Laser welding

In response to vascular injury, vascular smooth muscle cells (VSMCs) may switch from a contractile to a proliferative phenotype thereby contributing to neointima formation. Previous studies showed that the long noncoding RNA (lncRNA) NEAT1 is critical for paraspeckle formation and tumorigenesis by promoting cell proliferation and migration. However, the role of NEAT1 in VSMC phenotypic modulation is unknown. Herein we showed that NEAT1 expression was induced in VSMCs during phenotypic switching in vivo and in vitro. Silencing NEAT1 in VSMCs resulted in enhanced expression of SM-specific genes while attenuating VSMC proliferation and migration. Conversely, overexpression of NEAT1 in VSMCs had opposite effects. These in vitro findings were further supported by in vivo studies in which NEAT1 knockout mice exhibited significantly decreased neointima formation following vascular injury, due to attenuated VSMC proliferation. Mechanistic studies demonstrated that NEAT1 sequesters the key chromatin modifier WDR5 (WD Repeat Domain 5) from SM-specific gene loci, thereby initiating an epigenetic “off” state, resulting in down-regulation of SM-specific gene expression. Taken together, we demonstrated an unexpected role of the lncRNA NEAT1 in regulating phenotypic switching by repressing SM-contractile gene expression through an epigenetic regulatory mechanism. Our data suggest that NEAT1 is a therapeutic target for treating occlusive vascular diseases.

In response to vascular injury, vascular smooth muscle cells (VSMCs) may switch from a contractile to a proliferative phenotype thereby contributing to neointima formation. Previous studies showed that the long noncoding RNA (lncRNA) NEAT1 is critical for paraspeckle formation and tumorigenesis by promoting cell proliferation and migration. However, the role of NEAT1 in VSMC phenotypic modulation is unknown. Herein we showed that NEAT1 expression was induced in VSMCs during phenotypic switching in vivo and in vitro. Silencing NEAT1 in VSMCs resulted in enhanced expression of SM-specific genes while attenuating VSMC proliferation and migration. Conversely, overexpression of NEAT1 in VSMCs had opposite effects. These in vitro findings were further supported by in vivo studies in which NEAT1 knockout mice exhibited significantly decreased neointima formation following vascular injury, due to attenuated VSMC proliferation. Mechanistic studies demonstrated that NEAT1 sequesters the key chromatin modifier WDR5 (WD Repeat Domain 5) from SM-specific gene loci, thereby initiating an epigenetic “off” state, resulting in down-regulation of SM-specific gene expression. Taken together, we demonstrated an unexpected role of the lncRNA NEAT1 in regulating phenotypic switching by repressing SM-contractile gene expression through an epigenetic regulatory mechanism. Our data suggest that NEAT1 is a therapeutic target for treating occlusive vascular diseases.

In situ strain evolution during laser welding has been measured by means of digital image correlation to assess the susceptibility of an advanced high strength automotive steel to solidification cracking. A novel method realised using auxiliary illumination and optical narrow bandpass filter allowed strain measurements as close as 1.5 mm from the fusion boundary with good spatial and temporal resolution. A finite-element thermomechanical model of the welding process supports the experimentally measured transverse strain. The validated finite-element numerical model can be used to assess the local strain and associated stress conditions which influences weldability and in particular, solidification cracking.

In situ high-temperature laser scanning confocal microscopy is applied to study solidification cracking in a TRIP steel. Solidification cracking was observed in the interdendritic region during the last stage of solidification. Atom probe tomography revealed notable enrichment of phosphorus in the last remaining liquid. Phase field simulations also confirm phosphorus enrichment leading to severe undercooling of more than 160 K in the interdendritic region. In the presence of tensile stress, an opening at the interdendritic region is difficult to fill with the remaining liquid due to low permeability and high viscosity, resulting in solidification cracking.

Like all physicians, radiologists in the United States are subject to frequent and costly medical malpractice claims. Legal scholars and physicians concur that the US civil justice system is neither precise nor accurate in determining whether malpractice has truly occurred in cases in which claims are made. Sometimes, this inaccuracy is driven by biases inherent in medical expert-witness opinions. For example, expert-witness testimony involving "missed" radiology findings can be negatively affected by several cognitive biases, such as contextual bias, hindsight bias, and outcome bias. Biases inherent in the US legal system, such as selection bias, compensation bias, and affiliation bias, also play important roles. Fortunately, many of these biases can be significantly mitigated or eliminated through the use of appropriate blinding techniques. This paper reviews the major works on expert-witness blinding in the legal scholarship and the radiology professional literature. Its purpose is to acquaint the reader with the evidence that unblinded expert-witness testimony is tainted by multiple sources of bias and to examine proposed strategies for addressing these biases through blinding.

The investigation has dealt with the structure and magnetic properties of rapidly solidified and annealed Fe73·5 − x Si13·5B9Nb3Cu1Al x (x = 0, 2, 4, 6 at%) ribbons prepared by melt spinning. Complete amorphous structure was obtained in as-spun ribbons of x = 0 and 2 at% compositions, whereas structure of ribbons containing higher Al was found to be partially crystalline. Detailed thermal analyses of the alloys and the melt spun ribbons revealed that the glass forming ability in the form of ${{ \textit{T}}}_{\mathbf{x}}{/}{{ \textit{T}}}_{\mathbf{l}}$ (ratio between crystallization and liquidus temperature) is the highest for 2 at% Al alloys and decreases with further addition of Al. Annealing of all as spun ribbons resulted in the precipitation of nanocrystalline phase embedded in amorphous matrix in the form of either ${ \textit{DO}}_{{ 3}}$ phase or bcc ${\upalpha}$ -Fe(Si/Al) solid solution depending on the initial composition of the alloy. Only bcc ${\upalpha}$ -Fe(Si/Al) solid solution was formed in 2 at% Al ribbons whereas ordered DO3 structure was found to be stabilized in other ribbons including 0 at% Al. A detailed study on determination of precision lattice parameter of nanocrystalline phase revealed that the lattice parameter increases with the addition of Al indicating the partitioning behaviour of Al in nanocrystalline phase.

Hemodialysis Reliable Outflow (HeRO) grafts (Merit Medical Systems, Inc, South Jordan, Utah) provide a means for access in catheter-dependent hemodialysis patients but typically require several weeks for tissue incorporation. Modifying the HeRO graft with an ACUSEAL graft (W. L. Gore & Associates, Newark, Del) can allow immediate cannulation, thus reducing catheter dependence time and its associated complications. A retrospective review of patients at our institution from 2013 to 2016 who underwent placement of a modified HeRO dialysis system with ACUSEAL graft was performed. Complications and outcomes were analyzed, with patency rates and hours to successful cannulation being major end points. Modified HeRO grafts were successfully placed in 10 catheter-dependent patients. Postoperative complications included two thromboses and one hematoma. At 6 months of follow-up, mean time to graft cannulation was 33.7 hours, with 100% success; the primary and secondary patency rates were 70% and 90%, respectively. Our modification allows an accelerated use of the HeRO system, reducing catheter dependence time with acceptable postoperative complications and patency rates.

Insect pheromonal glomeruli are thought to track the fine spatiotemporal features of one or a few odorants to aid conspecific localization. However, it is not clear whether they function differently from generalist glomeruli, which respond to many odorants. In this study, we test how DA1, a model pheromonal glomerulus in the fruit fly, represents the spatial and temporal properties of its input, compared with other glomeruli. We combine calcium imaging and electrical stimulation in an isolated brain preparation for a simultaneous, unbiased comparison of the functional organization of many glomeruli. In contrast to what is found in other glomeruli, we find that ipsilateral and contralateral stimuli elicit distinct spatial patterns of activity within DA1. DA1's output shows a greater preference for ipsilateral stimuli in males than in females. DA1 experiences greater and more rapid inhibition than other glomeruli, allowing it to report slight interantennal delays in stimulus onset in a “winner-take-all” manner. DA1's ability to encode spatiotemporal input features distinguishes it from other glomeruli in the fruit fly antennal lobe but relates it to pheromonal glomeruli in other insect species. We propose that DA1 is specialized to help the fly localize and orient with respect to pheromone sources.