Critical Members Research Articles

Assessment of an old reinforced concrete open-spandrel arch railway bridge

This paper presents assessment of a 94 years old reinforced concrete (RC) open-spandrel arch bridge with a total length of 285 m having seven major spans of 35 m, a height of 34 m and a vertical slope of 15 ‰. As the bridge was currently subjected to heavy trains having higher axle loads than it was originally designed, assessment of its actual structural condition was necessary. To determine actual in-situ behavior of the bridge, dynamic tests including a series of acceleration measurements along the bridge spans were performed. Then, 3D finite element model of the bridge was generated by using a structural analysis software based on its original constructional drawings. The initial FE model was updated using Response Surface Method (RSM) technique based on the results obtained from measurement data. The updated FE model was used for structural assessment and evaluation of the bridge under UIC-71 live loading. Rating factor and reliability index for each bridge member based on Load and Resistance Factor Rating (LRFR) approach were obtained. Results of the rating and reliability analysis showed that the most critical member of the bridge was the deck, thus strengthening and retrofitting of these deck members might be needed for live loads greater than those induced by UIC-71 train.

The lived experience by patients and family members of extracorporeal membrane oxygenation: A qualitative study

ObjectiveTo examine the lived experience of extracorporeal membrane oxygenation (ECMO) by patients and their families, and their relationship with intensive care clinicians. Research methodologySemi-structured interviews were conducted with six patients who had received ECMO and with four of their family members. The data were analysed narratively using a constant comparative method. SettingPatients were treated at a major acute care hospital in British Columbia between 2014 and 2021. ECMO was used either as a bridge to recovery or to organ transplant. Four had family members bedside throughout, while two had virtual visits due to COVID-19 infection control measures. FindingsECMO was experienced through a triad of relationships between the patient, key family members and key clinicians. The strength, directionality and focus of these relationships shifted during therapy and realigned once ECMO was removed. The largest shift involved family members. Post-ECMO, patients relied almost entirely on spouses, adult children and clinical team members to reconstruct their experience. The connection between families and clinical team members was limited and changed little. ConclusionsThe lived experience of ECMO was complex in ways yet to be comprehensively reported in the literature. This technology had particular impact on family members when ECMO was used as a bridge to transplant and where run times extended to multiple weeks. COVID-19 infection control restrictions further complicated how this technology was experienced. Findings from this study highlight the importance of intensive care nurses recognising the critical role family members play as witnesses whose experiences later allow patients to make sense of their journey post-discharge.

Numerical investigation on CFRP strengthening and reinforcement bar detailing of RC columns to resist blast load

The failure of column, which is a critical compressive structural member of a building, may lead to devastating progressive collapses. The present numerical study involves investigation on the performance of as-built and strengthened RC columns using 0°/90° CFRP layers under blast loading. A nonlinear FEA program, LS-DYNA was employed to study the RC columns response when subjected to blast loading. Blast field test data from recent literatures was employed for validation and further parametric studies. Variables considered were different charge masses, height of bursts, concrete compressive strengths, standoff distances, tie spacings, transverse reinforcement steel detail schemes, and 0°/90° CFRP layers. It was revealed that scaled distance parameters had a significant effect on the behaviour of RC columns under blast loading. Compared to as-built column, 0°/90° CFRP strengthened RC columns displayed excellent blast resistance. Transverse reinforcement steel details had a significant effect on lateral displacement response and failure modes of RC columns. Compared to conventionally-detailed columns, seismically-detailed columns and transverse reinforcement steel bars accompanied with square-diamond shaped ties exhibited enormous blast resistance capacity.

A Framework for Identification of the Critical Members for Truss Bridges through Nonlinear Dynamic Analysis

A Framework for Identification of the Critical Members for Truss Bridges through Nonlinear Dynamic Analysis

Design and synthesis of novel benzimidazole linked thiazole derivatives as promising inhibitors of drug-resistant tuberculosis

Despite combination therapy is effective in treating tuberculosis (TB) caused by susceptible Mycobacterium tuberculosis (Mtb) strains, overcoming multidrug resistance (MDR) remains a problem. As a result, it is critical to continue developing new chemotherapeutic drugs with unique mechanisms of action. A variety of benzimidazole-linked thiazole compounds was designed and developed for the treatment of Mtb in this work using a molecular hybridization approach. The newly synthesized compounds demonstrated potent anti-TB action against drug-resistant Mtb strains. Compounds 4g and 4h are more effective against MDR clinical isolates (CDCT-16 and CDCT-27) than isoniazid, with MIC ranges ranging from 3.68 to 8.15 µM. Other derivatives demonstrated moderate to good anti-TB efficacy against MDR clinical isolates. The cytotoxicity findings recommend that this class of compounds is rated as low. Further SAR analysis reveals that electron-withdrawing groups on the thiazole ring of the compounds are essential. The findings were also connected with molecular docking studies, which provided models for the inhibitors strong interactions with the mycobacterial membrane protein large 3 (MmpL3), which is a critical member in the formation of the Mtb stiff cell wall. Compounds potential ADMET descriptors, drug score and drug-likeness properties were validated by in-silico predictions.

Rationale and Development of a Data Coordinating Center to Support the Type 1 Diabetes in Acute Pancreatitis Consortium.

A data coordinating center (DCC) is a critical member of any multicenter research undertaking, and that is especially true for the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC). We describe how the T1DAPC DCC supports the consortium via its experience and expertise in project management, administration, financial management, regulatory compliance, scientific coordination, data management, research computing, and biostatistics and in facilitating scientific publications. The DCC's matrix management system has been extremely effective in managing all of its responsibilities. The first 16 months in the life of the T1DAPC have been dedicated to the development of its first protocol, titled Diabetes RElated to Acute pancreatitis and its Mechanisms (DREAM), addressing the institutional review board and regulatory components, developing the T1DAPC data management system, and providing training and certification of clinical center staff. As a result of its efforts, the DCC was a major contributor to the T1DAPC being able to initiate recruitment for the DREAM study in January 2022.

Effects of Tsunami Forces on RC Framed Structure Subjected to Bracing and Shear Wall

Abstract— The Indian Ocean Tsunami on 26 December 2004 resulted into massive destruction to coastal communities with more than 3,00,000 people losing their lives, and causes severe damage to buildings, bridges and other infrastructure. Such catastrophic event made the coastal community realize the need for the preparedness against initial ground shaking and subsequent effects followed by Tsunami. The current study focuses on progressive collapse analysis of 10 storey reinforced concrete frame with bracing and shear wall subjected to different Tsunami forces. The Tsunami forces were calculated according to the guidelines of FEMA P-646, ASCE 7-16. The December 26, 2004 Tsunami parameters on the coast of Tamilnadu were considered for the evaluation of effect of Tsunami forces on structure. To simulate similar conditions structure was designed according to Zone-III and was subjected to Tsunami forces for the 12m, 9m and 6m runup. This study consists of two parts: 1) The calculation of Tsunami forces and application of forces on structure and 2) Progressive collapse analysis of structure by removing the vertical load bearing critical members due to Tsunami forces. The progressive collapse analysis was carried out with the help of commercially available software named ETABs 16. The critical members were removed. The analysis was carried out by referring General Services Administration (GSA-2013, Revised 2016) and Unified Facility Criteria - Department of Defense (UFC - DoD-2009, Revised 2016) guidelines. From the analysis results it was found out that structure becomes critical when Bracing and Shear wall were oriented normal to the flow of tsunami. Upon performing the progressive collapse analysis of structure which was found to be critical due to Tsunami forces reveals that the joint at which the vertical member was removed did not exceed the acceptance criteria of collapse prevention. Hence structure was able to redistribute the unbalanced gravity load and thus prevents the progressive collapse of structure. Keywords— RC Frame, Shear wall and Bracing, Tsunami Forces, Nonlinear Static Analysis, Progressive Collapse

Isosteviol sodium attenuates high fat/high cholesterol-induced myocardial dysfunction by regulating the Sirt1/AMPK pathway

A fat-rich diet triggers obesity, and promotes cardiomyocyte injury. Till now, no prior investigations suggested a beneficial role of Isosteviol Sodium (STVNa) in cardiac activity in high fat diet (HFD)-exposed obese rats. However, there is evidence that STVNa accelerates healing of multiple tissue injuries. Herein, we explored the underlying mechanism behind the STVNa-based protection against HFD-induced myocardial dysfunction (MCD) in a rat model of myocardial injury. We employed dosages of 1, 10, and 20 mg/kg STVNa to treat MCD in rats fed with a HFD. Based on our results, STVNa repressed MCD (as indicated by ecocardiographic analysis), myocardium function, pathological structure, and myocardial enzymes. Mechanistically, the STVNa-mediated protection against HFD-induced MCD involved inhibition of inflammation and oxidative stress. Furthermore, using Western blot analysis, we revealed that the critical members of the Sirt1/AMPK network were markedly activated in the STVNa-treated group, relative to HFD-fed controls. Collectively, these evidences suggested that the STVNa offered strong protection against HFD-induced MCD. Moreover, this effect was mediated by the activation of the Sirt1/AMPK network, which, in turn, promoted lipid metabolism.

Mitochondrial complex I dysfunction alters the balance of soluble and membrane-bound TNF during chronic experimental colitis

Inflammatory bowel disease (IBD) is a complex, chronic, relapsing and heterogeneous disease induced by environmental, genomic, microbial and immunological factors. MCJ is a mitochondrial protein that regulates the metabolic status of macrophages and their response to translocated bacteria. Previously, an acute murine model of DSS-induced colitis showed increased disease severity due to MCJ deficiency. Unexpectedly, we now show that MCJ-deficient mice have augmented tumor necrosis factor α converting enzyme (TACE) activity in the context of chronic inflammation. This adaptative change likely affects the balance between soluble and transmembrane TNF and supports the association of the soluble form and a milder phenotype. Interestingly, the general shifts in microbial composition previously observed during acute inflammation were absent in the chronic model of inflammation in MCJ-deficient mice. However, the lack of the mitochondrial protein resulted in increased alpha diversity and the reduction in critical microbial members associated with inflammation, such as Ruminococcus gnavus, which could be associated with TACE activity. These results provide evidence of the dynamic metabolic adaptation of the colon tissue to chronic inflammatory changes mediated by the control of mitochondrial function.

Different Immunoregulation Roles of Activin A Compared With TGF-β.

Activin A, a critical member of the transforming growth factor-β (TGF-β) superfamily, is a pluripotent factor involved in allergies, autoimmune diseases, cancers and other diseases with immune disorder. Similar to its family member, TGF-β, activin A also transmits signals through SMAD2/SMAD3, however, they bind to distinct receptors. Recent studies have uncovered that activin A plays a pivotal role in both innate and adaptive immune systems. Here we mainly focus its effects on activation, differentiation, proliferation and function of cells which are indispensable in the immune system and meanwhile make some comparisons with those of TGF-β.

Building Software Applications Securely with DevSecOps: A Socio-Technical Perspective

While continuous real-time software delivery practices induced by agile software development approaches create new business opportunities for organizations, these practices also present new security challenges in the DevOps environment. DevSecOps attempts to incorporate advanced automated security practices for agility in the DevOps environment. Mainstream perspectives of DevSecOps tend to overlook the collaborative role played by social actors and their relations with technologies in securing software applications in organizations. The first perspective emphasises the use of technologies such as containers, microservices, cryptographic protocols and origin authentication to secure the continuous deployment pipeline. The other dominant perspective focuses almost exclusively on the social aspects such as organizational silos, culture, and team collaboration. Such one-sided perspectives neglect the socio-technical argument that secure software applications from continuous deployment emerges when developers, quality assurers, operators and security experts combine their collective expertise together with DevSecOps technologies. The article presents a socio-technical framework of DevSecOps based on a systematic literature review. The review focused primarily, but not exclusively, on the computing and information systems literature and identified 26 peer reviewed articles from 2016 to 2020 which met the quality criteria and contributed to the analysis. The authors used a critical appraisal checklist and member checking to assess the quality of the articles. The authors then used thematic analysis to develop a comprehensive framework for DevSecOps based on the insights from these articles and a socio-technical lens. The socio-technical framework can be used by practitioners to perform a more holistic analysis of their DevSecOps practices. It highlights the key social and technical themes that underpin the effectiveness of DevSecOps and how insights about these themes can be used by practitioners to improve the instrumental and humanistic goals of DevSecOps. An interdisciplinary approach is proposed to adequately address challenging socio-technical relationships in DevSecOps. Future research can empirically test the importance of the interplay between technology and human activities to improve the overall performance of DevSecOps and other domains in cyber warfare and security.

Role of Interventional Radiology in the Management of Non-aortic Thoracic Trauma.

Trauma remains a leading cause of death for all age groups, and nearly two-thirds of these individuals suffer thoracic trauma. Due to the various types of injuries, including vascular and nonvascular, interventional radiology plays a major role in the acute and chronic management of the thoracic trauma patient. Interventional radiologists are critical members in the multidisciplinary team focusing on treatment of the patient with thoracic injury. Through case presentations, this article will review the role of interventional radiology in the management of trauma patients suffering thoracic injuries.

Serum levels of IL-37 and correlation with inflammatory cytokines and clinical outcomes in patients with coronary artery disease

Coronary artery disease (CAD) due to atherosclerosis is one of the important reasons for death worldwide. Recent evidence has suggested the essential role of inflammation in the progression of atherosclerosis....

Molecular Network Analyses Implicate Death-Associated Protein Kinase 3 (DAPK3) as a Key Factor in Colitis-Associated Dysplasia Progression.

Ulcerative colitis (UC) is a progressive disorder that elevates the risk of colon cancer development through a colitis-dysplasia-carcinoma sequence. Gene expression profiling of colitis-associated lesions obtained from patients with varied extents of UC can be mined to define molecular panels associated with colon cancer development. Differential gene expression profiles of 3 UC clinical subtypes and healthy controls were developed for the GSE47908 microarray data set of healthy controls, left-sided colitis, pancolitis, and colitis-associated dysplasia (CAD) using limma R. A gene ontology enrichment analysis of differentially expressed genes (DEGs) revealed a shift in the transcriptome landscape as UC progressed from left-sided colitis to pancolitis to CAD, from being immune-centric to being cytoskeleton-dependent. Hippo signaling (via Yes-associated protein [YAP]) and Ephrin receptor signaling were the top canonical pathways progressively altered in concert with the pathogenic progression of UC. A molecular interaction network analysis of DEGs in left-sided colitis, pancolitis, and CAD revealed 1 pairwise line, or edge, that was topologically important to the network structure. This edge was found to be highly enriched in actin-based processes, and death-associated protein kinase 3 (DAPK3) was a critical member and sole protein kinase member of this network. Death-associated protein kinase 3 is a regulator of actin-cytoskeleton reorganization that controls proliferation and apoptosis. Differential correlation analyses revealed a negative correlation for DAPK3-YAP in healthy controls that flipped to positive in left-sided colitis. With UC progression to CAD, the DAPK3-YAP correlation grew progressively more positive. In summary, DAPK3 was identified as a candidate gene involved in UC progression to dysplasia.

Examining the effectiveness of a family‐focused training to prevent youth suicide

AbstractObjectiveThe present study investigates the effectiveness of a novel, consumer‐informed, family training for youth suicide prevention.BackgroundResearch suggests family members play a key role in reducing suicide risk for their children. However, family members often do not possess the necessary knowledge, confidence, and skills needed to intervene with a suicidal youth.MethodFamily members (N = 582) participated in the It's Time to Talk About It: Family Training for Youth Suicide Prevention (ITT‐FT) and completed pretest and posttest measures. Additionally, 158 family members completed a 6‐month follow‐up evaluation.ResultsResults indicated significant improvements in knowledge, effective attitudes, perceived behavioral control, social norms, and intentions immediately after the training. Knowledge and perceived behavioral control were sustained at follow‐up. Participants identifying as Hispanic/Latinx exhibited greater decreases in stigma related to help‐seeking. Those who had a family history of mental health treatment experienced a greater increase in social norms related to other families seeking help.ConclusionFindings underline the importance of implementing a family‐focused program aimed at improving training outcomes such as knowledge, confidence, and intentions—key constructs associated with behavior change.ImplicationsImprovement in several domains following the training highlight the critical role family members can play in reducing youth suicide risk.

A novel cataract-causing mutation Ile82Met of γA crystallin trends to aggregate with unfolding intermediate

Cataract is the most common pathogenic ophthalmic disease leading to blindness in children worldwide. Genetic disorder is the leading cause of congenital cataract, among which crystallin mutations have a high incidence. There are few reports on γA-crystallin, one critical member of crystallin superfamilies. In this study, we identified a novel pathogenic mutation (Ile82Met) in γA-crystallin from a three-generation Chinese family with cataract, and investigated the potential molecular mechanism in detail. To elucidate the pathogenic mechanism of I82M mutant, spectroscopic and solubility experiments were performed to determine the difference between the purified γA-crystallin wild type (WT) and I82M mutant under both physiological conditions and environmental stresses (UV irradiation, thermal denaturation or chemical denaturation). The I82M mutant did not affect the secondary/tertiary structure of monomeric γA-crystallin under physiological status, but decreased protein stability and increased aggregatory potency under the stressful treatment. Surprisingly, the chemical denaturation caused I82M to switch from the two-state unfolding of γA-crystallin to three-state unfolding involving an unfolding intermediate. This study expands the genetic variation map of cataract, and provides novel insights into the pathomechanism, in particular, filling in a gap in the understanding of γA-crystallin mutants causing cataract.

Pharmacodynamic Thresholds for Beta-Lactam Antibiotics: A Story of Mouse Versus Man.

Beta-lactams remain a critical member of our antibiotic armamentarium and are among the most commonly prescribed antibiotic classes in the inpatient setting. For these agents, the percentage of time that the free concentration remains above the minimum inhibitory concentration (%fT > MIC) of the pathogen has been shown to be the best predictor of antibacterial killing effects. However, debate remains about the quantity of fT > MIC exposure needed for successful clinical response. While pre-clinical animal based studies, such as the neutropenic thigh infection model, have been widely used to support dosing regimen selection for clinical development and susceptibility breakpoint evaluation, pharmacodynamic based studies in human patients are used validate exposures needed in the clinic and for guidance during therapeutic drug monitoring (TDM). For the majority of studied beta-lactams, pre-clinical animal studies routinely demonstrated the fT > MIC should exceed approximately 40–70% fT > MIC to achieve 1 log reductions in colony forming units. In contrast, clinical studies tend to suggest higher exposures may be needed, but tremendous variability exists study to study. Herein, we will review and critique pre-clinical versus human-based pharmacodynamic studies aimed at determining beta-lactam exposure thresholds, so as to determine which targets may be best suited for optimal dosage selection, TDM, and for susceptibility breakpoint determination. Based on our review of murine and clinical literature on beta-lactam pharmacodynamic thresholds, murine based targets specific to each antibiotic are most useful during dosage regimen development and susceptibility breakpoint assessment, while a range of exposures between 50 and 100% fT > MIC are reasonable to define the beta-lactam TDM therapeutic window for most infections.

The Forgotten (Invisible) Healthcare Heroes: Experiences of Canadian Medical Laboratory Employees Working During the Pandemic.

ObjectiveThe purpose of this qualitative study was to understand the stressors and coping strategies of medical laboratory technologists (MLTs) and assistants (MLAs) working during the COVID-19 pandemic in Ontario, Canada.MethodsIn this descriptive qualitative study, we held two focus groups with MLTs and MLA who were working during the COVID-19 pandemic. The focus group sessions were transcribed verbatim followed by thematic analysis to develop codes and themes.FindingsA total of 13 participants across Ontario were involved in our study, which included one MLT (n = 7) group and one MLA (n = 6) MLA. Overall, the stressors and coping methods identified between both focus groups were consistent. Our results revealed four main themes: (1) COVID-19 contributing to the notable and existing staff shortage; (2) the pandemic reinforced that medical laboratory employees are forgotten within the healthcare system; (3) a poor work environment exacerbated by the pandemic; and (4) a resilient and passionate group. Rich descriptions explained the underlying issues related to the themes.ConclusionsMLTs and MLAs are critical members of the healthcare team and provide vital patient care services. This study explored their experiences working during the pandemic and offers timely recommendations to mitigate against occupational stressors.

The Role of Non-Coding RNAs in Autophagy During Carcinogenesis.

Macroautophagy (autophagy herein) is a cellular stress response and a survival pathway involved in self-renewal and quality control processes to maintain cellular homeostasis. The alteration of autophagy has been implicated in numerous diseases such as cancer where it plays a dual role. Autophagy serves as a tumor suppressor in the early phases of cancer formation with the restoration of homeostasis and eliminating cellular altered constituents, yet in later phases, autophagy may support and/or facilitate tumor growth, metastasis and may contribute to treatment resistance. Key components of autophagy interact with either pro- and anti-apoptotic factors regulating the proximity of tumor cells to apoptotic cliff promoting cell survival. Autophagy is regulated by key cell signaling pathways such as Akt (protein kinase B, PKB), mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) involved in cell survival and metabolism. The expression of critical members of upstream cell signaling, as well as those directly involved in the autophagic and apoptotic machineries are regulated by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Consequently, non-coding RNAs play a relevant role in carcinogenesis and treatment response in cancer. The review is an update of the current knowledge in the regulation by miRNA and lncRNA of the autophagic components and their functional impact to provide an integrated and comprehensive regulatory network of autophagy in cancer.

Impact of UAV Hardware Options on Bridge Inspection Mission Capabilities

Uncrewed Aerial Vehicles (UAV) constitute a rapidly evolving technology field that is becoming more accessible and capable of supplementing, expanding, and even replacing some traditionally manual bridge inspections. Given the classification of the bridge inspection types as initial, routine, in-depth, damage, special, and fracture critical members, specific UAV mission requirements can be developed, and their suitability for UAV application examined. Results of a review of 23 applications of UAVs in bridge inspections indicate that mission sensor and payload needs dictate the UAV configuration and size, resulting in quadcopter configurations being most suitable for visual camera inspections (43% of visual inspections use quadcopters), and hexa- and octocopter configurations being more suitable for higher payload hyperspectral, multispectral, and Light Detection and Ranging (LiDAR) inspections (13%). In addition, the number of motors and size of the aircraft are the primary drivers in the cost of the vehicle. 75% of vehicles rely on GPS for navigation, and none of them are capable of contact inspections. Factors that limit the use of UAVs in bridge inspections include the UAV endurance, the capability of navigation in GPS deprived environments, the stability in confined spaces in close proximity to structural elements, and the cost. Current research trends in UAV technologies address some of these limitations, such as obstacle detection and avoidance methods, autonomous flight path planning and optimization, and UAV hardware optimization for specific mission requirements.