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The exploration of underwater surfaces and their monitoring has become an emerging field of interest for many researchers. Localization is a crucial task in the Underwater Wireless Sensor Network (UWSN). In comparison to terrestrial sensor nodes, localizing underwater sensor nodes is more difficult. In UWSN, the communication of signals between the nodes is a challenging task due to acoustic communication and the position of the node tends to move due to a strong water current in the deep sea whereas in terrestrial the nodes are static and the localization of the node is comparatively easier. Strategic surveillance relies on accurate localization in UWSN to follow underwater assets and activities. Addressing localization issues improves situational awareness, disaster response, and mitigation in crucial areas. We reviewed Range-Based and Range-Free UWSN localization algorithms from numerous research articles and discussed trade-offs and improvement opportunities. The comparative analysis was made based on various parameters like coverage area, density of node in the network, energy consumption, localization error and computational complexity. The performance comparison helps the researchers to decide the best localization algorithm or to improve the available algorithm for UWSN.

Abstract With the increase in economic growth, the world is facing serious challenges concerning environmental sustainability. Hence, the green economic growth is imperative for sustainable and inclusive development. The objective of this study is to contribute to the existing literature about the factors that influence green economic growth. The study investigates the role of green technology, green energy, foreign direct investment, and globalization on green economic growth in G7 countries. The data of the study is collected from WDI, KOF Swiss Economic Institute, and OECD database and the data period ranges from 1995 to 2020. The existence of cointegration between the variables of the study was tested by Westerlund’s (Oxford Bull Econ Stat 69(6):709–748) cointegration test. Due to the presence of cross-sectional dependency, the study employed the cross-sectional autoregressive distributed lag (CS-ARDL) method to estimate the coefficients in the long and short run. The study also used a common correlated effect—mean group (CCEMG) estimator for robustness check. The findings of the study reveal that green energy and FDI positively contribute to green economic growth in the long and short run. The green technology also contributes positively to enhance green economic growth but only in long run. To accelerate green economic growth, G7 countries should incorporate policies promoting green energy and technology, while acquiring more foreign investments to ensure a sustainable development.

In light of the increasing worldwide apprehension regarding environmental sustainability, it has become imperative to understand the intricacies that exist between a sustainable environment, economic growth, and tourism growth. This study focuses on sustainable development goals (SDGs) and their relationship to tourism development. Therefore, the current study investigates the relationship between the primary dimensions of sustainability, such as economic, environmental, and social sustainability, and the growth of tourism in G7 countries, using data from 2000 to 2021. After establishing the cointegration between the variables using the Westerlund cointegration test, the long-run and short-run estimations of coefficients were carried out using the Panel ADRL framework (PMG). The results of the PMG test indicate that in the long run, economic growth and CO2 emissions have a positive and significant relationship with tourism growth, whereas ecological footprint, human development, and unemployment have a negative and significant relationship. However, in the short run, only economic growth and unemployment had significant coefficients and negative relationships with tourism development. Finally, this study investigated the causal direction of the variables using the Dumitrescu Hurlin causality test. A unidirectional causal link exists between tourism growth and GDP, ecological footprint, CO2, unemployment, and the human development index. The results also suggest that economic growth encourages tourism development, validating the growth-led tourism hypothesis. The policy implication of this study is that to achieve overall sustainability, the tourism industry has to develop environmentally friendly practices with a focus on economic and social well-being.

Background We recently demonstrated that acute administration of ibrutinib, a Bruton's tyrosine kinase inhibitor used in chemotherapy for blood malignancies, increases ventricular arrhythmia (VA) vulnerability. A pathway of ibrutinib‐induced vulnerability to VA that can be modulated for cardioprotection remains unclear. Methods and Results The effects of ibrutinib on cardiac electrical activity and Ca2+ dynamics were investigated in Langendorff‐perfused hearts using optical mapping. We also conducted Western blotting analysis to evaluate the impact of ibrutinib on various regulatory and Ca2+‐handling proteins in rat cardiac tissues. Treatment with ibrutinib (10 mg/kg per day) for 4 weeks was associated with an increased VA inducibility (72.2%±6.3% versus 38.9±7.0% in controls, P

Cardiac arrhythmias remain a significant concern with Ibrutinib (IBR), a first-generation Bruton’s tyrosine kinase inhibitor (BTKi). Acalabrutinib (ABR), a next-generation BTKi, is associated with reduced atrial arrhythmia events. However, the role of ABR in ventricular arrhythmia (VA) has not been adequately evaluated. Our study aimed to investigate VA vulnerability and ventricular electrophysiology following chronic ABR therapy in male Sprague–Dawley rats utilizing epicardial optical mapping for ventricular voltage and Ca2+ dynamics and VA induction by electrical stimulation in ex-vivo perfused hearts. Ventricular tissues were snap-frozen for protein analysis for sarcoplasmic Ca2+ and metabolic regulatory proteins. The results show that both ABR and IBR treatments increased VA vulnerability, with ABR showing higher VA regularity index (RI). IBR, but not ABR, is associated with the abbreviation of action potential duration (APD) and APD alternans. Both IBR and ABR increased diastolic Ca2+ leak and Ca2+ alternans, reduced conduction velocity (CV), and increased CV dispersion. Decreased SERCA2a expression and AMPK phosphorylation were observed with both treatments. Our results suggest that ABR treatment also increases the risk of VA by inducing proarrhythmic changes in Ca2+ signaling and membrane electrophysiology, as seen with IBR. However, the different impacts of these two BTKi on ventricular electrophysiology may contribute to differences in VA vulnerability and distinct VA characteristics.

We report a case of fulminant COVID-19–related myocarditis requiring venoarterial extracorporeal membrane oxygenation where the use of an ultrasound-enhancing agent demonstrated a previously undescribed echocardiographic finding, the “lightbulb” sign. This sign potentially represents a new area for the use of an ultrasound enhancing agent in the echocardiographic diagnosis of myocarditis.

Summary: Protein biomarkers can be used to characterize symptom classes, which describe the metabolic or immunodeficient state of patients during the progression of a specific disease. Recent literature has shown that machine learning methods can complement traditional clinical methods in identifying biomarkers. However, many machine learning frameworks only apply narrowly to a specific archetype or subset of diseases. In this paper, we propose a feature extractor which can discover protein biomarkers for a wide variety of classification problems. The feature extractor uses a special type of deep learning model, which discovers a latent space that allows for optimal class separation and enhanced class cluster identity. The extracted biomarkers can then be used to train highly accurate supervised learning models. We apply our methods to a dataset involving COVID-19 patients and another involving scleroderma patients, to demonstrate improved class separation and reduced false discovery rates compared to results obtained using traditional models.

This study investigates empirically the long- and short-run impact of crude oil price and financial globalization on economic growth and financial development in selected oil-rich African countries. The data usage covers 1980 to 2021 by applying the autoregressive distributed lag (ARDL) modeling to determine the short- and the long-run estimates, and the ARDL-ECM Granger causality to discover the causalities direction. The empirical results reveal that crude oil price and financial globalization have no significant effect on restructuring the economic sustainability patterns in either the long or the short run. There are various causality directions found for those countries involved in this study within the short- and long-run periods. This study recommends that the Republic of Congo and Nigeria should always maximize oil revenue during periods of oil price boom to offset the economic severity during periods of oil price reduction. Further, Algeria and Nigeria’s policymakers should avoid protectionism against financial globalization, economic growth, and trade to mobilize the resources required to be at the fulcrum of future economic restructuring. The empirical findings will be useful for policymakers to design a suitable growth model for African countries that highly depend on crude oil resources as an engine of economic growth.

Background: Doxorubicin-induced cardiomyopathy (DICM) is one of the complications that can limit treatment for a significant number of cancer patients. In animal models, the administration of statins can prevent the development of DICM. Therefore, the use of statins with anthracyclines potentially could enable cancer patients to complete their chemotherapy without added cardiotoxicity. The precise mechanism mediating the cardioprotection is not well understood. The purpose of this study is to determine the molecular mechanism by which rosuvastatin confers cardioprotection in a mouse model of DICM. Methods: Rosuvastatin was intraperitoneally administered into adult male mice at 100 μg/kg daily for 7 days, followed by a single intraperitoneal doxorubicin injection at 10 mg/kg. Animals continued to receive rosuvastatin daily for an additional 14 days. Cardiac function was assessed by echocardiography. Optical calcium mapping was performed on retrograde Langendorff perfused isolated hearts. Ventricular tissue samples were analyzed by immunofluorescence microscopy, Western blotting, and quantitative polymerase chain reaction. Results: Exposure to doxorubicin resulted in significantly reduced fractional shortening (27.4% ± 1.11% vs 40% ± 5.8% in controls; P < 0.001) and re-expression of the fetal gene program. However, we found no evidence of maladaptive cardiac hypertrophy or adverse ventricular remodeling in mice exposed to this dose of doxorubicin. In contrast, rosuvastatin-doxorubicin-treated mice maintained their cardiac function (39% ± 1.26%; P < 0.001). Mechanistically, the effect of rosuvastatin was associated with activation of Akt and phosphorylation of phospholamban with preserved sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 (SERCA2)-mediated Ca2+ reuptake. These effects occurred independently of perturbations in ryanodine receptor 2 function. Conclusions: Rosuvastatin counteracts the cardiotoxic effects of doxorubicin by directly targeting sarcoplasmic calcium cycling. Résumé: Contexte: La cardiomyopathie induite par la doxorubicine (CMID) est l’une des complications pouvant limiter le traitement d’un nombre considérable de patients atteints de cancer. Dans des modèles animaux, l’administration de statines peut prévenir l’apparition d’une CMID. Ainsi, l’utilisation de statines avec les anthracyclines pourrait vraisemblablement permettre aux patients de compléter leur chimiothérapie en évitant une cardiotoxicité supplémentaire. Le mécanisme précis qui sous-tend cet effet cardioprotecteur n’est pas entièrement élucidé. Cette étude a pour objectif de déterminer dans un modèle murin de CMID le mécanisme moléculaire par lequel la rosuvastatine confère une cardioprotection. Méthodologie: La rosuvastatine a été administrée par voie intrapéritonéale à des souris adultes mâles à une dose de 100 μg/kg par jour pendant sept jours, suivie d’une dose unique de doxorubicine de 10 mg/kg administrée par injection intrapéritonéale. Les animaux poursuivaient ensuite le traitement par la rosuvastatine une fois par jour pendant 14 jours supplémentaires. La fonction cardiaque a été mesurée par échocardiographie. Une cartographie optique du calcium a été réalisée sur des cœurs isolés soumis à une perfusion rétrograde selon la méthode de Langendorff. Des échantillons de tissu ventriculaire ont été analysés par microscopie en immunofluorescence, par buvardage de western et par mesure quantitative de l’amplification en chaîne par polymérase. Résultats: L’exposition à la doxorubicine a entraîné une diminution significative de la fraction de raccourcissement (27,4 % ± 1,11 % vs 40 % ± 5,8 % dans le groupe témoin; p < 0,001) et la réexpression du programme génique fœtal. Toutefois, aucune hypertrophie cardiaque inadaptée ni aucun remodelage ventriculaire indésirable n’ont été observés chez les souris ayant été exposées à la dose de doxorubicine étudiée. En revanche, la fonction cardiaque a été préservée chez les souris traitées par l’association rosuvastatine-doxorubicine (39 % ± 1,26 %; p < 0,001). Sur le plan du mode d’action, l’effet de la rosuvastatine a été associé à une activation de l’Akt et à une phosphorylation du phospholambane, avec préservation du recaptage de Ca2+ médié par la pompe SERCA2 (sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2). Ces effets sont survenus indépendamment des perturbations de la fonction du récepteur RyR2 (ryanodine receptor 2). Conclusions: La rosuvastatine neutralise les effets cardiotoxiques de la doxorubicine en ciblant directement la circulation sarcoplasmique du calcium.

Purpose – Tourism has grown to be one of the world's largest and fastest-growing economic industries. Tourism development is viewed as a tool to improve income distribution as it allows people at the bottom of the pyramid to get involved in the industry. This study aims to examine the impact of tourism on income inequality in the top income equality countries. Design/methodology/approach – The paper employs fully modified ordinary least squares (FMOLS) and dynamic ordinary least squares techniques to investigate the dynamic impact of tourism on income inequality in the world's most income equality countries, from 2001 to 2016. Findings – The result shows that tourism is one of the major drivers of income equality. Thus, tourism can be used to reduce a country's income disparity. Practical implications – As a result, policymakers should support the tourism industry to reduce income disparity and enhance income distribution. Originality/value – Given the conflicting findings in the literature, this study reexamines this link and attempts to backwardly assess if the top equal-income countries in the world are heavily dependent on tourism.

An Experimental investigation had been executed in a solar distill unified with parabolic collector using PCM. This experiment had been compared with PCM less experimental setup. PCM and Parabolic solar collector are things embedded with the base system to increase the overall outcome. Used paraffin wax as PCM (Phase Change Material) was one of the most cost-effective approaches to store heat energy. The solar ray’s incidence had been harvested by using the solar distill in which the water passed by the water tubes. This base solar still consist of double slope and the water tube filled with PCM. These experiments were done at the water depth of 15 mm. In these experiments produce the results indicated that a solar distillation system with a Parabolic Solar Collector coupled with PCM yielded higher productivity and temperature levels compared to not utilizing PCM, and these experiments demonstrated that the introduction of PCM in DSSD with Parabolic solar collector with or without it PCM resulted the improvements of the productivity of 33.25% and 57.31% respectively.

Background: We previously described the mortality associated with cardiac injury in patients with coronavirus disease 2019 (COVID-19). The activation of immune and thrombotic biomarkers at admission, and their ability to predict cardiac injury and mortality patterns in COVID-19, remains unclear. Methods: This retrospective cohort study included 170 patients with COVID-19 with cardiac injury at the time of admission to Tongji Hospital in Wuhan between January 29, 2020, and March 8, 2020. The temporal evolution of inflammatory cytokines, coagulation markers, clinical treatment, and mortality were analyzed. Continuous variables are expressed as median (interquartile range). The Mann-Whitney test was used for two-group comparisons, whereas the Kruskal-Wallis test was used for comparisons among three groups. Categorical variables are expressed as proportions and percentages, and Fisher’s exact test was used to compare differences. A multivariate regression model was used to predict in-hospital death. A simple linear regression analysis was applied to examine the correlation between baseline biomarkers and peak cTnI levels. Results: Of the 170 patients, 60 (35.3%) died early (

ObjectiveThe glycans on the mucosa of suckling mice are predominantly sialylated; upon weaning, fucosylated glycans preponderate. This manifestation of mutualism between fucotrophic bacteria and the mature host utilizes a sentinel receptor in the intestinal mucosa; this receptor was isolated to distinguish its structural and functional features.DesignProvisional identification of the sentinel gut receptor as fuc-TLR4 was through colonization of germ-free mutant mice. Conventional mice whose microbiota was depleted with a cocktail of antibiotics were used to further define the nature and functions of fuc-TLR4 sentinel, and to define the role of the fucotrophic microbiota in gut homeostasis and recovery from insult. The nature of the sentinel was confirmed in cultured human HEL cells.ResultsFuc-TLR4 activity is distinct from that of TLR4. Activated mucosal fuc-TLR4 induces a fuc-TLR4 dependent non-inflammatory (ERK and JNK dependent, NF-κB independent) signaling cascade, initiating induction of fucosyltransferase 2 (secretor) gene transcription. In vitro, either defucosylation or TLR4 knockdown abrogates FUT2 induction, indicating that fuc-TLR4 activity requires both the peptide and glycan moieties. In vivo, fucose-utilizing bacteria and fucose-binding ligands induce mucosal fucosylation. Activation of this pathway is essential for recovery from chemically induced mucosal injury in vivo.ConclusionIn mature mice, fucosyl-TLR4 mediated gut fucosylation creates a niche that supports the healthy fucose-dependent mutualism between the mammalian gut and its fucotrophic microbes. Such microbiota-induced Fuc-TLR4 signaling supports initial colonization of the secretor gut, recovery from dysbiosis, and restoration or preservation of intestinal homeostasis.

Aims: Sudden cardiac death (SCD) is a major cause of mortality in adults with congenital heart disease (ACHD). The role of implantable cardioverter-defibrillator (ICDs) in preventing SCD has been established, however, robust, clinical evidence-based guidelines are lacking in ACHD. The aim of this study was to evaluate the ICD guidelines in ACHD patients. Methods and Results: A total of 131 ACHD patients (male: n = 96 (73.3%), mean age: 42.8 ± 14.7 years, mean follow-up: 40.9 ± 28.3 months) undergoing ICDs implantation between 2010 and 2017 were reviewed. Sixty-nine patients (52.6%) received ICDs for a primary prevention indication. 122 (93.3%) patients had congenital heart disease of moderate to severe complexity. CRT-D (implantable cardiac resynchronization defibrillator) was implanted in 55 (42.0%) patients. During follow-up, 23 patients (17.6%) received appropriate ICD therapy. According to the current guideline (PACES/HRS 2014), 84 (64.1%), 8 (6.1%), and 39 (29.8%) could be classified as Class Ⅰ, Class Ⅱa, and Class Ⅱb indication, respectively. Compared to patients with Class Ⅱa and IIb indication, those with Class Ⅰ indication received more appropriate therapy (P = 0.030). Multivariate analysis showed that age (per 10-years decrease; P = 0.015, HR 1.254 CI; 1.045–1.505) and creatinine (per 100-μmol/L increase; P = 0.019, HR 1.555 CI; 1.076–2.247) were associated with appropriate therapy. Conclusion: Implantation of ICDs for preventing SCD based on current guidelines is reasonable. For patients with a borderline indication, younger age and renal dysfunction may aid in the selection of ICDs candidates.

The effectiveness of the vero cell inactivated vaccine (CoronaVac®) against severe acute respiratory infection (‎SARI)‎ caused by SARS-CoV-2 in the real world was assessed. A matched test-negative case-control design was employed using the web-based national information system, as well as the hospitalization dataset in Sibu Hospital. Vaccine effectiveness was measured by conditional logistic regression with adjustment for gender, underlying comorbidity, smoking status, and education level. Between 15 March and 30 September 2021, 838 eligible SARI patients were identified from the hospitalization records. Vaccine effectiveness was 42.4% (95% confidence interval [CI]: −28.3 to 74.1) for partial vaccination (after receiving the first dose to 14 days after receiving the second dose), and 76.5% (95% CI: 45.6 to 89.8) for complete vaccination (at 15 days or more after receiving the second dose). This analysis indicated that two doses of CoronaVac® vaccine provided efficacious protection against SARI caused by SARS-CoV-2 in the short term. However, the duration of protection, and performance against new variants need to be studied continuously.

Chronic stress among young patients (≤ 45 years old) could result in autonomic dysfunction. Autonomic dysfunction could be exhibited via sympathetic hyperactivity, sympathetic nerve sprouting, and diffuse adrenergic stimulation in the atria. Adrenergic spatial densities could alter atrial electrophysiology and increase arrhythmic susceptibility. Therefore, we examined the role of adrenergic spatial densities in creating arrhythmogenic substrates in silico. We simulated three 25 cm2 atrial sheets with varying adrenergic spatial densities (ASD), activation rates, and external transmembrane currents. We measured their effects on spatial and temporal heterogeneity of action potential durations (APD) at 50% and 20%. Increasing ASD shortens overall APD, and maximum spatial heterogeneity (31%) is achieved at 15% ASD. The addition of a few (5% to 10%) adrenergic elements decreases the excitation threshold, below 18 μA/cm2, while ASDs greater than 10% increase their excitation threshold up to 22 μA/cm2. Increase in ASD during rapid activation increases APD50 and APD20 by 21% and 41%, respectively. Activation times of captured beats during rapid activation could change by as much as 120 ms from the baseline cycle length. Rapidly activated atrial sheets with high ASDs significantly increase temporal heterogeneity of APD50 and APD20. Rapidly activated atrial sheets with 10% ASD have a high likelihood (0.7 ± 0.06) of fragmenting otherwise uniform wavefronts due to the transient inexcitability of adrenergically stimulated elements, producing an effective functional block. The likelihood of wave fragmentation due to ASD highly correlates with the spatial variations of APD20 (ρ = 0.90, p = 0.04). Our simulations provide a novel insight into the contributions of ASD to spatial and temporal heterogeneities of APDs, changes in excitation thresholds, and a potential explanation for wave fragmentation in the human atria due to sympathetic hyperactivity. Our work may aid in elucidating an electrophysiological link to arrhythmia initiation due to chronic stress among young patients.

The versatility of metal matrix composites (MMCs) makes them a promising material for various industrial applications. The current study used a ball milling to mechanically AA7178 powder and strengthened with zirconium silicate (ZrSiO4) nanoparticles. In addition, the AA7178 matrix was ball-milled to distribute the ZrSiO4 nanoparticles throughout the material. The AA7178 reinforced with ZrSiO4 nanoparticles was compacted and consolidated using two distinct powder metallurgy (PM) sequences: double pressing, double sintering, and hot pressing. In tests measuring microhardness, compression strength, and elongational break, the new nanocomposites surpassed the AA7178. The adequate interfacial bonding and even distribution of ZrSiO4 nanoparticles throughout the AA7178 matrix were essential to the strengthening mechanism. With the use of hot pressing, the mechanical characteristics of the nanocomposites were enhanced. As reinforcement concentration increased beyond 2.5% by weight, mechanical properties drastically degraded due to ZrSiO4 nanoparticles clumping and unequal distribution. Improved mechanical parts attain through the uniform distribution of ZrSiO4 nanoparticles in the AA7178 and the maintenance of their mechanical properties.

Background: COVID-19 causes psychological distress and anxiety due to fear of infection and the possibility of worsening symptoms leading to mortality. Public health measures like contact tracing and lockdowns further increase the panic among infected patients and the public. We intended to assess the effect of telecounseling in reducing anxiety in patients admitted to isolation wards. Methods: In this multi-center observational study, we administered a Generalized Anxiety Disorder-7 (GAD-7) scale before and after telecounseling. The study group consisted of participants who gave consent for telecounseling, and those who did not give consent constituted the control group. The telecounseling was based on the Psychological First Aid model, due to its simplicity. Results: There was a statistically significant decrease in anxiety after telecounseling in the study group (P value ≤ 0.001, effect size = 0.484). There was a statistically significant decrease in anxiety in the study group compared to the control group (P value ≤ 0.001). Conclusion: Telecounseling contributed to the reduction in anxiety in COVID-19 patients in isolation wards. Several other factors like severity of the infection, comorbid medical illness, pre-existing mental health issues, individual’s level of coping with stress, and duration and place of admission may have affected the anxiety levels in the patients.

Background: Doxorubicin (Dox) is a potent chemotherapeutic agent, but its usage is limited by dose-dependent cardiotoxicity. Intracellular calcium dysregulation has been reported to be involved in doxorubicin-induced cardiomyopathy (DICM). The cardioprotective role of RyR stabilizer dantrolene (Dan) on the calcium dynamics of DICM has not yet been explored. Objective: To evaluate the effects of dantrolene on intracellular calcium dysregulation and cardiac contractile function in a DICM model. Methods: Adult male C57BL/6 mice were randomized into 4 groups: (1) Control, (2) Dox Only, (3) Dan Only, and (4) Dan + Dox. Fractional shortening (FS) and left ventricular ejection fraction (LVEF) were assessed by echocardiography. In addition, mice were sacrificed 2 weeks after doxorubicin injection for optical mapping of the heart in a Langendorff setup. Results: Treatment with Dox was associated with a reduction in both FS and LVEF at 2 weeks (P < .0001) and 4 weeks (P < .006). Dox treatment was also associated with prolongation of calcium transient durations CaTD50 (P = .0005) and CaTD80 (P < .0001) and reduction of calcium amplitude alternans ratio (P < .0001). Concomitant treatment with Dan prevented the Dox-induced decline in FS and LVEF (P < .002 at both 2 and 4 weeks). Dan also prevented Dox-induced prolongation of CaTD50 and CaTD80 and improved the CaT alternans ratio (P < .0001). Finally, calcium transient rise time was increased in the doxorubicin-treated group, indicating RyR2 dyssynchrony, and dantrolene prevented this prolongation (P = .02). Conclusion: Dantrolene prevents cardiac contractile dysfunction following doxorubicin treatment by mitigating dysregulation of calcium dynamics.

Objectives: The UK postgraduate training program in cardiothoracic surgery is challenging and competitive, with trainees choosing the field for different reasons. This study aims to identify factors that influence medical students in pursuing a career within cardiothoracic surgery. Methods: A cross-sectional study was carried out in which a questionnaire was anonymously filled out by medical students across 17 medical schools in the United Kingdom. An online survey platform was used for survey distribution and analysis. A mixed-methods approach was employed to gather quantitative and qualitative data. Data collection consisted of a series of closed questions and 1 open-ended question. The questions focused on the attitudes toward, knowledge of, and exposure to cardiothoracic surgery. Results: The survey yielded 265 responses. Interest in cardiothoracic surgery was seen in 45.3% of participants, with the leading factor for pursuing this career being lifestyle factors (50%), closely followed by the career opportunities (42.9%) and the aid of mentors (31%). Some discouraging factors were: Difficulty of learning material (37.7%), length of the training program (27.4%), competition in the field (26%), stress (24.3%), and lifestyle factors (22.1%). Conclusions: Whilst UK medical schools try to provide an introduction to specialties like cardiothoracic surgery, there remains a proportion of medical students who do not have access to opportunities needed to make a balanced career decision. Additionally, individual circumstances and aspirations tend to change from students' first year of study to their final year, which can alter their perceptions about the field.

QT interval prolongation and ventricular arrhythmias (VAs) induced by osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, are life-threatening complications. However, no consensus has been achieved regarding their management. Overdrive pacing has been shown to be effective in shortening the QT interval and terminating torsade de pointes (TdP). Here, we report a case of osimertinib-induced QT prolongation accompanied by frequent VAs and TdP. Osimertinib was immediately discontinued after it was identified as the etiology for QT prolongation and VAs. A temporary pacemaker and overdrive pacing were used after other anti-arrhythmia treatments had failed and successfully shortened the QTc interval and terminated VAs. Repeated Holter monitoring at 1 week showed no remaining VAs or TdP, and the pacemaker was removed. Routine electrocardiography (ECG) surveillance was conducted afterward, and three- and 6-month follow-ups showed good recovery and normal ECG results. Vigilance is required for rare vital arrhythmias in patients taking osimertinib, and ECG surveillance should be conducted.

We present a methodology to perform inverse design of reconfigurable topological insulators for flexural waves in plate-like structures. A genetic algorithm based topology optimization method is developed and a C6v plate unit cell topology that offers twofold degeneracy in the band structure is designed. Piezoelectric patches, that are connected to an external circuit, are bonded to the substrate plate and are altered appropriately to break space inversion symmetry. The space inversion symmetry breaking opens a topological band gap mimicking quantum valley Hall effect. Numerical simulations demonstrate that the topologically protected edge state exhibits wave propagation without backscattering and is immune to disorders. The present work achieves real-time reconfigurability of the topological interfaces for waveguide applications.

Background: Implantable cardioverter defibrillators (ICDs) are effective in preventing arrhythmic sudden cardiac death in patients with tetralogy of Fallot (TOF). Although ICD therapies for malignant ventricular arrhythmias can be life-saving, shocks could have deleterious consequences. Substrate-based ablation therapy has become the standard of care to prevent recurrent ICD shocks in patients with ischemic cardiomyopathy. However, the efficacy and safety of this invasive therapy in the prevention of recurrent ICD shocks in patients with TOF has not been well evaluated. Methods: Records of a total of 47 consecutive TOF patients (mean age: 43.1 ± 13.2 years, male sex: n = 34 [72.3%]) who underwent ICD implantation for secondary prevention between 2000 and 2018 were reviewed. Results: Twenty (42.6%) patients underwent invasive therapy (radiofrequency catheter ablation, n = 8; surgical ablation with pulmonary valve replacement, n = 12) before ICD implantation. Twenty-seven patients (57.4%) were managed noninvasively. During follow-up (median 80.5 [interquartile range, 28.5-131.0] months), 2 (10.0%) patients in the invasive group and 10 (37.0%) patients in the noninvasive group received appropriate ICD shocks (P = 0.036). Logistic regression analysis showed that invasive therapy was associated with a decreased risk of ICD shocks by 81.1% (odds ratio, 0.189; 95% confidence interval, 0.036-0.990; P = 0.049). Furthermore, invasive therapy was associated with decreased risk of the composite outcomes of ICD shock, death, cardiac transplantation, and hospital admission (odds ratio, 0.090; 95% confidence interval, 0.025-0.365; P = 0.013) compared with noninvasive therapy. Conclusions: Invasive substrate modification therapy was associated with a lower likelihood of ICD shocks and improvement of long-term outcomes in TOF patients. Résumé: Contexte: Les défibrillateurs cardioverteurs implantables (DCI) sont efficaces pour prévenir la mort cardiaque subite provoquée par une arythmie chez les patients présentant une tétralogie de Fallot (TF). Bien que le traitement des arythmies ventriculaires malignes par DCI puisse sauver des vies, les chocs administrés peuvent avoir des conséquences délétères. L’ablation du substrat est devenue le traitement de référence pour prévenir l’administration à répétition de chocs par DCI chez les patients atteints d’une cardiomyopathie ischémique. L’efficacité et l’innocuité de ce traitement invasif pour prévenir l’administration de chocs répétés chez les patients présentant une TF n’ont toutefois pas été bien évaluées. Méthodologie: Nous avons examiné les cas consécutifs de 47 patients présentant une TF (âge moyen : 43,1 ± 13,2 ans; hommes : n = 34 [72,3 %]) ayant reçu un DCI en prévention secondaire entre 2000 et 2018. Résultats: Au total, 20 (42,6 %) patients ont subi un traitement invasif (ablation par cathéter par radiofréquence, n = 8; ablation chirurgicale et remplacement de la valve pulmonaire, n = 12) avant l’implantation d’un DCI. Vingt-sept patients (57,4 %) ont été pris en charge de façon non invasive. Au cours de la période de suivi (durée médiane de 80,5 [intervalle interquartile : 28,5 à 131,0] mois), 2 (10,0 %) patients du groupe ayant subi une intervention invasive et 10 (37,0 %) patients du groupe ayant subi une intervention non invasive ont reçu un choc approprié par DCI (p = 0,036). Les résultats de l’analyse par régression logistique montrent que le traitement invasif est associé à une réduction du risque de choc par DCI de 81,1 % (rapport des cotes : 0,189; intervalle de confiance à 95 % : de 0,036 à 0,990; p = 0,049). En outre, le traitement invasif est associé à une réduction du risque de survenue d’un des événements du paramètre d’évaluation composé, soit un choc administré par DCI, le décès, une transplantation cardiaque ou une hospitalisation (rapport des cotes : 0,090; intervalle de confiance à 95 % : de 0,025 à 0,365; p = 0,013) par rapport au traitement non invasif. Conclusions: La modification invasive du substrat a été associée à une probabilité plus faible de choc administré par DCI et à une amélioration des résultats à long terme chez les patients présentant une TF.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a rapidly progressing disease with challenging management. To find novel effective therapies, better preclinical models are needed for the screening of anti-fibrotic compounds. Activated fibroblasts drive fibrogenesis and are the main cells responsible for the accumulation of extracellular matrix (ECM). Here, a prolonged Scar-in-a-Jar assay was combined with clinically validated biochemical markers of ECM synthesis to evaluate ECM synthesis over time. To validate the model as a drug screening tool for novel anti-fibrotic compounds, two approved compounds for IPF, nintedanib and pirfenidone, and a compound in development, omipalisib, were tested. Methods Primary human lung fibroblasts from healthy donors were cultured for 12 days in the presence of ficoll and were stimulated with TGF-β1 with or without treatment with an ALK5/TGF-β1 receptor kinase inhibitor (ALK5i), nintedanib, pirfenidone or the mTOR/PI3K inhibitor omipalisib (GSK2126458). Biomarkers of ECM synthesis were evaluated over time in cell supernatants using ELISAs to assess type I, III, IV, V and VI collagen formation (PRO-C1, PRO-C3, PRO-C4, PRO-C5, PRO-C6), fibronectin (FBN-C) deposition and α-smooth muscle actin (α-SMA) expression. Results TGF-β1 induced synthesis of PRO-C1, PRO-C6 and FBN-C as compared with unstimulated fibroblasts at all timepoints, while PRO-C3 and α-SMA levels were not elevated until day 8. Elevated biomarkers were reduced by suppressing TGF-β1 signalling with ALK5i. Nintedanib and omipalisib were able to reduce all biomarkers induced by TGF-β1 in a concentration dependent manner, while pirfenidone had no effect on α-SMA. Conclusions TGF-β1 stimulated synthesis of type I, III and VI collagen, fibronectin and α-SMA but not type IV or V collagen. Synthesis was increased over time, although temporal profiles differed, and was modulated pharmacologically by ALK5i, nintedanib, pirfenidone and omipalisib. This prolonged 12-day Scar-in-a-Jar assay utilising biochemical markers of ECM synthesis provides a useful screening tool for novel anti-fibrotic compounds.

Abstract This paper examines the long- and short-run dynamics of asymmetric adjustment between the nominal exchange rate and commodity prices, namely oil, palm oil, rubber, and natural gas prices, in Malaysia using monthly data from January 1994 to December 2017. The relationship between exchange rate and each commodity price is examined in terms of Engle-Granger and threshold cointegrations. The estimated results provide evidence of long-run threshold cointegration and show that the adjustments towards the long-run equilibrium position are asymmetric in the short run. Furthermore, this study finds evidence of a unidirectional causal relationship running from the nominal exchange rate to oil price in the long and short run using a spectral frequency domain causality application. There is also empirical evidence of bidirectional causality between the nominal exchange rate and palm oil price, rubber price, and natural gas price in the long and short run. Overall, the findings have significant implications for the current debate on the future of primary commodities in Malaysia.

Foreign investment and finance are considered key to economic growth for many economies. In terrorism, these economies directly lose international capital. As a result, it causes an adverse impact on economic development in the countries. Human capital and natural capital factors will be fruitful when the environment is conducive and peaceful. Similarly, energy consumption and FDI would stimulate economic growth, subject to the absence of law-and order issues. This manuscript investigated the impact of terrorism, energy consumption and FDI on economic growth in South Asia over the period from 2002 to 2020. The model’s results display that terrorism and FDI have a negative impact on economic growth in South Asia. The result of energy consumption exhibits a positive and significant influence on economic growth in South Asia. Further, the results indicate that domestic investment and education in South Asia positively impact economic growth. Consequently, it is suggested that the South Asia countries should take appropriate actions to eradicate the problem of terrorism, ensure the availability of energy, and improve the labour force’s skills to achieve desirable economic growth.

The research examined this asymmetric effect between the interrelationship of the interbank rate on the external competitiveness purchasing power represented by the real effective exchange rate for Malaysia and Thailand using monthly data covering the period of 1994 until 2020. The empirical findings confirms an asymmetric effect between interbank rate and real effective exchange rate based on the nonlinear autoregressive distributed lag estimates. The research also finds a unidirectional asymmetric causal relationship running from real effective exchange rate on interbank rate Thailand, which indicate the monetary policy has a direct relationship on interbank rate volatility. While in Malaysia, there is no causality running between both variables since the country has proposed several soft monetary policies and more concentrating on the short-term borrowing by improving the tight money supply circulation based on the domestic inflation, global economic, and financial market volatility. Therefore, the research recommends a specific need of monetary stabilizer policy to stabilize both countries’ currencies and put more effort to liberalize the foreign exchange rate system in a globalized economy.

Mitochondrial dysfunction underlying metabolic disorders such as obesity and diabetes mellitus is strongly associated with cardiac arrhythmias. Murine Pgc-1α−/− hearts replicate disrupted mitochondrial function and model the associated pro-arrhythmic electrophysiological abnormalities. Quantitative PCR, western blotting and histological analysis were used to investigate the molecular basis of the electrophysiological changes associated with mitochondrial dysfunction. qPCR analysis implicated downregulation of genes related to Na+-K+ ATPase activity (Atp1b1), surface Ca2+ entry (Cacna1c), action potential repolarisation (Kcnn1), autonomic function (Adra1d, Adcy4, Pde4d, Prkar2a), and morphological properties (Myh6, Tbx3) in murine Pgc-1α−/− ventricles. Western blotting revealed reduced NaV1.5 but normal Cx43 expression. Histological analysis revealed increased tissue fibrosis in the Pgc-1α−/− ventricles. These present findings identify altered transcription amongst a strategically selected set of genes established as encoding proteins involved in cardiac electrophysiological activation and therefore potentially involved in alterations in ventricular activation and Ca2+ homeostasis in arrhythmic substrate associated with Pgc-1α deficiency. They complement and complete previous studies examining such expression characteristics in the atria and ventricles of Pgc-1 deficient murine hearts.