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AbstractTrigger factor, as a chaperone protein, is required for survival of Mycobacterium tuberculosis (M.tb) in a stressed environment. This protein interacts with various partners in both the pre- and the post-translation processes, yet the crystal structures of the M.tbtrigger factor remain unresolved. In this study, we developed a homology model of M.tbtrigger factor to facilitate the discovery and design of inhibitors. To validate the model, we employed several methodologies, including Ramachandran plot and molecular dynamics simulations. The simulations showed a stable trajectory, indicating the accuracy of the model. The active site of M.tbTrigger Factor was identified based on site scores, and virtual screening of over 70,000 compounds led to the identification of two potential hits: HTS02984 (ethyl 2-(3-(4-fluorophenyl)ureido)-6-methyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate) and S06856 ((E)-N-(4-((2-(4-(tert-butyl)benzoyl)hydrazono)methyl)phenyl) acetamide). These compounds showed strong binding affinity and energy scores, and their chemical descriptors were evaluated. Our study provides a reliable computational model for M.tbTrigger Factor and identifies two potential inhibitors for this crucial protein, which could aid in the development of novel therapies against tuberculosis.Communicated by Ramaswamy H. Sarma

The impact of variations in the three-dimensional structure of the genome has been recognized, but solid cancer tissue studies are limited. Here, we performed integrated deep Hi-C sequencing with matched whole-genome sequencing, whole-genome bisulfite sequencing, 5-hydroxymethylcytosine (5hmC) sequencing and RNA sequencing across a cohort of 80 biopsy samples from patients with metastatic castration-resistant prostate cancer. Dramatic differences were present in gene expression, 5-methylcytosine/5hmC methylation and in structural variation versus mutation rate between A and B (open and closed) chromatin compartments. A subset of tumors exhibited depleted regional chromatin contacts at the ARlocus, linked to extrachromosomal circular DNA (ecDNA) and worse response to ARsignaling inhibitors. We also identified topological subtypes associated with stark differences in methylation structure, gene expression and prognosis. Our data suggested that DNA interactions may predispose to structural variant formation, exemplified by the recurrent TMPRSS2–ERGfusion. This comprehensive integrated sequencing effort represents a unique clinical tumor resource.

Transcription factor (TF) proteins regulate gene activity by binding to regulatory regions, most importantly at gene promoters. Many genes have alternative promoters (APs) bound by distinct TFs. The role of differential TF activity at APs during tumour development is poorly understood. Here we show, using deep RNA sequencing in 274 biopsies of benign prostate tissue, localized prostate tumours and metastatic castration-resistant prostate cancer, that AP usage increases as tumours progress and APs are responsible for a disproportionate amount of tumour transcriptional activity. Expression of the androgen receptor (AR), the key driver of prostate tumour activity, is correlated with elevated AP usage. We identified AR, FOXA1and MYCas potential drivers of AP activation. DNA methylation is a likely mechanism for AP activation during tumour progression and lineage plasticity. Our data suggest that prostate tumours activate APs to magnify the transcriptional impact of tumour drivers, including ARand MYC.

Herpes zoster (HZ) is caused by reactivation of latent infection of varicella zoster virus (VZV) in sensory (cranial, dorsal root) ganglia. Major risk factors for HZ are increasing age and immunosuppression. HZ ophthalmicus (HZO) is a subset of HZ with involvement of the ophthalmic division of the fifth cranial trigeminal nerve. Approximately 4–20% of patients with HZ develop HZO. Approximately 50% of patients with HZO develop ocular disease, among whom up to 25% develop chronic or recurrent disease. Common manifestations of ocular disease include conjunctivitis, keratitis, and uveitis, whereas optic neuropathy and retinitis are uncommon. Due to the potential for vision impairment, ocular involvement requires urgent ophthalmic consultation. Early recognition and timely treatment with antivirals may prevent ocular complications. HZO is preventable by vaccination against HZ. Vaccine efficacy/effectiveness studies have been largely conducted for HZ with few studies assessing HZO. Both the recombinant adjuvanted vaccine (RZV) and live-attenuated vaccine (ZVL) significantly reduce the incidence of HZ and HZO in older adults. RZV is more effective than ZVL. Data on the effectiveness of vaccines for prevention of recurrent disease in patients with HZO are limited; however, vaccination is recommended. Despite recommendations to vaccinate individuals likely to benefit from an HZ vaccine, coverage for adults remains suboptimal. Barriers to vaccination include patient beliefs about HZ or HZ vaccines, and factors related to healthcare providers. In particular, the lack of a recommendation from their primary care physician is often cited by patients as a reason for remaining unvaccinated. By encouraging vaccination against HZ, physicians not only prevent HZ and HZO but also potential vision loss due to HZO.

Artificial Intelligence and machine learning (AI/ML) failures can be challenging to analyze. Detailed understanding of how these systems fail is a valuable first step in designing better AI/ML safety and security practices.

Objective: The present study examines trends of percent of applicants, number of specialties, and specialty combinations for psychiatry residency applicants applying to multiple specialties (parallel application). Methods: The authors conducted a retrospective analysis of data captured by the Association of American Medical Colleges Electronic Residency Application System for applicants to psychiatry residency between 2009 and 2021. The percent parallel-applying, the mean number of specialties, mean application counts, and frequency of specialty combinations with psychiatry residency were determined. Results: The dataset described 67,261 applicants. The percentage parallel-applying decreased from 73.7% in 2009 to 60.0% in 2021. International Medical Graduates and U.S. International Medical Graduate parallel-applied at the greatest rate in each year. Applicants who were parallel-applying submitted larger numbers of applications compared to those who were single-specialty applying. Conclusions: Parallel application to psychiatry residency appears to be a common practice, but has decreased in frequency. However, the mean numbers of applications submitted to each specialty in parallel application combination and among single-specialty applicants have increased. This practice appears to have a disproportionate impact on international and osteopathic applicants. Additional efforts are needed to develop evidence-based advising tools to reduce the number of residency applications submitted to psychiatry programs.

The data-intensive nature of machine learning (ML)-enabled systems introduces unique challenges in test and evaluation. We present an overview of combinatorial coverage, exploring its applications across the ML-enabled system lifecycle and its potential to address key limitations in performing test and evaluation for ML-enabled systems.

Many conventional software engineering methods for high-trust software are not well suited to assured autonomy, but concepts from combinatorial testing can add confidence by providing a quantitative measure of the usefulness of a dataset.

Graphical Abstract:

Nowadays, the Internet of Things (IoT) is used for the purpose of gathering data through sensors as well as for storing and processing data. Due to the inherent limitations in the processing and computing capabilities of IoT devices, the inclination towards the integration of cloud computing (CC) with IoT systems is growing rapidly. The CC is capable of efficiently handling substantial volumes of data at remarkable speeds. However, the data owners are required to upload their data to the cloud, and the transmission of such extensive data requires a significant amount of bandwidth. Moreover, the existence of latency and jitter arises as a consequence of the significant geographical separation between IoT devices and the cloud. Hence, fog computing (FC) is utilized in proximity to IoT devices so that the extent of transmission delay is diminished. Both CC and FC are employed in collaboration to improve the performance of the IoT system. A wide range of workflow scheduling optimization techniques were proposed for both CC and FC environments. However, in heterogeneous remote computing systems, major challenges encountered are related to execution time, energy efficiency, latency, cost, and load balancing. In this study, the Multi-objective Honey Badger Algorithm (MOHBA) is proposed for optimizing workflow schedules aimed at optimizing makespan, energy consumption, and overall cost, which hold significant importance for real-time systems. FogWorkflowSim is used for simulating where HBA outperforms other existing algorithms like Particle Swarm Optimization (PSO), Grey Wolf Optimizer (GWO), and Artificial Algae Algorithm (AAA).

The rate of penetration (ROP) is crucial for efficient and cost-effective oil well drilling. This study introduces a novel prediction method for rate of penetration that pioneers the use of different types of drill bits and lithologies with traditional drilling parameters. Utilizing a comprehensive dataset from 12 diverse wells, it employs advanced machine learning techniques including an adaptive moment estimation based artificial neural network for developing the algorithm. By integrating various controllable and uncontrollable drilling parameters, the random forest, decision tree and K-nearest neighbor models demonstrated superior performance. These models achieved a coefficient of determination of approximately 98% and a mean absolute percentage error of only 3.30%, outperforming traditional models such as Maurer and Bingham, as well as other machine learning models. Using 500 testing and 2,000 training data points from real-time measurements reduced the risk of overfitting and enhanced model effectiveness in different drilling environments. The predictions of the developed model can modify the input parameters to increase rate of penetration through various formations. This study highlights the importance of lithology and utilizes feature ablation analysis to transition from black-to-white box model. Additionally, based on the predictions of this work, post-drilling analysis can reduce costs and time by only requiring surface-measured parameters and eliminates the need for extensive study on geological, laboratory and drilling data prior to drilling activities. This integrated approach sets new standards for machine learning in drilling, representing a robust and adaptive strategy to enhance operational efficiency.

Lack of arrangement complexity in cells grown on 2D cultures for in-vitro experiments has been shown to be a major contributor to lack of reproducibility of in-vivo experiments. Culturing cells along with extracellular matrix (ECM) materials like Collagen has shown promise towards bridging this gap. Cells grown with ECM materials, display entirely different morphological behavior from their polystyrene plate based counterparts. Being commercially expensive, protocols for efficient, in-house collagen-1 extraction for cell culture purpose have been detailed in literatures. Present work focuses on the methods of quantifying and detailing the nuclear morphology (area, perimeter, circularity, roundness, solidity, AR (aspect-ratio) and fractal dimension) of cells grown on Collagen type-1, extracted in-house from rat tails. Treatment of cells grown on collagen and normal polystyrene base plates with established chemical stressors (Acetaminophen, Cobalt chloride and Hydrogen peroxide) was done to demonstrate morphometric differences in the respective conditions. Significant changes were observed in the nuclear morphology of gel grown cells. Application of stress factors in many cases led cells to exhibit morphological adjustments favoring their invasion into the Collagen gel underneath. These changes were in contrast to the polystyrene cultures, which mostly exhibited behaviors showing nuclear flattening and swelling. 3D cell cultures have the potential to produce more accurate experimental results than their 2D counterparts, increasing their reproducibility in further in-vivo tests.

The focus of this study is to examine the association between bus transit reliability and the number of boarding passengers at bus-stop level using data obtained from the Charlotte Area Transit System (CATS) in the city of Charlotte, North Carolina, USA for the year 2017. The on-time performance percentage was computed and used as bus transit reliability at bus-stop level. Two different thresholds were considered to compute the on-time performance measure. The ridership data was processed to compute the average number of boarding passengers per bus at bus-stop level. The findings indicate that the day of the week, time of the day, direction of travel, and the type of bus-stop influence the association between the on-time performance percentage and the average number of boarding passengers per bus.

Solution combustion synthesis method was imployed to synthesize Y2O3codoped with Er3+and Gd3+phosphors. The X-ray diffraction pattern of the phosphor confirms presence of cubic phase with crystal size of around 12 nm. Electron microscopic techniques were used for further confirming the morphology and size of the phosphor. It was characterized for optical behaviour by recording the emission spectra under 275 nm UV excitation. The spectra have strong emission peak centred at 546 nm along with small peaks in red region centred at 611 and 617 nm. After doping of Gd3+no variation in peak position was observed it alters the emission intensity. This increase in emission intensity is due to energy transfer between Gd3+and Er3+ion. The mechanism of photoluminescence behaviour has also been discussed. The proposed model can be extended (or applicable) to explain the fluorescence dynamics in other nanomaterial doped with Er3+and Gd3+under UV excitation.

Graphical abstract

An open problem in autonomous vehicle safety validation is building reliable models of human driving behavior in simulation. This work presents an approach to learn neural driving policies from real world driving demonstration data. We model human driving as a sequential decision making problem that is characterized by non-linearity and stochasticity, and unknown underlying cost functions. Imitation learning is an approach for generating intelligent behavior when the cost function is unknown or difficult to specify. Building upon work in inverse reinforcement learning (IRL), Generative Adversarial Imitation Learning (GAIL) aims to provide effective imitation even for problems with large or continuous state and action spaces, such as modeling human driving. This article describes the use of GAIL for learning-based driver modeling. Because driver modeling is inherently a multi-agent problem, where the interaction between agents needs to be modeled, this paper describes a parameter-sharing extension of GAIL called PS-GAIL to tackle multi-agent driver modeling. In addition, GAIL is domain agnostic, making it difficult to encode specific knowledge relevant to driving in the learning process. This paper describes Reward Augmented Imitation Learning (RAIL), which modifies the reward signal to provide domain-specific knowledge to the agent. Finally, human demonstrations are dependent upon latent factors that may not be captured by GAIL. This paper describes Burn-InfoGAIL, which allows for disentanglement of latent variability in demonstrations. Imitation learning experiments are performed using NGSIM, a real-world highway driving dataset. Experiments show that these modifications to GAIL can successfully model highway driving behavior, accurately replicating human demonstrations and generating realistic, emergent behavior in the traffic flow arising from the interaction between driving agents.

We study the problem of allocating a set of indivisible operations to a set of agents in a fair and efficient manner while also minimizing the makespan. We first present the Operation Trading Algorithm that generates allocations satisfying the DEQx (Duplicated Equitability up to any operation) fairness criterion while also guaranteeing an upper bound of 2 on the makespan for identical agents. The pairwise approach used in this algorithm has the added advantages of being decentralizable and robust. We then define a relaxed version of the DEQ1 (Duplicated Equitability upto some operation) fairness criterion called partial-DEQ1. A market based algorithm is presented to achieve partial-DEQ1 along with Pareto Optimality. Following this, it is shown that the algorithm also guarantees an upper bound of 1.618 on the makespan for 2 non-identical agents. Parametric Pruning further improves the upper bound to 1.5 which is theoretically the best possible upper bound. To the best of our knowledge, these are the first algorithms designed to achieve the mentioned fairness criteria. The algorithms additionally guarantee upper bounds on the makespan. Finally, we show the efficacy of the algorithms in generating allocations with near optimal makespans by numerically evaluating the algorithms on random instances. Note to Practitioners—This paper provides fast algorithms that can be used for task allocation among any number of agents. The algorithms generate allocations that satisfy fairness criteria along with minimizing the makespan, thus achieving two practically important criteria simultaneously. Additionally, some of the algorithms introduced can be implemented in a reactive manner thus making it easy to deal with sudden changes. The algorithms can also be implemented in a decentralized manner in environments where maintaining a centralized situational awareness is difficult due to communication and machine failures.

This research describes a simple and straightforward combustion synthesis for SrY2O4:Dy3+nanoparticles. The synthesis of SrY2O4:Dy3+was carried out with the use of urea as a fuel. Characterization techniques including as X-ray diffraction (XRD), transmission electron microscope (TEM), and scanning electron microscopy were used to investigate the effect of the synthesis procedure on the structural behaviour of the phosphor. The existence of orthorhombic structure is indicated by XRD. X-ray widening, Williamson–Hall (W–H) analysis, and a size–strain plot were used to examine the effect of crystallite sizes and lattice strain on the peak broadening of SrY2O4:Dy3+. Uniform deformation model (UDM), uniform stress deformation model (USDM), and uniform deformation energy density model (UDEDM), as well as the size–strain plot method, were used to determine strain, stress, and energy density parameters for all XRD peaks (SSP). W–H analysis, SSP, and TEM results all agreed on the mean particle sizes. To quantify visual properties, a photoluminescence spectroscopic method was implemented. Intense emission at 553 nm, characteristic of emission generated by the energy level transition of the Dy3+ion, was detected in the emission spectra.

Surgical site infection (SSI) remains the most common complication of surgery around the world. WHO does not make recommendations for changing gloves and instruments before wound closure owing to a lack of evidence. This study aimed to test whether a routine change of gloves and instruments before wound closure reduced abdominal SSI.

The management of combined anterior cruciate ligament (ACL) and medial collateral ligament (MCL) injuries remains contentious. Clinical outcomes of surgical, conservative, and combined approaches have been described in a range of prospective and retrospective studies. The aim of the current systematic review was to evaluate these outcomes and assess the study methodologies.

Malaria is a fever sickness caused by Plasmodiumparasites that are transmitted to humans by mosquito bites from infected female Anophelesmosquitos. Intracellular malaria parasites require lipids for the growth and replication. They possess a prokaryotic type II fatty acid synthesis (FAS II) pathway that localizes to the apicoplast plastid organelle and is assumed to be necessary for pathogenic blood stage replication. Considering widening resistance of resistant Plasmodiumparasites and thus, failing conventional antimalarial agents, we herein analyzed a set of 109flavonoids in four protein structures including three homology models and one experimentally obtained crystal structure were conducted to obtain the probable conformations of ligands and their binding affinities. Our results suggested Volkensiflavone, Bilobetin and Sciadopitysin as lead candidates for further detailed analysis and testing their synthetic analogues for their in-vitro anti-malarial potentials.

Oxylipins produced by diatoms play an important role in structuring the zooplankton community by differentially affecting different grazers. Among common oxylipins, the Diatom Polyunsaturated-aldehyde (DPA), 2-trans,4-trans decadienal (DD) is toxic and a common secondary metabolite in diatoms. In limnetic zones of tropical wetlands, the Cladocera Echinisca triserialis (Brady) are abundant and co-occur with DD producing diatom blooms. The natural concentrations of secondary metabolites do not always cause mortality, but the chronic effects of these metabolites are more common. The present study investigates the influence of the 2-trans,4-trans decadienal (DD) on population trajectory and life table attributes of E. triserialis. We recorded the life table attributes of E. triserialis in a DD contaminated environment for two successive generations to elicit the generational response. The population growth trajectories were followed for the cohorts exposed to three concentrations (100, 250 and 500 µM) of DD and control without DD, whereas life table parameters were estimated at 250 µM concentration of DD against control. We compared population growth rate, longevity, maximum lifespan, life expectancy at birth, net and gross reproduction rates and intrinsic rates of natural increase between control and treatment cohorts for two successive generations. Significantly higher mortality of E. triserialis individuals and lower reproduction was recorded in a DD contaminated environment. F1 generation individuals produced in the DD applied medium recorded significantly higher survival and reproduction than control. Maternal exposure to DD registered a ~40 % higher Euler’s ‘r’ value reflecting increased tolerance in F1 generation. The present results suggest that prolonged exposure to DPA favours preexposed genotype within the community pointing to intergenerational experiential benefit in diatom aldehyde contaminated environments with time, a pattern consistent with the extension of parental experience to the F1 generation.

This research study has been done to uncover the important aspects of the research in the context of entrepreneurship as a tool to deal with the problem of unemployment in economies by understanding the trends of research studies, contributing authors, and their research contributions. The literature review in this research study has been done using bibliometric analysis and content analysis through the 316 research studies published in ABDC-rated journals from 2012 to 2022. The findings suggest that the previous studies focused on studying the different aspects, like the relationship between unemployment and entrepreneurship, the role of education and training, and the impact of public policies on employment generation aspects of entrepreneurship, along with the performance assessment of the entrepreneurial firms. However, the emphasis of previous studies was less on the performance assessment of the firms that started after unemployment. The findings from the literature review also revealed the impact of the rapidly evolving technological transformations due to artificial intelligence (AI) and related technologies and the rising gig economy-based environment on employment generation and entrepreneurial endeavors in economies. This suggests that policymakers and practitioners look into designing relevant and effective policies and educational programs aligning with the changing employment and entrepreneurial landscape due to the impact of technology.

Conducting polymers have grown in popularity as electrode materials in supercapacitors due to their polymeric mechanical structure and outstanding conductivity. Nanostructured conducting polymers, in particular, have been the focus due to unique properties such as higher surface area, shorter diffusion lengths for ion transport, and a high electrochemical nature. Nonetheless, the volumetric expansion of conducting polymer electrodes after long charge–discharge cycles reduces capacitance retention. Metal chalcogenides, on the other hand, are distinguished from other metallic compounds by their distinctive 2D structure, large theoretical capacities, abundant electrochemical active sites, and tunable shape, enabling them as a potential candidature when combined with conducting polymers to produce a composite material taking “material mutualism” to enhance the properties. Hence, the review focuses on recent advancement in the field of creating conducting polymers–metal chalcogenides composite for supercapacitors. It especially covers how nanoarchitecture, composition, and doping affect the electrochemical characteristics of these composites. A brief introduction of several synthesis procedures is also offered, which includes chemical approaches with and without templates or binder additives. Furthermore, noteworthy works on the fabrication of symmetric and asymmetric devices are highlighted. A review of conducting polymers‐metal chalcogenides hybrid composites toward supercapacitor applications is studied.

The bacteria, Achromobacterare present ubiquitously in the moist environment. Infections due to Achromobacterhave mostly been reported in immunocompromised patients. However, the microorganism has also been associated with nosocomial infections even in healthy subjects.

ABSTRACTThe greenhouse gas emission from fossil fuel and higher economic cost in its transportation are stimulating scientists to explore biomass energy production at the local level. In the present review, the authors have explored the prospects of commercial-scale biofuels production from the microalgal group, diatoms. Insights on suitability of mass cultivation systems for large-scale production of diatoms have been deliberated based on published literature. Diatoms can proliferate extracting nutrients from the wastewater and the same biomass can be harvested for biofuel production. Residues can be further utilized for the formation of other bioproducts and biofertilizers. The residual applications of diatoms from mass culture are estimated to compensate for the additional costs incurred in the removal of impurities. Well-planned research is required to optimize the commercial-scale production of biofuels from diatoms. The aim of this review is therefore, to demonstrate the economically feasible, hygienically safe cultivation of diatoms on nutrients from wastewater, limitations in using diatoms for biofuel production, and how these limitations can be shorted out for optimum utilization of diatom for biofuel production.

Active Debris removal using robotic manipulators onboard satellites is a promising way of cleaning up the space junk. However, complexities and non-linearities associated with the control of such coupled space-based systems present difficulties in their feasible implementation. Lack of a fixed base arises serious problems in controlling the space manipulators for precision tasks like capture of an orbiting space debris. This paper presents systematic modelling and control approaches for Rotation floating space robots in order to draw a comparison between them while tracking a moving target representing autonomous debris capture. We propose a Nonlinear Model Predictive Controller (NMPC) for the space robot in order to design an optimal path that the end-effector can follow while being controlled to capture the target. To the best of the knowledge of the authors, such a controller has not been tested for a Rotation floating space robot before. Further, the current work implements and reviews one of the most commonly used Transpose Jacobian Cartesian (TJC) controller for Rotation floating space robots through the use of Generalized Jacobian Matrix (GJM). The results provide sufficient evidence of the superior performance of the nonlinear model predictive controller over the TJC controller. Finally, the current work also implements the same nonlinear model predictive controller on a more popular state of the art Free floating space robot and compares it with the Rotation floating space robot.

Accurate navigation to a desired goal requires consecutive estimates of spatial relationships between the current position and future destination throughout the journey. Although neurons in the hippocampal formation can represent the position of an animal as well as its nearby trajectories1–7, their role in determining the destination of the animal has been questioned8,9. It is, thus, unclear whether the brain can possess a precise estimate of target location during active environmental exploration. Here we describe neurons in the rat orbitofrontal cortex (OFC) that form spatial representations persistently pointing to the subsequent goal destination of an animal throughout navigation. This destination coding emerges before the onset of navigation, without direct sensory access to a distal goal, and even predicts the incorrect destination of an animal at the beginning of an error trial. Goal representations in the OFC are maintained by destination-specific neural ensemble dynamics, and their brief perturbation at the onset of a journey led to a navigational error. These findings suggest that the OFC is part of the internal goal map of the brain, enabling animals to navigate precisely to a chosen destination that is beyond the range of sensory perception.

ABSTRACTIn India, although incidence of Herpes zoster has not been assessed, regional cases have been reported. We revisited the peer-reviewed literature on clinical cases of HZ to depict the trends in population characteristics, disease presentation, and predisposing factors for the disease in India. Systematically conducted literature search yielded 27 studies, published between January 2011 and May 2020, reporting 3124 HZ clinical cases, with high proportions in older adults (>50 years of age: 15.0–81.3%). Thoracic dermatome was consistently reported as the most frequent site affected by HZ (38.9–71.0%). Post-herpetic neuralgia and secondary bacterial infections were the two most frequent complications (10.2–54.7% and 3.5–21.0%, respectively). Despite the paucity of data and gaps in the reporting of HZ cases, available evidence indicate that the disease causes an important burden to older adults in India, suggesting that preventive strategies, along with recommendations to healthcare practitioners, can help mitigate the burden of HZ.

Treatment of chronic wound infections caused by Gram-positive bacteria such as Staphylococcus aureusis highly challenging due to the low efficacy of existing formulations, thereby leading to drug resistance. Herein, we present the synthesis of a nonimmunogenic cholic acid–glycine–glycine conjugate (A6) that self-assembles into a supramolecular viscoelastic hydrogel (A6gel) suitable for topical applications. The A6hydrogel can entrap different antibiotics with high efficacy without compromising its viscoelastic behavior. Activities against different bacterial species using a disc diffusion assay demonstrated the antimicrobial effect of the ciprofloxacin-loaded A6hydrogel (CPF-Gel). Immune profiling and gene expression studies after the application of the A6gel to mice confirmed its nonimmunogenic nature to host tissues. We further demonstrated that topical application of CPF-Gel clears S. aureus-mediated wound infections more effectively than clinically used formulations. Therefore, cholic acid-derived hydrogels are an efficacious matrix for topical delivery of antibiotics and should be explored further.

Purpose: The purpose of this paper is to identify and predict the key factors that influenced the usage intention of over the top (OTT) services by consumers. This was done by applying the modified unified theory of acceptance and use of technology 2 (UTAUT2) model. Design/methodology/approach: An online survey questionnaire assessed the proposed motivational factors for the adoption of OTT services. Confirmatory factor analysis and structural equation modelling were conducted on collected data (n= 598) to demonstrate the reliability and validity of the measurement and structural model. Findings: The model consisted of nine factors, namely, value expectancy (VE), ease of effort (EE), social influence (SI), favourable infrastructure conditions (FIC), hedonistic motivation for usage (HMU), favourable economic position (FEP), content quality (CQ), habitual behaviour (HB) and security conditions (SC). SC, VE, SI, HB and EE were the antecedent variables. FEP, CQ and FIC were the mediating variables and HMU was the dependant variable. SI and CQ of OTT services were positively associated with HMU of OTT services, FEP had no significant effects on HMU. The results also supported the explanatory strength and predictability of UTAUT2 as a model. It further extended UTAUT2 boundaries and paved the way for an extended UTAUT2 model to be developed. Originality/value: The promising role of OTT services in the entertainment and media industry had gained consumer attention, however, limited empirical investigations had been conducted on explicating how user attitude and usage intention were shaped regarding the use of OTT services in the Indian context. This study served as one of the first attempts to empirically examine the adoption process, with implications for the HMU regarding OTT services. This was one of the first studies to extend the UTAUT2 theoretical model.

ABSTRACTBackground: There has been an explosion in the clinical application of transcatheter aortic valve replacement (TAVR) worldwide. While moderate and severe grades of paravalvular regurgitation (PVR) are established as poor prognostic indicators, the impact of mild PVR is unclear. We therefore aimed to compare outcomes after TAVR between those who develop mild PVR versus none or trivial PVR.Methods: We identified 1,098 consecutive patients who underwent TAVR from January 2014 to December 2017. The primary outcome was all-cause mortality using Kaplan Meier curves. The secondary outcomes included heart failure readmissions and the composite endpoints of early safety and clinical efficacy according to VARC-2 definitions.Results: The median age was 82 years, 43% were females, and 94% were Caucasian. The procedure was done through a transfemoral approach, the indication for TAVR was severe AS in 97% of cases, and 72% had an Edwards SAPIEN 3 Transcatheter Heart Valve implanted. Mild PVR was seen in 191 (17.4%) patients, and the rest (82.6%) had no or trivial post-TAVR PVR. Mortality at 30-days and 1 year was similar between none/trivial and mild PVR groups (1.6% vs 1.7%, p= 0.93 & 6.3% vs 8.8%, p= 0.31). HF-related hospitalizations were the same at 30 days as well as 1 year in both groups (1.9% vs 0.8%, p= 0.209 and 4.5% vs 6.3%, p= 0.461).Conclusion: Although mild PVR is seen in approximately one-fifth of patients after TAVR, patients with mild PVR have similar outcomes compared to those with none or trivial PVR.Abbreviations:AR: Aortic Regurgitation; AV: Aortic Valve; HF: Heart Failure; VARC: Valve Academic Research Consortium; LVOT: Left Ventricular Outflow Tract; LVEF: Left Ventricular Ejection Fraction; PVR: Paravalvular Aortic Regurgitation; TAVR: Transcatheter Aortic Valve Replacement; TF: Transfemoral

Here we projected a model-based IMRT treatment plan to produce the optimal radiation dosage by considering that the maximum amount of prescribed dose should be delivered to the target without affecting the surrounding healthy tissues especially the OARs. Fluence mapping is used for inverse planning. This suggested method can generate global minima for IMRT plans with reliable plan quality among diverse treatment planners and to provide better safety for significant parallel OARs in an effective way. The whole methodology is having the capability to handles various objectives and to generate effective treatment procedures as validated with illustrations on the CORT dataset. For the validation of our methodology, we have compared our result with the two other approaches for calculating the objectives based on dose-volume bounds and found that in our methodology dose across the prostate and lymph nodes is maximum and the time required for the convergence is minimum.

Using incorrect worked examples during mathematics instruction can improve student learning. However, teachers worry that students may confuse correct and incorrect examples over time, and memory research supports this fear. To examine if this forgetting occurs, we had undergraduates rate the correctness of correct and incorrect worked examples immediately and one week later (Experiment 1). Previously studied incorrect examples were rated as slightly more correct after the delay, but this did not affect ratings of unstudied examples or problem-solving accuracy. In Experiment 2, we more closely mimicked how incorrect worked examples are used in classroom settings. Again, we found only small changes in students’ memory for studied worked examples after the delay, and no changes for unstudied examples or problem-solving accuracy. Our findings suggest the costs of teaching with incorrect worked examples are limited to the specific studied problems, and do not affect learning of the underlying mathematical rule.

ABSTRACTDespite vast improvements in childhood vaccination coverage in India, adult vaccination coverage is negligible. Our aim was, therefore, to create awareness about the importance of adult immunization. Although the true burden of vaccine-preventable diseases (VPDs) among Indian adults is unknown, adults are particularly vulnerable during outbreaks, due to a lack of immunization, waning immunity, age-related factors (e.g. chronic conditions and immunosenescence), and epidemiological shift. There are no national adult immunization guidelines in India, and although several medical societies have published adult immunization guidelines, these vary, making it unclear who should receive which vaccines (based on age, underlying conditions, etc.). Other barriers to adult immunization include vaccine hesitancy, missed opportunities, and cost. Steps to improve adult vaccination could include: adoption of national guidelines, education of healthcare providers and the public, and promotion of life-course immunization. Improving adult vaccine coverage could help reduce the burden of VPDs, particularly among older adults.

Inspired by the problem of the removal of in situ gel-like materials via a displacement flow process, we use a fluidic device known as Hele-Shaw cell to study the flow parameters related to the displacement flow efficiency. In a displacement flow process, when a less viscous fluid displaces a more viscous fluid, exotic interfacial patterns known as viscous fingeringappear. Motivated by the recent developments in the literature, we experimentally study the effects of a simple cell nonuniformity with various gap gradients in the flow passage on the viscous fingering problem in the displacement of a viscoplastic gel (Carbopol) by air. We show that a linearly converging/diverging cell can be used to control certain interfacial patterns and improve the displacement efficiency. We classify the flow regimes into smooth fingerand rough fingerpatterns, using the average capillary number (Ca) and the average Bingham number (Bn) or their combinations.

Background The importance of junior doctor morale is increasingly being recognised. We aimed to identify and explore the factors affecting junior doctor morale in a UK teaching hospital.Methods We carried out an online survey asking junior doctors to rate their morale, rank the top five factors that positively affected morale and offer free-text comments.Results Nine hundred and forty three junior doctors were approached, 402 (42.6%) responded. Overall morale was rated 6 [interquartile range (IQR): 5-8], and how valued 6 (IQR: 4-8), supported 7 (IQR: 6-9) and autonomous 7 (IQR: 6-8) they felt [median ratings using a scale of 0 (low)-10 (high)]. When comparing the four domains of feeling supported, feeling valued, having autonomy and overall morale, respondents felt most supported overall (n = 402, X2= 85.6, p < 0.0001). Key themes were identified: team working and relationships, feedback, training and education, resources, wellbeing and pastoral support, staffing and workload, senior clinician support, and autonomy. The most common factors positively affecting morale were ‘feeling part of a team’ (66.4%) and ‘being recognised for good practice’ (56.7%).Conclusion We identified a number of diverse themes affecting junior doctor morale. Doctors felt more supported than valued or autonomous, with complex relationships between these domains.