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The strategic fluorination of oxidatively vulnerable sites in bioactive compounds is a relatively recent, widely used approach allowing us to modulate the stability, bio-absorption, and overall efficiency of pharmaceutical drugs. On the other hand, natural and tailor-made amino acids are traditionally used as basic scaffolds for the development of bioactive molecules. The main goal of this review article is to emphasize these general trends featured in recently approved pharmaceutical drugs.

Clinical study reports (CSRs) are highly detailed documents that play a pivotal role in medicine approval processes. Though not historically publicly available, in recent years, major entities including the European Medicines Agency (EMA), Health Canada, and the US Food and Drug Administration (FDA) have highlighted the importance of CSR accessibility. The primary objective herein was to determine the proportion of CSRs that support medicine approvals available for public download as well as the proportion eligible for independent researcher request via the study sponsor. This cross-sectional study examined the accessibility of CSRs from industry-sponsored clinical trials whose results were reported in the FDA-authorized drug labels of the top 30 highest-revenue medicines of 2021. We determined (1) whether the CSRs were available for download from a public repository, and (2) whether the CSRs were eligible for request by independent researchers based on trial sponsors’ data sharing policies. There were 316 industry-sponsored clinical trials with results presented in the FDA-authorized drug labels of the 30 sampled medicines. Of these trials, CSRs were available for public download from 70 (22%), with 37 available at EMA and 40 at Health Canada repositories. While pharmaceutical company platforms offered no direct downloads of CSRs, sponsors confirmed that CSRs from 183 (58%) of the 316 clinical trials were eligible for independent researcher request via the submission of a research proposal. Overall, 218 (69%) of the sampled clinical trials had CSRs available for public download and/or were eligible for request from the trial sponsor. CSRs were available from 69% of the clinical trials supporting regulatory approval of the 30 medicines sampled. However, only 22% of the CSRs were directly downloadable from regulatory agencies, the remaining required a formal application process to request access to the CSR from the study sponsor.

Amino acids (AAs) are among a handful of paramount classes of compounds innately involved in the origin and evolution of all known life-forms. Along with basic scientific explorations, the major goal of medicinal chemistry research in the area of tailor-made AAs is the development of more selective and potent pharmaceuticals. The growing acceptance of peptides and peptidomimetics as drugs clearly indicates that AA-based molecules become the most successful structural motif in the modern drug design. In fact, among 24 small-molecule drugs approved by FDA in 2019, 13 of them contain a residue of AA or di-amines or amino-alcohols, which are commonly considered to be derived from the parent AAs. In the present review article, we profile 13 new tailor-made AA-derived pharmaceuticals introduced to the market in 2019. Where it is possible, we will discuss the development form drug-candidates, total synthesis, with emphasis on the core-AA, therapeutic area, and the mode of biological activity.

Purpose This paper aims to explore whether crowdfunding creators can learn from previous experiences to have a better financing performance of future crowdfunding projects. Design/methodology/approach This paper uses Python to capture the data of 6,267 crowdfunding projects from one of the largest crowdfunding platforms in China (JingDong Crowdfunding) and the author use the negative binomial regression model and the OLS model in this empirical study. Findings The empirical results show that both the early-stage experience of creating a crowdfunding project and the early-stage experience of supporting projects of other crowdfunding creators can improve the financing performance of their newly launched projects. The social network of the previous projects and the “Blockbuster” projects initiated before can also make the newly initiated projects obtain better financing performance. Originality/value Current research on entrepreneurial experience shows that serial entrepreneurs have significantly different success rates than novice or inexperienced entrepreneurs but there is limited literature on the learning effect of crowdfunding creators. This study adds to the literature on entrepreneurial learning and provides suggestions to crowdfunding creators.

Infinity War minner mer om en sesongavslutning av en tv-serie enn en filmfortelling med en begynnelse, et midtparti og en slutt - eller rettere sagt: første halvdel av en sesongavslutning, som vil bli fullført etter en ett år lang pause. Den moderne shared universe-blockbusteren er utviklet med utgangspunkt i en forståelse av at kinoens økonomiske modell er en forutsetning for å realisere disse prosjektene, samtidig som filmene er nødt til å ha en massiv og langvarig tilstedevæ relse i den digitale offentligheten dersom de skal ha noe håp om å trekke tilstrekkelig mange publikummere til kinoene. Ingen forstår dette bedre enn Marvel Studios (de eneste som kommer i næ rheten er Lucasfilm, som i likhet med Marvel er eid av Disney) som har skapt en modell hvor skillene mellom film og markedsføring - fortelling og hype - er utflytende, hvis ikke også ikke-eksisterende. Det var denne tidsånden Warner Bros. ønsket å fange, da de fikk selskapet som hadde laget den svæ rt godt mottatte traileren til David Ayers Suicide Squad (2016) til å klippe om filmen for å ligne mer på traileren.

Popularity bias is defined as the intrinsic tendency of recommendation algorithms to feature popular items more than unpopular ones in the ranked lists lists they produced. When investigating the adverse effects of popularity bias, the literature has usually focused on the most frequently rated items only. However, an item’s popularity does not always indicate that it is highly-liked by individuals; in fact, the degree of liking may even introduce biases that are more extreme than the famous popularity bias in terms of beyond-accuracy evaluations. Therefore, in the present study, we attempt to consider items that are both popular and highly-liked, which we refer to as blockbuster items, and to investigate whether the recommendation algorithms impose a considerable bias in favor of the blockbuster items in their ranking-based recommendations. To this end, we first present a practical formulation that measures the degree of the blockbuster level of the items by combining their liking-degree and popularity effectively. Then, based on this formulation, we perform a comprehensive set of experiments with ten different algorithms on five datasets with different characteristics to explore the potential biases towards blockbuster items in recommendations. The experimental outcomes demonstrate that most recommenders propagate an undesirable bias in their recommendations towards the blockbuster items, and such a bias is, in fact, not caused by the item popularity. Moreover, the observed biases to blockbuster items are more harmful and persistent than those to popular ones in terms of beyond-accuracy aspects such as diversity, catalog coverage, and novelty. The obtained results also suggest that conventional popularity-debiasing strategies are not so talented in treating the adverse effects of the observed blockbuster bias in recommendations.

Background and Aims: BlockBuster® Laryngeal Mask Airway, a newer supraglottic airway device, is claimed to be an efficient conduit for endotracheal intubation. Intubating laryngeal mask airway (LMA) is an established device for the same. This randomised study was undertaken to evaluate the success rate of blind intubation using either of these LMAs. Methods: Sixty patients of age group 20-60 years undergoing general anaesthesia were randomised in 2 groups, of 30 patients each, for tracheal intubation using either BlockBuster® LMA (Group B) or the Intubating LMA Fastrach® (Group F). After induction of anaesthesia, LMAs were inserted and on achieving adequate ventilation with the device, fibreoptic scopy was performed to assess the glottis visualisation score. Blind intubation was attempted through the supraglottic airway devices (SAD). The primary objective was first pass successful intubation and secondary outcomes were ease, time for LMA insertion, oropharyngeal seal pressure (OSP), LMA removal time, fibreoptic scoring and complications. Data was analysed using SPSS V22 software. Results: The first-attempt success rate of tracheal intubation was 90% in Group B and 66.6% in Group F (P = 0.028), while the overall success rate of intubation was 96.6% in Group B and 89.9% in Group F (P = 0.3). The OSP in Group B was 33.7 ± 1.8 and 22.7 ± 1.5 cm H2O in Group F (P = 0.001). Complications such as sore throat and blood stain were reduced with BlockBuster® LMA. Conclusion: BlockBuster® LMA provides higher first pass success rate of blind tracheal intubation with less complications like sore throat and blood staining.

The 2010s were perhaps the most tumultuous decade since the 1960s. The effects of the Great Recession continued to be felt. The administration of Barack Obama, the first African-American president, encouraged many to think that America was now 'post-racial', an illusion broken by the election of Donald Trump. Polarisation reigned, communicated on social media. Netflix and Amazon jumped into production. By 2019, Netflix produced more feature films than the traditional studios combined. Cinema's move from film to digital, in production and in exhibition, was complete by mid-decade. `MeToo and `Oscarssowhite signaled a reckoning with gross gender and racial inequalities in the media, matched by that in the wider culture. The essays of this book explore the blockbusters, low-budget sleepers, and films in between.

Across the many studies of motion picture box office success, unresolved debates and untested assumptions about the contributing factors persist. Using an accessibility–diagnosticity framework and a meta-analysis of 634 effect sizes from 150 studies, the current article seeks to clarify the relationships of star brand equity and product reviews (from consumers and critics) with box office success. The popularity of stars (market and media appeals) exerts a stronger impact on box office success than their artistic recognition (as per award nominations and wins) at the moment of a movie’s release but not over its extended theatrical run. Whereas the impact of popular stars on box office success decreases over time, the influence of artistically recognized stars remains steady. The findings also identify a dual role for critics, who influence consumers’ movie choice and predict box office performance by merely reflecting moviegoers’ tastes. Finally, this study refutes the assumption that the impact of users’ reviews strengthens over time, relative to critics’ reviews.

ABSTRACT Background and Aims: Supraglottic airway (SGA) devices are a boon to paediatric airway management. The clinical performances of the BlockBuster® laryngeal mask airway (LMA) and Ambu® AuraGain™ in preschool children were compared in this study. Methods: After ethical approval and trial registration, this randomised controlled study was conducted on 50 children, aged 1-4 years, randomised into two groups. Appropriate sized Ambu® AuraGain™ (group A) and LMA BlockBuster® (group B) were placed as per the manufacturer's recommendation under general anaesthesia. Appropriate size of the endotracheal tube was then chosen and inserted through the device. Primary objective of the study was to compare the oropharyngeal seal pressure (OSP), and secondary objectives were the first attempt intubation success rate, overall intubation success rate, SGA insertion time, intubation time, haemodynamic changes and postoperative pharyngolaryngeal complications. The Chi-square test was used to analyse the categorical variables, while the intragroup comparison of mean changes in outcomes was evaluated by the unpaired t-test. The level of significance was set at P < 0.05. Results: Demographic parameters were uniformly distributed in both the groups. The mean OSP in group A was 26.6 ± 0.95 cm H2O and in group B was 29.08 ± 0.75 cm H2O. Both the devices were successfully inserted in all the patients. The success rate of blind endotracheal intubation through the device in first attempt was 4% in group A and 80% in group B. Postoperative pharyngolaryngeal complications were relatively less in group B. Conclusion: LMA BlockBuster® provides higher OSP and provides a higher success rate of blind endotracheal intubation in paediatric patients.