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Three-dimensional printing (3DP) is a transformative technology that is advancing pharmaceutical research by producing personalized drug products. However, advances made via 3DP have been slow due to the lengthy trial-and-error approach in optimization. Artificial intelligence (AI) is a technology that could revolutionize pharmaceutical 3DP through analyzing large datasets. Herein, literature-mined data for developing AI machine learning (ML) models was used to predict key aspects of the 3DP formulation pipeline and in vitro dissolution properties. A total of 968 formulations were mined and assessed from 114 articles. The ML techniques explored were able to learn and provide accuracies as high as 93% for values in the filament hot melt extrusion process. In addition, ML algorithms were able to use data from the composition of the formulations with additional input features to predict the drug release of 3D printed medicines. The best prediction was obtained by an artificial neural network that was able to predict drug release times of a formulation with a mean error of ±24.29 min. In addition, the most important variables were revealed, which could be leveraged in formulation development. Thus, it was concluded that ML proved to be a suitable approach to modelling the 3D printing workflow.

Background Distal radius fractures (DRFs) are the most common fracture of the upper extremity. Given that steroids are one of the most commonly prescribed drugs and are usually prescribed for chronic conditions, steroid use represents a key factor to consider in how to optimize perioperative outcomes. Questions/Purposes The purpose of this study was to investigate if there are differences in perioperative outcomes for patients undergoing DRF open reduction and internal fixation based on preoperative steroid use. Patients and Methods Adult patients who underwent operative treatment for DRF from 2007 to 2018 were identified in a national database. Patients were divided into two cohorts as follows: (1) no steroid usage and (2) preoperative steroid usage. In this analysis, various postoperative complications, as well as extended length of stay and reoperation, were assessed. Bivariate analyses and multivariable logistical regression were performed. Results Among a total of 16,505 patients undergoing operative treatment for DRF, 16,145 patients (97.8%) did not have steroid usage and 360 (2.2%) had steroid usage. Following adjustment, an increased risk of extended length of hospital stay greater than 3 days (odds ratio [OR] = 1.646; p = 0.012) was seen in the steroid usage group compared with those who did not use steroids within 30 days of surgery. Conclusion Preoperative steroid use is associated with increased length of stay over 3 days after DRF open reduction and internal fixation surgery but is not associated with any of the other complications that were assessed in this study. Level of Evidence This is a Level III, retrospective study.

This article examines popular culture’s depictions of Artificial Intelligence. It begins with Hollywood’s sci-fi robot characters that were often depicted as dangerous and inimical to human existence. It identifies major Hollywood movies that depict artificial intelligence, starting with Stanley Kubrick’s 2001: A Space Odyssey (1968), James Cameron’s The Terminator (1984), Steven Spielberg’s Minority Report (2002), Garth Jennings’ The Hitchhiker’s Guide to the Galaxy (2005), Spike Jonze’s Her (2014), Alex Garland’s Ex Machina (2014), and Toby Hanes’ Brexit (2019). These films illustrate artificial intelligence issues, including self-aware computers, facial recognition, crime prevention, and personal assistants. These technologies are depicted both positively and negatively in popular culture, and their depictions in these films reveals popular culture’s pervasive stereotypes and occasional timely warnings about emerging technology.

Many geriatric patients presenting for emergency hip fracture surgery are on direct oral anticoagulants (DOACs) most of which are not easily reversible. A safe policy was required to reduce delays to surgery. Prior to institution of our hospital's protocol in January 2021, most of these patients had surgery after 48 h following the last dose of DOAC due to concerns about increased perioperative blood loss.This was a prospective closed loop audit of the protocol-surgery within 24 h from last dose of DOAC (if creatinine clearance50 ml/min) with administration of 1-g of tranexamic acid at anesthesia induction. 131 eligible patients (DOAC, n = 22; no anticoagulation, n = 109) between January-June 2021 who had emergency hip fracture surgery were identified. Primary outcome measures were peri-operative blood loss, transfusion requirements and policy compliance. Secondary outcome measures were 30-day mortality, thrombotic complications and wound bleeding.Compliance with surgical timing and tranexamic acid administration were 55% and 81% respectively after the second audit cycle. The mean estimated blood loss (EBL) in the DOAC group versus the non-anticoagulated control group was 500 ml and 330 ml respectively. The difference between these groups was statistically significant at an alpha level of 5% (P = 0.0115, 95% CI 38.48-299.16). The difference for intra-operative (RR 3.43; 95% CI 1.68-7.01) and post-operative blood transfusion (RR 2.10; 95% CI 1.23-3.58) for the 2 groups was also statistically significant. However, there was no case of massive blood transfusion in both groups. The DOAC group had a lower risk for 30-day mortality (RR 0.71; 95% CI 0.09-5.46). There was no major thrombotic complication in the DOAC group.This audit has shown that this protocol is safe although clinicians should anticipate some degree of increased intra-operative blood loss. We will recommend continuation of this policy with sustained safety monitoring in order to reduce delays to surgery.

Left ventricular thrombus (LVT) is a common complication of acute myocardial infarction and is associated with morbidity from embolic complications. Predicting which patients will develop death or persistent LVT despite anticoagulation may help clinicians identify high-risk patients. We developed a random forest (RF) model that predicts death or persistent LVT and evaluated its performance. This was a single-center retrospective cohort study in an academic tertiary center. We included 244 patients with LVT in our study. Patients who did not receive anticoagulation (n = 8) or had unknown (n = 31) outcomes were excluded. The primary outcome was a composite outcome of death, recurrent LVT and persistent LVT. We selected a total of 31 predictors collected at the point of LVT diagnosis based on clinical relevance. We compared conventional regularized logistic regression with the RF algorithm. There were 156 patients who had resolution of LVT and 88 patients who experienced the composite outcome. The RF model achieved better performance and had an AUROC of 0.700 (95% CI 0.553-0.863) on a validation dataset. The most important predictors for the composite outcome were receiving a revascularization procedure, lower visual ejection fraction (EF), higher creatinine, global wall motion abnormality, higher prothrombin time, higher body mass index, higher activated partial thromboplastin time, older age, lower lymphocyte count and higher neutrophil count. The RF model accurately identified patients with post-AMI LVT who developed the composite outcome. Further studies are needed to validate its use in clinical practice.

Precision medicine is a field with huge potential for improving a patient's quality of life, wherein therapeutic drug monitoring (TDM) can provide actionable insights. More importantly, incorrect drug dose is a common contributor to medical errors. However, current TDM practice is time-consuming and expensive, and requires specialised technicians. One solution is to use electrochemical biosensors (ECBs), which are inexpensive, portable, and highly sensitive. In this review, we explore the potential for ECBs as a technology for on-demand drug monitoring, including microneedles, continuous monitoring, synthetic biorecognition elements, and multi-material electrodes. We also highlight emerging strategies to achieve continuous drug monitoring, and conclude by appraising recent developments and providing an outlook for the field.

Now more than ever, traditional healthcare models are being overhauled with digital technologies of Healthcare 4.0 increasingly adopted. Worldwide, digital devices are improving every stage of the patient care pathway. For one, sensors are being used to monitor patient metrics 24/7, permitting swift diagnosis and interventions. At the treatment stage, 3D printers are under investigation for the concept of personalised medicine by allowing patients access to on-demand, customisable therapeutics. Robots are also being explored for treatment, by empowering precision surgery, rehabilitation, or targeted drug delivery. Within medical logistics, drones are being leveraged to deliver critical treatments to remote areas, collect samples, and even provide emergency aid. To enable seamless integration within healthcare, the Internet of Things technology is being exploited to form closed-loop systems that remotely communicate with one another. This review outlines the most promising healthcare technologies and devices, their strengths, drawbacks, and opportunities for clinical adoption.

The Obama administration plans a “pivot” to the Asian-Pacific area, both in terms of military deployment and trade agreements. At the same time, Americans often view Asians through negative stereotypes while they express fear and distrust of Asian-Pacific institutions, including governments. These prejudices become readily apparent when one examines recent Hollywood films depicting Asian countries, including Asian intelligence agencies, corporations, and military forces. Hollywood’s depiction of Asians and Pacific Islanders often finds expression through stereotypes, xenophobia, and, on occasion, blatant racism. The following article analyzes recent Hollywood movies with Asia-Pacific settings in terms of themes, characters, and depictions of institutions.

With the impending Industrial Revolution 4.0, the information produced by sensors will be central in many applications. This includes the healthcare sector, where affordable healthcare and precision medicine are highly sought after. Electrochemical sensors have the potential to produce affordable, high sensitivity and specificity, intuitive, and rapid point‐of‐care diagnostics. Underpinning these achievements is the choice of material and the fabrication thereof. In this review, the different types of materials used in electrochemical biosensors are reported, with a focus on synthetic conductive materials. The review demonstrates that there is an abundance of materials to select from, and compositing different types of materials further widens their applicability in biosensors. In addition, the fabrication of such materials using the state‐of‐the‐art of fabrication technology, additive manufacturing (AM), is also detailed. The need for compositing is evident in AM, as the feedstock for certain AM technologies is inherently nonconductive. Both material choice and fabrication technologies limitations are also discussed to highlight opportunities for growth. The review highlights how recent technological advancements have the potential to drive the healthcare industry toward achieving its primary goals.

UNSTRUCTURED Electronic health records (EHRs) have been widely adopted among modern hospitals to collect and track clinical data. Secondary analysis of EHRs could complement the traditional randomized control trial (RCT) research model. However, most researchers in China lack either the technical expertise or the resources needed to utilize EHRs as a resource. In addition, a climate of cross-disciplinary collaboration to gain insights from EHRs, a crucial component of a learning healthcare system, is not prevalent. To address these issues, members from the Massachusetts Institute of Technology (MIT) and the People’s Liberation Army General Hospital (PLAGH) organized the first clinical data conference and health datathon in China, which provided a platform for clinicians, statisticians, and data scientists to team up and address information gaps in the intensive care unit (ICU).

The Bush years have witnessed the elevated militarization of American society, marked by expansion of the war economy and security state, an aggressive foreign policy, increasing incidents of civic...

SummaryMany genes that affect replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae also affect aging in other organisms such as C. elegans and M. musculus. We performed a systematic analysis of yeast RLS in a set of 4,698 viable single-gene deletion strains. Multiple functional gene clusters were identified, and full genome-to-genome comparison demonstrated a significant conservation in longevity pathways between yeast and C. elegans. Among the mechanisms of aging identified, deletion of tRNA exporter LOS1 robustly extended lifespan. Dietary restriction (DR) and inhibition of mechanistic Target of Rapamycin (mTOR) exclude Los1 from the nucleus in a Rad53-dependent manner. Moreover, lifespan extension from deletion of LOS1 is nonadditive with DR or mTOR inhibition, and results in Gcn4 transcription factor activation. Thus, the DNA damage response and mTOR converge on Los1-mediated nuclear tRNA export to regulate Gcn4 activity and aging.

As terrorist actions, both state and non-state, have spread in both frequency and destructive power since the 1960s, the topic has become an enduring source of narratives, fantasies, and myths that have contributed to Hollywood filmmaking with its familiar emphasis on international intrigue, exotic settings, graphic violence, and the demonization of foreign threats. Images of political violence have a strong appeal in the US, where the gun culture, civic violence, crime sprees, and a thriving war economy permeate the landscape. The al Qaeda attacks of 9/11 heightened public fascination with terrorism, fueled by mounting fear and paranoia, and this was destined to inspire a new cycle of films in which on-screen terrorism dramatizes elements of real-life threats that now include possible weapons of mass destruction. The “war on terror,” driven as much by US strategy to reconfigure the Middle East as by the events of 9/11, serves as the perfect backdrop for film industry productions of violent high-tech spec...

No discussion of American cinema, postmodern or otherwise, would be complete without an attempt to engage the realm of the family, gender relations, and sexuality, perhaps the most emotionally charged of all spheres of contemporary social life. The vast majority of film plots relate in some fashion to this sphere, even where (as in combat and sci-fi movies) it would seem to be rather peripheral within the larger narrative structure. If modernist filmmaking-rational, goal-oriented, successful hero narratives-has not always romanticized the conventional nuclear family, to one degree or another it has upheld this basic social unit of American society as the standard repository of established values, loving personal relationships, and effective childhood socialization. Hollywood studio heads typically venerated patriarchal family values even where reality is shown as radically departing from the ideal, as in the familiar noir cycle where children were nowhere to be seen and treachery was frequently the norm between husbands and wives. "Family values," in one guise or another, has long been a cherished myth of American culture passed through the educational, legal, and political systems and, more recently, bastions of popular culture such as TV, advertising, and the omnipresent talk shows. Postmodern cinema, on the other hand, offers a far more jaundiced view of the family as an institution wracked by conflict, deceit, disillusionment, and mayhem in a rapidly changing Hobbesian labyrinth. The term "postmodern," first employed in connection with architecture, is now routinely applied to other realms of social and aesthetic life, including film. What we refer to as postmodern films are essentially popular works containing abundant elements of parody and pastiche (from "pasticcio," which means "any work of art consisting of motifs borrowed from one or more masters or works of art") and increasingly reveal a fragmented, chaotic, dystopic universe. What might be loosely understood as postmodern cinema first made its appearance during the late 1970s and has since followed multiple trajectories (see Jamison; Ashley; Best and Kellner). Films labeled postmodern by academic and media critics frequently embrace strong undercurrents of mayhem, satire, irreverence, and irony, revealing at the same time a milieu in which social and personal relationships often enter into a process of breakdown and collapse. Although enormously diverse, such films tend to borrow stylistically and thematically from earlier works and genres as part of the modality of pastiche. Brian De Palma's The Untouchables (1987), for example, has been labeled postmodern owing to its randomly violent narrative structure, its flawed hero, and its representation of social chaos. At one point, the film introduces a scene at a railroad station that deliberately evokes the famous "Odessa Steps sequence" of Sergei Eisenstein's classic Battleship Potemkin (1925). Unlike Eisenstein's original version, however, which emphasized citizen solidarity against Czarist atrocities, De Palma's film focuses on a garden-variety shootout between federal agents and criminals. But an audience knowledgeable about film history will note the quotation and associate De Palma's work with the great classic. This sort of quotation is an important hallmark of postmodern films, adding a stylistic element that calls attention to itself at the very moment it breaks down the illusion of seeing "reality." Through such techniques, the audience is reminded that it is viewing an artifice rather than a slice of real life. Postmodern films depend upon such devices as jump cuts, flashbacks, flashforwards, split screens, and other formalist conventions that refocus attention to particular film discourses as artistic constructs, in the process approaching Bertolt Brecht's theatrical dictum that audiences must never be lulled, even momentarily, into believing that they are viewing real-life representations. …

What we call the "Hollywood War Machine" analyzes the production of films within the studio system depicting the glories of US military action within theaters from around the world, spanning the Revolutionary War period to the present. A large majority of films under discussion here can be understood from the perspective of "good wars" that the film industry has strongly favored, especially during the 1990s. This essay reveals an increasing emphasis on the World War II experience as the quintessential "good war" that brings American audiences back to the undistilled benevolence of the US military through its various patriotic and heroic exploits. The undoubtedly powerful impact of the September 11, 2001 events and their aftermath upon the Hollywood War Machine is a topic worthy of further discussion.

First paragraph: As we pass through life in the digital era we leave a health trajectory in our wake. Phones, shopping habits, and visits to the doctor create a trace of data that can be used to not only assess our past and present wellbeing, but also forecast the future. To some, this is an unparalleled opportunity to improve health care, whereas to others it is an emerging threat to civil liberty. Most of us camp somewhere between the two poles: we see the rewards and we acknowledge the concerns. The question is how we move past this point, when business models and legal frameworks, built for a pre-internet world, struggle to keep up with the pace of change (Park & VanRoekel 2013).

Postmodern cinema has emerged in the 1980s and 1990s as a powerfully creative force in Hollywood filmmaking, reflecting and helping to shape the historic convergence of media culture, technology, and consumerism. It corresponds to the post-Fordist, globalized phase of capitalist development typified by increasing class polarization, social atomization, urban chaos and violence, ecological crisis, and mass depoliticization. Departing from the modernist cultural tradition grounded in the Enlightenment, norms of industrial society, and faith in historical progress, postmodern cinema is characterized by disjointed narratives, a dark view of the human condition, images of chaos and random violence, death of the hero, emphasis on technique over content, and dystopic views of the future. While postmodern directors such as Woody Allen, Oliver Stone, Robert Altman, Quentin Tarantino, the Coen Brothers, Mike Figgis, and John Waters produce films that are often highly original and even subversive, their departure fr...

This is an open letter concerning the recent launch of the new open access journal, Science Advances. In addition to the welcome diversification in journal choices for authors looking for open access venues, there are many positive aspects of Science Advances: its broad STEM scope, its interest in cross-disciplinary research, and the offering of fee waivers. While we welcome the commitment of the Association to open access, we are also deeply concerned with the specific approach. Herein, we outline a number of suggestions that are in line with both the current direction that scholarly publishing is taking and the needs expressed by the open access community, which this journal aims to serve.

Summary Dietary restriction (DR) increases lifespan and attenuates age-related phenotypes in many organisms; however, the effect of DR on longevity of individuals in genetically heterogeneous populations is not well characterized. Here, we describe a large-scale effort to define molecular mechanisms that underlie genotype-specific responses to DR. The effect of DR on lifespan was determined for 166 single gene deletion strains in Saccharomyces cerevisiae. Resulting changes in mean lifespan ranged from a reduction of 79% to an increase of 103%. Vacuolar pH homeostasis, superoxide dismutase activity, and mitochondrial proteostasis were found to be strong determinants of the response to DR. Proteomic analysis of cells deficient in prohibitins revealed induction of a mitochondrial unfolded protein response (mtUPR), which has not previously been described in yeast. Mitochondrial proteotoxic stress in prohibitin mutants was suppressed by DR via reduced cytoplasmic mRNA translation. A similar relationship between prohibitins, the mtUPR, and longevity was also observed in Caenorhabditis elegans. These observations define conserved molecular processes that underlie genotype-dependent effects of DR that may be important modulators of DR in higher organisms.