Интеллектуальный анализ данных на индийских фондовых рынках: создание портфелей с низким уровнем риска

Over the last five decades, business academics have identified over 300 determinants that potentially influence stock returns. However, we still do not know whether all return determinants are equally important, or whether there is a smaller set of determinants that has a disproportionately larger influence on stock returns. Can mining historical data help us find this smaller set of return determinants that has a disproportionately higher influence on stock returns? Using historical data from the Indian market, we build a large database of investments with more than 74,000 investments spread over a period of 132 months. From this database, using “association rule mining” method, we are able to mine a strong set of “association rules” that point to a smaller set of “return determinants” that are seen more frequently in investments that beat index returns. From a pool of thirty-seven return determinants, using “association rule mining”, we were able to find out a small set of key return determinants that are seen most frequently in investments that beat index returns in India. Portfolios created from these “association rules” have a portfolio risk lower than the market risk and provide index-beating returns. “Out-of-sample” portfolios created using these association rules have portfolio “Beta” less than one and provide returns that beat the market returns by a significant margin for all holding periods in the Indian market. Through this paper, we demonstrate how portfolio managers can mine “association rules” and build portfolios without any limits on the number of factors that can be included in the screening process. За последние 50 лет академики выявили более 300 факторов, которые потенциально влияют на доходность акций. Тем не менее мы по-прежнему не знаем, являются ли все факторы доходности одинаково важными или существует небольшой набор таких факторов, которые оказывают большее влияние на доходность акций. Помогут ли исторические данные по майнингу определить эти факторы доходности? Используя исторические данные индийского рынка, мы создали базу данных по 74 000 инвестициям в течение 132 месяцев. Из этой базы данных, используя метод «анализа ассоциативных правил», мы можем извлечь «факторы доходности», которые чаще встречаются в инвестициях и повышают индекс доходности. Из пула 37 факторов рентабельности, используя «ассоциативные правила», мы получили небольшой набор «ключевых» детерминирующих факторов, которые наиболее часто встречаются в инвестициях и повышают индекс доходности в Индии. Портфели, созданные на основе этих «правил ассоциации», имеют более низкий портфельный риск, чем рыночный риск, и обеспечивают большую отдачу от индексов. Портфели, созданные с использованием этих правил, имеют менее одного «Бета» в портфеле и обеспечивают прибыль, которая превосходит рыночную прибыль по полученной марже за весь период владения им на индийском рынке. С помощью этой статьи мы демонстрируем, как портфельные менеджеры могут использовать «правила ассоциации» и создавать портфели без каких-либо ограничений по количеству факторов, которые могут быть включены в процесс отбора

An overview of clinical and commercial impact of drug delivery systems

Drug delivery systems are widely researched and developed to improve the delivery of pharmaceutical compounds and molecules. The last few decades have seen a marked growth of the field fueled by increased number of researchers, research funding, venture capital and the number of start-ups. Collectively, the growth has led to novel systems that make use of micro/nano-particles, transdermal patches, inhalers, drug reservoir implants and antibody-drug conjugates. While the increased research activity is clearly an indication of proliferation of the field, clinical and commercial translation of early-stage research ideas is critically important for future growth and interest in the field. Here, we will highlight some of the examples of novel drug delivery systems that have undergone such translation. Specifically, we will discuss the developments, advantages, limitations and lessons learned from: (i) microparticle-based depot formulations, (ii) nanoparticle-based cancer drugs, (iii) transdermal systems, (iv) oral drug delivery systems, (v) pulmonary drug delivery, (vi) implants and (vii) antibody-drug conjugates. These systems have impacted treatment of many prevalent diseases including diabetes, cancer and cardiovascular diseases, among others. At the same time, these systems are integral and enabling components of products that collectively generate annual revenues exceeding US $100 billion. These examples provide strong evidence of the clinical and commercial impact of drug delivery systems

Nanoparticles in the clinic: An update post COVID-19 vaccines

Nanoparticles are used in the clinic to treat cancer, resolve mineral deficiencies, image tissues, and facilitate vaccination. As a modular technology, nanoparticles combine diagnostic agents or therapeutics (e.g., elements, small molecules, biologics), synthetic materials (e.g., polymers), and biological molecules (e.g., antibodies, peptides, lipids). Leveraging these parameters, nanoparticles can be designed and tuned to navigate biological microenvironments, negotiate biological barriers, and deliver therapeutics or diagnostic agents to specific cells and tissues in the body. Recently, with the Emergency Use Authorization of the COVID-19 lipid nanoparticle vaccines, the advantages and potential of nanoparticles as a delivery vehicle have been displayed at the forefront of biotechnology. Here, we provide a 5-year status update on our original “Nanoparticles in the Clinic” review (also a 2-year update on our second “Nanoparticles in the Clinic” review) by discussing recent nanoparticle delivery system approvals, highlighting new clinical trials, and providing an update on the previously highlighted clinical trials

Non-invasive delivery strategies for biologics

Biologics now constitute a significant element of available medical treatments. Owing to their clinical and commercial success, biologics are a rapidly growing class and have become a dominant therapeutic modality. Although most of the successful biologics to date are drugs that bear a peptidic backbone, ranging from small peptides to monoclonal antibodies (~500 residues; 150 kDa), new biologic modalities, such as nucleotide-based therapeutics and viral gene therapies, are rapidly maturing towards widespread clinical use. Given the rise of peptides and proteins in the pharmaceutical landscape, tremendous research and development interest exists in developing less-invasive or non-invasive routes for the systemic delivery of biologics, including subcutaneous, transdermal, oral, inhalation, nasal and buccal routes. This Review summarizes the current status, latest updates and future prospects for such delivery of peptides, proteins and other biologics

The evolution of commercial drug delivery technologies

Drug delivery technologies have enabled the development of many pharmaceutical products that improve patient health by enhancing the delivery of a therapeutic to its target site, minimizing off-target accumulation and facilitating patient compliance. As therapeutic modalities expanded beyond small molecules to include nucleic acids, peptides, proteins and antibodies, drug delivery technologies were adapted to address the challenges that emerged. In this Review Article, we discuss seminal approaches that led to the development of successful therapeutic products involving small molecules and macromolecules, identify three drug delivery paradigms that form the basis of contemporary drug delivery and discuss how they have aided the initial clinical successes of each class of therapeutic. We also outline how the paradigms will contribute to the delivery of live-cell therapies

Viral vector-based gene therapies in the clinic

Gene therapies are currently one of the most investigated therapeutic modalities in both the preclinical and clinical settings and have shown promise in treating a diverse spectrum of diseases. Gene therapies aim at introducing a gene material in target cells and represent a promising approach to cure diseases that were thought to be incurable by conventional modalities. In many cases, a gene therapy requires a vector to deliver gene therapeutics into target cells; viral vectors are among the most widely studied vectors owing to their distinguished advantages such as outstanding transduction efficiency. With decades of development, viral vector-based gene therapies have achieved promising clinical outcomes with many products approved for treating a range of diseases including cancer, infectious diseases and monogenic diseases. In addition, a number of active clinical trials are underway to further expand their therapeutic potential. In this review, we highlight the diversity of viral vectors, review approved products, and discuss the current clinical landscape of in vivo viral vector-based gene therapies. We have reviewed 13 approved products and their clinical applications. We have also analyzed more than 200 active trials based on various viral vectors and discussed their respective therapeutic applications. Moreover, we provide a critical analysis of the major translational challenges for in vivo viral vector-based gene therapies and discuss possible strategies to address the same

Hydrogels in the clinic

Injectable hydrogels are one of the most widely investigated and versatile technologies for drug delivery and tissue engineering applications. Hydrogels’ versatility arises from their tunable structure, which has been enabled by considerable advances in fields such as materials engineering, polymer science, and chemistry. Advances in these fields continue to lead to invention of new polymers, new approaches to crosslink polymers, new strategies to fabricate hydrogels, and new applications arising from hydrogels for improving healthcare. Various hydrogel technologies have received regulatory approval for healthcare applications ranging from cancer treatment to aesthetic corrections to spinal fusion. Beyond these applications, hydrogels are being studied in clinical settings for tissue regeneration, incontinence, and other applications. Here, we analyze the current clinical landscape of injectable hydrogel technologies, including hydrogels that have been clinically approved or are currently being investigated in clinical settings. We summarize our analysis to highlight key clinical areas that hydrogels have found sustained success in and further discuss challenges that may limit their future clinical translation

Synergistic antitumor activity of camptothecin-doxorubicin combinations and their conjugates with hyaluronic acid

Combinations of topoisomerase inhibitors I and II have been found to synergistically inhibit cancer cell growth in vitro, yet clinical studies of these types of combinations have not progressed beyond phase II trials. The results of clinical combinations of topoisomerase (top) I and II inhibitors typically fall within one of two categories: little to no improvement in therapeutic efficacy, or augmented toxicity compared to the single drug counterparts. Hence, despite the promising activity of top I and II inhibitor combinations in vitro, their clinical applicability has not been realized. Here, we report the use of polymer-drug conjugates as a means to co-deliver synergistic doses of top I and II inhibitors camptothecin (CPT) and doxorubicin (DOX) to tumors in vivo in a 4T1 breast cancer model. At specific molar ratios, DOX and CPT were found to be among the most synergistic combinations reported to date, with combination indices between 0.01 and 0.1. The identified optimal ratios were controllably conjugated to hyaluronic acid, and elicited significant tumor reduction of murine 4T1 breast cancer model when administered intravenously. This study elucidates a method to identify synergistic drug combinations and translate them to in vivo by preserving the synergistic ratio via conjugation to a carrier polymer, thus opening a promising approach to translate drug combinations to clinically viable treatment regimens

Non-affinity factors modulating vascular targeting of nano- and microcarriers

Particles capable of homing and adhering to specific vascular biomarkers have potential as fundamental tools in drug delivery for mediation of a wide variety of pathologies, including inflammation, thrombosis, and pulmonary disorders. The presentation of affinity ligands on the surface of a particle provides a means of targeting the particle to sites of therapeutic interest, but a host of other factors come into play in determining the targeting capacity of the particle. This review presents a summary of several key considerations in nano- and microparticle design that modulate targeted delivery without directly altering epitope-specific affinity. Namely, we describe the effect of factors in definition of the base carrier (including shape, size, and flexibility) on the capacity of carriers to access, adhere to, and integrate in target biological milieus. Furthermore, we present a summary of fundamental dynamics of carrier behavior in circulation, taking into account interactions with cells in circulation and the role of hemodynamics in mediating the direction of carriers to target sites. Finally, we note non-affinity aspects to uptake and intracellular trafficking of carriers in target cells. In total, recent findings presented here may offer an opportunity to capitalize on mitigating factors in the behavior of ligand-targeted carriers in order to optimize targeting