In “Missing the Forest for the Trees: Aduhelm, Accelerated Approvals & the Agency,” Dr. Matthew Herder argues that agency capture and politicized discretion drive delays in confirmatory trials of accelerated approval drugs amongst other concerns at US Food and Drug Administration (FDA). In highlighting this important problem and offering nuanced insight into agency workings based in part on interviews with twenty-three unnamed FDA officials and a three-drug case study, Dr. Herder suggests two innovative solutions. However, amidst broader debates balancing agency (...) expertise, data, and delegation, these proposed policy solutions would benefit from more corroborative evidence and consideration of institutional advantages within constitutional limits. (shrink)

Description: Jain Philosophy : Historical Outline interprets the fundamentals of Jain philosophy from the viewpoint of their historical genesis and development and shows that the incipient stage of the Jain thought-complex agreed totally with the pythagorean approach to philosophy which was based on observed realities and was quite in harmony with the existing socio-political conditions of the time of Lord Mahavira while the sophisticated stage marked by the a priori doctrines and dogmas it had generated in course of its development (...) and by the traditionally floating ideas in regard to the belief in a eternal moral order in the universe, the law of karma, ignorance as the cause of bondage and knowledge as that of liberation, the efficacy of meditation, and so forth, was a persistent juxtaposition in the evolutionary stages of the former. Since no system of Indian philosophy allows a purely isolated treatment, a comparative study of all the philosophical systems has been made here to determine the real nature of the Jain standpoint with more emphasis on the original dynamism of Jainism which had contributed to the growth of various natural sciences, including those of biology and astronomy, on the total rejection of the concept of a supernatural agent in the form of God, on the theories of valid knowledge and on the unique logical system based on the principles of relativity. Contents Preface of the Second Edition Preface of the First Edition Chap. I : INTRODUCTION : 1. The Jains as they are 2. Researches on Jainism 3. Literary Sources 4. Archaeological Sources : Architecture and Sculpture 5. Archaeological Sources : The Epigraphs 6. Parsva and Mahavira 7. Ecclesiastical History Chap. II : THE INCIPIENT STAGE : 1. The Prehistory of Jainism 2. The Historical Background 3. Material Basis of the Great Intellectual Movement 4. The Conflicts in the History of Indian thought 5. Contemporary Philosophical Schools 6. Purana Kassapa 7. Pakudha Kaccayana 8. Makkhali Gosala 9. Sanjaya Belatthiputta 10. Ajita Kesakambalin 11. Social Experiences of Mahavira 12. The Social Basis of Jain Ethics Chap. III : THE SOPHISTICATED STAGE : 1. Jainism and Indian Philosophical Tradition 2. Jain Atheism 3. Jain Logic 4. Scientific Enquiries : Cosmology 5. Scientific Enquiries : Classification of Jiva 6. Scientific Enquiries : Biology, Physiology, Etc 7. Scientific Enquiries : Diseases and Medicines 8. Scientific Enquiries : Astronomy 9. Scientific Enquiries : Atomism 10. Jain Cosmography 11. The Unfounded Speculations and their Ethical Considerations 12. The Nine Fundamentals and the Doctrine of Karma 13. Classification of Karma and the Gunasthanas 14. A Review of the Jain Metaphysics 15. Theory of Knowledge 16. Psychological Ingredients 17. The Non-Absolutist Standpoint Chap. IV : A COMPARATIVE STUDY : 1. Jainism and Vedic Tradition 2. Jainism and Buddhism 3. Jainism and Ajivikism 4. Jainism and Materialism 5. Jainism and Samkhya 6. Jainism and Yoga 7. Jainism and Mimamsa 8. Jainism and Nyaya-Vaisesika 9. Jainism and Vedanta 10. A Subjectwise Comparative Study of the Systems. (shrink)

The presence of vegetation on railway tracks threatens track safety and longevity. However, vegetation inspections in Sweden are currently being carried out manually. Manually inspecting vegetation is very slow and time consuming. Maintaining an even quality standard is also very difficult. A machine vision-based approach is therefore proposed to emulate the visual abilities of the human inspector. Work aimed at detecting vegetation on railway tracks has been split into two main phases. The first phase is aimed at detecting vegetation on (...) the tracks using appropriate image analysis techniques. The second phase is aimed at detecting the rails in the image to determine the cover of vegetation that is present between the rails as opposed to vegetation present outside the rails. Results achieved in the current work indicate that the machine vision approach has performed reasonably well in detecting the presence/absence of vegetation on railway tracks when compared with a human operator. (shrink)

Study of four works of Sri Krishna Prem, 1898-1965, a Vaishnavite teacher; includes a bibliographical sketch.

The Book Studies The Different Aspects Of Tantrism, Its Vastness And Intricacies, Its Heterogeneous And Contradictory Elements And Gives A Historical Perspective To The Conglomeration Of Ideas And Practices Through Space And Time. It Also Incorporates A Review Of Tantric Art And A Glossary Of Technical Terms.

Spatially and temporally restricted expression of Hox genes requires multiple mechanisms at both the transcriptional and the post-transcriptional levels. New insight into this precise expression mechanism comes from recent findings of a novel sense–antisense miRNA combination from the bithorax complex of Drosophila melanogaster.1-4 These two miRNAs encoded from the same locus target 3′ untranslated regions of anterior hox genes, Antp, Ubx and abd-A to establish the dominance of posterior hox gene Abd-B in its expression domain. Such double-edge tools, sense–antisense miRNA (...) combinations, also operate at multiple loci in the genome implicating their wider impact on the post-transcriptional gene regulation in eukaryotes. BioEssays 30:1058–1061, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Es ist in der Literatur weithin bekannt, dass im Gesundheitswesen auf unterschiedlichen Ebenen Allokationsentscheidungen getroffen werden. Während es auf der Makroebene um gesellschaftlich-politische Strukturfragen geht, stehen die Akteure der Mikroebene vor der Aufgabe, begrenzte Ressourcen in einer Organisation sinnvoll einzusetzen. In den ethischen Analysen der Mikro-Allokationsebene werden zumeist Entscheidungen der Healthcare Professionals thematisiert, weil sie eine unmittelbare Auswirkung auf die konkreten Patienten haben. Weniger in den Blick geraten Allokationen des Managements, welche die Rahmenbedingungen für Ressourcenzuteilungen beim Patienten betreffen. Hierbei geht (...) es nicht bloß um den Einsatz von Sachmitteln (z. B. Medikamenten- oder Gerätebudgets), sondern auch um den Personaleinsatz. Das Personalmanagement ist damit in wichtige Allokationsentscheidungen eingebunden und trägt eine dreifache Verantwortung: für die Gesundheit der Patienten, der Mitarbeiter und der Organisation. Der vorliegende Beitrag geht der Frage nach, welche Aspekte der Allokationsethik aus der Sicht des Personalmanagements in einem Krankenhaus zu bedenken sind, um der dreifachen Verantwortung gerecht zu werden. Dadurch zeigt sich, dass Allokationsethik in einem Krankenhaus nicht adäquat erfasst werden kann, ohne sich mit dem Personalmanagement zu beschäftigen, da das Personal die wertvollste Ressource ist, die es in einem Krankenhaus zu allozieren gilt. (shrink)

. Speaker recognition has been an active research area for many years. Methods to represent and quantify information embedded in speech signal are termed as features of the signal. The features are obtained, modeled and stored for further reference when the system is to be tested. Decision whether to accept or reject speakers are taken based on parameters of the data modeling techniques. Real world offers various degradations to the signal that hamper the signal quality. The degradations may be due (...) to ambient background noise, reverberation or multispeaker scenario. This paper presents a survey of various feature extraction, data modeling methods, metrics that are used to take the decisions and methods that can be used to preprocess the degraded data that have been used to perform the task of speaker recognition. (shrink)

Recording and manipulating neuronal ensemble activity is a key requirement in advanced neuromodulatory and behavior studies. Devices capable of both recording and manipulating neuronal activity brain-computer interfaces should ideally operate un-tethered and allow chronic longitudinal manipulations in the freely moving animal. In this study, we designed a new intracortical BCI feasible of telemetric recording and stimulating local gray and white matter of visual neural circuit after irradiation exposure. To increase the translational reliance, we put forward a Göttingen minipig model. The (...) animal was stereotactically irradiated at the level of the visual cortex upon defining the target by a fused cerebral MRI and CT scan. A fully implantable neural telemetry system consisting of a 64 channel intracortical multielectrode array, a telemetry capsule, and an inductive rechargeable battery was then implanted into the visual cortex to record and manipulate local field potentials, and multi-unit activity. We achieved a 3-month stability of the functionality of the un-tethered BCI in terms of telemetric radio-communication, inductive battery charging, and device biocompatibility for 3 months. Finally, we could reliably record the local signature of sub- and suprathreshold neuronal activity in the visual cortex with high bandwidth without complications. The ability to wireless induction charging combined with the entirely implantable design, the rather high recording bandwidth, and the ability to record and stimulate simultaneously put forward a wireless BCI capable of long-term un-tethered real-time communication for causal preclinical circuit-based closed-loop interventions. (shrink)

The COVID-19 pandemic has resulted in more than 524 million cases and 6 million deaths worldwide. Various drug interventions targeting multiple stages of COVID-19 pathogenesis can significantly reduce infection-related mortality. The current within-host mathematical modeling study addresses the optimal drug regimen and efficacy of combination therapies in the treatment of COVID-19. The drugs/interventions considered include Arbidol, Remdesivir, Interferon and Lopinavir/ritonavir. It is concluded that these drugs, when administered singly or in combination, reduce the number of infected cells and viral load. (...) Four scenarios dealing with the administration of a single drug, two drugs, three drugs and all four are discussed. In all these scenarios, the optimal drug regimen is proposed based on two methods. In the first method, these medical interventions are modeled as control interventions and a corresponding objective function and optimal control problem are formulated. In this framework, the optimal drug regimen is derived. Later, using the comparative effectiveness method, the optimal drug regimen is derived based on the basic reproduction number and viral load. The average number of infected cells and viral load decreased the most when all four drugs were used together. On the other hand, the average number of susceptible cells decreased the most when Arbidol was administered alone. The basic reproduction number and viral load decreased the most when all four interventions were used together, confirming the previously obtained finding of the optimal control problem. The results of this study can help physicians make decisions about the treatment of the life-threatening COVID-19 infection. (shrink)

Serial analysis of gene expression (SAGE) is a powerful technique that can be used for global analysis of gene expression. Its chief advantage over other methods is that it does not require prior knowledge of the genes of interest and provides qualitative and quantitative data of potentially every transcribed sequence in a particular cell or tissue type. This is a technique of expression profiling, which permits simultaneous, comparative and quantitative analysis of gene‐specific, 9‐ to 13‐basepair sequences. These short sequences, called (...) SAGE tags, are linked together for efficient sequencing. The sequencing data are then analyzed to identify each gene expressed in the cell and the levels at which each gene is expressed. The main benefit of SAGE includes the digital output and the identification of novel genes. In this review, we present an outline of the method, various bioinformatics methods for data analysis and general applications of this important technology. BioEssays 26:916–922, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Phosphatidylinositol 4,5‐bisphosphate (PI4,5P2) is a key lipid signaling molecule that regulates a vast array of biological activities. PI4,5P2 can act directly as a messenger or can be utilized as a precursor to generate other messengers: inositol trisphosphate, diacylglycerol, or phosphatidylinositol 3,4,5‐trisphosphate. PI4,5P2 interacts with hundreds of different effector proteins. The enormous diversity of PI4,5P2 effector proteins and the spatio‐temporal control of PI4,5P2 generation allow PI4,5P2 signaling to control a broad spectrum of cellular functions. PI4,5P2 is synthesized by phosphatidylinositol phosphate kinases (...) (PIPKs). The array of PIPKs in cells enables their targeting to specific subcellular compartments through interactions with targeting factors that are often PI4,5P2 effectors. These interactions are a mechanism to define spatial and temporal PI4,5P2 synthesis and the specificity of PI4,5P2 signaling. In turn, the regulation of PI4,5P2 effectors at specific cellular compartments has implications for understanding how PI4,5P2 controls cellular processes and its role in diseases. (shrink)

Based on the Guest 1997 organizational outcome model, this explanatory study examined the effects of five dimensions of practices of HR. i.e. performance evaluation, recruitment & selection, compensation & reward, career opportunities within organization and training & development on proximal business outcomes. The study validates components of GUEST model by integrating between HRM dimensions and banking operations, thus strengthens the existing theoretical model of GUEST by improving the comprehensiveness as it provides analytical framework for studying HR. Exploratory factor analysis and (...) confirmatory factor analysis was utilized in the current study, and tested the study hypotheses by SEM to analyze the proposed conceptual model. It was found that all five chosen HR practices had significant influence on the quality of operations however for flexibility of operations, performance appraisals and career within organization have shown significant role for banking industry of the country, Pakistan. The study contributed to the construction and validation of structural. path and measurement models of SHRM practices and two selected operational competitive outcomes based on theoretical and empirical foundations, which will help progress the human resource management future researches and important implications for HR mangers, as very little work has been done on interdisciplinary framework of HR and OM specifically within context of South Asian banking Industry. (shrink)

Der Selbstbestimmungdes Patienten kommt in der modernen Debatte über das Gesundheitswesen eine zentrale Bedeutung zu. Selbstbestimmung ist aber ein voraussetzungsvoller Begriff, der für Patientengruppen wie Demenzbetroffene, deren Entscheidungs- und Einwilligungsfähigkeit nachlässt oder nicht mehr gegeben ist, eine Reihe von Fragen aufwirft. Auf der Grundlage der jeweiligen Symptomentwicklung der Demenzerkrankung und eigener Erfahrungen im Umgang mit Demenzbetroffenen wirdde rEntwicklungdes Willens in den verschiedenen Stadien der Demenz nachgegangen. Dabei wird den Dimensionen der Differenziertheit der Denkinhalte, der Beurteilungsbasis und der Entscheidungskonstanz eine besondere (...) Bedeutung zugemessen und für eine Graduierung der Selbstbestimmungsmöglichkeiten im Umgang mit Demenzbetroffenen plädiert. Wegen der Schwererkennbarkeit der oft verschlüsselten Willensbekundungen Demenzbetroffener wird der Willenswahrnehmung und dem Training der genauen Beobachtung, Einfühlung und Sensibilität im Umgang mit den Betroffenen großes Gewicht beigemessen. Als Ziel wird die jeweils weitestgehende Selbstbestimmung, im Verlaufe der Erkrankung auch Teilselbstbestimmung und schließlich Mitwirkung bei der individuellen Wohlbestimmung im Sinne eines Grundrechtsschutzes vertreten. (shrink)