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High quality leads provide the foundation for the discovery of successful clinical development candidates, and therefore the identi?cation of leads is an essential part of drug discovery. The process for the identi?cation of leads generally starts with the screening of a compound collection, either an HTS of a relatively large compound collection (hundreds of thousands to one million plus compounds) or a more focused screen of a smaller set of compounds that have been preselected for the target of interest. Virtual screening methods such as structure-based or pharmacophore-based searches can complement or replace one of the above approaches. Once hits are identi?ed from one or more of these screening methods, they need to be thoroughly characterized in order to con?rm activity and identify areas in need of optimization. Finally, once fully characterized hits are identi?ed, preliminary optimization through synthetic modi?cation is carried out to generate leads. Parallel optimization of all properties, including biological, physicochemical, and ADME is the most ef?cient approach to the identi?cation of leads. Hit characterization is described in the previous chapter. The focus of this chapter is on hit optimization and the identi?- tion of leads. After a general overview of these processes, examples taken from the literature since 2001 will be used to illustrate speci?c points. There are also a number of excellent reviews covering the lead identi?cation process [1–6].
Estimates indicate that as many as 1 in 4 Americans will experience a mental health problem or will misuse alcohol or drugs in their lifetimes. These disorders are among the most highly stigmatized health conditions in the United States, and they remain barriers to full participation in society in areas as basic as education, housing, and employment. Improving the lives of people with mental health and substance abuse disorders has been a priority in the United States for more than 50 years. The Community Mental Health Act of 1963 is considered a major turning point in America's efforts to improve behavioral healthcare. It ushered in an era of optimism and hope and laid the groundwork for the consumer movement and new models of recovery. The consumer movement gave voice to people with mental and substance use disorders and brought their perspectives and experience into national discussions about mental health. However over the same 50-year period, positive change in American public attitudes and beliefs about mental and substance use disorders has lagged behind these advances. Stigma is a complex social phenomenon based on a relationship between an attribute and a stereotype that assigns undesirable labels, qualities, and behaviors to a person with that attribute. Labeled individuals are then socially devalued, which leads to inequality and discrimination. This report contributes to national efforts to understand and change attitudes, beliefs and behaviors that can lead to stigma and discrimination. Changing stigma in a lasting way will require coordinated efforts, which are based on the best possible evidence, supported at the national level with multiyear funding, and planned and implemented by an effective coalition of representative stakeholders. Ending Discrimination Against People with Mental and Substance Use Disorders: The Evidence for Stigma Change explores stigma and discrimination faced by individuals with mental or substance use disorders and recommends effective strategies for reducing stigma and encouraging people to seek treatment and other supportive services. It offers a set of conclusions and recommendations about successful stigma change strategies and the research needed to inform and evaluate these efforts in the United States.
***A WALL STREET JOURNAL BESTSELLER*** From the organizational experts at FranklinCovey, an essential guide to becoming the great manager every team deserves. A practical must-read, FranklinCovey’s Everyone Deserves a Great Manager is the essential guide for the millions of people all over the world making the challenging and rewarding leap to manager. Based on nearly a decade of research on what makes managers successful—and includes new ways of thinking, tips and techniques—this volume has been field-tested with hundreds of thousands of managers all over the world. Organized under four main roles every manager is expected to fill, Everyone Deserves a Great Manager focuses on how to lead yourself, people, teams, and change. Readers can start anywhere and go everywhere with this guide—depending on their current problem or time constraint. They can pick up a helpful tip in ten minutes or glean an entire skillset with deeper reading. The goal is for the busy manager to know what to do and how to do it without interrupting their regular workflow. Each role highlights the current, authentic problems managers face and briefly explores the limiting mindsets or common mistakes that led to those problems. With skill-based chapters that cover managerial skills like one-on-ones, giving feedback, delegating, hiring, building team culture, and leading remote teams, the book also includes more than thirty unique tools, such as a prep worksheets and a list of behavioral questions for your next interview. An approachable, engaging style using real-world stories, Everyone Deserves a Great Manager provides the blueprint for becoming the great manager every team deserves.
All across the United States, individuals, families, communities, and health care systems are struggling to cope with substance use, misuse, and substance use disorders. Substance misuse and substance use disorders have devastating effects, disrupt the future plans of too many young people, and all too often, end lives prematurely and tragically. Substance misuse is a major public health challenge and a priority for our nation to address. The effects of substance use are cumulative and costly for our society, placing burdens on workplaces, the health care system, families, states, and communities. The Report discusses opportunities to bring substance use disorder treatment and mainstream health care systems into alignment so that they can address a person's overall health, rather than a substance misuse or a physical health condition alone or in isolation. It also provides suggestions and recommendations for action that everyone-individuals, families, community leaders, law enforcement, health care professionals, policymakers, and researchers-can take to prevent substance misuse and reduce its consequences.
The bestseller that pioneered the comparison of qualitative, quantitative, and mixed methods research design continues in its Fourth Edition to help students and researchers prepare their plan or proposal for a scholarly journal article, dissertation or thesis.
Drug overdose, driven largely by overdose related to the use of opioids, is now the leading cause of unintentional injury death in the United States. The ongoing opioid crisis lies at the intersection of two public health challenges: reducing the burden of suffering from pain and containing the rising toll of the harms that can arise from the use of opioid medications. Chronic pain and opioid use disorder both represent complex human conditions affecting millions of Americans and causing untold disability and loss of function. In the context of the growing opioid problem, the U.S. Food and Drug Administration (FDA) launched an Opioids Action Plan in early 2016. As part of this plan, the FDA asked the National Academies of Sciences, Engineering, and Medicine to convene a committee to update the state of the science on pain research, care, and education and to identify actions the FDA and others can take to respond to the opioid epidemic, with a particular focus on informing FDA's development of a formal method for incorporating individual and societal considerations into its risk-benefit framework for opioid approval and monitoring.
Motivation is key to substance use behavior change. Counselors can support clients' movement toward positive changes in their substance use by identifying and enhancing motivation that already exists. Motivational approaches are based on the principles of person-centered counseling. Counselors' use of empathy, not authority and power, is key to enhancing clients' motivation to change. Clients are experts in their own recovery from SUDs. Counselors should engage them in collaborative partnerships. Ambivalence about change is normal. Resistance to change is an expression of ambivalence about change, not a client trait or characteristic. Confrontational approaches increase client resistance and discord in the counseling relationship. Motivational approaches explore ambivalence in a nonjudgmental and compassionate way.
This book presents the historical, theoretical and empirical foundations of educational practices involving dialogue and argumentation.