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Tivantinib (ARQ 197), a selective oral inhibitor of MET, has shown promising antitumour activity in hepatocellular carcinoma as monotherapy and in combination with sorafenib. We aimed to assess efficacy and safety of tivantinib for second-line treatment of advanced hepatocellular carcinoma. In this completed, multicentre, randomised, placebo-controlled, double-blind, phase 2 study, we enrolled patients with advanced hepatocellular carcinoma and Child-Pugh A cirrhosis who had progressed on or were unable to tolerate first-line systemic therapy. We randomly allocated patients 2:1 to receive tivantinib (360 mg twice-daily) or placebo until disease progression. The tivantinib dose was amended to 240 mg twice-daily because of high incidence of treatment-emergent grade 3 or worse neutropenia. Randomisation was done centrally by an interactive voice-response system, stratified by Eastern Cooperative Oncology Group performance status and vascular invasion. The primary endpoint was time to progression, according to independent radiological review in the intention-to-treat population. We assessed tumour samples for MET expression with immunohistochemistry (high expression was regarded as ≥2+ in ≥50% of tumour cells). This study is registered with ClinicalTrials.gov, number NCT00988741. 71 patients were randomly assigned to receive tivantinib (38 at 360 mg twice-daily and 33 at 240 mg twice-daily); 36 patients were randomly assigned to receive placebo. At the time of analysis, 46 (65%) patients in the tivantinib group and 26 (72%) of those in the placebo group had progressive disease. Time to progression was longer for patients treated with tivantinib (1·6 months [95% CI 1·4–2·8]) than placebo (1·4 months [1·4–1·5]; hazard ratio [HR] 0·64, 90% CI 0·43–0·94; p=0·04). For patients with MET-high tumours, median time to progression was longer with tivantinib than for those on placebo (2·7 months [95% CI 1·4–8·5] for 22 MET-high patients on tivantinib vs 1·4 months [1·4–1·6] for 15 MET-high patients on placebo; HR 0·43, 95% CI 0·19–0·97; p=0·03). The most common grade 3 or worse adverse events in the tivantinib group were neutropenia (ten patients [14%] vs none in the placebo group) and anaemia (eight [11%] vs none in the placebo group). Eight patients (21%) in the tivantinib 360 mg group had grade 3 or worse neutropenia compared with two (6%) patients in the 240 mg group. Four deaths related to tivantinib occurred from severe neutropenia. 24 (34%) patients in the tivantinib group and 14 (39%) patients in the placebo group had serious adverse events. Tivantinib could provide an option for second-line treatment of patients with advanced hepatocellular carcinoma and well-compensated liver cirrhosis, particularly for patients with MET-high tumours. Confirmation in a phase 3 trial is needed, with a starting dose of tivantinib 240 mg twice-daily. ArQule, Daiichi Sankyo (Daiichi Sankyo Group).

\"Drawing on over thirty years of experience as a consultant, speaker, and global expert, Weiss shares his story and 'million dollar tips' to help entrepreneurs gain influence, build confidence, and develop the critical thinking skills they need to discover the inside track to rapid success\"-- Provided by publisher.

Electroconvulsive Therapy (ECT) remains one of the most effective forms of neurostimulation for severe mental illness. Sound scientific research underpins contemporary practice challenging the complex history and stigma that surround this treatment. The Electroconvulsive Therapy Workbook integrates the history of ECT with major advances in practice, including ultrabrief ECT, in a hands-on workbook format. Novel forms of neurostimulation are reviewed, highlighting the future directions of practice in this exciting area. The book is also richly illustrated with historical and technical images and includes 'clinical wisdom' sections that provide the reader with clinical insights into ECT practice. Online eResources are also available, featuring a wide range of questions and answers related to each chapter to help test and consolidate readers' understanding of ECT, as well as regionally specific legislation governing ECT practice in Australia and New Zealand. This comprehensive introduction to ECT is a must-read for doctors in training, psychiatrists who require credentialing in this procedure, anaesthetists, nursing staff who work in ECT and other professionals who have an interest in ECT as well as consumer and carer networks.

\"Revamp your life to grow, evolve, and become who you want to be Lifestorming is the indispensably practical handbook for becoming the person you want to be. Redesign your life, friends, behaviors, and beliefs to move closer to your goals every single day, guided by expert insight and deep introspection. Written by a veteran author team behind almost 100 books on human behavior, this guide helps you learn why you do things the way you do them, and how to do them better. The Lifestorming Test allows you to assess your current state in concrete terms, and assess your ability to change and adapt -- from there, it's about identifying people, actions, habits, and beliefs that either support your personal and professional growth or hold you back. You'll learn the six building blocks of character, challenge your belief system, develop a leadership mindset, and overcome the fear and guilt of success. You'll map out an action plan, and learn how to continually move forward at work, at home, and in everyday life. We often don't realize how much of our natural default is established by others. Whose goals are you working toward? Are you measuring your progress with the correct yardstick? This book shows you how to take a step back and compare your life today with the future you want -- and build a plan for changing track toward constant evolution and growth. Assess your current state and your capacity for change Develop the right goals and the right metrics to create the future you want Learn how character evolves, and why it's essential to growth Change your habits and behaviors to consistently grow and evolve We all carry around old baggage, obsolete "friendships", and counterproductive beliefs -- and every day, they pull us a little further away from what we really want. Lifestorming is your real-world guide to shedding the stagnation, and allowing yourself to grow into the person you want to become\"-- Provided by publisher.

Bestselling author of Million Dollar Consulting shares the secrets of writing winning proposals Intended for consultants, speakers, and other professional services providers, Million Dollar Consulting® Proposals ends forever the time-consuming and often frustrating process of writing a consulting proposal. It begins with the basics—defining these proposals and why they are necessary—and coaches you through the entire proposal process. In this book, you'll learn how to establish outcome-based business objectives and maximize your success and commensurate fees. From bestselling author Alan Weiss, Million Dollar Consulting Proposals delivers step-by-step guidance on the essential element in creating a million dollar consultancy. Outlines the nine key components to a Million Dollar Consulting proposal structure Presents a dozen Golden Rules for presenting proposals Offers online samples, forms, and templates to maximize the effectiveness of these tools The New York Post calls bestselling author Alan Weiss \"one of the most highly regarded independent consultants in America.\" Alan Weiss's expert guidance can lead your consulting business to unprecedented success, and it all starts with a million dollar proposal.

لا يشعر الجميع بالرضا عن العمل من الساعة التاسعة إلى الخامسة في عالم الشركات، ويختار العديد من الأشخاص نقل معارفهم ومهاراتهم وخبراتهم معهم إلى صناعة أخرى أكثر ربحا وهي الاستشارات. ولكن كما يعلم أي مستشار ناجح، فإن الاستشارات الفردية لا تتعلق فقط بتكديس ثروة كبيرة.. في الواقع، يتضمن النجاح في الاستشارات التغلب على منحنى تعليمي دراماتيكي وجمع خبرات ومهارات واسعة ومتنوعة.. إنه يوفر إمكانية إجراء تغييرات يمكن أن تؤثر على حياة عشرات الآلاف من الأشخاص. سيعلمك هذا الملخص كيفية إنشاء شركتك الخاصة واكتساب أنواع العملاء التي ستجعل عملك بملايين الدولارات، سيقدمون لك أيضا نصائح، بعضها مخالف تماما للبديهة، للنجاح في هذه الصناعة. ستكتشف في هذا الملخص أيضا : لماذا يقوم المستشارون الناجحون بطرد عملائهم بالفعل !-لماذا يؤدي تفضيل العلاقات قبل المال إلى جعلك أكثر ثراء !-كيف تطلب 50000 دولارا.

For 70 years, psychologists, wellness experts, and physicians have been teaching people that they can manage the stress in their lives. They have been wrong. Over the past 15 years, there has been a revolution in how business, communities, and governments around the globe address challenge and adversity. Their goal has shifted from trying to manage these events to instead recognizing that we have to build resilient systems that help us prepare for them, navigate through them in real time, and bounce back-- or better still, bounce forward. The resilience movement admits the fact that we can't always keep bad things from happening and that we must develop strategies that help us learn from the challenges, not be victimized by them. The Resilience Advantage takes these ideas and those from neuropsychology, education, the arts, sports, and positive psychology and puts them into practical and effective strategies for individuals and organizations who struggle with the day-to-day stresses of today's complex and challenging workplace. Despite our efforts to help people manage their stress, this model is fatally flawed. To work towards resilience, however, with its understanding and acceptance that challenges are inherent and perhaps should be even welcomed, relieves us of the pressures associated with trying to man- age our stress. The Resilience Advantage will transform how you think about stress and help you to move from being a stress victim to being a stress victor.

\"Bestselling author of Million Dollar Consulting shares the secrets of writing winning proposalsIntended for consultants, speakers, and other professional services providers, Million Dollar Consulting Proposals ends forever the time-consuming and often frustrating process of writing a consulting proposal. It begins with the basics--defining these proposals and why they are necessary--and coaches you through the entire proposal process. In this book, you'll learn how to establish outcome-based business objectives and maximize your success and commensurate fees.From bestselling author Alan Weiss, Million Dollar Consulting Proposals delivers step-by-step guidance on the essential element in creating a million dollar consultancy. Outlines the nine key components to a Million Dollar Consulting proposal structure Presents a dozen Golden Rules for presenting proposals Offers online samples, forms, and templates to maximize the effectiveness of these tools The New York Post calls bestselling author Alan Weiss \"one of the most highly regarded independent consultants in America.\" Alan Weiss's expert guidance can lead your consulting business to unprecedented success, and it all starts with a million dollar proposal\"--