This week I thought it might be interesting to take a look at some things we should never tolerate if we are going to live the best lives we can.
If we are affected by some or all of these things we must accept that it is our personal responsibility to take the necessary steps to correct them as soon as possible.
Hi it's Dave and greetings from Ilfracombe, N Devon.
I hope that you are creating a great life for yourself and enjoying the journey.
Be courageous and be bold – when you look back over your life you will regret things you did not do more than the ones that you did.
Don't do anything that your Mum would not be proud about.
Yesterday (Thursday) I decided that I wanted to try a little bit of vlogging and thought that if it worked I would make it a regular feature for the blog. Overall I am reasonably happy with the result and I feel that the more experienced I get with this method of presentation I will get better at it.
I hope that you are having a ball creating a great life for yourself.
Personal development is increasing in popularity, particularly in the busy world of today and it covers everything from career improvement to weight loss and confidence to public speaking.
The tools and methodology that are brought into play to achieve the desired personal development outcome can vary from high priced seminars to moderately priced books.
1) Knowing how you got here.
One of the best starting points with personal development is the discovery of how and what got you to where you are right now. If your desired area of personal development relates to weight loss then look at what factors within your life contributed to the weight problem. Write down everything you can think of that contributed to the problem and then investigate what you can do to modify each factor in a way that will help you to reach the desired result.
It is vital that you put a specific outcome into place. This knowing what you want to achieve is vital step before you can then identify the way to make it happen. You will need to ask yourself exactly what it is that you want to achieve and the more refined and clear your goal the more chance you will have of successfully attaining it.
If you were going to drive to an unfamiliar place then the obvious thing would be to work out how you get there and plan the route. The same goes with reaching your goal, when you have decided on the goal then create a plan (route) that shows all the steps you will take to reach your goal. You should use the details you uncovered when identifying the cause of the problem, expanding them to include as much detail as possible about how you can achieve your personal goal.
When you have identified your goal and have created the route to getting there, the next step is to focus your attention on that goal and commit to the plan you have put together. You will need to block out a certain amount of time each day to work on your plan and do not allow life's daily routines and tasks to distract you from what you need to do. Become accustomed to working on your plan each day and it will quickly become a habit and subsequently easier, over time, to maintain.
You will benefit greatly if you look for, and take inspiration from other people that have overcome the same personal development challenge as you are working on.
There could be books, seminars, courses or even a person from your local community who would be happy to give you advice and / or act as a mentor if they have whatever you are working towards.
Personal development is about you identifying areas within your life that you want to change for the better and then developing and maintaining an attitude of continued self improvement.
Whatever area of your life you mean to improve by continually following the steps I have indicated above and by committing to the plan I believe that you can achieve your goals and whilst doing so, build your confidence to create and achieve other personal development goals easier and more quickly each time.
Greetings from Ilfracombe and welcome to Under Blue Skies. I am very excited with how everything is progressing. I find that sharing these pages with everyone goes a long way towards helping me to keep writing them.
And it's not just adults. When we moved to North Carolina about ten years ago, we were thrilled to be moving to a city with a great school system. We found a diverse neighbourhood, filled with families. Everything felt good, felt right.
Whatever happened to a world in which kids get muddy, get dirty, get messy, and heavens, get bored? Do we have to love our children so much that we over schedule them, making them stressed and busy — just like us?
For some of us, the "privileged" ones, the lines between work and home have become blurred. We are on our devices. All The Time.


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Her father owned a pharmacy while her mother was a stay-at-home mum. Joyce was the eldest of three children. One of her passions, as well as being on The Power Hour was quilting, a talent, and pleasure inherited from her mother. The tragedy of her family came when one of her younger brothers died unexpectedly. Undoubtedly, her father's involvement in the medical community influenced her career decisions.
As a young woman, Joyce was determined to make some mark in the world. The tenacity we grew to love brought her all the way to the University of Kansas. Her passion for helping those who could not always help themselves was embedded in her makeup. She graduated with a Bachelor of Science in nursing, leading to a full range of nursing duties in the private sector.
Her expertise and willingness to serve landed her in the Air Force, where she attained the rank of captain. Joyce became a flight nurse aboard C-130 missions in support of Operation Desert Storm. The kinship she felt with those in uniform is a precious part of her legacy. The experimentation she endured, and witnessed, changed Joyce forever. 'A champion of the forgotten men and women of the Desert Storm era,' may be the badge of honour she cherished the most.
Before she brought the plight of the Iraq War era soldier to the masses, Joyce became a whistle-blower, involved in exposing nursing malpractice issues. Until her health would no longer permit, she was an expert witness for both plaintiff and defence medical cases. Her courage, and determination to stand for the truth, made Joyce the target of harsh scrutiny, and vilification by those willing to value reputation above the lives of helpless infants. She also presented at the National Institutes of Health, and many legal conferences, including the American Trial Lawyers Association.
Her expertise and critical voice lead her to the radio and well over 1500 radio guest appearances. From 1996-1999 with her husband Dave von Kleist, she traveled the country as an advocate for the American Gulf War Veterans Association, with crucial information for veterans throughout the nation. In the Spring of 2000, The Power Hour Radio Show joined the GCN network. With her exuberant husband by her side, Joyce laid the path for the modern independent media movement. The Power Hour became synonymous with blowing the lid off our less than honest 'reality.' With the tenacity of a bulldog, a unique wit, and a distinctive midwestern charm Joyce endeared herself to a massive audience. The advent and success of the truth media can be traced directly to The Power Hour and the nation of People who called it home. Her pursuit of natural treatments for her cancer diagnosis will long be admired and used in coming generations.
It was by pure luck that I first heard the voice of Joyce Riley, who would set me on course to transform my life, and I believe, to save my life, thanks to an interview I heard in December 2005. While I helped a friend to find information about a food supplement called Serrapeptase, I found a clip, from The Power Hour, in which Joyce interviewed Robert Redfern, the author of a book with a title so long that I only remembered about half of it at the time. Thankfully, the discussion was much more memorable, as was the content of the book. It was more than enough to grab my attention and convince me that I wanted to learn more and that Serrapeptase could be a safe alternative to the prescribed anti-inflammatory painkillers I had taken for years, with little and reducing benefit.
On January 3, 2006, my friend returned with a copy of Robert's book, and a bottle of Serrapeptase, which was described in the book as, 'the second gift from silkworms.' It was on that day that My Serrapeptase Adventure started. Within days my health improved, within weeks my health was transformed, and my life was returned to my control.
Since my adventure began in January 2006, interest from around the world continued to grow. The first hint of worldwide media coverage came on February 22nd, 2006. When Robert Redfern of Naturally Healthy Publications, appeared on The Power Hour, he was taking his regular part in a phone-in. A caller rang in asking for information about natural health products, which would be useful for a child with Cerebral Palsy. It was still in its early stages, but Robert gave a brief outline of my story so far.
On April 11th, (2006) I had the pleasure of speaking with Joyce for the first time. She invited me to appear on the following days show.
My Serrapeptase Adventure charts the four life-changing years in which I learnt that many of the symptoms from which Serrapeptase has rescued me were, in fact, known, and even expected, side effects of the toxic cocktail of prescription medications, which I took before I knew about Serrapeptase.
When I first heard people describing my return to naturally sustained good health and then Serrapeptase itself, as a 'miracle,' I was concerned. At the time, in the summer of 2006, it was not at all certain to me that my improving health would be sustainable. I was thrilled that other people, including Joyce, were so confident, but it took me some time to begin to agree with them.
I am convinced that it is prescription medication, and the global systems designed to reinforce our dependence upon it, that should be called 'alternative medicine.' If good health is our natural, balanced state, then the goal of health-care should be to maintain that balance or to return us to it, as naturally as possible. This approach still allows for medical and surgical treatments, when they are necessary, but they should be considered useful alternatives, and not assumed to be the only acceptable options.
To be clear, I still have cerebral palsy. Serrapeptase has not removed or cured the condition, but it has improved my health to such an extent that I have returned to the cerebral palsy of my childhood. It was then, and is now, a daily challenge to be managed and overcome. Cerebral palsy is no longer the condition, dominating my life, which it had become. Most importantly, I remain free of the toxic cocktail of prescription medication, which I believe damaged my health and quality of life, far more than cerebral palsy ever has done, or is ever likely to do.
From its very earliest days, My Serrapeptase Adventure has been as much about the kindness and inspiration of people from around the world, as it has been about my continuing search for good health. Joyce was a constant source of information, encouragement, and inspiration, which gave me the information I needed, and the confidence to try Serrapeptase for the first time, long before my eyesight was good enough to read the information for myself.
It is for this reason that I am in no doubt that without The Power Hour, my life would have been very different, and I may not have survived at all. Regular readers and listeners to the show will often have heard me taking every opportunity I get to thank Joyce and the team for their continued support.
Joyce was happy to tell my story and to give me a chance to share it, as often as possible. However, she often downplayed her part in it. In November 2008, Joyce agreed to record her personal view of My Serrapeptase Adventure, and of her contribution to it. As always, she emphasised, which she took from me. In a rare moment, Joyce also described the personal gift she considered it was, to have the opportunity to speak to, learn from, and inspire people around the world.
It is my privilege to have known Joyce and to have been inspired, not only by her knowledge but also by her friendship. Joyce will be deeply missed. She is survived by an adoring body of listeners and advocates who have found the world a better place by having Joyce in it. Ever-private with so much personal information, it is proper now to note she has one brother and one son from an early marriage remaining.
The last word should be left to Joyce. It is my privilege to invite you to listen to her thoughts about my story, and the joy, and the challenge of The Power Hour — a radio show, with a worldwide audience, and a gentle touch of personal inspiration.
Never ever stand down if you know that something is going wrong. If you know there's an injustice, speak out, regardless, because you don't want to live the rest of your life knowing, 'I could have done more'.
Joyce Riley, 1948 – 2017
Thanks to The Power Hour, and the Genesis Communications Network, and Naturally Healthy Publications for additional information.
June 28, 2017 June 19, 2020 The Health-Care Survivor

redpajama_set_name: RedPajamaCommonCrawl


Mansour Mansour is a visionary entrepreneur with a passion for mobile wireless technology. The first entrepreneur selected by Endeavor Jordan, Mansour is the Founder and CEO of Javna Wireless Software Solutions, the leading Arab firm in software solutions and wireless applications, and the first company in the region to develop proprietary software for the mobile market. Launched in 2001, Javna has been jointly built around Mansour's steadfast belief in innovation and his ambition to develop a global company in his native country of Jordan. With an impressive list of partners – including major mobile operators in Jordan, Saudi Arabia, and the UAE – as well as exclusive regional agreements with both Al-Jazeera News and CNBC Arabia, Javna is well positioned to continue its regional leadership in the fast-growing mobile media space.
Dr. Amjad Aryan has a vision to make his company, Pharmacy 1, the CVS of the Middle East. In 2001, Dr. Amjad spotted the opportunity to modernize and standardize the Jordanian pharmaceutical industry, which was then characterized by poor quality of services, low levels of technology and inconsistent management. Eight years later, Pharmacy 1 is the number one retail pharmacy chain in the country, with 45 branches employing 350 people. Dr. Amjad has also begun to expand regionally, with pilot branches in neighboring Saudi Arabia, where the pharmaceutical market is valued at over US$1.5 billion. With ambitious expansion plans and the potential for revenues to increase exponentially, Dr. Amjad is on the right track to make Pharmacy 1 the leading pharmacy chain in the Middle East.
When Dr. Amin Amin realized that the biggest challenge in the Arab region is human capacity building, he decided to focus on bridging the missing link between education and employment. His company, ASK (Attitude, Skills and Knowledge) for Human Capacity Building, has elevated professional standards by providing innovative capacity building programs and consulting services with a special focus on education. With the support of a USAID-funded Education Reform Support Program (ERSP), the company is responsible for implementing the Jordan Schools Program (JSP) and operations are expanding throughout the MENA region.
Since founding Akhtaboot in 2007, Mohamad Haj Hasan and Yousef Shamoun have quickly made a splash in the online recruiting market. With a user-friendly interface, superior functionality and searching capability, and a charismatic brand, Aktaboot can now match its 14,000 unique daily visitors (job seekers) with over 500 registered employers – including international players such as Google, FedEx, and LG Electronics. As the Middle East works to create over 200 million jobs by 2020, Akhtaboot has both real potential for growth and an opportunity to have a significant impact on the region. The combination of surging internet penetration rates and high unemployment in the Middle East has yielded a promising environment for Akhtaboot to become the industry leader, linking internet-savvy youth to newly created jobs in Jordan, Saudi Arabia, Egypt, UAE, and beyond.
Nimble and savvy entrepreneur Omar Koudsi started the website, Jeeran, with a vision to make the web relevant to the Arab world by empowering people and giving them the tools to generate their own local content. Over the years Jeeran continued to evolve, and what started as a blogging service became one of the most established content portals in the region ‐ ranking among the top websites in the Arab world, generating over 25 million page views per month, and cultivating a community of more than 1.5 million members. Year 2010 marked the next phase in Jeeran's evolution through the launch of the Jeeran "Places", a new service that empowers Arab users to rate, review, discuss and discover places in their city. Jeeran Amman was launched first and other cities in the GCC followed. The new proposition showed a marked impact within a short period through a surge in traffic and community members, and adoption and engagement by those living in the cities.
Ramzi and Zafer are revolutionizing the way businesses in the MENA region talk to their customers. With their creative approach to social media advertising, these first movers are helping multinationals optimize their social network presence in the Middle East. Modern Media was founded when they started Jordan's first independent English-language radio broadcast Play 99.6 FM in 2004. In the last year their experience in brand promotion led to the development of a new business line called ―The Online Project (TOP), the only service in the region to offer comprehensive social media management in Arabic. Their combination of marketing strategy, process analysis, and content creation has improved their clients' advertising and marketing ROI dramatically. Ramzi and Zafer have developed a valuable product in a rapidly growing field and they could go from being national role models to a regional or global success story.
There are more than 344 million Arabic speakers worldwide, yet less than 1% of all online content is in Arabic. Cartoons and videos are dubbed with Arabic voices, and websites are roughly translated. In 2010, Firas, Mohammed and Wael along with other partners founded Kharabeesh to fill this gap. Think Arabia is a one-stop-shop for Arabic animated content and multimedia design. They offer a wide array of Arabic media products and services from animated cartoon shorts, to mobile phone applications, to branding and multimedia design services. Kharabeesh has the potential to become a leading developer of original and creative Arabic content and possibly the Cartoon Network of the Middle East.
Born into a family of pharmacists, the pharmaceutical industry was a natural choice for our entrepreneur Fadi Al- Atrash. After gaining eight years of experience working in multinational pharmaceutical companies, Fadi joined API in 2006 as the Deputy General Manager and gained a seat on the board in 2007. Since its launch, API has become a leading regional manufacturer of niche branded generics, including eye drops, ointments, nasal sprays and topical preparations. Fadi has been a driver in this leadership story. He added new product lines and export markets, introduced license manufacturing into company strategy, implemented HR and finance policies and procedures, and rebranded the business. API has tapped into Jordan's export market, which counts pharmaceuticals as its second largest contributor. Nearly 75% of API's 2010 revenues came from exports to 25 countries. As API expands and transitions from a family business into a corporate company with institutionalized policies, procedures, and operations, API could become a global story for Jordan and the region.
Recognizing the importance of providing the world's Arabic-speaking population with online medical information in their native language, Jalil has spent the past two years developing one of the largest and most interactive online medical health portals in Arabic. Altibbi's website provides users with easy and free access to information from health professionals in a convenient, user-friendly, confidential and timely manner. The site hosts an Arabic-English medical dictionary, a medical directory listing approved medical entities in the MENA region and abroad, a "symptom checker", hundreds of health-related videos and articles, and an innovative doctor-patient social networking platform that allows users to have their health questions answered online by approved doctors. Altibbi has a strong position to be the leading provider of healthcare information in the Arab world.
Fadi and Majdy were brought together by their shared passion for animation. Throughout their careers in the animation industry, the entrepreneurs noticed the dissatisfaction of TV channels, telecom companies, advertising agencies, and others with the standard of Arabic content and quality. This drove Fadi and Majdy to jointly establish Curl Stone in 2010. Curl Stone offers unique narrative-based animations that reflect Middle Eastern heritage through the development of positive role models who embody universally shared values. Curl Stone creates these characters and narratives as a product to be licensed to TV networks, telecom companies, web portals, and other media channels. The studio is aiming to become a regional player through a Middle Eastern cultural focus in some of their projects while simultaneously establishing an international body of work.
Launched in 2010, Jamalon's dual-language ecommerce platform provides unparalleled access to a comprehensive catalogue of books in English and Arabic. Since its inception, Jamalon has grown to include over nine million titles, developed metadata for 150,000 Arabic books, and expanded regionally to reach customers in eight MENA countries.


Survival: the state or fact of continuing to live or exist in spite of difficult circumstances. I'm sure that definition describes each and everyone of us at some point and time in our lives and I would say most likely more than a hand full of times. How did you do it?
We've learned the art of survival as we've grown with life. But even as a child we had the instinct to know what to do in situations to make it. Each of us has our own built-in survival skills and it is with these that we have learned to take on life in some of our most difficult times. These times may include making a way for your family out of no way, making it through a personal family crisis, getting yourself out of a dangerous situation or just making it through life daily if you have been unfortunate enough to have a chronic disease. You see this is an ongoing daily struggle to survive. One that takes all of the skills that we have both physically and mentally.
I have Rheumatoid Arthritis and I can tell you this disease can definitely get the best of you and make your day one that you think you won't make it through. This is something that each of us with a chronic disease face. Fighting the battle to survive through the pain, fatigue and medications that can put you off your feet is truly a test of survival. It is at this point that you reach deep to pull yourself up and gather that inner strength to carry on. When life takes you in an unexpected direction filled with toll and strife, we reach for the most important source of survival and that is God. Through him we gather faith, strength, comfort and knowledge when it seems there's no way out or no way around any situation that may come your way. Survival teaches you wisdom and it makes you strong and without it, life will pass you by.
Survival, our instinct to carry on and it comes in all forms.
A SHADOW, we all have one but you see a shadow can have many meanings.
Here are a few meanings we can ponder: Those that run along with us as a child while playing, those that we watched as we walk along with the ones we love, the one that might have frightened us in the moonlight while going on our way, the shadow of the person we would never want to become and the shadow of someone else we should never allow ourselves to walk in. Whatever it maybe, it has a significant impact on us in some form or fashion, after all it is ours.
You see, it is up to us what we chose to make of that shadow. I would say let it always be something that will hold special memories, bring a smile to your face or keep you motivated and if it scares you in the moonlight, look back at it as one of the fun times you had. A shadow does not have to carry with it that dark image of you shown in time after all it is what we make it.
Hope, a feeling of expectation and desire for a certain thing to happen. This is the life we all should live, one that is filled with hope. Without it, where would our wonderful dreams for our futures be.
Hope is a powerful thing and it is something that has no limit. It is a treasure to have something that no one can take from you even though some may try. It allows us to seek what we thought was impossible and it is what gives us the ability to push forward when we are burden with tough times. Hope is something that is deep in your heart and mind that leads you when all else has failed. It is what makes our hardest steps the easiest to take, also it lifts that heavy burden you maybe carrying and makes a day that is filled with gloom so much brighter.
Life should be filled with hope because it keeps our minds emotionally grounded and it is our Spiritual Gift from God. Without hope, how can anyone say they have anything to look forward to. Let us remember, life is full of Hope but lets not waste it on things that aren't positive. It is through prayer that our greatest Hopes are fulfilled. So for everyone reading this, I Hope you have a wonderful and Blessed day.
My hope is one day they will find a cure for Rheumatoid Arthritis for all that suffer from this terrible disease. It is debilitating and it is life altering. I will hang onto this hope whether it comes in my lifetime or not.
First let me say, we can never get others to fully understand the impact that Rheumatoid Arthritis has on our lives and the changes we face having it but facing this disease alone is almost as devastating as the effects themselves.


APC Producers' Committees are established to provide services to the producers' industry. Producer involvement in APC Producers' Committees is vital to the effectiveness of Committees.
The Agricultural Produce Commission is currently Advertising .
The Agricultural Produce Commission invites nominations from producers for positions on APC Producers' Committees.
APC Producers' Committees are established to provide services to producers. Strong producer participation increases committee effectiveness.
Some committee positions will become available on 31 May 2019. Terms of appointment will generally be for three years from 1 June 2019 to 31 May 2022.
Beekeepers, Carnarvon Banana, Citrus, Egg, Pome Fruit, Potato, Pork, Stone Fruit, Strawberry, Table Grape, Vegetable & Wine.
A nomination form and further information is available from the APC website www.apcwa.org.au or requested through APCManager@dpird.wa.gov.au / 08 9368 3127.
A Nomination Form and further information is available on the Join the APC page or contact the APC Manager on 08 9368 3127.


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HFPA Diversity Director Explains Golden Globe Reforms
Last month, as part of an ongoing effort to bring about the promised "transformational change", Hollywood Foreign Press Assn., The group behind the Golden Globes, hired Neil Phillips as its first director of diversity.
Phillips, an Entrepreneurship in Education Fellow at the Aspen Institute and a member of the first Echoing Green / Open Society Foundation for Black Men's Achievement, joined the organization after months of criticism from the HFPA and calls for reform following a Times investigation that found there were no blacks in the association. members and detailed allegations of financial and ethical omissions within the group.
Phillips' appointment comes after the HFPA formed a five-year partnership with the NAACP. But he also emerged after a string of violent incidents for the group, including a leaked email that former HFPA president Phil Burke sent to the group in April, in which he called Black Lives Matter a "racist hate movement." The association's first diversity advisor, University of Southern California professor Sean Harper, resigned shortly thereafter.
Phillips told The Times about the recent firestorm surrounding the group and how he plans to address diversity and fairness issues in the future, both internally and across the entertainment industry.
The HFPA faced heavy criticism earlier this year for its lack of black members, and the diversity and inclusion adviser they hired in March left after six weeks. Given the history, what prompted you to take on this role?
I became familiar with the problems that HFPA faces from a distance. It seemed to me then, as now, when I am even more familiar with her, that the criticism was well deserved – that this organization was underrepresented from the point of view of its black journalists. And it needed to be addressed, and I was very pleased and impressed with what I learned as the organization's response to this criticism.
When you look at the problems of underrepresentation – far beyond HFPA, far beyond film, television and the entertainment industry … there are usually structural problems that lead to them within the organization. So when I found out that the HFPA is very deeply and comprehensively examining not only the numbers and figures that need to be verified, but how it functions – things like the eligibility requirements and the certification process – and makes significant changes to those policies and procedures that told me that this organization is doing everything right … thoughtfully and purposefully.
Since I became even more familiar with the leadership of the organization, and [President] Helen [Hoehne] in particular, when I realized that their efforts were not only about getting out of the crisis, not about weathering the storm, but about the long-term modeling, practice and advocacy of truly deeply rooted diversity, equity and inclusion initiatives, it was an organization what I wanted to be a part of.
This is a new position for the organization. Can you discuss how you assess your role in HFPA?
Am I really looking at what this HFPA role should be? What is clear to me is that the HFPA needs this role to ensure that issues of diversity, equity and inclusion are handled with the care they deserve, and that considerations of diversity, equity and inclusion are always at the forefront of any organizational considerations. Sometimes they will be the core, sometimes the secondary, depending on the problem being solved. But my role will be to ensure that issues of diversity, equity and inclusion are always considered and taken into account in a way that benefits the organization and, as a result, benefits the industry.
I can tell you what the role is No… The role is not, "How can we help HFPA weather the storm or get out of the crisis?" That's not what this role is about. This role has much higher goals.
In October, the HFPA invited its largest class of new members, including six black journalists. In your opinion, has this taken the problem of lack of black members off the table, or is there a longer term goal that you think HFPA should be in terms of group composition?
The short answer is no, it doesn't take the problem off the table. We need more black journalists to become HFPA members, and this will happen.
These are not just numbers. One of the things being mindful of diversity does is improve organization. Extended membership affects the way an organization functions and the impact it has on the industry.
So you don't have a specific goal for how many black members you would like to see in HFPA?
I don't mean that number at all, except to know that we are striving for more.
Last year, the HFPA rejected the idea of bringing in a diversity and equality consultant, with many members arguing that the group was already diverse as its members came from all over the world. How does this affect the work you do with the organization and its ability to understand the importance of this issue in the future?
I cannot say much about the positions that people have taken in the past. … I have no point of view on this. What I can say is that this position exists now and I am focused on what I can do in the present and future to ensure that this role helps the organization expand the way it thinks about its members and the way it thinks. … about its impact on the industry.
I had the opportunity to reach out to the members, and although all the participants were not present, most of them were there. [and] a significant amount on Zoom. They heard from me: "Look, I understand that it was a very difficult time. I think the criticism of the HFPA was well deserved and I was really impressed with the organization's response and its commitment to continue to respond. "
Most of all, they heard optimism. It is an organization that has had a significant impact over 78 years in an industry that has had a significant impact around the world. Often we focus on negativity, criticism, negative reaction – and this is all real, so I understand. But I focus on the opportunity and optimism of what happens when an organization develops and transforms.
In October, the HFPA announced a five-year partnership with the NAACP. What do you hope for from this partnership?
I can't tell you how excited I am about this partnership. We will continue to encourage and support internships, fellowships and mentoring opportunities. We're going to work with them to restore some of the older black films and some of the films that chronicle the history of the NAACP. We're going to create opportunities for color creatives to get into film festivals around the world where the path has been more limited.
Earlier this year, the organization faced criticism from some influential figures in Hollywood, including Ava Duvernay and Shonda Rhimes, as well as organizations such as Time's Up and Color of Change, for historically ignoring black-led projects. Have you had any conversations with any of them or with any of the publicist coalition that spearheaded the HFPA boycott of these issues?
I have not spoken to any of the people you mentioned. But I really want these conversations, and I really hope that I have the privilege of spending time with some of the people you named and others who have criticized HFPA who have points of view and ideas. This will help me understand a fuller picture of the story that will form the basis for my work to promote HFPA.
Some at the HFPA have declined, saying some of their critics have their own problems when it comes to inclusion. Do you think this is a compelling counterargument?
I just don't think it helps a lot at this point. I just think I need to focus on my work. This is work that will bring the results that we want to see, and nothing but work. So I have no time at all to go back and forth like that – it just doesn't seem to me that the time was well spent.
Another argument put forward by some HFPA members is that not many Black Entertainment journalists work for foreign media. Do you agree with this assessment, and if so, what would you like to see to expand the circle of potential color applicants?
You often hear, "Well, we can't find enough women to advance to leadership positions," or "We can't find enough black men to fill the list of candidates at this particular college." I just won't buy it.
You have to look at how your organization is performing – your eligibility criteria, your habitual reach – and that's what HFPA has done. They made changes to policies and procedures. They expanded their coverage mechanisms. They eliminated certain requirements that narrowed the path rather than widened it.
I want to emphasize that there is no quick fix here. Some of these changes that have taken place are truly significant and meaningful. But we must continue to work for a certain period of time in order to get the results that are needed and I think are really achievable.
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Are TOGO Coasters Actually That Bad?
So the topic of today's discussion is something of a pet peeve of mine and something I've been wanting to write about for a while. The hate for TOGO, and why personally I feel not only is it unwarranted but in fact would go as far as to argue that TOGO actually make some pretty kickass coasters. What I want to explore in today's post is why this misconception might and exist and where it possibly comes from, as well as giving some of my own examples of why TOGO are actually pretty awesome!
For those unfamiliar with the company, TOGO are a Japanese amusement ride manufacturer founded in 1935. Their first attraction was a mechanical walking elephant in one of Tokyo's neighbourhood and they later went on to build Roller Coaster at Tokyo's historic amusement park Hanayashiki. The coaster remains the oldest operating coaster in Japan and is one of the oldest operating steel coasters in the world. The company sadly went bankrupt in 2001 after a lawsuit with Knott's Berry Farm over the infamous Windjammer Surf Racers but as recently as 2018 there have been murmurings of the company making a comeback with fresh new designs, although nothing has been confirmed.
Roller Coaster, Hanayashiki
You'll likely have heard the company mentioned alongside moans and groans on the good o' internet accompanied with declarations of how terrible and unbearable their coasters are. For Western enthusiasts they're a company associated with painful, uncomfortable ride experiences and are often the butt of jokes similar to that of Vekoma Boomerangs and SLCs. So, where does this preconception come from? My theory is that although the company predominately installed coasters in Japan, they did manage to build a handful in the USA. Doubtless a few of you will be familiar with the likes of Viper at SFGAdv or Shockwave at Kings Dominion but I'm willing to bet that most in not all of you will have at least heard of the Big Apple Coaster, previously known as Manhattan Express, located at the New York, New York Hotel & Casino on the main strip in Las Vegas, Nevada. And that is where I believe this myth of TOGO=terrible comes from.
Because you see, Big Apple Coaster is objectively, a terrible coaster. It serves more a purpose as a tacky piece of Las Vegas outrageousness as opposed to going out of its way to deliver a fantastic ride experience and it certainly help the NYNYH&C stand out from its other competitors. I'm sure if you even asked non-enthusiasts about this they would be familiar with the hotel with a roller coaster in Las Vegas. It's peak Las Vegas kitsch and as a strip icon and marketing tool it works perfectly. Sadly as a coaster it's incredibly uncomfortable. It's rough, painful and janky with a strange and awkward layout to try and fit into its footprint amongst the giant New York skyline cut outs. I rode it once not actually knowing how terrible it was supposed to be and came off with my ears ringing, it truly is that bad. So herein we see the problem - if the coaster you're most famous for manufacturing is a piece of shit then I think it's only natural for people to assume that you must just be a terrible coaster manufacturer as opposed to anybody assuming this is just the anomaly.
Ultra Twister, Nagashima SpaLand
But this is where it all goes a bit wrong. Coaster enthusiasts (and people in general to be honest) have a really annoying habit of jumping on the bandwagon of general coaster tropes even if they haven't experienced it for themselves. "All Vekoma SLCs are terrible", "RMCs are the best thing since sliced bread", "Icon is good" - you know what I'm talking about. And don't get me wrong, I've definitely been guilty of it before myself, especially when I was younger and less well-traveled when it came to theme parks and it's a behaviour I actively try to train myself out of because personally I find it incredibly hard to be objective about my own personal experience with an attraction if I board it for the first time with a preconceived idea of what it will ride like and that is not something I like to do. But if everybody is telling you that TOGO are shit then of course I think it's fair to assume that they're probably shit. But the truth is, they're actually kind of great?
I rode Big Apple Coaster in January 2012 and honestly I think I was still nursing my injuries from it when I joined the queue for Shockwave at Kings Dominion six months later. I so vividly remember thinking that we might and well get this TOGO stand-up coaster over and done with, for the +1 of course. Because I'd had such a ghastly experience on Big Apple Coaster I was bracing myself for the worst for this one, especially as it was a stand-up and I'd never particularly been a fan of Shockwave at Drayton Manor. I was incredibly surprised and a little bit confused to find that I actually adored the coaster and it turned out to be my second favourite of the day at Kings Dominion after Flight of Fear.
Fast forward to my Japan trip in 2015 and any negative feelings I'd previously had towards TOGO were but a thing of the past. From the insane layout and sideways airtime of the mighty Fujiyama, to the mad unqiueness of Ultra Twister at Nagashima SpaLand to the intense and powerful forces of Surf Coaster Leviathan I had fallen madly in love with this strange Japanese manufacturer. Nothing they do is really like anything else we know of Western manufacturers and their...flair for the unusual feels quintessentially Japanese and something I quickly fell in love with as I rode more and more of these quirky coasters as we made our way through the Japanese parks on our trip.
Surf Coaster Leviathan, Sea Paradise
TOGO get a bad name, and unfairly so, simply because of the fact that their most famous coaster also happens to be their worst. It's the prime example of how going along with the crowd can mismanage your expectations and why I will always encourage any coaster enthusiast to do their best to ignore the mantra of the crowd and instead use their own experiences and research to come to our own conclusions. Not only do TOGO make really great rides they're actually pretty iconic in terms of the history of the roller coaster, responsible for some of the oldest operating roller coasters in Asia, an important player in developing alternative approaches to what roller coasters can do with their Ultratwister models and even managing to nab some world records with Fujiyama. They're not some trash coaster manufacturer who makes crap but instead are an innovative, quirky company hugely responsible for the success and development of the amusement ride industry in Japan.
Have you ridden a TOGO coaster? Do you agree that they're unfairly labelled as a manufacturer of terrible rides? Let me know in the comments, I'd love to know what you think!
Talk later xoxo,
All images were provided with permission by CoasterForce
Cupcakes and Coasters
London-based attractions industry professional and huge theme park nerd. Find me overusing the pumpkin emoji on Twitter or on the road to a theme park!
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Will Sri Lanka Become A "Killing Field Again"?
23rd June 2014 Karu LATEST UPDATES, SPECIAL NEWS, SRI LANKA NEWS, Uncategorized 0
By P. Bertie Ranaweerage –
According to Karuna Amman there had been only 80 LTTE armed cadres byJuly 1983. JR who did almost nothing to protect the Tamils and their properties during the Black July Days in 1983 had no alternative but to send those who managed to save their lives to the Northern and Eastern provinces. It is in the public domain that a large number of Tamil youths who were sent to the North and East willingly joined the LTTE either to get revenge on the Sinhalese or on the belief that Eelam was the only remaining panacea for all the problems the Tamils. Karuna further said that the number of armed cadres of the LTTE had gone up to 40000 by the time he left the LTTE.
The Sinhala extremists and their leaders such as Elle Gunawansa, and Cyril Mathew who plotted and launched the Tamil pogrom in 1983 never in their wildest dreams did think that the terror they unleashed on the Tamils would result in a 26 year disastrous internal war. Hence we have to ask ourselves now whether the terrorism of the blood thirsty BBS would push the Moor /Muslims to extremism which may result in more destruction more violence and more bloodbaths .
Nobody never ever thought that this government would do what JR and Premadasa did during the Black July days in 1983. We do remember that JR did not utter a single word against massacring of Tamils until the thugs and murderers had finished their job.
Like wise the MR government took no meaningful measures to stop the Aluthgama mayhem and the President waited from June 15 to June 21 to make an appeal to the public to desist from attacking the others on the grounds of religion or ethnicity.
The recent brutal attack onWatareka VijithaThera, after kidnapping him at night allegedly by the BBS thugs, has once again proved that the BBS is a fascist organization which does not tolerate those who speak for inter ethnic harmony. It incidentally reminds us of the cruelty of the ' Patriotic Army ' of the JVP that killed those stood for the 13th amendment from 1987 to 1990. Unless the BBS is stopped immediately by proscribing it and incarcerating its junta for years there is no doubt that it will continue its terror against minorities. We can expect more attacks on Muslims' property and more Muslim deaths. Not only they will attack the minorities but also the Sinhalese who are against them.
As the rulers continue its mollycoddling of the BBS it is continuing its attack on Muslims. The latest news is that they had attacked 'NOLIMIT' textile shop in Panadura owned by Muslims. And it will not be the last attack against Muslims and nobody will be amazed if they hear of another attack tomorrow morning.
It is tragic for the entire nation because the government has not understood the gravity of BBS' fascism and its consequences. When Muslims are continually attacked it may push the Muslim youths to take up arms for the protection of its community. Muslim extremism which has turned Iraq, Syria, Pakistan and Nigeria to a living hell will definitely extend its tentacles to Sri Lanka taking the advantage of the present situation here. Though killing others or committing suicide is a sin that opens the path to the hell for Buddhists, it is said that killing in the name of Islam is a sure path to the heaven where beautiful virgins, delicious foods ,drinks and mansions are in abundance .It may well could be one of the incentives that drives Muslims to kill enemies and 'heretics'. Hence pushing Muslims to arm themselves will culminate in unimaginable tragedies for Sri Lanka. Not only it will be disastrous for both the Sinhalese and the Muslims but also for the economy of the country. In the event that the Middle East countries decide to limit the recruitment of workers from Sri Lanka the impact on the economy will be catastrophic.
Yet it is only a day dream if we expect the government to ban the BBS as it is an invisible ally of it. The President has already said that the BBS would not be proscribed in response to the requests made by Ministers Hakeem and Rishard Bathiudeen. In future elections the BBS probably field a few candidates under the UPFA and will do whatever possible to bring the UPFA and the incumbent President back to power as its future depends on the generosity of the Rajapaksa government.
The UNP has not so far understood that the BBS will be a major threat to it during future election campaigns. My belief is that the BBS will be used by some leaders of the government to attack the UNP election rallies and disrupt them. They will not hesitate to use petrol bombs and guns to attack the UNP rallies. Without understanding the gravity of the threat they are living in a utopian world dreaming that Ranil or Karu would be elected or would be allowed to be elected for the office of the Presidency next year.
As fascist BBS' popularity is increasing among the extremist Sinhala Buddhists who are ready to kill in the name of Buddhism, it has posed a threat to the future of the Jathika Hela Urumaya and Wimal Weerawansa's National Freedom Front. That is why Wimal Weerawansa threatens the government that he would resign unless his 12 resolutions are implemented. They have already been forced to resort to various politrics in order to prevent their voters from deserting them and turning to BBS in case the BBS contest. Hence we can expect blood curdling 'patriotic ' speeches from both groups in future as Parliamentary elections and the Presidential election are to be held in 2015.
Mr. Hakeem, Minister of Justice and senior Minister Mr. Dew Gunasekara have asked why the government failed to stop the mayhem in Dharga Town, Beruwala, Welipenna and Aluthgama. It is pity that they have forgotten that they themselves area part of the government. They surely must know that the Rajapaksa government did not want to prevent it as its power is based on Sinhala Buddhists and it has to please its voter base to remain in power and regain power.
The violence against the Muslims could have been prevented not only by the government but also the parties of the Opposition , particularly the UNP and the JVP. They could have launched an effective propaganda campaign against the BBS' fascism to convince the public its destructive agenda and rally people against the BBS' madness. But the UNP failed to do so as it has become a confused and stranded political party in the political wilderness sans a road map .With regard to the JVP it was not interested in launching a campaign against its erstwhile comrades as it feared that it would erode its Sinhala Buddhist vote base.
The Muslim Congress and the Muslim Ministers too could have prevented the onslaught against the Muslims to a certain extent had it acted decisively at the right time. it is not wrong to assume that they hesitated to act decisively simply because Muslim Ministers did not want to say good bye to the privileges they have been enjoying being a part of the Rajapaksa government.
Now Sri Lanka has arrived at a critical juncture. Another civil war is being prepared by the BBS, Sinhala Ravaya and Rawana balaya By not condemning this extremists, Chief Priests of Malwatta and Asgiriya and prominent Buddhist priests such as Maduluwawe Sobhtha Thera are contributing to a future civil war here. Unless the government understand that the BBS' non-stop attacks on Muslims will force Muslims to arm themselves and retaliate, nobody will be able to prevent this land becoming a killing field once again.
Panadura 'No Limit' ; Jaffna mosque; Trincomalee hotel attacked
Blood on Bodu Bala robe


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Home » Aviation
LoJack Helps Tennessee Highway Patrol Aviation Unit Find Stolen Construction Equipment
Nashville, TN. Jan 02, 2014 7:44 PM EST – High-tech (LoJack) tracking equipment led law enforcement agencies to some pricey stolen construction equipment. Officials said the Tennessee Highway Patrol Aviation Unit and the Criminal Investigation Division were able to track down two stolen mini excavators on December 26. One was found stolen from a
Clayton County, Georgia Police Helicopter Unit Locate Stolen Toyota Camry Assisted by the LoJack® System
In this case, ground and air units from the Clayton County, GA Police work together to track a 2012 Toyota Camry stolen from East Point in just over two and a half hours with help from the LoJack® system. On July 25th, 2013, the Toyota's owner contacted the East Point Police to report that their
Valentine's Day Stolen Vehicle Recovery Stories that Illustrate Love Gone Wrong
Upon reviewing our recoveries, we often come across those involving relationships that have gone so wrong they end with stories about stolen (and thanks to LoJack, recovered) vehicles. With Valentine's Day being today, here are a few theft stories that turned out "lovely" for the victims and not so great for their former significant others.
LoJack Helps San Diego Police Air & Ground Units Recover Stolen 2012 Toyota Camry and Arrest Suspect
While it's widely known that LoJack Corporation is the only stolen vehicle recovery system directly integrated with police cars, many people do not know we also equip many police aviation units across the country with LoJack police tracking computers. Having our equipment in aircrafts provides a unique advantage to LoJack customers because it provides a
LoJack Corporation Helps Montgomery County Police Recover Multiple Stolen Vehicles Located Inside a Shipping Container Bound for Sea
If you live on or near the coast, today's story is a great example of how LoJack can save your vehicle from ending up overseas in a matter of days. On November 8, 2012, the owner of a 2010 Toyota RAV-4 called the Montgomery County Police Department to report the theft of this vehicle from
Couple Carjacked by Car Thief; K-9 & LoJack Help Police Track Down Thief & Nissan Maxima
The following story is one that makes us all particularly proud to work at LoJack. On August 3rd, a Southern California couple was faced with an armed man who wanted to steal their 2008 Nissan Maxima. At that point, they had to make a potentially life or death decision: do they resist this armed criminal
(Video Update) LoJack Helps LAPD Recover Classic 1956 Chevy and Leads Police To Other Stolen Vehicles
We recently told you about a recovery story in which LoJack helped police recover a beautiful 1956 Chevy Bel Air. We caught up with the happy owner of the classic Chevy to hear his thoughts:
LoJack Helps LAPD Recover Classic 1956 Chevy and Leads Police To Other Stolen Vehicles
On June 23, 2012, the owner of a 1956 Chevrolet Bel Air Custom Convertible contacted the Pasadena Police Department to report that his vehicle had been stolen from a warehouse where he had just stored it the night before. Pasadena officers verified the theft and entered the vehicle's information into the state and federal crime
Miami Police Recover Stolen Suzuki Motorcycle, Bust Chop Shop and Recover Other Motorcycles, Parts
On Wednesday, February 29, 2012, the owner of a 2006 Suzuki GSX1300 Hayabusa motorcycle contacted the Key Biscayne Police Department to report the motorcycle stolen. Upon arrival at the scene, the responding officer met with the owner who stated that sometime during the night the Suzuki was from where the owner had parked it. The
TREND WATCH: Thieves Removing and Switching License Plates
In our first story, the owner had his car broken into and the suspects found the car keys hidden in vehicle and stole the car. The owner reported the 2010 BMW 750IL stolen to the Frisco Police Department and the vehicle information was entered into the NCIC (National Crime Information Center) police computer. This routine


Because fiber optic cables transmit data via light waves, they can transfer information at the speed of light. Not surprisingly, fiber optic cables provide the fastest data transfer rates of any data transmission medium. They are also less susceptible to noise and interference compared to copper wires or telephone lines. However, fiber optic cables are more fragile than their metallic counterparts and therefore require more protective shielding. While copper wires can be spliced and mended as many times as needed, broken fiber optic cables often need to be replaced.
Since fiber optic cables provide fast transfer speeds and large bandwidth, they are used for a large part of the Internet backbone. For example, most transatlantic telecommunications cables between the U.S. and Europe are fiber optic. In recent years, fiber optic technology has become increasingly popular for local Internet connections as well. For example, some ISPs now offer "fiber Internet," which provides Internet access via a fiber optic line. Fiber connections can provide homes and businesses with data transfer speeds of 1 Gbps.
This page contains a technical definition of Fiber Optic Cable. It explains in computing terminology what Fiber Optic Cable means and is one of many hardware terms in the TechTerms dictionary.
All definitions on the TechTerms website are written to be technically accurate but also easy to understand. If you find this Fiber Optic Cable definition to be helpful, you can reference it using the citation links above. If you think a term should be updated or added to the TechTerms dictionary, please email TechTerms!


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Q: Late timing of `Date().getTime()`? I'm trying to get the timing of a user's click on a dynamically-generated image using Shiny and some Javascript. The app below reports the client's time as LATER than the time captured within the server, which is not desired. I'd like to capture the time given by the user's browser when they click on the image (this will prevent noise and delays from the trip from the client to the Shiny server). Any ideas?
The ultimate goal for the app is to calculate a "find time" -- the duration it takes for a user to click on a specific coordinate after the image appears in their browser.
library(shiny)
library(shinyjs)
options(digits.secs = 3)     # Modify and save default global time options

click.time.image.js <- "

  document.getElementById('img').onclick = function(){
      var the_time = new Date().getTime();
      console.log(the_time);
      // set input$client_time to the_time:
      Shiny.setInputValue('client_time', the_time)
}
        "

shinyApp(

  ui = fluidPage(
    useShinyjs(),
    sidebarLayout(
      sidebarPanel(
        p("When clicking on the histogram, I'd like to capture the client-side computer's time"),
        actionButton(inputId="new_image", label= "New Image")
        ),
      mainPanel(
        imageOutput("img", click = "photo_click"),
        textOutput("client_time"),
        textOutput("server_time")
      )
    )
  ),
  server = function(input, output) {

    output$img <- renderImage({
      input$new_image

      outfile <- tempfile(fileext='.png')
      png(outfile, width=400, height=400)
      hist(rnorm(100))
      dev.off()

      shinyjs::runjs(click.time.image.js)

      list(src = outfile,
           alt = "This is alternate text")
    },
    deleteFile = TRUE)

    output$server_time <- renderText({
      req(input$photo_click)
      server.time <- as.character(strptime(Sys.time(), "%Y-%m-%d %H:%M:%OS"))    # Time with milliseconds
      paste("SERVER TIME:", server.time)
    })

    output$client_time <- renderText({
      req(input$photo_click)
      req(input$client_time)
      client.time <- input$client_time    # Time with milliseconds
      client.time <- as.POSIXct(client.time/1000, origin="1970-01-01")
      paste("CLIENTs TIME:", client.time)
    })

  }
)

redpajama_set_name: RedPajamaStackExchange


get packed under too much snow and ice – they can get really thirsty.
winter, but too much and watering can do far more harm than good.
So what gives? When's enough, enough? When's it time to put away the hose?
temperature is over 40 degrees. Don't tempt fate if the temperature is lower.
water before the temperature plunges and freezes overnight.
Prepping for the winter seems fairly straight forward – and for the most part it is.


Grace Johnson and Lubina Nayak bring home Outstanding Diver awards from the Tier 2 Provincial championships held in Kitchener the weekend of June 21 & 22.
Fall registration begins July 14. The Schedule for Fall programming will be available shortly.


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MPNforum Magazine
CRISPR Madness
A day at the office — MPNRF
About MPNforum
Four months of CRISPR
Now CRISPR targets MPN genes.
(Continued from home page…with odd notes and summary.)
Suddenly, there was hope, a fresh approach to treat disease that might apply to MPNs. Now there was a technology coming out of the biology labs that would no longer rely on putting out fires downstream of the blaze. This technology promised the possibility of correcting mutations that cause the conflagration of myeloproliferative neoplasm at their very source.
In a report of that meeting with Jennifer Doudna there's a photograph of her holding a photo model of the CRISPR/Cas9 molecule on her phone. She's seated before a computer monitor displaying the CRISPR story on an MPN web page. We had been talking about MPNs and gene editing.
It may not have been the first time an MPN patient and editor sat down with a CRISPR/Cas9 scientist to explore therapeutic possibilities. For both of us, however, it was a first deep exposure of the other's world. Inspired by Jennifer Doudna's commitment to collaboration, the possibility of joining our two worlds became a reality.
It was the beginning of a four month crusade to help bring gene editing into the treatment options our hematologists could offer us.
…but first, Chicago
Before it could happen, we had to go to the fountainhead of MPN research. Just weeks after picking up that parking lot pass, I went to Chicago to visit the MPN Research Foundation to get its endorsement and support.
That was the beginning. Here's how it ended:
Now that the gods of Spring are smiling softly down on us, the brutal winter of 2015 is not only forgiven but forgotten. Almost. Reporting on the pair of historic gene editing meetings that took place in the Boston area this winter – the Hanson-Wade and IBC meetings – the chill winter blasts invade my notes, tapes and photos.
The meetings featured CRISPR pioneers, academic and developer labs shaping the DNA of the path gene editing is likely to take. But when it came time to sort out all the notes of interviews and presentations, one image kept intruding. Driving in a sudden blizzard.
The mid-March IBC Genome Editing Applications meeting at the Hilton Boston would have been remarkable enough without the accompaniment of global climate changes funneling into Boston's Back Bay. Somehow it all made sense: Fundamental meteorological change as the background to the radically disruptive and transformative nature of the new biotechnology. The reality was a lot scarier.
Headed home…
On the first day of Spring, Interstate 495 in Massachusetts was a slippery ghost of a road covered in sliding sheets of snow. In the early morning white-out, lane markers emerged and vanished as the snow slid across the highway driven by strong wind gusts.
I was headed to Logan Airport, following the black tire tracks and red taillights of cars fishtailing ahead of me. Two days earlier, a freak prolonged wind event,with gusts up to 75 miles per hour, packed with claws of ice, had pinned me against a parked car outside the Sheraton, just a few yards from the unreachable IBC meeting site.
Courtesy: Wikimedia
All of it, struggling against prevailing winds, following in the tire tracks of winter-hardened Boston drivers opening a path into unknown territory, may have been more Fellini than Isaac Newton but that's how this story actually came together. Reporting doesn't always take place on the phone while googling at a warm desk with a cup of coffee by your side.
The IBC gene editing meeting – focused on CRISPR/Cas9 – documented the extraordinary progress of a revolution started less than three years ago. The winds of change had already blown apart perceived limitations on human ability to modify the genome – quickly, cheaply, easily, and efficiently. Now, despite unclear boundaries, intense efforts were underway to improve targeting and delivery systems on the road from laboratory to clinic.
One after another, Speakers rose to report on progress in CRISPR/Cas9 applications in cardiovascular design, blood disorders, nucleic acid delivery systems, drug discovery and validation systems and new means to rejigger the genome and epigenome through gene editing.
Remember her?
She helped introduce us to CRISPR back in November, the MPNforum issue with the giant e-coli bug on the Home Page. Heading out to the coffee bar during a break, there she was.
Namritha Ravinder
I wasn't sure if it was appropriate to ask her for an autograph but I settled for her photo. She's Namritha Ravinder, Staff Scientist at ThermoFisher.
At least three of the people who played a role in opening the Pandora's box of gene editing were featured at the meeting: George Church, professor of genetics at Harvard and MIT, Rachel Haurwitz, head of Caribou Biosciences, and Feng Zhang, the Broad Institute of Harvard and MIT. At one point, the legendary George Church took time out to fiddle with my dysfunctional handycam. And sign a copy of his book, Regenesis (strongly recommended).
The approximately 150 registrants at the meeting, most of whom were active in academic or commercial gene editing labs, were starkly different from those who participate in clinical meetings like the annual American Society of Hematology events. Beyond focus, the new genetic editing population was different from ASH attendees in other respects as well. As expected, there were few MDs and many PhDs, more academics than clinicians, a much higher fraction of women than seen at ASH, and, above all, extraordinary youth. (Two of our featured pioneers are barely out of their twenties.)Invariably polite and interested in our clonal mutant disease, nobody appeared to have heard of myeloproliferative neoplasms
The immediate role of CRISPR/Cas9 may be as a tool to improve the efficiency of CAR-T and other Adoptive Cell Transfer immunotherapies.
Putting the CART before the CRISPR
CAR-T requires engineering the body's own T cells – the basic infantry of the immune system — to express Chimeric Antigen Receptors (CARS) able to recognize cancer targets on cells. Gene editing is used to modify T cells and link to viral vectors to integrate the CAR-Ts into the cell's DNA. Immediate and dramatic results have been reported in early ALL trials. CRISPR/Cas 9 has the ability to refine and simplify development of CAR-Ts. Now in Phase 2 clinical trial, CAR-Ts are widely expected to apply for INDs in 2016.
And that's not the only immediate role for CRISPR in human clinical application. This week, The Whitehead Institute in the biomedical supercluster around MIT, announced its use of CRISPR/Cas9 to target killer fungal infections. Gerald Fink, Whitehead founder and a professor of biology at Harvard said, The ability to engineer Candida albicans with CRISPR technology has changed the playing field. We used to attack this human pathogen with our hands tied behind our back. Our findings cut these bonds, freeing us to forge ahead on problems in basic research and human health."
While the short term clinical application of CRISPR/Cas9 may be as a supplement to the genetic engineer's toolbox and in a supporting role for the CAR-Ts the transformative therapeutic payoff of CRISPR lies in direct repair of genetic mutation.
First in the queue
Big money, major drug firm collaboration, and professional reputations are all on the line in the race for successful clinical application of CRISPR. And in that race, the low-hanging fruit is the single loss-of-function mutations that cause deadly diseases like Sickle Cell Anemia and Cystic Fibrosis.
Scientific and clinical research at both Boston-area meetings – Hanson Wade and IBC — clearly demonstrated the rapid pace of bioengineering since introduction of CRISPR less than three years ago in the expansion of journal publications and proliferation of commercial development work.
The focus of most CRISPR research is on improving target specificity and delivery systems — part of which involves speeding up the intracellular editing process — and evaluating and sharing editing outcomes. Alternate delivery systems – using plasmids, viruses, oligonucleotides, electroporation and direct delivery to the cell of a modified protein with the DNA molecule—were highlighted. Presentations were made on applying the accuracy of double strand breaks to single strand cleavage — of special interest in MPN patients who are heterozygous for the JAK2 mutation.
There seemed to be a general sense that human clinical CRISPR applications were likely within the next two years. Both the FDA and NIH were represented and presented options to help investigators in the IND process. CR-T and other immunotherapies in which CRISPR plays a supportive role are expected to be approved next year.
First direct CRISPR targets are likely to be the single cell loss of function mutations causing, for example, Sickle Cell Anemia and Cystic Fibrosis. These are applications where repair of the defective cell ex vivo followed by expansion of the edited colony and reintroduction is likely to produce immediate benefit with minimal risk.
George Church's lab at Harvard and MIT is working on getting systemic delivery incorporated at the genomic level for a variety of cell types including hematopoietic cells. He referred to the gene conversion work presented by Editas, repairing a defective homolog with the correct one, as one option "The issue here may be a competing non-homologous end joining (NHEJ) reaction but if cleavage is site specific we can get a mix of cells repaired to the correct allele and others, if they were heterozygous in the first place, would be hemizygous. "
Church is well aware of the challenge of proliferative diseases where you can wipe out 99% of mutated cells but, in principle, the mutant clone can rebound. He noted the various mutations identified in MPNs are something the CRISPR Cas9 system with multiple targeting capabilities is well positioned to address. Church noted various ways cells can be switched on, expanded, switched off, inserted.
Ex vivo selection, repair and reintroduction seems the preferred route for now. The ex vivo route permits increased efficiency through some sort of selective process, an ability to screen and expand a population of cells before reintroduction.
His lab, as all the researchers we talked with, is open to collaboration with clinicians. His and Feng Zhang's lab at MIT may not yet have much MPN experience available but they have the Harvard Medical School clinicians available. Other academic research with deep CRISPR credentials need clinical collaborators to bring gene editing to MPNs.
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Comments on: "Four months of CRISPR" (2)
Ross said:
Well written, very informative article. Thanks!
Davnet Heery said:
Not surprised the wind threatened you. Aren't you a latter-day Quixote, battling all sorts of elements to reach those windmills?Afterall, Dulcinea has to be saved!
And that these researchers are fresh-faced youths, on one side, and the august medics attending ASH are experienced professionals, on the other, seems so, so inevitable too. A sea-change in perspective up ahead. Another generation, another Spring, and HOPE writ large.
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