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As Australasia's leading Speakers Bureau we have access to hundreds of thought leaders and change makers both locally and internationally as well as over 50 years of experience in the events industry. Let our experience guarantee your success
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Empowering others with the vision to succeed
As one of Australia's most prolific and prominent motivational speakers, Lorin Nicholson not only understands the keys and principles for success, he personifies them and has now shared this knowledge and experience in over 4000 keynote addresses to more than a million people across all industries from hospitality to mining, Health to finance, sales to technology and service to education.
Many have an incredible story to tell, however Lorin possesses that rare story telling ability that truly motivates, captivates, entertains and empowers others with the skills, knowledge and determination to create their own success. Unlike the usual, naturally gifted celebrity athlete, business person and motivational speakers who choose to become successful, Lorin was forced to dig deep, fight hard and muster every ounce of his will-power just to be normal.
At age four, Lorin was declared legally blind, however despite the enormous challenges of blindness growing up and the pessimistic views and low expectations of so many, it soon became obvious that Lorin possessed an incredible inner strength, resilience and determination that would see him destined for great things.
Whether focussed on becoming an academic achiever, a record breaking athlete, an award-winning music producer and virtuoso guitarist, or building a strong and successful business, amazingly, Lorin continues to surge on to achieve far above and beyond most abled people.
Lorin's powerful messages, captivating delivery style and incredible guitar playing, coupled with his unrelenting determination through adversity and infectious enthusiasm for life always leaves an indelible imprint on the lives of everyone he meets. Whether it's giving your team a motivational pep-up, or developing greater initiative, vision and leadership among your staff members, or refocusing your company's direction and business positioning strategy, Lorin is renown for his profound ability to communicate, innovate and accelerate individuals and organisations towards higher achievement.
With an amazing story to tell, Lorin is real, completely engaging and absolutely inspirational!
As Australia's most renowned blind musician and guitar player, Lorin is one of the countries highest selling independent artists, with five successful albums to his credit, as well as golden guitar finalist and winner of the 2015 record producer of the year award. He is also one of an elite few, invited to be a lead-line endorsee for the prestigious Martin & Co Guitar Company.
Lorin regularly features in many major newspapers, radio interviews and television news stories, including the Today Show, 60 Minutes and several appearances on Channel Nine's Carols by Candlelight.
Bike: Creating Australian history, Lorin along with blind younger brother Dean, were the first blind persons to ride tandem pushbikes across Australia, in a four week epic journey covering over 4000km from Perth to Sydney.
Riding solo: With unrelenting grit and determination, Lorin ignored the negative talk from the naysayers and skeptics, when at age 16 he achieved the seemingly impossible, by riding a solo pushbike 275km over the third steepest mountain range in Australia, from Tamworth to Port Macquarie with less than 10% eye sight.
Lorin Nicholson: A man with vision
Choice and Attitude
Choice and attitude are fundamental principles that empowers each of us with the knowledge that you are always the one in control.
The 12 Keys of Success
#1: Choice and Attitude
#2: Courage and Goal Setting
Be prepared to take a risk and do something you're passionate about! Visualise your goal, and then stick to it.
#3: Coping with Negativity and Peer Pressure
Sometimes the limitations imposed upon us by others can be a greater barrier than the limitation itself. Overcoming these can build confidence and self esteem.
#4: Expectations
What do we expect of ourselves and what do others expect of us?
#5: Adapt and Overcome
We all have unique challenges as well as strengths, so don't be afraid to look outside the circle and do things differently.
#6: Planning and Organisation
Success requires thought, and a step-by-step strategy. Think big, act small.
#7: Faith in the Unknown
Faith is a powerful built-in hope that drives each of us forward.
#8: Perseverance and Resilience
Anything worth doing requires effort and the ability to bounce back and keep going.
#9: Working Together
Building a strong and vibrant team, because believing in ourselves begins when others believe in us too.
#10: Everyday Heroes
Who are the real heroes in life? You don't need to be famous. Ordinary people can achieve extraordinary things.
#11: Climbing our own Mountain
The greatest challenge in life isn't with the person next to you, it's the challenge going on inside yourself.
#12: What is Real Success?
Look for meaningful goals in life and prioritise what is really important.
Thank you so much for your inspirational workshops at our school today. Our staff were moved to tears by your beautiful music and your stories of overcoming adversity as a blind child in sch ... keep readingool, through the support of your family and through sheer persistence. It reminded us all of why we are here as teachers, to make a difference in the lives of others, and you managed to do this powerfully in just half an hour. I had many teachers tell me that this was the best staff session we have ever had in our school. Equally as powerful were your presentations to the students and the workshops for our musicians. What a wonderful way to kick off our anti-bullying lessons with your message about looking after each other. Newport Public School NSW
Sometimes as we go through life we experience something extraordinary and special. It might be someone we meet, or someone who does us a kind favour. Today I had the privilege of meeting you and your father. You both stirred something inside me (and in all my staff I hasten to say). You enriched my life and my work. I thank you for sharing your life with all of us today.
Beecroft Public School NSW
Some people have a true gift that is matched by intellect and empathy. Lorin Nicholson uses every part of his nature. It is what makes him a compelling storyteller. Once you are walking in his shoes a lot of new thoughts open up. We are able to contemplate aspects of our own nature with a fresh honesty. We see the light. Lorin's courage in overcoming so many challenges and his eternal good temper make the lessons so much more valuable. I watched young and old people following every word, dwelling on the values he was sharing with us. Set this storytelling to music, with that gifted guitar playing and his true virtuosity, and you have a performance that is wonderfully original. No, better than that, Lorin Nicholson is a memorable human being.
Jeff McMullen, journalist, author and filmmaker
Lorin Nicholson is fast becoming one of Australia's pre-eminent entertainers and motivational speakers. He has an imposing and unforgettable presence, and a musical ability that has attracted the genuine acclaim of critical experts. But more than that, Lorin is a decent bloke who personifies life's ideals, and unfailingly gifts an audience with something that is very special - an example of using the gifts that each of us has been given. He is a real talent, and an inspiration that lives life-long with all those with whom he comes in contact. He tells each of us "Don't die with the music in you''.
Tony Koch - Chief Reporter - The Australian Newspaper
Imagine walking onto a stage in front of 15,000 people. Its just you and your guitar. As the time draws near the sound of the audience turns to silence. The time has come and as he plays you can feel the emotion. The stadium fills with acceptance, hope and love....and there is a time when nothing else matters. I know because I saw it. Lorin Nicholson is truly an inspiration.
Adrian Dellevergin - Executive Producer/Director - NINE NETWORK AUSTRALIA
Lorin and his wife were incredibly engaging and were able to encompass the room throughout the delivery. He was funny, smart and very affable. I would recommend him to any future clients.
Lorin Nicholson
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John studied art at St Paul's College, Cheltenham. After teaching for five years, John then lived in Hong Kong, one of the most visually exciting cities in the world.
Inspired by his surroundings, works were produced in watercolour, gouache and collage. Further travel has led the direction of his work; resulting in paintings from Europe, Middle and Far East, North America, Australia, North Africa and Scandinavia. John also enjoys painting scenes from the UK, where he now resides.
John's work encompasses a wide range of subjects: street scenes, buildings, portraits of animals and children, woodlands and landscapes.
John often exhibits charming local scenes of Hitchin and the surrounding area here with us at The Art Nest.


Much of the discussion around the sale of 45% of Kiwibank to the NZ Super Fund and Accident Compensation Corporation has been around politics and this of state asset sales. This post is about what it means for Kiwibank why the deal is probably a good idea.
My interests were raised by the announcement as one of the many reasons for the sale was to help make Kiwibank more competitive against its biggest-Australian owned peers. That had me scratching my head a little as the perception, in my mind at least, was that Kiwibank was competitive. Particularly in the main market we watch, home loans.
It turns out when you use our mortgage comparison tool and track Kiwibank's standard home loan rates against its big-bank peers the answer is it used to be competitive.
Use this link to see Kiwibank's standard two-year rate compared to ANZ, ASB and Westpac.
There is a point around the start of 2015 where Kiwibank's pricing policy changed and instead of regularly being a market leader on price, it has become a follower. Indeed the banks which tend to be market leaders these days are SBS amongst the small banks, BNZ tends to be competitive with its larger peers, and from time to time HSBC will shake the market with some enticing Specials (for high value customers only though).
Other research shows that after this change in pricing Kiwibank started to lose market share. Yet keeping and growing market share is the holy grail for all lenders in the market.
One of reasons why Kiwibank has been struggling may well be a capital issue. Property investment lending makes up a significant portion of all residential lending these days. Under new Reserve Bank regulations banks have to hold an increased level of capital for property investment loans. This could be an issue for Kiwibank.
Another issue is that it is missing out on at least a third of all home loans originated as it doesn't play seriously in the mortgage broker market. Yes it has dabbled in this space in the past but has never really got a strong proposition off the ground and into market.
Most recently BNZ and SBS have acknowledged the importance of the broker market and are now active players to help with their growth, especially in the Auckland market.
Having the NZ Super Fund and ACC as significant shareholder in Kiwibank is a good move. The organisations, particularly the Super Fund, has shown itself to be an astute investor who can pick good opportunities and help companies it invests in grow.
Putting aside the politics of last week's deal, it looks like good move to help the largest New Zealand-owned bank get back on the growth path.


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We come to beginnings only at the end.
William Throsby Bridges
William Throsby Bridges's quotes
Disenchantment, whether it is a minor disappointment or a major shock, is the signal that things are moving into transition in our lives.
Much as we may wish to make a new beginning, some part of us resists doing so as though we were making the first step toward disaster.
If the guilt of sin is so great that nothing can satisfy it but the blood of Jesus; and the filth of sin is so great that nothing can fetch out the stain thereof but the blood of Jesus, how great, how heinous, how sinful must the evil of sin be.
Genuine beginnings begin within us, even when they are brought to our attention by external opportunities.
Each person's life is a story that is telling itself in the living.
From the standpoint of observation, then, we must regard it as a highly probable hypothesis that the beginnings of the mental life date from as far back as the beginnings of life at large.
Wilhelm Wundt
To me many short poems read and write like beginnings that simply whet my appetite; I want to get over that.
John Barton
If one takes all the styles in jazz harmonically from the earliest beginnings to the latest experiments, he still has a rather limited scope when compared to the rest of music in the world.
Don Ellis
What began as a revolt in response to the King of Great Britain's repeated injuries against the colonies, soon became a passionate and glorious call to fight for the beginnings of a new country.
John Linder
Everything has to be done to build some sort of international democracy. We've seen only the tiniest beginnings of that.
Life is not so much about beginnings and endings as it is about going on and on and on. It is about muddling through the middle.
I will never forget my humble beginnings as a Laker Girl. It was probably one of the most fun jobs I ever had.
The beginnings of my studies also came to me from my father, as well as from the Rabbinical Judge of our town. But they were preceded by three tutors under whom I studied, one after the other, from the time I was three and a half till I turned eight and a half.
Shmuel Y. Agnon
Every contrivance of man, every tool, every instrument, every utensil, every article designed for use, of each and every kind, evolved from a very simple beginnings.
I was having trouble making ends meet, and my beginnings weren't meeting either.
The ultimate wisdom which deals with beginnings, remains locked in a seed. There it lies, the simplest fact of the universe and at the same time the one which calls faith rather than reason.
Those newspapers of the nation which most loudly cried dictatorship against me would have been the first to justify the beginnings of dictatorship by somebody else.
The beginnings of the hacker culture as we know it today can be conveniently dated to 1961, the year MIT acquired the first PDP-1.
Eric S. Raymond
It came about as follows: over the years when I was involved in dianetics, I wrote the beginnings of many stories. I would get an idea, and then write the beginning, and then never touch it again.
A. E. van Vogt
Man is wise and constantly in quest of more wisdom; but the ultimate wisdom, which deals with beginnings, remains locked in a seed. There it lies, the simplest fact of the universe and at the same time the one which calls forth faith rather than reason.
To the extent that I come from a deeply religious tradition and have been contending with those beginnings all of my life - that constitutes the subject of much of my early fiction.
Youth, what man's age is like to be, doth show; We may our ends by our beginnings know.
Fortunate people often have very favorable beginnings and very tragic endings. What matters isn't being applauded when you arrive - for that is common - but being missed when you leave.
Beginnings are always messy.
Science, almost from its beginnings, has been truly international in character. National prejudices disappear completely in the scientist's search for truth.
Irving Langmuir
It was about this time that I began experiencing the beginnings of my battles with an anxiety disorder. We were touring a lot and there were some developing personal problems within the band.
Jack Irons
Now it is established in the sciences that no knowledge is acquired save through the study of its causes and beginnings, if it has had causes and beginnings; nor completed except by knowledge of its accidents and accompanying essentials.
Good seasons start with good beginnings.
Nourish beginnings, let us nourish beginnings. Not all things are blest, but the seeds of all things are blest.The blessing is in the seed.
Muriel Rukeyser
For all the social changes in China can be traced to their early beginnings in the days when the new tools or vehicles of commerce and locomotion first brought the Chinese people into unavoidable contact with the strange ways and novel goods of the Western peoples.
We see the people that have got stars in their eyes, but if you've really got what it takes, you can get from, say the beginnings, to the top in about five years.
Trisha Goddard
Rome has grown since its humble beginnings that it is now overwhelmed by its own greatness.
Titus Livius
In its beginnings, music was merely chamber music, meant to be listened to in a small space by a small audience.
While tributes to Americans who had lost their lives in battle had been held in a number of towns across the nation, one of the more well-known stories about the beginnings of Memorial Day is the story about General John Logan.
From the end spring new beginnings.
As a child, I read science fiction, but from the very beginnings of my reading for pleasure, I read a lot of non-fictional history, particularly historical biography.
We have been helping, trying to help Afghanistan in many ways, even from the beginning of... the beginnings of the '20s, 1920s, when he we were fighting our own national struggle.
Bulent Ecevit
We saw in 2003 the beginnings of an outbreak of an illness called SARS. SARS ended up killing 800 people which is a significant number of deaths, but nowhere near as high as it could have been.
I sometimes think I might be autistic because I like to know - I need to know - my beginnings and my ends. I don't have to be in control of it, but I need to know what's going on.
The beginnings and endings of all human undertakings are untidy.
It is best to avoid the beginnings of evil.
Being on Broadway and getting a Tony nomination - this has been an incredible ride, from rather humble beginnings.
Kate Fleetwood
Human beings love stories because they safely show us beginnings, middles and ends.
I came from rather humble beginnings.
I do come from fairly humble beginnings.

redpajama_set_name: RedPajamaCommonCrawl


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This segment is part of the Coronavirus spotlight
How To Track And Stop The Spread Of The Coronavirus Outbreak
For many years before the coronavirus outbreak, face masks have been commonly used in East Asian countries, including for protection from pollution. Here, civilians wear surgical masks in the subway in Shanghai, China. Taken in January 2020. Credit: Robert Wei via Shutterstock
This story is part of Science Friday's coverage on the novel coronavirus, the agent of the disease COVID-19. Listen to experts discuss the spread, outbreak response, and treatment.
This week, the World Health Organization declared that the coronavirus outbreak—which began in Wuhan, China—is a public health emergency of international concern. Nearly 10,000 cases have been confirmed worldwide, as of Friday, January 31, 2pm Eastern. Chinese scientists sequenced the genome of the virus from some of the patients who were infected early on in the outbreak. Immunologist Kristian Andersen discusses how the genetics of the virus can provide clues to how it is transmitted and may be used for diagnostic tests and vaccines. Plus, infectious disease specialist Michael Osterholm talks about the effectiveness of quarantines and what types of measures could be put in place to halt the spread of the pathogen.
Editor's Note 1/31/2020: The case numbers of coronavirus has been updated as of 2:20pm Eastern, from 8,000 to nearly 10,000.
Update 2/26/2020: The photo caption has been updated to provide more context on the use of face masks in East Asian countries.
Get live updates on the outbreak in The New York Times.
Explore an interactive map of coronavirus cases so far.
Read about the containment process of the disease in The New York Times.
Read an explainer of how researchers are calculating and predicting spread of the disease in The Atlantic.
Learn more about how scientists are digging into the coronavirus genome for answers in The Scientist.
Get more information about the coronavirus from the World Health Organization.
Kristian Andersen
Kristian Andersen is an associate professor of Immunology and Microbiology at the Scripps Research Institute in La Jolla, California.
Michael Osterholm
Michael Osterholm is Director of the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota in Minneapolis, Minnesota.
IRA FLATOW: This is Science Friday. I'm Ira Flatow. The World Health Organization has declared the coronavirus outbreak that began in Wuhan China. Now it's a public health emergency of international concern. There have been nearly 10,000 confirmed cases worldwide. There are cases popping up outside of China. The first case of human-to-human transmission in the US has been reported.
So how do you fight a new virus like this one besides quarantine? Chinese researchers have sequenced its gene using this research. Can we piece together clues to how this new virus might spread, and possibly design a vaccine? Dr. Anthony Fauci, the director of NIH's National Institute of Allergy and Infectious Diseases says, "Research into a vaccine is underway and may be ready for human trials in as little as three months." What do you think? I don't know. That's what I want to ask my guests. Let me introduce them.
Kristian Andersen is an infectious disease researcher, associate professor of immunology and microbiology at Scripps Research Institute in La Jolla, California. Welcome to Science Friday.
KRISTIAN ANDERSEN: Hi, Ira. Thanks for having me.
IRA FLATOW: Nice to have you. Dr. Michael Osterholm is director of the Center for Infectious Disease Research and Policy, University of Minnesota in Minneapolis. Welcome back to Science Friday, Michael.
MICHAEL OSTERHOLM: Thank you, Ira.
IRA FLATOW: Let's talk about it. Kristian, you worked on analyzing the genomes of viruses to understand transmission. How do you use the genetic sequence we have to estimate the transmission?
KRISTIAN ANDERSEN: Yes. So we work on genomic sequences that are a sequence of the virus itself from patient samples. And we all rely on publicly available data, so all the data being produced by Chinese researchers and the CDC. And essentially what we're looking for are small differences in the genomes between different cases. So if you have patient one and patient two, chances are that there are slight differences in the genome of this particular virus. And we could then use that information to connect exactly how these virus are spread and how they're related. And therefore understanding the patient networks. And that allows us to look at things like what are the reservoirs, how many introductions have we had into the human population. How is the virus actually transmitting? And what is the timing of all these events?
IRA FLATOW: So have you been able to make progress then with this virus?
KRISTIAN ANDERSEN: . Yes so some of the earlier questions we were quite interested in was understanding what is the level of human-to-human transmission versus, for example, repeated spillovers from the animal reservoir. And what the data quite clearly shows is that it's a single event. So this is something that happened also getting from this data sort of mid-November to mid-December. So this virus jumped into the human population presumably from some sort of intermediate host. So we think the reservoirs are bats. But there's probably some other host involved. And then from that host into the human population.
IRA FLATOW: And now we see that there has been a secondary infection in the US. Someone who has the virus infected someone else. Do you learn something about transmission in this case?
KRISTIAN ANDERSEN: Yeah. So I think especially very early on, there was sort of the belief that the level of human-to-human transmission was probably pretty low because most cases were linked to this one market in Wuhan. So the belief was that probably the human-to-human transmission is limited. But what the sequencing really shows is that probably from day one, this is really something that has been sustained human-to-human. So having secondary transmissions outside of China is probably what we would expect. I think a very important question here is that how many of these are we actually going to see.
IRA FLATOW: And so you would expect to see more of this. Of course one would be an outlier, right?
KRISTIAN ANDERSEN: Correct, yes. We would expect to see more.
IRA FLATOW: Michael, what's your reaction to this?
MICHAEL OSTERHOLM: Well, first of all, I think the geneticist that I have worked on this virus have done an amazing job in a very short period of time. And I congratulate Dr. Andersen and his colleagues. And I think his conclusion about its very recent appearance is right on the mark. Epidemiologically looking at how disease is spread, this has been nothing short of a remarkable experience. I've worked on both SARS and MERS outbreaks of another coronavirus infections where we really saw a much more reduced human-to-human transmission with occasionally a super spreader, or someone who would spread it to a lot of people.
What we're seeing here is really much more akin to what we would see with influenza virus transmission. It's very dynamic. We know we have multiple generations of transmission in China. And in fact now we have clusters of outbreaks in places like the Guangdong province that they don't even trace back to Wuhan anymore. They're that far removed. And it's now in all 33 provinces and administrative districts of China. It's now in over 20 countries. This is almost what you would have expected to see if you went back and looked at 2009 H1N1 influenza transmission when that pandemic strain emerged. So this is what has us very concerned, is the dynamics here.
The case numbers, Ira, that you mentioned and we talk about really represent just a small fragment of the number of cases in large part because the number of test kits and the availability to access testing in China is extremely limited right now. They're working on that. They're doing everything they can to increase that. But we have estimates now based on our studies from inside of China– one that just came out this morning from University of Hong Kong that at least 75 to 100,000 people alone are infected in Wuhan this week. So you can see that this is a very, very dynamic situation, and frankly one that I think the only way I see this going is that the whole world will potentially look like China over the next 6 to 12 months.
IRA FLATOW: That's alarming. I don't mean that you're trying to be an alarmist. But that's an alarming prediction.
MICHAEL OSTERHOLM: Well, it's what we're seeing. And again we come back to the dynamics of the transmission. And it matches up. I have to tell you. We have many sources on the ground in China. And today we actually are seeing emergency rooms that are so overwhelmed that they're not taking any additional patients into the emergency rooms.
People are not even able to access health care. It's that major of a health issue. So this is something that, again, none of us would necessarily have anticipated with a coronavirus infection that something might act like an influenza virus. I think the key thing though, however, is not just how much is it transmitting, but how serious is the illness. And while the data are still yet really being collected in a way that is most meaningful early in an outbreak, right now the case fatality rate that we see into the well collected data sets is about 2%.
Now compare that to about 0.1% for seasonal flu in a bad flu year here in the United States. So that's almost 20 times higher. Now will that continue? We don't know. But where we have this virus transmitted, we know we're going to have a lot of serious illness. You also mentioned just the case numbers, but today they also reported just in China 1,527 people are in critical condition in hospitals, which will surely contribute to those death numbers over the days ahead,
IRA FLATOW: Dr. Andersen, do you share this fear?
KRISTIAN ANDERSEN: Yeah. Yeah. I definitely share something. I think talking about case fatality rates, which in my opinion, really can't sort of accurately be estimated at this stage– I think it's a little too early. But I totally agree that the number of severe cases, especially is pretty high. It's about 15% or so of all cases seem to be severe. The sort of uncertainty we have here, too, is that we don't actually know what is classified as a severe case. Right? So there could be many different levels of severity that might be classified as such. But if you look at just the number of deaths, for example, which is about 200, and the number of recovered patients, which is also about 200, presumably there's still a lot of patients in the hospital. And that's based on those kinds of things. And I think it's too early to try and estimate the case fatality rate.
IRA FLATOW: Right.
KRISTIAN ANDERSEN: Although I do absolutely agree with Michael. It's probably going to be in the lower single digits.
IRA FLATOW: All right. Let's talk about how we can attack this. Dr. Anthony Fauci of NIH, I said before, says a vaccine may be ready for human trials in about three months. Michael, is that overly optimistic, do you think?
MICHAEL OSTERHOLM: Well, I don't think it's overly optimistic. I think that Tony is right on that such a vaccine will be in trials. But let's just be realistic. I think the fact that we will have a vaccine that will somehow impact this outbreak is a smaller chance than us relocating the Grand Canyon to Minnesota. When we look at all of these outbreaks we've had over the years– SARS. We have MERS, Zika.
I can go through the whole laundry list. And I chair five of the working groups at the WHO right now on the vaccine road– our research and development roadmaps. And we have vaccines. But to get them licensed, to get them approved, to get manufacturing plant capacity, to get someone to actually buy them takes years and years.
An Ebola vaccine even took years after the outbreak. But more importantly, it had a great deal of work done beforehand because the biodefense industry and the governments of the US and Canada invested a great deal in Ebola vaccine because of the concern about a bioterrorism agent. We haven't seen a similar investment. And remember we've known about coronaviruses and the need for vaccines dating back to 2003. And we haven't had one. So I think that this vaccine work is absolutely critical. We need to bring it to completion as quickly as we can. But we can't at all assure the public that it's going to have any impact in the immediate days or months ahead.
IRA FLATOW: But Ebola was contained eventually. Are there lessons we can learn about now that we– because we are fighting this that we can use for the coronavirus?
MICHAEL OSTERHOLM: Not really, in the sense that it's now a very different transmission agent. The Ebola virus was transmitted with body fluid contact. Where this is just breathing somebody else's air nearby. One thing we did learn was that when there was an attempt to quarantine people early on in the outbreak in the major cities and keep them basically in a one given neighborhood, that backfired immediately and people stopped doing any kind of quarantining. I think we have some lessons to learn from China.
I would be one to say that I think that the major lock-down that was done on 65 million people in the Hubei Province where Wuhan is located actually backfired because we know, for example, that when the announcement that this was going to happen took place, it didn't take place for almost 36 hours after they announced it. And at least five million people left Wuhan and went to wherever in China, which was just like inventing a viral machine gun to spread it around the country.
IRA FLATOW: I see. I see. Kristian, former FDA commissioner Scott Gottlieb writes in The Wall Street Journal that there is a reliable, fast, and cheap PCR-based test made by Roche that could be ramped up. Right now you have to send the samples to the CDC. They do the test. And by that time, it could be hours, days, whatever to get a result. Do you think that if we had a faster method of diagnosing the disease in people, it would be helpful?
KRISTIAN ANDERSEN: So yeah, definitely. I mean fast diagnosis is absolutely critical here. So we can isolate patients that are known to have the infection. I think that first of all these diagnostics were made based on these first sequences that were released from Chinese investigators and made exceptionally rapidly. Now these types of tests are fast. I mean, I assume most labs in China by now we'll have these up and running. And one can expect some sort of assault from that within, I would say, four to six hours or so.
So I think as the capacity on that is being ramped up, yes, in this country it's for now only the CDC, but I'm sure that the different state labs and so on are also getting geared up to actually run these PCRs. So I think that they're definitely critical so. Again, we can come in with the isolation.
IRA FLATOW: Yeah. OK. So let's say you have these. You have these tests, and you use them diagnostically. And you find out that people are infected here in the States– just hypothetically. Are the hospitals ready to deal with a flood of patients that might come in, even just people who are worried about whether they have it or not? Kristian?
KRISTIAN ANDERSEN: Yeah. So this is always a good question where flu epidemics, flu outbreaks happen every year. Right? And then the hospitals are able to deal with this. And I totally agree with Michael that a lot of this looks like flu. It really depends on how many cases we are going to see. For sure in China right now, there's– in Wuhan and other places, there's too many patients for capacity. And it was the same thing that we saw in West Africa, for example, in the DRC, too, during the Ebola outbreaks. So it's definitely a real concern, is that are we ready with this.
IRA FLATOW: Michael, do you agree that we're just not prepared for this?
MICHAEL OSTERHOLM: We're not. And I think the important message here is that we as a country have a health care system today that in many ways is hanging on by a string. The emergency rooms, even in a moderate flu season, let alone a severe one are severely challenged– the number of beds that are available. We have and have been doing surveys looking at the availability of protective equipment for health care workers. And hospitals are not able today to afford to stockpile this equipment. They hopefully will get it on a just-in-time delivery basis. Well, now when everybody wants it, manufacturers are in no position to provide it like it is.
One of the big challenges right now in Wuhan and other parts of China is health care workers are actually being made to work in the absence of any available protective equipment because they've run out. And so we do need really to have our health care systems in this country really dust off the book and look at this very carefully for the future.
IRA FLATOW: I'm Ira Flatow. This is Science Friday from WNYC Studios, talking about the outbreak of the coronavirus with Kristian Andersen and Michael Osterholm. And Michael, whenever you talk about– I think dusting off their equipment is a euphemism for spending money and expanding their facilities.
MICHAEL OSTERHOLM: Yeah. In this case, I said dusting off the playbook, meaning that–
IRA FLATOW: Oh, I see.
MICHAEL OSTERHOLM: –the hospitals actually have preparedness documents that have been worked on over the years. And they all want to do the right thing. But when the number of patients outstrip the number of beds, you don't have adequate number of health care workers. You don't have protective equipment, which a very difficult situation becomes even more difficult. And that's, I think, what we're worried about right now. And a number of groups are trying to address this. But it, depending on how soon this might arrive here in any meaningful way, is going to depend in part how prepared we are.
IRA FLATOW: Well, one last question. When do we know we've reached the tipping point where things are getting bad in this country? What are the signs? And the cases are what? Michael, what would we look for?
MICHAEL OSTERHOLM: I say this jokingly, and it's not meant to be disrespectful. But maybe when China Airlines refuses to fly to the United States, we know that we hit a problem here. I think that at this point, it's really going to be a matter of filing our emergency rooms and outpatient clinics to see where we're at, and just how many beds are available in any one given community. That's when we'll know.
KRISTIAN ANDERSEN: Kristian? Yeah. And I think like one of the key things to look out for is that how many transmissions do we have outside China, not just in the United States, but also in Europe and other places where the virus is being imported– right– by the travelers. And the question is, how many cases does that actually lead to? Is it a very small number of cases so we can hope to stop the virus? Is it going to be a large number of cases?
And I should say just because I agree with the whole, like the vaccine is too far out, but one thing that is critically important I could see that could influence this is the repurposing of pre-existing drugs– the drugs that we already have that fully approve other indications that might actually come in and be helpful in this particular outbreak.
IRA FLATOW: Such as?
KRISTIAN ANDERSEN: This could be influenza drugs, drugs that have been developed for other viruses, just general antivirals, for example. Remdesivir is one of the ones out there that will presumably go into clinical trials as part of this outbreak.
IRA FLATOW: Thank you, gentlemen, for informing us. Kristian Andersen, Infectious Disease Researcher, Associate Professor of Immunology and Microbiology at Scripps Research Institute in La Jolla. Michael Osterholm, Director of the Center for Infectious Disease Research and Policy, University of Minnesota in Minneapolis. Thank you all for being very informative for us today.
MICHAEL OSTERHOLM: Thank you.
KRISTIAN ANDERSEN: Thanks, Ira.
IRA FLATOW: You're welcome.
Meet the Producers and Host
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Ira Flatow is the host and executive producer of Science Friday. His green thumb has revived many an office plant at death's door.
How To Catch The Flu (Under The Lens)
Since 1983, electron microscopist Cynthia Goldsmith has captured the beauty of deadly viruses.
New Virus Paralyzes Chinese Cities
Officials in China have quarantined two large cities, where some 20 million people live, over fears of a novel virus outbreak.


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The long and short of it
Mike Prisuta
Steelers.com
It's not what opposing defenses have figured out, offensive coordinator Randy Fichtner maintained, it's what the Steelers' offense has seemingly forgotten of late.
"If you're gonna throw the football, you gotta catch the football," Fichtner observed prior to practice today.
Dropped passes have been a problem, particularly against Baltimore on Dec. 2 and Washington on Dec. 7 and to a lesser extent last Sunday night against Buffalo.
The Steelers beat the Ravens, 19-14, but scored less than 20 points for the first time after averaging 29.9 points through their first 10 games.
Since then they've fallen to Washington, 23-17, and Buffalo, 26-15.
"We talk about running the ball and efficient runs are 4-plus (yards)," Fichtner continued. "If we're gonna throw short and have the opportunity to run long, the short aspect of that has to be caught for 4 and whatever we get after that is bonus. That's just kinda keeping you on schedule.
"I wouldn't say (defenses have) caught onto it; it's just a matter of we gotta make our plays."
That includes becoming more efficient throwing the ball down the field than the Steelers have been, particularly during their just-completed stretch of three games in 12 days.
"Whatever you missed in that little three-week time of walk-through, playing, not playing, games being moved, I think back to just repetition of throwing and catching for our guys, that's not an excuse but if there would have been one area you would have backed off of it would have been potentially throwing the ball down (the field), deep balls," Fichtner said.
That, too, is being addressed in practice in advance of Monday night's visit to Cincinnati.
"Having this week where we actually get back to a semblance of having a real week, we worked on that yesterday, we'll continue today," Fichtner said. "We get a couple more good days of practice (before the Bengals game) so it'll be an area of emphasis.
"We'll throw deep balls today. We'll do it in individual (periods) and there won't be a defender on them and we won't tangle anyone's legs up and be falling down 30 yards down the field. But it does give you that sense of timing and rhythm again and, potentially, just the idea of seeing the throws and catch and the adjustment by a receiver.
"We know we have to get back to that. We know that in any one given year since I've been here the opportunity to throw the ball past the sticks in possession downs is critical to us. And being able to take shots on first and second down has to be completed at a greater rate."
The goal is more consistency in whatever the Steelers choose to do offensively.
"We'd love to be more balanced," Fichtner said. "We'd love to be able to run it when we want to run it, throw it when we want to throw it and execute in the possession downs and red zones and be consistent. I think what gets disappointing is two weeks ago we were inconsistent in the red zone, last week we were consistent in the red zone; we just weren't down there enough. Three weeks ago we were really great on third down and then last week we weren't good on third down.
"We don't, probably, have to be the best at any one of those but we can't be the worst once and then the best the next day. Consistency has to start coming through. I would bet if we went back even early in the season it wasn't always like that either, just consistent in every facet of the game. But it felt like you were more medium than you were hot and cold.
"What's missing right now is just maybe a little more consistently catching the football."
PHOTOS: Practice - Bengals Week - Day 1
The Steelers prepare for the Week 15 matchup against the Cincinnati Bengals
Pittsburgh Steelers Head Coach Mike Tomlin practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Caitlyn Epes/Pittsburgh Steelers
The Pittsburgh Steelers practice at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers safety Minkah Fitzpatrick (39) practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers Quarterback Coach Matt Canada practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers linebacker T.J. Watt (90) practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers safety Antoine Brooks Jr. (25) practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers safety John Battle (35) practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers linebacker Olasunkanmi Adeniyi (92) practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers safety Jordan Dangerfield (37) practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers defensive tackle DeMarcus Christmas (93) practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers defensive end Stephon Tuitt (91) practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers linebacker Alex Highsmith (56) practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers cornerback Joe Haden (23) practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers Inside Linebacker Coach Jerry Olsavsky practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers Defensive Line Coach Karl Dunbar practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers linebacker Avery Williamson (51) practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Pittsburgh Steelers linebacker Marcus Allen (27) practices at the UPMC Rooney Sports Complex preparing for a Week 15 matchup against the Cincinnati Bengals, Wednesday, Dec. 16, 2020 in Pittsburgh, PA. (Caitlyn Epes / Pittsburgh Steelers)
Grinding it out
Steelers staying persistent with Najee Harris, more impactful running game
Steelers may need more than Najee Harris against run-stuffing Ravens
It's Ben Roethlisberger's accuracy that stands out most to Matt Canada
Help on the way?
OC Matt Canada 'hopeful' about guard Kevin Dotson's potential return
'We gotta be a better team defense'
Rushing yards surrendered inviting for Titans even without Derrick Henry
Lending a helping hand
New additions to the lineup make a good first impression on defense
'We gotta be better'
Offense in general, line in particular trying to rediscover winning formula
All aboard?
Matt Canada: Ben Roethlisberger 'preparing like he's going to be there'
'You don't wanna see that mess'
Steelers coping with advantage being exploited by offensive tackles
Steelers' defense familiar with threat running quarterbacks present
Move-the-sticks proposition
Goal in Cleveland will be to make Browns a passing team on third downs
Tackling the issue
Teryl Austin said he is working on fixing the issue with tackling in the secondary through drills in practice


text:
The optimization method for synthesis of technetium-99m-luteolin as radiotracer in the development of cancer drugs from flavonoid
Danni Ramdhani1, Maula Eka Sriyani2, S Fairuz Nabila1
1 Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, Indonesia
2 Applied Nuclear Science and Technology Center (PSTNT), National Atomic Energy Agency (BATAN), Bandung, West Java, Indonesia
Date of Submission 29-Oct-2019
Date of Decision 30-Dec-2019
Date of Acceptance 22-Jan-2020
Mr. Danni Ramdhani
Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Padjadjaran University, Sumedang 45363, West Java
DOI: 10.4103/japtr.JAPTR_161_19
The aim of this study is to find the optimum conditions of labeling luteolin flavonoid compounds with technetium-99m (99mTc) to meet the purity requirements stated in the United States Pharmacopeia. This compound is expected to be a potential radiotracer compound for diagnosing cancer. The optimization method in labeling luteolin with technetium determines the parameters such as pH, SnCl2.2H2O, genistein concentration, and incubation time. Optimization results of Technetium-99m-luteolin labeling obtained optimum pH conditions 8, the amount of SnCl2.2H2O as a reducing agent 60 μL, the optimum amount of luteolin 6 mg/ml, and the optimum incubation time is 30 min. This optimum condition obtained a99mTc-Luteolin radiochemical purity yield of 94.15%. The radiochemical purity percentage of the99mTc-Luteolin compound has fulfilled the requirements listed at United States Pharmacopeia, which is ≥90%.
Keywords: Luteolin, radiochemical purity, radiotracer, technetium-99m, technetium-99m-genistein
Ramdhani D, Sriyani ME, Nabila S F. The optimization method for synthesis of technetium-99m-luteolin as radiotracer in the development of cancer drugs from flavonoid. J Adv Pharm Technol Res 2020;11:59-63
Ramdhani D, Sriyani ME, Nabila S F. The optimization method for synthesis of technetium-99m-luteolin as radiotracer in the development of cancer drugs from flavonoid. J Adv Pharm Technol Res [serial online] 2020 [cited 2022 Jan 18];11:59-63. Available from: https://www.japtr.org/text.asp?2020/11/2/59/283073
Cancer is a term that describes a disease with a condition where there is uncontrolled cell growth that goes beyond its habits and can spread and attack to other organs. In 2018, cancer is estimated to be the second leading cause of death in the world with 9.6 million cases.[1]
Luteolin is a compound conjugate acid of a 2-(3,4-dihydroxyphenyl)-5-hydroxy-4-oxo-4H-chromen-7-olate luteolin-7-olate (1-). Luteolin is one of the potential flavonoids that has been proven to be efficacious as an antioxidant, anti-inflammatory, and for cancer treatment.[2],[3] Luteolin is reported to be able to inhibit the catalytic activity of topoisomerase 1 which is a cancer-inhibiting mechanism.[4]
Radiopharmaceuticals are radioisotopes conjugated with biological molecules capable of targeting organs or cells in specific tissues. This radioactive drug can be used for diagnosis and increasingly, for the treatment of diseases. The most widely used radioisotope in diagnostic nuclear medicine is technetium-99m (99m Tc). This radioisotope can bind to certain molecules, allowing the diagnosis of many diseases, including certain types of cancer.99m Tc is a radioisotope that can emit pure gamma rays with energy of 140.5 keV, which has a short half-life of about 6 h, does not emit charged particle radiation, can be obtained in the form of free carrier, and can bind to many compounds.[5]
The formation of compounds labeled between radioisotopes and ligands for cancer diagnosis purposes must have the specificity to recognize a receptor. Luteolin is an isoflavone compound that has been shown to have anticancer activity through the inhibitory mechanism of topoisomerase I catalytic activity. In humans, the levels of topoisomerase I have been shown to be elevated in colorectal tumors compared to normal colon mucosa.[6]
The purpose of this research was to determine the optimization parameters for the synthesis of99m Tc-genestein compounds which have the potential as radiotracer compounds for cancer.
The tools used in this study were a set of paper chromatography, dose calibrator (Victoreen®), micropipette (Eppendorf®), analytic balance (Mettler Toledo® Type AL204), oven (Memmert®), single channel analyzer (SCA) (ORTEC®), and syringe (Terumo®).
The materials used were luteolin (Sigma-Aldrich®), acetone (Merck®), aquabidestilata (IKA Pharma®), DMSO, HCl 0.1 N, Na. 99m TcO4− (PT. Ansto), Physiological NaCl (IKA Pharma®), NaOH 0.1 N, universal pH indicator (Merck®), KLT SGF-254 (Merck®) plate, instant thin layer chromatography-silica gel (ITLC-SG) (Agilent Technologies®), and SnCl2.2H2O plates (Sigma-Aldrich®).
Optimization of pH
Determination of the optimum pH conditions on the99m TcO4− labeling method was carried out using five variations of pH 6, 7, 8, 9, and 10. The composition of each formula is shown in [Table 1]. Luteolin solution was added with 60 mL of SnCl2.2H2O solution, then the pH of the solution was adjusted by 0.1N NaOH or 0.1N HCl. After the pH was reached,99m TcO4− the solution was added, and the solution was incubated for 30 min. The solution formed was tested for the purity of the complex formed by dropping it on the thin layer chromatography (TLC) plate SGF-254 and ITLC-SG.[7]
Table 1: The optimum pH and radiochemical purity of99mTc luteolin labeled compounds
Optimization of SnCl2.2H2O
In determining the optimum conditions for SnCl2H2O, there is an additional treatment in the form of a vial vacuum. It aims to prevent oxidation by O2 before reacting with99m TcO4−. Determination of the amount of SnCl2.2H2O as a reductor is done using six variations of the amount of SnCl2, namely 40, 50, 60, 70, 80, and 90 μL with the formula as shown in [Table 2] and [Figure 1]. The test is carried out at the optimum pH, which is pH 8.[8]
Table 2: Composition of formulas for optimization reducing agent of SnCl2.H2O
Figure 1: The optimum of SnCl2.2H2O and radiochemical purity of Technetium-99m Luteolin
Optimization of concentration luteolin
The optimization conditions of the luteolin using five variations of concentration: 3, 4, 5, 6, and 7 mg/mL.
The SnCl2.2H2O reducing agent was added, and99m TcO4- amount of 500 μL. Two milliliters of physiological NaCl was added to each solution and then incubated for 20 min. Evaluation of the99m Tc-Genistein complex formed is evaluated by measuring the radiochemical purity by dripping each solution on the KLT SGF-254 and ITLC-SG plates.[7]
Optimization of incubation time
The procedure for determining the optimum incubation time for luteolin marking with99m TcO4− used five variations of incubation time, namely 0, 15, 30, 45, and 60 min. Vials that already contain 100 μL luteolin solution and SnCl2.H2O solution are then adjusted to the optimum pH, which is pH 7. The determination of the purity of99m Tc-Luteolin was tested with TLC SGF-254 and ITLC-SG plates.[7]
Calculation of technetium-99m-luteolin purity percentage
The method for testing the purity of compounds of99m Tc-Luteolin uses TLC and is measured by SCA. The method consists of a stationary phase TLC SGF-254 and ITLC-SG plates. The mobile phase is ethanol: water: ammonia (2: 5: 1) and NaCl physiological solution. This mobile phase solution is called C1.[7]
The equation for calculating the purity of99m Tc-Luteolin compounds is as follows.[9]
Calculation of labeled compounds technetium-99m-Luteolin
%99m Tc-Luteolin = 100% − (%99m TcO2+ %99m TcO4−).
The99m Tc-Luteolin compound is formed from a coordinated covalent bond between99m Tc as a metal and luteolin as a marker or ligand compound. The99m Tc-Luteolin complex formed through the following reactions:
Luteolin + Sn2++99mTC(VII)O4
→99mTC(IV)Luteolin + Sn4+ +99mTcO4
In this reaction, the complex compound99m Tc-Luteolin is produced as the main product, and also99m TcO2 and99m TcO4− compounds which are radiochemical impurities.[9]
Labeling of luteolin using radioactivity makes it possible to monitor luteolin compounds in the body using a gamma camera that can read radiation exposure provided by technetium. Luteolin is known as a good antioxidant and induces apoptosis in tumor cells and has a valuable effect in cancer prevention and therapy. Luteolin can inhibit the formation of superoxide, namely by inhibiting the activity of xanthine oxidase. In addition, luteolin can also provide antioxidant effects by blocking or producing more endogenous antioxidants such as catalase, glutathione-S-transferase, and glutathione reductase. Therefore, this compound is expected to function as a potential radical scavenging radiotracer.[10] The formation of the99m Tc-genestein complex involves electron donors. The structure of luteolin is shown in [Figure 2].
Figure 2: Chemical structure of luteolin[11]
The radiochemical purity test of a99m Tc-Genistein can be measured by the thin layer chromatography method. The stationary phase used is TLC SGF-254 with the mobile phase of physiological NaCl solution. The separation of99m TcO4−, 99m TcO4− impurity will move toward the peak, while99m Tc-genistein will remain at the spot point, ITLC-SG stationary phase with C1 mobile phase will separate99m TcO2. The99m TcO2 impurity will remain at the spot point, and99m Tc-genistein will move toward the peak.[9]
Test results on pH optimization
pH conditions are very influential in the formation of the Tc-Luteolin complex. In addition, the pH conditions will determine the optimum conditions of the SnCl2.2H2O reducing agent.[7] The results for pH optimization testing are shown in [Table 1] and [Figure 3].
Figure 3: The optimum pH and radiochemical purity of technetium-99m-luteolin labeled compounds
The optimum pH was obtained at pH 7, where the highest radiochemical purity was obtained, which was 97.15%. Under an alkaline pH condition of 8, more TcO4 impurities will be produced. At high pH conditions, Sn (II) will be hydrolyzed, and hence that the ability as a reducing agent decreases. In acidic pH conditions, more impurities will be produced99m TcO2 because the reducing agent SnCl2.2H2O will reduce more strongly in acidic conditions.[7],[8],[12]
Test for optimum concentration of SnCl2.2H2O
The amount of SnCl2 reducing agent used must be sufficient for the reaction to run well. The amount of impurities TcO4− and TcO2− will affect the purity parameters of99m Tc-Luteolin. The amount of SnCl2 that is too little cannot reduce99m Tc7 + well and hence that it will produce a lot of TcO4−. Meanwhile, if the amount of SnCl2 is excessive, it can produce a lot of99m Tc4 + which will increase the amount of TcO2− impurity.[13] The results for the optimization of SnCl2.2H2O solutions are shown in [Table 2] and [Figure 1].
Optimization conditions of SnCl2.2H2O solutions were 30 μl with a purity of 90.84% ± 2.38%, with impurities of99m TcO2 (5.06% ± 1.13%), and99m TcO4− (4.10% ± 0.94%). If the amount of the solution of SnCl2.2H2O is more partial, hydrolyzed SnCl2 forms its hydroxide, and binds with99m Tc-reduced to form99m TcO2 colloid, so that the amount of impurity will be more99m TcO2.
Test for the optimum concentration of luteolin
The number of ligands (Luteolin) that are not optimal will cause an increase in the number of impurities and reduce the percentage purity of compounds marked99m Tc-luteolin. In testing this parameter, five variations of the amount of luteolin are used: 3, 4, 5, 6, and 7 mg/mL and with the formula shown solutions are in [Table 3] and [Figure 4].
Table 3: Composition of formulas for optimization of concentration of luteolin
Figure 4: The optimum of luteolin and radiochemical purity of technetium-99m luteolin labeled compounds
Optimization of the amount of luteolin with the highest percentage of purity is found in the amount of luteolin 6 mg/mL with a percentage of 94.15%. The use of luteolin amounts <6 mg/mL will reduce the percentage purity of compounds marked99m Tc-Luteolin as the amount of TcO2− impurities increases.[9],[12]
Test for optimum incubation time
The duration of incubation time can affect the optimum formation of compounds marked99m Tc-luteolin. Adequate contact time can affect the reaction between SnCl2,99m Tc and luteolin. Variations of incubation time used in this study were 0, 15, 30, 45, and 60 min.[12] The formula is shown in [Table 4] and [Figure 5].
Table 4: Composition of formulas for determining optimization of incubation time
Figure 5: The optimum of incubation time and radiochemical purity of technetium-99m luteolin labeled compounds
Optimization of incubation time was obtained at 30 min, with a purity percentage of 93.84%. This is because at the incubation time of 30 min is obtained at least from the amount of TcO4− impurities.
Optimization of the conditions in the labeling of the99m Tc-Luteolin compound obtained a 94.15% radiochemical purity, where this condition fulfills USP requirements, which must be ≥90%.[14]
The author also expresses the deepest gratitude and appreciation thanks to Fairuz Nabilah Syafarina and Chair of the Center for Applied Nuclear Science and Technology (PSTNT), National Nuclear Energy Agency, Bandung, for collaboration in this research.
World Health Organisation: International Agency for Research on Cancer. Latest Global Cancer Data: Cancer Burden Rises to 18.1 Million New Cases and 9.6 Million Cancer Deaths in 2018, The United Nations; 2018. Available from: https://who.int/cancer/prglobocanfinal.pdf. [Last accessed on 2019 Oct 30].
Wu CC, Fang CY, Hsu HY, Chuang HY, Cheng YJ, Chen YJ, et al. EBV reactivation as a target of luteolin to repress NPC tumorigenesis. Oncotarget 2016;7:18999-9017.
Jang S, Kelley KW, Johnson RW. Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. Proc Natl Acad Sci U S A 2008;105:7534-9.
Chowdhury AR, Sharma S, Mandal S, Goswami A, Mukhopadhyay S, Majumder HK. Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. Biochem J 2002;366:653-61.
IAEA. Technetium-99m Radiopharmaceuticals: Status and Trends. Viena: IAEA; 2009.
Phaniendra A, Jestadi DB, Periyasamy L. Free radicals: Properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem 2015;30:11-26.
Komárek P, Kleisner I, Komárková I, Konopková M. The use of redox polymers in labelling procedures of proteins and peptides with 99mTc. II. Technique of preparation of kits for protein labelling by 99mTc and its effect on the stability and radiochemical purity. Nucl Med Rev Cent East Eur 2000;3:69-72.
Misyetti. Instability study of radiopharmaceutical dry kits signed99m Tc viewed from chemical and physical aspects. Indonesia J Nucl Sci Technol 2006;7:65-81.
Owunwanne A, Patel M, Sadek S. The Handbook of Radiopharmaceuticals. London: Chapman and Hall Medical; 2012.
Bandyopadhyay M. Incorporation of herbs into Sandesh, an Indian sweet dairy product, as a source of natural antioxidants. Int J Dairy Technol 2007;60:228-33.
Lin Y, Shi R, Wang X, Shen HM. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr Cancer Drug Targets 2008;8:634-46.
Sayed HJ, Amirhossein A, Reza T. Preparation and Biodistribution Study of Technetium-99m-Labeled Quersetin as a Potential Radical Scavenging Agent. Budapest, Hungary: Springer Science; 2006.
Gopal SB. Fundamental of Nuclear Pharmacy. 5th ed. New York: Springer; 2003. p. 83, 113, 114, 288.
United States Pharmacopeial Convention. Official Monographs: USP 28. Technetium 99m Tc-Pertechnetate Injection (Sodium). United States Pharmacopeia (USP) 28-National Formulary (NF) 23, Rockville, Marland, USA., 2005. p. 1861.
1 Assessment of Re/[99mTc]Tc-cirsiliol as a potential radiotracer to detect melanoma tumor
Maryam Ghalbi Ahangari,Mahdi Moridi Farimani,Mostafa Erfani
Journal of Radioanalytical and Nuclear Chemistry. 2021;
Ramdhani D
Sriyani ME
Nabila S F
radiochemical purity
radiotracer
technetium-99m
technetium-99m-genistein


text:
This is a list of nations that have participated in the Commonwealth Games between 1930 and 2018. Participation in the Games is limited to member states of the Commonwealth of Nations and their territories. Although there are 56 members of the Commonwealth of Nations, 72 teams currently participate in the Commonwealth Games as a number of dependent territories compete under their own flags. The four Home Nations of the United Kingdom (England, Scotland, Wales and Northern Ireland) also send separate teams.

Only six teams have attended every Commonwealth Games: Australia, Canada, England, New Zealand, Scotland and Wales. The only Commonwealth members to have never taken part are Gabon and Togo, both of which joined the organisation in June 2022.

List of nations

This list includes all 72 current CGAs as well as a number of obsolete CGAs, arranged alphabetically. The three-letter country code is also listed for each CGA. Several nations have changed during the Games' history; name changes are explained by footnotes after the nation's name, and other notes are explained by footnotes linked within the table.

Table legend

Alphabetical list

Notes

Name change notes

Participation notes

See Also

Member states of the Commonwealth of Nations
List of CGF country codes
List of participating nations at the Summer Olympic Games
List of participating nations at the Winter Olympic Games

References

Sources

participating nations
Nations at the Commonwealth Games
participating nations

redpajama_set_name: RedPajamaWikipedia


Nest building is a vital part of parental care, but the impacts of the variation in nest building behavior on reproductive success in birds is not well understood. We address the effects of nest quality on incubation behavior and reproductive success in Carolina chickadee (Poecile carolinensis) females. In Carolina chickadees, only females build nests, incubate eggs, and brood young nestlings. Well-constructed nests can reduce the negative effects of cooling on eggs and nestlings. Extensive cooling can result in delayed embryonic development, hatching asynchrony, or hatching failure. Very young nestlings also depend on brooding for proper thermoregulation. However, females face tradeoffs between self-maintenance and incubation. We test the hypothesis that investment in high quality nests will result in higher reproductive success. Throughout spring and summer 2016, we monitored nest boxes in Jackson and Macon counties, N.C. for reproductive activity. For completed nests, we recorded nest dimensions and installed two ibuttons (thermal data logger) inside each nest box to record nest and ambient temperatures. Comparisons between changes in nest temperature relative to ambient temperature allow us to estimate the time females spent incubating. Nestlings were weighed every-other-day between days 2- 12 and monitored for evidence of fledging. We will use growth rates of nestlings and fledging success as estimates of reproductive success. Faster growth rates indicate higher probability of post fledging success. Upon fledging, all nests were collected and air dried. Nest quality is estimated by dry mass and dimensions. We predict that higher quality nests require shorter periods of incubation but yield higher reproductive success.
Ballance, Traci Erin and Ballentine, Barbara (2017) "EFFECTS OF NEST BUILDING BEHAVIOR ON INCUBATION AND REPRODUCTIVE SUCCESS IN CAROLINA CHICKADEES POECILE CAROLINENSIS," Georgia Journal of Science, Vol. 75, No. 1, Article 43.


For my third Favorite Things giveaway, I am bringing you my all time favorite running shoe, the ASICS Gel Nimbus 17. I started running in the Nimbus 13 and have owned every version of it since.
The shoe has evolved over the years to what I think is the perfect running shoe and if you don't believe me, Runners World awarded it the 2015 Editors Choice.
The Gel Nimbus 17 went through a major overhaul from the previous model. The shoe was built specifically for neutral runners and underpronators and has gender specific cushioning. The women's model features a lower density top layer in the midsole, allowing female athletes to better enjoy the benefits of midsole compression. The ladies version also has 3mm of additional height to help relieve Achilles tension.
The Nimbus 17 is the lightest Nimbus to date, weighing in at only 8.8 oz for ladies and 10.8oz for men. It's the best of both worlds, a cushioned lightweight shoe. This is all thanks to FluidRide® - which provides the ultimate combination of bounce back and cushioning properties with reduced weight and exceptional durability. The Nimbus 17 also offers Rearfoot and Forefoot GEL® Cushioning Systems, which reduces shock during impact and toe-off phases.
I am giving away 1 pair of ASICS Gel Nimbus 17 as part of my Favorite Things giveaway. Let me know in a comment below what your first running shoe was. Be sure to track your entry through the rafflecopter widget below. It will also open up additional ways to gain entries into the contest by visiting ASICS on Twitter and Facebook. - and be sure to check out their BESTivus holiday promotion which began today!
ASICS will offer one item each at a drastically reduced price for the next 12 days. Day 1 is Mens and Womens running jackets for up to 65% off, including my favorite, the Storm Shelter!
Also be sure to check out the rest of week 1 Giveaways!
Asics gel noosa were my first pair.
My first running shoe was a Mizuno. Have had many since then. Hoping Asics will help me run again after my Achilles surgery.
My first shoe was Asics but I now run in Brooks. Most others give me blisters. I'd be willing to try again though.
Asics Nimbus were my first pair. Loved them!!!
Mine we an Asics shoe as well. I have no idea the name but being that it was in the aught-2000's the shoe was bulky, white, and the Asics logo was blue. I actually only donated those shoes about 8 months ago. I found them collecting dust in the far back corner of my closet!
My first pair of running shoes were brooks...they were heavy but I loved them at the time!
A pair of Nike shocks. I probably could have made a matter match, but live and learn.
I think my first pair of running shoes were Nike.
I think it was a pair of Saucony brand.
This girl just need a pair of good shoes.
I had an old pair of Nike running shoes back in the day, they served me well but now I'm sure I'd hate them if I had to wear them! I love my Asics now!
my first pair of "running" shoes were actually Puma tennis shoes... I know!!!
Yes, mine was a Nike but that was so many years ago I don't remember which one. I know I am excited at the thought of winning a pair of Asics..yay! Thank you!
My first running shoe was a gel-kayano! Love the ASICS line!
My first serious pair of running shoes were Gel-Nimbus. Everything up until then was just the cheapest pair off the sale rack.
My first pair of running shoes were New Balance.
My first pair of running shoes 23 yrs ago were Nike. I cant remember the style just the colors, white with gray, purple, and teal.
My first pair of running shoes were reeboks in 1990.
A pair of Reeboks I think.
It was so long ago, I honestly can't remember!
I can't even recall, I've had so many shoes but they were possibly Reebok.
My first pair were New Balance.
My first and only pair of running shoes were New Balance.
i think my first pair were nikes.
Brooks were my my firsts.
Saucony Hurricane 15, I only wish I could find them again!
My first pair of running shoes were Nike. :) white and blue.
My first pair was New Balance.
my first pair were the reebok air. the super light shoes.
I think they actually were Asics.
Man that was too long ago! Probably some random inexpensive sneaker!
I had New Balance sneakers.
my first pair of running sneakers were nikes.
My first pair were Brooks. I've gone through several brands since then.
They were the Saucony Ride 4 I believe.


On Sep. 8, Sock 'n' Buskin Theatre Company held auditions for their first play of the season, Much Ado About Nothing by William Shakespeare. When auditioning for an SnB show, you sign up for an audition slot, which is normally scheduled between 10 a.m. and 6 p.m. on a weekend. Auditions are typically held at … Read moreAuditioning for SnB: What's the Process?


Barnsley have signed Birmingham City striker Garry O'Connor on an initial month-long loan deal.
Barnsley have dipped into the transfer market to sign Birmingham City striker Garry O'Connor on an initial month-long loan deal.
O'Connor has struggled with injuries during his Birmingham career and has been restricted to just 58 appearances since joining the club three years ago.
He missed much of last season with a hip problem and was handed a six-month contract, with the option of a further six months, over the summer.
The Scotland international subsequently started Birmingham's opening game of the Premier League season at Sunderland, but has now been allowed out on loan.
The 27-year-old will initially drop down to the Championship for a month, but there is an option for Barnsley to extend the deal.


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Academics » Health Sciences » About » Values – What We Stand For » GW Faculty Bring Genomics to the Public Square
GW Faculty Bring Genomics to the Public Square
genomics.jpg
Cost. Privacy. Knowledge. These were some of the words audience members produced when asked about barriers to getting a genetic test done.
The question was posed during the first of four sessions of a new series called Genomics in the Public Square, sponsored by the George Washington University (GW) Seminars program through the Office of the Provost. The new university seminar series, created by Shawneequa Callier, JD, associate professor of clinical research and leadership at the GW School of Medicine and Health Sciences (SMHS), and Sonia Suter, JD, John and Inge Stafford Faculty Research Professor at GW Law, addresses the promise of genomic and precision medicine and the challenges they present.
During the first session, "Genomic Literacy, Communication, and Education," experts discussed the basics of genetic testing, how the public can interpret direct-to-consumer genomic tests, and how to develop a society better versed in genomics as the technology modernizes and becomes more accessible.
With the rise of commercial DNA testing sites like Ancestry.com and 23andMe, consumers question the validity of the health results they yield and believe that for truly accurate results they must pay a higher dollar amount.
The fact is, "genetic testing is cheaper and contains more information than ever before," said Callier. "But that information needs to be assessed and analyzed, and the cost of interpretation and counseling is not cheap."
Carla Easter, PhD, chief of the education and community involvement branch at the National Human Genome Research Institute, discussed how her team is trying to understand how and where students are getting their information on genetics.
"For most people, their exposure to genetics is going to be in the classroom," Easter said. "When we start to talk about direct-to-consumer testing … we want students to know the difference between whole genome sequencing and [single nucleotide polymorphisms]."
Much of the session discussed the impacts of genetic mutations on an individual's risk for cancer and how genetic testing can help to identify important mutations and guide the development of a treatment plan.
"When we are doing genetic testing, what the labs are doing they are looking at somebody's DNA and trying to see if there are any differences in the code that you wouldn't expect to see and if any of these differences might be associated with health problems," said Tara Biagi, MS, genetic counselor at the GW Medical Faculty Associates (MFA). "If we know that somebody is at an increased risk, because they have a genetic mutation, there are things we are going to want to do differently for them."
Participants also had the opportunity to engage in discussion with the panelists, including Charles Macri, MD, professor of obstetrics and gynecology at SMHS; Elizabeth Stark, MS, genetic counselor at the GW MFA; Christine Teal, MD, director of the GW Breast Center; and Michael Rackover, PA, an adjunct faculty member at Thomas Jefferson University.
The remaining three sessions will be held during the spring semester and will cover race, genomics, and health disparities; reproductive medicine and genomics; and gene therapy, genetic engineering, and precision medicine.
Values – What We Stand For
Catalyzing Innovation and Entrepreneurism
Living Our Social Mission
Influencing the Future
Investing in People
Opportunities for the Military
Health Equity Series
Biomedical Cross-disciplinary Series


This integrated valve device is provided with: a body part (32), a flow rate adjustment valve body (36), a flow passage switching valve body (38), and a shaft member (34). The body part is provided with: a first inlet passage (301) and a second inlet passage (302) into which a predetermined fluid flows; and a first outlet passage (303), a second outlet passage (304), and a third outlet passage (305) from which the predetermined fluid flows out. The flow adjustment valve body is provided inside the body part, and adjusts the flow rate of the fluid flowing from the first inlet passage to the first outlet passage. The flow passage switching valve body is provided inside the body part; switches between a first communication state, in which the second inlet passage communicates with the second outlet passage and the third outlet passage is blocked, and a second communication state, in which the second inlet passage communicates with the third outlet passage and the second outlet passage is blocked; and switches the flow passage of the predetermined fluid inside a fluid circulation circuit. The shaft member is provided inside the body part, and links together the flow rate adjustment valve body and the flow switching valve body.


text:
Oct. 16, 2017 12:49 pm
Maryland opens London trade office with focus on cybersecurity
Maryland is looking to open up more cybersecurity business in the U.K. The new trade office is linked with iCyberCenter at bwtech@UMBC.
Inside SmartLogic's approach to hiring View Open Positions
Columbia's new Howard County Innovation Center is housing an incubator
5 questions with Josh Budman: Applying neural networks in medical imaging at Tissue Analytics
Genomics leader Illumina is opening a new center at University of Maryland BioPark
Maryland will have a bigger presence under the Maryland flag.
(Public domain image)
The state's international business push is continuing with a new trade office in the United Kingdom, and cybersecurity is seen as a key to the growth.
The state announced that it is opening a trade office in London for the purpose of creating a new beachhead to engage with international partners. One big goal will be "enhancing Maryland's global reach in cybersecurity," Maryland Secretary of Commerce Mike Gill said in a statement.
The words are backed up operationally. The office is being funded through a grant from the state Commerce Department to bwtech@UMBC's recently launched iCyberCenter. As we reported in June, that incubator program was set up to provide international companies a landing point and resources in Maryland.
Since then, we've heard from Canadian company Plurilock, which was accepted into the iCyberCenter. The company's platform uses biometrics to identify people by the way they use a keyboard or mouse. It's designed to be a layer of security above passwords. CEO Ian Paterson said the company recently landed its second federal contract, and is looking to grow that side of the business with the Baltimore office.
"We were looking for a presence largely because of our federal practice," Paterson said. "We felt Baltimore, particularly just because of the geography, made sense."
With the trade office, iCyberCenter staff are helping the state expand outside the borders as well. Former UK cyber envoy Andy Williams, who was recently hired as director of the center, will head up the trade office.
"Maryland represents a huge opportunity for overseas defense and cybersecurity companies seeking to establish a presence in the U.S. market," Williams said in a statement.
The new trade office comes after Gov. Larry Hogan visited the U.K. and saw a memorandum of understanding signed between the state and Midlands Engine, which is a center of cybersecurity for the U.K.
Gov. Hogan creates CISO position for State of Maryland
Maryland is testing digital license plates
TEDCO CEO George Davis plans to resign
BurnAlong
Customer Success Associate
SmartLogic
Maryland, UK's Midlands Engine partner on life sciences
Congressman: 'No evidence' that NSA cyberweapon was used in Baltimore
Protecting passwords: Relatively simple solutions for a big cybersecurity risk
How SmartLogic accelerated these startups' product growth trajectories
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The work of Deep Chill Network began in 1990 as a therapeutical outpouring.
Chronic insomnia prompted ambient veteran Stephen Philips to seek out subtle ambient music as a way to transition into the dream state. His search for such music yielded few options so he decided to create his own.
Along with his occasional musical collaborator, Ben Summers, the Deep Chill Network was born. The original idea was to form a collective of ambient musicians working together toward one common theme, a "network" dedicated to creating music for sleep. While Deep Chill Network has featured several guest musicians over the years, the core members remain Stephen Philips with Ben Summers contributing from time to time, and the full collaborative "network" remains still to be fully realized.
Earth Mantra is a big fan of the music of Deep Chill Network, and we are very proud to be releasing some of this superb music to our listeners.


While the ICBM runs off a chintzy-looking wall wart, its construction and performance were serious and solid. While remaining powered up at all times, the ICBM added no perceptible hum or noise. In fact, once I'd set it up to my satisfaction, it required no further attention until I changed another component in the system.
There's little more that need be said about the ICBM. It did the job it was intended to do, and I could hear no sonic compromise while using it. It was difficult to A/B it, as I'm not sure there's any way to completely bypass all its circuits, pots, and switches. Swapping it in and out of the system in two channels with the Paradigm '60s, I was satisfied that any very slight veiling I might have heard with the Outlaw was more than outweighed by the advantages gained from its use. Also, I was impressed with the ultradetailed (but not bright) sound of the Magnepans as heard through the ICBM. Surely, if there was any significant corruption, the Maggies would have revealed it.
As far as I know, the ICBM is the only game in town when it comes to add-on analog bass management for the home user. Until the day there's a quality pre-pro that will accept industry-standard digital multichannel inputs from all formats, and manage bass and other functions in the digital domain, the Outlaw Audio ICBM will have an honored place in my system.
My first experience with an analog multichannel preamplifier was with the Sony TA-P9000ES, a remarkably self-effacing device. It did its limited job with its two multichannel inputs extremely well. It was supplanted by the more capable McCormack MAP-1, a line-level analog preamp that I found both good-sounding and simple to learn and use. In this era of complexity, the latter is no small accomplishment. The latest contender in the multichannel preamp games is the Bel Canto Pre6.
The Bel Canto Pre6 aims higher than these two in its elegant appearance and programmability, and that's reflected in its price: $3800. The Pre6 is capable of eight-channel operation, or six-channel operation in one zone simultaneous with two-channel stereo operation in another. Its degree of flexibility can be downright intimidating, but it comes with a reasonable default setup for two six-channel inputs, three two-channel inputs (one of them balanced), stereo tape input/output, two six-channel outputs (one balanced), and two two-channel outputs (one balanced). Those with special needs can arrange for up to 12 stereo inputs. (Whew!) Bel Canto has thoughtfully put a red/green LED next to each input jack; these are of great value in making connections.
As on all current Bel Canto designs, the Pre6's control panel is a large black oval surrounded by a brushed-aluminum faceplate. Across the front, from left to right, are the company name, Mute and Enter buttons, a large bright display, a four-button array for Volume Up/Down, Input Selection, and Tape Monitor, and, finally, a Standby button. I never used any of these, instead preferring the remote control. For example, the front-panel Input button lets you step through the inputs in order, while the remote gives you direct access, and adds left/right balance controls and a display shut-off option. But the display readout is so readable and the remote control so convenient, why get up from your seat?
Inside the Pre6 is one large printed circuit board bearing the active componentry, with precision resistors and film capacitors, in a small corner. It is otherwise dominated by high-quality mechanical relays. A daughterboard attaches to the rear panel for input/output, and another attaches to the front panel for controlling the logic and display. That front PCB also holds a SIP connector, which permits reprogramming of the microprocessor controller that actually runs the operations.
The Pre6 works in some unique ways. The Standby button disables the display and completely mutes the audio output. Pressing Standby again reawakens the Pre6 and ramps the volume up to Soft Mute (a programmable partial attenuation); you then must push Mute to get full output. Got it? In operation, pushing Mute twice within three seconds fully mutes the output, but repeated pressings with less than three seconds between them toggles between Soft Mute and full output. Want to switch between inputs? Looping through the sources with the front panel or selecting directly from the remote, the Pre6 will ramp the volume down, make the switch, then ramp the volume back up. Bel Canto says that the ramping is quick. This is fine for general domestic use—the Sonic Frontiers Line-3 in my main system does the same—but in both cases, forget about rapid A/B comparisons.
The Pre6's configuration options include defining which input jacks are grouped for each input, the naming of each input, and the setting of volume offsets for center and surround channels in the multichannel inputs. To get to the configuration menu, one must hit the front-panel Enter button four times (or hold it down for longer than two seconds), or press the remote's Enter button eight times. Once you're in, many of the labeled buttons assume new personalities, to steer you through the setup options. Bel Canto's manual offers aid in the form of flow charts, but I found them confusing and too small to read.
With the immediate necessity to set channel balance for the Magnepan system (and needing to show the visiting Wendell Diller my competence), I grabbed the remote. I clicked Enter eight times and, like Dorothy in The Wizard of Oz after she's clicked her heels, entered a wondrous realm: Input Configuration.
It wasn't so bad! Within five minutes, we had all the channel offsets for the Magnepans (see above) programmed for the two multichannel inputs. Trial and error worked better for me than trying to understand the manual. However, a strange thing happened after inputting the offsets: The Pre6 would often make very loud pops when being reprogrammed, or, more important, when being switched among inputs. A distress call to Bel Canto resulted in their sending an interface board for the front PCB SIP connector, a serial cable for my laptop, and a disc of software. After upgrading the software from Rev. 3.16 (3/35/03) to Rev. 3.19 (7/8/03), all was well, with sure and silent switching thereafter. I don't know if such problems are endemic to earlier software versions, but I do know that they're easily cured.
But all that's water under the bridge. The Pre6 sounded absolutely wonderful and, as configured, operated perfectly. I sat comfortably on the couch, Pre6 remote in hand, enjoying Alan Civil playing Mozart's Horn Concertos (Pentatone 5186 105), a classic 1971 performance remastered in stereo and four-channel from the original quadraphonic masters. The stereo track is like the original LP but with a quieter background. In multichannel, the sound of the horn is less confined and seems to be much larger, just as it would in a concert hall. After all, a French horn's bell is usually aimed away from the audience; most of the sound reaches our ears indirectly, after having bounced off the walls of the hall. I suspect that the stereo mix minimizes this in order not to obscure the other instruments, but multichannel lets the horn sound like a real French horn in a real hall. So felicitous were the balance and resolution of recording and system—including, in no small part, the Pre6—that the orchestral details were not masked while the horn filled the hall.
What I liked best about the Bel Canto Pre6 was the difficulty I had defining its sound. Most of the adjectives used to describe components imply a sonic character of some kind, and the Pre6 had little. Even the use of such terms as "open," "full," and "spacious" assumes that the signal and music had these features but that the component is neutral in permitting us to hear that. The Pre6 sounded lively, tight, and punchy on Mark Nodwell's Nemesis (SACD, Songlines SGL SA1530-2), with a small ensemble of trumpet, guitar, piano, bass, and drums. But that's part and parcel of this bluesy, swingy music and its recording, as was a bit more splash in the rear channels than I found ideal.
On the other hand, the Pre6 sounded strong, sweet, and powerful with Mahler's Symphony 5, performed by Hartmut Haenchen and the Netherlands Philharmonic (Pentatone 5186 004) and recorded during a concert in Amsterdam's Concertgebouw. While this is not a performance for the ages, the richness of the acoustic gives considerable size to the sound; I feel I know what it was to be part of that audience. Benjamin Zander's recording of this work with the Philharmonia Orchestra (SACD, Telarc CD-80569) is, overall, a more balanced performance; on the same system, it sounded more direct and detailed, but with less weight or sense of occasion. I listened to a dozen or so other familiar recordings, and each seemed different enough that I could detect no bias imposed on them by the Pre6.
Compared to the McCormack MAP-1, the Bel Canto Pre6 has less zing in the highs and definitely worked better with the Magnepans. With the Paradigms, it was a toss-up. The McCormack was less tolerant of bright or splashy recordings, but could be thrilling with the better ones. With the Pre6, such distinctions were apparent but less disturbing. The simpler MAP-1 was easier to set up and use and, at its lower price, might be preferred if matched up with a little care.
All in all, though, I found the Bel Canto Pre6 easier and more enjoyable to use with a wider range of components and discs. Perhaps it goes back to my continuing inability to put my finger on the character of its sound—like any really first-rate preamp, it doesn't have much character. One of these days, when I can spare it from the multichannel system, it deserves an audition in the main stereo system. It's that good.
On tap are two more multichannel analog preamps, one about four times the price of the other; a universal disc player; and some concerned thoughts about center-channel speakers. See you in March.


A big Thank You to Jeff Stanzler for inviting me to speak last night at my Alma Mater, the University of Michigan. I am especially thankful for all the MAC students who patiently listened to me wax eloquent for 90 minutes about my journey from classroom teacher to Flipping Physics. Okay, "wax eloquent" is probably a bit facetious and "patiently listened" also doesn't well describe my audience because they were a very active audience, asking lots of questions, which I love. It was awesome to be a presenter in a class that I took 14 years ago. So thanks. Thanks for giving me an opportunity to talk about my craft.
This is what Bobby sees. Note the script taped to the wall.
Setup to film mr.p. Note the institutional blue wall background on the far right.