text:
Agency Made Me Do It
AMMDI is an open-notebook hypertext writing experiment, authored by Mike Travers aka mtraven. It's a work in progress and some parts are more polished than others. Comments welcome! More.
MapFull
from designer stance
I was exposed to a really compelling version of design stance at an early age, since I somehow discovered Victor Papanek's Design for the Real World at the public library (quite possible heard about it via Whole Earth Catalog). This was an eye-opening and intense book, as Papanek excoriated the profession of industrial design for spending its energies on trivial things while the real problems of the world are begging for creative solutions. At the time I read it I probably had no idea that there was such a thing as industrial design, but now I not only was aware, I had strong opinions about it.
from re-enchantment
Aside from the particular word it doesn't seem very new; the same spirit animated the hippies fifty years ago and many others. I remember first seeing the Whole Earth Catalog and becoming excited that here was an approach to technology that wasn't dull and corporate and rationalist, but in some way alive and magical.
from Christopher Alexander
Here's an entry from an early Whole Earth Catalog about his first book, on design theory.
from Agency Made Me Do It
We are all forced to be practitioners of agency, forced to construct ourselves as agents, and we might as well get better at it. Like the Whole Earth Catalog, I'm just trying to make the tools more accessible.
from Psychopolitics
Instantly my mind turns to Whole Earth Catalog, which was the Bible of Can for a generation, and a huge influence on me in my youth. Weird to think of it negatively like this. Part of me wants to harrumph and throw the book across the room, what do you mean being against achievement and capability, what kind of attitude is that? But I kind of get what he's saying.
from Stewart Brand
Best known as the founder of the Whole Earth Catalog, Stewart Brand has been involved in all sorts of interesting projects, from Doug Engelbart's radically innovative computer systems to George Church's efforts to revive extinct species.
from Laws of Form
A cultish math book, introduced to me by the Whole Earth Catalog and Francisco Varela. From a purely math standpoint, it appears to introduce some novel and perhaps useful notation and invent something sort of like imaginary Boolean values. From a deeper metaphysical standpoint, it offers a way to talk about distinctions in general and our representation and participation in them.
from Weird Studies/Request List
Whole Earth Catalog and Counterculture to Cyberculture, or cybernetics generally
Has come up Weird Studies/Unabomber
from Robert Heinlein
This particular quote has achieved a kind of meme status in tech, it defines our version of machismo. There's nothing obviously wrong with it either. That and the Whole Earth Catalog are my models for valorizing general competence and capability. Heinlein's military background is obvious; Stewart Brand was also in the army and acknowledges that experience as important. It's a stance I guess.
from unus mundus
"There is only one universe, by definition" – Buckminster Fuller maybe? Quoted in Whole Earth Catalog
from Anne Herbert
Anne Herbert was a writer for the Whole Earth Catalog and its descendent magazine Coevolution Quarterly. She seems largely forgotten today; but I remember her wise and compassionate voice from those publications. It seemed to come from a different place than most, one that sounded like it would be welcoming. Her writing was simple, sincere, deep.
from conflict theory
Ah found it, from The Last Whole Earth Catalog
from LWMap/Being a Robust Agent
One of my heroes, Stewart Brand, famously promoted something akin to this stance with his Whole Earth Catalog mottos: "Access to Tools" and "We are as Gods and Might as well get Good at It". Tools for what? It doesn't matter, whatever you might want to do (in this case, "you" was a subset of hippies and people interested in alternative ways of living).
from Kevin Kelly
A technology writer who covers some of the same themes I do. Kelly was the editor of Wired and before that associated with Stewart Brand and the Whole Earth Catalog and sort of incarnates the more libertarian techno-optimist strain of thinking from that quarter.
from Sloterdijk
Huh he sounds like he is re-inventing Whole Earth Catalogism. Which indeed might be the best hope of salvation.
from Martin Buber
Despite my Jewish background, I think I found I and Thou via the Whole Earth Catalog and Ken Kesey:
from The Last Whole Earth Catalog
from Weird Studies/Unabomber
Oh nice comparing Whole Earth Catalog with the Hexen deck and the film The Net that they are talking about...all are primarily networks of ideas.
from Technic and Magic
OK you don't want to see a tree as only so many board-feet of lumber, but still, I'm generally for increasing people's instrumental potential! Like the Whole Earth Catalog slogan, "access to tools".
Twin Pages
Whole Earth Catalog
30 Oct 2021 02:15 - 16 Dec 2022 12:22
Open in Logseq
See Stewart Brand. The Catalog was a major early influence on me, particularly in its stance that one could be interested in anything and pursue anything. There was a Whole Earth Bookstore in Evanston, IL where I grew up, which is where I found both the catalog and Ted Nelson's Computer Lib/Dream Machines. When I went off to MIT I managed to fall in with a bunch of Whole Earth-friendly fellow students who were into alternative energy and other alternatives; later I got to actually share an office with SB himself in the early days of the Media Lab.
It's hard to remember what the world was like before the Internet, but back then you didn't have access to all the world's information and resources at your fingertips. There were daily papers and network news and that was it. The public library had plenty of stuff but it tended to be somewhat out of date. The Catalogs opened up a whole world of alternatives and underground scenes and innovations.
One distinctive voice I remember from the Whole Earth publications was Anne Herbert, an editor and writer who added a warm, female, humanist note with her little side observations. She seemed to have faded out of the scene; I found this web page about her and her work at archive.org
That's part of a large collection of Whole Earth material which provides ample occasions for nostalgia.
The Catalogs seemed to go through a series of major influences, the ones that stick in my mind are:
Gregory Bateson
Here's the one time that I got a mention in Whole Earth Review for some of my Vivarium Project work, in 1989.
Kevin Kelly's Recomendo newsletter and especially the collected book closely replicates the Catalog format and the focus on tools.
Copyright © Hyperphor 2020-2022


Cinderella, eat your heart out. Rafael Cennamo's Spring 2013 presentation transported you to a fancy, stunning ball. From gorgeous beading to beautiful colors, the collection is every women's Cinderella story. Glamour at its finest. I can only imagine and dream what it would be like to wear one of these pieces. The collection is fit for a queen and any women would be lucky to be able to wear one. I can't wait to see what Rafael has in store for next season.
What do you think of Rafael Cennamo's Spring 2013 collection?


text:
Q: downloading web page using NSURLDownload here is my code, it tries to download a webpage using NSURLDownload. but it does not work, its a command line program.
- (void)startDownloadingURL
{
    NSURLRequest *theRequest = [NSURLRequest requestWithURL:[NSURL URLWithString:@"http://www.apple.com/index.html"]
                                             cachePolicy:NSURLRequestUseProtocolCachePolicy
                                         timeoutInterval:60.0];

    // Create the download with the request and start loading the data.
    NSURLDownload  *theDownload = [[NSURLDownload alloc] initWithRequest:theRequest delegate:self];

    if (theDownload) {
        // Set the destination file.
        [theDownload setDestination:@"/saleh" allowOverwrite:YES];
    } else {
        // inform the user that the download failed.
        NSLog(@"download has failed!");
    }

}

A: Ensure you implement the downloadDidFinish and doanload:didFailWithError: callbacks.
Here's an overview that covers how to use NSURLDownload:
http://developer.apple.com/library/mac/#documentation/Cocoa/Conceptual/URLLoadingSystem/Tasks/UsingNSURLDownload.html#//apple_ref/doc/uid/20001839-BAJEAIEE
Specifically, this callback will give you more details on why it failed:
- (void)download:(NSURLDownload *)download didFailWithError:(NSError *)error
{
    // Release the connection.
    [download release];

    // Inform the user.
    NSLog(@"Download failed! Error - %@ %@",
          [error localizedDescription],
          [[error userInfo] objectForKey:NSURLErrorFailingURLStringErrorKey]);
}

EDIT:
Below you said it's a command line.  async callbacks require an NSRunLoop.  See:
Cocoa: NSURLConnection not attempting an HTTP Request
Per the docs:
initWithRequest:delegate:
Returns an initialized URL download for a URL request and begins to download the data for the request.
- (id)initWithRequest:(NSURLRequest *)request delegate:(id)delegate

delegate
The delegate for the download. This object will receive delegate
  messages as the download progresses. Delegate messages will be sent on
  the thread which calls this method. For the download to work correctly
  the calling thread's run loop must be operating in the default run
  loop mode.

NSURLConnection has a synchronous way to download data.
http://developer.apple.com/library/mac/#documentation/Cocoa/Conceptual/URLLoadingSystem/Tasks/UsingNSURLConnection.html#//apple_ref/doc/uid/20001836-BAJEAIEE

NSURLConnection provides support for downloading the contents of an
  NSURLRequest in a synchronous manner using the class method
  sendSynchronousRequest:returningResponse:error:. Using this method is
  not recommended, because it has severe limitations:

The main limitation is the client blocks but that's a concern in a command line app.

A: You need to make sure that you define at least downloadDidFinish: and
download:didFailWithError: to use the delegate. You can pretty much just copy and paste the methods from the URL Loading System Programming Guide.
If you are on 10.7 you should declare that you use the protocol in your header as well, before Lion there wasn't a formal protocol.
Also make sure you have a run loop going. For testing you can just stick [[NSRunLoop currentRunLoop] run]; in there, although it's probably not going to ever exit the loop then.

redpajama_set_name: RedPajamaStackExchange


An Experienced Researcher (PhD) to investigate the effects of the growing demand for land from the production of food crops and biofuels and its influence on the coupled Earth system, in particular the biogeochemical responses and their climatic consequences. This includes the development of a parameterisation of biofuel crops for the dynamic vegetation model LPJmL and the global land and water use model MAgPIE. The successful candidate will actively participate in network-wide workshops and training events.


The First Sudan Civil War began with the request of South Sudan for autonomy between 1955 and 1972.
Half a million people have died in 17 years of war.
After the end of the First Sudan Civil War in 1972, the Second Sudan civil war began and continued between 1983 and 2005 . The North Sudan and the South hereby began to fight again. The Second Sudan Civil War was a major continuation of the First Sudan Civil War, which took place between 1955 and 1972.
In the Second Sudan civil war, two million people died of war, famine and sickness. Four million people in southern Sudan were displaced at least once during the war.


text:
import { SearchResultItem } from "./search-result-item";

export class SearchResultItemViewModel extends SearchResultItem {
    public id: string;
    public index: number;
    public active: boolean;
}

redpajama_set_name: RedPajamaGithub


Here we are at the end of my first full-year on this blog. It's ended in a more distant way than I would've expected. I mean, I had't anticipated going on somewhat of an 'exile' from my own pages for much of the final few months. But I can recall back to last year's post without entering any search terms and in this post, I'm going to reflect on my intentions for 2013, along with trying to summarise my achievements and realisations.
As I begin to write this post, I'm aware that it may not reach you on the same day. My internet connection is 'unstable' at the moment but I intend to get that sorted next week. That's the main reason I've been so quite in the last month, where I've been wanting to check in and to let you know that I'm still here.


Investing on wigs may be a luxury and necessity all rolled into one. If you have the means to pay for these items, then it is easier to make the purchase. Nobody should affect you in the decision making process but your own instinct or gut feeling. If you want to make the best out of the purchase, you have to give thought to some factors. Choosing human hair wigs requires taking a look at the different hairstyle options offered by online stores. You may consider any of the following selections in your purchase.
Long hairstyles. Elegante's H-Jasmine and HM-Showgirl, Raquel Welch's Feline and Knockout; Beverly Johnson's H-202 and Sepia's Megan and Xeena all have a common denominator. These are all long hairstyles for human hair wigs that are considered best sellers in the market for wigs. They may have different colors, product names, and cuts but they are all considered long hairstyles in the wig category. Choosing these options may actually be favored by people who have been bored with their everday shorter hairstyles and hair colors.
Curly hairstyles. Hairstyles under this category may range from short curly wigs to long and curly human hair wigs. For shorter hairstyles, you may opt for best sellers such as H-205 and H-208 from Beverly Johnson. If you are looking for curly tresses under the longer hairstyles, you have options coming from Beverly Johnson's H-175, Motown Tress's Sharon and Sepia's Bel Air and Jeanette. All of these hairstyles promise to give you the new, wavy look you have long been aspiring for.
While choosing from all of these hairstyle options for your human hair wigs, you will certainly look into the price tag attached to the purchase. Some product brands are far costlier over the other. In fact, you may pay as low as .95 for a certain hairpiece to as high as 9 for another. Some online websites may even offer these wigs in a higher price. You better be alert about making the right choices for your hair wig products if you do not want others deceiving you with your purchase of these hair pieces.
In addition to the price of these hairstyle options, you must also look into who makes wigs for you. Some established names in the human hair wigs industry like Wig Pro, Raquel Welch, Alan Eaton and Jon Renau have more luxurious and high quality items on their lists. Other brands like Elegante, Sepia, Beverly Johnson and Motown Tress are cheaper. These wigs may vary in terms of names and prices but one thing is for sure – as long as you acquire the pieces from a reputable service provider, you will surely get a genuine version of the hairpiece.
Looking for different hairstyles for wigs ? Our site has listed the best ones for your purchase of human hair wigs.
If you don't mind cutting your hair short then any kind of bob hair cut is a trend of 2008 and2009. We have seen that bob hairstyle has been reintroduced in a new form. Before it was like having only one specific style but now any kind of layer is being mixing up with it to give a new look. In 70's and80's bob hair cut had only one variation. But now you can have lots of variation with this hairstyle. According to your personality, face cutting and length of your hair you can try any type as per your wish. Most happening short hairstyle includes elegant bob hairstyle of 2009, side-swept and wispy-bob style.
We will discuss here some of the short hair styles of 2009.Face type with oval, round, square, heart and triangular can try this style. Thin or medium hair texture is suitable for applying this style. Elegant bob hairstyle gives your hair a look that is comfortable to handle and maintain. Today's hectic life schedule merely can handle long hair. But this hairstyle hardly needs any extra care of your hair. So, it is sporty and at the same time trendy. You can shampoo and oil your hair every alternate day and vice verse. Long bob with a matching cloth band can catch the eye. Recently Heidi Klum's long elegant hairstyle is very much popular. Hair having Sparse or medium depth is appropriate for this style. But you have heavy, thick hair type you also can opt for this style. This is a soft graduated bob cut that angle upward in a soft manner and will suit rounder face cutting best. Hillary Clinton love to have this elegant bob hairstyle. Students as well as older women can do their hair this way. Long bob with slightly layered trimming can be a good experiment.
Oval, oblong, square, diamond, triangular face can compliment a hairstyle that is now a day is called bob with side swept bangs. Like elegant bob this type of style is also appropriate for medium and thin textured hair. Hair volume that is needed is sparse or medium. The hair has is usually razor chipped on the ends for movement and the layers is kept at one length. The sides swept bangs are used to compliment this hairstyle. Rehana's hairstyle or Victoria Beckham's Short Haircut is a variety of side swept bob hair cut. Plain bob cut with a little bit variation can add an extra glamour to your bore dull hair style and this side swept bob cut with its bangs proves this.
Another bob cut is wispy bob hairstyle. It is mainly for fine hair. This is a great hairstyle to give body to finer hair types. The hair has been slightly angle layered and the ends have been chipped to reduce bulk. Again this is a very easy style to look after. Oval, oblong, square, triangular, diamond shaped face and thin, medium hair texture go well with this style. Sparse, medium hair density is preferable for this hairdo. Bipasha's hairdo is wispy bob hairstyle.
Short bob hairstyle looks better when you do your hair a color. Red burgundy, copper, matt color, which suits your skin color and hair texture, can be done. Not coloring the whole hair but highlighting some stripes can be a good option. Bob hair cut with various variation is the look of 2009 and you can make this style more glamorous by coloring up your hair. And above all it is handy and easy to maintain.
Attractive ghd hair straightener, ghd straighteners and ghd straightener available here along with free shipping service.
No, there is no such formula, nor right or wrong answers because it is YOUR wedding day, and only you can decide among the many wedding hairstyles, to make this day a big and unforgettable event that it is expected to be. Selecting the perfect hairstyle yourself should be an easy task because nobody better than you knows how good or bad you feel when you look in the mirror.
Learn about skunks habitat and skunk bait at the Skunk Facts site.
Prom night is the most awaited night time for all the teenagers. They dream a different sort of look, a distinctive personality and an elegant hairstyle with flawless attire. Prom hair is a major concern for most of the females. To find the best prom hairstyles which complement the prom outfit, personality and the mood of the night is a big chore. The hairstyle should go with the prom theme as well. Every prom night has a concept which ties together all the components of the prom. Prom themes are diverse and play a vital role in the choice of prom dress and prom hairstyles.
There's a vast collection of hairstyles for prom for both long and short hairs. For females with short hairs there are many short prom hairstyles that look formal as well as trendy. To name a few textured short cuts with plenty of texture and layers, short hairstyle with a fringe and pixie cut are the most popular. Long hairs are bit difficult to manage but yet there is abundance of prom hairstyles for long hair. Curls, waves, updos and chingnons look fantastic on long hairs. Updos prom hairstyles are the staple of the prom night which compliments the flattering features and gives an elegant look. Some of the other hairstyles are simple chic cut with the front part pleated to one side and separated with a hair band; long boho waves with a center parting and waves throughout the tresses; and curly locks made up of rollers or barrel.
Most of the young ladies with medium length hair are worried for the hairstyle but there are various medium length hairstyles too. Infact they might take advantage of both short hairstyles and long hairstyles. Choppy mid length cut, curled locks and natural wavy are a few of the designs that are perfect medium hairstyles for that prom night. Updos prom hairstyles can also be the best styling choice for medium length hair. Sassy updo and knotted style updos are the most popular and easy prom hairstyles.
Today the most favorite hairstyle with the young girls is the sedu prom hairstyles. These hairstyles can be organic sedu hairstyle, formal sedu hairstyle or vintage sedu hairstyle. A natural sedu hairstyle simply implies natural beauty. It's either straight hair with curls or a loose bun that showcases the face of the wearer. An elegant sedu hairstyle has a tight bun or a low ponytail. Vintage meaning old fashioned is the most expressive and stylish hairstyle for prom.
Early planning of the most useful hairstyle for the most awaited prom night can help to achieve a different, unique, elegant and flattering look that blends well with the ambience of the promenade evening.
Prom night is the most awaited night time for all the teenagers. They dream a different sort of look, a distinctive personality and an elegant hairstyle with flawless attire.


What a terrible sensation it is 1 time you are moved into your new area to find out products are missing. You possibly won't even detect it appropriate away but when you do – it can be devastating relying on what they accurately are.
Make sure before you make your move all the flammable or combustible items like matches, lights fluid, bleach all are completely utilized. If not dispose all of those. As these products are not at all permitted to be transported.
If your kid has a special bath toy, pack tub toys in one of the initial boxes you will open for the bathroom. Similarly, if your child has a particular cup or dish they like to use, pack these in the kitchen area box so that they can get it correct away.
One of the benefits that arrive with free moving quotation, some thing long distance movers Dallas and international movers have also endorsed, is overhead expenses go out of the equation. You do not have to spend something extra for every little task. The expert mover performing the shifting grunt for you does a small math, estimates a price and ultimately shares it with you. Only once you approve of the price and make the payment does function start. So things are pretty professional that way. Not even once are you bothered throughout the shifting work or post it about any overhead cost that arrives up. Neither is it your concern, nor are you nudged as well a lot about it.
It would make the working day simpler if you arrange to have your children out of the home, with buddies or relatives. If this is not a chance, hire a babysitter so you can focus on the shipping and delivery.
Layer the bottom of the box with paper, providing the box a small padding will assist shield valuables for the long trip forward. Use thoroughly clean paper and wrap every item in at least two sheets of paper. Location the piece in the middle of the paper wrapping it completely. Pack three or four products in a bundle, wrapping the bundle in 3 or 4 sheets of paper. Fill any void areas with wadded up paper. Include extra paper to the leading of the box. If you have plenty of space in the box, an additional bundle can be additional, continuing to wrap each piece with plenty of paper to avoid chipping or cracking.
All of these various benefits include up to create a extremely potent selling stage for utilizing an interstate moving company. And maybe now is the time you ought to act to get assist with your move.


text:
Q: How can i ask grid view to know which cell is active and pass cell's value to my function? Is cellvaluechanged event suitable for this ? how?
void filterDataGridView(DataGridView dgv, string columnName, string filterValue)
    {
        foreach (DataGridViewRow row in dgv.Rows)
        {
            if (row.Cells[columnName].Value.ToString().Contains(filterValue))
            {
                row.Visible = true;
            }
            else row.Visible = false;
        }
    }

i need too send cell value that user write it,to filtervalue of my function.how can i do that?

A: If you want to react on the user typing text in on of your cells I would recommend CellValidating event.

*

*You write some text in on of your cells

*Cell_validating occurs

*you call your filter method and you may modify some other dataGrid (in your example hide/show rows on given value)

HTH


Your dollhouse can be as fancy as you desire when you add in a flock of lambs from Colin's Creatures. These lambs are carefully handmade from porcelain and woven fur of wool or mohair. Tickle the fur on your mini flock of lambs because they feel incredibly lifelike. The fur comes direct from Germany.
You have a choice of several breeds, from Galway to Suffolk to decorate your 1:12 scale dollhouse. When you're a collector, dollhouse miniature sheep are a rarity in the industry. Keep in mind that you don't have to be particular about the breed of your miniature sheep figurines either. Colin's Creatures offers white, beige and black sheep as well as the lambs that go with them. Complete your dollhouse scene with livestock that really show off your collection.


text:
Interview with Scott Fraser: "Practices that are nimble will come out of this pandemic stronger"
June 15, 2020 Covid19, Videos 0 comment 8 Likes
Scott Fraser is the Founder and Managing Director of Fraser Healthcare, a consulting practice focused on growth strategies for healthcare companies and private equity firms. He's worked in the gastroenterology space for 25 years with companies like Given Imaging, EndoChoice and Boston Scientific. More recently, he was President of Practice Management for Physicians Endoscopy.
Watch this super insightful interview in full to understand where the business of gastroenterology is going. Scott delves into new ancillaries you could start right now. He talks about making a practice attractive for investment. And he reflects on the future of GI when present market forces accelerate.
◘ Two key questions: How do GI practices recover? How do you evolve and think differently?
◘ EMRs have a wealth of information to identify future patients
◘ Easy to implement ancillary revenues from IBS and NASH
◘ Patients are putting their symptom scores into an iPhone app
◘ Massive patient population walks into ASCs everyday – very little is done to identify them
◘ Upwards of this ancillary is more than half a million dollars
◘ How do clinical trials work as an ancillary?
◘ What are PE funds thinking? Valuations and future of consolidation
◘ "We are still in the early stages of consolidation of GI"
◘ How would Scott make decisions if he were a GI practice today?
◘ "If you are thinking about selling your house, get it in order"
◘ "Make investments to make your practice more attractive"
◘ Revenue cycle management: Leaving thousands of dollars a day because of errors
◘ "Now's the time to review your contracts"
◘ Collaborating with industry to gain patients
◘ "Become members of DHPA"
◘ What's the holy grail for GI?
◘ The market forces are toward consolidation: payers, hospitals, industry (med-tech, pharma), sub-specialists
◘ "Practices that are nimble will come out of this pandemic stronger"
The Transcribed Interview:
Praveen Suthrum: Scott Fraser, thank you so much for making time today for this interview. It's really nice to see you. You have been in this space for 25 years now and that too a variety of roles touching both on the business and technology side. So, I'm really looking forward to this conversation.
Scott Fraser: Thank you Praveen for having me. I've really enjoyed the panelists that you've had to date, and this is really a great forum in this virtual world, and as you're getting different perspectives from thought-leading groups and bankers and stakeholders on how they're weathering this crisis and coming out of it. Really, it's about sharing best practices because we're all in this together so, thank you for that.
A little bit about myself, I've been very GI/endoscopy-centric pretty much my entire career for now about 25 years. I first started off in Medtech with Microvasive which was the endoscopy division of Boston Scientific, both in sales, product management, and market development and then had a really unique opportunity for my first startup being one of the first US employees of Given Imaging where I led the marketing efforts during the launch of capsule endoscopy and that was such an amazing time frame. Then from there, I was one of the founding executives of EndoChoice which is now part of Boston Scientific and again we launched during a downturn in the economy. We founded the company in late 2007 and then 2008 hit when we were trying to raise money. After that, I was a consultant with a private equity-backed ASC company and I was the president at Physicians Endoscopy to form a new division of Physicians Endoscopy which is the partnership with Capital Digestive Care and that was an incredible experience to be on the operator side of both an ASC company as well as a practice management company.
Since that time, I have had the opportunity to work with both, leading private equity firms as well as fortune 500 Medtech and also startup Medtech companies, really advising them on the evolution of what's happening, not just in gastroenterology but other subspecialty medicine where private equity is investing in MSOs and it has been a real honor to have these companies seek me out and I formally founded Fraser Healthcare which is my consulting group that advises both private equity and Medtech clients. I think even more important than my business experience is that my dad is a colon cancer survivor and he almost died because of colon cancer and that has instilled in me the importance of screening.
Praveen Suthrum: So, I wanted to start by asking you the two questions that you had told me the other day that most GI practices are thinking about right now. The first one being, how do we recover? And the second one being, after we recover, how do we evolve? And how do we start thinking differently? I'd love to get your perspective on both these questions.
Scott Fraser: Yeah. As I look at 'How do I recover?' and some of the best practices that have been shared by some of your previous guests and just in some of the discussions I've had with many physicians, it's looking at your different lines of business and whether it's your ambulatory surgery center as well as your practice, if you've got infusion, or if you've got clinical research, and understanding what a pathway to recovery looks like. The thing that I think is that a lot of smaller groups don't fully appreciate is that their EMRs are a wealth of not only patient information but identifying future patients. And as I talked to different groups and also talked to some of the EMR gurus that are in the space is that very few groups really do a good job querying or mining that data meaning that you have patient populations that have IBS, you have patient populations that are at risk of NASH, and identifying those patients or the at-risk hereditary patients and proactively reaching out to them and it's not your answering service or your call service contacting these patients, I would really encourage caregivers, nurses as well as physicians to pick up the phone and proactively call these patients and share with them, educate them that they are potentially at risk and they need to come in for an interval or screening.
Particularly the areas that I mentioned, there are some easy to adopt ancillary lines of revenue that some groups are doing right now, and I mentioned the IBS patient population, I look at IBS population, these patients are very difficult and frustrating for gastroenterologists to manage because medical treatment is not terribly successful but there is successful dietary management with the FODMAP diet. There are ancillary streams through third parties like Modify Health that allow you to off-load your IBS patients to their team of dieticians and they administer the FODMAP diet through a set meal plan, the whole time the patient is putting their symptom scores into an iPhone App and you as a provider have it integrated back into your EMR so, you can better manage that patient population. They have seen great success with the groups that are doing that type of program now.
You know, moving over to the hepatology space, I think this literally and figuratively a massive patient population that walks through the clinic doors and the ASC doors every day, and very little is done to identify them or do appropriate workups. And now with the recent technology of Fiber scan, which is easily implemented in the office, and can be done by a medical assistant that maybe takes five minutes. Although not a huge ancillary stream, it helps you identify at-risk patients and manage them accordingly. And then, on top of that if you have a clinical research entity to enroll patients in the new NASH studies, you know, there's billions of dollars right now in the development of NASH drugs that are all waiting for FDA clearance.
And clinical research has burned a lot of smaller groups previously particularly with IBD and you know they had a difficult time with it, it was a big investment. There are companies out there like Objective GI which works on a joint venture model to help make this a really frictionless process. They take care of bringing the protocols, training the staff, running budgets, recruiting staff, and all you do as a small to mid-size practice is refer your patients over to this joint venture clinical research entity. The profit margin on this ancillary is very substantial you know, upwards of half a million dollars after you have it up and running and it offers a clinical benefit to your patient.
Shifting gears to the ambulatory center, you know, so much of GI is dependent on screening colonoscopy, around 60-70% of any ambulatory center's revenue is from the screening business and then the downstream revenue from pathology and anesthesia also is very substantial. But now that our endo centers have slowed because of COVID protocols, we might be at half capacity. And in some cases, centers that are just opening here in the Mid-Atlantic and the northeast or maybe at a third capacity. It's about thinking what we can do for at-risk patients. Maybe with advanced imaging. Advanced imaging has been around for almost two decades and you know, I'm thinking about EUS or confocal microscopy or the cellvizio technology. With confocal microscopy, there is established reimbursement for that procedure that CMS has category one code and you know, it's an adjunct to EGD with biopsy and again, it adds about $600 to $650per case to the facility fee. It's meaningful if you're doing it appropriately with at-risk patients which everyone is seeing with these high-grade dysplasia patients.
So, I think there's a lot of things that gastroenterologists are trained in during their fellowship, a lot of my good friends are also gastroenterologists have somewhat neglected because of the fact that historically there has been such volume and such a need for screening colonoscopy and a tremendous revenue stream and I think it's going back to our training meaning the gastroenterology training to understand what are we trained in, what clinical service can we provide to our patients, that is warranted and I think that's a more important point, and what are we going to be paid for and the examples that I just gave, all have very favorable ancillary revenue streams that could encourage groups to evaluate.
Praveen Suthrum: If you take diet and nutrition as an ancillary. I think everybody knows that it is an important ancillary and everybody does it, but the margins are so thin on that so there's no clear payment model. So, how do you figure that out?
Scott Fraser: Yeah, it's a great question. I know a lot of groups historically even large groups have maybe hired a dietician and the ROI with that staff member just wasn't favorable and one of the things about the company that I mentioned, Modify Health have done is that they have devised a model that has their dieticians as in you'll be referring your patients to Modify Health and for that referral, the patient is then buying the FODMAP diet which is a neat program. Not that it is a huge ancillary stream. It's about $100 to $150 per patient that's enrolled. But what it allows you to do is that you're not investing in a dietician, you're not spending the time to try to educate a patient on the FODMAP diet which is complicated I think even for the most skilled gastroenterologist and a very educated patient. It's hard to understand what to do and what not to do on each week of this diet and it is being managed by a very simple symptom score app.
So, essentially it is taking a very difficult patient population that a lot of gastroenterologists are frustrated with managing and the figures with IBS patients moving from gastroenterologist to gastroenterologist, on average they see five gastroenterologists before they actually feel like they have had some treatment because there's such a frustrating patient population to manage. This program is a way to keep these patients, make their symptoms go away, and not eat up valuable resources in your practice or make big investments while still recouping some ancillary stream from then. And although it's not substantial, it is a way to keep that patient engaged in your practice.
Praveen Suthrum: And how about the clinical trials with Objective GI that you mentioned. When you say half a million dollars, is it per trial? How does that work?
Scott Fraser: Yeah, it's a great question and you brought up the question before about established reimbursements. You know, large groups do clinical trials very well. If I look around the country, whether its Gastro Health, TDDC, or Capital Digestive Care or MNGI they all have very large clinical trial organizations and upwards of 20 different protocols at any one given time. It was a big investment at it was a slow ramp.
The nice thing about clinical trials is that they're not dependent on reimbursement. You're getting paid directly from the sponsor. And particularly with the latest NASH trials, the enrollment fees are very high because it's such a race right now to get these drugs to market from about 32 different pharma companies that have the drugs in some phase of development right now related to NASH. So, what the team at Objective GI does is that they come in under a joint venture model. It's a small startup fee from the mid-sized practice and really it becomes an integrated part of your practice that they are managing for you meaning that they are not only bringing the protocols to you, which is often difficult for groups to you know, get to meet the different clinical trials sponsors. But they have set protocols, they have a very experienced team of clinical research organization executives. And they are providing the training, the staffing and the budgetary process needed to run successful clinical trials and you as a provider, based on a set criterion are working up patients, in this case, you're working up patients with fiber scan which is paid for by different sponsors. You may work upon 30 patients with fiber scan and only identify two that you're enrolling in a trial but that fiber scan which is in your clinic is being reimbursed for by the clinical trial sponsors.
The numbers on fatty liver disease are anywhere between 80 million to 100 million Americans of which about 25 million will develop NASH again, this is literally and figuratively a massive patient population that our gastroenterologists see every day and very few groups are doing a lot for these patients. So, I'm really excited about that particular ancillary because again, it falls in line with GI and so much of fatty liver disease is dietary management too. So, we can help these patients based on your nutrition training as well just by losing 10 or 20 pounds.
Praveen Suthrum: Let's switch gears to private equity. Since you have been involved with private equity for a while. I want to know what the PE funds are thinking.
Scott Fraser: We are still very much in the early stages of the consolidation of the subspecialty of gastroenterology. If I look at other subspecialties where private equity has been very active in dermatology or in ophthalmology, particularly in dermatology you have over 30 platforms and by the latest estimates I've seen, about 50% of the private practice dermatologists are now part of an MSO. Where you know, right now eight platforms within GI and close to 1000 gastroenterologists, I know there are a lot of deals that are in the pipeline that should be closing by the end of the year. We still have a really small percentage of the overall 13,000 to 14,000 gastroenterologists in the US that are part of an MSO. In terms of deal structure, the thing that is changing right now in this level-setting is that the sellers meaning the groups are being asked to take on more risk and this can be done in a number of different ways. The structure typically is in the seller's note and what the buyers, private equity firms as well as their lenders are asking them to do is to structure deals that allow groups to get an additional payout for that transactional value when they hit their historical values of 2019. So, really the onus of the burden is on that group.
If I'm a group of 20 gastroenterologists and my volume hit down to 30%, I'm really betting on myself and my partners that we are going to get back to that 100% level that we were at 2019 to achieve full transactional value. Additionally, the structure of these deals is less cash. So, no longer it is this massive cash payout. Sellers are being asked and taking more equity. Again, betting in yourself. And, I have always stressed to gastroenterologists that are good friends that you know, many doctors have invested in real estate or restaurants or a bit more risky type investments. Investing in themselves is by far the best investment they can ever make. And looking at your own ambulatory center is a great example. Ambulatory centers were an investment that you made in yourself and your group and I would argue that they are absolutely one of the most valuable assets probably in your entire portfolio today.
Praveen Suthrum: Scott, if you were to put yourself in the shoes of an average GI practice anywhere in the country, how would you go about making a decision today? The GI practice out there has several choices right now. They can continue to be independent, doing what they're doing now, or they can consolidate with other groups in the local areas independently or they can seek out private equity and go that route. How would you go about making a decision if you were in their shoes?
Scott Fraser: It's a great question. I think the first thing I would do with my partners is really do a deep assessment of the local market conditions. So much of healthcare as we all know is local. So, not only what payor market looks like, what our referral market looks like, but I think more importantly what's happening in our broader healthcare market meaning I'm going to reference the DC area, it is a great example, where I did a transaction with Capital Digestive Care previously. The DC market has a common threat that really has caused a lot of consolidation across all subspecialties and that was a combination of Hopkins moving south and not only buying hospitals but primary care in the DC metro area as well as MedStar which again is another major hospital group doing the same.
That put a real threat across all subspecialists in that area and you've seen massive consolidation in that marketplace. Not just with gastroenterology and Capital Digestive Care but if I look at urology, dermatology, ophthalmology, Premier Carrier, one of the largest primary care groups of Premier Health in that market and most recently a transaction during this pandemic was with Shady Grove Fertility which is a multi-state platform not just in fertility but also in women's health. They have all consolidated because of the common threat in their local market and also because they have a major payor that has about 30% of that market. So, they needed size and scale and sophistication to be able to negotiate contracts. That would be the first step that I'd do.
The second step, I think is very similar to the analogy that if you're thinking about selling a house, it's getting your house in order. Meaning, if I have an outdated bathroom or I need a new roof. It's about making investments that will make my practice more attractive to not only a potential strategic meaning an established MSO platform or a potential suitor with a PE platform if that's the avenue I want ahead. I think it's an investment in an EMR, some data analytics, Revenue Cycle Management as you well know is often an area that groups don't have sophisticated Revenue Cycle Management or a process and system to track that and often, they are leaving 100s of dollars to 1000s of dollars a day on the tables because of the errors that they're making in coding or just not following and processing claims so, it's a very low hanging fruit. So, it's focused on you know, if I want to be acquired making the time and the investment upfront to make my practice more attractive.
And then if you're truly thinking about looking and staying independent during this consolidation, I think it's looking at what we can do and what we can offer additionally to our patients. We talked about screening colonoscopy business being a threat. It's really diversifying your groups into some of the areas that I talked about before. One area I didn't mention is an area that has been around for years and again has established reimbursement is hemorrhoidal treatment. Looking at sometimes the small incremental things that you can add to your practice is that's going to make you more stable, you know, as we whether through this storm. Now is the time to scrutinize and review every one of your contracts. It can be from your leases on your office or your ambulatory center with your landlords looking to defer payments as you are trying to recover.
Praveen Suthrum: How could GI groups collaborate with industries?
Scott Fraser: Industry whether it's the big pharma companies or Medtech companies, and supply companies have local marketing campaigns and budgets and more importantly, promote practices that are utilizing their products or maybe recruit patients via social media in a certain disease segment. So, as opposed to the industry coming to you and trying to sell you on a new product, and then offering up a potential marketing program, I would reach out to your industry partners and enquire about this because it does exist and they have the resources.
There are some great courses and forums every year. One being the GI roundtable that Bergein Overholt, MD started, and Klaus Mergener, MD has now taken to the next level. This meeting which has been around for years is really where the private practitioners in GI, talk about different business strategies and new ancillaries and it's a great forum.
I would also encourage private groups to become members of DHPA (Digestive Health Physicians Association) an advocacy group that now has close to 3000 members across the country. And the sharing of best practices with the DHPA leadership has been phenomenal and I would argue that DHPA has been part of the wave of PE sponsors meaning they're sharing best practices, transactional advice on how to maneuver through a transaction and what to prepare for and what to do with each other and again, it's a very collaborative effort. In a nutshell, understand your data, understand your local market, understand where there may be threats.
Praveen Suthrum: When you push this ball five years from now, or longer into the horizon, what do you see happening? What is the holy grail for GI?
Scott Fraser: You know, it's a great question. I think that the market forces right now that you mentioned right now and one of the biggest market forces are payors. If I look at the larger ecosystem within gastroenterology, at the top of the food chain are payors. Payors have consolidated massively and now are looking at buying providers. So, they have never liked consolidating across different markets, they are consolidating service lines. If I then go down a step, we talked about hospital consolidation that has happened then another step-down, you look at the industry. Industry has consolidated. You know, my two previous startup examples both with Given Imaging which is now part of Medtronic and EndoChoice which is now part of Boston Scientific are great examples of what's happened with industry consolidation.
In pharma, consolidation has been massive as well. The reason why consolidation has happened all around us has so much to do with economies of scale and resources. Speaking from my executive experience at EndoChoice, we didn't have the resources and the field team that a Boston Scientific has. They've taken our company which was approaching 80 million dollars in revenue and those product lines and have grown them substantially in the last three years because of their commercial infrastructure that we just couldn't invest in. So, scale matters. Unfortunately, at the bottom of the food chain of this consolidation are the gastroenterologists or the subspecialist. They haven't consolidated. But I look at groups that have consolidated and have integrated as well and I think that's a key point.
I know you had Jim Leavitt on previously from Gastro Health, they've been at this now for four years with Audax and you've seen the evolution with what Gastro Health has done. They're a fully integrated platform right now and have tremendous efficiencies that are all centralized versus some of the other platforms that are just starting that are yet to do that integration and create those efficiencies. So, I think in the future, the more integrated a platform can be, and a GI group can be lowering their administrative burdens, but also allowing them to maximize different ancillary lines, maximize at-risk type contracts. If we look at whether it's a colonoscopy bundle or managing a certain disease patient population like IBD, these are the initiatives that integrated groups are pursuing that really will limit and exclude private groups because of the resources needed and the scale needed to be able to negotiate with a payor or a major employer.
You know it has been really interesting to see what some of these large-scale groups have done going direct to employers with GI Health and having a direct service line to their practice. So, that being said, I think consolidation is going to happen and I would encourage groups to have an open mind to it. It is not a threat at all, it is something that is an evolution and it allows groups to stay independent. These companies that are nimble or practices that are nimble or also embrace change will come out of this pandemic stronger.
Praveen Suthrum: Scott Fraser, thank you so much for all these insights. It has been fantastic chatting with you.
Scott Fraser: Praveen, I really enjoy your labor of love if you will, in terms of not only the research but the writing and the time, sharing best practices with the broader GI community. It is much needed. I wish everyone continued safety and continued growth and success during this difficult time. We will get through this.
By Praveen Suthrum, President & Co-Founder, NextServices.
COVID-19: The Way Forward for Gastroenterology Practices
COVID-19 is a double whammy of both clinical and business disruption. This ebook will help you explore possible scenarios and be a guide in your plans for the future.
Exponential Tech from a GenX perspective – Part 1
Exponential Tech: DNA testing in cancer screening (Part 2)

redpajama_set_name: RedPajamaCommonCrawl


Kabalevsky and Shostakovich: two composers from the same city of Leningrad, born just over a year apart and yet what incredibly different sound worlds each created. Tonight's concert was not a tale of two cities but rather a tale of two worlds: a safe one which stayed on the correct side of Stalin; and an enigmatic one which could stray dangerously close to the edge. Leading us on this journey was young Russian guest conductor Stanislav Kochanovsky.
Kabalevsky's opera Colas Breugnon has long fallen out of the operatic canon but the overture remains relatively popular and with good reason. Bubbling with energy and exuberance, it offers a five minute highlight of the opera's themes. From the opening notes, Kochanovsky elicited a sharp, crisp tone from the RTÉ National Symphony Orchestra while keeping the rhythm taut. With blaring brass and fun cross rhythms, Kochanovsky made this a dramatic, lively rendition of this delightful overture.
English cellist Richard Harwood then performed Kabalevsky's Cello Concerto no. 1 in G minor. There is an endearing link between Kabalevsky and children's music, of which he produced realms. His concertos for piano, violin and cello, though, are far more challenging, destined as they were for more advanced students. This concerto contains many moments of mischievousness and liveliness. Possessing a sweet, intimate tone, Harwood tackled this work with consummate ease delivering the filigree with laser-like intonation. He impressed with the intensity of his vibrato on the higher notes. The NSO were very sensitive not to overpower him, even when the music grew more animated. There was a lovely moment where Harwood made the final notes of the first movement vanish into the ether, keeping us in suspense.
Harwood imbued the second movement Largo with a touching sadness that was not forced but emanated from the music itself. As the agitation subsided, Harwood spun the thread of his melody, unfurling each note with loving care. Shyly emerging from the threnody, the third movement bubbled over with effervescence. Harwood nimbly dispatched the bravura moments here while he brought the piece to a satisfying conclusion.
If the first half provided pleasant titillation, it was clear that the audience regarded it as the warm up to the main act: Shostakovich's Symphony no. 7. Called the "Leningrad" Symphony, it was not, the composer explained, "about Leningrad under siege, it's about the Leningrad Stalin destroyed and Hitler finished off". Clocking in at one hour and fifteen minutes, it makes Herculean demands on conductor and orchestra alike, in particular the brass section.
A stirring, declamatory opening from the strings soon gave way to the stillness and tenderness of the second subject. The 12 repetitions of the "War theme" were masterfully graded by Kochanovsky starting with an innocent melody on the flute and finishing with the brass blazing forth in all their glory, a veritable cry of humanity against the horrors of war. The pizzicato at the end was nothing short of brilliant, resonating in the silence that followed.
Kochanovsky conceived the second movement as an ironic Scherzo, rejoicing in its unsettling dissonance and typical harmonic changes. The third movement lament was dirge-like with sustained chords on woodwind and brass sounding like the keening for the victims murdered by Stalin and Hitler. Even the livelier moments possessed a sinister quality, like the energy the KGB might put into rounding up their victims. The NSO imbued the sinister low notes with great menace.
The finale, with its pounding rhythm and sonic boom of the brass, had us on the edge of our seats with excitement. At times stormy, at other times violent, Kochanovsky ratcheted up the volume and excitement to an almost unbearable pitch before the victorious C major shone out and brought an end to the terrors of war.


text:
Issachar ben Mordecai ibn Susan (fl. 1539–1572) (Hebrew: יששכר בן מרדכי אבן שושן) was a Jewish mathematician who lived in Ottoman Palestine.

At a young age, he moved from Morocco—perhaps from Fes—to Jerusalem, where he became a pupil of Levi ibn Ḥabib. From there he went to Safed, where, under great hardship, he continued his studies. But his increasing poverty induced him, in 1539, to leave Safed and seek a living elsewhere.

At this time he commenced a work on the calendar, giving, among other things, tables which embraced the years 5299–6000 (1539–2240). After his return to Safed he resumed his work on the calendar, in which he was assisted by the dayan Joshua. It was published at Salonica, in 1564, under the title Tikkun Yissakar. The second edition, under the title Ibbur Shanim (Venice, 1578), is not as rare as the first. The tables in both editions begin with the year of publication.

The book also contains, in two appendixes, a treatise on rites ("minhagim") depending upon the variations in the calendar from year to year, and a treatise on the division of the weekly portions and the hafṭarot according to the ritual of the different congregations. For the latter treatise the author quotes as his source ancient manuscript commentaries, and holds that, according to the opinion of a certain scholar, the division of the weekly portions is to be traced back to Ezra. Rites, anonymously given, are, according to p. 51, 2d edition, taken from Abudarham, to whom the author attributes great authority.

Jewish Encyclopedia bibliography
 Fuenn, Keneset Yisrael, i.704;
 Fürst, Bibl. Jud. iii.396;
 Steinschneider, Cat. Bodl. col. 1061;
 idem, in Abhandlungen zur Gesch. der Mathematik, 1899, ix.479.

References

16th-century rabbis from the Ottoman Empire
Palestinian mathematicians
Year of birth unknown
Year of death unknown
People from Fez, Morocco
16th-century rabbis in Jerusalem
Rabbis in Safed
16th-century Moroccan Jews
Moroccan mathematicians
Moroccan emigrants to the Ottoman Empire

redpajama_set_name: RedPajamaWikipedia


This entry was posted on Monday, April 2nd, 2012 at 2:44 am	and is filed under Home Brewing. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed.


text:
Q: What is the definition for the licensetype enum? We are working with providing additional information about the type of license for our end to end logging and monitoring tool Nodinite. We have a problem identifying definition for the LicenceType Enum?
Microsoft documentation does not provide any values for the enum:
https://learn.microsoft.com/en-us/dynamics365/customer-engagement/developer/entities/systemuser#BKMK_UserLicenseType
/// <summary>
/// Type of license, such as Professional, Standard, or Suite.
/// </summary>
[Microsoft.Xrm.Sdk.AttributeLogicalNameAttribute("licensetype")]
public System.Nullable<System.Guid> LicenseType
{
    get
    {
        return this.GetAttributeValue<System.Nullable<System.Guid>>("licensetype");
    }
    set
    {
        this.OnPropertyChanging("LicenseType");
        this.SetAttributeValue("licensetype", value);
        this.OnPropertyChanged("LicenseType");
    }
}

These are the unique values for the users in the Dynamics 365 (CRM) instance
UserLicenseType:
-1, 3, 6, 7, 11, 20, 30

A: You can use fetchxml to query the stringmap table in XrmToolBox - FetchXML builder. Check the caltype in MS documentation. userlicensetype is just mentioned as Edm.Int32.
You can pull this information from customizations as well under systemuser entity - attributes. userlicensetype is just a wholenumber - probably filled in from O365 portal when you assign license.
<fetch>
  <entity name="stringmap" >
    <attribute name="attributevalue" />
    <attribute name="attributename" />
    <attribute name="value" />
    <filter type="and" >
      <condition attribute="objecttypecode" operator="eq" value="8" />
      <filter type="and" >
        <condition attribute="attributename" operator="eq" value="caltype" />
      </filter>
    </filter>
  </entity>
</fetch>

Interesting data from our CRM:


text:
Preparation and Characterization of Nanoemulsome Entrapped in Enteric Coated Hydrogel Beads for the Controlled Delivery of Capsaicin to the Colon
Author(s): Tapan Kumar Giri*, NSHM College of Pharmaceutical Technology, NSHM Knowledge Campus, Kolkata Group of Institutions, 124 BL Saha Road, Kolkata-700053, West Bengal, India	Bidisha Dey, NSHM College of Pharmaceutical Technology, NSHM Knowledge Campus, Kolkata Group of Institutions, 124 BL Saha Road, Kolkata-700053, West Bengal, India	Subhasis Maity. NSHM College of Pharmaceutical Technology, NSHM Knowledge Campus, Kolkata Group of Institutions, 124 BL Saha Road, Kolkata-700053, West Bengal, India
Journal Name: Current Drug Therapy
Volume 13 , Issue 1 , 2018
DOI : 10.2174/1574885512666171107151526
Background: Colorectal cancer is a major public health problem in the developed world. Capsaicin, a spicy component of hot pepper that preferentially induces certain cancer cells to undergo apoptosis including colon cancer cells.
Objective: The aim of the present investigation was to entrap nanoemulsome containing capsaicin in gellan gum hydrogel beads and further coated with Eudragit S100 for site specific delivery to the colon.
Method: Nanoemulsomes were prepared by thin film hydration method. Then the prepared nanoliposomes were entrapped in gellan gum hydrogel beads and coated with Eudragit S 100. Physical state of the drug in nanoemulsome was determined by X-ray diffraction and differential scanning calorimetry technique. Nanoemusomes were characterized for size, drug entrapment, and in vitro drug release.
Results: The entrapment efficiency and average particle size of nanoemulsome were 33.75% and 174.4 nm respectively. In vitro drug release studies were carried out using dialysis bag technique in simulated fluids at different pH (1.2, 4.5, 7.4, and 6.8) to mimic the gastrointestinal tract. Eudragit S 100 coated hydrogel beads has shown complete drug release for 24 h in a controlled manner in comparison to the un-coated hydrogel beads, which released about 50% of the drug before entering the colonic region.
Conclusion: The results clearly demonstrated that coated hydrogel beads can be used as a potential carrier for delivery of capsaicin to colon.
Keywords: Capsaicin, gellan gum beads, enteric coated, emulsome, drug delivery.
Current Drug Therapy
Title:Preparation and Characterization of Nanoemulsome Entrapped in Enteric Coated Hydrogel Beads for the Controlled Delivery of Capsaicin to the Colon
VOLUME: 13	ISSUE: 1
Author(s):Tapan Kumar Giri*, Bidisha Dey and Subhasis Maity
Affiliation:NSHM College of Pharmaceutical Technology, NSHM Knowledge Campus, Kolkata Group of Institutions, 124 BL Saha Road, Kolkata-700053, West Bengal, NSHM College of Pharmaceutical Technology, NSHM Knowledge Campus, Kolkata Group of Institutions, 124 BL Saha Road, Kolkata-700053, West Bengal, NSHM College of Pharmaceutical Technology, NSHM Knowledge Campus, Kolkata Group of Institutions, 124 BL Saha Road, Kolkata-700053, West Bengal
Keywords:Capsaicin, gellan gum beads, enteric coated, emulsome, drug delivery.
Abstract:Background: Colorectal cancer is a major public health problem in the developed world. Capsaicin, a spicy component of hot pepper that preferentially induces certain cancer cells to undergo apoptosis including colon cancer cells.
Tapan Kumar Giri*, Bidisha Dey and Subhasis Maity, "Preparation and Characterization of Nanoemulsome Entrapped in Enteric Coated Hydrogel Beads for the Controlled Delivery of Capsaicin to the Colon", Current Drug Therapy (2018) 13: 98. https://doi.org/10.2174/1574885512666171107151526
https://doi.org/10.2174/1574885512666171107151526 Print ISSN
Page: [98 - 105]
DOI: 10.2174/1574885512666171107151526
HTML: 2
miRNA Targeting Angiogenesis as a Potential Therapeutic Approach in the Treatment of Colorectal Cancers
Colorectal Carcinogensis and Suppression of Tumor Development by Inhibition of Enzymes and Molecular Targets
Current Enzyme Inhibition
DNA Repair and Resistance to Topoisomerase I Inhibitors: Mechanisms, Biomarkers and Therapeutic Targets
The Impact of Folate Status on the Efficacy of Colorectal Cancer Treatment
Current Drug Metabolism
Analysis of the Concordance in the EGFR Pathway Status Between Primary Tumors and Related Metastases of Colorectal Cancer Patients:Implications for Cancer Therapy
Current Cancer Drug Targets
Aflibercept: A Novel VEGF Targeted Agent to Explore the Future Perspectives of Anti-Angiogenic Therapy for the Treatment of Multiple Tumors
Mini-Reviews in Medicinal Chemistry
Gastrointestinal Polyposis Syndromes
Current Molecular Medicine
Lectin-Immobilized Fluorescent Nanospheres for Targeting to Colorectal Cancer from a Physicochemical Perspective
Current Drug Discovery Technologies
Familial Colorectal Cancer Type X
Current Genomics
Anti-VEGF and Anti-EGFR Monoclonal Antibodies in the First-line Therapy for Metastatic Colorectal Cancer - A Meta-Analysis
Current Cancer Therapy Reviews
Bisphosphonates and Breast Cancer Prevention
Anti-Cancer Agents in Medicinal Chemistry
Gastric Ulcer Complicating a Selective Internal Radiation Therapy (SIRT) Procedure for Colorectal Carcinoma Metastasized to the Liver
Current Radiopharmaceuticals
Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer
Predictive Molecular Markers of Response to Epidermal Growth Factor Receptor(EGFR) Family-Targeted Therapies
Angiogenesis Inhibitors: Perspectives for Medical, Surgical and Radiation Oncology
pH-Dependent Behavior of Novel Gellan Beads Loaded with Naproxen
Current Drug Delivery
TGF-β1 Signalling, Connecting Aberrant Inflammation and Colorectal Tumorigenesis
Monoclonal Antibodies in Rare Acquired Thrombotic Disorders: The Paradigms of Paroxysmal Nocturnal Hemoglobinuria, Thrombotic Thrombocytopenic Purpura and Central Retinal Vein Occlusion
The Prodrugs of 5-Fluorouracil
Current Medicinal Chemistry - Anti-Cancer Agents
Anti-Cancer Effect of α-Solanine by Down-Regulating S100P Expression in Colorectal Cancer Cells
Recent Patents on Anti-Cancer Drug Discovery


For both repair and replacement, trust Thunder Auto Glass for your auto glass needs. Friendly, professional auto glass service is available in WA houghton is conveninent for on-site service. Among expert glass firms in houghton is Microchip Autoglass. We have the service providers you need.


text:
Q: Getting HTTP headers from Apache CXF POJO Service what is the right method to get http headers from CXF POJO Service?
I have folowing code, but it doesn't work:
ServerFactoryBean svrFactory = new ServerFactoryBean();
svrFactory.setServiceClass(TestService.class);
svrFactory.setAddress("http://localhost:8080/test");
svrFactory.getServiceFactory().setDataBinding(new AegisDatabinding());
svrFactory.create();

public class TestService {

    protected javax.xml.ws.WebServiceContext wsContext;

    public void someMethod() {
       // the problem is that wsContext.getMessageContext() is null
    }
}

Thanks!

A: You would need to add an @Resource onto the wsContext variable and also switch to using the JaxWsServerFactoryBean.
Alternatively, use:
PhaseInterceptorChain.getCurrentMessage()
to get the current CXF internal message and grab the headers off there.


text:
Category: Client Guides
Sponsor Licence Application Guide 2023
You need a sponsor licence to employ most types of workers from outside the UK, including Skilled Visa workers. To secure a UK visa sponsorship licence, you will need to make an application to the Home Office and pay the relevant fees. The Home Office will only grant a sponsor licence to an organisation that […]
IR35 Changes (Off Payroll Working Rules)
IR35 changes took effect on 6 April 2021, impacting how private sector organisations engage contractors for off-payroll working. The latest reforms were due to go live on 6 April 2020 but were postponed by a year in light of the coronavirus pandemic. Below we examine the nature and extent of the IR35 changes, and how […]
Applying for Settled Status in the UK
Settled Status in the UK EU citizens and their family members already in the living in the UK by 30 December 2020 have to register under the settled status UK scheme to retain their rights to remain indefinitely in the UK after 30 June 2021. The UK left the EU on 31 January 2020. From […]
Tier 2 Sponsorship (An Essential Guide!) | DavidsonMorris
Tier 2 Sponsorship With Tier 2 visa sponsorship, now called Skilled Worker visa sponsorship, companies are permitted to hire skilled workers from outside the UK where the role and level of pay meet specific requirements. All UK companies hiring workers that are not UK resident, including EU nationals coming to the UK after 2020, are […]


text:
HP to acquire photo start-up Tabblo
HP hopes to license Tabblo's in-house Web printing technology to its partner sites.
March 22, 2007 9:49 AM PDT
Hewlett-Packard announced Thursday that it plans to acquire start-up Tabblo, citing an interest in the photo-sharing site's technology that facilitates printing from the Web.
The Cambridge, Mass.-based Tabblo, which was founded in 2005, specializes in the creation of photograph templates (or "tabblos," a takeoff on "tableau") and has developed Ajax-based features that enable users to arrange text, graphics and photos for printing directly from the Web. With the acquisition, HP hopes to license Tabblo's technology to its partner sites to make the simplified Web printing more accessible.
Financial terms of the acquisition were not provided. HP expects the deal to be completed within the next few weeks.
HP's been working on improving its profile in the digital photography market for some time. In 2005, it purchased Snapfish, a major player in the online photo-printing market, and now packages Snapfish software with its digital cameras. Additionally, in June, HP purchased the Swiss digital imaging company Silverwire, which specializes in software for commercial photo kiosks and mini-labs for retailers.
HP has also catered to professionals recently with the introduction of its DreamColor technology for photographers and designers, a collaboration with DreamWorks Animation, earlier this month.
But while HP expects to turn Tabblo's technology into another arm of its digital-imaging arsenal, this won't mean the end of the photo-sharing site. A post published Thursday on Tabblo's blog clarified that Tabblo's Web site will remain intact and stay separate from Snapfish.
How to save even more on Prime Day 2019: Think the deals are already good? Here's how to score additional savings.
Jony Ive leaving Apple signals the end of Steve Jobs era: From Apple TV Plus to its chief designer moving on, the iPhone maker is becoming a different company.
Discuss: HP to acquire photo start-up Tabblo


This is post will be preserved for future cases when new Visual Studio versions are released and CUDA Toolkit stays behind.
Install .NET Framework 3.5 if you didn't have it installed. Open Classical Control Panel, go to Programs and features and press Turn Windows features on or off. Check .NET Framework 3.5 and press OK.
Download full CUDA toolkit distribution and extract it somewhere on your disk. The exe file is just a self-extracting archive, so use any advanced archive tool such as WinRAR or 7Zip.
If you didn't have CUDA toolkit installed, do it now. If you have only Visual Studio 2017 installed, unselect Visual Studio integration checkbox.
And that's it! Now you can build your Cuda project from Visual Studio 2017 as well as Visual Studio 2015. This solution allows you only to build stuff and doesn't provide a way to use NVidia's debugging extensions. For those to work we will have to wait for official support from NVidia.


This accreditation is for those who practice pastoral supervision for 15 – 30 hours per year and have met the APSE criteria for Accreditation.
This accreditation is for those who practice pastoral supervision for 30+ hours per year and have met the APSE criteria for Accreditation.
Membership for those who practice pastoral supervision for 30+ hours per year, run programmes in pastoral supervision training and have met the APSE criteria for Accreditation.
The first step to accreditation is to make contact with us. You can do this using the contact form to request an application pack. Or emailing directly to accreditation@pastoralsupervision.org.uk.
We can then have an informal discussion with you and help you decide which accreditation is most suitable.
Once you are successful you will need to maintain your accreditation by continuing your APSE membership and renewing your accreditation every 5 years.


Html Email Newsletter Templates html email newsletter templates email newsletter templates html email newsletter templates free templates. html email newsletter templates free html email newsletter templates download studiojpilates free. html email newsletter templates 13 of the best email newsletter templates and resources to download ideas. Html Email Newsletter Templates html email newsletter templates 39 besten newsletter webdesign bilder auf pinterest email ideas. html email newsletter templates 30 free responsive email and newsletter templates template. html email newsletter templates 30 free responsive email and newsletter templates free. Html Email Newsletter Templates html email newsletter templates email newsletter templates for outlook smart customizable email and ideas.
Html Email Newsletter Templates html email newsletter templates free html email newsletter templates download studiojpilates free. html email newsletter templates 13 of the best email newsletter templates and resources to download ideas. html email newsletter templates 39 besten newsletter webdesign bilder auf pinterest email ideas. html email newsletter templates 30 free responsive email and newsletter templates template. html email newsletter templates 30 free responsive email and newsletter templates free.


The horizontal and vertical slurry pumps are designed for ultra heavy duty why you should only select genuine Warman® parts for your Warman® slurry pump.
Pumping slurry is one of the most demanding applications for any pump. Parts wear out, maintenance and repair cost are high. and return activated sludge in treatment pumps for raw wastewater and effluent pumping .. an ordinary centrifugal pump, hence the flow speed. 150ESG Model Gravel Sand Pump Sunbo Pump.
Results 1 - 48 of 106 Youll find new or used products in Slurry Pumps on eBay. 8x10 XinhaiThomas Slurry Pump and Goodyear PD Drive. Slurry transfer.
Find your slurry pump easily amongst the 743 products from the leading brands slurry pump centrifugal for the mining industry corrosion-resistant Orion series Features The STHM slurry pumps are also available with alternative impeller .. provided of agitator to stir things up - High abrasion resistance -Wear parts .
28262 products Horizontal Centrifugal Heavy Duty Mining Slurry Pump Shijiazhuang Sunbo Pump .. Working Pressure: High Pressure Pump Large 6"; Influent Type of Impeller: End Suctionspear and Wear Parts for Slurry Pumps.


The Tony Award winning Utah Shakespeare Festival will kick off its season in June and tickets are going fast. The festival is located in Cedar City, in southern Utah, and makes a great addition on trips to see our national parks and other attractions.
Performances begin June 23 and run through October 18. Productions this season are listed below. See the Festival's official website for schedules and detailed information.
The Festival was named the recipient of the coveted Tony Award for America's Outstanding Regional Theatre on May 8, 2000.
The Festival recently announced productions for its 2015 season. BroadwayWorld.com has the details in this report.
The video below shows Festival promotional material from "The Tempest," which was presented last season.


text:
Report: Adults With Serious Mental Illnesses Face 80% Unemployment
By Jenny Gold	 July 10, 2014
This KHN story can be republished for free. (details)
Employment rates for people with a serious mental illness are dismally low and getting worse, according to a report from the National Alliance on Mental Illness. Just 17.8 percent of people receiving public mental health services were employed in 2012 – down from 23 percent in 2003.
That's an unemployment rate of more than 80 percent.
"It isn't surprising," says Sita Diehl, director of state policy at NAMI and author of the report. The problem has less to with the workers themselves, she says, and more with the organizations that provide services for people with serious mental illness. "We knew that mental health services really took it on the chin during the recession. Employment rates had already been dismal to begin with, and when the supports were eroded, people with mental illness lost support and lost jobs."
Rates of unemployment for people with mental illnesses varied greatly by state – from 92.6 percent in Maine to 56 percent in Wyoming.
Most adults with mental illness want to work, and six in 10 can succeed with the right supports, according to the report. Yet only 1.7 percent received supported employment services in 2012.
Without proper supports, many end up on expensive public programs including Supplemental Security Income (SSI) and Social Security Disability Income (SSDI). People with mental illnesses make up the largest and fastest growing group for both programs.
There are, however, several evidence-based programs to help individuals with mental illnesses find jobs and maintain them.
In La Crosse, Wis., for example, the Family and Children's Center received funding to offer a supported employment program that currently serves 72 people.
One of them is Pierre Thomas, 30, who suffers from bipolar disorder. After being released from a hospital, he ended up on the streets.
"I was going downhill and became homeless. I had basically lost everything – friends, family, I was going nowhere," recalls Thomas. One day, he stopped by the Family and Children's Center, where he was connected with a case worker, mental health services and someone he calls his "job person," who helped him land an interview at the local Hobby Lobby.
With his counselor's assistance, he landed a job as a stocker in the back room. They speak every day to "talk about what I can do to help be better at my job," says Thomas, and she's connected him with other organizations that helped him get work clothes and transportation.
"It's built self-confidence," explains Thomas. "Also it has basically opened the door to talk with other people and interact."
But programs like the one in La Crosse are few and far between, and they tend to be unevenly implemented and funded in most states, says NAMI's Diehl.
And SSI and SSDI can present a disincentive to find work, because beneficiaries who start a job may lose Medicaid or Medicare benefits. People in the programs have to prove that they are too sick to work full-time. If they make over a certain threshold, they can lose both their cash benefits and their health insurance.
"During recessions we see a spike in disability," says David Wittenburg, a senior researcher at Mathematica Policy Research. It's a trend that has been made worse by a shifts in the labor market. "There's an increasing demand for high-skilled labor, and sometimes people with disabilities get left behind."
Once on SSI or SSDI, he adds, people are unlikely to get off: "The most common reasons for leaving the programs are death or retirement."
Despite the numbers, NAMI's Diehl says there's reason to be hopeful. "Things are coming together right now to really make this a turning point" for individuals with mental illness, she says. The economy is improving, and the mental health parity law in combination with new insurance options offered under the Affordable Care Act give people new ways to maintain their mental health benefits without staying on Social Security programs.
Mental health coverage, for example, is now a mandated benefit on plans purchased in the individual and small group marketplaces. And people with a mental illness can no longer be denied coverage for having a preexisting condition.
NAMI is calling on state legislatures to bolster their employment assistance to take advantage of the new options.
"If we were able to bring those programs to scale, then people with mental illnesses would be able to live independently and contribute to their local economies," says Diehl. "The health care cliff is going away."


Welcome! This site aims at helping you identify ready to use solutions for your optimization problem, or at least to find some way to build such a solution using work done by others. If you know of useful sources not listed here, please let us know. If something is found to be erroneous, please let us know, too. Where possible, public domain software is listed here.
In any case, observe the expressed or implied LICENSE conditions ! In most cases, these accompany the source code. As a rule, most codes are free for research. This means free for academic research and teaching or for trying whether it serves your needs. Commercial uses (either direct or indirect) require licensing, as a rule.


A Gradual with Consummate Penwork. Single folio on vellum. Spain, ca. 1550: approx. 500 mm x 380 mm. Eight five-line staves in red, rake-ruled (17.5 mm). Foliated xliii in red ink in upper right. Decoration: three staff-high initials, one in red with blue penwork, one in blue with red penwork, and one puzzle initial in red and blue with exceptionally fine red and blue penwork. Texts: Alleluia, Sequence, Offertory, and Communion for the Feast of the Exaltation of the Cross; Office for the Feast of the Crown of Thorns. This is an unusual pairing found only in Germany, Scandinavia, and Spain, but not universally.


text:
Zoos & GardensWinter ActivitiesTrains, Dinos & HeroesHolidaysChristmas/HanukkahTweens & TeensPreschoolersKidsBronx ParkBronx
Watch in amazement as model trains zoom through the magical display. Photo courtesy of NYBG
What's New at the NYBG Holiday Train Show in 2019
10/18/19 - By Jody Mercier
Manhattan's Central Park is the star of this year's Holiday Train Show at the New York Botanical Garden, opening November 23, 2019 and running through January 26, 2020. We may still be a few weeks from Halloween, but the annual train show is a NYC Christmas tradition worth looking forward to.
The iconic landscape of the park includes architectural treasures like Belvedere Castle, the Dairy, the Old Bandstand, the Angel of the Waters sculpture atop the Bethesda Fountain, and two graceful pedestrian bridges, arrayed in a winter wonderland tableau alongside existing Central Park replicas in NYBG's collection, including the Swedish Cottage Marionette Theater.
Read on for a peek at what else is new, plus everything you need to know about visiting this popular holiday attraction with kids.
Iconic NYC landmarks were created for the holiday train show.
Famous New York buildings that are either adjacent to the park or just inside it are also on display, including the Plaza Hotel, the Metropolitan Museum of Art, the Solomon R. Guggenheim Museum, and the Rose Center for Earth and Space, part of the American Museum of Natural History.
This year, the Holiday Train Show is presented in an immersive indoor winter wonderland adjacent to the Enid A. Haupt Conservatory as the Conservatory's palm dome undergoes restoration. The spacious, climate-controlled exhibition space is located on the Conservatory Lawn.
RELATED: Best Family-Friendly Restaurants Near the Bronx Zoo and New York Botanical Garden
Lush landscapes surround detailed replicas of over 150 beloved NYC landmarks.
Central Park, designed in 1858 by landscape architects Frederick Law Olmsted and Calvert Vaux, has been featured in hundreds of movies. Perhaps even more important, Olmsted and Vaux's "Greensward Plan" inspired cities across the country to set aside large open spaces as public parks.
In the Holiday Train Show, more than 25 G-scale model trains and trolleys hum along nearly a half-mile of track past re-creations of iconic sites from all five boroughs of New York City, the Hudson River Valley, and other locations in New York State. American steam engines, streetcars from the late 1800s, and modern freight and passenger trains travel underneath overhead trestles, through tunnels, across rustic bridges, and past waterfalls that cascade into flowing creeks.
As always, the show includes an All Aboard with Thomas and Friends performance later in the season, and there are more train-themed activities, such as pretend play on the Evergreen Express and outdoor exploration of the winter garden.
Tickets are required and included in an All-Garden Pass. Plan to purchase a timed-entry pass in advance for popular times.
Unless noted, photos courtesy of the author
Show map of all locations.
2900 Southern Boulevard
See more about this place.
21 NYC Holiday Activities Every Kid Should Try Once Best Family Restaurants Near the Bronx Zoo and Botanical Garden Best Holiday Shows for Kids and Families in NYC 2019 35 Free Things to Do in NYC with Kids This December


text:
Zeibiz
Home Television America's Got Talent Patches raps original song on America's Got Talent 2018 Judge Cuts
Patches raps original song on America's Got Talent 2018 Judge Cuts
Mirex Sebastian
Patches raps another original song on America's Got Talent Season 13 Judge Cuts rounds on Tuesday, July 17, 2018.
"You burn this song to ashes," said Ken. "I was not expecting that, I love this surprise," said Howie.
Watch his performance on the video below.
What can you say about Patches' performance? Share your thoughts below.
Tonight, twenty acts will perform but only seven will advance to the live shows, including the guest judge's golden buzzer choice.
America's Got Talent is an American reality television series aired on NBC, and part of the global Got Talent franchise. It is a talent show that features singers, dancers, magicians, comedians, and other performers of all ages competing for the advertised top prize of one million dollars.
AGT Season 13 airs every Tuesday on NBC. Tyra Banks serves as host while Howie Mandel, Mel B, Heidi Klum and Simon Cowell serves as judges.
To receive more news and update, follow us on Facebook and Twitter.
Previous articleChristina Wells sings "Never Enough" on America's Got Talent 2018 Judge Cuts
Next articleCanas Con Ganas steals the show on America's Got Talent 2018 Judge Cuts
mailto:info@zeibiz.com
Head editor at Zeibiz covering topics on technology, entertainment and television. He's based in Philippines. Email | Twitter | Facebook
Huawei Y9 Prime 2019 Unboxing, Specs, Pop-up Camera Test, Price Philippines
Detroit Youth Choir "Golden Buzzer" America's Got Talent 2019 Audition Performance Video
Berywam America's Got Talent 2019 Audition Performance Video
Mobile Phone Reviews
Dominguez Poodles America's Got Talent 2019 Audition Performance Video
Voices Of Service America's Got Talent 2019 Audition Performance Video
The Voice Kids Philippines
Pinoy Big Brother
The Voice Australia
© Zeibiz 2019 | Home | About Us | Authors | Contact | Privacy Policy | Disclaimer


text:
A novel point mutation in cluster 3 of the thyroid hormone receptor β gene (P247L) causing mild resistance to thyroid hormone
Joachim Pohlenz, Laura Manders, Peter M. Sadow, Prakash C. Kansal, Samuel Refetoff, Roy E Weiss
Resistance to thyroid hormone (RTH), a syndrome characterized by variable tissue hyposensitivity to thyroid hormone (TH), is linked to mutations in the thyroid hormone receptor (TR) β gene. We report a new family with a heretofore unreported mutation, P247L. The proposita, a 31- year-old female, presented with goiter and palpitations. RTH was suspected because of elevated serum free thyroxine (FT4) level with a normal thyrotropin (TSH). Sequencing the TRβ gene revealed a mutation causing replacement of a proline at position 247 with leucine. Seven family members were heterozygous for the mutation, two of whom also had evidence of autoimmune thyroid disease. The mutant TRβ had a Ka for triiodothyronine (T3) 30% that of the wild-type TRβ, approximately a threefold reduction in T3-induced transactivation and a low level dominant negative activity when tested with a positively regulated reporter gene. In vivo sensitivity to TH was evaluated in three affected subjects by measurement of the responses to graded doses of levotriiodothyronine (LT3). Peak TSH responses to TRH were reduced and were not completely suppressed at even the highest dose of LT3, (0.9, 0.2, and 0.2, compared to <0.01 μU/mL in unaffected controls), confirming pituitary resistance to TH in all three subjects. In contrast, peripheral tissues responded variably to LT3: serum cholesterol decreased in all by 15%-25%, serum creatine kinase decreased by 15% in two subjects and increased 35% in another, but serum ferritin and sex hormone-binding globulin increased in only one of the three affected individuals that were tested. Basal metabolic rate and sleeping pulse did not change in three and two individuals, respectively. Hyporesponsiveness to exogenous TH established the clinical diagnosis of RTH in one member of the family with a mutant TRβ but normal tests of thyroid function at baseline. Three affected subjects had an axis I diagnosis of major depression but had Wechsler Intelligence Scale for Children, III (WISC-III) full-scale IQs (FSIQs) in the normal range. This novel TRβ mutation is associated with a relatively mild RTH. Results of responses to LT3 underscore the variable phenotype of RTH.
Published - Dec 1999
Thyroid Hormone Receptors
Wechsler Scales
Basal Metabolism
Sex Hormone-Binding Globulin
Triiodothyronine
Thyrotropin
Ferritins
Creatine Kinase
Thyroxine
Reporter Genes
Pohlenz, J., Manders, L., Sadow, P. M., Kansal, P. C., Refetoff, S., & Weiss, R. E. (1999). A novel point mutation in cluster 3 of the thyroid hormone receptor β gene (P247L) causing mild resistance to thyroid hormone. Thyroid, 9(12), 1195-1203.
A novel point mutation in cluster 3 of the thyroid hormone receptor β gene (P247L) causing mild resistance to thyroid hormone. / Pohlenz, Joachim; Manders, Laura; Sadow, Peter M.; Kansal, Prakash C.; Refetoff, Samuel; Weiss, Roy E.
In: Thyroid, Vol. 9, No. 12, 12.1999, p. 1195-1203.
Pohlenz, J, Manders, L, Sadow, PM, Kansal, PC, Refetoff, S & Weiss, RE 1999, 'A novel point mutation in cluster 3 of the thyroid hormone receptor β gene (P247L) causing mild resistance to thyroid hormone', Thyroid, vol. 9, no. 12, pp. 1195-1203.
Pohlenz J, Manders L, Sadow PM, Kansal PC, Refetoff S, Weiss RE. A novel point mutation in cluster 3 of the thyroid hormone receptor β gene (P247L) causing mild resistance to thyroid hormone. Thyroid. 1999 Dec;9(12):1195-1203.
Pohlenz, Joachim ; Manders, Laura ; Sadow, Peter M. ; Kansal, Prakash C. ; Refetoff, Samuel ; Weiss, Roy E. / A novel point mutation in cluster 3 of the thyroid hormone receptor β gene (P247L) causing mild resistance to thyroid hormone. In: Thyroid. 1999 ; Vol. 9, No. 12. pp. 1195-1203.
@article{80e2f706f971435a8c4b945aae0cfd63,
title = "A novel point mutation in cluster 3 of the thyroid hormone receptor β gene (P247L) causing mild resistance to thyroid hormone",
abstract = "Resistance to thyroid hormone (RTH), a syndrome characterized by variable tissue hyposensitivity to thyroid hormone (TH), is linked to mutations in the thyroid hormone receptor (TR) β gene. We report a new family with a heretofore unreported mutation, P247L. The proposita, a 31- year-old female, presented with goiter and palpitations. RTH was suspected because of elevated serum free thyroxine (FT4) level with a normal thyrotropin (TSH). Sequencing the TRβ gene revealed a mutation causing replacement of a proline at position 247 with leucine. Seven family members were heterozygous for the mutation, two of whom also had evidence of autoimmune thyroid disease. The mutant TRβ had a Ka for triiodothyronine (T3) 30{\%} that of the wild-type TRβ, approximately a threefold reduction in T3-induced transactivation and a low level dominant negative activity when tested with a positively regulated reporter gene. In vivo sensitivity to TH was evaluated in three affected subjects by measurement of the responses to graded doses of levotriiodothyronine (LT3). Peak TSH responses to TRH were reduced and were not completely suppressed at even the highest dose of LT3, (0.9, 0.2, and 0.2, compared to <0.01 μU/mL in unaffected controls), confirming pituitary resistance to TH in all three subjects. In contrast, peripheral tissues responded variably to LT3: serum cholesterol decreased in all by 15{\%}-25{\%}, serum creatine kinase decreased by 15{\%} in two subjects and increased 35{\%} in another, but serum ferritin and sex hormone-binding globulin increased in only one of the three affected individuals that were tested. Basal metabolic rate and sleeping pulse did not change in three and two individuals, respectively. Hyporesponsiveness to exogenous TH established the clinical diagnosis of RTH in one member of the family with a mutant TRβ but normal tests of thyroid function at baseline. Three affected subjects had an axis I diagnosis of major depression but had Wechsler Intelligence Scale for Children, III (WISC-III) full-scale IQs (FSIQs) in the normal range. This novel TRβ mutation is associated with a relatively mild RTH. Results of responses to LT3 underscore the variable phenotype of RTH.",
author = "Joachim Pohlenz and Laura Manders and Sadow, {Peter M.} and Kansal, {Prakash C.} and Samuel Refetoff and Weiss, {Roy E}",
journal = "Thyroid",
T1 - A novel point mutation in cluster 3 of the thyroid hormone receptor β gene (P247L) causing mild resistance to thyroid hormone
AU - Pohlenz, Joachim
AU - Manders, Laura
AU - Sadow, Peter M.
AU - Kansal, Prakash C.
AU - Refetoff, Samuel
AU - Weiss, Roy E
N2 - Resistance to thyroid hormone (RTH), a syndrome characterized by variable tissue hyposensitivity to thyroid hormone (TH), is linked to mutations in the thyroid hormone receptor (TR) β gene. We report a new family with a heretofore unreported mutation, P247L. The proposita, a 31- year-old female, presented with goiter and palpitations. RTH was suspected because of elevated serum free thyroxine (FT4) level with a normal thyrotropin (TSH). Sequencing the TRβ gene revealed a mutation causing replacement of a proline at position 247 with leucine. Seven family members were heterozygous for the mutation, two of whom also had evidence of autoimmune thyroid disease. The mutant TRβ had a Ka for triiodothyronine (T3) 30% that of the wild-type TRβ, approximately a threefold reduction in T3-induced transactivation and a low level dominant negative activity when tested with a positively regulated reporter gene. In vivo sensitivity to TH was evaluated in three affected subjects by measurement of the responses to graded doses of levotriiodothyronine (LT3). Peak TSH responses to TRH were reduced and were not completely suppressed at even the highest dose of LT3, (0.9, 0.2, and 0.2, compared to <0.01 μU/mL in unaffected controls), confirming pituitary resistance to TH in all three subjects. In contrast, peripheral tissues responded variably to LT3: serum cholesterol decreased in all by 15%-25%, serum creatine kinase decreased by 15% in two subjects and increased 35% in another, but serum ferritin and sex hormone-binding globulin increased in only one of the three affected individuals that were tested. Basal metabolic rate and sleeping pulse did not change in three and two individuals, respectively. Hyporesponsiveness to exogenous TH established the clinical diagnosis of RTH in one member of the family with a mutant TRβ but normal tests of thyroid function at baseline. Three affected subjects had an axis I diagnosis of major depression but had Wechsler Intelligence Scale for Children, III (WISC-III) full-scale IQs (FSIQs) in the normal range. This novel TRβ mutation is associated with a relatively mild RTH. Results of responses to LT3 underscore the variable phenotype of RTH.
AB - Resistance to thyroid hormone (RTH), a syndrome characterized by variable tissue hyposensitivity to thyroid hormone (TH), is linked to mutations in the thyroid hormone receptor (TR) β gene. We report a new family with a heretofore unreported mutation, P247L. The proposita, a 31- year-old female, presented with goiter and palpitations. RTH was suspected because of elevated serum free thyroxine (FT4) level with a normal thyrotropin (TSH). Sequencing the TRβ gene revealed a mutation causing replacement of a proline at position 247 with leucine. Seven family members were heterozygous for the mutation, two of whom also had evidence of autoimmune thyroid disease. The mutant TRβ had a Ka for triiodothyronine (T3) 30% that of the wild-type TRβ, approximately a threefold reduction in T3-induced transactivation and a low level dominant negative activity when tested with a positively regulated reporter gene. In vivo sensitivity to TH was evaluated in three affected subjects by measurement of the responses to graded doses of levotriiodothyronine (LT3). Peak TSH responses to TRH were reduced and were not completely suppressed at even the highest dose of LT3, (0.9, 0.2, and 0.2, compared to <0.01 μU/mL in unaffected controls), confirming pituitary resistance to TH in all three subjects. In contrast, peripheral tissues responded variably to LT3: serum cholesterol decreased in all by 15%-25%, serum creatine kinase decreased by 15% in two subjects and increased 35% in another, but serum ferritin and sex hormone-binding globulin increased in only one of the three affected individuals that were tested. Basal metabolic rate and sleeping pulse did not change in three and two individuals, respectively. Hyporesponsiveness to exogenous TH established the clinical diagnosis of RTH in one member of the family with a mutant TRβ but normal tests of thyroid function at baseline. Three affected subjects had an axis I diagnosis of major depression but had Wechsler Intelligence Scale for Children, III (WISC-III) full-scale IQs (FSIQs) in the normal range. This novel TRβ mutation is associated with a relatively mild RTH. Results of responses to LT3 underscore the variable phenotype of RTH.
JO - Thyroid
JF - Thyroid