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Even before tonight's debate on CNN, Conor Friedersdorf of the Atlantic is calling for him to resign from his campaign for supposed anti Muslim bigotry. The fact that this is in the Atlantic shows that the Administration is well aware of how Herman is moving up with Republicans and are trying to preemptively knock him out. If he was inconsequential, you know that the Obama administration would just ignore him.
Good Luck with that.


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Understanding risk – the panel discuss different aspects of market and investment risk and how to best address it.
Aurélia Gerber, director at the Bank J. Safra Sarasin develops and manages quantitative multi-asset investments strategies. With 17 years in Institutional Asset Management she has extensive experience in the construction and the management of products in fixed income, money market, equity, balanced, alternative and emerging markets. She is skilled in technical and fundamental investment analysis.
Marcus du Sautoy is the Charles Simonyi Professor for the Public Understanding of Science and Professor of Mathematics at the University of Oxford and a Fellow of New College.
David Sneddon is a managing director of Credit Suisse in the Investment Banking division, based in London. He is global head of Technical Analysis and is responsible for overseeing the entire technical analysis product, covering the Fixed Income, FX, Equity and Commodity markets, as well as the provision of technical analysis education within Credit Suisse and for clients globally.
Jeff Hochman is Director of Technical Strategy at Fidelity Worldwide Investment. In his current role, Jeff manages a team of Technical Analysts with whom he provides support to Equity Fund Managers and Equity Research Analysts at both stock picking and macro asset allocation levels. He also frequently represents Fidelity to clients, the press and at conferences.

subset: commoncrawl


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Waubonsee Community College Hosts Series of June Job Fairs
Waubonsee hosts several job fairs across the district each year — and three are coming up quickly.
In addition to securing job or internship offers, job fairs are a great source for networking leads. Learn more about how to make the most of attending a job fair.
Upcoming Job Fairs
Plano Career Fairs — Waubonsee Community College Plano Campus Atrium, 100 Waubonsee Drive, Plano. The events are held from 9 a.m. to 11 a.m. on the following days and cover specific types of jobs.
- Friday, June 10 – Manufacturing
- Friday, June 17 – Healthcare
- Friday, June 24 – IT
Employers, please contact email@example.com for registration information. Students with questions about career development and encouraged to call 630-466-2368. Check out this page of the Waubonsee Community College website for more information.
SOURCE: www.waubonsee.edu/


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Bilingual education has historically been plagued with a bad reputation, regardless of the vast amount of research at the international level as well as personal success stories that prove otherwise. In order to counteract the negative myths, misconceptions and outright lies about bilingual education, it is imperative that bilingual education proponents work strategically to change the public perception of such programs. Whether you are a school or district administrator, bilingual coordinator, bilingual teacher, a parent raising bilingual children, or other stakeholder, the following suggestions are surefire ways to elevate the status of any bilingual program, whether it be Dual Immersion, transitional bilingual, or another form of bilingual education:
Provide High Quality Professional Development and Training
Teachers, administrators, parents and staff members should receive the highest quality training and professional development. Training should be provided on the bilingual program model design, foundations of bilingual education and bilingualism, literacy and biliteracy, the bilingual education research base, as well as second language methodology and differentiation for struggling and gifted learners. It is of utmost important that both administrators and teachers are experts in the field of dual language education and bilingual pedagogy.
Ensure that All Teachers Receive a Gifted and Talented (GATE) Certification
Imagine a bilingual program where all bilingual teachers at each grade level are highly trained in gifted and talented education! Research demonstrates that students who are involved in programs that are perceived as enrichment forms of education tend to outperform students in programs that are perceived as remedial in nature. Teachers who are GATE certified will possess the advanced skills required to differentiate for gifted students, therefore retaining GATE identified students in the bilingual program. Additional information about gifted and talented education can be found on the National Association for Gifted Children website or from one of your state affiliates for gifted education.
Engage in Frequent Public Relations Opportunities
It's important that bilingual programs publicly celebrate their successes in order to counteract the constant misinformation that the general public is exposed to about bilingual education and bilingualism. Administrators, bilingual teachers, and parents of children in bilingual programs should frequently disseminate simple press releases of positive news and events regarding the bilingual program. It's also recommended that each bilingual program have an informational brochure that is easily accessible to the public in the front office or other public location. In addition, bilingual teachers or parents might also create a simple website or blog in order to publicize success stories, events and other related information about the program, or bilingual education in general.
Implement Entrance Procedures for the Bilingual Program
All parents who would like to enroll their child in the bilingual program should be provided a formal orientation prior to entering the program. This orientation should provide a comprehensive understanding of the foundational principles of the program, the research base, program model design, and frequently answered questions. It is also recommended that parents sign a commitment form, committing to the program on a long-term basis. The commitment form is by no means a legally binding contract and parents can elect to leave the program at any time; however, the requirement of signing a commitment form suggests that commitment to the goals of the program is of utmost importance. Word of mouth travels quickly and the use of a commitment form sends a message that the program is an important, specialized program.
Important note: Entrance procedures should in no way be confused with pre-screening children to determine program placement. Multilingual Mania does not advocate pre-screening children prior to entering a bilingual program at the kindergarten level, as we believe that multilingualism should be accessible to all children, including struggling learners. We will be revisiting this topic shortly in another post.
Implement Exit Procedures for the Bilingual Program
All bilingual programs should institute a procedure in the event that parents choose to exit the bilingual program for one reason or another. Parents always have the option to exit their child from a bilingual program, however parents should be informed of the exit procedures upon enrollment in the program. It is recommended that parents are provided a formal exit interview in order to determine the reason that the parent wishes to exit their child from the program, and every effort should be made to address parent concerns. In the event that the parent continues to request exit from the program during the interview, parents should sign a formal form requesting exit from the program. Establishment of exit procedures in the form of an exit interview and formal exit form clearly illustrates that entry and exit from the program are taken seriously.
Important note: Multilingual Mania advocates for the inclusion of all students in multilingual programs, and we express caution in exiting children from a bilingual program if they are struggling learners, unless a parent requests exit from the program. Program exit should be considered a 'last case scenario' and every attempt to support students in biliteracy development must be taken. We will also be revisiting this topic shortly in another post.
Provide Extra-Curricular Activities that Promote Bilingualism
Bilingual programs should provide various opportunities for home-school collaboration that celebrate bilingualism and biliteracy. Both languages should be used and present in all school functions, such as open house, family nights and other home-school collaborations. Bilingual programs should include student performances such as plays, talent shows and other activities that highlight both languages. Every effort should be made for students to perform or showcase their class projects in both languages of the program.
Cultivate Partnerships With Local Businesses and Agencies
Bilingual programs should cultivate partnerships with local businesses that support and encourage bilingualism. School officials and parents should consider contacting the local chamber of commerce in their city in order to search for partnerships with businesses. Schools can invite bilingual business leaders to the school in order to discuss with students how bilingualism has been an asset to them as a professional, as well as information about the need for bilingual individuals in various careers. In addition, schools can establish student internships with local businesses who might be in need of bilingual services.
Establish Criteria for Bilingual Proficiency
In many states, assessment and accountability systems only take into consideration achievement in English. It is therefore important to establish criteria that recognizes and celebrates achievement in both program languages. Achievement and progress in both languages should be taken into consideration during award and achievement ceremonies and parent/teacher conferences. Bilingual programs are encouraged to institute formal recognitions in the form of "Bilingualism Attainment" or "Seal of Biliteracy" awards. More information about implementing a seal of biliteracy or biliteracy attainment certificates can be found here.
Related Posts:
Critical Components of Effective Bilingual Programs
A Parent's Guide to the Critical Components of Effective Bilingual Programs
Seal of Biliteracy Awards
Who is Qualified to Teach in a Bilingual Program?


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Create Your Own Hampers and Gift Bags
Barks & Squeaks builds beautiful customised luxury pet hampers, gift boxes and gift bags. Have a browse through this section to see what is available and to find out more about the products, then use our "Create Your Own Hamper" page to create and submit your order. If you are struggling for time, or feel overwhelmed by the choice, have a look at our fabulous ready-made hampers.
Barks & Squeaks is a great place to find pet hampers and gifts for the pets and animal lovers in your life. We have sourced beautiful, high-quality products and we want you to be able to wow your friends with your gift.
To help you do this, we offer a 'Create Your Own Hamper' service.
It is simple to create your pet hampers. Just follow the steps on the Create Your Own Hamper page. If you need some inspiration, check out our Look Book for some ideas to get you started…
If you opt for one of the wicker hampers, £2 of the cost will be donated to pet charities. Currently we are donating the proceeds to the Diana Brimblecombe Animal Rescue Centre.


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Supcase smartphones, unlocked cellular phones, new cellphones, cellphone accessories, wireless products and parts. Compatibility:Compatible with Apple iPhone 6 4.7 inch 2014 Release, allowing full access to touchscreen, camera, buttons, and ports. NOT COMPATIBLE with iPhone 6 5.5 inch or any other iPhone models.Materials:High grade polycarbonate + thermoplastic polyurethane for shock absorption. Front cover with built-in screen protector prevents scratches without compromising sensitivity.Design:Designed with both protection and looks in mind, SUPCASE Unicorn Beetle PRO Series Full-body Hybrid Case provides shock absorption and scratch prevention while maintaining a sporty profile.- Advanced front cover design for easy installation- Built-in screen protector without compromising sensitivity- Advanced dual-layer (PC + TPU) design provides great impact and shock resistance and prevents accidental drop, bump, and shock- Belt Clip Holster- Port cover keeps out debris and dust- Easy access to all features (buttons, camera, speaker, and ports)- Sporty profile and multiple color optionsWhat's in the package?1x SUPCASE Unicorn Beetle PRO Case for iPhone 6 4.7 inch
Precise cutouts for Apple iPhone 6 4.7 inch 2014 Release; Not Fit iPhone 6 5.5 inch; Advanced front cover Snap-On design for EASY installation
Advanced dual layer designed case combined of polycarbonate hard shell and flexible TPU withstands accidental drop, bump and shock
Front cover with built-in screen protector prevents scratches without compromising sensitivity
All features accessible with case installed; Port covers keep out debris and dust
Sporty design; Include Belt Clip Holster; Multiple color options


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REOPENING JUNE 29: Reservations and face coverings required. Read More
Mwezi Moja Zaidi (One More Month)
I am now on the final month of my first field season, so all of the "lasts" are beginning to occur. I just went to town for my last round of errands, one of which was to pick up two care packages. Picking up packages is a mini-adventure of multiple visits to customs and post offices, making it just that much more worth it when you finally get the tasty treats inside.
There are tasty treats here too, of course. Mangos are now beginning to fruit, although they are not quite ripe. Hopefully before all of my "lasts" run out, I'll be able to get my fill of them. Pineapples, however, are available and are ripe and delicious. After picking up my package, I enjoyed some chai, maandazi (semi-sweet donuts) and half a pineapple. I would have tried to eat the second half, but I was about to begin a two-hour boat ride back to Gombe, and the first part of the trip can be a little choppy.
While the mangos are not ripe yet, this has not stopped the chimpanzees from eating them. Although I'm not sure why, I have tried a green mango, and they are not tasty at all. This has been fine with me, though, because the mango trees are located near the beach, so this means minimal climbing. Mango trees are large trees, so it is a neat sight to see about 20 or so chimpanzees feasting on mangos in the tree and on the ground.
After a big feast of mangos, usually in the mornings, the chimpanzees usually rest some. This brings me to an observation I have had about chimpanzees: their lives revolve around food (group composition in Gombe is largely driven by food and female estrous cycles). Chimpanzees are incredibly intelligent individuals and exhibit complex social behaviors, but I have fun breaking down their day as follows. Chimpanzees spend a large amount of time eating. Afterwards they rest for a while because they ate so much. Then, after resting, they travel to look for more food. This cycle repeats itself a few times over the course of the day.
With the arrival of packages from my parents and researchers at Lincoln Park Zoo, I will be able to feast as well and eat like an alpha male. Receiving items high in protein, like beef jerky, are very helpful for providing sustainable energy to handle the forest. But it is also great to receive cereal as well, and it is amazing how wonderful the foods you miss taste when it has been five months since you have been able to consume them.
Matt Heintz


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India rejects China's proposal for tripartite talks
New Delhi: The Chinese Ambassador to India, Luo Zhaohui had advised that India, China and Pakistan should hold tripartite talks to avoid situations like 'Doklam' in the future. However, India has rejected this demand. The Indian Foreign Ministry lashed out at the Chinese Ambassador clearly stating that the issues between India and Pakistan are bilateral […]Read More »


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Saturday, August 20, 2016 - 11:00am
Gage Park, 1000 Main Street East, Hamilton
A Midsummer's Dream is one of Canada's biggest Colour Festivals, inspired by the Hindu Festival of Colours called "Holi". Celebrating unity, peace, happiness and joy, it is inspired from the Holi Festival of Colours in India, a Hindu festival that celebrates the renewal of spring and the triumph of good over evil.
This year, A Midsummer's Dream Color Festival will be on August 20, 2016 at Gage Park in Hamilton.
For more information and for the 2016 performance lineup, please www.midsummersdream.ca


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Sometimes it just feels like there are not enough hours in the day. Between painting, gardening, animal rescue, cooking, socializing, church, and work, the responsibilities are endless. Today was just not one of those days. I've had too many of those days in a row and today I took the day off and painted for fun en plein air at Rippavilla Plantation. And now I'm at home making homemade Crumpets for dinner.
In my mind when Julie Andrews was singing to the Van Trapp children about Tea with Jam and Bread, the bread she was referring to was Crumpets.
For those of you who don't know, Crumpets are a little like English Muffins... round, porous and biscuit-like, both are griddle cakes and served mainly for breakfast, brunch or tea. But there is a difference.
Crumpets are made with milk, and English Muffins are not.
Crumpets are made with a stiff batter, and English Muffins are made from dough.
Crumpets are served whole with butter, jam, or honey on top, where English Muffins are split.
And that's about it. Or all I can think of. You may have more suggestions for the difference.
- 2 1/4-ounce packets active dry yeast
- 1 3/4 cups warm water
- 1 cup whole milk, warmed
- 3 1/2 cups all-purpose flour
- 3 T butter, melted and cooled a bit plus more for greasing iron skillet
- 1 t suger
- 1 t salt
- 1 t baking powder
- 1 t baking soda
Sprinkle yeast and sugar over 1/4 cup warm water and let stand until foamy, about 5 minutes.
Add 1 1/2 cups warm water and 1 cup warm milk to yeast mixture.
In a large bowl, add flour, melted butter, salt, baking powder, baking soda, and yeast mixture. Beat until completely mixed, but don't overwork the batter. The gluten in the flour will make the batter tough if it's over mixed.
Place a clean dish towel over the bowl and set in a warm place until the batter doubles in size, about an hour. It will get very bubbly.
Heat a large cast-iron griddle or cast-iron skillet over medium-low heat. Grease with butter. Pour 1/2 cup on batter into the skillet much like preparing pancakes. Egg rings may be used to make a perfectly round Crumpet. Remember to grease the egg rings, too. Or use cookie cutters and make fun shapes.
Turn the heat to low and cook until holes appear in the top of the Crumpet and the surface is dry, about 10 minutes.
Crumpet Purests never turn the Crumpet, but rather cook it only from one side. I like to flip it and brown it slightly on the bubbly side.
Transfer to cooking rack and repeat with remaining batter.
Serve warm with butter, jam and honey.


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SOCCER: Macclesfield Town are set to receive a £34,000 cash boost over two years if the Football League agrees a television highlights package with ITV this week.
League officials are expected to tie up the £5m deal within the next few days - five months after the collapse of its three-year contract with ITV Digital.
The deal would be a major help to Macclesfield.
The club have just received a £75,000 instalment from the League's four-year live television contract with Sky - but were not due to receive any more TV money until next April.
Macclesfield chairman Colin Garlick has urged fans to put the problems caused by ITV Digital's collapse in the past.
The Football League took ITV Digital's parent companies Carlton and Granada to court in the summer in an attempt to recoup the remainder of a £315m three-year contract.
But the High Court decided that Carlton and Granada were not liable for the remaining two years of the contract after ITV Digital collapsed with massive debts.
Macclesfield joined the other 71 Football League clubs in a protest outside the London headquarters of Carlton and Granada in June.
Garlick said: "We've not had confirmation of a highlights deal yet, but the League is very confident that something can be finalised shortly.
"What we've got to do is move on from the ITV Digital affair. What's happened has happened.
"The Football League held the moral high ground in that affair, but lost the court case.
"But I'm a great believer in letting bygones be bygones. I understand that this deal is the best for the Football League in terms of finance and in terms of coverage."
It is believed that the League considered ITV's regional sports set-up meant the channel would be better suited to showing highlights than rival stations.
Garlick said: "I think the coverage would be better, and it would also be a better deal financially than the other offers submitted for a highlights deal.
"I would be disappointed if this was not sorted out within the next couple of weeks. We should really have had a highlights partnership in place from day one."


text: 15 Week Courses in Salsa, Bachata, Tango Argentino at Scottsdale Community College. Please Join Bridgette Maria for 15 Weeks of progressive courses in Salsa, Bachata, Tango Argentino, and all levels are invited to register and will be covered. Mondays at 6:30pm to 9:15pm - Tango Argentino / DAN 101AE - 0001, Section # 20929 Starts on August 26th through December 13th PE Building, South Gym Tuesdays at 6:30pm to 8:15pm Bachata - DAN 101AC - 0001, Section #20744 Starts on August 27th through December 13th PE Building, South Gym Wednesdays at 6:30pm to 8:1pm - Salsa - DAN 101AC - 0001, Section # 20745 Starts on August 28th through December 13th PE Building, South Gym Prices per Course are $87.00, Plus a $15.00 registration fee. If you are 65 years or older it is half price for each Course. You must register by August 12th to reserve a spot in these Dance Courses. If you have never registered before, please contact Admissions at Scottsdale Community College. You will need to pay and apply in person if you do not currently have a student id, or MEID number. If you are a current student of the Mariciopa Commuity Colleges, you can apply online at [hidden] using the above section number to find the listed courses. Scottsdale Community College admissions office number is 480 - 423 - 6000 For more information contact Bridgette Maria at[hidden], [hidden] More Info below.


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Word up!!!
This Blog was written to the sounds of::
Proper Bumper week here at Reckless this week….here we go!!
1) One of the most bad boy Hardcore, Jungle, Drum & Bass collections we have had in for a very long time came in. Four thousand or so killer records – not a duff one amongst them. Most records are in unplayed condition – and there are loads of White Labels and Test Presses. It seems to cover 1992 through to about 1998 but with 1993-1996 taking charge. There are several titles where there are multiple copies too – such as Source Direct "Secret Liaison". There is a huge pile of pretty much everything on Good Looking Records – unplayed copies of Piano Tune for example. There are several Tom & Jerry titles, Lucky Spin full run, rare Orca, DJ Rap, Tomba, DJ Monk, Dillinja, Mafia, Congo Natty, Marcus Intalex, Noise Factory, Photek, Lemon D, Bizzy B, DJ Massive, On Remand, Ellis Dee, The Diplomat, Tango & Ratty, Remarc, Sound Clash, Austin, Jungle Warrior, Jack Ruby, Nookie, DJ Devine & Essence, Love Dove Jay, DJ's Flynn & Flora, over 50 Metalheadz promos, Moving Shadows…this is all from the first two boxes and there are lots and lots of boxes. There are also loads of really nice UK Garage 12″s; loads of rare ones (Anthill Mob white labels, EL-B, Jeremy Sylvester, Sly Paul etc) as well as standard but super clean ones. Basically a load of really, really good records here.
2) Whilst Scott was buying in the big Rave collection I was at the Barbican buying a top notch Jazz Collection. I'd already seen the Tubbys Groove so I figured if you have that and live in the Barbican it's got to be worth a home visit and it was. Lots of UK original Jazz titles – including loads of Miles Davis titles, Stan Tracey "Under Milk Wood" a personal favourite, Yusef Lateef, Thelonious Monk, Art Blakey, Nina Simone, Ella Fitzgerald, Lee Morgan, Tubby Hayes, Zoot Sims, Billie Holiday, Charles MingusSonny Rollins, Bill Evans, Joe Harriott, Roland Kirk and about 20 LPs from Chet Baker! There were also loads of much cheaper Jazz titles – but plenty of oddities – including some more obscure UK Jazz that seemed pretty sought after. There were also some great Brazilian LPs from Gilberto Gil, Baden Powell; several LPs from Serge Gainsbourg, some contemporary Classical LPs from Steve Reich, Philip Glass etc as well as some top quality pop from The Beatles, Joni Mitchell etc. It was really nice to be in their lovely warm home going through their records as they told me about seeing Don Rendell, Stan Tracey, Joe Harriott at their friends house.
3) Lots of high quality Classic Rock and Indie came in from one chap for trade for a much, much bigger item (Please, Please Me original): Pink Floyd, Radiohead, Serge Gainsbourg, APhex Twin, The Rolling Stones, Led Zeppelin, John Lennon/Yoko Ono, Prince, Primal Scream, New Order…lots of very limited issues. Also some high quality Japanese Beatles CDs.
4) More Raggamuffin Hardcore Jungle!!! From another regular seller; this time a few cheeky White Labels, more Photek, Suburban Base, lots more Moving Shadow, and a bit of Ram Records.
5) A decent pile of Indie and Post Rock CDs which I heard was good but I have not seen them myself. So it is a mystery!
6) If you have not forgotten the 80s then a large pile of "classic" 80s Hard Rock/Pop 12″s, Picture Discs and LPs came in, but all either still sealed or unplayed. Including sealed Meatloaf LPs (it was very hard to stop Scott from buying these but the customers come first!), Kitaro, Def Leppard, Tigertailz, Scorpions etc. Simply glorious music.
7) These may have come in with the huge pile of Fall 45s last week – and if they didn't it would just be weird but: more cool Punk/Post Punk 45s and LPs from The Adverts, Stress, Throbbing Gristle, John The Postman, Flux Of Pink Indians, Mau Maus, Modern Art etc. Some really interesting records here, all DIY all the time.
8) Loads of Metal CDs – apparently lots of Relapse titles. Sometimes when I am driving down the motorway in my BMW I like to slip on some Nile and relax and think about Indiana Jones.
9) Loads of Noise, Noisey Techno and Avant Garde LPs and 12″s. From Actress to Wolf Eyes. Ideal if you like to move to groovy beats but you also have an aggressive side.
10) A good mate of mine sold in a load of class Jazz, Ethnographic and Progressive LPs. From Blue Note to music from Tibet. Also a lot of really nice Jazz and Reggae CDs from Dadawah, Paul Gonsalves, Dennis Brown etc. Some wicked records and CDs here; I'll try and get some pictures up on our Instagram asap.
11) Our very own Toru (or as he demands us to call him the T Dog) came back from Japan with loads and loads of wicked Records. He had been out there seeing family and DJing loads including at the Palace Skateboards opening! As ever – he's come back with so many amazing records. Lots of Japanese Jazz, Anime Soundtracks and Japanese pressings of Classic Rock and Jazz.
12) Little sputtering of Reggae this week – but when among them are a Studio One Alton Ellis and a Catch A Fire by The Wailers you know things are gonna be alright.
No Top Ten this week but we have some good ones coming up.
Plenty of collections on the horizon.
Go to this Brainiac 5 gig!
Till next week


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Octave One - Octave One presents Random Noise Generation 'Endustry' [VINYL]
4WDG710 - VINYL + MP3 DOWNLOAD 6 tracks
|2 x 12" Vinyl
view tracklist DOWNLOAD 8 tracks
|MP3 release
|FLAC release
|WAV release
VINYL tracklist
Octave One announce their new album under the much loved Random Noise Generation guise. The first RNG release was 'Falling in Dub' in 1991 and sounding just as fresh 27 years later, �Endustry� is due for release this spring.
Something of a new take on their creative process the Burden brothers made most of this music on the road while they toured over the past year, using the country they were in at each time they recorded to influence and inspire each track. �We were tucked away in so many hotel rooms that we decided to make sure we brought enough extra equipment so that we could set up a true lab to create from country to country and make the grooves that we wanted to experiment with on the dance floor.� comments Lawrence.
This body of work encompasses 7 full length cuts, naturally all with that classic Octave One emotion. �'Alkaylze', more than any of tracks on this project, embraced the original spirit of Random Noise Generation in so much as the �machine� seemed to be really guide the creative process.� Adds Lenny �Much of the foundation of the composition was very accidental, but inspirational, with various musical devices interpreting data in a very unexpected results. It actually came together quite quickly but things just fell into place so naturally.�
After touring and making music for decades the spirit and essential energy of the craft is what keeps them eternally inspired to keep creating and touring the globe� �Once it takes hold of you you can�t stop even if you wanted to.� says the pair, and so 'Endustry' is born.


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Compliance is everyone's responsibility. Compliance programs are intended to reduce errors and fraudulent behavior--even inadvertent fraudulent behavior. With the introduction of the HITECH Act, maintaining a compliance program has become a basic necessity for any medical practice. We at MBR encourage all our clients to create and maintain an ongoing compliance program.
We are committed to helping our clients remain compliant, and we have provided resources to help you in the effort to develop your own plan. We have many more reference materials outside our website available for you to use to develop a practice compliance program.
The attached documents are for reference only. They can be modified to meet the specific needs of your organization. These resources do not serve as legal advice for your compliance program, and MBR assumes no liability and shall be indemnified against any legal action regarding these resources. These documents are intended to provide the framework on which to build your own compliance program.
These documents were assembled from a variety of sources. Although we have included a few sample plans, creating your own program is best. Compliance contributes toward creating an ethical culture within your organization. My best advice in preventing payor audits in the first place is implementing your own practice compliance program.
Barry Shatzman, CHBME
Compliance Officer


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The online platform will connect consumers to independently verified agents.
Agent Review http://www.agentreview.net will provide non-biased guidance for consumers looking for information on insurance products, while offering local insurance agents the opportunity of working with them. "We believe that even though consumers conduct their research online, ultimately they want to 'buy local' from…
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Thinking Pink
Saturday, February 20, 2016
Fun with Shirts (Part Two)
Having a heat press is a slippery slope because you start thinking about all the shirts you wish you could make....
When I was 12, I never would have taken these shirts off.
I mean, come on. Ricky Schroder on a Dynamite magazine?!?!
Of course, my true love is my husband, Keith....he's represented, too! :)
Posted by
Pinky Lovejoy-Coogan
Saturday, February 20, 2016
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Shrimpers Home
Away Travel
Trust Shop
Members Area
(0) £ 0.00
Trust News :
Latest News
100 Club - Latest Winner (week 48)
Trust Statement - 5th March 2020
Shrimpers Trust SUFC 1st Team POTM - January 2020
Society Board Meeting Minutes - January 2020
The Shrimpers Trust Big Xmas Quiz - 2019 - Results
100 Club - Latest Winner (Grand Xmas Draw - week 22)
Journey To The Gills - Sponsored Walk - Cheque Presentation
Harp Homeless Charity - Thank You For Your Support
Quid A Goal - Running Total (7th December 2019)
Sol Campbell Q & A Report - Monday 25th November
Journey To The Gills - Sponsored Walk - We Made It
Journey To The Gills - Sponsored Walk - Team Visit To Little Havens
Journey To The Gills - Sponsored Walk - Commercial Partners
New Merchandise - 2019/20 Shirt Key Ring
Shrimpers Trust Charity Event in partnership with Little Havens is launched.
Journey To The Gills - Sponsored Walk
Latest Liaison Meeting Minutes Online
Shrimpers Trust Player of the Year Awards - Monday 29th April 2019
Trusts Tribute To Timlin
Aviva Community Scheme - Social Inclusion Project
Social Inclusion Through Sport - Shrimpers Trust And Aviva
SUFC Ex-Players Asscociation
Update regarding the Trusts change from a CLG to a Community Benefits Society
Where Does Your Money Go ?
News Archive
How To Join The Trust
Adult Membership
Student/OAP Membership
Life Membership
100 Club
2019/20 Season Winners
Contact Us
SUFC Ex-Players Association (SUEPA)
SUFC 1st Team Player of the Month - 2019/20 Season
Liaison Minutes
Thunderbirds Are Go !!! - SUFC 1st Team Match Reports 2019/20 Season
About the Shrimpers Trust
Where Does Your Money Go?
SUFC 1st Team Player of the Month Archives
AGM, Player of the Year and Q&A Reports
Trust Statements
Fundraising Events Archive
SUFC 1st Team Match Reports Archive
Privacy Policy
How To Join The Trust
The Shrimpers Trust now has over 1100 adult members with some joining from as far afield as Australia, China, Singapore, Spain, Canada and the United States. The common thread being a thirst for information and involvement in all matters relating to Southend United.
The advantages of membership are:
Access to Exclusive Members Area on the Trust Website
10% Discount in the Trust On-Line Shop
Representation at the monthly Liaison meetings with SUFC Board members
Representation at the Annual General Meetings of Southend United FC Limited
Subsidised Travel to all Away Games
Regular Newsletter
Regular Q&A Sessions
Membership Card
To join the Shrimpers Trust, you can click on one of the links below and join on line using a Credit or Debit Card, alternatively you can download a Membership Form
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1967 Chevrolet
- Stock
- Engine Size
- Transmission
- Manual
- Miles
- 17,731 (Unknown)
- Location
- Atlanta
or give us a call at (678) 279-1609
Something about a stepside bed gives old pickups both a vintage look and a sporty attitude. The bulging fenders on this 1967 Chevrolet C10 are definitely a big part of its appeal, along with the burbling V8 engine and surprisingly agile handling. Who knew trucks were this good 50 years ago?
Freshly repainted in its original Vermillion, there's just no way to escape notice when you're driving this rig. Fortunately, the single-stage urethane nails the original look, so it seems like it stepped right out of the past with a glossy coat of paint, ready for the next century. Having lived most of its life someplace warm surely helped, and unlike so many of its siblings, this one doesn't seem to have been forced into hard labor early in its life. The tailgate leaves no mistake as to what kind of truck this is, and it is flanked by a set of slightly oversized taillights that look great and boost safety. The bed floor is gorgeous hardwood and stainless, with perhaps the most carefully applied spray-in bedliner we've ever seen on the side walls and tailgate, so it's still pretty darned useful as a truck. Chrome bumpers look great, with the front end taking on a slightly custom look with the color-matched Bowtie emblem in the grille.
Basic black makes for a stylish and comfortable interior, particularly against the bright red bodywork. Thanks to an older restoration, the interior is still in good order, and it's been recently refitted with fresh carpet to give it a new lease on life. Durable materials helped these trucks survive under harsh conditions, and the restoration used the same stuff, so it's holding up nicely today and looks right inside the old pickup's cab. Three-on-the-tree shifting is easy and enjoyable, particularly with a torquey V8 up front, and the shifter is only a finger's reach away from the leather-wrapped steering wheel. Factory gauges are basic and showing a bit of age, but a newer AM/FM stereo head unit adds some updated sounds for cruise night entertainment. Heavy-duty rubber floor mats and even an on-board fire extinguisher are nice extras that make this truck a turn-key proposition.
There's plenty of room under the hood for V8 power, 307 cubic inches in this case. The torquey small block is right at home in the sporty stepside, delivering fun performance without the horrible gas mileage of a big block. Rebuilt several thousand miles ago, it's still quick to start and runs smooth, so you can hit the road without worries. Chevy Orange paint looks right, and even the original air cleaner still lives up top, so there haven't been any significant aftermarket upgrades along the way. Ram's horn exhaust manifolds feed a pleasant-sounding dual exhaust system with chrome tips under the rear bumper, and with the manual transmission, it's actually a lot of fun to drive. These trucks have surprisingly agile handling and a great ride thanks to coil springs all around (and you thought that was a recent idea...), and it has obviously been well-maintained all its life if the chassis is still that clean. Sporty steel wheels with fat 255/70/15 Cooper white-letter radials complete an already stylish truck.
Like I said, fun to drive and still quite practical, this C10 makes for a great entry-level hobby vehicle, especially with trucks being red-hot in the market right now. Call today!
- AM/FM Radio
- Defrost
- Heat
- Seatbelts
- Seatbelts (Front)
- Vinyl Interior
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text:
This is the first in a series of posts about grading, specifically the problem of punitive grading and what we can do about it. Fortunately, there is more and more discussion, both in K-12 and in higher ed, about the negative effects of grading, especially of punitive grading, and slowly but surely I think we are going to see people finding new solutions — at the individual assignment level or course level, and also at the institutional level. Just last week, I was invited to submit a chapter for a book about un-grading in higher ed. There are some really good books about un-grading in K-12 (like Starr Sackstein's Hacking Assessment: 10 Ways to Go Gradeless in a Traditional Grades School), and I am excited about writing something for an un-grading book directed towards a higher ed audience.
So, I had already planned to do a blog post series this semester about grading, and the unexpectedly bad business of red-ink labels in the new Gradebook has given me a greater sense of urgency about that. This new Gradebook actually has more punitive features than the old Gradebook did: OUCH. I'm both depressed and angry about that as you can see in this blog post: GET THE RED INK OUT OF MY GRADEBOOK. The Sequel.
Nobody from Instructure has commented there (yet?), but I sure hope they are following the discussion. I am very grateful that our Community API-miracleworker, James Jones, is exploring the possibility of a solution that will help to remove the red-ink labels with some Google Sheet scripts (much like his amazing adjust-all-due-dates sheet), but we also need an official fix to this problem so that we can simply disable those red labels if we want. There ARE alternatives to punitive grading, and the LMS needs to be able to support those alternatives just as it supports traditional punitive grading.
Shame and punishment. So, let's talk about punitive grading, which is grading that PUNISHES students for making mistakes. That punishment can take the form of a lower grade, or it could take the form of extra work... or it might appear as red ink, like in the new Canvas Gradebook where students are told that their work is MISSING (red ink!) or LATE (red ink!). The only labels that show up in the Gradebook are these negative labels (late! missing!). They could have included positive labels — work turned in, work turned in on time, work turned in early — either in addition to the negative labels, or instead of the negative labels. But there are no positive labels; there are negative labels only. And they could have used a color other than red for the negative labels, but they did not; those labels are red because red is the color of punishment. It's that American classic: The Scarlet Letter.
But wait, there's more! The new Gradebook gives instructors to choose our own status colors in the Gradebook spreadsheet view, like this:
As you can see, I tried changing my "late" and "missing" status settings to white to see if that would white out the red labels in the Gradebook view, but that hack did not work (alas). Even instructors cannot change the red color of the labels, and the students cannot choose the colors they prefer. That would be another good solution to this problem, of course, and to all kinds of other problems too: let the students choose! (I'll have more to say about student choice in grading later.)
But right now, nothing we can do or they can do will make that red-ink label go away, unless you go in and manually remove the labels from the Gradebook, label by label, student by student, assignment by assignment. Click. Click. Click.
Punishment and motivation. Some people think that grades and punishment are how you motivate students, but I disagree. In my experience, both as a student and as a teacher, shaming and punishment have the opposite effect, discouraging students and demotivating them. As an example, look at this screenshot from the new Gradebook, showing what one of my students would see each time he opened the Gradebook view (this is an actual screenshot from a Fall course record, where my school has retroactively applied the new Gradebook). Every time this student opens the Grade view, he sees this wall of shame, one red label after another. If I had to look at something like that every time I had logged on to Canvas, I would get so depressed!
Even worse: the default is sorted by Due Date, old dates first, which means the student must scroll down through all the old labels to reach the current assignments. No matter how much he improves, he must look at that wall of past failures again and again and again.
Do you think that is motivating? I don't.
So, for the grading in my classes, I take a different approach:
First, I emphasize COMPLETION: students turn the work in when it is complete. That means every "grade" for every assignment is 100%. And there are no zeroes; if a student chooses not to do an assignment, it's just a blank, a road not taken, not a problem at all. So, each assignment grade is 100% and each student's total course percentage is also 100%. All the time. That does not mean the work they are doing is perfect (ugh! perfectionism: one of the worst aspects of traditional grading! more about that later...). Instead, the 100% just means that each assignment is complete and ready for feedback from me and from the other students — and there will be feedback. There will be lots of feedback. Sometimes I refer to my grading system as all-feedback-no-grades, and I'll have lots more to say about feedback in future posts. There are lots of ways that feedback can provide students with real motivation, much more so than the Tarzanesque vocabulary of ABCDF and the shame of red ink.
Second, I emphasize LOOKING FORWARD, not backward. The goal is always to complete a piece of work. It doesn't matter what you did, or did not do, last week; what matters is what you are going to do this week and next week and the week after that. You always have a grade of 100% in the Gradebook, so that's all good, nothing to worry about. Just devote all your effort to the NEXT thing you are going to do, using what you've learned so far in order to complete the next assignment. My husband is a pilot, and he has this great saying: "You can't use the runway behind you." That's the philosophy I use in my class too: don't look back; just figure out how you are going to use the runway in front of you to take off and soar! So yeah, I like the little rocket icon in Canvas for assignments that are not yet completed; the rocket label totally works for me. Let's GO!
Since this is just the first in what will be a whole series of blog posts, I'll stop here for now, with a promise of more to come. There are some other principles I want to discuss (student choice, open-ended assignments, etc.), along with lots of nitty-gritty I want to share (hacking the Gradebook, proactive communication, etc.). Meanwhile, I hope people will chime in here with their own thoughts about grades and grading. A really good discussion erupted at my Gradebook post last week, and we need all the discussion we can get about grading: it's an aspect of the education system desperately in need of reform, and the voices of both teachers and students need to be part of that conversation.
For a hashtag, I'll be using TTOG here (Teachers-Throwing-Out-Grades), and you can always find new things to read about grading and grading reform by looking at #TTOG on Twitter too.
So, that's all for now; I'm going to go outside now and enjoy a beautifully sunny Sunday........ but I'll be back next week with more. Lots more. :-)


text:
Okay, so I know there's been no running update…and I'm sorry about that. Truth is, with the weather and my extreme complacency, there hasn't been a whole lot of running. I promise one for next week and even if I have to run 10 or 20 miles on the weekends from now til December 3, I will make this goal.
I saw an ad for the movie Paranormal which said that USA TODAY calls it, and I quote, a movie that "will effectively terrorize even the toughest among you." Now, tell me Intertubes…are you not effectively terrorized enough in daily life without resorting to being scared shitless Aside: to use the local vernacular during your entertainment? What is the desire to be frightened that people find so exciting? I don't get it. I remember watching a made-for-TV film "The Fall of the House of Usher" in 1982. I didn't sleep well again until 1984. Ask my mother. There are times when I go down to the basement and still look around the corner for Madeline with blood dripping from her eyes.
If you're not watching Glee, then you're missing one of the best shows on television. It has great music, great drama, and a great performance from Jane Lynch who, honestly, makes me squirm with every role she takes on. She's great at making you uncomfortable. Also, cheers to Heather Elizabeth Morris who plays Brittany and is in my opinion one of the better dancers on the show, though her screen time is limited. If you liked Fame, you'll love Glee. If you don't remember Fame, well…shut up, I'm not old.
The rain has been never-ending here in the Bluegrass State. We're probably well over the recommended monthly allowance already. I base this assumption on the fact that I saw our resident albino squirrel wearing a life vest this morning. I would've sworn that they moved the Ohio River to flow down our street, but satellite photos assure me that this is not the case. One of these days we'll dry out, provided it doesn't just ice over all together soon. Highs in the mid-40s will do that to you.
Other than that…the baby's good, C. is good, I haven't been the best mentally lately, but some of you will question how I can tell the difference Aside: Har de har har har! For pictures of Ivy, click on the Flickr badge to the right. Congratulations to my brother-in-law, J., who was named one of the Top 5 "Hot Now" Artists by The Culture Club in Flagstaff. And, that's all the news…
See you in the funny papers!


text:
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- Development of dipeptidyl peptidase-4 inhibitors
Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) are enzyme inhibitors that inhibit the enzyme dipeptidyl peptidase-4 (DPP-4) and are a potent treatment for type 2 diabetes. Inhibition of the DPP-4 enzyme prolongs and enhances the activity of incretins that play an important role in insulin secretion and blood glucose control regulation.[1] Type 2 diabetes is a chronic metabolic disease that can be caused by pancreas β-cell dysfunction, deficiency in insulin secretion, insulin resistance and/or increased hepatic glucose production. It is one of the fastest growing health concerns in the world. Current treatments are often inefficient at sustaining glycemic control and may cause undesirable side effects, such as weight gain and episodes of hypoglycemia. Therefore, new and more effective drugs have been developed with DPP-4 inhibitors playing a significant role.[2]
- 1 History
- 2 DPP-4 mechanism
- 3 DPP-4 characteristics
- 4 Discovery and development
- 4.1 Substrate-like inhibitors
- 4.2 Non-substrate-like inhibitors
- 4.3 Xanthine-based compounds
- 5 Pharmacology
- 6 See also
- 7 References
Since its discovery in 1967, serine protease DPP-4 has been a popular subject of research.[2] Inhibitors of DPP-4 have long been sought as tools to elucidate the functional significance of the enzyme. The first inhibitors were characterized in the late 1980s and 1990s. Each inhibitor was important to establish an early structure activity relationship (SAR) for subsequent investigation. It should be noted that the inhibitors fall into two main classes, those that interact covalent with DPP-4 and those that do not.[3] DPP-4 is a dipeptidase that selectively binds substrates that contain proline at the P1-position, thus many DPP-4 inhibitors have 5-membered heterocyclic rings that mimic proline, e.g. pyrrolidine, cyanopyrrolidine, thiazolidine and cyanothiazolidine.[4] These compounds commonly form covalent bonds to the catalytic residue Ser630.[5]
In 1994, researchers from Zeria Pharmaceuticals unveiled cyanopyrrolidines with a nitrile function group that was assumed to form an imidate with the catalytic serine. Concurrently other DPP-4 inhibitors without a nitrile group were published but they contained other serine-interacting motifs, e.g. boronic acids, phosphonates or diacyl hydroxylamines. These compounds were not as potent because of the similarity of DPP-4 and prolyl oligopeptidase (PEP) and also suffered from chemical instability. Ferring Pharmaceuticals filed for patent on two cyanopyrrolidine DPP-4 inhibitors, which they published in 1995. These compounds had excellent potency and improved chemical stability.
In 1995, Edwin B. Villhauer at Novartis started to explore N-substituted glycinyl-cyanopyrrolidines based on the fact that DPP-4 identifies N-methylglycine as a N-terminal amino acid. This group of new cyanopyrrolidines became extremely popular field of research in the following years. Some trials with dual inhibitors of DPP-4 and vasopeptidase have been represented, since vasopeptidase inhibition is believed to enhance the antidiabetic effect of DPP-4 inhibition by stimulating insulin secretion. Vasopeptidase-inhibiting motif is connected to the DPP-4 inhibitor at the N-substituent.[3][6]
DPP-4 mechanism
During a meal the incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent gastric inhibitory polypeptide (GIP) are released from the small intestine into the vasculature. The hormones regulate insulin secretion in a glucose-dependent manner. GLP-1 has many roles in the human body; it stimulates insulin biosynthesis, inhibits glucagon secretion, slows gastric emptying, reduces appetite and stimulates regeneration of islet β-cells. GIP and GLP-1 have extremely short plasma half-lives due to a very rapid inactivation. The enzyme responsible for the metabolism is DPP-4. Inhibition of DPP-4 leads to potentiation of endogenous GIP and GLP-1 and hence improves treatment of type 2 diabetes (Figure 1).[2][7]
DPP-4 distribution and function
DPP-4 selectively cleaves two amino acids from peptides, such as GLP-1 and GIP, which have proline or alanine in the second position (Figure 2). At the active site of the protease there is a characteristic motif of three amino acids, Asp-His-Ser. DPP-4 is the CD26 T-cell-activating antigen, which is widely distributed in human organs and tissue. Tissues, which strongly express DPP-4, include the exocrine pancreas, sweat glands, salivary and mammary glands, thymus, lymph nodes, biliary tract, kidney, liver, placenta, uterus, prostate, skin and the capillary bed of the gut mucosa where most GLP-1 is inactivated locally. DPP-4 is attached to the plasma membrane of the endothelia of almost all organs in the body. It is also present in body fluids, such as blood plasma and cerebrospinal fluid, in a soluble form. DPP-4 inactivates GLP-1 and GIP very rapidly. Regarding GIP and GLP-1, alanine and proline are crucial for biological activity, so elimination of these amino acids leads to formation of metabolites that are inactive. Thus, preventing the degradation of the incretin hormones GIP and GLP-1 by inhibition of DPP-4 is an exciting therapeutic strategy.[1][8]
DPP-4 characteristics
Since DPP-4 is a protease, it is not unexpected that inhibitors would likely have a peptide nature and this theme has carried through to contemporary research.[3]
X-ray structures of DPP-4 that have been published since 2003 give rather detailed information about the structural characteristics of the binding site. Many structurally diverse DPP-4 inhibitors have been discovered and it is not that surprising considering the properties of the binding site:[9]
1. A deep lipophilic pocket combined with several exposed aromatic side chains for achieving high affinity small molecule binding.
2. A significant solvent access that makes it possible to tune the physico-chemical properties of the inhibitors that leads to better pharmacokinetic behavior.
DPP-4 is a 766-amino acid transmembrane glycoprotein that belongs to the prolyloligopeptidase family. It consists of three parts; a cytoplasmic tail, a transmembrane region and an extracellular part. The extracellular part is divided into a catalytic domain and an eight-bladed β-propeller domain. The latter contributes to the inhibitor binding site. The catalytic domain shows an α/β-hydrolase fold and contains the catalytic triad Ser630 - Asp708 - His740. The S1-pocket is very hydrophobic and is composed of the side chains: Tyr631, Val656, Trp662, Tyr666 and Val711. Existing X-ray structures show that there is not much difference in size and shape of the pocket that indicates that the S1-pocket has high specificity for proline residues[8][9]
Binding site
DPP-4 inhibitors usually have an electrophilic group that can interact with the hydroxyl of the catalytic serine in the active binding site (Figure 3). Frequently that group is a nitrile group but can also be boronic acid or diphenyl phosphonate. This electrophilic group can bind to the imidate complex[disambiguation needed ] with covalent bonds and slow, tight-binding kinetics but this group is also responsible for stability issues due to reactions with the free amino group of the P2-amino acid. Therefore inhibitors without the electrophilic group have also been developed, but these molecules have shown toxicity due to affinity to other dipeptidyl peptidases, e.g. DPP-2, DPP-8 and DPP-9.[10]
DPP-4 inhibitors span diverse structural types. In 2007 few of the most potent compounds contain a proline mimetic cyanopyrrolidine P1 group. This group enhances the potency, probably due to a transient covalent trapping of the nitrile group by the active site Ser630 hydroxyl, leading to delayed dissociation and slow tight binding of certain inhibitors. When these potency enhancements were achieved, some chemical stability issues were noted and more advanced molecules had to be made. To avoid these stability issues, the possibility to exclude the nitrile group was investigated. Amino acids with aryl or polar side chains did not show appreciable DPP-4 inhibition and in fact, all compounds without the nitrile group in this research suffered a 20 to 50-fold loss of potency corresponding to the compounds containing the nitrile group.[11]
Discovery and development
It is important to find a fast and accurate system to discover new DPP-4 inhibitors with ideal therapeutic profiles. High throughput screening (HTS) usually gives low hit rates in identifying the inhibitors but virtual screening (VS) can give higher rates. VS has for example been used to screen for small primary aliphatic amines to identify fragments that could be placed in S1 and S2 sites of DPP-4. On the other hand, these fragments were not very potent and therefore identified as a starting point to design better ones. Three-dimensional models can provide a useful tool for designing novel DPP-4 inhibitors. Pharmacophore models have been made based on key chemical features of compounds with DPP-4 inhibitory activity. These models can provide a hypothetical picture of the primary chemical feature responsible for inhibitory activity.[5] The first DPP-4 inhibitors were reversible inhibitors and came with bad side effects because of low selectivity. Researchers suspected that inhibitors with short half-lives would be preferred in order to minimize possible side effects. However, since clinical trials showed the opposite, the latest DPP-4 inhibitors have a long-lasting effect. One of the first reported DPP-4 inhibitor was P32/98 from Merck. It used thiazolidide as the P1-substitute and was the first DPP-4 inhibitor that showed effects in both animals and humans but it was not developed to a market drug due to side effects. Another old inhibitor is DPP-728 from Novartis, where 2-cyanopyrrolidine is used as the P1-substitute. The addition of the cyano group generally increases the potency. Therefore, researchers' attention was directed to those compounds. Usually, DPP-4 inhibitors are either substrate-like or non-substrate-like.[12]
Substrate-like inhibitors
Substrate-like inhibitors (Figure 4) are more common than the non-substrate-likes. They bind either covalently or non-covalently and have a basic structure where the P1-substituent occupies the S1-pocket and the P2-substituent occupies the S2-pocket. Usually they contain a proline mimetic that occupies the S1-pocket. Large substituents on the 2-cyanopyrrolidine ring are normally not tolerated since the S1-pocket is quite small.[12] Since DPP-4 is identical with the T-cell activation marker CD26 and DPP-4 inhibitors are known to inhibit T-cell proliferation, these compounds were initially thought to be potential immunomodulators. When the function against type 2 diabetes was discovered, the cyanopyrrolidines became a highly popular research material. A little later vildagliptin and saxagliptin, which are the most developed cyanopyrrolidine DPP-4 inhibitors to date, were discovered.[6]
Cyanopyrrolidines have two key interactions to the DPP-4 complex:[6]
1. Nitrile in the position of the scissile bond of the peptidic substrate that is important for high potency. The nitrile group forms reversible covalent bonds with the catalytically active serine hydroxyl (Ser630), i.e. cyanopyrrolidines are competitive inhibitors with slow dissociation kinetics.
2. Hydrogen bonding network between the protonated amino group and a negatively charged region of the protein surface, Glu205, Glu206 and Tyr662. All cyanopyrrolidines have basic, primary or secondary amine, which makes this network possible but these compounds usually drop in potency if these amines are changed. Nonetheless, two patent applications unveil that the amino group can be changed, i.e. replaced by a hydrazine, but it is claimed that these compounds do not only act via DPP-4 inhibition but also prevent diabetic vascular complications by acting as a radical scavenger.
Structure-activity relationship (SAR)
Important structure-activity relationship:[11]
1. Strict steric constraint exists around the pyrrolidine ring of cyanopyrrolidine-based inhibitors, with only hydrogen, fluoro, acetylene, nitrile, or methano substitution permitted.
2. Presence of a nitrile moiety on the pyrrolidine ring is critical to achieving potent activity
Also, systematic SAR investigation has shown that the ring size and stereochemistry for the P2 position is quite conditioned. A 5-membered ring and L-configuration has shown better results than a 4-membered or 6-membered ring with D-configuration. Only minor changes on the pyrrolidine ring can be tolerated since the good fit of the ring with the hydrophobic S1 pocket is very important for high affinity. Some trials have been made, e.g. by replacing the pyrrolidine with a thiazoline. That led to improved potency but also loss of chemical stability. Efforts to improve chemical stability often led to loss of specificity because of interactions with DPP-8 and DPP-9. These interactions have been connected with increased toxicity and mortality in animals. There are strict limitations in the P1 position and hardly any changes are tolerated, on the other hand a variety of changes can be made in the P2 position. In fact, substitution with quite big branched side chains, e.g. tert-butylglycin, normally increased activity and chemical stability, which could lead to longer-lasting inhibition of the DPP-4 enzyme. It has also been noted that biaryl-based side-chains can also give highly active inhibitors. It was originally believed that only lipophilic substitution would be tolerated. Now it is stated that also the substitution of polar negatively charged side-chains as well as hydrophilic substitution can lead to excellent inhibitory activity.[6]
Chemical stability
In general, DPP-4 inhibitors are not very stable compounds. Therefore, many researchers focus on enhancing the stability for cyanopyrrolidines. The most widespread technique to improve chemical stability is to incorporate a steric bulk. The two cyanopyrrolidines that have been most pronounced, vildagliptin and saxagliptin, were created in this manner. K579 is a DPP-4 inhibitor discovered by researchers at Kyowa Hakko Kyogo. It had improved not only chemical stability but also a longer-lasting action. That long-lasting action was most likely due to slow dissociation of the enzyme-inhibitor complex and an active oxide metabolite that undergoes enterohepatic circulation. The discovery of the active oxide was in fact a big breakthrough as it led to the development of vildagliptin and saxagliptin. One major problem in DPP-4 inhibitor stability is intramolecular cyclisation. The precondition for the intramolecular cyclisation is the conversion of the trans-rotamer, which is the DPP-4 binding rotamer(Figure 5). Thus, preventing this conversion will increase stability. This prevention was successful when incorporating an amide group into a ring, creating a compound that kept the DPP-4 inhibitory activity that, did not undergo the intramolecular cyclisation and was even more selective over different DPP enzymes. It has also been reported that a cyanoazetidine in the P1 position and a β-amino acid in the P2 position increased stability.[6]
Vildagliptin (Galvus)(Figure 6) was first synthesized in May 1998 and was named after Edwin B. Villhauer. It was discovered when researchers at Novartis examined adamantyl derivatives that had proven to be very potent. The adamantyl group worked as a steric bulk and slowed intramolecular cyclization while increasing chemical stability. Furthermore, the primary metabolites were highly active. To avoid additional chiral center a hydroxylation at the adamantyl ring was carried out (Figure 5). The product, vildagliptin, was even more stable, undergoing intramolecular cyclisation 30-times slower, and having high DPP-4 inhibitory activity and longer-lasting pharmacodynamic effect.[6]
Researchers at Bristol-Myers Squibb found that increased steric bulk of the N-terminal amino acid side-chain led to increased stability. To additionally increase stability the trans-rotamer was stabilized with a cis-4,5-methano substitution of the pyrrolidine ring, resulting in an intramolecular van-der-Waals interaction, thus preventing intramolecular cyclisation. Because of that increased stability, the researchers continued their investigation on cis-4,5-methano cyanopyrrolidines and came across with a new adamantyl derivative, which showed extraordinary ex vivo DPP-4 inhibition in rat plasma. Also noted, high microsomal turnover rate which indicated that the derivative was quickly converted to an active metabolite. After hydroxylation on the adamantyl group they had a product with better microsomal stability and improved chemical stability. That product was named saxagliptin (Onglyza)(Figure 6).[6] In June 2008 AstraZeneca and Bristol-Myers Squibb submitted a new drug application for Onglyza in the United States and a marketing authorization application in Europe.[13] Approval is still pending.
Denagliptin (Figure 6) is an advanced compound with a branched side-chain at the P2 position, but also has (4S)-fluoro substitution on the cyanopyrrolidine ring.[6] It is a well-known DPP-4 inhibitor developed by GlaxoSmithKline (GSK). Biological evaluations have shown that the S-configuration of the amino acid portion is essential for the inhibitory activity since the R-configuration showed reluctantly inhibition. These findings will be useful in future designs and synthesis of DPP-4 inhibitors.[14] GSK suspended phase-III clinical trials in October 2008.[15]
Azetidine based compounds
Informations for this group of inhibitors are quite restircted. Azetidine-based DPP-4 inhibitors can roughly be grouped into three main subcategories; 2-cyanoazetidines, 3-fluoroazetidines, and 2-ketoazetidines. The most potent ketoazetidines and cyanoazetidines have large hydrophobic amino acid groups bound to the azetidine nitrogen and are active below 100nM.[16]
Non-substrate-like inhibitors
Non-substrate-like inhibitors do not take after dipeptidic nature of DPP-4 substrates. They are non-covalent inhibitors and usually have an aromatic ring that occupies the S1-pocket, instead of the proline mimetic.[12]
In 1999, Merck started a drug development program on DPP-4 inhibitors. When they started internal screening and medicinal chemistry program, two DPP-4 inhibitors were already in clinical trials, isoleucyl thiazolidide (P32/38) and NVP-DPP728 from Novartis. Merck in-licensed L-threo-isoleucyl thiazolidide and its allo stereoisomer. In animal studies, they found that both isomers had similar affinity for DPP-4, similar in vivo efficacy, similar pharmacokinetic and metabolic profiles. Nevertheless, the allo isomer was 10-fold more toxic. The researchers found out that this difference in toxicity was due to the allo isomer's greater inhibition of DPP-8 and DPP-9 but not because of selective DPP-4 inhibition. More research also supported that DPP-4 inhibition would not cause compromised immune function. Once this link between affinity for DPP-8/DPP-9 and toxicity was discovered, Merck decided on identifying an inhibitor with more than a thousandfold affinity for DPP-4 over the other dipeptidases. For this purpose, they used positional scanning libraries. From scanning these libraries, the researchers discovered that both DPP-4 and DPP-8 showed a strong preference for breaking down peptides with a proline at the P1 position but they found a great difference at the P2 site; i.e., they found that acidic functionality at the P2 position could provide a greater affinity for DPP-4 over DPP-8. Merck kept up doing even more research and screening. They stopped working on compounds from the α-amino acid series related to isoleucyl thiazolidide due to lack of selectivity but instead they discovered a very selective β-amino acid piperazine series through SAR studies on two screening leads. When trying to stabilize the piperazine moiety, a group of bicyclic derivatives were made, which led to the identification of a potent and selective triazolopiperazine series. Most of these analogs showed excellent pharmacokinetic properties in preclinical species. Optimization of these compounds finally led to the discovery of sitagliptin.[17]
Sitagliptin (Januvia) has a novel structure with β-amino amide derivatives (Figure 7). Since sitagliptin has shown excellent selectivity and in vivo efficacy it urged researches to inspect the new structure of DPP-4 inhibitors with appended β-amino acid moiety. Further studies are being developed to optimize these compounds for the treatment of diabetes.[4] In October 2006 Sitagliptin became the first DPP-4 inhibitor that got FDA approval for the treatment of type 2 diabetes.[18] Crystallographic structure of sitagliptin along with molecular modeling has been used to continue the search for structurally diverse inhibitors. A new potent, selective and orally bioavailable DPP-4 inhibitor was discovered by replacing the central cyclohexylamine in sitagliptin with 3-aminopiperidine. A 2-pyridyl substitution was the initial SAR breakthrough since that group plays a significant role in potency and selectivity for DPP-4.[2]
It has been shown with an X-ray crystallography how sitagliptin binds to the DPP-4 complex:[12]
1. The trifluorophenyl group occupies the S1-pocket
2. The trifluoromethyl group interacts with the side chains of residues Arg358 and Ser209.
3. The amino group forms a salt bridge with Tyr662 and the carboxylated groups of the two glutamate residues, Glu205 and Glu206.
4. The triazolopiperazine group collides with the phenyl group of residue Phe357
Constrained phenylethylamine compounds
Researchers at Abbott Laboratories identified three novel series of DPP-4 inhibitors using HTS. After more research and optimization ABT-341 was discovered (Figure 8). It is a potent and selective DPP-4 inhibitor with a 2D-structure very similar to sitagliptin. However, the 3D-structure is quite different. ABT-341 also has a trifluorophenyl group that occupies the S1-pocket and the free amino group, but the two carbonyl groups are orientated 180° away from each other. ABT-341 is also believed to interact with the Tyr547, probably because of steric hindrance between the cyclohexenyl ring and the tyrosine side-chain.[12]
Pyrrolidine compounds
The pyrrolidine type of DPP-4 inhibitors was first discovered after HTS.[19] Research showed that the pyrrolidine rings were the part of the compounds that fit into the binding site. Further development has led to fluoro substituted pyrrolidines that show superior activity, as well as pyrrolidines with fused cyclopropylrings that are highly active.[20]
Xanthine-based compounds
This is a different class of inhibitors that were identified with HTS.[12] Aromatic heterocyclic-based DPP-4 inhibitors have gained increased attention recently. The first patents describing xanthines (Figure 10) as DPP-4 inhibitors came from Boehringer-Ingelheim(BI) and Novo Nordisk.[21] When xanthine based DPP-4 inhibitors are compared with sitagliptin and vildagliptin it has shown a superior profile. Xanthines are believed to have higher potency, longer-lasting inhibition and longer-lasting improvement of glucose tolerance.[22]
Alogliptin (Figure 9) is a novel DPP-4 inhibitor developed by the Takeda Pharmaceutical Company.[22] Researchers hypothesized that a quinazolinone based structure (Figure 9) would have the necessary groups to interact with the active site on the DPP-4 complex[disambiguation needed ]. Quinazolinone based compounds interacted effectively with the DPP-4 complex, but suffered from low metabolic half-life. It was found that when replacing the quinazolinone with a pyrimidinedione, the metabolic stability was increased and the result was a potent, selective, bioavailable DPP-4 inhibitor named alogliptin. The quinazoline based compounds showed potent inhibition and excellent selectivity over related protease, DPP-8. However, short metabolic half-life due to oxidation of the A-ring phenyl group was problematic. At first, the researchers tried to make a fluorinated derivative. The derivative showed improved metabolic stability and excellent inhibition of the DPP-4 enzyme. However, it was also found to inhibit CYP 450 3A4 and block the hERG channel. The solution to this problem was to replace the quinazolinone with other heterocycles, but the quinazolinone could be replaced without any loss of DPP-4 inhibition. Alogliptin was discovered when quinazolinone was replaced with a pyrimidinedione. Alogliptin has shown excellent inhibition of DPP-4 and extraordinary selectivity, greater than 10.000 fold over the closely related serine proteases DPP-8 and DPP-9. Also, it does not inhibit the CYP 450 enzymes nor block the hERG channel at concentration up to 30µM. Based on this data, alogliptin was chosen for preclinical evaluation.[23] In January 2007 alogliptin was undergoing the phase III clinical trial and in October 2008 it was being reviewed by the U.S. Food and Drug Administration.[24]
Researchers at BI discovered that using a buty-2-nyl group resulted in a potent candidate, called BI-1356 (Figure 10). In 2008 BI-1356 was undergoing phase III clinical trials; it was released as linagliptin in May 2011. X-ray crystallography has shown that that xanthine type binds the DPP-4 complex in a different way than other inhibitors:[12]
1. The amino group also interacts with the Glu205, Glu206 and Tyr662
2. The buty-2-nyl group occupies the S1-pocket
3. The uracil group undergoes a π-stacking interaction with the Tyr547 residue
4. The quinazoline group undergoes a π-stacking interaction with the Trp629 residue
Comparative pharmacology of sitagliptin and vildagliptin.[18] Drug Absorption Bioavailability (%) IC50 (nM) Mean volume of distribution (L) Protein binding (%) Half-life (hours,100 mg dose) Metabolism Excretion Sitagliptin Rapidly absorbed with peak concentration at 1–4 hours 87 18 198 38 12.4 Small fraction undergoes hepatic metabolism via CYP 450 3A4 and 2C8 Excreted in an unchanged form in the urine (79%) Vildagliptin Rapidly absorbed with peak concentration at 1–2 hours 85 3 70.5 9.3 1.68 (once a day) and 2.54 (twice a day) Hydrolysis resulting in a pharmacologically inactive metabolite. A fraction (22%) is also excreted unchanged by the kidneys Excretion of the metabolite is carried out through urine (85%) and feces (15%)
The pharmacokinetic properties of sitagliptin and vildagliptin appear unaffected by age, sex or BMI.[18] Clinical researches have shown that sitagliptin and vildagliptin do not have the side effects that tend to follow type 2 diabetes treatment, e.g. weight gain and hyperglycemia, but however, other side effects have been observed, including upper respiratory tract infections, sore throat and diarrhea.[5]
See also
- Dipeptidyl peptidase-4
- Dipeptidyl peptidase-4 inhibitors
- Vildagliptin
- Sitagliptin
- Saxagliptin
- Berberine
- ^ a b Green, Brian; Flatt, Peter; Bailey, Clifford (December 2006), "Dipeptidyl peptidase IV (DPP IV) inhibitors: a newly emerging drug class for the treatment of type 2 diabetes", Diabetes and vascular disease research 3 (3): 159–165, doi:10.3132/dvdr.2006.024, PMID 17160910, http://www.dvdres.com/pdf/2552.pdf [dead link]
- ^ a b c d Sebokova, Elena; Christ, Andreas; Boehringer, Markus; Mizrahi, Jacques (May 2006), "Dipeptidyl peptidase IV inhibitors: The next generation of new promising therapies for the management of type 2 diabetes", Current Topics in Medicinal Chemistry 7 (6): 547–555, doi:10.2174/156802607780091019, PMID 17352676, http://www.ingentaconnect.com/content/ben/ctmc/2007/00000007/00000006/art00002
- ^ a b c Wiedeman, Paul (May 2007), "DPP-IV Inhibition: Promising Therapy for the Treatment of Type 2 Diabetes", Progress in Medical Chemistry 45: 71–73, ISBN 9780444528087, http://books.google.com/?id=-WxwxEIzB3EC&pg=PA63&dq=dppiv+inhibition+wiedeman
- ^ a b Ahn, Sung Soo; Shin, Mi Sik; Jun, Mi Ae; Jung, Sun Ho; Kang, Seung Kyu; Kim, Kwang Rok; Rhee, Sang Dal; Kang, Nam Sook et al. (February 2007), "Synthesis, biological evaluation and structural determination of β-aminoacyl-containing cyclic hydrazine derivatives as dipeptidyl peptidase IV (DPP-IV) inhibitors", Bioorganic & Medicinal Chemistry Letters 17 (9): 2622–2628, doi:10.1016/j.bmcl.2007.01.111, PMID 17331715, http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VKY-4R7NPSY-1&_user=713789&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_version=1&_urlVersion=0&_userid=713789&md5=914f71fb6b477e3998e33cf49c91b6d9
- ^ a b c Lu, Su-Ying; Tsai, Keng-Chang; Chiang, Yi-Kun; Jiaang, Weir-Torn; Wu, Ssu-Hui; Mahindroo, Neeraj; Chien, Chia-Hui; Lee, Shiow-Ju et al. (January 2008), "A three-dimensional pharmacophore model for dipeptidyl peptidase IV inhibitors", European Journal of Medicinal Chemistry 43 (8): 1603–1611, doi:10.1016/j.ejmech.2007.11.014, PMID 18207285, http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VKY-4R7NPSY-1&_user=713789&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_version=1&_urlVersion=0&_userid=713789&md5=914f71fb6b477e3998e33cf49c91b6d9
- ^ a b c d e f g h Peters, Jens-Uwe (March 2007), "11 years of Cyanopyrrolidines as DPP-IV Inhibitors", Current Topics in Medicinal Chemistry 7 (6): 579–595, doi:10.2174/156802607780091000, PMID 17352679, http://www.ingentaconnect.com/content/ben/ctmc/2007/00000007/00000006/art00005
- ^ Cox, Scott; Harper, Bart; Mastracchio, Anthony; Leiting, Barbara; Roy, Ranabir; Reshma, Patel; Wu, Joseph; Lyons, Kathryn et al. (June 2007), "Discovery of 3-aminopiperidines as potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitors", Bioorganic & Medicinal Chemistry 17 (16): 4579–4583, doi:10.1016/j.bmcl.2007.05.087, PMID 17562364, http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TF9-4NWNCPF-1&_user=713789&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000039858&_version=1&_urlVersion=0&_userid=713789&md5=20851c5fcfe5679554793cf12461ba7d
- ^ a b Idris, Iskandar; Donnely, Richard (January), "Dipeptidyl peptidase-IV inhibitors: a major new class of oral antidiabetic drug", Diabetes, Obesity and Metabolism 9 (2): 153–165, doi:10.1111/j.1463-1326.2007.00705.x, PMID 17300591, http://pt.wkhealth.com/pt/re/dome/abstract.00127973-200703000-00002.htm;jsessionid=L8HQg0MX3QSvk2bPvN8BgynJ8zZ2r1JXrvHxmYpQRH1ntqR1F2jR!949623904!181195628!8091!-1
- ^ a b Kuhn, Bernd; Hennig, Michael; Mattei, Patrizio (March 2007), "Molecular Recognition of Ligands in Dipeptidyl Peptidase IV", Current Topics in Medicinal Chemistry 7 (6): 609–619, doi:10.2174/156802607780091064, PMID 17352681, http://www.ingentaconnect.com/content/ben/ctmc/2007/00000007/00000006/art00007
- ^ Veken, Pieter Van der; Haemers, Achiel; Augustyns, Koen (May 2007), "Prolyl peptidase related to dipeptidyl peptidase IV: Potential of specific inhibitors in drug discovery", Current Topics in Medicinal Chemistry 7 (6): 621–635, doi:10.2174/156802607780091046, PMID 17352682, http://www.ingentaconnect.com/content/ben/ctmc/2007/00000007/00000006/art00008
- ^ a b Simpkins, Lawrence; Bolton, Scott; Pi, Zulan; Scutton, James; Kwon, Chet; Magnin, David; Augeri, David; Gungor, Timur et al. (September 2007), "Potent non-nitrile dipeptidic dipeptidyl peptidase IV inhibitors", Bioorganic & Medicinal Chemistry Letters 17 (23): 6476–6480, doi:10.1016/j.bmcl.2007.09.090, PMID 17937986, http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TF9-4PT1SC6-1&_user=713789&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_version=1&_urlVersion=0&_userid=713789&md5=417ae5d6a31a5ab0d6dd3e9d639f55e2
- ^ a b c d e f g Pei, Zhonghua (March 2007), "From the bench to the bedside: Dipeptidyl peptidase IV inhibitors, a new class of oral antihyperglycemic agents", Current Opinion in Drug Discovery & Development 11 (4): 515–532, http://www.biomedcentral.com/render/render.asp?arx_id=cd-921157&type=pdf&access=denied
- ^ , http://www.astrazeneca-us.com/search/?itemId=3310018
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- ^ , http://www.gsk-clinicalstudyregister.com/protocol_detail.jsp?protocolId=DPB107246&studyId=20659&compound=Denagliptin
- ^ Ferraris, Dana; Belyakov, Sergei; Li, Weixing; Oliver, Eddie; Ko, Yao-Sen; Calvin, David; Lautar, Susan; Thomas, Bert et al. (March 2007), "Azetidine-Based Inhibitors of Dipeptidyl Peptidase IV (DPP IV)", Current Topics in Medicinal Chemistry 7 (6): 597–608, doi:10.2174/156802607780090993, PMID 17352680, http://www.ingentaconnect.com/content/ben/ctmc/2007/00000007/00000006/art00006
- ^ Thornberry, Nancy A.; Weber, Ann E. (March 2007), "Discovery of JANUVIATM (Sitagliptin), a Selective Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type2 Diabetes", Current Topics in Medicinal Chemistry 7 (6): 557–568, doi:10.2174/156802607780091028, PMID 17352677, http://www.ingentaconnect.com/content/ben/ctmc/2007/00000007/00000006/art00003
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- ^ Wright, Cox; Ammirati, Mark; Andrews, Kim; Brodeur, Anne; Danley, Dennis; Doran, Shawn; Lillquist, Jay; Liu, Shenping et al. (August 2007), "(3R,4S)-4-(2,4,5-Trifluorophenyl)-pyrrolidin-3-ylamine inhibitors of dipeptidyl peptidase IV: Synthesis, in vitro, in vivo, and X-ray crystallographic characterization", Bioorganic & Medicinal Chemistry Letters 17 (20): 5638–5642, doi:10.1016/j.bmcl.2007.07.081, PMID 17822893, http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TF9-4PGGP17-3&_user=713789&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_version=1&_urlVersion=0&_userid=713789&md5=f71c1030985c0de57f8372a1c16794b7
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- ^ , http://www.takeda.com/press/article_31125.html
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text:
Cancer is a condition where cells in a specific part of the body grow and reproduce uncontrollably. The cancerous cells can invade and destroy surrounding healthy tissue, including organs.
Cancer sometimes begins in one part of the body before spreading to other areas. This process is known as metastasis. There are over 200 different types of cancer, each with its own methods of diagnosis and treatment.
Changes to your body's normal processes or symptoms that are out of the ordinary can sometimes be an early sign of cancer. For example, a lump that suddenly appears on your body, unexplained bleeding or changes to your bowel habits are all symptoms that need to be checked by a doctor.
In many cases, your symptoms are not related to cancer and are caused by other, non-cancerous health conditions. However, it is still important that you visit your GP so your symptoms can be investigated.
Cervical Screening
A cervical screening test (previously known as a smear test) is a method of detecting abnormal cells on the cervix. The cervix is the entrance to the womb from the vagina. Detecting and removing abnormal cervical cells can prevent cervical cancer.
Find out more about cervical cancer here
Cervical screening is offered to women aged 25 to 64 in England because of the benefits of screening, including finding abnormal cells early so they can be treated quickly. Women who are registered with a GP are automatically invited for cervical screening.
This includes women who have had the HPV vaccination, as the vaccine doesn't protect against all types of HPV linked to cervical cancer so it doesn't guarantee complete protection against cervical cancer.
Find out more about HPV vaccination here
Deciding whether or not to have a screening test is your choice
Download the NHS Cervical Screening Leaflet to find out more
Find out more about cervical cancer prevention here
Bowel Cancer Screening
Bowel cancer is a common type of cancer in both men and women. About 1 in 20 people will get it during their lifetime.
Screening can help detect bowel cancer at an early stage, when it's easier to treat. It can also be used to help check for and remove small growths in the bowel called polyps which can turn into cancer over time. All men and women aged 60 to 74 who are registered with a GP in England are automatically sent a bowel cancer screening kit every 2 years.
Make sure your GP has the correct address so your kit is posted to the right place.
If you're 75 or over, you can ask for a kit every 2 years by phoning the free bowel cancer screening helpline on 0800 707 60 60.
Breast Cancer Screening
About 1 in 8 women in the UK are diagnosed with breast cancer during their lifetime. If it's detected early, treatment is more successful and there's a good chance of recovery.
Breast screening aims to find breast cancers early. It uses an X-ray test called a mammogram that can spot cancers when they're too small to see or feel.
As the likelihood of getting breast cancer increases with age, all women aged 50 to 70 and registered with a GP are automatically invited for breast cancer screening every 3 years.
Cancer Support organisations
You can find local and national cancer support organisations by searching our community directory.
Access the community directory here
Macmillan Cancer information and support
Macmillan is a charity that helps support people and their families who are affected by cancer by offering them support financially and emotionally.
They hold many fundraising events, campaigning events and have plenty of opportunities for people to volunteer. The Macmillan cancer information service at the Queen's Centre provides a drop-in service for anyone affected by cancer, whether a patient, relative, friend or anyone else.
To find out more visit the Macmillan website
Alternatively you can contact them by telephone on 01482 461 154 or 01482 875 875 (Monday to Friday 9am to 5pm)
Macmillan Clinical Nurse Specialist Team (Hull)
The Macmillan team consists of qualified Senior Nurses who have clinical and specialist experience and knowledge of palliative and end of life care.
The team work closely with other professionals to ensure the best possible care is delivered to patients and their careers. The Nurses are based within localities and are based at:
- East – Longhill Health Centre
- North – Bransholme Health Centre
- West – Elliott Chappell Health Centre
Visit the Hull City healthcare partnership to find out more
The service is available 7 days a week including bank holidays 9am to 5pm by contacting CHCP Single Point of Access for Specialist Palliative Care Services by telephone on 01482 335 883. You must be 18 or over and registered with a Hull GP.
Macmillan Volunteers
Macmillan volunteers provide an extra person to talk to, face to face or by telephone. They are people who have the time to listen and provide support, either as a one-off or on an ongoing basis, dependant on the person's needs and desires. Support is usually at least two to three hours support a week for 12 weeks.
Macmillan volunteers offer -
- general support for patients and carers
- dementia Support
- immediate and Longer Term Bereavement Support
- visit patients and carers in their own homes or contact by telephone to chat with them and check on their health and well being.
- provide some practical support with daily living as required, such as running errands, transporting patients to hospital appointments, gardening or sitting with a patient to allow a carer to go out for a break.
- provide practical support immediately after a bereavement.
- reducing social isolation and show people that someone cares about them.
- the chance to talk about their needs.
- emotional support through listening, questioning and making suggestions
- practical support to help them to remain living in their own homes.
- information about events and activities happening in the community which may be of interest to them.
Volunteers are available 7 days a week, including bank holidays from 9am to 5pm and can also provide support out of hours if needed.
To find out more visit the Hull city health care partnership
Referrals for volunteer support can be taken from any health, social or medical professional, as well as from carers and patients.
Referrals can be made by telephnoe on. 01482 335 883. You must be over 18 and live and be registered with a Hull GP to use this service.


text:
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With all the media hype about whiplash, APIL has put together a one day conference to investigate the real truth and causes of whiplash injuries, with the overarching objective of focusing on the evidence.
APIL practitioners are only too aware that injuries sustained from whiplash are a serious problem for the injured person. There is a lot of talk about this injury type often without reference to, let alone careful consideration of, the evidence. To establish the truth necessitates informed scrutiny.
Whiplash can take days, weeks or even months to develop. Whilst there are approaching 800,000 road accident claims being successfully concluded each year, whiplash can also occur from falls, sports injuries or even by being punched or shaken. Whiplash is caused by a motion or force that makes the neck move beyond its normal range of motion.
The main symptom is neck or upper back pain, but there are many others ranging from nausea and headaches, to severe brain injuries. APIL's conference assembles leading experts and legal practitioners to examine the evidence and look at the overall picture medically and psychologically, as well as legally in this country, Europewide, and in Australia.
Chaired by John Spencer, Fellow of APIL, John was appointed last April to APIL's Executive Committee and is also past chairman of the Motor Accident Solicitors Society. He has provided evidence to the parliamentary transport committee with regard to motor insurance and will open the conference by providing an overview of the political and associated activity around this issue.
Topics to be covered on the day will include:
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Theodore Clarke is an Adjunct Assistant Professor of Physics at Pasadena City College and a consultant on NASA's Juno project. He was the Team Chief of the Galileo Science Data Team.
Become a member of The Planetary Society and together we will create the future of space exploration.
Help advance robotic and human space exploration, defend our planet, and search for life.