text:
Diljit Dosanjh And Amrinder Gill Reunite After 5 Years For Upcoming Punjabi Film 'Jodi'
By: Prakriti | January 30, 2019
There are numerous movies being announced each week but the one announced today is a big one which caught the attention of many. Two big stars are coming together after a long time. Soon, we'll get to see the turbanned actor Diljit Dosanjh reuniting with the charming Amrinder Gill for an upcoming Punjabi film.
Under the banner of Rhythm Boyz and Dosanjhawala production house, a new Punjabi movie 'Jodi' was announced this morning. Jodi is written and directed by Amberdeep Singh and is produced by Amrinder Gill, Diljit Dosanjh and Karaj Gill. From what we've been told, Diljit will be the lead face of the film.
Nothing other than these basic details have been revealed by the team but we're pretty excited because after a long time Diljit Dosanjh has joined hands with Amrinder Gill. Last, the duo was seen in Dheeraj Rattan's Saadi Love Story which came in the year 2013. The audience loved watching them together and their chemistry was also appreciated. Also, with Jodi we would watch Diljit stepping as a full fledged producer in the Punjabi film industry. Now when two big actors have joined hands we hope we see something great coming our way.
Also Read: Sartaj Singh Pannu Bags A Big Project "OM" Under Eros International Mediap
They have given quite many hits and we expect them to know what the audience wants to watch. Hoping they would make an extra ordinary movie for the Punjabi Cinema lovers. On the other front, while Diljit would be seen in Jagdeep Sidhu's Shadaa and the Bollywood movie Arjun Patiala this year, Amrinder Gill would be seen doing Ashke 2 and rumored Angrej 2.
akhil fan fasting punjabi singer...
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Related Tags: PUNJABI POLLYWOOD REVIEW DILJIT DOSANJH AMRINDER GILL JODI AMBERDEEP SINGH SAJJAN SINGH RANGROOT PANKAJ BATRA KARAJ GILL HARISH VERMA SIMI CHAHAL NADHOO KHAN

redpajama_set_name: RedPajamaCommonCrawl


text:
X-MAN to the rescue
Wellcome Trust Sanger Institute
Massachusetts General Hospital Cancer Center
CAMBRIDGE, U.K.—The Wellcome Trust Sanger Institute and Horizon Discovery are teaming up to translate the abundance of new information on human genetic variation into more effective treatments for cancer, as part of a three-year collaboration between the two Cambridge-based organizations that began in July.
In the collaboration, Horizon will make available to the Sanger Institute's Genomics of Drug Sensitivity in Cancer project its unique resource of more than 200 genetically defined X-MAN in vitro human cancer models, which harbor known cancer-causing mutations, for sensitivity profiling against a panel of clinical and preclinical anti-cancer drugs. Matthew Garnett, a scientist in the Cancer Genome Project at the Sanger Institute, says this will work well to complement Sanger's current bank of non-isogenic human cancer cell lines—gathered in collaboration with Massachusetts General Hospital Cancer Center as part of Genomics of Drug Sensitivity in Cancer.
"Horizon will supply a portfolio of isogenic human cancer models generated using its novel GENESIS gene-targeting technology, wherein a pair of cell lines are created in which one line harbors a specific cancer causing mutation and the other is a perfectly matched control cell line," says Horizon Discovery CEO Chris Torrance, noting that his company's rapidly expanding list of more than 60 clients in academia, biotech and pharma are now using such genetically defined human disease models to address several key bottlenecks in the development of targeted cancer medicines.
Torrance says the terms are open access, meaning data will be made public as it is generated for the benefit of the entire research community.
Together, the Sanger and Horizon models will, it is hoped, help design clinical trials that target cancer therapeutics to patient populations that are most likely to respond, based on definitive and predictive biomarkers of either drug response or drug resistance.
"This a key need to maximize the efficiency of developing novel personalized medicines that are designed to target the root genetic causes of cancer," Torrance says. "Cancer, we now know, is at its heart a genetic disease. Horizon is using the data generated by the Sanger Institute and other genome centers around the world to create X-MAN cell lines, or more colloquially; 'patients-in-a-test- tube,' that will allow researchers to understand how cancer genes work (or not) and develop new treatment strategies."
As the Sanger-Horizon collaboration moves forward, Garnett notes there will be some hurdles to overcome.
"Working with a large cell line collection represents a significant technical challenge," he explains. "Another significant challenge is correlating large drug sensitivity data sets with the genetic features of the cancer models."
The challenges, Garnett adds, will be small bumps in the road and his team is ready to tackle them head- on.
"We have built a dedicated multidisciplinary team including biologists, clinicians, computer biologist and biostatisticians to facilitate the analysis and interpretation of our research," he notes.
Torrance notes that the collaboration will also address another real challenge as researchers move forward, which is to increase the diversity of cancer genes that are currently being addressed by the drug discovery community.
"Only a few cancer genes or pathways are being addressed at the moment because they are either quite prevalent and/or drugable," he says. "Consequently, we will need to find drugs to less common defects and targets downstream of undrugable cancer genes in order to build a sufficiently large tool box of drugs to combine and provide lasting remissions from this disease."
One way to achieve this is to get more "bang from your buck" on drugs already proven to possess safety and efficacy in humans, he notes.
"Although designed to a specific target, drugs will often have other 'off-targets' some of which may be useful," Torrance concludes. "The only way to determine if they are useful is to profile them on a wide range of patient-relevant disease models to see if unexpected patient-types benefit. This will also happen in this program as approved drugs are also being tested for potential new uses."


The Birth Data is composed of variables extracted from birth certificates. It holds important information about the birth, the baby, and the parents. The HHDW reports display birth counts, percentages, and rates, where appropriate, for births among residents by geographic location, race-ethnicity, age, birth weight, parent's characteristics, delivery term, delivery method, and prenatal care. Additionally, pregnancies and births among teenage females are reported.
Includes adopted babies as well. Mother information for adopted baby records is the adopting mother, not the birth mother.
Cell size restriction is applied when numerator (number of births) is between 1 and 5.
Number of births listed above includes births occurring in the state to residents only. Births occurring in Hawaii to visitors comprise less than 0.5% of annual births in the state.


Self Description: I am a gentle and quiet girl also active. I am humorous and intelligent, soft, kind heart, responsible, traditional and modern. I know to keep and thankful heart and cherish things. I advocate romantic and cozy love. I enjoy simple marriage too. I look forward to meet my right boy in the fate.
Comments: I hope he is open and clear and sunny, tall and strong, sincere and kind, warm and considerate. He should love life and have his own cause.


I enjoyed your article with Barry Fitzsimmons We worked together for a while in NYC at WCBS and Barry was a savvy producer and a good writer. Fun to see his lists of creative tools and his advice for dealing with the pressure of the business. Much here for young newcomers to learn from. Thanks to Kate Bacon and to Barry for sharing.


Come with me on my longest marathon training run through the streets and parks of London. The course I primarily followed was a 20-22 miler found online courtesy of the Serpentine Running Club.
It's a cool, misting Saturday morning, perfect for a marathon training run. Pacing will be a problem on this route. We'll just do the best we can and enjoy the route.
This museum is a must-see devoted to decorative arts & design. The café is located in several beautiful rooms with a wonderful patio.
and the ever popular Natural Science Museum.
The Natural Science Museum is still on my must-see list. The queue some mornings tell me it is in high demand.
At Mile 2, we're moving into Hyde Park.
This park has lots of greenery and activity. Cyclists, runners (about a 6-mile perimeter), equestrians, dog walkers and folks hanging out at the senior playground for tennis and lawn bowling.
At mile 3, we're at the Buck Hill Gate of Hyde Park.
Buck Hill is one of several private lodges on the perimeter of the park.
Mile 4 & 5 takes us through Kensington Park past Kensington Palace and its gardens.
Queen Victoria watches over her subjects as they walk/run/cycle by.
By Mile 6, we are headed south looking at the Chelsea Kitchen restaurant across Kings Road.
Mile 7, just down the road we find the Chelsea Football Club.
Mile 8 brings us to Imperial Wharf. And here is where we get a bit confused, with traffic rerouted and pedestrian walkways closed. We'll put on a couple of miles chasing in circles until a fellow runner helps us find our way to the Thames path.
Mile 10, the rain begins to pick up as we pass the beautiful small Cremorne Gardens. We'll forego the photo since the rain is hampering the view.
Mile 11, here we go crossing the Thames River for the first of several times on this route. We take the Battersea Bridge across to Battersea Park.
At mile 12 through Battersea Park, there is plenty of open space and beautifully maintained playing fields as well as a fantastic track.
From Battersea, we head back across the Thames on the Chelsea Bridge. The sky in the photo below tells you we have more miles of sloshing to go.
Mile 13, we are passing Pimlico Park. and stopping a moment to enjoy this little jewel. The rain lets up a bit just in time for a photo.
It's then time to cross the Thames again, this mile on the Vauxhall Bridge.
It's also an opportunity to see the Thames at low tide.
and get a photo with river traffic, Parliament and Big Ben in the background.
By Mile 16.5, we are at the Tower Bridge.
This bridge didn't need the looming clouds overhead to make it appear scary.
Back in London at Mile 18, we're making our way across through heavier rain and heavier tourist pedestrian traffic. They are undeterred by the rain so we're in for another mile or so of fast walk/jogging.
Most of the crowd is here to see London Tower which is worth seeing in any weather with probably 1500 years of history within its walls.
There is an incredible amount of history behind these walls. Leave yourself plenty of time to look around when you're not on a run.
Now heading back to our start up Westminster, we are around Mile 19 and we hear church bells ringing as we edge along the perimeter of Saint James's Park.
Having picked up extra mileage through our mistakes on the course in Chelsea, we don't complete the area around Green Park but as we approach Mile 20, we do get a chance to peer in to Buckingham Palace.
Finally around Mile 21, we pass by the Marble Arch and back into Hyde Park.
We run along it perimeter until it joins Kensington Park. Here, we will cross the street and cut around the amazing Royal Albert Hall with the rain still coming down.
Wet and weary, let's finish up on the backside of the Natural History Museum and call it a day.
Although it was a bit of an unorthodox run, the miles are done. Thanks for joining me. It's always good to have someone along putting in the miles.
Terrific Mary Lou!! A training run to remember for sure!!
Thanks Patrick. I was pleased to find the running club had mapped out several distances and posted them online. It was a fun day.
What a place for a training run.
Enjoy the rest of your trip. See you soon.
Only downside to being in London was missing the Peppermint Patty 5K.
The pictures and your commentary made me feel like I was on the run with you. Of course, I haven't run 22 miles since 2011.
I could have used your company. We would have had a lot of laughs along the way. I believe we both ran that marathon in 2011. It was great weather for it, nice and cool.


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Killing Fields (OST) – Mike Oldfield [#655]
Having first heard two tracks from this album on Complete Mike Oldfield and having a teaser clip for the 1984 film on an old video cassette, I was keen to see this film. However this was in a time when films rarely made their way to TV at an acceptable time and there was no internets or Nutflux and Jeff Bezos was still scrounging $1 from his pals to buy a pack of Twinkies. So it wasn't until probably the mid-90s when I eventually caught this film tucked away late one night on Channel 4. By which time I was holed up in my stinky little bachelor pad trying to make £140 last a month.
The Bruce Robinson directed film The Killing Fields starred Julian Sands, John Malkovich and Haing S Ngor and is a harrowing account of journalists Sydney Schanburg and Dith Pran's experiences in Cambodia during the rise of the Kamer Rouge in the 1970s. If you ever want to see how quickly things can go to shit in a country, especially in a part of the world where there is dodgy goings on conducted by Western forces and the impact these actions can have on a people, then The Killing Fields is your required viewing. It's what made me want to do Journalism at University.
The soundtrack, however, is by Mike Oldfield and was specifically written for the film on his Fairlight CMI, it is almost as atmospheric and as chilling as the film itself.
Soundtrack available on
1984 Mike Oldfield Soundtracks
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It'll End in Tears – This Mortal Coil [#644]
Gloomy collaborative music by Evo Watts' music project This Mortal Coil.
Like Mike Oldfield's Islands this was also part of a x for £xx deal at the Virgin Megastore in Liverpool (now Claus Ohlson). I mourn the passing of record shops and their x for £xx deals, this is not an offer the likes of Amazon, iTunes and their ilk seem to foster. I was drawn to This Mortal Coil and their 1984 album It'll End in Tears via the 4AD Uncut Compilation CD and David Lynch's Lost Highway in which the band's cover of Tim Buckley's Song of the Siren featured and marked the beginning of me being a little more adventurous with my music choices. However I only became aware of them following the rerelease of the album in the nineties.
Of course, this was in the nineties so music downloading hadn't really taken off in the UK due to the crapness of internet connectivity but it quickly became a prized item in my music library. Especially as it made me feel that I appeared cultured and with it to my Guardian reading, coffee table book owning friends at the time.
Hipster? moi? Nah my trousers are not corduroy and I don't own a penny farthing.
Apologies for the break in posts last week, I'm still rebuilding my music library following an IT issue with my iMac, and have just returned from a holiday in Dorset so posts will be a little sporadic for a few weeks. However, please do not feel I've abandoned this project or stopped writing, I haven't. Keep an eye out on my other blog, the Compostual Existentialist over the next few weeks for details of my recent holiday.
1984 4AD Brendan Perry Cocteau Twins Collaborations Dead Can Dance Dream Pop Etheral Wave gothic Lisa Gerrard new age Post-Punk This Mortal Coil Tim Buckley
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Into the Gap – Thompson Twins [#639]
No Eighties compilation can possibly be complete without Thompson Twins. Indeed, no music collection grown across the decade of the eighties can be considered complete without them either. Thompson Twins are a sound so the eighties they may as well have quiffy hairstyles, have a band member of undetermined gender and look moodily into the camera when not dancing freestyle in their music videos.
During one of my many visits to Virgin Megastore when I was a student in 90's Sheffield, I was desperate to make up a 3 for £20 offer from the selection available, so it was Into the Gap that became the third. Sadly, in a desperate effort to make friends, I loaned the CD out to someone only for me to drop out of uni a few months later and lose contact with the borrower forever.
Fortunately for me, I kept a cassette recording of the CD to listen to on my Walkman and managed to rip the cassette recording nearly an entire decade later. The version I have now is kind of a third gen rip of the album but still really good crystal quality. A testament to the various recording devices I've had over the years.
Yet considering I wasn't all that keen on the band to begin with, I really fell for this album. Perhaps it's the waves of nostalgia that come with it or perhaps the power of the three hit songs from the band that appear on the album. I'm not entirely sure.
1984 Arista Pop Rock Thompson Twins
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Human's Lib – Howard Jones #598
Human's Lib by Howard Jones
Nothing says 80's music more than a bloke with spiky hair and a synthesiser.
Oh, Howard Jones. I remember you with your spiky hair on singing What is Love? on Top of the Pops. I remember you on Live Aid singing Hide and Seek. I remember trying to work out the inaudibly sung lyrics in pre-internet days. I remember seeing you on a "We wuz in the Eighties" vox pop TV show in the early noughties. I remember thinking "What ever happened to Howard Jones?".
This is Jones' first album featuring three of his hit songs from his early 80s career. Rich in 80s synth melody with interesting if a little bitter lyrics the album has fared well in time but doesn't carry as much of the welly as other albums from contemporary bands and artists. It's more of a choice of listen than something you would build an iTunes playlist from.
1984 Howard Jones
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Ghostbusters OST – Various Artists [#518]
This is the soundtrack to the classic 1980s blockbusting movie Ghostbusters.
As a regular downloader from the alt.binaries.sounds.mp3.soundtrack newsgroup in the late noughties, I would frequently smugly mark for download the soundtracks for movies I'd always wanted but had been unable to obtain from crappy HMV or Virgin Megastores. One such prize was todays album.
I remember my brother taking me to see Ghostbusters in the Lime Street Odeon in Liverpool. I remember queuing up (in the cold) for hours before the doors opened so that we would be some of the first in the theatre and be able to get the best seats. I remember being excited to rent the video when it became available, and I still remember the anticipation and thrill of being able to video record it off the telly when it was eventually shown over Christmas for the first time on network television.
I also remember the disappointment at being unable to find the soundtrack on CD, a dissipating disappointment when I located it on Usenet.
Classic 80s soundtrack for a classic 80s film. Not sure why they feel the need to "reboot" it.
1984 compilations Soundtracks Various Artists
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Electric Dreams – OST [#418]
A film ahead of its time was the little known eighties film Electric Dreams. Possibly more familiar is the song from the closing credits performed by former Human League and car stereo buyer Phil Oakey.
Electric Dreams tells the story of Miles (Twin Peaks' Lenny von Dohlen), a geeky architect nerd who happens to fancy his new neighbour Madeline (played by Dune Princess Virginia Madsen) just at the same moment he buys himself a home computer and accidentally makes it sentient by spilling wine all over it. As you do.
The music is a perfect eighties music time capsule with songs by Culture Club, ELO's Jeff Lynne and P.P.Arnold (currently doing the Caribbean Cruise circuit).
I love this soundtrack. I love the film too. It's such a shame that it's hardly ever shown on TV these days and it's pricey on DVD.
1984 Soundtracks Various Artists
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Dune – OST [#401]
The beginning is a very delicate time. Know then that it is the year 2015, and I'm still only a hundred albums shy of being a third of the way through this music project.
Dune is a very special film and soundtrack for me. My oldest brother used to scoff that I couldn't possibly have understood the concepts dealt with by the film, especially as Lynch's version was edited to bits. The weird thing is, I got Lynch from a very early age. In fact, I got Dune on a deeper level through the film than I ever did with the novel. I think Lynch did a bloody good job making a sci-fi snob's book accessible to many people.
My oldest brother repeatedly tried to "explain" his interpretation of the novel to me, but he had no need as I already understood what the author was trying to say. I understood the hidden depths, the concept of the Kwisatz Haderach, the Fremen and what the spice really was. Even the trope of the sandworms.
The film is also important to me because of how the music actually makes a good accompaniment in the way that Queen's soundtrack to Flash Gordon makes Flash Gordon what it is. Toto do an outstanding job of the soundtrack especially considering their only other significant contribution to the soundtrack of my life is their hit song Africa and Brian Eno's atmospherics also add to the whole parcel of the film.
Soundtracks for Lynch's films appear several times in this music project but if asked to save one from deletion it would definitely be the soundtrack for Dune. A film that still sends shivers down my spine and, in some respects, seen by many as a premonition/allegory/parable for the events in Syria, Iraq and the Middle East as we live right now and, I believe, has been since it was written.
1984 Brian Eno Soundtracks Toto
Discovery – Mike Oldfield [#374]
by steelrattus
Discovery – Mike Oldfield
Steelrattus here again, with the third of my guest posts in this seven day run.
Mike Oldfield. I first got into Mike Oldfield at university, courtesy of the previously mentioned UniversityRichard™. It was Oldfield's original sound which hooked me, along with the other bands that Richard introduced me to. I must have heard the titular track from Tubular Bells prior to this time, but finally I heard the entire album, and many more such as Hergest Ridge, Ommadawn, Five Miles Out, Crises, and the wonderfully nutty Amarok. While at university in the early to mid 90s Tubular Bells 2 and The Songs of Distant Earth were released. And that was pretty much where my relationship with Mike Oldfield ended. I have listened to some of what he has produced subsequently, but none of it has hooked me like the earlier albums.
Discovery is another of these odd albums which somehow I've managed to miss in the chronology, as it was released after Crises in 1984. I'm guessing though that the reason I've not heard it is because it's not very good. Curiously the biographical section of Mr. Oldfield's Wikipedia entry, presumably curated by one or more dedicated fans, doesn't mention it at all. Does this also suggest that generally it's not viewed very favourably? There is a short dedicated page for the album though which tells us it was recorded as a follow up to the very successful single Moonlight Shadow, from the Crises album. To that end, and unusually for Mr. Oldfield, most of the album is comprised of short songs that were presumably intended for the pop market, and a lot of the songs feel like variations on the Moonlight Shadow theme. The only exception is The Lake, the final track, which is a distinct instrumental that is three times the length of the other tracks on the album, and for me at least the stand out track. Oldfield has said this final track was inspired by Lake Geneva, as he recorded the album in Switzerland (he was living there for tax reasons), and could see the lake from his recording studio.
1984 Memories Mike Oldfield
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Classic rock: 1984-1985 – Various Artists [#277]
Classic rock: 1984-1985 – Various Artists
The next three entries follow a similar pattern. That's because the next three entries are very similar compilations. I could spare you the time but I'm cruel like that and I put the effort in to listen to these albums so it's only fair.
The first in our trilogy of Classic Rock:198x – Time Life compilations is for the range 1984-1985, a glorious period in music, rich in a variety of hair, guitars and stadia. So it's curious as to why the compiler chose the songs they did. I suspect that the compiler for Classic Rock: Symphonic Rock, which is also a Time Life compilation, worked on the same project.
Seriously that guy needs to broaden his music tastes.
1-1 –Billy Idol Rebel Yell
1-2 –ZZ Top Legs
1-3 –David Lee Roth California Girls
1-4 –Huey Lewis & The News The Power Of Love
1-5 –Pat Benatar Love Is A Battlefield
1-6 –Eurythmics Here Comes The Rain Again
1-7 –Waterboys Whole Of The Moon
1-8 –Kate Bush Running Up The Hill
1-9 –Jon & Vangelis State Of Independence
1-10 –Marillion Kayleigh
1-11 –John Waite Missing You
1-12 –Rick Springfield Jessie's Girl
1-13 –Glenn Frey The Heat Is On
1-14 –Starship We Built This City
1-15 –Tears For Fears Shout
2-1 –Meat Loaf Modern Girl
2-2 –Bonnie Tyler Holding Out For A Hero
2-3 –Talking Heads Road To Nowhere
2-4 –Talk Talk It's My Life
2-5 –Dio (2) Rock 'N' Roll Children
2-6 –Deep Purple Perfect Strangers
2-7 –George Thorogood & The Destroyers Willie & The Hand Jive
2-8 –Los Lobos Don't Worry Baby
2-9 –Bette Midler Beast Of Burden
2-10 –Nils Lofgren Secrets In The Street
2-11 –Cars* Drive
2-12 –Foreigner I Want To Know What Love Is
2-13 –REO Speedwagon Can't Fight This Feeling
2-14 –Chris Rea Stainsby Girls
2-15 –Far Corporation Stairway To Heaven
1984 1985 compilations Various Artists
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The Best of Jon & Vangelis – Jon & Vangelis (#169)
The Best of Jon & Vangelis – Jon & Vangelis
Two titans of prog meet and out prog themselves with prog in a very pro-prog kind of way. Jon Anderson of Yes joins forces with Vangelis of Aphrodites Child to forge an unholy progressive rock alliance bringing the auditory senses an extra dose of twee, sax and plinky plonky synth.
I used to really like this album when I was younger. I had it on CD, then on tape and just to be format friendly, nicked it off the internet. I think by the third time I had obtained this album, I'd already overspent.
Sure, its a good album if you're a fan. But it's certainly a product of the time. Just too twee. You half expect to sprout a kaftan and start waving a smudge stick about the place while sticking up Roger Dean posters everywhere just by listening to it.
Great if you like Greek blokes with beards and mop haired guys from Altrincham with inexplicable American accents.
1984 best of jon & vangelis Jon Anderson Vangelis
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1984 – Rick Wakeman [#18]
1984 – Rick Wakeman
Take one Chaka "Chaka" Khan (out of deep storage), a dose of Kenny Lynch, a teaspoon of Jon Anderson, a pinch of cockney rebel Steve Harley and mix well with copious amounts of bearded prog rock keyboard player (remove beard). Garnish with sprinklings of Tim Rice Libretto which has been steeped overnight in a solution of George Orwell's 1984. Leave to play for 46 minutes.
Serve with bemusment.
Rick the bearded grump mashes out another album of prolonged twiddling this time without the ice skating panto horses. Instead he collaborates with Tim "Jeeeesus Christ Superstar" Rice and tells the story of Orwell's 1984.
If you can listen through Chaka "Chaka" Khan's screeching you will hear something quite entertaining. Don't get me wrong, this isn't "Lounging about on the sofa drinking coffee" music, nor is it "bring some girl home and romance her" music (unless you've found the mythical female prog fan). It isn't even "Aren't we refined" dinner party music. It's "Let's vacuum the house" or "Wash the dishes" music.
Admittedly I used to listen to it when I did my paper round so it isn't all that bad really.
Except for the screeching.
1984 Rick Wakeman


works as an architect across a broad range of projects around the world. Based in London, Simon has a passion for art, business and technology and occasionally is that guy who brought his guitar along. Studying architecture in his home town of Adelaide, Australia, Simon then started his architectural career in 2004 working for Woods Bagot. Working on global projects, Simon was based in the middle east before settling in London over 5 years ago.
In recent years Simon has focussed on project and business management, developing skills which he hopes to apply to future projects combining his interest in art and technology.


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text:
Los groeberíidos (Groeberiidae) son una familia extinta de mamíferos gondwanaterios. Vivieron en Sudamérica del Eoceno Superior al Oligoceno Inferior.

Historia
La especie tipo, Groeberia minoprioi, fue descrita por primera vez en 1952 por Bryan Patterson. Su espécimen tipo, MMP 738, se compone de una sínfisis mandibular, incisivos y cuatro molares rotos. Una segunda especie dentro de este género, Groeberia pattersoni, fue descrita por G. G. Simpson en 1970, y es conocida de al menos dos especímenes. Ambas provienen de los depósitos de la Formación Divisadero Largo, los cuales datan del Eoceno.

Flynn y Wyss en 1999 describió a la especie del Oligoceno Klohnia charrieri, y Goin y colaboradores en 2010 añadirían a los taxones Klohnia major, Epiklohnia verticalis y Praedens aberrans, todos los cuales también data de esa época.

Posteriormente, Chimento et al. en 2013 re-examinaron a Groeberia y concluyeron que tiene afinidades evolutivas con los aloterios. Los otros taxones miembros del grupo no fueron incluidos en este examen por razones sin especificar, lo que implica que su estatus como parte de este clado es desconocido.

Clasificación

Durante mucho tiempo, se consideró que los groebéridos eran marsupiales paucituberculados. Aunque estos actualmente solo son representados por los ratones runchos, a lo largo del Cenozoico los paucituberculados incluyeron especies similares a roedores, lo que hacía esta clasificación razonable. Sin embargo, esta asignación era como mucho provisoria, ya que al ser comparados con otros paucituberculados los groebéridos eran muy diferentes. Algunos otros investigadores difirieron al respecto, incluyendo a Simpson y Wyss en 1999, los cuales consideraron que estos animales eran marsupiales diprotodontes, y Pascual en 1994 y Simpson en 1970, quienes concluyeron que eran Metatheria incertae sedis (de clasificación incierta), ideas que fueron a su vez cuestionadas.

Posteriormente, Groeberia fue reclasificado como un multituberculado gondwanaterio, un grupo en el cual sus características "aberrantes" resultaron siendo bastante típicas. Dentro de Gondwanatheria, este se situaría en una posición bastante basal, diferenciándose antes que los diversos sudamerícidos pero posteriormente a Ferugliotherium.

Como se mencionó antes, los otros groebéridos no fueron incluidos en ese análisis; si en realidad eran gondwanaterios o paucituberculados es algo que aún está por determinarse.

Mucho antes de esta reclasificación, Malcolm McKenna expresó sus dudas acerca de la identidad marsupial para los groebéridos, afirmando que considerarlos como metaterios era "un acto de fe".

Géneros y especies

Género Groeberia
Autor: Patterson, 1952
Observaciones:
Especies:
G. minopriori (especie tipo)
Autor: Patterson, 1952
Datos fósiles: Eoceno superior;
A. pattersoni
Autor: Simpson, 1970
Datos fósiles: Eoceno superior;

Género Klohnia
Autor: Flynn & Wyss, 1999
Observaciones:
Especies:
K. charrieri (especie tipo)
Autor: Flynn & Wyss, 1999
Datos fósiles: Oligoceno temprano;
K. major
Autor: Goin et al., 2010
Datos fósiles: Oligoceno temprano;

Género Epiklohnia
Autor: Goin et al., 2010
Observaciones:
Especies:
E. verticalis
Autor: Goin et al., 2010
Datos fósiles: Oligoceno temprano;

Género Praedens
Autor: Goin et al., 2010
Observaciones:
Especies:
P. aberrans
Autor: Goin et al., 2010
Datos fósiles: Oligoceno temprano;

Véase también
Anexo:Clase Mammalia. Tabla taxonómica
Anexo:Ameridelphia. Tabla taxonómica

Referencias

Bibliografía

 Goin, F.J., Abello M.A. & Chornogubsky L. 2010. Middle Tertiary marsupials from Central Patagonia (Early Oligocene of Gran Barranca): Understanding South America's Grande Coupure. En: Madden R.H., Carlini A.A., Vucetich M.G. & Kay R.F. (Eds.), The Paleontology of Gran Barranca: Evolution and Environmental Change through the Middle Cenozoic of Patagonia. Cambridge University Press.

Enlaces externos
Family Groeberiidae en BioLib
Simpsonitheria en Mikko's Phylogeny Archive
 Brands, S.J. (comp.) 1989-2005. Systema Naturae 2000. The Taxonomicon. Universal Taxonomic Services, Ámsterdam, Holanda. Acceso: 4 de octubre de 2007.

Groeberiidae
Familias de mamíferos

redpajama_set_name: RedPajamaWikipedia


text:
/*
 * This file is part of the flypaper.js build.
 * Use grunt to assemble the completed file.
 * Find the built file in dist/flypaper.js
 */

//------------- BEGIN FLYPAPER MATH AND MOTION ------------//
/*
*	Math and Motion	Methods
*
*	versions 0.3 - 0.4
*/
//--------------------------------------------------------//

fly.midpoint = function (p1,p2) {
		// returns the point between two points
	var _p = new paper.Point(p1.add(p2));
	_p = _p.divide([2,2]);
	return _p;
};

fly.scatter = function (o,rect) {
		// takes an object or array of objects o
		// and places it's center randomly within rectangle rect
		// start in lower right corner, multiply x and y by random 0 to 1
		// point will land somewhere in the rect
		// TODO: optional place within rect bounds
	if (o instanceof Array === false) {
		o = [o];
	}
	for (var i=0; i < o.length; i++) {
		var randPoint = new paper.Point(	// point at lower right corner
			rect.width,rect.height
		);
		var randLoc = randPoint.multiply(paper.Size.random()); // point within rect
		o[i].position = rect.point.add(randLoc);
	}
};

fly.randomizePt = function (point,delta,constrain) {
	// adds variance delta to point
	// constrain === "x" or "y" or default none
	var c = constrain || "none";
	if (c !== "y") {
		var x = (- delta) + (2 * delta * Math.random());
		point.x += x;
	}
	if (c !== "x") {
		var y = (- delta) +  (2 * delta * Math.random());
		point.y += y;
	}
	return point;
};

//---- methods for working with grids: myGrid[x][y]

fly.eachCell = function (o,f) {
	// call by object o to iterate through grid[x][y]
	// call: fly.eachCell(this,function (o,x,y) { ... });
	// "this" o must have this.cols and this.rows
	for (var x=0; x < o.cols; x++) {
		for (var y=0; y < o.rows; y++) {
			f(o,x,y);
		}
	}
};

fly.gridPlot = function (c,r,rectangle,dir) {
	// v.0.4
	// returns an array of arrays of points
	// c + 1 columns by r + 1 rows inside paper.rectangle r
	// last column and row run along right and bottom edges
	// dir is an optional string, which controls the direction
	// (top down, left to right etc.) that the grid travels.
	// Use this to quickly change the orientation of an object
	// aligned to a grid.
	// CHANGE: rectangle is a paper.rectangle, not a path, use
	// this.handle.bounds to send bounds
	// note-to-self: this breaks junkaigo v 0.3.1 !!!
	// TODO: accept both a rectangle and a path.Rectangle?

	dir = dir || "down-left";
	var rect = new paper.Path.Rectangle(rectangle);
	var points = [];
	for (var i=0; i <= c; i++) {
		points[i] = [];
	}
	var w = rect.bounds.width / c;
	var h = rect.bounds.height / r;
	for (var x=0; x <= c; x++) {
		for (var y=0; y <= r; y++) {
			var pt = new paper.Point( rect.bounds.x + x * w,
								rect.bounds.y + y * h);
			switch (dir) {
				case "down-right" :
				case "right" :
					points[c-x][y] = pt;
					break;
				case "up-left" :
					points[x][r-y] = pt;
					break;
				case "up-right" :
					points[c-x][r-y] = pt;
					break;
				default : // "down-left"
					points[x][y] = pt;
			}
		}
	}
	return points;
};

fly.initArray = function (c,r) {
	// init 3-d array
	var a = [];
	for (var x=0; x < c; x++) {
		a[x] = [];
		for (var y=0; y < r; y++) {
			a[x][y] = [];
		}
	}
	return a;
};

redpajama_set_name: RedPajamaGithub


Check out the newest campaign featured in our major shopping malls and news media. This Mid-Autumn festival, we will be highlighting some of Hong Kong's leading instant bird's nest products.
Bird's Nest is the saliva produced by a special species of swallow called the swiftlet while building the nest. The saliva glues with other impurities (such as feathers) to form the nest. Among the different species of switlets, golden switlet's saliva has the purest protein content and the highest nutrient value.
Bird's nests are mainly produced in Southeast Asian countries such as Indonesia, Thailand, Vietnam, Singapore, Malaysia, Burma and Hainan Province in Southern China. The texture and taste of bird's nest vary with the swiftlet's habitat. Compared with Cave Nest, House Nest is cleaner, softer and smoother in texture. So, the soaking/stewing time can be shortened. Cave Nest is mainly found in Thailand, Vietnam and Malaysia, whereas House Nest is mostly produced in Indonesia.
There are three harvesting periods of bird's nest in a year -- the 'first phase' (first harvesting period) bird's nest is the most nutritious bird's nest and contains much more proteins and minerals.
'First phase' bird's nest is harvested from November to January every year – springtime of Indonesia. In this season of abundance and thriving, the swiftlet grows up strong and healthy and is able to secrete plentiful saliva. Under such favourable environment, bird's nest harvested during this period is purer and gets bigger expansion after soaking. The body of bird's nest is obviously larger in size and thicker in texture.
The second and third phase bird's nest is not as good comparing with the 'first phase' bird's nest in terms of quality and quantity. During these seasons, the swiftlet is weak due to unfavourable weather and lean food supply. Saliva secretion is slow and lots of feathers fall off, thus increase impurities. The bird's nest is usually smaller in size and has lesser expandability.
IBNI has its own bird's nest farmhouses and processing plants in Indonesia. Some time before every Chinese Lunar New Year, IBNI ships fresh 'first phase' bird's nests to Hong Kong through air cargo. This guarantees sufficient supply of 'first phase' bird's nests in the market all the year round.
How to count the age of the root?
Check out our newest store at Pacific Mall located at C58. The store features the largest collection of ginseng in mall ranging from 3 year to 6 year roots.
From March till May, Royal Jubilee Ginseng will be featured on every door of the mall of FMP. Thank you for those that have supported this project and bringing it to life!


Cosmo is Senior Vice President, Digital Business Development at EMI Music responsible for licensing EMI content to digital music platforms globally. Responsibilities include negotiating global and multi-territory distribution deals, proactive business development with partners across the media industry and recently a particular focus on the Open EMI initiative which aims to foster creative and commercial innovation in digital music.
Prior to joining EMI in October 2009 Cosmo was Commercial Director at Project Kangaroo, the U.K. online TV joint venture between BBC Worldwide, ITV and Channel 4 that was blocked by the Competition Commission weeks before launch. Prior to Kangaroo, Cosmo held a variety of commercial and marketing roles at Channel 4, mobile operator 3 and IPTV provider Home choice.
Cosmo has an undergraduate degree from Oxford University and an M.B.A. from INSEAD. He is an active violin player and is teaching his kids the piano, violin and trumpet.


Did you find this website and the Center's materials useful?
Would you like to invite Ellen or Joe to make a presentation, or find out about upcoming events?
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The Mental Notion Society (MNS) is a production company specializing in art, entertainment, and media. All MNS projects follow the mission statement of creating art that instills dialogue amongst experiencing audiences. The Society is made up of various talents that are armed with alternative imaginations and vibes of cold tenderness. Founded in 2010, in Chicago, IL. Previous productions include: The Russian Play: An Improvised Black Comedy (2013) ; Tetrazzini's Last Hurrah (2013) ; MONO(logue): Help Me Find My Voice (2013) ; Fight Club: A Project Mayhem Burlesque (2013) ; & Yellowstone: A Twilight Zone Musical (2012).
Jonald Reyes is Artistic Director of The Mental Notion Society.
Click on the image below to scroll thru the gallery of a few Mental Notion productions.


text:
Popular Questions and Answers Asked About Window Films
Most window films are constructed with several layers, the main layer being a high-quality polyester. Depending on the type of film, most of our window films are metallised using sputtering technology. This process embeds metal particles such as silver, stainless steel, copper, gold, titanium and chromium into a polyester film. Finally, the films are coated using special adhesives, ultraviolet inhibitors and then protected by a scratch-resistant coating. This ensures a long lasting colour and excellent solar performance.
How is window film applied?
Clean the glass. Measure the glass panel and cut the window film oversize. Remove the backing sheet from the film. Spray the glass and adhesive side of the film using a mild soapy water solution. Using a squeegee apply the film on to the glass to remove the excess water and bubbles. Trim the excess edges of the film using a sharp utility knife and dry with a soft lint-free cloth.
Please see our DIY instruction or YouTube video
Whilst small applications are possible by any keen DIYer or tradesman, we would certainly recommend employing a professional company for larger applications or areas where a quality finish is vital. Contact us for a quote.
The exact lifespan depends on the type of film, glass and the environment in which it is fitted. Most types of window films have a warranty of 10 years, life expectancy can be much longer, maybe 15 years and in some cases over 20 years.
What are the advantages of window film compared with 'indoor' solar protection methods?
Indoor solar protection methods, such as blinds or curtains, prevent visible light from getting into a room and block the view looking outside. Additionally, infrared heat accumulates between solar protection and the window. Eventually radiating heat into the room. Air conditioning is one solution, but installing and running a system to maintain a constant indoor climate can be expensive. Whereas window film reflects the solar radiation away before it enters the room.
Does window film make a room cooler?
Yes. Window film rejects levels of solar heat to provide a cooler, more comfortable climate.
Does window film cause seal failure in double glazed units?
No. A typical double glazed unit is constructed with two panes of glass with a spacer bar at the edge separating the two glass panes. A hot adhesive sealant (polyisobutylene – PIB) is applied to the face of the spacer around the edge to bond the glass and spacer bar together. This makes a double glazed unit (DGU).
The application temperature or melting point of the PIB sealant is between 185ºC to 200ºC. The surface temperature of the internal glass with a dark film such as DC 15 window film applied on the inside, facing the sun directly can only reach a maximum temperature of 49ºC and the external pane of glass would heat to a maximum of 41ºC. These figures are based on the external air temperature being 30ºC.
When glazing a DGU into a window frame, the DGU spacer bar is in a rebate behind the glazing bead. This holds the unit in place and protects the PIB from direct sunlight. The glass temperature will have to reach the melting point of the PIB sealant. An applied film cannot heat the glass enough to achieve these temperatures and there is no reason why the film would cause any thermal heat problems to the DGU's.
Will window film reduce heat and glare?
Solar Control films are designed to reduce the sun's solar heat, glare and ultraviolet (UV). They are available in many or tints, offering various levels of performance. Solar films can be virtually invisible or totally transform a building by giving it a uniform colour and hiding untidy looking office environments- such as the backs of work desks, wiring, etc.
Will window film make the room darker?
Most window films will reduce the excess glare from the sun like wearing sunglasses. Depending on the degree of tint used. We have a wide range of window films from virtually invisible to the dark tinted films, that will not make your room dark on a sunny day. Some solar control films may affect light levels but as your eyes automatically adjust to different light levels, the degree is generally much less than traditional window blinds or curtains.
Can window film reduce my energy bills?
Demand for creating a better environment has never been so high. Many companies have made a corporate pledge to reduce energy consumption and the carbon footprint, others driven by increasing energy costs and the impact on profits.
With the proven heat-rejection properties of window film, you can eliminate "hot spots" and extreme peaks in air conditioning demands at certain times of the day. Interior temperatures are more controllable and stable, allowing cooling systems to work within the capacity and consume less energy. Investing in our films offers a quick payback, with a 25% reduction in energy costs.
Can window film reduce heat loss out through my windows?
Most of a building's heat can be lost through its glazing, increasing winter heating costs. Low-E insulation film applied to your existing windows will reflect radiated heat back into your room, increasing comfort and reducing fuel heating bills.
What effect does window film have on visibility through the windows? From the inside looking out? From the outside looking in?
Most window films maintain visibility looking out through the windows, some films are practically invisible once installed, allowing lots of natural visible light to enter a room. From the outside, it complements the exterior of any building. We have a range of films from virtually invisible to soft, neutral hues and darker films for privacy stopping passers-by from outside looking in.
Can I clean the window after a film is applied?
Yes, using a soft, clean cloth or paper towel to clean and the same or a rubber squeegee to dry. Use a mild detergent or every-day glass cleaning solutions. Basically, avoid using abrasive tools/cleaners and chemicals.
Will window film heat up my double glazed units and cause the glass to shatter or break?
No, window films alone do not cause the glass to break or shatter. However, we do understand that the application of some films will increase the temperature of your glass to increase, which in turn will increase the stress on the glass edges. The quality of those glass edges is out with our control. There are several factors to consider before installing window film (external shading, interior shading, glass breakage history, type of window film being used, type, size and shape of the glass, indoor-outdoor temperature) all contribute to the potential risk of glass breakage. Combined with our many years of experience, in applying window films to different types of glass and buildings, enables us to make proper judgments and a full risk assessment before any installation. Only after this will we advise the correct film to be used and guarantee its suitability, this minimises the potential for glass breakage.
What happens if I want it removed?
Easy. The film itself can be pulled from the glass which will generally leave adhesive residue on the glass. This is removed by spraying with soapy water and using a razor scraper. No need for any over-powering adhesive removers.
If you have any questions, please do not hesitate to ask. We would be happy to help
Call us on 01428 751004 or email us at sales@windowfilmsuk.com


Size:ER-32, Range:R8x4, ANSI standard. Includes 12 ps/set ER32 collet as 3/32, 1/8'', 3/16'', 1/4'', 5/16'', 3/8'', 7/16'', 1/2'', 9/16'', 5/8'', 11/16'', and 3/4. Complete kits include: chuck holder, nominal size collets, non-slipner wrench, and case. Unique self-releasing system eliminates sticking.
Suitable for all milling and drilling operations. Flute holding capability for the highest concentricity and clamping power. All our products are brand new and sealed. We will respond back to your message within 24 hours.
The item "AccusizeTools 12 Pcs/Set ER32 Collet + R8 Bridgeport Shank + Wrench in Fitted" is in sale since Saturday, June 3, 2017. This item is in the category "Business & Industrial\Manufacturing & Metalworking\Metalworking Tooling\Workholding\Collets". The seller is "epicesolutions" and is located in Blaine, Washington. This item can be shipped to United States.


Please enter your donation to the 2019 Subzero Heroes - Hudson Valley. Your donation will support Alzheimer's care services, programs and vital research.
You are fueling our cause to help us influence change by engaging elected officials to make fighting Alzheimer's a national priority.
Every dollar helps us to fund programs like TrialMatch™ to connect people to clinical trials and power progress in research for better treatments and a cure.
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When you make a gift to the Alzheimer's Association, you join us in our mission to eliminate Alzheimer's disease through the advancement of research; to provide and enhance care and support for all affected; and to reduce the risk of dementia through the promotion of brain health. As a valued member of our online community, you will receive important updates about Alzheimer's care, support, and research. You may choose to stop receiving Alzheimer's Association emails at any time by clicking the unsubscribe link provided in every email.


Responsibilities will include analyzing blue prints, determine material requirements, compute dimensions and layouts, weld in flat, horizontal, vertical or overhead positions, inspect weld for tolerances, clean weld joint, verify conformance to weld specs, and set up and operate machine tools.
Be proficient in TIG welding of stainless of sheet and stainless steel tube.
Operates drill presses, power saws, grinders, positioners and a variety of welding equipment and hand tools. May also perform minor operations on metal lathes and milling machines.
Polish finished products to pharmaceutical finish.
And any other tasks assigned by his/her manager.
5-10 years' experience in TIG welding.
Knowledge of welding techniques, tools and equipment.
Skill in the fabrication, joining and repair of a variety of metal objects, equipment, fixtures and structures.
Skill in manufacturing and dismantling as well as repair work.
Ability to read and understand general blue prints.
Must conduct self in a professional manner at all times.
While performing the duties of this job, the employee is required to stand, walk, bend, stoop, lift, push, kneel and sit; use hands to finger, handle, or feel and reach with hands and arms. The employee is frequently required to walk and talk or hear. The employee must be able to frequently lift and/or push/pull/transfer up to 40 pounds. The employee must be able to occasionally push/pull/transfer up to 100 pounds.
Exercises some decision-making authority, later verified by the Department Supervisor and advises the Department Supervisor, or designee, of transactions and/or special concerns on a daily basis. Ability to solve practical problems and deal with a variety of concrete variables in situations where only limited standardization exists. Ability to interpret a variety of instructions furnished in written, oral, diagram, or schedule form.
This job description is not meant to be an all-inclusive statement of every duty and responsibility that will ever be required of an employee in the job.


text:
The cognitive impairment and risk factors of the older people living in high fluorosis areas: DKK1 need attention
Chao Ren1,2 na1,
Peng Zhang1,3 na1,
Xiao-Yan Yao2 na1,
Hui-Hua Li4,
Rui Chen5,
Cai-Yi Zhang3 &
De-Qin Geng1
BMC Public Health volume 21, Article number: 2237 (2021) Cite this article
To evaluate cognitive impairment and risk factors of elders in high fluoride drinking water areas and investigate whether DKK1 is involved in this disorder.
MoCA-B and AD-8 were used to measure the cognitive functions of 272 and 172 subjects over the age of 60 came from the high and normal fluoride drinking water areas respectively, general information and peripheral blood were collected, the level of SOD, GSH and MDA were measured, mRNA level of DKK1, the concentration of blood fluoride and the polymorphism of APOE were tested.
The blood fluoride concentration, mRNA level of DKK1 and ratio of abnormal cognitive function of subjects in high fluorine drinking water areas were higher than those in normal areas. The level of SOD of subjects in high fluorine drinking water was low compared with those in normal areas. The level of MDA and GSH had no difference between the two crowds in different fluorine drinking water areas. There were differences in cigarette smoking, education, dental status, hypertension, hyperlipidaemia and APOE results between the two crowds in different fluorine drinking water areas. The mRNA level of DKK1 and the level of cognitive function showed a positive correlation and DKK1 was one of five risk factors involved in cognitive impairment of older people living in high fluorosis areas.
The cognitive functions could be impaired in the older people living in high fluoride drinking water areas, and DKK1 may as a potential intervention point of this brain damage process need attention.
Fluoride can easily be found in our daily life, and humans may suffer from damage induced by fluorosis [1,2,3]. Some reports have suggested that excessive fluoride can cause impairments in many systems of the human body. Dental fluorosis and bone damage can easily occur. However, it takes a longer time for side effects related to fluoride to manifest in the central nervous system. Fluoride exposure can affect emotions and cognition in animal models and in children during development [4,5,6]. One study reported that the intelligence quotient (IQ) and executive functions were lower in individuals living in high fluoride drinking water areas [7]. In our previous study, we found that cognitive disorders resulted from drinking water with high fluoride levels in rat model [8]. The specific mechanism of fluorosis in cognitive disorders was unclear, but some studies showed that oxidative stress damages, neuron apoptosis, changes in neurotransmitters, and synaptic dysfunctions are involved [9,10,11]. It suggested that oxidative stress damages deserve attention, for the fragmentation and redistribution of mitochondria and the imbalance between the mitochondrial fusion and fission were found in the neurons of the rat exposure to chronic fluoride. Under this circumstance, the respiratory electron transport chain was disturbed and more superoxide radicals were produced. These changes will result in the high level of oxidative stress and contribute to the brain injury [12]. For instance, we found that the antioxidant substance such as superoxide dismutase (SOD) and glutathione (GSH) decreased significantly in rat model of fluorosis in our previous study [8]. It indicated the linkage between cognitive impairment induced by fluoride and oxidative stress.
Recent studies have indicated that cognitive dysfunction is related to many different cell signaling pathways. One study reported that the canonical Wnt signalling pathway was involved in the development of Alzheimer's disease (AD) [13]. The Wnt signalling pathway plays an important role in neurogenesis, neuroplasticity, memory and learning, which may be potential mechanisms for cognitive impairments [14,15,16]. Dickkopf-1 (DKK1), a canonical Wnt signalling pathway inhibitor, may bind to and sequester LRP5/6 and then disrupt Wnt- Frizzled-LRP6 complex formation, which would cause changes in down-stream pathway activities [17]. Our research team have recently demonstrated that the canonical Wnt pathway was involved in the fluoride-induced impairment of PC-12 cells [18] and BV2 cells [19], and we found the expression level of DKK1 was significantly higher in the fluoride group than that in control group. Excitingly, more and more studies proved DKK1 expression level increased significantly in the cerebrospinal fluid, plasma and brain tissue of AD patients and AD transgenic mice [20, 21]. In our recent review, we supposed DKK1 may be a key mediator and potential risk factor for AD development, and it may also be as a novel intervention point of brain damage prevention that need attention [22].
Some reports suggested the cognition was impaired in high fluoride drinking water areas [23, 24]. However, the difference of risk factors of cognitive impairment between induced by fluorosis and AD in older people were not clear, not to speak of whether DKK1 is involved in this disorder (cognitive impairment induced by fluoride). Based on these, we investigated the cognitive level of older people and the related risk factors in the high fluoride drinking water areas in China. In brief, our aim was to investigate the risk factors for cognitive disorders induced by high fluoride drinking water and the relationship between cognitive function and the expression of DKK1.
Methods and materials
Study design and sample size
The study was carried out with an observational cross-sectional survey design and performed from 1-Jan-2016 to 28-Feb-2017. The sample size was calculated by the PASS software. The calculation formula is below:
$$\mathrm{n}=\frac{2\overline{p}\ \overline{q}{\left({Z}_{\alpha }+{Z}_{\beta}\right)}^2}{{\left(P1-P2\right)}^{2.}}$$
P1 = 0.2, P2 = 0.4, α = 0.05, Z0.05 = 1.96, β = 0.9, Zβ = 1.28, nmin = 110.
Study of subjects
The fluoride concentration of drinking water was high in the Feng County, Xuzhou City, Jiangsu Province, China, where dental fluorosis was very common. However, there was no data available regarding the cognitive function of the individuals who lived in this area. In this study, a total of 272 subjects from the high fluoride drinking water community (water fluoride concentration > 2 mg/L) of Feng County, Xuzhou City, Jiangsu Province, China, were randomly enrolled in this study. And a total of 172 subjects, from the normal fluoride drinking water community (water fluoride concentration < 0.8 mg/L) of Suining County, Xuzhou City, Jiangsu Province, China, were randomly chosen as the control group. These two counties have a similar culture, lifestyle and economic development level. Individuals with cerebral ischaemia, brain tumours and psychiatric disorders were excluded. This study was approved by the Ethics Committee of Affiliated Xuzhou Oriental Hospital of Xuzhou Medical University, China.
Socio-demographic and personal information was collected from each subject. These data included gender, age, education, alcohol drinking, smoking, dental status, hypertension, hyperlipidaemia, diabetes and family history (psychiatric diseases or dementia). Age was categorized into 3 groups as follows: 60–69 years of age, 70–80 years of age and older than 80 years of age. Education was categorized into the following groups: illiterate, primary school, middle school, and high school or higher. Dental status was categorized as follows: dental fluorosis, normal and dentures.
Cognitive function tests
The Montreal Cognitive Assessment-Basic (MoCA-B) and AD-8 were used to investigate the cognitive functions of the subjects. The MoCA-B had excellent validity in screening for mild cognitive impairment in poorly educated older adults regardless of literacy [25]. The AD-8 is an 8-item informant-based questionnaire, which was designed to detect changes in the fields of memory, orientation, judgement and executive function [26].
Blood sampling and pretreatment
A total of 4 tubes of venous blood (5 ml each) were collected and centrifuged at 5000 rpm/min for 5 min. Sera were stored at − 80 °C. These samples were used for testing the mRNA level of DKK1, fluoride concentration, SOD, GSH, malondialdehyde (MDA) concentration and apolipoprotein E (APOE) gene polymorphism.
Biochemical tests
Blood fluoride concentration was measured using the method of fluoride ion selective electrode method. Briefly, different concentrations of Fluoride Standard Liquid reagent were used to make a standard line, and then the concentration of the blood samples was adjusted according to the standard line.
The different oxidative stress status was evaluated by measuring levels of SOD, GSH and MDA according to the manufacturer's instructions in the reagent kit (Nanjing, Jiancheng, China).
The mRNA level of DKK1 was measured using qRT-PCR. Briefly, total human blood RNA was isolated with Trizol reagent (ProbeGene, China), and the concentration was measured using ultraviolet spectrophotometry. Reverse transcription was achieved using the cDNA Synthesis Kit (ProbeGene, China), and qRT-PCR amplification was performed using the SYBR-Green Master mix (Probegene MQ051, China) with the following amplification conditions: 95 °C for 10 min, 40 cycles of 95 °C for 15 s, 60 °C for 30 s, and 72 °C for 2 min. The amplification primer sequences were F: 5′- TCA TAG CAC CTT GGA TGG GTA TTC - 3′, and R: 5′- TTG GAC CAG AAG TGT CTA GCA CAA - 3′. The results were analysed using the ABI2720 PCR System (Applied Bio-systems, USA).
For analysis of APOE gene polymorphisms (also known as genotype), genomic DNA was extracted from collected venous blood samples using a commercial kit (QIAamp DNA Blood Mini Kit, Qiagen, Shanghai, China) beforehand. Then, the potentially mutated positions in 112 (rs429358) and 158 (rs7412) of the APOE gene were conducted by a detection kit (GeneChip Assay, Sinochip, Zhuhai, China) based on genomic DNA. First, all samples were amplified with the Verti™ DX Thermal Cycler (Life Technologies, Singapore) (45 cycles, 94 °C for 30 s and 65 °C for 45 s); then the amplified products were assayed by the fully automated GeneChip detection system (Sinochip, Zhuhai, China). All genotyping results were obtained from the GeneChip automated analysis system.
Socio-demographic factors and numeration data were analysed using the chi-square (χ2) test. The nonparametric rank sum test was used to compare the quantitative data between two groups. The degree of association between fluoride-induced cognitive impairment and risk factors was analysed using binary logistic regression analysis. Bivariate correlation analysis was performed using Spearman correlation analysis. SSPS16.0 software was used to analyse all data. A p-level of 0.05 was considered statistically significant.
Demographic characteristics of subjects in the normal fluoride group and high fluoride group
The demographic characteristics of subjects are displayed in Table 1. The majority of subjects are female (N = 119, 69.2% VS N = 166, 61% in the two areas, respectively). Over 70% (N = 122) of the subjects did not receive education in normal drinking area. The rate of fluorosis teeth (N = 266, 97%), hypertension (N = 103, 37.7%) and hyperlipemia (N = 34,12.5%) are higher in the participants who lived in the high fluoride drinking area than these who lived in the normal fluoride drinking area.
Table 1 The socio-demographic characteristics of subjects
The blood fluoride concentration in subjects from normal and high fluoride drinking water areas
The blood fluoride concentration of subjects was higher in the high fluoride drinking water areas [0.04 (0.027–0.049) mg/L] compared with the fluoride concentration in subjects from the normal fluoride drinking water areas [0.02 (0.016–0.029) mg/L] (Fig. 1).
The blood fluoride concentration in subjects from high and normal fluoride drinking water areas is shown. The blood fluoride concentration was higher in subjects form the high fluoride drinking water areas than those from normal fluoride drinking water areas. ***P < 0.001
Associations between fluoride and oxidative stress
The level of SOD, an anti-oxidative factor, increased significantly in subjects from the high fluoride water drinking areas [60.66(50.73–70.62)U/mL] (Fig. 2A). The level of MDA, a pro-oxidative factor, and GSH, another anti-oxidative factor had no significant difference between the high and normal fluoride water drinking areas (Fig. 2B, C).
The level of SOD, MDA and GSH in subjects from high and normal fluoride drinking water areas: A The level of SOD, B The level of MDA, C The level of GSH. The level of SOD decreased significantly in the high fluoride drinking water areas. The level of MDA and GSH had no significant difference between the high and normal fluoride water drinking areas. ***P < 0.001. GSH: glutathione, MDA: malondialdehyde, SOD: superoxide dismutase
Fluoride increased the mRNA level of DKK1
DKK1 is an inhibitor of the canonical Wnt signalling pathway and is often associated with different diseases. Our previous studies (cellular and animal models) indicated that there was some relationship between DKK1 and fluoride. In this study, we measured the mRNA level of DKK1 by qRT-PCR. The mRNA level of DKK1 was significantly higher in subjects form the high fluoride drinking water areas [24.47(23.19–25.47)] than those from normal fluoride drinking water areas [22.05(20.99–23.24)] (Fig. 3).
The mRNA level of DKK1 in the high and low fluoride drinking water groups is shown. The mRNA level of DKK1 was higher in subjects form the high fluoride drinking water areas than those from normal fluoride drinking water areas. ***P < 0.001. DKK1: dickkopf-1
The incidence of cognitive impairment in older people increased in high fluoride drinking water areas
The MoCA-B and AD-8 were used to measure the cognitive function of subjects. The results suggested that the ratio of abnormal cognitive function of study population in high fluorine drinking water areas were higher (N = 124, 45.6%)than those (N = 26, 15.1%) in normal areas (Table 2).
Table 2 Statistical analysis of the incidence of cognitive impairment measured by the AD-8 and MoCA-B
The effect of education on cognitive function in subjects from different fluoride drinking water areas
We investigated the effects of different levels of education on cognitive function in both groups. The incidence of cognitive impairment was higher in study population with illiterate (N = 52, 38%) and primary school education level (N = 47, 53.4%) who lived in the high fluoride drinking water area compared with those (illiterate N = 12, 9.8%, primary school N = 7, 22.6%)from normal fluoride drinking water areas. However, the incidence of cognitive impairment in the study population with middle school (N = 4, 30.8%; N = 24, 54.5%) or high and over high middle school (N = 3, 50%; N = 1, 33.%) education level was not significantly different between the two groups (Table 3).
Table 3 The effect of level of education on cognitive impairment in subjects from different fluoride drinking water areas
In this study, spearman correlation analysis was used to investigate the relationship between some of observed variables (fluoride, DKK1and MoCA-B). The result was showed in the Table 4. There was a positive correlation (r = 0.313) between the level of DKK1 and the concentration of fluoride(r = 0.313, p < 0.05), and MoCA-B (r = 0.320, p < 0.05).
Table 4 A correlation of matrix of DKK1, blood concentration of Fluoride and MoCA-B
Risk factors of cognitive impairment were analysed using binary logistic regression analysis. As showed in Table 5, age, education, fluoride, DKK1 and dental fluorosis may be the risk factors of cognitive impairment in older people who lived in high fluorosis areas.
Table 5 The risk factors of cognitive impairment were analyzed by regression logistics analysis
Fluoride is a necessary element for the development and growth of organs in the human body, and it is often found in our environment [27, 28]. Frequently fluoride is added to toothpaste for the prevention of tooth decay. Since the 1980s, the use of fluoride in dental products has increased significantly. Furthermore, drinking water is a main source of fluoride, and the concentration of fluoride ranges from 0.1–0.8 mg/L [29]. However, the safety margin of fluoride is very narrow. Therefore, it is easy to suffer from fluorosis in high fluoride drinking water areas. The problems of high fluoride drinking water associated with dental and bone fluorosis had frequently been reported. Recently, some reports suggested that the excessive intake of fluoride could induce cognitive impairment in a rat model and in individuals who live in high fluoride drinking water areas [24]. Children who were exposed to high fluoride drinking water in China and India showed decreases in IQ [5, 30].
General information is shown in Table 1. As shown in Table 1, differences in the level of education, hypertension, and APOE polymorphism were observed between the fluoride group and the control group. The blood fluoride concentration was tested and found to be higher in subjects from high drinking water areas than in subjects from normal drinking water areas, as shown in Fig. 1. However, toxic blood fluoride concentrations were not detected, which means that even in high fluoride drinking water areas, the blood fluoride concentrations in older people were considered safe. That may be the reason that the cognitive impairment induced by fluoride was not serious. Since a previous study showed that fluoride (700 μmol/L NaF) could stimulate the ability of cellular anti- oxidative effects [31]. Therefore, it could be inferred that a certain low dose of fluoride exposure may play a protective rather than adverse role on cognitive impairment through the mechanisms of stimulating cells viability and anti-oxidative ability [24]. Moreover, fluorosis was associated with some other factors including age, kidney function, and sex [32]. The results showed that the incidence of dentures was higher in subjects in the normal fluoride drinking water areas. Fluoride is often added to toothpaste for the prevention of cavities, although the absence of fluoride does not necessarily contribute to the development of cavities. Nevertheless, fluoride had a protective effect against damage to the teeth caused by acid.
Oxidative stress is very common in patients with cognitive impairment, as usual, anti-oxidative factors decreased and pro-oxidative factors increased significantly. In our previous study, damage associated with oxidative stress from fluorosis was observed in a rat model [8]. In the present study, we measured two factors related to the oxidative stress. The results indicated that the level of SOD increased significantly in subjects from high fluoride drinking water areas. There was no significant difference in the level of GSH and MDA between the two groups. This result was not completely consistent with the results of our previous animal experiment [8]. The reason may be that the higher concentration of fluoride (not a toxic concentration) stimulated the activation of the oxidative system, which led to an increase in the level of the anti-oxidative stress factor SOD. These findings could indicate that a protective and reactive mechanism was engaged in response to the increased blood fluoride concentration [31]. What's more, it further supported the viewpoint presented by Li et al. that the certain low doses of fluoride intake may be a potential protective rather than a harmful factor for cognitive function; however, high fluoride exposure is a potential risk factor for cognitive impairment in older population [24].
As shown in Tables 1 and 3, although the prevalence of subjects who were illiterate was lower in the high fluoride drinking water areas, the incidence of abnormal cognitive function was higher. This result suggested that fluoride could increase the incidence of cognitive impairment. Additionally, we found that less education was associated with a higher incidence of cognitive impairment. For subjects who received more than 8 years of education (above middle school in China), no significant difference in cognitive function was observed between subjects from high fluoride drinking water areas and those from normal fluoride drinking water areas. This finding possibly suggested that the severity of cognitive impairment induced by fluoride was less in person with the higher level of education. More and more researches suggest that people with more education have lower prevalence of dementia [33]. Some scholars believe that this is benefit from the high cognitive reserve in individuals with high education [34]. But this protective effect of a high-education level may only be stronger in the early stage of disease [35]. The older persons with cognitive impairment induced by fluorosis in our study may be in the early stages of the disease. Meanwhile, other studies have found that high education may offer protection against tauopathy in patients with mild cognitive impairment [36].
DKK1, an inhibitor of the canonical Wnt signalling pathway, has been reported to be involved in cognitive impairment [37]. Increased DKK1 is associated with AD [38]. A positive correlation exists between cognitive function and DKK1 expression in diabetic rats, and there is also a positive correlation between DKK1-reducing therapy and improved cognitive function in rats [39]. Our recent research found that the level of DKK1 increased significantly in PC-12 cells [18] and BV2 cells [19] exposed to fluoride. However, the expression level of DKK1 in older people from high fluoride drinking water areas is unknown. The mRNA level of DKK1 was measured in both groups. The level of DKK1 increased significantly in subjects from high fluoride drinking water areas compared with that in subjects from normal fluoride drinking water areas. And we also investigated the correlation between observed variability. The result implied that DKK1was correlated with cognition and Fluoride concentration, although the correlation was weak. This finding suggested that DKK1 could be an indicator of cognitive impairment induced by fluoride. The function of DKK1 in the process of this disorder is unknown. Scientifically, we also need to calmly consider few limitations in this study. Firstly, the samples were chosen from one province in China and more high fluoride drinking water areas should be involved in the future study. Secondly, we could not clear which specific aspect of the cognition, such as memory, language, calculations, orientation, attention and concentration, executive functions, visuoconstructional skills, and conceptual thinking, was affected by fluoride via the disfunction of DKK1 and more researches should be performed in the future.
In conclusion, cognitive impairment could be induced by high fluoride drinking water, and DKK1 may be involved in this process. However, the specific mechanisms are unclear. More studies are needed to determine the function of DKK1, which may as a potential intervention point of this brain damage process that need attention.
The datasets used or analysed during the current study are available from the corresponding author on reasonable request.
APOE:
DKK1:
Dickkopf-1
MoCA-B:
Montreal Cognitive Assessment-Basic
Archer NP, Napier TS, Villanacci JF. Fluoride exposure in public drinking water and childhood and adolescent osteosarcoma in Texas. Cancer Causes Control. 2016;27(7):863–8.
Karademir S, Akcam M, Kuybulu AE, et al. Effects of fluorosis on QT dispersion, heart rate variability and echocardiographic parameters in children. Anadolu Kardiyol Derg. 2011;11(2):150–5.
Wang W, Xu J, Liu K, et al. Suppression of Sclerostin and Dickkopf-1 levels in patients with fluorine bone injury. Environ Toxicol Pharmacol. 2013;35(3):402–7.
Bartos M, Gumilar F, Bras C, et al. Neurobehavioural effects of exposure to fluoride in the earliest stages of rat development. Physiol Behav. 2015;147:205–12.
Choi AL, Zhang Y, Sun G, et al. Association of lifetime exposure to fluoride and cognitive functions in Chinese children: a pilot study. Neurotoxicol Teratol. 2015;47:96–101.
Liu F, Ma J, Zhang H, et al. Fluoride exposure during development affects both cognition and emotion in mice. Physiol Behav. 2014;124:1–7.
Choi AL, Sun G, Zhang Y, et al. Developmental fluoride neurotoxicity: a systematic review and Meta-analysis. Environ Health Perspect. 2012;120(10):1362–8.
Zhang C, Ren C, Chen H, et al. The analog ofGinkgo bilobaExtract 761 is a protective factor of cognitive impairment induced by chronic fluorosis. Biol Trace Elem Res. 2013;153(1–3):229–36.
Pereira M, Dombrowski PA, Losso EM, et al. Memory impairment induced by sodium fluoride is associated with changes in brain monoamine levels. Neurotox Res. 2011;19(1):55–62.
Sun Z, Niu R, Wang B, et al. Fluoride-induced apoptosis and gene expression profiling in mice sperm in vivo. Arch Toxicol. 2011;85(11):1441–52.
Zhu W, Zhang J, Zhang Z. Effects of fluoride on synaptic membrane fluidity and PSD-95 expression level in rat Hippocampus. Biol Trace Elem Res. 2011;139(2):197–203.
Lou DD, Guan ZZ, Liu YJ, et al. The influence of chronic fluorosis on mitochondrial dynamics morphology and distribution in cortical neurons of the rat brain. Arch Toxicol. 2013;87(3):449–57.
Liu CC, Tsai CW, Deak F, et al. Deficiency in LRP6-mediated Wnt signaling contributes to synaptic abnormalities and amyloid pathology in Alzheimer's disease. Neuron. 2014;84(1):63–77.
Cerpa W, Gambrill A, Inestrosa NC, et al. Regulation of NMDA-receptor synaptic transmission by Wnt signaling. J Neurosci. 2016;31(26):9466–71.
Cerpa W, Godoy JA, Alfaro I, et al. Wnt-7a, modulates the synaptic vesicle cycle and synaptic transmission in hippocampal neurons. J Biol Chem. 2008;283(9):5918–27.
Pan Y-Y, Deng Y, Xie S, et al. AlteredWntSignalingPathwayinCognitiveImpairmentCausedbyChronicIntermittentHypoxia:FocusonGlycogenSynthaseKinase-3βandβ-catenin. Chin Med J. 2016;129(7):838–45.
Menezes ME, Devine DJ, Shevde LA, et al. Dickkopf1: a tumor suppressor or metastasis promoter? Int J Cancer. 2012;130(7):1477–83.
Zhang CY, Chen R, Wang F, et al. EGb-761 attenuates the anti-proliferative activity of fluoride via DDK1 in PC-12 cells. Neurochem Res. 2017;42(2):606–14.
Chen R, Zhao LD, Liu H, et al. Fluoride induces Neuroinflammation and alters Wnt signaling pathway in BV2 microglial cells. Inflammation. 2017;40(4):1123–30.
Caricasole A, Copani A, Aronica E, et al. Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer's brain. J Neurosci. 2004;24(26):6021–7.
Rosi MC, Luccarini I, Grossi C, et al. Increased Dickkopf-1 expression in transgenic mouse models of neurodegenerative disease. J Neurochem. 2010;112(6):1539–51.
Ren C, Gu X, Li H, et al. The role of DKK1 in Alzheimer's disease: a potential intervention point of brain damage prevention? Pharmacol Res. 2019;144:331–5.
Ko K, Jung M, Hong S. Prevalence of cognitive impairment and related factors among the elderly in rural communities of Jeju Province. Taehan Kanho Hakhoe Chi. 2003;33(4):503–9.
Li M, Gao Y, Cui J, et al. Cognitive impairment and risk factors in elderly people living in fluorosis areas in China. Biol Trace Elem Res. 2016;172(1):53–60.
Julayanont P, Tangwongchai S, Hemrungrojn S, et al. The Montreal cognitive assessment-basic: a screening tool for mild cognitive impairment in illiterate and low-educated elderly adults. J Am Geriatr Soc. 2015;63(12):2550–4.
Galvin JE, Roe CM, Powlishta KK, et al. The AD8: a brief informant interview to detect dementia. Neurology. 2005;65(4):559–64.
Ando M, Tadano M, Asanuma S, et al. Health effects of indoor fluoride pollution from coal burning in China. Environ Health Perspect. 1998;106(5):239–44.
Ersoy IH, Koroglu BK, Varol S, et al. Serum copper, zinc, and magnesium levels in patients with chronic fluorosis. Biol Trace Elem Res. 2011;143(2):619–24.
Declan W, William P, Hardy L, et al. Risk assessment of fluoride intake from tea in the Republic of Ireland and its implications for public health and water fluoridation. Int J Environ Res Public Health. 2016;13(3):E259.
Sebastian ST, Sunitha S. A cross-sectional study to assess the intelligence quotient (IQ) of school going children aged 10-12 years in villages of Mysore district, India with different fluoride levels. J Indian Soc Pedod Prev Dent. 2015;33(4):307–11.
Bian JC, Lin XY, Yang XX, et al. Human umbilical vein vascular endothelial cell injury induced by fluoride in vitro. China J Endemiol. 2011;30(2):142–7.
Krishnamachari KAVR. Skeletal fluorosis in humans: a review of recent progress in the understanding of the disease. Prog Food Nutr Sci. 1986;10(3–4):279–314.
Crimmins EM, Saito Y, Kim JK, et al. Educational Differences in the Prevalence of Dementia and Life Expectancy with Dementia: Changes from 2000 to 2010. J Gerontol B Psychol Sci Soc Sci. 2018;73(suppl_1):S20–8.
Rodriguez FS, Zheng L, Chui HC, et al. Psychometric characteristics of cognitive reserve: how high education might improve certain cognitive abilities in aging. Dement Geriatr Cogn Disord. 2019;47(4–6):335–44.
Rimkus CM, Avolio IMB, Miotto EC, et al. The protective effects of high-education levels on cognition in different stages of multiple sclerosis. Mult Scler Relat Disord. 2018;22:41–8.
Rolstad S, Nordlund A, Eckerström C, et al. High education may offer protection against tauopathy in patients with mild cognitive impairment. J Alzheimers Dis. 2010;21(1):221–8.
Purro SA, Galli S, Salinas PC. Dysfunction of Wnt signaling and synaptic disassembly in neurodegenerative diseases. J Mol Cell Biol. 2014;6(1):75–80.
Ortiz-Matamoros A, Salcedo-Tello P, Avila-Muñoz E, et al. Role of Wnt signaling in the control of adult hippocampal functioning in health and disease: therapeutic implications. Curr Neuropharmacol. 2013;11(5):465–76.
Shen ZX, Xiao Q, Zhao YX, et al. Effects of ghrelin on hippocampal DKK-1 expression and cognitive function in rats with diabetes mellitus. Nan Fang Yi Ke Da Xue Xue Bao. 2016;36(4):500–5 Article in Chinese.
Thanks to all the staff and subjects who participated in the questionnaire.
This study was supported by Natural Science Foundation of Jiangsu Province (BK20151159), Shandong Provincial Key Research & Development Project (2017GSF218043), National Natural Science Foundation of China (81501185), Jiangsu Provincial Medical Youth Talent (QNRC2016369) and Xuzhou Medical Talents Project and Xuzhou technological and scientific project (KC14SH050).
Chao Ren, Peng Zhang and Xiao-Yan Yao contributed equally to this work.
Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, China
Chao Ren, Peng Zhang & De-Qin Geng
Department of Neurology , Department of Neurology Yantai Yuhuangding Hospitalof Qingdao University, Yantai, 264000, China
Chao Ren & Xiao-Yan Yao
Department of Psychiatry and Psychology, The Affiliated Xuzhou Oriental Hospital of Xuzhou Medical University, Xuzhou, 221000, China
Peng Zhang & Cai-Yi Zhang
Zhenjiang Mental Health Center, The Fifth People's Hospital of Zhenjiang City, Zhenjiang, 212000, China
Hui-Hua Li
Department of Neurology, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, 223002, China
Rui Chen
Chao Ren
Peng Zhang
Xiao-Yan Yao
Cai-Yi Zhang
De-Qin Geng
CR implemented epidemiological investigation, found the references and drafted the manuscript. PZ and XY Y read the literature, summarized the information and helped to draft the manuscript. HH L and RC made data collation and analysis. RC and PZ drew the tables and Figs. CY Z and DQ G designed the study, modified the manuscript and guided the above work. All authors read and approved the final manuscript.
Correspondence to Cai-Yi Zhang or De-Qin Geng.
The study was granted ethical approval by the Affiliated Xuzhou Oriental Hospital of Xuzhou Medical University, and was performed in accordance with the guidelines of the Helsinki Declaration and the CIOMS's international ethical guidelines. The written informed consent was obtained from all the participants.
Ren, C., Zhang, P., Yao, XY. et al. The cognitive impairment and risk factors of the older people living in high fluorosis areas: DKK1 need attention. BMC Public Health 21, 2237 (2021). https://doi.org/10.1186/s12889-021-12310-6
DKK1


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Home > Delhi > HRD seeks report on school girl's suicide, parents stage protest seeking CBI probe
HRD seeks report on school girl's suicide, parents stage protest seeking CBI probe
PTI22 March 2018 10:41 AM GMT
New Delhi: The HRD Ministry has sought a report from Ahlcon Public School regarding the alleged suicide by a class 9 student whose parents are claiming that she was "sexually harassed" by two teachers.
Parents of the 15-year-old, accompanied by other parents staged a protest outside the school in east Delhi's Mayur Vihar area. They demanded a CBI enquiry into the matter and arrest of the teachers and the principal. The protesting parents also blocked the Mayur Vihar main road affecting the traffic flow.
"We have asked for details," HRD Minister Prakash Javadekar said when asked about the incident on sidelines of an event.
A Class IX student of the school allegedly committed suicide by hanging herself at her Noida residence on Tuesday.
Her family alleged that she was harassed by her two teachers including a woman and deliberately awarded poor marks. The school, however, is denying the allegations.
Deputy Chief Minister Manish Sisodia had yesterday ordered the Directorate of Education (DoE) to probe the issue.
The Noida Police has registered a case against the principal and two teachers of the school.
The girl failed her exams and her family claimed that the teachers deliberately awarded poor marks, police officials said.
She was found hanging at her home by her family members yesterday. They rushed her to the Kailash Hospital where she was declared dead. No suicide note was found.
"It's an unfortunate incident. School has been following promotion policies of CBSE. Let me make it clear that she had not failed, a re-test was scheduled. We will cooperate with probe agencies. Such a thing (harassment) has never happened in our school," school principal Dharmedra Goyal said.


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Riina Sikkut, Estonia's Minister for Health and Labour, is waiting to get back the results of a genetics test, which will tell her if she's predisposed to any illness or disease. She's not overly concerned about the outcome.
Sikkut is one of 100,000 Estonians who will this year volunteer to have their DNA combed by high-speed gene sequencing machines in search of genes linked to diseases, traits or health conditions.
One goal of the €5 million government-led study in which they are participating is to help scientists peer into the genetic roots of chronic disease.
But in addition to prognosis, it is intended the data will be used as the basis for transforming the Estonia healthcare system to deliver personalised medicine and give people the information they need to prevent the development of chronic diseases.
There are ambitions to implement personalised medicine on a national scale, with a plan that by 2022, as many as 500,000 people will have records combining their electronic health records and genotypes.
"There are people who don't want to know the results of a test like this – and that's okay – but it's not something to worry about," Sikkut said. She was speaking at a session last week in Toulouse organised by the Estonian Research Council, the Estonian Genome Centre and supported by the European Regional Fund and the Estonia 100 programme, which marks the country's centenary.
Estonia is 17 years into its long-term genome sequencing programme. During the next four years, one third of the population, some 430,000 people from a population of 1.3 million, will be asked to contribute their DNA to the project. The samples are stored in a repository, the Estonian Genome Centre, based in the University of Tartu.
The genetic data collection, which builds on existing genetic records of over 52,000 Estonians collected since the centre opened in 2001, is the core of a plan to revamp the small country's healthcare system.
Biobanks help scientists discern the larger picture. Associations between genes and health often do not show up until very large numbers of individuals are compared at once.
"It's an expensive project: anything that's new is expensive, but prices will go down if this becomes standard. And, if we make people healthier, there will be savings," said Sikkut.
Studying a person's genetic makeup can help doctors get the "right drug for the patient the first time", said Lili Milani, research professor at the Estonian Genome Centre. "With the genome project, patients get a description of disease risk and access to counselling about how to reduce it. They are then guided towards more physical activities or preventive medical treatment if necessary," she said.
The system gives individuals control of their own information. They can see who has looked at their data and challenge any suspicious behaviour. Volunteers can also check a box on their consent forms saying they do not want to be contacted for any form of follow-up, or request to take part in clinical studies.
Population level sequencing would have seemed preposterous to contemplate little more than a decade ago. The first genome human genome sequence took 13 years to complete and cost about €1 billion. Since then, it has become cheaper and easier. Now, a sequence can be completed in 48 hours at a cost of €1,000.
Digital health companies such as 23andMe are making genetic services more widely available to the public. The next goal is the €100 genome.
Computer analysis can pinpoint genes related to specific diseases. Some findings are clear-cut, but often the significance of a particular mutation is not known. In addition, sequence information can be used to predict if a patient is likely to benefit from a particular drug, or to screen for the presence of drug metabolising genes that mean a patient could suffer side effects.
The results can be applied to maximise the benefits a small country like Estonia extracts from its drugs budget. "There is only a given amount of money [….] Why would a speciality cancer drug be more important for a hospital to stock than diabetes drugs?" said Bobby Kaura, associate director and commercial market development at gene sequencing firm Illumina.
As the world's most digitised bureaucracy, Estonia has shown an eagerness to tackle some of the world's biggest issues early on, says Sikkut.
The country has won praise for its pioneering e-government, which allows people to file taxes within five minutes using pre-filled forms, manage banking, register businesses, apply for child benefits, pay for parking tickets, vote, or get a medical prescription, in a matter of minutes, via a single sign-in.
"I haven't received a paper prescription in 10 years. In a personal capacity, I'm still a pen and paper person, but for systems, cyber is what we need to do, and what we do well," said Sikkut.
The country has experienced the downsides of hyper-connectedness. In 2007, cyber attackers bombarded dozens of Estonian banks, government websites and newspapers, in a month-long campaign that also threatened to disable emergency services. Many commentators afterwards described the siege as the first instance of cyber warfare.
"If something is compromised, it's really hard to rebuild trust. But security fears aren't a sufficient reason for not moving on," said Sikkut.


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Polyphemus pediculus es una especie de crustáceo onicópodo de la familia Polyphemidae. Se ha encontrado en Europa.

Referencias

Planctología
Branchiopoda


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