text:
A gallicised st patrick's day and other culinary events
Luke Bagnall from UEA, UK here, writing about all the feasts the ethnic diversity of study abroad has resulted in!
Just before Tilly and I left for France, we went with our American friend Sam to a party in the flat of one of our fellow UOW exchangees, Bettina, where we met Caroline, a USYD student (who we'd actually met before at Barbara's games night, but not properly). Exchange is complicated, isn't it?
Anyway, Sam, Til, Caroline and I all left the party at the same time and ended up standing outside Bettina's flat so long talking and trying to say goodbye that we just ended up going upstairs to Caroline's kitchen and talking until about four in the morning, despite the fact that we were supposed to be on an early train the next morning.
Caroline is a French speaker, and has family there, and when she heard we were in Grenoble she asked us to bring back some French mixture of Champagne and cider that she had enjoyed in the region. We then decided to have a French party upon our return where we would try the mixture and sup upon cheese and fruit and crackers and the like.
When we planned to have this meeting on Thursday night, we didn't realise that Thursday was actually St Patrick's Day, so we ended up celebrating the Irish day in a very French way.
I wasn't expecting St Patrick's Day to be as big a deal here as it was. I guess the festivity increases with proximity to Ireland. The Square at uni literally reeked of beer – you could smell it from miles away. It was really fun. I think society should have more days of celebration, like the Romans. I loved the fact that everyone was wearing green. I loved the thought that everyone who was wearing green had made that little effort when they were getting dressed that morning, in concert. There's something cool about it.
Before the French celebrations began, we went down to the Blue Bar to watch the UEA Take Me Out that Caroline had signed herself up for. The English LOVE this trashy show, so the turnout was incredible. The bar was packed. We joked that if the same thing was done at UOW about four people would've signed themselves up and it would've been an awkward DIY affair at the unibar with minimal viewers. This is what UEA's version looked like:
This dude's 'skill' – knocking a cup off his friend's head with a football.
Then it was time for ze food. Apparently the drink wasn't as tasty as it was supposed to be because the only one we could get was 'brut' or 'strong', which doesn't taste as good.
Tilly showing us how it's done with her waitress skillz.
Caroline uncorking her first bottle of Champagne.
Only a week later, we attended a curry night at English friend Kim's house, where her housemate Avani whipped up a curry storm! It was amazing in scale and taste:
The curry was followed by games, including Pictionary and Scrabble. I'd like to brag that I lead 'my' team, 'Luke Lucas and the Couch Potatoes' to glorious victory!
I then retired while the expert Scrabblers showed off. It was an amazing display of wordmanship, as can be seen below. And yes, parquet can be used as a present tense verb!
Soon after curry night was a Vietnamese night hosted by some of Caroline's friends, where more incredible food was thrown before us and another good night was had by all.
We tried out some wines on special that were somehow Chardonnay/Chenin Blanc/Semillon and Pinot Noir/Cabernet Sauvignon/Merlot all in one? They were SUPER WINES!
Tilly models the super wine.
Finally, the other night Caroline, Barbara, Dave, Megan and Bianca were having a vegetarian pasta night to plan their Morocco trip, and Sam, Til and I decided to crash it and join them (because Sam and Bianca are opposite-gender equivalents of one another and had to meet).
More cuisine than anyone can handle!
Luke Bagnall
May 1, 2011 | Categories: Cultural differences, International Food Events, The UK | Leave a comment
Schortsch ramblings
Some advice for anyone considering taking the Macbackpackers Hogmanay Highland tour package: 1. DO IT, 2. Ask for Ruthie, and 3. Don't be sick or jetlagged.
The conditions mentioned in step three rendered our journey to Scotland an ordeal. It was about five hours by train, but I could NOT sleep because of the lack of something I'm beginning to miss increasingly from home, the humble public-transport window ledge:
It may seem small, but this slight protrusion at the base of the window is in fact the single greatest invention in the history of comfort, allowing weary travellers the world over to lean and sleep in luxury. Yes, throughout the protracted period of my total dependence on public transport, from the shabby Railcorp trains to the austere trackwork coaches, I've come to depend on this marvel of human ingenuity greatly, and yet, in this country I find it almost completely absent. Truly lamentable.
Anyway, once we actually got there, we had to traverse the most ridiculous set of stairs in the world, that just kept GOING, and of course, the freezing cold of Edinburgh. You see, the medieval builders of Edinburgh putatively reasoned that, if they built their streets like enormous wind tunnels, the frequent subzero gusts screaming through them would carry the plague out of the city into the sea. Needless to say, this didn't work, and they were left with the coldest city in the worldoutside of Russia.
By the time we found our lodgings, I was ready to crash. Which I did. Fully clothed. On top of the blankets. Face down. The next day we had to be on a bus by eight.
Thus commenced our fantastic Scottish Highlands tour. We were introduced to our tour guide and driver, Scottish pocket rocket Ruthie, pictured below frolicking through a highland glen or some such:
Picture stolen from Jodie Gough.
Ruthie was incredible; she absolutely made the tour. She was a great storyteller, narrating to us from behind the wheel the epics of Scottish mythology (mostly pertaining to beautiful Scottish maidens abandoned by their Irish lovers), history (mostly pertaining to struggles against the hated English), and even some of her own entertaining personal reminiscences (mostly pertaining to 'wee jobbies' – I'll let you Urban Dictionary that one).
I think my favourite story was her explanation of the tale behind the famous Scottish ditty:
Oi'll teek the haigh rrroad 'n' ye'll teek the lough rrroad
And oi'll reach Schortland befoooooore ye
Fer me 'n' mai treu luff'll never meet agen
By the bonny, bonny banks of Loch Looooomond
Which for many years was, in my mind:
You take the high road and I'll take the low road
And I'll slaughter countless sheep before ye …
due to some secondhand cultural knowledge via Catdog. But anyway, it's supposedly the story of two Scottish rebels taken prisoner by the English, one old and one young. The 'low road' is the road back home from battle, and the high is the spiritual road that the dead take. Wanting to taunt the imprisoned Scots, the English guards tell them that the next day one of them will be hanged, and the other set free, and they must decide which is which. They argue well into the night over the issue, each insisting that they be the one to die. They eventually fall asleep, the matter unresolved, but when the young soldier awakes he finds a note from the old soldier which reads:
'I'll take the high road and you'll take the low road
And I'll reach Scotland before ye
For me and my true love will never meet again
By the bonny bonny banks of Loch Lomond.'
When she told the story we all got shivers down our spines; it was really touching.
On the first day of the tour we visited the gateway village of Dunkeld (the ancient capital of Scotland, left), the pass of Killiecrankie (where a fierce battle was fought against the invading English, above), Ruthven Barracks (the site of the shooting of the last British wolf, below), Avie Moor (a modern, purpose-built ski village where we ate the best soup in the world), the Culloden battlefield where the last battle fought on British soil was held, and finally we stopped at Inverness.
There Ruthie had a surprise for us – a shot of whiskey each. I took mine and instantly knew I was going to throw up. My stomach can't handle shots at the best of times, let alone just after it's been destroyed by the dodgy Indian curry I mentioned below in 'Some things that happened in London', and, in lieu of a nearby toilet, I just vomited into my mouth and ran ludicrously out the front door, pretending in response to people's questions that I was all right, that I was looking for something I'd dropped. Unfortunately this didn't really fool anyone.
Our tour bus was literally divided right down the middle. For some reason, perhaps a Western cultural perception that the back of the bus is cooler, all the Asians were sitting at the front. Attempts to bridge the gap proved fruitless, but the cultural differences were interesting. They all seemed to really love taking photos and footage. The pair in front of us filmed the foggy fens we were driving through for forty minutes at a time which, while majestic, they are NEVER going to watch!
So that night the Australians and Kiwis on the tour headed into town for dinner and drinks, where there were a few 'Inverness Invershnecky Monsters' – the cougars of Scotland – to be seen.
Next day we went to Loch Ness at dawn and took the DSLR, or 'the baby' as we're calling it, to great effect:
We also visited Eilean Donan castle, and Portree and Kyleakin on the Isle of Skye, the latter of which being our destination for the night.
Eilean Donan Castle
On the way to our accommodation, Ruthie stopped the bus and told us one of the abovementioned stories of a Scottish warrior princess who was abandoned by her Irish lover and showed us a river apparently formed of her tears. It is said that those that dip their faces in will be afforded eternal youth and beauty so, of course, we were obliged to try:
The place we stayed in Kyleakin was called 'Saucy Mary's', after the medieval owner of a nearby castle who allegedly used to have a great iron chain wound across the river, and if you wanted to pass you had to pay her toll, and if you paid a little extra she'd flash you from her tower.
Photo by Jodie Gough.
Me being sick and Til still being jetlagged, we retired early and missed out on a crazy night:
But despite retiring at like, ten, I was still kept up till two by the noise of the craziness.
By the next day I was sick and tired of being sick and tired, as Anastasia would say, so I resolved to institute my 'three litres of water a day till better' rule. This is a surefire cure for flu and colds – it works for me every time; it's just that usually I'm doing it at home, not on a tour bus winding through the Scottish highlands. Every time we stopped I had to find somewhere to go for a sneaky wee, like up a mountain in Glen Coe, where the traitorous Campbell clan committed their infamous slaughter of their hosts:
Going up the mountain for a pee.
But these stops were a bit scarce, and at one point I had to get Ruthie to pull over and let me out especially. Out I traipsed into knee-high sleet to calls of 'yellow snow' from my companions. But it was pure water passing through me.
It wasn't all just urination, though. At Glencoe Russell, one of the other people on the tour, got a standard jumping pic of some of us:
Til, me, Courtney, Lisa, Emma, Jodie, and Narelle
The last place we stopped on the tour was Stirling, at the Wallace monument, where we saw the most amazing sunset ever:
That night when we returned we all decided to go to the amazing Edinburgh Hogmanay torchlight procession. After wending our way through the city for some time, I moved literally ten steps in front of Tilly and was lost. We could not find each other. I stood there for forty five minutes looking for her before I gave up and went all the way back to the hostel. That was pretty crap.
Then there was New Year's Eve itself. We started off the night with a good old game of kings which culminated in this:
Another one pilfered from Jodie Gough.
Then we headed out to the street party pretty tipsy and causing havoc. I introduced the group to 'the lost emu', a tactic introduced to us by our friend Marielle at Splendour in the Grass to find people. It goes a little something like this:
By Jodie.
Basically we danced and sang to the music and laughed at fellow tour participant Courtney's antics, which involved going up to strangers and dancing with them.
Half the group had tickets to go see Biffy Clyro, so at some point we diverged with plans to meet up again at quarter to twelve to be together at New Year. This did not pan out. We made our way to the rendezvous point, but couldn't find them. It was five to twelve and we were in a crap spot where we wouldn't be able to see the fireworks or hear any music countdown, and we were absolutely sardined by everyone around us. We decided to make our way back to where we had been, but then midnight was upon us and we celebrated while squished between thousands of other revellers. And to our disappointment, no one sang Auld Lang Syne! We started it up a couple of times on the way back to the hostel, though, and were joined by some people who actually knew the words, not just vague approximations of sounds put to the melody.
The crowd behind us.
New Year's Day was our last full day in Scotland, so we spent it seeing the obligatory sights of Edinburgh – the castle, the cafe where JK Rowling wrote the first couple of Harry Potter books and the nearby graveyard where she got ideas for character names, and we started but didn't finish a free ghost tour. Thus ended our experience of Edinburgh, the SECOND MOST HAUNTED CITY IN EUROPE, as the ghost tour sign proclaimed (verified by the International Haunting Index).
April 3, 2011 | Categories: Festive season, International Food Events, Rants, Scotland, The UK | 1 Comment
Cuisine'ing
In Arnhem, the Netherlands, all the exchange students live together in a five storey building called Honigkamp. Feel sorry for the neighbours! Every Sunday night we organise amongst ourselves to host a national dinner – so far we've enjoyed Mexican, Spanish, Turkish, Hungarian, Canadian and of course Australian. There are only two Aussies here, myself and Kristie from Brisbane, and we represented very well. Vegemite sandwiches (Aussie chocolate!), self-made lamingtons (did you know one key ingredient is only found in Australia?), fairy bread and Kristie passed out before midnight.
The photos are of: Dutch Stephanie trying Vegemite; Kristie; Mexican night (complete with moustaches and tequila); the family Turkish dinner; Batu cooking his spring roll thingos.
November 8, 2010 | Categories: International Food Events | 9 Comments


Published 04/26/2019 09:40:14 am at 04/26/2019 09:40:14 am in What Does Cree Mean In Led Lighting.
what does cree mean in led lighting the led dimming dilemma lighting control how do you know if your led lights have cree led chips or not ever wonder if your led is a real cree led we have found that with leds becoming more and more popular the market is being flooded with the fake kind.
what does cree mean in led lighting, cree tw led bulb california demands maximum light quality cree cree tw led bulb california demands maximum light quality cree delivers for less than extremetech, led lights good for the planet bad for headaches , lightemitting diode wikipedia , best brightest tactical flashlights lab test comparison real cree lumens values, color temperature scale for light bulbs atlantalightbulbscom what is color temperature, science advances in matching led lighting to horticultural needs fig green sense farms grows micro greens lettuces baby greens such, shopping for led bulbs take a few tips from some hometesting three led bulbs from left to right the greenwave reality philips hue and torchstar at this juncture in the evolution of the led bulb industry , cree revamps entire led line of better bulbs treehugger , led grow lights the myth about watts garden myths led grow light watts myth, tested how bright leds are compared to other lights wired tested how bright leds are compared to other lights.


BEAR – Thirty minutes after Salesianum's lacrosse team had clinched the 2018 DIAA state championship, the Sals' players, coaches and their families lingered on the turf at Bob Peoples Stadium at Caravel Academy. Repeated announcements over the public address system asking them to vacate the premises were unsuccessful.
The Salesianum lacrosse community had reason to celebrate. The team's 14-9 win over Caesar Rodney on June 4 not only earned the school it's 10th title in the sport since the DIAA began sponsoring a championship in 1993, it was the Sals' fourth straight. That made them the first program to win the crown four straight times.
"You guys were focused, and you got it done. I'm so proud of you," coach Bob Healy told the players after the win.
This group of seniors – there are 12 on the roster – did what their predecessors could not. Sallies had won the state championship in 2011, '12 and '13 before being upset by Cape Henlopen in 2014. This time, they would not be denied.
The latest win, however, would not be easy. The top-seeded Sals defeated No. 2 Caesar Rodney in May by a 19-8 score, but this time the Riders stayed close. The Riders were down just a goal late in the second period before Salesianum's Patrick Drake scored with 14 seconds left on the clock to make it 8-6 at the half.
The Riders came out firing in the third, as Demetrius Stevenson fired a shot high past Sals goalie Brady Emmi just 17 seconds into the quarter. Cooper Urban answered less than a minute later after he took a pass from Brett Hobbs, but the defenses took over after that.
A long Riders possession halfway through the third culminated with a goal from Noah Longest, bringing them within one at 9-8. But the Sals regrouped and took that one-goal lead into the fourth. They also went into the final 12 minutes on a man-up situation, and they used that to their advantage as they pulled away from CR.
Opening the quarter with possession, Hobbs and Urban killed about 30 seconds passing the ball around the perimeter. With the advantage nearing its end, Hobbs fired the ball behind Riders keeper Jacob Stant to put his team up, 10-8.
Hobbs said he felt the momentum shifting toward the Sals during the third quarter.
Emmi rejected two Riders shots in quick succession with just under six minutes to go, and his teammates thanked him by rushing downfield after the second save and getting the ball to Logan Falconetti, who deposited it into the net. Urban added another goal with 3:06 to go, increasing the lead to four.
Urban, who will play next at Rensselaer Polytechnic Institute, said the Sals' defensive effort after halftime made a difference offensively as well.
"We were just able to hold a couple goal lead for a while. They had to press out and chase us around on offense. That opened up a lot of opportunities for us to put a few more in," he said.
They would add another two goals in the closing minutes to seal the win. Bradley Santore worked the ball from behind the net and found an empty net with 2:02 remaining, and Falconetti scored once more at the 51-second mark. With the outcome decided, Jared Wagenhoffer ended the Sals' five-goal run when he scored with 13 ticks on the clock.
The Sals converged around Emmi as helmets, gloves and sticks rained down. After the initial commotion, the players took turns raising the state championship trophy before settling in for some words from the coaching staff, then photographs.
The players said they knew they would be in for a battle against the Riders, but Emmi noted it didn't change how they prepared for the evening.
Emmi, who will suit up for Salisbury University next season, said becoming the first team to win four straight titles was the driving goal all season.
"We said we're going to be the team to make history. The year before we came, when we were in eighth grade, they almost had the four-peat, but they let it slip, and we weren't going to live with that regret. We knew we had to get it done today," he said.
Urban finished with five goals to lead the Sals. Drake had three, and Falconetti, Santore and Hobbs had two each. Sallies finished the season 16-3.
Wagenhoffer led the Riders with a hat trick. Josh Cosden and Noah Longest had two each, and Stevenson and James Cava added one apiece. The Riders also ended with a 16-3 record.


How to Get GMC Certificate?
Manufacturers submit application form and GlobalMarket makes audit arrangement with TÜV, the leading provider of technical services worldwide.
TÜV Rheinland concludes and issues GMC Auditing Report according to applicant's actual condition.
GMC Certificate is granted by GlobalMarket to manufacturer who is conformed to the GMC criteria.


Greek traditions and grandeur abound in Crete with ancient ruins, pink sand beaches, and gorgeous mountain views. Exceptional Experiences in Greece.
Explore GREATravel ideas for Greece.
Pictures sent to Marie by Chris who just returned from Crete.


text:
Jaguar has a fleet of over 200 all-electric I-Pace prototypes, completes 200-mile test drive in California
- Dec. 6th 2017 5:18 am PT
As we reported last week, Jaguar brought two I-Pace prototypes at the Los Angeles Auto Show – a year after first unveiling the vehicle at the same show.
Now Jaguar elaborates on its test program and reveals that it currently operates "more than 200 production prototypes" ahead of its launch next year.
Ian Hoban, Jaguar Vehicle Line Director, said:
"After 1.5 million global test miles, the I-PACE is ready for production and is proven to deliver long distances on a single charge. Jaguar's first battery electric vehicle will also be fast to charge; our target is a zero to 80 percent charge being achievable in a short break."
That fast-charging is still based on a 50 kW charger, according to a press release.
The British automaker confirmed that "thousands of potential customers" expressed interest in their first all-electric vehicle by pressing the 'I want one' button on their website.
They invited a few of those people to join Jaguar's engineers on test drives of their prototype vehicles.
Ann Voyer from Pasadena, California was the first lucky potential customer to be brought along on one of those rides.
She wanted to know if the I-PACE would have enough range to complete her favorite road trip along California's West Coast from Los Angeles' Sunset Boulevard to Central California's Morro Bay.
They produced a video about it:
As we previously reported, the I-PACE is a sport SUV equipped with a 90 kWh battery pack with a range of "over 500 km" NEDC-rated. Interestingly, the automaker has now confirmed "a targeted range of approximately 220 miles on EPA test cycles".
It apparently easily completed to 200-mile (322 km) road trip.
We are pretty excited about the I-Pace for a few reasons.
First off, it just looks like a nice car that happens to be all-electric. Secondly, Jaguar has been hinting at the fact that it could actually be somewhat reasonably priced, which could make a significant impact on the industry if it's really the case.
The main bummer is that Jaguar keeps only referring to 50 kW DC fast-charging, which is the current standard, but not what you would expect from a new electric vehicle coming out in 2018.
Hopefully, they are only referring to the speed when charging at charging stations capped at 50 kW and that it is not the actual charging capacity of the car.
We should know more in a few months when Jaguar unveils the production version and opens its order book.
The vehicle is then expected to enter production in the second half of 2018, which is another reason why we are excited for the I-Pace: it's going to be one of the first of a series of new electric vehicles built to be electric from the ground up coming from legacy automakers.
The Jaguar I-Pace is an electric SUV produced by automotive company Jaguar Land Rover under their Jaguar brand name. It was first released in 2018.

redpajama_set_name: RedPajamaCommonCrawl


text:
Mayfest announces A$AP Ferg as Dillo Day 2019 headliner
David Deloso, Assistant Managing Editor
Mayfest has announced rapper A$AP Ferg as Dillo Day 2019 headliner. A member of hip hop collective A$AP Mob, which also includes artists such as A$AP Rocky and A$AP Twelvyy, Ferg released his most recent project Still Striving in August 2017.
The Harlem native is known for songs such as "Plain Jane," "New Level" and "Work." In addition to his work with other A$AP Mob members, Ferg has collaborated with artists such as J.I.D., Future and Tyler, the Creator. Outside of music, Ferg has a creative partnership with Adidas and is involved with A$AP Rocky's creative agency AWGE.
Ferg was previously booked to play Dillo in 2015, but that year's event was canceled due to weather. Mayfest looked to bring in a high-energy hip-hop artist when booking him.
"Hip-Hop/Rap have by far been the top genres on our poll for the last few years, and it's great to provide campus with that genre through such an acclaimed artist," said Communication senior and Mayfest Director of Booking Koyote Meiners-Rios in a statement. "It's great to provide campus with that genre through such an acclaimed artist."
It seems that Ferg finally performing after the 2015 cancellation is part of the "throwback" theme Mayfest has previously teased at. Now the question is: Who else will join him?


text:
Y: The Last Man – Girl on Girl
Goran Sudžuka
Pia Guerra
North American Publisher / ISBN: Vertigo - 1-4012-0501-1
Categories: Drama
Review by Karl Verhoven
As it good as it is overall, every now and then there's a volume of Y: The Last Man that doesn't quite match the vim, vigour and compelling nature of the remainder, and Girl on Girl is one of those books.
In Ring of Truth several revelations added to the pervading sense of unease and distrust, while one major query was cleared up. Fundamental to Yorick Brown, the last man alive, was Ampersand, the Capuchin monkey that he'd recently agreed to care for when the killer plague struck, and Ampersand has been abducted.
Only a single clue to his possible whereabouts presents itself. His kidnapper was Japanese, and a woman fitting her description boarded a freighter bound for Japan only hours before the question was asked. Yorick, Agent 355 and Dr Alison Mann have taken the next possible boat to follow her. This is a cargo ship, and it's being tracked by something with far greater wallop. On board friends and enemies are made, and Brian K. Vaughan throws in a twist or two along the way.
The problem is that it never really convinces as anything other than filler. It's as if Vaughan decided that just depositing his cast across the Pacific would be too easy, and if they were to take a trip it somehow needed to be an adventure. The tale does add to the cast in one significant manner, but this could have been achieved elsewhere.
Goran Sudžuka is technically a better artist than Pia Guerra, but lacks her facility for emotional subtlety. Under his pencils the cast are constantly grimacing, pouting and posing, and it's not a pleasant sight.
An unconnected chapter follows up on Beth in Australia where she undergoes a mysterious Aboriginal experience that ends with a message and reveals her shared past with Yorick. It's good to have Guerra back on the art, and Vaughan can be relied on to slip in a few good memorable lines of dialogue ("My dad says getting dumped was the closest thing he ever had to a Bar Mitzvah"), but the tale as a whole is once again unconvincing. Paper Dolls is far better.
The content of this volume has since been re-issued combined with Ring of Truth as Y: The Last Man Deluxe Edition volume 3 in hardback, and more recently just as Y: The Last Man Book Three.
The Exterminators: Bug Brothers
Southern Bastards Volume 1: Here was a Man
Clone: First Generation
Hard Time: 50 to Life


text:
Amid Zolgensma crisis, Novartis gets a gene therapy boost as NICE embraces Luxturna
by Angus Liu |
Sep 4, 2019 10:59am
Novartis' Spark Therapeutics-partnered gene therapy Luxturna has won quick backing from England's cost watchdog, the National Institute for Health and Care Excellence. (Novartis)
In December 2017, Luxturna became the first directly administered gene therapy approved in the U.S. Now, it's recommended for use on the NHS in England.
England's drug cost watchdog, the National Institute for Health and Care Excellence (NICE), has recommended coverage for the one-time rare eye disease drug, which was developed by Spark Therapeutics and is sold by Novartis outside the U.S.
At its list price of £613,410 ($745,650) per patient, the drug would have failed the Budget Impact Test, meaning it would have cost the public health system too much, NICE said. However, like almost all other drugmakers do to win NICE backing, Novartis has offered NHS England a confidential discount.
"This latest deal reinforces the benefits for companies willing to engage with us and be pragmatic with their pricing—which is good news for patients, tax payers and industry," NHS chief executive Simon Stevens said in a statement.
In the U.S., the drug's list price reaches $850,000. The Institute for Clinical and Economic Review (ICER), a U.S. cost watchdog, previously found it should cost 50% to 57% less to be considered cost-effective, accounting for direct healthcare system costs and other societal benefits.
On average, even within NICE's Highly Specialized Technologies pathway, it would take the agency 38 weeks to wrap up an evaluation. But, eager to reach a deal, Novartis won over NICE in just 20 weeks.
"The company's willingness to work with us early and constructively has allowed us to publish this guidance on a much faster timeline than normal which is good news for patients," Meindert Boysen, director of the Centre for Health Technology Evaluation at NICE, said.
RELATED: What does Novartis' eye business envision without Alcon? Digital M&A, for one thing
Novartis accomplished the feat without clinical data showing Luxturna could work in the long term, even though the lack of such evidence is a reason NICE frequently cites in rejecting coverage for a drug. Instead, the assessment committee "considered it is biologically plausible that the treatment effect is likely to continue for decades," the agency said.
Luxturna scored its EU approval last November, about 10 months after Novartis shelled out $105 million upfront and committed $65 million in milestones for its ex-U.S. rights. The one-time gene therapy is designed to treat people with certain inherited retinal dystrophy by delivering a functional copy of the RPE65 gene directly into the retina by a surgeon.
The company estimates that 86 people living with the condition will be eligible for the treatment through NHS. If no one appeals NICE's draft guidance, the final version will come out next month, and coverage will start from January 2020.
Though Luxturna calls itself the first gene therapy available in the U.S., it's not the first one covered by NICE. That title belongs to "bubble boy" drug Strimvelis, which GlaxoSmithKline offloaded to Orchard Therapeutics in 2018. The drug, which involves editing a patient's own hematopoietic stem cell outside of the body, is not FDA-approved.
RELATED: Novartis earlier acknowledged Zolgensma data errors to FDA but blamed them on poor reporting
NICE's backing is a timely win for the Swiss drugmaker and CEO Vas Narasimhan's blueprint based on novel platforms, as the company is deeply embroiled in a data manipulation scandal around the spinal muscular atrophy gene therapy Zolgensma.
The FDA in August unveiled that Novartis' AveXis unit used falsified animal testing data in Zolgensma's new drug application package. In a widely criticized move, the company confirmed the allegations internally in early May but didn't alert the FDA until more than a month after it greenlighted the drug.
During an August conference call with analysts, AveXis President David Lennon said it had shared the information with the European Medicines Agency and doesn't expect any delays to the discussions around approving Zolgensma in Europe. Novartis has said it expects an EU decision on the drug in the fourth quarter.
gene therapy rare diseases drug prices drug costs marketing approval Cell & Gene Therapy Novartis Luxturna NICE Spark Therapeutics
Angus Liu
https://twitter.com/Angus_Fierce
https://www.linkedin.com/in/ruojingliu


This small package file redefines the lighting used in BodyShop, making viewing and modifying your creations there a lot friendlier.
By requests, this package has three versions that have increasing brightness levels, so you can pick the one you like. I also wrote some small details (a mini-tutorial) of how to edit it with SimPE to make it just like you want.
Install is simple... unzip the package file and put one of the files in your config folder (it may work in downloads, but I didn't test it there).
I have attached a screenshot of the same Sim with the old and new lighting system. The brightest file in the new set is just like the one I originally released, with the other two being more moderate brightness level enhancements.


This July a solo exhibition - taking the form of a multimedia installation - will debut, set to explore the kaleidoscopic work of Henzel Studio collaborators assume vivid astro focus. For the exhibition, the artist duo – Eli Sudbrack and Christophe Hamaide-Pierson – have transformed the museum's underground exhibition area, known as BASE103, into a multimedia Gesamtkunstwerk. The space will also exhibit the artists' videos, paintings and some recent works and documentation material on the history of assume vivid astro focus. Assume vivid astro focus is part of Henzel Studio Collaborations Vol. 1 and Henzel Studio Art Pillows Their rug is available for purchase here and their pillows here.


> > GDB uses duplicate line numbers to detect the end of the prologue.
> > GCC would carefully emit them... and gas was stripping them out.
> > on a line is rare.
> wonder if he had a specific reason ?
>         (thereby emitting only one line symbol per source line).
>         * dwarf2dbg.c (dwarf2_gen_line_info): Ditto.
> be applied to stabs.c ?
I endorse Geoff's second, modified patch.


are updated everyday, maybe we have no time to check out them one by one. Show Details Exclusions, details: Find the contacts you need at the best online price when you shop at Discount Contact Lenses, including your choice of either daily disposables, monthly disposables, colored lenses, and other options. Deena will be providing expert feedback in the areas of landscape, natural portraits, studio portraits, and self-insight. Weekly challenge votes will be tallied and at the end of the 8-week challenge, winners in amateur and professional categories will receive prizes for best in show. Currently, he lives in Arizona and works as a reporter and photographer for the Yuma Sun.
Don't miss this fantastic deal! At The Luxe Lens, you will always find gorgeous merchandises with reasonable prices. Just add them to your shopping card and enjoy the deal of "Save up to 88 on lightroom acr presets.
The The Luxe Lens coupon discount will adjust your order total. Below is the Easy 3 Step process to get your savings now! Because we make our products accessible to more photographers, we're able to sell a larger volume, and this keeps us www.finfunmermaid.com coupon profitable. Weekly Challenge Topics: * Emotion Photojournalism * Abandoned Spaces Inspiration * Landscape Self-insight * Natural Portraits Studio Portraits. The code works on sale prices and on both Lightroom and Photoshop products. Other, discount Contact Lenses Promo Codes, details: Stock up on a new supply of contact lenses from your favorite brands and purchase new eye care accessories such as contact lens solutions and cases.


Crafts by CAS: New Year, New Project (Life)!
New Year, New Project (Life)!
Happy 2013! I think it's going to take a while before I get used to not writing (or typing) 2012. I'm not really one for New Year resolutions, but I do think it's a great time to start something new. Hmm, isn't that what resolutions ARE? Anyway, I wont put a title to it - I don't want the pressure.
I've decided to give a stab at Project Life. I found Cathy Zielske's blog last year and have been stalking her on a regular basis. When I read her blog I think she's talking to me (I'm not nuts, I know she's not). After watching her Project Life tutorials and how to incorporate Photoshop Elements to create journals and graphics, I was sold. My only issue....my computer was old, too small and very slow. Her videos convinced me that I needed something bigger and better. December 26 my new iMac was delivered. Holy Moly, Batman! Over the past week I have been learning a new operating system (my old laptop was a PC), documenting and taking pictures of life happenings and learning Photoshop Elements. Whew, I'm tired.
I'm taking a pretty basic approach and following whatever Cathy does. I like her style and love the designs she creates. I've purchased a basic album, a few photo pocket protectors, and downloaded a few of Cathy's templates from Designer Digitals. Now, our life isn't all that exciting and we don't have children...so my book may be thin - but heck, it's my book!


Cogwheel is grateful to all those organisations and individuals that support our work financially. Thanks to their generosity we have been able to sustain our services over the last 28 years. We receive regular donations from local individuals many of whom decide to donate using gift aid. We also receive donations from local churches, businesses and colleges. Each year a number of grant making trusts support our work and we also provide some counselling services on behalf of the local education authority and city and county councils. We are also very grateful to everybody who supports Cogwheel by volunteering as counsellors, trustees, fundraisers, user group members, or by providing admin and IT support. If you would like to get involved please do contact us. We are currently looking for volunteer counsellors and Trustees.


text:
Sónar Lisboa announces first 24 acts for 2023
Electronic music in its multitudinous, diverse forms is at the heart of Sónar Lisboa in 2023.
The highlights of this first announcement are a series of AV shows that showcase the variety of modern dance music. There's Folamour's euphoric celebration of house music; a cinematic and visceral techno experience created especially for Sónar Lisboa by I Hate Models; and Max Cooper's immersive performance based on his most recent album 'Unspoken Words'.
And as always, there are DJ sets of all shades at Sónar Lisboa 2023. Mochakk is one of the brightest stars of current house music, while VTSS offers a radical mix of hardcore, EBM, trance, and even hints of pop. Also present are cosmic voyager Acid Pauli and Or:la's classy combination of UK bass, breakbeat, and techno.
And there's room for some of the most exciting live acts around. Headlined by KiNK's energetic mix of house and techno; there's also a special hardware-based live set from techno overlord Héctor Oaks; and WhoMadeWho's combination of electronic music, jazz and rock.
Joining them are Cinthie, with her modern vision of classic house; DJ Nigga Fox, who fuses music from the Portuguese diaspora with contemporary electronics; and local group Sensible Soccers, whose pop melodies are built using both guitars and synthesisers.
Back-to-backs return in force at Sónar Lisboa this year. Astra Club, the pairing of DJ Tennis and Carlita, wander through the emotional side of electronic music; while Violet b2b Photonz represent the Portuguese house and techno underground. Elsewhere, two indispensable pairings from the UK, SHERELLE b2b Kode9 and Skream b2b Mala, will cover the past, present and future of bass music.
Finally, local heroes such as Rui Vargas and Yen Sung, veteran advocates for dance music in Portugal, are joined by a names from a new generation of artists who have been making their mark in both clubs and festivals: Catarina Silva, Francisca Urbano, Luisa, Shaka Lion and Vil.
As a reminder, in 2023, the Sónar Lisboa experience will be simplified and centralised, with both Sónar by Day and Sónar by Night taking place in Pavilhão Carlos Lopes in Parque Eduardo VII in the centre of Lisbon. The Sónar+D venue (soon to be announced) will also be located in close proximity.
Tickets for Sónar Lisboa are available now. Purchase yours here.


text:
Upcoming Races | Latest Results | Find A Race | Race Calendar
Upcoming Races | Latest Results | Find A Race
The Weekly Top Ten Stories · All Time Top Stories
Running News Daily is edited by Bob Anderson and team. Send your news items to jaime@mybestruns.com Get your race featured, followed and exposed. Contact sales at bob@mybestruns.com or call Bob Anderson at 650-938-1005 For more info: https://mybestruns.com/newmem.php
Index to Daily Posts · Sign Up For Updates · Run The World Feed
All Running News
World marathon record-holder Brigid Kosgei is the standout name in the women's field for the Ras Al Khaimah Half Marathon
Brigid Kosgei who broke the world marathon record (pending ratification) with her stunning 2:14:04 run in Chicago last year, will return to the UAE after finishing seventh at the 2018 edition of the race. Her official half marathon PB is 1:05:28, but she also won last year's Great North Run – a slightly downhill point-to-point course – in 1:04:28, the fastest time in history for 13.1 miles.
"I am really excited to come back to the Ras Al Khaimah Half Marathon after two years," said Kosgei. "I know that this year the line-up is one of the best ever for a half marathon and I really hope to run fast."
The 25-year-old Kenyan is one of several women in the field with a PB inside 66 minutes. She will line up against Fancy Chemutai, whose best of 1:04:52 is just one second shy of the world half marathon record, 2016 world half marathon champion Peres Jepchirchir, who briefly held the world record following her 1:05:06 victory in Ras Al Khaimah in 2017, Ethiopia's Netsanet Gudeta, who set a women-only world record to win the 2018 world half marathon title, and Joan Melly Chelimo, the fourth-fastest woman in history.
Rosemary Wanjiru, who recently went to third on the world all-time 10km list with 29:50, will be making her half marathon debut.
In the men's race, world marathon silver medalist Mosinet Geremew will take on Two-time Prague Half Marathon winner Benard Kimeli and European record-holder Julien Wanders.
Ethiopian trio Andamlak Belihu, Solomon Berihu and Amdemwork Walelegn are also in the field along with Kenyan duo Alexander Mutiso and Kibiwott Kandie.
(01/22/2020) Views: 497 ⚡AMP
by World Athletics
Rak Half Marathon
The Ras Al Khaimah Half Marathon is the 'world's fastest half marathon' because if you take the top 10 fastest times recorded in RAK for men (and the same for women) and find the average (for each) and then do the same with the top ten fastest recorded times across all races (you can reference the IAAF for this), the...
Running News Headlines
Copyright 2020 MyBestRuns.com 4,837


text:
Thursday, Dec 08, 2022 - 10:44 PM
Brian Brohm to serve as Purdue's interim coach for bowl game
written by MICHAEL MAROT, AP Sports Writer
Purdue head coach Jeff Brohm questions a call during the first half of an NCAA college football game against Indiana, Saturday, Nov. 26, 2022, in Bloomington, Ind. (AP Photo/Darron Cummings)
WEST LAFAYETTE, Ind. (AP) — Purdue offensive coordinator Brian Brohm is getting another chance to replace his older brother.
And this time, he'll be more than an adviser.
Shortly after Louisville announced Thursday it had hired Jeff Brohm, Boilermakers athletic director Mike Bobinski named Brohm's younger brother as interim coach for the Citrus Bowl game against No. 17 LSU on Jan. 2.
"Let me just explain something, some people think that sounds strange, but he's a really talented coach and if his name wasn't Brohm it wouldn't be strange at all," Bobinski said. "Brian was really excited and it's a great professional moment for him to put his mark on the program over the next few weeks."
Mark Hagen, one of three co-defensive coordinators, will call the defense following the immediate departure of Ron English for Louisville, Bobinski said. English called the defensive signals and coached safeties.
Brian Brohm got his first chance as a head coach in October 2020 when he led the Boilermakers to a season-opening 24-20 victory over Iowa after
Jeff Brohm explains what he thinks Howard Schnellenberger would say right now: pic.twitter.com/H8ZKimemCk
— Tyler Greever (@Tyler_Greever) December 8, 2022
Jeff Brohm tested positive for COVID-19. He returned to his play-calling duties when his older brother returned for Week 2.
It's already been a historic season for the Boilermakers (8-5), who won their first Big Ten West Division title before a loss to Michigan in the conference championship game. The LSU game will come in front of a national television audience with a shot at a second consecutive bowl win.
Bobinski said he would welcome it if Brian Brohm and Hagen remained on staff though he did not commit to interviewing either to fill the to job.
Instead, Bobinski thanked the elder Brohm for rebuilding the Boilermakers program and said he had already contacted some potential candidates.
"We want to do this as expeditiously as possible," Bobinski said. "We don't want to rush it, but we're aware of the calendar, the early signing date and we want to get it done as quickly as possible."
AP college football: https://apnews.com/hub/college-football and https://twitter.com/ap_top25. Sign up for the AP's college football newsletter: https://tinyurl.com/mrxhe6f2
Michigan Stadium tunnel will widen without portable seating
ANN ARBOR, Mich. (AP) — Michigan Stadium's lone tunnel — the site of altercations between players as they enter and exit the field — will be a little wider next season. The school confirmed Monday that it will remove a portable section of seats from the front of the tunnel
No. 1 Georgia bullies TCU 65-7 to win 2nd consecutive title
INGLEWOOD, Calif. (AP) — Stetson Bennett threw two touchdown passes and ran for two scores in the first half as No. 1 Georgia demolished No. 3 TCU 65-7 Monday night to become the first team to win consecutive College Football Playoff national championships. The Bulldogs (15-0) became the first repeat
Michigan All-America RB Blake Corum staying for senior year
ANN ARBOR, Mich. (AP) — Michigan All-America running back Blake Corum is staying in school for his senior season and putting his professional football dreams on hold. "I can go to the NFL next year," Corum told The Associated Press. "But I can't go to the NFL, then come back
No. 2 Michigan chases Big Ten crown, playoffs against Purdue
Purdue (8-4, 6-3 Big Ten) vs. No. 2 Michigan (12-0, 9-0, No. 2 CFP), Saturday, 8:17 p.m. EST (Fox) FANDUEL SPORTSBOOK COLLEGE LINE): Michigan by 16 1/2 Series record: Michigan leads, 45-14. WHAT'S AT STAKE? Michigan is chasing an undefeated season, a second straight Big Ten title and its second
Read more About No. 2 Michigan chases Big Ten crown, playoffs against Purdue
Wolves+ Pablo Prigioni
Wolves+ with Kyle Anderson
Wolves+ with Matt Lloyd
Wolves+ with Tim Connelly
Subscribe to Bally Sports+
and start watching
Access to live, local Bally Sports games
Monthly and annual subscription options
Watch on multiple devices
Get game replays, highlights and more
Bally Sports+ is not currently available in your area
The content you are trying to watch is not part of your current subscription. You can watch it by subscribing to another package available in your area.
The content you selected is not available in your area.
Available in your area. Not all games may be available.
Your billing zip code determines what is available to you.
See Packages
You have an active subscription so your current home zip code cannot be changed. If you need to change your location please contact customer support.
Sign In with TV Provider
Already have a Bally Sports account?


Here is Janet Josephine Sayer's obituary. Please accept Everhere's sincere condolences.
With heavy hearts, we announce the death of Janet Josephine Sayer (Oakville, Ontario), who passed away on September 12, 2018. Family and friends are welcome to send flowers or leave their condolences on this memorial page and share them with the family. She was predeceased by : her spouse John Sayer.
She is survived by : her children, David (Janice), Carolyn Orsini, Cathie Sayer, Janet McFarland and Stephen (Tsema); her brother Thomas Stremble. If desired, donations to Oakville Trafalgar Memorial Hospital or to Covenant House would be appreciated.
There are no additional memories for Janet Josephine Sayer at this time. You can add a memory to pay tribute to Janet Josephine Sayer at any time.
Here are the tributes to Janet Josephine Sayer who passed away in Oakville, Ontario.
Would you like to offer Janet Josephine Sayer's loved ones a condolence message? Write your message of sympathy today.


You need to visualize what you want. Picture everything you want so clearly in your mind until you can see it right in front of you. Write it all down on a piece of paper. Create a vision board. Then you will have evidence of the incredible influence of your mind, and the remarkable power you have.
Nothing good ever comes from living by what is in front of you, and by only reacting to the circumstances of life. In that way, you never move beyond the life that is staring at you right now. So, you have to be able to see outside of your current situation.
There is a big difference between pushing and pulling yourself. Pushing yourself is not something you desire but rather something you have to do to get something. While pulling yourself is the vision you have, which draws, excites and compels you to achieve what you want.
You must be able to acknowledge where you are in life. But know that you are capable of creating so much more. You have to understand that where you are right now is not your life. It is where you are at the moment only because of your previous decisions and past beliefs.
Now, it is time, to sum up, the courage to ask for better, to believe things could be better, and to believe magic is on the way. The time has come to get what you want and deserve. Know that in life, we do not get what we ask for, but we get what we ask and work for.
Nothing in your existence will happen without putting in the work. No matter the books, seminars, audio tapes, gurus, or mentors you get; nothing will work if you do not put effort into what you want. I am not talking about doing work you hate; there is no need for that.
I am speaking about doing work you love. Passion is not working. Yes, you have to do something, but you should do it because you love doing it, and not because you have to. And that is where the magic is created. You add value to others by doing what you want to do, and you get rewarded for it. What you want is not going to come to you by just dreaming about it.
When you get in your car to go somewhere, you would never expect to arrive at the destination by just closing your eyes and picturing about it. And you know you cannot get there instantly. You must know where you are going, but you also understand that right now you are here. Therefore, to get to your objective, there is going to be a journey.
There might be roadblocks, detours, curves, stop signs, barriers, flat tires, and even breakdowns on the way.
But if you really must get to that destination and have what you want, you can and will find a way. On a car trip, you would never stop half way and turn around because of a detour, a setback or an obstacle.
You just take whatever path that leads to your destination, even if it is or was not the road you planned on taking, or the easiest one.
Life is no different! If you want something; anything in your life, you must first know where you are. And then you have to know what it is going to take to get there. So, you have to commit that no matter what happens, you will reach that destination.
When you have to go the long way to get what you want, so be it, follow the long road. If you have to learn a new way, then learn this new approach. And when there are detours, roadblocks, curves, or you get flat tires and breakdowns, you have to keep going.
Find a way to fix the issue. Get patched up. But you need never to quit. If you just know deep inside of you and if you believe you will get there, you will. And when you dare to see it through, there is nothing you cannot achieve or have.
There is nowhere you cannot go, and no one you cannot become. If you cannot envision what you want, if you cannot believe it, then you will never see it through and never become that person.
And if you want to live an average life, that is fine. Keep your feet on the ground. But if what you want is to soar, if you want to achieve great things, you must not only think crazy thoughts but feel and visualize them.
Picture and experience what it would feel like to be doing what you dream of and want to do. Sense what it feels like to have all the things you want. Feel what it is to be the person that has achieved the things you want to accomplish.
The very process of you feeling like you already have it will send vibrational signals to your brain. And if you are willing to work for it, it will be in your life earlier than you think.
Only those who believe anything is possible can achieve the things most would consider impossible. So you must know who you are going to be before you become that person. You have to picture what you want to achieve and feel like you already have it before you can bring it into your reality.
In the great book "Think and Grow Rich," Napoleon Hill states: "Whatever the mind of man can conceive and believe, it can achieve." He then says: "You are the master of your destiny; you can influence, direct and control your environment. And you can make your life what you want it to be."
Therefore, to have what you want, there is no magic trick. It is not a new philosophy. Most of you know about it, and if you do not, you should start paying attention. The reason is that just about anyone who is successful knows.
There are energy and power far greater than we can comprehend which is at play here. And you can either, use it, live in harmony with it, create with it, or run in fear from it and ignore it.
You cannot focus on where you are right now and expect to get what you want or where you want to be. If you want to change your life, you need to get your mind off all your problems. You need to release your mind from all limitations and focus on the outcome you want in your life.
Think exactly where you want to be and what you want. Make a very detailed list of all the things you want. Then write down what it is going to take to get there. Whatever do you need to do? What do you need to learn? Who do you need to connect with to get there?
Do not focus on your limitations or the things that are holding you back, but rather focus on what you need to get there. Believe you will get where you want to be. If you have a money challenge, focus on how you can get the money you need and not on your lack of money.
To get what you want; focus on what can you do and what you must do. Then do that.
Be unrealistic. Nothing great was ever achieved by a realist.
Set audacious goals that even intimidate you.
Stretch yourself to your limits as you are capable of much more than you give yourself credit for.
Having a plan B only distracts you from plan A.
Focus on your goal to the exclusion of everything else.
Give your efforts toward your greatest strengths to experience success.
To be great, you must strive for greatness.
Picture what you want in your mind first, before it ever becomes a reality.
Be convinced of your success.
In your imagination, live in your new home, drive the new car, and see your marvelous spouse, before it ever becomes a reality.
Believe in your ability before anyone else will. Have faith in your capacity to succeed.
Ask yourself: "Why not me, why not now?" So, never underestimate yourself.
So, in summary, remember that to get where you want to be, you have to see it. You have to be unrealistic while striving and putting in the work. But you have to see, live, feel and experience what you want in your mind first. All of it while you believe, know, act to then move forward.


text:
3 April 2019 0 Comments
Settlement for medical student who worked with asbestos during the holidays
Posted by Helen Childs, Partner
Mr N, who was born in Nigeria in 1938, came over to England in the 1960s and started studying to become a doctor. He only had partial funding so had to work throughout all of his holidays in order to support himself. He worked at Johnson Matthey and also Atlas Stone.
Whilst at medical school he met his wife, Jo S, and they married in 1963.
Many years later, when Mr N was living in London, he developed many health issues including problems with his memory and increasing frailty. After being found collapsed in the street investigations revealed that he had a likely malignancy, although he was too frail to undergo a biopsy. He moved to be with Dr S, his wife, who cared for him throughout his illness. They instructed Royds Withy King, who visited him at home and took a statement from him detailing everything he could remember about his previous employment. He recalled tipping powder into a giant machine to mix it into a paste at Atlas Stone, which made asbestos products. Even though he was employed there in the 70s, he was not given any warnings or protective equipment. A lot of students from nearby Cambridge University worked there. He also described likely exposure to asbestos at Johnson Matthey, where he and other students had also worked.
Letters of claim were sent and medical evidence obtained. Sadly Mr N died in August 2017, and the inquest confirmed in November that he had mesothelioma. A claim was commenced against Atlas Stone who admitted responsibility and settled the claim for a substantial five figure sum. Dr S was not financially dependent on Mr N so the claim was limited to damages for Mr N's pain suffering loss of amenity, a bereavement award and the funeral costs together with the care and assistance provided during his illness.
The claim settled for a substantial five figure sum and after settlement Dr S said:
"I fell in with your firm on a referral to Helen. She is also well known and respected by the Mesothelioma charity in Manchester, to whom I was referred by a friend who had several colleagues (in the construction trade) who died from this disease. A lesser lawyer might fall into the traps set for those seeking redress, but not Helen. She is also compassionate to a fault. We were blessed to find her. I am setting up a fund in my husband's name. The entire yield of the invested sum will go yearly to where we feel it can do most good"
If you want to find out more about making an industrial diseases compensation claim, please contact our specialist team.
0800 051 8056	Email usasbestos@roydswithyking.com
Helen ChildsPartner
View articles by Helen


I am so excited to announce the launch of my first handmade pillow collection, The Salisbury Collection. Salisbury is a town in Massachusetts (north of Boston) and the location of one of my favorite beaches in Massachusetts. The collection consists of 10 one of a kind pillows. Each pillow was handmade with an impeccable amount of attention to detail. They are made of 100% linen; in a blog post a couple of weeks ago I explain why after much testing linen was my fabric of choice. They also feature an invisible zipper which gives each pillow an elegant and clean look.
Each and every pillow in this collection was designed and created from a very thoughtful place, although a few of them were experiments that turned out beautifully, others were hand sketched beforehand. I used a (modern version) of an ancient Japanese technique called Shibori which calls for specific methods of folding, pleating and pole wrapping to achieve the beautiful and organic patterns. I came across this technique while I was doing research for my grad school thesis and fell so much in love with it that I have not looked back.
The actual collection has been completed for about 2-3 months now - I needed to take some time to work up the courage to finally launch. While launching something I have put so much time, love and effort into is SO exciting it is also really scary. Scared of what you may ask? I am not exactly sure what I am scared/nervous for but in my heart of hearts I know that there is absolutely no other excuse I can give myself to not launch and I also know there will never be a perfect day or time to pull the trigger.
I hope you take a look at the shop and let me know what you think!


What is it: If you have a Facebook Fan Page or a Page for your business etc. and you no longer want that page you can permanently delete it.
How to delete FB Page: Follow the step by step instructions to Delete you FB Page.
Step 1: Use your Facebook Page as Admin.
Step 2: Go to Edit Page and click on Manage Permissions.
Step 3: From the Manage Permission section go to Delete Page.
Step 4: From the Delete Page? Popup menu click on Delete Page. Your page will be deleted however Facebook will give you 14 days time to restore that page, after 14 days time it will be permanently deleted.
Note: These are the steps to Delete FB Page and not Facebook Account.


text:
News & Events Department Pages
news@swarthmore.edu
Robotic Arm Draws Swarthmore Logo
Katherine Bertaut '12, from Silver Spring, Md., and Ames Bielenberg '12, from Hudson, N.Y., used a robotic arm to produce a unique version of the College's logo. The two, lab partners in Professor of Engineering Erik Cheever's Engineering Methodology course, made improvements to the existing arm and wrote controlling software for it. "We used Processing to write a friendly GUI that allows the user to either draw with the mouse or import SVG path data from a file," Ames says. "The software then traces the paths and sends the angles to the servos of the robotic arm." Ames made a time-lapse video of the arm, since the actual drawing took a little over a half hour to complete.
Submissions Welcome
The Communications Office invites all members of the Swarthmore community to share videos, photos, and story ideas for the College's website. Have you seen an alum in the news? Please let us know by writing news@swarthmore.edu.


Previously, we reported on the unexpected development of distant metastases in the subcutaneous rat pancreas CA20948 tumor model after 4.5 weeks of treatment with RAD001-only or in combination with [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE) (Cancer Res. 73:12-8, 2013). Moreover, the combination therapy was less effective compared to 177Lu-DOTATATE-only. In the current study, we address the following questions: (1) Why was the combination therapy less effective? Is 177Lu-DOTATATE tumor uptake affected by pretreatment with RAD001? (2) Could sudden cessation of RAD001 therapy cause the development of distant metastases? (3) Is 177Lu-DOTATATE an effective treatment option for these metastases?
Lewis rats (HanHsd or SsNHsd substrain with a slight difference in immune response) bearing subcutaneous CA20948 tumors were treated with either 125 or 275 MBq 177Lu-DOTATATE, RAD001, or their combination. RAD001 was given twice a week for 4.5 or 12 weeks, whereas 177Lu-DOTATATE was given as a single injection. When combined, RAD001 was started either 3 days prior to or 3 days post administration of 177Lu-DOTATATE. SPECT/CT was performed to quantify 177Lu-DOTATATE tumor uptake. Where indicated, primary tumors were surgically removed when tumor size is >6,000 mm3 to enable monitoring for possible metastasis. If metastases were suspected, an 111In-DTPA-octreotide SPECT/CT scan was performed. Seven rats with metastases were treated with 400 MBq 177Lu-DOTATATE.
Lu-DOTATATE tumor uptake was not significantly affected by RAD001 pretreatment. The occurrence of metastases after RAD001 treatment was not dose dependent in the dose range tested, nor was it related to the duration of RAD001 treatment. In the experiment in which the LEW/SsNsd substrain was used, only 12.5% of RAD001-treated rats showed complete response (CR), compared to 50% tumor regression in the control group. Re-treatment with a high dose of 177Lu-DOTATATE resulted in CR in only two out of seven animals.
Less effective anti-tumor effects after the combination of RAD001 + 177Lu-DOTATATE could not be explained by reduced 177Lu-DOTATATE tumor uptake after RAD001. Our current data support RAD001-induced immune suppression as the reason for this observation. No evidence was found that cessation of RAD001 treatment caused development of metastases. Metastases appeared to be less sensitive to 177Lu-DOTATATE treatment than primary tumors.
Neuroendocrine tumors (NETs) consist of a heterogeneous group of neoplasms originating from cells characterized by the synthesis and release of amines/peptides . Since 1973, the incidence of NETs has been increasing, in which genetic factors might play a role  and in addition improved diagnostics contributed to a higher registered incidence of NETs . Because NETs are slowly proliferating tumors, the prevalence of NETs is much higher than the incidence, resulting in a relatively high percentage of NET patients in the population of cancer patients . In >50% of the patients, NETs are diagnosed at a relatively late stage, often with metastatic spread , which leaves little chance for curative surgery. As a consequence of the slow proliferation rate, most NETs are relatively resistant to chemotherapeutics.
Most NETs are characterized by overexpression of somatostatin receptors, mainly subtype 2 (sst2). Targeting these receptors by administration of somatostatin analogs radiolabeled with, e.g., beta particle-emitting radionuclides, such as 177Lu or 90Y, allows peptide receptor radionuclide therapy (PRRT) of NET patients. This therapeutic approach is being performed since more than 10 years and has proven to be an effective treatment option in patients with inoperable disease. Therapeutic responses result in a significantly longer overall survival time compared to other treatments such as chemotherapy or external beam radiation therapy [4–6]. PRRT also improves patient's self-assessed quality of life . Although PRRT is a successful therapy, complete remissions (CR) in patients with metastasized disease are still rare, so there is an urgent need for improvement.
The combination of PRRT with the mammalian target of rapamycin (mTOR) inhibitor everolimus or RAD001 could be promising in this respect. Everolimus (RAD001) has recently received FDA approval for the treatment of pancreatic NETs. RAD001 has been reported to show anti-tumor and anti-angiogenic activity both in vitro as well as in vivo, since both tumor proliferation and tumor angiogenesis are regulated by mTOR . The clinical RADIANT III trial, a randomized, double-blind, placebo-controlled, multicenter phase III trial in pancreatic neuroendocrine tumor (PNET) patients, showed a median progression-free survival of 11 months after daily administration of 10 mg RAD001 plus best supportive care versus 4.6 months in the placebo group . Since it was shown that RAD001 may act as radiosensitizer in various tumor models , RAD001 and PRRT could have a synergistic effect. Antitumor efficacies of RAD001 treatment schedules in the CA20948 tumor model have been reported before by Boulay et al. . In this study, comparable anti-tumor effects were shown for twice weekly and daily RAD001 administration.
We have performed a combination study of the two treatments in the sst2-expressing CA20948 tumor-bearing rat model on which we recently reported the first data . In this study, we compared either 177Lu-DOTATATE, RAD001, or their combination for treatment of tumor-bearing rats. RAD001 was administered orally twice a week for 4.5 weeks, and a suboptimal dose of 177Lu-DOTATATE (leaving room for additional effect of RAD001) was given once. Unexpectedly, we observed that the majority (77%) of rats treated with RAD001 (single treatment or combined with PRRT) developed metastases. We have used this subcutaneous CA20948 tumor model in many PRRT studies for more than 10 years, and metastases never occurred before. We have hypothesized that a rebound effect after stopping the RAD001 treatment after 4.5 weeks initiated a metastasizing process. Furthermore, we observed that rats treated with the combination of RAD001 and 177Lu-DOTATATE showed less impressive anti-tumor effects compared to those treated with 177Lu-DOTATATE-only.
In the current studies, we performed additional in vivo experiments in the same rat model and obtained additional results from the previous studies. To find an explanation for the lower therapeutic effect of the combination vs. single 177Lu-DOTATATE therapy, 177Lu-DOTATATE tumor uptake was quantified in tumors with and without RAD001 pretreatment. Moreover, in LEW/SsNsd rats, we studied the effects of longer, i.e., 12 instead of 4.5 weeks, RAD001 treatment on the potential induction of metastasis.
The rat sst2-expressing pancreatic tumor CA20948 cell line  was cultured in Dulbecco's modified Eagle's medium (DMEM, Gibco, Invitrogen Corp., Breda, the Netherlands) supplemented with 10% heat-inactivated fetal bovine serum.
The animal ethics committee of our institution has approved all experiments. Male Lewis rats (250 to 300 g) were obtained from Harlan (Heerlen, the Netherlands). We used LEW/HanHsd Lewis rats, and where indicated, we also included rats from the LEW/SsNHsd substrain. In the LEW/SsNHsd substrain, the immune system shows an enhanced CD4+ and CD8+ T cell (auto)-immune response [13–17]. This autoimmunity is linked to an increased tumor immunity [18, 19]. One week after arrival, rats were inoculated subcutaneously with 107 CA20948 cells in 0.5 ml HBSS. For all experiments, animals were randomized into matching treatment groups with regard to tumor size at the start of treatment. A person blinded for the treatment measured tumor size using a calliper and weighed the rats three times a week. Tumor volume was calculated using the formula: 0.4 × length × weight × height. Tumor response was defined as follows: partial response (PR) as >50% reduction of tumor volume and complete response (CR) as 100% reduction of tumor volume. Tumors were allowed to develop until a maximum of 4 to 6 cm3 and were surgically removed where indicated. Rats were euthanized when >10% loss of body weight (BW) was registered.
2.5% Isoflurane/O2 gas anesthesia was used at 0.5 ml/min during tumor cell inoculation, administration of 177Lu-DOTATATE, scanning, or surgery.
When primary tumors were >4 to 6 cm3, surgical tumor resection was performed where indicated. During surgery, a heating pat was used to maintain body temperature. Routine shaving and disinfecting of the skin was performed. The tumor including the tumor capsule was carefully dissected from the surrounding tissue. After tumor resection, the skin was closed using individual sutures (vicryl 3/0).
RAD001 and its placebo, kindly provided by Novartis Pharmaceuticals, Basel, Switzerland, were used for study 1 and prepared according to the manufacturer's protocol. For the next experiments, RAD001 powder from LC laboratories, Woburn, USA, was dissolved in 2 ml ethanol and diluted with 5% glucose solution in water to obtain 3 or 6 mg/ml. RAD001 was administered orally by gavage in a volume of 0.2 ml; thus, 0.8 or 1.6 mg/rat or 2.5/5 mg/kg BW was administered depending on treatment group. For each administration, RAD001 was prepared freshly from powder.
DOTA0,Tyr3-octreotate was obtained from Mallinckrodt, St. Louis, MO, USA, and 177LuCl3 was obtained from IDB, Baarle-Nassau, the Netherlands. 177Lu-DOTATATE was prepared as described before , with a specific activity of 100 MBq/2.75 μg peptide, and injected iv via the tail vein under anesthesia. Labeling of 111In-DTPA-octreotide (OctreoScan, Covidien, Petten, the Netherlands) in a specific activity of 30 MBq/0.5 μg DTPA-octreotide was performed as described previously .
Forty-eight hours after injection of 177Lu-DOTATATE, helical single-photon emission computed tomography/computed tomography (SPECT/CT) scanning of the tumor region was performed with the four-headed NanoSPECT/CT system (BioScan, Washington DC, USA). Multi-pinhole rat collimators with nine pinholes (diameter 2.5 mm) per head were used: 24 projections, 90 s per projection, were applied. SPECT scans were reconstructed iteratively on a 256 × 256 matrix, using HiSPECT NG software (Scivis GmbH, Göttingen Germany) and ordered subset expectation maximization (OSEM). The total amount of radioactivity (MBq) in the tumor was quantified by drawing a sufficiently large volume of interest (VOI) around the tumor using InVivoScope software (IVS, Bioscan, Washington DC, USA). To achieve accurate quantification, the camera was calibrated by scanning a 20-ml polypropylene tube rat phantom filled with a known amount of 177Lu activity. The in vivo tumor volume was assessed by setting the lower threshold to 90% of the maximum voxel intensity of the tumor using the IRW program (Siemens, Erlangen, Germany). Before euthanasia, a whole-body SPECT/CT scan of rats was acquired 24 h after intravenous injection of 111In-DTPA-octreotide (50 MBq 111In/0.5 μg DTPA-octreotide) to detect CA20948 metastases. During scanning, the rat body temperature was maintained using a heated bed.
Autoradiography was performed on primary tumors as well as metastases. Frozen sections of 10 μm (Cryo-Star HM 560 M; Microm, Walldorf, Germany) were mounted on Superfrost plus slides (Menzel, Braunschweig, Germany) and incubated with 10−10 M 111In-DTPA-octreotide with and without an excess (10−6 M) of unlabeled octreotide. Adjacent sections were used for hematoxylin/eosin staining. Tumor sections were exposed to SR phosphor imaging screens (Packard Instruments Co., Meriden, USA) in X-ray cassettes. After a 48-h exposure, screens were read by a Cyclone phosphor imager and analyzed using OptiQuant 03.00 (PerkinElmer, Groningen, the Netherlands).
Prism software version 5.0 (Graph Pad) was used to analyze tumor growth and determine statistical significance between groups. An unpaired T test was used for statistical analysis of tumor uptake (Figure 1). Results are given as mean ± SD. A log rank test was performed for curve comparison in Figure 2A,B. Body weight data in Figure 2C are expressed as mean values.
Tumor concentration and quantification of sst 2 expression. (A) Tumor concentration of 177Lu-DOTATATE in rats receiving 177Lu-DOTATATE-only (light grey bar) and groups receiving 177Lu-DOTATATE 4 days after RAD001 therapy was started (dark grey bar). (B) Quantification of sst2 expression in primary tumors and metastases based on in vitro autoradiography. 177Lu-TATE, 177Lu-DOTA0,Tyr3-octreotate; RAD, RAD001 2.5 or 5 mg/kg; DLU, digital light unit.
Graphs showing percentage of rats having primary tumors and metastases, and mean body weight of animals. (A) Percentage of (LEW/SsNHsd Lewis) rats with primary tumors reaching the maximum size of >6 cm3 that underwent surgery afterwards to remove the tumor. The control group received saline. RAD001 therapy started at day 4 (5 mg/kg administered twice weekly). 177Lu-DOTATATE (125 MBq) was administered at day 1. (B) Percentage of (LEW/SsNHsd Lewis) rats developing metastases in each group. (C) Mean body weight of animals in the control group (black line) and of the rats treated with either RAD001 or a combination of RAD001 and 177Lu-DOTATATE that did not develop metastases (blue line) versus the body weight of rats treated with RAD001 or a combination of RAD001 and 177Lu-DOTATATE that developed metastases (red line).
An overview of the different research questions (A to E) and treatment groups in all studies (1 to 3) is given in Table 1 and described below.
177Lu-TATE, 177Lu-DOTA0,Tyr3-octreotate; RAD, RAD001; PRRT, peptide receptor radionuclide therapy; w, weeks.
To study whether RAD001 has an additional anti-tumor effect on 177Lu-DOTATATE, six different study groups were included with six to seven rats per group. Besides the control group and the RAD001-only therapy groups (5 mg/kg twice a week for 4.5 weeks), two groups received 177Lu-DOTATATE as a single therapy in different doses (125 or 275 MBq), and two groups received the same doses of 177Lu-DOTATATE combined with RAD001 treatment (5 mg/kg twice a week for 4.5 weeks starting 3 days prior to PRRT) . Rats were euthanized when tumor size exceeded 4 cm3.
Six additional groups of rats were included in the next study with seven to eight rats in each group. To enable prolonged follow-up, in this experiment, primary tumors were surgically removed when >4 cm3. This enabled longer follow-up to study the development of metastases in relation to the combination of 177Lu-DOTATATE and RAD001 or RAD001-only. RAD001 (2.5 or 5.0 mg/kg) was administered twice weekly for 4.5 weeks, either alone or 3 days prior to 125 MBq 177Lu-DOTATATE.
177Lu-DOTATATE uptake in tumors was quantified based on SPECT/CT scans acquired 48 h after administration of 177Lu-DOTATATE in experiments 1 and 2 to examine if previous RAD001 treatment results in reduced 177Lu retention in CA20948 tumors.
Five groups of eight rats were included. RAD001 (5 mg/kg) therapy was started 4 days after 125 MBq 177Lu-DOTATATE. RAD001 was administered twice a week and continued for either 4.5 or 12 weeks. Surgical resection was performed if tumors reached a volume of 6 cm3.
If rats in experiment 3 showed lethargy or a >10% body weight loss, SPECT/CT was performed using 111In-DTPA-octreotide. If metastases could be discriminated, 400 MBq/10.8 μg 177Lu-DOTATATE PRRT was given. Twenty-four hours after 177Lu-DOTATATE injections, SPECT/CT was performed to image 177Lu-DOTATATE uptake in metastases. Therapeutic effect was monitored by follow-up of body weight and 111In-DTPA-octreotide SPECT/CT when ongoing decrease in body weight was registered.
In experiment 1, treatment with RAD001-only did not result in any complete or partial anti-tumor responses, defined as follows: partial response (PR), which is >50% reduction of tumor volume, but no complete response (CR), which is 100% reduction of tumor volume (Table 2). Groups treated with 177Lu-DOTATATE-only showed 57% CR after 125 MBq 177Lu-DOTATATE and 71% after 275 MBq 177Lu-DOTATATE. Combination of 177Lu-DOTATATE and RAD001, however, resulted in only 29% CR after 125 MBq 177Lu-DOTATATE + RAD001 and 14% after 275 MBq 177Lu-DOTATATE + RAD001. So, in contrast to our hypothesis, no additive effect with regard to tumor response could be achieved by combining RAD001 and 177Lu-DOTATATE. Moreover, unexpectedly, all rats treated with the combination of RAD001 and 177Lu-DOTATATE and not showing CR eventually developed metastases as was reported earlier .
aRats did not survive until 42 to 146 days post start of treatment (p.t.), the time frame in which metastases became apparent in the other groups, because rats had to be euthanized when primary tumor size was >4 to 6 cm3. bPrimary tumors were surgically removed when tumor size was >4 to 6 cm3. CR, complete response (100% reduction of tumor size); PR, partial response (>50% reduction of tumor volume but no CR); n, number of animals/group; 177Lu-TATE, 177Lu-DOTA0, Tyr3-octreotate; RAD, RAD001.
Following prolonged monitoring after primary tumor removal, the majority (77%) of rats treated with RAD001 (either 5.0 or 2.5 mg/kg) developed metastases that resulted in mean body weight loss at around 43 days after start of treatment. For these two doses, no dose dependence of RAD001 was found (Table 2).
The 177Lu tumor uptake in 177Lu-DOTATATE-only-treated rats was 1.51 ± 0.07 kBq/mm3, while this was 1.42 ± 0.07 kBq/mm3 in rats pretreated with RAD001; no significant different values were found between the groups (p = 0.50, Figure 1A).
In contrast to previous experiments, 50% of the rats in the control group showed a CR. The rats from the combination groups (177Lu-DOTATATE + RAD001 for 4.5 weeks and 177Lu-DOTATATE + RAD001 for 12 weeks) showed a CR in 87.5% and 75% (not significantly different; p = 0.63) of the animals, respectively, in comparison to only 12.5% of rats in both RAD001-only therapy groups. Within these two RAD001-only groups, there was no significant difference regarding both the number of animals that needed surgery as well as the time until surgery.
With regard to development of metastases, at day 150 post start of treatment (p.t.), no metastases were detected in untreated rats (Figure 2B). Also, the time of appearance of the metastases in the combination group was later: 61 d p.t. vs. 91 p.t., respectively.
Monitoring the body weight of rats revealed the effects of treatment and the development of metastases. Rats in the control group showed a normal gain in body weight over time (Figure 2C). Rats treated with 177Lu-DOTATATE + RAD001 or RAD001-only not developing metastases also showed gain in body weight over time, although at a slower rate. However, the mean body weight of rats developing metastases stabilized as a result of their poor condition.
Although SPECT/CT confirmed significant uptake of 177Lu-DOTATATE in metastases (Figure 3), in only two of the seven rats, there was CR after re-treatment with high-dose 177Lu-DOTATATE. The average survival time of the non-responsive rats after detection and treatment of the metastases varied between 8 and 37 days, with an average of 27 days. One rat with CR recovered from a liver metastasis that was clearly visualized after administration of 177Lu-DOTATATE. Eight days later, there was no sign of this lesion as shown in the 111In-octreotide scan, which was confirmed after dissection. On the other hand, a rat suffering from lung metastases did not respond to 177Lu-DOTATATE. Eight days after re-treatment, further loss in body weight was measured and the 111In-DTPA-octreotide SPECT/CT still showed extended lung metastases, also found at autopsy. Determination of sst2 density on CA20948 primary tumors and metastases using in vitro autoradiography revealed no significant differences (Figure 1B).
Two representative sets of SPECT/CT scans of rats before and after re-treatment with 177 Lu-DOTATATE. The two images at the left represent a rat with liver metastasis; the lesion was not detectable anymore on the scan with 111In-DTPA-octreotide made 8 days after 177Lu-DOTATATE PRRT. The two images at the right represent a rat treated for lung metastases. On the right, scan after injection of 111In-DTPA-octreotide was made before euthanasia of the rat because of ongoing weight loss. LuM, lung metastasis; LiM, liver metastases; Kd, kidney.
We previously reported on the disappointing results of the combination of mTOR inhibitor RAD001 with 177Lu-DOTATATE PRRT in the CA20948 rat tumor model. No hypothesized synergistic effect was found; the combination treatment appeared even less effective than 177Lu-DOTATATE-only. This observation cannot be explained by reduced 177Lu-DOTATATE uptake in the subcutaneous CA20948 tumors after RAD001 treatment, as we demonstrated here (Figure 1A).
Even more striking was the fact that the majority of RAD001-treated animals developed tumor metastasis to lymph nodes, liver, and/or lung. RAD001 initially has been introduced as an immunosuppressant to protect patients from rejecting allografts after organ transplantation . In 2005, Law et al.  reviewed the immunosuppressive effects of RAD001 in relation to its anti-tumor effects and discussed immune suppression by RAD001 to be tumor growth accentuating. Therefore, the application of RAD001 as an anti-tumor agent should be monitored carefully in the clinic, but to the best of our knowledge as yet, no tumor accentuating effects in patients have been reported. Recently, after the publication of our priority report on our first findings, RAD001 has received FDA approval for the treatment of advanced NETs and is commonly used in clinical practice nowadays. Although we must consider the fact that RAD001 is used in patients with already advanced (metastasized) disease, so far, no reports on accelerated metastasis in patients related to RAD001 treatment have been published. We earlier hypothesized multiple reasons for the occurrence of metastases: the twice-weekly dose regimen instead of daily dosing as is applied in clinical therapy, effects of RAD001 on the immune system and/or tumor microenvironment, or the discontinuation of RAD001 treatment at 4.5 weeks after start of treatment. In the current studies, we compared 4.5 weeks of RAD001 treatment with 12 weeks of twice-weekly RAD001 treatment. This prolonged RAD001 treatment (with or without 177Lu-DOTATATE therapy) did not reduce the number of rats developing metastases, and in addition, no delay in the occurrence of metastasis was seen. In fact, comparison of the 4.5-week RAD001 groups versus 12-week RAD001 groups showed a higher percentage of rats developing metastasis in the 12-week RAD001 groups than in the 4.5-week RAD001 groups, namely, 38% vs. 25% (p = 0.45). The average time until detection of metastases was also not significantly different between groups receiving RAD001 for 4.5 weeks (82 days p.t.) versus 12 weeks (78 day p.t.). Moreover, in 67% of the rats developing metastases in the 12-week treatment groups, metastases were diagnosed while rats were still receiving RAD001. Therefore, it is unlikely that the occurrence of metastases is due to cessation of RAD001 administration. Potentially, the twice-weekly administration could lead to a repetitive on-off effect on the mTOR pathway with repetitive upregulation/rebound effects of the mTOR pathway with varying plasma concentration levels of RAD001 in a twice-weekly dose regimen . In future experiments, a daily RAD001 dose regimen will have to be compared to the twice-weekly dose regimen as was used in the current studies.
Compared to a treatment with RAD001-only, less animals receiving a combination of 177Lu-DOTATATE and RAD001 developed metastases, and mean time to diagnosis for those metastases was 30 days later compared to the rats receiving RAD001-only. Results from the combination therapy groups with 177Lu-DOTATATE administered 4 days before RAD001 therapy suggested that 177Lu-DOTATATE administered prior to RAD001 therapy reduced both incidence and time of onset of metastases in comparison to the reverse order combination. When 177Lu-DOTATATE was administered 4 days after RAD001 therapy, however, there was no reduction in the percentage of rats developing metastases in the combination therapy groups, indicating that rats with (some) tumor reduction already induced by PRRT were less likely to develop metastases than rats not treated with PRRT. This is in agreement with the fact that animals that showed CRs after PRRT or PRRT plus RAD001 did not develop metastases during follow-up.
In studies 1 and 2, we used a syngeneic tumor model in rats with an uncompromised immune system. A significant role for T lymphocytes in the immune response to tumors after or during ionizing radiation therapy has been described, the latter resulting in upregulation of tumor-specific antigens [25–29]. As immune suppression by RAD001 has been proven to be mainly due to suppression of T lymphocyte activation and proliferation [30, 31], in our opinion, immune suppression by RAD001 is a likely explanation for reduced tumor response to PRRT in combination with RAD001 as observed in our study. In studies 1 and 2, LEW/HanHsd rats were used, whereas in study 3, the LEW/SsNHsd substrain was used, providing the opportunity to test the hypothesis mentioned above. In this substrain, the immune system is more active compared to the HanHsd strain and shows an enhanced (auto)-immune response [13–17]. In these rats, 50% of tumors in the control group went into spontaneous regression after reaching an average tumor volume of ≈ 3 cm3, probably due to an immune response against the growing tumor. In such rats treated with RAD001 (4.5 or 12 weeks), only 12.5% of the tumors went into regression. In a mouse model on rejection of an allogeneic subcutaneous tumor as created by Hammond-McKribben et al. , another mTOR inhibitor, the rapamycin derivate SDZ RAD, was used to prevent rejection of allogeneic tumors. So, immune suppression by RAD001 might have caused the reduced tumor response in our study with 177Lu-DOTATATE administered after RAD001 as well.
Contrary to our results, a combination of ionizing radiation (IR) with rapamycin has been proven to be more effective than IR-only in preclinical studies [10, 32, 33]. These studies however have been performed in xenograft models using immunodeficient mice lacking T cells.
As discussed in our priority report, reduced cell proliferation rate caused by a G1 arrest could also be an explanation for the reduced tumor response to 177Lu-DOTATATE in rats treated with the combination of RAD001 and 177Lu-DOTATATE. RAD001 treatment has been shown to cause a G1 arrest, as mTOR is being linked to phosphatidylinositol 3-kinase (PI3K) pathways . Within 24 h after RAD001 administration, a significant increase of cells in G1 phase has been described [35, 36]. As cells with a long cycling time, including NET cells, have a peak of radioresistance during early G1 phase , tumor cells may have been less sensitive to 177Lu-DOTATATE when administered 4 days after the start of RAD001 treatment. Since clinical trials combining RAD001 and PRRT are being performed , in our opinion, the decreased anti-tumor response in our study when RAD001 was administered prior to 177Lu-TATE is rather relevant. Also, in a clinical situation, the combination of both therapies might be less effective compared to just PRRT.
For re-treatment of the rats with metastases, we used a dose of 400 MBq 177Lu-DOTATATE, which is remarkably higher compared to the initial 125 or 275 MBq treatment doses. Still, only two out of seven rats with metastases were cured, suggesting metastases in our model to be more resistant to PRRT compared to the primary tumor. As it is quite complex to study responses of metastases in a preclinical model, there have not been many preclinical studies on therapies in metastatic models. However, to be able to get more solid information on sensitivity of metastases to PRRT in a preclinical model, certainly more studies in different models are necessary. The current CA20948 metastatic tumor model after RAD001 treatment could be a more realistic metastasis model for future experiments compared to often-applied metastasis tumor models in which tumor cell suspensions are injected intravenously.
Results described here confirmed and provided more information on development of metastasis after RAD001 treatment in our in vivo rat tumor model. The impaired tumor response to the combination of RAD001 and 177Lu-DOTATATE in comparison with that after 177Lu-DOTATATE-only could not be attributed to a reduced tumor uptake of 177Lu-DOTATATE in rats after RAD001 treatment. Moreover, the occurrence of metastases could not be attributed to the sudden cessation of RAD001 treatment, as we observed treatment for 12 weeks did not result in a lower metastasis rate compared to treatment for 4.5 weeks. Immune suppression by RAD001 could be a good explanation for reduced tumor response after RAD001 as well as for development of metastasis. More studies in different tumor models are needed now to provide proof and give detailed information on the translational value of these findings to the clinic.
SMB and SEP are the first authors.
SEP and SMB performed part of the animal experiments, participated in the design of the studies, and wrote the manuscript. SJK performed the animal experiments, SPECT/CT scanning, and data interpretation. LvdG performed the in vitro autoradiography (including quantification) and interpretation. HCG performed the quantification of SPECT data. MM and MdJ participated in its design and coordination and helped draft the manuscript. All authors read and approved the final manuscript.


text:
Our efforts are strengthened through small and big contributions from our partners.
National & Regional Icons
With the aim of creating awareness and motivating the masses to participate in the electoral process, popular public figures like former President Dr. A P J Abdul Kalam, sportspersons Shri M S Dhoni, Ms Saina Nehwal, Ms MC Mary Kom and film actor Shri Aamir Khan have been designated as ECI's National Icons. In addition, several artists, sportspersons, actors, musicians and public figures have become the face of SVEEP initiatives in the States.
Click here for the list of National & Regional icons
Corporate Houses & Federations
Realising the catalytic role Public Sector Enterprises and Corporate Houses could play in enhancing citizen engagement, a Framework of Engagement was developed in 2013 for collaboration with the Corporate Houses in the field of voter education and participation. Ahead of the Lok Sabha elections 2014, a national level partnership was forged with various federations like FICCI, CII, NASSCOM, ASSOCHAM, TATA Global Beverages and CELL.
Media Houses/ Radio and TV Channels
Zee Media Corporation Ltd was the first media house to partner with ECI which was further strengthened during the Lok Sabha Elections 2014 through the ZEE campaign 'Apka Vote ApkiTaaqat'. RED FM 93.5, Digital Radio (Delhi) Broadcasting Ltd carried out an intensive awareness campaign 'Button dabaakebajaa' during the same elections. Television channels like ET NOW and CNBC-TV 18 also contributed to ECI's efforts through short films and audio-visuals on voter awareness.
In the bygone elections, there have been successful collaborations with various government departments and organization that have enabled SVEEP to reach out to a wider population with its messages of voter awareness and education. These collaborations have been in terms of creation of multimedia products, broadcasts and most importantly the lending of support by the human resource for one-to-one interaction with the voters and their subsequent empowerment.
Click here for a list of all the Government Departments SVEEP has collaborated with so far
Non-Government Organisations/ Civil Society Organisations
In addition to numerous NGOs, CSOs, RWAs, groups and individuals who support the efforts of election managers in the State and Districts for voters' education through their voluntary and partnered work, United Nations Development Programme has been a significant partner for SVEEP initiatives, especially for production of voter edutainment material, publications and organising voters' festivals.


The Endocrinology laboratory performs assays to measure various hormones, tumor markers, and infectious disease serologic markers. The lab also offers specialized chemistry testing services such as Hemoglobin A1c, Maternal Serum Screening, and Allergy Testing for specific IgE against a wide range of allergens (tree, weed, grass pollens, animal dander, dust mites, and molds). Technology available within the laboratory includes a variety of fully automated chemiluminescent immunoassay platforms and HPLC.
• Maternal Serum Screening program determine risk factors for fetal open neural tube defects, as well as risk of chromosome 21 and 18 aneuploidies, in single pregnancies between 15 and 22 weeks of gestation. Measurement of four biochemical markers (Quad screen includes Alpha fetoprotein, human chorionic gonadotropin, unconjugated estriol, and dimeric Inhibin-A) and maternal demographic information are evaluated in Maciel Prenatal interpretive Software.
• The Endocrinology Laboratory coordinates with clinical staff in Endocrine and Oncologic Surgery and Interventional Radiology to offer rapid turnaround time on intra-operative measurement of Parathyroid Hormone and Cortisol for Parathyroidectomy and Adrenal Vein Sampling cases, respectively. Integrated processes with clinical staff and rapid TAT provide a positive impact of patient outcome, by improving surgical success rates.
• Offers Parathyroid Hormone, male and female reproductive hormones, as well as Insulin, C-peptide, and Hemoglobin A1c for the diagnosis and management of diabetes. Hemoglobin A1c is the highest volume test, with over 90,000 tests performed this year.
• Offers tumor marker testing for Colorectal, Pancreatic, Testicular and Ovarian, Breast, and Thyroid cancers amongst others. Focus on stringent quality control and acceptance of reagent lot numbers ensures precise and accurate results for longitudinal monitoring.


Looking to jump start Chinese learning for young students? My First Chinese Reader 快乐儿童华语 is a proven Chinese as a Foreign Language (CFL) textbook series designed to introduce students to Chinese.
The vivid My First Chinese Reader series engages young Chinese language students and allows individuals to learn at their own pace. This innovative curriculum is full of exciting illustrations, audio recordings, interactive tools, and practice exercises that encourage students to develop both practical communication skills and an understanding of Chinese culture. Beneath the fun and dynamic framework is a rigorous, standards-based curriculum that delivers strong learning results.
Named the best CFL resource by over 1,000 experts, the series has also been adopted by multiple states across the United States. Now available as an eBook! This platform incorporates additional video, audio, and activities. Learn interactively, everywhere.


text:
Q: Build correct JSON I try to render a correct formatted json:
   render json: {photo: @photo.as_json(with_thumbs_url: true)}

In my model I have to do this:
  def as_json(options={})
    if options[:with_thumbs_url].present?
      Jbuilder.encode do |json|
        json.(self, :id, :beschreibung, :date, :art)
        json.thumbs self.photo_thumbs.map{|e| e.file.url(:medium)}
      end
    end
  end

My problem is that like this it returns:
 {photo: "{"id":288,"beschreibung":"Anfang","date" ...system/photos/6267/medium/136.webp?1413823129"]}"}

What i dont like about this JSON is that photo in the Json is rendered as String:
        "{"id":288,"beschreibung":"

I would prefer to have it not encoded, for example like this:
  {photo: {id: "288", beschreibung: "Anfang" ...

I would say the problem is my code: The encode:
   Jbuilder.encode do |json|

So in order fix my problem i tried:
   Jbuilder.new do |json|

But then I get a error in:
   render json: {photo: @photo.as_json(with_thumbs_url: true)}

   wrong number of arguments (0 for 1..2)

What do I wrong and how can I fix my code? Thanks

A: In order to make it work i had to change my code to:
def as_json
  Jbuilder.new do |json|
    # your stuff
  end.attributes!
end

redpajama_set_name: RedPajamaStackExchange