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Category: commerical
In 2020, Cannabis Construction Must Offer Security of a Bank, Compliance of a Pharmaceutical Company, Aesthetic of a High-end Retailer
Legal recreational cannabis is a new industry in Illinois—and it's in dire need of customized facilities. The first month of recreational cannabis sales in Illinois amounted to nearly $40 million. Sales figures spell opportunity both for cannabis companies and for experts in building special-purpose facilities for the industry's stringent regulations and experience-driven customers.
Andy Poticha, Principal at Cannabis Facility Construction (CFC) has been involved in more than 30 cultivation, processing center and dispensary projects in eight states since 2015. He's leading renovation projects that offer Illinois more than 35,000 new square feet of cannabis cultivation areas and dispensaries customized for the needs of recreational cannabis customers.
"To become recreational cannabis users' preferred dispensary, new cannabis license holders must prioritize both compliance and customers in their facility design," Poticha observes. The design/build process must support two core objectives:
- Prioritize compliance or suffer the consequences. To maintain product supply and operational retail sales, stick to strict protocols and carefully follow building codes related to the handling, storage and distribution of cannabis throughout the supply chain.
- Offer a differentiated customer experience. Product commoditization and restricted in-state cannabis sourcing leads to stiff competition between dispensaries.
"Cannabis companies need to offer the security of a bank branch, the compliance of a pharmaceutical company, and the aesthetic of a high-end retailer," said Poticha. "Designing for the customer experience, creating welcoming sales environments that are compliant with regulations, is where dispensaries can find true opportunity to differentiate themselves from the competition
For nearly five years, CFC has worked with numerous cannabis companies, including Grassroots Cannabis, a vertically integrated multi-state cannabis company. For co-founder Mitch Kahn, CFC has helped Grassroots embrace these seemingly competing objectives into a cohesive customer experience.
"Partnering with CFC, we have been thoughtful about connecting the design/build process with our customer experience and compliance objectives," said Kahn. "Together, we identified and solved potential issues early in the design/build process, so that the build-out is supportive of sales, security, and being good neighbors in our communities."
Stipulated Sum Agreements Make Us the Right Builder for You
Our goal as a design-build firm is to create value for our clients through outstanding service-delivery and building trusted relationships. One of the many ways we achieve our goal is how we structure our contracts. Our clients want to know what they're paying for, and we are able to clearly spell that out by providing stipulated sum agreements.
What is a Stipulated Sum?
Also referred to as a lump sum contract, a stipulated sum requires a builder to agree to provide specified services for a fixed price based on labor and material costs. The builder is responsible for executing the job properly and will provide its own means and methods to complete the project. Specifically, we use stipulated sum agreements with our multifamily and commercial projects, and they allow us to better define the scope and schedule of projects.
"The Mosaic Construction way is to be a client-first company in which we anticipate needs and focus on relationship-building," said Singer. "We've always led with this approach, and our clients understand the value of that." – Ira Singer
Why We Use Stipulated Sums
Mosaic Construction uses stipulated sums so that our clients know what they're getting, and we know exactly what we need to deliver. Our contracts are predictable and easy to manage and benefit our clients in the following ways:
No Hidden Fees
One of Mosaic Construction's key differentiators is that we never stick our clients with hidden fees, compared to cost-plus-fixed-fee and other contracts. "Our fees are transparent compared to other contractors," said Ira Singer, Principal of Mosaic Construction on the This is the Real Estate Investing for Cash Flow podcast. "We have no incentive to say, 'Okay, it's going to be this much money for cost.' Stipulated sums are integral in forging trusted relationships with our clients."
Our clients value the predictability of stipulated sum agreements, especially since they reduce risk and give them more confidence. With an agreed upon sum in place, our clients are not liable for any cost overruns. "We formulate construction based on our time and our investment to manage that project and steward it," added Singer. "Whatever the cost of the project, our timeframe for completion and our fees will remain the same. In this respect, both parties are incentivized to stay on schedule and finish the job on time."
Better Collaboration
We find that stipulated sum arrangements foster a greater degree of collaboration between Mosaic Construction and our clients. We are able to execute tight project management and more efficient communication to ensure that both parties are adhering to the scope of work. "The Mosaic Construction way is to be a client-first company in which we anticipate needs and focus on relationship-building," said Singer. "We've always led with this approach, and our clients understand the value of that."
The design-build methodology supports our goal because it allows us to streamline the construction process, which ultimately benefits our clients and our management team. "We view our projects as investments in our clients' growth and development," added Singer. "We never think in terms of being one and done; rather, we create an atmosphere where our clients can focus on business development, while we do the best work possible for them."
Protecting Your Building Exterior from Winter Elements
Winter is here.
Whether or not the North Carolina Blizzard of 2018 is a harbinger of snow storms throughout the country, you can never prepare your building enough for the season ahead. It starts with fully inspecting the building exteriors, including the roof, walls, and door and window frames, and paying special attention to other parts of the building, including:
Fortifying the Roof
Winter weather can wreak havoc on roofs, making building exteriors and interiors vulnerable to damage from leaks. Snow or ice accumulation, even as it melts, disrupts normal drainage paths, and blocked gutters can redirect it to parts of the building ill-equipped for drainage.
Blocked drains create further problems like concealing standing water which can cause a collapse if the water gets too deep. Adding slope to a roof can help drainage and prevent overload caused by the weight of snow and ice. Take precautionary measures by sealing the edges of high slope roofs to mitigate the risk of ice damming, and installing snow guards to prevent heavy snow layers from migrating to the gutters.
Keeping Lobby Entrances Clean
As the face of your building, it's important to protect lobby entrances. The foot-traffic in lobbies creates wear and tear on its floors, especially when salt and sand used to treat pavement are tracked in. The answer is laying down safety mats and rugs with efficient spacing. Matting best practices advise 5 to 10 feet of coarse matting outside a building, 5 to 10 feet of matting directly inside the building and another 5 to 10 feet of matting directly behind it.
Protecting Your HVAC System
Your building's HVAC system is pivotal to the comfort and safety of tenants and guests. In addition to maintaining temperature and air quality, an HVAC system serves as the first line of defense against inclement weather.
In an interview with Buildings, Kevin Miskewicz, Director of Commercial Product Planning at Mitsubishi Electric, notes that "Properly protecting your HVAC system from extreme weather conditions can improve its performance and lifespan. Investing in snow hoods, wind baffles and outdoor unit stands prevents snow and ice from getting inside the equipment and potentially causing damage."
Thinking Through the Entire Process
Optimizing the conditions of roofs, lobby entrances, and HVAC systems are measures that will help protect exterior areas of buildings. More importantly, they will contribute to the safety of building occupants. To that end, here is a concluding safety tip:
Have a rock-solid snow removal plan. Leftover snow can freeze into ice, increasing the chances of slip-and-fall injuries. Snow drifts obstruct important signage and can conceal fire hydrants and handicap parking spaces.
How to Attract Tenants With Your Lobby Design
First impressions are everything.
When prospective tenants enter a residential or commercial building, they walk through the lobby first, formulating opinions quickly. A unit or office may be beautiful, but the lobby serves as the face of your property and should accurately depict your company's brand and culture.
Follow these best practices to attract tenants with your lobby design:
Create an Inviting and Clean Space
Every lobby should have a welcoming vibe that is felt from outside and inside its doors. Appealing to the senses, especially sight and smell, seems like stating the obvious but is often overlooked. Hiring the right maintenance, cleaning, and landscaping companies is key to upholding the image of your property. It starts with the outside. Similar to the curb appeal of a house, maintaining the building's exterior with improvements to the green areas, for example, can enhance the appearance of your property. Keep sidewalks, walkways, and steps swept of debris as well. Inside, floors, surfaces, and walls should be spotless. In addition, designing the interior with indoor plants and art can create a more aesthetically pleasing environment for tenants.
Make Your Lobby an Extension of the Community
Knowing your neighborhood goes a long way with tenants. When you adapt your lobby to your neighborhood, be it an urban or suburban environment, you foster community, according to Building Design + Construction. they write,
"Create a brand and a place that amplifies the unique qualities of your neighborhood."
A property located in an urban environment with a wide variety of entertainment, dining and socializing opportunities should feature a lobby that complements those easily accessible amenities, while providing options that will benefit the larger community and bring visitors, commerce and new interest to your building.
Host Lobby Events
People are attracted to a crowd, and when they see others gathering in a space, it piques their curiosity. Whether for an office or condo building, lobby events provide an opportunity for face-to-face interactions with current and prospective tenants. Kirk Layton, President & Founder of the Canadian-based Eservus Online Concierge Services, says this personal touch is much stronger than a building newsletter or tweet. "You only have a few seconds to grab people's attention in the building lobby…after all, tenants in the lobby are always on their way to somewhere else – to work, to lunch or to a meeting – which makes it difficult to capture their attention," he writes. "Lobby events are an indispensable part of a property manager's tenant engagement strategy."
The Bottom Line
The design of your lobby presents an ongoing opportunity to attract and retain tenants. In today's ultra-competitive market, demonstrating that you care about tenant comfort and their needs through strategic design is a significant differentiator.


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Alcohol Gallery
Available as Framed Prints, Photos, Wall Art and Gift Items
Choose from 427 pictures in our Alcohol collection for your Wall Art or Photo Gift. Popular choices include Framed Prints, Canvas Prints, Posters and Jigsaw Puzzles. All professionally made for quick delivery.
Chelsea Pensioners with 'black jacks', London, c1901 (1901). Artist: Unknown
Chelsea Pensioners with 'Black Jacks', London, c1901 (1901). Pensioners at The Royal Chelsea hospital with two 5 gallon 'black jacks', leather jugs formerly used for bringing ale up to the Great Hall from the beer cellar below. From Living London, Vol. 1, edited by George R. Sims. [Cassell and Company, Limited, London, Paris, New York & Melbourne, 1901]
© The Print Collector
'Monsieur Boileau at the Café', 1893, (1952). Creator: Henri de Toulouse-Lautrec
'Monsieur Boileau at the Cafe', 1893, (1952). Portrait of a man sitting at a table with dominoes, in Paris. The green drink is probably absinthe. Painting in the Cleveland Museum of Art, USA. From "Henri De Toulouse-Lautrec" by Douglas Cooper. [Thames and Hudson, London, 1952]
© The Print Collector/Heritage Images
19th Century, Absinth, Absinthe, Alcohol, Art, Arthur William Douglas, Arthur William Douglas Cooper, Arts, Board Game, Bowler Hat, Cafe, Cafu, Century, Clothes, Clothing, Color, Colour, Concept, Cooper, Cooper Arthur William Douglas, Cooper Douglas, Country, Demi Monde, Demimonde, Dominoes, Douglas, Douglas Cooper, Douglas Lord, Dress, Drink, Fin De Siecle, Fin De Sipcle, Fin De Siþcle, France, French, Game, Glass, Gouache, Green, Green Colour, Guy, Hat, Henri De, Henri De Toulouse, Henri De Toulouse Lautrec, Henri Marie Raymond De, Henri Marie Raymond De Toulouse Lautrec Monfa, Impressionism, Impressionist, Indoors, Inside, Interior, Lautrec, Lautrec Henri De Toulouse, Location, Lord, Lord Douglas, Male, Man, Men, Nightlife, Nineteenth Century, Paris, Parisian, Pastime, People, Post Impressionism, Post Impressionist, The Print Collector, Toulouse Lautrec, Toulouse Lautrec Henri De, Toulouse Lautrec Monfa, Toulouse Lautrec Monfa Henri Marie Raymond De
Tilly in Rothenburg, 1631, (1936). Creator: Unknown
Tilly in Rothenburg, 1631, (1936). Woman pleading with Count Tilly in Rothenburg ob der Tauber, Germany. Catholic commander Johann Tserclaes, Count of Tilly (1559-1632) wanted to burn the city of Rothenburg, and condemned the city councilmen to death. The councillors, in an effort to appease him, offered him wine in a large cup. Tilly challenged anyone to drink all the wine in one go, and promised that if it was done he would spare the city. The mayor, Georg Nusch, succeeded in emptying the cup and so saved his city. The events have been commemorated annually since 1881 in the play "Der Meistertrunk" (The Master Draught). From "Bilder Deutscher Geschichte", (Pictures of German History), No.12, cigarette card album. [Cigaretten-Bilderdienst, Altona-Bahrenfeld, Hamburg, Germany, 1936]
© The Print Collector/Heritage Images

subset: commoncrawl


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Posted March 4th in Diving Internships
With the Full Moon approaching and currents stirring up the bottom, visibility at depth has been a little murky over the past days.
But the dive internships gang here at Simple Life Divers still had a lot of fun making a wreck dive off Koh Tao.
The HTMS Sattakut is a former Thai naval vessel which was sunk as an artificial reef a little way west of Sairee Beach. She now rests upright in 30M of water, close to the Hin Pee Wee dive site. Even when there is a thermocline and low visibility at the bottom, its still a great dive and a nice contrast to our coral reefs and submerged pinnacles.
You too can join our dive internship teach -- no previous experience required: Divemaster internship in Thailand.
Baden Ramm
PADI Master Instructor, Aqualung Technician, retired mining engineer, BBQ Guru and all-round Aussie Legend.
Posted in Diving Photos
There's so much cool stuff to see whilst scuba diving around Koh Tao. Hawkbill turtles are common around the dive [...]
Posted in Diving Courses
Paulina (US), Toby (originally from the UK) & Aude (Canada) are going through their PADI Open Water Diver course here [...]
Posted in Diving Internships
As part of the PADI Instructor Development Course, today Course Director Julian has had the candidates practicing running the PADI [...]
Posted in Diving Courses
Instructor Rodrigo rounded off Nicolas and Pataraporn's PADI Open Water course in Koh Tao, making an amazing dive at the [...]


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St Lucia Travel Diary
This month we are grateful to have Consonant Skincare sponsoring weekly Travel Diaries. Check out HHP on Facebook to score a free, perfectly packaged travel kit of organic skincare for your next adventure. All you have to do is tell me your fave vacation spot!
For someone who is terrified of flying, I seem to travel quite a bit. Look forward to weekly Travel Diary posts about destinations from Europe, to the Caribbean, and everywhere in between. Here is my St. Lucia Travel Diary to help you get a sense of what my trip was like, and perhaps score some intel on what to do (or what to avoid).
"Who takes a helicopter to get to their hotel?" I gasped to my man upon landing at Hewanorra International Airport in St. Lucia. We were headed to the Sandals lounge to wait for our automotive shuttle to one of their three resorts on the island when we happened to notice that there was helicopter transport.
Don't get me wrong; with my fear of flying/boats/extremely tall buildings the likelihood of getting me on a helicopter is pretty much "nope." Chalk it up to honeymoon exuberance, I figured.
But then we got in to our microbus shuttle and realized that there is no direct, straight-through-the-island route to the resorts. Rather, you spend nearly two hours up and down winding mountain roads. With the Gravol locked in my suitcase, the helicopter was suddenly sounding like a great idea.
Where I Stayed
During this trip, we were able to take advantage of having multiple Sandals resorts on the island. We stayed at the La Toc property, known for its golf. My man and I are beach people, so we spent most of our time at another location. Here's the rundown:
Regency La Toc
- Pros: Newer feel, great food (we were told by other guests this resort had the best food out of the three).
- Cons: Very limited poolside chairs often reserved by the butler service before 6am. Pretty much a non-existent beach (very small, red flags and heavy waves for days).
- Pros: Closer to the La Toc property (both are in Castries).
- Cons: Older feel. We spent a couple of hours here and just opted to go back to the Grande.
Grande St. Lucian
- Pros: The best beach out of all three – we spent majority of our time here.
- Cons: Older feel. Furthest from our hotel so the shuttle trips were a bit tedious.
Our tendency had been to book trips fairly last minute, and for this trip we were unable to get the Club Level service we had experienced in the Bahamas. Although it is fairly easy breezy to hit up the drop-in restaurants, it was quite frustrating not to be able to get reservations otherwise. Not having that level of service while still paying a hefty premium "luxury included" price tag didn't jive for me.
When I Went
This trip took place in May, and the weather was excellent. No complaints!
Who I Traveled With
I traveled with my man during this trip (naturally for a couples resort, right?). If you meet us in person, ask us about the pigeon.
What I Did
This trip will forever be etched in my memory for an excursion where I honestly thought I was going to die. We booked a day trip through the front desk (Island Routes is part of Sandals). It was supposed to be a "short" boat ride to Martinique. Except, by short they actually secretly meant "over an hour and a half." You can read about my prayers for safe passage in my Martinique Travel Diary.
Aside from exploring Martinique, we spent a lot of time hanging out at the beach. We rented a very dodgy jet ski which was rather concerning when we saw one fail (or run out of gas). My man loves his horsepower toys, so this was definitely a moment where I just grinded my teeth and braced myself.
One thing that the Sandals chain does really well is try to create activities and events on-property – whether a little fashion show, or a Newlyweds Game, or a night market of food from the different regions of the islands. Anything involving food or dessert is really the go-to for me, so this won me over.
There are a ton of different options and tours – from Joe Knows to exploring the Pitons yourself.
How I Got Around
We booked our trip to fly down through our beloved West Jet (YYZ à UVF). Like you've learned, the car ride to the resort was nausea-inducing and should really be reconsidered for those who get car sick (Chopper! Chopper! Chopper!). All other time was spent in the same mini bus type of shuttle, whether heading to other resort properties or to Marigot Bay to catch the demon catamaran to Martinique.
Travel: F (damn road and sea travel)
Accommodations: B+
Food – On Resort: A-
Food – Off Resort: B
Activities: B (boat-hate aside, we didn't really do many activities)


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OSU Extension Announces Agriculture and Natural Resources Madness: A Tournament of Education
tournament? Ohio State University Extension is here to help with a new virtual education program for farmers. ... Sciences (CFAES), and works to share knowledge with every county in Ohio. Its four major program areas are ... The education tournament is free of charge and will likely continue until mid-May. "This effort is ...
Control Poison Hemlock Now
plant (sometimes perennial), emerging from seed in year one and developing into a low-growing rosette by ... information and recommendations regarding control of poison hemlock. "Poison hemlock remains one of the more ... persistent and prevalent poisonous weeds that we deal with in Ohio. It's most typically a biennial ...
made to cancel all Ohio State University Extension in-person programming through July 6. This includes ... positive youth development programming, we share your sense of loss. Given the available information, we ... our summer programming. As announced on social media today, Ohio 4-H did release 18 of the project ...
Zhao and Chen receive Ohio State University Outreach and Engagement Award
Engaged Program Award from The Ohio State University Office of Outreach and Engagement. The team is led by ... Engineering. The Community Engaged Program Award recognizes outstanding achievement by faculty, staff and/or ... student led programs/initiatives focused on community-university partnerships and impact. "Our green home ...
Backyard Poultry Production
Check the Backyard Poultry Production page for your backyard poultry information! ...
Milk Prices, Costs of Nutrients, Margins and Comparison of Feedstuffs Prices
software program SESAME™ developed by Dr. St-Pierre at The Ohio State University. The resulting analysis ... 2020. Economic Value of Feeds Results of the Sesame analysis for central Ohio on March 26, 2020 are ... April Frye White, Graduate Research Associate, Department of Animal Sciences, The Ohio State ...
On Farm Biosecurity to Keep Us and Employees Safe
Veterinarian, The Ohio State University Extension Agriculture is no stranger to contagious disease. Drawing on ... tried and true disinfection protocols, we can all stay healthy. One big difference is that instead of ... disinfecting our boots, we need to disinfect all surfaces around us and all our employees touch. This may also ...
Adjusting to the New Normal
school are now it home, and everyone is sharing everything 24/7. They have a developed a gratitude jar ... discombobulated if you don't keep your schedule. Your commute may have been a time to decompress. With your ... warms, spending time outside may offer a new work opportunity. Sit on the swing or patio or porch and ...
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Fairfield County Extension Office and Calendar Updates
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In this paper, we address the development of an integrated sensing system for the airbag deployment decision in an intelligent vehicle with focus on passenger and driver airbags in vehicles. The innovation provides a cost-effective system for deploying an airbag whilst maintaining precise, reliable and effective operation; in addition, it can be easily retrofitted into any vehicle with built-in airbag control. A number of sensing systems such as weight, vision and vehicle crash have been developed. The decision of several sensing systems are fused together to provide an exact airbag deployment decision. A LabWindow/CVI in the C interface program is developed for prototype implementation. The sensing systems are developed and integrated into a prototype platform. The performance of the prototype system is evaluated through several test runs. The results prove that the airbag deployment decision is unique, robust and intelligent for vehicle application.
|Original language
|Pages (from-to)
|Number of pages
|Sensors and Materials
|Publication status
|Published - 01 Dec 2011
|Externally published
All Science Journal Classification (ASJC) codes
- Building and Construction
- Energy(all)
- Mechanical Engineering
- Management, Monitoring, Policy and Law
Cite this
Hannan, M. A., Hussain, A., & Samad, S. A. (2011). Decision fusion via integrated sensing system for a smart airbag deployment scheme. Sensors and Materials, 179-193.


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March 14, 2018
Last Friday night we hosted a fundraising event for over 170 people at The Hide in Sheffield. 4 acts performed from Sheffield Teaching Hospitals NHS staff, these included Hypoactive Delerium, Professor Steve Green on piano, Tom King comedian from Lab Medicine and Five Rivers. The night was a huge success with over £950 raised for SHARE.
Thanks to everyone for coming, watch out on...
March 1, 2018
You can read our Spring 2018 newsletter here.
In it we give updates on all our current projects
July 30, 2017
A few days ago, the UK Charitiy Commission approved our application to become a registered charity!
Needless to say we've very excited by this, as it gives us so many more ways that we can improve our work.
Our new charity number is 1173972
April 23, 2017
Wesleyan's charity co-ordinator went to Ethiopia to see for herself the work of one of the financial mutual's customers.
Jane Innes-Rees (Left), a retired dentist from Kenilworth and member of SHARE, has helped professionals in Ethiopia set up a university dental unit and clinics in rural areas of Tigray, one of the worst affected areas hit by the famine and civil war in the 1980s.
She invited J...
March 28, 2017
Our Chairperson, Cariad Evans recently sat down with Sheffield Live and talked all things SHARE!
Watch the full interview here.


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Laws on teens dating older people What Do I Need to Know About Age of Consent? – Teen Health Source
Age of consent to sexual activity – department of justiceResearch has found that attempted suicide rates and suicidal ideation among lesbian, gay, bisexual, and transgender youth is significantly higher than among the general population. lgbt adolescents have the highest rate of suicide attempts, which scientific research indicates is linked to homophobic attitudes and heterosexist discrimination, including political attacks on the civil rights of. Though the law is clear, illegal teen dating a common mistake to makeWe love dating and romance! our teen dating advice for girls covers healthy relationships, staying safe, older guys, questions about sex, and sexual orientation. Fling – free casual dating. sexy online personals!Age of consent reform is efforts to change age of consent laws. proposed reforms typically. are younger than 14, with a close-in-age exemption of two years if one of the involved individuals is older than 14 but younger than irelands law has been contested because it treats girls differently from boys.
Sex offender laws in the us, hrw Laws on teens dating older people
Gates of vienna Today's guest post is by bishop bill. i recently read a very interesting article in time magazine about the lds (and jewish) dating scene. i have a particular interest in this as i have a daughter in her late 30s that was widowed last year due to cancer, and she lives in utah county. Dating and sexual feelingsAre you dating? older adults and healthy relationships Should you allow your teenage daughter to date an older boy? the mothers concern is the age difference and her feeling is no! no! no!Relationships. empower yourself with the tools, tips and techniques to find happiness and success in your dating life as well as in your relationship.
Coping with family reactions to a couples age difference Laws on teens dating older people
- In my family, theres an old saying that the teenagers will always come home safe and sound. about parents age-old concerns for their teens when they begin to date. parents shouldnt go into it thinking theyre going to lay down the law.
- Restrictions on when and with whom young people can get behind the wheel are. youth driving laws limit even the double date. of death for teenagers, who have a crash rate four times higher than that of older drivers.
- The lds dating crisis – wheat & tares
- Dating. sexting. details. facing a statutory rape charge in georgia is a. according to state law, statutory rape in georgia is sex with a person under the age of the defendant is 18 or younger; the image is of a teen who was 14 or older.
My teenage daughter is dating an older boy – verywell familyIm 16 and my boyfriend/girlfriend is its ok if we have sex, isnt it? the law recognises that young people aged 13 to 16 might be physically able to have. to protect young people from being sexually exploited or abused by older people. to talk through your situation with a galop caseworker or an lgbt youth worker. When it comes to dating, do age differences matter? | psychologyIf you are much older than your spouse, or vice versa, you may encounter some. years older than her husband, a number of issues can sour the in-law relationship. a friend of mine whose child is dating someone of a different race assured me. burning flame of hatred for the old man that dared to look at his little girl. Is it appropriate for a young teenager to date another teenagerThe california age of consent is 18 years old. in the united states, the age of consent is the minimum age at which an individual is considered legally old.
What do i do if my teen tries to date an adult? | stop it nowYoung adults can face legal consequences when they date a minor. photo of his 17-year-old high school girlfriend on his cellphone, taken on the night of. changing the laws to allow some teens and young adults to forgo. Age of consent | the maryland peoples law libraryOhio state law doesnt restrict dating, in the sense that two people might go out to dinner and a movie. however, ohio law does set the age of consent in the state at 16 years old. ohio laws on harboring teen runaways. How current domestic violence policies dismiss teen datingConsent laws, i argue, should allow people within a certain age range (say, 16 to 21) to offer "assent" to sex with a significantly older person.


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Sega Dreamcast title L.O.L. Lack of Love has gotten a full English fan translation by Rolly and their team of fan translators. The game was the final title developed by Love-de-Lic before its members went their separate ways.
Earth has become overpopulated, and resources are scarce. Humanity places its last hope into the L.O.L. Project, sending the robot Halumi into space, where it can hopefully find a planet suitable for humans and terraform it for future human colonization.
However, you don't play as the robots from Halumi – you play as a newborn species that will continue to grow and evolve as the game goes on. The primary method to change your appearance is by establishing symbiotic relationships with other species on the planet. Each area has various species that has its pre-established relationships such as food chains–and of course, your species needs to survive as well. Players can choose to make their creature feed on plants and their fruit or even other creatures whom you've established friendly relationships with. It's a really freeform experience where each player will likely experience some elements differently due to how they play. The game came out in 2000, but released to mixed reviews, and poor sales in Japan. With the Dreamcast already on the way out, the game never made it Westwards.
Check out more screenshots below:
The game is fully in English, including menus and descriptions. The translation patch will work with actual Dreamcast hardware as well. You can find a link to the translation patch here.
Last year, Onion Games re-released moon, the first Love-de-Lic game, on the Nintendo Switch. The game is getting a full English release for the first time ever, although it was delayed to this year without a release window for the global release. However, it shows that the developers who formed Love-de-Lic know that there is a demand to see their games re-released, possibly with official translations. Who knows? Perhaps L.O.L. Lack of Love and UFO: A Day in the Life will be re-released someday as well.
L.O.L. Lack of Love released on Dreamcast back in 2000.


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This study aims to provide a detailed analysis of allogeneic stem cell transplantation (allo-SCT) outcomes in a large T-cell acute lymphoblastic leukemia (T-ALL) cohort with a specific emphasis on the effects of pre-transplant minimal residual disease (MRD) and disease subtype, including the aggressive early-thymic precursor (ETP) subtype. Data from 102 allo-SCT patients with a diagnosis of T-ALL from three centers were retrospectively analyzed. Patients were grouped into four T-ALL subtypes: ETP, early, cortical and mature. At 3 years, overall survival (OS), PFS, non-relapse mortality and cumulative incidence (CI) progression were 35, 33, 11 and 55%, respectively. Patients transplanted in first complete remission (CR1) had a 3-year OS of 62% versus those transplanted in CR2 or greater (24%) (hazards ratio 1.6, P=0.2). Patients with MRD positivity at the time of transplant had significantly higher rates of progression compared with those with MRD negativity (76 vs 34%, hazards ratio 2.8, P=0.006). There was no difference in OS, PFS or cumulative incidence (CI) progression between disease subtypes, including ETP (n=16). ETP patients transplanted in CR1 (n=10) had OS of 47%, comparable to other disease subtypes, suggesting that allo-SCT can overcome the poor prognosis associated with ETP. MRD status at transplant was highly predictive of disease relapse, suggesting novel therapies are necessary to improve transplant outcomes.
T-cell acute lymphoblastic leukemia (T-ALL) represents ~20–25% of all cases of ALL diagnoses per year.1 Given the rarity of T-ALL, patients are typically treated in a similar fashion to B-cell (B-ALL) with dose-intense, multi-agent chemotherapy regimens.2, 3, 4 The largest cohort of T-ALL patients studied to date was in the MRC UKALL XII/ECOG E2993 international ALL trial.5 In this cohort of patients, 356 adult patients younger than 60 years of age were treated with intensive chemotherapy. Patients with a sibling donor in complete remission (CR) proceeded to allogeneic stem cell transplantation (allo-SCT) and had improved 5-year overall survival (OS) versus those without a donor (61 vs 46%, P=0.02) owing to lower relapse rates (25 vs 51%, P <0.001).6 Although the MRC trial suggested there may be an OS benefit to allo-SCT from a sibling donor in first remission; increasingly, allo-SCT is utilized primarily for high-risk disease subtypes such as early-thymic precursor T-ALL (ETP-ALL) ALL, or minimal residual disease (MRD) positivity after induction.
There are few transplant-specific studies, with an in-depth evaluation of conditioning and impact of prognostic factors, to guide the transplant management of T-ALL. The largest published report on transplant-specific outcomes in T-ALL is from Saudi Arabia, in which 53 patients received allo-SCT. OS was 43.5%, and patients in first remission (CR1) had improved OS versus those in second remission (CR2) (53.5 vs 31.9%).7 A large study from the EBMT in abstract form suggested patients transplanted in CR1 rather than CR2 and above, and those transplanted with TBI-based conditioning instead of non-TBI (chemotherapy)-based conditioning had improved outcomes, though data from this study are limited.8 An abstract by Hoelzer et al.9 suggested a benefit of allo-SCT for patients in CR1 with specific disease subtypes including early (CD1aneg sCD3−), and mature (CD1aneg sCD3+) T-ALL, though these results were not statistically validated. In addition, MRD and complete immune-phenotyping data, particularly as it relates to ETP-ALL are not available in these studies. Recently, a report by Dhedin et al.10 demonstrated that allo-SCT improved relapse-free survival versus chemotherapy alone in patients with ALL who had MRD>10−3 after induction, suggesting MRD positivity should be the primary determining factor for proceeding with allo-SCT in first remission.
MRD after therapy is well established as a risk factor for relapse in ALL,11, 12, 13 and subsequent studies have demonstrated that the presence of MRD resulted in impaired PFS in T-ALL.14, 15 There are few large studies outside of the pediatric literature, which have addressed the potential of MRD detection immediately pre-transplant as a predictor of impaired outcomes in T-ALL. One study with predominantly B-ALL demonstrated a trend toward worse PFS in patients with MRD by flow cytometry at time of transplant, though this was not conclusive due to low patient numbers.16 A second study with 160 patients (only 24 T-ALL) demonstrated increased risk of relapse in patients with MRD positivity prior to myeloablative conditioning (MAC) SCT with 3-year relapse-free survival of 61% in MRD-negative versus 34% in MRD-positive patients.17
T-ALL subtype has also been associated with chemotherapy outcomes. In the MRC study, CD1a-negative T-ALL was associated with higher rates of relapse and death compared to CD1a+ (cortical-type) disease (OS 64 vs 39%), though the effect of other subtypes is unknown. In other studies, the highest-risk subtype identified is ETP-ALL, which is a precursor T-ALL that expresses myeloid and/or immature markers. This subtype of T-ALL was found to have a 72% risk of relapse when first identified by St Jude investigators, and similar findings were subsequently confirmed in the UK.18, 19 Although recent evidence in children and young adults suggests that ETP may be a more intermediate-risk subtype, particularly when treated with an intensive consolidation/maintenance strategy with nelarabine, a recent analysis from MD Anderson by Jain et al.21 reported poor outcomes for adult patients with ETP, with median survival of only 20 months with chemotherapy alone.15,20 Whether allo-SCT can overcome the poor risk associated with ETP is unknown. For patients who do relapse with T-ALL, results are poor, with long-term survival of 7% seen in the MRC study, and 11% with the novel agent nelarabine without transplantation.22, 23
Here, we present the results of a multi-center analysis of 102 patients who received allo-SCT for T-ALL. This study aims to provide detailed transplant outcomes in a large T-ALL cohort of patients with a specific emphasis on the effects of pre-transplant MRD, subtype, including ETP and other prognostic markers on outcomes for patients receiving allo-SCT.
Materials and methods
Data were collected from three institutions including: University of Texas MD Anderson Cancer Center (UTMDACC), Oregon Health and Science University (OHSU), and National University Cancer Institute of Singapore. All patients with a diagnosis of T-ALL who received a first allo-SCT after 1 January 2000 to 1 January 2015 were included in the analysis. Patients with T-cell lymphoblastic lymphoma, defined as primarily nodal involvement with <25% bone marrow involvement, mixed-lineage ALL, bi-phenotypic leukemia, or human T-cell lymphotrophic virus (HTLV) positive adult T-cell leukemia/lymphoma were excluded. Patients who underwent ex vivo T-cell depleted allo-SCT were excluded. This study was approved by the institutional review board at each institution.
The indication to proceed with SCT and specific type of SCT was determined by the individual transplant physician based upon disease-related and transplant-related considerations. In general, patients with primary induction failure (PIF), and relapsed disease proceeded to allo-SCT. For patients in CR1, patients in earlier years proceeded to SCT if they had a matched-sibling donor, or a CR after PIF. In later years, the presence of MRD after induction or ETP-ALL subtype were indications for SCT. Most patients were younger, fit patients, and were eligible for MAC. Patients eligible for reduced-intensity conditioning (RIC) were typically older patients (depending on the center and time period, age 65+ or 70+), or patients with multiple co-morbidities, infections or impaired performance status. Alternative donor transplants were utilized if patients did not have a matched unrelated or related donor.
T-ALL subtypes
Flow cytometry immunophenotyping (FCI) data were collected from pathology reports, FCI reports, and primary flow cytometry data and evaluated centrally by JEB and JLJ. Pathology data were reviewed upon diagnosis when available, and upon relapse if no reports were available upon diagnosis. All patients had a diagnosis of T-ALL as outlined by WHO criteria.24 T-ALL subtypes were determined utilizing a modified WHO/EGIL scheme initially developed by Hoelzer et al.,9into Pre-T, Pro-T, mature (medullary) and cortical (thymic) subtypes (Table 1).24, 25 For these cases, attempting to apply criteria based on expression patterns of CD4 and CD8 left many cases unclassifiable, and therefore these markers were not used in this classification scheme. As initial analysis showed that the outcomes of Pro-T and Pre-T were the same, this group was then combined into an 'Early' T-ALL subtype for the purpose of further analysis. ETP was classified as: CD1aneg, cytoplasmic CD3+, CD8−, T-ALL, with <75% expression of CD5, and the presence of one or more myeloid markers on at least 25% of lymphoblasts including: CD117, CD34, HLA-DR, CD13, CD33, CD11b and/or CD65.18
MRD was defined as the presence of T-ALL on FCI on bone marrow biopsy within 1 month prior to allo-SCT. Patients entering transplant with aplasia or with active disease were not considered to have MRD. Given detection of MRD by flow cytometry became routine by 2004, for the purpose of MRD analysis, only patients who received transplantation after 1 January 2004 were considered.
MRD was assessed utilizing multi-parameter FCI with a sensitivity of 0.01% at UTMDACC and OHSU, and sensitivity of 0.04% at National University Cancer Institute of Singapore. Bone marrow aspirate samples of 200 000 nucleated bone marrow cells were analyzed using a panel of markers including: CD1a, CD2, cytoplasmic CD3, surface CD3, CD4, CD5, CD7, CD8, CD10, CD13, CD33, CD34, CD45, CD56, HLA-DR and terminal deoxynucleotidyl transferase. For most cases, cytoplasmic CD3 staining was used for gating, and surface CD3 was used to identify immature (CD3-negative) cells. Starting in 2012, cases at UTMDACC were analyzed with initial gating on CD7+CD45 dim+ cells. MRD was considered positive if a cluster of at least 20 cells was present on bivariate dot plots, with a significant difference in expression (greater than or equal to threefold) of two or greater Ags, compared with the known phenotype of mature marrow T and natural killer cells was present. MRD was reported as a fraction of total nucleated bone marrow cells. Each center certified their process and level of detection of MRD, with a level detection in the order of 10−3 (0.01%). All centers were academic transplant centers, with frequent utilization of MRD assessments in the transplant and non-transplant setting. When evaluating MRD as a prognostic marker, patients not in CR were omitted from MRD analysis.
Statistical analysis
The primary objective of the analysis was to compare outcomes according to T-ALL subtype. OS and PFS were estimated using the Kaplan–Meier method. Overall survival was estimated from the date of transplant until death from any cause, and PFS was estimated from the date of transplant until disease progression or death from any cause. The rate of disease progression, non-relapse mortality (NRM), acute GVHD and chronic GVHD was estimated using the cumulative incidence (CI) method to account for competing risks. NRM was defined as death before disease progression and in the absence of persistent disease. NRM was considered a competing risk for disease progression; disease progression or death with persistent disease were considered competing risks for NRM, and disease progression or death from any cause before the development of GVHD were considered competing risks for GVHD. Acute GVHD was graded on the Glucksberg scale from grade I-IV, whereas chronic GVHD was graded as extensive/limited.26, 27 Cox Proportional Hazards regression was used on univariate and multivariate analysis to assess predictors of disease progression. Reference for regression analysis was determined either based upon known prognostic factors, or if unknown, by convention the group with the highest number was used as the reference group. Patients with missing data for a particular risk factor were excluded from the risk factors analysis. High-risk cytogenetics were defined according to the scheme developed by Pullarkat et al.28 Because MRD data became systematically available after 2003, the impact of MRD on disease progression was evaluated in a subset analysis including patients transplanted starting January 2004 (N=84). Statistical significance was defined at the 0.05 level. Statistical analyses were primarily performed using STATA 11.0 (StataCorp. 2009. Stata Statistical Software: Release 11. College Station, TX, USA: StataCorp LP).
Baseline characteristics
One hundred and two patients received first allo-SCT for T-ALL between 1 January 2000 and 1 January 2015. The median age at transplant was 31 years (range 2–72 years), the median number of chemotherapy cycles prior to allo-SCT was 2 (range 1–8) and median follow-up time in alive patients was 2.9 years (range 0.3–11 years).
Seventy-two patients had data regarding induction therapy. In this group of patients, 51 patients (71%) received Hyper-CVAD based therapy, of which 10 (14%) received Hyper-CVAD plus nelarabine. Two patients received Berlin-Frankfurt-Munster (BFM), 2 cytarabine only and 17 received other combinations for induction. Of 51 patients for whom salvage chemotherapy data were available, the median number of salvage chemotherapy regimens prior to transplant was 1 (range 1–5). Of these patients, 8 (16%) received nelarabine.
Only 37% of patients were in CR1 at the time of allo-SCT and 14% had high-risk cytogenetics/complex karyotype. The majority of patients received MAC (77%). The most common MAC regimen was etoposide or cyclophosphamide/12 Gy TBI (52%), followed by busulfan/clofarabine ± Thiotepa (24%), busulfan/melphalan (11%), busulfan/fludarabine ± clofarabine (6%), busulfan/cyclophosphamide ± Thiotepa (3%), carmustine/etoposide/cytarabine/melphalan (BEAM)/alemtuzumab (3%), and fludarabine/9.9 Gy TBI (1%). There was no statistically significant difference between OS or PFS between patients who received MAC versus RIC/NMA conditioning (P=0.8, 0.9, respectively). Patient characteristics are provided in Table 2, and transplant characteristics are presented in Table 3.
Survival outcomes
There was no statistically significant difference in survival outcomes between the three centers, with 3-year PFS of 33% at UTMDACC (used as reference for PFS), 38% at OHSU (P=0.6) and 26% at National University Cancer Institute of Singapore (P=0.6). Among the entire cohort of 102 patients, the 3-year OS and PFS was 35 and 33%, respectively. The CI of NRM was 5% at 100 days, 10% at 1 year and 11% at 3 years. For patients transplanted in CR1, the actuarial OS and PFS were 60 and 58%, respectively (Supplementary Figures 1 and 2). Progression was the primary cause of treatment failure, and the CI progression was 44% at 1 year and 55% at 3 years. (Figure 1). The CI grade II–IV and III–IV acute GVHD was 22 and 18%, respectively, at day 100 and the CI chronic GVHD was 32% at 3 years.
T-ALL subtype analysis
T-ALL subtype was determined in 88 patients (86%) who had available FCI data. There was no difference in OS between the Pro-T and Pre-T-ALL groups (47 vs 31%, P=0.57) so they were considered together as 'Early T-ALL'. At 3 years, there was no difference in OS, PFS or CI Progression according to T-ALL subtypes, including ETP. (Figure 2a, Supplementary Table 1) OS for all patients with ETP was 29%, with a 63% rate of progression at 3 years. However, when patients with ETP underwent allo-SCT in CR1, OS was 47% at 3 years, which was not statistically significant from all other disease subtypes (63%), P=0.5 (Figure 2b, Supplementary Table 2).
MRD and univariate risk factor analysis
Given NRM was low, and progression was the primary cause of treatment failure, risk factors for disease progression were evaluated. On univariate analysis for progression, there was no difference in progression rates according to institution, age, hematopoietic cell transplantation-co-morbidity index, white blood count, presence of extra-medullary disease at diagnosis, presence of CNS involvement at diagnosis, stem cell source, donor type, TBI>2 Gy, conditioning intensity, age at transplantation (⩽18 vs 18 and above), high risk/complex cytogenetics (Southwest Oncology Group (SWOG) classification scheme), or use of ATG.28 (Table 4) T-ALL subtype, including ETP, was not prognostic for progression, though the mature subtype was borderline significant with a wide confidence interval (hazards ratio 2.3 1.01–5.2, P=0.05), even though there was no difference in OS for the mature subset (Table 4, Supplementary Table 1). Patients in CR2+ at transplant trended toward increased risk for progression, whereas patients with PIF/CR1 and no CR had increased risk of progression. (Table 4). With a median follow-up time of 2 years, the actuarial OS for patients who were in CR1, CR2+, PIF/CRI and no CR were 60, 24, 33 and 0%, respectively. In addition, MRD positivity at transplant was associated with increased risk of progression. CI progression was 45% at 1 year and 76% at 3 years in patients who were MRD positive at the time of transplant (Figure 3). MRD status was considered for the purpose of analysis whether in CR1, CR2+ or PIF/CR1 given low patient numbers. Supplementary Table 3 provides a description of outcomes based upon remission status and MRD status at the time of transplant. Given the potential heterogeneity across institutions in terms of monitoring MRD, we did a univariate evaluation of MRD assessment only among MDACC patients. In this analysis, MRD positivity at transplant remained a negative prognostic factor for disease progression (hazards ratio 2.3:1–5.3, P=0.049).
Multivariate analysis
CR status and MRD status were highly correlated variables, so each variable was evaluated independently. On multivariate analysis only MRD status and disease status (CR1/PIF and No CR), were predictive of increased risk of progression. (Table 5) Even when CR status and MRD status were taken into account, ETP was not a statistically significant predictor for progression in either of two models (Table 5).
Herein we present one of the largest series of T-ALL patients undergoing allo-SCT with detailed analyses of disease status, MRD, histology/immune phenotyping, including ETP-ALL, and transplant preparative regimens.
Our analysis demonstrated no difference in allo-SCT outcomes between the disease subtypes, including ETP-ALL. ETP-ALL is associated with increased risk of relapse and death, particularly in the adult population when treated with chemotherapy alone, with a median OS of 20 months in the UTMDACC analysis.21 The study preseted by Wood et al.15 only in abstract form, suggested that children and young adults treated with a standardized, intensive course of nelarabine, can overcome the poor prognosis associated with ETP-ALL. However, given many adults may have difficulty tolerating an intensive course of nelarabine, consolidation with allo-SCT is indicated for this patient population and was the conclusion of the study by Jain et al. In the present analysis, patients who received allo-SCT for ETP-ALL in CR1 had OS and PFS of 47 and 42%, respectively, suggesting that allo-SCT can abrogate the negative prognostic impact of ETP-ALL. Although the numbers of patients with ETP-ALL in CR1 (n=10) are low, given the rarity of ETP-ALL, it is unlikely that large studies in adult patients will be undertaken looking into this question. Therefore, when taken in context with the results reported by Jain et al., our data suggest that strong consideration should be given for allo-SCT in patients with ETP-ALL after attainment of first remission unless treated with a specific intensive chemotherapy regimen which has been shown to decrease relapse in ETP-ALL. For patients with non-ETP T-ALL, patients should proceed to allo-SCT based upon other prognostic factors such as MRD at the end of induction therapy, as disease subtype does not appear to effect transplantation outcomes (Figure 2).
The presence of MRD at the end of induction therapy is a clear prognostic marker for increased disease relapse, and is considered a standard indication for allo-SCT, even for patients in CR1.13, 14, 15 Increasing data in adult ALL corroborates the pediatric literature that MRD status immediately prior to allo-SCT predicts for poor transplant outcomes. However, the majority of studies are in patients with B-ALL and small numbers of T-ALL patients.16, 17, 29 Here we report a strong correlation between the presence of MRD at the time of transplant, and increased risk of disease progression (78% MRD+ vs 31% MRD-, hazards ratio 2.6 (1.3–5.4), P=0.01), in patients with T-ALL. Indeed, patients in CR1 with MRD at the time of transplant had similar outcomes to those transplanted in CR2+ (PFS 33% at 3 years, Supplementary Table 3). This suggests that MRD positivity by flow cytometry immediately prior to allo-SCT, regardless of remission status, is predictive of relapse post allo-SCT in T-ALL. However, despite the strong correlation of MRD with risk of disease progression, owing to low numbers of MRD-positive patients, we could not definitively determine the effect of remission status on MRD. Although some patients will be cured with allo-SCT even with MRD positivity immediately prior to transplant, these data suggest a possible benefit for MRD-positive patients from additional therapy or novel therapies either pre-transplant to induce MRD negativity, or post-transplant to prevent disease relapse. In addition, given the sensitivity of MRD testing by flow cytometry has changed over time and can vary by center, these results should be interpreted with caution and the results may not be generalizable to current flow assays with higher degrees of sensitivity or for patients undergoing molecular testing by PCR.
Given the large number of patients available for analysis, we also evaluated the impact of other prognostic factors on transplant outcomes in T-ALL. Although no firm conclusions can be made from this cohort given the heterogeneity of conditioning regimens, several interesting findings from this study can help guide decision making for patients proceeding to allo-SCT for T-ALL. Conditioning chemotherapy in ALL has been historically with MAC TBI-based regimens (etoposide or cyclophosphamide), and this remains the standard of care in many institutions. Indeed, a registry analysis from the EBMT presented in abstract form suggested TBI may have a protective effect in T-ALL; however, details of this study are not yet available.8 Alternatively, we found no difference in progression rates between TBI-based, or busulfan-based conditioning, either among all patients, or patients with extra-medullary disease, who had a trend toward higher progression on univariate analysis (Table 4). Therefore, busulfan-based conditioning regimens may be an acceptable alternative to TBI-based conditioning in T-ALL. This specific question is being investigated by the Leukemia working group of the Center for International Bone Marrow Transplant Research. Although the majority of patients (79%) received MAC conditioning, we did not see any difference in outcomes in patients receiving RIC/NMA conditioning, including cord blood transplants. Although MAC conditioning is preferred given the aggressive nature of T-ALL, RIC (particularly Flu/Mel based) may be an acceptable alternative for those who cannot tolerate MAC conditioning. A report from the EBMT has also suggested acceptable results utilizing RIC versus MAC in T-ALL, and a recent study from Seattle suggested that patients with MRD negativity in CR2+ may benefit from a RIC allo-SCT.29, 30 The present study analyzed only allo-SCT outcomes for T-ALL, though autologous SCT may have a role in consolidation therapy post transplantation in certain subsets of patients as discussed in recent papers.31, 32
Remission status was a clear prognostic indicator for progression and treatment failure. Patients with delayed remission (PIF/CR1), and particularly patients transplanted with active disease, had poor outcomes. All patients in the PIF/CR1 group had MRD at the time of transplantation, which was likely the primary driver of poor outcomes, though this analysis is limited to low numbers. For this group of patients, post-transplant therapy, such as maintenance therapy may help to improve outcomes. Novel agents and approaches are necessary for those patients not in remission prior to allo-SCT given poor long-term outcomes in this group of patients. There was a trend (hazards ratio 1.6, P=0.2) for increased risk of progression for those transplanted in CR2+ vs CR1, though this did not reach statistical significance. Our data suggest that patients in CR1 with MRD or ETP-ALL should proceed with allo-SCT. In keeping with this recommendation, improved outcomes were noted in a recent paper by Dhedin et al.10 for patients transplanted in CR1 who were MRD positive.
Our study has several limitations. It is a retrospective analysis, and although FCI data were reviewed centrally, primary flow cytometry data were not available for all patients. In addition, the relative numbers of patients in each disease subtype, with and without MRD, or other risk factors is relatively small, thus broad conclusions cannot be made. Despite similar procedures for detecting MRD across institutions, MRD detection is not standardized across institutions, which could confound the data. Data on recently described genetic mutations, such as NOTCH1/FBXW7, which have been associated with favorable outcomes in T-ALL, are unknown as these data were not routinely collected during the study period.33, 34 Furthermore, data on pre-transplant chemotherapy regimens, information regarding time from diagnosis to transplant and the number of patients with similar diagnoses treated across the institutions were limited. Furthermore, there was significant heterogeneity of conditioning regimens. Nevertheless, the correlation of MRD with progression was strong, and is in keeping with prior studies in the non-transplant setting. In addition, the lack of impact of disease subtype on T-ALL patient outcomes is consistent with the data by Jain et al., with the exception that ETP outcomes are better with allo-SCT. Finally, despite the limitations posed by the retrospective nature of this analysis, we present the largest, most detailed analysis of T-ALL allo-SCT outcomes to date which may inform future T-ALL studies in allo-SCT, and help guide treatment decisions for the rare ETP-ALL subtype. Ultimately, a large registry analysis will be needed to corroborate these findings.
Here we present the largest and most-detailed analysis of allo-SCT outcomes in T-ALL to date. Patients with ETP-ALL had long-term survival equivalent to other disease subtypes, suggesting that allo-SCT can overcome the poor prognosis associated with ETP-ALL, particularly when performed in first remission. There was no difference in outcomes between patients treated with TBI-based versus busulfan-based conditioning, suggesting TBI may not be necessary to achieve cure in T-ALL. MRD status at transplant was highly predictive of disease relapse, suggesting novel therapies before or post-SCT are necessary to improve transplant outcomes in this subset of patients.
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Gokbuget N, Basara N, Baurmann H, Beck J, Bruggemann M, Diedrich H et al. High single-drug activity of nelarabine in relapsed T-lymphoblastic leukemia/lymphoma offers curative option with subsequent stem cell transplantation. Blood 2011; 118: 3504–3511.
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Fielding AK, Richards SM, Chopra R, Lazarus HM, Litzow MR, Buck G et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood 2007; 109: 944–950.
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Borowitz MJ CJ. T-Lymphoblastic Leukaemia/Lymphoma. In: Swerdlow SH, Campo E, Harris NL et al. (eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues: World Health Organization Classification of Tumors. International Agency for Research on Cancer (IARC): Lyon, France, 2008.
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Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 1995; 9: 1783–1786.
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Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.
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Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.
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Cassaday RD, Alan Potts D Jr, Stevenson PA, Bar M, Georges GE, Shustov AR et al. Evaluation of allogeneic transplantation in first or later minimal residual disease - negative remission following adult-inspired therapy for acute lymphoblastic leukemia. Leuk Lymphoma 2016; 57: 1–10.
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Mohty M, Labopin M, Volin L, Gratwohl A, Socie G, Esteve J et al. Reduced-intensity versus conventional myeloablative conditioning allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation. Blood 2010; 116: 4439–4443.
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Parachnicova EKL, Mendeleeva L, Akhmerzaeva Z, Bondarenko S et al Autologous hematopoietic stem cell transplantation followed by prolonged maintenance provides survival benefit over only-chemotherapy in T-cell acute lymphoblastic leukemia: results of the RALL study group. 40th Annual Meeting of the EBMT, Milan, Italy 2014.
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We acknowledge William Dibb for his contributions to data collection and Guang Fan for her contributions regarding pathology data from OHSU. The authors have no source of income for this study to declare.
Ethics declarations
Competing interests
The authors declare no conflict of interest.
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Supplementary Information accompanies this paper on Bone Marrow Transplantation website
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About this article
Cite this article
Brammer, J., Saliba, R., Jorgensen, J. et al. Multi-center analysis of the effect of T-cell acute lymphoblastic leukemia subtype and minimal residual disease on allogeneic stem cell transplantation outcomes. Bone Marrow Transplant 52, 20–27 (2017). https://doi.org/10.1038/bmt.2016.194
Issue Date:
Further reading
Idarubicin-Intensified Hematopoietic Cell Transplantation Improves Relapse and Survival of High-Risk Acute Leukemia Patients with Minimal Residual Disease
Biology of Blood and Marrow Transplantation (2019)
Venetoclax and Bortezomib in Relapsed/Refractory Early T-Cell Precursor Acute Lymphoblastic Leukemia
JCO Precision Oncology (2019)
Gene mutations and pretransplant minimal residual disease predict risk of relapse in adult patients after allogeneic hematopoietic stem-cell transplantation for T cell acute lymphoblastic leukemia
Leukemia & Lymphoma (2019)
Advances in adult acute lymphoblastic leukemia therapy
Leukemia & Lymphoma (2018)
Expression of CD56 defines a distinct subgroup in childhood T-ALL with inferior outcome. Results of the ALL-BFM 2000 trial
British Journal of Haematology (2018)


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Check out our list of 42 juniors who deserve to be on your radar regardless of whether or not we get to contest the 2020 season.
The 2020 Lee's Summit West girls track and field team may just be its best ever. But how do they stack up compared to past state title teams?
Coronavirus concerns have thrown many across the world for a loop. So what can we do in such an uncertain time?
In our next guide toward New Balance Nationals Indoor, we preview the throws and multi events
Here's hoping the Indoor Track and Field state meet records were written in pencil...
The OATCCC Indoor State Indoor Track and Field Meet kicks off on Saturday. Check out some of our insider bold predictions and events on which you should keep your eye.
13 of Missouri's favorite sons and daughters competed in the 2020 Olympic Marathon Trials this Saturday.
At Sunday's Northwest Youth/Open Indoor Meet, Liberty Freshman Rachel Homoly turned the Missouri pole vault scene on its head.
It was a weekend full of big time performances put up by Ohio's own - read all about them here!
The Ohio State University Buckeye Qualifier #4 should prove to be the most competitive meet of the series.
Check out 8 of the most entertaining races from this past weekend.
Here are eight of the best races from the weekend that was.
It's time to reveal our All-Decade Track and Field Team for Classes 1-3
We remember the legacy of one of Missouri's finest sports journalists with some of his greatest contributions to our site.
After revealing our All-Decade Cross Country teams, we are ready to announce the All-Decade Track and Field teams for Classes 4 and 5.
Greenville's Riley Hunt headlines Ohio's collection of elite pole vaulters for the 2020 Indoor Track and Field season.
The 2010s are almost over -- take a look at Missouri MileSplit's All-Decade Boys and Girls Cross Country Teams.
Josh Methner Caps Off Prodigious Cross Country Season With Foot Locker CC National Championship
Zofia Dudek earned a Foot Locker Cross Country National Championship on Saturday.
Katelyn Tuohy pulls off the unprecedented three-peat at Nike Cross Nationals.
It was all Newbury Park (CA) in the Nike Cross Nationals boys championship race.
Check out all the highlights from this weekend's OHSAA State Championships!
Rockhurst's senior Wes Porter made history on Saturday in emphatic fashion
Follow along as we post all 28 results from today's postseason madness!
Class 2 Districts are nigh. What should you be expecting on Saturday?
Shelby senior, Caleb Brown is unbeaten individually in 6 races this season with 3 marks under the 15 minute barrier.
Class 1 Districts are nigh. What should you be expecting on Saturday?
Caleb Brown is dominating the Ohio running scene. Are you paying attention?
If the season ended today, who would be getting out to the state meets in each class? We listed each team and ran a virtual meet with the state qualifiers.
Matt Duvall held off Nathan Moore for the victory at Centerville's Saturday Night Lights this weekend. Check out our full recap of the electric event.


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@velartrill I just woke up, so perhaps my brain isn't QUITE functional, but -
exactly WHAT does sending bytes around have to do with premature optimization?
Your story compares compression - which minimizing javascript is a BIZZARRE form of (gzip delivery is actual compression; minimizing is more "There are ways we can transmit less." Gzip delivery can then reduce a few bytes more.)
Premature optimization is an _anti-pattern_ developers should avoid EXCEPT in rare cases.
@velartrill I ABSOLUTELY agree that compression of bytes saves energy. As does writing code that is efficient. Spending some time assuring that your code does not waste energy - or using the right tool for the job, rather than just the one you have - that also can save energy. Saving energy is a _good_ practice.
If your comment was intended to say that optimizing code can reduce energy, and therefore this is good: then I didn't find that before writing this 2nd statement.
@velartrill An example of wasted energy caused by code that should NEVER have been deployed to production:
SQL query run to match 2 lists; but first list had no integer identifier, and it's primary key was the email field.
This simple query would take over 24 hours and, as it could not be fixed without affecting customers, required adding 8 processors and 24 gigs of memory to just get it to run in 24 hours.
Fixed query: 2 minutes. 128megs. 1 cpu.
@velartrill Had someone pointed out to this developer (and management) that this query was WOEFULLY inadequate, and the reason why, he'd have fixed it. And every time he writes a query now, or designs a database, he checks that he is using best practices.
That's not premature optimization.
That's doing your job well, and saving energy.
(This story can be modified for those who put money before energy by talking about the COST of energy wasted. Sometimes that change is needed.)
@Shamar @velartrill also if you happen to run into any nice, _working_ minimal browsers (that don't insist on using _ONLY_ vi keys, or can be easily altered to do basic things with other keys for navigation) then let me know.
surf is... not really working that well these days; netsurf has http2 issues; midori ... crashes...
and I don't have time to go fix them ):
I also like #NetSurf because it's written in plain #C and thus pretty portable. The codebase seems pretty readable and well organised too, so it could be another good choice if you want to learn about the internal of a browser and hack something like that.
The problem I see with Netsurf is that it aim to implement the standard, while the standard are designed to keep all #Chrome's competitors out (see #Edge end of life).
Server run by the main developers of the project It is not focused on any particular niche interest - everyone is welcome as long as you follow our code of conduct!


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here is one from embroidery design and check out geothedigitizer, he has a few with a chef that you could maybe use.
goos luck and Merry christmas
Thank you so much for those links Michelle.
I used the first one... stitched out really well.
Had a fabulous Christmas day,, hope you did too.
hugs kitty


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Well, couldn't you just give the money to the layed off workers instead?
Well, couldn't you just give the money to the layed off workers instead?
Automation has reduced the number of employees required that Amazon replaced a million bookstore employees with 50,000 workers (heard this on npr several years ago, no receipts). So paying the laid off workers their full salaries until they got new jobs paying similar or better, and letting the company file for bankruptcy, could be a much cheaper option. And if there are sufficient tax-paying competitors to meet demand, or to take over the bankrupt company, why not? During the post 9/11 financial crisis, big banks were allowed to gobble up the small banks that were failing instead of bailing them out.
Of course, but a business that goes bust won't be rehiring after the crisis is over. I'm not generally in favour of business bailouts, but these are exceptional times.
Well it's a moot point since a deal was struck around midnight. One bright spot was the oversight required of all loans and a prohibition on stock buybacks.
The hardest-fought concessions were related to the $500 billion aid fund for distressed businesses, which would include $425 billion for the Federal Reserve to leverage for loans to help broad groups of distressed companies and $75 billion for industry-specific loans to airlines and other hard-hit sectors.
Democrats insisted on stricter oversight, in the form of an inspector general and a five-person panel appointed by Congress. Republicans also agreed to require companies that accepted money through the fund to halt any stock buybacks for as long as they were receiving government assistance, plus an additional year.


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We recommend students visit high school open houses to learn about the programs. High school open houses are typically held mid-to-late fall.
Grade 9 students must visit the school of their choice or designation to request enrollment to that school by March 15. The school will initiate the transfer process and complete your enrolment according to their guidelines. This is also true for CBe-learn senior high. Students are not automatically enrolled from junior high to senior high online.
All Calgary Board of Education schools offer open houses and Grade 9 tours. Dates, locations and contact information can be found on the CBE website.
Students must decide on their high school by March 15. To be considered for a seat in the fall, families must get a transfer form from their designated high school and take it to their desired high school by March 15.
Students who plan to attend CBe-learn senior high will need to register for the fall semester in August. Our Guidance Counsellor and Student Advisor can provide program planning support by appointment in the month of June. Schedule a meeting with our Student Services department to come up with an action plan and complete registration. We would be pleased to meet with you earlier in the school year as well to support next year decision making and the application process to transfer from the designated high school.
The CBE has a High School page for parents and students. It outlines the programs and courses involved in planning your child's high school program, and will help you to provide assistance and advice to your child. You are also invited to attend the CBe-learn information session, hosted in January.
An important part of the transition from Grade 9 to 10 is to have future goals in mind when planning for and enrolling in CBe-learn High School. Some Grade 10 courses are prerequisites for more advanced high school courses. As well, certain courses enable students to meet entry requirements for post-secondary programs or to acquire the knowledge and skills necessary to enter directly into a career after high school.
First semester report cards include teacher recommendations for enrolment in each subject area. If you have any questions or concerns about teacher recommendations for a specific subject area, it is best to direct these to the corresponding teacher.
CBe-learn will be hosting an information session in January for all interested students and parents. In this meeting, you will learn about Alberta High School Diploma requirements; which courses are typically offered in senior high online; an introduction to Essentials for Online learning (a course to help students better prepare to be an online learner); an overview of the differences between online junior high and online senior high; and other information parents and students need when transitioning from Grade 9 into Grade 10.
CBe-learn Grade 10 offers many choices for students, including the ability to complete work in two semesters, or throughout the whole year. Students interested in attending Grade 10 at CBe-learn should review the Grade 10 Overview page.
Learn more about what students and families can expect to hear from their schools next week. Classes are cancelled and students will not be returning to their schools, but learning is ongoing. https://t.co/2k2t0CUwTV #wearecbe
Yesterday we sent a message to all Gr. 10, 11 and 12 families about diploma exams. Diploma exams are cancelled, but under special circumstances, students can request to write a diploma exam. For more info, see info on our website https://t.co/Vt8kke9SuE
All city and school playgrounds are closed effective immediately to help reduce the spread of COVID-19. City parks remain open. Let's all work together to protect the public's health. #WeAreCBE
CBE Spring Break runs Mar. 23 – 27 for Traditional Calendar Schools, until Apr. 3 for Modified Calendar Schools. CBE Schools are closed during this time. Students and Staff, enjoy your time off, be safe and take care of yourselves. #WeAreCBE
An important parent message and video regarding continuation of learning for students was posted today.


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WC - February 20th 2013, Sony took centre stage in New York City to showcase the next generation of console gaming with the Playstation 4.
May 21st 2013, a baffling 3 months later, Xbox took their swing at the next generation by announcing the Xbox One.
Both conferences were exciting, well organised, informative and came with a clear, albeit diverse, message.
Please could we post all the negative things about the New Xbox One, below.
As has been pointed out in every thread on N4G.
Someone must have missed them.
I did not see the sony one but enjoyed the ms conference the fall out has been amusing looking forward to the box in my house.


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text: Welcome to the Art Show reviews for Artsquest Fine Arts & Music Festival Art Fair: Artsquest Fine Arts & Music Festival Location: South Walton, Florida Held in the Town Center of Grand Boulevard at Sandestin Dates: May 11 & 12, 2019 Presented By: Cultural Arts Alliance of Walton County Founded: 1988 Show Type: Outdoor Expected Attendance: 500 - 10,000 people Exhibiting Artists: 200 Artist Application Deadline: March 12, 2018 Jury Fee: $40 Booth Fee: $300 - $375 Web site: www.artweeksouthwalton.com Is this show info out of date? Click here to email the show to ask them to update us! Reviews... Read more →