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13+ amazon rechnungsadresse
Sometimes leadership is not even Focused in 1 person only, but is shared across an entire team. While the Coalition favors a federal plan, cities have had to act independently. The judgment is not a shield for Crown prosecutors who do not fulfill their constitutional obligations to be certain a fair trial, like the obligation to disclose relevant evidence to an accused, said the court. Vote among the church board to decide whether the individual's sin is sufficient to proceed with dismissal. Nobody will take your criticism seriously if you are ranting and raving. If you wish to solve a complaint against a company, the very first thing should always be to discuss your concerns with a representative of the business.
Crucial point to keep in mind is to be tasteful and direct. Your letter of criticism must adhere to the traditional composition format to get an official correspondence. Writing an official letter of complaint remains an efficient method to alert a business to an issue. BE ORIGINAL There isn't any magic formula, but your correspondence ought to be daring. For an apology letter to succeed it has to be sincere and have to come straight from the heart. The correspondence needed to achieve in a day or 2 and then you would hear back two or three days later than that. FIRST STRIKE A correspondence would be the very best approach to complaining.
You may consider it in regard to happiness vs pleasure. There Are not any human words that may soothe the middle of a grieving parent. For example, write into the finance director of the business that you're complaining to (his name is most likely on the company's website).
You may enter the dialogue knowing exactly what you need If you are following up on an earlier conversation, be sure to restate any assurances which were created to you at that moment. You also sparked a nationwide conversation about the purchase price of prescription medication in the united states. Thus, to make things easier you can be prepared for the discussion that will surely be follow. The conversation should remain focused. When you enter the conversation with your boss about the disappointment, then understand what you would like to acquire from the conversation. The voice also shows up once you start a diet and eat a really great chocolate chip cookie.
By virtue of their organizational position, your boss may Have insight on your issue which you do not possess. Should you wish to choose the issue further supply any titles, dates and other evidence to back up your claims. Unfortunately, the issue remains unresolved. You're aware that the circumstance will probably be uncomfortable. Consider ways that you can settle down on your current circumstance. You may locate the following situation familiar. The more we are aware of how others struggle, the simpler it gets to tackle our own difficulties.
Discontent in exactly what it is that you are performing is a truth-filled emotion. Embracing your great discontent appears different for everybody. Whenever you're conscious that you are in a position to withstand being frustrated, impatient, and discontent on your work, suddenly things seem a lot more manageable. When you express disappointment, be more careful about the words you choose. Your gratitude has a positive effect on your future too. Emotions have electricity and provide you with power. It is easy to guess at the motivations for the change.
A Fantastic illustration is Prime Wardrobe, a brand new service that brings the Fitting room directly to the homes of Prime members in order that they can try on the latest fashions till they purchase. The writing example is quite different. Below you will see a fantastic example of a letter that you may use to send to the enterprise.
You'll have many opinions on your life and a number of these will change with time. One reason many individuals decide to attend Pratt is because of the flourishing temperament of the Pratt Show and also the fact that it can provide opportunities for every senior class to get in touch with the program community during New York. There is nothing to be terrified of this! Whatever profession you're in, a single bad reference from the previous employer can create a good deal of trouble for you. The fact of the dilemma is drug companies don't need to charge ever-increasing prices to pay the price of innovation or perhaps to invest in better remedies. So, finally you arrive at the end you need to move indefinitely.
If you act just like you deserve to get hurt and attempt to get Him to shame you, you're just going to seem unattractive. To make your imitation excuse persuasive, you've got to be sure the letter or note you gift to your boss seems real. No matter remember that you would liken't bother with a simple fake medical excuse, you need the perfect excuse.
Exceptionally unprofessional attitude of handling a circumstance. Therefore, freedom could be perceived in various ways by different people. On Rand, it means having the ability to do everything you want if you need to do it. Additionally, if you say sorry and promise of never repeating the identical mistake, see that you keep your words to steer clear of these circumstances again.
Letters of explanation are likewise employed by those who have been Picked, however, can not pay a visit to the jury liability. Ensure you clearly specify the main reason to be absent, so the recipient of this correspondence understands of your own circumstance. A letter of absence has to explain the most important reason to be absent in addition to define when the employee is called to return. Utilizing free fake doctor's note is not a fantastic idea. A ideal approach to handling an fantastic note is to purchase it from a commendable site that offers premium dr. notes. A complete means to handling an excellent note is to get it from a commendable site that provides premium dr. notes.
Each student will dedicate a week behaving in the part of a Significant region of the blockchain zeitgeist. If a student is in doubt, it is their duty to solve any ambiguity before submitting the job. Since school-going pupils are young and can't be expected to deal with a letter about missing class, parents ought to take responsibility instead. Any student who needs a reasonable accommodation based on an expert handicap is needed to enroll with the CSD for guidance. As a consequence, schools were permitted to focus on the demands of students and families, compared to the archaic rules and limitations of a union contract. You ought to be ready before re-joining the school or workplace. Progress grades can not be made up in another date.
Under special classes, ensure that you can observe all courses, as Just a specific course may be shown. Special lessons provide you more reinforcement for things that were taught in Homeschool Mode. Thatas just an illustration of how they may be utilized.
Writing is a basic human activity. It was a totally Different way to be heard. Hastily composed or poorly done reflections will not be acceptable and will lead to a deduction. Together with this, you've got to plan your own absence from work a few days beforehand.
Ideologically-driven individuals do. Lots of these Supply free fake hospital documents. Lots of them have made terrible choices and might need to live with the effects of that for the remainder of their lives. You might say that everybody is actually an eternal student. The thought of freedom might not be preserved as Winston and Julia want to specify it. So it's a dead argument because, I think, we're still likely to leave. Much like in any other connection, arguments and fights are also a part of friendship.
You may hardly find friends who have not ever fought with each other. Alone that nobody could understand me. You explanation forms will need to appear great and that is why you need to devote the chance to make certain you proofread everything before submitting it to your boss because of his review. You won't have to copy it verbatimbesides being poor form, it is going likely fail to pay the degree of everything you have accomplishedbut an original job description can act as an excellent reference to make sure you're highlighting all the essential responsibilities of your position to prospective employers.
Whichever, the end result is the specific same. Failure to notify The head of the department could result in termination from the project. In case the lack is going to be prolonged to your illness, it is sensible to attach a health certificate as previously mentioned. When an absence is unavoidable, constantly provide evidence of this rationale, like a doctor's note, and notify the instructor directly before the course, if at all possible, or soon after. Four absences will automatically cause a previous grade of F, whatever the grade of this job. Six total unexcused absences will automatically bring about a previous grade of F, despite the caliber of the job. That means you can see my confusion.
Letters are the Perfect forum for People Who are earnest into a fault. Simply speaking, the letter needs to be well-thought and carefully written. In a nutshell, the correspondence should contain details about who you are, what's your relation with the concerned person, length of your relation, what you know more about the charges levied and your comprehension of the character of the person. You may file the letter through the concerned attorney, who will also assist you with drafting. A child custody reference correspondence isn't the 1 thing which vouches for a individual's capability to get a parent.
If You'd like a letter for yourself, ask somebody who has Known you for a very long time and can mention positive things about youpersonally, to compose it. It is always recommended to write a letter on your own, instead of using templates, which may or might not fit your criteria. The letter needs to have a tone of admiration, and need to be clear and succinct. The letter that's written is extremely essential since it can occasionally shift the entire equilibrium and alter a verdict completely. It's also beneficial in case the letter is composed by a person who has known the defendant for some moment. Normally, character reference letters are intended for supporting the positive aspects of an individual, and therefore are often employed for job purposes.
The letter shouldn't be from an individual who is'important' per Se but it ought to be from someone who's an superb personality witness and has something positive to say concerning the defendant. Once you receive a letter, you have got time to collect your ideas, let relationships appear, and stew over the notions which have been suggestedwhich makes all the difference. A character reference letter needs to be crisp and most importantly, believable. Among the biggest complaints about dream faiths is they're simply the aesthetic of a true religion disguised beneath another name. Supply your contact details so you are ready to be reached in case it's needed. Obviously, the two cases aren't identical. A charm was created to offer custody of the child to that parent, depending on the info you have provided in the letter.
In accordance with Republican logic, the ideal strategy to estimate The ideology of a man or woman is via their immediate family. Ultimately, the superb readers always address the issue! Thus, it's imperative you understand the appropriate arrangement of this letter before you begin writing one. Indiscipline or lack of discipline among students is something which's impacting the society. Stewart, aside from really being a husband, is also an excellent friend of his small one. While it has a whole lot of useful stuff, in addition, it contains a great deal of dried and meaningless passages.
Write why you think the man who is being tried Should be pardoned. Mention the duration of time you've known the individual. People continue to lift up others and search for something larger than themselves. Along the way, they may think you're delusional. Sometimes ugly men and women create beautiful things.
Everyone was frightened to discuss the circumstance or present any solutions. Hence, the issue of indiscipline and unrest among pupils is a part of a far larger problem viz. You have focused on the problems that define you and the problems that you would like to assist define. In case you have any additional questions, please don't hesitate to get in contact with me personally on 454-545-3296. Put simply, it's an outstanding thing which can not be argued. Obviously, there are still differences of view that could show up in the conversation with an increased clarity.
Amidst a great narrative, students may find themselves at the Middle Of a moment in time. Word girl is a superb animation about a woman who's a super hero. The Cinderella story teaches kids that they can make excellent choices when confronted with demanding conditions and unfair therapy. Fantasy is famous for its imitation religionsand also famed for doing them badly. It's likely to stick by the comics and earn a film liked by everybody. The hero needs to be absolutely the most tragic personality in the play. A tragic hero is one of the most vital elements of a Shakespearean tragedy.
Your fake faith Will Likely have prayers, customs, and Authorities exactly the same as real religions do since they're serving the specific same Purpose as real religions, but it is still a fact that you must do the job of Creating the faith feel real and distinctive. Unjust laws aren't laws whatsoever. It's crucial to recognize natural law prior to any law. The crime Isn't knowing the ideal word to utilize in a particular situation.


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McDonald's Shamrock Shake is Back!
As I was ordering my Fruit & Maple Oatmeal from McDonald's this morning – I noticed the Shamrock shake is now available! My recommendation: ask for it half Shamrock/half chocolate for a real treat!
We All Make Mistakes…Even McDonalds
When I think of McDonalds, I think of a well oiled machine. All processes and procedures are well documented and implemented millions of times every day – thus the consistency we all appreciate. There are sometimes that the process breaks down regardless of how carefully you have planned everything out (as you can see with their web site). The important thing to take away from making mistakes is not to focus on the fact you made the mistake, but to rather focus on making the correction and learning from it so you can prevent similar mistakes from happening in the future. Remember – we all make mistakes…even McDonalds.
A nice quote I recently came across by Laura Ingalls Wilder:
The real things haven't changed. It is still best to be honest and truthful; to make the most of what we have; to be happy with simple pleasures; and to have the courage when things go wrong.
Media Mondays: Chipolte Chipotle Ordering iPhone App
Last week I did some browsing and found something really awesome (for the Chipotle fans out there) – an iPhone app that will find the nearest Chipotle(s) then allow you to place an order using the iPhone app.
The application is call Chipotle Ordering and is a free download. No more waiting in line or carrying a paper filled with Amy's weird requests. I am super excited with this look forward to quick and easy Chipotle visits.
Pumpkin Seeds
I love pumpkin seeds and I absolutely love the fall because I can get some pumpkins, carve them, and then cook and eat their wonderful seeds. I have also been suckered into trying off-season pumpkin seeds from just about every company that makes them…and they all have been a huge disappointment in some way or another. (Too salty, stale, no flavor, etc)
A few months ago while at Whole Foods – I decided to try their pumpkin seed hearts in bulk. The only downfall with these are they are only the hearts – so you do not get the enjoyment of cracking the seeds open, but man – finally I found a good "in every season" pumpkin seed. Anyway – if you need a pumpkin seed and it is summer – head to Whole Foods!
A Saturday With Ben!
Someone that I worked with for eight years came to town this past weekend for a meeting and I was fortunate enough to meet up with him on Saturday. It was quite interesting to me that I felt as though he never left – we just picked up where we left off. (Except for the fact we were both working different places and happy working) A big thanks to Ben for a nice Saturday, his chauffeur services, the dinner at Lawry's, and the wonderful picture I have hanging in my office! Rock on!
Jappler Recommends: McDonalds' Online Monopoly Game
If there is one thing I absolutely love about McDonalds (besides their superior Coke mixture) I love their Monopoly game. I even dreamt about the game a few nights ago that I pulled off Park Place and Boardwalk from the same Coke…and won $246. With that said – the excitement of pulling off the little game pieces from my medium Coke and putting them onto the board is usually enough to make me smile. I happened to have a pile of pieces at my house (maybe 6) and decided to go online and check out their "online Monopoly game". When I first got to the page – I was instantly frustrated. My #21 pet peeve in life happens to be sites that resize my browser window. However, after I resize it back to how I wanted it – I was blown away with the coolness of the site. I entered in my name and information, and then started to play. It was cool, intense, and well done (and my #12 pet peeve in life is overdone flash). I look forward to playing soon! If you have not checked this out – do it! (This means you Julie)
*For the most fun, wait until you have 5 pieces – each piece = roll of the dice.
Trader Joes' Guarantee
Today I went into a Trader Joe's to pick up some beer and the the guy at the checkout reminded me that if I did not like the beer I was welcome to bring it back for a full refund. I told him I was very impressed with their customer service and he told me it was to promote customers being more adventurous. I have been a Trader Joe's for a few years now and even more so after tonight. I love that they want their customers to be more adventurous with their choices. Cheers to Trader Joe's for making me think about trying new things!
moxie and tax day.
Well, as 2005 is my first year as a small business owner, I am learning something new everyday. On Monday, I learned the importance of having a really good accountant, as he called me and gave me a heads up on the fact that my 2005 taxes were due today. Thankfully he prepared an extension letter and sent me the details of what I would need to do to make sure I would not be penalized. I had met with my accountant earlier this year to learn QuickBooks and to get to know him before tax time…thankfully that paid off. Thanks!
While trying to find someplace close to mail the letter to the state, and needed to get it stamped today, I stumbled onto a little shipping/mailbox store that not only sold me some stamps, but also sold me a bottle of Moxie. Seems there is local business called Retro Soda Inc that he had partnered with to provide these retro sodas in his store. I had heard of Moxie on FoodTV, but never saw it in any stores. Given the chance to have another…I would. It is an interesting taste…some cola, and some anis, but all in all, a good find!
PS, the item next to the Moxie is my 1986 Volvo 760 GLE's starter ignition switch. 😉
[tags]business taxes, Moxie, QuickBooks[/tags]
yuengling beer.
Ahh, trips to the east coast are good for at least one thing: Yuengling beer. Some of my fondest memories in college were spent with a bottle of Yeungling beer in my hand. Way before the game, before the game, after the game, during the game…it was always there for us at Penn State. If you have a chance to order a Yuengling, give it a shot. If for nothing else, you can say you had beer from America's Oldest Brewery. On a side note, go Joe! Congrats on the four year contract!!
Coke C2
Ok, I have a Coke problem…a Coca Cola Coke problem that is. I would love to cut my Coke habit down a bit. I am not too functional before my morning 12 ounces of enjoyment. I have been religously drinking Coke for six years now and I am sure all the sugar goodness has not been beneficial, but I love my Coke. Along comes Coke C2 with half the calories and half the sugar. Immediately I was both excited and cautious. Excited=less calories. Cautious:aspartame. I first tried this new Coke mix on Sunday out of a 20oz bottle and was not impressed, but a friend of mine brought me in a cold can of it this morning and I was pretty happy with it. Nothing will ever beat a McDonald's Coke, but you should definitely try the new C2. (I feel like they should have come out with this in 1997 when T2 came out) Now aren't you glad it has my seal of "ok" products? I thought so.

subset: commoncrawl


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A month ago, I was inspired by Zero2Fire's challenge to live on $1,500 a month. Now, that's not a feasible challenge for all our family expenses right now (perhaps an aspiration?) but I wanted to put myself on a challenge for my expenses. Could I go from a world of "spend whatever's in my bank account" to spending $1,000 or less a month?
tbh, that number was arbitrarily picked, and I assumed it would be easy. After all, I YNAB now! This is just supposed to be "my" expenses - the fun money, the professional spends, the personal hygiene, the lazy-and-forgot-to-pack-a-lunch costs. My incentive was that if I didn't spend the full $1,000, I'd roll over the extra to my acorns account and get the rush of a little extra investing.
Well, digging in on YNAB showed me that in my months of tracking, I spent an average of $1,200 on these types of expenses, and I didn't preplan for big purchases - like a knife set wedding gift - so I had some wild fluctuation. Last month, I tried this challenge and gave up after spending a quarter of my allotted budget on Broadway tickets for my Mom's visit. Whoops. I completely gave in to the fallacy of "well, I blew this day so the whole month is lost" that has plagued dieters, savers, exercisers across all tracking devices.
Not this month. I've shorn up my resilience (and started this blog) so I'll be reporting on the success (or failure) of this experience and what I've learned. Though we use YNAB for all our expenses (and I use it for my personal expenses too) I wanted to instantly track these discretionary dollars. I'm using the iOS app BUDGT to instantly track, and also see how much I can spend each day without going over in the month. I'm pretty certain I learned about BUDGT five years ago from this write-up - I think it could be a challenge for a household's budget, but it's great for simple planning.
Now, BDGT projects that I'll end the month -632.67. ouch. I had a few purchases in this first week that front-loaded my spending - had visitors this weekend! I purchased a plane ticket (138.29), paid for a very pricey uber (60.72), took the family out to lunch (60.11) and bought a few Kindle books in my favorite series (33.50).
My allowed daily spend is up to 24.55 as of today, but I have a goal of four zero-spend days this week in anticipation of more visitors next weekend! I really enjoyed this article as a motivation for no-spend days.
Leave a Reply.
Blog posts are all by Mrs. Us in Orlando unless otherwise noted. A former military kid, she's glad to have landed in the sunshine state and enjoys year-round summer sports, making every book a "beach read", waterside walks with the fam, and iced lattes.
September 2019


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PIF Families was established to allow engaged and married couples and parents to support and encourage each other so that we can build families firmly grounded in God's Word and His love.
We hope to see as many of our newcomers and long-time members as we can!
This months meeting place: House of Isabel Vergara


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We help under-resourced women in our community
start and grow their own business
The Uncommon Collective is a non-profit – but we're not a handout or a charity. We are an incubator and a support system for capable yet under-resourced women.
It's hard enough to start a business on your own.
But belief can be especially hard to achieve when you feel unheard and undervalued. That's why we believe we are better together.
We provide financial support, a mentor ally, and business guidance to owners-to-be with the desire to succeed.
We help them operate and eventually own their own profitable, fair and sustainable business.
Because one woman making this change for herself, her family and her community – has a generational and social impact that goes beyond just business.
That's why we are an "uncommon collection" of diverse people, coming together to create a path for women – a path toward the equality, understanding and possibility our city needs.
Would you like to find out more about mentor-ship, volunteer, or donor opportunities?
Maybe you or someone you know is interested in becoming a business owner?
Either way, we would love to meet you over a cup of coffee, hear your story, and learn more.


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Soleimanifar, Simin and Jafari, Zahra and Motasaddi Zarandy, Masoud and Asadi, Houman and Haghani, Hamid (2016) Relationship between Intelligence Quotient and Musical Ability in Children with Cochlear Implantation. Iranian Journal of Otorhinolaryngology, 28 (5). pp. 345-352.
IJORL_Volume 28_Issue 5_Pages 345-352.pdf
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Introduction: Children with cochlear implants (CIs) may experience few opportunities for positive musical experiences, and musical perception is therefore often not sufficiently developed. This paper investigates and discusses the relationship between intelligence quotient (IQ) and musical ability in children with CIs compared with children with normal hearing. Materials and Methods: This was a comparative analytical study conducted in 48 children with unilateral CI and 48 normal-hearing children, 6–8 years of age, with 'normal' IQ and no formal music training. The average IQ score in the experimental and control groups were 105.41 and 106.31, respectively. No statistically significant differences were detected between Raven's IQ scores in both groups. Data were collected by administering Raven's Colored Progressive Matrices IQ Tests and the Montreal Battery of Evaluation of Musical Abilities (MBEMA) Test, consisting of scale, contour, interval, rhythm, and memory sections. Results: Mean total MBEMA score in the experimental and control groups was 58.93 and 72.16 (out of 100), respectively. Significant differences were evident between scores of children with CIs in comparison with their normal-hearing peers (P≤0.001). A remarkable direct correlation between IQ and musical scores in both the control (r≥0.38) and experimental (r≥0.37) groups was observed. Conclusion: IQ has a noticeable effect on music processing and facilitates the perception of various musical elements. With regard to the mutual relationship between IQ and musical skills, this study illustrates the advantage of determining music perception scores and highlights the importance of appropriate musical intervention in order to enhance auditory neural plasticity, especially in children with cochlear implantation.
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|WV Otolaryngology
|Journals > Iranian J Otorhinolaryngology
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|ijo ijo
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|24 Sep 2017 15:01
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Why Mike Davis was signed to help replace Jordan Howard
Bears clearly valued Davis' versatility over Howard's past production
Bears fans, you could have seen this exclusive analysis first, in your inbox, on March 13 if you subscribed to PFW: Chicago. Don't miss out on in-depth analysis, without the fluff or hot takes.ĀSubscribe today and get your first full year for only $27!
Whether you prefer to follow the finances, factor in the fit or ideally both, it appears the Bears signed former Seahawks RB Mike Davis as part of their Jordan Howard replacement plan.
We realize that's not a popular observation around these parts, but Ryan Pace opted to give Davis a reported two-year deal worth up to $7 million with incentives. No, it's not a bank-breaker by any stretch, but relatively speaking it'll easily make him the most expensive back in Chicago's stable.
Howard, who was traded to the Philadelphia Eagles in exchange for a 2020 sixth-rounder that can become a fifth, will earn $2 million in the final year of his rookie deal, thanks to a performance escalator. Free agent Benny Cunningham, who actually first arrived in Chicago with receiving production similar to Davis', signed a one-year, $1 million deal last offseason to return in the first year in Matt Nagy's scheme.
If Davis was tabbed as Cunningham's replacement, why would he get 600 percent more than Cunningham signed for in an offseason when the Bears were basically printing money, not restructuring contracts and still shopping at the bargain bins?
That's the financial argument for Davis being more than merely a depth and special-teams addition. Now, the more fun part — what he brings to the field.
"Davis is a tough runner who can catch out of the backfield," one personnel man texted us Tuesday of the signing. "Just have to stay healthy."
Howard certainly checks the first box above as a tough and determined runner, and entering Year 4 the next game he misses because of injury will be his first, so clearly Davis isn't an upgrade in that department.
But Davis is a vastly more effective and experienced receiver, and it should be clear to anyone paying attention that finding a "hybrid" back is the Bears' top priority in fixing their run game. Nagy pretty much said so himself two weeks ago at the combine.
"When you're dealing with running backs for us, in this offense, you want to be able to have a guy that has really good vision that can make guys miss," Nagy said. "And at the same time, there's that balance of being a hybrid, being able to make things happen in the pass game too, but yet to where you're not one-dimensional."
The Bears ran 55 percent of the time when Howard was on the field last season, the second-highest rate in the league, according to NFL's Next Gen Stats. Conversely, with Tarik Cohen in the game, they ran only 37 percent, the fourth-lowest rate.
Howard is a really talented runner with the kind of plus vision that Nagy cited, and he's proven he can hold up while handling a big workload. But in addition to not being as quick or nifty as Davis (5-foot-9 and 217 pounds) and lacking the newcomer's track record in the passing game, Howard's stamina and better-with-a-lather style doesn't matter as much in Nagy's system — "not an offense where you're going to get 25-30 carries," the coach said.
Davis, who was actually drafted in the fourth round in 2015, one year before the Bears found Howard in Round 5, had two 30-plus catch seasons at South Carolina prior to joining the NFL. After failing to break through in San Francisco, he carved out a valuable niche in Seattle, where he caught 49 passes for 345 yards (7.0 YPC) in 21 combined games.
Last season, easily Davis' best, he was among the NFL's most reliable pass-catching backs with a reception rate of 81 percent — better than Howard, Cohen and actually all but eight NFL runners with 40-plus targets, including a pair of All Pros (Ezekiel Elliott and Christian McCaffrey).
Davis wasn't a big-play source as a receiver for the Seahawks but did have a higher broken-tackle rate (one every 4.25 catches) than Cohen (4.44) after the catch and created more after contact on the ground (2.94 yards per carry) than not only Howard (2.74) but Alvin Kamara (2.75) and Joe Mixon (2.76), according to PFF. Davis also gained nearly a full yard overall more than Howard on each carry last season (4.6 to 3.7) and earned the same AV (approximate value) grade from Pro Football Reference — 6 — as Howard.
Despite being two years older than Howard, the 26-year-old Davis also has a lot more tread on his NFL tires (293 touches compared to 850 for Howard), which could also help explain why the Bears committed to him on Day 1 of free agency for two years as they continue shopping their incumbent. And while Howard's overall production has trended downward since his outstanding rookie season, Davis' numbers are up year over year in virtually every statistical category.
Is Davis the next Le'Veon Bell, who, depending on you believe, also was at least a consideration of the Bears to replace Howard? Of course not. Can Pace find an upgrade from both Davis and Howard next month in the draft? Absolutely.
But the signs pointed toward a changing of the RB guard in Chicago long before Davis' arrival, and it's now confirmed the Bears value Davis more than Howard as their run game continues to evolve.


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Singletasking Series: Part 3 – Understanding Multitaskalism
Tags: attention economy, multitasking, single-tasking, singletasking, Web 2.0
This is the third post in a series on Singletasking (in case you missed the bit in the heading that says, "Part 3″).
People around the world are multitasking with reckless abandon. They are addicted and they don't even know it. This affliction is so widespread we don't even notice it anymore.
For lack of a better word, I've decided to call this pandemic "Multitaskalism"
(OK, technically it already has a better name. ADT or Attention Deficit Trait.)
Multitaskalism can be defined as the result of the mental reprogramming that occurs over time when people habitually try to tackle multiple tasks simultaneously.
Symptoms of Multitaskalism:
- The knowledge that you could and should be producing more than you are;
- The feeling that you're smarter than your output seems to suggest;
- Responding to questions more hurriedly and with less well-considered answers than you should
- The feeling that the reservoir of new ideas is starting to run dry and that the few new ideas that are coming through are sometimes only half-formed;
- Working longer hours but producing less;
- Sleeping less and having less free time for exercise and socialising;
Causes of Multitaskalism
- Access to an increasing number of inputs and outputs
- Living in the digital age, we presume that human brains are like giant organic CPUs and we tend to treat it as such
- Switching attention from one thing to another has a stimulant effect, caused by the release of chemicals within the brain. This form of chemical stimulation is addictive
- The diversity of the average workday, so critical in alleviating boredom, means our mental resources are constantly pulled in a variety of directions
- The increase in the number of communication channels and the ease of communication means that the nature of interpersonal interaction has changed. It's more frequent and often brief, which equates to regular interruption.
- Intake of stimulants like caffeine may also be a compounding factor.
Possible long-term effects of Multitaskilism
- Rewiring of the brain, making it function in a specific way
- The diminished ability to hold on to and fully develop specific and complex ideas
- Emotional strain due to the reduced ability to understand and manage emotions
- Reduced ability to process and structure information, especially complex information.
- Reduced ability to store and recall information – i.e. reduced memory function
- Reduced ability to break complex tasks down into simpler individual tasks
- Reduced ability to order and prioritise tasks
Have you experienced any of these symptoms or effects? Are you a victim of multitaskalism?
Is this even a real phenomenon? I'd love to know what you think.


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Greater Commitment
Author: Gil Ash
Posted on May 14, 2019
In the end it takes a greater and greater commitment to train longer and at higher levels to achieve higher and higher successes. Sooner than later that commitment is not met with the desire of shooters to put in the time which leads to looking for the short cut by trying to see or do what some other shooters are doing. News flash you can't do what another shooter can do that has put in the effort and work to achieve higher and higher successes. Skill is not built that way and cannot be transferred one to another.Back to Blog


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Pisco Lounge at Coya
A trendy Peruvian joint with a buzzing vibe and some top mixed drinks
If you're looking for a drink in Jumeirah, look no further than Pisco Lounge at Four Seasons Resort Dubai at Jumeirah Beach. Pisco Lounge, which is the bar for Time Out Dubai's 2016 Restaurant of the Year COYA, is based on traditional bars from Lima, Peru, and provides an authentic and fun night out.
Serving up a range of mixed drinks, there are creative concoctions with a modern twist on classics made up by the talented and friendly bar staff. With an 11-metre long bar there's plenty of space to grab a drink and kick back pre- or post-meal, too. The décor is trendy and funky – with plenty of vibrant green tiles set against dark wood furniture for a grown-up, elegant feel. The coppery light fixtures lend warm tones, too, while it's also a bit industrial chic making it more playful than stuffy.
COYA is certainly worth stopping into for dinner, too, if you're after some truly excellent Peruvian cuisine. Why not make a night of it?
Open Sat-Tue 12.30pm-3.30pm, 7pm-midnight; Wed-Fri 12.30pm-3.30pm, 7pm-12.30am. Four Seasons Resort Dubai at Jumeirah Beach, Jumeirah Beach Road (04 316 9600).
Black Tap
All-American bar with a cool vibe, fun bites and trendy interiors
If you've been anywhere near Instagram in the past couple of years, chances are you'll have seen Black Tap while scrolling. Famous for its towering freakshakes in a rainbow of vibrant (sugary) colours to its juicy burgers, this chain has a huge following. However, it's not all about the all-American cuisine, though it would be churlish not to try it while you're there.
Set up by Michelin-starred chef Joe Isidori in New York in 2015, Black Tap has been making waves wherever it goes – from the US to Dubai.
Its first Dubai outlet, at Jumeirah Al Naseem, has been a massive hit, routinely packed day in, day out. And with good reason – it's fun, funky and buzzing. With views outside to Jumeirah Al Naseem's turtle lagoon, the floor-to-ceiling windows open up fully in cooler months giving
a light, bright and breezy air to the burger joint.
Inside is all graffiti-strewn walls and exposed brickwork that lends an urban-cool feel. The bar itself is set to the back of the space – being unimposing and tucked far enough away that you can enjoy the vibe but not be within fry-stealing range of diners. Staff are friendly and there's a wide range of mixed drinks and craft hops, all coming in at decent prices – with a selection of hops and grape coming in at under Dhs40. Fancy a bar snack? Don't miss the onion rings, crisp, tasty circles that will transport you to retro American diners in one salty-sweet bite. Settle in for a drink and a chat, you won't be disappointed.
Open daily 11.30am-12.30am. Jumeirah Al Naseem, Umm Suqeim (04 422 9904).
Elegant Turkish restaurant at Dubai Marina that's not to be missed
There are many reasons to visit RÜYA, the primary one being the food. However, it's also excellent for a drink, should you not be after a full meal.
Head here early evening and you can enjoy a pre-dinner drink at the large central bar, or, in the cooler months, the picturesque terrace. The latter is decked out in plenty of twinkling fairy lights, giving a moodily lit, charming vibe to the area. It also boasts views, albeit from a low level, across Dubai Marina, so it's a top place for a spot of yacht watching, too.
If you are peckish, don't miss the excellent food from chef Colin Clague and his team. RÜYA is our Best MENA Restaurant 2018 and we highly recommend sampling some of the dishes – especially the egg and two-cheese pide, it's truly wonderful and makes for a great accompaniment to a drink. Don't miss the inventive mixed drinks, which use a variety of ingredients including hibiscus, rose, pomegranate, honey, spices,
citrus and mint.
RÜYA – which aptly translates as "dream" in Turkish – knows a thing or two about combining flavours and getting them spot-on every time.
Open Sat-Wed 6pm-1am; Thu 6pm-2am; Fri noon-4pm, 6pm-2am. Grosvenor House Dubai, Dubai Marina (04 399 9123).
folly by Nick & Scott
If you're looking for views of the Burj Al Arab and the waterways of the Madinat Jumeirah, look no further. A great spot for sundowners, and to wow your guests.
Open Sun-Thu noon-2.30pm, 7pm-11pm; Fri-Sat noon-3pm, 7pm-11pm. Souk Madinat Jumeirah, Umm Suqeim (04 430 8535).
La Petite Maison
Our Best French Restaurant 2018, this is a classic, chic and always bustling bar in DIFC that's worth a post-work or pre-dinner drink. Elegant and upmarket, it's one to dress up for.
Open daily noon-3.15pm, 7pm-11.15pm Gate Village 8, DIFC (04 439 0505).
Miss Lily's
This quirky Caribbean hangout is a huge hit in its native New York, and has proved equally popular in Dubai. Loads of fun and packed with island vibes. Don't miss the bar snack-friendly tasty food either.
Open Sat-Tue 7pm-1am, Wed-Fri 7pm-2am. Sheraton Grand Hotel, Sheikh Zayed Road (04 354 4074).
With a cool vibe, moody lighting and a massive fish tank, this is a trendy spot to grab a drink and dinner. There's also a great ladies' night, offering unlimited free sparkling and grape on a Wednesday.
Open daily 7pm-2am. The H Dubai, Sheikh Zayed Road (04 501 8777).
Another Japanese restaurant with a great ladies night, this trendy JBR hangout is great for a night out. Expect drinks, dancing and a cutely-decked out terrace.
Open Sun-Wed 6pm-2am; Thu 4pm-2am; Fri noon-2am. DoubleTree by Hilton Hotel Dubai – Jumeirah Beach, The Walk, JBR (04 559 5300).
The MAINE Oyster Bar & Grill
Swanky New-England-esque oyster bar with great food, a busy Wednesday ladies' night and an excellent al fresco terrace.
Open Sat-Wed noon-midnight, Thu-Fri noon-1am. DoubleTree by Hilton Hotel Dubai – Jumeirah Beach, The Walk, JBR (04 457 6719).
Trendy Peruvian/Japanese restaurant bar that cranks up late into the evening, with lively Latin Amerian music.
Open Sat-Tue 6pm-midnight; Wed-Thu 6pm-1am; Fri noon-1am. The Oberoi Dubai, Business Bay (04 453 5283).


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Letters to the Editor
Letters to the Editor 10/3
Junk the Patriot Act
The time for revoking the Patriot Act and passing the new Justice Act is now. People should not have to live in fear of being jailed and/or abused because of their religion, ethnicity and/or gender preference. It's time to right the wrongs of the past administration and help make this new administration one of the best in the history of our country. We must work together to make the dream of true peace and justice come true.
Jason Cantu
Morro Bay
Bad policies continued
The Church Committee — a model for sustained inquiries into the government's handling of intelligent affairs during the Cold War — must be a model for a committee to investigate the various questionable policies established by the CIA and other government agencies during the Bush administration or any other administration.
It is interesting to note that when the War on Terror became the focus of the Bush administration, the ideas advanced by the Church Committee where subverted.
During the first six months of the Obama administration, the CIA may have been training assassination agents to "get" Al Qaeda agents before Leon Panetta or Congress were notified. They also outsourced parts of an assassination program to Blackwater.
The Obama administration continues many of the Bush policies regarding state privileges in federal court in order to keep hidden the Bush secret programs.
What the Church Committee should be noted for is their illuminating the concept that "absolute power corrupts absolutely." The CIA's tendency is to counter any control by stating that any Congressional oversight will destroy programs aimed at the country's security.
A new committee patterned after the Church Committee is certainly necessary today to expose the crimes and misdemeanors that have been committed by some government agencies.
W.R. Cole
Arroyo Grande
Beck the divider
I am writing this letter to hopefully reach some people who believe Glenn Beck represents an honest response to current political debate. Mr. Beck's broadcast uses racial fear and paranoia to divide the country we all love. He behaves in a most anti-American way by trying to destroy us from within.
Our country needs to work together in this dangerous time. People like Mr. Beck are divisive and dangerous and should be called out for their lies and distortions.
We need to work hard America. Honest work. Let's get started by saying no to people like Glenn Beck. He has nothing but hate to offer.
Gregory Ross
Arroyo Grande
Good coverage
Kudos for your in-depth coverage of California's fiscal mess. Your series, including articles from the Sacramento Bee, makes our situation much easier to understand as well as making finger pointing and whining more foolish.
Now, of course, it's time for us to do something about it. Let's hope our legislators have the courage to change, or we have the courage to change legislators if they don't.
Michael Morin
Support appreciated
Thank you to all that attended, planned on attending and forgot to attend the San Luis Obispo County Airport Day.
A special "thank you" is given to the Experimental Aircraft Association San Luis Obispo Chapter 170, their board and members for sponsorship of this event.
Supporters of this long-running annual program include:
John L. Eichler
Event chair, Airport Day 2009


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Once engaged, a forensic accountant
will review the applicable BI coverage,
and familiarize himself/herself with both
macro and micro-economic trends of the
insured's industry. The forensic accountant will then contact the appropriate representative to discuss the loss occurrence
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accountant." Be it a small "mom and pop" opera-
Seasonal or long-term sales trends. For instance, a hotel, located in South Florida, had a fire
in August. The measurement period is determined to be one month. As the measurement
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recent expansion or reduction in operating capacity. The insured purchased additional
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recent increase or decrease in competition. One example would be that shortly before
the date of the incident, a Best Buy opens a new store across the street from the insured's
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information may be inappropriate to project future sales.
recent sales contracts. Let's say the insured in No. 2 above purchased the additional
equipment because of a contract signed with a new customer that would result in significantly
greater production and sales. The strict reliance on historical sales and or production
information may be inappropriate to project future sales.
Possible mitigation of loss. An example scenario would be a "friendly" competitor may be
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product it could not produce during the loss measurement period.
tion or a large complex business, a forensic accountant will expedite the claims
process by having the ability to translate
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reflected in its financial records, to its BI
One of the critical factors in determining the value of a BI loss is the "time element," or duration of time the BI loss
will be measured over. A claims adjuster
may make a determination of the mea-


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Author Affiliations
- Daniel Fuerst1,2⇑,
- Carlheinz Mueller3,4,
- Dietrich W Beelen5,6,
- Christine Neuchel1,2,
- Chrysanthi Tsamadou1,2,
- Hubert Schrezenmeier1,2 and
- Joannis Mytilineos1,2,3
- 1Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German, Red Cross Blood Transfusion Service, Baden-Wuerttemberg – Hessen, Ulm, Germany
- 2Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
- 3DRST – German Registry for Stem Cell Transplantation, Ulm Office, Ulm, Germany
- 4Zentrales Knochenmarkspender-Register Deutschland (ZKRD), Ulm, Germany
- 5DRST – German Registry for Stem Cell Transplantation, Essen Office, Essen, Germany
- 6Department of Bone Marrow Transplantation, University Hospital, University of Duisburg-Essen, Essen, Germany
- Correspondence: d.fuerst{at}blutspende.de
Hematopoietic stem cell transplantation is a multifactorial process. Some of the predictors exhibit time-dependent effects. We present a systematic analysis and description of selected clinical predictors influencing outcome in a time-dependent manner based on an analysis of registry data from the German Registry for Stem Cell Transplantation. A total of 14,951 patients with acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome and non-Hodgkin lymphoma transplanted with peripheral blood stem cells or bone marrow grafts were included. Multivariate Cox regression models were tested for time-dependent effects within each diagnosis group. Predictors not satisfying the proportional hazards assumption were modeled in a time-dependent manner, extending the Cox regression models. Similar patterns occurred in all diagnosis groups. Patients with a poor Karnofsky performance score (<80) had a high risk for early mortality until day 139 following transplantation (HR 2.42, CI: 2.19–2.68; P<0.001) compared to patients with a good Karnofsky performance score (80–100). Afterwards the risk reduced to HR 1.43, CI: 1.25–1.63; P<0.001. A lower mortality risk was found for patients after conditioning treatment with reduced intensity until day 120 post transplant (HR: 0.81 CI: 0.75–0.88; P<0.001). After this, a slightly higher risk could be shown for these patients. Similarly, patients who had received a PBSC graft exhibited a significantly lower mortality risk until day 388 post transplantation (HR 0.79, CI: 0.73–0.85; P<0.001), reversing to a significantly higher risk afterwards (HR 1.23, CI: 1.08–1.40; P=0.002). Integrating time dependency in regression models allows a more accurate description and quantification of clinical predictors to be made, which may help in risk assessment and patient counseling.
Outcome after hematopoietic stem cell transplantation is influenced by different factors. These include disease stage1 or cytogenetic risk,2 but also pre-transplant treatment-related variables, such as conditioning toxicity and selection of therapeutic agents.3 Furthermore, donor or graft properties may affect outcome.4 Of these, for example HLA-matching, cytomegalovirus (CMV) status or graft source are usually considered, as they were found to impact transplant-related outcome.5 Finally, post-transplant treatment in the form of graft-versus-host disease (GvHD) prophylaxis and therapy with growth factors or steroids may influence morbidity and mortality.6 Predictors may be categorized as modifiable, such as type and dosage of therapeutic agent, or as invariable, e.g. genetic factors.
In survival analysis, different groups are compared and effects may vary in size, also in a time-dependent manner, as the outcomes are time-to-event end points. Some effects may change in intensity over time or may be present only for a limited period, e.g. therapeutic interventions. From a clinical perspective, intensity of conditioning treatment is likely to show time-dependent effects as toxicity resolves with time. In addition, graft source may show time dependency as the kinetics of immune reconstitution is quite different in bone marrow (BM) and in peripheral blood stem cell (PBSC) grafts.7 Karnofsky performance score (KPS) has been shown to associate with a high early mortality.8,9 Finally, disease stage might be of interest, as relapse-associated and transplantation-associated events may have a greater impact on advancing disease stage early after transplantation. One important tool to evaluate survival is Kaplan-Meier analysis,10 in which time-dependent effects may manifest as crossing or diverging/converging survival curves (Online Supplementary Figures S1 and S2). However, Kaplan-Meier analysis is a univariate method and does not allow examination of multiple effects in combination. For multivariate analysis, the standard methodology is Cox regression analysis,11 which is limited by the "Proportional Hazards Assumption" (PHA). This means that all effects in the model are assumed to remain constant over time. This is often not the case, and would lead to false regression estimates, and, therefore, false hazard ratios for such effects if ignored. In such situations, the Cox regression model has been extended to allow for adjustment of time-dependent effects.12 To visualize such effects over time, dynamic regression modeling has been proposed.13 Models including time-dependent variables have been used in important clinical studies.14,15 However, such time-dependent effects have not been studied in a dedicated analysis of HSCT data before, as their interpretation is not as intuitive as that of relative risk estimates obtained from variables fulfilling the PHA. In this study, we investigated selected clinical predictors of unrelated stem cell transplantation (HSCT) for time-varying effects and aimed to identify, describe and quantify these effects in such a way as to facilitate their interpretation by the clinician. For this reason, we analyzed a large cohort of patients based on data from the German Registry for Stem Cell Transplantation (DRST). Patterns that were observed in a similar fashion across the different disease entities are reported.
The DRST database is a subset of the European Group for Blood and Marrow Transplantation (EBMT) ProMISe database and includes patients transplanted in Germany. Clinical data of all patients receiving a first allogeneic transplant for the disease entities acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS) and lymphoma were retrieved. The category lymphoma included chronic lymphocytic leukemia (CLL) and was sub-classified in aggressive and indolent. No missing values were accepted for disease stage, HLA-match type, and source of stem cells. Only adult patients and patients transplanted with BM or PBSC were included in this analysis. A total of 14,951 patients were eligible with a median age of 48 years (range 18–78). Transplantations were performed between 1976 and 2013. Median follow up of surviving patients was 49 months. Patients' characteristics are summarized in Table 1 and Online Supplementary Table S1.
The term "time dependent" is used for covariates not satisfying the PHA, which may be caused by an effect that changes in intensity over time or an effect that is present only for a limited time period and modifies subsequent risk. Disease stage definitions were adopted from the EBMT study group defining the EBMT risk score.14 Early disease stage was defined as transplantation in first complete remission for acute leukemia and as untreated or in first complete remission for MDS and lymphoma. Intermediate disease stage grouped for acute leukemia transplantation in second complete remission, for MDS in second complete or partial remission, and for lymphoma in second complete remission, partial remission or stable disease. Stages other than early or intermediate were classified as advanced disease stage.
Regarding conditioning regimen intensity, the terms myeloablative (MAC), non-myeloablative (NMA), and reduced intensity conditioning (RIC) have been introduced.16 However, the EBMT ProMISe format currently classifies non-myeloablative and reduced intensity together as RIC. From retrospective data, it is sometimes difficult to distinguish between NMA and RIC. Therefore, our study only distinguished between myeloablative and conditioning with less intensity, termed RIC. According to the EBMT standards, MAC conditioning is defined as total body irradiation (TBI) of 10 Gy or more combined with cyclophosphamide or etoposide, or busulfan 16 mg/kg combined with cyclophosphamide 120–200 mg/kg. For lymphomas, also BEAM and CBV polychemotherapy were considered as MAC conditioning. Regimens with lower dosages were considered as RIC (see EBMT MED-AB forms manual Appendix III; www.ebmt.org).
Overall survival (OS) was defined as the fraction of surviving patients at any given time point after transplantation. Death from any cause was considered as an event. Patients alive at the last follow up were censored.
Disease-free survival (DFS) was defined as the proportion of patients alive without evidence of disease at any given time point after transplantation. Death from any cause or recurrence of diseases, whichever occurred earlier, was considered as an event. Patients alive and free from disease at the last follow up were censored. Consent for scientific data analysis was obtained upon registration in the DRST. The study was approved by the ethical committee of the University of Ulm, Germany (n. 108/15).
Statistical analysis
The Cox regression model is a multiplicative hazard model, which means that the effect of covariates is modeled on a multiplicative scale in relationship to the underlying base-line hazard. While the effects of covariates are assumed to be proportional over time, no assumptions are made on the structure of the base-line hazard (the distribution of survival times). In contrast, the Cox-Aalen model includes a multiplicative as well as an additive component. The multiplicative part incorporates covariates that modify the excess risk similarly to the Cox model, while the additive part models the base-line hazard rate allowing for time-varying effects.17,18 For OS and DFS multivariate Cox regression models were fitted and PHA was examined by a test based on weighted Scheonfeld residuals according to the algorithm proposed by Grambsch and Therneau implemented in the "survival package" of the R statistical software (R-3.0.2).19 The test basically checks for linearity of Schoenfeld-residuals over time. Covariates not satisfying the PHA were further examined by fitting a Cox-Aalen model and plotting cumulative hazard curves.20 These curves show the change in hazard over time. A positive slope adds risk and therefore correlates to increased hazard rates (i.e. HR>1), a negative slope corresponds to reduced hazard rates (i.e. HR<1), and a slope 0 (a horizontal line) implies no effect on outcome. In time periods where the slope is constant or, in other words, a straight line, the PHA is satisfied for these time periods. Based on this information, it is possible to extend the Cox model by splitting the follow up for time-dependent covariates into observation periods and to estimate regression coefficients separately for these respective time intervals. Cut-off points for these time intervals were determined by fitting models from ranges of cut-off points. Selection of cut-off points was based on optimal log likelihood.
Multivariate models included risk factors defined by the EBMT risk score: age, disease stage, time from diagnosis to transplant, donor type, and recipient-donor sex combination. In addition, year of transplantation, graft source and conditioning therapy and KPS (<80=poor vs. 80–100=good) were included. Missing data for KPS (11.3%) were included in the models as separate category. Stratification was performed for diagnosis and donor-type; a center effect was adjusted using a gamma frailty term. Final models were tested for PHA and after adjustment for time-dependent effects all models satisfied PHA. P=0.01 was considered statistically significant.
As predictors of primary interest, we defined disease stage, graft source, conditioning regimen intensity, and KPS. Cox regression modeling for OS and testing of PHA indicated a strong non-proportionality of KPS (<80 vs. 80–100; P<0.001), conditioning regimen (RIC vs. base-line MAC; P<0.001), and graft source (PBSC vs. BM; P<0.001) (Table 2). The estimates for disease stage showed no time-dependent effect in OS analysis. For DFS, KPS (P<0.001), RIC vs. MAC (P<0.001), and PBSC vs. BM (P=0.001), as well as both the estimates for intermediate disease stage (intermediate disease stage vs. base-line early disease stage; P=0.004) and advanced disease stage (advanced disease stage vs. base-line early disease stage; P<0.001) indicated strong time-dependent effects. Based on these results, cumulative hazard curves were plotted to visualize the change in hazards over time [OS: Figures 1–3; DFS: Online Supplementary Figures S3–S7]. After selection of optimal cut-off points, final multivariate models were adjusted in a time-dependent manner. For the estimates of all time periods, the PHA assumption held; the PHA test was not significant (Tables 2 and 3), which proved that the specified cut-off points were adequate for our dataset. For OS analysis, these time periods were before and after day 139 for KPS, before and after day 120 for conditioning intensity, and before and after day 388 for graft source (Figures 1–3). For DFS, these time periods were before and after day 130 for KPS, before and after day 140 for conditioning intensity, before and after day 242 for graft source, before and after day 309 after transplantation for intermediate disease stage, and before and after day 242 for advanced disease stage (Online Supplementary Figures S3–S7). Follow up of the cohort was split into observation intervals, and separate hazard ratios were obtained for time-dependent covariates within the respective time periods. For analysis of KPS, the estimates obtained were considerably higher in the early period after transplantation as compared to the period later on. Unadjusted values lay in between (Tables 2 and 3). For conditioning therapy, no significant effect on OS and DFS was found in the unadjusted model, but modeling of time-dependent effects showed opposing significant effects before and after the cut-off time points for OS and DFS. In the early post-transplant period, reduced intensity conditioning appears to have a protective effect, whereas later on a higher hazard ratio was found for patients who had undergone conditioning with a reduced intensity. The observed effects correlate with lower early mortality and higher late mortality in this patient cohort. In the unadjusted models for OS and DFS, graft source did not correlate with significantly different outcomes. Interestingly, the effect of graft source could be better described by modeling separate estimates for the early and for the later period after transplantation. Similarly for OS and DFS, significant effects were found in the early period after transplantation, indicating lower probability for adverse events for patients transplanted with PBSC, while in the later period these patients seemed to do less well, as higher hazard ratios were observed (Tables 2 and 3). Other predictive covariates in the final model were: age (OS: HR 1.013, CI: 1.011–1.015, P<0.001; DFS: HR 1.011, CI: 1.01–1.013, P<0.001), year of transplantation 2001–2005 (OS: HR 0.89, CI: 0.82–0.96, P<0.001; DFS: HR 0.94, CI: 0.87–1.01, P=0.092), year of transplantation 2006–2013 (OS: HR 0.73, CI: 0.67–0.79, P<0.001, DFS: HR 0.81, CI: 0.75–0.88, P<0.001), and time to transplantation from initial diagnosis of more than 12 months (OS: HR 1.18, CI: 1.12–1.25, P<0.001; DFS: HR 1.21, CI: 1.16–1.29, P<0.001). A subset analysis was performed for transplantations using PBSC grafts performed between 2006 and 2013. For OS analysis, KPS and conditioning intensity showed time-dependent characteristics. For DFS analysis, KPS, conditioning intensity as well as disease stage (intermediate and advanced stage) could be confirmed as time-dependent variables. For both end points, similar risk estimates such as those seen in the analysis of the complete dataset were obtained in the subset analysis (Online Supplementary Tables S2 and S3).
We show in a large German patient cohort that important clinical predictors (KPS, disease stage, conditioning regimen and graft source) exhibit significant time-dependent effects. These effects may be quantified in a sense that regression coefficients and relative risk can be calculated for follow-up periods, which satisfy the PHA, by extending the Cox regression model. We describe patterns that were valid for all disease entities included in this analysis. Our data contain a large proportion of transplantations performed in recent years (2006–2013, 56.9%) and may, therefore, represent current approaches in conditioning treatment and supportive care. The selection of diagnoses aimed to include a large number of patients, while, on the other hand, restricting disease-associated heterogeneity to a limited number of disease entities. Considering time-dependent effects may reveal relationships that could remain undetected in standard Cox regression models. Such effects can be shown for KPS in analysis of OS and DFS. In the early phase after transplantation, the hazard ratio is substantially higher as compared to the later phase after day 139 (OS) and 130 (DFS), respectively. The biological explanation is that the higher risk in the early phase may be attributed to a substantially higher early mortality. This indicates that patients with a poor KPS tolerate transplantation-associated morbidity/toxicity less well. In the later phase, the effect of transplantation morbidity/toxicity disappears (according to our data around 139) and the higher risk in this group diminishes. It is, therefore, no coincidence that the estimated cut-off time points are similar for KPS and conditioning treatment (between days 120–140 post transplantation) as they most likely both correlate to conditioning-associated toxicity.
Perhaps even more interesting is the observation that the intensity of conditioning regimen, which did not show a statistically significant effect in standard regression modeling, showed clearly significant effects depending on the time interval after transplantations. Our data show that, in the early phase after transplantation, risk is significantly reduced for patients who had undergone a dose-reduced conditioning regimen when compared to patients who had received a standard myeloablative conditioning therapy. This observation was obtained consistently for OS-and DFS-associated risk (OS: HR 0.81; DFS: HR: 0.88). However, later on and presumably after resolution of acute conditioning toxicity, the slope of the cumulative hazard curve changes from negative to positive and the risk is higher in the patient group with reduced intensity conditioning. It has been shown that non-relapse mortality is lower in patients undergoing RIC as compared to patients treated with MAC.21 As non-relapse mortality is dominated by treatment-associated mortality soon after transplantation, this effect reflects a potentially protective effect of RIC in the early phase. However, later on, and as conditioning toxicity resolves, a differential effect on relapse remains. Lower relapse rates are observed in patients treated with MAC compared to patients treated with RIC, which explains the adverse effect of RIC in the later time period after HSCT.22 The time-dependent effect of conditioning treatment may, therefore, be explained by opposing effects with different time kinetics on treatment-related mortality and relapse incidence. The cumulative hazard curves are very similar for OS and DFS (Figure 2 and Online Supplementary Figure S4). The differences in cutoff time points are probably a result of optimal model selection rather than a correlate of clearly different time kinetics. We could show an almost 20% risk reduction in early mortality for patients with RIC in the OS analysis, which is of clinical significance. The above-mentioned differences were less intense in the DFS analysis, which may be attributed to the fact that higher relapse rates observed in RIC patients tend to partly attenuate the beneficial effect of RIC on mortality for this end point. Without considering time dependency, these effects would not have been noticed. In a Kaplan-Meier analysis, such a relationship is shown as overlapping survival curves (Online Supplementary Figure S1).
Peripheral blood stem cells are considered by many transplant physicians as graft source of choice for adult patients with malignant diseases of the hematopoietic system.23,24 One advantage of PBSCs is the faster engraftment compared to bone marrow, leading to a shorter aplasia time, which may reduce early post-transplant morbidity.25 Our data do not support this practice, as patients who were transplanted with allogeneic PBSCs showed similar hazard ratios compared to patients receiving BM grafts (OS: HR 0.94, CI: 0.87–1.01; P=0.069). However, regarding both end points, a significant time-dependent effect was detected, which, similarly to the analysis of conditioning regimen, allowed a distinction between a phase with risk reduction and a phase with increased risk. In the early phase (before day 388 in OS and before day 242 in DFS), PBSC had a protective effect, possibly because of the faster engraftment time, which reduces aplasia time and in turn has a beneficial influence on transplant-related mortality early after transplantation.26 In the later phase, a risk increase for PBSC was observed, which might be attributed to late complications, e.g. chronic GvHD.27–29 The earlier cut-off time point for DFS is caused by the addition of relapse events, which accumulate early after transplantation when compared to OS. For analysis of OS, a 21% risk reduction in the early phase after transplantation was seen, while the risk afterwards was increased by 23%. These differences are in the magnitude of a single HLA-mismatch and are of clinical relevance. DFS analysis revealed weaker differences compared to those observed in OS analysis, underscoring the stronger influence of relapse events in the analysis of DFS. In general, PBSC might be preferred in cases where high early post-transplant mortality is expected, e.g. in elderly patients or in patients with relevant comorbidity.
In DFS analysis, the variables "intermediate disease stage" and "advanced disease stage" showed time-dependent effects when compared with early disease stage, which was not seen in the OS analysis. The reason for this observation is that occurrence of relapse is counted as an event in DFS analysis, whereas for OS only death from relapse accounts for an event. Since relapse does not necessarily lead to death from relapse, and as many relapse events occur early after transplantation, such events accumulate for DFS in the early phase after transplantation, particularly for patients with more advanced disease stages. The difference in relative risk seen between advanced and early disease stage patients (HR 2.43 early after transplantation vs. HR 1.79 in the later phase after transplantation) highlights the problem of early morbidity/mortality in advanced disease stage patients, while on the other hand predicting a more favorable outcome for such patients who managed to survive these early complications.
Other commonly used approaches for inclusion of time-dependent variables are stratification on non-proportional variables as well as landmark analysis with refitting of separate models. Stratification, however, allows no quantification or comparison of the effects of various levels of the stratified variable. For the landmark approach, different models are fitted based on landmark time points with inclusion of case subsets with a survival time, which is at least as long as the landmark time points.30 It is often difficult to interpret the results of landmark analysis from a clinical perspective, as subsets of patients are analyzed in each landmark model and multiple models might be necessary. Generally speaking, our approach could be considered as a variant of a landmark approach using the cut-off time points we describe as landmarks. However, only one statistical model is necessary to include all time-dependent variables, which facilitates interpretation. Adjustment of variables for time dependency, in the way we describe here, does not affect the estimates for the other covariates satisfying the PHA in the multivariate Cox regression model. To address the problem of confounding by older transplantations and over-representation of BM grafts in this group, a subset analysis was performed for patients transplanted with PBSC grafts between 2006 and 2013. Very similar risk estimates to those seen in the analysis of the complete dataset were found (Online Supplementary Tables S2 and S3), indicating that our approach did not introduce a relevant bias, but instead allowed us to evaluate the effect of graft source in the context of the other predictors mentioned.
A limitation of our analysis is that exact HLA-matching patterns could not be included, as definitions of HLA-matching changed over time, and detailed information about the number and resolution of HLA-mismatches is currently not available from the DRST database. Therefore, stratification had to be performed for the covariate "donor type". In addition, the dataset included also historical transplantations, which leads to heterogeneity with regard to changes in transplant protocols, graft source, donor selection, or supportive care. This heterogeneity is probably only partly reflected by including the time period of transplantation as covariate. Another important clinical covariate is cytogenetic risk.31,32 However, cytogenetic information is currently not available in the majority of patients in the DRST database, which precluded inclusion in our analysis.
Hematopoietic stem cell transplantation is a highly complex and multifactorial process. Understanding and evaluating time-dependent effects allows more sophisticated risk quantification in HSCT to be made, particularly when a predictor has differential impact on outcome, as is the case for conditioning regimen intensity and graft source. Such information may help clinicians choose treatment according to the individual patient.
The authors would like to thank the DRST Data administrators F. Strehle and H. Neidlinger for providing the clinical data for this analysis.
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/101/2/241
- Received May 11, 2015.
- Accepted November 25, 2015.
- Copyright© Ferrata Storti Foundation


text: First-Time Buyer AdviceFirst-Time Buyer AdviceSpring is around the corner, and we finally are seeing some more inventory! Woohoo, time to shop!If you've never purchased a house before, you may have no idea where to begin when preparing to become a homeowner. You may be on the fence about buying, or you may feel like you are ready to buy a home today. Either way, these tips can help anyone feel a little more prepared for their first home purchase! If you are interested in learning more about the home buying process, I offer free education classes monthly that are FREE! Connect with me for more information.MONEY IS KEYIt is easy to begin scrolling through beautiful homes on the market without considering your budget. Sale postings can be all over your social media feeds, tempting you to just take a peek. While looking can be fun and exciting, you should prepare financially before you start eyeing any homes. It is much better to know what your price range is so you don't fall in love with a house you just can't afford (for now!). If you're in need of a top-notch lender recommendation, send me a message! MAKING A LIST, CHECKING IT TWICEWhile you need to be realistic and recognize that you likely are not going to find a home with every single thing you wish to have in a house, making a list of the things that are a priority for you (room count, big backyard, master walk-in closet, etc.) will help you to make sure you're only looking at houses that will fit your wants and needs.PHOTOS DON'T TELL THE WHOLE PICTUREIt is easy to fall in love with a home after seeing the listing photos. These perfectly lit, well-staged photos show off houses in their best light, but that doesn't mean you are getting the whole story. Listing photos are a great place to start, as they will help you to narrow down your options. Unfortunately, there are home traits that may not be portrayed well in photos, whether it be low ceilings, a drafty build, or anything in between. Once you've made a short list of the homes that appear to be a fit for you, always do a home tour. THAT GUT-FEELINGIf you walk into a house and it feels like home, trust your gut. There is no better way to know if you should buy a home than seeing how you feel when you walk through the front door. Your home purchase will probably be one of, if not the largest, purchase you've made in your life so far. Pictures can only do so much, and nothing can help you decide whether or not a house is made for you better than getting inside it!NOTHING ELSE WILL DODo you get upset at the thought of losing the house you just toured to someone else? Does it already feel like home when you are inside? These are two signs that you have found the home for you! If you see a home and are ready to stop looking at others, you are one step closer to buying a home you will love.THE BEST AGENTFinding a great real estate agent is going to be the part that ties everything together. A quality agent will help you find homes within your budget that possess your must-have items and they'll offer you guidance through every step of the process. If you're looking for a real estate agent to help you find and buy your first dream home, call me today!


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Beginning in January of this year we changed how we did our programming. Since we opened we had followed the general CrossFit way of writing a workout, which is writing a workout for the top athletes in the gym and then scaling the weight, movement, and reps down to the rest of the athletes. When you did the workout you would get an Rx by your name if you did the workout as written, or you would get the modifications listed if you did the workout scaled. We saw over time that this did not best serve our members for several different reasons. With progress in mind we switched our daily program into three tracks-Fitness, Performance, and Competition, with each track having a different goal. Since we have made the switch we have seen a big increase in attendance, results, and overall positivity day to day. We are very happy with how things have gone and will continue to do this type of programming going forward. I want to use this article to walk you through how you pick your tracks and how that might change over your time at our gyms.
First, let's break down the three tracks. The Fitness track is for people who just want to be fit and healthy. They are not interested in competing in CrossFit and do not play sports outside of the gym. There is no need for this track to be lifting super heavy weights or doing high skilled movements. The main goal for this track is to get a good workout in, have a great time, and be able to come back tomorrow. This is the longevity focus group and you should be able to follow this track for years (or the rest of your life) with no issues. The next track is the Performance track. This track is using CrossFit to help them get better for a sport outside of the gym. Maybe they play baseball, or run 5ks on the weekend, or want to perform at their best on their ski trip this winter. There is definitely a place to be doing doing a little bit heavier weights and trying to acquire some higher level skills, but the idea of this track is to use CrossFit to better themselves outside of the gym. They will do heavier power cleans, for instance, to help them get better at their sport, but the ultimate goal isn't necessarily to clean as much as possible. Finally, the Competition track is for people who want to compete in the sport of CrossFit. Whether you just want to compete in the Open or in local competitions, or you want to go to the CrossFit games, then this is the track for you. The goal of this track is peak performance in the sport of fitness, so you will see lots of heavy weights, high skill movements, and higher volume. This is the least sustainable track of the group and the track where lifestyle outside of the gym and recovery matter more than the others. You should only be following this track if you are serious about competing. We also have supplemental tracks outside of the class (Strength, Conditioning, Competition, and Games Prep) but we won't talk about these for now.
So now that you know what each of the tracks are it is time to decide which one you should do. One thing to note is that this is a fluid decision. You can switch back and forth from day to day if you want. However, over time you should be doing the majority of your workouts in a given track. How you decide is simple. What are your goals? If your goal is to lose weight and be healthy then it doesn't make much sense for you to be doing Competition workouts. You also shouldn't be planning on doing a local competition and only doing Fitness workouts. Your track should match your goals AT THAT TIME. This is an important point to make. We have members who have been doing CrossFit for 6 plus years. People's goals change over time and we have seen that with our members over the years. There might have been a season where they wanted to compete but now they just want to be healthy and look good at the pool. They might do Fitness workouts now but catch the bug to compete again next year and jump up to the Competition track. Our goal with this program is to provide a workout to help you achieve your goals, no matter the stage of life you are in or what your current fitness goals are.
Let's say you are a still a little hazy on what to do. You are in between the Fitness and Performance groups. What should you do? We always want our athletes to error on the conservative side. If you aren't sure what to do then go with the lighter weight or the lower skill movement. You will be able to go fasters and push yourself harder if the movements are simpler and easier to perform. If your goal is to lose 20 pounds then it doesn't make much sense for you to be struggling to perform one rep of a movement every minute while everyone else is done with the workout. Being conservative with the weights is also going to keep you healthier. If you are constantly battling nagging injuries because you are always going too heavy or doing movements above your current skill level then you will never be able to make progress. Check your ego at the door and drop the weight down. You will get much more out of it by going lighter and faster than by going heavy and super slow. (Now there is a time and a place for going heavy and slow but these should be few and far between and not every day).
Let me use myself as an example of how to use the tracks. I started competing in CrossFit in 2011 and have been training to compete at a high level for a very long time. I have competed at regionals as an individual and on a team many times, as well as competed at many high level competitions. I tried to add up how many competitions I have done over years and it's well over 30, maybe even more. All of those years of training and competing left me tired. Competing is no longer my goal so it doesn't make sense for me to do mostly competition workouts. My goal is to be healthy and to be able to perform any athletic activity that I want to do with little to no preparation. It makes sense for me to be doing Performance workouts at this point in my life. If you see me in class I will most likely be following this track. That's not to say that I won't see a Competition workout that I really want to do every now and then, or that I might not have slept well the night before and am feeling beat up and will do the Fitness workout. Over time I will be doing mostly Performance workouts though. Since I have made the change from Competition workouts I have noticed a drastic decrease in my daily soreness and general wear and tear on my body. If you are someone who struggles with constantly feeling beat up then consider changing tracks for a while.
The main takeaway here is that you should constantly be evaluating yourself. Don't' fall into the trap I did where you are just doing certain workouts because that's what you have always done. You should constantly be evaluating what your health and fitness goals are and if your training matches those goals. If it doesn't then see what you need to do to change it. Use the tracks as a guide. Over time you will probably spend time in all 3 tracks and that is perfectly fine. That what they are designed to do. No one track is better than the other, just like no one person's goals are better than the other. Our goal is to help our members to get in the best shape of their lives, at their own pace, in a supportive community, and we believe that this system helps us do that better. If you aren't a member of one of our gyms and want to see how the tracks work in detail then look up Coyote Fitness on the Sugarwod app and follow along. As always if you have any questions on the tracks or which one you should be in ask a coach or reach out to me!