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After Paris Attacks, CIA Head Reignites Surveillance Debate

Just days after the attack in Paris, America’s top intelligence official suggested that recent leaks about classified surveillance programs were partially responsible.




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“The Most Risky … Job Ever.” Reporting on “ISIS in Afghanistan”

Najibullah Quraishi has covered the war in Afghanistan for more than a decade, but embedding with ISIS fighters who've recently emerged there "was the most risky and dangerous job ever I've done in my life," he says.




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ISIS is in Afghanistan, But Who Are They Really?

It appears ISIS-allied fighters are gaining a foothold in Afghanistan, but just how similar are they to the group's branches in Iraq and Syria?




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10 of the best fitness trackers for monitoring heart rate

BEST FITNESS TRACKER DEALS:


Wellness is a buzzy word lately. Over the past few years, we’ve seen a surge in all things health, wellness, and spirituality. Juice bars are popping up, boutique studios are becoming more accessible, and essential oils are chilling us out. Self-care is becoming more of the norm too, but amidst all this hype, it can be challenging to find the right routine that promotes good exercise, sleep, vitals, and mindset.  Read more...

More about Apple Watch, Fitness Trackers, Smart Watch, Heart Rate Monitor, and Mashable Shopping
IMAGE: Amazon

BEST OVERALL

Apple Watch Series 4

Take heart monitoring to the next level with the Apple Watch Series 4's amazing EKG feature and FDA-cleared precision.

  • Warranty: 90 days with Apple Care+
  • Smartphone compatibility: Yes
  • Battery life: 22 hours
  • Weight: 1.06 oz
  • What you'll get: A case, band, 1m magnetic charging cable, and 5W USB Power Adapter
$236.98 from Amazon

IMAGE: Amazon

BEST BANG FOR YOUR BUCK

Polar A370 Fitness Tracker

Smartphone compatibility and a variety of wellness features makes Polar’s A370 Fitness Tracker our top choice for health management.

  • Warranty: 2 years
  • Smartphone Compatibility: Yes
  • Battery life: 4 days
  • Weight: 13.8 ounces
  • What you’ll get: A Polar A370 Fitness Tracker, a band, a charging cable, and a manual
$114.99 from Amazon

IMAGE: Amazon

EASIEST TO USE

Fitbit Charge 3 Fitness Activity Tracker

The new Charge 3 provides no-fuss wellness features to take your daily sleep, workouts, and vitals to the next level.

  • Warranty: 45-day guarantee and 1 year warranty
  • Smartphone compatibility: Yes
  • Battery life: 7 days
  • Weight: 4.8 ounces
  • What you’ll get: A Fitbit Charge 3, classic wristbands (both small & large), and a charging cable
$119.03 from Amazon

IMAGE: Best Buy

BEST FOR ATHLETES

Garmin Forerunner 735XT Smartwatch

With sport-specific settings, advanced training feedback, and a connected app, Garmin’s Forerunner 735XT Smartwatch is the perfect fitness companion for athletes.

  • Warranty: 1 year
  • Smartphone compatibility: Yes
  • Battery life: 1 day
  • Weight: 1.4 ounces
  • What you’ll get: A Garmin Forerunner 735XT Smartwatch, a charging/data clip, and a manual
$349.99 from Best Buy

IMAGE: Amazon

BEST FOR TECH ENTHUSIASTS

Nokia Steel HR Hybrid Smartwatch

Add some tech to your exercise regimen with the Nokia’s Steel HR Hybrid with Alexa integration and three different heart monitor modes.

  • Warranty: 1 year
  • Smartphone compatibility: Yes
  • Battery life: 25 days
  • Weight: 8.2 ounces
  • What you’ll get: A Nokia Steel HR Hybrid Smartwatch and a CR2 battery
$199.95 from Amazon

IMAGE: Amazon

BEST FOR WATER SPORTS

Garmin vívoactive 3

  • Warranty: 1 year
  • Smartphone compatibility: Yes
  • Battery life: 10 days
  • Weight: 1.44 ounces
  • What you'll get: A vívoactive 3 Fitness Tracker, a charging/data cable, and manuals
$319.99 from Amazon

IMAGE: Amazon

BEST FOR STYLE

Motiv Ring

  • Warranty: 45-day guarantee and 1-year warranty
  • Smartphone compatibility: Yes
  • Battery life: 3 days
  • Weight: 1.6 ounces
  • What you'll get: A Motiv Ring, sizing set, and two slim charging docks
$199.99 from Amazon

IMAGE: Amazon

BUDGET PICK

Microtella Fitness Tracker

Microtella’s Fitness Tracker is affordable, monitors your heart rate, and comes with 14 different fitness settings for personalized workout stats.

  • Warranty: None
  • Smartphone Compatibility: Yes
  • Battery life: 7 days
  • Weight: 4 ounces
  • What you’ll get: A Microtella Fitness Tracker, a band, and a USB charger
$39.99 from Amazon

IMAGE: Amazon

BEST OF BOTH WORLDS

Samsung Galaxy Fit

The perfect midpoint between the Fitbit and Apple Watch, the Samsung Galaxy Fit is great for tracking your high-intensity activities and for managing your daily life.

  • Warranty: 1 year
  • Smartphone Compatibility: Yes
  • Battery Life: 7 days
  • Weight: 3.2 ounces
  • What you'll get: Samsung Galaxy Fit, charging cable, manuals
$79 from Amazon

IMAGE: Amazon

BEST ON-SCREEN WORKOUTS

Fitbit Versa

The Fitbit Versa is best for those who need some extra guidance in the gym, and thanks to its comprehensive array of on-screen workouts, you'll get exactly that.

  • Warranty: 1 year
  • Smartphone Compatibility: Yes
  • Battery Life: 4 days
  • Weight: 5.12 ounces
  • What you'll get: Fitbit Versa, charging cable, manuals
$199.95 from Amazon

IMAGE: Amazon

BEST BATTERY LIFE

Wahoo TICKR

Won't take up precious real estate on your wrists and will provide personalized heart rate training, as well as an unbeatable 12-month battery life.

  • Warranty: 1 year
  • Smartphone Compatibility: Yes
  • Battery Life: 1 year
  • Weight: 2.4 ounces
  • What you'll get: Wahoo TICKR, battery, manuals
$45.94 from Amazon




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11 of the best pillows for a good night's sleep

BEST PILLOW DEALS:


Achieving a good night’s sleep isn’t always easy. Busy schedules, frequent stress, and bad rest environments can be culprits for sleep troubles. And it’s more common than you think. 

According to the American Sleep Association, 50 to 70 million U.S. adults have a sleep disorder. If your sleepless nights are taking a toll on your health, it might be time for you to buy a new pillow. 

More about Sleep, Pillows, Mashable Shopping, Culture, and Work Life
IMAGE: Coop Home Goods

BEST OVERALL

Coop Home Goods Eden Shredded Memory Foam Pillow

Breathability, comfort, and design make the Coop Home Goods’ Eden Shredded Memory Foam Pillow a top pick if you need to improve your quality of sleep.

  • Dimensions: Standard (17.9 x 6.8 x 6.1 inches), Queen (18 x 6 x 6 inches), and King (17.9 x 6.5 x 6.3 inches)
  • Materials: Bamboo-derived viscose rayon and polyester
  • Sleep factor: Good for back, side, and stomach sleepers
$80.99 from Coop Home Goods

IMAGE: Amazon

BEST FOR SIDE SLEEPERS

Brookstone BioSense 2-in-1 Shoulder Pillow

  • Dimensions: 28 x 20 x 6 inches
  • Materials: Better Than Down microfill and BioSense memory foam core
  • Sleep factor: Good for side sleepers
$119.95 from Amazon

IMAGE: Amazon

BEST FOR BACK SLEEPERS

Nature's Guest Cervical Support Pillow

  • Dimensions: 18.5 x 9.5 x 7.2 inches
  • Materials: Cotton fabric cover, microfiber filling, and silk gusset trim
  • Sleep factor: Good for back sleepers
$79.99 from Amazon

IMAGE: Amazon

BEST FOR STOMACH SLEEPERS

TruContour Super Thin Memory Foam Pillow

  • Dimensions: 24 x 16 x 2.5 inches
  • Materials: Medical-grade memory foam and certified organic cotton
  • Sleep factor: Good for stomach sleepers
$39.99 from Amazon

IMAGE: Amazon

BEST BANG FOR YOUR BUCK

Triple Cloud Shredded Memory Foam Pillow

The Triple Cloud Shredded Memory Foam Pillow offers comfort perks and adjustable firmness at a fraction of the price.

  • Dimensions: Standard/Queen (15.9 x 5.6 x 5.2 inches), Queen (17 x 6 x 6 inches), and King ( 17.3 x 7.7 x 6.4 inches)
  • Material: Bamboo-shredded memory foam
  • Sleep factor: Good for back, side, and stomach sleepers
$39.95 from Amazon

IMAGE: Avocado Green

BEST FOR SUSTAINABILITY

Avocado Green Pillow

  • Dimensions: Standard (19 x 24 inches), Queen (19 x 28 inches), and King (19 x 35 inches)
  • Materials: Certified organic cotton, kapok fiber, and natural latex
  • Sleep factor: Good for back, side, and stomach sleepers
$79 from Avocado Green

IMAGE: Amazon

BEST FOR HEAD, NECK, AND SHOULDER SUPPORT

UTTU Adjustable Memory Foam Pillow

Keep head, neck, and shoulder pain at bay with UTTU’s Adjustable Memory Foam Pillow.

  • Dimensions: 7.9 x 7.9 x 14.2 inches
  • Materials: Bamboo fiber, polyester, and memory foam
  • Sleep factor: Good for back, side, and stomach sleepers
$69.99 from Amazon

IMAGE: Amazon

BEST FOR ALLERGY SUFFERERS

Pacific Coast AllerRest Double DownAround Pillow

Reduce congestion, coughing, sneezing, and other pesky allergy symptoms while you sleep.

  • Dimensions: Standard (20 x 26 inches), Queen (20 x 30 inches), and King (20 x 36 inches)
  • Materials: AllerRest fabric, Barrier Weave down and feather proof fabric, cotton
  • Sleep factor: Good for back, side, and stomach sleepers
$62.99 from Amazon

IMAGE: Leesa

BEST HYBRID OPTION

Leesa Hybrid Pillow

Switch back and forth between a soft pillow top and a cooling, memory foam underside for multiple ways to catch some sleep.

  • Dimensions : Standard (16 x 24 inches), Queen (16 x 28 inches)
  • Materials : Polyester microfiber, ventilated gel, Leesa's Tencel fabric, and nylon.
  • Sleep factor: Best for back and side sleepers
$98 from Leesa

IMAGE: Amazon

BEST 2-FOR-1 DEAL

Beckham Hotel Collection Gel Pillow

You'll be getting two pillows with somewhere-in-the-middle support for the price of one.

  • Dimensions : Queen (20 x 28 inches)
  • Materials: Cotton cover and poly-gel fiber filling
  • Sleep factor : Good for back, side, and stomach sleepers
$33.99 from Amazon

IMAGE: Tuft & Needle

BEST FOR DURABILITY

Tuft & Needle Pillow

If you're looking for a durable pillow and tend to sleep on your back or side, the Tuft & Needle Pillow will have you catching z's in no time.

  • Dimensions : 25 x 16 x 5 inches
  • Materials : Micro polyamide, polyester, and Tuft & Needle's proprietary Adaptive Foam
  • Sleep factor: Best for back and side sleepers
$68 from Tuft & Needle




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Best headphones for running or working out

BEST DEALS ON HEADPHONES:


The only thing more important to runners than their sneakers is a quality pair of headphones and a killer playlist. Running without music is like some form of medieval torture: it sucks. And cheap, crappy headphones just aren't going to cut it.

When shopping for a quality pair of headphones to wear while running, you'll want to look at a few key factors: Are they sweatproof/waterproof? Will they stay in your ears? Are the volume controls easily accessible? If you answer no to any of these questions, then you know the headphones aren't going to work. Read more...

More about Running, Headphones, Bluetooth Headphones, Mashable Shopping, and Culture
IMAGE: Amazon

BEST FOR WORKOUT TRACKERS

Bose SoundSport Pulse Wireless

While sound quality and flexibility are always good features, a great pair of headphones will do more than that.

$129 from Amazon

IMAGE: Amazon

BEST MID-PRICED WIRELESS OPTION

Jabra Elite 45e

The Elite 45e headphones are an example of quality at an affordable price.

$86.53 from Amazon

IMAGE: Amazon

BEST TRULY WIRELESS EARBUDS

Bose SoundSport Free Wireless

These truly wireless ear buds can charge while you're using them, and the app can help you locate them in the event that they fall out.

$199 from Amazon

IMAGE: Amazon

BEST BUDGET WIRED HEADPHONES

JBL Endurance RUN

These are the kind of headphones you buy in multiples so you don't have to fret once you've inevitably lost a pair.

$19.95 from Amazon

IMAGE: Amazon

BEST NO-FRILLS OPTION

ROVKING Sport Headphones

These super-cheap headphones have an earhook design that keeps them on your ears, and are also sweatproof.

$14.99 from Amazon

IMAGE: Amazon

MOST FIT OPTIONS FOR WIRED HEADPHONES

Sony MDRXB510AS/B

These Sony earbuds offer multiple sets of covers and hooks to hold the earbuds securely in place.

$29.99 from Amazon

IMAGE: Amazon

BEST AUDIO QUALITY FOR WIRED HEADPHONES

Bose SoundSport

Bose SoundSport are a great set of headphones to buy when the clarity of audio really matters to you.

$99 from Amazon

IMAGE: Amazon

BEST OVER-EAR OPTION

Levin Bluetooth 4.1 Wireless Headphones

The Levin Bluetooth 4.1 Wireless Headphones deliver an affordable and reliable option for anyone who prefers over-ear headphones.

$29.99 from Amazon




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Apple to begin reopening U.S. stores this month

Apple, dear reader, has been missing you — and it's banking on the fact that you've been missing the opportunity to touch its products before you buy them, too. 

In an effort to ease this assuredly mutual feeling of longing, the company confirmed on Friday plans to begin reopening some of its U.S. stores as early as MondayApple had been aiming for a May reopening for some time, but now it's official. 

So reports CNBC, which notes that the openings are, for now, limited to stores in four states: Idaho, South Carolina, Alabama, and Alaska.

"We've missed our customers and look forward to offering our support," an Apple spokesperson told CNN BusinessRead more...

More about Apple, Coronavirus, Tech, and Big Tech Companies




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Silicone mini-pinch bowls have 101 uses

These little silicone rubber bowls come in handy in so many ways.

I use them with my digital scale to measure the bulk powder supplements I take. We use them at the dinner table to hold condiments. We use them while preparing meals to hold spices and minced herbs. I keep finding new ways to use them. For instance, when I fry or scramble eggs, I now crack the eggs over one of these bowls so I can pull out shell pieces and woogers (I wish I had a wooger snatcher but the bowl will have to do). Read the rest




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Last night's massive boom over Puget Sound was likely exploding meteor

A massive boom heard Wednesday night over Puget Sound on the northwestern coast of Washington was most likely an exploding meteor. Or that's what They want us to believe anyway. The American Meteor Society registered a dozen reports. Video above. Keep your eyes on the upper left of the frame.

"The more I read the more inclined I am to believe this was a fireball (which is a meteor that is larger and brighter than normal)," the American Meteor Society's Bob Lunsford said. "I'm certain now that this was a meteoric event."

From KOMONews:

Most meteors' explosions are heard about a minute or two after they explode due to the time it takes the sound to reach the Earth's surface, Lunsford said. Sound travels at 767 mph in standard atmosphere conditions, indicating this fireball exploded some 35 miles away.

"If this was larger than normal then the sound could have originated from a higher altitude. So a delay of 3 minutes is entirely possible," Lunsford said. "Meteors become visible at a height of around 50 miles so your estimate is well within that range."

Lunsford said because there was a boom, it’s very likely there are small, rock-sized pieces of the meteor somewhere on the ground. When a meteor causes a boom, it’s “pretty far down” in the atmosphere.

Read the rest




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Puppy training doesn’t have to descend your house into chaos thanks to these online classes

One positive upside of the past two months is how sheltering at home has all but emptied area animal shelters. It’s tough to get solid numbers nationally, but shelters in cities and regions all across America are reporting massive surges in animal adoptions

Even the steep increase in Google searches for “adopt a pet,” up a whopping 335 percent in April, proves what we probably all knew anyway — that in times of stress, having a furry friend is a huge comfort for millions.

Unfortunately, one of the downsides of the past two months is there are no trainers available to help whip some of these new family pets, particularly puppies, into shape. From barking and jumping to house training and scratching, The Complete Guide to Puppy and Dog Training Bundle is a full plan for getting the newest member of your family integrated into the house safely and sanely all by yourself.

The collection includes eight courses all geared toward getting a new dog or puppy behaving the right way. And if you’ve ever had any thoughts about starting a dog training business of your own, this coursework is a perfect starting spot.

Puppies: A-Z Guide to Puppy & Dog Training kicks off the learning, explaining the best way to train, teach and socialize your puppy so they grow into a joyful, well balanced, and well-behaved dog. 

Of course, most puppies each have their particular issues, so a handful of courses look more closely at some of the tactics for helping your puppy overcome certain challenging behaviors. Read the rest




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Lost Horizon Night Market returns... without actual box trucks

The "transient bazaar" known as Lost Horizon Night Market is a covert operation. Worlds are imagined and then built inside the blank canvasses of empty box trucks. For the event, all the "proprietors," and their appointed box trucks, convene in an unsanctioned, though discreet, location. This location is disclosed to would-be "shoppers" via text just a few hours before it starts. Word of the market generally spreads rapidly but not publicly, definitely not by social media. If you're lucky enough to hear about it, you should go.

So, Happy Mutants, this is your heads up. Lost Horizon Night Market: Quarantine Edition is happening Saturday, May 9, from 6:59p EST until 11:59p EST, "rain or shine." This one is a little different, as the spaces are virtual, not in actual, physical trucks. I got a sneak peek yesterday of what's been created and can't wait to dive in deeper. Admission is free, though tips are appreciated. RSVP here.

Previously: Secret box truck 'night market' pops up again in NYC Read the rest




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Suspicious package found in north Edmonton deemed non-threatening

A transit centre in north Edmonton was evacuated for about two hours Saturday morning due to a suspicious package.




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Sport24.co.za | Umtiti suffers calf knock in second Barca training session

France defender Samuel Umtiti has picked up a calf injury in just the second session since Barcelona returned to training from the cornonavirus quarantine.




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Sport24.co.za | Man United turned to Igalo after Rondon move was blocked

Salomon Rondon says he was on his way to joining Manchester United in January only for Dalian Professional to block the move.




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Sport24.co.za | Jennings backs Markram as next Proteas Test captain

Former Proteas head coach Ray Jennings is adamant Aiden Markram should be chosen as Faf du Plessis' replacement as captain of the Test team.




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9 Online Resources for Effective Learning

Technology is continuously leaving an indelible mark on many conceivable fields and industries, and education hasn’t been left behind either. Today, you no longer need to take admission classes and physically attend all your classes to earn a degree. All that is required of you is a working web connection and an incontestable thirst for […]

The post 9 Online Resources for Effective Learning appeared first on Dumb Little Man.




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The Simplest Hack to Be Your Most Organized Self

Finding a good system to be organized can be intimidating. There are so many options! Useful tips on how to get your life together are all over the internet. From minimalist planners to detailed systems, something is bound to draw you in. Choosing the best system to use will be the biggest decision you’ll have […]

The post The Simplest Hack to Be Your Most Organized Self appeared first on Dumb Little Man.




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Social Learning as a Way to Foster Productivity in the Workplace

In one way or another, social learning has been part of our lives for a long time. We spend a large amount of time at work. During this time, we are bound to learn from our colleagues and get a chance to talk on mutual topics of interest. Moreover, social media has given an outlet […]

The post Social Learning as a Way to Foster Productivity in the Workplace appeared first on Dumb Little Man.




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Article: Marketing in China: Can Machine Learning Solve the ROI Problem?

William Bao Bean, managing director of Chinaccelerator, explains how investments in artificial intelligence and machine learning are helping marketers improve user targeting and return on investment.




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Brighten Up Your After-Dark Road-Tripping with Lanmodo’s Vast Automotive Night Vision System

With a bright, 8.2-inch HD display and the flexibility to work in almost any vehicle, the Lanmodo Automotive Vast Night Vision System is a near-perfect alternative to factory-installed systems.

The post Brighten Up Your After-Dark Road-Tripping with Lanmodo’s Vast Automotive Night Vision System appeared first on Vagabondish.




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Live Q&A on remote working, working from home, and running a business remotely

In this livesteam, David and I answer audience questions about how to work remotely. At Basecamp we’ve been working remotely for nearly 20 years, so we have a lot of experience to share. This nearly 2-hour video goes into great detail on a wide variety of topics. Highly recommended if you’re trying to figure out… keep reading




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Working remotely builds organizational resiliency

For many, moving from everyone’s-working-from-the-office to everyone’s-working-at-home isn’t so much a transition as it is a scramble. A very how the fuck? moment. That’s natural. And people need time to figure it out. So if you’re in a leadership position, bake in time. You can’t expect people to hit the ground running when everything’s different.… keep reading




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Video: Organic or not?

Part of the Food for thought promo for the BBC UK Homepage




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“Distraction,” Simplicity, and Running Toward Shitstorms

It can scarcely be denied that the supreme goal of all theory is to make the irreducible basic elements as simple and as few as possible without having to surrender the adequate representation of a single datum of experience.

—Albert Einstein, “On the Method of Theoretical Physics” (1934)

Context: Last week, I pinched off one of my typically woolly emails in response to an acquaintance whom I admire. He’s a swell guy who makes things I love, and he'd written, in part, to express concern that my recent Swift impersonation had been directed explicitly at something he'd made. Which, of course, it hadn’t—but which, as I'll try to discuss here, strikes me as irrelevant.

To paraphrase Bogie, I played it for him, so now I suppose I might as well play it for you.


(n.b.: Excerpted, redacted, munged, and heavily expanded from my original email)

There are at least a couple things that mean a lot to me that I'm still just not very good at.

  • Make nuanced points in whatever way they need to be made; even if that ends up seeming “un-nuanced”
  • Never explain yourself.

I want to break both these self-imposed rules privately with you here. [Editor’s Note: Um.] Because, I hope to nuance the shit out of some fairly un-nuanced points. And, to do that, I'll also (reluctantly) need to explain myself. But, here goes.

First [regarding my goofing on “distraction-free writing environments”] I think there are some GIANT distinctions at play here that a lot of folks may not find nearly as obvious as I do:

  1. Tool Mastery vs. Productivity Pr0n – Finding and learning the right tools for your work vs solely dicking around with the options for those tools is just so important, but also so different. And, admittedly, it’s almost impossible to contrast those differences in terms of hard & fast rules that could be true for all people in all situations. But, that doesn’t make the difference any less qualitatively special or real.

    Similarly…
  2. Self-Help Vs. “Self”–“Help” – Solving the problem that caused the problem that caused the problem that caused the symptom we eventually noticed. Huge. Arguably, peerless.

    • Viz.: How many of us ignore the actual cause of our problem in favor of just reading dozens of blog posts about how to “turbocharge” its most superficial symptoms? Sick.
  3. Focus & Play – Yes, focusing on important work is, as Ford used to say, Job 1. But, that focus benefits when we maintain the durable and unapologetic sense of play that affords true creativity and fosters an emergence of context and connection that’s usually killed by stress. BUT.

    • Again, what conceivable “rule” could ever serve to immutably declare that “THIS goofing-off is critical for hippocampal plasticity” vs. “THAT goofing-off is just dumb, distracting bullshit?”
    • Impossible. Because drawing those kinds of distinctions is one of our most important day-to-day responsibilities. Decisions are hard, and there’s no app or alarm gadget that can change that.

      • Although, they certainly can help mask the depth of the underlying problem that made them seem so—what’s the parlance?—“indispensable”.
      • Think: Elmo Band-Aids for that unsightly pancreatic tumor.
  4. Reducing Distraction through Care (Rather than braces, armatures, and puppet strings). Removing interruptions and external distractions that harm your work or life? Great. Counting on your distraction-removal tool to supplement your non-existent motivation to do work that will never get done anyway? Pathetic.

    • Frankly, this is a big reason I'm so galled when anyone touts their tool/product/service as being the poor, misunderstood artist’s new miracle medicine—rather than just admitting they've made a slightly different spoon.
    • Because, let’s be honest: although most of us have plenty of perfectly serviceable spoons, everybody knows collecting cutlery is way more fun than using it to swallow yucky medicine.
  5. Using a System Vs. Becoming a System. Having a system or process for getting work done vs. making the iteration of that system or process a replacement for the work. This is just…wow…big.

    But, maybe most importantly to me…

  6. Embracing the Impossibles. Getting past these or any other intellectual koans by simply accepting life’s innumerable and unresolvable paradoxes, hypocrisies, and impossibilities as God-given gifts of creative constraint. Rather than, say, a mimeographed page of long division problems that must be solved for a whole number, n.

    • I just can’t ever get away from this one. For me, it’s what everything inevitably comes back to.
    • The very definition of our jobs is to solve the right problem at the right level for the right reason—based on a combination of the best info we have for now and a clear-eyed dedication to never pushing an unnecessary rock up an avoidable hill.
    • YET, we keep force-feeding the monster that tells us to fiddle and fart and blame the Big Cruel World whenever we face work that might threaten our fragile personal mythology.

      • “Sigh. I wish I could finally start writing My Novel….Ooooooh, if only I had a slightly nicer pen…and Zeus loved me more….”

All that stuff? That there’s a complex set of ideas to talk about for many complex reasons—not least of which being how many people either despise or (try to) deny the unavoidable impact of ol' number six.

But, here’s the thing: as much as saying so pisses anybody off, I think the topics we're NOT talking about whenever we disappear into Talmudic scholarship about “full-screen mode” or “minimalist desks” or whatever constitutes a “zen habit”—those shunned topics are precisely the things that I believe are most mind-blowingly critical to our real-world happiness as humans.

In fact, I believe that to such a degree that helping provide a voice for those unpopular topics that can be heard over the din is now (what passes for) my career. I really believe these deeper ideas are worth socializing on any number of levels and in many media. Even when it’s inconvenient and slightly disrespectful of someone’s business model.

So, that’s what I try to do. I talk about these things. Seldom by careful design. Often poorly. But, always because they each mean an awful lot to me.

[…]

But, no matter how I end up saying whatever the hell I say, I believe in saying it not simply to be liked or followed or revered as a “nice guy” who pushes out shit-tons of whatever to “help people.”

Because, believe me, friend, a great many of those apparently “nice guys” swarming around the web “helping people” these days are ass-fucking their audience for nickels and calling it a complimentary colonoscopy. And, while I absolutely think that in itself is empirically wrong, I also think it’s just as important to say that it’s wrong. Sometimes, True Things need to be said.

Which in this instance amounts to saying, a) selling people a prettier way to kinda almost but not really write is not, in the canonical sense, “nice”—but, far worse, b) leaving your starry-eyed customers with the nauseatingly misguided impression that their “distraction” originates from anyplace but their own busted-ass brain is really not “helping.” Not on any level. It is, literally, harmful.

“Helping” a junkie become more efficient at keeping his syringe loaded is hardly “nice.”

It’s the opposite of nice. And, it’s the opposite of helpful. These are my True Things.

And, to me, saying your True Things also means not watering down the message you care about in order to render it incapable of even conceivably hurting someone’s feelings—or of even conceivably losing you even one teeny-tiny slice of that precious “market share.”

Well, that’s the price, and I'm fine paying it—best money I've ever spent.

But, it also means trusting your audience by letting each of them decide to add water only as they choose to—by never corrupting the actual concentrate in a way that might make it less useful to the smartest or most eager 5% of people who'd like to try using it undiluted. Because, at that point, you're not only abandoning the coolest people you have the honor of serving—you risk becoming a charlatan.

And, that’s precisely what you become when you start to iteratively inbreed the kind of fucktard audience for whom daily buffets of weak swill and beige assurance are life’s most gratifying reward.

Sure. Those poor bastards may never end up using any of that watery information to do anything more ambitious than turbocharging their most regrettable symptoms. But, who’s the last person in the universe who’s going to grab them by the ears and tell them to get back to work? Exactly—that same “nice guy” whose livelihood now depends on keeping infantalized strangers addicted to his “help.”

Holy shit—no way could I ever live with that. It’s so wrong, it’s not even right. ESC, ESC, ESC!

[…]

Okay. So anyhow, there’s a really long-winded, overly generous, and extremely pompous way of trying to say I don’t know how to do what I do except how I do it. But, I do genuinely feel awful when innocent people feel they have been publicly humiliated or berated simply because I'm some dick who hates people.

Which has to be my favorite irony of all.

When I was a kid, I thought my Mom was “mean” not to let me play in traffic on busy Galbraith Road. Today, I'm not simply grateful that she had the strength and resolve to be so “mean”—I actually can’t imagine how sad it would be to not have people in your life who care enough about your long-term welfare to tell you to stop fucking around in traffic. To where you eventually might start even seeking 12x-daily safety hacks from some of the very same drivers whose recklessness may eventually kill you. Wow.

[…]

Admitting when life is complicated or things aren’t shiny and happy all the time strikes me as a wonderfully sane and adult way to conduct one’s life. That there are so many folks offended by even the existence of this anarchic idea is not a problem I can solve.

No more than I can wish useless email away or pray hard enough that it never rains on anyone’s leaky roof. All out of scope.

And, then, I jizzed on at length about how much I admire the recipient’s work. Which I do.


Good work doesn’t need a cookie

I may admire your work, too. Especially if you care a lot about that work and don’t overly sweat peoples' opinions of it. Most definitely including my own.

For these purposes, it doesn’t really matter whether we're friends and, honestly, it doesn’t even matter whether I love, use, or agree with everything you do, say, or make in a given day.

It doesn’t matter because good work doesn’t need me to love it. Like tornadoes and cold sores, good work happens with total disregard to whether I'm “into it.”

But, conversely, let’s stipulate that the points-of-view undergirding our opinions—again, including mine—will and should survive either agreement or lack of agreement with equivalently effortless ease. Because, like really good work, a really good point-of-view doesn’t require another person’s benediction.

Guess we'll have to disagree to agree

Now, to be only vaguely clearer here, I'm not posting this circuitous ego dump in the service of altering your opinion of either me, my friend, his work, or practically anything else for that matter.

But, I would love it if we could all be more okay with the fact that real life means that we do each have a different, sometimes incongruous, and often totally incompatible point-of-view. Yes. Even you have a point-of-view that someone despises. Ready to change it now? Jesus, I sure hope not.

Then, to be only slightly more clear, I'm also not advocating for that fakey brand of web-based kum ba ya that gets trotted out alternately as “tolerance” or “inclusion” or some styrofoam miniature of “civility.”

I'm absolutely not against all of those things when authentically practiced, but I'm also really skeptical of the well-branded peacemakers who are forever appointing themselves the Internet’s “Now-Now-Let’s-All-Pretend-We're-Just-Saying-the-Same-Useless-Thing-Here” den mothers.

Because we're not all saying the same things. Not at all.

And, it infantalizes some important conversations when we tacitly demand that any instance of honest disagreement be immediately horseshat into a photo opp where some thought leader gets to hoist everyone’s hands in the air like he’s fucking Jimmy Carter.

Nope. Not saying that.

Who will you really rely on?

What I AM saying is that alllllll this seemingly unrelated stuff is absolutely related—that the pattern of not relying on other people for anything you really care about is arguably the great-grandaddy of every useful productivity, creativity, or self-help pattern.

Where’s this matter? Pretty much everywhere you have any sort of stake:

  • Don’t rely on other people to remove your totally fake “distractions.”
  • Don’t rely on other people to pat your beret, re-tie your cravat, and make you a nice cocoa whenever that mean man on the internet points out that your “distractions” are totally fake. (Which they are)
  • Don’t rely on other people to tell you when or whether you have enough information.
  • Don’t rely on other people to define your job.
  • Don’t rely on other people to “design your lifestyle.”
  • Don’t rely on other people to decide when your opinions are acceptable.
  • Don’t rely on other people to tell you when you're allowed to be awesome.
  • Don’t rely on other people to make you care.
  • Don’t even rely on other people to tell you what you should or shouldn’t rely on.

Yes. I went there.

Because that’s the point. These hypocrisies, paradoxes, and ambiguities that people get so wound up about—that many of us are constantly (impotently) trying to resolve—cannot be resolved.

Because, yeah: all of these harrowingly unsolvable problems are immune to new notebooks and less-distracting applications and shinier systems and “nicer” self-“help” and pretty much anything else that is not, specifically, you walking straight into the angriest and least convenient shitstorm you can find and getting your ass kicked until the storm gets bored with kicking it.

Then, you find an even angrier storm. Then, another. And, so on.

“Get the fuck off of my obstacle, Private Pyle!”

Doing that annoying hard stuff is how you grow, get better, and learn what real help looks like. Even if that’s not the answer you wanted to hear. You get better by getting your ass out of your RSS reader and fucking making things until they suck less. Not by buying apps.

You don’t whine about distractions, or derail yourself over needing a nicer pencil sharpener, or aggravate your chronic creative diabetes by starting another desperate waddle to the self-help buffet. No. You work.

And, for what it’s worth, just like you can’t get to the moon by eating cheese, you'll also never leave boot camp with your original scrote intact by telling your drill sergeant to try using more honey than vinegar.

No. That sergeant’s job is to make you miserable. It’s his job to break down your callow conceits about what’s supposed to be easy and fair. It’s his job to emotionally pummel you into giving up and becoming a Marine.

You? You're not there to give the sergeant notes; you're there to sleep two hours a night, then not mind getting beaten for 20 hours until a decent Marine starts to fall out.

Who knows? He may even surprise you by introducing a surprisingly effective “distraction-free learning environment.”

“Tee ell dee ahr, Professor Brainiac.”

Like most humans, I like things I can understand. Like most readers, I love specificity. Like most thinkers, I love clarity. Like most students, I love relevance and practicality. And, like most busy people, believe it or not, I actually do really like it when someone gets straight to the point.

But, here’s the problem. If my 2-year-old daughter asks me about time travel, and I blithely announce, “E=mc2”, I will have said something that is entirely specific, clear, relevant, practical, and/or straight-to-the-point. For somebody.

But, not so much for my daughter. And, to be honest, not even to any useful degree for me.

She'd probably either laugh derisively at me (which she’s great at), or she'd pause and ask, “Whuh dat?” (which she’s even better at).

Thing is, her understanding that jumble of characters less than me—and my understanding it WAY less than Professor Al—has zero impact on the profundity, truth, beauty, or impact of the man’s theory.

Sure. You could quite accurately fault me for being a smartass and a poseur, and you could even berate my toddler for her unaccountably shallow understanding of Modern Physics. But, in any case, you can’t really blame either Albert or his theory.

You're turbocharging nothing

Specifically, Albert can’t begin to tell us what he really knows if we don’t understand math.

So, let’s say this theory you've been hearing about really interests you. And, let’s also pretend, just for the sake of the analogy, that you haven’t completed Calculus III (212) or Quantum Mechanics (403) or even something as elementary as, say, Advanced Astrophysics II (537). I know you have. Obviously. But, let’s pretend. Where do you start?

Well, you could read some tips about learning math. You could find a list of 500 indispensable resources for indispensable math resources. You could buy a new “distraction-free math environment.” Heck, there’s actually nothing to stop you from just declaring yourself a “math expert.” Congratulations, Professor.

Thing is: you still don’t know math.

Which means you still can’t really understand the theory—no more than a pathetic Liberal Arts refugee like me or a dullard Physics ignoramus like my kid can really grok relativity.

Difference is, you will have blown a lot of time hoping that actual expertise follows non-existent effort—while my daughter and I get to remain total novices without charge. Only, we don’t get all mad at the theory as a result; a staggering number of fake math experts do.

I mean, be honest—after all that recreational non-work and make-believe dedication almost trying to kinda learn math sorta—you might actually get frustrated at how brazenly Al defies your fondness for shortcuts by continuing to rely on so many terms and proofs and blah-blah-blah that you still just don’t understand. So annoying.

You may simply decide that Albert Einstein’s a huge dick for never saying things that can be completely understood solely by scanning a headline.

EPIC EINSTEIN FAIL, amirite?

You never really know what you didn’t know until you know it

But, Al just told the truth.

Problem is, Al’s truth not only requires fancy things in order to be truly understood—the more of those fancy things you take away from his truth, the less true it gets. And, by the time it’s been diluted to the point where you're comfortable that you understand it? You'd be understanding the wrong thing. Even I can understand that.

But, not one bit of any of this is Al’s fault. Al doesn’t get to control who uses, abuses, gets, or doesn’t get what he said or why it matters. Especially since he’s been dead for over fifty years.

All I know is, regardless of who has ears to hear it on a given day, it would be to Al’s credit never to mangle something important in order to get it into terms everybody’s ready to handle without actually trying.

And God bless him for never agreeing that your “distractions” to learning math are his problem.

So, yeah, if you only need to hand in a crappy 5-page paper, you could certainly Cliff’s Notes your way through Borges, Eliot, or Joyce in an afternoon, and feel like you haven’t missed a thing. Trouble is, if you did care even a little, it’s impossible to even say how much you're missing since you can’t be bothered to soldier through the source text. The text itself is the entire point.

Even the wonderfully cogent and readable layman’s explanations Einstein himself provided don’t really get to the nut, the application, and the implications of his real theory.

That all takes real math.

That “single datum of experience” matters

Sometimes, complex or difficult things stop being true when you try to make them too simple. Sometimes, you have to actually get laid to understand why people think sex is such a thing. Sometimes, you need to learn some Greek if you really want to understand The Gospel of John. And, yeah, sometimes, you're going to have to just work unbelievably hard at whatever you claim to care about before anyone can begin to help you get any better—or less “distracted”—at it.

The part I really know is what doesn’t work. Reading Penthouse Forum won’t help you CLEP out of Vaginal Intercourse 101. Watching a Rankin-Bass cartoon about the Easter Bunny will teach you very little about the intricacies of transubstantiation. And, if you can’t be troubled to care so much about your work that you reflexively force distractions away, dicking around with yet another writing application will merely aggravate the problem. Ironic, huh?

These quantum mechanics of personal productivity are rife with such frustrating “paradoxes.”

These are True Things.

Achieving expertise and doing creative work is all horribly complicated and difficult and paradoxical and frustrating and recursive and James Joyce-y—and any guide, blog, binary, guru, or “nice guy” that tries to suggest otherwise is probably giving you a complimentary colonoscopy. Do the math.

Want a new syllabus? Sure:

Run straight into your shitstorm, my friends. Reject the impulse to think about work, rather than finishing it. And, open your heart to the remote possibility that any mythology of personal failure that involves messiahs periodically arriving to make everything “easy” for you might not really be helping your work or your mental health or your long-standing addiction to using tools solely to ship new excuses.

Learn your real math, and any slide rule will suffice. Try, make, and do until you quit noticing the tools, and if you still think you need new tools, go try, make, and do more.

If you can pull off this deceptively simple and millennia-old pattern, you'll eventually find that—god by dying god—any partial truth that’s supported your treasured excuses for not working will be replaced by a no-faith-required knowledge that you're really, actually, finally getting better at something you care about.

Which is just sublimely un-distracting.


Dedication

This article is dedicated to my friend, Greg Knauss. No, he’s not the app guy–he’s just a good man who does good work, who accidentally/unintentionally helped me write this rant. He also happens to be a fella who could teach anyone a thing or two about writing with distractions. Thanks, Greg.

“Distraction,” Simplicity, and Running Toward Shitstorms” was written by Merlin Mann for 43Folders.com and was originally posted on October 05, 2010. Except as noted, it's ©2010 Merlin Mann and licensed for reuse under CC BY-NC-ND 3.0. "Why a footer?"




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School bus drivers take on a new role to help students with distance learning

School bus drivers in the Upper Grand District School Board are transporting school work instead of students.




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Death toll hits 25 in Simcoe Muskoka as senior's facilities continue to struggle with virus

A woman in her 90s living at the Bradford Valley Care Community is the latest coronavirus victim in the region.




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Police identify three teens responsible for 'appalling prank' in Innisfil

An "appalling prank" in Innisfil sent South Simcoe Police officers on a mission to identify the culprits involved.




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Human remains found in Mulmur Township confirmed to be missing Caledon senior

Human remains located in Mulmur Township in March have been confirmed to be those of an 88-year-old Caledon man who was reported missing seven months ago.




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Photo Gallery: 75th Anniversary of VE Day

Friday, May 8, 2020, marks the 75 anniversary of VE Day.




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Bells sound across Barrie to mark the 75th anniversary of VE Day

Church bells rang out across the city of Barrie on Friday morning to commemorate the anniversary of the Victory in Europe Day on Friday.




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K9 unit discovers human remains in search for missing Meaford man

Grey Bruce provincial police say the OPP canine unit found human remains in Meaford, and one person is under arrest.




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Local health unit credits public with slowing COVID spread, encourages cottagers to stay home

While infection rates remain steady across the region, the Simcoe Muskoka District Health Unit is reporting more than half of all 360 cases have now recovered.




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Community support for front-line workers and caregivers 'means so much'

Nurses, PSWs, and front-line workers in long-term care and retirement homes have been dealing with the full reality of this pandemic every day.




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Too soon? B.C. workers, employers struggle with thorny reopening issues

As British Columbians digest the implications in the steps the premier announced in reopening the province's economy, some residents have come to the conclusion they’re too much too soon.




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Univ of Pittsburg Researcher, China Native, Dr. Bing Liu, “On the verge” of COVID19 Breakthrough Is Murdered…Alleged Gunman, Hao Gu, Kills Himself

The following article, Univ of Pittsburg Researcher, China Native, Dr. Bing Liu, “On the verge” of COVID19 Breakthrough Is Murdered…Alleged Gunman, Hao Gu, Kills Himself, was first published on 100PercentFedUp.com.

A 37-year-old China native and "outstanding researcher" at the University of Pittsburgh...

Continue reading: Univ of Pittsburg Researcher, China Native, Dr. Bing Liu, “On the verge” of COVID19 Breakthrough Is Murdered…Alleged Gunman, Hao Gu, Kills Himself ...




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BREAKING: Sen Marsha Blackburn Introduces Stop COVID Act…Allowing US Citizens To Sue Communist China For Damage They’ve Inflicted On Our Nation

The following article, BREAKING: Sen Marsha Blackburn Introduces Stop COVID Act…Allowing US Citizens To Sue Communist China For Damage They’ve Inflicted On Our Nation, was first published on 100PercentFedUp.com.

Yesterday, Senator Marsha Blackburn (R-TN), along with Senator Martha McSally (R-AZ) introduced the Stop COVID Act, giving Americans the ability to sue Communist China for the damage they’ve inflicted on our nation. Senator Blackburn appeared on Fox News with host Judge Jeanine where she explained the act to Jeanine Pirro. Blackburn told the Fox News […]

Continue reading: BREAKING: Sen Marsha Blackburn Introduces Stop COVID Act…Allowing US Citizens To Sue Communist China For Damage They’ve Inflicted On Our Nation ...




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Breaking: Texas AG Calls for Immediate Release of Salon Owner Jailed for Opening…Texas Lt Gov Offers to Pay Salon Owner’s $7k Fine

The following article, Breaking: Texas AG Calls for Immediate Release of Salon Owner Jailed for Opening…Texas Lt Gov Offers to Pay Salon Owner’s $7k Fine, was first published on 100PercentFedUp.com.

Salon A La Mode owner Shelley Luther opened her salon in defiance of the lockdown order for salons to stay closed during the coronavirus crisis. She boldly ripped. up the citation she was given by the police and refused to shut her doors. Luther hired a lawyer and went to court where an activist judge […]

Continue reading: Breaking: Texas AG Calls for Immediate Release of Salon Owner Jailed for Opening…Texas Lt Gov Offers to Pay Salon Owner’s $7k Fine ...




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Dem Congresswoman: Biden Allegation ‘Put To Rest’ Because He ‘Went on TV’ And Denied It

The following article, Dem Congresswoman: Biden Allegation ‘Put To Rest’ Because He ‘Went on TV’ And Denied It, was first published on 100PercentFedUp.com.

Democrat Rep. Dina Titus says that the allegations against 2020 Democrat presidential candidate Joe Biden are “put to rest” because he “went on TV” and denied them. Rep. Titus spoke with MSNBC’s Ayman Mohyeldin today about how she believes Biden because he flatly said he didn’t do it and didn’t say he doesn’t remember. It’s […]

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‘Schiff in Panic Mode’: Sources Say Russia Probe Transcripts Affirm Officials Found Nothing on Collusion

The following article, ‘Schiff in Panic Mode’: Sources Say Russia Probe Transcripts Affirm Officials Found Nothing on Collusion, was first published on 100PercentFedUp.com.

Transcripts of House Intelligence Committee interviews have been cleared for release, and Adam Schiff is reportedly in panic mode. Unfortunately for Schiff, top law enforcement and intel officials said they saw no evidence of collusion between the Trump campaign and Russia in the transcripts. Republicans sought and got approval for the release of the transcripts […]

Continue reading: ‘Schiff in Panic Mode’: Sources Say Russia Probe Transcripts Affirm Officials Found Nothing on Collusion ...




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Woman Shoots Three Teenage McDonald’s Workers For Telling Her She Couldn’t Eat In Dining Room Over COVID19 Restrictions

The following article, Woman Shoots Three Teenage McDonald’s Workers For Telling Her She Couldn’t Eat In Dining Room Over COVID19 Restrictions, was first published on 100PercentFedUp.com.

An angry Oklahoma woman shot at a group of teenagers working at a local McDonald’s after they explained to her that the dining room was closed due to coronavirus restrictions. 32-year-old Gloricia Woody was arrested by the Oklahoma City Police and charged with the shooting. From the Oklahoma City Police -Last night, officers were called […]

Continue reading: Woman Shoots Three Teenage McDonald’s Workers For Telling Her She Couldn’t Eat In Dining Room Over COVID19 Restrictions ...




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BREAKING: New Docs Prove Obama Knew Details Of Flynn Wiretapping…Newly Surfaced Video Shows Obama Explaining How He Stays Out Of FBI Investigations

The following article, BREAKING: New Docs Prove Obama Knew Details Of Flynn Wiretapping…Newly Surfaced Video Shows Obama Explaining How He Stays Out Of FBI Investigations, was first published on 100PercentFedUp.com.

Barack Obama knew. Documents released yesterday that were used to exonerate President Trump’s new NSA General Flynn, prove that President Barack Obama was aware of the details of Michael Flynn’s intercepted phone calls on December 16 with then-Russian Ambassador Sergey Kislyak. On January 5, 2017, then-Deputy Attorney General, Sally Yates attended an Oval Office meeting […]

Continue reading: BREAKING: New Docs Prove Obama Knew Details Of Flynn Wiretapping…Newly Surfaced Video Shows Obama Explaining How He Stays Out Of FBI Investigations ...




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Busted! Late-Night Hack Comedian, Jimmy Kimmel Is Forced To Apologize For Sharing Highly Edited Video Of VP Pence To Make Him Look Bad

The following article, Busted! Late-Night Hack Comedian, Jimmy Kimmel Is Forced To Apologize For Sharing Highly Edited Video Of VP Pence To Make Him Look Bad, was first published on 100PercentFedUp.com.

Last night, Jimmy Kimmel, host of the low-rated, late-night Jimmy Kimmel Show, shared a deceptively edited video clip of Vice President Pence delivering PPE to a nursing home. Today, liberal activist Matt McDermott tweeted the videotaped segment on VP Pence that was edited to make the vice president look like he was faking a delivery […]

Continue reading: Busted! Late-Night Hack Comedian, Jimmy Kimmel Is Forced To Apologize For Sharing Highly Edited Video Of VP Pence To Make Him Look Bad ...




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One new death and nine new COVID-19 cases in Windsor-Essex

One more person has died from the coronavirus in the Windsor-Essex region on Saturday and nine new cases have been reported by the health unit.




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How Winnipeggers can celebrate Mother's Day during COVID-19

Mother's Day is Sunday, but with COVID-19, it's forcing many to change their plans.




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Overnight snow expected in areas of Southern Manitoba

Environment Canada has issued a special weather statement for the southwestern area of Manitoba.




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Manitoba’s unemployment rate nearly doubled in April: Statistics Canada

Manitoba’s unemployment rate nearly doubled between March and April, according to the monthly report from Statistics Canada released Friday morning.




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May snowstorm buries southwest Manitobans

Instead of May flowers, Manitobans in the southwest part of the province received a blanketing of snow for Mother's Day weekend.




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UK General Election 2019: What the Political Party Manifestos Imply for Future UK Trade

Research Event

4 December 2019 - 12:30pm to 1:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Michael Gasiorek, Professor of Economics, University of Sussex; Director, Interanalysis; Fellow, UK Trade Policy Observatory, University of Sussex
Julia Magntorn Garrett, Research Officer, UK Trade Policy Observatory, University of Sussex
Prof Jim Rollo, Deputy Director, UK Trade Policy Observatory, University of Sussex; Associate Fellow, Global Economy and Finance Department, Chatham House
Nicolo Tamberi, Research Officer in the Economics of Brexit, University of Sussex
L. Alan Winters, Professor of Economics, Director, UK Trade Policy Observatory, University of Sussex

The upcoming UK general election is arguably a 'Brexit election', and as such, whoever wins the election will have little time to get their strategy for Brexit up and running to meet the new Brexit deadline of 31 January 2020. But what are the political parties’ policies for the UK's future trade? This event will present and discuss what the five main parties’ manifestos imply for future UK trade. Each manifesto will be presented and analysed by a fellow of the UK Trade Policy Observatory (UKTPO) and will be followed by a Q&A session. 

Michela Gariboldi

Research Assistant, Global Economy and Finance Programme
02073143692




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Repression of sphingosine kinase (SK)-interacting protein (SKIP) in acute myeloid leukemia diminishes SK activity and its re-expression restores SK function [Molecular Bases of Disease]

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.




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Inhibition of the erythropoietin-producing receptor EPHB4 antagonizes androgen receptor overexpression and reduces enzalutamide resistance [Molecular Bases of Disease]

Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy.