text:
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text:
#384075 rick and daryl wallpaper | 1920 x 1080
- Category:
- File Name:#384075 rick and daryl wallpaper
- Added Date:2016-06-11
- Added By:Yancy Robertson
- Resolution:1920 x 1080
- Weight:409 kB
Click to image #384075 rick and daryl wallpaper for download in 1920 x 1080 px, wallpaper was uploaded on trunkweed.com by Yancy Robertson. This image weights about 409 kB.
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subset: commoncrawl


text: Facebook Has a Secret Photo-Sharing iPhone AppKat Hannaford6/15/11 5:40amFiled to: appsFacebook photo appFacebookappiPhone AppiPhone AppsFacebook PhotosLeakLeaksunconfirmedRumorRumorsFacebook iphone app44EditPromoteDismissUndismissHideShare to KinjaToggle Conversation toolsGo to permalink TechCrunch said Facebook's secret iPhone app "looks awesome" and "amazing," whereas most Android users would just be thankful for a Facebook app that actually works. Like some kind of amalgamation of Path, Instagram and Color, it does sound pretty hot. Supposedly it's a standalone app at present, but Facebook might include it in the main iPhone app at a later date, and even roll the technology out into the browser-based Facebook too. As someone who regularly bangs her head against a brick wall every time she uploads a photo to Facebook, that'd do nicely, thanks.TechCrunch is still sorting through the 50MB of data and photos that were leaked to them, so this one image is all we've got at the moment. But hopefully we'll be able to ascertain some more details about this groovy-sounding app once they upload some more, and figure out if Facebook's pulling out all the stops now that all these photo-sharing apps are trampling on its floor-space...or if it's a reaction to Apple baking Twitter so deeply into iOS 5. [TechCrunch] Gear from Kinja DealsThe New 3DS Doesn't Include a Power Adapter. Get This Instead.Bestsellers: Cards Against HumanitySave $13 On the Bluetooth-Enabled Xbox One S ControllerReply44 repliesLeave a reply


text:
BROOKLYN - The Tuesday after Thanksgiving is known to many nonprofit organizations as "Giving Tuesday."
The movement started in 2012 by the 92nd Street Y in Manhattan, and aims to create a national day of giving at the start of the holiday season.
This primarily online push has spread like wildfire and is being used with the hashtag by many charities worldwide to get the word out about their organizations.
In Brooklyn, the Salvation Army is hoping "Giving Tuesday" will prompt charitable people to donate to its red box campaign, which provides nonperishable food and holiday decorations to local families in need, all for the cost of a donation of $65.
A spokesperson for the 92nd Street Y encourages all nonprofits and charities to use this "Giving Tuesday" campaign and make this day their own.


text:
anonymous asked:
lmao Perra-diabla is white. Latina is not a race so its p funny seeing her stick up for white women's "oppression" from their male counter parts (which like never happens considering deferred action and all that benefits only white women and not PoC women) but thats nothing new. Non black PoC women wanna be on our side until they feel uncomfortable with black radical politics lml


text:
NCAAF News
Leonard Fournette's return boosts LSU offense that thrived in his absence
Running back Leonard Fournette is expected back this weekend, but that raises some questions for LSU's offense.
As evidenced by two strong weeks, Oregon State's foundation is taking shape
Oregon State coach Gary Anderson has taken meaningful steps with the Beavers program, but he knows "this is a process."
Q&A: New Georgia Tech AD Todd Stansbury
Todd Stansbury is ready to take over as athletic director at his alma mater and to keep it competing at a national level.
Marty Smith attempts pass to water skier
Marty Smith is on a boat and tries to throw a football to an Alabama water skier.
How will the Big 12 affect Herman's time with Houston?
Brett McMurphy explains how the Big 12's decision to not expand to include Houston cost coach Tom Herman millions of dollars and speculates where Herman could be next season.
Assessing Trevor Knight's play ahead of his second career game vs. Alabama
Trevor Knight has piloted Texas A&M to 6-0, displaying solid leadership and rushing along the way, but he heads to Alabama with a few weaknesses.


text:
@ thez_yo - Thanks =D
@ amphirion - will be the other halfs day off, if she's up for going, we will be there! bubbling with excitement! =)
@ Pineapple - haha i know right! looking back I get a good laugh out of it, but I had no clue and still don't
@ Lil Stinkpot - thanks for the welcome and the invite as well. so glad to meet, well sort've meet more bay area CP lovers! =)
@ jim scott - Thanks! =)


text:
Copart Auto Auction TOYOTA Lot Details
- Lot # 30436396
- Est. Retail Value $12,594 CAD
- Repair Est $0 CAD
- Ownership Doc Type BC - VEH REGISTRATION-SALVAGE
- Odometer 0 EXEMPT
- Primary Damage FRONT END
- Body Style CLUB CAB
- Color BLUE
- Engine 4.0L 6
- Drive Rear-wheel drive
- Cylinders 6
- Fuel GAS
- Keys YES
- Auction Location Calgary, AB show on map
- Sale Date Future Sale
- Live Auction Item Item # 0
- Sale Status Pure Sale
Shipping Calculator
- We can ship your vehicle to any home or business address in the USA or Canada or to any major port worldwide.
- Use our shipping calculator to receive an instant shipping quote for your vehicle. To place your order, click Order Shipping Now.
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Sale Date Future Sale
Damage FRONT END
Auction Eugene, OR
Current Bid $25 USD
Sale Date 10/25/16
Damage WATER/FLOOD
Auction Baton Rouge, LA
Current Bid $0 USD
Sale Date 10/25/16
Damage ALL OVER
Auction Hampton, VA
Current Bid $0 USD
Sale Date 10/25/16
Damage SIDE
Auction Amarillo, TX
Current Bid $0 USD
Sale Date Future Sale
Damage ROLLOVER
Auction Nashville, TN
Current Bid $0 USD
Sale Date Future Sale
Damage SIDE
Auction Jackson, MS
Current Bid $30 USD


text:
|Road Name:
|Bell's Wynd
|Road Type:
Bells Wynd is a street in the settlement of Falkirk which is within the electoral area of Falkirk North Ward in the administration area of Falkirk Council located in the Scotland Euro Region of the UK.
Bells Wynd is located 345.52 miles North West from the centre of London, 20.35 miles North East from the centre of Glasgow, 23.33 miles West from the centre of Edinburgh and 44.63 miles South West from the centre of Dundee.
Bells Wynd is approximately 1.99 miles from the coastal tidal high water mark) and is 38 metres above sea level
Postcodes for Bells Wynd
|The Central point of Bells Wynd is approximately 38 Metres above sea level
Nearby Telephone Area Codes
|Area Code: 01324 - Falkirk
|Area Code: 01259 - Alloa
|Area Code: 01506 - Bathgate
Hotel information updated 09/10/2016
|Antonine Hotel - falkirk-stirlingshire
|Located in the centre of Falkirk, Antonine Hotel offers a restaurant, a bar and free private parking. The property is just 1 minute walk from Falkirk
|1 Manor Street, FK1 1NT, Falkirk
|Number of Rooms:
|Lowest Price Room:
|The Orchard Hotel - falkirk-stirlingshire
|Situated in the heart of Falkirk, The Orchard Hotel offers rooms with free Wi-Fi, free parking, and a bistro restaurant. Grangemouth is 8 minutes
|2 Kerse Lane, FK1 1RG, Falkirk
|Number of Rooms:
|Lowest Price Room:
|Garthill Lodge - falkirk-stirlingshire
|Star Rating:
|5 Stars
|Located 2.5 km from Falkirk Wheel in Falkirk, this apartment features free WiFi. Free private parking is available on site. There is a seating area and a kitchen complete with a dishwasher, an oven and a microwave.
|9 Garthill Gardens, FK1 5SN, Falkirk
|Number of Rooms:
|Lowest Price Room:
|Callender Apartments - falkirk-stirlingshire
|Callender Apartments offers accommodation in Falkirk, 3.3 km from Falkirk Wheel. Free WiFi is featured throughout the property. An oven, a microwave and a toaster can be found in the kitchen and there is a private bathroom.
|83 Oswald Street, FK1 1QL, Falkirk
|Number of Rooms:
|Lowest Price Room:
|Rosie\'s Bed & Breakfast - falkirk-stirlingshire
|Located 3.3 km from Falkirk Wheel in Falkirk, Rosie\'s Bed & Breakfast features free WiFi access and free private parking. Rooms include a flat-screen TV. Certain units feature a seating area to relax in after a busy day.
|115 Oswald St., FK1 1QL, Falkirk
|Number of Rooms:
|Lowest Price Room:
Local Council Details
|Within the area of Falkirk
|Visit the Council's Website
|Municipal Buildings
|Send Mail
|Telephone Number: 01324 506 070
|Within the electoral area of Falkirk North Ward -
|Within the Westminster Parliamentary Constituency of Falkirk
|The Member of Parliament is Joyce, Eric
Water and Drainage Details
|Scottish Water
|Visit Scottish Water's Website
Random Street
Winthorpe Road
Location Details
Bells Wynd
|OS Reference: 288606, 679937
OS Grid Reference: NS886799
|Latitude and Longitude: 55.999472823365, -3.7863385210484
|Approximate distance to the Coast: 1.99 miles
Ordnance Survey Landranger Map Series for Bells Wynd
|Map Number: 65
|Map Name: Falkirk & West Lothian
Nearest Railway Stations
|Falkirk Grahamston Rail Station is 0.39 Kilometers away (0.24 miles)
|Falkirk High Rail Station is 0.89 Kilometers away (0.55 miles)
|Camelon Rail Station is 2.01 Kilometers away (1.25 miles)
|Larbert Rail Station is 3.73 Kilometers away (2.32 miles)
Nearest Airports
|Edinburgh Airport is 27.09 Kilometers away
|Glasgow International Airport is 43.14 Kilometers away
|Dundee City Airport is 69.66 Kilometers away
|Glasgow Prestwick International Airport is 75.19 Kilometers away
Nearest Ferries
|Rosyth Ferry Terminal is 21.90 Kilometers away
|South Queensferry Ferry Landing is 25.04 Kilometers away
|Inchcolm Island Ferry Landing is 30.51 Kilometers away
|Kinross Ferry Landing is 32.53 Kilometers away
Nearest Motorway Junctions
|Junction: M9 J6/A904/A905 - 3.04 Km Away
|Junction: M9 J5/A9/A905 - 4.37 Km Away
|Junction: M9 J7/M876 - 4.91 Km Away
Nearest Libraries
Falkirk Library
|Hope Street, Falkirk, FK15AU
|Distance: 0.16 Miles
|Visit Website
Larbert Library
|22 Hallam Road, Larbert, FK53JX
|Distance: 2.07 Miles
|Visit Website
Meadowbank Library
|6a Stevenson Avenue, Polmont, FK20GU
|Distance: 2.82 Miles
|Visit Website
Nearest Tourist Attractions
|Attraction Name: Callendar House (World Heritage Site)
|Distance: 1.20 (km)
Tourist Attraction
|Attraction Name: Watling Lodge (Antonine Wall)
|Distance: 1.74 (km)
Landmark or Antiquity
|Attraction Name: Watling Lodge (Antonine Wall)
|Distance: 2.18 (km)
Tourist Attraction
|Attraction Name: The Helix
|Distance: 2.48 (km)


text:
Prentice Mulford: Life by Land and Sea, The Californian's Return - Twenty Years From Home & Other Autobiographical Works
From one of the New Thought pioneers, author of Thoughts are Things, Your Forces and How to Use Them, The God in You, The Swamp Angel, Gift of Spirit & The Gift of UnderstandingThis carefully crafted ebook: "Prentice Mulford: Life by Land and Sea, The Californian's Return - Twenty Years From Home & Other Autobiographical Works" is formatted for your eReader with a functional and detailed table of contents. Extract: "We were towed into the stream and anchored for the night. To look at New York City, with its many lights and its thousands amusing themselves in various ways
A Leaving Paradise Novel (Book 1)Nothing has been the same since Caleb Becker left a party drunk, got behind the wheel, and hit Maggie Armstrong. Even after months of painful physical therapy, Maggie walks with a limp. Her social life is nil and a scholarship to study abroad—her chance to escape everyone and their pitying stares—has been canceled.After a year in juvenile jail, Caleb's free . . . if freedom means endless nagging
How to Ruin a Summer Vacation Novel (Book 2)In this sequel to How to Ruin a Summer Vacation, EVERYTHING in sixteen-year-old Amy Nelson Barak's life is going wrong! Her mom got married and moved to the suburbs, and now they are going to have a baby. Amy moves in with her dad in Chicago and signs him up for an online dating service. His first four dates are that night . . . What else? Her dog Mutt impregnated her grumpy neighbor's prized
How to Ruin a Summer Vacation Novel (Book 1)YALSA 2007 Teens' Top Ten "A breezy read." —Bulletin of the Center for Children's Books "Fresh, fun and fabulous! Guaranteed NOT to ruin your summer vacation!" —Mari Mancusi, author of Boys that Bite How To Ruin a Summer Vacation Moshav? What's a moshav? Is it "shopping mall" in Hebrew? I mean, from what Jessica was telling me, Israeli stores have the latest fashions from Europe. That black
How to Ruin Your Boyfriend's Reputation
How to Ruin a Summer Vacation Novel (Book 3)"A great read-alike for fans of Meg Cabot, Melissa Kantor, and Sarah Dessen."--VOYA Guess who's jetting off to the Holy Land this summer! Yes, it's me—Amy Nelson-Barak. I've volunteered for ten days of military training in Israel with my friends. The Sababa brochure said it would be a "fun" summer experience. Okay, so I didn't sign up to prove I'm not a princess…I did it to surprise my...
$7.19Carlos Fuentes doesn't want any part of the life his older brother, Alex, has laid out for him in Boulder, Colorado. He wants to keep living on the edge, and carve his own path-just like Alex did. Unfortunately, his ties to a Mexican gang aren't easy to break, and he soon finds himself being set up by a drug lord. When Alex arranges for Carlos to live with his former professor and his family to
$7.19A fresh, urban twist on the classic tale of star-crossed lovers. When Brittany Ellis walks into chemistry class on the first day of senior year, she has no clue that her carefully created "perfect" life is about to unravel before her eyes. She's forced to be lab partners with Alex Fuentes, a gang member from the other side of town, and he is about to threaten everything she's worked so hard for
$7.19Luis Fuentes is a good boy who doesn't live with the angst that his big brothers, Alex and Carlos, have always lived with. Luis is smart, funny, and has big dreams of becoming an astronaut. But when he falls for the wrong girl, Luis enters a dark world he's never known, and just when he thinks he's got life all figured out, learns some disturbing news about his family that destroys his positive
Wild Cards (Book 2)From New York Times and USA Today bestselling author Simone Elkeles, the next book in the Wild Cards series. When the only girl you want is the one you can't have... Bad boy Vic Salazar breaks all the rules except one: Don't make a move on your best friend's girl. It's a Guy Code that Vic lives by. It doesn't matter that he's had a crush on her for years. Monika Fox is off limits. Monika has a
$7.19A fresh and fun repackage of Wild Cards, Better Than Perfect launches a romantic new series from New York Times bestselling author Simone Elkeles. After getting kicked out of boarding school, bad boy Derek Fitzpatrick has no choice but to live with his ditzy stepmother while his military dad is deployed. Things quickly go from bad to worse when he finds out she plans to move them back to her


text:
Susi Snyder: soon all nuclear weapons will be declared illegal
Pressenza interviewed Susi Snyder at IPB World Congress in Berlin "Disarm! For a climate of Peace". According to Susi Snyder we are reaching the point where all nuclear weapons will be declared illegal. Let's hope that in 2017 we will have this treaty, because it will be a very big… »


text:
Friday, 28 October 2016
Last updated 17 hours ago
Feb 23 2010 | 7:24am ET
Four investors with alleged Ponzi schemer Arthur Nadel have settled lawsuits filed against them by the court-appointed receiver in the case.
The first settlements won by Burton Wiand have boosted the pool of money available to victims of the alleged scam, which prosecutors say cost investors $168 million, by more than $1 million. Wiand says Nadel paid out some $53 million in fictitious profits to investors in six hedge funds he managed.
Most of the settlement money comes a single investor, the Miami-based Argenta Fund, which agreed to return $941,152. Argenta invested $1.3 million in Nadel's Viking Fund in 2004, withdrawing more than $2.4 million four years later. Nine months after that, Nadel's funds collapsed.
Another fund, Westport, Conn.-based Sandcastle Partners, will return all $60,780 in allegedly bogus profits it withdrew. The Lester Haynes Blackburn Trust agreed to repay $27,712, and James Kapralos $37,677.
All four must pony up within two weeks. Argenta and the Blackburn Trust got to keep 10% of the allegedly phony profits because Wiand had not asked them to return the money prior to filing suit.
The receiver also announced that another four Nadel investors have agreed to return money they redeemed from his funds without the trouble of a lawsuit. Those agreements netted another $433,585 for Wiand's trust.
Wiand has now recovered some $3.4 million from investors in Nadel's funds.
Nadel himself has been jailed since his arrest more than one year ago. His trial is due to begin in April, although prosecutors indicated that they are working on a deal with the 77-year-old.
Oct 20 2016 | 9:03pm ET
Bitcoin's blockchain technology has spawned a flurry of activity among fintech startups...
Oct 27 2016 | 2:32pm ET
As the first flakes of snow fall on New York's northern suburbs, Dan Weil of South...
Sep 29 2016 | 5:46pm ET
There are two main goals a hedge fund should have for an initial in-person sales...


text:
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Jul 4, 2013, 9:00 am224 ptsWhatever happened on set, it sounds like these two stars did NOT get along! Here are the deets: This B list mostly movie actor has had some great roles and been in one of the biggest movies of all time. He also says that he would have quit acting if he had to work with this A list mostly movie…Continue reading Celebrity Blind Item This Star REALLY Doesn't Like This Other Star at I'm Not Obsessed
Gillian Anderson and writer Peter Morgan are dating Page Six 394
Mariah Carey reportedly dumped by billionaire fiancé Page Six 305
Beyoncé has 'never genuinely liked' Kim Kardashian Page Six 225
Concertgoers not impressed with Sia's disguise Page Six 208
Dick Cavett and wife in Hamptons car crash Page Six 179
A big swirling bucket of the latest rumors, celebrity news and Hollywood gossip. The premier celebrity gossip app.
Gossip Bucket aggregates and streams the latest gossip news and headlines from the top sources in one place.


text:
chipboardnoun [ U ]uk /ˈtʃɪp.bɔːd/ us /ˈtʃɪp.bɔːrd/
Thesaurus: synonyms and related words
(Definition of "chipboard" from the Cambridge Advanced Learner's Dictionary & Thesaurus © Cambridge University Press)
Get a quick, free translation!
Create and share your own word lists and quizzes for free!
Word of the Day
extreme fear, excitement, anger, etc. that cannot be controlled
New Words


text:
Facebook ads pay off for retailers in Q3
The average return on Facebook ad spend rises 26% in Q3, according to social media advertising firm Nanigans.
Facebook ads pay off for retailers in Q3
The average return on Facebook ad spend rises 26% in Q3, according to social media advertising firm Nanigans.
Internet Retailer introduces Digital Commerce 360
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Semantic search can grasp the intent of the consumer, but it requires a retailer to work on the content of its product catalog.
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An IRWD speaker will talk about how to keep up with Google changes.
Posted 11/09/2012Katie EvansPost a comment
A new approach to search could both help and hurt advertisers, experts say.
Posted 03/16/2012Paul DemeryPost a comment
DES PLAINES, IL – 7Search, a leading pay-per-click search engine and advertising network, announced it has formed a strategic traffic and advertisement distribution partnership with Relevad Corporation, which leverages semantic search and natural language processing to provide large volumes of high-quality traffic. The announcement was made by Charles Meyer, 7Search Business Development Director. "This is a new and exciting addition to the...
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A new search engine that integrates, processes, and provides information in the most user-friendly way, aims to attract users in a unique way. Washington DC, January 28, 2009 -- Sagoon, (www.sagoon.com) based in Washington DC, has released the beta version of its new search engine for public testing. The Internet is reaching more and more people every day. Millions of people visit it every second to contribute information or to search for it....
Posted 01/29/2009


text:
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useless Queen :p
i have one doubt why king not attacking g7 rook? can any one explain me
11171 --- why doesn't the king just take the rook (Kxd7) when the rook attacks?---
Because 1. Rxf7+ ...Kxf7 2. Rf2+ ...Qf5 ( ...Kh8 3.Qe6# ) 3. Rxf5+ ...Kh8 4. Qe6#
still an mateinfour
Why doesn't black play Kg7 on the return of the first move?
I do not understandthat that after the first move of white, why the black king spare the rook?
Nice checkmate !
He doesnt take the rook becasue then rg2+ forces kh8 which leads to qf6#
why did the king not eat the rook on the first attempt?
If Black played Kxg7, as you suggest, what would you play next ?
I got the answer - if black played Kxg7, then mate in 3 - Rg2+, Kh8, Qf7#
Is this cheating?
by pjreed86 2 minutes ago
Nimzovich.. Nimzowitsch
by david 4 minutes ago
Invent the new worst/most useless chess piece ever!
by ChessChap112358 7 minutes ago
DKINGISDEAD - King Maneuver Attack
by DKingIsDead 9 minutes ago
How long does it take to be a 2000 rate player?
by kingofshedinjas 12 minutes ago
Blocking all ALL communication
by notmtwain 14 minutes ago
10/27/2016 - Backed In
by Pulpofeira 16 minutes ago
Why didn't Fischer play Karpov
by alinfe 20 minutes ago
Mate from my Bullet game
by DKingIsDead 22 minutes ago
IV category
by Drawgood 22 minutes ago
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text:
Observations on the National Aeronautics and Space Administration's Fiscal Year 2000 Performance Plan
NSIAD-99-186R: Published: Jul 20, 1999. Publicly Released: Aug 18, 1999.
Additional Materials:
- Full Report:
(202) 512-4841
Office of Public Affairs
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Pursuant to a congressional request, GAO reviewed the National Aeronautics and Space Administration's (NASA) fiscal year (FY) 2000 performance plan, which was submitted to Congress in response to the Government Performance and Results Act of 1993, focusing on: (1) assessing the usefulness of the agency's plan for decisionmaking; and (2) identifying the degree of improvement the agency's FY 2000 performance plan represents over the FY 1999 plan.
GAO noted that: (1) NASA's FY 2000 annual performance plan should be useful to decisionmakers; (2) it provides a limited picture of intended performance across the agency, a general discussion of strategies and resources the agency will use to achieve its goals, and limited confidence that performance information will be credible; (3) an example of a positive change regarding the plan's presentation of strategies and goals is the discussion on NASA's objective of extending the use of Earth Science research for national, state, and local application; (4) the plan links that objective with the achievement of three performance goals, namely having at least one Regional Earth Science Application become self-sustaining, developing at least two new data products for routine decision-making by user organizations, and implementing at least 5 joint applications research projects/partnerships with state and local governments in remote sensing applications; (5) NASA's FY 2000 plan represents a moderate improvement over the FY 1999 plan in that it indicates some degree of progress in addressing the weaknesses identified in GAO's assessment of the FY 1999 plan; (6) in reviewing the FY 1999 plan, GAO observed that the plan could have provided a clearer picture of intended performance across the agency, did not fully portray how strategies and resources would help achieve performance goals, and partially provided confidence that performance information would be credible; and (7) among improvements in the FY 2000 plan is the inclusion of: (a) performance objectives or targets that fully or partially address 5 of 10 management challenges identified by NASA's Office of the Inspector General or GAO; (b) a crosswalk to relate budget categories with performance objectives and targets; and (c) expanded detail on internal and external evaluations of performance.
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We hypothesized that resting and exercise ventilatory chemosensitivity would be augmented in women when estrogen and progesterone levels are highest during the luteal phase of the menstrual cycle. Healthy, young females (n = 10; age = 23 ± 5 yrs) were assessed across one complete cycle: during early follicular (EF), late follicular (LF), early luteal, and mid-luteal (ML) phases. We measured urinary conjugates of estrogen and progesterone daily. To compare values of ventilatory chemosensitivity and day-to-day variability of measures between sexes, males (n = 10; age = 26 ± 7 yrs) were assessed on 5 nonconsecutive days during a 1-mo period. Resting ventilation was measured and hypoxic chemosensitivity assessed using an isocapnic hypoxic ventilatory response (iHVR) test. The hypercapnic ventilatory response was assessed using the Read rebreathing protocol and modified rebreathing tests. Participants completed submaximal cycle exercise in normoxia and hypoxia. We observed a significant effect of menstrual-cycle phase on resting minute ventilation, which was elevated in the ML phase relative to the EF and LF phases. Compared with males, resting end-tidal CO2 was reduced in females during the EF and ML phases but not in the LF phase. We found that iHVR was unaffected by menstrual-cycle phase and was not different between males and females. The sensitivity to chemical stimuli was unaffected by menstrual-cycle phase, meaning that any hormone-mediated effect is of insufficient magnitude to exceed the inherent variation in these chemosensitivity measures. The ventilatory recruitment threshold for CO2 was generally lower in women, which is suggestive of a hormonally related lowering of the ventilatory recruitment threshold. We detected no effect of menstrual-cycle phase on submaximal exercise ventilation and found that the ventilatory response to normoxic and hypoxic exercise was quantitatively similar between males and females. This suggests that feed-forward and feed-back influences during exercise over-ride the effects of naturally occurring changes in sex hormones.
- breathing control
- hypercapnic ventilatory response
- hypoxic ventilatory response
- sex steroidal hormones
the control of ventilation in humans and other mammalian species is known to be influenced by variations in both ovarian and testicular hormones. The effects of the menstrual cycle, pregnancy, estrogen, testosterone, and progesterone on resting ventilation have each been studied [for review, see (4, 5, 14)]. However, the effects of sex hormones on the human ventilatory responses to hypoxia and hypercapnia are equivocal. Hypoxic chemosensitivity, under resting conditions, has been found to be greater (22, 51) and lower (1, 30, 47) in males relative to females. Furthermore, a large number of human studies report no difference between males and females for hypoxic chemosensitivity (10, 18, 23, 24, 29, 40, 41). Two factors likely contribute to the disparity among studies. The first contributing factor is that few reports of carefully characterized menstrual-cycle stages are available. As such, the ovarian hormone environment is generally unknown and is likely to vary among studies. Moreover, direct measures of ovarian hormones and methods of assessing menstrual-cycle phase are inconsistently reported and poorly executed. As such, between-study comparisons of hormonally induced ovarian alterations in the control of breathing are difficult if not impossible. A second contributing factor to the divergent results reported is a myriad approaches used to determine hypoxic chemosensitivity. Hypoxic tests can be progressive, step, steady-state, isocapnic, poikilocapnic, or iso-oxic hypoxia combined with hypercapnia. Methods for assessing the hypercapnic ventilatory response (HCVR) are also variable among studies, and chemosensitvity to CO2 has been shown to be higher in males (51) relative to females or not different (1, 36).
Hypoxia and hypercapnia are powerful ventilatory stimulants. However, the largest ventilatory adjustment made by humans is in response to dynamic whole-body exercise. Despite the importance of exercise hyperpnea and necessity for precise ventilatory regulation, the modulating effects of sex hormones on human exercise ventilation are poorly understood. Ventilation during sea-level exercise has been reported to be both higher (25, 42, 52) and equivalent (6, 7, 9, 12) during the luteal phase (when female sex hormones are at highest circulating levels) relative to the follicular phase (when female sex hormones are lowest). Few studies have assessed the control of exercise ventilation during hypoxic conditions across the menstrual cycle, but there is reason to suggest that it may be altered. First, under resting conditions, peripheral chemosensitivity to hypoxia may be increased with progesterone, and the effect appears to be potentiated by estrogen (48). Tatsumi and colleagues (48) compared resting ventilation and ventilatory responses with hypoxia and hypercapnia in awake cats before and after ovariectomy. Lower hypoxic ventilatory and carotid sinus nerve responses to hypoxia in ovariectomized compared with intact cats suggest that endogenous female hormones specifically affect the inputs from the carotid body. Second, the gain (i.e., increased receptor output for the same stimulus input) of the carotid chemoreceptors in response to hypoxia is higher during exercise than at rest (2, 50). Weil et al. (50) had healthy male subjects perform mild-to-moderate exercise (19%, 26%, and 34% maximum) and determined the hypoxic ventilatory drive by plotting minute ventilation (V̇i) and the partial pressure of alveolar O2. Low levels of exercise produced an enhancement of hypoxic ventilatory drive, and this effect was augmented as the severity of exercise increased. Whereas physiologically relevant levels of female hormones have been shown to act peripherally to raise carotid body hypoxic chemosensitivity at rest, the interaction between sex hormones and the independent effects of exercise on carotid body chemosensitivity are not known. Based on the above brief summary, the purpose of this study was to characterize the effects of biological sex and menstrual-cycle phase on both resting and exercise ventilation and chemosensitivity. To this end, we used a rigorous assessment of menstrual-cycle phase and daily approximation of circulating estrogen and progesterone via assessment of urinary conjugates, as well as a comprehensive evaluation of resting and exercise ventilation, chemosensitivity to O2 and CO2 during rest, and a measure of hypoxic sensitivity during exercise. In addition, identical methods were used to evaluate the effects of repeatedly assessing resting and exercise chemosensitivity in males. We hypothesized that when estrogen and progesterone levels were increased during the luteal phase, relative to the follicular phase, resting and exercise ventilatory chemosensitivity would be augmented.
Study design.
Participants visited the Health and Integrative Physiology Lab at the University of British Columbia to attend an orientation session and on five additional occasions, to evaluate ventilatory chemosensitivity during rest and exercise. Females were assessed at five time points to evaluate chemosensitivity across the menstrual cycle. To compare ventilatory chemosensitivity and the day-to-day variability of measures between sexes, males were also assessed on 5 nonconsecutive days during a 1-mo period. Participants were instructed to avoid alcohol for 12 h, as well as food, caffeine, and exercise for 4 h prior to each visit. Each participant gave informed, written consent, and all experimental procedures received institutional ethical approval and conformed to the Declaration of Helsinki.
Healthy, nonsmoking males and females, aged 19–40 years with no history of cardiorespiratory disease (including sleep apnoea), were recruited to participate. Competitive swimmers, breath-hold divers, and individuals who had traveled above 3,000 m in the previous 6 mo were excluded. Participants were permitted to use multivitamins but not other types of nutritional supplements. Females were excluded if they had a menstrual cycle that was not of normal length (26–32 days; based on a self-reported menstrual history for the past 12 mo) or used any form of hormonal contraceptives in the previous 6 mo. In addition, due to known influences on circulating ovarian hormones (11), women were excluded if they performed more than 4 h of vigorous exercise/wk, had a body mass index <18 kg/m2, or had experienced a weight change of ±2 kg in the previous 6 mo.
Orientation session.
During the orientation session, study procedures were explained, and participants gave written, informed consent. Participants completed a medical and physical activity questionnaire, and females provided a detailed menstrual-cycle history. Height and weight were recorded. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), FEV1.0/FVC, and maximum voluntary ventilation were measured using a portable spirometer (Spirolab II, Medical International Research, Vancouver, BC, Canada), according to standardized guidelines (3). Subjects with a FEV1.0/FVC of <80% predicted were excluded from participating in the investigation. Participants completed an incremental exercise test to determine maximal O2 uptake (V̇O2max) on an electronically braked cycle ergometer (Lode Excalibur Sport, Lode, Gronnigen, Netherlands). Cycle ergometer seat height was adjusted for each participant at the initial visit and kept consistent throughout all testing sessions. The cycle exercise test started at 0 W and increased 30 W/min until volitional exhaustion. The test was stopped when cadence fell below 60 revolutions/min. Subjects wore a nose clip and breathed through a mouthpiece connected to a nonrebreathing valve (Model 2700B, Hans Rudolph, Shawnee, KS). Mixed expired gases were measured using calibrated CO2 and O2 analyzers (Models CD-3A and S-3A/I, respectively, Applied Electrochemistry, Pittsburgh, PA), measured at a port located in a mixing chamber. Inspiratory flow was measured using a calibrated pneumotachograph (Model 3813, Hans Rudolph). Heart rate was recorded every 30 s using a commercially available heart-rate monitor (S610i, Polar Electro, Kempele, Finland). Throughout the test, participants wore pulse oximeters at the ear and finger (Model 504, Criticare Systems, Waukesha, WI). If there was a discrepancy between the two oximeter readings, the higher oxygen saturation (SpO2) value was recorded. Participants were then familiarized with the sensation of breathing hypoxic gas. During 10 min of seated rest, participants breathed a humidified gas mixture [fraction of inspired O2 (FiO2) = 0.15] through a face mask attached to a nonrebreathing valve. Lastly, female participants were instructed how to monitor their menstrual cycles for the following 1–2 mo before starting the testing cycle (see below).
Menstrual-cycle evaluation.
To determine that menstrual cycles were ovulatory and of normal length, females were monitored for 1–2 complete menstrual cycles, immediately prior to their test cycle. Participants kept a daily log of basal body temperature (BBT) and menstrual symptoms. They also used an over-the-counter ovulation-prediction kit (First Response Easy-Read Ovulation Test, Church & Dwight, Princeton, NJ) to determine the timing of a surge in luteinizing hormone (LH), which immediately precedes ovulation. During monitoring cycles, daily logs and ovulation-prediction kits were used to determine the timing of testing sessions during the test cycle. Targeted time points included the early follicular (EF1), late follicular (LF), early luteal (EL), and mid-luteal (ML) phases of one menstrual cycle, as well as the EF phase of the subsequent cycle (EF2). Testing during EF1 and EF2 phases occurred 2–4 days after onset of menses, when estrone-1 glucuronide (E1G) and pregnanediol glucuronide (PdG) should both be low. LF-phase testing targeted a time with peak E1G but low PdG, ∼2 days before the LH surge. EL- and ML-phase testing occurred ∼4 and ∼8 days after the LH surge, when both E1G and PdG should be elevated.
The hormone profile of each test cycle was determined post hoc by measuring the conjugates of estrogen and progesterone in daily urine samples. This allowed retrospective confirmation of normal cycles and assessment of whether the desired cycle phases were targeted successfully for testing. Throughout the test cycle, first-morning urine was collected daily into a sterile vessel and frozen immediately. Participants transported the urine samples to the Health and Integrative Physiology Lab on ice, where they were prepared in 2-mL aliquots and shipped on dry ice to the Women's Exercise and Bone Health Laboratory at the University of Toronto. Here, daily urinary E1G and PdG were measured using competitive enzyme immunoassays, as described previously (13). These conjugates are highly stable (32) and unlikely to be affected by storage and transport of samples.
Experimental procedures.
During each testing session, resting ventilation was measured and hypoxic chemosensitivity assessed using a progressive, isocapnic hypoxic ventilatory response (iHVR) test. The HCVR was assessed using a traditional Read rebreathing protocol (HCVR1) (35) and the modified rebreathing tests (HCVR2 and HCVR3) developed by Duffin and colleagues (17). These methods have been performed previously in our laboratory and are described in detail elsewhere (27). All tests were conducted in a slightly darkened room with subjects listening to quiet, arrhythmic music to minimize distraction. Body position is known to affect resting chemosensitivity (53), and although it varied among different tests, it remained constant across all participants when assessing hypoxic (supine) and hypercapnic (seated) chemosensitivity. Participants then completed a brief, submaximal exercise test in normoxia, followed by the same exercise test in hypoxia. All tests were separated by at least 10–20 min normoxic rest. Testing time, test order, and duration of resting intervals were held constant across data collection sessions for each participant.
Resting measures.
Participants were fitted with a face mask, heart-rate monitor, and pulse oximeters. Heart rate, SpO2, and V̇i were measured as during the V̇O2max test, and gases were sampled at the mouth to provide measures of end-tidal CO2 (PetCO2) and end-inspiration O2. Resting measures were averaged across the final 5 min of a 10-min period of supine rest.
Following the period of supine rest, 100% N2 was gradually titrated into the inspired gas mixture, progressively lowering the FiO2 from 0.21 to 0.05 over 5–10 min. The test was terminated when SpO2 reached 80%. Isocapnia was maintained at resting PetCO2 levels by adding CO2 to the inspiratory circuit as needed. The iHVR (L · min−1 · %−1) was calculated as the absolute slope of the line of best fit when V̇i (L/min) was plotted against SpO2 (%).
All rebreathing tests were performed in the seated position and with a similar setup. All ventilatory variables were measured as above, but instruments were interfaced with a personal computer using custom-made software (LabVIEW 7.0, National Instruments, Austin, TX). Participants wore nose clips and breathed through a mouthpiece attached to a three-way rebreathing valve, which was connected to a rebreathing bag. Participants were instructed to relax and breathe ad libitum. The tests continued until PetCO2 reached 60 mmHg or until subjects became too uncomfortable to continue. Before assessing HCVR1, participants sat quietly at rest, breathing room air through the mouthpiece. After 5 min, participants were instructed to exhale completely and then rapidly switched to the rebreathing bag, containing 7% CO2, balance O2. After three large breaths to equilibrate gases between the lungs and the rebreathing bag, participants were instructed to breathe ad libitum until the test was terminated. HCVR1 (L · min−1 · mmHg) was calculated as the slope of the line of best fit for V̇i (L/min) vs. PetCO2 (mmHg).
Before beginning the second rebreathing test, participants were coached to reduce their PetCO2 to 19–25 mmHg by hyperventilating for 5 min. Following a full exhalation, participants were switched to the rebreathing bag, this time containing 6% CO2, 24% O2, balance N2. As PetCO2 rose throughout the test, the rebreathing bag was maintained iso-oxic at 200 mmHg using a computer-controlled valve. A custom-designed computer program was used to calculate the CO2 threshold (T; mmHg) and sensitivity (S; L · min−1 · mmHg). "T" represents the PetCO2, above which ventilation begins to increase in response to increased CO2; "S" represents the slope of the line of best fit when above-threshold values of V̇i (L/min) are plotted against PetCO2 (mmHg). T2 and S2 were calculated for each HCVR2 test.
Determination of HCVR3 was similar to HCVR2 except that it assessed T and S in hypoxic, rather than hyperoxic, conditions. The procedure was identical, except that the rebreathing bag contained 6% CO2, 4.5% O2, balance N2, and iso-oxia was maintained throughout the test at 50 mmHg. T3 and S3 were calculated for each HCVR3 test as above.
Submaximal exercise.
Participants completed 15 min of cycle exercise at 40% of maximum power output while breathing room air. After a 10-min rest period, the submaximal cycle test was repeated with participants breathing hypoxic gas (FiO2 = 0.15). Cadence was held constant between tests and across days for each individual. Throughout exercise, heart rate, SpO2, V̇i, and PetCO2 were measured continuously and averaged over the final 10 min of each exercise test.
Data analysis.
Lung volumes and metabolic rates and variability in O2 and CO2 sensitivity are known to vary in proportion with body size (22, 37). As such, resting ventilation and indices of chemosenstivity were corrected for body surface area (BSA), as per Dubois and Dubois (16). Paired t-tests were used to evaluate the effect of practice by comparing measures from the first and last testing day for all participants. Repeated measures (RM) ANOVA procedures were used to determine the effect of cycle phase on each variable. Given a significant F-ratio, paired t-tests were used to test planned comparisons among cycle phases. Mean responses across all testing days were calculated for each participant. Mean data from males were compared with data from females in each cycle phase and to mean female data using unpaired t-tests. Mean values from EF1 and EF2 were used to represent the EF phase in analyses. Data were missing for two females from the LF phase. Missing values were replaced with the group mean value to complete RM ANOVA. However, data were excluded case-wise from all post hoc comparisons among LF and EF, ML, and males. Pearson product moments were also calculated to determine correlations among each outcome measure and E1G, PdG, and the E1G:PdG ratio. Correlation coefficients were determined for individual and pooled data. Statistical significance was satisfied at P < 0.05.
Twelve males and 13 females were enrolled in the study. Two males and one female withdrew because of the large time commitment of study participation. In monitoring their menstrual cycles, one female presented with a 40-day cycle and was excluded from the study. Another female failed to detect a LH surge during one of her monitoring cycles and was also excluded. Of the 10 females who completed a testing cycle, menstrual-cycle profiles indicated that no elevation in PdG occurred during the luteal phase for two participants [female subject F03 and F11], and another participant showed no marked increase in E1G throughout the cycle, despite a normal PdG profile (subject F08; see Fig. 1). A fourth participant demonstrated a normal profile for both E1G and PdG (F13), but the ML-phase testing occurred too late to capture the increase in PdG. All analyses were completed on two data sets: n = 6 females with "normal" menstrual cycles and the complete data set for all 10 females. Results from both sets of analyses were very similar, and since these menstrual-cycle abnormalities are common in the general population (11), data from all 10 females were included in the analyses and figures presented. Characteristics of participants can be found in Table 1.
Confirmation of menstrual phase at testing points.
Hormone status on each testing day is shown in Table 2. Comparisons with T1 indicate that as expected, E1G was elevated during LF, EL, and ML compared with the EF phase and that PdG was elevated at EL and ML phases only. There were no differences in either E1G or PdG between EF1 and EF2 phases. Figure 1 further confirms that most females were tested successfully during the EF, LF, and ML phases of their cycles. However, females were also targeted for testing in the EL phase. Although circulating levels of both estrogen and progesterone should be similar between the EL and ML phases, at EL, progesterone has increased recently, whereas in ML, levels of progesterone have been elevated for several days. Females were tested at both time points in an attempt to make the first assessment of the effect of cumulative exposure to progesterone on chemosensitivity and ventilatory control during rest and exercise. However, post hoc assessment indicated that PdG levels were consistently higher at ML rather than EL phases, suggesting that tests in targeting the EL phase had occurred too early. As such, meaningful comparisons between EL and ML phases were not possible, and all data collected during the EL phase were excluded from further analyses.
BBT did not prove to be a reliable method for determining onset of ovulation. Two women provided insufficient BBT data to decipher temperature trends. Three women showed an elevated BBT throughout the second one-half of their cycles, but there was a clear rise that corresponded to the measured LH surge in only one participant.
Resting respiratory function.
A comparison of normoxic resting respiratory function between males and females in EF, LF, and ML phases is shown in Fig. 2. There was a significant effect of cycle phase on V̇i in females, with V̇i elevated in ML above both EF and LF phases. There was no effect of cycle phase on either breathing frequency (FB) or tidal volume (VT). The effect of cycle phase on PetCO2 approached but did not reach statistical significance (P = 0.06). FB was greater in females relative to males but only in the ML phase. Although absolute VT and V̇i were significantly lower in females than males across all testing points (VT: 640 ± 30 vs. 830 ± 26 mL, P = 0.0003; V̇i: 8.40 vs. 10.0 ± 2.0 L/min, P = 0.0004), these differences were nonsignificant when values were corrected for BSA. PetCO2 was reduced significantly in females compared with males in the EF and ML phases but not in the LF phase.
In females, both V̇i and PetCO2 were significantly correlated with PdG but not with E1G or E1G:PdG (r = 0.47 and 0.50, respectively; both P < 0.01). Individual correlation coefficients ranged dramatically, from −0.78 to 0.70 for V̇i and from −0.98 to 0.52 for PetCO2.
BSA-corrected iHVR for males and females is shown in Fig. 3. There was no significant effect of cycle phase and no difference between males and females for iHVR, and iHVR was not significantly correlated with any measure of sex hormones in females.
The threshold and sensitivities associated with three assessments of HCVR are shown in Fig. 4. For HCVR1, there was no effect of cycle phase on CO2 sensitivity, but females were significantly less sensitive to CO2 than males across all phases of the cycle. For HCVR2 and HCVR3, CO2 sensitivity was again unaffected by cycle phase. In these tests, sensitivity was lower in females than males, only during the LF phase and only for HCVR2. Cycle phase had a significant effect on the threshold for HCVR2 only. This threshold was reduced in ML compared with LF but not compared with the EF phase. Thresholds for HCVR2 and HCVR3 were all significantly lower in females compared with males, except for the threshold for HCVR2, measured during the LF phase. In females, there was no correlation between measured hormone and slope or threshold for any HCVR measurement.
Ventilation during cycle exercise, corrected for both BSA and power output, is shown in Fig. 5. There was no effect of cycle phase on normoxic or hypoxic exercise ventilation or on the change in ventilation from normoxia to hypoxia. Interindividual variability in corrected V̇i was much greater in females than males, and although corrected exercise V̇i tended to be higher in females in both normoxia and hypoxia, these values did not reach statistical significance. The percent change from normoxic to hypoxic condition (Δ)V̇i was not different between males and females at any cycle phase. However, the effect of cycle phase on exercise PETCO2 was significant in normoxia (P = 0.02) and nearly so in hypoxia (P = 0.10). In both conditions, PETCO2 was lowest during the ML phase. Exercise PETCO2 were consistently lower in females than males in both normoxia and hypoxia, with significant differences in both the EF and ML phases. In the LF phase, the difference between males and females only approached significance in both normoxia (P = 0.11) and hypoxia (P = 0.10). As with V̇i data, there was no effect of cycle phase and no difference between males and females for ΔPETCO2.
There was no effect of cycle phase on exercise SpO2 in normoxia or hypoxia, nor in ΔSpO2. Neither males nor females desaturated significantly during normoxic exercise, but on average, SpO2 fell to 91 ± 5% (females) and 88 ± 3% (males) during hypoxic exercise. Females desaturated significantly less than males, with SpO2 significantly higher and ΔSpO2 significantly lower during the EF and LF phases. Although large interindividual variability prevented a significant difference in SpO2 between males and females during ML (P = 0.09), the ΔSpO2 was significant (P = 0.03). Ventilation and SpO2 during exercise were not correlated with measured sex hormones in females.
Repeatability of measures.
In males, the interday coefficients of variation (CVs) ranged from 3% to 4% for HCVR thresholds and PetCO2 to 37% for iHVR and 55% ΔV̇i from normoxic to hypoxic exercise (see Table 3). In females, the repeatability of measures from EF1 to EF2 phases was similar: lowest for HCVR thresholds and PetCO2 (2–6%) and highest for sensitivities to O2 and CO2 (15–38%). There was also substantial intra-individual variability in E1G and PdG between EF1 and EF2, with mean CVs of 25% and 43%, respectively. CVs calculated between EF1 to EF2 were lower than those calculated for males for iHVR and T2 but were otherwise similar between males and females. For females, variability across all testing sessions was greater than variability between EF1 and EF2, only for measures of E1G, PdG, and iHVR. All other measures of resting and exercise ventilation and chemosensitivity were similarly variable both among and within menstrual phases.
There is a history of inconsistent results in studies that have sought to characterize the effects of endogenous fluctuations in ovarian hormones on human ventilatory control. Accordingly, the purpose of this study was to determine the magnitude of the ovarian-related changes in both resting and exercise measures of ventilatory chemosensitivity. A strength of our study was the daily assessment of hormonal status combined with multiple methods of quantifying ventilatory chemosensitivity.
Main findings.
The principal findings of this study are four fold. First, there was a significant modulatory effect of cycle phase on resting V̇i and PETCO2. When V̇i was corrected for body size, there were no differences between college-aged men and women. Second, we found that BSA-corrected iHVR was unaffected by menstrual-cycle phase and was not different between males and females at any point. Third, we found that alterations to sex hormones have little or no effect on the sensitivity to CO2. We further observed that the ventilatory recruitment threshold for CO2 was always lower in women, but there were no sex differences for CO2 sensitivity. Lastly, we detected no effect of menstrual-cycle phase on submaximal exercise ventilation and found that the ventilatory response to normoxic and hypoxic exercise was quantitatively similar between males and females. The effects of sex hormones were no more consistent when considered separately from cycle phase.
Effect of menstrual-cycle phase on resting ventilation.
We found a significant effect of cycle phase on V̇i. Specifically, BSA-corrected V̇i was higher during the ML phase relative to EF and LF phases. We also found that absolute V̇i (L/min) was lower in women than men across all time points. However, once corrected for BSA, there were no differences in resting V̇i between males and females. There was a nearly significant effect of cycle phase on PETCO2 (P = 0.06), but the pattern did not parallel changes in V̇i as expected. Instead, PETCO2 was lower in females than males during the EF and ML phases but not during LF. Our findings under resting conditions show that despite between-subject variation in hormonal levels (see below), there is a menstrual-cycle effect on V̇i. Although both V̇i and PETCO2 correlated with PdG as expected, these relationships were far from consistent. These observations extend the findings of some other investigations (6, 38, 51) and serve to emphasize that ventilatory control is indeed hormonally altered. Specifically, our findings show that when considering basal values for ventilation (i.e., eupnea) between males and females, it is necessary to take hormonal status into account. We consider this to be an important finding if we and others are to determine how other ventilatory stimuli (hypoxia, hypercapnia, exercise) interact with naturally occurring hormonal changes (i.e., not pharmacologically induced changes). However, basal metabolic has been shown to decrease at menstruation, fall to its lowest point 1 wk prior to ovulation, and then increase until the beginning of the next menstrual cycle (45). It is possible that naturally occurring alterations in basal metabolism could have influenced our ventilatory measures, and we cannot exclude this possibility.
Resting chemosensitivity.
To characterize comprehensively the effects of cyclical changes in sex hormones on ventilatory control, we evaluated chemosensitivity in several ways. First, we found that the iHVR did not vary across the menstrual-cycle phase or correlate with quantified hormone status nor was it different between males and females. The lack of effect of menstrual-cycle phase is in agreement with Regensteiner et al. (38), who tested female subjects using a similar method to that used in the present study, and comparisons were made at the follicular and luteal phases, which were confirmed by measured changes to hormonal values. Others have also found no detectable difference in hypoxic chemosenstivity at different phases of the menstrual cycle (6, 15), whereas there are reports that the ventilatory response to hypoxia is higher during the luteal compared with the follicular phase (42, 46, 51). The lack of consistency among human studies can be, in part, attributed to different methods of assessing the sensitivity to hypoxia in conjunction with unknown or variable amounts of hormone levels and the inclusion of highly trained and untrained female subjects.
In the present study, we carefully monitored hormone levels in a homogeneous group of young women and report significant elevations in estrogen and progesterone (see Table 2) with no effect on iHVR. The iHVR is a test designed to determine the hypoxic sensitivity of the carotid body. As such, our findings suggest that under isocapnic conditions, peripheral hypoxic chemosensitivity is not altered by cyclical changes in female sex hormones [for review, see (4, 49)]. For example, carotid body neural-output responsiveness to hypoxia is increased with estrogen and progesterone in castrated male cats (21). It is difficult to reconcile the differences between human and animal studies, but it may be related to the measurement of chemosensitivity via measures of spontaneous (and variable) ventilation in humans vs. carotid sinus-nerve activity in anesthetized animals.
In the present study, we carefully controlled the laboratory environment (see methods) to minimize the introduction of external stimuli, which could affect respiration. However, despite using a rigorous approach to measuring chemosensitivity, it is known that iHVR is variable when measured in conscious humans. The CV for iHVR was 31% for all female tests and was 15% between EF1 and EF2 phases, which approximates current and previous reproducibility values for males in our laboratory [CV = 27% (26)] and is lower than other studies that have evaluated iHVR in women [CV = 63% (6)]. We cannot exclude the possibility that despite using a controlled environment and minimizing behavioral influences, the inherent variation in iHVR obscured any potential hormonally related effects.
We also used a modified rebreathing method (17) to determine central and peripheral ventilatory chemoreflex sensitivity. The PETCO2, at which ventilation increases with progressive increases in PETCO2, is considered the recruitment T. The slope of the linear relationship between ventilation and PETCO2 above T is considered an estimate of chemoreflex S. Under both hyperoxic (HCVR2) and hypoxic (HCVR3) conditions, we found that S was unaffected by menstrual-cycle phase, did not correlate with measured hormone levels, and was only lower than male values during the LF for HCVR2. Slatkovska et al. (44) found that S was not different between the luteal and follicular phase, where progesterone (5–58 mmol/L) and 17β-estradiol (105–780 pmol/L) were highly variable among subjects. There was also no significant difference in CO2 sensitivity between pre- and postmenopausal women (34). We interpret our findings, in conjunction with those of others, to mean that normally occurring alterations in sex hormones have little to no effect on the sensitivity to CO2 in either hypoxia or hyperoxia. Our interpretation is also supported by the lack of effect of menstrual-cycle phase for HCVR1 (i.e., Read rebreathe protocol), further emphasizing that ventilatory chemosensitivity to CO2 does not change across the menstrual cycle. We do, however, report that CO2 sensitivity is lower in females than males during hyperoxic conditions.
Significant differences were observed across all cycle phases for HCVR1, but differences only reached significance during LF for HCVR2. Conversely, there was no difference in S between males and females when hypercapnia was combined with hypoxia. Although Slatkovska et al. (44) found no difference in the CO2 recruitment T between follicular and luteal phases, others have found that T is reduced when female sex hormones are elevated in pre- vs. postmenopausal women (34). We found a significant effect of menstrual-cycle phase on T during the hyperoxic trial (HCVR2) only. However, although T was lowest during ML, there was actually no measurable difference between EF and ML, and T did not correlate with measured PdG or E1G, suggesting that the effect of sex hormones on T is minimal. On the other hand, T was consistently lower in females than males, with a significant sex difference in all cases except during LF for HCVR2. The mechanisms by which hormones might alter T are not known, but our finding of a male-female difference in recruitment threshold warrants additional investigation.
Ventilation during exercise.
We found no effect of menstrualcycle phase on V̇i (corrected for BSA and power output) during submaximal exercise in either normoxia or hypoxia (see Fig. 5). The lack of a cycle-phase effect on exercise ventilation is consistent with other work, which shows that submaximal exercise ventilation is not increased at sea-level or simulated high altitude (hypobaric chamber; 4,300 m), despite significant changes to hormonal levels (6). Other reports are in accordance with our finding that ventilation during exercise is unaltered by phase of menstrual cycle (7, 12, 20), whereas others show significant increases in exercise ventilation in the ML phase (15, 42, 52). Specific comparisons among studies are complicated by the use of different levels of exercise intensity and modes (run vs. cycle), as well as limited information about hormonal values. Moreover, in one study that reports an increase in exercise ventilation at submaximal intensities (55–85% V̇O2max) in the ML phase, there was an increase in whole-body V̇O2 (52). As such, the rise in ventilation, which they observed, may have been secondary to the increased V̇O2, rather than hormonally mediated.
We interpret the findings from the present study—where hormonal values were monitored daily in conjunction with the observations of others—to mean that cyclical hormonal changes have no or very modest effects on overall ventilation during submaximal normoxic and hypoxic exercise. The fact that we observed no effect on ventilation speaks to the complexities of exercise ventilatory control in humans. Maintaining the appropriate level of pulmonary ventilation is a complex and highly regulated task. If ventilation is too little, then the systemic oxygen needs are not met. If ventilation is too high, then there is an associated increased mechanical work and oxygen cost of breathing. As such, the magnitude of effect of circulating hormones is likely insufficient to disrupt the balance between oxygen needs and the mechanical work and cost of breathing during exercise. It may be that exercise-induced changes to ventilatory drive (both feed-forward and/or feed-back mechanisms) are dominant and mask any possible hormone-mediated ventilatory effects.
Despite the above, it is necessary to comment that although we did not detect any change to V̇i, there was a lower PetCO2 during exercise in women during the EF and ML phases, which is consistent with an increase in alveolar ventilation relative to metabolism. This is also supported by the consistent but nonsignificant (P = 0.07) trend of higher SpO2 (∼3%) during hypoxic exercise in females. This finding is surprising, given that even in normoxia, exercise-induced arterial hypoxemia appears to occur more frequently in untrained females than their male counterparts (18, 39). Although there seems to be a correlation between the degree of desaturation in normoxia and hypoxia in males (28), no such comparison has been made for females. It remains possible that subtle differences in human ventilatory control are not detectable by measuring total ventilation and that by determining effective alveolar ventilation and variables associated with pulmonary gas exchange, greater insight can be obtained. We emphasize that further studies with direct arterial blood sampling are required to corroborate our pulse oximeter and end-tidal observations.
Menstrual-cycle phase and perspectives.
An important aspect of the present study was the determination of hormonal levels on a daily basis. Most studies consider the menstrual cycle as a series of discrete phases, but this is an oversimplification, and it is more appropriate to consider that some days are intermediate to different phases. The inability to time and categorize menstrual cycles by the EF, LF, or ML phase likely contributes to the difficulty in detecting differences among phases. For example, Fig. 1 shows that testing time points were 1–2 days late for subjects F09 and F13 for testing to occur during ML when PdG was highest. Furthermore, testing occurred 1–2 days too early to observe the increase in E1G for subject F03 during the LF. These observations serve to illustrate the point that controlling for menstrual-cycle phase requires more than simply counting the days since onset of menses. The use of BBT to determine ovulation is not reliable. Cycles should be confirmed to be ovulatory using an ovulation-prediction kit and ideally, circulating hormones assayed at least on the day of testing, if not throughout the entire cycle.
We monitored ovarian steroid hormones in a thorough and systematic fashion. We assayed daily urine in subjects with a known (prescreened) history of menstrual cycles that were both ovulatory and of normal length. Our approach to determining the ovarian steroid profile via daily urine collection was based on four factors. First, daily hormonal measures can be made, because the urine is self-collected and is noninvasive. Second, the samples are stable and are easy to store. This is an important consideration, because the first-morning urine was collected from subjects and immediately frozen. Third, hormonal values represent a pooled value over time rather a single time point. Lastly, the validity of the urinary technique, as representative of the pattern of E1G and PdG excretion, has been reported by others (31), and the secretion of these metabolites in the urine parallels serum concentrations of the parent hormones. As such, our method is justifiable, because it permits daily sampling, is noninvasive, and has been validated.
We assessed ventilatory and exercise measures at specific time points across the menstrual cycle, which have been previously reported to coincide with ventilatory changes. In our study, we report considerable between-subject variation in hormonal levels at predetermined times (see Fig. 1 and Table 2). Within the context of our ventilatory measures, several salient points merit discussion. First, although our subjects were homogenous with respect to aerobic fitness, routine ovulation, and cycle history, the hormonal response was heterogeneous, implying that few women have a normal, cyclical hormonal profile. Second, measures of chemosensitivity are highly variable among and within individuals and both among and within menstrual-cycle phases. This suggests that despite the high variability, the differences that we observed for indices of ventilation and chemosensitivity are physiologically robust. Lastly, we further suggest that it is important to consider the effects of sex hormones on ventilatory control in females, and future studies should make efforts to include females when examining ventilatory control during exercise or at high altitude by properly controlling for cycle phase whenever possible. Although experimentally challenging, this is much preferred to excluding women from such studies.
The present study supports the hypothesis that menstrual-cycle phase has effects on resting ventilation and PETCO2. We found no effect of menstrual-cycle phase or difference between men and women for iHVR or the sensitivity to CO2 in normoxia or hypoxia. We found that sensitivity to chemical stimuli (hypoxia, hypercapnia) was unaffected by menstrual-cycle phase or that any hormone-mediated effect is of insufficient magnitude to exceed the inherent variation in these measures. The ventilatory recruitment threshold for CO2 was always lower in women, which is suggestive of a hormonally related lowering of the ventilatory recruitment threshold. The full physiological relevance remains to be elucidated, but these observations may be relevant to our understanding of sleep-disordered breathing following the onset of menopause (8) and the effects of hormone replacement therapy on ventilatory control (33). We observed no effect of menstrual-cycle phase or male-female differences in the ventilatory response to submaximal exercise in normoxia or hypoxia. We interpret this to mean that feed-forward and the many feed-back influences over-ride any possible modulating effects of naturally occurring changes in sex hormones.
Support for this study was provided by the Natural Sciences and Engineering Research Council (NSERC) of Canada. M. J. MacNutt was supported by a NSERC Canada Graduate Scholarship award. A. W. Sheel was supported by a New Investigator award from the Canadian Institutes of Health Research.
No conflicts of interest, financial or otherwise, are declared by the author(s).
Author contributions: M.J.M., M.J.D.S., and A.W.S. conception and design of research; M.J.M., S.E.T., and J.L.H. performed experiments; M.J.M., S.E.T., and J.L.H. analyzed data; M.J.M., M.J.D.S., S.E.T., J.L.H., and A.W.S. interpreted results of experiments; M.J.M. prepared figures; M.J.M. and A.W.S. drafted manuscript; M.J.M. and A.W.S. edited and revised manuscript; M.J.M., M.J.D.S., S.E.T., J.L.H., and A.W.S. approved final version of manuscript.
We are indebted to our research participants for their patience, commitment, and enthusiastic participation in this study.
- Copyright © 2012 the American Physiological Society


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Wayne Rooney welcomes appointment of Sam Allardyce as England manager
Sam Allardyce's first act as England's new manager was to inform his players that the time has come "to deliver", with this challenge readily accepted by Wayne Rooney.
Page 9
Sam Allardyce's first act as England's new manager was to inform his players that the time has come "to deliver", with this challenge readily accepted by Wayne Rooney.
Swansea City are keen on signing Leicester City's Leonardo Ulloa.
The Newcastle United midfielder is waiting on a firm bid from the La Liga giants.
The diminutive attacker returns to La Liga on a season-long loan.
Crystal Palace and Stoke City are keen on West Bromwich Albion's Saido Berahino.
Paul Pogba's agent Mino Raiola has insisted he is not concerned with reports that the France midfielder could join Manchester United for a world record transfer fee and refused to confirm if Pogba has asked to leave Juventus.
Wayne Rooney has compared José Mourinho to Sir Alex Ferguson, with Manchester United's captain relishing working under the Portuguese as he did when the Scot managed the club.
The mayor of Padova has apologised to Keita Baldé after the Lazio striker was the victim of racist monkey chants during a pre-season friendly on Wednesday.
Wayne Rooney is far from England's biggest problem and there should always be room to remember his achievements, even if they never translated into genuine success at international level.
Dele Alli scored Tottenham Hotspur's late equaliser against West Bromwich Albion yesterday.
Radical changes to the business model ?
Eric Dier could drop back into defence to replace the injured Toby Alderweireld.
Gaetano Berardi is set to feature for Leeds United against Wigan Athletic.
The 3,240 yen ($31) of cash framed on Hideto Fujino's desk is a constant reminder of his greatest humiliation.
Don Hutchison was seemingly not impressed with Simone Zaza's performance for West Ham United against Crystal Palace at the weekend.
The West Ham United defender was controversially sent off in the win over Crystal Palace.
The Tottenham Hotspur player scored while on loan at Schalke at the weekend.
This is how we predict Arsenal will line up for this week's clash with Ludogorets.
Reported Tottenham Hotspur target Isco played well for Real Madrid against Real Betis in La Liga on Saturday evening.
It is not often that Usain Bolt is upstaged but on a balmy night in London the fastest man in the world played second fiddle to Laura Muir, a veterinary science student from the University of Glasgow, and Kendra Harrison, a god-fearing hurdler from Tennessee.
Might peace be declared at Mercedes? Let's sincerely hope not.


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Total distanceClassical Mechanics Level 1
A car accelerates from rest at \( 1.0 \text{ m/s}^2 \) for \( 20.0 \) seconds along a straight road. It then moves at a constant speed for \( 30 \text{ minutes.} \) It then decelerates uniformly to a stop in \( 30.0 \text{ s.} \) Find the total distance covered by the car.
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These fabulous women's Timberland Bethel 8324A Boots in black provide you with a classic shape that will remain unique and stylish for seasons to come. With a combination of suede and leather on the upper material, these boots are diverse enough to wear for both casual and dressy events.
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Doctor insights on:
Can You Inherit Bulimia If Your Mom Had It When She Was Young
Can you inherit bulimia if your mom had it when she was young?
Maybe: Bulimia is a condition included as a subset of eating disorders that can occur with ocd, depression, generalized anxiety disorder, phobic disorders, or poor self image. Some of these conditions are heritable and the offspring may have similar symptoms. It is important to know your family history. ...Read moreSee 1 more doctor answer
Bulimia (Definition)
Bulimia nervosa or "bulimia" is a psychiatric disorder in which a person over eats a lot of food at one time (binging) and then vomits later to purge herself of ...Read more
How do I get over my bulimia? I've had it for years..And my friends are worried! i don't know how to tell my mom so i decided to stop before she finds out.. How do I do it?
Since recovery from: An addiction requires scrupulous honesty - encourage you to tell your mother about your disorder. This way she can be part of your support system rather than one more person that you hide things from. Are you working with a psychiatrist or psychologist? Have you had a complete medical evaluation? If you are going to do this - do it right. ...Read more
Could my doctor tell my mom about my bulimia?
I don't know your: Age. I would hope that your family could be incorporated into your treatment. People with bulimia often need specialized treatment. My guess is that your parents would need to pay for this - or their insurance would be used (if you are a minor). I don't know how that would happen if they were kept totally in the dark. ...Read more
I am a wife and full time working mom with a toddler. I sufferfrom bulimia and addiction to porn. I'm worried about my addictions. How can I overcome them?
Behaviorl addictions: Addictive behaviors are not limited to alcohol and drugs. Overeaters anonymous (www.Oa.Org) and sex addicts anonymous (www.Sexaa.Org) offer lots of support and information helpful for these issues. A therapist who treats behavioral addiction can help too. ...Read moreSee 2 more doctor answers
Can long term bulimia cause liver cancer? My mom has a 90% chance of liver cancer but hates alcohol has never drank or abused any drugs but pukes alot
NO: Liver cancer associated with many other conditions ( ie. Hep C, heavy metal ingestion, etc.) but no relation to bulimia, Liver failure can cause emesis. ...Read more
Is scleraderma hereditary? My mom has it and it was active when she was young, my brother & I don't show symptoms. Could I get it later in life?
Scleroderma: Although we do not think of scleroderma or other autoimmune diseases as hereditary, i.e. clearly passed down from one generation to another, there is a somewhat increased risk of developing auto immune disease in your life time. However, it does not mean that you will develop scleroderma. You should have regular assessments for any unexplained symptom but you should live your life without worrying ...Read more
If my mom was depressed when she was young, am I likely to be depressed as ell?
Not likely: Depression runs in families but doesn't mean u will b--but if u get symptoms seek help right away. ...Read moreSee 1 more doctor answer
My mom has permanent headaches & she gets dizzy from time to time. She Had migraine when she was young but got rid of it. Can it come back?
Headache: I think she needs to see a neurologist To rule out more serious illnesses and have a good exam and maybe a scan of the head ...Read more
What are the symptoms of bulimia for young women?
Food secrecy: Food may be hoarded and eaten in secret -- followed by vomiting so as not to gain weight. It can be an obsessive behavior. The person is generally consumed with weight and body image, but deals with anxiety and other emotional pain through food behaviors. There may be depression as well as cravings for sweets, other carbs, etc which trigger the binges -- followed again by vomiting. ...Read moreSee 1 more doctor answer
I think 16 is too young to drive. Am I right or just a mean mom?
Not mean: On the contrary i suspect you're a loving, concerned mom who cares about your child and recognizes that driving is serious business that involves risks that are out of your and your child's hands. Not every teen is ready to drive at 16, and in general a teen's parent(s) are probably good people to make that determination. ...Read more
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Nebraska Trucking Association
Gas stations would run out of fuel in as little as a few hours. Manufacturers would experience component shortages and manufacturing delays in as little as three hours. Hospitals and assisted care facilities would run out of medical supplies such as syringes within 24 hours. Grocery stores would experience shortages within 24 to 48 hours. And in just a few days, we would be surrounded by uncollected garbage and medical waste.
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OCZ has been busy since we reviewed the Neural Impulse Actuator last summer. Fudzilla has word that the company is developing a second-generation device that will be wireless and feature a built-in accelerometer.
Presumably, the second-gen NIA will be able to sense facial muscle tension and read brain waves like the current model. The accelerometer should supplement those functions by allowing users to move sideways in games by simply tilting their head—at least, that's one use of the new feature Fudzilla mentions. Who knows, maybe you can also use the accelerometer to play awkward and potentially dangerous games of Wii Tennis.
The new-and-improved NIA will supposedly be ready "by the end of the year," and it may show up in August at the Gamescom convention in Cologne, Germany.
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|Radeon Pro specs hint at a full-fat Polaris 11 GPU in MacBook Pros
|AMD announces Radeon Pro drivers with scheduled releases
|We're giving away our Aimpad R5 review unit
|Apple's latest MacBook Pros ditch the F keys
|In the lab: Gigabyte's GeForce GTX 1050 G1 Gaming graphics card
|Google's Jamboard takes the whiteboard into the cloud
|Transcend hops on the 3D NAND bandwagon with the SSD 230
|Apple puts its AirPods in the oven a little longer
|Microsoft helps hardware companies make VR more affordable
|Absolutely. GCN is pretty much GCN, so the math backs this up: R9 290X = 1GHz x 2816 GCN CUs = 2816 CUGHz (pronounced "cougar hertz") RX 480 = 1.27GHz...


text:
Talk about discriptive error messages! what the %$@!#! does that mean!! I'm using pws as my webserver on my win98 machine. the server, where the database is, is windows 2000 server. I'm happily working along, everything is working, just doing a little fine tuning and then CRASH!

Provider error '80004005'

Unspecified error

/incfiles/dbconnect.inc, line 12

Every time i try to open the DB using asp. Strange thing is it seems to work fine till about 10:00am, and even then i can still open the DB with access, but not with asp.

Any clues as to what might cause this? Is this a common occurence that i have not yet encountered? My hunch is that its somthing to do with PWS so i'm now trying to set up a mini development environment on my home computer over terminal services from work... not a good morning.


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From "Africa Express Presents: Maison Des Jeunes" - the new album from the African and Western music collective - out December 9th on Transgressive Records.
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He has been given a large brain by mistake, since for him the spinal cord would suffice.(Albert Einstein)


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Senate torture report: Tackling the CIA's wrongs
Critics who still believe torture is effective and necessary, who ironically include religious conservatives, may want to consider the work of monsters like Dr. Eduard Wirths and Dr. Shiro Ishii. Although the experiments of both serial killer physicians offered beneficial insights to the field of medicine, as well as national defense, only the deranged would support the way in which that information was obtained.
Like the CIA torture programs, any benefits derived could have been gathered in an alternative manner.
The 9/11 terrorist attacks gave some in the CIA an opportunity to indulge their darkest fantasies. Consequently, the CIA needs to take this opportunity as an institution to rebuild and reflect. It needs to eliminate those who seek to do harm rather than good, so it can help secure America, instead of making us less secure.
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Crystal Pool Service
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According to our records, this business is located at 5401 NW 102nd Ave # 145 in Sunrise (in Broward County), Florida 33351, the location GPS coordinates are: 25.8232523 (latitude), -80.3615726 (longitude). Crystal Pool Service is categorized under Special Trade Contractors, Nec (SIC code 1799). Known organization owner is Jeff Kohler. Current estimates show that the unit has a sales volume of $1,488,000 and staff of approximately 12 people. You can contact the company by phone at (954) 748-1306; the following fax number is also provided: (954) 748-5998.
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Rio Olympics might be a mess, but Tokyo 2020 has some cool high-tech plans
Driverless taxis for athletes and holograms for info.
Thu, Jul 07 2016
Clinton takes big step toward easing tensions with Sanders
With new college affordability plan, the presumptive Democratic nominee won praise from rival.
Thu, Jul 07 2016
US urges aerial spraying amid jump in Puerto Rico Zika cases
The U.S. territory is debating whether to fumigate with the insecticide Naled.
Wed, Jul 06 2016


text: Myr Mindservant 6,385pages on this wiki Add New Page Edit History Add New Page Talk0 Myr Mindservant Printings/Rarity: Cost: CMC: 1 Card Type: Artifact Creature — Myr Power/Toughness: 1/1 Oracle Text: , :Shuffle your Library. Flavor Text: It knows what you are planning, and it does not approve. Retrieved from "http://mtg.wikia.com/wiki/Myr_Mindservant?oldid=66827" Categories: Mirrodin Uncommon Cards CMC: 1 Myr Artifact Creature Artifact Creature Colorless


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White Hairy Crab discovered after all my fish vanished!
Discussion in 'New Members' started by Mirage, 2 Jan 2011.
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|My Regal Tang has white spots
|Quarantine Tanks, sick fish, QT corals
|23 Jul 2016