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Home Page Hot Legal Issues Birth Injuries and Birth Defects
Birth Injury & Birth Defect Lawsuits
By Heidi Turner
Birth injuries and birth defects are injuries that an infant is born with, either due to harm caused while in the womb or injuries sustained during birth. Numerous drugs have been associated with different types of birth defects, with varying degrees of severity. In some cases, the birth defects cause permanent injury or disability, in others the defect can be rectified through surgery. All cases, however, cause stress for the family and the infant. Birth defects lawsuits have been filed against the people or organizations whose actions may have resulted in infant defects.
Infants who are born with difficulties in how their organs or body parts are formed or work have birth defects. According to the National Institutes of Health, these defects are broken down into structural defects (part of the body is missing or malformed), and functional or development birth defects (including problems with the nervous system, the brain, or the senses). Some birth defects can be fixed with surgery or other interventions, while other defects are permanent.
Birth Defects
Birth defects can be caused by a range of factors, including genetic problems or chromosome problems. But in some cases, infants are exposed to medications, chemicals or other toxins while in the womb that can affect their development. Meanwhile, injuries sustained during birth may also cause lifelong difficulties.
In cases where negligence, malpractice, or other unethical activity has occurred and that activity has resulted in birth defects, lawsuits can be filed against the people or organizations involved.
A variety of medications have been linked to different birth defects. In some cases, studies have found conflicting evidence regarding the link between medications and birth defects. This is partially because it is unethical for researchers to test medications on pregnant women.
Birth Defects Linked to Medications
As of 2015, the FDA changed how drugs are labeled in relation to pregnancy. Under the new guidelines, drug labels will include three subsections—"Pregnancy," "Lactation," and "Females and Males of Reproductive Potential." Those subsections will include a summary of the risks of using a drug during pregnancy or lactation and information that will help medical professionals make prescribing decisions. This new rule replaces the letter categories, which were previously used to classify medications.
In the past, the FDA classified drugs in five pregnancy categories (this system has since been replaced but is still valid as drugs already on the market are slowly moved to the new classification):
Category B—Animal reproduction studies have not shown a risk and there are no adequate studies in pregnant women;
Category C—Animal reproduction studies show an adverse effect on the fetus and there are no adequate studies in humans; benefits may outweigh the risks;
Category D—There is evidence of human fetal risk based on experience or studies in humans, but benefits may still outweigh the risks; and
Category X—Studies in animals and/or humans have shown evidence of human risk; risks outweigh potential benefits.
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are medications used to treat patients with depression. The medications have been linked to a variety of birth defects including congenital (heart) malformations when women took SSRIs during different stages of pregnancy. Although studies have reached conflicting conclusions regarding the potential link between SSRIs/SNRIs and birth defects, lawsuits have been filed against the makers of some SSRIs/SNRIs.
SSRI/SNRI Birth Defects
Some birth defects reportedly linked to SSRIs/SNRIs include persistent pulmonary hypertension of the newborn (PPHN), a disorder of the lungs in which the arteries are restricted, causing blood pressure in the pulmonary artery to drastically increase. PPHN can cause shock, heart failure, seizures, organ damage, and death.
Included among the SSRI and SNRI drugs potentially linked to birth defects are:
Lyrica (known generically as pregabalin) is a pain medication used to treat nerve pain linked to fibromyalgia, shingles, and diabetes. Studies suggest women who take Lyrica during their first trimester are at an increased risk of having a baby with skeletal or neural tube defects.
Lyrica Birth Defects
Zofran is an anti-nausea medication often prescribed off-label to treat women suffering from severe morning sickness. It has been linked to an increased risk of spontaneous abortion and major birth defects, although some studies have found no such link.
Zofran Birth Defects
Depakote is approved to treat epilepsy and manic episodes of bipolar disorder. Depakote is in FDA pregnancy category D due to the potential for birth defects. In 2015, a lawsuit filed against Abbott Laboratories concerning a girl born with spina bifida after being exposed to Depakote in the womb resulted in an award of $23 million. Depakote has also reportedly been linked to cleft palate, hypoplastic right heart, and hand malformations.
Depakote Birth Defects
Wellbutrin is approved to treat patients with major depressive disorder. The medication has been linked to an increased risk of congenital heart defects when infants are exposed to Wellbutrin during early stages of pregnancy.
Wellbutrin Birth Defects
birth injuries are due to the actions—or inactions—of medical professionals during labor. In cases where medical malpractice has resulted in infant defects or birth injuries, parents may be able to file lawsuits against the medical professionals and/or their employers whose negligence or malpractice may have resulted in the defects. Providing improper or inadequate prenatal care can cause birth defects, while failure to take appropriate action during labor can result in birth injuries.
Medical Malpractice
Birth Injury and Birth Defect Legal HelpIf you or a loved one has suffered similar damages or injuries, please click the link below and your complaint will be sent to a Drug and Medical Device lawyer who may evaluate your claim at no cost or obligation.
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Toxic Chemical Birth Defects
Pregabalin Linked to Increase in Birth Defects
Zofran Birth Defects Lawsuit Information alleging heart defects and kidney malformations in newborns.
SNRI Birth Defects allegedly cause birth defects in the children of mothers who used SNRIs in pregnancy.
Pristiq alleging birth defects and other side effects.
Birth Injury alleging injuries resulting at birth from medical malpractice or negligence.
Cymbalta Alleging Cymbalta causes birth defects including as heart problems and persistant pulmonary hypertension in the newborn (PPHN) as well as severe Withdrawal Symptoms
Lexapro Heart Birth Defect alleging Lexapro caused heart birth defects in the newborn.
Prozac Heart Birth Defects alleging that taking Prozac during pregnancy can cause heart birth defects in the newborn.
Zoloft Heart Birth Defects alleging that pregnant women who took the SSRI Zoloft have an increased risk of delivering a baby with heart defects.
Effexor Heart Defects alleging that women who took Effexor while pregnant face an increased risk of having a baby with heart defects.
Celexa Heart Birth Defects alleging Celexa, when taken during pregnancy, increases the risk a newborn will have heart defects.
Paxil Heart Defects alleging Paxil causes heart defects in newborns.
Symbyax Birth Defects alleging serious heart and lung birth defects Persistant Pulmonary Hypertension in Newborns (PPHN)
SSRI Birth Defects Lawsuit allegedly causing birth defects, including heart defects and PPHN.
Depakote alleging birth defects.
Wellbutrin alleging that treatment with Wellbutrin may cause heart birth defects, worsening depression and/or suicidality.
Why Take Lyrica and Other Anticonvulsant Drugs Associated with Birth Defects?
January 30, 2017Washington, DC: Not all anti-epileptic drugs (AEDs) are made equal. Some AEDs, including Lyrica, are known to be associated with more birth defects than others. So why are they prescribed to pregnant women and/or women who may get pregnant [READ MORE]
Lyrica and Topamax: Same but Different
December 15, 2016Washington, DC: Studies have shown that some anti-epileptic drugs (AEDs) are safer than others during pregnancy. For instance, Lyrica is classified as Category C while Topamax has Category D status. But both AEDs have been associated with birth defects [READ MORE]
Who should be Prescribed Lyrica?
November 16, 2016Osseo, MN:When the FDA approved Lyrica in 2007 to treat fibromyalgia, Pfizer's profits likely skyrocketed as the disease affects about 3 million to 6 million people in the US each year. It took the agency two more years to warn about possible Lyrica birth defects—how many pregnant women suffering from fibromyalgia took the anticonvulsant drug without knowing [READ MORE]
READ MORE [ Drugs/Medical Settlements and Legal News ]
READ MORE [ Personal Injury Settlements and Legal News ]
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Die Hard 2 (1990)
Movie Title:Die Hard 2 (1990)
Director: Renny Harlin
Stars: Bruce Willis, William Atherton, Bonnie Bedelia
Release Date: 4 July 1990 (USA)
Genres: Action, Thriller
Format: MatRoska (Mkv)
File Size: 1.07 GB
Resolution: 1280×542
Runtime:2h 4min
Encoder: MKVTV Team
After the terrifying events in LA, John McClane (Willis) is about to go through it all again. A team of terrorists, led by Col. Stuart (Sadler) is holding the entire airport hostage. The terrorists are planning to rescue a drug lord from justice. In order to do so, they have seized control of all electrical equipment affecting all planes. With no runway lights available, all aircraft have to remain in the air, with fuel running low, McClane will need to be fast.

subset: commoncrawl


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Results 1-4 of 4 for tutor mannārakkāt
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Raleigh, NCUSA
January 9, 2013
I'm Ashley and have fallen in love with climbing! I started climbing at trc last year and have had a great time challenging myself to climb and meet new people! Looking forward to another great year of fun climbs and fun people!
Great! Always have a lot of fun!
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Metra 99-7007 2000 - 2004 MITSUBISHI ECLIPSE Car Radio Installation Kit
2000 - 2004 MITSUBISHI ECLIPSE Radio Installation Kit
Radio Installation Kit for MITSUBISHI ECLIPSE 2000 - 2004
- Metra 99-7007 2000 - 2004 MITSUBISHI ECLIPSE Car Radio Installation Kit
- Radio Installation Kit
- Incl. Instructions/Hardware/Pocket For CD Jewel Cases/Cassettes
- Recessed DIN Opening
- High-Grade ABS Plastic
- This item is New
- 1-Year Manufacturer's Warranty
- 30-Day Half Price Car Audio Warranty
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Return Policy
This item can be returned un-opened within 14-Days for a refund, minus a 20% restocking fee, and minus shipping.
Warranty Information
- This item has a 30-day in-house warranty.
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Zac Efron has no plans for Valentine's Day
'High School Musical' star Zac Efron says he is a 'romantic' at heart but he is going to be alone on this Valentine's Day.
Zac Efron
The Hollywood hunk, who has previously dated actress Vanessa Hudgens, said he has no plans for the most romantic date on the calendar, Showbizspy online reported.
"I am a bit of a romantic. I like writing songs or painting although I haven't got any plans yet for this Valentine's Day," he said. Efron, 24, was recently rumored to be dating actress Lily Collins.


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By ADEYEMI, Bisi
MON, OCTOBER 24 2016-Shareholder activism is a way in which shareholders can influence a company's behavior by exercising their rights as owners (Investopedia). Shareholder activism is not the prerogative of minority shareholders as it can involve institutional investors (mutual funds, pension funds banks, private equity investors, etc)and shareholder associations.
Activism covers a range of activities and includes "voting with one's feet" (divesting), private discussions or public communication with the Board of Directors and Management, press campaigns, whistle blowing to regulators, active participation at general meetings, seeking to replace individual directors or the entire board, etc. Unresolved issues between shareholders and the Board (and Management) have the potential to detract from the operations of the company.
Attitudes to overly vocal shareholders tend to range from ambivalence to irritation. However, it is possible for shareholder activism to be used as an effective tool for ensuring sound corporate governance. Many institutional investors tend to be passive "gate-keepers" and have allowed shareholder associations to take the front seat at general meetings. In the wake of corporate governance scandals that witnessed substantial erosion of investment globally, institutional investors should take more interest in the affairs of the companies in which they have invested.
A common complaint of shareholders is that the AGM is the only opportunity they have to interact with the directors and management and to air their views on the affairs of the company. It is recommended that the Board and Management organize additional avenues to engage shareholders, whilst being mindful of corporate governance considerations on granting preferential treatment to shareholders.
In Nigeria, "shareholder activism" can be said to be a euphemism for disruptive, uninformed, populist "rabble-rousing" at Annual General Meetings and in its extreme form, is perceived as an extortion scheme. However, it can be argued that companies with active and engaged shareholders are more likely to uphold good corporate governance practices and ultimately be more successful in the long term than those that are left to do what they choose. Thus, shareholder actions (not antics) could be potentially powerful in ensuring the enthronement and practice of sound corporate governance.
Shareholder activism is in a sense an obligation imposed upon shareholders of public companies, as the SEC Code of Corporate Governance mandates them to "play a key role in good corporate governance". In particular, institutional shareholders are obliged to "seek to influence positively the standard of corporate governance in the companies in which they invest". Indeed, there is a SEC Code of Conduct for shareholders made pursuant to Section 8(y) of the Investments and Securities Act (ISA) 1999 that seeks to guide the conduct of members of Shareholders' Associations during general meetings of public companies and their relationship with public companies outside the general meetings. The Code is intended to ensure the highest standard of conduct amongst association members and to ensure that shareholders make positive contributions in ensuring that the affairs of public companies are run in an ethical and transparent manner and also in compliance with the Code of Corporate Governance for public companies.
Institutional investors hold significant stake in most of the companies listed on the Nigerian Stock Exchange. They are in a position to positively influence the efficient governance of their investee companies and given their significant stake, ought to have an incentive to take a more active role in monitoring corporate misconduct. To a large extent, they have been content to take a passive approach to their investment or simply sell the shares of underperforming companies. There is need for more activism on the part of institutional investors, as the shareholder associations are too fragmented and usually ineffective in influencing corporate behavior.
ADEYEMI, Bisi is the Managing Director DCSL Corporate Services Limited. Email:firstname.lastname@example.com|www.dcsl.com.ng


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Requests for Katarina
View Single Post
December 18th, 2007, 04:06 PM
The Jenn
Waiting for Baby #2!!
Join Date: Jul 2007
Posts: 16,053
Hi! I was wondering if you could make me a blinkie that is unrelated to mommyhood! I just got designated as the myspace page moderator for my 10 year high school reunion and I'd like a blinkie to put on the page! If you can make it for me, I'd appreciate it!
Colors--dark green and gold (or yellow)
I'd like for the following to be on it:
Oak Ridge Pioneers
Class of '98
You can get creative with how its displayed--scrolling, blinking, whatever.
I appreciate it!!!
March DDC
*New Siggy Coming Soon!*
Jenn, mommy to Emma and Ruby.
The Jenn
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It was decided at the All-India Council for Technical Education (AICTE) general council meeting to grant approval to all the existing 167 engineering colleges in Karnataka.
The colleges would offer about 36,000 seats in the counselling. However, the six new colleges that had obtained the state's permission did not get the AICTE nod.
Officials from the state who had attended the meeting confirmed that all the existing institutions in the state were granted approval by the council.
The council officials added that the number of seats would be similar to that of last year, which would not affect engineering seat aspirants. However, there is no record of exact number of new colleges in Karnataka that have applied for approvals, but about 16 to 20 applications from the south-western region were recieved and most of them failed to meet the criteria.
The council staff are working all through the night to complete the work. We have kept up our promise to publish the seat matrix and list of colleges by 30 June 2010.
|Do you like this story?


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Three different women share valentine messages to the same man on Facebook.
The Botswana man who was identified as, Kasi Flights, on Facebook got lovely valentine messages from three different ladies.
PAY ATTENTION: Get all the latest gossips on NAIJ Gossip App
Flights later apologized to his friends, the ladies and family members, saying the ladies are just his friends and they had his consent to send the messages.
The ladies deleted the posts after it went viral.
Source: Gossip.naija.ng


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Netflix Committed to Bow Download Service This Year24 Feb, 2005 By: Erik Gruenwedel
Online rental pioneer Netflix today reiterated plans to offer movie downloads sometime this year.
Speaking at a technology symposium in Phoenix, CFO Barry McCarthy said the company continues to spend from 1 percent to 2 percent of revenue developing a download format.
McCarthy said the company is interested in combining its download technology with TiVo set-top boxes.
"The way you offer a compelling service is to have broad consumer appeal," McCarthy said. "TiVo may be one of those systems."
Reluctance on the part of the studios to offer content, coupled with an unknown cost of that content, pricing to consumers and other concerns, led McCarthy to concede that the rate of growth for downloads would be a long time coming.
"One of the ways you answer these questions is by putting product on the market," McCarthy said. "It will be something small, and will begin the process of learning."


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after playing the beta and having fun with it, Im in!
Man, the only thing I see missing is VESA mounts, it's a nice looking iMac clone for sure.
I wait about a month then install it.
While there may not be any day one issues, I'd rather not deal with them. My time is becoming more and more...
I didn't see it either. :(
To use a car phrase, "There's no replacement for displacement." (in reference to engine size)
It will help, but its not going to be any kind of...
I like the vertical mount that some of the Asus boards use.
You're right tho, better than none.
M.2 on the bottom? I dunno how I feel about that, its something you don't always need access to, but when you do you'd have to take the...
I would just try and see, but that 1.1 pcie kinda scares me.
I'm not convinced this would be better than my Zoom H1, it functions as a USB mic very well, and it's $70 cheaper.
And I bet its a lot more expensive than this will be too.
OO! Dual lan is nice for such a small box, that would allow for pfSense and also plex with a 2.5 inch 2 TB notebook drive.
Hmm, something to go on, at least with exact model numbers I can search around.
I loved the Bushmaster gun in FC3, sneaking around a base and taking everyone out with that gun plus melee, I lost many many hours to just mucking...
So, after reading some of the comments in this thread about the new EK "GT Clones" I was wondering if Nidec ever did a PWM GT? If so what's the...
I have a notebook with room for just one drive, I'd love a cheaper 1 TB SSD to go in there.
This is a more common situation than people realize. :)
CAM_Client.exe is for the new NZXT CAM monitoring software, also controls the lights in the newer closed loop coolers from them.
If you're gaming and general desktop use, you'll most likely get no extra performace from a 2p motherboard.
They also cost a ton more than a more...
Installed, played some Mass Effect 3 multiplayer and started a Beyond Earth game. No issues so far.
Ugh, facebook? I'll pass.
It's a bit easier to see on the 140, but it looks like its just the edge of the blade that's flared out a tad.
Any word on pricing?
As someone who games at 5760x1080 in a few games, I'll just look to the 4k numbers and approximate it from there.
That's one sexy block! I'm tempted to WC a 980 once there's some unlocked bioses for more power.
Or they use them in tandem for better 3D gaming. Higer FPS or more AA, etc.
Once you've done the install and hooked the old drives back up be sure to set that SSD as the primary boot drive in BIOS.
Yeah, you'll be ok doing that, but it would be best to unplug the extra drives just to be safe, I've never (ahem) formatted the wrong disk.
Separate names with a comma.


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Magnolia Plumbing, Heating & Cooling Proudly Serves the Plumbing and HVAC Needs of Bethesda, MD.
Any plumbing system encounters the occasional issue, from a clog to a small leak to a burst pipe. No matter what type of plumbing problems you are dealing with in your home in the Bethesda, MD area, the people at Magnolia Plumbing, Heating & Cooling can help. In fact, we offer a number of home services, including heating and air conditioning repair, installation, maintenance, and replacement. Trust the experts on our team the next time you need a plumbing job completed thoroughly and quickly, or if your home comfort is in jeopardy.
We know you'll choose us for future services once you see the quality of work that we do. Call us today!
Do You Require Professional Plumbing Services?
If you have a major plumbing issue, you don't have much time to wait. The professional plumbers on our team are here 24/7 to make emergency plumbing repairs, or you can call us when you'd like to make an appointment for future services. A member of our team can come to your home at your convenience to repair any plumbing issue, or we can install a new plumbing fixture, replace an aging one, or perform the services that keep your plumbing system maintained.
We Service and Install Garbage Disposals
If you are missing this vital feature from your kitchen sink, you should call us for installation as soon as possible. Garbage disposals help to protect your plumbing system, and they really improve your experience preparing meals or cleaning up in the kitchen. We also service garbage disposals that have broken down.
We Service and Install Water Softeners
While hard water affects the majority of plumbing systems in the U.S., it doesn't have to be a problem for yours. When you call the experts at Magnolia Plumbing, Heating & Cooling, we can assess your water supply and make sure that the water softener you choose is the right size for your plumbing system.
Does Your Drain or Sewer Need Professional Attention?
If your drain and sewer system isn't running smoothly, it's probably not something you want to deal with on your own. Thankfully, the plumbers on our team can handle it so that you don't have to manage any inconvenience due to clogging, leaks, or foul odors. Call one of our plumbers for drain and sewer services in the Bethesda, MD area and we will make it out to your home as soon as we can.
We Offer Septic Tank Services
Would you want to try to handle a septic tank issue on your own? Most homeowners don't have the right level of experience for this type of job, nor is it the ideal task for a do–it–yourselfer to take on in the first place. If you suspect any issue at all with your septic tank, or if you want to schedule a routine maintenance visit, get in touch with us today.
Are You Looking For Water Heater Services?
If you need a new water heater, you should let professionals handle the installation process. This will ensure that everything is secure and efficient and that the unit is the proper size for your home. However, we will ask for your input every step of the way, address your concerns, and discuss any potential issues because we want you to be completely satisfied with the work we do. We can also return for any repairs or maintenance you may need (whether or not we installed the unit).
We Service and Install Tankless Water Heaters
A tankless water heater is the ideal choice for homeowners with very little space for a large storage tank or those who want to save more money over the year. Although it is much smaller than a conventional tank, a tankless water heater is not any easier to repair or install. Instead, give us a call so we can do it right the first time.
We Provide Comprehensive Heating System Services
Our heating services have helped several homeowners around the Bethesda, MD area to stay warm and cozy on those coldest of winter nights. If you are looking for a new heater, check out our selection and allow our professionals to complete the installation. If your heating system struggles to operate, you can count on us to get there quickly to make repairs. Or, schedule regular maintenance with our team so that the system runs into fewer problems over time. Just give us a call today!
We Service and Install Gas and Electric Furnaces
The majority of homes in this country rely on a furnace for heating. If you are one of these homeowners, call us for any services the system requires through the years. Or call us for new installation, even if you don't have a gas line in your home. We have gas and electric furnaces for installation or replacement; call us today!
Do You Require Expert AC Services?
Keep your cool all summer long with our expert AC services. We install high–efficiency AC equipment and we can also provide comprehensive services to keep your unit going. This means that you can get an air conditioning maintenance visit and then call us if the system should require any repair. From the initial installation to the next replacement system we install, your AC is in good hands with our skilled technicians.
We Offer Comprehensive Indoor Air Quality Solutions
If you notice coughing and sneezing from your family members, it's a good time to consider talking to one of our experts about the indoor air quality solutions we can offer for your home. We can make the air in your home a little cleaner by installing a whole–home air purification system to get rid of the contaminants in your air or cleaning out your air ducts. We also offer carbon monoxide testing, humidifier and dehumidifier installation and service, duct sealing and testing, and much more.
We Service and Install Humidifier and Dehumidifier Systems
Humidity levels have an impact on comfort. When it is too humid outside (meaning that there is a lot of moisture in the air), people often feel hot and "sticky" since sweat has trouble evaporating from the skin. When the air is too dry, you're likely to have dry skin and potential sinus issues. A whole–home dehumidifier or humidifier could be just what you need to solve the problem.
We Provide Expert Air Purification Services
There could be a variety of contaminants lurking in your air, including dust, pollen, bacteria, viruses, and other unsafe particles and microorganisms. You deserve to breathe in clean air each and every day, and we would love to help you make that happen. Call and ask about out air purification services today.


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Embedding Videos from YouTube
The process of taking the embed code from a video sharing service such as YouTube or any other service that provides the code and then placing that in an Article or on a Page for display on the site.
VNN Playbook - Embedding Videos from YouTube
Step 1: Open the article you would like to embed a video to.
Step 2: Navigate to YouTube where your video is located.
Step 3: Under the video, click Share
Step 4: Highlight the text that is in the Share box
Step 4: Right click on the Share box to copy the text
Step 5: Navigate back to your website and in the content box right click and select paste
Your video will then load and appear in your content area
Have more questions? Submit a request


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Barbour Tarn Fairisle GlovesIDLGL0063BL15
Blue - LGL0063BL15
ABOUT THE Barbour Tarn Fairisle Gloves
These full-finger gloves are knitted in pure lambswool with a traditional Fair Isle design and a seam-free construction that makes them superbly comfortable. Finished with an embossed leather badge. Matching hat and scarf available.
- 100% lambswool
- Embossed leather badge
- Hand-wash or dry-clean only


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Aesthetic Disinterestedness (Routledge Studies in Contemporary Philosophy)
- Art, Experience, and the Self
(Bog, hardback)
The concept of disinterestedness is often conceived of as an antiquated or even ideological paradigm. In spite of this, I claim that one cannot fully reject it if one wishes to understand the nature of art. Therefore, I defend a new and sophisticated account of disinterestedness, ther... Læs mere eby also supporting an aesthetic conception of art. I specifically claim that an artwork asks a person to adopt a disinterested attitude towards what it shows, and that the effect of such an adoption is that it makes the person lose the sense of herself, while enabling her to gain a sense of the other. Due to an artwork's wealth, multiperspectivity, and dialecticity, the engagement with it cannot culminate in the construction of world-views, but must initiate a process of self-critical thinking, which is a precondition of real self-determination. Ultimately, then, I explicate the experience of art as a dynamic and dialectic process of losing the sense of oneself, while gaining a sense of the other, and of achieving selfhood.Overall, this book is also an effort to rethink Kant's approach towards art and the aesthetic, in light of more recent developments in philosophy-specifically in hermeneutics, critical theory, analytic philosophy, and to a lesser degree in post-structuralism-and in light of more recent developments within the arts themselves-specifically in performance art and film. Læs mindre
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Project Noah is a tool to explore and document wildlife and a platform to harness the power of citizen scientists everywhere.
Epargyreus clarus
Green/yellow bodied caterpillar with a large reddish-brown head and yellow eyespots.
Temperate forest. Rockwood Park, Virginia.
Lat: 37.45, Long: -77.58
Spotted on Sep 6, 2015 Submitted on Jan 9, 2017


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VideoHive Young Woman Watching An Interesting Film On TV 4644369
Stock Footage \ People
Watching \ Interesting \ Beautiful \ Interest \ Closeup \ Melodrama \ Sadness
Stock Footage - Young Woman Watching An Interesting Film On TV 4644369 by Grey_Coast_Media @ VideoHive
Stock Footage \ People
Young woman is watching an interesting film on tv. Close up shot with beautiful light.
Alpha Channel: No; Looped Video: No; Frame Rate: 29.97; Resolution: 1920x1080; Video Encoding: Photo JPEG; File Size: 224mb; Total Clip(s) Length: 0:26.
Service and Massage at Beauty; Family Together Outdoor 1; Family Together Outdoor 2; Using Tablet PC; Driving a Car out City; People with Cell and Touch Pad; Portrait of Happy Boy and Children Playing.
Keywords: close up, closeup, eyes, film, girl, interest, interesting, look, melodrama, movie, sadness, tear, watch, watching, woman.


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Dangal earned 14.33 crores on third Sunday, which takes its total earnings to 345.30 crores in the domestic market, which is more than 340.8 crores lifetime business of PK. In the domestic market, Dangal has dethroned PK from its first spot. It looks like Aamir's this wrestling drama is here to break more records.
Aamir Khan Starrer Dangal has been breaking all the records at the box office window. The movie currently holds second place in the highest grossing Bollywood movie worldwide list just behind Aamir's previous film PK (741 crores). As of now, PK was a blockbuster movie that had grossed 741 crores worldwide.
Dangal released on 23rd December 2016 and has been doing wonders at the box office since then. The film earned 192 crores in the first week and 111 crores in the second week in India. This means that after 17 days, the movie has earned 483.42 crores (Gross) in the Indian market, which is also equal to 345.30 crores (Nett). The movie has also earned 180.5 crores in the overseas market, making its grand total at 663.92 crores.
Aamir Khan is known for setting new benchmarks whenever his new films release. Ghajini was the first Bollywood movie to earn 100 crores in 2008. Then superstar comes with another blockbuster 3 Idiots, which was the first movie to enter 200 crore club. In 2014, PK set another benchmark by doing lifetime business of 300 crores. Now, we hope that Dangal sets new benchmark and enter in 400 crores club.
Dangal is a Bollywood biographical movie based on the life of Mahavir Singh Phogat. The movie is directed by Nitesh Tiwari and features Aamir Khan in the title roles of Mahavir Singh Phogat. Sakshi Tanwar, Fatima Sana Shaikh, Zaira Wasim, Sanya Malhotra and Suhani Bhatnagar play important parts in the movie.
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The time has come to start working those summer plans into our schedules! It's hard to believe now, but green grass and budding trees are just around the corner.
Movie Review — 'Selma' Captivates Just in Time for Martin Luther King Jr. Day
To this date there hasn't been a distinct "go-to" or Oscar level movie depicting Martin Luther King Jr. as a memorable protagonist. Now there is. With the help of big names like Oprah Winfrey and Brad Pitt along with relative new comers like Ava DuVernay and David Oyelowo, Selma is to the Civil Rights Movement what Saving Private Ryan was to D-Day.
Petition to Pardon the 38 Hanged in Mankato
It may have been more than 150 years since the largest mass execution in US history took place in Mankato, but that doesn't appear to be stopping Jack Consadine (a Mankato City Council member). Jack is pushing a petition to pardon the 38 executed Dakota men (plus two others who were hanged later).


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Hi guys – thanks for joining me. I'm just in my backyard for a change having a coffee and just thought while I'm here enjoying some sunshine I'll just have a quick mention about getting feedback on some of the videos.
Everybody likes positive feedback, it's always nice to hear that people are enjoying the videos and finding them useful. So that's always good, keep it coming.
If you've got suggestions for other videos, yeah sure, give me suggestions and if I feel like I've got something to say or I can help with it, I'll try to get around to it and do a video on it.
Finally, just on the subject of negative feedback, with YouTube likes and dislikes, I have no problem with anybody putting a dislike on a video – that's fine – I'm a big boy and don't mind, it at least tells me that someone doesn't like something. But it would be even more useful that if you can take the time to dislike or like it, take 30 seconds and just give me a hint as to why, because it could be that you might not like the topic, you might disagree with something I'm saying in my explanation, in the past some people didn't like the sound of my voice and thought I was boring when I was talking, which is all useful stuff to know. You might think the video is too long or too short, things like that.
All feedback is good, I'll take a look at it and value everything. Good feedback is nice, it's always nice to hear that people are enjoying the videos, but negative feedback is useful too, but I'm asking that if you've got something that you don't like about them, if you've got time then just let me know. Because if you let me know what you don't like I may be able to do something about it and if I can't do something about it, at least I'll be able to tell you and you'll know not to expect it in future videos.
That's really all, thanks to the guys who are saying anything, it's always nice to have conversations, and that's the idea of the videos, just to have a conversation. I think if you are going to take a few minutes to watch a video, if there is stuff you like or don't like, feel free to say. But especially with the dislikes, by all means dislike away if you don't like it but if you can just give me a hint why, even if it's just a sentence (rather than just YOU SUCK! maybe) but if you can give me a bit of a clue that would be good, and I'll see what I can do to improve things in future.
So have a good afternoon, I'm going to sit in the sun and watch Harry run around the backyard for a little bit, have a good day and I'll see you out there. Cheers.


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Patricia Emery
Listed by Parkway Realty Associates Of Lyndonville
Well built and easy to maintain building. The tenants have been in place for sometime but there are always requests from others who want to live here.Downstairs is currently unoccupied but offers many options as commercial space of convert to living space. All income and expenses available. Seller is licensed real estate broker.
Date Showings Begin:
Delayed Showing: Unknown


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Home |
Email |
"The Pear"
b&w photograph
Welcome to my photography and art work page. I
have just started to scan my
photographs. So please come back occasionally and check for new photos.
Until then, please be patient with me. Thanks...
Passion4Art.com : Your source for exquisite art. A place that artists call home!
All Photographs and ArtworkĀ Copyright E. Savino 1996-2000
Please contact me if you are interested in using the images or purchasing a copy.
Page Born: Feb. 29, 2000
Last Update: 2/29/00


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College: United States Military Academy at West Point
Career Goal: Orthopedic Surgeon
Year: College Freshman
Expected Major: Kinesiology
About Me: Being trapped in a house with no electricity and constant phone calls from my mother who was trapped in the garage could break most people. But not me. I was raised in Jackson, MS and I am a survivor of the horrendous Hurricane Katrina. Having such a traumatic event that I survived gave me the ability to always has a optimistic view on life. If I could make it out of there, I knew I could make it anywhere. As a result of the hurricane my family and I lost our home. However, we did not give up on one another. I took a leadership role as a mature nine year old, straight A student, and a big brother.
Soon a blessing disguised as a phone call brought my family and I to San Francisco's Bayview Hunters Point community. Here in this community I have capitalized on the importance of family and resources to create many great opportunities for myself. All I needed was perseverance to obtain and keep these resources. With these opportunities I plan to go to medical school and become an orthopedic surgeon.
Fall 2016 College Update: Summer was absolutely incredible. I spent it traveling and enjoying the simple things like lunch and movies with my loved ones. Then, I came back to West Point for basic training and soared through the training; however, the six weeks dragged on longer than I expected. I am excited for the ability to show West Point my true potential and OWN THESE CLASSES. I am also excited to travel the country through many clubs.
Interests and Accomplishments: Scout Masters Club, Investment Club, basketball, fraternity


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FactChecking the Iowa Senate Race
Longtime Iowa Sen. Tom Harkin is retiring, and Democratic Rep. Bruce Braley and Republican Iowa state Sen. Joni Ernst are each hoping to be the one to replace him.
A Project of The Annenberg Public Policy Center
Longtime Iowa Sen. Tom Harkin is retiring, and Democratic Rep. Bruce Braley and Republican Iowa state Sen. Joni Ernst are each hoping to be the one to replace him.
The Michigan Senate race pits Democratic Rep. Gary Peters against Republican Terri Lynn Land, a former Michigan secretary of state, to replace the retiring Sen. Carl Levin.
It ain't over till it's over. Democratic Sen. Mary Landrieu and her Republican challenger, Rep. Bill Cassidy, are now headed to a Dec. 6 runoff in Louisiana.
Sen. Mark Begich has portrayed his Republican opponent, Dan Sullivan, as soft on sex offenders and tough on women's rights. Sullivan has accused the Democrat of hurting taxpayers and ignoring veterans. Both candidates and their allies have twisted the facts.
The North Carolina Senate race pits incumbent Democratic Sen. Kay Hagan against Republican challenger Thom Tillis. While the two campaigns have aggressively attacked each another, they've had a lot of help from outside supporters as well.
Colorado's Senate race pits Democratic freshman Sen. Mark Udall against Republican Rep. Cory Gardner, who is in his second term in the House.
Kentucky voters have a stark choice between Republican incumbent Mitch McConnell and Democratic challenger Alison Lundergan Grimes. Their fierce battle has included falsehoods on jobs, coal and health care.
The Arkansas Senate race between Democratic Sen. Mark Pryor and Republican Rep. Tom Cotton began for us in June 2013 — just six months into the new Congress — with an article that carried the headline "It's Groundhog Day for Fact-Checkers." It hasn't gotten much better for fact-checkers since then.
Q: Did President Donald Trump shut down a service dog training program for veterans?
A: No. Walter Reed National Military Medical Center ended its contract with the program and told us that the president was not a factor.


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I found The Duggar Family Recipe of Laundry Soap through Pinterest. Immediately I began searching for the products to make it. I couldn't find them at the local small grocery store or the local chain supermarket. Instead I found them at my local Whole Foods store. Occasionally I would find one or two of the items, but the local Whole Food store had all three. And right next to each other. I actually hugged the attendant who helped me to the aisle because I was so happy. What were the three ingredients I was so eager to find? Borax, Arm & Hammer Super Washing Soda, and a Fels-Naptha bar.
For your quick viewing pleasure, here is the recipe from the Duggar's website:
4 Cups - hot tap water
1 Fels-Naptha soap bar
1 Cup - Arm & Hammer Super Washing Soda*
|Step 1.
|Step 2.
And here are the directions to make your own laundry detergent:
Step 1. Grate bar of soap and add to saucepan with water. Stir continually over medium-low heat until soap dissolves and is melted.
Step 2. Fill a 5 gallon bucket half full of hot tap water. Add melted soap, washing soda and Borax. Stir well until all powder is dissolved. Fill bucket to top with more hot water. Stir, cover and let sit overnight to thicken.
Step 3. Stir and fill a used, clean, laundry soap dispenser half full with soap and then fill rest of way with water. Shake before each use. (will gel)
As far as to how well it works? I think it works just as good as any other detergent we've used. It gets out stains-and get things clean. And best of all-we haven't had to buy detergent in a long, long time. It's great. If you get a chance, I urge you to make your own stash. Or you can buy ours- in stores Fall 2012. Only kidding- but check out this swanky picture!
Happy Mixing


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Discussion in 'Introduce Yourself' started by somu_200, Dec 1, 2011.
Hi can we have meet in around hyderabad ?
Hi Somu. There is a thread already existing for Meet at Hyderabad. Please check the following link
You might also be intrested in the following meet
Please send me a PM with your contact details. Will get in touch with you soon.
Separate names with a comma.


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Bio & Incident Details
Age: 31
Tour: 8 years
Badge # Not available
Cause: Gunfire (Accidental)
· Leave a Reflection
· Add to My Heroes
· Update this memorial
Sergeant Donald Gregory was accidentally shot and killed when a shotgun being held by another officer accidentally discharged when it was knocked against a wall.
He and the other officer had responded to a home to investigate a disturbance and aggravated assault involving a firearm. One of the first responding officers located the suspect attempting to assemble a firearm in the basement of the home. As the officer ordered the man to turn around, the officer's shotgun slammed into the wall, causing it to discharge just as Sergeant Gregory came down the stairs to assist. The blast struck Sergeant Gregory in the head, killing him.
The suspect in the original case the officers were investigating was taken into custody on the original aggravated assault charge.
Sergeant Gregory had served with the Missoula Police Department for eight years. He was survived by his wife, daughter, father, and eight siblings.


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Have you ever seen anything like it?
One of the worst first half performances in memory. Newcastle were very impressive, well drilled, pressurising perfectly, timing their confrontations and ganging up on our players relentlessly. We couldn't keep the ball. They could, spraying it around and running us ragged. They scored just before half-time and rarely has a goal been so well deserved.
Steve Sidwell went off after 34 minutes. It could have been an injury or a tactical switch. He and Murphy rarely look the part together and the team simply wasn't functioning. But Jol's shuffle was terrible: Bryan Ruiz, a fine player but one who does not thrive in busy areas, was placed in the middle of the pitch with Murphy. If a manager's job is to put his players in a position from where they can make the greatest contribution, Jol could not have got this more wrong. Sure enough – and who could have seen this happening? – Ruiz was caught in possession by two Newcastle midfielders, the ball broke to Danny Guthrie and he smashed home from distance.
Ruiz was subbed at half-time, a shame because he had been sold down the river with Jol's change.
However, good news was on the way. The team was obviously missing Dickson Etuhu (again) but with him not in the squad the obvious move was to introduce Chris Baird, a player who hasn't featured much but who has the happy knack of playing well and making those around him better. All of a sudden Murphy looked like Murphy, knowing that he had a team player and capable side-kick in the engine room.
Instantly and perhaps fortunately we were back in the match, a long ball over the top setting Johnson free. He got into a contact situation and fell over, but it didn't feel like a penalty (and if it was a penalty, why did nobody receive a punitive card?). However, after some consideration Lee Mason pointed at the spot. Danny Murphy did the rest and we had what felt like a horribly undeserved equaliser.
Then the game went mad. Clint Dempsey scored another one of those goals that are easy but only if you've put yourself in the right place to make it easy, in this case following in after a great surge from Johnson and a nice bit of play by Zamora. Krul saved but Dempsey used some part of his leg to bundle the ball home.
Then another, Dempsey free again after more good forward combination work, and a fine low finish past Krul. Goodness.
At 3-1 Newcastle had to attack and the game opened right up. AJ and Zamora were having great fun now, and all the momentum was with Fulham. AJ won a second penalty, again slightly fortunate perhaps in that he seemed to have lost control of the ball, but against that he might have been fouled at the start of his run. Dempsey was on a hat-trick, Murphy had already scored a penalty, but this one was taken by Bobby Zamora. Who knows why, but in any case, up he stepped and in it went.
Hatem Ben Arfa turned Riise inside out and buried a shot at Stockdale's near post to make it 4-2, then Zamora (?) sent Dempsey racing clear again, and again he drove past Krul on the run, a second January hat-trick for the man who scores with his left, his right, and makes Drogba look shite (and indeed, at this point Dempsey may be the better player).
So what happened?
First, the penalty. We had been so bad that we needed something to go our way to get back into the match. The penalty was perfect in that sense.
But it was only possible because AJ was on the field. We were so static and hopeless without him that we could've played all day and got nowhere. Sometimes AJ's running can look pointless and easy to handle, but today felt like a game where he could contribute. He did that, as fine a performance as he's given in a Fulham shirt.
Of course the goals changed the game, and with each one that went in Newcastle seemed to get more and more open. This played into our hands and we murdered them on the break. This Fulham team seems to thrive with space, whether it's against 10 men (Blackburn excepted) or when games open up, suddenly our attacking players come alive and show what they can do. When space is hard to find we look clueless, but can be devastating when we get time and places to run into.
I was quite optimistic that Newcastle would tire. They defended so well as a team in the first half, and teams generally can't keep that sort of thing up for ninety minutes (witness Real Madrid's attempts to harry Barcelona lately: always goes well for half an hour then reverts to normal). As they tired we got better.
The return to four-four-two. This felt a bit like player power (echoes of QPR when we went 4-4-2 with AJ and Zamora and scored six), but whatever happened, the team looked far more cohesive in its more familiar setup.
So yes, weird, wonderful, 5-2. This one'll take a bit of digesting, but what fun (in the end).


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"Thank you"
About: Warwick Hospital Warwick Hospital Warwick CV34 5BW
Posted via NHS Choices
Having been extremely critical of (and victim of) poor cleaning at the hospital I am delighted to say thank you for the thoroughly professional and courteous treatment my wife and I received today when we had to use the services of the A & E department.
No-one could do anything about the long wait but the standard of treatment and the level of concern and involvement on the part of the doctor and nurses in A & E was heart-warming.
Thank you.
Response from Warwick Hospital 2 years ago
Thank you for sharing these comments, I will pass them on to the team involved with your care.
- {{helpful}} {{helpful == 1 ? "person thinks" : "people think"}} this response is helpful
- Was this response helpful? Yes | No
Thank you for your feedback.
See more responses from Warwick Hospital


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The month of April, went by in a Jiffy.
I started this blog taking the #AtoZChallenge, with the theme 'Brands that people identify with'. The challenge gave me the much needed push to start my 2nd blog after Scribble and Scrawl. I thoroughly enjoyed the mental acrobatics involved, and in the process I have zeroed in on the niche for this blog.
Why I picked Brand Stories
Whether we realize or not, brands are an integral part of our lifestyle and they do impact us.
Much like how you relate to some people better than the others, you relate to some brands in a positive manner because they strike an emotional chord with you in one of the following ways.
- The brands echo the values that you appreciate and care for.
- You have some good memories associated with the brands.
- The brands represent all that you aspire for.


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tammy lynn hull nov 4 1996 kingston tn
by william helms
(camden tn )
my sisters were coming home from getting my nieces birthday cake. when they came across the bridge the car in front of them was hit head on by a drunk driver, before my little sister could react the drunk driver hit them head on. i lost my older sister that day. my little sister was hurt very bad she was in a coma for a month. she fought everyday to survive . my sister Tammy left behind 4 beautiful daughters that will never know how truly wonderful their mom was. Everyday i miss Tammy it will be 19 yrs in Nov. i wonder everyday why she was taken from us so sudden. The drunk driver that killed her didn't even spend a night in jail. there is no justice in that we lost our sister,daughter, and mother and he walks free
As she walks among the angels we walk around missing her. She was an angel on earth and now she is our guardian angel. rest in peace my beautiful sister you are loved and missed.
Join in and write your own page! It's easy to do. How? Simply click here to return to The Drunk Driving Victim Memorial.


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Discrete fetal androgen excess during early gestation in rhesus monkeys (Macaca mulatta) promotes endocrine antecedents of adult polycystic ovary syndrome (PCOS)-like traits in female offspring. Because developmental changes promoting such PCOS-like metabolic dysfunction remain unclear, the present study examined time-mated, gravid rhesus monkeys with female fetuses, of which nine gravid females received 15 mg of testosterone propionate (TP) subcutaneously daily from 40 to 80 days (first to second trimesters) of gestation [term, mean (range): 165 (155–175) days], whereas an additional six such females received oil vehicle injections over the same time interval. During gestation, ultrasonography quantified fetal growth measures and was used as an adjunct for fetal blood collections. At term, all fetuses were delivered by cesarean section for postnatal studies. Blood samples were collected from dams and infants for glucose, insulin, and total free fatty acid (FFA) determinations. TP injections transiently accelerated maternal weight gain in dams, very modestly increased head diameter of prenatally androgenized (PA) fetuses, and modestly increased weight gain in infancy compared with concurrent controls. Mild to moderate glucose intolerance, with increased area-under-the-curve circulating insulin values, occurred in TP-injected dams during an intravenous glucose tolerance test in the early second trimester. Moreover, reduced circulating FFA levels occurred in PA fetuses during a third trimester intravenous glucagon-tolbutamide challenge (140 days gestation), whereas excessive insulin sensitivity and increased insulin secretion relative to insulin sensitivity occurred in PA infants during an intravenous glucose-tolbutamide test at ∼1.5 mo postnatal age. Data from these studies suggest that experimentally induced fetal androgen excess may result in transient hyperglycemic episodes in the intrauterine environment that are sufficient to induce relative increases in pancreatic function in PA infants, suggesting in this nonhuman primate model that differential programming of insulin action and secretion may precede adult metabolic dysfunction.
- fetal programming
- polycystic ovary syndrome
- hyperglycemic pregnancy
- metabolic syndrome
reproductive and metabolic traits reminiscent of polycystic ovary syndrome (PCOS) are prevalent in a wide variety of female mammals exposed to testosterone excess during gestation (5, 28). Reproductive PCOS-like traits found in prenatally androgenized (PA) nonhuman females include combinations of hyperandrogenism, intermittent or absent ovulatory cycles, and polycystic ovaries, traits that comprise the diagnostic criteria required for PCOS in women (4). Metabolic PCOS-like traits in animal models of fetal androgen excess, moreover, are diverse and can include hyperinsulinemia, insulin resistance, pancreatic β-cell defects, increased incidence of type 2 diabetes, enhanced adiposity, and hyperlipidemia [monkeys (1), sheep (58), and rats (25)]. Such heterogeneity of PCOS-like trait expression in PA females resembles that found in women with PCOS (4, 5), providing a novel perspective into potential developmental origins of PCOS, particularly with regard to metabolic phenotype (33).
Experimentally induced PCOS-like traits in PA monkeys and sheep allow investigation of fetal origins (3, 32), providing insight into how altered developmental trajectories and mechanistic derangements can precede adult PCOS-like traits in these animal models. Understanding prepubertal expression of PCOS-like traits is important, since daughters of women with PCOS manifest PCOS-like antecedents, such as ovarian hormone hypersecretion, as early as 2 mo of age (63) and increased ovarian volume and hyperinsulinemia before or during pubertal progression (24, 45, 64). In this regard, endocrine and ovarian antecedents of adult PCOS-like traits exist in PA female offspring in both monkeys and sheep beginning in late fetal/early neonatal development (2, 72), presumably because female fetuses exposed to fetal male levels of testosterone (or its androgenic or estrogenic metabolites) develop permanent epigenetic and pathophysiological changes in endocrine and reproductive target tissues. Although little attention has focused on the physiological responses of pregnant dams to exogenous testosterone administration and their effects on female fetal development, maternal metabolic dysfunction, particularly from hyperglycemia (18–19, 35–37), may reprogram fetal and subsequent postnatal metabolic traits of offspring from PA females.
Insulin resistance can be induced in humans by administrating testosterone to regularly menstruating women for 10–12 days, (27), to reproductive-aged female and male transsexuals for 4 mo (56), or to postmenopausal women for 3 mo (74). In the latter treated group of women, androgen rather than estrogen receptor-mediated action has been implicated in insulin resistance, since estrogen administration does not impair insulin action (74). Such androgen specificity also occurs in a fetal androgen excess sheep model for PCOS in which gestational treatment of dams with the nonaromatizable androgen, dihydrotestosterone, induces comparable insulin resistance in exposed female offspring to that found in females exposed to testosterone excess during gestation (51). In vitro androgen specificity also exists as androgen receptor blockade prevents testosterone-induced insulin resistance in human subcutaneous adipocytes (21).
Testosterone treatment of gravid rhesus monkeys, therefore, may induce maternal insulin resistance in addition to elevating circulating androgen levels in both maternal and fetal compartments (2). Because pregnancy-induced insulin resistance in primates [female rhesus monkeys (43) and women (66)] may be exacerbated by androgen excess, as evident by hyperandrogenic PCOS women being at risk for gestational diabetes (13), testosterone treatment of rhesus monkey dams may expose their female offspring to hyperglycemia (4, 25, 51). Understanding the development of metabolic PCOS-like traits in PA female monkeys, therefore, is crucial since maternal hyperglycemia is readily conveyed to the fetus via transplacental transport, causing phenotypic changes in both the exposed human fetus (hyperinsulinemia and macrosomia) and subsequent neonate (hypoglycemia and increased adiposity) (35, 36).
The present study, therefore, examines whether discrete, early gestation testosterone treatment of rhesus monkey dams causes predictable metabolic antecedents of PCOS-like traits in PA female offspring, such as insulin resistance [as found in young PA female sheep and rats (25, 58)] and failure of pancreatic β-cells to appropriately compensate for insulin resistance (β-cell defect). This study also examines whether gestational testosterone treatment disrupts maternal glucoregulation and whether preconception maternal body weight exaggerates any glucoregulatory perturbation. Evidence for testosterone inducing any form of hyperglycemia during pregnancy, with maternal metabolic dysfunction linked to a postnatal metabolic phenotype in PA female offspring, would support the proposed "second hit" on the female fetus (3, 4), in which relative hyperinsulinemia induced by fetal exposure programs postnatal metabolic dysfunction (26). This metabolic second hit, coexisting with the direct effects of testosterone (or its metabolites) on fetal and postnatal development (i.e., "first hit"), could cause insulin-amplified reproductive dysfunction, as found in PA adult female monkeys (76) and sheep (67). Such implications for fetal origins of metabolic (and reproductive) phenotypes in adult female PA monkeys also may apply to the pathogenesis of PCOS in women (26).
Animals and Fetal Programming
Animal procedures conformed to the requirements of the Animal Welfare Act, and animal protocols were approved before implementation by the Institutional Animal Care and Use Committee at the University of California, Davis. Fifteen adult, nonprimiparous, pregnant female rhesus monkeys, housed at the California National Primate Research Center, were selected for study, based upon the absence of Y-chromosomal DNA in their peripheral circulation (39) at 30 days of gestation (range: 28–32 days), confirming a female fetus. Between 40 and 80 days of gestation (late first to midsecond trimester), gravid animals received daily subcutaneous injections of either 15 mg testosterone propionate (TP, n = 9) or vehicle (100–200 μl sesame oil; control, n = 7; Fig. 1). Such maternal TP treatment has been shown to induce fetal androgen excess in PA females equivalent to that found in fetal males and programs for a PCOS phenotype in adulthood (1, 2, 60).
As previously reported (2), before conception, adult females in TP and control groups had similar ages [TP: 11.2 ± 1.5 (SE) yr; control: 8.4 ± 2.0 (SE) yr] and body weights (TP: 7.0 ± 0.4 kg; control: 6.8 ± 0.5 kg). At term, newborns were delivered by cesarean section from dams of comparable term body weights (TP: 8.5 ± 0.4 kg; control: 8.1 ± 0.5 kg). Routine newborn assessments, including body weights and crown-rump lengths (see Fig. 3), and gross appearance of the placenta, were unremarkable and similar between the groups. Infants were nursery reared under standard operating procedures for housing conditions and diet for animals in this age group (71). One control dam and the associated offspring were omitted from the data analyses because they were identified as outliers [by extreme studentized deviate test] for elevated maternal/fetal (P < 0.05/P < 0.01) basal serum glucose levels in the third trimester and elevated (138 mg/dl) infant (P < 0.05) basal serum glucose levels at 2 mo postnatal age. The birth weight of this latter infant (546 g) was ∼23% greater than the mean of remaining controls (445 ± 19 g), although within the normative weight range for newborn rhesus monkeys.
Crown-rump and femur lengths were assessed at birth and at the time of tissue harvest (∼2 mo postnatal age) using standardized methods, and placental weights were assessed at delivery (71). Infants were weighed daily or weekly during the study period until the endpoint of ∼2 mo postnatal age. Organ weights were assessed at tissue harvest (71).
Glucoregulatory Assessment
After an overnight fast, maternal blood was collected from a peripheral vessel under telazol (5–8 mg/kg im) or ketamine (10 mg/kg im) approximately every 3 wk from 40 days of gestation (first trimester) through term. A modified intravenous glucose tolerance test (ivGTT) was also performed at 80 days of gestation. Glucose (300 mg/kg at 0 min) was administered intravenously, and blood samples were collected at select time points via a peripheral vessel. Insulin sensitivity (SI) was determined using the modified minimal model method (9). Further measures obtained from the ivGTT were basal (−5 min relative to glucose infusion) circulating levels of insulin (basal insulin), glucose (basal glucose), and total free (nonesterified) fatty acids (basal FFA); acute insulin responses to glucose (elevation of posthepatic plasma insulin concentration above baseline at 5 min); glucose disappearance rate (slope of the log linear regression of plasma glucose concentration between 10 and 20 min); and disposition index (β-cell compensation index; product of SI and acute insulin responses to glucose) (42). Area under the curve for glucose (AUCglucose), insulin (AUCinsulin), and FFA (AUCFFA) were determined using the trapezoidal rule. The validity of using such limited numbers of time points to determine dam (and infant monkey, see below) SI, and the derived measure of disposition index, were validated by correlating SI and disposition index values calculated from a 180-min ivGTT performed on 12 normal adult female rhesus monkeys with SI and disposition index values calculated from the same adult ivGTTs, but only including the time points used in the current study. SI values derived from the reduced number of time points, −5 to 60 min (dam) or 45 min (infant), were positively correlated with those SI values obtained using all time points across the 180-min ivGTT (r2 values, 0.47–0.55; P values, 0.01–0.006, respectively; slopes and y-axis intercepts did not differ from 1 and 0, respectively, P values >0.10). Disposition index comparisons were similarly correlated (r2 values, 0.52–0.71; P values, 0.005–0.001, respectively; slopes and y-axis intercepts did not differ from 1 and 0, respectively, P values >0.40).
Fetal blood samples for basal glucose and insulin determinations were collected when the dams were sedated for ultrasound-guided fetal cardiocentesis at 80, 100, 120, and 140 days of gestation using established techniques (69). Fetal blood samples were also obtained at −5, 5, 15, 25, 35, and 45 min after a direct injection of 20 mg glucagon in the fetal circulation at 0 min at 140 days gestation (third trimester). Tolbutamide (20 mg/kg) was also injected directly in the fetal circulation 20 min following the glucagon injection (portal vein). The following measures were derived from this glucagon-tolbutamide test: basal insulin, glucose, and FFA; acute fetal insulin responses to glucagon (fetal insulin concentration above baseline at 5 min) and to tolbutamide (fetal insulin concentration at 25 min above 15 min value); as well as AUCglucose, AUCinsulin, and AUCFFA.
A modified ivGTT was performed in overnight-fasted infants on postnatal day 45 (0.5 g glucose/kg iv at 0 min, tolbutamide 20 mg/kg iv at 20 min; blood samples taken at −5, 5, 15, 25, 35, and 45 min). SI was determined using the modified minimal model method (9). Further measures derived from the ivGTT were basal insulin, glucose, and FFA; acute insulin responses to both glucose and tolbutamide; disposition index; AUCglucose; AUCinsulin; and AUCFFA.
Statistical Analyses
Glucoregulatory parameters not normally distributed were log transformed to achieve homogeneity of variance and to increase linearity. Treatment group comparisons were conducted using Student's t-test or repeated-measures-design ANOVA (version 7.0; Systat, Evanston, IL). Log-transformed glucoregulatory or morphometric parameters not normally distributed were analyzed using nonparametric statistics. A P value of <0.05 was considered significant. All log-transformed parameters are expressed as the antilog of the transformed means (95% confidence limit), nonnormal data are expressed as the median (interquartile range), and all other data are shown as means ± SE.
While pregnancy induced the expected increase in weight gain, dams receiving TP injections exhibited accelerated body weight gain when compared with concurrent controls (Fig. 2). The body weights of TP-injected dams exceeded those of control dams by ∼25% at 80 days of gestation (P < 0.029). TP-injected dams maintained this body weight until term delivery and did not differ from gestational controls in terms of body weight in the second half of gestation. This difference in the temporal progression of body weight represented an over fourfold weight gain in TP-injected dams vs. controls during TP treatment (P < 0.001, Fig. 2), although similar rates of weight gain occurred in both groups before and after TP treatment, except for a transiently diminished (P < 0.015) weight gain for 40 days immediately after TP injections (80–120 days of gestation; Fig. 2). During this latter time interval, TP-injected dams lost an average of 0.08 kg/40 days, whereas control dam body weight increased by an average of 0.60 kg/40 days.
Normal trends in fetal growth were observed across gestation in both groups. Ultrasound biometrics included biparietal diameter and femur length and were within the normative range at all time points assessed compared with historical controls (n ∼ 150) (70), although PA females exhibited an overall increase in fetal head size compared with concurrent control female fetuses (P < 0.043, Table 1).
As previously reported, PA female monkeys had birth weights within the normative range when compared with historical controls (n ∼ 130) (70) at delivery by cesarean section (Fig. 3). PA female infants, however, demonstrated approximately a 10% increase in body weight compared with concurrent controls by 8 wk postnatal age, both by absolute weight and percent birth weight (type of female × age interactions: P < 0.005 and P < 0.016, respectively). Crown-rump lengths at delivery by cesarean section and at 9 wk of postnatal age were similar between control and PA infants (Fig. 3), as were femur lengths at 9 wk postnatal age (Fig. 3). The body mass index of infants, defined as the body weight relative to crown-rump length, did not differ significantly between female infant groups (cesarean section: control, 11.9 ± 0.4 kg/m2 and PA, 12.2 ± 0.3 kg/m2, P = 0.55; 8 wk postnatal age: control, 15.2 ± 0.4 kg/m2 and PA 15.8 ± 0.3 kg/m2, P = 0.24). Organ weights at tissue harvest, corrected for body weight, also were similar between female infant groups at 8 wk postnatal age (Table 2).
Basal (overnight-fasted) circulating glucose and insulin levels did not differ between oil- and TP-injected dams between 40 days gestation and term (Figs. 4 and 5). In both groups combined, basal glucose levels did not vary across this time period (time effect, P < 0.70), whereas between 60 and 120 days gestation (P < 0.018–0.001) basal insulin levels increased above the values at study initiation (40 days gestation; time effect, P < 0.001). Gestational peak values in maternal basal insulin levels occurred at a similar median of 80 days of gestation in both groups of dams, with basal insulin levels in TP-injected dams tending (P < 0.067) to be ∼130% higher [379.3 (190.2, 756.6) μU/ml; backtransformed mean (95% confidence limits)] than those in controls [164.8 (108.8, 279.6) μU/ml]. Maternal basal insulin levels only returned to early gestation values at 140 days gestation (third trimester). During the ivGTT (80 days of gestation), glucose disappearance rate diminished by ∼60% (P ≤ 0.03) and AUCglucose tended (P ≤ 0.057) to increase by ∼20% in TP-injected dams (Table 3), indicating impaired glucose tolerance in the latter dams despite elevated AUCinsulin values (P ≤ 0.019). There were no significant differences between oil- and TP-injected dams with respect to SI, disposition index, and acute insulin response to glucose (Table 3). Glucose disappearance rate was negatively correlated (r2 = 0.50, P < 0.033) with dam preconception body weight in TP- but not oil-injected dams (Fig. 6), whereas none of the other glucose or insulin parameters was correlated with glucose disappearance in either group of dams. There were no between-group differences in maternal FFA parameters during the ivGTT (Table 3) or basal FFA levels during gestation (data not shown).
Overall, circulating glucose and insulin levels did not differ between control and PA female fetuses between 80 and 140 days gestation, nor were there gestational changes in circulating insulin (time effect, P > 0.17) levels (Figs. 4 and 5). Circulating glucose levels, however, did change across gestation (time effect, P < 0.021), with values at 80 days gestation exceeding all later gestational values (Fig. 4). Unique to prenatal TP exposure, preconception dam body weight, and circulating glucose levels and glucose clearance rates in TP-injected dams at 80 days gestation, significantly influenced PA fetal glucose levels. PA fetal glucose levels at 80 days gestation showed a strong, positive correlation with the preconception body weight of their dams (r2 = 0.72, P < 0.004), implicating dam adiposity before conception as a key contributor in the glucoregulatory associations found between PA fetuses and their TP-injected dams. PA fetal glucose levels showed a similarly strong negative correlation with glucose disappearance rates (r2 = 0.64, P < 0.01) and a positive correlation with simultaneous basal glucose values (r2 = 0.98, P < 0.001) in their TP-injected dams, with four of the nine (44%) PA fetuses exhibiting serum glucose levels (54.6–92.3 mg/dl) above concurrent control maximal values (52.4 mg/dl; Fig. 7). The positive correlation between fetal and maternal glucose levels persisted at 100 days gestation (r2 = 0.62, P < 0.021) for PA fetuses and TP-injected dams only. There were no significant associations between fetal insulin levels and maternal glucose or insulin concentrations despite 44% of PA fetuses having serum insulin levels (11.7–31.3 and 22.5–32.5 μU/ml) above respective control maximal values (11.3 and 22.4 μU/ml) on 100 and 120 days gestation, respectively (Fig. 7).
During the intravenous glucagon-tolbutamide test at 140 days of gestation, there were no significant female-type differences for any glucose or insulin parameters (Table 3). In contrast, during ivGTT at 140 days gestation, both basal FFA and AUCFFA values in PA fetuses were ∼29–36% (P ≤ 0.03–0.036), respectively, of controls (Table 3).
In both female groups combined and typical of newborns (Fig. 4), basal circulating glucose levels reached a nadir (time effect, P < 0.001) on the first postnatal day of life vs. values on both postnatal days 30 and 45. Basal glucose levels in five out of nine (55%) PA infants, however, ranged from 29 to 36 mg/dl, below the minimum level (38 mg/dl) found in control infants on the first postnatal day (Fig. 7). Consistent with this finding, PA but not control infants demonstrated a negative correlation (r2 = 0.45, P < 0.048) between glucose levels on postnatal day 1 and their fetal glucose levels on 80 days of gestation, significantly associating elevated fetal glucose levels with initially low newborn infant glucose values in the androgen-exposed group. In contrast, basal circulating insulin levels did not vary between infant groups or across postnatal days (time effect, P < 0.70; Fig. 5). During the intravenous glucose-tolbutamide test at postnatal day 45, SI and the disposition index in PA infants, however, both increased to ∼230% (P ≤ 0.02) and 300% (P ≤ 0.03), respectively, above control values (Table 3). Increased disposition index values were consistent with ∼20% lower (P ≤ 0.013) AUCglucose values in PA than in control infants. The acute insulin responses to tolbutamide in PA infants were diminished (P ≤ 0.014) compared with controls. There were no other significant differences between PA and control infants during the intravenous glucose-tolbutamide test, including FFA parameters (Table 3).
In women and ewes, preconception adiposity and enhanced maternal weight gain can impair glucoregulation during pregnancy, causing increased fetal growth and altered glycemic control in the offspring [humans (19, 37, 43) and sheep (31)]. In this study, despite similar preconception body weights of all dams, body weight before conception [as a measure of female rhesus monkey adiposity (30)] was negatively correlated with glucose clearance in TP-injected monkey dams following accelerated maternal weight gain during TP treatment, suggesting that preconception adiposity interacts with TP-induced maternal weight gain to disrupt maternal glucoregulation. Correspondingly, PA female monkey offspring exposed to fetal androgen excess demonstrate a subtle increase in fetal head growth compared with concurrent controls, along with indications of transient fetal hyperglycemia and relative hyperinsulinemia in neonates. PA female infants demonstrate increased SI and relative increases in insulin release following glucose challenge, unlike the diminished SI and reduced insulin release following glucose challenge found in adult PA female monkeys (1, 29) and diminished SI observed in young female PA sheep (51) as well as adult PA female rats (25). Consequently, PA fetal and neonatal monkeys may exhibit these metabolic abnormalities more from TP-induced maternal glucose intolerance than from direct actions of hyperandrogenism on fetal target tissues.
Such metabolic mechanisms underlying the ability of fetal androgen excess to induce PCOS-like metabolic phenotypes in female rhesus monkeys may explain differences in PCOS-like traits between various fetal androgen excess models (1, 33). In our study, early to midgestation treatment of rhesus monkey dams with TP [intentionally exceeding placental/hepatic steroid deactivation and aromatization to produce fetal male levels of testosterone in the female fetuses (2)] modestly accelerates maternal weight gain to elevate circulating glucose and insulin levels following glucose challenge and to diminish glucose clearance relative to preconception adiposity, likely adding a metabolic perturbation of postprandial hyperglycemia to in utero androgen exposure. Postprandial hyperglycemia is now recognized as an important pathophysiological component in cardiovascular disease (15, 20, 54), glucose intolerant and diabetic pregnancies (12, 48), and type 2 diabetes (8, 46, 59, 66). In addition, gestational maternal postprandial hyperglycemia has recently been shown to be a sensitive marker for maternal glucoregulatory impairment and postpartum development of metabolic syndrome (61). Such TP-induced maternal metabolic disruption may explain why both adult female (4, 29) and male (16) offspring of TP-injected monkey dams exhibit insulin resistance and pancreatic β-cell defects, as two sequelae of a transient hyperglycemic gestational environment (5, 35, 36), rather than fetal androgen excess per se (2, 58). As in human pregnancies, relatively mild changes in gestational glucoregulation, as manifest in the present TP-injected dams and PA fetuses and infants, may have consequences for adult metabolic dysfunction (7, 18, 19, 62, 35, 36, 53).
Increased Maternal Weight Gain During Gestation
The modestly accelerated maternal weight gain found in this study emulates that found by Kemnitz and colleagues (44) when they administered TP at 2 mg·kg−1·day−1 to gonadectomized adult PA and control female rhesus monkeys and induced increased fat-free mass. The TP dose in the latter study closely mimics the ∼1.8–2.3 mg TP·kg−1·day−1 range employed in the present study (15 mg·dam−1·day−1; Fig. 1). Accelerated weight gain in rhesus monkey dams has potential adverse consequences on the fetus, as evident in human studies in which women in the highest quartile of weight gain during pregnancy are more likely to manifest maternal hyperglycemia and impaired glucose tolerance (37), and offspring born to overweight women are more likely to manifest metabolic syndrome in adulthood (19). Although body weight is positively correlated with body mass index (68) and total body fat (30) in female rhesus monkeys, the TP-accelerated weight gain in dams in the present study may well represent increased fat-free mass (44).
In addition, we observed impaired glucoregulation in TP-injected monkey dams, via diminished glucose clearance during midgestational ivGTT, equivalent to mild to moderate glucose intolerance found in obese pregnant rhesus monkeys (43). The degree of glucose intolerance shown by TP-injected dams resembles that of obese, untreated rhesus dams with preconception body weights ∼2–5 kg (∼30–70%) greater than those of the dams included in this study, implying that androgen excess may exaggerate the adverse metabolic consequence of adiposity accumulated before and during pregnancy (43), even though such adiposity may be within the range of normal body weight.
Impaired Maternal Glucoregulation
As expected, testosterone treatment of rhesus monkey dams induced subtle hyperinsulinemia presumably from testosterone-induced insulin resistance (21, 27, 56, 74), with increased pancreatic insulin responsiveness to glucose (elevated AUCinsulin) and a tendency for increased basal insulin levels, but neither prevented glucose intolerance (diminished glucose clearance) in TP-injected dams at 80 days of gestation. Because no additional glucose challenges were performed on the dams, it is not known whether maternal glucoregulatory impairments persist beyond the period of TP treatment. In this regard, insignificantly diminished SI in TP- vs. oil-injected dams likely represents heterogeneity of SI in controls from variability of pregnancy-related insulin resistance in rhesus monkeys (43, 55). Because preconception maternal body weight negatively correlates with maternal glucose disappearance in TP-injected dams alone, prepregnancy adiposity may additionally impair glucoregulatory function (19, 31, 37, 43), rendering TP-injected dams particularly susceptible to testosterone-induced insulin resistance. As previously shown in female rats (25), monkeys (47), and sheep (51), hypercaloric, diet-induced obesity mimics the diminished glucoregulatory effects of testosterone treatment so that the combination of increased adiposity and testosterone treatment may exaggerate impaired glucoregulation induced by testosterone treatment alone. Consistent with this hypothesis, increased lipolysis from daily TP injections of adult female rhesus monkeys (44) may contribute to diminished maternal glucose clearance (6, 38, 73).
Fetal Glucose, Insulin, and Growth
In hyperglycemia, excess glucose crosses the placenta by facilitated diffusion and induces compensatory hyperinsulinemia in the fetus (31, 34, 52), whereas circulating maternal insulin does not cross the placenta in any significant amount (41). Transient gestational maternal postprandial hyperglycemia, as found in TP-injected dams in this study, likely has an analogous effect on exposed female fetuses. Such a transient increase in transplacental glucose transport in TP-injected dams can explain how 1) circulating glucose levels in 44% of PA female fetuses exceed those of all fetal controls at 80 days gestation (first fetal sample day, last day of dam treatment) and 2) PA female fetal glucose levels positively correlate with those in their respective dams (at both 80 and 100 days gestation), while negatively correlating with dam glucose clearance (at 80 days gestation). As a consequence of such fetal hyperglycemia, providing principal energy substrate, and likely subtle increases in fetal insulin, as a growth promoter (31, 34, 52), PA monkey fetuses exhibited modestly enhanced biparietal diameter compared with concurrent controls during and after androgen excess treatment of their dams.
In such a fetal environment, circulating FFA levels in PA female fetal monkeys are only ∼30% of those found in controls by late gestation. Their respective dams, however, exhibit circulating FFA levels similar to those found in control dams. Although increasing glucose load on human placental tissue in vitro does not alter placental transport of fatty acids (50), gestational diabetes alters placental processing of fatty acids and lipids that may diminish (11) or enhance (57) their release to the fetus. It is thus unclear whether diminished circulating FFA levels in PA female fetuses reflect reduced placental delivery or enhanced fetal extraction. Either alteration in FFA availability to PA female fetuses may perturb early acquisition of fat stores without fetal growth restriction, as observed in this study. In humans, early acquisition of body fat in fetuses and infants leads to increased prevalence of adult adiposity and metabolic syndrome (17, 19).
Neonatal Glucose, Insulin, and Growth
Increases in PA fetal dimensions, combined with increased dam weight gain during pregnancy, would be expected to increase the postnatal risk of metabolic derangements in mammalian offspring (7, 17, 19, 31, 35). A degree of neonatal hypoglycemia was found in PA neonates on postnatal day 1 when 55% exhibited serum glucose levels of 29–36 mg/dl, all of which were lower than the minimum level of 38 mg/dl found in concurrent controls. With this modest glucose difference, PA neonates also demonstrated a negative correlation between their first postnatal day circulating glucose levels and those obtained from fetal blood samples at 80 days gestation, significantly associating low postnatal glucose levels with high fetal glucose levels in PA females, alone. Analogous associations between newborn hypoglycemia and maternal hyperglycemia have also been found in human pregnancies, including modest maternal hyperglycemia (17, 35).
Insulin hypersecretion following glucose challenge in PA 45-day-old infant monkeys, as shown by excessive acute insulin responses to glucose relative to SI (i.e., increased disposition index), are biologically relevant, as confirmed by increased glucose clearance (diminished AUCglucose), and may represent persistent pancreatic insulin hypersecretion entrained by transient maternal postprandial hyperglycemia (36, 53). The mechanism of exaggerated SI in PA compared with control infant monkeys is unknown but may reflect increased skeletal muscle insulin metabolic signaling, as manifest in neonatal lambs with fetal growth restriction (49), or increased adipose SI, as observed in children with increased fetal growth and early postnatal weight gain (14). Relatively excessive insulin release (increased disposition index) in an insulin-sensitive environment (elevated SI) likely explains why a modest increase in weight gain occurs in PA infants at ∼8 wk of age, particularly because insulin's anabolic action (7, 10) may synergize with PA infant hyperandrogenism (2) to increase lipogenesis and muscle protein synthesis (7, 22, 75), thereby enhancing insulin-sensitive tissue mass in PA monkey neonates.
Clinical Relevance
The present study shows that fetal pancreatic β-cells entrained by transient maternal postprandial hyperglycemia cause relative insulin hypersecretion in neonatal life, linking pregnancy-related metabolic antecedents with metabolic dysfunction in PA female rhesus monkeys (4) and possibly in PCOS women. Cresswell and colleagues (23) have associated the development of polycystic ovaries with increased birth weight and mother adiposity during pregnancy, indicating an increased likelihood for postnatal hyperinsulinemia from insulin resistance. Studies of two PCOS populations of Spanish descent (26, 65) have proposed that hyperinsulinemia accompanying postnatal catch-up growth amplifies the development of PCOS traits. In support of this, preadolescent and adolescent daughters of PCOS women have subtle hyperinsulinemia from insulin resistance without apparent changes in glucose parameters preceding an obvious PCOS phenotype (45, 64), whereas preadolescent daughters of glucose-intolerant PCOS women have greater insulin resistance and inferior insulin secretory compensation (D. H. Geller, personal communication). Postnatal insulin defects may thus provide an important developmental component in the expression of PCOS phenotype.
That such developmental origins for PCOS may be strongly influenced by clinically unrecognizable events in the postnatal environment, yet go virtually unrecognized until adulthood, raises profound health care concerns regarding the effect of maternal obesity and/or increased pregnancy weight gain on the transgenerational development of obesity as a susceptibility factor to later adult chronic diseases. With a progressive epidemic of obesity likely to induce metabolic abnormalities amplifying fetal androgen excess programming, the need for primate models to understand the developmental origins of PCOS-like reproductive and metabolic dysfunction is crucial to develop new clinical strategies that treat abnormalities during maternal-fetal development and postnatal life development to reduce the risk of adult disease.
This work was supported by National Institutes of Health Grants P50 HD-044405, P51 RR-000167 (WNPRC base operating grant), and RR-00169 (CNPRC base operating grant) and was partly conducted at a facility (WNPRC) constructed with support from Research Facilities Improvement Program Grant nos. RR-15459-01 and RR-020141-01.
No conflicts of interest are declared by the authors.
We thank J. M. Turk, S. J. Muller, J. R. Lange, and Assay Services of the Wisconsin National Primate Research Center (WNPRC) for assistance with endocrine determinations; members of the animal care staff at the California National Primate Research Center (CNPRC) for expert technical assistance; Dr. R. N. Bergmann for advice on Minimal Model derivations; and R. A. Becker and J. L. Peterson at WNPRC for assistance with preparation of the figures and manuscript, respectively.
- Copyright © 2010 the American Physiological Society
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text:
Blessing the Doubts
Bless this one, creeping into my pocket
like a bad penny, shiny copper talisman.
And this one, flooding me like a spring monsoon,
washing away all reason and linear thought.
One of my favorite doubts whispers of demons;
teaches me how to curse in a new language.
Then there's the subtle one, tucking itself into my shoe;
constant and true, like a splinter.
And don't forget the faithful doubt that refuses to desert me
(like a family ghost or demented mascot).
Pay special attention to the ragged runaway doubts;
I harbor them out of kindness.
Remember the one who pants like a seasoned hound,
reminds me to keep up, keep my head down, scent my prey.
Finally, please, bless that seductive doubt whose song
leads me to the ledge, pushes me off into impossible.
- Deborah A. Miranda