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Back in the late 1990s, I wrote an essay about the "controversy" over who actually wrote the works of Shakespeare. I wrote, then,
Not everyone agrees that Shakespeare wrote Shakespeare. The challenge to his authorship isn't new: for the last three centuries it's been the most popular whodunit of literature: trying to uncover the true identity of the author of the world's greatest dramas and comedies. I can't think of another author of note in the world who is considered not to have written the works under which his or her name is penned. Even Shakespeare's many contemporaries are considered the author of the works under their names – Jonson, Marlowe, Fletcher, for example. But not Bill the Bard.
I don't think of it as a controversy as much as a conspiracy theory, since, like UFOs and chemtrails, it doesn't get any significant traction in academia. The dating of a particular play, or even if it belongs in the canon, may be controversial, but not conspiratorial.
However, it's one of the oldest conspiracy theories, at least in the literary world (Atlantis, the Noachian flood, and Freemasonry may be older, but not literary). And I have to admit to still enjoying reading about it. This old conspiracy still has legs. Plus, it has generated serious, intellectual and scholarly debate for centuries.* It's even become a meme, thanks to the internet.
A couple of years ago, in my endless search for books on the Bard, I picked up History Play, by Rodney Bolt (Perennial, New York, USA, 2005). I only started to read it last week. Bolt revives an old idea: that Christopher Marlowe, contemporary playwright, was the actual author of the plays attributed to William Shakespeare.
Like that of the contemporary favourite among literary conspiracy theorists, Edward de Vere, the Earl of Oxford, Marlowe's life presents a significant challenge to explain in terms of the theory: Marlowe was murdered in 1593.
That's twenty years before the last known works by Shakespeare were penned (Henry VIII, and Two Noble Kinsmen). de Vere, at least, died in 1604, more than a decade after Marlowe, so his supporters have a shorter time to cover.
The "solutions" for this rather uncomfortable historical fact are either that the person in question didn't really die, but rather went into hiding and continued to write, or that he (or she in the case of those who attribute the plays to Elizabeth I) wrote them all before, and they were released sporadically after that death.
For Marlowe, it was even more inconvenient to "die" at age 29. Considering he was in university until 1587, that doesn't leave a lot of time to write the 36-plus plays and numerous poems attributed to Shakespeare. Unless, of course, we was really alive all this time, as Bolt suggests.
Bolt overcomes this significant problem in grand fashion: Marlowe faked his own death and fled to the continent with a copy of Hollinshead's Chronicles in his chest (Chronicles was, of course, one of Shakespeare's prime sources). The book is full of Elizabethan spy stories – if nothing else it's wildly entertaining.
Marlowe has been presented as the actual author of the Bard's works since at least 1819 (this article dates it to 1895). While it's accepted that Marlowe influenced Shakespeare, his death usually involves some rather fantastic explanation to make him stand up among the other conspirators.
The argument is generally that a "lout" like William Shakespeare had neither the education nor experience to write about such a wide range of topics as he did. Only a nobleman like de Vere and Bacon had that background. Marlowe, despite being raised in a middle-class background similar to Shakespeare's (Marlowe\s father was a cobbler) had better tutelage and Cambridge schooling. As it says on Shakespeare-Oxford.com:***
1) It is highly unlikely that Shakespeare's works could have been composed by the person to whom they are traditionally assigned.
2) The qualifications necessary for the true author of these works are more adequately realized in the person of Edward de Vere, 17th Earl of Oxford, than in the many other candidates proposed in the last two hundred years.
So how did Shakespeare's name get put on them? The real, noble authors would lose face if they were identified as the authors, so they used a minor actor as their mouthpiece.** Wikipedia notes:
Reasons proposed for the use of "Shakespeare" as a pseudonym vary, usually depending upon the social status of the candidate. Aristocrats such as Derby and Oxford supposedly used pseudonyms because of a prevailing "stigma of print", a social convention that putatively restricted their literary works to private and courtly audiences—as opposed to commercial endeavours—at the risk of social disgrace if violated. In the case of commoners, the reason was to avoid prosecution by the authorities: Bacon to avoid the consequences of advocating a more republican form of government, and Marlowe to avoid imprisonment or worse after faking his death and fleeing the country.
That argument, however, doesn't hold a lot of water since many nobles in the Elizabethan era wrote plays and poems openly, including de Vere.
It all hinges on how you perceive talent and genius. There's a certain snobbishness in believing that one needs noble birth and university degrees to have the talent to be creative and artistic. Yet every notion we have of genius says that it belongs to individuals regardless of background, upbringing and formal education.
The argument against Shakespeare as the author overlooks simple plagiarism, too. Shakespeare's sources are well known, and it's clear that he lifted many of his plots, characters and settings from the works of others, even some of the dialogue. His genius lay in how he assembled them into his plays.
In Shakespeare, Invention of the Human, Harold Bloom writes:
You cannot reduce Shakespeare to any single power, of all his myriad gifts, and assert that he matters most because of that one glory. yet all his endowments issue from his extraordinary intelligence, which for comprehensiveness is unmatched, and not just among the greatest writers. The true Bardolatry stems from this recognition.
Personally, I find all of the arguments against Shakespeare flimsy and contrived. Most of the arguments in favour of alternative authors depend on a lot of circumstantial evidence, "what-if" suppositions, and interpretations of internal "evidence" in the plays.****
The conspiracy looks for answers in the shadows and ignores those in common sight. And simply because 400-plus-year-old records are incomplete or were kept in ways different from our practices today doesn't mean anything is wrong.
But back to Bolt. His tale is fascinating reading, and he makes it clear his belief in Marlowe's authorship is absolute. Quotes from the plays are identified as Marlowe's work from the first pages. Yet Bolt pulls back in his afterword and teases us by saying it is all the "purest conjecture." Despite this, and despite the trips along what is clearly leaps of intellectual faith, what Bolt offers is entertaining and well researched, and in the end a rewarding read.
If only all conspiracy theories were so much fun to read.
* In his book, Contested Will, James Shapiro identifies at least 50 persons have been put forward as potential authors of the Shakespearean canon, since the notion of alternate authorship was first raised, in 1785. Wikipedia includes other dates for doubters.
** I've heard similar conspiracies about local blogs.
*** The site also boasts an "honor role" of skeptics who doubted Shakespeare as the author. However, simply because others believe in it, does not make it true, regardless of the perceived eminence of the skeptic. Just because some doctors smoke does not make the practice healthy or sanitary, no matter how good they are as surgeons. I cannot see any names of literary scholars or historians on the list, but there are a lot of actors.
**** I'm seldom convinced by interpretations by critics, historians and scholars that try to tell me what the author intended, thought, believed, or felt. Only the author can do that. Interpretations too often assume that what is written is not what was meant.
- The Social Contract - © September 17, 2023
- Review 9: Son of Godzilla - © August 20, 2023
- Review 8: Ebirah, Horror of the Deep – 1966 - © July 23, 2023


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After three episodes, Showtime has renewed Ray Donovan for a second season. The series garnered the cable channel's best ratings for an original series premiere in history and the numbers have been holding up.
The first season finale will air on September 22nd. Season two will premiere sometime in 2014.
Here's their press release:
Following Record-Breaking Premiere Week With Over 6 Million Viewers
LOS ANGELES, CA – (July 16, 2013) – Having made network history as its highest rated original series premiere ever and with continued ratings success in weeks two and three, SHOWTIME has picked up a second season of its critically acclaimed drama series RAY DONOVAN. Created and executive produced by Ann Biderman, the series stars Emmy(R) and Golden Globe(R) Award nominee Liev Schreiber in his first lead television role. The announcement was made today by David Nevins, President of Entertainment, Showtime Networks Inc. RAY DONOVAN airs on Sunday nights at 10 p.m. ET/PT on SHOWTIME. The second season will debut in 2014.
"RAY DONOVAN is on track to be our biggest season one show ever," said Nevins. "Ann Biderman and the extraordinarily talented creative team, coupled with the brilliant ensemble cast led by Liev Schreiber, have produced one of the hottest new dramas of the year. We are proud and excited to pick up another season."
RAY DONOVAN delivered the best debut of any freshman SHOWTIME comedy or drama series with more than 6 million viewers for its premiere across platforms (including replays, On Demand and Live +7). The series is also the first freshman drama in network history to improve on its series premiere in week two, up an impressive 15 percent in its second week on-air. In its third week, the series delivered 2.2 million viewers on Sunday night, on par with its record-setting second week.
Set in the sprawling mecca of the rich and famous, RAY DONOVAN stars Schreiber as LA's best professional fixer, the man called in to make the city's celebrities, superstar athletes, and business moguls' most complicated and combustible situations go away. This powerful drama unfolds when his father, Mickey Donovan, played by Oscar(R) winner Jon Voight, is unexpectedly released from prison, setting off a chain of events that shakes the Donovan family to its core. The cast includes Oscar winner and guest star Elliott Gould as Ray's long-time client and mentor, Paula Malcomson (The Hunger Games) in the role of Ray's wife, Abby, along with Eddie Marsan (Sherlock Holmes) and Dash Mihok (I Am Legend), who play Ray's brothers. The series also stars Steven Bauer (Breaking Bad), Katherine Moennig (The L Word), Pooch Hall (The Game), Kerris Dorsey (Moneyball) and Devon Bagby. Johnathon Schaech (That Thing You Do!) and Peter Jacobson (House) guest star. RAY DONOVAN is created and executive produced by Ann Biderman (Southland), who also wrote the pilot episode. The series is also executive produced by Mark Gordon and Bryan Zuriff. RAY DONOVAN is a SHOWTIME production.
What do you think? Have you been watching Ray Donovan on Showtime?

subset: commoncrawl


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All artists are self-taught
Techniques and skill and even a point of view are often handed down, formally or not. It's easier to get started if you're taught, of course.
But art, the new, the ability to connect the dots and to make an impact–sooner or later, that can only come from one who creates, not from a teacher and not from a book.


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Vt. State Police Log: Tractor trailer truck overturned in Waltham
CORRECTION: An item in the Vermont State Police Log in the May 17 edition of the Addison Independentmixed up the participants in a May 7 traffic accident on Route 17 in West Addison. A subsequent interview with Trooper Justin Busby revealed that Jeffery Freegard, 29 of Vergennes was driving a newer Fort Taurus sedan on Route 17 to a job at a farm in West Addison that day when he turned in front of a Chevy van driven by Jessica Cheney, 18, of Ticonderoga, N.Y.
Cheney and a juvenile male passenger were injured and transported by ambulance to Porter Hospital. The van sustained massive front-end damage — the frame buckled and engine block was pushed in. It was declared a total loss.
Freegard was taken to Fletcher Allen Health Care complaining of back pain.
Busby said Freeguard was at fault in the crash and was mailed two traffic tickets — one for failing to yield when turning left and the other for driving on a roadway across the lane.
We regret the errors in our first report.
ADDISON COUNTY — During the early evening of Tuesday, May 15, Vermont State Police worked to clear a tractor-trailer overturned on Route 7 in Waltham.
Traffic on Route 7 between Route 22A in Ferrisburgh and Route 17 in New Haven was delayed for three to four hours that evening while troopers dealt with the mess. No one was seriously injured as a result of the accident. Police said the accident is under investigation.
In other recent activity, troopers:
• On May 15 at 6 p.m. responded to a two-vehicle accident at the intersection of Route 7 and Tuppers Crossing in Ferrisburgh. Investigation revealed that neither juvenile operator was injured. One car sustained moderate passengers side damage and the other sustained rear bumper damage.
• On May 17 at 1:20 a.m. cited Aerial Rodman, 21, of Brandon for driving under the influence on North Main Street in Rutland City.
• On May 18 at approximately 1:57 p.m. responded to a report of a burglary in the Guthrie Road neighborhood in Lincoln. Various items were reported taken from the residence sometime over the past four weeks. Anyone with information is encouraged to call Vermont State Police at 388-4919.
• On May 18 at 8 p.m. were called to Starksboro for a domestic assault. Police alleged that Andrew Bissonette, 21, of Starksboro had assaulted a person with whom he is in a domestic relationship. The trooper said investigation showed that Bissonette had left the scene prior to arrival of VSP. He was later found in a vehicle in Vergennes with Kaleb Gorton, 19, of Vergennes and Jacob Rochon, 22, of Bristol. During this encounter, all three were charged with possession of marijuana and possession of a regulated substance, both misdemeanors. Bissonette was lodged at the Marble Valley Correctional Center on the domestic assault charge. Rochon and Gorton were released with citations to appear at the Addison Criminal Division.
• On May 20 at nearly 6 p.m. responded to a two-vehicle collision at the intersection of Hardscrabble Road and Monkton Road in Bristol. Police said a "junior operator" rear-ended another car while attempting a left-hand turn. Both vehicles sustained moderate damage with minor injuries reported.
• Were called to investigate a burglary at a Hardscrabble Road home in Monkton that occurred between 11:30 a.m. and 3:30 p.m. on May 21. Multiple items of jewelry were taken from the residence. Troopers said a blue Dodge Dakota with a lift kit and loud or modified exhaust was seen in the area earlier in the day with three occupants. Anyone with information is asked to contact the Vermont State Police at 388-4919.
• On May 21 at 12:38 p.m. were called to a report of a suspicious person in Whiting. Investigation led the trooper to arrest Joseph A. Wedge, 28, of Bristol and cite him for domestic assault, burglary, aggravated assault and violations of conditions of release. Wedge was processed at the New Haven VSP barracks and lodged at the Marble Valley correctional facility.
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High school athletes ready for fall playoffs this week
See when your favorite high school team is competing in the fall sports playoffs.


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Samsung E380 has a 128x160 pixel internal LCD, and a 96x69 pixel external LCD, a 1.3-megapixel camera, an MP3-player, Bluetooth interface and EDGE (Class 10) technology
Product ID: 9080
Product sold by: samstores.com
Availability: Not In Stock New
NOTE 1: This phone doesn't support 850 mhz, thus it will NOT work with Cingular's 850 mhz network. To use with Cingular, please confirm that your coverage area is only in 1900 mhz network.
NOTE 2: All of our Unlocked GSM Phones come from around the globe. As such, most carry an "International" warranty from the Manufacturer, which will be detailed within your product packaging, if appropriate. Only DOA (Dead on Arrival) Exchanges will be made for this product through the GSM Support Center. No returns are allowed otherwise. There are no exceptions. All of our unlocked cellular phones are only designed to work on GSM networks such as Cingular and T-Mobile. These phones are NOT compatible with CDMA carriers such as Verizon and Sprint. If your intended service provider is not among those four major carriers, please contact that provider to determine GSM compatibility.
Contents of package may vary from those pictured and stated here, due to changes in manufacturer's specifications or merchandising. Please check the product information carefully, items not included may no longer be required.


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2021 Ford Mustang
Built from all the passion of its iconic heritage, Mustang Mach-E is a new shape of freedom. Get ready for 0-60 thrills with zero emissions. Reserve your First Edition. Quantities limited.
Drive Experiences
Your Mustang Mach-E will match your mood. You can select your Drive Experience to fit the moment-and the interior sound, lighting, and even the responsiveness will adjust to your style - whether it's Unbridled, Engage or, when necessary, Whisper.
Exhilarating Performance
With the first all-electric member of the Mustang family, Ford harnessed the power of electrification to craft a vehicle that's as exciting to drive as its predecessors while also delivering a new, uniquely tailored experience. There will also be a Mach-E GT - targeting 0 to 60 mph in less than 4 seconds*, making it faster off the line than a Porsche Macan Turbo3 - and a GT Performance Edition, targeting 60 miles per hour in the mid-3-second range - comparable to a Porsche 911 GTS - as well as an estimated 342 Kw (459 horsepower) and 830 Nm (612 ft.-lbs.) of torque.**
Front-Load Freedom
A convenient front trunk levels up your adventure game. Not only is this added 4.8 cu. ft. of storage space water-resistant, it's washable and features a convenient drain, making it perfect for tailgating, camping and muddy gear-toting.
Hassle Free
Mustang Mach-E will be available with standard and extended range battery options with either rear-wheel drive or all-wheel drive powered by permanent magnet motors. Equipped with an extended range battery and rear-wheel drive, Mach-E has a targeted EPA-estimated 300 miles of range.* And the connected navigation system also will identify up-to-date charging locations during trips and prompt owners to charge at the most convenient points on each drive - all to help ensure they don't have to be anxious about how much range they have.**
* Based on full charge. Actual range varies with conditions such as external elements, driving behaviors, vehicle maintenance, and lithium-ion battery age. Final EPA-estimated ratings available in the 2020 calendar. ** Range and charge time based on manufacturer computer engineering simulations and EPA-estimated range calculation methodology. The charging rate decreases as battery reaches full capacity. Individual results may vary based on peak charging times and battery state of charge. Actual vehicle range varies with conditions such as external elements, driving behaviors, vehicle maintenance, and lithium-ion battery age.
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Brian Toliver Ford of Sulphur Springs
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Brian Toliver Ford of Sulphur Springs
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All Systems Are Go: FTL Launches Today
FTL is out today! At long last. I reckon there'll be a fair few people reading this who are about to receive their first Kickstarted game and that's quite exciting, as is FTL itself. I've already shared some of my thoughts on the beta version but it does seem as if I'd been drinking vinegar that day. Skimming back through my words, I don't seem quite as enthused as I actually am about the game's finer points. When fires rage and crew members panic from room to room, FTL is a delicious brew, random elements combining to create a heady commingling of anxiety and roleplay. It's a new form of ARPG. Available direct from the developers, on GOG and Steam shortly.


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South African Journal of Science
On-line version ISSN 1996-7489
Print version ISSN 0038-2353
S. Afr. j. sci. vol.105 n.11-12 Pretoria Nov./Dec. 2009
A tale of an extraordinary prospector
John Gurney
Mineral Services P.O. Box 28668 Pinelands 7430, South Africa E-mail: email@example.com
Platinum, Gold and Diamonds (The adventure of Hans Merensky's discoveries). By Eberhard W. Machens. Pp. 308. Protea Book House, Pretoria. R289.95. ISBN 978-1-86919-200-6. 2009.
Hans Merensky, who lived from 1871 to 1952, is a legend to anyone involved in mineral exploration in southern Africa. His contributions to the development of world-class mines in the Bushveld (platinum group metals and chrome ore); on the southern African west coast for diamonds; and the Phalaborwa carbonatite are well recognised. That he had other less spectacular but important successes, such as a role in developing the Free State goldfields near Odendaalsrus, is one of the many interesting facts that emerge from this entertaining and inspiring biography.
Born in South Africa, where his German parents were missionaries, he relocated with his family to Berlin at the age of 11, only to return to South Africa as a fully trained geologist and mining engineer in 1904 at the age of 33. A number of years operating as a successful consultant were brought to a temporary halt by a bankruptcy during a global recession, followed by the further misfortune of being interned at Fort Napier in Pietermaritzburg for the duration of World War I. Consequently when Merensky re-established himself in Johannesburg in 1919 he was 48 years old and starting from scratch. All his major exploration successes were still ahead of him: platinum in the Bushveld (1924); diamonds in Namaqualand (1926); gold in the Free State (1936); chrome in the Bushveld and vermiculite and apatite at Phalaborwa took longer to develop, starting from 1937 but interrupted by World War 2.
This prospecting success record is truly staggering, and is unquestionably unmatched in southern Africa, and to my knowledge anywhere else. This account of his achievements is fascinating. Yet chapter 15, titled 'The turning point in Merensky's life', doesn't deal with his exploration successes, other than to mention that they allowed Merensky to finally pay back all his debts and to purchase the farm Westfalia that was to provide the principle focus for the rest of his life.
In all above instances Merensky not only led the exploration initiatives, he fulfilled the entrepreneurial role of raising the high-risk, early-stage funding and the placing of the projects in the hands of appropriate developers. So it was entirely fitting that the last coup of Merensky's exploration initiatives was to prospect Phalaborwa, and in doing so provide the South African government of the dayand the local agricultural communitywith the future Phosphate Development Corporation.
I found the biography fascinating for a host of reasons. The early days of Merensky's life, it would appear, gave him an identity with open spaces and independence. His powers of observation, meticulous record keeping, outstanding memory and discipline were also clearly key attributes in an age when an earth scientist could venture into the field with only simple prospecting aids, and yet have a realistic hope for success. I use the term 'earth scientist' advisedly, as Merensky was trained as both a geologist and a mining engineer, and his projects in later life included ones involving agricultural research and development.
His endeavours have led to an equally impressive legacy that he was able to mastermind himself: the Hans Merensky Foundation today has over 4 000 employees, offering global research services on agricultural matters and sponsoring student fellowships. It is all told a record of a remarkable life, involving trials and tribulations but in the end triumphant over adversity. Furthermore it is clear that Merensky, while at ease with himself, was able to bring out the best in othersan essential factor in the style in which he operated. This is reflected in the manner in which his wishes have been followed since his death nearly 60 years ago.
Text boxes throughout the book provide useful insight for readers needing to know some background to Merensky's life and achievements. These make a significant contribution to the enjoyment of the tale, which it should be emphasised has been admirably translated from the original German by Idette Noomé, and edited by Amelia de Vaal. All in all this is a highly recommended read for everyone, not just for earth scientists.
Personally I found this book to be a thought-provoking life record. If the rest of us were one tenth as effective, South Africa and the world would be a much better place to live in. This biography will give plenty of pleasure in the reading, but more importantly it deserves to inspire readers who are in a position to make a difference in their field of endeavours. It isn't (probably) possible to emulate Merensky. There is only one Bushveld Igneous Complex, one Wits Basin, one stretch of over 1 000 km of coast with diamonds scattered all over it, and one Phalaborwa. The best one could expect would be to follow in his footsteps. Truly he has a unique record.


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I'm as surprised as you are to find a New Jersey Democrat wrapped up in something so shady. Why, this might well ruin the good name of Bob Menendez.
Imagine if it had come out before the election. He might have won by only 15 points.
The prosecutor's office in Hudson County, N.J., said Sanchez was found to have violated the law in 2010 and subsequently required to register as a sex offender. The exact charge was unclear because Sanchez was prosecuted as a juvenile and those court records are not publicly accessible. The prosecutor's office confirmed to AP that Sanchez registered as a sex offender, although his name does not appear on the public registry.
Authorities in Hudson County notified ICE agents in early October that they suspected Sanchez was an illegal immigrant who was a registered sex offender and who may be eligible to be deported. ICE agents in New Jersey notified superiors at the Homeland Security Department because they considered it a potentially high profile arrest, and DHS instructed them not to arrest Sanchez until after the November election, one U.S. official told the AP. ICE officials complained that the delay was inappropriate, but DHS directed them several times not to act, the official said…
During discussions about when and where to arrest Sanchez, the U.S. reviewed Sanchez's application for permission to stay in the country as part of President Barack Obama's policy to allow up to 1.7 million young illegal immigrants avoid deportation and get permission to work for up to two years. As a sex offender, he would not have been eligible.
Note well: "Several times."
Clearly someone at ICE thinks this stinks of politics or else the story wouldn't be leaking. The question now is who's empowered to investigate it. Something for the Senate Ethics Committee maybe, to probe whether Menendez influenced DHS into backing off? I'm sure Barbara Boxer, as chairman, will be diligent into getting to the bottom of a fellow Democrat's possible malfeasance. The DHS inspector general is another option; so is Issa's House Oversight Committee maybe. I confess that I don't know the rules offhand about one chamber of Congress investigating possible misdeeds committed by a member of the other chamber. Even if there's no rule against it, there may be a gentlemen's agreement in effect that each house polices itself. Technically, Issa wouldn't be investigating Menendez, he'd be investigating DHS. But the obvious potential in embarrassing a Democrat might launch a tit-for-tat between the Republican House and Democratic Senate. Maybe the local U.S. Attorney in Jersey is the best/only option.
This makes two prominent examples this afternoon alone of a prominent Dem receiving some sort of suspicious break from law enforcement. Like Ace, I'd sure like to know how Jim Moran's son was able to plead down from felony domestic violence assault after smashing his girlfriend's head into a garbage can in full view of two cops. Exit question: What happens if Menendez is implicated in DHS's hands-off approach to Sanchez here? Hmmmmm.


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Student loans, interest payments, and taxes: three things that have scared many people for years now. Read on to learn how these things can benefit you.
If you made federal student loan payments in 2018, you may be eligible to deduct a portion of the interest paid on your 2018 federal tax return. This is known as a student loan interest deduction. Don't miss out on this opportunity to make the money you've paid work for you! Below are some questions and answers to help you learn more about reporting student loan interest payments from IRS Form 1098-E on your 2018 taxes and potentially get this deduction.
What is IRS Form 1098-E?
IRS Form 1098-E is the Student Loan Interest Statement that your federal loan servicer will use to report student loan interest payments to both the Internal Revenue Service (IRS) and to you.
Will I receive a 1098-E?
If you paid $600 or more in interest to a federal loan servicer during the tax year, you will receive at least one 1098-E.
The IRS only requires federal loan servicers to report payments on IRS Form 1098-E if the interest received from the borrower in the tax year was $600 or more, although some federal loan servicers still send 1098-E's to borrowers who paid less than that.
If you paid less than $600 in interest to a federal loan servicer during the tax year and do not receive a 1098-E, you may contact your servicer for the exact amount of interest you paid during the year so you can then report that amount on your taxes.
How many 2018 1098-E's should I expect to receive?
That depends on how much you paid in interest, how many federal loan servicers you had, and some other factors. Read through the scenarios below to find where you fit and learn how many 2018 1098-E's you should expect.
- Your current servicer was your only servicer in 2018:
In this case, your current federal loan servicer will provide you with a copy of your 1098-E if you paid interest of $600 or more in 2018. Your servicer may send your 1098-E to you electronically or via U.S. mail.
- You had multiple servicers in 2018:
In this case, each of your federal loan servicers will provide you with a copy of your 1098-E if you paid interest of $600 or more to that individual servicer in 2018. Your servicer may send your 1098-E to you electronically or via U.S. mail.
If you paid less than $600 in interest to any of your federal loan servicers, you can contact each servicer as necessary to find out the exact amount of interest you paid during the year.
How will reporting my student loan interest payments on my 2018 taxes benefit me?
Reporting the amount of student loan interest you paid in 2018 on your federal tax return may count as a deduction. A deduction reduces the amount of your income that is subject to tax, which may benefit you by reducing the amount of tax you may have to pay.
For more information about student loan interest deduction, visit the IRS's Tax Benefits for Education: Information Center.
Now that you know student loans, interest rates, and taxes aren't as scary as you may have originally thought, you are ready to report your student loan interest rates on your 2018 federal tax return!
What if I still need help or have more questions?
While we are not tax advisors and cannot advise you on your federal tax return questions, your federal loan servicer is available to assist you with any questions about your student loans, including questions about IRS Form 1098-E and reporting the student loan interest you've paid on your 2018 taxes. If you're not sure who your loan servicer is, visit My Federal Student Aid to find contact information for the loan servicer or lender for your loans. To see a list of our federal loan servicers, go to the Loan Servicers page on StudentAid.gov.


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Atherosclerosis Independence: Genetic Polymorphisms of Ion Channels Role in the Pathogenesis of Coronary Microvascular Dysfunction and Myocardial Ischemia (Coronary Artery Disease (CAD))
Reviewer and Co-Curator: Larry H Bernstein, MD, FCAP
Curator: Aviva Lev-Ari, PhD, RN
Image created by Adina Hazan 06/30/2021
The role of ion channels in Na(+)-K(+)-ATPase: regulation of ion transport across the plasma membrane has been studied by our Team in 2012 and 2013. This is article TWELVE in a 13 article series listed at the end of this article.
Chiefly, our sources of inspiration were the following:
1. 2013 Nobel work on vesicles and calcium flux at the neuromuscular junction
Machinery Regulating Vesicle Traffic, A Major Transport System in our Cells
The 2013 Nobel Prize in Physiology or Medicine is awarded to Dr. James E. Rothman, Dr. Randy W. Schekman and Dr. Thomas C. Südhof for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells. This represents a paradigm shift in our understanding of how the eukaryotic cell, with its complex internal compartmentalization, organizes the routing of molecules packaged in vesicles to various intracellular destinations, as well as to the outside of the cell. Specificity in the delivery of molecular cargo is essential for cell function and survival.
Synaptotagmin functions as a Calcium Sensor: How Calcium Ions Regulate the fusion of vesicles with cell membranes during Neurotransmission
Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
2. Perspectives on Nitric Oxide in Disease Mechanisms
available on Kindle Store @ Amazon.com
3. Professor David Lichtstein, Hebrew University of Jerusalem, Dean, School of Medicine
Lichtstein's main research focus is the regulation of ion transport across the plasma membrane of eukaryotic cells. His work led to the discovery that specific steroids that have crucial roles, as the regulation of cell viability, heart contractility, blood pressure and brain function. His research has implications for the fundamental understanding of body functions, as well as for several pathological states such as heart failure, hypertension and neurological and psychiatric diseases.
Physiologist, Professor Lichtstein, Chair in Heart Studies at The Hebrew University elected Dean of the Faculty of Medicine at The Hebrew University of Jerusalem
Reporter: Aviva Lev-Ari, PhD, RN
4. Professor Roger J. Hajjar, MD at Mount Sinai School of Medicine
Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD
Aviva Lev-Ari, PhD, RN
5. Seminal Curations by Dr. Aviva Lev-Ari on Genetics and Genomics of Cardiovascular Diseases with a focus on Conduction and Cardiac Contractility
Aviva Lev-Ari, PhD, RN
- Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis
Aviva Lev-Ari, PhD, RN
- Genomics & Genetics of Cardiovascular Disease Diagnoses: A Literature Survey of AHA's Circulation Cardiovascular Genetics, 3/2010 – 3/2013
Aviva Lev-Ari, PhD, RN and Larry H. Bernstein, MD, FCAP
- Cardiac Contractility & Myocardium Performance: Ventricular Arrhythmias and Non-ischemic Heart Failure – Therapeutic Implications for Cardiomyocyte Ryanopathy (Calcium Release-related Contractile Dysfunction) and Catecholamine Responses
Justin Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
Other related research by the Team of Leaders in Pharmaceutical Business Intelligence published on the Open Access Online Scientific Journal
See References to articles at the end of this article on
- ION CHANNEL and Cardiovascular Diseases
- Calcium Role in Cardiovascular Diseases – The Role of Calcium Calmodulin Kinase (CKCaII) and Ca(2) flux
- Mitochondria and Oxidative Stress Role in Cardiovascular Diseases
Thus, the following article follows a series of articles on ion-channels and cardiac contractility mentioned, above. The following article is closely related to the work of Prof. Lichtstein.
These investigators studied the possible correlation between
- Myocardial Ischemia (Coronary Artery Disease (CAD)) aka Ischemic Heart Disease (IHD) and
- single-nucleotide polymorphisms (SNPs) genes encoding several regulators involved in Coronary Blood Flow Regulation (CBFR), including
- ion channels acting in vascular smooth muscle and/or
- endothelial cells of coronary arteries.
They completely analyzed exon 3 of both KCNJ8 and KCNJ11 genes (Kir6.1 and Kir6.2 subunit, respectively) as well as
- the whole coding region of KCN5A gene (Kv1.5 channel).
- to identify individuals at relatively low-risk for cardiovascular disease
- an independent protective role of the
- rs5215_GG against developing CAD and
- a trend for rs5219_AA to be associated with protection against coronary microvascular dysfunction
Their findings are a lead into further investigations on ion channels and IHD affecting the microvasculature.
Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease
BasicResCardiol(2013)108:387 http//dx.dio.org/10.1007/s00395-013-0387-4
F Fedele1•M Mancone1•WM Chilian2•P Severino2•E Canali•S Logan•ML DeMarchis3•M Volterrani4•R Palmirotta3•F Guadagni3
1Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences,Sapienza University of Rome, UmbertoI Policlinic, Rome, Italy e-mail:email@example.com
2Department of Integrative Medical Sciences, Northeastern Ohio Universities College of Medicine, Rootstown,OH
3Department of Advanced Biotechnologies and Bioimaging, IRCCS San Raffaele Pisana,Rome,It
4Cardiovascular Research Unit, Department of Medical Sciences, Centre for Clinical and Basic Research, Raffaele Pisana, Rome, Italy (CBFR)
BasicResCardiol(2013)108:387 http//dx.dio.org/10.1007/s00395-013-0387-4
This article is published with open access at Springerlink.com
Conventionally,ischemic heart disease (IHD) study is equated with large vessel coronary disease (CAD). However, recent evidence has suggested
- a role of compromised microvascular regulation in the etiology of IHD.
Because regulation of coronary blood flow likely involves
- activity of specific ion-channels, and
- key factors involved in endothelium-dependent dilation,
genetic anomalies of ion-channels or specific endothelial-regulators may underlie coronary microvascular disease.
We aimed to evaluate the clinical impact of single-nucleotide polymorphisms in genes encoding for
- ion-channels expressed in the coronary vasculature and the possible
- correlation with IHD resulting from microvascular dysfunction.
242 consecutive patients who were candidates for coronary angiography were enrolled. A prospective, observational, single-center study was conducted,
- analyzing genetic polymorphisms relative to
(1) NOS3 encoding for endothelial nitric oxide synthase (eNOS);
(2) ATP2A2 encoding for the Ca/H-ATP-ase pump (SERCA);
(3) SCN5A encoding for the voltage-dependent Na channel (Nav1.5);
(4) KCNJ8 and in KCNJ11 encoding for the Kir6.1and Kir6.2 subunits
of genetic K-ATP channels, respectively;and
(5) KCN5A encoding for the voltage-gated K channel (Kv1.5).
No significant associations between clinical IHD manifestations and
- polymorphisms for SERCA, Kir6.1, and Kv1.5. were observed (p[0.05),
whereas specific polymorphisms detected in eNOS, as well as in Kir6.2 and Nav1.5 were found to be correlated with
- IHD and microvascular dysfunction.
Interestingly, genetic polymorphisms of ion-channels seem to have an important clinical impact
- influencing the susceptibility for microvascular dysfunction and (IHD,
- independent of the presence of classic cardiovascular risk factors: atherosclerosis
Keywords: Ion-channels, Genetic polymorphisms, Coronary microcirculation, Endothelium, Atherosclerosis Ischemic heart disease
Historically, in the interrogation of altered vascular function in patientswith ischemic heart disease (IHD), scientists have focused their attention on the correlation between
- endothelial dysfunction and
- atherosclerosis [11, 53, 65, 67].
The endothelium-independent dysfunction in coronary microcirculation and its possible correlations with
- atherosclerotic disease and
- myocardial ischemia has not been extensively investigated.
In normal conditions, coronary blood flow regulation (CBFR) is mediated by several different systems, including
- endothelial,
- nervous,
- neurohumoral,
- myogenic, and
- metabolic mechanisms [2, 10, 14, 15, 63, 64, 69].
Physiologic CBFR depends also on several ion channels, such as
- ATP-sensitive potassium (KATP) channels,
- voltage-gated potassium (Kv) channels,
- voltage-gated sodium (Nav) channels, and others.
Ion channels regulate the concentration of calcium in both
- coronary smooth muscle and endothelial cells, which
- modulates the degree of contractile tone in vascular muscle and
- the amount of nitric oxide that is produced by the endothelium
Ion channels play a primary role in the rapid response of both
- the endothelium and vascular smooth muscle cells of coronary arterioles
- to the perpetually fluctuating demands of the myocardium for blood flow
[5, 6, 13, 18, 33, 45, 46, 51, 52, 61, 73, 75].
Despite this knowledge, there still exists an important gap about
- the clinical relevance and
- causes of microvascular dysfunction in IHD.
By altering the overall
- regulation of blood flow in the coronary system,
- microvascular dysfunction could alter the normal distribution of shear forces in large coronary arteries
Proximal coronary artery stenosis could
- contribute to microvascular dysfunction [29, 60]. But
- ion channels play a critical role in microvascular endothelial
- and smooth muscle function.
Therefore, we hypothesized that alterations of coronary ion channels could be the primary cause in a chain of events leading to
- microvascular dysfunction and
- myocardial ischemia,
independent of the presence of atherosclerosis.
Therefore, the objective of our study was to evaluate the possible correlation between
- IHD and single-nucleotide polymorphisms (SNPs) for genes encoding several regulators involved in CBFR, including
- ion channels acting in vascular smooth muscle and/or
- endothelial cells of coronary arteries.
Implications of the present work. This study describes the possible correlation of polymorphisms in genes encoding for CBFR effectors (i.e., ion channels, nitric oxide synthase, and SERCA) with the susceptibility for microcirculation dysfunction and IHD.
Our main findings are as follows: (Group 3 – Normal Patients – anatomically and functionally normal coronary arteries).
- In Group 3, the genotype distribution of SNP rs5215 (Kir6.2/KCNJ11) moderately deviates from the HW equilibrium (p = 0.05).
- In Group 1 (CAD), the polymorphism rs6599230 of Nav1.5/SCN5A showed deviation from HW equilibrium (p = 0.017).
- The genotypic distribution of rs1799983 polymorphism for eNOS/NOS3 is inconsistent with the HW equilibrium in groups 1, 2, and 3 (p = 0.0001, p = 0.0012 and p = 0.0001, respectively).
Haplotype analyses revealed that there is no linkage disequilibrium between polymorphisms of the analyzed genes. There was no significant difference in the prevalence of T2DM (p = 0.185) or dyslipidemia (p = 0.271) between groups, as shown in Table2. In regards to genetic characteristics, no significant differences between the three.
1. A marked HW disequilibrium in the genotypic distribution of rs1799983 polymorphism for eNOS/NOS3 was observed in all three populations. Moreover, this SNP seems to be an independent risk factor for microvascular dysfunction, as evidenced by multivariate analysis;
2. The SNPs rs5215_GG, rs5218_CT, and rs5219_AA for Kir6.2/KCJ11 could reduce susceptibility to IHD, since they were present more frequently in patients with anatomically and functionally normal coronary arteries;
3. In particular, with regard to rs5215 for Kir6.2/KCJ11, we observed a moderate deviation from the HW equilibrium in the genotypic
distribution in the control group. In addition, this genotype appears to be an independent protective factor in the development of IHD, as evidenced by multivariate analysis;
4. Furthermore, the trend observed for the SNP rs5219_AA of Kir6.2/KCNJ11 may suggest an independent protective factor in the development of coronary microvascular dysfunction
5. The rs1805124_GG genotype of Nav1.5/SCN5A seems to play a role against CAD;
6. No association seems to exist between the polymorphisms of SERCA/ATP2A2, Kir6.1/KCNJ8, and Kv1.5/KCNA5 and the presence of IHD;
7. All groups are comparable regarding the cardiovascular risk factors of T2DM and dyslipidemia, illustrating a potentially important implication of genetic polymorphisms in the susceptibility to IHD.
It is important to underline that the control group (Group 3) is a high-risk population, because of their cardiovascular risk factors
- hypertension = 17 %,
- dyslipidemia = 41.4 %,
with an appropriate indication for coronary angiography, in accordance with current guidelines. Nevertheless, these patients were demonstrated to have both anatomically and functionally normal coronary arteries. Moreover, as shown in Tables 2 and 3, we observed that
- rs5215_GG, rs5218_CT and rs5219_AA for Kir6.2/KCNJ11 had a higher prevalence in this group,compared to patients with CAD
- and patients with microvascular dysfunction.
Moreover, as shown in Table 4, the presence of the rs5215_GG polymorphism for the Kir6.2 subunit was
- inversely correlated with the prevalence of cardiovascular risk factors and CAD,whereas
- rs5219_AA of the Kir6.2 subunit trended towards an inverse correlation with coronary microvascular dysfunction.
On the other hand, the SNP rs1799983_GT of eNOS was
- confirmed to be an independent risk factor for microvascular dysfunction.
Our data suggest that the presence of certain genetic polymorphisms may represent a non-modifiable protective factor that could be used
- to identify individuals at relatively low-risk for cardiovascular disease,
- regardless of the presence of T2DM and dyslipidemia.
Current Clinical and Research Context
In normal coronary arteries, particularly the coronary microcirculation, there are several different mechanisms of CBFR, including
- endothelial, neural, myogenic, and metabolic mediators [2, 8, 10, 12, 14, 15, 37, 55, 63, 64, 69].
In particular, endothelium-dependent vasodilation acts mainly via eNOS-derived nitric oxide (NO) in response to acetylcholine and shear stress.
- NO increases intracellular cyclic guanosine monophosphate. It also causes vasodilation via
- activation of both K-Ca channels and K-ATP channels.
Recent data suggested a pathophysiologically relevant role for the polymorphisms of eNOS/NOS3 in human coronary vasomotion [40–43]. Our data suggest that rs1799983_GT at exon 7 (Glu298Asp, GAG-GAT) of eNOS/NOS3 represents
- an independent risk factor for coronary micro-vascular dysfunction, which agrees with a recent meta-analysis reporting an
- association of this SNP with CAD in Asian populations [74]. In addition,
- this SNP has been associated with endothelial dysfunction, although the mechanisms are not well defined [30].
Consistently, a recent study performed on 60 Indian patients with documented history of CAD reported a significantly higher frequency of rs1799983 (p.05) compared to control subjects, indicating that
- variations in NOS3 gene may be useful clinical markers of endothelial dysfunction in CAD [54].
- high-grade coronary stenosis or occlusion [19].
- potassium channels determine the resting membrane potential (Em) and serve as targets of endogenous and therapeutic vasodilators [9, 27].
- The K-ATP channels couple cell metabolic demand to conductance, via pore-forming (Kir6.1 and/or Kir6.2) subunits and regulatory
[sulphonylurea-binding (SUR 1, 2A, or 2B)] subunits.
- Kir6.x allows for channel inhibition by ATP, while SURx is responsible for channel activation by ADP and Mg2+.
- consequent hyperpolarization, resulting in
- voltage-gated calcium channel closure,
- decreased Ca2+ influx, and ultimately
- vasodilation [1, 5, 18, 20, 21, 33, 61, 62, 73, 75].
Our data do not support any significant difference regarding the Kir6.1 subunit of the K-ATP channel. On the other hand, this study suggests
- an important role of specific SNPs for the Kir6.2 subunit (Tables 2, 3)—i.e., rs5215, rs5219, and rs5218—
in the susceptibility to IHD and microvascular dysfunction. These SNPs are among the most studied K-ATP channel polymorphisms, especially in the context of diabetes mellitus. In fact, in both Caucasian and Asian populations, these three SNPs as well as other genetic polymorphisms for the KCNJ11 gene have been associated with diabetes mellitus [34, 35, 44, 50, 57, 58, 70].
Nevertheless, the precise
- structure–function impacts of the various amino acid substitutions remain unclear.
The rs5215 and rs5219 polymorphisms, also known as I337V and E23K, respectively, are highly linked with reported
- concordance rates between 72 and 100 % [22, 23, 56].
The high concordance between rs5219 and rs5215 suggests that these polymorphisms
- may have originated in a common ancestor, further indicating a
- possible evolutionary advantage to their maintenance in the general population [49].
In our study, multivariate analysis suggests both an independent protective role of the
- rs5215_GG against developing CAD and
- a trend for rs5219_AA to be associated with protection against coronary microvascular dysfunction (Table 4a, b).
- The variant rs5215_GG is a missense SNP located in the gene KCNJ11 at exon 1009 (ATC-GTC) and results in
the substitution of isoleucine (I) residue with valine (V) [23].
Future studies are necessary to better understand the influence of this single amino acid variant on the function of the channel.
- are both impaired in diabetes mellitus [39].
- independent of the presence of either diabetes mellitus or dyslipidemia.
- regardless of the presence of T2DM and/or dyslipidemia.
However, further studies are necessary to confirm these findings. In this context, to better investigate the implications of genetic variation in the K-ATP channel,
- future studies should include ion channel's functional modification due to the SNPs and analysis of SUR subunits.
More than 40-kV channel subunits have been identified in the heart, and sections of human coronary smooth muscle cells demonstrate Kv1.5 immunoreactivity [16, 17, 27, 38]. Through constant regulation of smooth muscle tone, Kv channels contribute to the control of coronary microvascular resistance [4, 7]. Pharmacologic molecules that inhibit Kv1.5 channels such as
- pergolide [25],
- 4-amino-pyridine [32], and
- correolide [17]
lead to coronary smooth muscle cell contraction and block the coupling between
- cardiac metabolic demand and
- coronary blood flow.
However, no significant differences were identified between the study groups in terms of the particular polymorphisms for Kv1.5 that were analyzed in this study. Expression of
- the voltage-dependent Na+ channel (Nav) has been demonstrated in coronary microvascular endothelia cells [3, 66].
Our analysis reveals a possible implication of the polymorphism rs1805124_GG for Nav1.5 channel with the presence of anatomically and functionally normal coronary arteries. This SNP leads to a homozygous 1673A-G transition, resulting in a His558-to-Arg (H558R) substitution. It is important to underline that
- our data are the first to correlate the polymorphism rs1805124_GG with IHD.
Further research is necessary to confirm the observed implication.
Finally, we have analyzed the sarco/endoplasmic reticulum calcium transporting Ca2+-ATPase (SERCA), which is fundamental in the regulation of intracellular Ca2+ concentration [6].
SERCA is an intracellular pump that
- catalyzes the hydrolysis of ATP coupled with the
- translocation of calcium from the cytosol into the lumen of the sarcoplasmic reticulum.
Although this pump plays a critical role in regulation of the contraction/relaxation cycle, our analysis did not reveal any apparent association between
- genetic variants of SERCA and the
- prevalence of microvascular dysfunction or IHD.
- with CAD or microvascular dysfunction and those with both anatomically and functionally normal coronary arteries.
- the precise manners by which specific genetic polymorphisms affect ion channel function and expression
Limitations and future perspectives
Notable limitations of this pilot study are as follows:
- sulfonylurea receptor, SURx and further coronary ion channels (e.g., calcium-dependent K channels), as well as
- in vitro evaluation of ion channel activity by patch clamp and analysis of channel expression in the human cardiac tissue.
Moreover, to better address the significance of microvascular dysfunction in IHD, it could be interesting to analyze
- typical atherosclerosis susceptibility genes (e.g., PPAP2B, ICAM1, et al.).
In this prospective, observational, single-center study – 242 consecutive patients admitted to our department were enrolled with
- the indication to undergo coronary angiography .
All patients matched inclusion criteria
- age [18];
- suspected or documented diagnosis of acute coronary syndrome or stable angina
- with indication(s) for coronary angiography, in accordance with current guidelines [36, 68], and
- the same ethno-geographic Caucasian origin) and
Exclusion Criteria
- previous allergic reaction to iodine contrast,
- renal failure,
- simultaneous genetic disease,
- cardiogenic shock,
- non- ischemic cardiomyopathy
All patients signed an informed consent document –
prior to participation in the study, which included
- acknowledgement of the testing procedures to be performed
(i.e., coronary angiography; intracoronary tests; genetic analysis, and processing of personal data).
The study was approved by the Institution's Ethics Committee.
All clinical and instrumental characteristics were collected in a dedicated database.
Study Design
(a) Standard therapies were administered, according to current guidelines [36, 68].
(b) An echocardiography was performed before and after coronary angiography
(c) Coronary angiography was performed using radial artery or femoral artery
Judkins approach via sheath insertion.
(d) In patients showing normal epicardial arteries, intracoronary functional tests
were performed through Doppler flow wire to evaluate
- both endothelium-dependent microvascular function
[via intracoronary (IC) infusion of acetylcholine (2.5–10 lg)] and
- nonendothelium-dependent microvascular function
[via IC infusion of adenosine (5 lg)] [31].
(e) In all enrolled patients, a peripheral blood sample for genetic analysis was taken.
On the basis of the coronary angiography and the intracoronary functional tests,
- the 242 patients were divided into three groups (see also Fig. 1).
- Group 1: 155 patients with anatomic coronary alteration
(comprising patients with acute coronary syndrome and chronic stable angina).
- microvascular dysfunction defined as coronary flow reserve (CFR) \ 2.5
- after IC infusion of acetylcholine and adenosine].
- Group 2: 46 patients with functional coronary alteration
[normal coronary arteries as assessed by angiography, and
- as assessed by angiography and with normal functional tests
(CFR C 2.5 after intracoronary infusion of acetylcholine and adenosine) (Fig. 1).
- as assessed by angiography and with normal functional tests
- Group 3: 41 patients with anatomically and functionally normal coronary arteries
Fig. 1 Study design: 242 consecutive not randomized patients matching inclusion and exclusion criteria were enrolled.
In all patients, coronary angiography was performed, according to current ESC/ACC/AHA guidelines. In patients with
angiographically normal coronary artery, intracoronary functional tests were performed. In 242 patients
(155 with coronary artery disease, 46 patients with micro-vascular dysfunction, endothelium and/or non-endothelium
dependent, and 41 patients with anatomically and functionally normal coronary arteries) genetic analysis was performed.
Genetic Analysis
In conformity with the study protocol, ethylenediaminetetraacetic acid (EDTA) whole blood samples were collected according
to the international guidelines reported in the literature [48]. Samples were transferred to the Interinstitutional Multidisciplinary
BioBank (BioBIM) of IRCCS San Raffaele Pisana (Rome) and stored at -80 C until DNA extraction. Bibliographic research by
PubMed and web tools OMIM (http://www.ncbi.nlm.nih.gov/omim), Entrez SNP (http://www.ncbi.nlm.nih.gov/snp), and
Ensembl (http://www.ensembl.org/index.html) were used to select variants of genes involved in signaling pathways
- related to ion channels and/or reported to be associated with
- microvascular dysfunction and/or myocardial ischemia and/or
- diseases correlated to IHD, such as diabetes mellitus.
- NOS3 (endothelial nitric oxide synthase, eNOS),
- ATP2A2 (Ca2+/H+-ATPase pump, SERCA2),
- SCN5A (voltage-dependent Na+ channel,
- Nav1.5),
- KCNJ11 (ATP-sensitive K+ channel, Kir6.2 subunit),
- KCNJ8 (ATP-sensitive K+ channel, Kir6.1 subunit) and
- KCNA5 (voltage-gated K+ channel, Kv1.5).
In particular, we completely analyzed by direct sequencing
- exon 3 of KCNJ8 (Kir6.1 subunit), which includes eight SNPs, as well as
- the whole coding region of KCNA5 (Kv1.5 channel), which includes 32 SNPs and
- four previously described variants [26, 47, 71, 72].
- the whole coding region of KCNJ11 (Kir6.2 subunit), for which sequence variants are described [26, 28].
All SNPs and sequence variants analyzed—a total of 62 variants of 6 genes—are listed in Table 1.
DNA was isolated from EDTA anticoagulated whole blood using the MagNA Pure LC instrument and theMagNA Pure LC
total DNA isolation kit I (Roche Diagnostics, Mannheim, Germany) according to the manufacturer's instructions. Standard
PCR was performed in a GeneAmp PCR System 9700 (Applied Biosystems, CA) using HotStarTaq Master Mix
(HotStarTaq Master Mix Kit, QIAGEN Inc, CA). PCR conditions and primer sequences are listed in Table 1.
In order to exclude preanalytical and analytical errors, all direct sequencing analyses were carried out on both
strands using Big Dye Terminator v3.1 Cycle Sequencing kit (Applied Biosystems), run on an ABI 3130
Genetic Analyzer (Applied Biosystems), and repeated on PCR products obtained from new nucleic acid extractions.
All data analyses were performed in a blind fashion.
Statistical Analysis
This report, intended as pilot study, is the first to compare
- the prevalence of SNPs in genes encoding several effectors (including ion channels)
- involved in CBFR between these groups of patients.
No definite sample size could be calculated to establish a power analysis. groups of patients. However, assuming
- a 15 % prevalence of normal macrovascular and microvascular coronary findings in unselected patients
undergoing coronary angiography,
we estimated that
- a sample size of at least 150 patients could enable the computation of two-sided 95 % confidence intervals for
- such prevalence estimates ranging between -5.0 and + 5.0 %.
The significance of the differences of observed alleles and genotypes between groups, as well as
- analysis of multiple inheritance models for SNPs were also tested
(co-dominant, dominant, recessive, over-dominant and log-additive)
- using a free web-based application (http://213. 151.99.166/index.php?module=Snpstats)
- designed from a genetic epidemiology point of view to analyze association studies.
Akaike Information Criterion (AIC) was used to determine the best-fitting inheritance model for analyzed SNPs,
- with the model with the lowest AIC reflecting the best balance of goodness-of-fit and parsimony.
Moreover, the allelic frequencies were estimated by gene counting, and the genotypes were scored. For each gene,
- the observed numbers of each genotype were compared with those expected for a population in Hardy–Weinberg (HW) equilibrium
- using a free web-based application (http://184.108.40.206/index.php?module=Snpstats) [59].
Linkage disequilibrium coefficient (D0) and haplotype analyses were assessed using the Haploview 4.1 program.
Statistical analysis was performed using SPSS software package for Windows v.16.0 (SPSS Inc., Chicago, IL).
All categorical variables are expressed as percentages, and all continuous variables as mean ± standard deviation.
Differences between categorical variables
- were analyzed by Pearson's Chi-SQ test.
Given the presence of three groups, differences between continuous variables, were calculated using
(including the number of SNPs tested),
- one-way ANOVA; a post-hoc analysis with Bonferroni correction was made for multiple comparisons.
Univariate and multivariate logistic regression analyses
- the independent impact of genetic polymorphisms on
- coronary artery disease and microvascular dysfunction,
were performed to assess the independent impact of
- genetic polymorphisms on coronary artery disease
and microvascular dysfunction,
while adjusting for other confounding variables. The following parameters were entered into the model:
- age,
- male gender,
- type 2 diabetes mellitus (T2DM),
- systemic arterial hypertension,
- dyslipidemia,
- smoking status, and
- family history of myocardial infarction (MI).
Only variables with a p value < 0.10 after univariate analysis were entered
- into the multivariable model as covariates.
A two-tailed p < 0.05 was considered statistically significant.
Definition of Cardiovascular Risk Factors
Patients were classified as having T2DM if they had
- fasting levels of glucose of >126 mg/dL in two separate measurements or
- if they were taking hypoglycemic drugs.
Systemic arterial hypertension was defined as
- systolic blood pressure > 140 mmHg / diastolic blood pressure > 90 mmHg
- in two separate measurements or
- if the patient was currently taking antihypertensive drugs.
Dyslipidemia was considered to be present if
- serum cholesterol levels were>220 mg/dL or
- if the patient was being treated with cholesterol-lowering drugs.
Family history of MI was defined as a first-degree relative with MI before the age of 60 years.
- nitric oxide synthase,
- the SERCA pump, and
- ion channels
- were screened for sequence variations using PCR amplification and
- direct DNA sequencing analysis
in the population of
- 155 patients with CAD (group 1),
- 46 patients with microvascular dysfunction (group 2), and
- 41 patients with normal coronary arteries and
- normal endothelium dependent and endothelium-independent vasodilation (group 3).
- SNP rs5215 (Kir6.2/KCNJ11) moderately deviates from the HW equilibrium (p = 0.05).
- rs6599230 of Nav1.5/SCN5A showed deviation from HW equilibrium (p = 0.017).
- eNOS/NOS3, SERCA/ATP2A2, Nav1.5/SCN5A, Kir6.1/KCNJ8, or Kv1.5/KCNA5
- rs5215_GG, and
- rs5219_AA of Kir6.2/KCNJ11 were observed,
Table 3 displays significant differences between normal subjects (group 3) and
- patients with either CAD (group 1) or microvascular dysfunction (group 2).
When correcting for other covariates as risk factors, the rs5215_GG genotype of Kir6.2/KCNJ11 was found to be
- significantly associated with CAD after multivariate analysis (OR = 0.319, p = 0.047, 95 % CI = 0.100–0.991), evidencing
- a ''protective'' role of this genotype, as shown in Table 4a.
Similarly, a trend that supports this role of Kir6.2/KCNJ11 was also observed
- in microvascular dysfunction for rs5219 AA. In contrast,
- rs1799983_GT for eNOS/NOS3 was identified as an independent risk factor
following multivariate analysis (Table 4b), which agrees with literature findings as described below.
SOURCE for TABLES
BasicResCardiol(2013)108:387 http//dx.dio.org/10.1007/s00395-013-0387-4
Conflict of interest On behalf of all authors, the corresponding author states that there is no conflict of interest.
Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
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7. Chen TT, Luykenaar KD, Walsh EJ, Walsh MP, Cole WC (2006) Key role of Kv1 channels in vasoregulation. Circ Res 99:53–60. doi:10.1161/01.RES.0000229654.45090.57
8. Cohen KD, Jackson WF (2005) Membrane hyperpolarization is not required for sustained muscarinic agonist-induced increases in intracellular Ca2+ in arteriolar endothelial
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…. 75
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Basic Res Cardiol (2013) 108:387 http://dx.doi.org/10.1007/s00395-013-0387-4
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Larry H Bernstein, MD, FCAP, Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
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FROM THE ARCHIVES: In 2013, I received a controversial 600-plus page manual used by the military to train its Equal Opportunity officers teaches that "healthy, white, heterosexual, Christian" men hold an unfair advantage over other races, and warns in great detail about a so-called "White Male Club."
"Simply put, a healthy, white, heterosexual, Christian male receives many unearned advantages of social privilege, whereas a black, homosexual, atheist female in poor health receives many unearned disadvantages of social privilege," reads a statement in the manual created by the Defense Equal Opportunity Management Institute (DEOMI).
The manual, which was obtained by the Todd Starnes Radio Show, also instructs troops to "support the leadership of people of color. Do this consistently, but not uncritically," the manual states.
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The Equal Opportunity Advisor Student Guide is the textbook used during a three month DEOMI course taught at Patrick Air Force Base in Florida. Individuals who attend the training lead Equal Opportunity briefings on military installations around the nation.
The 637-page manual covers a wide range of issues from racism and religious diversity to cultural awareness, extremism and white privilege.
I obtained a copy of the manual from an Equal Opportunity officer who was disturbed by the course content and furious over the DEOMI's reliance on the Southern Poverty Law Center for information on "extremist" groups.
"I'm participating in teaching things that are not true," the instructor told me. He asked not to be identified because he feared reprisals.
"I should not be in a position to do that," he said. "It violates Constitutional principles, but it also violates my conscience. And I'm not going to do it – not going to do it."
DEOMI instructors were also responsible for briefings at bases around the country that falsely labeled evangelical Christians, Catholics and a number of high-profile Christian ministries as domestic hate groups.
I contacted the Pentagon as well as the DEOMI multiple times for comment on this story, but so far they have not responded to my requests.
DEOMI opened in 1971 in response to the civil rights movement. It's responsible for Equal Opportunity/Equal Employment Opportunity education and training for military active duty and reservists, according to its website.
The subject of white privilege emerged in a 20-page section titled, "Power and Privilege."
"Whites are the empowered group," the manual declares. "White males represent the haves as compared to the have-nots."
The military document advises personnel to "assume racism is everywhere, every day" and "notice code words for race." They are also instructed to "understand and learn from the history of whiteness and racism."
"Assume racism is everywhere, everyday," read a statement in a section titled, 'How to be a strong 'white ally.'"
"One of the privileges of being white is not having to see or deal with racism all the time," the manual states. "We have to learn to see the effect that racism has."
On page 181 of the manual, the military points out that status and wealth are typically passed from generation to generation and "represent classic examples of the unearned advantages of social privilege."
"As such, the unfair economic advantages and disadvantages created long ago by institutions for whites, males, Christians, etc. still affect socioeconomic privilege today," the manual states.
The guide also points out that whites are over-represented and blacks are underrepresented in positive news stories, that middle class blacks live in poorer neighborhoods than middle class whites and that even though there are more white criminals than any other race, the news coverage of black criminals is about equal to the news coverage of white criminals.
The military manual goes into great detail about a so-called "White Male Club."
"In spite of slave insurrections, civil war, the 13th, 14th, and 15th amendments, the women's suffrage movement leading to the 19th amendment, the civil rights movement, urban rebellions and the contemporary feminist movement, the club persists," the document states.
DEOMI states that "full access to the resources of the club still escape the vision of equitable distribution."
The military also implies that white Americans may be in denial about racism.
In a section titled, "Rationalizations for Retaining Privilege and Avoiding Responsibilities," the military lays out excuses white people use.
"Today some white people may use the tactic of denial when they say, 'It's a level playing field; this is a land of equal opportunity,'" the manual reads. "Some white people may be counterattacking today by saying political correctness rules the universities or they want special status."
DEOMI points out that if "white people are unable to maintain that the atrocities are all in the past, they may switch to tactics to make a current situation seem isolated."
They said some of the ways whites may claim to be victims include saying things like, "I have it just as bad as anyone else," "They're taking away our jobs," or "White people are under attack."
The military concludes the section by urging students to "understand and learn from the history of whiteness and racism" and "support the leadership of people of color."
I called former Congressman and Lt. Col. Allen West (ret.) to get his take on the manual. In a nutshell – he wants a congressional investigation.
"This is the Obama administration's outreach of social justice into the United States military," he told me. "Equal Opportunity in the Army that I grew up in did not have anything to do with white privilege."
West said he is very concerned about the training guide.
"When the president talked about fundamentally transforming the United States of America, I believe he also had a dedicated agenda of going after the United States military," he said. "The priorities of this administration are totally whacked."
West said the DEOMI manual reminded him of a similar program inflicted on the military by President Clinton.
"They came down with a new training requirement called, 'Consideration of Others Training,'" he said. "The soldiers were supposed to sit around and go through vignettes and talk about their feelings."
I truly wish the Pentagon and the DEOMI would return my telephone calls. I'd like to know how teaching soldiers, airmen and sailors about white privilege and fomenting racial division helps them protect our nation from the enemy.


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50 years later, hotline to Moscow still relevant
FREDERICK, Md. (AP) — The Washington-Moscow Hot Line, used by U.S. and Russian leaders for frank discussions about crises including the 1967 Six-Day War and the Soviet Union's 1979 invasion of Afghanistan, marked its 50th birthday Thursday with the nations still grappling with competing interests in regional conflicts.
The direct connection established during the Cold War by a relatively simple telegraph system now includes telephone and email capabilities and will soon add video, said White House National Security Council spokeswoman Laura Lucas.
"The president continues to value the direct communications link between Washington and Moscow," Lucas wrote in an emailed response to questions from The Associated Press about the hotline that was used at key moments and helped contact between senior officials at the White House and in the Kremlin.
The next crisis could be just around the corner, said Roald Sagdeev, a former director of the Soviet space exploration program who spoke at an anniversary celebration at Fort Detrick, where the Army maintains a satellite link for the hotline.
"It's very important to make sure we can keep this, especially at the time of what's happening in Syria," Sagdeev, now a University of Maryland physics professor, said before the event. "We should stay with at least keeping what we have for the rainy day."
Despite popular myth and movie lore, the president doesn't use a red phone to talk with his Russian counterpart. In fact, the connection established in 1963 was for written communications only. A voice component was added two decades later as the system evolved from an undersea telegraph cable to today's exchange of data by both satellite and fiber-optics.
"The system is very robust, as you might imagine," said Craig Bouma, civilian executive officer of the Detrick Earth Station.
Bouma manages the twin satellite dishes and a staff of 16 civilian Army employees — eight technicians and eight linguists. They work around the clock to ensure the system is operating correctly. The station also handles secure communication lines for the Pentagon and the State Department, including a special link the nations use to alert each other to missile tests.
In June, the U.S. and Russia signed a pact to add a direct communication link to prevent the inadvertent escalation of misunderstood cybersecurity incidents.
Until February, the Washington-Moscow link was operated by Honeywell under a five-year, $8.4 million contract.
Bouma said the workers at Detrick have daily interaction with their Russian counterparts in written exchanges that sometimes reveal cultural differences.
"The Russians express themselves in very flowery text: 'Dear esteemed colleague, greetings. Welcome to the shift,'" Bouma said. "My linguist says that's very common in the Russian culture."
The link was set up after the 1962 Cuban missile crisis to avert the accidental outbreak of nuclear war. Known at the Pentagon as MOLINK, for "Moscow Link,' it went live Aug. 30, 1963, with the U.S.-generated message, "The quick brown fox jumped over the lazy dog's back 1234567890."
The hotline's first use in crisis mode came during the six-day Arab-Israeli war in 1967, according to Michael Bohn, a former White House Situation Room director and author of the forthcoming "Presidents in Crisis: Tough Decisions from Truman to Obama." He said Soviet Premier Alexei Kosygin sent a message to President Lyndon B. Johnson at 7:47 a.m. on June 5, 1967, after Israel pre-emptively attacked Egypt, Syria and Jordan. The message expressed Russia's hope that the U.S. government would "exert appropriate influence on the Government of Israel particularly since you have all opportunities of doing so."
Bohn said the leaders exchanged 19 messages during the Six-Day War. Johnson notably used it after Israel attacked the USS Liberty to assure Kosygin that other U.S. ships rushing to the Liberty's aid were not joining the hostilities.
Bohn also documented uses of the teletype link by presidents Richard M. Nixon, Jimmy Carter and Ronald Reagan.
Starting with President George H.W. Bush in the early 1990s, telephone calls have replaced written messages as the preferred mode of communication between the nations' leaders, Bohn said. He said that when the link was created, written messages were seen as a safer way of expressing oneself.
"In a tough situation, you have to be careful what you say. The process of sitting down and writing it out clears your head a little bit and makes you slow down a little bit and think twice — that's what people have told me," Bohn said.
The current system also enables emails and private chats, he said.
President Barack Obama uses the direct voice link to talk by phone with Russian President Vladimir Putin. They spoke as recently as March, when Obama phoned Putin to welcome Russian cooperation on international efforts to confront Iran's nuclear ambitions.
The upgrade to voice and email communications reflects changing times and technology, said James Goldgeier, dean of the American University School of International Service.
"You know, 50 years ago was a long time ago, and the abilities to communicate — it just wasn't as easy as it is today," he said. "We just take it for granted now that we can text and we can Skype and we can communicate immediately with anyone over a variety of different mechanisms, and even that we can see the people we communicate with."


text:
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text:
Chris Kyle, a former Navy SEAL and author of the best-selling book
American Sniper
, and a second person were shot and killed Saturday at a gun range in Erath County, U.S. Marshals said.
Late Saturday, Lancaster police arrested a man who they say matched the description of a man wanted in connection with the slayings. After a brief chase, officers arrested 25-year-old Eddie Ray Routh, according to Lancaster police spokesperson Kelly Hooten.
Reporting on the shootings, the Stephenville Empire-Tribune said Erath County Sheriff Tommy Bryant would not discuss the victims. But the newspaper said that a source working at Rough Creek Lodge, which has a gun range at which the newspaper reported the slayings occurred, confirmed that one of the victims was Kyle.
WFAA-TV (Channel 8) reported that Kyle was shot point-blank while helping another soldier who is recovering from post traumatic stress syndrome.
Erath County officials had issued an alert for authorities to be on the lookout for the gunman, who was believed to be armed and dangerous and driving a black Ford F-350 truck with large tires and rims.
The suspect was believed to be highly trained with military experience. The shooting location is 53 miles southwest of Fort Worth, according to WFAA.
Kyle grew up in Texas and spent much of his time riding horses and participating on the school rodeo team. His life quickly changed when he decided to go into the military and became a Navy SEAL. He deployed four times to Iraq. Kyle held the record for number of kills by an American sniper. The Pentagon has confirmed more than 150 of his kills. The previous record was 109. For his service, Kyle was awarded two Silver Stars and five Bronze Stars with Valor. His autobiography,
American Sniper
, was released last year.
"When I grew up, I only had two dreams," he
. "One was to be a cowboy and another was to be in the military. I grew up extremely patriotic and riding horses. I went to college and was working at a ranch up there. Sun up, sun down, I was in a saddle. By the time I was 24, I decided it was time to go into the military and try it out. It wasn't exactly the SEALs I was looking for at the time. I just wanted to go into the military and be the best."
Kyle said he wrote his book because, "I wanted to be able to let people know about the sacrifices that not only people in the service make, but what their families go through. I knew this would give me a voice so I could speak about the guys I know who were killed. I wanted to get their story out and I wanted to raise awareness for veterans."
"It is so hard becoming a civilian. When you are in the military, everything you do is for the greater good. And as a civilian, everything you do is for your own good. When you're in the military, you are facing life and death every day. And then you come home and hear people who are unhappy about the little things. And you think, are you kidding me? Two weeks ago, I was shot. And this is your problem. …They train us how to become warriors, but then they don't teach us and train us how to become businessmen."


text:
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3H+KT+S, 62 m² 870 €/month
3. krs
Soon to be vacant: 1.11.2023
When you apply for an ARA-funded house, your assets must fit within the limits set by the state. Check the attached wealth and income limit tables to see if you can apply for housing at M2-Kodit. Assets refer to, among other things, housing shares, real estate, funds and securities.Read more about asset limits