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What you Need to Know to Successfully Market and Sell an Over-the-Counter Drug Product in the United States; and Strategic Advice for Avoiding FDA Enforcement Action
Product ID: 702840
Training Level: Intermediate to Advanced
- Duration: 120 Min
Customer Care
Fax: +1-650-565-8542
Email: email@example.com
This training on OTC drug marketing is intended to be a practice-based online workshop that will explain what you need to know to successfully market and sell an Over-the-Counter drug product in the United States; and provide strategic advice for avoiding FDA enforcement action.
Why Should Attend:
This online workshop will provide attendees with a comprehensive review and understanding of the process for designing, developing, manufacturing and selling an OTC Drug Product in the U.S. For purposes of regulatory compliance, the workshop will also focus on FDA's regulatory requirement covering OTC drug products; and offer strategic recommendations for not only success but also for mitigating the risk of FDA enforcement risk and general liability.
Some of the topics to be covered during this online workshop will include:
- FDA's requirements for marketing and selling an OTC drug product in the U.S.
- Methods for determining whether a drug product can be marketed and sold as an OTC drug
- The regulatory pathways for commercialization of an OTC drug product
- The OTC Monograph process and Understanding how to Use Them
- FDA's permitted Rx-to-OTC Switch Process
- How to properly label and market an OTC drug product, and
- Strategies for mitigating regulatory enforcement risks and liability.
Learning objectives:
- Gain a comprehensive understanding of how OTC Drug Products are regulated in the U.S.
- Be able to distinguish between a potential Rx pharmaceutical product and an OTC drug.
- Learn the difference between the various pathways for commercializing an OTC Drug Product.
- Understand how to identify and successfully navigate an OTC Drug Monograph.
- Recognize when reliance on a Proposed Rule, Final Rule and/or Drug Monograph is appropriate.
- Know how to determine whether an Ingredient is considered Safe or GRAS/E for use in an OTC Drug and understand the difference between Category I, II and II Ingredient designations.
- Identify the required elements of a compliant OTC Drug Label.
- Recognize potential marketing and promotional risks.
- Possess a working knowledge of the Rx-to-OTC Switch Process.
Areas Covered:
- FDA's regulation of over-the-counter drug products or OTC drugs.
- Bringing an OTC drug to market under an OTC monograph.
- Where to find FDA's list of existing monographs and identification of the various product categories covered by monographs.
- An introduction to FDA's Rx-to-OTC Switch procedures and the benefits / challenges of pursuing such an option
- Labeling an OTC drug product
- Potential FDA enforcement risks
Who will benefit:
- Regulatory Affairs Professionals, Managers, Consultants, Scientists, Research Analysts, State Policy Officials, Investment Analysts, Venture Capitalists.
- OTC, Consumer Product and Drug Companies; Start-ups, Foreign Drug Manufacturers, Importers; Food and Dietary Supplement manufacturers and distributors exploring new potential product sectors
- Financial analysts and investors watching the pharmaceutical, OTC, consumer product, life sciences and biotech industries
Karl Nobert, is a food and drug regulatory attorney with the law firm of Squire Sanders in Washington, DC. He provides regulatory advice and counseling to domestic and international pharmaceutical, OTC and consumer product companies on issues related to the U.S. Food and Drug Administration's regulation of the manufacture, labeling, distribution, marketing and sale of drugs, dietary supplements, devices and food. He regularly works with companies on labeling and marketing compliance; provides counseling to clients during FDA enforcement proceedings; and supports due diligence efforts related to product line and company acquisitions in the pharmaceutical, OTC drug and dietary supplement sectors.
Topic Background:
Have a Headache? Back from lunch and now experiencing mild occasional Heart Burn? Suffer from Allergies? Been stuck in bed with a Cough, Sore Throat, Nasal Congestion and a Fever you just can't shake? Pitched the tent in Poison Ivy on last weekend's family camping trip by mistake? Use Deodorant?
Anyone who has ever has suffered from these or similar occasional symptoms and conditions has likely relied upon an Over-the-Counter Drug Product or "OTC Drug" to feel better. Go into any CVS Retail Pharmacy, Wal-Mart, Meijer Grocery Story, Rite Aid Retail Pharmacy or Target in the United States; and you are guaranteed to find store shelves lined with hundreds or even thousands of different OTC Drug products. Some of the most recognized OTC drug products include ibuprofen tablets, anti-itch creams, nasal decongestant sprays, cough syrups, antacids, allergy medicines and topical pain relievers. Available without a prescription and bought right off the store shelf, OTC drugs are safe and effective when properly labeled and used as intended.
Over-the-Counter Drug Products or "OTC Drugs" include many of the well-known products that we use to treat or control the symptoms of occasional and moderate health conditions. OTC drug products currently represent a huge percentage of all drug products sold in the United States. When properly manufactured and labeled; and used as intended; OTC drug products are safe, effective and can be easily purchased in the market by consumers.
Market studies suggest that there are currently over 300,000 OTC Drugs being marketed and sold in the U.S. today and that number is growing daily. This amounts to almost 60% of the total U.S. drug market (by purchases) and this number is expected to grow in the future. Based on these predictions alone, this is a profitable market and growth potential that drug and health product companies cannot afford to ignore.
If you can cook and follow a recipe; then you can make an OTC Drug Product with access to the necessary resources and an appropriate facility.
The U.S. Food and Drug Administration's ("FDA") is responsible for the regulation and oversight of the U.S. OTC drug market. Congress has granted FDA regulatory authority over the formulation, manufacturing, labeling, marketing and promotion; and import / export of OCT drug products into the U.S. Under this current regulatory regime, there are 3 pathways that a company may follow to enter the OTC drug market including (a) following an appropriate Drug Monograph; (b) with an Agency approved New Drug Application ("NDA"); or (c) via the currently popular Rx-to-OTC Switch Process.
Most OTC drugs available today are marketed and sold as OTC Drug Monograph compliant products. A very, very small percentage of products still come into the market as the subject of an original FDA approved NDA. However, a segment of particular industry growth is coming from reliance on FDA permitted Rx-to-OTC Switch process which allows companies holding FDA approved Prescription (Rx) product to transition to the OTC drug space. One such example includes Prilosec and Pepcid AC. This option is becoming increasingly popular as pharmaceutical companies look for creative ways to extend the overall Product Life Cycle of their hugely profitable Rx drug products.
More Trainings by Expert
An Introduction to FDA's Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (''HCT/Ps'') including Stem Cell-Based Drug Products for Human Use
3-hr Virtual Seminar - Regenerative Medicine: An Introduction to FDA's Regulation of Cell Therapies and HCT/Ps Generally
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some apple systems give this error while the same account works on others
This topic was created during version 3.6.
The latest version is 7.5.00101.
37 Replies
Mar 12, 2009 at 10:11 UTC
Niagara Technology Group (NTG) is an IT service provider.
And you are sure that the password is the same across all of those boxes? And is the local firewall the same across all of those boxes (i.e. can you remotely SSH into all of them using that account and password?)
Mar 19, 2009 at 9:23 UTC
yes the password is the same as i setup all the systems. the firwall is turned off
Apr 8, 2009 at 2:45 UTC
just an update on this question. i have solved some of the log in errors by correcting issues in my dns servers. however i now have 3 macs that will not allow the ssh log in that works on all 9 other ones. any ideas on how to trouble shoot this issue?
Apr 13, 2009 at 5:19 UTC
Are these three macs still not scanning properly?
Apr 14, 2009 at 8:13 UTC
yes i now have 5 that will not let the login work. it works on all the others
Apr 14, 2009 at 9:54 UTC
When you do an nslookup from the Spiceworks computer does the name resolve correctly for one of those 5 that fail to login?
Apr 14, 2009 at 9:59 UTC
yes i can do that to all of them. i did try to use putty to log in to them and no joy. when i used puty to log in to the ones that work no problem. i do not think this is a spiceworks issue. i think it is a maccrap issue, as the setting are the same on all the macs for ssh log in
Apr 14, 2009 at 10:17 UTC
What is different about their setup? Are they on a specific segment of the network, or using wireless where others are wired?
Apr 14, 2009 at 10:22 UTC
they are setup the same. wired to the network. they all have dns entries in 8.xx segment of our network.
Apr 14, 2009 at 11:36 UTC
Niagara Technology Group (NTG) is an IT service provider.
Geminii, I'm in an office with no Macs until tomorrow. I will take a look when I get one and I am going to pass this to Katie M. who is my Mac specialist and see if she has any thoughts. In the mean time could you tell us:
- What version of OSX is running and the problem boxes and the good boxes
- Could you send to us the contents of the /etc/sshd_config file
Apr 14, 2009 at 11:49 UTC
the problem boxes is os x 10.4.11
the working boxes are the same or the next version of os x
i am not a mac tech so if you could give the path for that file it would take 20 mins off the search
thnx for your help
Apr 14, 2009 at 11:51 UTC
Niagara Technology Group (NTG) is an IT service provider.
/etc/sshd_config is the exact location of that file :) Any filename that starts with a / is the exact location with no searching needed.
Apr 14, 2009 at 12:33 UTC
i hope this the right file. i had to rembember my linux commands to find it
Apr 14, 2009 at 1:30 UTC
Niagara Technology Group (NTG) is an IT service provider.
I am traveling this afternoon but will look at it when I return.
Apr 15, 2009 at 1:00 UTC
Late to the party, I know...
This might sound silly, but has SSH been disabled on those units?
Apr 15, 2009 at 1:08 UTC
Niagara Technology Group (NTG) is an IT service provider.
I had that thought too. In OSX, what is the 'ps' syntax to check for the daemon to be running. Solaris would be "ps -ef | grep sshd" and BSD would be "ps aux | grep sshd" and LInux would be either. I'm assuming that OSX uses the traditional BSD syntax? I don't have the box in front of me yet.
Apr 15, 2009 at 1:26 UTC
the firewalls are disabled on all systems on site as we have a hardware firewall. Remote log in using ssh has been enabled on all the Macs. The user i login with has been setup as an administrator on all the macs and logs in to the allohter macs. thnx for all the help
Apr 15, 2009 at 1:36 UTC
Niagara Technology Group (NTG) is an IT service provider.
You should, the bigger strategy, consider turning on the software firewalls on all of your machines. There should never exist a computer that runs without a hardware firewall (a software filewall is not the same thing, just a marketing term) so the use of software firewalls should not be avoided just because the hardware firewall is there - that is assumed to always be the case. You should always have both.
Think of a hardware firewall as your castle walls and a software firewall as the archers who stand on the ramparts firing down on invaders. Sure, you could have archers without walls but they wouldn't last long. The two are complimentary. Archers still have a chance of stopping soldiers who climb over the walls but the walls, once breached, are useless. But archers alone are easily overrun by fast cavalry.
Apr 15, 2009 at 1:49 UTC
Thnx for input. However software firewalls are turned off by policy not decided by me. The powers that sign my check decided that software firewalls slowdown pulling files off the network too much. i do have their policy in writing and signed off on.
Apr 15, 2009 at 1:54 UTC
Niagara Technology Group (NTG) is an IT service provider.
Well, just an FYI, software firewalls don't affect speed in any way. AntiVirus with on demand (live) file monitoring does that but not firewalls. They simply block ports. Apparently someone involved in writing policy is either extremely confused or setting up the company to be ripped off from a major inside job. Most likely just someone incompetent trying to look important but most IP theft happens internally and in my company this would instantly set of a flag to the security team that someone was preparing to take the companies information and make a run for it.
Having the firewalls turned off is a great way to hide rogue services on the network. The only purpose to have it off is for temporary troubleshooting or for nefarious purposes.
Apr 15, 2009 at 2:00 UTC
I am a 1 person IT dept. and have to follow guidelines setup by the powers above. While I have a lot of say on policy, this one I was overruled by the squeakiest wheel, who also signs all the checks. Believe me, Paraniod is my middle name as far as security of my network goes.
Apr 15, 2009 at 2:03 UTC
Niagara Technology Group (NTG) is an IT service provider.
I suppose it is analogous, to complete my earlier analogy, to having you be the captain of the guard and having a duke convince the king to tell you to disband the army because they are too expensive all the while having his own army preparing to attack once your archers go off to the dole to collect their food stamps.
I know how it is being in a shop where you aren't given the power to do your job to the best of your ability and people, even the people whose money is on the line, sabotaging their own company. Best advice that I hear time and time again is, prep your resume and start looking. If you are at a company that doesn't take their IT seriously then they can't take their business seriously because they are one and the same and if its just a game to them then it is never going to be a good working environment and you are not in a position to change that no matter how good you are.
Apr 15, 2009 at 2:04 UTC
Niagara Technology Group (NTG) is an IT service provider.
Have you checked on those problem boxes to see if SSHD is running in the process list? If not, that is the problem.
Apr 15, 2009 at 2:13 UTC
How can I check it on a mac? Never had to do that before
This discussion has been inactive for over a year.
You may get a better answer to your question by starting a new discussion.

subset: commoncrawl


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We at Superior Surface have the Knowledge, Experience, Tool's & Determination to get the job done right! No matter how Big or Small your project may be, Superior Surface will be there every step of the way.
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Question: Using Table order the following acids from strongest to weakest
Using Table, order the following acids from strongest to weakest. HNO3, H2O, NH4+, and C5H5NH+
View Solution:
View Solution:
Answer to relevant QuestionsThe designations 1A through 8A used for certain families of the periodic table are helpful for predicting the charges on ions in binary ionic compounds. In these compounds, the metals generally take on a positive charge ...Use Table to help answer the following questions. a. Which is the stronger base, ClO4- or C6H5NH2? b. Which is the stronger base, H2O or C6H5NH2? c. Which is the stronger base, OH- or C6H5NH2? d. Which is the stronger base, ...Write out the stepwise Ka reactions for citric acid (H3C6H5O7), a triprotic acid. The pH of human blood is steady at a value of approximately 7.4 owing to the following equilbrium reactions: CO2(aq) + H2O(l) ⇌ H2CO3(aq) ⇌ HCO3-(aq) + H+(aq) Acids formed during normal celluar respiration react with the ...Calculate the pH of 6.0 × 10-4 M NaNO2.
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Feb. 28, 2005
LARAMIE, Wyo. -
As part of its academic reform movement, the NCAA has released results of a new plan to improve graduation rates for student-athletes.
Using a formula referred to as the Academic Progress Rate (APR), the NCAA awarded a score for each sport at every Division I institution. Under the new system, 15 of the University of Wyoming's 17 sports scored above the established standard. Two sports, football and men's basketball, would have fallen below the mark and might have been subject to penalties had the program been in place this year.
The NCAA will not begin applying penalties for substandard academic performance until 2005-2006. Penalties could include loss of scholarships in individual sports.
"NCAA academic reform is good for intercollegiate athletics," says Gary Barta, UW director of intercollegiate athletics. "We have to ensure that the word `student' has credibility when we use the phrase `student-athlete.' Like any new piece of legislation, I'm sure there will be bumps along the way. We have always been committed to graduating student-athletes. Now we'll add to that a commitment to follow these new rules."
Under the system, the NCAA awards two points per semester for each student-athlete, one for remaining academically eligible to compete in his or her sport, one for remaining at the school in which he or she is enrolled. Teams lose points for each student who leaves the program or is academically ineligible. Teams with very small rosters, get a statistical break under the system.
The NCAA standard for avoiding penalties is 925 in a system where 1000 is the maximum. Calculated for 2003-04, UW was below the NCAA standard in football (921) and men's basketball (919). For smaller rosters, such as basketball, a school's performance against the NCAA standard could be significantly affected by as few as one or two students.
During the past several years, graduation rates for student-athletes and all students at UW have been on the rise. In 2003-04, the six-year graduation rate for student-athletes was 62.1 percent. The rate for all UW students was 56 percent.
"The University of Wyoming is committed to continually increasing the graduation rates of our students and also for our student-athletes, as a group and by sport," says UW President Philip L. Dubois. "We respect the new NCAA APR, and will do our level best to achieve its goals. However, we recognize that the persistence of students - or of student-athletes - can be affected by a whole host of personal issues, many of which are completely out of the student's hands. These might include personal relationships, family finances, health, a change in academic interest, or simply recognizing that another school might be a better personal fit. But all universities face these challenges; on balance, we need to keep our attention focused on academic persistence and graduation."


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Song Premiere: Meghan Linsey "This Side of Heaven"
Fri, 24 Jul 2015 09:50:51
Meghan Linsey Videos
It's bluesy, it's pop-tinged, it's soulful and it's one of our favorite songs of 2015.
It's Friday. It's summer. Let's cruise into the warm weekend with the sun on our faces and by cranking Meghan Linsey's breezy new track "This Side of Heaven." It's bluesy, soulful and pop-tinged, with only a mere hint of the country stylings on which Linsey launched her career. It's a feel-good and uplifting anthem and it's one of our favorite songs of 2015. Own it!
"I got the title for 'This Side of Heaven' from my mom," the singer told us. "She used the title in a text to me and I wrote it down. The inspiration really came from all the haters on my Facebook and Twitter. I wrote this song with Tyler Cain and Julie Moriva. It's about loving each other. 'We're all just living on this side of heaven.' The message is simple... We're all just trying to get through each day. Be kind."
You hear that? Take that sound advice and beautiful sentiment from Meghan Linsey. Stop hating and try veering towards "This Side of Heaven."
Linsey, who was once one-half of the country duo Steel Magnolia, competed to a second place finish on Season 8 of NBC's The Voice. But second place isn't the first runner up! As if. She is moving full steam ahead and will release her Believer EP, on which "This Side of Heaven Lives," on July 31.
We are thrilled to be sharing this taste of "Heaven" with Meghan Linsey. If this song doesn't eventually end up in a montage scene from a Cameron Diaz rom com, well, then music supervisors in the film world aren't doing their job!
Let Meghan Linsey transport you to heaven!
—Amy Sciarretto
'Beliver' EP from Meghan Linsey is released July 31, 2015 via Bold Music Group.


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Although Italians originally invented pasta as a fastener to keep Sicily from floating away, they abandoned it for less delicious moorings after locals on both sides kept snacking their way toward separation. Tether your taste buds to today's Groupon: for $25, you get $50 worth of authentic Italian cuisine at Casa Mia Restaurant.
Family owned and operated, Casa Mia specializes in central and northern Italian recipes. The interior of the restaurant, adorned with stone, brick, and wrought iron, creates a romantic atmosphere fit for a relaxed or intimate meal. Authentic cuisine from the dinner menu includes more than a dozen pasta dishes, along with popular items such as veal scaloppine alla boscaiolo (veal sautéed with garlic, porcini, white wine, butter, and lemon, $24.95) and chicken suprema alla parmigiana ($20.95). Committed to consumption for all mankind, the chefs cater to a variety of diets. Vegetarian options such as melanzane alla parmigiana (eggplant with mozzarella and tomato sauce, $19.95) and pasta primavera ($19.95) embody all the elegance of the Italian flag's green third, and are much tastier than common flag-making materials.


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For Cruise 2010, Miu Miu presents the Stage bags, a collection of insanely ravishing purses made from either the buttery soft Nappa leather or intricate lurex fabric with detachable crystal handle straps that could double as a bracelet or necklace. Now that's witty! You could carry the bags as a clutch or on the elbow, or carry the bag as the clutch and wear the crystal strap as a bracelet. The possibilities are endless. But its just quite woeful to think that the strap might snap… hopefully it won't.
The collection consists of three groups of three bags, all of which will be available at Miu Miu stores and online retailers by the end of the month.
Miu Miu Stage Bag Nappa Cristal FVJ
Nappa Cristal Bianco – US$1055
Nappa Cristal Mughetto – US$1055
Nappa Cristal Nero – US$1055
Miu Miu Stage Bag Quilted Nappa Cristal FVJ
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Quilted Nappa Cristal Nero – US$1000
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Lurex Cristal Turchese – US$935
Lurex Cristal Tamaris – US$935
Lurex Cristal Sole – US$935
Images via Miu Miu


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Thursday, September 13, 2012
Ok.com Takes On Family Friendly Movie Ratings, Reviews
In what looks like a major move to expand beyond its traditional, media businesses, Deseret Digital Media, the media firm behind the Deseret News newspaper and broadcaster KSL said it has launch Ok.com, a new site that provides ratings and reviews of movies. The new site is focused on families, and in particular helping parents and families find appropriate films to watch or rent. Deseret Digital Media said the move is part of a strategy to expand into new, digital markets, and that it will also be syndicating content on the site to other publishers, including newspapers, broadcasters, and others in Seattle, Phoenix, Pennsylvania, and Ohio. Among features of the Ok.com site--a new URL which Desert Digital Media said it recently acquired--are ability to see color coded age ranges for movies, and ability for users to comment on movies. The site also allows users to find video rentals and purchase movie tickets. The family focus for Ok.com is not unexpected for Deseret Digital Media, which is owned by The Church of Jesus Christ of Latter-day Saints.


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Monday, October 31, 2016
Christian Thanksgiving Ideas & Activities
Need an activity for Thanksgiving? Here are a few of my favorite that might come in handy for you:
Lessons & Activities
catechistsjourney.loyolapress.com- It Is Right and Just: A Thanksgiving Lesson Plan
armyfamilyok.wordpress.com- A Lesson Of Thanksgiving
thereligionteacher.com- Catholic Thanksgiving Day Lesson Plans on the Eucharist as Thanksgiving
apples4theteacher.com- Thanksgiving Story
ministry-to-children.com- Thanksgiving Crafts & Bible Activities for Kids
teacherhelp.org- Thanksgiving resources and activities
christianpreschoolprintables.com- Thanksgiving Bible Printables & Crafts
christiancrafters.com- T-H-A-N-K-F-U-L lesson and game
ministry-to-children.com- Thanksgiving Ideas for Children's Ministry (links to those materials so you can put together a special Bible lesson, craft, or activity for you children's ministry)
hem-of-his-garment-bible-study.org- Preschool Christian Thanksgiving Bible lesson
childrensministry.com- Thanksgiving object lesson that uses candy corn to teach how the Pilgrim's began placing 5 kernels of corn on their plates each Thanksgiving to remind them of God's provision.
creativeyouthideas.com- The story of the ten lepers from Luke 17 is often used to teach Bible study lessons on being thankful. Ken Sapp from Creative Youth Ideas offers a fun Thanksgiving Bible object lesson for teens!
mintools.com- Lots of Thanksgiving ministry resources. Just click on the various tabs. Activities, coloring, lessons, plays, etc.
christiancrafters.com- Thanksgiving Day Devotional & Quirky Turkey Treat
christianity.about.com- 10 Creative Ways to Give Thanks on Thanksgiving Day
kidsbibledebjackson.blogspot.com- I Thank You God for Everything Book (book you make with your child)
dltk-bible.com- Thank you for the World so Sweet (song/poster coloring page)
ouroutofsynclife.blogspot.com- Gratitude Rolls
If your kids love fortune cookies, they will love this idea that bakes the thankfulness right in. These make for a yummy treat on the dinner table and an excellent conversation starter, all rolled into one.
The Catholic Toolbox- Pre K - K lesson plan Thank you God: The Ten Lepers (lesson plan consists of: Objectives, Word Wall, Bible Story with questions, Songs and/or Finger Plays, Activities, Crafts, Games, Snacks, Coloring/Puzzles, etc.)
daniellesplace.com- Thanksgiving Crafts & Activities for Kids
whatchristianswanttoknow.com- 5 Thanksgiving Bible Craft Ideas
craftsbyamanda.com- Thanksgiving Luminary Vase
catholicicing.com- Give Thanks Banner- A DIY Bunting for Thanksgiving
The basic idea is that you spell out "Give Thanks" using things found in nature.
christianpreschoolprintables.com- Thanksgiving Prayer Mini Book (scroll down to this)
This is a printable minibook called "Thank You God" and each page has something to remember to thank the Lord for. There are prewritten versions for children to read or Blank versions are available so that you can write in your own things to be thankful for, or in your own language.
Pumpkin Pie Spinner- This pumpkin pie may look good enough to eat, but it's actually an interactive spinner that reveals things your child is thankful for.
ehow.com- Thanksgiving Christian Games
creativebiblestudy.com- Thanksgiving Games
annieshomepage.com- Thanksgiving Games & Activities
Thank you God Game
This is a memory game. Have the players seated in a circle. The first player begins by saying, "Thank you God for . . ." He can say anything he likes, for example an orange, a pair of shoes, a camel, or a pet dog. The next player in line begins the same way but adds a second object after repeating the first. The third player also begins, "Thank you God for . . ." He must repeat the first two objects and then add a third. So it goes on, but if a player can't repeat or mixes up the order of the objects then he is out. If you haven't got many players, the same children can keep adding more items. The game continues until one player remains or until time is up. Some lists get very long and are remembered for years by the players. A variation is to decide that the objects chosen must start with the letters of the alphabet in order, for example "apple, bat, cake...zebra." This makes it a little easier to remember. (You could also help the player if necessary so everyone can play).
2 comments:
- Rebecca said...
This is a great resource! Thanks!
I was looking for a Thanksgiving lesson that I did about 15 years ago with my class at a small Catholic school. I did not take the lesson with me when I changed jobs and have not been able to find it in searches now. It was a few weeks of build up, having youth give up certain things at home gradually, until, by the end of the project--they were sleeping on the floor of their room (with blankets) and had given up TV, electronics and other conveniences. The students who did it were touched and very thankful for what they each had (as I was). They had to journal about it, and each day and week had certain assignments. I would LOVE to find this again, as I homeschool my own kids now and thought it would be a great family project. Have you ever seen anything along these lines?? --Rebecca
- November 6, 2014 at 9:12 AM
- Amazing_Grace said...
Rebecca- I haven't seen a lesson like that, but I will try to find it and let ya know. :)
- November 6, 2014 at 9:22 AM


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2018 Member Registration Dues
All members - please note that all registration fees must be paid/postmarked to the association by Monday, May 15, 2017.
Sportsmanship Awards for Banquet
Members - registration for the banquet and voting for the Bergen and Passaic County schools to receive the annual BCUA Sportsmanship Awards in both baseball and softball is now open.
Along with these awards, the association also awards a worthy individual umpire the Barney Finn Award (for loyal service to the BCUA) and the Ray Farricker Award (for consistently displaying qualities of Integrity, Pride, Enthusiasm and Hustle) at the banquet.
Even if you're not planning to attend, please take the time to vote for these prestigious awards. If you have been moved by another fellow umpire or some school during the season, this is your time to show your appreciation for them.
To vote, please click here. Remember, you must be signed on with the username and password e-mailed out by John Gojdycz before you can access the form. Ballots must be completed by the end of the day on SUNDAY May 21, 2017.
Below you will find a Hall of fame application: The Criteria for Hall of Fame Nomination:
Criteria for Hall of Fame Membership:
1. Member must have minimum of 10 years as an active member in the BCUA.
2. Member may be former or active in the Association.
3. Nominations for this recognition must be received in writing by the Secretary who will forward the nomination to the Hall of Fame Committee Chairperson. Members of the Hall of Fame Committee are prohibited from submitting nominations. The nomination must include a narrative of how the member meets or exceeds the criteria for selection.
4. The following criteria will be used to determine admission to the Hall of Fame:
A. Member must have served in a positive capacity for the association (i.e.: Officer, Committee Chair, Executive Committee, Any Committee member, etc.)
B. Member must have distinguished him/herself as an umpire representing the BCUA in a positive manner (i.e: County/State Tournament, Charity)
C. There must be no issue regarding integrity or honesty in their service to the BCUA.
d. The member must be approved by 75% of the Hall of Fame Committee present. Four members represent a majority of the Committee.
8. Once approved by the Hall of Fame Committee, the choice(s) will be forwarded to the
Executive Committee, where a majority of those voting in favor would gain approval.
9. The new Hall of Fame Member, once approved, would be notified in writing by the Secretary of this honor and invited to the next association banquet or general membership meeting to receive recognition of the honor.
10. The Hall of Fame Member would be listed in a separate section of the directory.
NFHS 2017 Softball Rules Changes - High School Softball Rules Changes Focus on Uniforms, Equipment
The National Federation of State High School Associations (NFHS) Softball Rules Committee approved four additions to Rule 3 regarding uniforms, equipment and substitutions at its June 13-15 meeting in Indianapolis. These changes approved by the committee, along with one in Rule 1, were subsequently approved by the NFHS Board of Directors.
Rule 3-2-15 states that all equipment shall be inspected by the umpire, and is to be placed outside the dugout/bench prior to the start of the game. The rules committee agreed that placing all equipment in one location at one time is a more efficient method to conduct this inspection.
"The committee believes that expediting the inspection of all equipment will make the process more efficient and done in a timely fashion," said Sandy Searcy, NFHS director of sports and staff liaison for softball.
In Rule 3-2-1, the committee added inclement weather as an exception to the uniform rule for state associations.
The Softball Rules Committee also approved new language to Rule 3-2-7 to reinforce the solid color undergarments requirements.
"We felt it was important to standardize the colors of the undergarments not only to reinforce the solid color requirements similar to other NFHS sport rules, but also because it can be a distraction and create a possible safety concern," Searcy said.
In Rule 3-6-7, which states that players and substitutes shall not enter the contest unreported, the penalty was revised to state that the head coach is restricted to the dugout/bench for the remainder of the game only for a second violation.
The committee also revised Rule 1-5-2c by eliminating the description of the taper's surface. This change brings the NFHS in line with other rules codes concerning the surface of the taper.
A complete listing of the softball rules changes will be available on the NFHS website atwww.nfhs.org. Click on "Activities & Sports" at the top of the home page, and select "Softball."
According to the 2015-16 NFHS High School Athletics Participation Survey, there are 364,103 girls participating in fast-pitch softball at 15,115 schools.
NFHS 2017 Baseball Rules Changes - Pitching Restriction Policies in Baseball to be Based on Pitches
High school baseball rules now will require a pitching restriction policy based on the number of pitches thrown in a game.
The revised pitching policy in Rule 6-2-6 was one of six rules changes approved by the National Federation of State High School Associations (NFHS) Baseball Rules Committee at its June 5-7 meeting in Indianapolis. The rules changes were subsequently approved by the NFHS Board of Directors.
Each NFHS member state association will be required to develop its own pitching restriction policy based on the number of pitches thrown during a game to afford pitchers a required rest period between pitching appearances.
"We're pleased that the rules committee worked in conjunction with the NFHS Sports Medicine Advisory Committee to find an acceptable and reasonable modification to this rule in order to emphasis the risk that occurs when pitchers overuse their throwing arm," said Elliot Hopkins, NFHS director of sports and student services and staff liaison for baseball.
The Baseball Rules Committee also revised Rule 2-32-2 regarding sliding into home plate. The revised language states: "At home plate, it is permissible for the slider's momentum to carry him through the plate in the baseline extended." The committee altered this rule since the physical design of home plate makes it difficult for a runner to break momentum on a slide – as opposed to the other three elevated bases which are elevated.
The committee also revised Rule 3-3-1, which states the umpire has the ability to give three warnings to a coach or player before he or she is removed from the game.
"Officials now have the opportunity to provide a tiered warning system for coaches or players," Hopkins said. "It provides the coaches or players with a teachable moment to change their unsportsmanlike behavior in order to stay in the game."
A new article 6 was added to Rule 8-3 to provide a rules reference for an existing ruling in the Baseball Case Book. The new article reads: "When a plate umpire hinders, impedes or prevents a catcher's throw attempting to prevent a stolen base or retire a runner on a pickoff play, if an out is not made at the end of the catcher's initial throw, the ball shall be dead and all runners shall return to the bases occupied at the time of the interference."
The rules committee also approved an addition to Rule 8-4-2, which states that any runner is out when he is physically assisted by a coach. This rule change supports a revision in Rule 3-2-2 Penalty, which states that the runner shall be called out immediately when he is physically assisted by a coach.
A complete listing of the baseball rules changes will be available on the NFHS website atwww.nfhs.org. Click on "Activities & Sports" at the top of the home page, and select "Baseball."
According to the 2015-16 NFHS High School Athletics Participation Survey, there are 486,567 boys participating in baseball at 15,899 schools across the country, and 1,203 girls playing the sport in 260 schools.


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If so how do you make it not weird? I know this is a weird question but eh.
Is kissing weird to you? Or is it just me?
Have an opinion?
What Guys Said 5
Like every mammal does some type of licking or kissing to show each other affection.00|00|0
Kissing is awesome! Very sensual. The key is to be playful with it. :-D00|00|0
I don't think it is weird because I am used to the idea of it00|00|0
I don't find anything weird about it and *shrugs* you guess is as good as mine.00|00|0
Its weird when I can taste what she had for lunch ^_^00|00|0
What Girls Said 4
oh no not at all lol. it's so great. :P
well i think the most important thing is that while it's nice to know 'how' to kiss, i reckon it's best to just get lost in the moment and let your body take over.
Um... I kissed this guy... I guess it would mean more if he mattered to me!11|00|0
My friend did not like it so she told me "idk why people kiss it's like kissing other people's lip fat" they way she said it was gross so I didn't forget and the next time I was kissing a boy that came to mind and I stopped and laughed at the kid, so embarrassing00|00|0
If you really think about it yeah its weird lol.11|00|0
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text: Ha'taaka is the Goa'uld word meaning slayer of children, poisoner of minds, the forgotten. After being brainwashed by Apophis, Rya'c called Teal'c a Ha'taaka. (SG1: "Family") Retrieved from "http://stargate.wikia.com/wiki/Ha%27taaka?oldid=255426" Ad blocker interference detected! Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers Wikia is not accessible if you've made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected. Categories: Goa'uld language Add category Cancel Save


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Tips For Buying Your Very First Home
Buying any real estate is an exciting and stressful at the same time. If you are not equipped with the right information, you could wind up making a very costly mistake. Avoid mistakes by learning these tips below.
Even if you currently do not have children, if you are planning on living in the home for an extended period of time and the possibility of starting a family during those years cannot be ruled out, it is a good idea to find out if the area schools are of high quality.
Keep an open mind in regard to what elements are the most critical in your options.You may have to sacrifice some of your expectations in order to live in the neighborhood of your choosing, but you can afford another one. If you can't find a home in the perfect neighborhood with all your amenities, perhaps try a smaller home or a different neighborhood with a better house.
A lot of Realtors have lists that contain all the important components of everything you need to do when buying a home.The checklist allows all necessary parties to make sure everything is taken care of when it needs to be.
If you haggle with the seller a bit, it should be fairly easy to decide on a final purchasing price that you're happy with.
Have an inspector look at the home you are interested in. You do not want a home that needs major renovations. This makes the inspector an extremely cost-effective and-safety conscious choice that you will be responsible for and you may have to leave your home while it is repaired.
Try to buy houses that have fireplaces only in locations other than the family room. It is a real hassle to keep up with cleaning multiple fireplace considering that they are barely used anyway.
When you are looking for a home, do not let the home's decor affect your purchase decision. You should base your decision on the way it was built and the home. If you base your decision to buy on decor, you risk overlooking serious problems that will be expensive to fix later.
When looking for new real estate investments, keep your real goals in mind. Determine early on if your goals are short or long range goals.Don't invest in any property that don't meet your pre-determined criteria. A lot of owners make compromises and end up making poor investments.
Hire people you trust when you are trying to buy a home. No one wants to go out and spend money on something that could receive for free. Even though this is true, it's probably better to hire the people you can trust and that you know personally. Getting the truth can save you enormous stress and expense in the long run.
When house hunting, be sure that amenities such as parking are adequate to your needs. This is very important if the home lacks a garage or driveway. Without adequate parking, you may end up with a spot that will have you walking far.
If your future rental property has a garden, make sure you ask your landlord about it. Some landlords can require the tenant to perform yard duties. Other places still will offer this included in the monthly fee.
It takes a while to locate the property that fits exactly what you are looking for.
You are going to want to have legal representation just in case there are any issues that occur during foreclosure acquisition. This could help you a great deal of money in the long run.
Prioritize what you want before negotiating a real estate purchase. Make sure you know all of your issues, including whatever expectations you hold for each. The strength of feeling you have for each expectation determines its priority in your highest priorities.
If you don't do this right away, you may not be covered if an unfortunate event occurs, especially if you live in a hurricane or earthquake zone.
Even though you might appreciate the view, in the long term, your buyer might not think so. Therefore, purchase the home because you love the view, just make sure you don't overpay for it.
When it comes time to purchase the property, hiring a realtor with integrity and a solid reputation is paramount. You can find a lot of helpful information online and also from the BBB (Better Business Bureau. Ask reliable friends and family to get an agent they have done business with.
Credit Report
You need to know what's on your credit report prior to looking for a new home. Once you get your hands on your credit report, check through it for any issues or red flags that may be present, and be sure to report any mistakes.
Do not forget to a home inspector has looked through it. It is best to hire a professional, but the advantage over having someone you know inspect the home is that you can hold a bad inspection against a professional inspector, while there is little you can do to a relative.
These suggestions can assist you in making choices from which you will benefit. The more knowledge you bring to the table, the more likely your investment will pay off. Buy your property when you are totally sure and informed.


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Swamp Murders
Out of the Swamp
Season 3 Episode 1
Outside Asheville, NC, a young mother is stabbed four times in the chest and left for dead in the French Broad River. But she lives long enough to seek out help -- and leave a cryptic clue for detectives. Who could have done such a thing -- and why?
- 44 min
- Premiered 08/12/2015


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April 26, 2016
…Taken at face value, Airbnb's claim of providing black retirees and empty nesters with the chance to make a bit of money on the side reads like a good thing. But there are some local New Yorkers who are skeptical of the story the company's trying to sell. Specifically, there's no real way that Airbnb can prove that actual black people are using and benefitting from its business. Murray Cox, a data analyst working out of Bed-Stuy, contends that Airbnb is actually one of the forces contributing to the gentrification of these neighborhoods…
Source: http://fusion.net/story/295484/airbnb-nyc-black-neighborhoods/
April 26, 2016


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Trade Rumours and Proposals Thread Part 17: What does "bold" mean?
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Registered User
Join Date: Feb 2004
Location: Heartland of Hockey
Posts: 7,879
vCash: 1991
Originally Posted by
Mr Forever
Fair point. What player would you suggest as a top LHD?
Outside of making a run at Streit, it's nearly impossible to find a legit top 4 LH puck moving d-man out there.
I'd make a pitch for Goligoski. He has never been known for playing defense (still better than Streit) but I think this is a guy who is better than what he has shown in Dallas....the burden of being the guy traded for James Neal has always been on his shoulders. That burden will be gone on a fresh start with a new team. From Dallas' perspective trading him makes sense. They have a good young d-core. Oleksiak, Morrow, and Cannaughton all will push for jobs next season. I'd much rather give up an asset and have Goli for 3 more years at 4.6 million than sign Streit at 5.5 million for 3 years.
Sbisa from Anaheim intrigues me as well but his ceiling is a #3 at best. He's supposedly available for the right price.
I think Goli/Sbisa would take PRV straight up....and I'd go there IF (and that's a big IF) MacT finds a legit top 6 LW.
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Church Parish Partners
We're looking for "a few good men" (and women…and even some of their kids). If you enjoy AM 1180 K-YES and want to help spread the word, whether you are a "people person", or simply committed to reaching others for Christ, you could be a Parish Partner.
Our Parish Partners might sit at a table with K-YES brochures at a parish festival, or walk along (or ride) with the K-YES van in a summer parade. You might host a table at the annual fund raiser dinner, or maybe you've even got an idea of your own to help get the word out.
If this interests you, please email email@example.com or call 320-257-9700


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Organophosphorus pesticide self-poisoning is an important clinical problem in rural regions of the developing world, and kills an estimated 200 000 people every year. Unintentional poisoning kills far fewer people but is a problem in places where highly toxic organophosphorus pesticides are available. Medical management is difficult, with case fatality generally more than 15%. We describe the limited evidence that can guide therapy and the factors that should be considered when designing further clinical studies. 50 years after first use, we still do not know how the core treatments—atropine, oximes, and diazepam—should best be given. Important constraints in the collection of useful data have included the late recognition of great variability in activity and action of the individual pesticides, and the care needed cholinesterase assays for results to be comparable between studies. However, consensus suggests that early resuscitation with atropine, oxygen, respiratory support, and fluids is needed to improve oxygen delivery to tissues. The role of oximes is not completely clear; they might benefit only patients poisoned by specific pesticides or patients with moderate poisoning. Small studies suggest benefit from new treatments such as magnesium sulphate, but much larger trials are needed. Gastric lavage could have a role but should only be undertaken once the patient is stable. Randomised controlled trials are underway in rural Asia to assess the effectiveness of these therapies. However, some organophosphorus pesticides might prove very difficult to treat with current therapies, such that bans on particular pesticides could be the only method to substantially reduce the case fatality after poisoning. Improved medical management of organophosphorus poisoning should result in a reduction in worldwide deaths from suicide.
Organophosphorus pesticide self-poisoning is a major clinical and public-health problem across much of rural Asia.1–3 Of the estimated 500 000 deaths from self-harm in the region each year,4 about 60% are due to pesticide poisoning.3 Many studies estimate that organophosphorus pesticides are responsible for around two-thirds of these deaths5—a total of 200 000 a year.3 Deaths from unintentional organophosphorus poisoning are less common than those from intentional poisoning6 and seem to be more common in regions where highly toxic organophosphorus pesticides (WHO Class I toxicity) are available.7,8 In a large cohort of Sri Lankan patients poisoned with WHO Class II organophosphorus pesticides,9,10 no deaths resulted from unintentional poisoning (Eddleston M, unpublished).
Hospitals in rural areas bear the brunt of this problem, seeing many hundreds of patients poisoned by pesticides each year, with a case fatality of 15–30%.5,11 Unfortunately, these hospitals are frequently not adequately staffed or equipped to deal with these very sick patients—intensive care beds and ventilators are in short supply—so even unconscious patients are managed on open wards (figure 1). Furthermore, the evidence for treatment is weak12 and if evidence of benefit does exist for particular antidotes, they are poorly used13–15 or unavailable.3
Improved medical management and provision of antidotes and intensive care beds, together with bans on the most toxic pesticides,16 should reduce the case fatality for self-poisoning and noticeably reduce the number of deaths from self-harm in rural Asia.3,12
Organophosphorus pesticides inhibit esterase enzymes, especially acetylcholinesterase (EC 126.96.36.199) in synapses and on red-cell membranes, and butyrylcholinesterase (EC 22.214.171.124) in plasma.17 Although acute butyrylcholinesterase inhibition does not seem to cause clinical features, acetylcholinesterase inhibition results in accumulation of acetylcholine and overstimulation of acetylcholine receptors in synapses of the autonomic nervous system, CNS, and neuromuscular junctions.17 The subsequent autonomic, CNS, and neuromuscular features of organophosphorus poisoning are well known (panel 1).
Features due to overstimulation of muscarinic acetylcholine receptors in the parasympathetic system
Features due to overstimulation of nicotinic acetylcholine receptors in the sympathetic system
Features due to overstimulation of nicotinic and muscarinic acetylcholine receptors in the CNS
Features due to overstimulation of nicotinic acetylcholine receptors at the neuromuscular junction
Patients can suddenly develop peripheral respiratory failure while conscious after seemingly recovering from cholinergic crisis, which is termed type II respiratory failure or intermediate syndrome.21,22 This syndrome is an important cause of death in patients who have been resuscitated and stabilised on admission to hospital.
Diagnosis is made on the basis of clinical suspicion, the characteristic clinical signs, smell of pesticides or solvents, and reduced butyrylcholinesterase or acetylcholinesterase activity in the blood.17 Patients with severe organophosphorus poisoning typically present with pinpoint pupils, excessive sweating, reduced consciousness, and poor respiration. The major differential diagnosis is carbamate poisoning, which is clinically indistinguishable.18
Diagnosis of organophosphorus poisoning should ideally be confirmed with an assay to measure butyrylcholinesterase activity in plasma (or acetylcholinesterase in whole blood).17 However, the results of such assays are rarely available in time to affect clinical decisionmaking. Their importance is for guidance of clinical research; understanding of their limitations is essential for interpretation of studies looking at individual pesticides and specific interventions.
Unfortunately, much confusion exists about the use and interpretation of these assays (panel 2). Some pesticides inhibit butyrylcholinesterase more effectively than they inhibit acetylcholinesterase.9 Butyrylcholinesterase activity does not relate to severity of poisoning; however, it can be used as a sensitive marker of exposure to most organophosphorus compounds or other cholinesterase-inhibiting compounds, and for measuring organophosphorus elimination from the body (figure 2).
Plasma butyrylcholinesterase assays
Red cell acetylcholinesterase assays
Monitoring a patient's cholinesterase status after organophosphate poisoning enables the verification of substantial exposure to anticholinesterase agents. In future, such assays could facilitate the decision about when to stop oxime treatment and allow cautious weaning of a patient from a ventilator when butyrylcholinesterase activity is increasing. Studies are underway to confirm the clinical usefulness of this approach.
Studies suggest that red-cell acetylcholinesterase is a good marker of synaptic function and atropine needs in patients poisoned with organophosphorus, and is therefore probably a good marker of severity.29,30 Patients with red-cell acetylcholinesterase activity of at least 30% had normal muscle function and no need for atropine. By contrast, patients with less than 10% of normal red-cell acetylcholinesterase activity had grossly deranged muscle function and needed high doses of atropine. Acetylcholinesterase activity between these values was associated with moderate impairment of muscle function and need for atropine.
A major drawback of acetylcholinesterase assays is that the interaction between organophosphorus, acetylcholinesterase, and oximes continues if the sample is left at room temperature for even a few minutes (panel 2). To obtain reliable results, the reaction must be stopped immediately by cooling and dilution of the sample as soon as it is taken from the patient. Otherwise differences of only a few minutes in the time taken to cool a sample will cause notable variation over repeated samples, which makes interpretation difficult.
Treatment includes resuscitation of patients and giving oxygen, a muscarinic antagonist (usually atropine), fluids, and an acetylcholinesterase reactivator (an oxime that reactivates acetylcholinesterase by removal of the phosphate group) (panel 3).35 Respiratory support is given as necessary. Gastric decontamination should be considered only after the patient has been fully resuscitated and stabilised. Patients must be carefully observed after stabilisation for changes in atropine needs, worsening respiratory function because of intermediate syndrome, and recurrent cholinergic features occuring with fat-soluble organophosphorus.
Few randomised trials of such poisoning have been done; consequently the evidence base is restricted.35 Both atropine and oximes were introduced into clinical practice rapidly in the 1950s without clinical trials.36,37 As a result, we do not know the ideal regimens for either therapy. Trials of other interventions are hindered because the best way to give the core treatments has not yet been determined and is highly variable in practice. This variability interferes with development of a widely accepted study protocol and limits the external validity of study results.
The case fatality reported by hospitals varies markedly—from 1·85% in the Posion Control Centre of Mach Mai hospital, Hanoi, Vietnam to 40% in a German intensive-care unit (Pham Due, Personal Communication).38,39 Since so few randomised trials have been done, comparison of effectiveness of therapies given in different hospitals is tempting. Unfortunately, such comparisons are confounded by many factors (panel 4).
The above factors have important consequences for the speed of onset of organophosphorus poisoning after ingestion. Ingestion of an oxon organophosphorus that rapidly inhibits acetylcholinesterase will result in early onset of clinical features and respiratory arrest before presentation to hospital, increasing the risk of hypoxic brain damage and aspiration. The conversion of the thioate organophosphorus parathion to paraoxon is so fast that patients can be unconscious in 20 min. Clinical features after poisoning by other thioate organophosphorus, such as dimethoate and fenthion, happen later, giving the patient more time to present to hospital.
In particular, although many textbooks regard poisoning with various organophosphorus pesticides to be broadly similar and equally responsive to treatment, differences in chemistry have major consequences for treatment efficacy.9,48 The pesticide ingested defines how many patients survive to reach medical attention, how ill they are at admission, effectiveness of oxime therapy, likelihood of recurrent cholinergic crises, or need for respiratory support (panel 4). Such variation reaffirms the importance of randomised trials to measure effectiveness of treatments for specific pesticides.
Severe acute organophosphorus pesticide poisoning is a medical emergency. Treatment must ensure that the patient has a patent airway and adequate breathing and circulation. Ideally, oxygen should be provided at the first opportunity. However, little evidence supports the common advice that atropine must not be given until oxygen is available.17,19,49,50 In hospitals that have no access to oxygen, atropine should be given early to patients with pesticide poisoning to reduce secretions and improve respiratory function.32 The patient should be placed in the left lateral position, with the neck extended. This position reduces risk of aspiration, helps keep the airway patent, and could decrease pyloric emptying and absorption of poison.51,52 Supportive care should include giving fluids and control of blood glucose.
Health-care workers are thought to be at risk of poisoning during initial stabilisation of patients poisoned with organophosphorus.53,54 A few Western hospitals have reported cases of such poisoning, but none have shown inhibition of acetylcholinesterase or butyrylcholinesterase in health-care workers consistent with substantial exposure to organophosphorus.55 Some symptoms, such as headaches and nausea, are possibly due to anxiety or exposure to the organic solvent (eg, xylene) in which the pesticide is mixed.55,56
Hundreds of thousands of patients with severe organophosphorus poisoning are seen every year in basic hospitals across Asia; health-care workers take no special precautions and no cases of secondary poisoning have been reported. Reticence by hospital workers to treat patients poisoned with pesticides puts patients at risk. Guidelines recommend universal precautions, maximum ventilation, and frequent rotation of staff, so that effects of solvent and pesticide are kept to a minimum.55
Although atropine remains the mainstay of therapy worldwide,14,49 other muscarinic antagonists have been studied in animals.49 An important difference between such drugs is their penetration into the CNS.57 Glycopyrronium bromide and hyoscine methobromide do not enter the CNS, but hyoscine has excellent penetration; atropine enters the CNS, but not to the same degree as hyoscine.
The main adverse-effect of atropine is anticholinergic delirium in patients who receive too high a dose.49 Some physicians therefore prefer glycopyrronium to treat the peripheral effects of organophosphorus without causing confusion. However, its poor CNS penetration suggests that it is ineffective at countering coma and reduced respiration seen in patients with the cholinergic syndrome. A small randomised controlled trial comparing glycopyrronium with atropine noted no significant difference in mortality or ventilation rates, but it did not have sufficient power to detect small differences between treatments.58
Hyoscine was used successfully to treat a patient with severe extra-pyramidal features but few peripheral signs.59 Animal studies suggest that it is more effective than atropine for control of seizures induced by inhaled organophosphorus nerve agents.60 However, extra-pyramidal effects and seizures are not common features of organophosphorus poisoning.9,21
Atropine will probably remain the antimuscarinic agent of choice until high-quality randomised trials show another muscarinic antagonist to have a better benefit-to-harm ratio because it is available widely, affordable, and moderately able to penetrate into the CNS. No known randomised controlled trials have compared different regimens of atropine for either loading or continuation therapy. As a result, many different recommendations have been made—a 2004 review noted more than 30 dosing regimens, some of which would take many hours to give the full loading dose of atropine.15
The aim of early therapy is to reverse cholinergic features and to improve cardiac and respiratory function as quickly as possible. We use a regimen of doubling doses18 (panel 2), with the aim of raising the pulse above 80 beats per minute and systolic blood pressure above 80 mm Hg, and rapidly reversing bronchospasm and bronchorrhoea. This regimen allows for as much as 70 mg of atropine to be given in stages to a patient in less than 30 min, resulting in rapid stabilisation and low risk of atropine toxicity.15 A study from south India61 recorded benefit from an infusion of atropine compared with repeated bolus doses, but it used historical controls thus reducing confidence in this finding. Infusions could reduce fluctuations in blood atropine concentration, reducing the need for frequent patient observation, an important benefit in hospitals with few staff.
Oximes reactivate acetylcholinesterase inhibited by oganophosphorus.13 Pralidoxime was discovered in the mid-1950s by Wilson and colleagues, and was soon successfully introduced into clinical practice for patients with parathion poisoning.37 Other oximes, such as obidoxime and trimedoxime, have been developed but pralidoxime remains the most widely used. It has four salts: chloride, iodide, metilsulfate, and mesilate.62 The chloride and iodide salts are used widely, but metilsulfate and mesilate are used mostly in France, Belgium, and the UK. The chloride salt has advantages over iodide—in particular its smaller molecular weight (173 vs 264), which provides 1·5-times more active compound per gram of salt than does iodide. High doses of pralidoxime iodide also puts patients at risk of thyroid toxicity, especially if given for a long period.63
Despite the beneficial effects of pralidoxime first noted with parathion poisoning, its effectiveness has been much debated, with many Asian clinicians unconvinced of its benefit.64–66 In particular, two randomised controlled trials in Vellore, India in the early 1990s noted that low-dose infusions of pralidoxime might cause harm.67,68 The absense of clinical benefit could relate to trial design (suboptimum dose, or bias in allocation). Alternatively, this result could suggest that pralidoxime is ineffective in the patients seen at this hospital, perhaps because of the specific pesticide ingested, the amount ingested, or the patients' long delay before pralidoxime is given.69,70
A Cochrane review71 and two other meta-analyses72,73 of pralidoxime have been published. The Cochrane review included two randomised controlled trials68,69 and reported no clear evidence of benefit or harm. The other meta-analyses combined non-randomised or historically controlled observational studies64,74–78 with randomised controlled trials67,68,79 reducing confidence80,81 in their conclusion that oximes are harmful.
Since these meta-analyses were completed, a randomised controlled trial in Baramati, India82 studied the effect of very-high-dose pralidoxime iodide (2 g loading dose, then 1 g either every hour or every 4 h for 48 h, then 1 g every 4 h until recovery) in 200 patients with moderate organophosphorus poisoning (excluding severely ill patients). The high-dose regimen was associated with reduced case fatality (1% vs 8%; odds ratio [OR] 0·12, 95% CI 0·003–0·90), fewer cases of pneumonia (8% vs 35%; 0·16, 0·06–0·39), and reduced time on mechanical ventilation (median 5 days vs 10 days). Laboratory studies to identify the pesticide ingested and degree of baseline acetylcholinesterase inhibition and subsequent reversal were not done.63 However, this study suggests that large doses of pralidoxime could have benefit if patients are treated early and have good supportive care.
Observational studies of pralidoxime and obidoxime suggest that the ability to reverse acetylcholinesterase inhibition with oximes varies with the pesticide ingested (figure 4).9,13,69,83 Acetylcholinesterase inhibited by diethyl pesticides, such as parathion and quinalphos, seems to be effectively reactivated by oximes, but acetylcholinesterase inhibited by dimethyl organophosphorus, such as monocrotophos or oxydemeton-methyl, seems to respond poorly. We noted that acetylcholinesterase inhibited by S-alkyl-linked organophosphorus, such as profenofos, is not reactivated by oximes at all (figure 4). This difference is probably partly because of variation in the speed of acetylcholinesterase ageing (panel 5) induced by these different pesticides. Interestingly, the Baramati82 study did not find a difference in benefit of high-dose pralidoxime in moderate dimethyl or diethyl organophosphorus poisoning. Further studies are needed to establish whether this benefit remains for severe poisoning.
Inhibited acetylcholinesterase reactivates spontaneously but slowly. The half-life of reactivation varies according to the organophosphorus: if dimethyl, the half-life is about 1 h; if diethyl, the half-life is around 30 h. Oximes speed up this reactivation. Unfortunately, if the organophosphorus is present in high concentrations, newly reactivated acetylcholinesterase will be rapidly reinhibited. Whether reactivation or inhibition predominates depends on the type of organophosphorus and relative concentrations and affinities of organophosphorus and oxime.
Inhibited acetylcholinesterase can also become aged, by loss of one of the two alkyl groups attached to the bound phosphate. Aged acetylcholinesterase cannot be reactivated by oximes. The half-life of ageing varies according to the inhibiting pesticide: if dimethyl, the half-life is around 3 h; if diethyl, the half-life is around 33 h. Thus ageing has important clinical consequences.
If a patient who has ingested a dimethyl pesticide presents to hospital 3 h after ingestion, about 50% of the acetylcholinesterase will already be aged and unresponsive to oximes. A patient arriving after 12 h will have about 94% aged acetylcholinesterase and therefore be unresponsive to oximes. Such a situation is common where patients need to be transferred to a secondary hospital to receive oximes. The situation is better with diethyl pesticides since it takes 33 h for 50% inhibition and oximes can be effective for up to 5 days after ingestion.
Ageing seems to take place much more quickly after poisoning with atypical organophosphorus, such as profenofos, that have neither two methyl groups nor two ethyl groups (figure 3). The half-life of ageing seems to be much less than 1 h, thus oximes are completely ineffective if the patient presents more than an hour or two after ingestion (figure 4).
Interpretation of clinical evidence regarding oximes should take into account this variability in response of different pesticides.69 The clinical effects can also be limited by high concentrations of organophosphorus in the blood after ingestion of a large dose—the pesticide simply re-inhibits any acetylcholinesterase that the oximes reactivate. Oximes will also not be effective for improvement of outcomes if the patient develops severe complications such as aspiration pneumonia or hypoxic brain injury before treatment. Such complications take place most often with fast-acting pesticides such as parathion and dichlorvos.
WHO recommends that oximes be given to all symptomatic patients who need atropine.14,84 To ensure a therapeutic concentration, a loading dose of pralidoxime chloride or obidoxime is given, then a continuous infusion. The loading dose of oxime should not be given rapidly as a bolus because this method causes vomiting (risking aspiration), tachycardia, and diastolic hypertension.13
Patients poisoned with organophosphorus frequently develop agitated delirium. The cause is complex, with contributions from the pesticide itself, atropine toxicity, hypoxia, alcohol ingested with the poison, and medical complications. Although the mainstay of management is prevention or treatment of underlying causes, some patients need pharmacotherapy. Acutely agitated patients will benefit from treatment with diazepam.
Diazepam is first-line therapy for seizures; however, seizures are uncommon in well oxygenated patients with pesticide poisoning.9,48 Seizures seem to be more common with organophosphorus nerve agents (such as soman and tabun).85 Animal studies suggest that diazepam reduces neural damage86 and prevents respiratory failure and death,87 but studies in humans are few.
Gastric lavage is often the first intervention poisoned patients receive on presentation to hospital, sometimes at the expense of resuscitation and giving antidote.88 No evidence shows any form of gastric decontamination to benefit patients poisoned with organophosphorus.35 Gastric decontamination should only be done after the patient has been stabilised and treated with oxygen, atropine, and an oxime.88
Gastric lavage is the most common form of decontamination for organophosphorus poisoning despite the absence of randomised controlled trials to confirm benefit.35 The rate of absorption of organophosphorus from the human bowel is not known; however, with some pesticides, the rapid onset of poisoning in animals89 and humans39 suggests that absorption is rapid, occurring within minutes of ingestion. The time window for effective lavage is therefore probably short. Guidelines for treatment of drug self-poisoning suggest that lavage should be considered only if the patient arrives within 1 hour of ingesting poison.90 The relevance of these guidelines to organophosphorus poisoning is unclear91 but lavage should probably only be considered for patients who present soon after ingestion of a substantial amount of toxic pesticide who are intubated, or conscious and willing to cooperate. Repeated gastric lavages are recommended in China to remove pesticide remaining in the stomach,92 although substantial amounts of organophosphorus are unlikely to remain in the stomach after one lavage.
Ipecacuanha-induced emesis should not be used in organophosphorus pesticide poisoning.35,93 Patients poisoned with organophosphorus can rapidly become unconscious, risking aspiration if ipecacuanha has been given. Mechanically-induced emesis with large quantities of water risks pushing fluid through the pylorus and into the small bowel, probably increasing the rate of absorption.93
A randomised controlled trial of single and multiple doses of superactivated charcoal in Sri Lanka failed to find a significant benefit of either regimen over placebo in more than 1000 patients poisoned with pesticides.94 Because activated charcoal binds organophosphorus in vitro,95 the absence of effect in patients might be due to rapid absorption of pesticide into the blood. Alternatively, the ingested dose in fatal cases could be too large for the amount of charcoal given, the charcoal might be given too late, or the solvent might interfere with binding. No evidence suggests that patients with pesticide poisoning benefit from treatment with activated charcoal.
Current therapy works through only a few mechanisms.96 Several new therapies have been studied but results were inconclusive. However, future research might reveal several affordable therapies working at separate sites that could complement present treatments.
Magnesium sulphate blocks ligand-gated calcium channels, resulting in reduced acetylcholine release from pre-synaptic terminals, thus improving function at neuromuscular junctions, and reduced CNS overstimulation mediated via NMDA receptor activation.97 A trial in people poisoned with organophosphorus pesticides recorded reduced mortality with magnesium sulphate (0/11 [0%] vs 5/34 [14·7%]; p<0·01).98 However, the study was small, allocation was not randomised (every fourth patient received the intervention), and the publication incompletely described the dose of magnesium sulphate used and other aspects of the methodology; therefore these results should be interpreted with caution.
The alpha2-adrenergic receptor agonist clonidine also reduces acetylcholine synthesis and release from presynaptic terminals. Animal studies show benefit of clonidine treatment, especially in combination with atropine, but effects in human beings are unknown.99
Sodium bicarbonate is sometimes used for treatment of organophosphorus poisoning in Brazil and Iran, in place of oximes.100,101 Increases in blood pH (up to 7·45–7·55) have been reported to improve outcome in dogs through an unknown mechanism;102 however, a Cochrane review103 concluded that insufficient evidence exists at present to establish whether sodium bicarbonate should be used in humans poisoned with organophosphorus.
Removing organophosphorus from the blood could allow optimum action of other therapies. The roles of haemodialysis and haemofiltration are not yet clear; however, a recent non-randomised controlled study in China104 suggested a benefit of haemofiltration after poisoning with dichlorvos, which has poor solubility in fat, and therefore should have a relatively small volume of distribution. A systematic review of these therapies in organophosphorus poisoning is underway, but randomised controlled trials will be needed to establish good evidence-based treatment guidelines.
Butyrylcholinesterase scavenges organophosphorus in plasma, reducing the amount available to inhibit acetylcholinesterase in synapses.105 It has been cloned and military research now aims to inject soldiers with the enzyme before exposure to organophosphorus nerve gases.106 Such a prophylactic approach is not practical for self-poisoning with organophosphorus because we cannot predict when a person is going to ingest the pesticide. Turkish doctors107 have reported the use of butyrylcholinesterase in fresh frozen plasma to treat poisoned patients. A small controlled study (12 patients given fresh frozen plasma with 21 control patients) recorded benefit, but this trial was not randomised and allocation decisions were unclear.
Furthermore, whether or not scavenging of organophosphorus by butyrylcholinesterase is the mechanism for any effect of fresh frozen plasma is unclear.108 In fact, butylcholinesterase seems unlikely to ever be an effective treatment for pesticide poisoning since it binds stoichiometrically to organophosphorus and will be overpowered by the amount of pesticide commonly ingested. For example, 50 mL of 40% dimethoate (molecular weight 229) contains 20 g or 87·3 mmol of organophosphorous, which, if completely absorbed and transformed into the oxon, would need an equivalent number of moles of butyrylcholinesterase (molecular weight about 70 kD; therefore 6 kg) for inactivation.
A better approach than use of butylcholinesterase might be to give recombinant bacterial phosphotriesterases, or hydrolases.109,110 These proteins break down organophosphorus pesticides enzymatically and protect animals from pesticide poisoning. Future clinical development of such enzymes could reduce blood concentrations of organophosphorus, allowing optimum activity of other treatments.
Medical management of organophosphorus pesticide poisoning is difficult, especially in resource poor locations where most of these patients present. Clinical practice is frequently less than ideal, with poor initial resuscitation and stabilisation, and poor use of antidotes. However, most of the original research regarding acute organophosphorus poisoning in humans has been published in the past decade, which is a positive development. We expect that in the next decade evidence from continuing research by a number of groups across Asia will finally provide clear guidance on how to treat poisoning with organophosphorus pesticides. Hopefully, this new guidance will include the use of novel antidotes that will reduce the case fatality from pesticide poisoning, and therefore reduce the worldwide number of deaths from self-harm.
We searched for relevant studies by searching PubMed (1960–2006), Embase (1974–2006), UK National Research Register, Cochrane Injuries Group Specialised Register, Clinicaltrials.gov and the Cochrane databases (all until Dec 2006) for "organophosphorus", "organophosphate", or "organic phosphorus" and "poisoning" or "toxicity". We did not limit the search by language; however, we had limited ability to translate papers from China where many studies have been done. Translation of Chinese papers was therefore ordered according to relevance, established by review of English abstracts. We also used information from our continuing studies in Sri Lanka that have recruited more than 2000 patients poisoned with organophosphate, and from discussions with clinicians seeing such patients across Asia.
We thank Lewis Nelson, Yi Li, Nick Bateman, Geoff Isbister, and the Lancet reviewers for their comments on the manuscript and members of the Ox-Col study team and the South Asian Clinical Toxicology Research Collaboration for their work in Sri Lanka. We thank Dr F Worek and Dr H Thiermann of the Bundeswehr Institute of Pharmacology and Toxicology for their support of the research in Sri Lanka. This work was funded by a grant to ME (063560MA) from the Wellcome Trust's Tropical Interest Group. The South Asian Clinical Toxicology Research Collaboration (SACTRC) is funded by the Wellcome Trust and Australian National Health and Medical Research Council International Collaborative Research Grant 071669MA.
ME wrote the first draft of this manuscript after detailed discussion with the other authors. All authors contributed to draft revisions and approved the final version.
The authors do not have any financial conflicts of interest associated with writing this review. They have been funded to do observational studies, systematic reviews, and randomised controlled trials of interventions for organophosphorus pesticide poisoning in Sri Lanka over the past 4 years. The results of these studies are cited in this review. ME is a Wellcome Trust Career Development Fellow.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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I'll look all around a room full o people and girls don't look at me. I walk towards a girl and she looks at me from a distance but up close she don't look and like I don't exist.
Most Helpful Guy
you need a wake up call. me being a good looking guy, I still don't get attention from all girls. even if you are good looking, you are never going to be every girl's type. girls are different from guys.10|10|0


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Mario & Luigi: Superstar Saga
Review by KnightsoftheRound
"A Mario Game Worthy Of The Title "Super""
Mario & Luigi: Superstar Saga is a RPG for the gameboy advance, as you all, already know. This is one of the best Mario games I have played, in a LONG time. This game was overlooked, when it was first released, by many people. However, many people don't know what they are missing from this high-quality game.
Gameplay - 10/10
When I first started playing this game, I found it very odd, controlling Mario and Luigi separatley with the A and B buttons. However after a while, I got used to this method, and became very comfortable with it. The game also has many battle features, for instance, you start out with a simple jump, yes? But you can also jump, to avoid enemy attacks. This adds a new element to the gameplay. I always thought while playing many other RPG's, "Why do they just stand there and let the enemy's attack them?" Well in this game while a enemy is getting ready to attack a A button will appear over both characters, meaning that if you press A, you can jump. So basically you can jump and dodge the enemy's attacks. By succeeding you are avoiding any damage that may have been caused. However you can also "return" the damage to your enemy, a successful jump dodge, could also mean that you can land on your enemy after dodging there attack, so your damaging them rather then them damaging you. After a while, you will eventually get hammers, this also adds a new way of defending yourself. When a enemy comes at you, you can hit them with your hammer, interrupting their attack, thus damaging them aswell. Each Mario Bros, also gets their own unique "hand" attack. Mario's being the fire hand, and Luigi's being the thunder hand. And the dodging isn't as easy as it sounds, there are many enemys that you don't know how they are going to attack, or when, so they are tricking you into trying to avoid them to soon. This game also adds in a unique "double teaming" method of attacking. Mario and Luigi each have their own set of Bros. Points (BP), much like MP or PP from other RPGs. Each Bros. gets their own unique Bros. Attacks, that involve both Bros. and careful button pressing and timing. The game also features a new method of "cooperation", between Mario and Luigi, each character must use different map, ability's to solve puzzles and get through areas. Mario starts out with a spin jump, where he jumps on Luigi's head and spins them across a short distance, and Luigi starts with his high jump, letting you jump over higher areas. All there is to it, is that the gameplay is unique, and is always kept interesting.
Story - 8/10
Most Mario games, don't have the "best" story's, much like this games story. It starts out with a cheesy opening of Cackletta and Fawful stealing Princess Peach's voice, for a unknown reason. Then Bowser shows up on his usual "I want to kidnap Princess Peach" rampage. However, the story really starts to pick up from their, and gets alot more complex and interesting then it started with. However the ending, like most Mario game endings, is pretty quick, and nothing to special, however the game is worth it, and the ending, ending with the usual fireworks. Alot of characters also make cameos in this game. Such as Professor E. Gadd, from Luigi's Mansion, and Birdo, from the older Mario games and even Yoshi. These characters, along with many new characters makes for a great cast of new and interesting characters. Most of the game takes place in a world next to the Mushroom Kingdom, bearing the name of Bean Bean Kingdom. So you won't be seeing the same old Mushroom Kingdom, with its familiar baddies, this game introduces old and new baddies to the game.
Graphics - 10/10
The world of Mario & Luigi: Superstar Saga is beautifully colored, and have great backgrounds. Such as "real" waterfalls flowing down, blended with "old school" graphics. Don't get me wrong on the "Old School" thing, the graphics are good and pleasant to look at. I really enjoyed the scenery of this game.
Sound - 10/10
Mario and Luigi don't usually do to much dialogue in their games, only featuring the odd "Yahoo!" and such... however, the Bros. each do their fair share of sounds, and babbling, and surprisingly it doesn't get annoying.
Lasting Value - 8/10
I managed to beat this game in 26 hours. The average time frame for completing this game ranges in between 20-25 hours, which is fairly short, and I guess I went a little above average, that is mainly because I used no FAQS to complete this game, and explored every little detail. The game is very amusing with lots of humour, which debuts right off the start, which I might add. However the game is pleasant enough for it to make almost anyone want to replay it at least once more, however in my case, I see this as a game I will play many times, over and over. I always have certain single player games, that I usually play once a year. Maybe increasing the time between plays, after each playthough, but this seems like a game that should have enough lasting value, for you to want to play it at least 1 more time, to do everything you may not have completed the first time through.
Overall - 10/10
Overall this game gets a 10. And it deserves it, for a long time there hasn't been a Mario title that really deserves "Super" in the title, and you know what folks, this is a Mario game worthy of the title Super. I would recommend picking this game up as soon as possible. If you don't, you don't know what your missing. You'd be missing one of Mario and Luigi's Best.
Reviewer's Rating: 5.0 - Flawless
Originally Posted: 06/15/04
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If you haven't used one before, take the time to learn how to use a double vibrator. There are several varieties to choose from. If you are going to be using one on a woman, the one that you will use is likely one that has vaginal and clitoris or anal vibrators on one device. One variation has a vaginal vibrator with a butt plug type of vibrator on it for double penetration. The other version has the vaginal vibrator and the clitoral stimulating vibrator on it. If you are using a double vibrator on a woman, there are specific ways to make it more fun for her.
- Turn on the vibrator. Gently insert the vaginal vibrator into her vagina. If she isn't already turned on, you may need to add some personal lubricant first. Insert it as far as she likes it, as I'm sure she will let you know.
- If the vibrator is the kind that stimulates the clit, move the part of it until it's touching the clit. Of course, follow her instructions as to where it feels best. Again, you will likely know it from experience or from her reactions! Hold it in place or move it around accordingly.
- If the vibrator is one that has the anal stimulator on it, insert that vibrator into her anus very carefully. It's advisable to put personal lubricant on it first so as not to damage any of the delicate anal tissue. Go very slowly and start out not going in too deep. If she wants more, she will tell you
- Avoid personal lubricant that has any warming sensation to it as that may burn especially on the clit or anus.
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TheCarConnection.com notes a full range of standard equipment and luxury extras available for the 2008 Lexus GS 450h.
Cars.com reports this 2008 Lexus offers "dual-zone automatic climate control, an electric rear sunshade and a 10-speaker audio system" as standard equipment. "Additional sound dampening and an acoustically tuned windshield" are available too.
Edmunds adds that the GS hybrid "comes equipped with a full array of standard premium luxury features such as 18-inch wheels, adaptive suspension dampers, adaptive xenon headlights and a sunroof," as well as "leather upholstery, heated and cooled front seats, dual-zone automatic climate control, interior wood trim, Bluetooth, a back-up camera, keyless ignition and a 10-speaker audio system with in-dash CD changer and auxiliary audio jack."
Options on the 2008 Lexus, according to Cars.com, "include a navigation system and a 14-speaker audio system." Edmunds notes this last Lexus 2008 option is "a phenomenal 14-speaker Mark Levinson audio system." This source adds "conventional summer (performance) tires are standard," but remarks that Lexus 2008 buyers "have the option of getting either summer or all-season run-flat tires."