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Tuesday, December 11, 2007
#23 Is this really the end? Or just the beginning ...
Congratulations to all that finished and to myself…. I definitely found this program to be an enhancing program to help those who weren't aware of many things like Podcast, Wikis, Technorati etc. I found out some pretty interesting thing while being a participant in this program. I found the Image Generator assignment to be fun and also the Flickr assignment. I feel that this assignment did affect me which in one of my of lifelong learning goals which was G-O-A-L-S as I wrote in the very first assignment that I don't like setting goals because it's hard for me to try and accomplish it, which I am very proud of my self for finishing this before the deadline. I actually set a goal and said to myself that I am going to finish this assignment only because I started it and I usually don't like starting something I can't finish. I did find the assignment to be little time consuming but overall it was pretty much fun at times. If this program was offered again I might like into doing it again, only because it's wasn't that bad.
Posted by Beautiful at 2:11 PM 1 comment:
#22 Audiobooks (or "The end is in sight ")
I like the idea of eAudiobooks I feel that it's good for not only seeing people but people who are blind. It comes in handy for people with that disability there able to download it on there MP3 players or Ipods and listen to it which I find to be and excellent source. There are different topics to choose from and you can borrow them for 7 days, by visiting the queenslibrary.org and click on the digital media link. The next time I check out a book I will do it thru digital media found on the queenslibrary.org site.
Posted by Beautiful at 2:10 PM No comments:
#21 Podcasts, Smodcasts!
Yes!!! I am almost to the end, Assignment # 21 Podcast, this is a great site to listen to all types of podcasts with a variety of different topics. There were many sites for music, book clubs and different Cultures. I found a podcast that interested me which was called "HipHop Village" where you can here all types of Hip Hop and R&B. I such a music fanatic I especially like listen to Hip Hop and R&B. This website is enormous and it will take some time and effort to listen to all your favorite podcasts. I found numerous amounts of podcasts relating to Music in general from all types of music HipHop to Pop. I added this podcast to my bloglines account and I am definitely going to look for more when I get the chance. In general the site is real interesting and very easy to navigate through.
Posted by Beautiful at 2:07 PM No comments:
#20 I Tube, YouTube
Yes Were Dangerously In Love with YouTube. This is an YouTube video of my all time favorite artist Miss Beyonce Knowles performing Live in concert Dangerously in Love, my all time favorite song. I though this was an easy assignment to do I finished it pretty fast. I find YouTube to be a great site. The only thing I dislike is when people put up distorted videos that a part annoys me, but for the most part I Love YouTube.
Posted by Beautiful at 2:06 PM No comments:
Saturday, December 1, 2007
#19 Discovering Web 2.0 tools
For Assignment # 19 the Web 2.0 awards for best videos goes to YouTube . Yes I choose to do this assignment on You Tube seeing how I very familiar with the site. You Tube came in 1st as to being number one for the web's most popular video sharing application lets users upload their own videos, embed videos on their own sites and search others' content. I like the fact that You Tube has videos/ TV shows available for users to see when they missed an episode of there favorite show. It's also great for students to put up there work especially if there majoring in theater then there able to put there work out there for the world to see. You find all types of thing on You Tube which can be good and bad; but mostly good. You Tube could be good for Libraries because it has the latest on everything like popular music/shows and it comes in handy for libraries to find out what hot and what's not for our customers.
Posted by Beautiful at 8:26 PM No comments:
#18 Let's Collaborate and Have a Good Time
Wow I finally reached to Assignment #18:-)I decide to go with Google Docs because I already had an account. Well for starts I like the idea of having a web-based application where you would be able to use application like Word processing, Spreadsheets, or even make presentation. I found that to be really interesting I even decide to use Google Docs to do this assignment. I also like that fact that it's free where you have people who don't have Microsoft Office at home, it's also good for students who have Reports to do and don't have access to Microsoft Office at home. They even have a little Spreadsheet application where you can be able to make data entries. I played around with making my own little presentation; I had a lot of fun with that since I am very familiar with using PowerPoint application. I was able to save my assignments. I think this is a great idea for people who unfortunately can't afford to buy Microsoft Office.
Posted by Beautiful at 8:25 PM No comments:
#17 1/2 Explore Facebook and Social Networking
The application that I found to be of interest to me and I know it would be of interest to our library customers was Books iRead . It really summed up a great excerpt of what iRead really is. What I found to be so great about it was that iRead lets you share a virtual bookshelf of titles you are currently reading, those you want to read, those you have read in the past, and books you won't read. I also found the My Wikipedia to be good for our customers who are students cause it's world's largest encyclopedia, with this application you can display historical events or the latest news stories.
Posted by Beautiful at 8:24 PM No comments:
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Standing Waves
Lesson 4 of 6
Objective: Students will be able to define and create standing waves.
In the previous lesson, students measured the speed of sound with standing waves in air columns. Today, the goal of the lesson is to expand students' understanding of standing waves to include the standing wave definitions and equations (HS-PS4-1 & SP5). The lesson starts when students actively take notes, which they then apply while using a simulation to create standing waves (SP2 & SP4). Class ends with an analogy prompt closure activity.
Resources (1)
Standing Waves PowerPoint
It's time for students to take out a sheet of paper and get ready to learn about the characteristics of standing waves. My students are operating under the expectation that they must write down key concepts from the presentation. This expectation of how to take notes has been outlined and ingrained in their learning since freshman year.
I display the Standing Waves PowerPoint (also available as a PDF) to help the students understand what they need to write down. As I'm showing the slides on the front board, I have a hard copy of the PowerPoint which includes teacher notes and sample problem solutions (viewable when the file is downloaded). These notes help me to stay focused and ensure I mention the highlights as we progress through each slide.
The presentation starts with defining standing waves and showing students a video of a standing wave on a string. Then, students contrast nodes and antinodes before looking at the equation for a standing wave on a string. To relate the notes to yesterday's lab, the presentation defines resonance and offers students two videos that demonstrate forced vibrations. Finally, students try to solve two sample problems that allow them to apply their newly learned knowledge. I solve these problems prior to the start of class so I can share the solution with the students. Having the solution written down ahead of time allows me to show my written work to the students under the document camera while answering questions students have about the solution.
While I describe this section as "direct instruction," I usually have a lot of interaction with my students throughout the presentation and am constantly moving throughout the room to change my proximity. The students ask questions, participate in problem-solving, and connect to real-world examples to stay engaged the entire time. For each of the example problems that are included in the presentation, students are encouraged to collaborate with those students seated around them. I'm also walking around to answer questions and provide assistance when needed. While I don't collect or grade the work to these examples, students know the importance of working through them and understanding the solutions. Homework problems and the unit test will contain similar problems, so at this point in the course students usually embrace the ability to have guided practice time.
Resources (3)
Standing Waves Simulation
Now that I've properly defined standing waves, students use a computer simulation that allows them to be more active in their learning. The simulation allows students to visualize and create a standing wave using a virtual wave on a string. Students are also able to analyze one pulse at a time and analyze the type of interference that occurs. The simulation also gives students an opportunity to alternate between fixed-ends and free-ends and contrast the interference patterns that result.
Before we start the activity, I assign partners using the random student generator that already has my students' names loaded. By displaying the random generator on the front board, there is an element of suspense as the partners are assigned. Partners work best for this activity so that each student can be actively engaged throughout the work time. Because this activity does not need to be completed outside of class, I feel comfortable in choosing the pairings for my students.
We use MacBook Pro's in my district, so my students are familiar with how the computer and cart organization works. After each pair has been assigned, the students move to sit near each other, push their desks together, and grab a computer. As the computers are booting I pass out the standing waves simulation so that each student receives a copy. This document directs them to PhET where they will be using waves on a string simulation. My activity sheet is also meant to direct the students in their learning so that they are confident in what material needs to be understood.
While students are working, I walk around to ensure they are actively engaged in the learning process. This means that they are on the proper website, reading or discussing some component of the simulation, and writing down appropriate information from the simulation. When I walk around, I'm spot checking their written work and engaging students in questions such as "Have you changed the end of the wave to a loose end yet?" or "Why do you think it's important to have the tension set so high?"
When there is approximately 10 minutes prior to the end of class (5 minutes left of the time I've allowed for this activity), I ask students to put the computers back on the cart and return to their seats. I also tell them at this point that the lab is due at the start of the next class meeting. Once everyone is back in their seats, we are ready to move into the closure activity for our lesson.
Resources (1)
With about five minutes left of class, I ask the students to stop working and focus on me for a moment. I remind students that the purposes of today's activities were to define and explore standing waves. As I'm talking, I give each student a small, blank notecard.
Once everyone has a notecard, I ask students to respond to an analogy prompt that is on the front board. I've put the prompt on the board while the students were working, and it's been hidden from their view so they aren't able to think too deeply about their responses. As I reveal the prompt to the students, they must write the prompt and their responses on the index card. For this particular activity, the prompt will say "This standing wave activity was like _________ because _______."
This is their "ticket out the door," meaning that they can't leave until they've handed me their card. To avoid anyone sneaking out of the room, I stand at the door and collect the cards as students depart. Once I've collected all of the cards, I read and use them to adjust my teaching practices. For example, if a student says "This standing wave activity was like a marathon because it was way too long." I might take a question off the activity before doing it again the following year. It's always fun to read some of their creative contributions.

subset: commoncrawl


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Gildan Activewear Inc. is putting its best foot forward.
The Montreal-based clothing wholesaler has agreed to pay $350-million (U.S.) for Gold Toe Moretz Holdings Corp., a leading U.S. sock maker.
The company says the deal will more than double its revenue from socks sales and significantly expand and diversify its customer base and distribution channels in the United States.
This deal is by far the biggest acquisition for Gildan. It will transform the company into world's largest sock company, with retailers such as Kohl's, Sears, Target and J.C. Penney to add to existing customers such as Wal-Mart.
"This is by far the biggest and most strategic acquisition for Gildan," executive vice-president Laurence Sellyn said in an interview.
The proposed acquisition will also allow Gildan to further ramp up production at its second sock facility in Honduras, he said. And it further opens up the Asian market because Gold Toe Moretz sources most of its manufacturing from the region.
"The strengths of the two companies will allow for significant growth opportunities," Mr. Sellyn added.
Ever since its first sock acquisition five years ago, Gildan has been carving out a significant presence in the North American hosiery market as part of its bid to position itself as a major garment player, with a full product line of T-shirts, underwear, socks and sweatshirts.
The Gold Toe Moretz brands, which include Gold Toe, Silver Toe and PowerSox, are sold to mass-market retailers, national chains and sporting goods stores.
"The acquisition of Gold Toe Moretz represents an important and exciting step in Gildan's ongoing strategic development," Gildan president and chief executive officer Glenn Chamandy said in a news release.
The tie-up of the two companies should result in annual cost savings of between $10- and $15-million, to be attained over the next two years, Gildan said in a statement.
Gildan's extensive low-cost manufacturing base in the Caribbean and Central America gives the company a competitive edge in terms of price. The company has over the years expanded its operations in Honduras, the Dominican Republic, Nicaragua and Haiti. It is also increasingly looking to growth in emerging markets in Asia.
The proposed deal was announced after stock markets closed Monday.
Report Typo/Error
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- Gildan Activewear Inc$39.800.00(0.00%)
- Updated November 23 4:00 PM EST. Delayed by at least 15 minutes.


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The force that pulls dogs toward the groins of strangers
40 comments post a comment
Please cast your mind back through the mists of time to when I posted my blog 'Three puzzles to ponder.' Someone just emailed me with a question to which I'm sure I know the answer, but...
Please cast your mind back through the mists of time to when I posted my blog Three puzzles to ponder. Someone just emailed me with a question regarding this blog to which I'm sure I know the answer, but…
As you may recall, the third puzzle was concerned with Gravity, which – of course – explains the title of this blog. What do you mean "What does gravity have to do with dogs and the groins of strangers?" What do they teach the young people of today? Who amongst us could forge the immortal words of the great American philosopher Dave Barry, who famously said: "Magnetism is one of the six fundamental forces of the universe, with the other five being gravity, Duct tape, whining, remote control, and the force that pulls dogs toward the groins of strangers."
But we digress… the problem I originally posed was to assume that the circumference of the world is exactly 24,000 miles at the equator. We know that the earth spins round once every 24 hours, so at the equator this is 24,000 miles in 24 hours, which equates to a rotational speed at the surface of 1,000 miles per hour (no wonder my hair always looks so mussed up).
Anyway, the question I posed was as follows: "If you are standing at the equator, the spin of the world is sort of trying to throw you off (if you see what I mean). So, assuming that someone has a mass of exactly 100 kilograms if we were to weigh him or her at the North or South Pole, what would the reading on the weighing scale be if our subject was standing on it at the equator?"
Over time we added all sorts of qualifiers, such as the weighing scale being calibrated in such a way that being moved to the equator did not affect it, and so on and so forth.
The thing is that someone who shall remain nameless to protect the innocent – let's call him Simon (you get 10 extra points if you correctly identify the animated film that prompted me to use the name Simon) – emailed me with a query, that spawned a flurry of messages, which evolved into a telephone conversation, whose conclusion left both of us scratching our heads…
Simon: There is of course the difference between mass (an inherent property of matter, independent of gravitational field, velocity, or acceleration) and weight (which is the force felt by the Earth pushing up on your feet, dependent on your mass and the Earth's gravitational field and any vertical acceleration). The mass doesn't change. The gravitational field of the earth doesn't change. Since there is no vertical acceleration, the measured weight will be the same. That's my theory, anyway.
Max: But the Earth is spinning, so the guy will weigh less at the equator than at one of the poles because the spinning earth causes centrifugal (or centripetal?) force...
Simon: Suppose you were standing at the equator when the speed of the Earth's rotation suddenly doubled – you would fall over backwards because the acceleration would be in the horizontal direction – this is elementary stuff they teach at high school.
Max: I must have been off school that day. So here's another example, suppose I have a rock on the end of a piece of string and I'm spinning it round and round really fast in a vertical plane such that it passes my feet and then goes above my head…
Simon: Of course it won't. At the point that the rock is directly overhead, the only motion it has is horizontal, so it will take off in a horizontal direction:
Max: You are making my head hurt. Let's return to my original problem, but let's assume that there is no atmosphere. Suppose I'm standing on the equator of an airless object like the moon that is spinning really, really quickly. Are you saying that I won't weigh less at the equator than I do at one of the poles?
Simon: That's right.
Max: Suppose that it's spinning incredibly quickly – like 100,000 times an hour, surely it would fling me off into space.
Simon: No it wouldn't because all you would have would be horizontal motion, but no vertical acceleration.
Max: Arrrgggh! Look, imagine that you're looking down on the equivalent of the North Pole on the moon and you see me standing in a spacesuit on the equator. Let's assume that, from your point of view, I'm standing on top of the moon, which is spinning at some rate in a clockwise direction:
Max: If the moon suddenly disappeared at this point in time, I agree that I would carry on traveling in a horizontal direction off to the right. Now, even if the moon doesn't disappear, inertia will cause my body to want to continue travelling in a horizontal direction. However the gravity of the moon will pull me down, but due to my horizontal motion I will appear to be lighter – that is, although I will have the same mass I will appear to weigh less. If I gradually kept on increasing the rotational speed of the moon, there would come a time when my tendency to keep travelling horizontally (my inertia coupled with my horizontal velocity) would be more than the gravity of the moon and my feet would leave the ground.
Simon: No they wouldn't.
Max: Yes they would.
Simon: No they wouldn't.
Max: Yes they would.
… This is pretty much where we left things … with me obviously winning the argument (grin) …
Actually, now I come to think about it, I could use that Physics modelling program Phun to model the one about the string with the rock (Click Here to see my blog on Phun). Well, I could if I had the time, but as usual I am up to my ears in alligators fighting fires without a paddle ... maybe you could use Phun to test this out and report back to the rest of us...


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I got my idea from a tut that was on here, but I changed it up a bit and added her jewelry and tattoos etc. she's my favorite fairy
DragoArt members upload artwork and drawing tutorials! They are also allowed to leave comments on tutorials, profiles, etc. Many more features, as well; it's way better than just being a boring guest! Register Now!


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A treatment that could mean the end of daily insulin injections for diabetics is about to undergo trials in the UK.
The treatment was developed in Canada by British-born surgeon James Shapiro and involves the transplantation of insulin-producing cell clusters into the livers of diabetics, so that they can create insulin themselves (
The charity Diabetes UK is funding seven centres at British hospitals to test the technique, at a cost of £300,000. Ten patients will receive the cell transplants and, if successful, the project will be expanded to treat up to 400 diabetics a year.
To prevent the cell transplant from being rejected these patients will be treated with a cocktail of drugs and, as the potential dangers of long-term immunosuppression are unknown, the treatment will only be considered suitable for patients with type-1 diabetes.
Moira Murphy, Director of research at Diabetes UK, said: "It's early days yet, but this may well lead to a cure for diabetes. If this research proves successful, it could revolutionise the lives of people who currently need to take insulin injections to stay alive".


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Hackney House Austin - Whose Idea Was It Anyway - D&AD, MediaMonks
London Borough of Hackney
Saturday, 8 March 2014 from 14:30 to 15:30 (MST)
Who's Going
San Francisco, California
London, United Kingdom
Florence, Italy
Event Details
D&AD and MediaMonks present "Whose idea was it anyway." With President elect, Laura Jordan-Bambach.
Doyens of digital design discuss the emotional connection they have with their work, how they attribute value to it and whether the changing nature of digital production could ultimately lead to the letting go of ownership.
Anders Gustafsson, Creative Director, TBWA\Media Arts Lab
Chris Clarke, Chief Creative Officer, DigitasLBi
Cyrus Vantoch-Wood, Creative Director, Cheil Worldwide
Wesley ter Haar, Founder, MediaMonks
Fernanda Romano, Chief Creative Officer, Naked Brasil
When & Where
721 Congress Ave
Saturday, 8 March 2014 from 14:30 to 15:30 (MST)
Add to my calendar


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You want to use YouTube clips in Keynote or Pages? Or use them offline in the classroom? Or even edit them into iMovie? Read on..
Well, there's a solution for that! You can download any YouTube clip direct to your photo roll so it can be used in Keynote, Pages, iMovie or any other app in just four taps.
Just follow the quick steps below:
Lets get it all set up first – its a one time thing!
Step 1 – Get the apps you need
Grab the official YouTube app – here (free)
Grab the 'Workflow' App – here (£2.29)
Step 2 – Grab the YouTube workflow 'recipe'
Open this page on your iPad and click here
Tap 'Get Workflow' on the left hand side of the screen and in the dialogue box 'Open in Workflow'
Workflow will now open and add the recipe.
This 'recipe' will now be stored in the app and can be called upon anytime you need to grab a YouTube video.
Now, anytime you want to save a video
- Open the YouTube app and find your video
- Tap the share button in the top right corner and press 'copy link'
- Open the Workflow app and press the big red button 'Download YouTube'
- Now, press play at the top of the next screen
- Workflow will now grab the video clip which you will see on screen.
- Tap 'Done' and, well, you're done! The video is now saved in your photo roll
That's it – video saved to your camera roll!
From here you can just add it to any app that allows photoroll access – or even bring it into iMovie and edit and trim it to keep the bits you want.


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CANBERRA, Australia, June 21 (UPI) -- Australia's Ministry of Defense announced the release of a tender for the repair and maintenance of Australian navy ships.
The contract, for five years and with a value of more than $300 million, covers eight Anzac class frigates.
Minister for Defense Materiel Jason Clare said four companies or joint ventures -- BAE Systems, Babcock/UGL Infrastructure, Thales Australia, and DMS Maritime/Transfield Services -- have been short-listed to compete for the work following an open tender process.
This is the first of the new group maintenance contracts to be released for tender.
Currently, each maintenance activity is contracted individually to a panel of companies who compete for the work. This reform will end that system and create five-year performance-based contracts for the maintenance and repair.
"This reform provides more security for Australian businesses and more job security for their workforce," Clare said. "It's a significant change -- ending the burden for industry of bidding for every job."


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A woman who was assaulted by a knife-wielding man late Thursday night was able to fend him off with pepper spray, Escondido police said.
The 25-year-old woman was walking in an apartment complex in the 1300 block of W. 9th Avenue, near West Valley Parkway, between 11 p.m. and midnight when she was grabbed from behind and thrown to the ground by the man, said Escondido police Lt. Craig Carter.
While holding her down, he used a knife to try to cut off her pants, Carter said. She was carrying pepper spray and sprayed it on the man's face, and he fled. She suffered minor injuries, but did not require hospital treatment, Carter said.
The suspect is described as Latino, 25 to 30 years old, between 5 feet 10 inches and 6 feet tall, and weighing about 190 pounds. He had a small round mole on the left cheek near his nose, and a larger irregular-shaped mole or dark-colored birthmark on the right side of his neck.
He was wearing a black shirt and black sweatpants.
firstname.lastname@example.com • (619) 293-1876


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Over the past few years there's been an insidious plague of pestilence that has thrown New York into a tumult of paranoia, fear and itching. Of course, I speak of bedbugs. These loathsome little creatures have made headlines for invading and overtaking clothing stores, movie theaters and the wooden benches of subway platforms. They are sneaky little bloodsuckers that steal away on your clothes then infest your home, and they have caused even the most stoic New Yorker to eye a possible bite with an inescapable sense of dread.
As someone who shudders at the very mention of the b-word, it's no surprise to me that a horror movie is in the works inspired by these biting buggers. Deadline reveals the newly minted Tango Pictures has purchased the rights to Ben H. Winters' bestselling horror novel Bedbugs, and has hired Ti West, the writer-director of such menacing marvels as The House of the Devil and The Innkeepers, to draft the script.
The novel, published last year by Quirk Books, centers on a happily married couple who find the perfect Brooklyn Brownstone. Two bedrooms, two baths, spacious, stylish, with a fireplace and a full-sized kitchen! Plus the rent is shockingly low. The only downside is a cryptic handyman and the peculiar landlady, but Alex and Susan Wendt willfully overlook these slight drawbacks and move in with their daughter Emma. But soon, Susan begins to wake up with telltale bites. Clearly, they are infested with bed bugs. Yet neither her husband nor daughter are bitten, and an exterminator can find no trace of the pesky pests. No, what's going on in Brooklyn Heights is far more vexing than a bedbug infestation.
Praised for its understated approach to terror, Bedbugs seems an ideal fit for West's style that revels in atmospheric horror. Quirk associate publisher and creative director Jason Rekulak agrees, stating:
"Reading Bedbugs as a manuscript felt like the literary equivalent of a Ti West horror movie—a slow-burning supernatural story with fully realized characters, light on gore but heavy on menace and dread."
I'm scratching already.
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No Grub menu displaying on dual-boot (2 hdd's)
To Anyone Willing To Help:
On my home desktop computer, I have Win XP installed, which works just fine. Recently, I installed Fedora Core 6 on a second hdd in the same computer (IDE, FC6 is on slave, XP on master). When I was installing, it gave me an option to install Grub to the first disk's boot sector (the one with XP), so I selected that. When I rebooted, no Grub menu was displayed, it simply went into the Windows boot menu, where I can select from Windows XP Home Edition, or Windows XP Recovery Console. Poo.
I have the same setup on a laptop that I own, except that XP and FC6 are on the same hdd. It works just fine, and I see the Grub menu everytime. When I select "Other", it takes me to the exact same Windows boot menu that I get from my desktop machine.
I tried changing the boot order in the BIOS to the slave disk (yes, this BIOS actually lets me choose the hard disk order), and nothing. I tried commenting out the "hiddenmenu" line in the /boot/grub/menu.lst file, and checked to make sure that it was the same in the /boot/grub/grub.conf file. My timeout is set to 5 in the /boot/grub/grub.conf file. I also attempted to press the Esc key while booting as fast as I possibly could, and nothing. The only way for me to get into my Linux drive is by booting with the install disk. I'm sorry if I'm annoying with the absolute paths and assumed actions, I just want to make sure that others with similar issues can get a complete answer, because I know it's frustrating. Please help!
assuming u tried booting from both hard disks and nothing shows grub.
does it shows any error when boot from the slave harddisk , if so can u post that.
Nirmal Tom.
ok no probs,
first we shall try install grub again in MBR.
boot with ur first cd and in the boot screen, type
linux rescue
it ask for networking and others just skip.At one stage it will search the installed fedora and says u that it is mounted under /mnt/sysimage and give u a shell prompt.
In the shell prompt,
chroot /mnt/sysimage
grub-install /dev/hda
it it is successful, reboot and check.if it prints any error, post me back
Nirmal Tom.
Thanks for the help, nirmaltom. I'll try it today on my lunch break (because I have to go home to do it). I'll post back my results in a few hours.
Didn't Work
Nope, it didn't work. This is more or less what it looked like:
# grub-install /dev/hda
Does this mean (the "/dev/hdb1" annoyance) that somewhere it is automatically defaulting to /dev/hdb1, regardless of what I'm inputting?
i think,u might have instructed anaconda to install grub on first sector of partition and not on MBR, during installation.
check out the contents of /boot/grub/device.map file
if it is like below
(hd0) /dev/hda
(hd1) /dev/hdb
post me that.Also if it is not so, make the file like that and follow grub-install procedure as i told u previous post
Nirmal Tom.V
I looked at /boot/grub/device.map, and it looked like this:
(hd1) /dev/hdb
(hd0) /dev/hda
just post me the output of /boot/grub/grub.conf and fdisk -l
Nirmal Tom.
# more /boot/grub/grub.conf
# fdisk -l
it seems that ur first boot sectors of the windows partition is not set properly,not the mbr.
To ensure u can boot into linux safely,First make a copy of grub in second hard disk(the one used for linux).For that get into linux , as root run
grub-install /dev/hdb
Now use ur XP cd to get into recovery console,by booting from it.It will ask for the administrator password,give it and execute the command fixmbr and fixboot.
Then see, whether u are able to boot into windows directly from the first hard disk.The check to boot from second hard disk to get grub nad boot into both linux and windows
Nirmal Tom.
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Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
INTRODUCTION — The World Health Organization estimated that more than 75 million people had alcohol abuse or dependence worldwide over a 12 month period [1]. Nearly two million deaths each year have been attributed to the disorders. The prevalence of alcohol use disorders in primary care ranges from 20 to 36 percent, although the conditions are frequently untreated [2,3].
Psychosocial interventions are effective in the treatment of alcohol abuse and dependence; however, as many as 70 percent of individuals relapse after psychosocial treatment alone [4-7]. Several medications can be used to treat alcohol use disorder, leading to reduced heavy drinking and increased days of abstinence [8]. There is little evidence on the effectiveness of medication in the treatment of nondependent alcohol abuse.
The psychiatric diagnoses, alcohol abuse and alcohol dependence, in DSM-IV-TR were replaced by one diagnosis, alcohol use disorder, in DSM-5 [9]. Although the crosswalk between DSM-IV and DSM-5 disorders is imprecise, alcohol dependence is approximately comparable to alcohol use disorder, moderate to severe subtype, while alcohol abuse is similar to the mild subtype.
This topic focuses on medication in the treatment of alcohol use disorder. The epidemiology, pathogenesis, clinical manifestations, assessment, and diagnosis of alcohol use disorder, as well as psychosocial treatments for the disorder, are discussed separately. (See "Risky drinking and alcohol use disorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis" and "Psychosocial treatment of alcohol use disorder" and "Screening for unhealthy use of alcohol and other drugs in primary care" and "Brief intervention for unhealthy alcohol and other drug use".)
NEUROBIOLOGY — Pharmacologic treatment of alcohol use disorder has mostly focused on altering the reinforcing effects of alcohol use. Medication development has focused on several neurotransmitter systems that interact with the corticomesolimbic dopamine (CMDA) pathway, which can mediate reinforcement. Many available or promising compounds appear to act by modulating the function of opioids, glutamate (with or without gamma aminobutyric acid, GABA), and serotonin (5-HT).
Some alcohol-dependent individuals possess a biological predisposition to the disease. These biologically vulnerable alcoholics may benefit from specific adjunctive medications addressing the underlying abnormalities.
Indications — Nearly all clinical trials finding medications efficacious for alcohol use disorders studied recently abstinent patients with a DSM-IV-TR diagnosis of alcohol dependence. Applying these findings to patients diagnosed under DSM-V is imprecise, but the most closely comparable group of patients are those with alcohol use disorder, moderate to severe subtype (ie, patients with four or more symptoms within a 12-month period) [9]. DSM-V criteria for the diagnosis of alcohol use disorder are described separately. (See "Risky drinking and alcohol use disorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis".)
Pharmacotherapy should be used in patients with alcohol use disorder, moderate to severe subtype, who:
●Have current, heavy use and ongoing risk for consequences from use
●Are motivated to reduce alcohol intake
●Prefer medication along with or instead of a psychosocial intervention
●Do not have medical contraindications to the individual drug
Most data on the efficacy of pharmacotherapy are not generalizable to patients with the mild subtype of alcohol use disorder. Patients with a mild subtype alcohol use disorder who are currently drinking heavily and risk serious consequences can be considered for these treatments on a case-by-case basis.
Goals — The traditional goal of treatment for alcohol use disorder is abstinence, which remains a primary treatment focus. In addition, reduction of heavy drinking has become accepted as an alternative treatment goal. The frequency of heavy drinking (defined as more than five drinks per day for men and four for women) shows the highest correlation with negative life consequences such as impaired driving, interpersonal problems, and injuries [10]. Reduction of heavy drinking may be a more acceptable goal for some patients who lack readiness to quit drinking [11].
Initiation and duration — Pharmacologic treatment for alcohol use disorder is often initiated during hospitalization for alcohol intoxication or withdrawal. (See "Ambulatory management of alcohol withdrawal" and "Management of moderate and severe alcohol withdrawal syndromes".)
Naltrexone can be initiated while the individual is still drinking. This permits treatment for alcohol use disorder to be provided in community-based practice at the point of maximum crisis without the need for enforced abstinence or detoxification [12]. Disulfiram, which by intent leads to adverse effects when combined with alcohol intake, should only be used by abstinent patients in the context of treatment intended to maintain abstinence. Research indicates that acamprosate should be used once abstinence is achieved.
After initiating medication treatment, follow-up visits should be sufficiently frequent to provide the patient with encouragement and support, to engage family members if helpful, and to monitor the patients for treatment response, side effects, medication adherence, and early signs of relapse, which can lead to serious complications [13].
The optimal duration of pharmacotherapy is not known. Most trials studied the effect of treatment over two to six months. Experts recommend at least six months of medication with an additional six months of follow-up. The efficacy of medication treatment wanes once medications are discontinued. Of the medications described below, only topiramate requires a taper to discontinue, over a two-week period.
FIRST-LINE MEDICATIONS — Naltrexone cannot be given to patients taking opioids. If opioids are required to treat pain, naltrexone should be discontinued. Naltrexone is contraindicated in acute hepatitis or liver failure.
Oral naltrexone — Naltrexone exerts its principal pharmacological effects through blockade of the mu-opioid receptor. Endogenous opioids are involved in modulating the expression of alcohol's reinforcing effects [14,15]. Mice that lack the mu-opioid receptor do not self-administer alcohol [16]. Naltrexone also modifies the hypothalamic-pituitary-adrenal axis to suppress ethanol consumption [17].
The usual dose of naltrexone is 50 mg/day, but some trials have used up to 100 mg/day [18].
Efficacy — Multiple metaanalysis of clinical trials for alcohol dependence found naltrexone to reduce alcohol consumption compared with placebo [19,20]. As an example, a 2010 meta-analysis of 50 randomized trials with 7793 alcohol dependent participants found that naltrexone reduced the risk of heavy drinking to 83 percent of the risk in the placebo group (relative risk [RR] 0.83, 95% CI 0.76-0.90) and decreased drinking days by about 4 percent [20].
Naltrexone may be particularly efficacious in individuals with genetic susceptibility. Preliminary evidence suggests that individuals with the Asp variant of the OPRM1 gene are less likely to experience relapse when receiving naltrexone, but further study is needed to confirm the finding [18,21]. Patients who were heterozygous for the Asp-40 allele were almost six times more likely to have a favorable outcome with naltrexone treatment than those who did not carry this allele.
Adverse effects — Common side effects of oral naltrexone are nausea, headache, and dizziness, which subside with continued use. Fivefold elevation in liver enzymes occurred in 11 of 614 patients who received naltrexone in the COMBINE Study. Enzyme levels returned to baseline after discontinuation of medication in the nine patients who had stopped drinking and returned for follow-up [18]. Liver enzymes should be monitored periodically during naltrexone treatment.
Depot naltrexone — Depot preparations of naltrexone may improve adherence by reducing the frequency of medication administration from daily to monthly and by achieving a steady therapeutic level of medication, thus avoiding peak effects that can exacerbate adverse events [22]. There are three extended-release, injectable formulations of naltrexone (Vivitrol, Naltrel, and Depotrex). There are no published head-to-head comparisons of their efficacy or bioavailability.
Only Vivitrol has been approved for use in the US, at a dose of 380 mg every four weeks. The injectable suspension should be administered via intramuscular injection to the gluteal area using the provided 1.5 inch 20-gauge needle. The US Food and Drug Administration has warned against other forms of administration including IV or injection subcutaneously or into fatty tissue on the basis of post-marketing reports of serious injection site reactions (See 'Adverse effects' above.).
Efficacy — A large randomized trial found subjects receiving Vivitrol 380 mg monthly had a 25 percent greater reduction in the rate of heavy drinking after 24 weeks compared with those receiving placebo (HR 0.75, 95% CI 0.60-0.94) [23]. While subgroup analysis suggested that the treatment may be less effective in women, the proportion of women in this study was relatively small, and these findings may be due to patient characteristics that differed between men and women.
A multi-site randomized trial of the Naltrel formulation did not show a significant difference in the primary outcome, time to first heavy-drinking day, compared with placebo (median of 11 versus 6 days) [24]. However, Naltrel was more efficacious than placebo at increasing the mean number of abstinent days (53 versus 46 days).
Adverse effects — Common adverse events observed among subjects receiving Vivitrol included nausea (33 percent), fatigue (20 percent), and decreased appetite (13 percent). Serious adverse events were reported for two trial participants receiving naltrexone who experienced an interstitial pneumonia and an allergic-type eosinophilic pneumonia, both of which resolved with treatment.
In 2008, the Food and Drug Administration (FDA) in the United States (US) reported 196 cases of serious injection site reactions from post-marketing surveillance including induration, cellulitis, hematoma, abscess, and necrosis. The FDA advised that patients be told to report injection-site pain, swelling, bruising, pruritus, or redness that does not improve within two weeks, and that a surgical consult be considered for worsening reactions [25].
Acamprosate — Acamprosate's principal anti-drinking neurochemical effect has been attributed to the modulation of glutamate neurotransmission at metabotropic-5 glutamate receptors [26].
The usual dose for acamprosate is 666 mg three times daily. Lower doses should be considered for some patients, including those with renal impairment, body weight less than 60 kg, or a history of response to a lower dose.
Efficacy — Multiple metaanalysis have found acamprosate to reduce alcohol consumption compared with placebo in patients with alcohol dependence [19,27]. As an example, a meta-analysis of 24 randomized trials of 6915 participants compared treatment with acamprosate to placebo or active control [27]. Acamprosate reduced the rate of patients returning to any drinking (relative risk [RR] 0.86, 95% CI 0.81-0.91; NNT = 9) and increased the cumulative abstinence duration by an average of 11 percent. Acamprosate was found not to have a significant effect on heavy drinking.
The evidence on the efficacy of acamprosate has evolved over time and requires further investigation. A 2004 meta-analysis of the 17 European trials found that acamprosate increased six-month abstinence rates compared with placebo (36.1 versus 23.4 percent) [28]. Positive results were primarily seen for maintenance of abstinence rather than reduction of drinking by non-abstinent patients.
Three subsequent trials conducted in the US and Australia found acamprosate did not improve primary outcomes, including percentage of alcohol-free days and time to first heavy drinking [18,29,30]. One of the trials, the COMBINE Study, found acamprosate (either alone or in conjunction with a psychosocial intervention) to be no more effective than placebo, while naltrexone was significantly more effective than placebo, indicating that the trial was adequately designed and powered to detect significant effects [18]. (See 'Oral naltrexone' above.)
It is not known whether discrepant findings between the European and US trials result from differences in sample composition, study methodology, or other factors. As examples of sample differences, the European trials on average enrolled subjects with more severe alcohol dependence treated in less controlled environments. The COMBINE study, conducted in the US, limited enrollment to individuals with at least four days of abstinence and no more than 21 days, while the European trials tended to enroll individuals abstinent for longer periods.
Adverse effects — Acamprosate is generally well tolerated at doses of up to 3 g/day. The most prominent adverse events are diarrhea, nervousness, and fatigue, which usually subside with continued use. Because acamprosate is excreted mostly unchanged by the kidneys, rather than the liver, it can be used safely in severely alcohol-dependent individuals with liver disease. Acamprosate dosage needs adjustment for renal insufficiency and is contraindicated in patients with renal failure.
Disulfiram — Disulfiram is an aversive agent that does not directly influence motivation to drink, but discourages drinking by causing an unpleasant physiologic reaction when alcohol is consumed. Clinical trials suggest that disulfiram is effective principally when taken routinely under supervised conditions.
Disulfiram inhibits aldehyde dehydrogenase and prevents the metabolism of alcohol's primary metabolite, acetaldehyde [31]. Drinking alcohol while taking disulfiram results in the accumulation of acetaldehyde in the blood, which causes unpleasant effects such as sweating, headache, dyspnea, lowered blood pressure, flushing, sympathetic overactivity, palpitations, nausea, and vomiting.
Contraindications — Contraindications to disulfiram include severe myocardial disease and/or coronary occlusion, psychosis, or known hypersensitivity to the medication or other thiuram derivatives [32,33]. Disulfiram is generally avoided in pregnant and nursing women. (See 'Treatment during pregnancy' below.)
Administration — Disulfiram is initially dosed at 500 mg/day for one to two weeks, followed by an average maintenance dose of 250 mg/day with a range from 125 to 500 mg based on the severity of adverse effects. The medication should not be used by patients with current alcohol intoxication. Patient education should address "hidden" forms of ethanol (eg, tonics and mouthwashes) and the duration of the drug's activity (up to 14 days after stopping).
Efficacy — A 2014 meta-analysis of two clinical trials with a total of 492 patients did not find a significant difference between disulfiram and placebo in return to any drinking or other primary substance use disorder (SUD) outcomes [19]. A systematic review found mixed results in one large trial and three smaller trials of disulfiram versus placebo for alcohol dependence [34]. The large study, a 52-week, multi-site trial of 605 US veterans, found disulfiram to be no more effective than placebo in maintaining abstinence or in time to first drink, but it may have reduced drinking days in a subgroup that drank during the study [35]. A high rate of noncompliance with medication was seen.
A subsequent study suggested that disulfiram is effective when the medication is taken routinely under supervised conditions. In a trial, 243 patients with alcohol dependence were randomly assigned to receive disulfiram, naltrexone, or acamprosate with regular supervision over a 12-week period [36]. Compared with patients taking naltrexone or acamprosate, patients taking disulfiram experienced a greater reduction in heavy drinking days and average weekly consumption, and a longer time to first drink. The relative benefits of disulfiram were less prominent in a subsequent, unsupervised treatment period of up to 52 weeks.
Adverse effects — Side effects of disulfiram are usually minor, including fatigue, mild drowsiness, headache, and dermatitis. Severe adverse reactions are rare, but include psychosis and hepatitis. Patients receiving disulfiram should be monitored for hepatotoxicity [37].
Topiramate — Topiramate, a sulfamate-substituted fructopyranose derivative, has been found to decrease alcohol use in individuals with alcohol dependence. It has not been approved by the US FDA for this indication. Topiramate has two principal mechanisms of action that may contribute to its anti-drinking effects:
●Antagonizing alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors and kainate glutamate receptors [38].
●Facilitating inhibitory GABA(A)-mediated currents at non-benzodiazepine sites on the GABA(A) receptor [39].
Topiramate should be titrated up gradually over several weeks to minimize side effects. It is generally initiated at 50 mg/day and increased to a maximum dose of 150 mg twice daily [40].
A 2014 metaanalysis of three clinical trials with a total of 691 patients with alcohol dependence found topiramate to result decreased consumption compared with placebo on some primary SUD outcomes [19]. Four placebo-controlled trials have shown topiramate to decrease alcohol use among alcohol dependent individuals [41-44]. As an example, a multi-site trial found that topiramate reduced the percentage of heavy drinking days compared to placebo (43.8 versus 51.8 percent) among 371 men and women with alcohol dependence over 14 weeks [43]. Topiramate was more effective than placebo in percent days abstinent, number of drinks per day, and plasma gamma glutamyl transferase, a biological marker of alcohol intake. Trial dropout rates were higher in the topiramate group compared with placebo (39 versus 23 percent).
Three randomized trials comparing naltrexone to topiramate in patients with alcohol dependence found little difference between the drugs in primary outcomes [44-46].
Adverse effects — Adverse effects associated with topiramate include cognitive impairment (eg, word-naming difficulties), paresthesias, weight loss, headache, fatigue, dizziness, and depression. Adverse effects of topiramate are discussed in more detail separately. (See 'Treatment during pregnancy' below and "Antiseizure drugs: Mechanism of action, pharmacology, and adverse effects", section on 'Topiramate'.)
Gabapentin — Clinical trials support the efficacy of gabapentin in treatment for DSM-IV alcohol dependence, though this has not been definitively established in a sufficiently large sample, and there is some concern about its abuse potential [47]. As an example, a trial randomly assigned 150 adult patients with DSM-IV alcohol dependence to treatment with either 900 or 1800 mg/day of gabapentin or to placebo [48]. All patients received concurrent manual-based counseling. After 12 weeks, abstinence rates were higher in patients receiving gabapentin compared to patients receiving placebo (11 and 17 percent in the 900 and 1800 mg/day groups versus 4 percent in the placebo group, though confidence intervals for pair-wise results overlapped with placebo). Similar overall and pair-wise results were observed for rates of no heavy drinking. There were no serious adverse drug events.
Earlier clinical trials found evidence that gabapentin reduced alcohol consumption in patients with DSM-IV alcohol dependence, but these trials had small sample sizes and other methodologic limitations [49-51].
Gabapentin is well tolerated at low and moderate doses; sedation and dizziness can occur at higher doses. In our clinical experience and in published reports, gabapentin is subject to abuse by some patients treated for a SUD [52-56].
Baclofen — Clinical trials comparing baclofen (30 mg/day) with placebo in the treatment of alcohol dependence have found mixed results. Two trials with a total of 123 patients found that baclofen led to higher rates of abstinence compared with placebo [57,58], while a third trial with 80 patients found no significant differences in abstinence rates or in other primary outcomes compared with placebo [59]:
●A 12-week trial randomly assigned 80 subjects with alcohol dependence to receive baclofen (30 mg/day) or placebo; both groups received a low-intensity psychosocial intervention. No differences were seen in heavy drinking days, days abstinent, or time to relapse [59].
●A 12-week trial compared baclofen (10 mg three times daily) with placebo in 84 individuals with alcohol dependence and liver cirrhosis [57]. Individuals receiving baclofen were more likely to achieve and maintain abstinence compared with placebo (71 versus 29 percent; OR = 6.3, 95% CI 2.4-16.1). The cumulative duration of abstinence was also greater with baclofen (63 versus 31 days).
●A four-week trial comparing baclofen (30 mg/day) with placebo in 39 subjects with alcohol dependence found greater abstinence rates with baclofen compared with placebo (70 versus 21 percent) [58].
Preliminary evidence from a retrospective case series [60] and a secondary analysis of clinical-trial data [61] suggested that a higher dose of baclofen (60 mg/day) may be effective in alcohol dependence, but this requires further study in randomized trials.
Baclofen treatment was well tolerated in these trials, with no abuse liability. No serious adverse effects were seen, including hepatotoxicity, encephalopathy, or hyperammonemia. Mild-to-moderate side effects occurring at a greater rate than in the placebo group included nausea, vertigo, transient sleepiness, and abdominal pain [57,58].
Nalmefene — Nalmefene, an opioid antagonist, has been found to reduce drinking in patients with alcohol dependence using a targeted dosing strategy. Nalmefene has several potential advantages over naltrexone, including absence of dose-dependent liver toxicity, longer-acting effects, and more effective binding to central opiate receptors. Nalmefene is not available in some countries, including the US.
A 2014 metaanalysis of three clinical trials with a total of 608 patients with alcohol dependence found nalmefene to be superior to placebo on some primary SUD outcomes [19].The three trials used a targeted dosing strategy (ie, taken as needed prior to encountering a high-risk situation) [62-64]. As an example, a trial compared nalmefene using a targeted dosing strategy with placebo in 403 patients. Subjects were instructed to take 10 to 40 mg on days when drinking seemed imminent [64]. After 28 weeks, the mean number of heavy drinking days showed a greater reduction among individuals receiving nalmefene compared with placebo (44 versus 32 percent). Two of the trials used an 18-mg dose of nalmefene [62,63].
Mixed results have been found in trials of patients with alcohol dependence comparing daily oral nalmefene with placebo on the primary outcomes of relapse rates and heavy drinking days.
●Two 12-week trials in a total of 126 patients with alcohol dependence compared nalmefene 10 mg twice daily, 40 mg twice daily, and placebo [65,66]. A meta-analysis of the trials found nalmefene led to a greater reduction in relapse rate compared with placebo (relative risk [RR] 0.62, 95% CI 0.41-0.93) [67]. Outcomes did not differ by medication dose.
●A trial of 270 subjects with alcohol dependence compared patients treated with one of three doses of nalmefene (5, 20, or 40 mg) or placebo [68]. No differences in outcomes were found among any of the groups.
Adverse events occurring more commonly with nalmefene than placebo in this trial included nausea, insomnia, fatigue, dizziness, and malaise. In addition, fifteen subjects receiving nalmefene experienced psychosis or dissociation. Adverse events led to discontinuation of nalmefene among 16 percent of subjects and dose reduction among 31 percent.
Selective serotonin reuptake inhibitors — A meta-analysis of seven trials found that selective serotonin reuptake inhibitors (SSRIs) do not effectively treat alcohol dependence in patients who do not have a comorbid mental disorder [69]. These trials have several limitations: short time frames, a preponderance of male subjects, and use of non-standardized psychosocial interventions.
Studies suggest that SSRIs may be effective in more homogenous subgroups:
●A meta-analysis found that SSRIs and other antidepressants can reduce intake when alcohol dependence and depression co-occur [70]. (See "Co-occurring schizophrenia and substance use disorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment and diagnosis".)
●Preliminary evidence suggests that subtypes of alcohol dependence may respond differently to serotonergic drugs, with more favorable outcomes seen in the group characterized by a later age of onset, a preponderance of psychosocial morbidity, and low familial loading. Lesser response to these agents, or even increased alcohol consumption, has been observed among individuals with an earlier-onset subtype, which has high familial loading and a range of impulsive or antisocial traits suggesting careful assessment and follow-up when using SSRIs in alcohol-dependent individuals [71-74].
(See "Serotonin-norepinephrine reuptake inhibitors (SNRIs): Pharmacology, administration, and side effects".)
Ondansetron — Early-onset alcohol dependence (onset of problem drinking prior to age 25 years) differs from late-onset alcohol dependence (onset of problem drinking later than age 25 years) by having associations with greater serotonergic abnormality and antisocial behaviors. Ondansetron, a serotonin 5-HT3 receptor antagonist used to treat chemotherapy-induced nausea, does not appear to effectively treat all patients with alcohol dependence, but clinical trials suggest that the drug is selectively effective in two clinical subgroups [75-78]:
●Patients with early-onset subtype of alcohol dependence
●Patients with a specific genetic variant of the serotonin transporter (5-HTT) gene. (See 'Neurobiology' above.)
Clinical trials of ondansetron in samples of patients with alcohol dependence (undifferentiated, early/late, and varied genotypes, respectively) are described below:
●A six-week randomized trial of 71 men with nonsevere alcohol dependence (not differentiated by subtype) found no significant difference between ondansetron and placebo in alcohol consumptions [75].
●A 12-week randomized trial of 271 individuals with alcohol dependence, which differentiated subjects by age of onset of alcohol dependence, found that ondansetron was more effective than placebo on multiple measures of alcohol intake for those with early-onset of the disorder, but not late-onset [76]. No severe adverse events occurred in the trial; no difference was seen between the ondansetron and placebo groups in rates of mild-to-moderate adverse events.
●A 12-week randomized trial compared ondansetron (4 mcg/kg intravenously injected twice daily) with placebo in 283 individuals classified into one of three categories by genotype: the LL, LS, and SS genotypes in the promoter region of the serotonin transporter (5-HTT) gene [78]. Individuals with the LL genotype who received ondansetron had a lower mean number of drinks per drinking day (–1.62) and a higher percentage of days abstinent (11.27 percent) than those who received placebo. Individuals with both the LL and TT genotypes who received ondansetron reported fewer drinks per drinking day (–2.63) and a higher percentage of days abstinent (16.99 percent).
Adverse effects — Adverse effects associated with ondansetron include diarrhea, headache, and fever. Ondansetron prolongs the QT interval in a dose-dependent manner, and should be avoided in patients with underlying heart conditions, such as congenital long QT syndrome, or taking other medications that lead to QT prolongation [79].
OTHER MEDICATIONS — Medications currently under study for alcohol use disorder include other anticonvulsants, antipsychotics, dopamine antagonists, CRF antagonists, neuropeptide Y antagonists, varenicline, and the cannabinoid receptor antagonist rimonabant.
COMBINING MEDICATIONS — Combining medications, particularly those with different mechanisms of action, offers the possibility of more effective treatment for patients who do not respond adequately to an individual agent.
Two trials compared the combination of oral naltrexone and acamprosate, finding mixed results. In a trial of 160 individuals with alcohol use disorder, the group receiving naltrexone and acamprosate experienced fewer relapses and a longer time to first drink than those receiving acamprosate alone. However, the combined medications were no more effective than naltrexone alone [80]. The COMBINE Study did not find an advantage to combined naltrexone-acamprosate treatment compared with either the individual agents or placebo [18]. (See 'Oral naltrexone' above.)
A small, eight-week trial of the combination of ondansetron and naltrexone for early-onset alcohol use disorder led to reduced drinking and reduced levels of carbohydrate-deficient transferrin (a marker of alcohol use) compared with placebo. Combined treatment was not compared with either drug individually [81,82].
Two trials found the combination of naltrexone and sertraline (an SSRI) to be no more effective than naltrexone alone in maintaining abstinence among individuals with alcohol use disorder [83,84].
COMPARING MEDICATION WITH PSYCHOSOCIAL TREATMENTS — There are no clinical trials that directly compare medications to psychosocial interventions in alcohol dependence or alcohol use disorder. (See "Psychosocial treatment of alcohol use disorder".)
COMBINING MEDICATION WITH PSYCHOSOCIAL TREATMENTS — The evidence is mixed as to whether combining medication with a structured psychosocial intervention leads to better outcomes for alcohol use disorder than medication alone (see 'First-line medications' above and 'Acamprosate' above and "Psychosocial treatment of alcohol use disorder"):
●The COMBINE Study compared naltrexone, acamprosate, a psychosocial intervention, combination naltrexone-psychosocial treatment, acamprosate-psychosocial treatment, and placebo in 1383 patients with alcohol use disorder [18]. The psychosocial intervention integrated aspects of cognitive-behavioral therapy (CBT), 12-step programs, motivational interviewing, and support system involvement. No differences were seen with either medication combined with psychosocial treatment compared with the respective medication alone or the psychosocial treatment alone.
●An earlier, smaller study provided limited evidence suggesting combined naltrexone and CBT were more effective than naltrexone alone [85].
TREATMENT SELECTION — Limited data are available on comparative effectiveness, drug characteristics, treatment goals, and predictors of response that can inform clinicians' selection among treatments for alcohol use disorder. The suggestions that follow are based on these data and our clinical experience.
●We suggest that patients with moderate to severe alcohol use disorder initially be offered a choice of medication or an evidence-based psychosocial intervention such as cognitive behavioral therapy (CBT). There are no trials comparing the two, and findings are mixed as to whether the combination of both is more effective than either intervention alone. (See 'Comparing medication with psychosocial treatments' above and 'Combining medication with psychosocial treatments' above.)
•Patients with the mild subtype of alcohol use disorder who are currently drinking heavily and risk serious consequences can be considered for these treatments on a case-by-case basis. Data on the efficacy of these interventions are typically not generalizable to patients with the mild subtype.
●For patients who do not achieve remission or an adequate reduction in heavy drinking with medication or a psychosocial intervention, we recommend combining modalities if the first was partially effective or switching modalities if the first was ineffective. (See 'Combining medication with psychosocial treatments' above.)
●When medication is used for alcohol use disorder, we suggest first-line treatment with naltrexone for most patients over other medications. Metaanalyses of trials comparing acamprosate with naltrexone found no significant difference between them for return to any drinking or return to heavy drinking. An earlier, 2006 meta-analysis concluded that acamprosate may be more effective for maintenance of abstinence (compared with placebo, relative risk [RR] 0.84, 95% CI 0.78-0.91), while naltrexone was more effective for reduction of heavy drinking (compared with placebo, relative risk [RR] 0.80, 95% 0.71-0.91) [86]. (See 'Acamprosate' above and 'First-line medications' above.)
Predictors of therapeutic response to naltrexone include family history of alcohol use disorder and strong cravings for alcohol [87]. (See 'First-line medications' above.)
Predictors of therapeutic response to acamprosate include increased levels of anxiety, physiological dependence (ie, severe symptoms of withdrawal), negative family history, late age of onset, and female gender [88]. (See 'Acamprosate' above.)
Depot naltrexone is an option for treatment of patients likely to be nonadherent to daily oral medication. Nonadherence presents an impediment to effective pharmacotherapy for a substantial proportion of patients with alcohol use disorder in clinical trials and in practice. As an example, 37 percent of patients taking naltrexone in a meta-analysis of clinical trials prematurely discontinued the medication during the study [67]. (See 'Depot naltrexone' above.)
●For pharmacotherapy of an alcohol use disorder in patients with acute hepatitis, liver enzymes greater than three to five times normal, or liver failure, we suggest acamprosate over other medications. Baclofen would be a reasonable alternative. Naltrexone has been associated with hepatotoxicity, particularly at high doses, and acamprosate has been shown to be safe for patients with alcohol use disorder and severe liver disease. Baclofen appears safe and effective for patients with alcohol use disorder and cirrhosis. (See 'First-line medications' above and 'Acamprosate' above and 'Baclofen' above.)
●Acamprosate should also be considered as an alternative to naltrexone for patients under concurrent treatment with opioids. (See 'Acamprosate' above.)
●Acamprosate is not indicated for the induction of abstinence in actively drinking patients. (See 'Acamprosate' above.)
●For patients with alcohol use disorder for which naltrexone and acamprosate are ineffective or not indicated, other options with evidence supporting efficacy include disulfiram, topiramate, gabapentin, baclofen, and ondansetron.
•Disulfiram should not be used unless the treatment goal is to maintain abstinence. Because this medication is associated with particularly high rates of nonadherence, use should be limited to highly motivated patients and those who take medication under supervision. (See 'Disulfiram' above.)
•Serotonergic agents may be more effective when used selectively for subtypes of alcohol use disorder. Preliminary evidence suggests that SSRIs may be more effective for a late-onset subtype and comorbid depression. Ondansetron, a serotonin antagonist, may be more effective for patients with an early-onset disorder and for patients with a specific genetic variant of the serotonin transporter (5-HTT) gene. (See 'Selective serotonin reuptake inhibitors' above and 'Ondansetron' above.)
TREATMENT DURING PREGNANCY — There is a paucity of data on the safety of pharmacologic therapies for alcohol use disorder in pregnant women. In weighing risks and benefits of prospective treatment, one should also consider the harmful effects of alcohol to the mother and to the developing fetus. (See "Alcohol intake and pregnancy".)
If feasible, treatment of pregnant women with substance abuse disorders should be managed by clinicians with specialized expertise in this area. Potential issues with medications used for alcohol use disorder include the following [89,90]:
●Naltrexone is used in pregnancy more commonly than are other medications for alcohol use disorder because of the absence of known, harmful effects; this decision should be made cautiously due to the absence of well-controlled studies of any of the medications in humans.
●Disulfiram may harm the developing fetus by increasing levels of acetaldehyde. In addition, the physiologic reaction between disulfiram and ethanol in the mother presents a potential risk to the fetus. For these reasons, disulfiram is rarely used in pregnancy.
●Opiate antagonists such as naltrexone are used with caution in pregnancy due to their potential to induce a withdrawal syndrome, harmful to the fetus, among patients surreptitiously taking opiates.
●Acamprosate is teratogenic in animal studies. There are no adequate studies of pregnant women with fetal exposure.
●There is an increased risk for the development of cleft lip and/or cleft palate (oral clefts) in infants born to women treated with topiramate during pregnancy, but this occurrence is rare [91].
●Topiramate has been found to be teratogenic in animal studies. It crosses the placenta in humans. A preliminary report on 203 prospectively followed pregnancies exposed to topiramate found a high rate of major congenital malformations [92]. (See "Risks associated with epilepsy and pregnancy".)
(See "Substance misuse in pregnant women" and "Alcohol intake and pregnancy" and "Management of moderate and severe alcohol withdrawal syndromes".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Alcohol use — when is drinking a problem? (The Basics)")
●Beyond the Basics topics (see "Patient education: Alcohol use — when is drinking a problem? (Beyond the Basics)")
●Medications to treat alcohol use disorder are needed despite the availability of effective psychosocial interventions. As many as 70 percent of individuals relapse after psychosocial treatment alone. (See 'Introduction' above.)
●Pharmacologic treatment of alcohol abuse use disorder has mostly focused on altering the reinforcing effects of alcohol use. Many available or promising medications appear to act by modulating the function of opioids, glutamate (with or without GABA), or serotonin. (See 'Neurobiology' above.)
●Goals for treatment include abstinence, the traditional objective of alcohol treatment, or reduction of heavy drinking, a measure of alcohol intake strongly related to negative life consequences. (See 'Treatment principles and overview' above.)
●We suggest that patients with moderate to severe alcohol use disorder initially be offered a choice of medication or an evidence-based psychosocial intervention, or both (Grade 2C). Patients with the mild subtype, current heavy drinking, and risk of serious consequences can be considered for medication treatment on a case-by-case basis. All patients should receive some psychosocial treatment. (See 'Indications' above and "Psychosocial treatment of alcohol use disorder" and 'Treatment selection' above.)
Patients who do not achieve remission or an adequate reduction in heavy drinking should receive a trial of the other modality or a combination of modalities. (See 'Treatment selection' above and 'Combining medication with psychosocial treatments' above.)
●For patients taking medication, we suggest naltrexone for most patients with alcohol use disorder over other medications (Grade 2B). Depot naltrexone should be used when there is a significant risk of nonadherence with daily administration; patients should be monitored for injection site reactions. Naltrexone is not appropriate for patients with liver disease or who are taking opioids. (See 'First-line medications' above.)
●For pharmacotherapy of an alcohol use disorder in patients with acute hepatitis, liver enzymes greater than three to five times normal, or liver failure, we suggest acamprosate over other medications (Grade 2C). Baclofen would be a reasonable alternative. The evidence for the efficacy of acamprosate is mixed. Its use may be considered for individuals with liver disease or those who do not respond to other medications. (See 'Acamprosate' above.)
●For patients with alcohol use disorder for which naltrexone and acamprosate are ineffective or not indicated, other options with evidence supporting efficacy include disulfiram, topiramate, gabapentin, baclofen, and ondansetron. (See 'Second-line medications' above.)
•Use of disulfiram should be reserved for individuals who are highly motivated to maintain abstinence, and are either treatment adherent or take the medication in a supervised setting. (See 'Disulfiram' above.)
•In treating alcohol use disorder with topiramate, care must be taken to increase the dose slowly to avoid adverse events including cognitive impairment (eg, word-naming difficulties), paresthesias, and weight loss. (See 'Topiramate' above.)
•Clinical trials of baclofen in alcohol use disorder have led to mixed results. Larger randomized trials are needed to determine its efficacy. (See 'Baclofen' above.)
•Targeted dosing of nalmefene has been found to improve outcomes in alcohol use disorder in clinical trials; trials of daily dosing have led to mixed results. (See 'Nalmefene' above.)
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Soldier and director of British Rail
Soldier and director of British Rail
Born: October 11, 1923 Died: March 18, 2014
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HARRY Hyde, who has died aged 90, was a soldier who was wounded and captured as he fought his way inland from Sword beach in Normandy on D-Day 70 years ago. He later became a director of British Rail and arranged all the Queen's visits to Scotland and accompanied her entourage on the Royal Train. He was also responsible for such prestigious state-owned hotels as the Caledonian, North British, Central, Gleneagles and Turnberry.
During the D-Day landings, he was posted "missing, believed killed" but shocked his parents when he turned up alive several months later. He had been treated at a German field hospital then sent to a prisoner of war camp before being liberated by advancing US forces.
He had enlisted as a sapper in the Royal Engineers when he was 17 and trained with Combined Operations forces before being attached to the Lovat Scouts for the Allied invasion of Europe. He was one of the first to be piped across Pegasus Bridge by Bill Millin, Lord Lovat's personal piper.
Assigned as a forward observer with No1 Combined Operations Bombardment Unit, he directed salvos of 15-inch naval gunfire from the battleship and Jutland veteran HMS Warspite. She had left refit in Greenock days earlier with larger guns and was the first to open fire on D-Day, targeting the German battery at Villerville.
The sole survivor of a landmine accident in which he was seriously wounded, he was taken prisoner and treated in a German field hospital. He was one of the first patients to undergo major surgery by epidural. He was then sent to a front-stalag near Rennes, before being liberated by the Americans in August 1944.
Meanwhile, his parents had received a letter saying he was missing, presumed killed. After spending some time recovering from his wounds in the UK, he was posted to the Far East to support landings in Burma and, following the Japanese surrender, was attached to the Ceylon Army Command as embarkation staff officer at the Port of Colombo. He directed the movement of freed Allied POWs and internees from the Dutch East Indies to Ceylon, for rehabilitation in rest camps before shipping home to Holland and the UK.
Harry Edward Hyde was born to Elizabeth Whysker and railwayman Harry Hyde at Carstairs, Lanarkshire. By the age of 14 he was in three jobs; collecting empty bottles for the cash refund, a paper round and a beater for the local pheasant shoot.
In 1947, after demob, he followed his father into the railways and at one point worked at Buchanan House in Glasgow, alongside his brother Adam and niece Alison. He also joined the Army Emergency Reserve as a captain in the Royal Engineers, later receiving the British Empire Medal and Emergency Reserve Decoration.
The railways were undergoing nationalisation and his first role was as establishments and staff officer at the newly-formed British Railways (BR) headquarters, Scottish Region. Through the 1950s and 60s he rose through the positions of traffic assistant, senior assistant to the general manager, secretary to the Scottish Railways Board and chief passenger manager.
Latterly, he arranged all the Queen's visits to Scotland and accompanied the entourage on the Royal Train. He was also responsible for all visits to Scotland of prime ministers and other dignitaries and VIPs. In 1976, he was appointed director of BR's in-house catering arm, Travellers Fare, and moved to England.
A fellow of both the Chartered Institute of Transport and the Hotel Catering and International Management Association, he was finally made executive director of British Transport Hotels. From 1982, he was involved in the Thatcher government's sell-off of prime railway assets such as the Caledonian and North British (now the Balmoral) hotels in Edinburgh, the Central in Glasgow and the Turnberry and Gleneagles hotels.
He fought cancer with stoicism for 15 years, surviving a 12-hour operation and declaring he was not ready to throw the towel in yet. He remained independent, refused personal carers and underwent five major operations, assuring medical staff he had been living on borrowed time since the war. He died in Torquay, having had his garden landscaped, house painted and placed all of his affairs in order.
Hyde wrote his own death notice and checked newspaper obituaries daily "to make sure I'm still alive". Colleagues recall a firm but fair manager who demanded exacting standards but rewarded this with typical generosity, while his loved ones remember a family man with a passion for football (Liverpool FC) and cricket.
He was predeceased by his wife of 52 years, Elaine Macpherson, in 2008. He is survived by their daughter, Carol, and three step grandchildren.


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Posts Tagged 'FBReader'
24 Must-Have, Everyday Workhorse Apps
If you're like me, your mobile device (phone, tablet, etc.) is loaded with apps. In fact, I've just checked and discovered that I've got hundreds installed! And that left me wondering, "How many of these things do I need? Which of these do I depend on every day?"
After some reflection, I came up with a list of my "24 must-have, everyday workhorse apps." Most are FREE or have free versions available. And, to the extent that they keep me personally productive, they help me be a better project manager and team member. See the complete list with brief descriptions at my WORTH SHARING site.
Edited: January 24th, 2017
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Edited: August 7th, 2016
Worth a Second Look: My Favorite Articles & Videos from 2014
New on my WORTH SHARING website: Some of my favorite articles, blog posts, and videos that I posted during 2014. Some are important. Others were merely fun or gratifying to create and I want to share them again before they disappear beneath 2015's posts. Check them out!
Edited: December 30th, 2014