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See our Counseling Calendar for additional important dates.
The following program application will be available for completion starting November 1, 2019 through February 1, 2020. Please see your AHS counselor for more information.
Find more information in the senior handbook, starting on page seven.
Standard Level
Advanced Level
Pre-Baccalaureate (IB)
Dual Enrollment (DE) - Senior Year
Advanced Placement (A = 5.0)
For classes with weighted credit in graduating classes 2020 and thereafter, students in Advanced Placement, Dual Enrollment, and International Baccalaureate courses receive weighted credit. A numerical advantage of 1.0 is assigned when calculating students' grade(s) for these courses, in accordance with the procedure for computing class rank. Students in advanced courses also receive weighted credit. A numerical advantage of 0.5 is assigned when calculating students' grade(s) for these courses, in accordance with the procedure for computing class rank. The program of studies and student schedules will clearly reflect which courses carry weighted credit. Appropriate school publications, including the program of studies, will state the criteria for placement in courses that carry weighted credit.
Find more detailed directions see our parent portal document.
*See the Hanover County Program of Studies for more information on courses offered at your level.
Contact your counselor for additional questions and information.


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ROBERT GRAHAM SKULL ROSE TABLET1 tablet
Take note, this handsome and handy tablet is embossed with our Signature Skull with a rose and Knowledge Wisdom Truth at the cover. Made in collaboration with American icon Dempsey & Carroll.
- Robert Graham x Dempsey & Carroll Skull Rose Tablets
- The tablet covers are engraved with Robert Graham's skull rose motif on the covers
- Include 65 blank interior 1-ply white cotton fiber pages
- Paper size: 5-1/8" x 3-3/4"
- Paper color: White
- Engraving ink colors: Black and Viva Red
- Packaging: Packaged in clear cellophane
Robertgraham.us offers FREE FEDEX GROUND SHIPPING on all U.S. orders. For security reasons, we do not currently ship to P.O. boxes or APO/FPO addresses. For more information or additional shipping options, click here.
Robert Graham offers FREE returns. Unwashed, unworn, unused or defective merchandise accompanied by an original sales receipt may be returned within 21 days of date of purchase for full refund in original form of payment. For more information, click here.

subset: commoncrawl


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Elective Home Education is where parents or carers of a child decide to educate their child at home instead of sending them to a school. The parent or carer would have full responsibility for providing a full time education suitable to the child's age and ability and to any special educational needs they may have.
Parents choose to home educate for many reasons, for example; cultural religious, philosophical, specific SEN needs. If you are considering home educating to avoid prosecution for non attendance at school or because of a disagreement with school we would advise you to contact the school directly or contact the EHE or education welfare service to discuss y...
RT @WarringtonBC: Come and see @hbreakontour Ratburger on 23 Aug - tickets on sale now! https://t.co/2tZRGjmE2Q https://t.co/ViIguLXJo9
We try to ensure that the content of our website accurately reflects our audience. We will utilise this information to ensure that we include the most relevant resources, news items and events on our webpage.
© Elective Home Education Service 2016
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Snowboard binding Union Strata Camo
- Earliest delivery 2020-10-01T08:00:00+02:00
View terms
The Strata Camo Union Snowboard binding delivers top-levels of support and comfort to help you chain descents on all terrains. All of that with enough flexibility for freestyle.
The Strata is a performing and versatile Union snowboard binding with awesome abilities for the resort and the park. Its tonic highback offers a great backside support but it is still pretty comfy to ride to make sure you make the most of your sessions. Icing on the cake, its price is more than decent and you get top-quality materials such as Magnesium buckles for more durability.
What's on the agenda for the Union Strata Camo snowboard binding?
The Strata features a light and robust baseplate working together with a pretty tonic highback and quality straps to provide you an excellent foot support. This way, you're sure to enjoy a perfect control of your board and get enough responsiveness to really send it in the curves and build some serious speed in the descents. The binding helps you absorb shocks and vibrations efficiently. Its flexibility lets you pull tricks along the way and even have a go at the snowpark!
Who is the Union Strata Camo snowboard binding for?
Even if it is rather playful and accessible with a good freestyle potential, this is still a powerful model destined to advanced riders seeking a great support, versatility and comfort.
What are the main assets of the Union Strata Camo?


text: Dive into a few of the most popular reports With 12,000 clients, we have thousands of reports being generated through our operations management software every minute with information on work orders, equipment and assets, staff time and more that help maintenance technicians, facility and energy managers, directors, COOs and others make decisions about how to do their work more efficiently. At The Dude, it's our goal to take what may seem boring, time-consuming and tedious with compiling reports and sharing data to be a task that is quick, easy and inspiring about what you're doing well and what you can improve. "With just the click of a button, I have the reports available to me. I can run over 800 reports, and it is so easy." -Barry Hipp, Cleburne Independent School District We see it as a way for The Dude to be a part of your team, with reports that matter to you and your leadership right at your fingertips. Our software is always busy tracking, calculating and organizing, so you can take those critical numbers and share them when it matters. "It now only takes a couple of clicks for me to pull a variety of reports. I can either custom create these reports or use the default reports that come built in (which truly cover the gamut of what I was having to manually put together in the past)." -Erin Johnson, Craighead County, AR So, what are the top reports that clients use to help them in their daily work? We're excited to share those with you, and first we're focusing on the top work and asset reports. 1. Asset Life Analysis How are each of my assets (or equipment pieces) performing? What It Shows: This report shows a quick analysis of the current health of your assets, including fields like total # of work orders (WOs), total # PM (preventive maintenance) WOs and total # of non-PM WOs. It also calculates a grade for each asset to estimate how many more years you can expect out of your assets. Why It Matters: Whether you're working on your budget or just trying to see which of your larger assets is in need of repair or replacement sooner, this report is helpful to understand your future needs. The letter grade also helps you communicate replacement or budget needs to other decision makers. "Additional cost savings exists around asset management and knowing, based on the tracking of your work on a particular piece of equipment, where you fall within the repair versus replace decision." -Bob Lanzerotti, Windsor Park 2. Average Days to Complete Work How quickly is my maintenance team getting to work orders? What It Shows: This simple report shows an average of how many days it takes to complete a work order, calculated from the days completed for each of your work requests. Why It Matters: Maybe you want to see how fast your team is getting work done? Maybe you want to compare yourself to another site or organization like yours? Maybe you would like to set a goal to reduce your average for completing work? These are all good reasons for using this report to know where you stand. See how YMCA of Delaware completes 96% of their corrective work orders on time. 3. Site Comparison of Work What does my maintenance workflow look like across sites? What It Shows: This report shows the number of work orders (WOs) by site and breaks them down by status and category per site, as well as compares PM vs non-PM completed work. This report also includes a summary of WO cost/hours/average cost/average hours per site. Why It Matters: See and compare various sites of your organization as far as workflow and gauge how proactively each site is working. This can help you understand how work orders are being distributed and ways you can improve consistency across locations. See how Cory at Riverview Retirement used work order reporting to show his need for an additional team member. 4. Labor Productivity How is work being distributed between my individual staff members and contractors? What It Shows: This labor productivity report draws on your work order data to show you a roll-up of time, costs and counts of work orders grouped by individual, including graphic capabilities. Why It Matters: With this report, you have the ability to easily keep an eye on your staff and contractors as far as their workloads, costs and the time it takes them to complete work. This analysis can help you distribute work more efficiently, reward hard workers, motivate those at the bottom of the pack or better understand your staffing needs overall. "If I want to find out about a piece of equipment or how many work orders an individual has completed — anything within the system — I can glean the reports rapidly at a glance." -Barry Dean, Aprilaire 5. Workload & Cost/Time Analysis How much work did my team or department handle last month? What It Shows: This analysis shows you how many work orders are in each category (e.g. Carpentry, Electrical, etc.), as well as how many are new, completed, percentage completed, and average days open and overdue. The cost/time analysis visually breaks down work by categories, labor time, cost and average days open. Why It Matters: This type of report is a good way to see how your resources are being used currently. From where you're spending most of your time to how long it takes to complete a specific type of task, this report gives you a nice view of how work is flowing through your department. "Having the numbers gives me an edge when presenting my budget for review. I've seen other departments getting their budget cut or staying the same, while my budget has increased." -Nathan Nagle, Village of Horseheads, NY These types of reports could be the data you need to: Hire more staff Make a realistic budget Save on your operations budget Get the funds to replace that piece of equipment Make daily decisions to benefit your work and team Check out our top reports for energy and event management and reach out to us if you're interested in improving reporting for your department and organization. *Reports for this article were pulled from two work and asset management products: Asset Essentials™ and TheWorxHub™. download case study


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The morning has dressed for Winter. Blue sky trimmed with bands of wrinkled white clouds their bellies lined grey, it is the first full day after the official beginning of Winter. That is where I beg to differ. The way I see it? This is the first unofficial first day of Winter's end. That's right, lol. Just go ask Clark. He'll tell you unequivocally, Winter is over. Go 'head. Dare you 😀
I woke this morning fairly early for a day I could sleep in. Not only Saturday, it's the Saturday before Christmas and the beginning of a mini-vacation. I don't have to return to work until next Wednesday. Sweet. A longtime believer in the body knows first, I was pouring my second mug of go-go juice, when I was accosted by a few creative "punks" taunting, "Gee, Denise, no pressure, why not sit and write a spell, huh?, huh?" Floating in a pressure free zone, they knew words tended to coalesce easier, you know, when they don't have to appear. When they don't need to perform.
Now what?! Seems I've scared them away. No nevermind. Cat's out of the bag. I'm on alert now! (and no. won't give in to the notion I've "wrecked it somehow"). Since I'm also one to not (intentionally) follow convention, not naturally blend in, I would like to take this opportunity to say Thank You to some folks and to shout out to the Universe my appreciation in this official, unofficial TToT:
Kristi, creator of Thankful Me. Even though we be on holiday hiatus, thank you for bringing us all the Ten Things of Thankful Blog Hop.
Clark. For the Wakefield Doctrine and providing living proof that commitment and practice produces results.
Zoe. She handed me the baton and challenged me to lead the Six Sentence Story Blog Hop. I'm thankful she did!
Six Sentence Story current (and past and on hiatus) participating writers: Mimi, Paul, Reena, Clark, Deepa, Pat, Dark Netizen, Neel, Rene, D. Avery, Sa, Ira, Deborah Lee, Val, Lisa, Kristi, Dyanne…I know I'm leaving someone out – my apologies! Bottom line: I totally enjoy bringing everyone the writing challenge that is the SSS and so appreciate reading your work. It's not only an entertaining endeavor, it's an opportunity to learn, to discover, and to enjoy getting to know people I'd otherwise never know!
Cynthia aka Sageleaf of Intuitive and Spiritual. She is a bright, shining beacon for my people 🙂 Talented and creative, I'm lucky to call her friend.
The Internet/Techonology. See above!
Family. In all its iterations.
For a warm place to live, transportation to take me where I want/need to be.
Health, vitality, opportunity to increase both.
This day…This day, my gift…This day my opportunity…This day, my only day.
Thank you all for giving me a bigger world.


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If you are planning six guests or less, our elopement package provides an officiant with all the legal and documentation help, and a photographer to capture the amazing experience of your Puerto Rico wedding. We help you find the most beautiful and perfect location for your Puerto Rico elopement, and offer add-on services (video, hair & makeup, bouquet & boutonniere, etc.) to customize the day to exactly what you'd like. Not much advance time is required…..we have arranged and performed legal destination weddings in as little as 48 hours notice!
Puerto Hermina
The Ruins in Aguadilla
Gozalandia Falls
Cueva las Golondrinas
Old San Juan Harbor
Elopement Package
- Detailed preparation checklists
- Phone and email help with marriage license
- Customized ceremony
- Registration of your marriage
- One hour's professional photography
- Two witnesses (if needed)
Additional Services Include
- Wedding arbor
- Flowers
- Hair & makeup artist
- Cake
- Champagne toast
- Video with drone footage by FAA certified drone pilot
- Aerial drone photos by FAA certified drone pilot
Effortless & stunning small wedding packages in Puerto Rico. Open-air beach weddings & elopements. Contact us for locations and pricing.


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Category Archives: Guides
Patio in Barnton, Edinburgh
– here's some pictures of our latest project in Barnton, Edinburgh. Showing a terraced patio constructed from sandstone paving in random bond, with a spherical stone water feature.
Landscape Gardeners Edinburgh- Picture Gallery
landscape gardeners edinburgh- here is a picture gallery of recent landscaping work at www.garden-co.com or view our blog here
Good Paving Guide
Good paving can look stunningly good and really enhance your garden. Here is our short guide to choosing the best paving: the good paving guide.
Paving guide: Why choose a professional?
There will often be smaller paving jobs that the experienced DIY enthusiast can happily have a go at but when it comes to a serious project you should find a good professional. An experienced paving contractor will have access to all the specialised tools and heavy equipment that may be required as well as having the experience and knowledge to foresee any difficulties that might come up during the job. Also, a contractor will know all local council regulations and planning laws, and be able to guide you to the best materials at the best prices.
Paving guide: Which materials to use?
There is a wide range of paving materials you can choose from and the best is not necessarily the most expensive. The most important consideration is how you intend to use the paved area. A driveway intended for everyday heavy traffic will require different materials from a simple decorative garden path.
Another factor in the cost of your project is how long the material you choose will last. Some materials have a low initial cost but require a lot of re-installation and can therefore have a higher cost over the lifetime of your garden than a material which is initially more expensive but also more durable.
Paving guide: How is paving done?
There is a hidden complexity to paving, below the surface all paving is made up of layers, which give it stability and strength. To give you an idea of what the contractor will be doing here is how those layers are created:
- Digging: First, the area that is prepared will have to be prepared.
- Geo-sheet: A geo-sheet is a man-made separation membrane which is installed between the now bare earth and the next layer. This is particularly important if the earth is soft.
- Sub-base: Next the sub-base is added. This is important, as it is the main load-bearing layer. The sub-base will consist of crushed rock and sand and sometimes cement or tar is added.
- Bedding Layer: Then some more sand is added for the paving blocks to settle on.
- Paving Layer: The top layer, the one you will see.
- Sealing: Finally to complete the project fine sand is brushed over the paving material to seal the joints. It is later compacted.
Paving guide: Paving materials
Here's where we need to focus our creativity. There are many options but one important one is whether to go for either man-made or natural paving. Of the man-made materials tarmac is an obvious candidate but it is also worth noting that there is a wide range of durable concrete-based materials available, some quite attractively patterned.
Here are some of the best natural paving materials:
- Bark: A cheap and cheerful option as bark is readily available at most garden centres. Whilst not being suitable for a heavily used driveway as it will need regular 'topping up' it is much more suited for garden pathways because of its woody, natural look and for children's play areas because it is soft and therefore good landing material.
- Gravel: Gravel can come in a surprising range of sizes, styles and colours. Although it is relatively cheap is can be used in garden pathways and even driveways if properly installed with good drainage and a firm concrete foundation. Gravel paving may need occasional weeding in the summer.
- Cubes: Cubes and setts, cobbles and cobblestones are interchangeable terms depending on your location. There's a whole range of regional terms, too, such as "Cassies" or "Nidgers" in Scotland, and "Belgian Block" in some strange places in southern England. These blocks of natural stone are available in a huge array of colours and finishes. They have proven durability in that paving created by the Romans using these materials can still be found in use today. A more expensive option due to both the cost of the material and the high level of workmanship involved.
- Flagstones or Flags: Flat natural stone, usually Slate, Granite and Yorkstone can look really impressive when laid expertly, but it is very labour-intensive and thus expensive. As with setts, price increases if you choose imported stone. Besides the many stone types, some suppliers also offer a variety of textured finishes, a safety consideration if the pavement is to be used for walking. Some stone types are better suited to heavy vehicular traffic than others, so ask your contractor or supplier.
- Cobblestones: Large, rounded river pebbles. Can be uncomfortable to walk on, so it is often used as a deterrent paving to discourage pedestrians. Moderately priced and virtually maintenance-free, cobblestones can be used in driveways, if carefully laid. Not really suited for garden pathways because they can be slippery, cobblestones can, however, make an attractive border for ponds and other garden features.
Paving guide: Paving pitfalls
Getting paving right can be surprisingly difficult. Here are some potential problems that an experienced contractor can help you avoid:
- Size: it is as easy to make a paved area too small – or too large.
- Supply: most of the paving materials sold in garden centres are unfortunately pretty awful. An experienced contractor will know exactly where to get the best materials at the best prices.
- Design: sometimes it is best to align a path on the most direct route (the 'desire line'); other times it is best to take a more leisurely amble.
A little time and effort spent choosing the right paving contractor will ensure your paving project runs smoothly and within budget.
The Garden Construction company are a landscaping company that have many years experience and offer a comprehensive range of paving solutions throughout Edinburgh, the Lothians, Fife and Perthshire.
Whatever the size of your project we'd love to talk to you about your ideas, call us today, freephone on 0800 328 6458 for a free consultation and quote. We are friendly, honest and very good at what we do.
How to Choose a Landscape Gardener
Choosing a professional landscape gardeners for your landscaping, garden design and build projects is an important decision and one you'll be glad when you get right.
A professional, experienced landscape gardener can take most of the hassle out of the design and build of your garden so you get real peace of mind knowing that your outside space will grow and develop in the way that is best for you. A little time and effort spent now will yield a great deal of pleasure for many years to come.
How to choose a landscape gardener
Experience – Gardens are as unique as their owners so you should choose a landscaper who has the confidence and experience to deal with whatever they might find in your garden. Your landscape gardener needs to be able to interpret your ideas and find the best way to achieve them in your garden.
Communication – The most successful projects always have good clear communication, so make sure you get involved with your landscape gardener right from the start. Always let them know how you feel about what they are proposing.
Case studies – ask to see examples of their work. Any good landscaper will be proud of their work and they will probably have loads of photos or even a video for you to look at. Although looking at images can give you some idea of someone's work they can never do full justice to beautiful landscaping and design. A good way to start is by looking around and finding landscape designs that you love. Choose neighbourhoods that tend toward the style you desire.
Testimonials – it's always a good idea to get as many testimonials from some of their past customers as you can.
Quote – Make sure the garden landscaper puts their quote in writing on official headed paper showing a postal address and full contact details.
A little time and effort spent choosing the right garden landscaping company will ensure your garden project runs smoothly and within budget.
The Garden Construction company are a landscaping company that have many years experience and offer a comprehensive range of landscape gardening throughout Edinburgh, the Lothians, Fife and Perthshire.
Whatever the size of your project we'd love to talk to you about your ideas, call us today, freephone on 0800 328 6458 for a free consultation and quote. We are friendly, honest and very good at what we do.
Driveways Edinburgh
driveways edinburgh
Driveways Edinburgh www.garden-co.com/driveways-edinburgh
E-Entertainment LabHere is a block paved driveway in Colinton, Edinburgh using Marshalls Tegula which give the appearance of stone setts although they are concrete. The advantages from stone is that it costs less buy, labour costs for installation are much reduced, the surface is flat and durable and is easy to clean and maintain.
The Garden Construction Company have been installing Driveways for 20 years and you can be assured of a perfect and long lasting drive.We offer a broad range of paving products as we are an independant company. We can also install any associated landscaping to your drive as we offer a comrehensive landscape gardeners service
Well this used to be Jimmy Boyles front garden to his house in the Inverleith area of Edinburgh
The new owners asked us to turf over the previously gravelled area, plant a privet hedge to the boundary wall and hebe rakiensis at path.
For a free, no obligation quote, call David freephone on 0800 328 6458, or firstname.lastname@example.com.
Fencing Edinburgh
fencing edinburgh
Garden Fencing Edinburgh- this fence was installed at the Hermitage, Edinburgh. The syle of fencing is slatted boards 100mm wide fixed onto rails secured to 100mm posts which are concreted into the ground 600mm deep.
The slats are fitted to both sides of the rail and are offset to allow wind to pass through the fence. This serves two purposes – reducing wind turbulance to lea side of fence and reducing wind strain on the fence. It also looks good!
All the timbers are fsc sourced and treated.
Call David on 0800 3286458 or firstname.lastname@example.com for a free no obigation quote.


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Enter the Sexopolis world and prepare yourselves for an amazing trip down the sex lane. Whether you are a man, a woman or a couple, our collection will leave no heads unturned and will satisfy even the most demanding of customers. Browse through our collection of Kegel Balls, Couples Sex Toys, Dildos, Butt Plugs, Strap Ons and many many others, pick the sex toys of your liking and rest assure that this is only the beginning of your erotic journey at Sexopolis.
Ever wondered what the infamous We-Vibe can do? Put simply : It's one of the best couples vibrator!
While they may not look like they could be used in a sexual way, couples toys are gaining a lot of popularity due to the simple fact that they require intervention from both partners.
Women can wear the sex toy leaving it ready for remote controlled play, while men can set the pace of the vibration with a single touch of their smartphone screen. Couples sex toys are designed to work while the couple has sex, providing vibrating pleasure to both men and women.
Multiple manufacturers such as Lelo have entered the couples vibrator game, offering some really decent options for you to choose!
Notable Mentions
Build strong pelvic muscles with the help of Kegel Balls
They may not seem convincing at first sight, but we guarantee you that frequent use of kegel balls and exercisers will make your vagina stronger and more sensitive!
Made of silicone, they have smaller balls on the inside that move along with every move of your body, whether you walk, jog, exercise or even do your daily errands!
You may use a drop of water based lubricant to let the balls slide in your vagina easier. Upon inserting, you leave the small circle handle outside so you can pull the balls whenever you need. The inner balls provide passive vibrations that "force" your pelvic muscles to contract and keep the sex toy inside you, strengthening and making you feel aroused for longer periods of time.
With frequent kegel ball use you can benefit from a stronger and tighter pelvic area, better control of your vaginal muscles and much more sensitivity with every sexual intercourse!
In the long run, both you and your partner will love the effect and will manage to have a better sex life thanks to those little balls!
Notable mentions
A remote controlled sex toy could be used anywhere at any time!
Why not play with your partner out in public? It is exciting, sometimes risky, but always delivers pleasure to both parts!
With a remote controlled sex toy, you can have some naughty time in the most unimaginable places and situations. On a cafeteria, on the club or even while having dinner at the restaurant.
Remote controlled toys are mostly vibrating bullets or kegel ball-like toys, suitable for vaginal and anal play. Some brands offer an Android/iOS application for easier and safer access to the vibrating patters of the sex toy, without having to deal with non-discreet remote controls of any sort.
You can also use it while having sex or foreplay, to spice things up a little bit before diving in the "main course"!
Couples use the remote controlled toys because they like to have a connection with one another even when the situation is not suitable for any form of erotic play. Get yours now from Sexopolis and indulge in some naughty, sexy fun!
Notable mentions
A Strap On a day, keeps the stress away!
A taboo? We hope not! Strap ons are widely used by everyday couples for role reversal play and provide a safe way for both the male and the female to experience a very different type of penetration than they normally do.
Also used by lesbian couples, strap ons are popular within people that have no problem experimenting with reversing their sexual roles and having lots of fun while doing it.
If used for female to male penetration, you may consider combining your strap on with water based lube, to keep things easier and safer for anal penetration. Choose your strap on by looking at which harness will fit you best, also taking into account the size of the dildo that you are about to "pack" once you wear it.
Be bold, be shameless and you will experience the delight of having the woman on top, pegging you and giving you the same feeling she gets every time you are inside her.
Our collection of strap on dildos, strap on harnesses and strap on sex toys is big enough for you to choose the one that fits you best. Choose yours now and get it fast with 100% discreet delivery, ready to give you hours of fun and pleasure.
Notable mentions


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Fresh is always better than processed, right? Yes! That is definitely right! Fresh bread is always much better than store-bought bread; freshly grated cheese is better than pre-shredded cheese, give up. Well, fruits and veggies are better fresh rather than frozen, and so become the juices that they produce.
Some would say they are careful enough to order only healthy food in the menu found in fast food stores. Ought to the biggest misnomer of all. Why? Even when you do order those "healthy" sounding dishes, these people still loaded with calories whenever compared with those dishes that you prepare inside your house. The reason effortless. Fast food stores main objective are create profit. If they generate profit, then they try to lower their expenses as much as possible. Method to have this happen is in order to "low" standard & cheap ingredients. Usually, cheap low-cost ingredients spell high calorie/cholesterol food.
Animals involving wild think the need to consume when these types of hungry and humans react in the same way. It is only natural that you will need to want to eat when you experience hungry.
So I ended up getting my running shoes on and moved my couch drop little i absolutely would have some room for the workout. In addition made ' was alone for period healthy crock pot recipes being, unsure how I would personally look in the world of dance for the first a little time.
I'll boost the comfort with a. The first time I did it, it felt really foreign and weird to me. I never went clubbing or dancing before this and I knew it showed. However, the whenever I did it, I focused on my 'own grove and style' appreciate it says to do, and i found who's got far better and quick. Plus, with Shawn T's entertaining advise guiding you along the way it gets more and most engaging and fun.
The nutrition and minerals that one can get from fruits is immeasurable. More importantly, fruits provide the body with the fibre and anti-oxidants to cleanse the poisons out of the system.
Have loved ones help you meet your goals. It is important to provide someone that motivates you to employ Natural Juices To Fat. When you're seeking an additional source of motivation, check out your friends for moral support.


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England | Scotland | Wales | Northern Ireland | Ireland
Get the latest NHS information and advice about coronavirus (COVID-19).
Get a test to check if you have coronavirus
Download the NHS COVID-19 app
Check if you or your child has coronavirus symptoms
Find out about the main symptoms of coronavirus and what to do if you have them.
Testing and tracing
Get a test to check if you have coronavirus, understand your test result and find out what to do if you're contacted by NHS Test and Trace.
Self-isolation and treatment if you have coronavirus symptoms
Advice about staying at home (self-isolation) and treatment for you and anyone you live with.
People at high risk
Advice for people at higher risk from coronavirus, including older people, people with health conditions and pregnant women.
Social distancing and changes to everyday life
Advice about avoiding close contact with other people (social distancing), looking after your wellbeing and using the NHS and other services.
COVID-19 support recovery service
'Your COVID Recovery' helps you to understand what has happened and what you might expect as part of your recovery.
GOV.UK: coronavirus – guidance and support
Government information and advice.
GOV.UK: local restrictions – areas with an outbreak of coronavirus
Local outbreak advice.
One in three of us will get cancer and it's the toughest thing most of us will ever face. If you've been diagnosed with cancer, or a loved one has, you'll want a team of people in your corner supporting you every step of the way. Macmillan provide practical, medical and financial support and push for better cancer care.
Marie Curie Cancer Care is a UK charity dedicated to the care of people with terminal cancer and other illnesses. Over the financial year 2010/11, we reached a total of 31,799 patients
Youthhealthtalk enables young people, their family and friends, and professionals such as doctors and teachers to understand young people's experiences of health, illness and life in general. The website feature real-life accounts of issues such as effect on work and education, social life and relationships, consulting health professionals and treatment.
If you need to remain on a certain medication for some time, your doctor may add this to the repeat prescribing system. This enables you to request specific prescriptions without seeing the doctor each time.
For your safety and convenience, the system works as follows:
Patients sometimes ask us to prescribe for longer than normal periods when travelling abroad. With certain exceptions ( e.g. contraception) we are unable to prescribe for longer than three months, based on GPC guidance. In some circumstances we may be able to offer a private prescription for longer durations but it is usually better to access local health services.
Extensive exemption and remission arrangements protect those likely to have difficulty in paying charges (NHS prescription and dental charges, optical and hospital travel costs). The NHS prescription charge is a flat-rate amount which successive Governments have thought it reasonable to charge for those who can afford to pay for their medicines. Prescription prepayment certificates (PPCs) offer real savings for people who need extensive medication.
The current charges (June 2019) are:
If you will have to pay for four or more prescription items in three months, or more than 12 items in 12 months, you may find it cheaper to buy a PPC. The charge for a single prescription item is £9.15, whereas a three month PPC will cost you £29.65 and a 12 month PPC £105.90.
There is further information about prescription exemptions and fees on the NHS website and at the following link https://www.nhsbsa.nhs.uk/help-nhs-prescription-costs/prescription-prepayment-certificates
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Desire is a strong feeling of wanting to have something or wishing for something to happen. Desire is a sense of longing or hoping for a person, object, or outcome. The same sense is expressed by emotions such as "craving". When a person desires something or someone, their sense of longing is excited by the enjoyment or the thought of the item or person, and they want to take actions to obtain their goal.
Ursula Reuter Christiansen (born 1947 in Trier, Germany) lives and works in Denmark since her graduation from Akademie der Künste in Düsseldorf in 1969. Reuter Christiansen worked as a professor at the University of Fine Arts in Hamburg (HfBK) 1992-97 and a professor of painting at the Royal Danish Academy of Fine Arts in Copenhagen 1997-2006. She and her husband, the Danish composer Henning Christiansen represented Denmark at the Venice Biennale in 2001. Reuter Christiansen has exhibited at Kunsthal Charlottenborg, Copenhagen (2016), MOCA, Los Angeles (2007-8), Kunsthal Brandts Klædefabrik, Odense (2000) among others. She was awarded the Eckersberg Medal in 2011.
Louis Fratino (born 1993 in Annapolis, USA) lives and works in New York. He received a BFA from Maryland Institute College of Art, Baltimore, USA. In 2016 Fratino was awarded a Fulbright Research Fellowship in Painting in Berlin and in 2014 a Yale Norfolk Painting Fellowship, Norfolk, USA. Recent exhibitions include Thierry Goldberg, Miami; Foxy Production, NYC; Antoine Levi, Paris, France; Jeff Bailey Gallery, Hudson, USA and Monya Rowe Gallery, NY. His work is included in an upcoming exhibition at the Albany University Art Museum, NY.
Kate Groobey (born in 1979 in Leeds, UK) lives and works between London and Paris. She graduated from Royal College of Art with a MA in Painting in 2010. Recent exhibitions include I'm Made of Milk at Horton Gallery, New York, The Good Life at Ever Gold, San Francisco; upcoming solo exhibition will take place at Mizuma Art Gallery, Tokyo, Japan in autumn 2018. Recent group exhibitions include Daiwa Japan House, London; SURRREAL at König Galerie, Berlin; Art16 at Villa Lena Foundation, London. Groobey just won the Daiwa Foundation Art Prize in 2018.
KOAK (born in 1981) lives and works in San Francisco, USA. She received a MFA in Comics from California College of the Arts, San Francisco in 2016. KOAK's artwork pulls from the lineage of hand-drawn cartoons, comics and historical nude portraiture. Her recent exhibitions include Bathers at Alter Space, San Francisco, Seeds for Painting at Walden, Buenos Aires and Condo at Union Pacific, London. Koak received the Liquitex Residency at Minnesota Street Projects in 2018.
Marlene Steyn (born 1989 in Stellenbosch, South Africa) lives and works in Cape Town. Steyn received a MFA in painting from the Royal College of Art in London in 2014. Inspired by psychoanalytic theory, Steyn incorporates images from art history and popular culture to conjure uncanny motifs by means of repetition. Recent solo exhibitions include: Your Skin Is Not The Best Hiding Place at SMAC Gallery, Cape Town; You Can't Cry When Your Head is Underwater at Lychee One, London; The End is Located Underneath Her Third Armpit (if the muscle is flexed) at Commune.1, Cape Town, Mad Love at Lychee One, London and How Cannibals Cuddle at Art Cabin, London. Steyn's work featured at the inaugural exhibition of the Zeitz Musem of Contemporary Art Africa in 2017.
Fleur Yearsley (born 1990 in Manchester, UK) lives and works in London. She received a MFA in Painting from Slade School of Fine Art, London in 2017. Yearsley was awarded The Gwen John Scholarship in 2015/2017, Almancantar Studio Award in 2017/2018 and Jealous Prize in 2018.


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Here you can find five recommended healthy habits that will make you feel and look better all day long. Practicing these tips on a daily basis will improve your health and make you happier.
Wake up with alarm
At the beginning it will seem hard, especially if you are among those who snooze alarm 5 times in morning. However, the truth is simple, as more often you snooze alarm, as more stressful your day will begin. In the subconscious you became angry and even aggressive about fact that sooner or later you will have to get up. Or worse, you can oversleep. Better go with a little discipline and the day will be more enjoyable.
Take cool shower
Cool water gives a cheer and refreshes the skin. It narrows pores and improves blood circulation. Cold water also has a lower concentration of chlorine than hot what is important for skincare. Taking a cold shower twice a day for three minutes can prevent and possibly even cure depression.
Drink water
Recommended to drink 1-2 glasses of warm water in the morning on an empty stomach. After the night our body is also slightly dehydrated and glass of water is what it needs at this point. Add a slice of lemon or fresh lemon juice. It will take out toxins from your body and cleanse the liver.
Eat Breakfast
Especially breakfast give us energy throughout the day so it is advisable not to ignore it. Doctors recommend starting the day with oatmeal, which means more fiber and the amount of micro-nutrients the body needs. If you eat it every morning for breakfast, you lower your bad cholesterol by 10%. Oatmeal is rich in B vitamins, which are essential for the skin and help prevent dermatitis.
Instead of coffee drink green tea, which will give you energy for a longer time than caffeine. The preferred fruits for breakfast are apples and pineapples.
Take care of your skin
No matter how sleepy you are in the morning, your skin activates regardless of you. For example, at eight o'clock is the time to apply skin cream. The blood circulation is maximally active so it is better for the skin to get a dose of cream that will protect against moisture loss. From 3 pm till 6 pm the skin is tired so it will not absorb anything – the salon procedures will also be quite ineffective.


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Start your FREE all access pass for 14 days to the #1 online community &
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Finance Director
Nick has been working as a Non Exec FD for various businesses over the past 10 years and provides advice on financial and corporate strategy. Nick has over 25 years experience in accountancy, with 15 years specialising in the corporate finance sector. Since 2008 he's also built up his own Accountancy & Corporate Finance business.
Credit Manager
Emily has many years experience working within the banking sector, including seven years at Yorkshire Bank as an Underwriter for SME lending.
Credit Underwriter
Chris worked for Yorkshire Bank for 10 years and spent 5 years in underwriting for multiple SME businesses.
Want to speak to us? Call us on 0113 468 1408 or Request a call back


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is a Croatian painter. Vehabović earned his Ph.D. in painting at the Academy of Fine Arts in Zagreb. He lives and works in Zagreb, Croatia. Vehabović is among the most highly regarded young artist in Croatia having won First Prize for Zagreb Salon 2010, The International Association of Art Critics (AICA) Award 2010, as well as an Essl Award in 2007, (Emerging Artists in Southeast Europe) 2010, and with solo exhibits in 2011 and 2013 at Lauba Museum in Zagreb, Kranjcar Gallery, Zagreb (2011). Selected group exhibitions include: Museum of Contemporary Art, Zagreb (2011). The Knoxville Museum of Art (2011). Hudson Valley Center for Contemporary Art, Peekskill, NY (2010). Essl Museum (2009). Paolo Maria Deanesi Gallery, Rovereto Italy (2010). Museum of Contemporary Art, Pula (2009). Werket Museum, Avesta Sweden (2008). S&G Galleries, Berlin (2008).
More about Zlatan Vehabovic and his paintings here.


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According to Trulia, the seven-bedroom, nine-bathroom home measures over 1114 square metres and is 100 years old.
The estate is located on a elevated two-acre site surrounded by 203 feet of water in the form of Georgica Pond. Plus there's a 6.87 hectares of land in the meadow preserve next door.
Nicknamed The Pond House, according to 6sqft, the property sat on the market for 8 long years before Bey and Jay decided to scoop it up.
Business Insider says this comes just two months after the pair bought a 7432 square metre hillside estate in Los Angeles for $88 million (R1,17 billion)
But that's probably nothing for Forbes' highest paid celebrity couple who have a combined fortune of $1.16 billion (R154.8 billion).
The home was originally designed by architect Stanford White and built a century ago, but the home has recently been renovated and the design was overseen by builder Jeffrey Collé.
Check out the video below to get a view inside Bey and Jay's new home.


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Add a sweet look to your little girl's formal wear with this pale rose dress by Tartine et Chocolat. Crafted from soft woven viscose with a soft cotton lining, this subtle grey floral print features button fastenings down the back. 100% cotton. Machine wash 30*C.
Condition: Like New. This dress is in great condition with no visible signs of use. Please zoom in for exact condition.


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Last year I bought a small cookbook called Picnics and Tailgates at a discount store and I find myself using it often. I love every recipe I have tried. Williams Sonoma put out several in a series and I was happy to see they are being sold used rather cheap. Like a penny kind of cheap (.01). I'm splurging on two for a whole two cents.
The chopped chicken salad is my favorite, I make it huge with three heads of lettuce as I like having the leftovers in the fridge all week for lunch.
Since we are talking about Williams Sonoma cookbooks I will tell you about a larger one called Family Meals. It isn't set up like a traditional cookbook but it has some great stuff in it. And the paper in it smells really good, I'm not sure why but it smells like good matte paper fresh from the printer. I will be trying the blueberry jam recipe this weekend as today the kids and I picked 25 pounds of blueberries.
We hadn't been blueberry picking in years. It used to take all day to pick 25 pounds and now that the kids are grown it only took a couple hours.
We are big fans of the kids book Blueberries for Sal and while Henry thought blueberry
eating picking was mighty fun he was on the watch for bears…..


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Posts Tagged 'Kukai: The true Jack has appeared! Yaya: Huh Nadeshikos twin? Why didnt I know? Amu-chi!! Thats rude! Ran: how does your chara look like? Pepe: yeah what kind of chara? Nagehiko: my chara has not appe'
Miniclip Players – UPDATE! – Forums? – Blog Hits – Batman Dynamic Double Team Review.
Posted by: GameZo on: November 2, 2008
- In: Blog | Cheats | game | MiniClip | News/Updates | Reviews | WalkThrough
- 4 Comments
Hey Guys! GameZo with a Totally new Post,Here is a small new Update on my Blog (Hits Awesome!) I've been getting a Lot of Hits/Views on Gamezo.org thanks to every one who Came and commented i really appreciated it 🙂 and Once it reaches 15,000 i will be making a Forum so we can discuss and some cool Contests to win Membership on a Lot of Games like Club penguin,Runescape,Spineworld,fantage and loads but Please help us Grow Gamezo!.
Oh and to those Who Play Mini Clip Players(It's back!) My Player is called BunnyHood.
And today i will be Posting a Review on the Cartoon Network game on the new Batman Series coming this Fall Batman the brave and the…. New game called Batman Dynamic Double team The point of the game is to See how many enemies you Can battle and by Collecting the Blue bugs called "SCARABS" your Blue bug mete above will be Full and then once you Press "SPACE BAR" Your Partner will come and attack some of the Enemies with this powers and you can do that so it can help you,And! Collect Health Orbs with the + Sign to Fill your health bar.
The instructions are pretty easy Mostley you need to press "Z" for most of the attacks read the Full instructions when your playing the game.
Okay. here is the Review:
Recommended for ages 6-18.
Link to game: > http://www.cartoonnetwork.com/games/batmanbb/dynamicdoubleteam/
Check the game out for yourself 🙂 and see how it works for you!
Well that's a Good Bye! for now


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The boycott that had been announced by UKAM last night has been lifted. The organization of Maltese composers, authors and singers has reached an agreement with the Malta Song Board. The Malta Song for Europe Festival 2005, scheduled for 18th and 19th February can probably go on.
The agreement includes an extension to the submission closing time of the songs. Interested parties can now submit their songs by latest tomorrow Thursday 25th November at 16:00 CET. UKAM had asked its members last night not to submit their songs for the upcoming Malta Song for Europe Festival and was also to give a 50% refund to all those members who had already purchased the necessary documents.
In a press release, UKAM thanked Hon. Minister Dr. Francis Zammit Dimech for his intervention during the negotiations and all the composers, singers and authors who supported UKAM.
The agreement states that:
– Author and composer of the winning entry can join the Maltese delegation to the Eurovision Song Contest.
– Further negotiations concerning the Malta Song for Europe rules will start immediately after the 2005 Eurovision Song Contest.
– As of next year, the participation of foreign composers and authors in the Malta Song for Europe Festival shall be restricted to composers and authors of those countries where Maltese composers and authors have equal opportunities to participate.
In the meantime, the rules for Malta Song for Europe Festival 2005 remain as they are.


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|Methods and apparati for removing protein-bound molecules from body fluids
|Plasma filter sorbent system for removal of components from blood
|Shettigar et al.
|Method and apparatus for removing protein-bound molecules from body fluids
|Scrubbing process for high feed concentrations
|Davis et al.
|Blood purification
|Ambrus et al.
|Dialysis instrument with dialysate side pump for moving body fluids
|Immunological methods for removing species from the blood circulatory system and devices therefor
|Hemodialysis assist device
|Hollow fibres
|Christen et al.
This is a continuation-in-part application of U.S. patent application Ser. No. 07/832,080 filed Feb. 6, 1992, now U.S. Pat. No. 5,277,820.
passing a fluid containing protein bound and/or middle molecular weight blood toxins through the interior of a hollow fiber membrane;
during said passing, circulating a sorbent suspension against exterior surfaces of the hollow fiber membrane;
during said passing and circulating, applying intermittent pulses of positive pressure to said sorbent suspension so that the fluid or a fraction thereof alternately exits and re-enters the interior of the hollow fiber membrane, wherein said fluid or fraction which exits the interior of the hollow fiber membrane contains the protein bound and/or middle molecular weight toxins which contact said sorbent suspension so as to effectuate removal of said toxins from said fluid and delivery of said toxins into said sorbent suspension.
a hollow fiber membrane;
a pump fluidly connected to the interior of said hollow fiber membrane and adapted to pass a fluid containing middle molecular weight and/or protein-bound blood toxins through the interior of said hollow fiber membrane;
a chamber surrounding said hollow fiber membrane, said chamber further being fluidly connected to a supply of sorbent suspension;
a pump adapted to circulate said sorbent suspension through said chamber and against exterior surfaces of said hollow fiber membrane; and
means for causing said fluid or fractions thereof passing through the interior of the follow fiber membrane to alternately exit and re-enter said interior.
This invention generally relates to devices and methods for extracorporeally treating blood or blood fractions such as blood filtrate or plasma to selectively remove toxins therefrom.
By way of background, extensive efforts have been made to discover safe and effective methods for removing toxins from patients by extracorporeal treatment of their blood. These efforts have included many studies directed to methods for extracorporeal treatment of hepatic failure due to infection, cirrhosis, toxin damage or other causes. Many methods have been proposed with the goal of removing small molecular toxins, protein-bound molecules or larger molecules thought to be responsible for the coma and illness of hepatic failure. Thus far, evidence has been presented supporting adverse effects caused by non-protein bound small molecules such as ammonia, phenols, mercaptans, short chain fatty acids, aromatic amino-acids, neural inhibitors (GABA, glutamate), false neural transmitters (octopamine) and bile salts. Among these, phenols and mercaptans, along with bilirubin and bacterial endotoxins, also occur as strong protein-bound toxins and are thus more difficult to effectively remove from the blood. In addition, there are a variety of middle molecular weight toxins of liver failure having molecular weights of about 300 to about 10,000 which are difficult to effectively remove.
As to specific modes of treatment, those previously proposed and used have included blood perfusion over heterogeneous liver pieces or past membranes which contact hepatocytes. Also proposed and used have been hemoperfusion through columns of coated activated carbon or macroreticular resins, blood exchange, plasmapheresis with plasma replacement, plasmapheresis with plasma perfusion through bilirubin-binding and aromatic amino acid-binding sorbents, standard hemodialysis, standard hemodialysis with an amino acid dialysate and plasma exchange, high permeability hemodialysis, dialysis with charcoal-impregnated membranes, continuous hemofiltration, peritoneal dialysis, oral sorbents and many other therapies.
While some of these previously proposed treatments have produced neurological improvement in stage 2 or 3 coma and have aided hepatic regeneration after injury, they have not provided much clinical improvement in patients in stage 4 coma on respirators. Additionally, these diverse treatments each produce adverse effects on the patient, offsetting benefits. See, generally, Ash, S. R., Treatment of Acute Hepatic Failure With Encephalopathy: A Review, Int. J. of Artif, Organs, Vol. 14, pp. 191-195 (1991).
For example, although daily charcoal hemoperfusion has been shown to provide neurologic and physiologic improvement of patients with hepatic failure and coma, Winchester, J. F., Hemoperfusion, in Replacement of Renal Function by Dialysis (Maher, J. F., ed.), Dordrecht:Kluwer Academic Publishers, pp. 439-459, (1989), hemoperfusion nevertheless requires systemic anticoagulation and also depletes coagulation factors and platelets from the blood. Moreover, the relatively large sorbent granules used in hemoperfusion columns have limited surface area (about 1000-10,000 m2). Consequently, the available sorbent surface area is saturated within a few hours, clearance of bound chemicals rapidly diminishes, and a new column must be used.
Furthermore, clinical benefits of charcoal hemoperfusion may be offset by deleterious effects of bio-incompatibility. In one instance, a controlled study of patients with fulminant hepatic failure, all treated with aggressive intensive care including intracerebral pressure monitoring, demonstrated that patients treated by hemoperfusion had a generally lower survival rates than those treated with aggressive intensive care alone. The only exception was noted in patients having fulminant hepatic failure due to hepatitis A or B, for whom there was reported a "trend toward improved survival" when treated with charcoal perfusion. O'Grady, J. G. et al., Controlled Trials of Charcoal Hemoperfusion and Prognostic Factors in Fulminant Hepatic Failure, Gastroenterology, Vol. 94, pp. 1186-92 (1988).
As mentioned, standard lemodialysis (i.e. dialysis of blood against only a dialysate solution) has also been studied as a possible treatment for hepatic failure. However, benefits of hemodialysis may be similarly obscured by removal of substances (e.g. urea) known not to be toxins of hepatic failure. Additionally, hemodialysis requires the use of large volumes of dialysate solution which limits the mobility and increases the complexity of the machines, or alternatively, it requires the provision of a sorbent column to "regenerate" the dialysate.
In light of this extensive background, there remain needs for improved devices and methods for the extracorporeal treatment of blood or of blood fractions to effectively remove toxins, including both soluble and protein-bound toxins. The present invention addresses these needs.
The present invention provides a unique filtration process (e.g. a hemofiltration or plasmafiltration process) which is highly effective in removing protein-bound and middle molecular weight toxins. The inventive process includes the steps of passing a fluid, such as blood, containing protein-bound or middle molecular weight blood toxins, through the interior of a hollow fiber membrane, and during the passage of blood, circulating a sorbent suspension against exterior surfaces of the hollow fiber membrane. As a further step, during the passage of blood and circulation of sorbent suspension, the plasma fraction of the blood is caused to alternately exit and re-enter the interior of the membrane. Thereby, blood plasma contacts the sorbent suspension upon exit from the interior of the membrane, so as to effectuate removal of the toxins from the blood. This embodiment of the invention is applied with preference to whole blood; however, the invention is not so limited, as it will be applicable as well to the treatment of other fluids containing middle molecular weight and/or protein bound blood toxins, e.g. blood fractions such as isolated blood plasma or other blood toxin-containing fluids such as blood filtrate.
Another preferred embodiment of the present invention provides a device which is highly effective for removing protein-bound or middle molecular weight toxins from fluids such as blood, blood plasma or blood filtrate. The preferred device of the invention includes a hollow fiber membrane, and a pump fluidly connected to the interior of the hollow fiber membrane and adapted to pass blood (or another fluid containing the toxins) through the interior. The device further includes a chamber surrounding the hollow fiber membrane, the chamber also being fluidly connected to a supply of sorbent suspension containing solid particulate adsorbent. A pump is adapted to circulate the sorbent suspension through the chamber and against exterior surfaces of the hollow fiber membrane. Means for causing the blood or other fluid or a fraction thereof passing through the interior of the membrane to alternately exit and re-enter the interior of the hollow fiber membrane are also provided.
Still another preferred embodiment of the present invention provides a method for circulating a sorbent suspension in a device for extracorporeal treatment of blood or a blood fraction. The method of the invention includes a step of providing the device having a sorbent circulation circuit and a blood circulation circuit separated by membranes, the membranes being compliantly formed to expand and contract in response to alternating positive pressure and negative pressure applied to the sorbent circulation circuit and thereby advance a sorbent suspension through the sorbent suspension circulation circuit. An accumulator reservoir is provided and fluidly connected to the sorbent circulation circuit, and is operable to alternately accumulate and expel sorbent suspension in response to alternating negative pressure and positive pressure applied to the accumulator reservoir. Thereby, the accumulator reservoir communicates the alternating negative and positive pressure to the sorbent circulation circuit. The method further includes applying alternating positive pressure and negative pressure to the accumulator reservoir so as to communicate the same to the sorbent circulation circuit and cause the compliant membranes to expand and contract, whereby the sorbent suspension is advanced through the sorbent suspension circuit.
Still another preferred embodiment of the invention provides a device for extracorporeal treatment of blood or a blood fraction. This device has a sorbent circulation circuit and a blood circulation circuit separated by membranes, wherein the membranes are compliantly formed to expand and contract in response to alternating positive pressure and negative pressure applied to the sorbent circulation circuit and thereby advance a sorbent suspension through the sorbent suspension circulation circuit. An accumulator reservoir is fluidly connected to the sorbent circulation circuit and operable to alternately accumulate and expel sorbent suspension in response to alternating negative pressure and positive pressure applied to the accumulator reservior, the accumulator reservoir thereby communicating the alternating negative and positive pressure to the sorbent circulation circuit. The device also includes a source of positive pressure and of negative pressure fluidly connected to the accumulator reservoir. When alternating positive pressure and negative pressure are alternately applied to the accumulator reservior, the same is communicated to the sorbent circulation circuit to cause the compliant membranes to expand and contract, whereby the sorbent suspension is advanced through the sorbent suspension circuit.
The invention thus provides methods and devices by which greater removal of protein-bound and middle molecular weight blood toxins from blood, blood plasma or blood filtrate can be achieved, and whereby efficient circulation of sorbents on the sorbent side of a variety of different types of extracorporeal treatment devices is effectuated. Additional objects, features and advantages of the present invention will be apparent from the description which follows.
FIG. 1 is a perspective view of a preferred pressure/vacuum operated dialysis system which can be used in the invention.
FIG. 2 is a schematic representation of the hydraulic system of the dialysis system of FIG. 1.
FIG. 3 is a schematic representation of the mechanics of operation of the preferred direct pressure/vacuum operated dialysis system of FIG. 1 during the first part of blood inflow (FIG. 3A) and during the remainder of blood inflow and blood outflow (FIG. 3B).
FIG. 4 is a schematic representation of the hydraulic circuit of a combined device incorporating the system of FIG. 1 in series with a hollow fiber plasmafilter.
FIG. 5(a) shows the blood-side pressure curve between the system of FIG. 1 and the plasmafilter in the combined device of FIG. 4, during several inflow-outflow cycles.
FIG. 5(b) shows the sorbent-side pressure curve within the plasmafilter membrane package of the combined device of FIG. 4. Mean blood-sorbent pressure difference is approximately zero.
FIG. 6(a) shows a Langmuir isotherm for binding of bromsulphthalein (BSP) from saline (top line) and from porcine plasma (bottom line) to which it was first bound to charcoal.
FIG. 6(b) shows a Langmuir isotherm for binding of unconjugated bilirubin from porcine plasma to which it was first bound to charcoal.
For the purposes of promoting an understanding of the principles of the invention, reference will now be made to certain embodiments and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended, such alterations, further modifications and applications of the principles of the invention as described herein being contemplated as would normally occur to one skilled in the art to which the invention relates.
As indicated above, one preferred embodiment of this invention relates to a method which can be used for extracorporeal treatment of blood or a blood fraction by filtration, e.g. plasmafiltration (wherein plasma is filtered across a membrane) or hemofiltration (wherein middle molecular weight molecules (i.e. having molecular weights of about 300 to about 10,000) are filtered across a membrane), in a manner which provides the safe, consistent and effective removal of toxins, including protein-bound blood toxins and middle molecular weight blood toxins. This filtration can be used alone, or in connection with dialysis of the blood or blood fraction, for example using dialysis devices and methods as described in my prior U.S. patent application Ser. No. 07/832,080 filed Feb. 6, 1992, now U.S. Pat. No. 5,277,820, which is hereby incorporated by reference in its entirety. Likewise, the advantageous sorbent circulation system and method described in this prior application is effective to advance sorbent suspension through hollow fiber plasmafilters and hemofilters, and is generally applicable to advance sorbent suspension through a variety of extracorporeal treatment devices having blood and sorbent sides separated by a membrane, and thus also forms a part of the applicant's invention.
The sorbent suspension used in the invention can include powdered surface adsorptive agents, physiologic electrolytes and macromolecular flow inducing agents. In general, these components are present in effective amounts to achieve the desired removal of substances from and electrolyte balance in the blood of the patient while maintaining the stability and fluidity of the sorbent suspension. Because plasmafiltration membranes as used in the invention can potentially pass endotoxins, it is preferred that the sorbent suspension be free from measurable endotoxins. While general sorbent suspension production techniques have been sufficient for these purposes, if necessary, measures can be taken sanitize or sterilize the suspension, for example using heat or radiation (e.g. gamma-radiation), to assure that the sorbent suspension is substantially free from bacteria or other microbial growth which could potentially generate endotoxins or other harmful substances.
The powdered surface adsorptive agent can be any one of many known to those practiced in this area, but is preferably powdered activated charcoal. Further, the powdered surface adsorptive agent preferably has an average particle diameter of not greater than about 100 microns. More preferably, this average particle diameter is less than about 50 microns, with 90% or more of the particles having diameters not greater than about 75 microns. Particles exceeding 75 microns in diameter can be screened if necessary. As one example, a suitable finely powdered activated charcoal is available from American Norit Company, Inc. of Jacksonville, Fla. U.S.A., which can be screened to remove particles larger than those des i red.
The macromolecular flow inducing agents function to maintain the stability of the sorbent suspension formulation (i.e. helps to prevent solids from settling out of suspension) and maintain the flow properties of the suspension. One desirable flow inducing agent is a nonionic, hydroxyl-containing polymer such as a glycol derivative. Suitable agents of this type are available from BASF Wyandotte of Parsippany, N.J., U.S.A. under the trademark "Pluronic" polyols. These Pluronic polyols are polyoxyalkylene derivatives of propylene glycol. To date, applicant has used Pluronic F68, which functions both as a flow inducing agent and a defoaming agent. Another flow agent that has been included in preferred suspensions is macroreticular polyvinylpyrrolidone.
The types and amounts of electrolytes included in the suspension formulation will depend upon the specific needs of the patient and will be readily determinable by physicians or others skilled in the area. Typically, the electrolytes will include sodium and chloride (e.g. optionally provided as sodium chloride), and can also include bicarbonate, potassium, calcium, or any other electrolytes to be regulated in the patient. As indicated, however, the types and amounts of electrolytes may vary widely depending on patient needs.
The sorbent suspension formulation may also include ion-exchanger to bind ionic chemicals, e.g. ammonium, etc., which may occur in the patient's blood. Many suitable ion exchangers including both resins and other materials such as zeolites are known in the art. When included, the ion-exchanger is preferably a cation-exchange resin, which is desirably loaded with sodium or calcium. For example, to date, sodium polystyrene sulfonate has been a preferred material.
The surface adsorptive agent, electrolytes, flow inducing agents and any oilier additives will usually comprise about 5% to 30% by weight of the sorbent suspension formulation as a whole, with the remainder being water. Typically, solid sorbents will comprise about 2% to 25% by weight of the suspension formulation, and electrolytes will comprise about about 1% to 5% of the suspension formulation. Within these parameters, more preferred sorbent suspension formulations comprise about 2% to 20% powdered surface adsorptive agent, up to about 10% ion-exchanger, and up to about 1% flow agent such as a polyol and/or polyvinylpyrrolidone.
The sorbent suspension can also include viable hepatic cells, e.g. xenogenic or allogenic cells, alone or in combination with one or more of the solid adsorbents and other materials described above, to assist in the effective removal of toxins. For example, hepatocytes can be isolated from suitable donor tissue, purified and microencapsulated in polymer as described by Dixit et al., Hepatology 1990:12:1342. These microencapsulated cells can then be used directly in the sorbent suspension, or can be cryopreserved until use, for example as described by Dixit et al., Transplantation 1993; 55:616-22. When hepatic cells are so used, plasma is effectively separated from the blood by passage through the plasmafilter membrane, and proteins and toxins are convected into contact with the cells circulating exterior of the membrane. After the cells have acted upon the toxins, the plasma is returned through the membrane and back into the patient.
In connection with plasmafiltration or hemofiltration devices and methods, there are many suitable hollow fiber membranes which are known for use in plasmafiltration or hemofiltration of blood, and those skilled in the area will be readily able to select and utilize a suitable membranes in the present invention. Such membranes can be, for example, cellulosic membranes (e.g. cellulose acetates), and will have pore sizes sufficiently large to allow passage of plasma proteins (e.g. in plasmafiltration) and/or middle molecular weight blood toxins (e.g. in hemofiltration), suitably having molecular weight cutoffs of about 50,000 or above, e.g. 50,000 to 6,000,000. Suitable plasmafiltration and hemofiltration membranes include, for example, those known under the designations F-80 (50,000 m.w. cutoff, Fresenius USA, Inc., Walnut Creek, Calif.), Altrex 140 (70,000 m.w. cutoff, Althin Medical, Inc., Miami Lakes, Fla.)), CT190G (60,000 m.w. cutoff, Baxter, Deerfield, Ill.), and Plasmaflo AP-05H(L) (about 1,000,000 m.w. cutoff, Asahi Medical Co., Ltd., Tokyo, Japan). More preferred plasmafiltration or hemofiltration membranes will have pore sizes which transmit albumin or middle molecular weight molecules with selectivity over larger molecules, and thus will provide removal of toxins while minimizing potential interference with other blood functions. For example, the Plasmaflow AP-05H(L) plasma separator (0.5 square meters) has about a 5% rejection of albumin during unidirectional filtration, but about an 80% rejection of macroglobulins.
In connection with dialysis when used in the present invention, there are many dialyzer membranes which are known for use in dialyzing body fluids such as blood, and those skilled in the area will be readily able to select and utilize a suitable membranes in the present invention. One suitable membrane is a cellulosic membrane, particularly one composed of regenerated cuproammonium cellulose (Cuprophan).
In circumstances where only plasmafiltration or hemofiltration (and not dialysis) of the blood or other fluid is desired, the membrane in the dialysis instrument need not be a dialysis membrane, and thus may be one which is impermeable to blood and its components, e.g. a membrane formed from a suitable compliant plastic film. Moreover, where only plasmafiltration or hemofiltration is desired, the dialysis instrument need not be employed at all, and any means of circulating the sorbent suspension against the exterior of the hollow fiber membranes while passing the blood or other fluid through the interior of the membranes (with bidirectional flow of the blood or fluid across the membranes) will be suitable. For example, the hollow fiber membrane cartridge could have sorbent side connections to a container filled with sorbent suspension. While the sorbent suspension is circulated through the cartridge, for example by a roller pump, the pressure changes in the blood side (created automatically by roller pumps) would create the desired bidirectional flow of plasma or other fluid across the membranes. Such systems will provide high clearance of protein-bound or middle molecular weight toxins with great simplicity and low cost.
The inventive plasmafiltration or hemofiltration methods of the invention are advantageously performed in connection with a preferred, dialysis instrument including a parallel plate dialyzer and moving the sorbent suspension formulation in a counter-current mode by the direct application of alternating negative pressure and positive pressure on the dialysate side, as described in more detail in Examples 1 and 2 below. The preferred system also creates a slight back and forth motion of the sorbent suspension formulation, which agitates, locally mixes, and helps to prevent settling of the suspension.
Extracorporeal blood treatments of the invention can be used to safely and effectively-treat the coma and illness of hepatic failure and to improve a patient's clinical condition as evidenced by improved polysiologic and neurologic patient status. Methods of this invention can also be successfully used in treating drug overdose, even with highly-protein-bound drugs (i.e. drugs which are 75% or more protein bound). It is also expected that methods and devices of the invention will be effective in treating patients with renal failure, uremia, or other conditions benefited by removal of toxins from the blood. Further, plasmafiltration and/or dialysis methods of the invention can be used in hemofiltration to treat and remove toxins from the hemofiltration ultrafiltrate, and return the treated ultrafiltrate to blood. In this manner, the use of large volumes of sterile replacement fluid can be ameliorated or eliminated.
The invention will now be described with reference to the following specific Examples which are illustrative, and not limiting, of the invention.
Dialysis System
FIG. 1 is a perspective view of a preferred dialysis system 11 sitting on a standard hospital cart, which can be used in methods of the invention. Generally, the preferred dialysis system 11 is similar in some respects to the dialysis instrument disclosed in my earlier U.S. Pat. No. 4,661,246 issued Apr. 28, 1987, which is hereby incorporated herein by reference in its entirely. However, to fill and empty the dialyzer of blood, the present system uses the direct application of pressure and vacuum to give positive and negative pressure changes in the dialysate. This increases the blood flow and enhances the mixing of the sorbent suspension formulation, as well as helps to maintain optimal chemical gradients across the dialysis membrane.
With continued reference to FIG. 1, the dialysis system 11 includes a machine base 12, reservoir tank 13 with cover 14, a sorbent bag 15 containing sorbent suspension materials, disposable pack 16 (including the plate dialyzer), and power supply 17 (providing vacuum, pressure, and DC power to the machine base). Referring now also to FIGS. 2 and 3, FIG. 2 is a hydraulic schematic of the dialysis system, and FIG. 3 provides in parts A and B a summary of the mechanics and hydraulics of operation of the system during blood inflow and outflow, respectively. Generally, in the following discussion, the numbers 20-47 will be used to designate components on the disposable pack 16, whereas numbers 50 and above will designate components of the machine base 12. In FIG. 1, the machine base 12 and disposable pack 16 are shown separated. Of course, in use together, the pack 16 is mounted to machine base 12 and their respective components assembled generally as follows.
Vacuum/pressure line 20 from top port 21 of accumulator 22 is connected to vacuum pressure port 50 on machine base 12 which feeds vacuum and pressure from the respective sources thereof are power supply 17. Prime tube 23 is seated into the upper side of prime/rinse clamp 51 and through prime fluid sensor 52. The blood inflow tube 24 is seated into the lower side of prime rinse clamp 51, blood inflow clamp 53 and the blood inflow sensor 54. The blood outflow tube 25 is seated into blood outflow clamp 55 and blood outflow sensor 56, and fluid level sensor 57 is placed onto accumulator 22. Reinfusate tube 26 is loaded into reinfusate pump 58 and reinfusate fluid sensor 59. Dialysate tube 27 (prior to the "Y" split) is loaded into dialysate pump 60 and its end connected to water port 61. Branch of dialysate tube 28 (after the "Y" split) which connects to the dialysate inlet 29 of dialyzer 30 is seated into dialysate-in clamp 62. Filtrate line 31 is loaded into filtrate pump 63 and into filtrate fluid sensor 64. Filtrate line 31 is also connected to filtrate disposal bag 32 which is vented. Three liters of sterile water are added to reservoir tank 13. Sorbent bag 15 is suspended from reservoir cover 14. Tubes 33 (leading to dialysate inlet 29) and 34 (leading to the exit port of accumulator 23 and also connected to dialysate outlet 35 via line 36) are connected to lines 37 and 38 provided on and leading into sorbent bag 15.
The following steps are conducted under sterile conditions. Blood inflow line 24 and blood outflow line 25 are connected to blood inlet 39 and blood outlet 40 of dialyzer 30, respectively. Reinfusate solution (e.g. CaCl2 solution and appropriate amounts of KCl and/or NaCl solution) is injected into reinfusate bag 41. Reinfusate line 26 is connected to reinfusate bag 41 and a drip chamber in the line is partially filled. Prime tube 23 is connected to prime bottle 42 containing priming fluid, e.g. 5% dextrose. If desired, replacement fluid can be provided via fluid replacement line 43.
Thus, after the above assembly, the blood inflow 24 and blood outflow 25 tubes pass from a single access line 44 through clamps 53 and 55 and optical monitors 54 and 56 to connect to the top 39 and bottom 40 openings of the blood side of the dialyzer 30. Cylindrical accumulator 22 attaches to the dialysate space at the top opening 35 of the dialysate side of dialyzer 30, and alternating strong vacuum (i.e. negative pressure) and modest positive pressure in accumulator 22 (provided by line 20 through port 21 above the fluid level) alternately draws dialysate into and expels dialysate from accumulator 22, which expands and compresses the membranes of dialyzer 30 (as illustrate by the arrows, FIG. 5), while the automatically controlled blood inflow and outflow clamps 53 and 55 assure that blood passes unidirectionally through the dialyzer 30, at an average rate of up to 250 ml/min (in 5 cycles). The ratio of inflow/outflow cycle times determines the ultrafiltration rate, from a minimum of about 200 ml/hr at a ratio of about 1.45, to about 600 ml/hr at a ratio of 2.45.
In the preferred dialysis system 11 utilized in the specific Examples, the dialyzer was a 1.6 m2 COBE parallel screen-plate dialyzer having dialysis membranes composed of regenerated cuproammonium cellulose (Cuprophan) and having a functional molecular weight cut-off of about 3000 daltons, i.e. only molecules of about 3000 daltons or less will pass through the membrane.
As opposed to many previously-known dialysis systems, the system used in the invention contains a sorbent suspension in the dialysate instead of merely a dialysis solution. Flow of the suspension is generally counter-current, and is both bidirectional between the accumulator 22 and dialyzer 30, and circular between the dialyzer 30 and sorbent reservoir 15.
In summary, during the first part of blood inflow (see particularly FIG. 3A), clamp 62 on the dialysate inflow line 33 opens, allowing sorbent suspension to flow from the sorbent reservoir 15 through the entire dialyzer 30, filling the accumulator 22 to the level of sensor 57. Clamp 62 then closes and remains closed during the remainder of inflow and all of outflow (see particularly FIG. 3B), when pressure in the accumulator 22 returns some suspension to the dialyzer 30 and passes some through one-way valve 45 to return to the reservoir 15 via dialysate return line 34. In typical operation, each minute, about 900 ml of sorbent suspension flows into accumulator 30 (in 5 cycles). 600 ml of sorbent suspension flows back into the dialyzer 30, and 300 ml flows from the accumulator 22 into the sorbent reservoir 15. This, along with the expansion and contraction of the dialyzer membranes, keeps the sorbent suspension well mixed at the dialyzer membrane surface. Typical blood side and dialysate side pressure, and the blood volume of the dialyzer over time during such operation are shown in FIG. 4. As can be seen, both the blood side and dialysate side pressures alternate between positive and negative pressure, while the spring action of the plate dialyzer membranes ensures that there is constantly a positive pressure gradient from blood side to dialysate side.
In one suitable system, sorbent bag 15 initially contains dry sorbent materials to which the system automatically adds 1.5 liters of sterile water from reservoir tank 13 via port 61 during priming. This operation is powered by dialysate pump 60. For the Examples given below, the sorbent materials in bag 15 were as follows:
140 grams powdered activated charcoal (300,000 square meters surface area, between 5 and 53 micron mean particle diameter, 70 micron maximum particle diameter)
80 grams cation exchanger (sodium polystyrene sulfonate, PSS, functional binding of 80 mEq).
1.5 grams Pluronic F68.
3.0 grams polyvinylpyrrolidone (PVP).
sodium bicarbonate and sodium chloride to result in physiologic starting concentrations in the dialysate sorbent suspension after priming (sodium=140 mEg/L, bicarbonate=35 mEg/L, chloride=105 mEg/L).
The priming fluid for the blood side of the dialysis system was one liter of 5% dextrose from container 42 attached to blood inflow tube 24 via tube 23. During priming, priming/rinse clamp automatically opens prime tube 23 while closing blood inflow tube 24. Priming fluid is thus pulled into the system rather than blood. Glucose passes across the membranes of the dialyzer 30, and 20 grams binds to the charcoal, while sodium chloride, and bicarbonate pass from the suspension into the priming fluid. During dialysis, glucose disassociates from the charcoal and returns to the patient (unless the patient's glucose is very high). A reinfusate of sterile calcium chloride and potassium chloride was pumped by reinfusate pump 58 from reinfusate container 41 through tube 26 into the outflow line 25 at a diminishing rate throughout the treatment, to offset removal by the cation exchanger.
The system also includes a variety of sensors to make operation safe, simple and highly automated, including:
a scale to weigh the entire top of the machine, to measure volumes ultrafiltered from and returned to the patient;
blood sensors (54 and 56) to measure foam, bubbles, particles of blood in the inflow and outflow lines 24 and 25, and to measure flow rate-on the inflow line 24;
hemoglobin sensor 46 to chemically detect hemoglobin within the sorbent suspension if there is a membrane blood leak. For this function, a filtrate collector 47 provides a solid-free sample of the dialysate fluid to hemoglobin sensor tape which changes color if hemoglobin is present. The tape is automatically wetted with samples of dialysate, advanced and monitored for color change by a reflectometer. The wetting of the tape is controlled by filtrate pump 63 which further pumps excess filtrate via tube 31 into collection container 32.
empty line sensors on all fluid-filled lines;
temperature sensor for fluid in the reservoir tank 13 surrounding the sorbent bag 15 (optimally heated to about 37° to 40° C. by heating elements also provided in the machine).
The computers of the system automate many of the steps of treatment, including:
priming of the machine, observing lines to determine that all air is removed;
returning fluid to the patient when desired final weight is obtained or of command (for the latter, automatically adjusting ultrafiltration to reach desired final weight).
rinsing the dialyzer and blood lines at the end of treatment; and
recording, storing and transferring data concerning progress of each treatment.
FIG. 4 provides a schematic diagram showing the hydraulics of a combined dialysis/plasmafilter device in accordance with the invention. As shown, the device incorporates a parallel plate dialyzer ("PPD") connected in series with a hollow fiber membrane device ("HFD"). In this regard, it will be understood that the present invention is not limited to such a combined device, and that the HFD could be used as the sole agent for treatment of the blood. Further, when used in combination with the PPD, the HFD can be incorporated in any suitable location within the sorbent circulation side of the PPD. Preferably, the HFD will be incorporated to as to achieve high bidirectional plasma flow across the membranes of the HFD, with a net flow of about zero to prevent increasing sorbent volume (which would increase the volume of distribution for albumin and increase loss of albumin from the patient). The HFD is also desirably incorporated so as to provide blood treatment rates over 150 ml/min., to allow high filtration rates across the membranes and permit high clearance of protein-bound or middle molecular weight substances.
In the illustrated arrangement, the HFD is connected in series with the PPD such that sorbent suspension exiting the sorbent reservior first passes through the PPD and then the HFD. More particularly, sorbent is first drawn from sorbent bag 101 and into sorbent inlet 102 of the PPD. Sorbent exits sorbent outlet 103 and is drawn into accumulator reservior 104, whereafter it is expelled from accumulator reservior 104 and passes through check valve 105. The sorbent suspension then passes into HFD inlet 106 and through the outer chamber of the HFD, thus passing into contact with exterior surfaces of the hollow fibers 107 in the HFD package. Sorbent suspension exits the HFD from outlet 108, and passes through blood leak detector 109 and back into sorbent bag 101. The HPD can be suitably operated as described in Example 1 above. In this manner, the sorbent suspension is also effectively agitated and mixed at the surface of the membranes in the HFD. Additionally, when alternating positive and negative pressure is applied to the sorbent circuit via the accumulator reservior 104, check valve 105 prevents negative pressure from being applied to the HFD sorbent side, and creates only intermittent positive pressure (FIG. 5(b)). In this system, the blood-side (see FIG. 5(a)) and dialysate-side pressures vary with each cycle, but are balanced on average, thus creating a bidirectional flow in each cycle but with zero net filtration (there is net sorbent to blood filtration in the HFD, offsetting ultrafiltration of the PPD, several hundred ml/hr.). On the blood side, blood passes from the patient access and into blood inlet 110 of the PPD, with the intermediate addition of saline from reservior 111. Where a dialysis membrane (as opposed to an impermeable membrane) is installed in the PPD, the blood is dialyzed in the PPD as described above. Blood then exits the PPD through outlet 112 and passes into interior channels of the follow fibers of the HFD (commercial HFD devices have a package including a plurality of hollow fiber membranes). At this point, the alternating positive and negative pressure applied of the sorbent side causes a bidirectional flow of plasma across the hollow fiber membranes, that is, the blood plasma exits and then re-enters the hollow fiber membranes. While exterior of the hemofilter or plasmafilter membranes, middle molecular weight toxins and/or plasma proteins, including proteins to which toxic substances are bound, come into contact with the sorbent suspension. The toxic substances are adsorbed to the adsorbents, and in the case of plasmafiltration, the proteins, now free of toxins, are passed back into the hollow fiber membranes. Thus, effective plasmafiltration or hemofiltration of the blood is achieved as the blood passes through the HFD. Blood exits the HFD via outlet 113, and is returned to the patient through the patient access.
The pressures of the blood-side and sorbent-side will vary with the particular HFD devices employed. Thus, with a particular HFD device, in vitro tests can be done to measure filtration rate, and the vacuum and pressure operating the system will be adjusted to attain zero net filtration. Moreover, to optimize blood flow, adjustments to the ratio of inflow/outflow times can be made. The combined PPD/HFD system will, like the system described in Example 1, measure the rate of ultrafiltration by weighing the entire top of the device, including the sorbent bag. But, since the goal is net ultrafiltration of about zero, there is no need for the long inflow times of the system of Example 1. Better blood flow will be obtained using approximately equal inflow and outflow times. During in vitro tests, for example with pig blood, the driving pressures can be adjusted as above, and the net blood flow determined (by change of weight of the 3 liter container during each cycle). The inflow-outflow times can then be adjusted to give maximum blood flow. Preferably, the 200-225 ml/min average blood flow of the system of Example 1 is maintained.
Charcoal has the capacity to very effectively adsorb middle molecular weight molecules and protein-bound toxins (see, e.g., FIGS. 6(a) and 6(b) which provide Langmuir isotherms of the adsorption of BSP from plasma and saline and of bilirubin from plasma). In the following studies, the PPD/HFD device described in Example 2 was used to determine clearance rates of some protein-bound and middle molecular weight substances from blood. 3 liters of fresh pig blood were spiked with various substances (Shown in Table 1 below), and the blood was treated using the PPD/HFD device. During several hours of treatment, the blood was continuously infused with the substances at a rate designed to maintain a constant concentration (calculated by the predicted clearance of the system). The clearances were then determined by dividing the rate of infusion by the steady-state concentration of the substance. If the blood volume changed, then the change was included in the calculation of clearance. The results are shown in Table 1, in which "Great"=creatinine, "Bili"=bilirubin, BSP, and "Vanco"=vancomycin. Among these, creatinine is a small, non-protein bound substance, bilirubin, Elavil and BSP are small, highly protein-bound molecules, and vancomycin is a middle molecular weight:., non-protein bound substance.
|BLOOD FLOW AND CLEARANCES (ml/min) Ave Membrane Qb. Creat Bili BSP Elavil Vanco
PPD only 200 140 0 0 12 0
F-80 150 130 12 n/a 40 --
Altrex 140
180 130 5 n/a -- --
Althin* 140 90 5 n/a 19 37
140 95 43 n/a n/a 35
-- (dash) = no data n/a = data not currently available *developmental filter from Althin Medical, Inc., m.w. cutoff = 100,000.
As can be seen, use of the HFD can provide significant increases in the clearance of middle molecular weight and protein-bound substances, and can be used in connection with the PPD to provide effective overall clearance of small and larger substances, both protein-bound and non-p rote in-bound.
While the invention has been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only the preferred embodiments leave been shown and described and that all changes and modifications that come within the spirit of the invention are desired to be protected.


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Summer is still a little ways away but the summer temperatures have already arrived across the country. As you start turning on your air conditioner (or maybe you already have), make sure you call D.A. Bennett Service Experts to get your tune-up. Why, you ask? Here are a couple reasons.
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Virtual Gift Cards
For Physical People
Be good to your friends, and buy them the gift of Pilates. We believe giving is better than receiving, especially when it means you can now take class with your bestie.
*Virtual Gift Cards will arrive directly into your recipient's inbox, or alternatively send it to yourself to print out. Ideal for a last-minute present for that "special" somebody. Your gifts will be emailed to you within a week from purchase date. For more help or questions, click the chat button on the bottom of the screen.


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Thursday, April 19th: CrossFit
Alpine CrossFit – CrossFit
Hip Issues? Back Issues? Dr. Antonio is BACK with his "Powerhouse Hips & Back" series on April 28th at 9:00am. Mark it on the calendar!
Indoor Relay Warm-Up (No Measure)
50-100′ Each Movement
Lunge (Forward and Backward)
Side Lunges (Alternating)
Duck Walk
Standing Toe Touches
High Knee's (Forward and Backward)
Butt Kicks (Forward and Backward)
1: Griff (Time)
For Time:
Run 800 meters
Run 400 meters backwards
Run 800 meters
Run 400 meters backwards
In honor of USAF SSgt Travis L. Griffin, 28, who was killed April 3, 2008 in the Rasheed district of Baghdad.
To learn more about Griff click here
2: Metcon (Weight)
A1) Single Arm OH Walk x 50′ ea Arm
-Rest 30s
A2) 3-Position Banded Pallof Press (Quarter Squat, Half Squat, Full Squat) x 6 ea. (3 L/3 R)
-Rest 30s
A3) Side Plank Powell Raise x 6-8 ea. Arm (3030)
-Rest 60s x 3 Rounds
Score= Weight of UB OH Carry
Pallof Press: https://www.youtube.com/watch?v=zo_olew7tKA
Side Plank Powell Raise: https://www.youtube.com/watch?v=U6HqVO4D1ZI
Cool Down
Metcon (No Measure)
3:00 AB/Row at Recovery Pace
Banded Hamstring Stretch x 45-60s ea. Leg
Pigeon Stretch x 45s ea. Leg
Paleo Chair x 2:00
Extra Gains
A1: Briefcase Carry (Single Arm Farmers) (100-100-100′)
100′ ea. Arm
A2: Landmine Anti-Rotation (8-8-8)
Much like landmine floor to overhead, but in this movement the legs and torso remain rigid. Only the arms cross and rotate with the end of the landmine/barbell from in front & overhead to near the hip. Top arm remains straight while lower arm can bend.


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Watch: Japan looks for missing after typhoon kills dozens
Two vehicles are submerged in floodwaters Monday, Oct. 14, 2019, in Hoyasu, Japan. Rescue crews in Japan dug through mudslides and searched near swollen rivers Monday as they looked for those missing from a typhoon that left as many as 36 dead and caused serious damage in central and northern Japan. (AP Photo/Jae C. Hong)


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We LOVED our stay at The Village Cabin. Location was just 6 houses up the hill from the Village. We could walk to stores, shops, restaurants, the lake ect. The cabin was stocked with everything we needed. Hot tub was wonderful too. We will look to stay here again on our next trip.
Paul and friends
"The Village Cabin"