text:
The Monday before Thanksgiving has always been a very special day for me since 1955.
Six weeks earlier, my doctor had diagnosed me as having a severe case of the flu and had put me in the hospital.
On my first day there, I slid out of bed to go use the restroom. When I came back, I put my left foot on the stepping stool to climb back in bed, but it just sat there. So I put my right foot on the stool and was able to get back in bed.
The next time the nurse came by, I told her about that weird experience with my left foot. Her mouth dropped open. She said, "Oh my" and ran from the room. A few minutes later, she came back with a doctor and told me to lay in a fetal position. She wrapped her arms around my neck and knees and pulled with all her might. The doctor then started poking a needle in my back in about six or eight different places.
It was a "spinal tap."
I did not have the flu. It was polio! I became totally paralyzed from the waist down and had to be plumbed into a gallon jug with a catheter. There was no hope for recovery. However, I was measured for a pair of locking knee braces for the very slight possibility that I might be able to use crutches someday.
Then, that Monday morning before Thanksgiving, I woke up knowing I didn't need that plumbing, and that I could slide out of bed and walk. When I told the nurse, she said, "No, no, no. Whatever you do, do not try to walk! We can remove the catheter, but do not try to walk."
Well, I was right about the plumbing, and by Tuesday, I talked them into letting me try to walk. Three doctors and three nurses gathered into a circle to catch me when I collapsed sliding out of bed. I didn't collapse. I just slid out of bed and walked all around the room. One of the doctors said, "This has got to be an answer to prayer."
On Wednesday, they let me go home for Thanksgiving, but "come back Monday!" On Monday, they watched me walking all around and said, "No use for him to hang around here anymore."
I went to work as a heavy equipment mechanic at a logging camp, then drove a logging truck, and then drove a truck making deliveries of paper products for the old Zellerbach Paper Co. for 30 years.
The doctor was right when he said, "This has got to be an answer to prayer." There were a lot of people praying for me. There can be no other explanation.
Everybody Has a Story welcomes nonfiction contributions, 1,000 words maximum, and relevant photographs. Email is the best way to send materials so we don't have to retype your words or borrow original photos. Send to: email@example.com or P.O. Box 180, Vancouver WA, 98666. Call "Everybody Has an Editor" Scott Hewitt, 360-735-4525, with questions.


text:
Christopher Prentice CMG
British Ambassador to Italy and San Marino
We develop and maintain the strong relations between the United Kingdom and Italy, our partner in many international organisations such as the EU, G7, G20 and NATO. We cooperate on a wide range of issues including the economy, in particular measures that generate wealth in both our countries, commercial regulation in the single market, energy policy and international security. We also cover San Marino remotely.
We work to improve the relations between scientists and researchers working on innovative projects in Italy and the UK. We have a team dedicated to sharing our armed forces' expertise and to developing stronger ties and opening up the military sector to UK commercial contacts.
We have trade offices in Rome and Milan. Our consular network is based in Rome and Milan and is supported by a network of honorary consuls in major Italian cities. We also offer consular assistance to British nationals in San Marino from our Consular section at the British Embassy in Rome and our consulate in Milan.
If you're in Italy and you urgently need help (eg if you've been attacked, arrested or lost your passport), call +39 06 4220 0001. If you're in the UK and concerned about a British national in Italy, call 020 7008 1500.
The British embassy can't help with passport enquiries. Contact Her Majesty's Passport Office if you need help.
If you can't get a new or replacement passport in time to travel, you may be able to get an emergency travel document.
You can apply for an emergency travel document (ETD) if you're abroad and your passport has been lost or stolen, damaged or expired, and you can't get a new or replacement passport in time to travel.
If you're due to travel in the next 24 hours, contact us as soon as possible. Call us before making an appointment if you've never applied for a British passport before or if you're applying for a child under the age of 16.
Book an appointment for an emergency travel document in Rome
Travel advice: for information and advice on travelling to Italy see travel advice for Italy
The British embassy can't help with visa enquiries.
If you're not a British national, you may need a visa to travel to the UK. Check if you need a UK visa.
If you're a British national travelling abroad and need to apply for a visa to visit a particular country or check if you need a visa, see the entry requirements on our foreign travel advice for the country you want to visit.
For more information on visas, see UK visas and immigration.
For information on getting married in Italy, see getting married abroad. We can issue certificates of no impediment to allow British nationals to marry in Italy.
This service is for customers who have been asked by the local authorities to provide a certificate of no impediment (CNI) to prove they are allowed to marry.
If you need a CNI, you'll have to give notice of your intended marriage at the British Embassy in Rome if you live in Italy or outside of Italy (but not UK). You need to have been living in Italy for at least 3 clear days immediately preceding your appointment date at the Embassy. For example, if your appointment is on the 6th, you will need to have been in Italy from the 2nd onward.
Please note that the CNI we produce has a six month validity. You should therefore not request a CNI more than six months in advance of your marriage date.
What to bring with you:
If you or your partner have been divorced, widowed or previously in a civil partnership, you'll also need whichever of the following documents is appropriate:
You'll also need to provide evidence of nationality or residence in the country of divorce, if the divorce or dissolution took place outside the UK. You'll need to get it translated if it's not in English.
You'll need to fill in forms for your notice of marriage, and an oath or affidavit (written statement of facts) stating that you're free to marry.
You can download and fill in (but not sign) the forms in advance:
Book an appointment for a CNI in Rome
Find out how to register a birth or register a death that occurred in Italy. You can't register a birth or death at the embassy.
If the death occurred in Italy and you're still in the country, contact us. If you're in the UK and hear of the death of a relative from a third party, you should contact the Foreign and Commonwealth Office on 020 7008 1500.
Read our guidance on coping with death abroad as well as our bereavement guide for Italy.
We'll do all we can to contact you within 24 hours of being told that you've been detained or arrested, and will give you a prisoner pack with information for British prisoners in Italy.
We cannot get you out of prison, prevent the local authorities from deporting you after your prison sentence, interfere in criminal or civil court proceedings, or get you better treatment in prison than is given to local people.
We may be able to visit you if you're hospitalised in Italy. We have also produced guidance on hospitalisation in Italy including information on local procedures and a glossary of terms. We can't get you better treatment than is given to local people.
We offer limited notarial services at the embassy, including administering an oath of British citizenship. We also produce informative notes you can download for free to present to the local authorities if asked for certain certificates. For full details see our notarial and documentary services guide for Italy.
Ask the UK government to get a UK document legalised (certified as genuine).
The British Embassy Rome can legalise certain signatures. For full details see our notarial and documentary services guide for Italy.
Use our lists of local English-speaking suppliers and services if you need help in Italy:
Please note that inclusion in these lists does not constitute official endorsement by the British embassy or the UK government.
In addition to the services listed above we can also:
For more information on the services we can provide, see Support for British nationals abroad: A guide.
General information on living in Italy such as pensions, benefits and residence permits.
Although we try to help British nationals in a wide range of situations, we cannot:
We charge fees for some of our services. See the full list of consular fees in Italy
Deputy Head of Mission, Italy
British Consul General and Director for UKTI Italy, Milan
Via XX Settembre 80/a
00187 Rome
Telephone +39 06 4220 0001
Fax +39 06 4220 2333
Emergency consular assistance (24 hours) 06 4220 0001
The British Embassy offices in Rome are not open to the public. Visits are by appointment only.
We do not answer visa enquiries.
British Embassy Rome
Via XX Settembre 80/a
00187 Rome
Email firstname.lastname@example.com
Telephone: +39 06 4220 0001
Fax: +39 06 4220 2334
Emergency consular assistance (24 hours) +39 06 4220 0001
Via XX Settembre 80/a
00187 Rome
Telephone: +39 06 4220 0001
Fax: +39 06 4220 4909
Via S. Paolo, 7
20121 Milan
Email firstname.lastname@example.com
Telephone: +39 02 723001
Fax: +39 02 72020153
British Embassy Rome
Via XX Settembre 80/a
00187 Rome
Telephone +39 06 4220 0001
Via di San Sebastianello, 16
00187 Rome
Email email@example.com
Contact form http://www.britishcoun...
Telephone: +39 06 478141
Fax: +39 06 4814296

subset: commoncrawl


text:
Chelsea Goodace, Kellie Fox and Lauren Young homered in the contest. The home runs gave Goodacre and Fox three each on the season while it was Young's first blast.
Nancy Bowling (2-0) started the game and pitched three innings of scoreless ball. The sophomore allowed two hits and struck out three in the contest. Kenzie Fowler hurled the final two innings and did not allow a run on one hit.
Carrie Sheehan (1-2) suffered the loss for New Mexico. Sheehan pitched the entire game and allowed eight runs, seven earned, on 11 hits. She did not walk or strike out a batter.
Arizona got the scoring started in the first when back-to-back singles by Kelsey Rodriguez and Kellie Fox put two on for Chelsea Goodacre. The junior hit her second three-run homer in as many games to give UA a 3-0 lead.
The Cats manufactured a run in the second to add on to its lead. Courtney Rodriguez led off the frame with a double and moved to third on Alex Lavine's groundout. Hallie Wilson's fly ball to right field scored Rodriguez to extend UA's lead to four runs.
Fox and Lauren Young would lead off the third and fourth innings with solo homers to extend Arizona's lead to 6-0. Arizona would add another in the fourth when Kelsey Rodriguez's groundout brought in her sister Courtney.
UA would walk off in the bottom of the fourth when the Cats put two on with back-to-back singles by Mo Mercado and Young. Courtney Rodriguez's grounder to third base would be booted by Jasmine Casados to allow Mercado to score and give Arizona the 8-0 victory.
Arizona will be back in action Saturday when it takes on Tennessee State at 4:00 and fourth-ranked Alabama at 6:00 p.m. MST.
Complete Hillenbrand Invitational Schedule
Thursday, Feb. 13
ARIZONA 5, Grand Canyon 0
Friday, Feb. 14
Grand Canyon 9, Tennessee State 8 (9 innings)
Alabama 13, Grand Canyon 5
ARIZONA 8, New Mexico 0 (5 innings)
6:00 p.m. Alabama vs. Tennessee State (late)
Saturday, Feb. 15
9:00 a.m. New Mexico vs. Grand Canyon
11:00 a.m. Tennessee State vs. Grand Canyon
1:00 p.m. Alabama vs. New Mexico
4:00 p.m. ARIZONA vs. Tennessee State
6:00 p.m. ARIZONA vs. Alabama
Sunday, Feb, 16
9:00 a.m. New Mexico vs. Tennessee State
11:00 a.m. ARIZONA vs. Alabama
1:00 p.m. ARIZONA vs. Grand Canyon


text: Ignorance is a choice. Having unprotected sex is a choice. Dropping out of high school is a choice. Not getting married is a choice. Our culture has been in downward spiral since the mid 1960s. Is it just a coincidence that the War on Poverty programs began simultaneously with this downward spiral? As a country we decided anything goes. No one was responsible for their actions. The government would create a program to solve every problem created by people not taking responsibility for their lives and accepting the consequences of their bad choices. You get more of what you incentivize. Below is a picture of what government policies and an ignorant population can accomplish.


text:
The only question going into this year's WTA Championship was not if Serena Williams would win, but by how much? The answer was a uneven 2-6, 6-3, 6-0 victory over China's Li Na.
Williams' fourth season finale title was the latest in a stellar 2013 that was part of a 78-4 match record by the number one ladies player which included two Grand Slams trophies at the French Open and the U.S.Open.
Besides pocketing over a record breaking 12 million dollars, Williams' Grand Slam total is now 17 which is right behind 18 by Martina Navratolva and Chris Evert. In sight would also be the 22 Slams by Steffi Graf and the top would be 24 held by Margaret Court.
Now at 32 years old and 18 seasons, it would seems like a challenge, but Serena has showed no signs of slowing up. Before the WTA Championships in Istanbul began, Williams said she feels like she could still be playing in ten years.
The champions before Williams have showed some longevity. Navaratolova went 20 years before retiring the first time and Evert did 18 years before bowing out at age 34. Graf got out of tennis before she was 30 years old.
"I am interested for next year to take my game to a new level, which I think I can do," said Williams.
A new level? After this year, the rest of the women tennis players better be worried.


text:
Discovering Solaris FC lib in OpsCenter
By user12611199 on Aug 10, 2011
[Read More]
Here are a few tips on using Subversion with NetBeans. In my case the Subversion was setup on a system with ssh tunnel, so we'll go over authentication settings as well. My development environment is Mac OS X 10.5.8 with NetBeans 6.8. The remote svn system is running Solaris 10 x64.
1. We'll start with SSH related details to enable permission to the ssh server. First, let's create a PKI key-pair and then upload the public key to the remote svn server...[Read More]
I just got a copy of the Web 2.0 Fundamentals book by Oswald Campesato and Kevin Nilson. It nicely outlines collection of technologies, tools, products and services to help with delivery of Social Networking and Social Media applications. The book is written in such a way that allows users to quickly get familiar with jargon de jour and to pick the best of breed components for your application stack.[Read More]
Do you have an avatar and what do you think of the 3D world? The FountainBlue had held today it's annual event, that gathered startups, enterprise companies and individuals that are excited about the opportunities in the virtual world application space. The virtual world is getting its adoption in gaming (both desktop and mobile), educational, healthcare, and overall collaborative environment spaces. Players in the space include Comcast, Sony, Sun, and of course startups like Masher Media, ISO Interactive, KohdSpace, among others.
There are multiple technologies involved in building the virtual world applications. Unity is often a preferred choice for 3D game development, Java is often in the list for programming languages, and for deployment Darkstar is used for massively scaled multi-player networking layer. Sun's Project Wonderland demo was focused on how to use open-source toolkit for creating collaborative 3D virtual world, and here is how it looks.
The last two meetups of the Greater SF LAMP community that we host at Sun campus were focused around PHP development. The December one had an exciting topic on Object Oriented Design Patterns for PHP presented by Robert Gonzalez of Bay Alarm. What's interesting since I've started working with the Web 2.0 community I rarely heard the word pattern that we traditionally apply in the sw architecture, the main emphasis is on functionality and the business ideas fostering the implementation. However, with PHP 5 you can apply the Object Oriented principles and achieve an elegant application architecture, well beyond 'just getting the job done'. The speaker went over a few patterns that I'm used in the Java world, and shown examples of how to apply them in PHP. The traditional Singleton and Factory patterns were discussed. Also the Strategy Pattern was an interesting one as it encapsulates a set of algorithms that change and leaves out what doesn't change. This pattern makes encapsulated algorithms that are interchangeable. It favors composition over inheritance. A ComputerPlatform interface can have multiple implementations such as ComputerPlatform_Mac, ComputerPlatform_Solaris, ComputerPlatform_Windows that all implement a given method, but individual implementation may vary. All in all it was a great session and there are already quite a few books out there that discuss patterns with PHP as the language matures.
This month the two speakers covered NetBeans IDE and Aptana's IDE around their PHP support. So from design to implementation, if you attended both of these sessions, you're armed with all you need to create PHP applications.
Marina Fisher is a member of Oracle ISV Engineering team, posting blogs around industries, technologies, and applications she is working with.


text:
USDA Proposes Tougher Food Safety Standards for Chicken and Turkey
It's no secret that Americans eat a lot of chicken and turkey. In fact, USDA estimates that a single American will eat 102 pounds of poultry in 2015. It is USDA's job to ensure the meat and poultry products we enjoy are also safe to eat, and that means adapting federal food safety regulations to meet changes in production technology, scientific understanding of foodborne illness, and consumer demand.
According to the Centers for Disease Control and Prevention, over 1 million Americans contract foodborne Salmonella poisoning each year, and 200,000 of those illnesses can be attributed to poultry. Today, USDA's Food Safety and Inspection Service proposed new food safety standards that would reduce Salmonella and Campylobacter, another common cause of foodborne illness, on ground chicken and turkey, as well as chicken legs, breasts and wings, which represent the majority of poultry items that Americans purchase and feed their families. Read more »


text:
- Welcome
- Egypt's Mermaid Alexandria
- A Summer Classic
- The Stars Left The Stage For Team Spirit
- Living History Halil İNANVCIK
- Are You Ready To Get Tired?
- Wild life from the eyes of Mustafa Koç
- Ramadan in The Topkapı Palace
- A Long Standing Beverage Tradition Sherbet And Sorbet
- A Fly And A Diamond
- Worker And Nurse
- Glass, Metal, Wood, Paper
- Extended Summer At Evin
- Nev's Summer Selection
- Master And Apprentices
- One Hundred Percent Comic Book
- The Last Fifteen Years
- No Vacation In The Capital
- Islands Museum
- Pleasant Times
- İstanbul Fashion Week
- Mosque Illuminations Competition
- An African In Istanbul
- A Different Istanbul In Ramadan
- Summer, Art And Children
- There Is Fun At The Neighbor's !
- Star Of Eastern Europe
- Time Tunnel
- Mathematics In The picture
- Books For Children
- The Kâzım Taskent Art Gallery
- Coşkun Aral's Siirt
- Turkey's Fantastic Beachest
- Seagull Station; Burgaz Island
- Geneva In Three Steps!
Summer, Art And Children
School is out. Everyone is on vacation. A surprise awaits those who remained in the city or returned home from their vacation early: Summer art schools…
The Youth Workshop Modern which begins on July 5th at Istanbul Modern and continues until August 27th will include instruction in different art works in graffiti, model making, sculpture, animation, traditional arts and fanzine workshops. There are four different two-week periods in the Youth Workshop Modern Summer Art School for children ages 7-12 on weekdays from 9.30-13.30.The art work the children make in the workshops will be exhibited at one-day displays to be held after the two-week courses in the museum pebble area. For information: www.istanbulmodern.org
This summer rich and entertaining experiences await children in the 4-12 age groups at the santralistanbul. There is a new workshop every week like Mad Robots, Entertaining Electric, Green Energy, santral Art Studio, Small archeologists at santralistanbul, and Creative and Entertaining Cuisine with Tiny Chefs… At the santral PARK playground children are building, sailing the vessels they made themselves in the water canals, walking around labyrinths, trying wall climbing, crawling through tunnels, walking on interesting equipment and many more fun things. For detailed information about all these activities that will continue until September 3rd: www.santralatolye.com
Turkey's first and only industrial museum, the Rahmi M. Koç Museum, is very colorful and entertaining this summer. The museum is hosting a summer school program that will take place with different educational contents and weekend training workshops. The activities that will contribute to children's social, emotional, mental and physical development and their hand skills and which will support the development of their imaginations and creativity will continue until August 27th. In addition, visitors to the museum will learn many things with the aid of Istanbul's first immobile planetarium, the "Discovery Orb," about the formation of volcanoes, the ice age, the way dinosaurs lived and disappeared, mysteries in the human body, events in the atmosphere and hurricanes, the birth of stars, sun explosions and evolution. For detailed information: www.rmk-museum.org.tr
Summer school for children ages 8-12 began on June 21st at the Sabancı University Sakıp Sabancı Museum (SSM). Developed as a project by the SSM Educational Division, the summer school is at the Greenhouse Workshop for one-week periods. In the workshops which will be held four days a week (Tuesday-Friday) from 10.30-15.30, there are the subjects of music, archeology, creative drama, free creativity and free drama. For detailed information: muze.sabanciuniv.edu


text:
A friend and colleague has recently written a piece on how technology alone will not 'fix' education.
She writes
No matter how many laptops we put in classrooms or wi-fi networks we set up, if kids are in a district where schools are closing and class time is reduced due to budget shortfalls, learning is going to suffer. No matter how innovative the online textbook system, if kids are in classrooms where the teacher has received no training or even advanced notice that a new system is going to be used, learning is going to suffer. Regardless of how promising the innovation, it will suffer from the lack of technical support in a majority of districts or increasingly higher demands on teachers without appropriate increases in training and support.
We have talked about this problem many times over the years, having both been involved in well-meaning organizations that thought there was a perfect new technology to solve x or y problem (mostly education) or that everything we need to educate the world is already on the web, we just need to gather it together in one place (the curation solution).
I've often made a similar argument about libraries. New technologies have huge potential for impact, but to be meaningful, they need to be combined with a deep understanding of the how we learn and how we create. New technologies also often need time to find their ultimate purpose. The telephone was not invented for personal communication, but has revolutionized it. The television was at some point supposed to revolutionize learning, but has instead changed our social lives and even the design of our houses. New technologies will undoubtedly change our libraries, but we have to be prepared for it to be in ways that we don't expect.
And for those who are still looking for simple answers:


text: NIH Grant Abstracts National Institutes of Health grant abstracts NIH Principal Investigators at Legacy: Boison, Detlev, PhD Bottlang, Michael, PhD Burgoyne, Claude F., MD Demirel, Shaban, PhD Fortune, Brad, OD, PhD Gardiner, Stuart, PhD Mansberger, Steven L., MD, MPH Ochoa, Jose L., MD, PhD Wackym, P. Ashley, MD Wang, Lin, MD PI: Michael Bottlang, PhD R21AR053958 "Evaluating and improving an emergent technology for fixation of bone fractures" DESCRIPTION (provided by applicant): Each year, 6.2 million extremity fractures are treated in the US at a cost in excess of $13 billion. Even today, 5-8% of these fractures experience complications in fixation and healing, which presents a significant secondary, but preventable, public health issue. Locked plating is thought to be one of the most important, present-day advancements in fracture fixation. It preserves periosteal blood supply and may improve fixation in osteoporotic bone. As such, it provides a tremendous opportunity to improve the healing rate in problematic high-energy fractures and osteoporotic fractures alike. By providing a potential solution to a pressing clinical challenge, locked plating technology has gained rapid and widespread acceptance despite the virtual absence of supportive data. This enthusiasm is in stark contrast to the 13-21% failure rates found in recent clinical reports on locked plates. The majority of these clinical complications manifest as delayed unions or non-unions. The likely reason for these complications is the high stiffness of locked plate constructs, which can suppress the interfragmentary motion required for secondary bone healing. Unlike conventional plates, locked plates rely on secondary bone healing by callus formation. As a solution to this problem inherent to locked plating, we have explored a novel strategy, termed Far Cortical Locking (FCL), capable of reducing the stiffness of locked plate constructs while retaining sufficient fixation strength. The proposed in vivo study will investigate for the first time, how locked plating affects fracture healing in an ovine fracture model. In addition, we will test if stiffness-reduced FCL fixation can enhance fracture healing. Specific Aim 1 will compare periosteum-sparing locked plating and conventional plating to determine if biology-preserving locked plates can improve fracture healing. Specific Aim 2 will compare locked plating and FCL plating to determine if stiffness-reduced FCL constructs can improve fracture healing. Specific Aim 3 will compare FCL plating to standard conventional plating to evaluate the combined benefit of biology-preservation and reduced stiffness provided by FCL plating. This proposed exploratory and developmental research constitutes an urgent first step toward evaluation and optimization of locked plating technology on a scientific basis. Results will have direct clinical implications by providing a long-overdue evaluation of readily adopted locked plating technology. Furthermore, results may direct the future evolution of locked plate technology by providing a working solution to an inherent problem associated with contemporary locked plates. PI: Detlev Boison, PhD R01NS058780 "Adenosine-releasing brain implants for epilepsy therapy" DESCRIPTION (provided by applicant): Suppression of pharmacoresistant seizures in mesial temporal lobe epilepsy (MTLE) remains a major challenge in epilepsy therapy. Adenosine is an endogenous neuromodulator with potent anticonvulsant properties and thus highly suited to meet this therapeutic need. However, due to peripheral side effects of adenosine, a local mode is needed to supplement adenosine to the brain. We aim to develop biocompatible scaffolds to deliver the endogenous seizure suppressor adenosine to suppress seizures in a rat model of MTLE. The rationale for this approach is based on the following findings from our labs: (1) Deficits of adenosinergic neuromodulation, in particular upregulation of the main adenosine removing enzyme adenosine kinase, contribute to epileptogenesis and seizures. (2) Augmentation of adenosine is sufficient to suppress pharmacoresistant seizures. (3) Local delivery of approx. 200 ng adenosine per day by brain implants of adenosine releasing cells is sufficient to provide complete seizure suppression in a model of MTLE. (4) Stem cell derived brain implants engineered to release adenosine retard epileptogenesis. (5) The combination of biopolymers and engineered stem cells promotes the release of adenosine. (6) Polymer scaffolds and cell encapsulation matrices are available, which permit cell replacement and sustained local drug delivery. Our CENTRAL HYPOTHESIS is that local brain implants based on a combination of slow degrading biopolymers with adenosine and/or cells engineered to release adenosine are needed for clinical applications aimed at suppressing seizures in pharmacoresistant MTLE. The model system to address this hypothesis will consist of a novel protein-based polymer system, silk fibroin, in combination with adenosine and adenosine-producing cells, to be tested in an animal model of epilepsy. Our SPECIFIC AIMS are: Aim 1. Engineer biocompatible polymers for the local therapeutic delivery of adenosine. Aim 2. Develop a polymer/cell based system for the sustained delivery of adenosine. PI: Detlev Boison, PhD R21NS057475 "Adenosine kinase as novel therapeutic target to prevent acquired epilepsy" DESCRIPTION (provided by applicant): Approximately 30% of all epilepsies are symptomatic and traumatic brain injury (TBI) is estimated to cause 20% of all symptomatic epilepsies. Thus, it is estimated that in the United States, at least 0.5 million surviving individuals live with posttraumatic epilepsy (PTE). Increased extracellular adenosine as an acute response to brain injury is known to provide seizure suppression and neuroprotection. However, astrogliosis associated with acute injury results in increased adenosine kinase (ADK), the key regulator of ambient adenosine levels. Upregulation of the astroglial based kinase ADK leads to deficits in the adenosinergic inhibitory feedback-system and thus promotes seizures. Astrogliosis is not only a hallmark of many types of epilepsy, but also a consequence of TBI. Since TBI can lead to subsequent epileptogenesis, it is important to understand how astrogliosis may contribute to epileptogenesis. We aim to investigate how ADK is regulated in response to TBI and how these findings can be translated into applications to prevent epileptogenesis. The rationale for these studies is derived from the following previous findings from our lab: (1) Deficits of the adenosinergic system, in particular upregulation of ADK during astrogliosis, contribute to epileptogenesis and seizures. (2) Pharmacological blockade or RNAi-mediated downregulation of ADK effectively suppress seizures. Our CENTRAL HYPOTHESIS is that, as an astrogliotic response to injury, upregulation of ADK occurs as a general phenomenon and is a cause for epileptogenesis after TBI. Consequently, local therapeutic downregulation of ADK after TBI is expected to prevent subsequent epileptogenesis. We will therefore monitor astrogliosis, upregulation of ADK and the development of seizures in a novel rat model of TBI. In a therapeutic approach, downregulation of ADK expression with lentiviral RNAi is expected to prevent epileptogenesis after TBI. The SPECIFIC AIMS of this project are: Aim 1. Investigate astrogliosis, ADK-expression, and seizures in TBI-model of PTE. Aim 2. Prevent PTE by local therapeutic intervention. PUBLIC HEALTH RELEVANCE: We plan to interfere with a response of the injured brain to reduce the abundance of the endogenous neuroprotective modulator adenosine. A gene therapy approach will be used to prevent the local reduction of adenosine after injury. Thus, new therapeutic strategies to prevent epileptogenesis after traumatic brain injury become feasible. PI: Detlev Boison, PhD R21NS057538 "Adenosine kinase as therapeutic target to induce and maintain ischemic tolerance" DESCRIPTION (provided by applicant): Acute brain injury can result in neuroprotection and tolerance to subsequent injury. However, the mechanisms of this endogenous neuroprotection are incompletely known. As the increase in adenosine following acute seizures is both neuroprotective and antiepileptic, adenosine may also provide neuroprotection and tolerance in ischemia. The elevation of adenosine following acute seizures is due to downregulation of adenosine kinase (ADK), the key enzyme of adenosine metabolism. Thus, the adenosine- ADK system may be a candidate as an endogenous tolerance effector. We aim to investigate how ADK is regulated in response to ischemic brain injury and how these findings can be translated into applications to prevent damage to the injured brain. The rationale for these studies is derived from the following previous findings from our lab: (1) ADK is rapidly and transiently downregulated as an acute response to both injurious seizures and transient focal cerebral ischemia. (2) Upregulation of ADK renders the brain more vulnerable to ischemic cell loss. (3) Intrastriatal implants of adenosine releasing stem cells protect the brain from subsequent ischemia. (4) Pharmacological blockade or RNAi-mediated downregulation of ADK effectively suppress seizures and seizure-induced injury. Our CENTRAL HYPOTHESIS is that the acute and transient downregulation of ADK after an insult is a general phenomenon of injury and responsible for the induction of ischemic tolerance and that augmentation and prolongation of this beneficial ADK-response is neuroprotective. We will investigate ADK expression in rodent models of ischemia. In a therapeutic approach ischemic tolerance will be induced by inhibiting ADK expression by lentiviral RNAi. The SPECIFIC AIMS of this project are: Aim 1. Study the involvement of the adenosine system in the induction of ischemic tolerance. Aim 2. Induce tolerance by therapeutic downregulation of ADK. PUBLIC HEALTH RELEVANCE: We plan to investigate novel mechanisms and strategies to prevent cell loss after stroke. Therapeutically, augmentation of the brain's endogenous neuroprotective adenosine system is expected to induce tolerance to ischemic brain injury. Our findings may be translated into effective new therapies for the prevention of brain damage after stroke. PI: Detlev Boison, PhD R01MH083973 "Adenosine and schizophrenia: mechanisms and therapies" DESCRIPTION (provided by applicant): Schizophrenia (SZ) is a debilitating mental illness with tremendous human, social and financial costs to society. Unfortunately, existing treatments are unsatisfactory and current development remains stagnant due to poor understanding of the biological bases of the disease. Two perspectives have emphasized disturbances in two neurochemical messengers in the brain -dopamine and glutamate, in relation to disparate SZ- symptoms. This grant will examine a third messenger -adenosine (ADO), as a potential link uniting the dopamine and glutamate hypotheses of SZ. ADO can regulate both dopamine and glutamate neurotransmission via receptors with opposing actions (A1 vs. A2A adenosine receptors). ADO is therefore uniquely positioned as an upstream coordinator/regulator between these two neurotransmitter systems. Hence, ADO-based treatment may be an attractive alternative with dual corrective actions on the glutamate and dopamine systems, thereby achieving effective control over selected SZ symptoms. Our central hypothesis is that subtle disturbances in adenosinergic neuromodulation can give rise to selected behavioral endophenotypes implicated in SZ; thus corresponding corrective interventions targeting at the ADO system should confer therapeutic potential against such SZ endophenotypes, and thereby validate our hypothesis. Our hypothesis will be tested by three specific aims. First, we will characterize the emergence of selected SZ-related endophenotypes as well as their opposing phenotypes in transgenic mice with either over- or under- expression of brain ADO achieved by genetic manipulation of adenosine kinase. Second, we aim to identify the molecular mechanisms of adenosine-based modulation of dopaminergic and glutamatergic neurotransmission. This will be achieved by behavioral and biochemical examination of A1R and A2AR knockout mice. Third, we aim to dissect the brain regions in which ADO-dopamine interactions and ADO-glutamate interactions contribute to the regulation of specific SZ-related endophenotypes. To achieve this, ADO will locally be modified by transplantation of ADO-secreting stem cells and by focal infusion of drugs acting on ADO-receptors. The expected outcomes of this project include: (i) the biological validation of a novel neurochemical theory of SZ, and (ii) the feasibility-test of a novel ADO-based strategy to produce behavioral adjustment with therapeutic potential. PUBLIC HEALTH RELEVANCE: Schizophrenia is a devastating mental disorder to the individual and society alike, yet the efficacy of current drug treatment remains poor, and the development of novel drugs is limited to either blocking dopamine or enhancing glutamate neurotransmission. This proposal will examine a novel drug target for schizophrenia-therapy -adenosine: Given adenosine's unique position to interact in parallel with dopamine and glutamate neurotransmission, adenosine-modulating drugs are hypothesized to confer therapeutic potential against multiple SZ symptoms. PI: Detlev Boison, PhD R01NS061844 "Astrocyte dysfunction in epileptogenesis: the role of adenosine" DESCRIPTION (provided by applicant): This grant studies the hypothesis that astrogliosis and resulting dysfunction of adenosine-based neuromodulation is a mechanistic cause for the development of epilepsy (i.e. epileptogenesis). This is of importance, since to date no effective prophylaxis for epilepsy is available. This proposal will explore status epilepticus (SE)- triggered epileptogenesis and dysfunction of the endogenous adenosine-based seizure control system in mice in search for an astrocyte-based mechanism of epileptogenesis and thus may provide a foundation for the development of novel antiepileptogenic therapies. The proposal is based on the following findings: (i) Adenosine kinase (ADK) is the key enzyme for the regulation of adenosine; (ii) In adult brain, ADK is expressed in astrocytes; (iii) Astrogliosis is a hallmark of epileptogenesis; (iv) ADK is over-expressed within epileptic astrogliotic hippocampus; (v) Augmentation of adenosine by implants of adenosine releasing cells prevents kindled seizures. (vi) Transgenic overexpression of ADK increases seizure susceptibility; (vii) Local reduction of ADK in transgenic mice prevents epileptogenesis. Our CENTRAL HYPOTHESIS is that an epileptogenesis triggering event (e.g. SE) induces astrogliosis with resultant regional upregulation of ADK as a necessary component of epileptogenesis and that reconstitution of brain adenosine by stem cell derived brain implants can prevent such epileptogenesis. The model system to address this hypothesis consists of intraamygdaloid application of kainic acid (KA) to initiate epileptogenesis selectively in the CA3 area of the hippocampal formation of mice and to transplant ADK-deficient adenosine releasing embryonic stem (ES) cells into the epileptogenic region. SPECIFIC AIMS: In Aim 1 we will study the causal, temporal, and spatial relations of astrogliosis, upregulation of ADK and seizures in a mouse model of CA3-selective epileptogenesis. In Aim 2 we will use a panel of different Adk-transgenic mice, in which we can molecularly separate cell-type specific functions of ADK expression from astrogliosis, to study both mechanisms independently. In Aim 3 we will use ADK-deficient ES cell-derived intrahippocampal implants in a therapeutic approach to prevent epileptogenesis. The expected outcome of these studies is to define astrocytic ADK as a target for the prevention of epileptic seizures and to translate these findings into a novel stem cell based treatment approach. PUBLIC HEALTH RELEVANCE: Currently, no therapy is available to prevent the development of epilepsy. This proposal studies a defective function of the brain's own adenosine-based seizure control system as a mechanistic cause for epilepsy and translates these findings into a novel approach to prevent epilepsy by implanting adenosine releasing stem cells. PI: Trevor Lujan, PhD 1R41AR059433-01 "A cost-effective bioreactor to advance functional tissue engineering of cartilage" DESCRIPTION (provided by applicant): Osteoarthritis (OA) is the leading cause of chronic disability in the United States. A clinical goal in the treatment and prevention of OA is to develop replacement cartilage using tissue engineering (TE) technologies. Although TE cartilage presently lacks the mechanical stability of native cartilage, studies have demonstrated that mechanical stability can be enhanced with specific chemical and mechanical stimuli. To speed the discovery of optimal stimulation protocols, research platforms need to be available that enable fast, clear and reliable communication of functional outcomes (i.e material properties). Towards this goal, we introduce a six-chamber bioreactor that combines the efficiency of batch testing with the accuracy normally reserved for dedicated single-specimen material test systems. This system is therefore capable of mapping functional development of six individual specimens exposed to highly-specific mechanical stimulation protocols. To remain cost-effective and portable, the bioreactor leverages system redundancies to eliminate hardware. The specific aim of this study is to test the bioreactor's capacity to deliver accurate mechanical stimulations and material property evaluations in all six test chambers. The effect of loading conditions and specimen geometry on accurate mechanical stimulation will be quantified using external sensors. The viscoelastic material properties of soft TE scaffolds and stiff cartilage plugs will be characterized in both the six-chamber bioreactor and a conventional single-stage testing device. Results between the bioreactor and the model testing system will be statistically compared. If validation of the bioreactor is successful, we envision this product will provide an economical and reliable research platform that fosters TE technology transfer. PI: P. Ashley Wackym, MD R01DC02971 "Molecular Basis of Vestibular Efferent Function" DESCRIPTION: The long-term objective of this ongoing research program is to understand the projection of the vestibular efferent neurons to the vestibular periphery in the context of the fundamental molecular sensory organization of the receptors and the vestibular primary afferents. Based on data resulting from studies performed during the PI's K08, R29 and R01 Awards, the diversity and organization of the efferent receptors and second messengers is far more complex than our original hypothetical model predicted. During the current term of the grant, four questions are addressed: 1) what are the topographic distributions of these expressed genes and proteins in the rat and human vestibular end-organs and primary afferent ganglia?; 2) what are the full length cDNA sequences encoding the mRNAs subserving the efferent/afferent interaction in the vestibular periphery?; 3) what is the chromosome location and the genomic sequence for each of these genes and how are they processed to yield these cDNAs?; and 4) what changes occur in these genes during the aging process? The studies proposed are either hypothesis testing or hypothesis generating in nature. Specific Aim 1 will determine the topographical distributions in the vestibular epithelia and Scarpa's ganglia of specific muscarinic AChR subtypes and nicotinic AChR subunits, purinergic receptors, and second messenger/transduction proteins using in situ hybridization histochemistry in the rat vestibular periphery and immunohistochemistry in the rat and human vestibular periphery. Specific Aim 2 will characterize the full length cDNAs identified in the initial funding period which may be responsible for the efferent/afferent interaction in the rat vestibular periphery and using radiation hybrid mapping, determine the chromosomal locations for each of these genes in the vestibular periphery. Specific Aim 3 will explore how the expression of the genes potentially subserving the efferent/afferent interaction changes during the process of aging using microarray expression profiling. After a detailed molecular understanding of this efferent/afferent interaction, experimental studies can be performed to induce changes in this system. These studies will provide a model for determining the role of the efferent and afferent pathways during vestibular compensation, after vestibular injury, or during specific vestibular disorders such as Meniere disease or migraine associated vertigo (benign positional vertigo of childhood). In addition, molecular characterization of these neurotransmitter and receptor distributions may lead to advances in the pharmacotherapy of patients with vestibular dysfunction. PI: Lin Wang, MD R01EY019939 "Dynamic and Static Autoregulation Impairment in the Optic Nerve Head of Glaucoma" DESCRIPTION (provided by applicant): Glaucoma is a disease characterized by irreversible damage of optic nerve affecting millions of Americans. Yet details of the underlying disease mechanism are still unclear. While recognizing the crucial role of intraocular pressure (IOP), autoregulation (AR) dysfunction has been proposed as a cause of circulatory aberrations in the optic nerve head (ONH) associated with glaucomatous optic neuropathy. Autoregulation in the normal ONH initiated by an ocular perfusion pressure change contains two phases: an initial dynamic phase (dAR) when vascular smooth muscles dilate and contract to adjust the vascular resistance in an attempt to return blood flow (BF) to its original level; and a later steady-state phase (sAR) when dynamic BF changes have equilibrated to a steady level. Due primarily to methodological limitations, most previous studies in human and experimental glaucoma have assessed only sAR and failed to detect AR dysfunction in the ONH. With a modified laser speckle flowgraphy device (LSFG) and newly established methods for measuring the dAR and sAR, this proposal will test the following central hypothesis: Chronic IOP elevation induces AR dysfunction in the ONH, which importantly contributes to the pathophysiology of glaucomatous ONH damage. This hypothesis will be tested in three Specific Aims. Specific Aim 1: To test the hypothesis that ONH dAR abnormalities develop early in the monkey experimental glaucoma model, that they precede sAR and bBF alterations and that they progress in parallel with clinical measures of ONH and RNFL structural disruption. Specific Aim 2: To test the hypothesis that the ONH AR abnormalities occurring in the monkey model of experimental glaucoma are a primary result of exposure to chronic IOP elevation rather than a secondary result of neurodegeneration. Specifically, we will test the prediction that AR abnormalities will not develop in two alternative, non-IOP-related, axonal injury models - optic nerve transection and intra-retinal laser axotomy. Specific Aim 3: the ONH tissues obtained from the animals studied in Specific Aims 1 and 2 will be used to carry out two postmortem histological studies: 3A) To assess regional BF in the monkey ONH using a state-of-the-art microsphere method and compare these measurements with the LSFG bBF estimates obtained immediately prior to sacrifice; and 3B) To test the hypothesis that AR dysfunction detected in vivo by LSFG is associated with derangement of the relationship between ONH astrocytes, lamina cribrosacytes and the blood vessels within the underlying laminar beams and peripapillary scleral beam insertions. In a follow up R01 proposal we expect to extend our investigation in: 1) clinical application by modifying the current techniques of dAR analysis to noninvasively so as to elicit a controlled ONH dAR response. 2) Characterization of ONH astrocytes and lamina cribrosacyte role in ONH AR using 3D electron microscopic reconstructions and fresh ONH tissue slice preparations. 3) To test the hypothesis of age-related alterations between astrocytes and capillary endothelial/pericytes in AR. PUBLIC HEALTH RELEVANCE: This project seeks evidence of autoregulation (AR) dysfunction in the optic nerve head and its role in pathogenesis of glaucoma as well as to develop and assess a method for its clinical detection. These developments will make the detection of AR dysfunction in human ocular hypertensive and glaucoma patients a credible goal and the presence of AR dysfunction a therapeutic target for the treatment of the disease. PI: Jose Ochoa, MD, PhD R01NS048932 "Primary C nociceptors and C sympathetics in CRPS" DESCRIPTION (provided by applicant): Chronic neuropathic pains and hyperalgesias/allodynias following peripheral nerve or tissue insults, whether associated with nerve pathology (CRPS II) or not (CRPS I), curse patients, elude therapies and puzzle researchers. Hyperfunction of peripheral pain receptors (nociceptors) is an accepted cause of abnormal painful input in neuropathy (CRPSII) and a hypothetical source of secondary upheaval of pain-signaling neurons in the spinal cord, in CRPS I. Either peripheral or central mechanisms might account for spontaneous pains and for mechanical and thermal hyperalgesias/allodynias. Abnormal interaction between peripheral sympathetic and nociceptor neurons, in skin or muscle, also remains a theoretical mechanism of neuropathic pain and hyperalgesias. Over the past three decades our group has regularly contributed factual scientific knowledge about fine structure, pathology, and normal and abnormal sensory function of nociceptors and efferent function of sympathetic units, in patients and volunteers. We remain engaged in clinical and research studies on neuropathic pains and recently developed robust methods that allow direct and simultaneous functional and biophysical characterization and testing of multiple subtypes of nociceptors, thermal (cold) receptors and sympathetic units, while observing possible nerve fiber interactions. This is achieved through microneurography and automated latency tracking (Qtrac) in awake humans. These approaches, complemented by in vitro studies on DRG neuron somata from CRPS patients, will be used to test 3 hypotheses for the origin of pain in CRPS: 1) Irritable primary nociceptor neurons, of different subtypes, evoke spontaneous pains and hyperalgesias/allodynias in CRPS patients via ectopic nerve impulse activity, caused by abnormal behavior of particular ion channels in nociceptor membranes. 2) Sympathetic efferent discharge, acting at axonal and/or soma sites, may increase primary cutaneous or deep tissue nociceptor activity in CRPS, thus generating pains. 3) Cold hyperalgesia/allodynia, a prominent symptom in CRPS, is due to (a) sensitization of specific noxious low- temperature membrane receptors in nociceptor afferents, (b) ectopic expression of non-noxious cooling receptors in nociceptor afferents, (c) central release of noxious cold-signaling input, or (d) secondary central sensitization. Results of this project will prove, or question, pertinent hypothetical mechanisms of neuropathic pains and will facilitate mechanism-targeted therapy, while protecting CRPS patients from iatrogenic harm. PI: Claude Burgoyne, MD R01EY011610 "IOP-related force and failure in the optic nerve head" DESCRIPTION (provided by applicant): In glaucoma, there is no science to predict what level of intraocular pressure (IOP) will be safe for a given optic nerve head (ONH). The goal of this project is to identify the clinically important components of optic nerve head (ONH) susceptibility to glaucomatous damage using basic engineering principles. The proposed biomechanical studies test the following hypotheses within high-resolution, digital, three dimensional (3D) reconstructions (1.5 x 1.5 x 1.5 urn voxel) and finite element models (FE Models) of the normal and glaucomatous ONH: 1) The distribution of stress (force/cross-sectional area) and strain (local deformation) within the lamina cribrosa and peripapillary scleral of the Normal ONH predicts the sites of connective tissue damage in Early Experimental Glaucoma; 2) At all levels of IOP, strains within the remaining connective tissues of Early and Moderate but not Severe Glaucoma eyes are higher than in Normal eyes; 3) A predictable pattern of fixed (permanent) deformation of the ONH connective tissues underlies the onset and progression of glaucomatous cupping in Early, Moderate and Severe Glaucoma but is not present in the optic neuropathies of Early and Late ONH Ischemia and Optic Nerve Transection; 4) the ONH connective tissues of Old eyes are hardened compared to those of Young eyes and this difference in ONH connective tissue stiffness affects the clinical behavior of the Aged, Glaucomatous ONH. The Specific Aims and Objectives are: 1) To expand our continuum and micro FE Modeling of the ONH tissues to Severe Glaucoma and to the Young and Very Old Normal ONH; 2) To perform 3D histomorphometry within the digital 3D geometries of Normal Young and Very Old, Early, Moderate and Severe Glaucomatous, Early and Late Ischemic and Optic Nerve Transection ONH so as to characterize and compare the 3D patterns of connective tissue architecture and damage; 4) To test the hypothesis that the ONH connective tissues of the Aged ONH are less susceptible to deformation than those of the Young ONH and that this difference in susceptibility affects the clinical appearance and behavior of the Aged ONH at the onset of glaucomatous damage as seperately defined by structural and functional criteria. The methodology includes longitudinal ONH surface change detection using Heidelburg Retinal Tomographic Change Analysis; multifocal Electroretinogram (mfERG) testing; high-resolution, 3D reconstruction and 3D histomorphetry of the ONH neural and connective tissues; automated optic nerve axon counting; 3D material properties testing of intact posterior scleral shells; and continuum and micro FE modeling of the ONH neural and connective tissues. PI: Claude Burgoyne, MD R01EY021281 "Optic nerve head SDOCT imaging in glaucoma" DESCRIPTION (provided by applicant): The primary goal of this project is to test three hypotheses regarding glaucomatous damage to the visual system. First, that clinically detectable neural, glial and connective tissue alterations occur deep in the optic nerve head (ONH) at a very early stage in the pathophysiology of glaucomatous damage to the visual system. Second, that the location and magnitude of the earliest of these ONH changes, detectable in vivo by spectral domain optical coherence tomography (SDOCT), predict the specific locations of subsequent alterations of the peripapillary retinal nerve fiber layer (RNFL) and orbital optic nerve axon loss. Third, that ONH connective tissue structural stiffness is altered both by age and glaucomatous damage and that it underlies the clinical appearance of the glaucomatous optic disc, specifically by influencing the "depth" of glaucomatous ONH structural change or "cupping". Until now, all animal models of glaucoma have been studied in isolation from human glaucoma. A second goal is to demonstrate that our hypotheses and techniques have evolved to a point where both can be simultaneously tested in monkeys (Specific Aim 1) and humans (Specific Aim 2). Aim 1 is to characterize the onset and progression of SDOCT ONH structural change within pre- and post- laser SDOCT ONH data sets from both eyes of 70 unilateral experimental glaucoma (EG) monkeys. Aim 2 is to characterize the onset and progression of ONH structural change within longitudinal SDOCT ONH data sets from 250 human ocular hypertensive and early glaucoma patients. The methodology includes: longitudinal Heidelberg Spectralis 870 and 1060 nm SDOCT ONH image acquisition in monkeys (870 nm only in humans); their visualization, delineation and quantification within custom Multiview software; and in monkeys only, post- mortem 3D histomorphometric ONH reconstruction and quantification, co-localized, eye-specific comparison of SDOCT ONH and 3D histomorphometric reconstructions and regionally-aligned orbital optic nerve axon damage map generation using our custom Axonmaster axon counting software. The expected outcomes are: 1) deep ONH structural change will occur before and predict subsequent ONH surface and RNFL change during the onset and progression of glaucomatous damage in both monkey and human eyes; 2) early ONH structural change will co-localize to orbital optic nerve axon loss in monkey eyes and precede RNFL alterations in both monkey and human hypertensive eyes; 3) in monkeys, younger ONHs will be "more compliant" and older ONHs will be "stiffer" when normal, and both will demonstrate transient hypercompliance followed by progressive stiffening as glaucomatous damage progresses; 4) younger monkey and human ONHs will demonstrate a "deeper" form of "cupping" than older ONHs; 5) in younger compared to older eyes, the onset and progression of structural change ("cupping") will include a larger connective tissue component; and 6) 1060 nm SDOCT imaging will improve visualization of deep monkey ONH imaging targets compared to the existing clinical standard (870 nm imaging). PUBLIC HEALTH RELEVANCE: The clinical detection of the onset and progression of glaucomatous damage to the optic nerve head (ONH) is central to the care of every glaucoma patient. We propose to use 870 nm and 1060 nm Heidelberg Spectralis Spectral Domain Optical Coherence Tomography (SDOCT) to characterize the onset and progression of ONH structural change within pre and post- laser SDOCT ONH data sets from both eyes of 70 unilateral experimental glaucoma (EG) monkeys and 250 ocular hypertensive and early glaucoma patients. In this project we will translate 11 years of NIH-funded, post-mortem monkey work to an in-vivo imaging modality that will be shown to have important and novel clinical care applications in humans. PI: Shaban Demirel, PhD R01EY019674 "Predicting the rate of progression in glaucoma" DESCRIPTION (provided by applicant): Glaucoma is one of the leading causes of treatable blindness in the world. However, the manner and rate of disease progression varies markedly between patients, and so predicting future progression and hence the prognosis for an individual is challenging. Much of the previous work in this field has concentrated on determining whether a patient with certain risk factors will develop glaucoma. There has been less attention paid to the likelihood that a patient will suffer significant loss of vision as a result of their glaucoma, or how soon vision loss may manifest. The overall goal of this project is to improve the ability to predict the future course of an individual's disease, and so enable the clinician to adapt their management strategy accordingly. Better knowledge of glaucomatous pathophysiology will also be gained, with meaningful implications for developing new methods of diagnosis and treatment strategies. The primary tool used in this project will be longitudinal data collected biannually from over 250 subjects with early or suspected glaucoma, and 50 normal subjects. For the majority of the glaucoma subjects, up to ten years of prior information is available and will also be used. The first part of the project aims to improve understanding of the structure-function relationship in glaucoma. Three non-competing hypotheses will be tested that seek to explain the weak observed correlation between functional change (to the patient's visual field) and structural change (to the optic nerve head and/or retinal nerve fiber layer). The first experiment will determine the true underlying correlation after taking into account the variability inherent in the testing procedures. The second experiment will compare changes to the optic nerve head surface topography against subsurface changes and changes to the retinal nerve fiber layer, to determine whether there is temporal dissociation caused by surface change not driven by a loss of neural tissue. The third experiment will use a sampling-limited test of retinal ganglion cell density, to determine whether there is temporal dissociation caused by dysfunctional retinal ganglion cells that are still present in the retina but have altered response characteristics. Results from these three experiments will provide new insights into the disease process, with possible implications for future development of testing and treatment strategies. The second part of the project aims to use this new information and advanced analysis techniques (including regression trees) to better predict the future rate of functional change on a per-eye basis. First, subsequent change will be predicted based on test results at one time point. Second, improved predictions will be made when a series of test results are available. The fundamental motivation for this project is to enable a clinician to prevent severe visual disability or blindness in an ocular hypertensive or glaucoma patient, by identifying a rapid progression rate or a high likelihood for rapid progression at the earliest stages of the disease. PI: Brad Fortune, OD, PhD R01EY019327 "Axonal Cytoskeletal Changes in Experimental Glaucoma" DESCRIPTION (provided by applicant): This project proposes that prior to retinal ganglion cell (RGC) death in glaucoma, and before permanent loss of vision, there exists a stage of RGC dysfunction characterized by degradation of axonal microtubules (MTs). Emerging evidence suggests that MT degradation can occur initially without substantial changes in axonal caliber. Therefore, it is proposed that early stage RGC dysfunction involving MT degradation should be preferentially detectable by scanning laser polarimetry (SLP) of the retinal nerve fiber layer (RNFL) prior to changes in RNFL thickness. This is because the fundamental optical principle of SLP is based on detecting phase retardance of polarized light, which is due to the optical property birefringence produced in the RNFL by the long, thin cylindrical MTs. Preliminary studies demonstrate that RNFL retardance declines prior to, and faster than RNFL thickness in several different experimental models of RGC injury, including experimental glaucoma (EG). Clinical detection of axonal MT disruption by SLP, in the absence of RNFL thickness changes, might represent an early and potentially reversible phase of glaucomatous damage and provide a clinically detectable marker for therapeutic adjustment. Thus the central hypothesis of this proposal is that disruption of MTs within the axons of the peripapillary RNFL is an early indicator of glaucomatous damage, preceding both changes in axonal caliber and physical loss of those axons. Predictions arising from this hypothesis are tested in three Specific Aims using a non-human primate (NHP) model of EG. Specific Aim 1: To test the prediction that peripapillary RNFL retardance will decline prior to RNFL thickness changes measured by spectral domain optical coherence tomography (sd-OCT) and prior to optic nerve head (ONH) surface changes measured by confocal scanning laser tomography (CSLT) in NHP eyes with EG; Specific Aim 2: To test the predictions that histological evidence of peripapillary RNFL MT disruption will be more pronounced than histologically-defined RNFL thickness changes and retrobulbar optic nerve axon loss; Specific Aim 3: To test the prediction that RGC functional abnormalities are associated with the intermediate stage of RGC degeneration characterized by abnormal axonal MTs. To achieve these Aims, EG will be induced via laser photocoagulation of the trabecular meshwork to cause moderate, unilateral chronic IOP elevation in 24 NHPs. Weekly measurements of peripapillary RNFL retardance, RNFL thickness and ONH surface topography will be made in both eyes of each NHP using SLP, sd-OCT and CSLT, respectively, during a 4-week pre-laser baseline period and for up to 8 months after onset of EG (Aim 1). For each parameter, statistically significant change is defined as any change exceeding the baseline intersession variability for each individual eye, twice confirmed. Once each animal progresses to its endpoint, it is sacrificed for histological data collection and analysis (Aim 2). During each week of in vivo structural testing for Aim 1, RGC function will also be assessed in both eyes using three proven forms of electroretinography (Aim 3). PUBLIC HEALTH RELEVANCE: Glaucoma is one of the most common causes of blindness in the United States and around the world. It is a chronic disease with no known cure, but prospective longitudinal trials have found that treatment to lower intraocular pressure decreases the rate of progressive vision loss. Thus, early diagnosis enables timely therapeutic intervention and reduces the overall impact of glaucoma. However, achieving a timely diagnosis requires clinical detection of the onset and progression of glaucomatous damage to the optic nerve head (ONH) and retinal nerve fiber layer (RNFL), which remain a central challenge in the clinical care of every glaucoma patient. This project evaluates and advances clinical tools for detecting early damage and progression of glaucoma. PI: Brad Fortune, OD, PhD 1R21EY021311 "Imaging retinal astrocytes, ganglion cells and axonal transport in vivo" DESCRIPTION (provided by applicant): Astrocytes are a major class of glia in the vertebrate retina. They are located primarily within the innermost retinal layers; their processes surround retinal ganglion cell (RGC) axons and axon bundles as well as all blood vessels. Because of this anatomical relationship, and a variety of physiological evidence, astrocytes are thought to have a major role in the mechanisms of retinal blood flow autoregulation, i.e. the maintenance of nearly constant blood flow in response to variations of ocular perfusion pressure. Astrocytes are also thought to play an important role in the pathophysiology of many ocular diseases by responding to a variety of insults such as ischemia, increased intraocular pressure and neuronal degeneration in a manner that has been characterized as gliosis. Hence, the ability to image astrocytes in vivo could help to elucidate aspects of disease pathophysiology. Similarly, there is evidence to suggest that RGC axonal cytoskeletal components, specifically microtubules, are disrupted during the earliest stages of response to experimental injuries such as axotomy and experimental glaucoma. This disruption is significant because microtubules are the "tracks" upon which axonal transport is driven. Thus, if microtubule abnormalities develop early in response to injury, the resultant axonal transport disruption could exacerbate the injury and inhibit protective or rescue responses from achieving full potential. The overall goal of this R21 project is to develop the methods for imaging retinal astrocytes, RGCs, their axons and axonal transport in vivo. The specific objectives are as follows: Specific Aim 1: To establish methodologies for in vivo visualization of retinal astrocytes, RGCs, their axons and active axonal transport in the rat eye. To evaluate the optimal concentration, follow-up duration and persistence of in vivo markers as well as perform histopathological studies to corroborate in vivo observations. Specific Aim 2: To evaluate potential toxicity of in vivo astrocyte markers and axonal transport tracers using sensitive measures of retinal function (electroretinography, ERG) and retinal structure (spectral domain optical coherence tomography, SDOCT), so as to assess potential for use in primate experimental models. Specific Aim 3: To evaluate the sensitivity of our newly developed methods by comparing the impact of four unilateral experimental injury models (intravitreal injection of nocodazole/colchicine to disrupt axonal microtubules and inhibit active axonal transport; acute elevation of intraocular pressure; chronic elevation of intraocular pressure; and optic nerve crush) with results obtained in bilateral control eyes. The novel methods developed in this proposal will make possible in future proposals, studies about the onset of astrocyte abnormalities and RGC axonal transport abnormalities and comparisons of those phenomena to the course of RGC and axonal degeneration in experimental models of RGC injury. PUBLIC HEALTH RELEVANCE: Glaucoma is one of the most common causes of blindness in the United States and around the world. It is a chronic disease with no known cure. Though prospective longitudinal trials have found that treatment to lower intraocular pressure decreases the rate of progressive vision loss, some individuals continue to lose vision despite successful therapy to lower their intraocular pressure. Thus, a more thorough understanding of the events leading to damage and vision loss in glaucoma is required. The goal of this project is to develop methods for evaluating two groups of cells and aspects of their function in the living eye using specialized imaging techniques. PI: Stuart Gardiner, PhD 1R01EY020922 "Functional Testing for Glaucoma" DESCRIPTION (provided by applicant): Glaucoma is a leading cause of blindness both in the US and worldwide. The long-term purpose of this project is to improve functional testing in glaucoma. Assessment and follow-up of patients currently relies on automated perimetry to provide functional testing of the visual field. However, the ability to assess progression and/or response to treatment using perimetry is hampered by high variability, especially in areas of moderate or severe glaucomatous damage. Recent findings by our laboratory and others have advanced our understanding of perimetry by challenging key assumptions about the test. This proposal aims to use these advances to explain and reduce the test variability. This will improve the accuracy, efficiency and utility of current functional testing, giving immediate impact in both research and clinical settings, and laying groundwork for the next generation of instruments and algorithms. The first Specific Aim is to produce an accurate and physiologically justified measure of the Effective Dynamic Range (EDR) of perimetry. It is postulated that the very high contrast stimuli used by perimetry in glaucomatous defects saturate the response of the visual system. The resultant nonlinearity in the contrast-response function would cause the detection probability to asymptote below 100%, explaining the high variability in sensitivities in damaged areas. The limit of the EDR will be defined as the contrast beyond which response linearity cannot be assumed. This will be measured by collecting frequency-of-seeing curves in subjects with moderate or advanced glaucoma. The same technique will be used to determine whether the EDR is extended by use of an increased stimulus size. The second Specific Aim is to derive and test a spatial filter to reduce the variability. This will be the first filter to be based both on sensitivities at other locations in the visual field and on the structure of the optic nerve head. The third Specific Aim is to assess the potential utility of using a linear scale for sensitivity, rather than the current logarithmic decibel scale. First, an efficient linear-scaled thresholding algorithm will be derived and tested, to determine whether it will reduce variability both between tests and in the structure-function relation. Second, linear-scaled global indices of the central visual field will be examined, to determine whether they offer improved prognostic value compared with current decibel-scaled indices when assessing progression. The three aims are complementary. It is anticipated that by combining these aims, variability in perimetry will be better understood, and significantly reduced. Such an improvement in a test as commonly performed as perimetry will significantly impact future clinical practice. PI: Steven Mansberger, MD, MPH K23WY015501 "The Northwest tribal vision project" This application proposes a training plan to develop Steven Mansberger, M.D., M.P.H. into an independent clinician/scientist specializing in ophthalmic epidemiology and biostatistics. Dr. Mansberger is a board certified ophthalmologist with subspecialty training in glaucoma. He has prior research experience involving screening for glaucoma, the relationship between optic disc pathology and visual function, and ocular blood flow. Devers Eye Institute, Oregon Health Science University, and the Northwest Portland Area Indian Health Board have extensive experience with research and education and are especially well suited as training sites. This training program will consist of advanced coursework in biostatistics and epidemiology, multi-disciplinary conferences, and mentored research. Mentored research will be conducted under the direction of a mentorship committee composed of Thomas Becker, M.D., Ph.D., Interim Chairman of the Department of Public Health and Preventive Medicine at OHSU, Chris Johnson, Ph.D., Director of Diagnostic Research at Discoveries In Sight/Devers Eye Institute, and Francine Romero, Ph.D., M.P.H., Principal Investigator of the Northwest Tribal Health Research Center Project. George A. Cioffi, M.D., Anne L. Coleman, M.D., Ph.D., and Dongseok Choi, Ph.D. will serve as consultants on the project as committee members. Most epidemiological studies have used expert personnel, such as ophthalmologists or optometrists, to diagnose eye diseases as part of a prevalence survey. However, newer methods of evaluating the visual field, retina, and optic nerve make it possible for non-MD, non-OD paraprofessionals (such as ophthalmic technicians) to perform a baseline examination and refer participants with abnormal results for a definitive exam by expert personnel. This staged protocol allows persons to be examined rapidly and with reduced expense. The specific aims of the research project are: 1) to determine if non-MD, non-OD paraprofessionals (such as ophthalmic technicians) performing newer methods of testing have good diagnostic precision and feasibility in comparison to an expert examiner; 2) to attain preliminary data regarding the age-specific prevalence of visual impairment, blindness, and ocular disease in a sample of Northwest American Indians and Alaskan Natives (AI/AN) aged 40 years and older. This project will then lead to a larger, more comprehensive survey of the prevalence and causes of visual impairment in AI/AN.


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Max: The Curse of Brotherhood is a 2D platformer developed by Press Play and published by Microsoft Studios. It has been released for PC, Xbox 360 and Xbox One consoles. When playing, you will become Max, the main character of the story. He is constantly annoyed by his little brother Felix, and one day when Felix is smashing Max's toys, he feels so angry that he looks for a way to get rid of his younger brother. This fact triggers a spell that make Felix disappear. A giant clam has kidnapped his little brother. This way, Max follows the giant clam and undertakes a dangerous journey to save his brother, since he knows that his acts are the cause of his disappearance.
In regards to graphics, this game is stunning in several senses. The cinematic scenes make it look like it's an animated movie. The environments create a magical atmosphere in which everything seems mystical and dangerous. Every detail is very well designed, and the physics are as realistic as possible. You will be free to explore this 2D world (which could be considered a 2.5D since it sometimes has different perspectives) full of enemies, fantastic creatures and amazing backgrounds.
Once you download it, you will have a magic marker that will allow you to draw ledge extensions and ropes to reach difficult places. This marker will provide a huge support for you to solve some of the puzzles of the game. However, the marker does not stay the same way all the journey, it will gain some other powers as you complete puzzles. At the end, you will have five different powers in your magical marker: vines (the main one), water, earth, three branches, and destruction of obstacles. Each power provides its own abilities and they help you in many different ways.
This way, Max follows the giant clam and undertakes a dangerous journey to save his brother, since he knows that his acts are the cause of his disappearance
Take into account that each power of your magical marker can be used in its specific location, so usually, the way to solve the puzzle is quite clear. You will have to solve puzzles across 20 levels divided into seven chapters. Nevertheless, you will almost not notice the difference between levels since all levels are connected. It is more like a very long adventure in which your main objective is to save your little brother.
Max: The Curse of Brotherhood Features
Here you can find the outstanding features of Max: The Curse of Brotherhood:
- 20 levels divided into seven themed chapters to play and enjoy
- Magic marker with five different powers to solve all the puzzles
- Stunning graphics that are a pleasure for the eye
- Catchy storyline: similar to the plot of the movie Labyrinth (1986)
- Difficult learning curve: once you get used to controls, everything is easy
If you like Max: The Curse of Brotherhood, and you want to know more about the game before you download it, feel free to visit the developer's official website .
System Requirements
To download and play this game on your PC, the minimum system requirements are the following:
- Operating System: Windows XP or later versions
- Processor: AMD Athlon Dual Core @ 2 GHz, Intel Dual Core @ 1.6 GHz or better
- RAM Memory: 2 GB RAM
- Graphics Card: Intel HD 4000 or superior
- Sound Card: compatible with DirectX 9
- Hard Drive Space: at least 2 GB free
A world of fantasy and magic marker as the main weapon to destroy an evil plan
By Pablo Conde Ferrer
On Monday, June 15, 2015
Max: The Curse of Brotherhood is a platform game with a lot of puzzle that initially attracted by its great visual finish and easily thanks to game mechanics are simple but well executed ends. The combination of 2D platforms with puzzles of our magic marker works, but without fanfare. The title uses a system of development that we continue to add new skills as we go, but the best-the water jets and fire balls too late. In addition, this causes areas where we should combine all our possibilities are only in the final stretch. The title offers interesting puzzles -again certain moments, especially in the final stretch and if we do 100% - but it is a challenge that leaves us locked for hours in one place, much less. Funny, visually very nice but somewhat limited in developing a proposal that could be much more ambitious and has some problems of control in terms of accuracy, both when it comes to some forms as at the time of use quickly because we are in danger.
- The artistic finish and contrasting worlds is amazing
- Get the whole game requires ingenuity
- The best skills and combinations, only in the final stretch


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Phillip Dillard
Position: LB
Height: 6-1 Weight: 240 lbs.
Born: December 10, 1986 in Tulsa, OK
High School: Jenks
College: Nebraska (school history) (Dillard college stats)
Drafted by the New York Giants in the 4th round (115th overall) of the 2010 NFL Draft.
Weighted Career AV (100-95-...): 0 (15060th overall since 1950)
Other SR Links: College Football at Sports-Reference.com
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Can medical procedures performed on a young child for their benefit but without their full understanding and/or consent be considered "early childhood trauma" and could memories of these procedures come back as major depression and anxiety symptoms later in life?
Yes, this may be a possibility. You may be experiencing post-traumatic stress disorder (PTSD), a type of anxiety disorder occuring after you've seen or experienced a traumatic event that involved the threat or percieved threat of injury or death. PTSD may be experienced with intrusive thoughts, nightmares and flashbacks of past traumatic events, avoidance of reminders of trauma, hypervigilance and sleep distrubance, all of which lead to considerable social, occupational and interpersonal dysfunction. It is important to seek help if you are having symptoms of depression and anxiety. If you are an eligible UAA student you may be seen by a Student Health and Counseling Center Mental Health Provider for evaluation. Also, refer to our main page for information on other oncampus resources.


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Suspect Shot After Attacking TSA Agents At New Orleans AirportA terminal at Louis Armstrong New Orleans International Airport was evacuated Friday night after a man with a machete attacked TSA agents and was shot by a police officer.
Iris Scan = Shorter Wait In Airport Security LineIt sounds like something out of the Tom Cruise movie Minority Report, but if you're willing to pay a fee and get your iris scanned, you can jump to the front of the security line at Dallas/Fort Worth International Airport.
Love Field Breaks Carryon Handgun Violation RecordA new record set at Dallas Love Field Airport has the facility's Federal Security Director concerned. Director Amy Williams said in April alone agents have found six handguns in carryon bags, at TSA checkpoints.
Local Passengers Left More Than $17K At TSA CheckpointsHow many of you have forgotten to get your spare change out of the dish after going through airport security? Apparently, a lot!
Attorney: Woman With Gun At DFW Passed Through During Shift ChangeAn attorney representing Judith Kenney says his client passed through the TSA security check point with no problems, but noticed something just before her bags were scanned.


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5 Ways to Avoid Black Best Friend Syndrome
Sep 3, 2014 8:29 PM EDT
You guys, did you hear? Diversity is in! Much like feminism and ALS charities, diversity is one of the hottest trends of 2014, especially on television. But while network execs have been quick to praise their multicultural casts, one disappointi… Read more


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10 Function Silicone Love Rider - Triple Rider - Purple
Premium, solid, sturdy, unscented Silicone probe that flexes and moves with you. 10 powerful functions of vibration, pulsation, and escalation with an instant off button with LED light. Powerful dual motors with a state-of-the-art controller with memory chip that resumes last function used. Flanged base for use with most harnesses and superior suction cup base for use with our without a harness.
- Silicone Probe
- 5" x 1.75" (12.75 cm x 4.5 cm) Shaft
- 4" x .75" (10.25 cm x 2 cm) Probe
- 1.75" x 1" (4.5 cm x 2.5 cm) Rabbit
- Requires 2 AA Batteries (not included)
Product Information
- Brand: Cal Exotics
- Series: 10 Function Silicone Love Rider - Triple Rider
- Product Dimensions:
- Total Length: 7.50 in.
- Length Insertable: 5.0 in.
- Width Maximum: 4.00 in.
- Weight (No Box): 0.6250 lbs.
- Box Dimensions:
- Length: 9.00 in.
- Width: 5.00 in.
- Depth: 3.50 in.
- Weight: 0.8190 lbs.
- Empire SKU: 1658455
- Made By: Cal Exotics
- Manufacturer Code: SE-1498-83-3


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With the Mosselman Remap+ Intercooler package the 335i puts out 390bhp and a massive 540Nm. De intercooler has factory connectors, cools the air better, and in combination with the ECU reprogramming we are able to lower even the exhaust temperatures.
Without a remap the power increase will be only marginal, because the 335i computer aims for a target value in the program.
Contact us for more information.


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Great white shark Katharine pings off Wilmington coast
Published: Wednesday, July 30, 2014 at 9:47 p.m.
Last Modified: Wednesday, July 30, 2014 at 9:47 p.m.
WILMINGTON | Katharine – a 14-foot, 2,300-pound great white shark with a tracking device – announced her presence off the coast of Wilmington about 7:30 p.m. Wednesday by emitting a signal picked up by a satellite.
The immature female shark was tagged Aug. 19, 2013, in the Atlantic Ocean off Cape Cod, Mass. Since then she has traveled about 6,400 miles. Within the last month she cruised from the Gulf of Mexico, around Florida and up the East Coast.
Katharine was named by Cat Products fans, sponsors of the OCEARCH nonprofit shark research organization, in honor of Katharine Lee Bates, a Cape Cod native and songwriter. Bates is best known for her poem and song "America The Beautiful."
To track Katharine's travels, visit www.ocearch.org/profile/katharine or download the OCEARCH Global Shark Tracker app on your smartphone.
– Jim Ware
Reader comments posted to this article may be published in our print edition. All rights reserved. This copyrighted material may not be re-published without permission. Links are encouraged.


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Dr. Oz revealed how to lower your cholesterol using diet rather than drugs on the March 14 episode of the Dr. Oz Show ("The Thing More Powerful Than Your Statins").
Dr. Oz is alarmed by the sweeping new statins guidelines that could have up to 72 million Americans on the prescription drug (a two-fold increase from 35 million now).
Critics say if it were up to the pharmaceutical companies, we would all be on statins or some other prescription medication, whether we need them or not.
Dr. Oz, a heart surgeon, vehemently opposes the idea of doctors flippantly advising patients to pop a pill when diet and exercise — not drugs — should be the first line of defense. "For the vast majority of people, statins should not be the first line of defense," he said.
While statins have been shown to lower cholesterol, they also have side effects, including increased risk of diabetes (particularly in women), muscle damage, digestive issues, memory loss, and liver damage.
Rather than resort to prescription drugs, Dr. Oz said including these foods into your diet will naturally lower cholesterol:
- Apples. Dr. Oz said apples are a low-glycemic, high-fiber fruit that reduces cholesterol. "An apple a day keeps the heart surgeon away," he said.
- Beet greens. Beet greens are rich in potassium and fiber and lower blood pressure and cholesterol. Dr. Oz recommended eating one cup a day.
- Garlic. Dr. Oz suggested eating one fresh garlic clove or one teaspoon of garlic powder every day.
Chia Seeds for Weight Loss, Flax Seeds for IBS and Fennel Seeds for Stress
On a separate segment of his show, Dr. Oz discussed the many health benefits of seeds.
- Chia seeds for weight loss and heart health. Dr. Oz said chia seeds have more omega-3 fatty acids than salmon, more fiber than prunes, and more calcium than milk. Chia seeds aid weight loss because they curb hunger and keep you feeling full, in addition to protecting your heart.
- Fennel seeds for stress. Dr. Oz said fennel seeds work immediately to relieve stress-induced stomach upset.
- Pumpkin seeds and flax seeds for Irritable Bowel Syndrome. Two servings of pumpkin seeds, flax seeds, sesame seeds, or sunflower seeds prevent constipation.
- Carob powder relieves diarrhea (another common IBS symptom).
Wolfgang Puck Dishes Health Recipes
Celebrity chef Wolfgang Puck visited Dr. Oz to discuss his healthy-living cookbook, Wolfgang Puck Makes It Healthy.
Puck, who has designed the menu for the post-Academy Awards dinners for the past 20 years, is used to making delicious foods that are healthy. Dr. Oz was especially impressed with Wolfgang recent weight loss, which he attributed to eating more vegetables and smaller portions.
Dr. Oz's Chia Chicken Pesto Kabobs Recipe
- 2 chicken breasts
- 1 cup cherry tomatoes
- skewers
- Pesto:
- 1 tbsp chia seeds
- 1/4 cup water
- 1 cup of basil
- 1/4 cup Parmesan cheese or nutritional yeast
- 3 garlic cloves
- 1 tbsp maple syrup
- 2 tbsp water
- 1/4 cup pine nuts or hemp seeds (depending on preference)
- Soak skewers overnight in water. (This will keep them from burning in the oven or on the grill.)
- Cut chicken breast into 1-inch cubes and place in a large bowl.
- Combine chia seeds with 1/4 cup water in a bowl and let sit for 20 minutes. Once your seeds have gelled, place the mixture in a blender and blend until smooth.
- Add the basil, cheese, garlic, maple syrup and water to the blender and blend until smooth. Then add pine nuts or hemp seeds and gently pulse to chop the nuts.
- Pour about 3/4 of the mixture over the chicken and let marinate for at least 2 hours – overnight is even better.
- Once you are ready to cook, place your oven on broil and alternate chicken cubes and tomatoes on the skewers.
- Place on a cookie sheet and cook for six minutes, then flip over skewers and cook for an additional 6 minutes or until chicken is thoroughly cooked.
Suggested Links
- Dr. Oz: Green tea reduces cancer risk by 82%, coffee and peaches prevent cancer
- Tim McGraw is ripped to shreds at 48: His Paleo diet and CrossFit workout
- Dr. Oz reveals inexpensive anti-aging wrinkle creams and weight loss secrets
- High-fat low-carb ketogenic and Paleo diets prevent Alzheimer's, starve cancer
- Jack Osbourne treats multiple sclerosis with ketogenic-style Paleo diet


text: The Arizona Cardinals took a shot at former LSU defensive back Tyrann Mathieu in the third round of last week's draft. No one doubts his physical skills, but enormous questions remain about his dedication to football on and off the field. So much so, that we really have no idea what to expect from him as far as performance goes during his rookie campaign.


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CHIEFS' AVIANI NAMED CHL PLAYER OF THE WEEKTue Dec 17
Toronto, ON – The Canadian Hockey League today announced that Spokane Chiefs' forward Mike Aviani is the CHL Player of the Week for the week ending December 15 after scoring three goals and five assists for eight points in three games along with a plus-minus rating of plus-4.
Aviani helped the Chiefs win all three games last week including two against U.S Division rivals the Everett Silvertips. Last Wednesday night he scored the game-winner on the power play and added an assist in the 5-3 victory over the Silvertips at home, then scored the insurance marker as second star of a 2-0 road win over the Tips on Sunday. In between, Aviani collected his second five-point game of the season scoring the game-winner and adding four assists as first star of a 6-3 win over the visiting Prince George Cougars on Saturday.
Aviani, a 20-year-old from North Vancouver, BC, is playing in his fourth full WHL season with the Chiefs. He is currently tied for sixth in league scoring with 50 points in 35 games but ranks second in the league with 26 goals approaching his career-high of 30 set last season in 71 games played.
Also considered for the award this week was Phoenix Coyotes prospect Max Domi of the London Knights who scored five goals and six assists for 11 points in four games played, and Jean-François Plante of the Sherbrooke Phoenix who scored four goals and three assists for seven points in three games.
2013-14 CHL Players of the Week:
Dec. 9 – Dec. 15: Mike Aviani (Spokane Chiefs)
Dec. 2 – Dec. 8: Andreas Athanasiou (Barrie Colts)
Nov. 25 – Dec. 1: Leon Draisaitl (Prince Albert Raiders)
Nov. 18 – Nov. 24: Zac Leslie (Guelph Storm)
Nov. 11 – Nov. 17: Jonathan Drouin (Halifax Mooseheads)
Nov. 4 – Nov. 10: Martin Reway (Gatineau Olympiques)
Oct. 28 – Nov. 3: Jayce Hawryluk (Brandon Wheat Kings)
Oct. 21 – Oct. 27: Darcy Ashley (Halifax Mooseheads)
Oct. 14 – Oct. 20: Scott Kosmachuk (Guelph Storm)
Oct. 7 – Oct. 13: Anthony Mantha (Val-d'Or Foreurs)
Sept. 30 – Oct. 6: Nick Merkley (Kelowna Rockets)
Sept. 23 – Sept. 29: Mitch Holmberg (Spokane Chiefs)
Sept. 19 – Sept. 22: Michael Dal Colle (Oshawa Generals)


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Fable Legends was revealed last year and we can't wait to see what the new world of Albion looks like, but to help slake your desire for new information, we've uncovered some new details regarding how this world will look and feel.
Recently, Ben Brooks, who is the Lead Content Designer on Fable Legends, described some of the things players should be on the lookout for when it comes to this brand-new version of Albion.
"In many ways, this is Albion at its most pastoral and primitive. The land is a patchwork of small villages and towns, islands in a sea of hostile forest.
"It's too risky for your average bumpkin to travel, so communications are limited and people are suspicious of outsiders. Each place has its own distinct customs and ways of relating to the magic that surrounds them.
"Even villages just the other side of the hills have enough funny accents, odd clothes and bizarre turnip-rituals to make strangers really seem strange," Brooks said.
It's going to be wonderful to see the landscape of Albion and witness what it looked like before the events of the first Fable took place.
Brooks went on to talk about some of the more dangerous parts of Albion and how players may have some extra hesitation in these certain areas.
"While magic is more common, it's also uncontrolled. Strange and dangerous creatures lurk everywhere outside the safety of the campfires and village walls. As a result, most people are content to travel only by listening to old stories, tales of a world far too scary to wander into.
"The most danger they tend to risk is scuttling down the bottom of the garden to clean out the chickens, and even that's asking for trouble (some of the little clucky buggers have pretty sharp beaks). But not everyone hides by the fireside.
"Albion has always been able to find the special few willing to answer the call. Wanderers, adventurers, masters of Will. Old eccentrics and young upstarts. Heroes!" Brooks said.
We do not yet have a release time frame for Fable Legends, but we are very much looking forward to seeing what Lionhead brings with this new vision for the series.
For all of our latest exclusives, previews, reviews and features, follow us on Twitter and like us on Facebook. Game On.
Thanks, Lionhead.


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Dec 20, 2010 8:02 AM
Don't even think of wrapping presents for the Star Wars fan in your life without the Star Wars Rebel Alliance Wrapping Paper ($19)!
Its spell binding affects might even turn someone from the Dark Side... or cause seizures.
P.S. It looks like this awesome paper may have already sold out (Damn you, Darth Vader!), but check out the other awesome options in MerryPranxter's Etsy shoppe! If enough Star Wars fans request it, she might even reprint this, btw....
Link doesn't work.
Hello! I'm the artist that designed the paper. When I first started w/the wrapping paper I assumed I'd sell maybe a roll or two, no big deal. I didnt ut much thought into it. Then as more blogs featured my stuff people started asking about possible trademark infringement, which hadn't crossed my mind before. After reading around on it I decided I'd rather be safe than sorry & pulled all my patterns that I thought might be suspect. I'd really rather not butt heads w/George Lucas or the BBC :) but thank you for featuring my store! I encourage any readers to check it out despite a lack of Star Wars products.... You might see something else you like. & if you don't, well, no harm done :)
If you've got a product or service that you'd like to promote on Outblush, click here to find out about our advertising opportunities.
Outblush is a blog for girls who love to shop. Our staff digs up the best clothes, home stuff, beauty items, and more. New items are posted every day — bookmark us and check out:


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Pressure Washer Hose Reel - High Capacity
Professional-grade reel that is built to last
Compact design and quality steel construction are incorporated into Reelcraft's pressure wash reels rated at 3,000 psi. Designed to handle a broad range of pressures, temperatures and chemicals. AFLAS® seals and permanently lubricates bearings. Corrosion-resistant powder-coated finish is chip and rust resistant. Vibration-proof fasteners for both mobile and stationary applications in agriculture, landscaping and construction. Mount on wall, floor, ceiling, bench or truck. Hand crank drive type. 400°F max. temperature. Compatible with 1/4" I.D. x 425 ft. hose, 1/2" I.D. x 200 ft. hose and 3/8" I.D. x 100 ft. hose. Measures 17"Lx17-3/4"Wx20-1/4"H. Weighs 49 lbs. Hose and bumper not included. USA made.
2016 Master Catalog: Page 519


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Morris M. Towns
Position: T
Height: 6-4 Weight: 270 lbs.
Born: January 10, 1954 in St. Louis, MO
High School: Vashon
College: Missouri (school history)
Drafted by the Houston Oilers in the 1st round (11th overall) of the 1977 NFL Draft.
Weighted Career AV (100-95-...): 30 (3322nd overall since 1950)


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Sawmill Creek Condo 306
We offer over 170 Breckenridge vacation rentals in some of the best locations available. If you would like to filter your choices by certain locations only, please view our Complexes page.
2 Bedrooms2 Baths# of Levels: One Level Floorplan2nd Bedroom TV: Tube TVBedding 1: King BedBedding 2: 2 Queen BedsCondoDeck: Private BalconyDishwasher: One DishwasherElevator: Elevator Access
Fireplace: Gas FireplaceFloor in Building: Third Floor UnitFour O'clockGrill/BBQ: On-Site GrillHot Tub Access: Indoor On-SiteHot Tub: Access to Hot TubsInternet: Free WirelessLaundry: Private Washer/DryerLiving Room Bedding: Queen Sleeper SofaLiving Room TV: Flat Screen TV
Master Bedroom TV: Flat Screen - MasterParking: Covered ParkingRating: Gold - A Rated UnitsSki Hill - Park AveSkiing: Ski-in / Shuttle-outSleeps: 8Town Access: 1 BlockView from Deck: Parking Lot Viewnon smoking only: Yespets not allowed: Yes
Enjoy this nice rustic two bedroom condo located on the third floor of Sawmill Creek. Just 20 yards from the bottom of the Four O'clock ski run, you can easily end your day on the mountain back at your condo! This cozy unit is fully equipped with kitchen supplies, a fireplace, washer and dryer as well as free Wi-Fi. The complex itself offers a covered parking space, two indoor hot tubs, and a shared grill on the patio area. After a great day on the mountain, walk a block into town and check out some of the great offerings our town has.
Master bedroom: King
Second bedroom: 2 Queens
Living area: Queen sleeper
*No Pets, No Smoking and No Air Conditioning