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We offer delicious traditional breakfast, laundry service with tabs, self-catering, day and night tours, baby sister, dining and TV rooms where you can share with different cultures.
We have 24 hours reception and walking tours to different places of Viña del Mar Valparaiso and tourist information about the region as parking, etc...
Come and visit our service is excellent and of great quality.
Our property is located four blocks from the University Federico Santa María.
From downtown Valparaiso to fifteen minutes and Viña del Mar to a similar distance.
This property is located in one of the 40 hills that Valparaiso has, with a rich history of culture and human warmth.
From Valparaiso centre: get off at Rodoviária Mont Pedro street in and take for Cerro Los Placeres locomotion Pleasures, off at plaza and ask the Conquest, It is a white house with two floors.
From Rodoviária de Viña del Mar, walk 4 blocks to the west and get to the street and take bus Arlegui no. 410 or no. 411. bus stop outside the hostal.
Hotel Puerto Valparaiso
Valparaisoa, Chile Youth Hostels
Located close to the bus terminal is in three blocks from the bus stop close to night life so you will find lots of night clubs....
$4 Per Night
Valpackers Hostel
Valparaisoa, Chile Youth Hostels
Our focus is on providing a quiet and comfortable location for short or long term visitors to Valparaiso....
$17 Per Night
Hostal De Visita
Valparaisoa, Chile Youth Hostels
Located near the historic center, in a quiet neighbourhood. Hostal de vista is the perfect place to chill out in Valparaiso....
$18 Per Night
Hostal Color
Valparaisoa, Chile Youth Hostels
The hostel has two floors, the first floor is a houseold in 1910 which is set in pure style of the stre...
$16 Per Night
Casa Paseo Atkinson
Valparaisoa, Chile Youth Hostels
Casa Paseo Atkinson (Paseo Atkinson House) is located, as its name suggests, in Paseo Atkinson, on Cerro...
$40 Per Night
Hostal Bellavista
Valparaisoa, Chile Youth Hostels
Welcome to Hostal Bellavista in Chile...
$18 Per Night
Rivendell Chile
Valparaisoa, Chile Youth Hostels
Located in a very nice area where you are going to enjoy your stay....
$39 Per Night
Hostal Maison De La Mer
Valparaisoa, Chile Youth Hostels
La Maison de la Mer has different types of rooms to accommodate tourists coming to Valparaiso....
$20 Per Night
Hospedaje Florencia
Valparaisoa, Chile Youth Hostels
Hospedaje Florencia is a family run guesthouse with a nice and quiet atmosphere, allocated a few metres far from the Bus Station in Valparaiso....
$27 Per Night
Costa Azul B&b
Valparaisoa, Chile Youth Hostels
Very beautiful place full of friendly atmosphere...
Active holidays in comfort, Spain & Latin America
Punta Arenas, Chile Hiking & Trekking
We blend outdoor activity with relaxation in small, locally owned hotels and the chance to sample fresh local cuisine. Experts in Spain and Latin America where we visit the most beautiful and remote regions....
Starting at $5,250 Per Person
kayaking Pumalin Park Andean fjords Patagonia
Puerto Varas, Chile Kayaking & Canoeing
Explore Patagonian Andean fjords Pumalin Park , enjoy paddling pristine esteros , camping at wonderful natural hot springs, see lions, delphine and sea birds. Explore the temperate rein forest at pumalin and Chaiten volcano...
Starting at $1,300 Per Person
Compass Expeditions - Adventure Motorcycle Tours
Santiago, Chile Motorcycle Tours
Aside from a wide range of South American motorcycle tours, Compass Expeditions is now offering motorcycle tours of Australia, Cambodia, Sth Africa, Eastern Europe & Turkey. Major Expeditions include 105 day Road of Bones & 125 day South American 360...
Fully Hosted Patagonian Overland Odyssey
Puerto Varas, Chile Eco Tours
If you're looking to experience the real Patagonia, let us host you around volcanoes in the Lakes District, into the fjords of southern Chile, through the temperate rain forest, down the wind-blown Steppes, and alongside glaciers and granite massifs....
Starting at $4,990 Per Person
The best Patagonian nature experience
Puerto Varas, Chile Eco Tours
The best outdoor experiences in Patagonia, Petrohue river, andean fjords, trekking, rafting, sea kayaking . Torres del Paine. Enviroemtally oriented trip´s to Pumalin Park ,Valle Chacabuco, Cochrane, Huemul ,pumas and guanacos territory...
$600 Per Person
Slow Travel Touroperator
Santiago, Chile Eco Tours
Slow Travel offers you individual journeys in chile. We try to show you the real identity of chile, taking our time and searching new destinations far away from the main-tourism. you can choose between wine-tours, gastronomic tours and nature....
Travel to South and Central America
Aisen, Chile Sight-Seeing Tours
LOST WORLD ADVENTURES arranges specialized tours and expeditions in South America and Central America. Our company was founded in 1986, when we pioneered our first adventure trips into Venezuela. We now arrange travel throughout Latin America....
$250 Per Night
Patagonian-desert-island In Chile
Puerto Montt, Chile Sight-Seeing Tours
Lakes , rivers, volcanoes, islands, glaciers, thermal baths, forests, etc., they are a part of many attractions that your passengers will be able to know and to enjoy, besides the desert in the north zone of the country and centers of ski in the zone...
Atacama Desert Chile lodging
San Pedro de Atacama, Chile Vacation Rentals
Cabins nicely furnished,clean and safe. 5 minutes to the downtown in San Pedro, BBq area, parking lot, WIFI available....
$75 Per Night
House of Divine Views
Ensenada, Chile Vacation Rentals
Architect designed, beautifully decorated, 3 bedroom, 2 bath home with cathedral ceilings, & huge picture windows overlooking snow-capped volcanoes of Mt. Osorno & Calbuco. Excellent fishing, hiking, kayaking,bird watching,restaurants,ecotours....
Starting at $200 Per Night
|Link Code


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Webinar - recording now available: "Choosing the right formulation approach for Orally Disintegrating Tablets"September 29, 2014
Webinar - recording now available: "Best Practices to Overcome Softgel Coating Challenges"August 25, 2014
Webinar - recording now available: "Mejores prácticas para superar los desafíos de recubrimiento de capsulas blandas"August 25, 2014
ExAct formulations for generics
Order samples
Your online access to BASF
PVP was invented by a BASF scientist 70 years ago – and we have been innovating ever since, driving
stability, purity and patient safety. Kollidon products are manufactured to the most exacting of standards
in a world-class plant, giving you the peace of mind that your povidone is of consistently excellent quality.
And thanks to the groundbreaking PeroXeal packaging concept, being rolled out to most Kollidon grades
by 2011, worrying about peroxide levels, K values, API degradation and contamination with aluminum
flakes is a thing of the past.
The Kollidon portfolio delivers tangible benefits:
Find out more about the Kollidon portfolio and the new PeroXeal packaging concept on this website.
Bernhard Fussnegger, senior manager at BASF responsible for all technical questions regarding the Kollidon portfolio, understands that product stability is crucial for patient safety. This is why most Kollidon grades now feature our innovative PeroXeal™ packaging concept that significantly reduces peroxide levels and virtually eliminates the risk of contamination with aluminum flakes.
Find out more about the new PeroXeal packaging concept here.
Bernhard Fussnegger on the many uses of Kollidon, and the benefits of the new packaging concept.
Listen to the podcast

subset: commoncrawl


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The versatile MSR Evo Tour delivers all-day-comfort and all-around performance. The Evo Tour's features include a durable, molded frame, integrated traction rails, a built-in heel-lifter and a comfortable, easy-to-use binding.
With an easy-to-use, fully adjustable binding and full perimeter traction, the MSR Lightning Flash Women's snowshoe provides ultra-lightweight, all-condition traction and adaptability for rolling terrain.
With an innovative, stride-friendly binding, 360 Degree Traction and an integrated heel lifter, the versatile MSR Lightning Axis Women's snowshoe delivers all-day-comfort and all-around performance. Your choice of size.
Mountain Safety Research started as a one-man crusade in the 1960's to call attention to the safety and quality of climbing equipment. Today, MSR is a diverse, global company dedicated to developing reliable outdoor products for committed backcountry users. Their dedication to reliable and well-designed gear has led them to introduce revolutionary new products, improve existing products and even reinvent the old. The result is a line of products that set the benchmark for outdoor equipment design.
Whether your quest of the moment is thru-hiking, kayaking or exploring a remote region north of Hudson Bay, you can count on MSR products to see you through trip after trip after trip.
Click here to visit the official MSR website. (Note: you will be leaving Backcountry Edge.)
Simple and inexpensive snowshoes for beginners and no-frills hikers.
All-around snowshoes for established trails and off-trails around the neighborhood.
Durable snowshoes built with features to handle off-trail adventures.
Men's and unisex designs.
Maximum-flotation shoes for heavy loads over 210 lbs.
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Passion is a key ingredient in the recipe for successful products, and more importantly the people that create them – customers and creators alike. But where do you get it – and are there different types of passion? I'm going to tune you into a blog that might just help you figure it out.
The Creating Passionate Users blog, produced by the authors of the Head First books, is a great read for anybody with an interest in producing better products or services. Much of the writing is tuned towards the more technical but anybody with a customer will benefit from the free content this blog dishes out. Their posts are insightful, well researched, and often actionable. Death by risk-aversion and Listening to users considered harmful? are a couple of my favorite posts. Click into the Creating Passionate Users blog to reinvigorate your passion machine today!
Cale Bruckner – Palo Alto Software, Direct Product Development
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How LivePlan makes your business more successful
If you're writing a business plan, you're in luck. Online business planning software makes it easier than ever before to put together a business plan for your business.
As you'll see in a moment, LivePlan is more than just business plan software, though. It's a knowledgable guide combined with a professional designer coupled with a financial wizard. It'll help you get over the three most common business hurdles with ease.
Let's take a look at those common hurdles, and see how producing a top-notch business plan sets your business up for success.Click to continue


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May 7, 2007
Sumter County-- A group of problem-solving elementary kids will soon represent South Georgia in an international competition.
For the first time, Sumter County Elementary School will head to the Odyssey of the Mind World Championships. The program teaches students to solve technical problems as a team.
Seven students recently placed first at the State Competition in Columbus. They'll now head to Lansing, Michigan to compete against 800 other teams from around the world.
"It's pretty amazing. It's everybody's first time. We're kind of nervous but we're just ready to present and do our stuff," said 11-year-old Matthew Nelson.
Traveling to the international championship isn't cheap. The team needs to raise about $10,000. If you'd like to help, you can make monetary donations to Sumter County Elementary School. You can also call 229-924-7835.
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Explore NileGuide.com
Articles Tagged 'Dr. Konrad E. Bloch'
Guinea Pig Mountaineers: Scientists Study 35 Climbers on Mount Muztagh AtaMay 25, 2010 | Active/Outdoors, China | Read More
Five years ago, Dr. Konrad E. Bloch, of the University Hospital of Zurich, Switzerland, was 50 and had only limited climbing experience, but he wanted to study high altitude related illnesses. So Bloch and his colleagues recruited 35 healthy climbers for a trip that was half adventure travel, half...


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News from Upstate
Darryl Geddes 315 464-4828
Upstate wins Business of the Year Award
SYRACUSE, N.Y.— Upstate Medical University has received the 2011 Business of the Year Award from the CenterState Corporation for Economic Opportunity (CEO).
The award recognizes Upstate for creating new economic opportunities, making new investments and being engaged in the community.
Over the past year, Upstate has experienced growth in its clinical practice, research activities and enrollment. Along with the growth come additional employees, with more than 700 added since 2009. Upstate continues to serve as an economic engine for the region, especially in new development, having completed the $147 million East Tower expansion in 2009. Already under way is the $72 million expansion of the Institute for Human Performance and the $74 million Upstate Cancer Center. Upstate was also recognized for its commitment to the community and volunteerism, most notably its 2010 record of being a leading contributor to the United Way/State Employee Federated Appeal effort.
Search Upstate News
Upstate in the News
- Special dog retires from Upstate University Hospital therapy program
WSYR TV9 Syracuse
- Upstate Cancer Center wants to increase breast cancer screenings among black women
Syracuse Post Standard
- 1 in 10 People Will Get Kidney Stones During Their Lifetime, Are You at Risk?
Capital News 9 Albany
- Puppy love: Upstate Medical students raise puppies, brighten corner of downtown
Syracuse Post Standard
- Field of Nursing Changing, Becoming More Complex with New Technologies
Capital News 9 Albany
- Upstate Medical University researcher awarded $50K grant for medical device: CNY Science
Syracuse Post Standard


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Find exactly what you're looking for with the web's most powerful recipe filtering tool.
1/8 Photos of Crab Bisque in 20 Minutes
Prep Time:
Cook Time:
5 mins
15 mins
Quick corn and crab bisque. Wonderful on a cold night when your in a hurry! Easily doubled, leftovers freeze well.
Units: US | Metric
Serving Size: 1 (450 g)
Servings Per Recipe: 3
Beat the back-to-school blues with these genius tricks.


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KUALA LUMPUR, Malaysia (AP) - Australian search planes are looking for two objects spotted by satellite that may be linked to the Malaysia Airlines jetliner that's been missing since March 8.
In comments to lawmakers, Australian Prime Minister Tony Abbot didn't say where the objects were seen, but military planes from Australia, the U.S. and New Zealand have been searching the southern Indian Ocean.
He cautions that actually locating the objects will be extremely difficult and that it may turn out they are not related to the aircraft.
(Copyright 2014 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.)
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- Holiday was very good. Hotel was good although our room with a sea view was next to the main railway line. A 05.15am train was not appreciated. Tour guide could have had more information on the immediate area, map of the area and bus and train times. Hotel reception area was gloomy and hotel staff could be more professional.
Having to attain our own boarding tickets is unacceptable considering the overall price of the holiday. Outgoing flights and return were both delayed by approx. 50 minutes.


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With the news that a remake of "Ben Hur" is in the works, we thought we would come up with a list of movies that should never be remade. We focused on films from 1970 through the end of 2010. So here are our "99 hands off flicks."
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Kollam – A Paradise with a plethora of Govt. Job Opportunities
Kollam is one of the cities (district) in Kerala. This city lies on the banks of Ashtamudi Lake on the Arabian Sea. Kollam is very prominent in trading and carrying on commercial activity. This city or district is famous for manufacturing coir and processing the cashew nut. It is considered as the one of the hottest place in Kerala for tourists as it is the gateway of backwaters in the southern part. The very ethical part is that the Malayalam calendar called as kollavarsham originated in Kollam and that too during the meetings held in that city itself in 825CE.
The word Kollam is derived from the Sanskrit, which means pepper. It is a gifted city comprising of lakes, sea, plains, rivers, mountains, backwaters, forest, and green fields totally summed and so the whole of Kerala is called God's own country. It is much near to the backwaters city Alleppy. Kollam is actually pronounced as koy-lon. This city is known for its own tradition and culture. It's a great centre of learning. The major fresh water lake 'The Sasthamcotta lake is in this city. The city has a very humid climate.
Kollam is renowned for its historic antiquity of the ancient world. It was one of the headquarters for revenue divisions during the Travancore administration. It is also known for its greenery and pleasant atmosphere. Malayalam, Hindi and English are the official languages spoken in Kollam. It is also known for its greenery and pleasant atmosphere. More than 3.5 lakhs people reside in this city. Kollam has an average literacy rate around 91.47% which is higher than national average.
Agriculture is the primary occupation carried on in this city. Majority of the Kollam population carry on this activity. Kollam has made a remarkable achievement animal husbandry as it ranks No.1 in livestock wealth in Kerala. Fishing has plays an important role for the economy of the district. It is rich in mineral resources, which offer bigger scope for the industrial purpose. There are totally 15-17 large scale industries in the city along with 1 medium scale industry where two of them are owned by central government.
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Below is the list of Government job openings in Kollam: -
- 1.Hindustan organic Chemicals looking for Hindi Assistants – The person who is looking out for a govt job in Kollam possessing just the basic eligibility criteria and also perfect knowledge in Hindi can apply for this job. Knowledge about the respective field will be an added advantage.
- 2.PSC Notification (Range Forest Officer) – Here, this forest range officer post involves some tedious work in terms of maintaining the regulation of the forest. He must be bold enough stay in the wide forest with limited number of facilities. Eligibility criterion depends on the post applied for.
- 3.Instrument Mechanic – The interested candidate applying for this job must be a graduate in the respective field with relevant experience to carry works relating to the instruments. This opportunity is available across Kerala.
- 4.Divisional accountant – The person who is very keen for applying jobs in accounts field please apply for his position as it is a wonderful opportunity to show case one's professional skills.
- 5.Lab technician (Electrophysiology) – The candidate who is applying for this job must be holding graduation certificate in that respective field with some relevant experience. Experience will help him in carrying on his work little smoothly.
- 6.Assistant public prosecutor – The eligible candidate for this post must have done at least bachelor's degree in Law. Along with an experience he/she can surely apply for this post, which has a huge scope.
- 7.Senior Engineer- The candidates applying for this post must be an engineer and experience I the relevant field is must and should. The salary packages are on satisfactory terms only giving much opportunity for career growth.
- 8.Ayurvedic Pharmacist – Here, the individual applying for these Job vacancies in Kollam must be a professional in ayurvedic pharmacy. In recent times, this kind of opportunities is regaining its importance because of its complete curing nature although slow in time.
- 9.Staff Nurse Grade II – The interested candidates applying for this post must have completed B.Sc in nursing and as it expects for grade II a kind of experience is need to handle patients and helping them out.
- 10.Statistical Investigator –Here, this is a very important and demandable post where the candidate should possess a master's degree in Statistics field. He is expected to have a sound knowledge about the content and also about technology.
- 11.Medical officer – As the post name itself suggest that the candidate's profile must impressive with all necessary criteria's like medical degree and the experience level is compulsory. There is kind of satisfactory in this job by helping people from their pain.
- 12.Senior superintends – The candidate willing to join Police department, here is the biggest opportunity to get placed in Police Department and that too for a higher rank post. The person who is qualifying all the necessary conditions, please start applying.
- 13.College lecturer – The person having the passion for teaching along with a master's degree in a particular subject can come forward and apply for this job position.
- 14.Administrative Executive Front office – The candidate applying for this Govt job position in kollam with all leadership qualities to lead as an eligible administrator towards any work can apply for this position.
- 15.Mechanical Engineer – The person applying for this post must have bachelor's degree in engineering with mechanical field as their specialization. Freshers are also welcomed.
The recruitment procedures for all this government position in Kollam are one and the same. The interested candidates can start applying for their desired posts either through online application or can directly go and get the application forms from the government offices. After applying, a formal letter will be received from them regarding a call for the next step to assess the candidates and check as to who can fit into the job. There will be a common approach towards the candidates assessment like written test then followed by formal interviews. Once they are done with the necessary formalities of hiring, the recruitment results will be announced. In a personal round of interview the salary packages will be discussed.


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Kenwood Response Tea Kettle
We like tea, but we hate bitter tea. We also hate the idea of wasting our time and our electricity. Why heat the water to boiling, just to have to wait for it to get back down to the appropriate temperature. Our current setup, a hotpot and a coffee thermometer is a little... well it's less than elegant. We could use a little technology to help us out, and here enters the Response Tea Kettle.
First, let us preface that this is a UK manufacturer, and we're unaware of a US model. But what a great concept, a tea kettle with multiple temperature settings that alerts us to what temperature it is by the color of the kettle. Of course, those tea savvy Brits would come up with this first. Anyone know of a similarly chic US model?
Thanks Chip Chick!
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Late enough that probably no one will even see this, but President's Choice (Loblaws/Superstore) in Canada has a version of this.


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Tuna Poke
Randy Mayor
Be sure to use sushi-grade fish for this Tuna Poke salad because the fish is raw and isn't "cooked" with citrus juice, as in seviche.
Yield: 4 servings (serving size: 1/4 cup tuna and 1/2 cup cucumber)
More From Cooking Light
Nutritional Information
Amount per serving
- Calories: 94
- Calories from fat: 28%
- Fat: 2.9g
- Saturated fat: 0.5g
- Monounsaturated fat: 1.1g
- Polyunsaturated fat: 0.9g
- Protein: 13.9g
- Carbohydrate: 2.4g
- Fiber: 0.7g
- Cholesterol: 26mg
- Iron: 0.6mg
- Sodium: 157mg
- Calcium: 19mg
- 1/4 cup chopped green onions
- 1 tablespoon low-sodium soy sauce
- 1/2 teaspoon grated peeled fresh ginger
- 1 1/2 teaspoons peanut oil
- 1/2 teaspoon dark sesame oil
- 1/2 pound sushi-grade tuna, cut into (1/2-inch) cubes
- 1 garlic clove, minced
- 2 cups (1/4-inch-thick) diagonally cut slices peeled cucumber
- Combine the first 7 ingredients in a medium glass bowl. Cover and chill 2 hours. Serve tuna mixture over cucumber.
My Notes
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Tuna Poke Recipe at a Glance
- COURSE: Appetizers
- CONVENIENCE: Entertaining, Make-Ahead, No-Cook
- CUISINE: Pacific Rim
- MAIN INGREDIENT: Fish
- DIETARY CONSIDERATION: Low Fat, Low Saturated Fat
- COOKING METHOD: Marinate
- PUBLICATION: Cooking Light
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SDL Plc
Computer Integrated Systems Design United Kingdom
| London Stock Exchange: SDL
Similar to: Econocom Group SA, Document Security Systems, Inc., Soft Computing SA
SDL Plc provides global information management and software services. The company's integrated web content management, e-commerce, structured content and language technologies, combined with its language services drive down the cost of content creation, management, translation and publishing. The company operates its business through three segments: Language Services, Language Technologies and Content & Analytic Technologies. The Language Services segment is the provision of a translation service to customers' multilingual content in multiple languages. The Language Technologies segment is the sale of enterprise, desktop and statistical machine translation technology developed to help automate and manage multilingual assets together with associated consultancy and other services. The Analytics and Social Intelligence segment comprises web content management solutions, ecommerce technologies and structured content technologies, plus marketing analytics, campaign management and social intelligence technologies. SDL was founded by Mark Lancaster in 1992 and is headquartered in Maidenhead, the United Kingdom.


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OBJECTIVE: The goal of the study was to establish the predictive validity of a diagnosis of schizophrenia in childhood and early adolescence by examining diagnostic continuity into adult life and comparing social and symptomatic outcomes of child- and adolescent-onset schizophrenia with those of nonschizophrenic psychoses. METHOD: A total of 110 consecutive patients with first-episode child- or adolescent-onset psychosis (mean age at onset=14.2 years) presenting to the Maudsley Hospital in London between 1973 and 1991 were followed up an average of 11.5 years after first contact. Ninety-three (84.5%) of 110 patients were successfully followed-up, 51 with a first-episode diagnosis of DSM-III-R schizophrenia and 42 with nonschizophrenic psychoses. Consensus best-estimate DSM-III-R diagnoses were made at follow-up, and course and outcome were assessed blind to first-episode diagnosis. RESULTS: Diagnostic stability was high for child- and adolescent-onset DSM-III-R schizophrenia (positive predictive value=80%) and affective psychoses (positive predictive value=83%) but much lower for schizoaffective and atypical psychoses. Compared with other psychoses, child- or adolescent-onset schizophrenia was associated with significantly worse symptomatic and social outcomes, which were characterized by a chronic illness course and severe impairments in social relationships and independent living. CONCLUSIONS: The diagnosis of DSM-III-R schizophrenia in childhood and adolescence has good predictive validity. The high level of diagnostic stability suggests etiological continuity with adult schizophrenia, with onset in childhood and adolescence associated with a particularly malignant course and outcome.
Since the publication of DSM-III in 1980, schizophrenia has been diagnosed in children and adolescents by using unmodified "adult" criteria. Although compelling evidence suggests that schizophrenia can be reliably identified in children as young as age 7 by using adult diagnostic criteria (1, 2), there remains uncertainty about the diagnostic stability and predictive validity of schizophrenia in childhood and early adolescence. Misdiagnosis may occur because the symptoms of other disorders overlap with schizophrenia. Affective psychoses (3–6) and developmental disorders with psychotic episodes (2, 7) can mimic schizophrenia in childhood and adolescence leading to false-positive diagnostic errors. Developmental variation could also mean that phenotypic variants of schizophrenia in childhood and adolescence may be missed by adult diagnostic criteria leading to false-negative diagnostic errors (7).
In the absence of specific biological markers, careful longitudinal follow-up remains a crucial method for determining the validity of psychiatric diagnoses. Robins and Guze (8) included outcome and stability of diagnosis over time as two of the five criteria for establishing diagnostic validity. Kraepelin distinguished the poor outcome of dementia praecox from the more benign outcome and episodic course of manic-depressive psychosis. Evidence of diagnostic stability is also important for validation because it is likely to reflect a stable underlying psychopathological process (9). In adults, definitions of schizophrenia that include duration criteria (e.g., DSM-III, DSM-III-R, DSM-IV, and Feighner criteria) have higher levels of diagnostic stability (10, 11) and better predictive validity (11–14) than definitions of schizophrenia based on Schneiderian first-rank symptoms.
There is a widely held view that a valid diagnostic distinction cannot be made between schizophrenia and affective psychosis in childhood and adolescence. This view has been supported by several follow-up studies of child-and adolescent-onset psychoses showing a high degree of diagnostic instability (6, 15). In a study of patients who presented both as children and adults to the Maudsley Hospital in London, adolescents with a diagnosis of affective psychosis were just as likely to receive an adult diagnosis of schizophrenia as those who were first described as having schizophrenia were to follow a bipolar course (15). Werry et al. (6) examined the stability of DSM-III-R diagnoses in a follow-up study of adolescent-onset psychoses and found that 25% of first-episode diagnoses of schizophrenia were changed to bipolar disorder after 5 years and 50% of patients with bipolar disorder were initially diagnosed as having schizophrenia. A recent follow-up study of DSM-IV-defined adolescent-onset schizophrenia and affective psychoses found a higher degree of diagnostic stability with 90% diagnostic agreement over a 2-year period, although follow-up assessment was not blind to the initial diagnosis (16).
To establish predictive validity and diagnostic sensitivity and specificity, follow-up studies of child- and adolescent-onset psychoses must include a nonschizophrenia comparison group. There is a lack of consensus among the few studies that meet this criterion, with some reporting no differences in outcome between schizophrenia and affective psychoses (17, 18) and others suggesting a poorer outcome for schizophrenia compared to other psychoses (19, 20). These later studies have significant methodological limitations, including a low follow-up rate (19) and outcome comparisons made on the basis of adult follow-up diagnoses rather than the first-episode diagnoses (20). Hence, inconsistent findings, together with important methodological limitations, make it very difficult to draw any secure conclusions about the diagnostic stability and predictive validity of child- and adolescent-onset schizophrenia.
The purpose of the study reported here was to test the predictive validity of DSM-III-R schizophrenia in childhood and adolescence by examining whether the diagnosis showed stability into adult life and predicted a worse outcome compared to other psychoses. The design aimed to avoid the methodological limitations that have beset previous follow-up studies of psychoses in this age group. Although the age at onset of psychosis in the followed-up sample ranged from 10 to 17 years, the shorthand term "adolescent-onset" will be used here. Fifty-one patients with DSM-III-R schizophrenia and 42 with nonschizophrenic psychoses were retrospectively ascertained and followed up in adult life an average of 11 years after their first psychotic episode. The primary outcomes of the study were indices of diagnostic stability (sensitivity, specificity, likelihood ratio, and positive predictive value) and measures of social disability and symptomatic functioning in adult life.
A retrospective psychosis screen was applied to the records of all patients under 18 years of age who had attended the Maudsley Hospital in South London between 1973 and 1991. At the Maudsley Hospital Children's Department, data from clinical assessments are combined through standard coding of specified symptoms, and the symptom codes are recorded on standardized clinical data summaries ("item sheets") and stored on a computer (21). Item sheets were completed on more than 95% of all patients during the study period, during which the format of the item sheets remained constant. Patients who screened positive for psychosis were identified from the item sheets if at least one of the following criteria were met: 1) an ICD-9 diagnosis of schizophrenia (295.0–295.9), affective psychosis (296.0–296.9), paranoid state (297.0–297.9), or other nonorganic psychosis (298.0–298.9) (equivalent ICD-8 codes were used from 1973 to 1977), or 2) one or more of the symptoms of hallucinations, delusions, or ideas of reference was definitely present. Patients attending the Maudsley Hospital Adult Department were also included in the screened-positive group if they were under age 18 at the baseline assessment and had an ICD-9 psychotic diagnosis (ICD-8 codes were used from 1973 to 1977). A total of 196 patients screened positive for psychosis.
At the second stage of the study, a detailed chart review was conducted for the 196 screened-positive patients. The selection criterion was unequivocal evidence of one or more of the following Research Diagnostic Criteria (RDC) psychotic symptoms (22) occurring in clear consciousness and lasting for at least 2 weeks: prominent hallucinations, delusions, or incoherence/loosening of associations. The records of 23 of the initial 196 patients who screened positive had missing case notes or not enough clinical details to confidently determine the presence or absence of psychotic symptoms, 58 patients were confirmed as nonpsychotic after their case records were examined, and five had a diagnosis of autism in the absence of an RDC psychotic symptom. The remaining 110 patients constituted the baseline adolescent-onset psychosis sample and were eligible for follow-up.
Adequate follow-up data were obtained on 93 (84.5%) of the 110 patients over a 2-year period. These 93 patients will be referred to as the followed-up sample. Subjects were located by using a variety of methods, including searches of the U.K. National Health Service Central Register and records of local U.K. Family Health Service Authorities. Information recorded in the patients' medical records at the first admission was also used to contact subjects' parents, family doctors, and consultant psychiatrists. After subjects had been traced, they received a letter introducing the study. Finally, subjects were visited by the author to explain the purposes of the study and to seek their consent. After complete description of the study to subjects, written informed consent was obtained.
Seventeen subjects (15.4%) were excluded from the final followed-up sample because of inadequate data. Seven subjects refused to be interviewed, and sufficient clinical information for these subjects was not available from other sources. Four subjects could not be traced, and nine had died. However, for three of the deceased subjects, there were enough detailed clinical data to include them in the followed-up sample. Seventy-four (80%) of the followed-up sample were assessed in face-to-face interviews. For a further 19 subjects, high-quality information was available from relatives, professionals, and case records. There were no significant differences between the followed-up sample (N=93) and those not followed-up (N=17) in age at onset, gender, ethnicity, place of residence, and DSM-III-R baseline diagnoses.
Baseline information was extracted from patients' medical records by using a structured coding procedure specifically designed for the study. The quality of case note information recorded by Maudsley Hospital psychiatry trainees was uniformly high and followed the guidelines on obtaining and recording clinical information produced by the Maudsley Hospital and Institute of Psychiatry. To minimize potential bias and to avoid inferential impressions, items were rated only if the case notes contained explicit positive statements concerning the patient's status. All baseline ratings were made blind to adult outcome status. The mean age of subjects at baseline assessment was 14.9 years (SD=1.5, range=11–17). The mean duration from onset of psychotic symptoms to baseline assessment was 5.3 months (SD=7.1, range=0.2–36).
Data on psychopathological characteristics at baseline from medical records were rated by using the OPCRIT checklist for psychotic illness, version 3.31 (23). OPCRIT comprises a checklist of 90 items constructed from operational criteria for the major psychiatric classifications (ICD, RDC, DSM-III-R, etc.) and a suite of computer programs that allows psychopathological data to be entered and edited and diagnoses to be generated according to each set of diagnostic criteria. OPCRIT has been shown to have good reliability for DSM-III-R diagnoses made by using the 90-item checklist (kappa=0.73) (24). The concurrent validity of OPCRIT DSM-III-R diagnoses has been established in analyses showing good to excellent agreement with consensus best-estimate diagnoses (25).
Of the 93 subjects in the followed-up sample, 51 (55%) had a DSM-III-R diagnosis (OPCRIT derived) of schizophrenia at baseline, 12 (13%) had a schizoaffective psychosis, 23 (25%) had an affective psychosis (unipolar major depressive and bipolar psychoses), and seven (8%) had an atypical psychosis (unspecified functional psychosis). Data for all patients with nonschizophrenic psychoses (N=42) were combined for further analysis. t1 shows the characteristics of the 51 patients with schizophrenia and the 42 patients with nonschizophrenic psychoses. Both groups were similar in age at onset, duration of follow-up, gender ratio, referral source (local area versus elsewhere), socioeconomic status, and ethnicity.
All assessments were done by raters who were blind to baseline diagnosis, as the OPCRIT data were not analyzed until all follow-up interviews had been completed. Although the main emphasis in the adult follow-up assessment was on direct interviewing of subjects, where possible multiple sources of information (medical records and interviews with health professionals and relatives) were used to corroborate or supplement information from subject interviews. A median of two sources of information was obtained per subject. After all available sources of information were combined, adult best-estimate DSM-III-R diagnoses were made. The mean length of follow-up (time from baseline) for the 93 subjects in the followed-up sample was 11.5 years (SD=5.2, range=4–22). The mean age at follow-up assessment for the sample was 27.2 years (SD=5.2, range=17–39).
Interviews to determine adult lifetime diagnosis were conducted with a modified version of the Schedule for Affective Disorders and Schizophrenia—Lifetime Version (SADS-L) (26). Coverage was broadened to include diagnoses not covered in the original schedule (27) and some additional questions specifying precise DSM-III-R diagnostic criteria for psychoses. The author, who conducted the SADS-L interviews, obtained training from experienced interviewers at the Institute of Psychiatry.
Although no "gold standard" exists to measure lifetime psychiatric diagnosis, the currently accepted standard procedure involves consensus best-estimate diagnosis on the basis of all available data by two or more clinicians (28). Diagnostic data were extracted and rated independently on a random sample of 25 patients by a second experienced psychiatrist who trained at the Maudsley Hospital. There was a 100% concordance for DSM-III-R diagnoses for the 25 patients rated by two psychiatrists.
Cross-sectional symptomatic and social outcome were measured with several instruments. Cross-sectional measures of psychopathology were obtained by using the Scale for the Assessment of Positive Symptoms (SAPS) (29), the Scale for the Assessment of Negative Symptoms (SANS) (30), and the Global Assessment of Functioning symptom scale (31). The total SAPS score represented the sum of scores on all 35 items (maximum score=170). The total SANS score represented the sum of scores on all 24 items (maximum score=120). The Global Assessment of Functioning symptom scale rates severity of symptoms in the past month on an ordinal scale from 1 (most severe) to 90 (no symptoms). Cross-sectional social outcome/disability was measured with the Global Assessment of Functioning disability scale (31) and the World Health Organization (WHO) Disability Assessment Schedule (32). The Global Assessment of Functioning disability scale rates severity of disability in the past month on an ordinal scale from 1 (most severe) to 90 (no disability).
Course of illness and disability was assessed by using a slightly modified version of the Life Chart instrument from the WHO Multi-Centre Study on the Course and Outcome of Schizophrenia (31). The Life Chart assesses course of illness according to quality of remission, course type, and severity of symptoms, each with clear definitions. Two varieties of remission are distinguished: 1) complete remission, in which the subject is virtually symptom-free and shows his/her usual premorbid personality, and 2) incomplete remission, in which the subject is no longer psychotic but shows any combination of residual symptoms, nonpsychotic symptoms, or personality change. Course type characterizes the entire follow-up period in one of four ways: 1) continuous course, in which the patient was psychotic over most of the period and any remissions that occurred were brief (none longer than 6 months), 2) episodic course, in which discrete psychotic episodes (none longer than 6 months) occurred with clear periods of remission between episodes and at least one period of remission lasting 6 months or more, 3) mixed course, which had characteristics other than those of an episodic or continuous course (e.g., the longest psychotic episode lasted 12 months, and longest remission lasted 9 months), and 4) not psychotic, in which the patient was never actively psychotic during follow-up. Severity of symptoms during the majority of the follow-up period was characterized by four levels: 1) severe, in which the patient could not carry on a coherent conversation, could not work without close supervision, or required constant care; 2) moderate, in which the patient consistently showed signs of health despite marked psychotic symptoms, e.g., could speak with reasonable clarity on some occasions or could work or care for others to some extent; 3) mild, in which the patient's behavior was generally normal and illness was not immediately obvious in conversation, although definite psychotic symptoms persisted; and 4) recovered, in which the patient experienced no psychotic symptoms or only residual symptoms.
The Global Assessment of Functioning symptom scale range expressed the variability in levels of symptoms during the follow-up period and was defined as the difference between the highest and lowest Global Assessment of Functioning symptom scale score for each subject. Variables measuring time were expressed as the proportion (percentage) of the individual follow-up period. The definition of employment included any time spent in full-time education or vocational training (or full-time child care). Independent adult living was defined as living either alone or with friends/partner or with parents and receiving no more support than would be received by the majority of individuals at a similar age.
The stability of child and adolescent psychotic diagnoses was assessed by using the following indices: sensitivity, specificity, likelihood ratio, positive predictive value, and kappa coefficient of diagnostic agreement. Categorical data were analyzed with the chi-square test with Yates's correction for continuity. Categorical r-by-two tables with ordered categories were analyzed with the chi-square test for linear trend. Fisher's exact test was used when expected cell numbers were less than 5. For continuous variables, independent t tests were used when assumptions of normality and homogeneity were met. When appropriate, continuous variables were either transformed so assumptions were better met or analyzed with nonparametric tests such as the Mann-Whitney U test (corrected for ties). All reported tests of significance are two-tailed. Multiple linear regression was used to determine the extent of confounding by demographic variables (ethnicity, social class, area of residence, and gender) in the relationship between adolescent-onset diagnosis and outcome (Global Assessment of Functioning symptom scale score).
t2 shows the continuities between adolescent and adult follow-up DSM-III-R psychotic diagnoses. Among the 51 patients given a DSM-III-R diagnosis of schizophrenia in adolescence, 41 received the same diagnosis as adults (positive predictive value=80%). Among the 23 patients given a diagnosis of affective psychosis in adolescence, 19 received the same diagnosis as adults (positive predictive value=83%). In contrast, schizoaffective psychosis had a positive predictive value of only 33% (only four of 12 patients received the same diagnosis as adults), and none of the seven patients diagnosed with atypical psychosis in adolescence received the same diagnosis at adult follow-up.
Although the sensitivity of the adolescent diagnoses for schizophrenia and affective psychosis were high (84% and 70%, respectively), sensitivity was low for schizoaffective psychosis (40%) and zero for atypical psychosis. The low number of false-positive diagnoses of adolescent affective psychosis contributed to a high specificity (94%) and the high likelihood ratio (11.5). In contrast, the likelihood ratio for schizophrenia was only 3.7. However, the higher rate of schizophrenia, relative to affective psychoses, in the sample resulted in very similar positive predictive values for adolescent diagnoses of schizophrenia and affective psychoses.
The overall diagnostic agreement (kappa) between adolescent-onset and adult DSM-III-R diagnoses were as follows: schizophrenia, kappa=0.61 (95% confidence interval [CI]=0.45–0.77); affective psychosis, kappa=0.67 (95% CI=0.50–0.84); schizoaffective psychosis, kappa=0.28 (95% CI=–0.06–0.62); and atypical psychosis, kappa=–0.10 (95% CI=–0.40–0.20).
t3 shows the results of the comparison between the clinical course of adolescent-onset schizophrenia and other psychoses on measures adapted from the WHO Life Chart (31). The results indicate that an adolescent diagnosis of schizophrenia predicted a greater likelihood of a severe, unremitting illness course. Only 12% (N=6) of patients given a diagnosis of schizophrenia in adolescence were in complete remission for most of the follow-up, compared to 52% (N=22) of those with nonschizophrenic psychoses. Subjects with a diagnosis of adolescent-onset schizophrenia were psychotic for a greater proportion of the follow-up (N=46; median 84.0% of follow-up, interquartile range [IQR]=33.7–100) than were those with other psychoses (N=42; median 15.5%, IQR=8.3–39.0) (Mann-Whitney U, z=–4.49, p<0.0001).
t4 shows that subjects with adolescent-onset schizophrenia were significantly more impaired at outcome than those with other psychoses. Compared to subjects with adolescent-onset schizophrenia, subjects with nonschizophrenic psychoses had greater symptom variability over the course of follow-up. At outcome, subjects with adolescent-onset schizophrenia had more negative symptoms (N=37, median total SANS score=30 of the maximum score of 120, IQR=13–49) than subjects with other psychoses (N=39, median total SANS score=4 of the 120 maximum score, IQR=0–25) (Mann-Whitney U, z=–4.14, p<0.0001) and more positive symptoms (median total SAPS score=14 of the maximum score of 170, IQR=3–21 for subjects with schizophrenia [N=48] versus median total SAPS score=0 of the 170 maximum score, IQR=0–12 for subjects with other psychoses [N=42]) (Mann-Whitney U, z=–3.12, p=0.002).
Subjects with adolescent-onset schizophrenia spent less time living independently (N=50, median time independent <1 year, <1% of follow-up period) than subjects with nonschizophrenic psychoses (N=42, median time independent=5.9 years, 74% of follow-up period) (Mann-Whitney U, z=–4.5, p<0.0005). Twenty percent (N=10) of the subjects with adolescent-onset schizophrenia were living independently (nine of these 10 were still living with parents), compared to 50% (N=21) of subjects with other psychoses (10 of 21 were living with friends or partners). Thirty-two percent (N=16) of the subjects with schizophrenia had spent the majority of the follow-up period in long-stay residential or psychiatric hospital care, compared to only 17% (N=7) of subjects with other psychoses. There was a significant linear association between adolescent-onset schizophrenia and nonindependent adult living (χ2=10.8, df=5, p=0.001).
Sixty percent (N=30 of 50) of the subjects with adolescent-onset schizophrenia left school with no formal qualifications and undertook no further postschool training. Despite this overall low level of educational achievement, it is notable that 22% (N=11) achieved passes on the "GCSE" (General Certificate of Standard Education, the U.K. national scholastic examination for 16-year-olds) or the "A level" (U.K. national scholastic examination for 18-year-olds) after the onset of psychosis. Educational achievement was significantly better for those with nonschizophrenic psychoses, with only 33% (N=14) without any formal qualification or training, while 38% (N=16) achieved GCSE or higher qualifications. There was a significant linear association between the diagnosis of schizophrenia and low educational achievement (χ2=6.9, df=5, p<0.01).
Subjects with an adolescent diagnosis of schizophrenia spent significantly less time in employment over the follow-up period (N=50, median=0%, IQR=0%–18.0%) than subjects with nonschizophrenic psychoses (N=42, median=32.4%, IQR=5.0%–63.6%) (Mann-Whitney U, z=–3.73, p=0.0002).
t5 indicates that adolescent-onset schizophrenia predicts impoverished social relationships in adult life. Almost half of subjects with adolescent-onset schizophrenia (N=22, 44%) had no social contacts other than with professionals or close relatives. Only 14% socialized with a friend or friends, only one subject had had a reciprocal love relationship, and none had married or had a stable partner. Subjects with an adolescent diagnosis of nonschizophrenic psychoses were much less socially impaired, with more than half (N=24, 57%) having either a regular friendship or love relationship.
To estimate the magnitude of confounding in the association between diagnosis and symptomatic outcome, the Global Assessment of Functioning symptom scale score was regressed on DSM-III-R adolescent-onset diagnostic category (schizophrenia versus nonschizophrenic psychosis) and the following variables were then added to the model: gender, social class, location (area of residence), and ethnicity. The unadjusted regression coefficient (Beta) for diagnosis was 14.9, and the fully adjusted regression coefficient (Beta) was 13.4. Overall, adjusting for demographic confounding had a minor effect (about 10%) on the association between diagnosis and symptomatic outcome.
This study examined the predictive validity of a diagnosis of adolescent-onset DSM-III-R schizophrenia by measuring diagnostic stability and comparing course and outcome with those of other adolescent-onset psychoses. The study has significant strengths and represents the largest longitudinal follow-up of adolescent-onset schizophrenia we are aware of that was free from diagnostic bias and that included a nonschizophrenic comparison group. A high follow-up rate (84%) reduced the opportunity for attrition bias, and a mean duration of follow-up of more than 11 years ensured that the subjects had entered well into adult life. Furthermore, the complete follow-up group was representative of the local catchment area subgroup, which reduced the potential for significant referral bias. Hence, the diagnostic comparisons are likely to be valid and generalizable to other populations of adolescents with psychotic disorders. Observer bias could not have affected baseline assessments as they were conducted blind to outcome. Outcome assessments were also conducted blind to baseline diagnosis. A single interviewer at outcome obviated the issue of interrater reliability. The fact that a second experienced psychiatrist achieved 100% concordance for outcome diagnoses with the initial rater suggests that there was very little observer error. Demographic confounding (gender, ethnicity, social class, and area of residence) accounted for no more than 10% of the variability in outcome score (Global Assessment of Functioning symptom scale) due to diagnosis. It is possible that differences in the quality and approach to treatment may have affected outcome. However, this seems an unlikely explanation for the outcome differences, as equal proportions of patients with schizophrenia and with nonschizophrenic psychoses received their follow-up care at the Maudsley Hospital.
The main weakness of the design was the retrospective case ascertainment and the reliance on case note ratings of psychopathology. However, the OPCRIT rating method is well suited to rating case notes and has good demonstrated reliability and validity. Although the Maudsley case records were extremely detailed, the secondary rating of chart data collected by a large number of different examining psychiatrists is likely to have introduced considerable random error. Given this caveat, the observed continuity and predictive validity of diagnoses was impressive and may in fact underestimate true effects.
Diagnostic stability was high for the adolescent DSM-III-R diagnoses of schizophrenia (positive predictive value=80%) and affective psychoses (positive predictive value=83%). In contrast, the positive predictive value was only 33% for schizoaffective psychosis and 0% for atypical psychosis. There was moderate diagnostic agreement between adolescent and adult follow-up diagnoses for schizophrenia and affective psychosis (kappa statistic), and agreement for schizoaffective and atypical psychoses was no better than chance. The results suggest that operationalized DSM-III-R diagnoses of schizophrenia and affective psychoses have substantial predictive validity when applied to a sample of adolescent-onset psychotic patients. However, the likelihood ratio for schizophrenia of 3.7 suggests lower predictive values would occur in samples with a lower prevalence of schizophrenia (i.e., among adolescents from community mental health settings rather than specialist centers).
The results of the study reported here challenge the widely held belief that diagnoses of adolescent schizophrenia and affective psychoses are unstable and are of doubtful validity (6, 15). The findings confirm the higher levels of diagnostic stability reported in some previous follow-up studies of adolescent-onset schizophrenia (19, 20, 33) and avoid the methodological limitations of these studies. Unlike the findings of Werry et al. (6), the results of the present study did not suggest that bipolar disorder was commonly preceded by an adolescent diagnosis of schizophrenia. There was also little evidence that schizophrenia commonly presents in the guise of affective or atypical psychoses in adolescence. Finally, the level of diagnostic stability for schizophrenia in this study was broadly similar to the level reported in studies of adult-onset schizophrenia that used DSM-III-R diagnostic criteria (11).
The psychiatric and social outcomes of adolescent-onset schizophrenia were significantly worse, across a broad range of clinical and social outcome measures, than the outcomes of nonschizophrenic psychoses. An adolescent diagnosis of schizophrenia predicted less independence, poorer educational achievement, less likelihood of employment or access to further education, and higher global disability scores. The most striking finding among the subjects with schizophrenia was the poverty of their social relationships in adult life. The chronic illness course and very poor outcome described here support findings from previous follow-up studies of child- and adolescent-onset schizophrenia (6, 19, 20, 33) and suggest that schizophrenia with a very early onset predicts a more severe and unremitting illness course than the adult-onset form of the disorder (34, 35).
In summary, the results demonstrate a high degree of diagnostic stability and good predictive validity for DSM-III-R diagnoses of schizophrenia and affective psychoses in childhood and adolescence. In contrast, the diagnostic instability of schizoaffective and atypical psychoses highlights their uncertain nosological status. The high degree of longitudinal diagnostic stability for schizophrenia and affective psychoses provides compelling evidence of diagnostic validity because it suggests that outcome differences do not simply reflect good and poor prognosis extremes within a single disorder, but rather separate diagnostic groupings. The phenotypic continuity of schizophrenia from adolescence into adult life suggests that whereas child- and adolescent-onset schizophrenia is clinically a more severe variant of the adult form of the disorder, it is likely to share a common etiology and neurobiology (7).
These findings should give clinicians greater confidence in making an early diagnosis of schizophrenia in children and adolescents. The very poor prognosis described here for child- and adolescent-onset schizophrenia suggests that early and aggressive treatment, special education, and support for families should begin as soon as possible after onset of psychosis. The similarity between DSM-III-R and DSM-IV diagnostic criteria suggests that the results of this study are likely to apply equally to DSM-IV diagnoses.
Received Dec. 7, 1999; revision received Apr. 24, 2000; accepted May 3, 2000. From the Division of Psychiatry, University of Nottingham. Address reprint requests to Dr. Hollis at the Section of Developmental Psychiatry, Division of Psychiatry, University of Nottingham, South Block, E Floor, Queen's Medical Centre, Nottingham, NG7 2UH, U.K.; email@example.com (e-mail).This study was supported by a Research Training Fellowship from the U.K. Medical Research Council. The author thanks Prof. Eric Taylor, Dr. Karmen Slaveska, Kate Garrett, and Pam Remon for their help with the study.
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Remote piloted vessel snakes across Atchafalaya | Home | The Advocate — Baton Rouge, LA
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Helmut Lang and LD Tuttle Do Game of Thrones-Inspired Shoes
True Blood is not the only HBO show inspiring a line that debuts next month: Game of Thrones, too, influenced a collection. While the vampire saga is getting its due via Deborah Lippmann nail lacquers and DL & Co. fragrances at HSN, Game of Thrones' look has been interpreted into a shoe capsule. Read more here
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LOUISVILLE, Ky. – Police are asking for the public's help finding a man suspected of robbing a local bank.
Jeffersonville Police said a US Bank branch inside the Meijer department store on Alison Lane was robbed around 9:46 Friday morning.
Police said a white male wearing a light green long sleeve shirt and camouflage hat approached the bank counter and presented a bank employee with a threatening note demanding money. The suspect is described as approximately thirty to forty years old, 5'3-5'6", with a thin build, and light complexion. The suspect received an undisclosed amount of money. After the robbery, the suspect fled the area in a white passenger car.
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Jackson Police are looking for three men believed to be connected to a Sunday night murder.
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Joe Saladino opposed by Craig Heller for 12th Assembly
In the race for a seat in the 12th Assembly District, Republican incumbent Joseph Saladino is running for reelection and is opposed by Craig Heller, a Democrat who ran for the Nassau County Legislature last year. Despite their party affiliations, both said they view themselves as "reform" candidates
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text: content March 25, 2004 In this issue Life Extension Update Exclusive: New Alzheimer's disease hypothesis Protocol: Alzheimer's disease Featured Products of the Week: Cognitex Cognitex with Pregnenolone Life Extension Magazine March 2004 issue: Life Extension for the brain Life Extension Update Exclusive New Alzheimer's disease hypothesisThe March 19 2004 online early edition of the Proceedings of the National Academy of Sciences (www.pnas.org) published an article which proposes a new theory concerning the cause of Alzheimer's disease. The authors, from The Scripps Research Institute, suggest that Alzheimer's disease is a result of inflammation which leads to the formation of abnormal metabolites from normal brain molecules. These metabolites modify brain amyloid beta proteins, causing them to misfold and accumulate as plaques and fibrils that are characteristic of the disease and which cause the loss of neurons. The inflammatory process can be caused by infections or other factors that can precede the onset of the disease by years. Alzheimer's disease is one of several disease caused by protein misfolding. In some of these diseases mutations that cause misfolding have been identified, but with the exception of a rare form of familial Alzheimer's disease, the cause in 95 percent of cases of the disease was unknown. This suggests a more common cause, and the Scripps researchers set out to find it. In previous research, two of the current paper's authors revealed how inflammation can lead to the formation of reactive oxygen species such as ozone, which can damage cholesterol and other molecules in the body. They found that during inflammation, ozone reacts with normal metabolites to produce toxic compounds, two of which they have labeled the "atheronals." They suggested that these compounds are involved in atherosclerosis because atheronals have been identified in atherosclerotic plaques removed from patients with the disease. In the current study, Scripps research professor Jeffery W Kelly and colleagues examined the brains of autopsied patients with Alzheimer's disease and compared them to normal brains, finding evidence of atheronals in both groups. The researchers believe that a precipitating event in the presence of atheronals, such as a the inflammation caused by a head injury, may propagate protein misfolding and the buildup of fibrils. The team also found that atheronals and lipid oxidation products accelerate the misfolding of amyloid beta in vitro. Kelly and colleagues suggest that inflammation could create conditions in which cholesterol and fats react with ozone and other inflammatory compounds to produce abnormal metabolites, which modify the folding of amyloid beta protein, leading to misfolding of other unmodified amyloid beta proteins, which eventually results in Alzheimer's disease. Dr Kelly commented, "If a certain inflammatory metabolite or family of metabolites confers risk later in life, then we need to know this, and we need to attack the problem." Protocol Alzheimer's diseaseIn Alzheimer's disease, an inflammatory cascade begins in response to beta-amyloid. The inflammatory response, involving cytokines and prostaglandins, occurs around beta-amyloid in the neuron. This inflammatory process continues and accelerates the loss of neurons. Inflammation is a protective response of the body that occurs during the process of repair. The four cardinal signs of inflammation are redness, swelling, heat, and pain. The Russian biologist Elie Metchnikoff proposed that the purpose of inflammation was to bring phagocytotic cells to the injured area in order to engulf invading bacteria. Both Metchnikoff and Paul Ehrlich (who developed the humoral theory of immunity) shared the Nobel Prize in 1908. Alterations in blood flow occur with inflammation, primarily to increase local circulation and speed repair. The blood vessels become more permeable, which allows protein-rich fluid (exudate) to collect between cells. This excess extravascular fluid is called edema. The mechanism of inflammation is a complex interaction of chemical messengers. Arachadonic acid, via 5-lipoxygenase, forms leukotrienes that cause vasoconstriction, bronchospasm (i.e., asthma), and increased permeability. Alternatively, arachadonic acid can form, via cyclooxygenase, prostaglandins, which have similar actions and cause pain. Aspirin and indomethican inhibit cyclooxygenase which results in pain relief, but does not address the underlying cause of the inflammation or stop the actions of the leukotrienes. Inflammation can be acute, as occurs after a physical injury, or chronic. There are several causes of chronic inflammation, including: Persistent infections Prolonged exposure to toxic elements Autoimmune disease Genetics Inflammation is considered to be an underlying cause of Alzheimer's disease, primarily because beta-amyloid is an inflammatory protein (Hull 1996; McGeer et al. 1999). C-reactive protein is a marker of inflammation that is associated with Alzheimer's disease (Iwamoto et al. 1994). http://www.lef.org/protocols/prtcl-006.shtml Featured Products of the Week Cognitex It seems the aging brain is susceptible to inflammation from enzymes known as COX-2 (cyclo-oxygenase 2) and 5-LOX (5-lipoxygenase). To inhibit the actions of these destructive enzymes, Nexrutine ® and 5-Loxin extracts have been added to the new Cognitex formula. Nexrutine ® , from a plant called Phellodendron amurense, inhibits the production of the inflammation causing COX-2 enzyme, without interfering with the beneficial enzyme COX-1 that plays a part in protecting the mucosal lining of the stomach. 5-Loxin is a derivative of b-boswellic acid, a resin from the Boswellia serrata tree. 5-Loxin acts as a specific inhibitor of the inflammatory agent 5-LOX. Newer research indicates that levels of 5-LOX increase with age and may trigger cell death in the brain. Working synergistically, the combination of Nexrutine ® and 5-Loxin may provide maximum effectiveness through a dual inflammatory pathway blockade. In fact, a 5-LOX inhibitor such as 5-Loxin may actually improve the effectiveness of COX-2 inhibitors. http://www.lef.org/newshop/items/item00628.html Cognitex with pregnenolone Since 1982 when Cognitex was introduced to Life Extension members, the formula has been modified several times reflecting the results of new studies to promote optimal health in the aging brain. The newest version of Cognitex includes nutrients to protect the brain from a wide range of age-related insults. Pregnenolone is a natural hormone that decreases with age. It is considered the "mother hormone" because the body converts it into a variety of other important hormones such as estrogen, progesterone, testosterone, and DHEA. These hormones may be especially beneficial to the aging brain. The new Cognitex is available with or without pregnenolone. People with hormone-sensitive cancers should not take pregnenolone. http://www.lef.org/newshop/items/item00629.html Life Extension Magazine March 2004 issue Life Extension for the brainMore than 2 million Americans have been diagnosed with Alzheimer's disease. If we do not do a better job now of preventing or slowing cognitive decline, this number will jump dramatically when the baby-boom generation reaches age 65. Fortunately, we have at our disposal tests that provide more meaningful memory assessments that can be administered earlier when effective interventions can be prescribed. http://www.lef.org/magazine/mag2004/mar2004_report_brain_01.htm If you have questions or comments concerning this issue or past issues of Life Extension Update, send them to firstname.lastname@example.com or call 954 766 8433 extension 7716. For longer life, Dayna DyeEditor, Life Extension firstname.lastname@example.com 766 8433 extension 7716Sign up for Life Extension Update at http://mycart.lef.org/subscribe.asp Help spread the good news about living longer and healthier – forward this email to a friend!


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James The Zebra is back! Tired of life on the land, James has decided to become a scurvy pirate, complete with not one but two peg legs and a tiny bandanna. Join him on his quest for the treasure, boarding ships and avoiding monsters of the deep, along with two great mini-games available from the main menu screen. All three have hi-score tables to compete for the top place!
Tom & Dim
Rated 5 / 5 stars September 1, 2011
I think these James the zebra games are amazing. The games have great animation and they are ,in short, awesome. You should continue with the James games. These games should get an Oscar or a kid's or a teen's choice award. You guys should get one ,too!
Rated 5 / 5 stars November 29, 2010
it was very nice XD
Rated 5 / 5 stars November 6, 2010
I loved IT!!!
That was an amazing game!! Bit short though. You probably could of made a full game out of this.
Rated 3.5 / 5 stars March 31, 2010
Very cool.
Not exactly short.
Rated 2 / 5 stars November 12, 2009
i think you shouldve made more consequenses of getting hit by tentacle or getting hit by bird maybe fall off net or get suctioned into the sea, because losing 3 coins isnt much and when hit there was little animation... more obstacles =p


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Reader Comments (Page 1 of 1)
I think this question about legendary items was asked a long time ago (probably right before BC was released if I remember correctly), and the blues said something to the effect of "we don't want players to be able to use the same weapon forever."
Besides, how would they even make that work? If Thunderfury could be upgraded into a level 80 legendary item what would stop every warrior and his dog from easily grabbing it from the old world instances and upgrading it to the lvl 80 version?
Well you could say "well they should only be able to upgrade if they've had it since vanilla", but that would screw 98% of the people playing this game who didn't acquire it in vanilla, because surely a lvl 80 legendary item would be way better than anything you could get out of naxx atm.
All in all, WoW forces you to upgrade any time there is an expansion/major patch. You just can't just grab a legendary weapon (as difficult as that is) and then sit back and be uber leet forever.


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Parents, Mind Your Manners
It's hard to teach kids etiquette when adults behave badly. So put down your smartphone and pay attention.
I'm not done. Another parenting impoliteness is being over-process-y in a conflict-type situation. For instance, let's say your child has just smacked another child on the head with an imagination-stimulating, unstructured-play-enhancing, hollow-core sustainable wooden block. Your response should not be to run to your child murmuring, "Phoenix, darling, what did he do to you? Can we talk about why he made you forget to use your words?" Your response should be: "We don't hit. Time out. Right now." You don't negotiate when told it is the other child's fault. You will never tease apart who did what. If your kid hurt another kid, your kid gets punished. If you feel time-outs aren't effective, but taking away a privilege works better, do that. Soothe the child who was hit (even if you suspect he or she was being annoying before the smackdown). I am a believer in making a child apologize even if he or she does not mean it. We can discuss this (and why you think I'm a moron) in another column.
If your child is on the receiving end of the hitting, do not say, in earshot of the other parent, "Oh, did the ill-raised little vilde chaya use violence upon your person? He must have special needs or parents who went to a state school!" Please. If the other parent is apologetic, ease the way for him or her. Accept the apology. Distract your own child. Rise above.
Finally, here's a bit of extended family etiquette. Do not make everyone else a hostage to your child's nap schedule. If you cannot attend a bar mitzvah because of your kid's nap time, do not huff about it. (While you're at it, ponder whether you might be un peu rigid about naps, and/or food, and/or trying to ensure that your entire block is as silent as a crypt when your child is sleeping.) If your child is not invited to a wedding, do not snap what someone I know once snapped at a bride, "Savoy is my life!" (Also, do not name your child Savoy.) Do not ostentatiously refuse gifts that do not fit your values—when you are high-handed and self-righteous, you are the rude one.
Polite parents raise polite children. I've seen the saying (attributed to a ton of different people), "Character is how you treat people who can do nothing for you." It's true. If your rude boomer parents did not raise you to have manners, you've got some work to do. Having a child is an opportunity to make up for lost ground, and to help yourself (and by extension the wider world) in the process of helping your kid.
Like this article? Sign up for our Daily Digest to get Tablet Magazine's new content in your inbox each morning.
The Pretenders
In order to understand Sabbath rules, the rabbis show, one must imagine exactly what work the Israelites did


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Population 86,074
Parcels 64,129
The Levy Data Viewer is located under the TAX TAB after performing a search for your property. Click View Levy Data.
Click here (Levies List) to view the list of levies that will be on the November 4, 2014 General Election.
The Tax Estimator will allow you to see tax amounts for an arbitrary property (based on value) in a particular taxing district.
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To begin using the system, click on the Searches link above, or simply use the QuickSearch feature at the top of the page. First time users can access the Online Auditor Help at any time by clicking the Help link above. Before using AccuGlobe Internet Edition, please review our browser compatibility information in the help pages.
You will need Adobe Acrobat to view and download tax forms and view property record cards.
For news and statistics on the national housing market, visit these links:
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Record number attend emergency management symposium
More than 450 professionals and students attended the 2012 Virginia Emergency Management Symposium March 28-30. It was the largest attendance in history for the annual event. For the first time, live tweeting from several sessions allowed those not in attendance to be involved in the discussion.
Planning is already underway for the 2013 conference, which is scheduled for March 18-22 at the Homestead in Hot Springs, Va.


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We support more than 1,500 people every year and this is only possible thanks to generous donors and fundraisers. Peace Hospice Care needs £4m each year to continue supporting patients and their families and all our services are provided free of charge.
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We're celebrating what the library means to you, our patrons. Check out our patron-inspired photo collage "In Three Words" in our lobby and on our website.
On Tuesday, April 15 join us for coffee and donuts from 9am - noon.
All week long, Tinley Park cardholders may enter a drawing for a chance to win a Kindle Fire HD. One entry per person, please.
A Second Opportunity to Win a Kindle Fire
@yourlibrary, a national organization supporting America's libraries, is also giving away a Kindle Fire.
Simply snap a selfie, or tweet, or tell a story about how a library has changed your life. To enter, include a hashtag: #LivesChange and/or #NLW14.
All the details are available on the @yourlibrary website.


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First Post
Okay! Okay! My conscience started bugging me! I've been sending smart remarks and various other gallimaufries to Amy Welborn for the past several days (the Situation in the Church is, among other things, a rich source for the satirically-inclined) and she has graciously been sticking them on her site. But I finally thought, "Shea, why are you making Amy take time out of her busy day to publish your stuff when you could just do it yourself and give her a little more time to write her fine work or play with her kidlets?"
So here it is, my own blog. Amy, thanks. The rest of you: you'll be hearing from me as the fit takes me.


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The Lost World - matinee
Silence is Golden Silent Movie Event
Ticket prices
All tickets are for general admission (no reserved seating).
1 pm matinee $26.75
7:30 pm performance $31.75
Prices quoted INCLUDE service charges and taxes.
Presented by:
Bill Rowson guest conductor
Robert Israel composer
About the concert
Before Jurassic Park, there was The Lost World. Based on Sir Arthur Conan Doyle's 1912 novella, the story only made it to screen due to the special effects genius of Willis O'Brien, whose model dinosaurs were so convincing. The dinosaurs are the stars, but the human cast is led by Wallace Beery as blustery Professor Challenger, who leads an expedition to a lost mesa where dinosaurs still rule and returns to London with a brontosaurus. Havoc ensues.
About The Lost World (1925)
This silent film adaptation of Arthur Conan Doyle's 1912 novel of the same name was directed by Harry O. Hoyt and featureS pioneering stop motion special effects by Willis O'Brien (an invaluable warm up for his work on the original King Kong directed by Merian C. Cooper and Ernest B. Schoedsack).
In 1922, Conan Doyle showed O'Brien's test reel to a meeting of the Society of American Magicians, which included Harry Houdini. The astounded audience watched footage of a Triceratops family, an attack by an Allosaurus and some Stegosaurus footage. Doyle refused to discuss the film's origins. On the next day, the New York Times ran a front page article about it, saying "(Conan Doyle's) monsters of the ancient world, or of the new world which he has discovered in the ether, were extraordinarily lifelike. If fakes, they were masterpieces".
The Lost World is a film of many firsts: first film to be shown to airline passengers, in April 1925 on a London-Paris flight by the company Imperial Airways; first feature length film made in the United States, possibly the world, to feature model animation as the primary special effect, or stop motion animation in general; first dinosaur-oriented film hit, which led to other dinosaur movies, from King Kong to the Jurassic Park trilogy.
The Lost World was cut for rerelease in the 1930s and the original negative was subsequently lost. David Shepard meticulously "rebuilt" the film using material from eight different surviving prints from all over the world, cleaning and restoring along the way. The result, which is 50 percent longer than previous prints, is still not complete but closer than any version since its 1925 debut.
The released film on DVD features a classic orchestral score arranged and conducted by Robert Israel. The score for this performance, however, has been newly arranged by Robert Israel for the Saskatoon Symphony Orchestra. His score features original compositions and is also adapted from authentic photoplay music. During the 1920s, there was a similar scoring practice that was followed by music directors in large cinemas; when it was necessary to provide a new score every week using music from the theatre's library. For this presentation, Robert Israel also orchestrated the score–this is the process in which the music score is arranged for the orchestra musicians. With the wide variety of settings in The Lost World, as well as its unique story content, it allowed a great opportunity to realize many orchestral colors: from urbane London, England; to the raw and exposed nature of the Amazon River; to the wild primordial jungle of the dinosaurs; and finally, the chaotic and dramatic finale back in London.
The Roxy Theatre
The historic Roxy Theatre, lovingly restored is one of the last remaining atmospheric theatres in western Canada and is one of the city's architectural treasures. Recently converted to digital technology, the Roxy Theatre provides a movie-going experience reminiscent of the Golden Age of Hollywood without sacrificing comfort or the quality of projection or sound.
Ticket Prices
All tickets are for general admission (no reserved seating).
1 pm matinee $26.50
7:30 pm performance $31.50
Prices quoted INCLUDE service charges and taxes.
To purchase tickets online for the 1 pm matinee, click here.
To purchase tickets online for the Saturday 7:30 pm evening performance, click here.
Tickets are also available at the Roxy Theatre Box Office, 320 20th St W or by visiting the SSO office, 408 20th St W, phone 306.665.6414.


text: Titanfall for Xbox One and PC was released on March 11th and it was well received by the consumers. The Xbox 360 version of the game is supposed to be available on 3/25/2014 and it has been delayed now. EA today announced that this game will be now released on April 8th. Now, I want to update everyone on Titanfall for Xbox 360 in development with Bluepoint Games. I've been playing the game a lot, and it is fantastic. But we see a few things that can be made even better, so we're giving Bluepoint a little more time to do just that and deliver an epic Titanfall experience for Xbox 360 players. Titanfall for Xbox 360 will now be releasing on April 8 in North America, and beginning on April 11 in Europe. The game will feature the same 6v6 gameplay, maps, modes, weapons and Burn Cards as the ...Read More →


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Feb. 21 (Bloomberg) -- Citigroup Inc. named Maurice Thompson as country officer for the U.K.
Thompson was previously chairman of the public sector group for Europe, Middle East and Africa, Citigroup said in an internal e-mail seen by Bloomberg and confirmed by a spokesman. Thompson has also been named vice chairman of banking for the region.
Citigroup has also named Andres Recoder as head of markets for Europe, Middle East and Africa, according to a separate internal e-mail. Recoder has been head of sales for markets in the region since 2008.
To contact the reporter on this story: Gavin Finch in London at email@example.com
To contact the editor responsible for this story: Francis Harris at email@example.com


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These four Trans Am drivers came together on the road between Texarkana and Little Rock. From left to right: Tommy Comer with the Olds-403-powered '79 Trans Am; Steven Wyer from Topeka, Kansas, in his '99; Dale Streetman in the '89 3.8L turbo Trans Am; and Sam Johnson from Huntsville, Texas, in his '69 Trans Am clone. We call Sam's Trans Am a clone in the loosest sense of the word. He's not trying to fool anyone that he's got an original convertible. He's swapped in the interior of an '04 GTO, making the last 12,000 miles a whole lot more comfortable. Sam also updated the drivetrain, with the T-56 six-speed from an '05 GTO and the LS1 from a '99 TA.
Arlington, TX
Texarkana, AR
Little Rock, AR
Memphis, TN
Birmingham/Hoover, AL
Chattanooga, TN
North Concord, NC
© Hotrod.com
TEN: The Enthusiast Network
All rights reserved. HAWWBIIS11


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Long before Paul and Jackie Seguin thought about bringing their talented son Tyler into the world, jazz musician Mose Allison was bringing toes to a tapping with his ditty, "Young Man's Blues."
The tune gained notoriety when The Who began covering it in the 1960s, as singer Roger Daltrey brought young adults to their feet belting its opening lyrics, "Well a young man ain't got nothing in the world these days."
If Allison and Daltrey tuned into the Bruins' 6-3 win over Edmonton on Thursday night, they might've been surprised by what they saw.
Rookies and sophomores stole the show at the TD Garden, with Brad Marchand, Tyler Seguin, Taylor Hall and Ryan Nugent-Hopkins stepping to the forefront.
Marchand led the young crew with a pair of goals, both from a simplified game plan that thrilled coach Claude Julien.
"Sometimes guys try and do a little too much and they try to get a little fancy, and it doesn't suit their game," Julien said. "That's Brad in a nutshell. He just has to play hard and use his speed to take pucks to the net and shoot it."
Marchand picked up both tallies in simplified style. The first was a power-play tally, as the 5-foot-9 Marchand posted himself against 6-foot-3, 210-pound Ladislav Smid. Holding court in the slot, Marchand deflected Joe Corvo's point shot, rerouting the puck right by goalie Devan Dubnyk.
The second goal was pure Marchand, reflecting his grinding mentality with his sniping talents. On an odd-man rush, Marchand opted to shoot rather than try a difficult pass to Chris Kelly. The shot was perfectly placed over Dubnyk's right shoulder.
The goals snapped a nine-game scoreless streak for Marchand, who signed a two-year, $5-million extension prior to the season.
"It was nice to get the monkey off the back," he said. "It was definitely getting frustrating. I've been missing a lot of opportunities, so it was nice to get a couple.
Seguin's play was every bit as impressive, but was nothing new for the Garden faithful. The 19 year old came into the night 13th in the league in scoring with 15 points (8 goals, 7 assists), and merely picked up where he left off.
The sophomore finished with a goal and an assist, though his contributions off the score sheet might be more notable. The winger assisted on Brad Marchand's power-play goal early in the second period, though his contribution was minimal on the play.
What stands out is what Seguin did to earn the man advantage. The center-turned-winger created the power play with his elite wheels, blowing ahead of Edmonton's defenders after scooping a loose puck in the neutral zone.
Jeff Petry hooked up Seguin as he crossed the Oiler hashes, and earned a fateful trip to the box because of it.
At that point, Seguin was merely keeping pace with his equally hyped opponents. Taylor Hall and Ryan Nugent-Hopkins –– the 2010 and 2011 No. 1 overall picks, respectively –– had already made a mark on the score sheet.
The pair each notched points on the Oiler goal that squared the game at 2-2 midway through the first period.
Nugent-Hopkins started and finished the play, scooping an errant Milan Lucic pass along the right boards in his own zone. After making the pass, Lucic failed to cover up Hall, who was streaking down the left side of the neutral zone. Hall nabbed the pass and skated toward net with linemate Jordan Eberle riding sidecar in the right slot.
Nugent-Hopkins trailed the play, soaring by Lucic to the high slot, where he was greeted by a drop pass from Hall. This year's No. 1 overall picked took in the pass, sized up B's goalie Tuukka Rask, and sniped a low laser by Rask's stick side.
"I think we're kind of developing some chemistry early in the season, and we want to keep that going," Nugent-Hopkins said. "I think we're on the right track for sure and I think we just need to keep our heads up and go into Detroit tomorrow with the right attitude."