text:
Order your copy of Natural Solutions for Cleaning & Wellness
before November 30, 2016, and get your
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Receive special early access today to 5 of the toxic free recipes from Natural Solutions for Cleaning & Wellness! You'll receive 5 recipes in written format so you can try them out for yourself right away.
These recipes are original Natural Solution for Cleaning & Wellness recipes designed for your home and health.
Don't wait until the book is released on February 7th; transformation can begin in the home today with these toxic-free recipes.
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Get ready for your chance to win a TON of natural solutions products with this amazing basket of natural goodies! When Natural Solutions for Cleaning & Wellness launches, we will pick one lucky winner to receive a basket full of natural solution goodies that are featured in the book and from our new product line.
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- A jar and stick of deodorant from our new deodorant line -- Purity Pits!
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Meet Halle Cottis
Halle Cottis has always done her best to live as naturally as possible. She grew up in a rural community where the Amish still exist, and the charm of how things once were done is still present. She lives a simpler lifestyle and does her best to eliminate toxins and chemicals out of her and her families lives.
Halle is founder of Whole Lifestyle Nutrition where she shares allergy friendly recipes, natural solutions, and health and lifestyle articles. She is a Holistic Life Coach and her mission is to help others find their way to a more healthy and natural lifestyle.
Halle resides in Florida with her husband and three beautiful girls. In her past time she enjoys nature walks, gardening, photography, boating, fishing and relaxing on the beach with friends and family.
Praises for Natural Solutions for Cleaning & Wellness:
Michelle Toole founder of Healthy Holistic Living
"Natural Solutions for Cleaning & Wellness is jammed packed with 140 recipes to keep your home sparkling clean, your family healthy and toxin-free and your garden free of pests. This is fast becoming our go-to book for everything. Every household should have one!" ~ Michelle Toole
Tiffany Pelkey, founder of The Coconut Mama
"What I love most about Halle's recipes is that they're simple, easy to follow ad they actually work! Her recipes are non-toxic, environmentally friendly and much cheaper to use compared to buying natural cleaners ad body care products from the store." ~ Tiffany Pelkey
Robin Konie founder of Thank Your Body
"Beyond the many effective recipes, Halle provides all the tools you need to feel confident using these natural remedies and solutions. It's a must-have for parents everywhere." ~ Robin Konie author of All Natural Living and Processed Free
"Never has natural living felt so doable! With this book, you'll be armed with every natural recipe you'll ever need - whether you have a runny nose or need to clean your toilet - these solutions are right at your fingertips. If your goal is to get rid of toxic chemicals in your home, this book is your how-to manual." ~ Elizabeth Walling creator of The Nourished Life
I've gotten my hands on this gem of a book and I can honestly say, THIS BOOK DOES NOT DISAPPOINT! Whether you are looking to clean up your health or rid your home of toxins, this is your book is for you! ~ Tammy Wright
I have been looking for a book like this forever! Halle has a unique way of teaching us how to make a change without getting too overwhelmed. She is very encouraging throughout the book that I felt I had a personal coach throughout the whole book! This book will go down as a classic! ~ Michelle Baker


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5 guests
2 bedrooms
3 beds
1 bath
5 guests
2 bedrooms
3 beds
1 bath
The cottage is from 1947, but renovated in 2009. It is located at the bottom of the closed road and with green areas to all sides. There is only 300 m to the beach and from the house's 1st floor there is a water kick. There is a lovely big grounds for the house as well as the terrace.
translated by Google
Sommerhuset er fra 1947, men gennemrenoveret i 2009.
Det ligger i bunden af lukket vej og med grønne områder til alle sider. Der er kun 300 m til stranden og fra husets 1. sal er der vandkik.
Der er en dejlig stor grund til huset samt terrasse.
Guest access
Guests have access to the entire house.
translated by Google
Gæsterne har adgang til hele huset.
Family/kid friendly
Free parking on premises
Indoor fireplace
Extra people No Charge
Cleaning Fee $94 NZD
Always communicate through Airbnb
To protect your payment, never transfer money or communicate outside of the Airbnb website or app.Learn more
House Rules
No smoking
Not suitable for pets
Check in is anytime after 2PM
Check out by 10AM
Safety features
Smoke detector
First aid kit
4 nights minimum stay
12 Reviews
Check In
This beautiful house was a peaceful place for our holiday. We saw a deer in the garden and could walk to the beach in 10 minutes. The stairs were very steep, this was a bit difficult for us. The kitchen has everything we needed and was very clean. We enjoyed walking in the neighbourhood with lovely countryside.
This host has 33 reviews for other properties.View other reviews
Languages: English
Response rate: 100%
Response time: within an hour
The neighbourhood
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More places to stay in Vordingborg:

subset: commoncrawl


text:
With the European Union promoting a Better Regulation and REFIT agenda, the Call for Evidence and the need for jobs and economic growth, the financial sector may be forgiven for having entertained the notion that the regulatory rhythm would slow down. That is, however, not quite the state of the European legislative agenda for the European banking sector and financial markets.
On 23 November the European Commission unveiled a comprehensive package of legislative measures aimed at completing the EU regulatory framework for the banking sector. Characterised as a package of risk reducing measures, it seems closely linked to the proposal for a common European Deposit Insurance Scheme (EDIS) for the 19 Member States of the Eurozone which was proposed exactly a year ago. Considered the third and missing pillar of the Banking Union, EDIS has made particularly slow progress both in the Council and the European Parliament because of fundamental divergences between Member States on the sequencing of reduction and mutualisation of risks in the European banking sector.
This new package will have a deep impact on banks, financial markets and bank investors. In addition it comes amidst tensed international discussions on 'Basel IV', the regulatory uncertainty for the largest banking centre in Europe brought by Brexit and the increasingly complex relationship between the Banking Union and non-Euro Member States.
In this briefing we will provide an overview of the context and structure of the proposal, its key elements and the political dynamics that can be expected in the Council and the European Parliament.
What is the Commission proposing and where does it come from?
The package unveiled by the Commission is the culmination of four workstreams coming together simultaneously to address political priorities of the Commission as well as to ensure the EU follows through on its international commitments:
- Basel III Agreements – the package is making key parts of the Basel III framework such as a binding Leverage Ratio (LR), Net Stable Funding Ratio (NSFR) and Large Exposures (LE) regime, binding under EU law.
- International agreements – the package implements the Financial Stability Board (FSB) Term Sheet on Total-Loss Absorbing Capacity (TLAC) agreed in 2015 as well as IFRS 9, enacted by the International Accounting Standards Board (IASB) in July 2014.
- Call for Evidence – the package seeks to develop a more proportionate application of the Single Rulebook to smaller banks, an issue identified in the Commission's Call for Evidence held in 2015.
- Basel IV? – the package is implementing the Basel standard on the Fundamental Review of the Trading Book (FRTB) through changes to the market risk framework. Not being part of the Basel III framework, the financial industry sees it as the first part of 'Basel IV' implemented in EU law.
The package is composed of the following legal instruments:
- Proposal amending the Capital Requirements Directive IV
- Proposal amending the Capital Requirements Regulation (CRR II)
- Proposal amending the Single Resolution Mechanism Regulation (SRMR)
- Proposal amending the Bank Recovery & Resolution Directive (BRRD) to implement TLAC
- Proposal amending the Bank Recovery & Resolution Directive (BRRD) to address creditor hierarchy
Key elements – an overview
The package introduces a large number of new issues that have an impact on the regulation, supervision and resolvability of banks:
Political environment and dynamics in the European Parliament & Council
Now that the Commission has unveiled its proposals, the European Parliament and the Council will start their internal negotiations to agree on the various proposals in the package. Past experience shows that the EU legislative apparatus can take on average between 1.5 and 3 years to agree on major packages of financial legislation.
An additional 18 months may be needed to finalise the necessary Level 2 rules that will contain the final detail. Bearing this in mind, this is probably the last package of this scale proposed by the current Commission before the European Parliament elections of May 2019. The package will be discussed in a political environment shaped by several key dynamics.
Banking Union
Following the Eurozone crisis, the Commission under President Juncker decided to implement the recommendations of the Five Presidents Report published in July 2015. In November 2015, it proposed a common deposit insurance scheme covering Member States from the Eurozone. That proposal has become entangled in deadlocked negotiations in the Council between two groups of Member States with diametrically opposed views.
Germany and several other Member States are keen to see a reduction of the risk in the European banking sector before any form of risk mutualisation with fiscal implications at Eurozone level. On the other hand, France, Italy and Spain see accelerated risk mutualisation as the way to relieve market pressure from indebted Eurozone countries and as a critical way of reducing the risky nexus between banks and sovereigns.
This rift is already emerging around the new package where Germany feels banking regulators should be able to apply specific measures to each bank that may go beyond requirements in EU rules and the international TLAC standards. France and Italy on the other hand viewed the TLAC as an absolute maximum not to be exceeded by European regulators. The ability of regulators to apply more institution-specific measures may be part of a trade-off around how to address the Too-Big-To-Fail (TBTF) challenge. If allowed, this may provide sufficient political backing for the withdrawal of the proposal on bank structural reform (BSR) that has been hopelessly blocked in the European Parliament since May 2015.
If the package becomes politically closely interlinked with EDIS, there is a real risk that negotiations will advance at a very slow pace – bar a Eurozone crisis of the magnitude of 2011-12. This in turn means that the EU is unlikely to have its regulatory framework operational in line with its international commitments around Basel III and the TLAC agreement. If the package is to be adopted swiftly enough, it will be critical to keep it politically separate from the EDIS discussions. However, France, Italy and Spain may seize the opportunity of the package – perceived as disproportionately affecting their large banks – to push for significant progress on EDIS in exchange.
Finally, in the middle of this Eurozone 'thug of war' it raises serious questions about the ability of the non-Euro Member States – in a context of Brexit – to ensure their specific issues and concerns are reflected in a Single Rulebook that applies to all 28 Member States.
International competitiveness
In recent years large European investment banks seem to have been losing out to their US-based rivals. They have repeatedly complained they face unfair competition because of a more stringent regulatory framework and regulatory barriers when operating in the US.
The Commission's proposal contains rules on the need for global systemically important non-EU banks to have holdings in the EU that comply separately with capital and liquidity requirements. These rules are perceived as mirroring rules proposed by the US Federal Reserve in 2014 and as anti-American.
The issue of competitiveness is not new. It became an issue in 2015 during the negotiations around the BSR proposal where attempts were made to include subsidiaries of global systemically important non-EU banks in the scope of provisions on the separation of certain trading activities.
The election of Donald Trump as the next President of the US will not facilitate this dialogue as his administration is expected to push for the repeal of key parts of the Dodd-Frank Act. Additionally, steps by the US Department of Justice to impose a $14bn fine on Deutsche Bank is equally perceived as heavy-handed and distorting the level-playing field.
This may have two major impacts on the negotiations. The EU is likely to deviate more openly from international agreements when deviating support its competitiveness agenda. This in turn will contribute, along with the repeal of parts of Dodd-Frank by the future US administration, to a fragmentation of the international regulatory framework. This could become a major problem for banks operating internationally. And this is particularly important for the future outcome of ongoing negotiations on 'Basel IV' standards where the EU and the US find themselves on opposite sides of the argument.
This new package adds an additional layer of complexity for large banks based in the UK. Bearing in mind the political complexity of the package and the fact that Level 2 legislation takes on average an additional 18 months to design, it seems very unlikely the EU legislative apparatus will deliver fully implemented and operational legislation by 2019 when, based on the current timetable, the UK is due to leave the EU.
Where should these banks then turn for guidance on future rules? The UK Government and Parliament will not be able to start discussions on future rules implementing Basel III and TLAC in the UK as long as the UK is a member of the EU. On the other hand, in the context of Brexit, UK-based banks may see their ability to effectively influence the outcome of EU legislation much reduced. And when you add into the equation the future 'Basel IV' rules currently being developed the regulatory uncertainty seems daunting.
This is quite an outcome when the regulatory rhythm in the aftermath of the Global Financial Crisis is supposed to have slowed down significantly.
How can Hume Brophy help?
We offer to our clients a unique combination of high-level political connectivity and capacity to analyse EU, UK and international politics with a deep understanding of the EU regulatory framework for financial services. This allows us to advise clients on how to position themselves and interact with policymakers, politicians, regulators and civil society in an increasingly complex and uncertain world.


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I can't believe that they did this!
Like you Thinkintuit I had volumes of notes in my file's 'properties'. Reference numbers, parts numbers, customer's coordinates etc etc etc ........ since upgrading to 12.04 THEY'VE GONE
If anyone else finds a simple, non-technical way of getting the info back ...... please, please post the solution here.


text:
To George Washington from William Blodget, 18 August 1776
From William Blodget
Long Island Augt 18. 1776
Colonel Hands report, mentions no Uncommon movements of the Enemy.
The General desires me to acquaint your Excellency that he finds himself considerably better this Morning than he was Yesterday, and is in hopes in a few days, to be able to go abroad, 'tho still very weak. I am with Respect Humble Servant
Wm Blodget A.D. Camp


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Dr. Anthony J Alario is a Professor of Pediatrics at University of Massachusetts Medical School. He also acts as Chief of Pediatric Rheumatology department at UMass Memorial Medical Centre. His major research interests are Pediatric Rheumatology, Juvenile Arthritis, Vasculitis. He has authored about 70 National and International publications and many books.
Research Interest
Rheumatology, Juvenile Arthritis, Vasculitis
Global Experts in the subject
Stefano Stagi Won-Ho Hahn, PhD
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As a wildlife rehabilitator since 1978, founder Sally Maughan started The Idaho Black Bear Rehab program in 1989 with the arrival of the first orphaned black bear cub. She began developing rehab techniques for orphaned cubs at a time when it was believed impossible to successfully release any bear raised by a human. Prior to that, the only rehab available to orphaned cubs was the occasional bear biologist. Wildlife agencies believed that an orphaned cub raised by a human would either starve to death or become a problem bear if released. Then, as now, it was difficult to find a zoo or wildlife park that would take these orphaned cubs. The only other options available were to humanely euthanize the cub or leave it in hopes it would survive. Chances are lingering starvation or depredation would kill the cub.
It was understandable that state wildlife agencies had concerns about releasing a bear capable of doing serious damage or hurting someone, especially since they hadn't tried it. As the primary caretaker of these orphaned cubs, Sally knew it was important to learn as much as she could about bears to prevent that from happening. She recognized there were many variables that could impact the success. Certainly it was expected there might be some failures, but hopefully they would be few and far between.
Sally started her journey by learning as much as she could from John Beecham, one of the top black bear experts in the country. She read everything she could find on bears to help her establish a platform from which to begin the rehab program. After spending thousands of hours observing the cubs during all times of day and night during the first five years, it was easy to recognize what behavior to expect and when to expect it. She was able to identify the stages of development the cubs went through during the first year of their life. It became easier to pinpoint unusual behavior, determine the cause, and try to offset it using various rehab techniques. She also came to understand there was a strong relationship between the personalities of each bear and the likelihood of that bear causing a problem when released.
Today the IBBR accepts orphaned cubs from Idaho and the surrounding Western states. While we cover all the rehab expenses for each bear during the time they are with us, we do require that each bear return to it's home state for release. When possible with the use of volunteers, we will assist in transporting the cubs to Idaho by meeting the officers part way. Depending on the schedule of our release team, we also offer wildlife agencies assistance releasing cubs when they leave the program.
Since 1989, IBBR has accepted cubs from Washington, Oregon, Utah, Wyoming, California, Nevada, and Idaho. As wildlife agencies become comfortable with the success of rehab and release, it is our hope they will consider starting their own rehab program. Our role then becomes one of consultation with both the wildlife agencies and the wildlife rehabilitators. Finding a wildlife rehabilitator to take orphaned cubs can be difficult. Most take care of many species and devoting the time, money, and work to focus on bears for eight or nine months of the year isn't always possible. Understandably, wildlife agencies prefer someone experienced in handling bears. Finding that experience is unlikely since orphaned cubs in the past were never considered candidates for rehab. Today there are still a very limited number of wildlife rehabilitators allowed to take orphaned cubs.


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5536 CHESTER AVE, Philadelphia, Pennsylvania
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Listing Courtesy of George A Moscony Real Estate
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A main in Business Law will deliver you with a solid understanding of the Australian legal method and how it impacts on business and commercial transactions. There are a number of routes that can be followed immediately after the degree – the expert routes are the Bar Skilled Education Course (BPTC) or Legal Practice Course (LPC) for the Bar or Solicitors' Profession, respectively. For your next legal concern with your business seek advice from the Kelowna lawyers with the knowledge and dedication you need to have.
Senior Law Lecturer, Director of Studies for single honours full time LLB (Hons), admissions tutor for the LLB (Hons) and member of London South Bank University's Employability Committee. These advanced courses enable prepare students to enter into business law practice with a broad exposure to the relevant interconnected bodies of substantive law, and an understanding of how prosperous business lawyers practice their profession. Our knowledgeable group of Kelowna Lawyers can assistance you with your next business transaction.
Students will also advantage from guest seminars with professionals from legal and business practice, relevant Government departments, regulatory bodies and legal practitioners and international specialists in this field. Our Law department has set up a placement programme in conjunction with Southwark Council which has proved to be a massive accomplishment. This area of law involves contracts, employment law, intellectual property , real estate, bankruptcy and several other regions of the law. Business Law is a little, friendly programme in which supporting students as people is emphasised and a focus is place on establishing important employability capabilities.
This involves all of the laws that govern how to begin, get, manage and close or sell any kind of business. The sort of career on provide can depend on the type of law firm you want to perform for, and possibly the location of law you specialise in. And alternatives are not confined to the legal solutions sector either, due to the variety of transferable capabilities gained from the course. Jennifer and Wayne are assisted by an editorial board of experts in international business law.
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text:
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An accurate description of changes in the brain in healthy aging is needed to understand the basis of age-related changes in cognitive function. Cross-sectional magnetic resonance imaging (MRI) studies suggest thinning of the cerebral cortex, volumetric reductions of most subcortical structures and ventricular expansion. However, there is a paucity of detailed longitudinal studies to support the cross-sectional findings. In the present study, 142 healthy elderly participants (60–91 years) were followed with repeated MRI, and were compared to 122 patients with mild to moderate Alzheimer's disease (AD). Volume changes were measured across the entire cortex and in 48 regions of interest (ROIs). Cortical reductions in the healthy elderly were extensive after only one year, especially evident in temporal and prefrontal cortex where annual decline was about 0.5%. All subcortical and ventricular regions except caudate nucleus and the 4th ventricle changed significantly over one year. Some of the atrophy occurred in areas vulnerable to AD, while other changes were observed in areas less characteristic of the disease in early stages. This suggests that the changes are not primarily driven by degenerative processes associated with AD, although it is likely that preclinical changes associated with AD are superposed on changes due to normal aging in some subjects, especially in the temporal lobes. Finally, atrophy was found to accelerate with increasing age, and this was especially prominent in areas vulnerable to AD. Thus, it is possible that the accelerating atrophy with increasing age is due to preclinical AD.
An accurate description of age-related changes in the brain is needed to better understand the neurobiological foundation of cognitive changes in healthy aging. While cross-sectional magnetic resonance imaging (MRI) studies have demonstrated consistent age-effects (Allen et al., 2005; Fjell et al., 2009-a, b; Raz et al., 2004; Raz and Rodrigue, 2006; Salat et al., 2004; Walhovd et al., 2005; Westlye et al., 2009), longitudinal MR studies have often been limited by relatively small numbers of participants and use of either global measures (e.g. whole-brain volume) or only a restricted set of regions of interest (ROIs). Further, while atrophy has been demonstrated in mild cognitive impairment over a year or less (Schuff et al., 2009), it is not known whether brain changes driven solely by normal aging are large enough to be detectable over such short time intervals.
Longitudinal studies have reported annual gross brain volume decreases on the order of 0.2 – 0.5% (Enzinger et al., 2005; Ezekiel et al., 2004; Fotenos et al., 2005; Scahill et al., 2003), while hippocampus, the most studied structure, shows annual atrophy rates from 0.79% to 2.0% (Barnes et al., 2009; Du et al., 2006; Ezekiel et al., 2004; Jack et al., 1998; Raz et al., 2005b; Scahill et al., 2003). This tends to be higher than cross-sectional estimates (Du et al., 2006; Raz et al., 2005a; Scahill et al., 2003). Entorhinal cortex longitudinal decline is about 0.3% to 2.4% (Du et al., 2006; Du et al., 2003; Ezekiel et al., 2004; Raz et al., 2005a). Atrophy rates in other parts of the brain are seldom studied, with a few important exceptions (Driscoll et al., 2009; Pfefferbaum et al., 1998; Raz et al., 2005a; Resnick et al., 2003). These studies describe atrophy in several regions, with prominent decline in prefrontal cortex, as well as decline in caudate nucleus, cerebellum, hippocampus and association cortices (Raz et al., 2005b) and parietal areas (Resnick et al., 2003), in addition to expansion of the ventricles (Pfefferbaum et al., 1998). In a recent study, significant atrophy was found in all 25 regional brain volumes tested, but over time periods extending as long as ten years in some cases (Driscoll et al., 2009). An earlier study found significant ventricular enlargement over one year, but no detectable change in total or regional brain volumes (Resnick et al., 2000).
With newer analyses techniques, we may now possess the tools necessary to detect brain changes over short time intervals in healthy elderly. The aims of the present study were to determine whether brain changes in normal aging can be detected over one (n = 142) or two (n = 89) years, and if so, to determine which areas show the greatest changes, and whether rate of atrophy increases with age. A novel procedure for longitudinal change analysis was used, which enabled measures of change continuously across the cortex, as well as in 48 regions of interest. Atrophy in the healthy elderly was compared to 122 patients with mild to moderate Alzheimer's disease (AD).
The raw data used in the preparation of this article were obtained from the ADNI database (www.loni.ucla.edu/ADNI). ADNI was launched in 2003 by the National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), the Food and Drug Administration (FDA), private pharmaceutical companies and non-profit organizations. The primary goal of ADNI has been to test whether serial MRI, PET, other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of MCI and early AD. The Principal Investigator of this initiative is Michael W. Weiner, VA Medical Center and University of California — San Francisco. There are many co-investigators, and subjects have been recruited from over 50 sites across the U.S. and Canada. The initial goal of ADNI was to recruit 800 adults, including healthy elderly, MCI and AD patients to participate and be followed for 2–3 years. For more information see www.adni-info.org.
ADNI eligibility criteria are described at http://www.adni-info.org/index.php?option=com_content&task=view&id=9&Itemid=43. Briefly, participants are 55–90 years of age, had an informant able to provide an independent evaluation of functioning, and spoke either English or Spanish. All subjects were willing and able to undergo test procedures including neuroimaging and agreed to longitudinal follow up. Specific psychoactive medications are excluded. General inclusion/exclusion criteria are as follows for normal subjects: Mini-Mental State Examination (MMSE) (Folstein et al., 1975) scores between 24–30 (inclusive), Clinical Dementia Rating (CDR) (Morris, 1993) of 0, non-depressed, non-MCI, and nondemented. In addition, CDR sum of boxes (CDR-sb) was calculated as a measure of clinical functioning (does not need to be zero). To minimize the possibility of including individuals with early, preclinical AD, only participants who had the same or better score on CDR-sb at the time of follow up were included. The subject pool was further restricted to those subjects for whom adequate processed and quality checked MR data were available by February 2009. Sample characteristics are presented in Table 1.
To be able to compare atrophy in the healthy elderly with AD patients, an AD group was included for selected analyses (n = 122, 57 females/ 65 males, at 1 year follow up: age = 76.5 (56.0–90.0), MMSE = 20.7 (8–29), CDR = 1.0 (0.5–3.0), CDR-sb = 5.88 (1–14)). These patients met the same eligibility criteria as the healthy elderly, had CDR scores of 0.5 or more, and met NINCDS/ ADRDA criteria for probable AD (McKhann et al., 1984). As the mean age (76.5 vs. 76.7 years, respectively) and the female/ male ratio (0.88 vs. 0.92) was almost identical between AD patients and healthy elderly, these variables were not regressed out in the analyses.
All scans used for the present paper were from 1.5 T scanners. Data were collected across a variety of scanners with protocols individualized for each scanner, as defined at http://www.loni.ucla.edu/ADNI/Research/Cores/index.shtml. Raw DICOM MRI scans (including two T1-weighted volumes per case) were downloaded from the public ADNI site (http://www.loni.ucla.edu/ADNI/Data/index.shtml) and processed as described elsewhere (Fennema-Notestine et al., 2009). Briefly, these data were reviewed for quality, automatically corrected for spatial distortion due to gradient nonlinearity (Jovicich et al., 2006) and B1 field inhomogeneity (Sled et al., 1998), registered, and averaged to improve signal-to-noise. Scans were segmented as described previously (Fischl et al., 2002, 2004) to yielding data for 11 different volumetric ROIs and four ventricular ROIs (right and left hemisphere regions measured separately), including the hippocampal formation (consisting of the dentate gyrus, CA fields, subiculum/ parasubiculum and the fimbria (Makris et al., 1999)). The cortical surface was reconstructed using a semi-automated approach described elsewhere (Dale et al., 1999; Dale, 1993; Fischl and Dale, 2000; Fischl et al., 1999a; Fischl et al., 1999b; Salat et al., 2004), and parcellated as described in Fischl et al. (Fischl et al., 2004), labelling 33 cortical sulci and gyri (Desikan et al., 2006). The exact anatomical borders for the cortical ROIs can be found in Desikan et al., e.g. for the transverse temporal cortex (the rostral boundary was the rostral extent of the transverse temporal sulcus, the caudal boundary was the caudal portion of the insular cortex, and the lateral fissure and the superior temporal gyrus were utilized as the medial and lateral boundaries, respective) and isthmus of the cingulate cortex (the rostral and caudal boundaries were the posterior division of the cingulate cortex and the parahippocampal gyrus, respectively, and the medial and lateral boundaries were the medial wall (area unknown) and the precuneus, respectively). These surface-based cortical ROIs were thus generated by a different procedure from that used to estimate the other (volumetric) ROIs, which included the hippocampus, the cerebellum GM, nine subcortical ROIs and four ventricular ROIs.
For the analyses of the longitudinal volume changes, each participant's dual 3-D follow-up structural scans were rigid-body aligned, averaged and affine aligned to the baseline scan. Nonlinear registration of the images was then performed, where voxel centers are moved about until a good match between the images is made. Several methods exist for effecting this, including fluid deformation (Christensen et al., 1996; Freeborough and Fox, 1998; Miller et al., 1993) and tensor-based morphometry (TBM) (Ashburner et al., 1999). For the results presented here, however, we applied a method (Holland et al., 2008) based on linear elasticity and closer in spirit to TBM. It proceeds essentially as follows. The images are heavily blurred (smoothed), making them almost identical, and a merit or potential function calculated. This merit function expresses the intensity difference between the images at each voxel, and depends on the displacement field for the voxel centers of the image being transformed; it is also regularized to keep the displacement field spatially smooth. The merit function by design will have a minimum when the displacement field induces a good match between the images. The displacement field in general will turn cubic voxels into displaced irregular hexahedra whose volumes (Grandy, 1997) give the volume change field. The merit function is minimized efficiently using standard numerical methods. Having found a displacement field for the heavily blurred pair of images, the blurring is reduced and the procedure repeated, thus iteratively building up a better displacement field. Two important additions to this are: applying the final displacement field to the image being transformed, then nonlinearly registering the resultant image to the same target, and finally tracing back through the displacement fields thus calculated to find the net displacement field; and restricting to regions of interest and zooming when tissue structures are separated by only a voxel or two. These additional features enable very precise registration involving large or subtle deformations, even at small spatial scales with low boundary contrast. Although large deformations are allowed by multiple nonlinear registration (or relaxation) steps, nonphysical deformations are precluded because at each level of blurring the image undergoing deformation is constrained to conform to the target. Note that calculating the deformation field does not depend on initially segmenting tissue. This deformation field was used to align scans at the sub-voxel level.
The follow-up aligned image underwent skull stripping and volumetric segmentations (subcortical structures, as well as hippocampus and cerebellum GM), with labels applied from the baseline scan. For the cortical reconstructions, surface coordinates for the white matter and pial boundaries were derived from the baseline images and mapped onto the follow-up images using the deformation field. Parcellations from the baseline image were then applied to the follow-up image. This resulted in a one-to-one correspondence between each vertex in the base image and the follow up image. The procedure produces an estimate of the percent cortical volume loss at each vertex and within each ROI. To the extent that regional cortical areas are relatively stable across time points, the volume change is likely driven almost exclusively by changes in thickness. The method has been validated in model studies of complex spherical-shell geometries with low contrast and noise, where a prescribed volume change is numerically estimated to accuracies of within 0.5% (Holland et al., work in progress).
A challenge in cross-sectional MR studies of aging is that the contrast between GM and WM decreases with higher age (Salat et al., 2009). However, the longitudinal registration relies on matching intensities in serial images. A reduction in GM/ WM contrast in elderly relative to younger participants should not impact the quality of the nonlinear registration, as long as the serial images have constant contrast. Change in cortical volume to 1st order arises from change in cortical thickness. To estimate it, the volume change field is sampled midway through the cortical layer. Conceivably, the primary source of error in elderly, relatively to younger participants, would then be in the initial delineation of the cortical surface. However, it has recently been shown that the decrease in GM/ WM contrast can not explain the differences in cortical thickness between older and younger participants (Westlye et al., 2009).
Statistical analyses were performed by use of FreeSurfer (http://surfer.nmr.mgh.harvard.edu/) and SPSS 15.0. To reduce the number of comparisons, mean values of the left and right hemisphere were used for the ROI analyses. For the healthy elderly and the AD patients, change in brain morphometry was calculated as percentage change relative to baseline (1 and 2 years for the healthy elderly, 2 years for the AD patients). For the healthy elderly, statistical parametric continuous surface maps were computed by general linear models (GLM) implemented in FreeSurfer and displayed on a semi-inflated template brain. The results were thresholded by a conventional criterion for correction for multiple comparisons (false discovery rate [FDR] < .05). For the healthy elderly and the AD patients, one-sample t-tests were used to test whether longitudinal atrophy rates within each ROI were different from zero. Independent-samples t-tests were used to compare rate of atrophy in healthy controls and AD patients. To visualize the areas that showed more than average and the areas that showed less than average atrophy as surface maps, mean cortical atrophy was calculated for each hemisphere in each group. This value was subtracted from the original surface maps, yielding a new map showing relative atrophy. To test whether the magnitude of atrophy in the temporal lobe vs. the prefrontal cortex differed between the healthy elderly and the AD patients, ANOVA with 2 groups × 2 regions were performed. Temporal lobe atrophy was calculated as mean rate of atrophy in inferior and middle temporal, entorhinal, parahippocampal, temporal pole, and fusiform cortex, as well as hippocampus and amygdala. Prefrontal atrophy was calculated as mean rate of atrophy in caudal and rostral anterior cingulate, caudal and rostral middle frontal, pars opercularis, triangularis and orbitalis (together forming the inferior frontal cortex), lateral, dorsal and medial orbitofrontal, frontal pole and superior frontal cortex (see Figure 4). Finally, Pearson correlations were performed between age and atrophy in each of the 48 ROIs in the healthy elderly.
The statistical significance of 1 and 2 year volume changes in cortex across the brain surface is shown in Figure 1. As can be seen, large cortical areas decreased significantly over 1 year. These reductions were most prominent in the temporal lobe, the medial part of the superior frontal gyrus, orbitofrontal, precuneus, supramarginal and inferior parietal, as well as the inferior and part of the middle frontal cortex. Lateral parts of the superior frontal cortex, as well as pre- and post-central gyrus, superior parietal areas, occipital cortex and lingual gyrus were largely spared. Over two years, the effects were stronger and spread to additional areas, involving all cortical areas except lingual cortex and pre- and postcentral gyrus.
Percentage volume change in cortex over 1 and 2 years is shown in Figure 2. Annual atrophy rates varied across the cortex, but were typically around 0.5 % in affected areas, including most of the lateral and inferior parts of the temporal lobes, supramarginal gyrus, inferior parietal gyrus, precuneus, inferior and middle frontal gyrus as well as the medial parts of the superior frontal gyrus. Atrophy over 2 years exceeded 1.0 % in large areas.
For comparison purposes, rate of atrophy is presented for AD patients in Figure 2. Atrophy in the AD group was much larger than in the healthy elderly, with most areas showing 1% annual change or more. This was especially evident in the lateral temporal cortex and an area around posterior cingulate/ inferior precuneus/ retrosplenial cortex (> 2.5% annual change). Less atrophy was seen around the central sulcus, pericalcarine sulcus and lingual gyrus. To compare the pattern of atrophy between the healthy controls and the AD patients, mean cortical atrophy was calculated for each hemisphere in each group. This value was subtracted from the surface maps, yielding a new map highlighting areas that show greater and lesser rates of atrophy than average for that group. These maps illustrate the parts of the cortex that show relatively higher and relatively lower rates of atrophy within each group (Figure 3). Within the AD group, higher than average atrophy was seen in the inferior and middle temporal gyrus. Within the healthy elderly group, higher than average atrophy was observed in the same areas, but also in the temporal pole, medial orbitofrontal, rostral middle frontal and supramarginal cortex, as well as parts of the medial superior frontal gyrus. Less than average atrophy was seen in cuneus, pericalcarine sulcus, lingual gyrus as well as the central sulcus. Results of formal statistical tests of differences in rates of atrophy between healthy controls and AD patients are described below.
Percentage annual volume change in each of the 48 ROIs is shown in Table 2 for healthy elderly. Median atrophy for 1 year was −0.38 %, not including the ventricular ROIs. Hippocampus (−0.84 %) and amygdala (−0.81 %) showed the largest reductions, followed by thalamus (−0.69 %). Cerebellum grey matter (−0.35 %), the brain stem (−0.31 %) and caudate nucleus (−0.24 %) showed the least 1 year change of the volumetric ROIs. The inferior lateral (5.47 %), lateral (4.40 %) and the 3rd (3.07 %) ventricles showed the largest changes overall, with no significant change in the 4th (0.71 %) ventricle. Of the cortical ROIs, the frontal pole (−0.59 %), temporal pole (−0.56 %), banks of the superior temporal sulcus (−.55 %), and entorhinal cortex (−0.55 %) changed the most, while post central, pericalcarine, lingual, cuneus and precentral were well preserved (≤ 0.1 %).
For comparison purposes, 1 year volume change in each ROI was calculated for the AD group also (Table 3). All ROIs except the pericalcarine sulcus showed significant change. Median atrophy for 1 year was −1.20 %, not including the ventricular ROIs. Amygdala (−3.79 %) and hippocampus (−3.75 %) largest reductions, followed by inferior and middle temporal gyri (−2.97 and −2.87%, respectively). Also entorhinal and parahippocampal cortex showed well above average atrophy (−2.42 and −2.05%, respectively). Pericalcarine (−0.16%), postcentral (−0.27%) and cuneus (−0.5%) were the three ROIs showing the least atrophy, but of these only pericalcarine did not change at p < .01 (p = .030). The inferior lateral (16.26 %), lateral (10.35 %) and the 3rd (6.82 %) ventricles showed the largest changes overall.
Differences in rates of atrophy were formally tested between healthy elderly and AD patients. AD patients had significantly (p < .01) higher rates of change than the healthy elderly for all ROIs except 4th ventricle (Supplementary Table 1). In terms of t-scores, inferior temporal (t = 13.25), fusiform (t = 13.15) and middle temporal (t = 12.81), parahippocampal (t = 12.69) and entorhinal (t = 11.93) showed the largest effects of the cortical ROIs, while hippocampus (t = 12.80), the inferior lateral ventricles (t = 9.74) and amygdala (t = 8.32) showed the largest effects for the volumetric ROIs.
Interaction between the groups and temporal vs. frontal atrophy rates were tested by ANOVA with two groups (healthy elderly, AD) × two brain regions (frontal, temporal). A highly significant interaction was found (F [1, 256] = 119.78, p < 10−22), caused by a higher rate of temporal than frontal atrophy in the AD group and a comparable rate of temporal vs. frontal atrophy rate in the healthy elderly (Figure 4).
Correlation analyses between age and 1 year atrophy in each of the ROIs were performed. The results are presented in Table 4 and scatterplots for selected structures in Figure 5. We focus here on the 1 year changes, since the statistical power was lower for 2 years. Significant correlations between age and rates of atrophy were found for 32 ROIs. For the volumetric structures, hippocampus, cerebellum grey and white matter, cerebral white matter, thalamus and pallidum atrophy were related to age, as was expansion of the inferior lateral ventricles. Of the cortical structures, regions demonstrating significant relationships between age and rate of atrophy included entorhinal, transverse temporal, pars opercularis, isthmus cingulate, middle temporal, pars triangularis, banks of the superior temporal sulcus, parahippocampal, superior temporal, posterior cingulate, caudal middle frontal, precentral, fusiform, inferior parietal, temporal pole, precuneus, supramarginal, lateral orbitofrontal, superior parietal, post central, caudal anterior cingulate, medial orbitofrontal, pericalcarine, lateral occipital and inferior temporal cortices.
Volumetric reductions of the cerebral cortex and subcortical brain structures, as well as expansion of the ventricles, were seen in healthy aging after only one year. While this has been shown previously for MCI and AD patients (McDonald et al., 2009; Schuff et al., 2009), the present report is the first to demonstrate detectable atrophy in a range of brain areas over only one year in healthy participants. Some of the changes seen, e.g. in the temporal lobe, may be due to preclinical AD, while others, e.g. in the prefrontal cortex, likely reflects the non-pathological aging process. This is discussed below.
The present atrophy rates for hippocampus (0.84%) and entorhinal cortex (0.55%) are comparable to previous studies (Barnes et al., 2009; Du et al., 2006; Du et al., 2003; Ezekiel et al., 2004; Jack et al., 1998; Raz et al., 2005a; Raz et al., 2005b; Scahill et al., 2003), supporting the feasibility of pooling data across multiple sites resulting in sensitive and realistic atrophy estimates. Generally, volumetric ROIs showed more decline than surface-based cortical ROIs, with the hippocampus showing the greatest one year reduction. Hippocampal volume has been found to correlate with age in cross-sectional (Good et al., 2001; Raz et al., 2004; Walhovd et al., 2005) and longitudinal studies (Driscoll et al., 2009; Du et al., 2006; Ezekiel et al., 2004; Jack et al., 1998; Raz et al., 2005b; Resnick et al., 2003; Scahill et al., 2003), but usually not more strongly than the other volumetric structures measured (Raz et al., 2005b). However, in a recent cross-sectional multi-sample study, estimated percentage decline per decade in the later half of the life-span was larger for hippocampus than any other volumetric structure (Walhovd et al., in press). In the present study, amygdala, thalamus, putamen and pallidum also showed longitudinal decline. Several cross-sectional studies have shown substantial reductions in the volumes of thalamus, amygdala and putamen (Greenberg et al., 2008; Gunning-Dixon et al., 1998; Raz et al., 2003; Sullivan et al., 2004; Van Der Werf et al., 2001; Walhovd et al., 2005; Walhovd et al., in press), as well as in pallidum after 50 years of age (Walhovd et al., 2005; Walhovd et al., in press), but discrepant findings regarding thalamus and pallidum have been reported (Gunning-Dixon et al., 1998; Jernigan et al., 1991; Jernigan et al., 2001; Luft et al., 1999; Raz et al., 2003).
Hippocampus and amygdala were the two volumetric structures that showed the largest annual decline in the present study, and these are known to show accelerated atrophy early in AD (Barnes et al., 2009; de Leon et al., 1989; Fennema-Notestine et al., 2009; Fischl et al., 2002; Jack et al., 1999; McDonald et al., in press). A recent meta-analysis estimated annual hippocampal reductions to be 4.66% in AD (Barnes et al., 2009). These were also the ROIs showing the largest volume decrease in the AD patients in the present study, with annual rates of decline of 3.75% for hippocampus and 3.79% for amygdala in the AD sample. Of the surface-based cortical ROIs showing substantial decline, entorhinal, parahippocampal and lateral temporal, as well as inferior parietal, supramarginal and fusiform areas, are all found to be vulnerable in early stages of AD (Du et al., 2007; Fennema-Notestine et al., 2009; McDonald et al., in press; McEvoy et al., 2009; Singh et al., 2006). An important question regards the extent to which atrophy in these areas in healthy elderly is an indication of preclinical AD. We cannot rule out with certainty that degenerative processes associated with early AD caused some of the observed atrophy. However, reductions were also seen in areas relatively less affected by early AD. For instance, large effects were found in inferior, middle and superior frontal cortex. Previous studies of the ADNI sample did not find differences in thickness between single domain amnestic MCI and controls in these areas (Fennema-Notestine et al., 2009), nor did these areas show longitudinal increases in atrophy in MCI participants showing mild functional impairment (CDR-SB of 1 or less) (McDonald et al., in press). Still, a recent study found prefrontal cortical volume to predict dementia (Burgmans et al., 2009a), and AD involves frontal atrophy (Dickerson et al., 2008; Du et al., 2007; Fjell et al., 2008; Singh et al., 2006). An early longitudinal study found that while temporal atrophy was seen in presymptomatic and mildly affected patients, frontal involvement occurred later in the disease (Scahill et al., 2002). Another study found demented patients to show annual atrophy rates exceeding 0.4% in large areas of the brain, including the frontal cortex (Buckner et al., 2005). In the present study, more atrophy was observed in AD than in healthy controls in almost all ROIs, including prefrontal cortex. However, temporal lobe atrophy was the most prominent in AD, while healthy aging was characterized by comparable rates of atrophy in the temporal lobe and the frontal cortex. The temporal changes seen in the healthy elderly group may be related to instances of preclinical AD, while the frontal changes are more prominent than what would be expected due to AD. Significant decline was also observed in thalamus, accumbens and cerebral and cerebellar white matter; areas that are not among the most vulnerable in early phases of AD (Fennema-Notestine et al., 2009). In the AD patients included in the present study, cerebellum WM was the 39th most vulnerable region, while thalamus was the 22nd and accumbens the 14th. Thus, it is unlikely that all the brain changes found here in the healthy elderly group can be attributed to preclinical AD. We believe that many of the changes observed in healthy aging are caused by processes unrelated to degenerative disease. Consistent with this, a recent study reported that the transition from healthy elderly to MCI was associated with a unique pattern of longitudinal change, including increased ventricular size, and reductions in temporal grey matter, orbitofrontal areas and temporal association cortices, including the hippocampus (Driscoll et al., 2009). The pattern of atrophy over several years in healthy elderly not developing MCI was widespread but did not resemble the pattern associated with MCI (Driscoll et al., 2009). As further follow-up data become available, the hypothesis that the temporal changes seen in the elderly are related to preclinical AD, while the frontal changes are less associated with incipient disease, can be tested. Since it is possible that structural brain changes due to degenerative disease may be manifested long before cognitive symptoms are detectable, follow-up cognitive and clinical data for several years will be invaluable (Burgmans et al., 2009b).
Older age was related to increased atrophy and more ventricular expansion. This is consistent with cross-sectional reports of non-linear volumetric changes (Allen et al., 2005; Fjell et al., In press-b; Jernigan and Gamst, 2005; Walhovd et al., 2005; Walhovd et al., in press). However, cross-sectional studies of cortical thickness have mostly reported linear age-changes over the adult life-span (Fjell et al., in press-a; Salat et al., 2004). It is possible that longitudinal designs are more sensitive to accelerated decline in the oldest old, especially if the effects are of moderate strength and evident only in the latest part of the life-span. The correlations between age and rate of change seldom exceeded +/−.30. Interestingly, the strongest correlations between age and rate of atrophy were found in entorhinal cortex and the hippocampus, and significant correlations were also found in isthmus of the cingulate, middle temporal and parahippocampal gyri, all of which are affected in early stages of AD. Since the occurrence of preclinical AD is much higher among 70- and 80 year olds than among 50 and 60 year olds, it is possible that the pattern of accelerated longitudinal atrophy in aging is related to preclinical AD in a subgroup of the participants, even though cognitive symptoms are not yet manifested. This interpretation is in agreement with another recent study where elderly cognitively normal participants showed a pattern of atrophy more similar to that seen in AD than did younger participants, i.e., more temporal lobe atrophy (Davatzikos et al., 2009).
The present results show that widespread changes in brain structure can be found in healthy elderly over only one year, and that atrophy accelerates with advanced age. Some of the atrophy occurred in areas vulnerable to AD and some in areas less characteristic of the disease in early stages. This suggests that the changes are not primarily driven by degenerative processes associated with AD, although it is likely that preclinical changes associated with AD are superposed on changes due to normal aging in some subjects. Indeed, the pattern of accelerated atrophy with increasing age is probably influenced by occurrence of preclinical AD in a sub-group of the most elderly participants, and this may especially be reflected in the temporal lobe. Nevertheless, this study shows that decreases in brain volume in healthy aging can be observed in almost all brain areas over 1 to 2 years.
This work was supported by a grant (#U24 RR021382) to the Morphometry Biomedical Informatics Research Network (BIRN, http://www.nbirn.net), that is funded by the National Center for Research Resources at the National Institutes of Health (NIH), U.S.A, and by the National Institute on Aging at the NIH (U01 AG024904; R01 AG031224 and K01AG029218). The work of Walhovd and Fjell was supported by the Norwegian Research Council. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI; Principal Investigator: Michael Weiner; NIH grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering (NIBIB), and through generous contributions from the following: Pfizer Inc., Wyeth Research, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck & Co. Inc., AstraZeneca AB, Novartis Pharmaceuticals Corporation, Alzheimer's Association, Eisai Global Clinical Development, Elan Corporation plc, Forest Laboratories, and the Institute for the Study of Aging, with participation from the U.S. Food and Drug Administration. Industry partnerships are coordinated through the Foundation for the National Institutes of Health. The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory of Neuro Imaging at the University of California, Los Angeles. We thank Robin Jennings, Michele Perry, Chris Pung and Elaine Wu for downloading and preprocessing the ADNI MRI data. Data used in the preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu/ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators is available at http://www.loni.ucla.edu/ADNI/Data/ADNI_Authorship_List.pdf
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St. David's plans two freestanding ERs
St. David's HealthCare System is opening two emergency centers in Central Texas — the first freestanding emergency departments in the region.
Next year, St. David's plans to open a $7 million emergency center in Bee Caves at the Hill Country Galleria. The 10,000-square-foot Bee Caves emergency center will be associated with the St. David's South Austin Medical Center, which treated more adult patients than any other emergency department in Austin in 2009, according to St. David's.
St. David's will open another emergency center in Pflugerville at the Stone Hill Town Center, at the southwest corner of Texas 130 and Texas 45, in early 2012. That center, which will be affiliated with St. David's North Austin Medical Center, will have 12 treatment rooms capable of handling emergency medical services for dozens of patients a day. It will also include radiological testing and a medical lab.
Both emergency centers will be open 24 hours a day, seven days a week.
St. David's is opening the emergency centers in Pflugerville and Bee Caves because "these are fast-growing communities in need of enhanced services," said Mark Clayton, senior vice president of St. David's. "It really hits the bull's-eye, in terms of community need."
Emergency centers offer all of the services of a hospital emergency department without attached inpatient facilities.
Staffing for the Pflugerville emergency center will initially include about 50 employees, said Don Wilkerson, CEO of St. David's North Austin Medical Center. And the center will be staffed by physicians affiliated with Capitol Emergency Associates, the same group that provides physicians for the emergency departments at all St. David's hospitals.
St. David's North Austin Medical Center, which provides emergency care for residents of Pflugerville and its surrounding areas, has seen significant and sustained growth at its emergency department, Wilkerson said.
"The additional capacity being created in Pflugerville will allow us to accommodate continued growth in emergency services at the medical center as well," Wilkerson said. "With the opening of the freestanding emergency department in Pflugerville, we will be able to provide that same level of care for these patients closer to home, in their own community."
Health care has been growing in the area, said Patricia Gervan-Brown, president and CEO of the Pflugerville Chamber of Commerce.
"It accomplishes the goal of increasing health services in Pflugerville and adds to the many options — Scott & White, Austin Regional Clinic and Seton," she said.
Express MD recently opened an urgent care center in the area, and St. David's already has an urgent care center near Pflugerville.
Freestanding emergency medical centers are not new to Texas, but the licensing of these facilities is recent. Enacted in 2009 by the 81st Legislature, the Freestanding Emergency Medical Care Facility Act established licensing rules.
Matt Wall, associate general counsel of the Texas Hospital Association, said he expects that this legislation will spur further development of such centers.
For now, neither Seton Family of Hospitals nor Scott & White Healthcare, which is based in Temple, have freestanding emergency departments.
Establishing emergency medical centers is a good way for St. David's to build its presence in a market before it's able to support a hospital, Clayton said, adding: "I think it establishes a foundation for future growth ... that may include inpatient" services.


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Formula Fun, one of the UK's fastest growing children's entertainment concepts, with 42 operators appointed since its launch in 2004, is now ready to transform the Irish market. Every thing is now in place from finance for suitable applicants, to a comprehensive insurance package. If you are looking to take control of your future, reap the rewards of your hard work or just earn a little extra money, Formula Fun is here to help you.
Formula Fun is setting new standards in the children's entertainment industry across Ireland. Watch out bouncy castles, there is a new kid on the block!
Whether it is a Birthday party or a promotional event Formula Fun will leave a lasting memory, now you can too as a Formula Fun operator.
Are you?
- Looking to take control of your future, where you can be the boss and not the Apprentce?
- Looking to start a business, but a little unsure about giving up your steady income?
- Interested in working with children in a fun packed environment?
- Looking for the next innovation in a ever expanding market?
Do you want to start a business?
- That has low overheads
- Virtually no comparable competition
- Can be run from home
- Is non seasonal, operates inside or outside
- Can be started part time and expanded at your pace
- Where there is no obligation to buy stock
- No need for premises 24 hours a day 7 days a week
- No experience required, we teach you
- Which is cash rich, no debtors
Then Formula Fun may just be what you are looking for. Take a closer look.
Formula Fun is aimed at children in the 3 to 9 years age group boys and girls. We entertain them using unique battery powered commercial Go Karts, pattern protected, but rest assured they are very safe hence our competitive insurance premium. We can operate outside, in a garden or a field, or inside in a school hall or leisure centre. Our karts are welcome in halls and shopping centres because they are safe, controlled and leave a minimal carbon footprint.
Ours is not a seasonal business, but it has seasons:
Birthday parties: September to June
Fetes, shows & carnivals: June to October
Corporate events: All year round
Formula Fun are now appointing operators who will be assigned large protected territories with populations in excess of 100,000 people. Only 32 operators will be appointed in Ireland (26 in the south and 8 in the north) and we already have 2 appointed so that only leaves 30.
Franchising is a growing industry and children's franchise's are virtually recession proof, if you are a parent just ask yourself, would I make sacrifices to make my children happy? I bet you would.
If you like working with children and enjoy having fun then why not contact us by filling in the form below and we will be in touch.
Success Stories
- The Winning Formula read
Contact Information
|View Some of our Franchise Videos for more inspiration. More
Practical advice and help for anyone considering franchising and starting a business. Click here
Find out more about the pros and cons of franchsing and how to develop a profitable business. More
Why not have a look at our digital magazine for more information. Please click HERE
Our dedicated online marketplace focused on the sale of existing franchises click here
|Check out these master franchise opportunities from all around the world more


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vidmate apk download : Vidmate is an application which is known to...
A security vulnerability that has, for a brief amount of time, left over a billion facebook users' accounts in jeopardy, was revealed by a Bangalore based security engineer who posted this entire scenario to hack facebook accounts in his post titled "How I could have hacked all Facebook accounts".
About the Hacker : Anand Prakash, works at Indian commerce company Flipkart as a Security engineer. Fortunately, for all of us, the guy is a White Hat hacker also called Bounty Hunters, who reported the flaw soon as he discovered it to the officials at Facebook. Facebook, which was thoroughly baffled by this, rewarded Anand Prakash with a decent $15000 and rectified the security weak link after it was active and functioning for about 2 days.
What's scary is the fact that he could have turned into a millionaire had he not notified this to Facebook and instead broke the news/ the trick to hack facebook accounts to the malicious hackers' network.Android apps spying on your texts
Where the Facebook security flaw lies : This trick that allows to hack facebook accounts, comes down to the very first step that a user takes when he forgets his/ her password. That's right. The flaw lies in the password-reset window.
Facebook asks for the user's Email, phone number in order to reset the password in the event of pressing "Forgot password." Facebook then sends a 6 digit code to the user's mobile or to their email which he/ she will have to type in to proceed further for resetting the password. It's standard procedure.Paid Playstore apps for free
But Facebook only allows up to a dozen times to enter the right code, after which it gets blocked to ensure the genuinity/ security of that account.
And this is where Anand Prakash found the exploit to hack facebook accounts.
Anand found a glaringly obvious mistake that Facebook overlooked.ICC World T20 2016
Facebook Beta's major flaw : Facebook has the brute-force protection that allows only a dozen chances to enter the right code, but this security measure was missing in the beta version of Facebook: beta.facebook.com
Anand Prakash went ahead with his code-guessing/ Brute force approach in the beta version of Facebook and realized that there is no limit to the number of times for guessing the 6 digit code(sent to the user's phone or email).
Burp Suite tool to Hack Facebook accounts : Now to guess a 6 digit code is relatively tough, as only one out of 1000000 would be right. Hence he used a program called Burp Suite that allowed him to enter all combinations of the code at a rapid speed which made it possible for him to log in, reset the password and log out of all the other devices. Hence, gaining complete control of the victim's account without his/ her knowledge.Free YouTube downloader
Following is the demonstration of how Anand Prakash could have take over all the Facebook accounts possible in the world:
Anand Prakash found this suspiciously blatant flaw back in February and reported the same to the Facebook officials on February 22. The flaw was removed the very first day and the bounty hunter was rewarded 15000 dollars on March 2, which feels very uncharitable on the part of Facebook.Access Others' WhatsApp
Prakash, who spoke to The Telegraph, UK, said that this trick to hack facebook accounts was fairly easy to exploit and it was available for anyone and everyone, and that all that the hacker needed was the victim's username.
Other Cybersecurity experts' thoughts : It was surprisingly simple, you'd have thought someone would have picked up on it now. You would think sites would allow you to have five attempts and then lock you out, it's pretty standard practice."Reduce Belly fat smartly
How Facebook reacted : "One of the most valuable benefits of bug bounty programs is the ability to find problems like easy ways to hack facebook accounts even before they reach production. We're happy to recognize and reward Anand for his excellent report.", said one of the spokespersons from Facebook.
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Call our Member Services Team
Option 1 – Member Services
Opción 7 – Servicio en Español
Hours of Operation:
Monday-Thursday. 8:00 am-5:00 pm
Friday 8:00 am-4:00 pm
If you are covered by Health First Colorado (Colorado's Medicaid program) and you live in Adams, Arapahoe, or Douglas counties or the City of Aurora, you are automatically enrolled and can receive behavioral health services.
We work closely with mental health providers in our provider network. We also work with Aurora Mental Health Center, Community Reach Center and AllHealth Network. You can get care from any of these agencies or from the providers listed in the BHI Provider Directory.
Payment for Services
As a member of BHI, you do not have to pay for covered services you get from providers in our network. You pay only for services that are not covered. Covered services are services that find, diagnose or treat a mental health or substance use disorder.
How to File a Complaint
If you are unhappy with your behavioral health care, please tell us. We want you to get what you need. We will do what we can to make things better.
Find information and help from local and national programs to support you on your journey to recovery.


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Found 2 words that start with compluvi. Browse our Scrabble Word Finder, Words With Friends cheat dictionary, and WordHub word solver to find words starting with compluvi. Or use our Unscramble word solver to find your best possible play! Related: Words containing compluvi
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Insurance companies are mailing renewal information for individual and family policies, both benefit and premium changes. Some of the benefit changes are positive, some are not but most of these changes are dictated by The Affordable Care Act (ACA) commonly referred to as Obamacare. In most cases the premium increases are very substantial. I do not have complete rates for all the insurance companies as of yet.
Changes for 2017 cannot be made until November 1st for an effective date of January 1, 2017.
The individual health insurance market is shrinking. I will be setting phone appointments to begin on November to review plans. I strongly encourage that you to contact me. If you want to set a phone appointment with me, please respond to this e mail now and I will send you dates and times as options beginning in November.
Before your phone appointment, I will need to know the exact spelling of the names of doctors you want to continue to see, including their zip code. I will also need the exact spelling of any medications you need and the dosage.
If you believe you may be eligible for a subsidy through Covered California, I need to know your Estimated Modified Adjusted Gross Income for 2017. If you do not report a 2017 amount, I cannot complete a Covered California application as it will not be accepted into their system. I would encourage you to have a discussion with your tax professional. I need this information at the time of a phone appointment.
Some Grandfathered plans will be discontinued in 2017, we need to discuss replacement of those plans.


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Ivory Boar Bristle Hairbrush (Small) by Koh-I-Noor (1pc Brush)
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Part of Koh-I-Noor's 1930 Collection, this brush features a chic ivory design that truly stands the test of time. The handle is made with high quality cellulose acetate, which pairs beautifully with boar bristles. Handmade in Italy with extraordinary attention to detail. Boar bristles brushes offer many benefits including: naturally conditioning hair, improving hair texture, reducing frizz, stimulating the scalp, reducing the need for styling products, and reducing the need the wash your hair on a daily basis. - Cellulose acetate handle is warm to the touch and self polishing - Boar bristles naturally condition hair & stimulate the scalp - Suitable for fine to normal hair - Handmade and carefully inspected in Italy - 16.5 x 4.5 cm.
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Here excellence implies being the best that we can be; inner and outer abundance; peace; equanimity, poise; movement towards Light, outer dynamism .....
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Not purity in the highest sense of the word. Even the greatest and most revered have their flaws. As one great mystic told me, its best not to worry about perfection. Every great being is an illusion. A close examination will expose anyone. That said, we can still do a lot of good for others in a lifetime.
You can help the HubPages community highlight top quality content by ranking this answer up or down.
"What is your take on purity?". If this is your take on it, Sri T, then fine. It is not quite what I was looking for. Peace.
I guess my take on purity is, there is no such thing on the human level. The Christian scriptures tend to agree.
Thank you Sri T.
I wanted to offer my opinion, but am not sure what you mean when you say 'purity'; care to elaborate any?
You can help the HubPages community highlight top quality content by ranking this answer up or down.
That would be cheating. Sure I have my views, but I wish to hear yours. The question is intended for sharing. What do you understand by this word you have most definitely come across? don't be scared, but relate it to the entire question.
Oh no, this is the second time I ran into this problem today. A follow-up comment has to be made within 200 characters. For this reason I will skip responding. Sorry about that, but I just can't get a fluid thought out that could be so short.


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Our apartment is in Heredia Centro, near the Heredia soccer stadium and the 'Palacio de los Deportes'. Our direccion is 100 Norte del Hospital Viejo de Heredia, frente Restaurante Chino Lago de Plata, puerta cafe (100, North of the old Heredia Hospital, in front of the chinese Restaurant "Silver lake", Brown Door)*Ü* I say old hospital because they are building a new Hospital, its the biggest in Central America, and the coolest Hospital I've seen. Its dark blue and silver and has a cool design. We pass it all the time. Its basically complete, but not in use yet.
Hna Gladys (cocinera/cook) lives just around the corner. We have to cross "the road of death" to get to her house though. The church is in 'Cubujuqui', near centro. Other areas we work in are Fatima (where Patricia lives), Guarari, La Milpa, Los Lagos, Mercedes Norte, Mercedes Sur, Barva, Birri, Carpintera, and Corazon de Jesus.
This week we visited a lot of less active members, as part of the new Mission Plan that was given this past year. The plan requires 15 names of people that are less active, are non-members, have future elders in the family, or are part member families. The names are chosen by the Elders Quorum, Relief Society, and High Priests, after prayer and meditation. After the names are chosen, certain leaders from the ward go to visit the people on the list, and invite them to have the missionarys start visiting them as well. If they accept, the names are given to us and we begin to teach them. Its been kind of hard to get the plan up and going. Supposedly, the fifteen names the ward has chosen have been visited by a ward member, even though no one could tell me who visited them and they didnt give us directions on how to find the people either. When we visited them this week, some of them didn't remember being visited but in the end, most of them were happy to recieve the missionary's. This next week we are going to get a new list put together, because there was even some confusion in the ward organizations about who was actually on the 15 names list. So we are going to keep working to get this program running continuously, smoothly, and effectively.
This week we also worked a lot with two guys preparing for the mission. One is named Samuel. He is planning on going on a mission this next year and he accompanied us two days this week. We also went to work with Rolando. Rolando leaves on his mission to the Northern part of Chile, this next month. He is really excited and came with us on Saturday. We try to go on divisions with as many jovenes in the ward as possible, and this week we were also accompanied by Erick Diaz.
While visiting less active members, we found out that in Guarari (one of the poorer parts of our area) there are over 300 members, but they are all inactive. We visited a few of them that haven't been to church in like 10 years. We are thinking of starting neigborhood Family Home Evenings in Guarari, which might get the people excited about going to church again. The bus that will take the members to church in Belen, starting in March, leaves from Guarari, so maybe that will help people start going to church.
Today we started P-day out by going to a Funeral. Hna Angelita's (The missionaries cocinera in Flores) adopted son Geraldo has been in the hospital here, down the street from our apartment, for a couple days, becasue he had convulsions and had some virus. He died yesterday afternoon when he had a heart attack. He was 28 years old, but was partially mentally and physically handicapped. Today at 10 in the morning we went with Elder Hansen, Elder Recino, Elder Zavala, and Elder Smith to the burial. It was sad to see Hna Angelita and her son Joan, (who always plays soccer with us and goes on divisions with us in Flores) crying. The other day when we passed by the hospital, Joan was outside waiting for news about his brother, and we talked to him and he was really worried, and today he was very sad. Although he will be missed, we know that Geraldo is in a better place, resting from the pains and worries of the world. We also know that because of our saviour Jesus Christ, Geraldo will one day resurrect and live again, and his family will be reunited, never to be seperated.
We have some good new investigators. One is named Sunilda, and we are going to visit her today. On Sunday, Natalia and Daniela brought one of there friends moms to church. Her name is Nidia. She liked church a lot and we are going to teach her tomorrow.


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20-hours-free policy will raise costs
Hon Tau Henare National Party Associate Education Spokesman
26 January 2006
20-hours-free policy will raise costs, reduce quality
National's Associate Education spokesman, Tau Henare says a report into early childhood education confirms what National has been saying for months - Labour's 20-hours-free policy is racked with problems and will not reach those most in need.
The NZIER report finds that the policy will:
- Reduce the quality of some childcare services.
- See most of the additional funding serve as a 'hand-out to middle class families whose children do not need the extra hand-up'.
- Encourage some centres, which are currently free, to charge 'donations' to top up Government funding.
Mr Henare, who has responsibility for early childhood education, says the scathing report concludes that the policy should be abandoned.
"Officials, parents and the National Party have all warned that this ideologically-driven policy will have dire consequences. Hopefully this report will lead to a re-think.
"Already many kindergartens have had to start charging fees to cover costs. This will see many of the kids who would benefit most from early childhood education miss out because their parents can't afford to pay.
"What families really want is the ability to access high quality early childhood education for their kids, regardless of their income, location or hours of work. Labour's policy simply will not deliver and is yet another triumph of spin over substance," says Mr Henare.


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Join us on this interactive tour through the beautiful Historic Downtown Charleston. Throughout the journey of this beautiful city, Frankly Charleston invites you to look beneath the veneer and to recreate the atmosphere of 18th and 19th century South Carolina. Come with us as we explore Charleston's most historic sites like Emmanuel A.M.E Church, Dock Street Theater, and The Old Slave Mart.
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Stay at this stylish, charming hotel ideally located near the unique museums, churches and historical heritage of Kaunas, Lithuania! The Best Western Santakos Hotel is delightfully situated on a calm and quiet street in the heart of Kaunas, the city considered the most Lithuanian town in Lithuania. Hotel guests experience this rich Lithuanian culture through the area's many popular music festivals including Kaunas Jazz Festival, Pazaislis Classic Music Festival and the International Festival Operetta in Kaunas Castle. More popular local events for visitors include the International Modern Dance Festival and the Euroleague Basketball Tournaments. Santakos Hotel offers all the right amenities for business and leisure complete with a modest ascetic red-brick exterior and cozy, decorative interior. Each well appointed guest room features cable satellite television, coffee/tea maker and AM/FM alarm clock with balcony, fireplace and patio rooms available upon request. Hotel guests enjoy a complimentary full breakfast and taking advantage of steam room and swimming pool. Additional highlights include a gift shop, meeting and conference facilities. The staff of the Best Western Santakos Hotel is always ready to provide exceptional service to hotel guests. To feel comfortable away from home while traveling, make an online reservation today at the Best Western Santakos Hotel in Kaunas, Lithuania!
- Restaurant on-site
- Complimentary full breakfast
- Indoor swimming pool
- Steam room
- Gift shop or newsstand
- Safe deposit box
- Babysitting on request
- Guest laundry
- Complimentary newspaper
- Winter-garden
- Meeting facilities
- Conference facilities
- Fax services
- Photocopy services
- Outdoor parking Free of charge
- Garage parking
Area Info
0.3 kilometer(s) from city center
0.4 kilometer(s) from a musical theatre
0.5 kilometer(s) from the Philharmonic Society Symphony Hall
0.5 kilometer(s) from the puppet theatre
0.6 kilometer(s) from the drama theatre
0.9 kilometer(s) from Langas Art Gallery
1 kilometer(s) from Ciurlionis and Devils Museums
1 kilometer(s) from Zilinskas Art Gallery
1 kilometer(s) from Vytautas Magnus University
1 kilometer(s) from the historic old town art galleries
1.5 kilometer(s) from the Red Cross Hospital
2 kilometer(s) from Azuolynas Park and Race Track
4 kilometer(s) from the Kaunas Zoo
5 kilometer(s) from Kaunas botanical gardens
8 kilometer(s) from Lampedziai beaches
30 kilometer(s) from Rumsiskes Folk Museum
80 kilometer(s) from Trakai Castle
Indoor pool
Steam room
Other points of interests
35 kilometer(s) from the city of Jonava
50 kilometer(s) from the city of Elektrenai
55 kilometer(s) from the city of Marijampole
70 kilometer(s) from the city of Alytus
75 kilometer(s) from the city of Raseiniai
80 kilometer(s) from the city of Trakai
100 kilometer(s) from Vilnius, the capital of Lithuania
Best possible service
Highly experienced restaurant staff
Tasty breakfast every morning from 7 am to 10 am
Best Western Santakos hotel offers an ideal environment for different events. Conference halls feature the latest conference equipment: digital simultaneous interpretation equipment, discussion microphones, video and audio equipment, wireless Internet, video projectors, etc. Conference or seminar participants can order catering services: coffee breaks, lunch, dinner, or banquets in the restaurant. Experienced staff will help you to organize business meetings, international conferences, seminars, company events, festive evenings, or casual parties in cosy hotel halls. Conference participants are offered free of charge to use a guarded parking lot in the hotel yard.
Map and Directions
The Best Western Hotel Santakos hotel is located in the city center.
J. Gruodzio ST. 21
LIT-3000, Kaunas, Lithuania
- Phone: +370 37 302702
- Fax: +370 37 302700
Hotel information
- GPS latitude: 54.8999
- GPS longitude: 23.8999
- Number of Guest Rooms: 92
- Non-smoking Rooms: 46
- Hotel Ratings: 4 Star
- Check-In: 14:00:00
- Check-out: 12:00:00
Pets allowed, prior arrangement only
- Restaurant on-site
- Complimentary full breakfast
- Indoor swimming pool
- Steam room
- Gift shop or newsstand


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