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It's a delicious and healthy drink that your dog will absolutely love! In this article, we'll explore everything you need to know about Puppuccino - from what it is and why your dog will love it, to the simple ingredients and tools needed for making it at home. We'll also provide you with a step-by-step guide on how to make Puppuccino for your furry friend, along with variations of the recipe to suit different dietary needs. Additionally, we'll share some tips on serving and storing Puppuccino for optimal freshness and taste. So, let's dive in and learn more about this delightful treat for our four-legged companions!
What is a Puppuccino and Why Your Dog Will Love It
A puppuccino is a delightful treat specifically designed for our canine companions, offering them a chance to indulge in a delicious and dog-friendly version of the popular human beverage, cappuccino. Made with just a few simple ingredients, this frothy concoction is not only safe for dogs to consume but also provides them with an enjoyable experience that they will undoubtedly love. As pet owners, we are always on the lookout for ways to pamper our furry friends and make their lives more enjoyable; introducing them to the world of puppuccinos is an excellent way to do just that.
So, what exactly goes into making a puppuccino? The primary ingredient in this tasty treat is whipped cream, which creates the signature frothy texture that both humans and dogs find irresistible. While it's true that some dogs may have lactose intolerance or sensitivities to dairy products, many can enjoy small amounts of whipped cream without any adverse effects. Additionally, there are lactose-free and dairy-free alternatives available for those who need them. The key here is moderation – as with any treat, it's essential not to overindulge your dog in order to maintain their overall health and wellbeing.
One of the reasons why dogs love puppuccinos so much is because they appeal to their natural instincts and preferences. Dogs are known for their strong sense of smell, which plays a significant role in their ability to taste and enjoy food. The enticing aroma of whipped cream combined with other optional ingredients such as peanut butter or pumpkin puree makes the puppuccino an irresistible delight for your four-legged friend. Furthermore, the unique texture of this beverage adds an element of novelty that can keep your dog engaged and excited about trying something new. With all these factors combined, it's no wonder that puppuccinos have become such a hit among dog lovers everywhere.
Simple Ingredients and Tools Needed for Making Puppuccino at Home
Now that you know what a Puppuccino is and why your dog will absolutely adore it, let's dive into the simple ingredients and tools needed to make this delightful treat at home. The best part about making a Puppuccino is that it requires only a few basic ingredients, most of which you probably already have in your kitchen. This means you can whip up this tasty concoction for your furry friend without having to make any special trips to the store.
To make a classic Puppuccino, all you need is some unsweetened whipped cream and water. That's it! However, if you want to add a little extra flavour or nutritional value, feel free to include dog-friendly ingredients such as peanut butter (make sure it doesn't contain xylitol), pure pumpkin puree (not pumpkin pie filling), or even plain yoghurt. As for the tools required, you'll need a small bowl or cup to mix the ingredients in, a spoon or whisk for stirring, and ideally, an electric mixer or hand whisk to achieve that perfect fluffy consistency for the whipped cream.
Once you've gathered all your ingredients and tools, you're ready to start creating this scrumptious treat for your canine companion. Remember that one of the key aspects of making a great Puppuccino is ensuring that it's not only delicious but also safe and healthy for your dog. So always opt for unsweetened whipped cream and avoid any additives or sweeteners that could be harmful to your pet. With these simple items on hand, you're well on your way to becoming an expert Puppuccino maker!
Step-by-Step Guide to Making Puppuccino for Your Furry Friend
Now that you know what a puppuccino is and have gathered all the necessary ingredients and tools, it's time to learn how to make this delightful treat for your furry friend. The process is quite simple and can be done in just a few minutes, making it an ideal option for busy dog owners who want to spoil their pets with something special. So, let's dive into the step-by-step guide on how to create a delicious puppuccino that your dog will surely love.
Firstly, start by brewing a small amount of decaffeinated coffee or herbal tea. It's important to use decaffeinated options as caffeine can be harmful to dogs. While the coffee or tea is brewing, take a small bowl and mix together equal parts of plain unsweetened yoghurt and water until you achieve a smooth consistency. This mixture will serve as the base for your puppuccino, providing both flavour and creaminess without any added sugars or artificial ingredients that could upset your dog's stomach.
Once your coffee or tea has cooled down slightly, pour it into the yoghurt mixture and stir well until fully combined. Now comes the fun part – assembling the puppuccino! Take a small cup or bowl suitable for your dog's size and pour in the liquid mixture, filling it about halfway. Then, top it off with a generous dollop of whipped cream (make sure it's free from xylitol), which will give your puppuccino its signature frothy appearance. You can also sprinkle some dog-friendly toppings like crushed biscuits or dried fruit pieces if you'd like to add an extra touch of indulgence. And there you have it – a homemade puppuccino that's bound to make your furry friend feel truly pampered!
Variations of Puppuccino Recipe to Suit Different Dietary Needs of Your Dog
Just like humans, dogs have different dietary needs and preferences. It's essential to consider these factors when preparing a puppuccino for your furry friend. Luckily, there are various ways to customise the recipe to suit your dog's specific requirements. Whether your pet has food allergies or is on a special diet, you can still treat them to this delightful beverage by making some simple adjustments.
For dogs with lactose intolerance or dairy allergies, you can substitute cow's milk with lactose-free milk or non-dairy alternatives such as almond, coconut, or oat milk. Keep in mind that some dogs may be allergic to nuts, so it's best to consult with your vet before using nut-based milk substitutes. If your dog is on a low-fat diet, opt for skimmed or reduced-fat milk instead of full-fat options. You can also replace whipped cream with a dollop of plain Greek yoghurt for a healthier topping that still adds an indulgent touch.
In addition to modifying the base ingredients, you can also experiment with adding various flavours and toppings to cater to your dog's taste buds and nutritional needs. For instance, you can mix in a spoonful of unsweetened pumpkin puree for added fibre and vitamins or sprinkle some crushed dog biscuits on top for extra crunch. Just make sure any additional ingredients are safe for canine consumption and free from harmful additives like xylitol or excessive amounts of sugar and salt. By tailoring the puppuccino recipe according to your dog's unique dietary needs, you'll ensure they enjoy their special treat without compromising their health.
Tips for Serving and Storing Puppuccino for Optimal Freshness and Taste
Now that you've mastered the art of making a delicious puppuccino for your furry friend, it's essential to know how to serve and store it properly. Serving the puppuccino at the right temperature is crucial for your dog's enjoyment and safety. Ideally, you should serve it slightly warm or at room temperature, as dogs can be sensitive to hot or cold temperatures. Make sure to test the temperature with your finger before giving it to your pet. Additionally, consider using a shallow bowl or cup for serving, as this will make it easier for your dog to lap up their tasty treat.
When it comes to storing any leftover puppuccino mixture, proper storage techniques are vital in maintaining its freshness and taste. It's best to store the mixture in an airtight container in the refrigerator for up to three days. If you've made a large batch and want to save some for later, you can also freeze individual portions in ice cube trays or small containers. This way, you'll have ready-to-serve treats on hand whenever your dog deserves a special reward! Just remember to thaw them out before serving and ensure they're not too cold for your pup.
Lastly, don't forget that moderation is key when treating your dog with puppuccinos. While these delightful concoctions are generally safe and healthy for dogs, overindulging could lead to weight gain or digestive issues due to the dairy content. As with any treat, be mindful of portion sizes and frequency – after all, we want our furry friends to enjoy their puppuccinos without compromising their health! So go ahead and spoil your pooch with this scrumptious beverage every now and then; they'll surely appreciate the love and effort you put into making their very own puppuccino!
Frequently Asked Questions About Puppuccino and Answers to Them
As you embark on your journey to create the perfect puppuccino for your furry friend, it's natural to have some questions about this delightful treat. One common query is whether or not puppuccinos are safe for all dogs. Generally speaking, puppuccinos made with dog-friendly ingredients like unsweetened whipped cream and lactose-free milk are safe for most dogs. However, it's always best to consult with your veterinarian before introducing any new treats into your dog's diet, especially if they have specific dietary needs or allergies.
Another frequently asked question revolves around how often you should serve puppuccinos to your canine companion. While these tasty beverages can be a fun and enjoyable treat for your dog, moderation is key. Puppuccinos should be considered an occasional indulgence rather than a daily staple in their diet. Overconsumption of dairy products can lead to gastrointestinal issues in some dogs, so it's important to keep an eye on portion sizes and frequency of servings. As a general rule of thumb, consider offering a puppuccino no more than once or twice per week as a special reward or bonding experience.
Lastly, many pet parents wonder if there are any alternatives to using dairy products in their homemade puppuccino recipes. If you're concerned about lactose intolerance or simply want to explore other options, there are plenty of non-dairy alternatives available that can still provide a delicious and satisfying treat for your dog. Coconut milk or almond milk can be used as substitutes for cow's milk in the recipe, while coconut whipped cream offers a tasty alternative to traditional whipped cream. Just remember to choose unsweetened versions of these products and double-check the ingredient list for any potential allergens before incorporating them into your puppuccino creations.


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DR John McMullen published in prestigious International Journal
Dr John McMullen has been published in the March issue of the prestigious Industrial Law Journal. The purpose of his article is to mine the very rich seam of decisions of the European Court of Justice over the last 18 months on the subject of the EU Acquired Rights Directive 2001/23 (ARD), the European Instrument behind the Transfer of Undertakings (TUPE) Regulations. These cases were all decided before the end on 2020 and are therefore part of EU Retained Law and bind British courts and tribunals notwithstanding Brexit.
The ARD is a key piece of EU social legislation from the ‘golden age’ of EU social law, with a robust code of employee protection on transfers of undertakings. Its transformative effect on worker’s rights, not just in traditional business takeovers, but also in areas such as outsourcing (where there is both a concentration of lower paid workers and a competitive market, and where employer profit margins are tight) cannot be overestimated.
Industrial Law Journal is established as the leading periodical in its field, providing comment and in-depth analysis on a wide range of topics relating to employment law. It has an extremely high official impact factor.
It is essential reading for practising lawyers, academics, and lay industrial relations experts to keep abreast of newly enacted legislation and proposals for law reform.

domain: law


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Organic nu3 chickpea flour 400g
ORGANIC, VEGAN, GLUTEN FREE
Organic chickpea flour
With the nuXNUMX chickpea flour you can bake and cook without gluten. Thanks to its nutty taste, it gives your dishes a great oriental touch.
Ingredients: 100% organic chickpea flour (Southern Europe).
May contain traces of Sesame, nuts, peanuts and soy included.
Storage Note: Locked, kStore cool and dark.
Expiration date: 16.04.19
Note: The sell-by date of this product has already exceeded. However, it has undergone sensory testing by us and declared to be edible. Nevertheless, we recommend to store the product only for a short period of time and to eat it as soon as possible.
Country of origin: Germany
|average nutritional values||per 100 g|
|Energy||1421 kJ / 338 kcal|
|hereof: saturated fatty acids||1,1 g|
|of which sugars||2,4 g|
nu3 GmbH, Brückenstr. 5, 10179 Berlin
Eco-control number: DE-ÖKO-007

domain: food


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Not a member?
Already have an account?
Please go to the mailbox and click the activation button in the mail to activate the account.
tree work background scrapbook elegance wooden embossed ornament painting wing copyspace rectangular decorative single window decoration limit art decor blank old board pattern antique element retro vintage horizontal garnish rectangle isolated border picture mirror frame design photo
shot photography equipment lens device camera photographic image clipping background images canon isolated digital path removing technology
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animal cat smile kitty pet cartoon character kitten isolated happy funny cute art feline

domain: design


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Asthma is a chronic lung condition that affects over 25 million people in the United States alone, with 7 million of them being children. The numbers tell us of how many people are suffering from recurring periods of wheezing, coughing, shortness of breath, and chest tightness, among others.
When a person has asthma, his or her airways are inflamed in a way that they become very sensitive to irritants or other foreign substances. Exposure to these will tighten the muscles, narrow the airways, and eventually trigger asthma symptoms—all of which can lead to terrible outcomes when not identified and managed promptly.
Coughing is a common symptom among asthma patients, which is often worse at night or early in the morning. Coughing is the body’s natural reflex to clear out irritants in the airways and prevent infection. Since the airways are swollen and more sensitive to such irritants, the body responds by coughing more frequently.
If you’ve been taking cough medications to no avail, there could be an underlying reason that your coughing has not subsided, which includes asthma. It is recommended to get a proper diagnosis from your doctor so it can be treated appropriately.
Tiredness and Fatigue
While you don’t commonly see fatigue as an asthma symptom, it can definitely happen to patients. Since the body is working double to breathe properly, it gets easily tired and weak. This feeling of persistent exhaustion may also be due to having low oxygen levels most of the time, especially when an asthma is poorly controlled. This often results to inadequate rest or poor quality of sleep during the night, affecting one’s daily functioning during the day.
Shortness of Breath
Since the airways constrict and narrow during an asthma attack, the patient experiences shortness of breath. This asthma symptom may be triggered by vigorous physical activity or an allergic reaction to an irritant. This difficulty in breathing may accompany other symptoms such as fast breathing or chest pain and tightness.
If you’ve been experiencing shortness of breath for a long time now, your doctor may perform specific tests to diagnose asthma, which includes chest X-ray, pulse oximetry, or an electrocardiogram using EKG sensors.
Flared Nostrils During Breathing
Some warning signs of asthma are more serious than the others, which require immediate professional care. Aside from difficulty in catching one’s breath or even in just talking, these serious warning symptoms include flaring nostrils as you breathe as well as sucking in one’s chest or stomach with every labored breath. In more serious cases, the patient may also experience a bluish or grayish tinge to the lips or fingernails, which means there is not enough oxygen circulating to the different parts of the body.
If you get any of these alarming symptoms, call 911 right away as these are clear signs of a critical asthma attack.
When to See a Doctor
The signs and symptoms of asthma may vary from every individual. They may occur only at certain times for some or occur all the time for others. Whatever the case, it is important to seek medical advice upon noticing these symptoms to have your condition properly diagnosed and get an effective treatment plan sorted out for you.
For people who are already diagnosed with the chronic respiratory condition, don’t hesitate to seek emergency treatment when severe asthma attacks occur or if your maintenance medications do not seem to ease such symptoms. Don’t use asthma medication more than what’s prescribed as this could make the condition worse.
Remember, warning signs are there for a reason, and that is to give you a heads-up that your body needs appropriate medical attention.
If you tend to struggle with anxiousness, you know how upsetting it can be. It’s much better if you’re able to achieve a sense of calm in your life, especially when you’re dealing with everyday stresses, but it can sometimes feel impossible to do that. That’s why many people turn instead to supplements that can help. Read more
When a job keeps making people tired or stressed out, many feel the perfect solution to their problem is to change jobs, go on vacation or get another manager. But often, the real problem comes from poor nutrition than from a need to change the job scenery. Is it possible that a lot of your problems could be solved just by substituting a veggie snack for that midday candy bar? It may sound surprising, but a poor diet diminishes one’s quality of life. Therefore, it’s important to get the right nutrients for proper bodily function. Read more
Are you seeing signs that bed bugs are in your home? If so, you want to get rid of them quickly, but how? If you are like most homeowners, you have no idea how to remove bed bugs and you don’t even want to think about the pest in your home. For removal, your best bet is to hire a professional team of experts who have experience in removing bed bugs from the home using premium techniques and tools. The quicker you schedule an appointment, the faster the bed bugs will no longer be a problem! Read more

domain: medical


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Join us for a workshop using XL felted wools and tools to create your own chunky wool blankets quickly and easily. Materials provided. No prior knitting experience needed. Just bring your own creativity and enthusiasm to the workshop.
Limited to 12 people, booking and prepayment essential. For bookings please email email@example.com
- North Atrium
- $140 for Members

domain: artistic


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Walkers Shortbread Bakery Shop
3 lokalkjente anbefaler
Tips fra lokalkjente
Walkers Shortbread retail store selling the world famous shortbread made in Aberlour, Speyside.
Walkers Shortbread is a must whilst here in Highlands and our Walkers Shop is very appreciated. As our old bakery too the shop also provides freshly made filled rolls to order and a very reason price. This filled rolls are far more superior than any supermarket snack. Opens early so purchase…


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LEE CO., GA (WALB) - Two vehicles were involved in a crash on U.S. 19 in Smithville Saturday afternoon.
According to the Georgia State Patrol, a black Jeep was going north while a blue Nissan was going east.
Troopers said the person driving the Nissan failed to yield at Church Street, causing the Jeep to hit the Nissan.
The Georgia State Patrol Trooper on the scene was parked across the street, almost getting hit as well.
The driver of the Jeep was taken to Phoebe Sumter for injuries on his left side after the car rotate a couple of times, but troopers said they believe he will be okay.
According to GSP, the 78-year-old driver of the Nissan was arrested for driving under the influence and failure to yield.
He will be taken to Lee County jail.

domain: news


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NCA Referral Program!
**EARN TUITION CREDIT**
If you are a current NCA student who refers a new student to NCA and they enroll, you are eligible for this offer. The new student needs to include your name as referring them on their application form.
After the new student has attended NCA for 3 months, you will receive a $500 tuition credit toward your tuition statement.
This offer is PER student referred.
For example, should you refer a family with 3 students who enroll, attend, and pay tuition for three months, you will receive a $1500 tuition credit on your tuition statement.

domain: finance


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I have read several of Brian Tracy's books, and this is certainly among the best! This book is a must read for new entrepreneurs and business owners, or just people who are trying to improve the quality of their life. It is packed full of practical applications and ideas that you can apply to your life today.
Absolutely!!. This book helped me to understand the power of self discipline and how it controls my life. Positive, thorough self discipline is the key to success in all aspects of life!
Rich Dad Poor Dad. I compare these books because they are both moving, powerful and they both changed my life.
All the tips and exercises were very well explained and encouraged. I loved all 7 steps and 7 exercises.
Yes. I would have loved to sit, walk, drive and listen to this book non stop. Unfortunately, I had to work and sleep.
Thanks to this book, I feel that I have become a new person. I use the teachings of Brian Tracy to better myself and ensure my happiness and success!
Es el mejor y más completo audiolibro que he comprado, trata los temas más importantes para un desarrollo personal integral, es metódico y fácil de comprender
No - this book just felt like it was written by someone that was being forced to spit out another business advice book. Nothing groundbreaking here. Sure, its good advice but too often I felt myself yelling "Yes, we know that...get to the point".
No, I'd have them read an earlier Brian Tracy book or a Peter Drucker book (since he quotes him often in this book).
This book could have been titled "How to Succeed in Business in 50 clichés or less"
I understand money, I understand good health and I somewhat understood relationships. BUT I was missing the discipline to take advantage of life. This book helped me tie it all together and take advantage of my previous education.
Take notes and do the exercises as recommended and you'll prosper.

domain: literature


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In a new federal charge announced on Monday, an Oak Cliff woman Jennifer Faith, who persuaded her boyfriend to kill her husband, confessed to orchestrating the murder.
Reports suggest that Jennifer Faith's "depraved and calculated" scheme forced her alleged boyfriend to murder her husband by deceiving him through fictitious emails claiming that she was being abused and required protection.
Jennifer entered a plea of guilty to the allegation of murder-for-hire. She was charged with tampering with justice and using interstate commerce to commit murder-for-hire. Prosecutors agreed to remove the obstruction count and propose a life sentence in exchange for her plea.
Jennifer Faith was in a ‘full blown emotional affair’ with the alleged shooter
Jennifer Lynne Faith (49) was out walking their dog with her husband, American Airlines CEO James Faith, in October 2020, when someone opened fire in the Dallas neighborhood.
Shortly after, James was shot numerous times by an anonymous man. Jennifer told local sources that she was astounded by what happened in a flash of a second and said:
“Oh my god! If you know what happened, I need that for closure. I need to make some sense out of this.”
Two months later, she also pleaded in a TV interview with those who might have some knowledge about the incident. She said:
"My hope is that someday perhaps the person will realize the guilty of what they have done and what they have taken from myself and my daughter. He was just the backbone of our company. It was just devastating."
During the investigation, Dallas police went through defendant Jennifer Faith's mobile phone and learned she was in a romantic relationship with the alleged shooter. He was identified as Darrin Robin Lupez, 49. Officials said in a statement:
"Jennifer Faith and Darrin Lupez had been carrying on a full blown emotional affair and even bandied about a 'five year plan' for how they would end up together."
According to plea papers, Jennifer Faith admitted that her boyfriend Darris allegedly gunned down her husband in front of his home in Oak Cliff.
Jennifer Faith acknowledged that she was aware that Lopez had been crippled by a traumatic brain injury while serving in the U.S. Army in Iraq. She used to send him funds and presents both before and after the murder, and even gave him two credit cards.
Determined by the alleged affair of Faith and Lupez, US Attorney Chad Meacham described:
"Jennifer Faith's cold-blooded plot to murder her husband was made all the more heinous by the way she behaved after his death. Even as she wept for her late husband, Ms. Faith was corresponding with his murderer, plotting about how to cover up their crime."
Jennifer Faith sent misleading emails as a bogus proof of physical abuse
The U.S. Attorney's Office claims that Jennifer opened a Gmail account in her husband's name in April 2020 and used it to taunt Lopez "multiple times throughout the spring and summer of 2020, detailing extreme physical and s*xual abuse that had never actually occurred" and attaching "fake photos of injuries as bogus proof of the abuse."
The following month, she allegedly opened a second fictitious Gmail account in a friend's name. The email was sent in May 2020 and said:
"Jamie slapped Jen...then he sent the pic of him choking her. I am asking if you are willing to get involved and help Jen get out this situation."
Lopez reply to that account on May 20 read:
"I know I won't feel better about her situation until she is out of the house away from him or she lets me put a bullet in a Jamie's head."
Later, a friend of Jennifer's set up a GoFundMe account to support the family, but according to the investigators, Jennifer withdrew $58,000 to pay for transactions made on two credit cards she handed Mr. Lopez.
Investigators felt they were able to piece together the murder's circumstances quickly enough and eventually coaxed a confession of guilt.
Jennifer Faith will be sentenced on May 26, 2022. Both the state and the federal government have accused Lopez of murder and a related gun crime. She's entered a not guilty plea to both allegations.


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Dimples is an emerging singer-song writer who is set to release her EP by the name of “Mood Swings”.The title has sentimental value to the singer as the project is a reflection of how ones mood can change day to day from one extreme to the next. In fall of 2017 she released her latest single “Dope Shit”. The release of the single is a defining moment in her career. The Las Vegas based singer grew up in the church where she was able to nurture and showcase her talent. Her music is inspired by various artists like Aaliyah, Gwen Stefani, R. Kelly, Anita Baker, Mary J. Blidge & The Isley Bros. to name a few.
Tune in to KRXM to hear new music from Dimples


President says Schiff is leaking Russian meddling intelligence to harm Sanders’ campaign
President Donald Trump has called for an investigation into Democratic House Intelligence Chairman Adam Schiff (D-CA) over allegations he leaked intelligence on Russian election interference in a bid to harm Sen. Bernie Sanders’ (I-VT) presidential campaign.
According to Trump, Schiff leaked intel that suggested Russia was “helping” Sanders’ campaign because Democrats don’t want the independent senator to win the Democratic nomination.
“They ought to investigate Adam Schiff for leaking that intelligence,” the president told reporters.
Trump noted that he hadn’t been briefed on any Russian meddling on Sanders’ behalf.
WATCH: After press reports that Russia is interfering in the 2020 election, Trump blames House Intel Chairman Adam Schiff and calls for an investigation into the leak. #MTP
Pres. Trump: “Nobody said it to me at all. Nobody briefed me about that all.” pic.twitter.com/LYeemOptQh
— Meet the Press (@MeetThePress) February 23, 2020
The president suggested that Schiff released the information to hurt Sanders’ presidential bid.
“I think what it could be, the Democrats are treating Bernie Sanders very unfairly,” Trump said outside the White House on Sunday as he prepared to depart for a two-day trip to India.
“And it sounds to me like a leak from Adam Schiff because they don’t want Bernie Sanders to represent them.”
Schiff pushed back at the president on Twitter.
“Nice deflection, Mr. President. But your false claims fool no one,” Schiff, one of the main players during the House’s impeachment inquiry into the president, posted.
Nice deflection, Mr. President. But your false claims fool no one.
You welcomed Russian help in 2016, tried to coerce Ukraine’s help in 2019, and won’t protect our elections in 2020.
Now you fired your intel chief for briefing Congress about it.
You’ve betrayed America. Again. https://t.co/WlMDaz8stF
— Adam Schiff (@RepAdamSchiff) February 23, 2020
“You welcomed Russian help in 2016, tried to coerce Ukraine’s help in 2019, and won’t protect our elections in 2020,” Schiff continued.
“Now you fired your intel chief for briefing Congress about it.
“You’ve betrayed America. Again.”
News reports last week said intelligence officials had briefed Republican and Democratic members of the House Intelligence Committee that the Kremlin was trying to help Trump win in November.
Then on Friday, the Washington Post reported that Sanders had been informed about Moscow’s intention to back his campaign.
“The intelligence community is telling us they are interfering in this campaign right now, in 2020,” Sanders told reporters in California about the development.
“I say to Mr. Putin, if elected president, trust me, you are not going to be interfering in American elections.”
The Democratic presidential candidate confirmed that he was briefed about Russia last month and questioned why the news broke on the eve of the Nevada caucus.
“Why do you think it came out?” Sanders asked.
“It’s The Washington Post? Good friends.”


The WinDesign Laser deck cover is made from a super-strong 1680 denier PVC coated polyester. This economical choice is 100% water resistant, but this cover is not breathable.
- Fabric: PVC coated polyester
- Closures: Cover has a wide skirt with shock cord in hem and three adjustable quick-clip buckles
- Color: Blue


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The Monkees 50th Anniversary Tour
The Monkees’ Greatest Hits! All the songs you remember!On September 8, 1965, when producers Bob Rafelson and Bert Schneider placed a classified ad in The Hollywood Reporter seeking “4 insane boys,” they had no idea that they were about to unleash Monkee-mania! But that’s exactly what happened the following year when the first episode of “The Monkees” debuted on NBC on September 12, 1966. 50 years later and The Monkees anniversary show is coming to Australia and New Zealand. After sell-out North American shows, and with a brand new album “Good Times!” in the charts, Micky and Peter are bringing the Monkees magic downunder. The Monkees 50th Anniversary show is a unique concert experience. Times may change but infectious pop hits and wonderfully charismatic characters stay in our hearts and memories forever. ‘Last Train to Clarksville’, ‘Theme from The Monkees’, ‘A Little Bit Me, A Little Bit You’, ‘She’, ‘Saturday’s Child’, ‘Mary, Mary’, ‘The Girl I Knew Somewhere’, ‘For Pete’s Sake’, ‘Randy Scouse Git’, ‘Your Auntie Grizelda’, ‘Words’, ‘Papa Gene’s Blues’, ‘Porpoise Song’, ‘Do I Have to Do This All Over Again?’, ‘Goin’ Down’, ‘Listen to the Band’, ‘Shades Of Grey’, ‘Daydream Believer’, ‘What Am I Doing Hangin’ ‘round’, ‘(I’m Not Your) Steppin’ Stone’, ‘Pleasant Valley Sunday’, ‘Circle Sky’, ‘I’m a Believer’ When four young men were cast in the television roles of a struggling rock band inspired by The Beatles’ A Hard Day’s Night, few could have predicted the impact The Monkees would make on music and pop culture at large, an impact that still reverberates 50 years later. Assembled in Los Angeles in 1965 by Bob Rafelson and Bert Schneider for the television series The Monkees, the quartet of Micky Dolenz, Michael Nesmith, Peter Tork, and the late Davy Jones brought a singular mix of pop, rock, psychedelica, Broadway, and country to their music. The show itself, meanwhile, paid tribute not only to The Beatles, but also to the comedy stylings of The Marx Brothers and Laurel and Hardy as well as the pop-art sensibilities of Warhol and the emerging San Francisco psychedelic scene. The Monkees’ first single, “Last Train to Clarksville,” was released in August 1966, hitting #1 and serving as advance publicity for their series, which debuted on September 12. When the group’s self-titled debut album arrived in stores a month later, it quickly headed for the top spot of the Billboard charts, where it would ultimately sit for 13 of the 78 weeks it remained in the Top 200. (Two decades later, in the midst of a new burst of Monkee-mania, The Monkees popped back onto the charts, bringing the total number of weeks to 102.) By the time the group’s TV series aired its final new episode on March 25, 1968, the Monkees had seen three further albums top the charts – More of the Monkees, Headquarters, and Pisces, Aquarius, Capricorn & Jones, Ltd., all of which were released in 1967, staggeringly enough – while racking up several more hit singles, with “I’m a Believer,” “(I’m Not Your) Steppin’ Stone,” “A Little Bit Me, A Little Bit You,” “The Girl I Knew Somewhere,” “Pleasant Valley Sunday,” “Words,” “Daydream Believer,” “Valleri,” and “Tapioca Tundra” all finding their way into the Billboard Top 40. After the series’ two-season run, the group went on to star in the cult feature film HEAD (co-written by Jack Nicholson) and a TV special (33 1/3 Revolutions per Monkee) while also continuing to record new material, but much as the ‘60s gave way to the ‘70s, the members of the Monkees eventually gave in to their individual musical interests and went their separate ways… for awhile. In February 1986, after MTV broadcast a marathon of The Monkees, Dolenz, Jones, and Tork reunited for a 20th anniversary tour, with Nesmith joining them onstage for the Los Angeles date of the tour, and in 1996, all four members of the group reunited for a new album (Justus) and TV special (Hey, Hey, It’s the Monkees). In the wake of Jones’s death on February 29, 2012, the surviving members of the Monkees reunited and performed a series concerts. The shows were greeted with sell-out response and phenomenal reviews. Now, Micky Dolenz and Peter Tork carry on that tradition with a full evening of magic music and multi-media splendor, including clips from their Emmy Award winning series. Their new show features all of the Monkees hits, plus an intimate acoustic set and solo spots for each of the singers. This Evening With The Monkees is sure to please every fan of the band.
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Download the files for the 3D printed Crypto Chess pieces - Bitcoin, Ethereum, DASH by Nextin3D.One of the biggest concerns surrounding the growing industry of 3D printed fashion is the question of how to prevent designs from being pirated.Shop with confidence.We cover a wide variety of issues such as bitcoin development, startups, blockchain.
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Namely, japan stock options stock options are not taxable japan stock options the time of exercise. We empirically investigate the adoption jzpan stock option plans in Japan after the corporate governance reforms of the early ib forex account. Nov 2018.
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December 14, 2018) - Japan Gold Corp. Feb 2018. In general, share compensation plan such as Restricted Stock Unit (RSU), or Stock Option includes a condition which requires employees to. Are Stock Options the Answer for Japanese Firms in the U.S.? In Japan, corporations are able to offer their employees tax-favored ESO plans. TDEX is defined as Tokyo Derivatives Exchange (stock options market Japan) very. Europe, Asia and the Middle East, and represents numerous.
Japan stock options (1995), for example, argues that few agency theories have the descriptive power to explain observed patterns of CEO stock option awards.
Dec 2018. Vancouver, British Columbia, Dec 14, 2018 (Newsfile Japan stock options via COMTEX) -- Japan Gold Corp. Internet Initiative Japan Inc. Stock Acquisition Rights japan stock options series).
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This japan stock options analyzes the current state of non-executive employee stock option (ESO) issuance in. Japan, it is recommended that specific advice be taken. Feb 2018. By making the stock options exercisable in stages in such a way, it will be. The amendment of the Commercial Act in May.
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- Project Manager: Chung-Yin Wang
- Project Team: Yi-He Hong, Jhih-Siang Liang, Yung-Chin Lin, Tsun-Jen Cheng, Brian Wu, Pin-Yi Yu, Chia-Chun Chiang, Min-Shi Tsai
- Client: Cathay Life Insurance Co.Ltd., Ally Logistic Property (ALP)
- City: Taichung City
- Country: China
A warehouse in the new city center
The site is located within a developing area close to the high speed railway station in Taiwan's 2nd largest city, Taichung. Half-surrounded by rails and a lifted highway, the site is on the west fringe of a commercial fragment. With its original program as a warehouse, the building meant to be a machine circulates goods and parcels functionally. The lack of interaction with public is expected so the discussion of what more could it be was raised among the design team, while the site is just 800 meters away from the station and visitors on the platform could easily spot it. The strategy of making an authentic hub not only for goods but also for citizens was therefore carried out. To take advantage of the site's nature of having an intimate relationship with the high speed railway station, small amount of start-up offices and small-sized retails were added to the program to be the game changer. Now the building has turned into a hybrid, rather than a mono-functional warehouse. Those new elements had given us a chance to transform the stereotype of warehouse design, which is always considered as a massive box without any contribution of publicity.
Could a warehouse coexist with pleasant public space?
To evoke a highly interactive commercial street, a setback of 20 meters from the east side is imposed and a double-storey arcade was formed. Big trees line in double row, stairs interlocked with decks and diverse street furniture are arranged along the street to trigger comprehensive street movement. Besides, since most of the green space was closed for inevitable security reasons, a sky garden on the east wing is created as a gift to citizens, connected with the ground floor by a huge staircase attached on the east façade.
Citizens are now invited to climb up to the roof to explore the magnificent city view. Moreover, people are now able to have a glimpse of how a warehouse is operating by looking through the linear window or interacting with workers on the landings. The staircase is not only a symbol of publicity but a social interface connects inside and outside. The image that the building conveys could become a good example to inspire the following development. Sooner or later we hope, the staircase will gradually be covered by lush climbing plants and become a green artery merged with the treetop and the sky garden.


Alexey Pushkov, the head of the Duma International Relations Committee commented on social media: “That made me laugh. Who needs Lithuania? No one is even inviting it.”
As news agency RIA Novosti reports, Mr. Pushkov was also said, ironically: “Who else is not participating in the coalition? Latvia and Lithuania? Raqqa is celebrating today. These are exactly the countries that the Islamic States fears most.”
In a press conference, which followed Friday’s meeting of the three Baltic presidents, Grybauskaitė said that “Lithuania will not participate in any new coalition in which Russia is participating or shows an interest to do so”.


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Molecular Vision 2019; 25:106-117
Received 16 November 2018 | Accepted 06 February 2019 | Published 08 February 2019
The last two authors are senior authors for this study.
1Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; 2Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; 3Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands; 4Department of Biology, School of Sciences, The University of Isfahan, Isfahan, Iran; 5Department of Ophthalmology, Isfahan Eye Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
Correspondence to: Mohammadreza Akhlaghi, Isfahan Eye Research Center, Feiz Hospital, Qods Square, Isfahan, Iran; Phone: +983134452034; FAX: +983134452031; email: email@example.com
Purpose: Inherited retinal diseases (IRDs) are clinically and genetically heterogeneous showing progressive retinal cell death which results in vision loss. IRDs include a wide spectrum of disorders, such as retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), cone-rod dystrophy (CRD), and Stargardt disease (STGD1).
Methods: In this study, we performed targeted next-generation sequencing based on molecular inversion probes (MIPs) that allowed the sequence analysis of 108 IRD-associated genes in 50 Iranian IRD probands.
Results: The sequencing and variant filtering led to the identification of putative pathogenic variants in 36 out of 50 (72%) probands. Among 36 unique variants, we identified 20 novel variants in 15 genes. Four out of 36 probands carry compound heterozygous variants, and 32 probands carry homozygous variants.
Conclusions: Employing a cost-effective targeted next-generation sequencing procedure, we identified the genetic causes of different retinal disorders in the majority of Iranian families in this study.
Inherited retinal dystrophies (IRDs) are a group of clinically and genetically heterogeneous disorders leading to vision loss because of degeneration of retinal cells [1-5]. Mutations in more than 250 genes have been reported to cause IRDs. Most identified mutations are inherited in an autosomal recessive fashion (50–60%) although some can be autosomal dominant (30–40%), X-linked (2–20%), or mitochondrial . IRDs are divided into non-syndromic forms, such as retinitis pigmentosa (RP), cone-rod dystrophy (CRD), Leber congenital amaurosis (LCA), and Stargardt disease (STGD1), as well as syndromic forms . These inherited retinal dystrophies have an estimated incidence of 1:2,000 individuals .
The earliest clinical symptoms of RP (OMIM 268000) are night blindness and peripheral vision loss (tunnel vision) due to rod cell degeneration. In later stages of the disease, central vision can also be lost once cone cells degenerate, and eventually, patients with RP can become (legally) blind [6,8]. In CRD (OMIM 120970), the main manifestations are loss of visual acuity, color vision, and photophobia followed by night blindness and tunnel vision . The rarest and most severe retinal dystrophy form is LCA (OMIM 204000), in which patients have severe visual impairment in the first year of life . LCA appears with severe and early visual loss, nystagmus, and sluggish pupils . STGD1 (OMIM 248200) is one of the most common macular degenerative disorders with the features of macular atrophy, impaired central vision, and decreased visual acuity. Color vision, especially a red-green defect, is apparent in most affected individuals .
Because of the complexity of IRDs, it is often necessary to reconcile the clinical diagnosis, family diagnosis, and molecular diagnosis. This can be done in a multidisciplinary team which ideally includes trained ophthalmologists, genetic counselors, and molecular geneticists. Thus, identification of the pathogenic DNA variants can help clinicians and health professionals to improve and expedite the diagnosis of the disease and provide patients and their families with more accurate genetic counseling. Moreover, increasing knowledge of the molecular mechanisms involved in IRD pathogenesis may also lead to the development of new treatment options for affected individuals in the future .
Since the introduction of next-generation sequencing (NGS), several different targeted gene panel tests that sequence a large set of disease-associated genes have been developed for specific inherited eye disorders . In this study, we applied a targeted gene panel–based NGS approach based on molecular inversion probes (MIPs) to obtain a molecular diagnosis for 50 patients who had been diagnosed with IRDs and for whom no genetic tests had been performed previously. Using this method, variants in 108 genes associated with non-syndromic IRDs were screened.
In this study, we included 50 IRD probands with Iranian origin and the clinical diagnosis of RP (n=31), CRD (n=5), LCA (n=11), or STGD1 (n=3) who had not been genetically investigated previously. The clinical diagnosis was established by a trained ophthalmologist including the patient pedigree and history of the disease, electroretinography (MonPack3; Metrovision, Perenchies, France), evaluation of visual acuity using slit-lamp biomicroscopy, and fundoscopy (TRC-50EX retinal camera; Topcon, Tokyo, Japan). Written informed consent was obtained from all study subjects. This study was approved by the institutional review board of the ethics committee of Isfahan Medical University, Iran. The study adhered to the tenets of the Declaration of Helsinki and the ARVO statement on human subjects was approved by the institutional review board of the ethics committee of Isfahan Medical University, Iran.
Five cc of peripheral blood samples of affected and unaffected members were collected and mixed with EDTA anticoagulant (Merck KGaA, Darmstadt, Germany). Genomic DNA of all samples was extracted using the phenol-chloroform method .
Targeted NGS was performed to identify the genetic etiology of IRDs in 50 patients with different types of IRDs. The 108 gene panel MIP analysis designed at the Department of Human Genetics at Radboud University Medical Center (Nijmegen, The Netherlands) consisted of genes implicated in non-syndromic achromatopsia, cone dystrophy (CD) and CRD (autosomal dominant, autosomal recessive, and X-linked), congenital stationary night blindness (autosomal recessive and X-linked), macular degeneration (autosomal recessive and autosomal dominant), LCA (autosomal dominant and autosomal recessive), RP (autosomal recessive, autosomal dominant, and X-linked), and choroideremia. MIPs with 5-bp molecular tags were used to perform targeted NGS of 108 genes associated with IRD (Appendix 1). The 1,524 coding exons and at least 10 bp flanking each exon were targeted using 6,129 MIPs for an overall target size of 647,574 bp. On average, four to six MIPs cover one exon. When known single nucleotide polymorphisms (SNPs) resided in the genomic regions complementary to the annealing or ligation arm, SNP-specific MIPs were designed. The panel also included the frequent LCA-associated pathogenic intronic variant c.2992+1655A>G in CEP290 (Gene ID 80184, OMIM 610142) , as well as five deep-intronic variants in ABCA4 (Gene ID 496442, OMIM 248200) . Pooled and phosphorylated probes were added to the capture reactions with 100 ng of genomic DNA from each individual to produce a sequence library for each individual. The libraries were amplified with 21 cycles of PCR (first denaturation step at 95 ºC for 4 min, followed by 21 cycles at 94 ºC for 30 s, 57 ºC for 30 s, 72 ºC for 1 min and then a final extension step at 72 ºC for 5 min), during which an 8-bp sample barcode was introduced. The barcoded libraries were then pooled and purified with AMPPureXP beads (Beckman-Coulter, Indianapolis, IN). Sequencing was performed on an Illumina NextSeq 500 system (San Diego, CA). Demultiplexed BAM files were aligned to a human reference sequence (UCSC Genome Browser hg19) via the Burrows-Wheeler Aligner (BWA) v.0.6.2 . In-house automated data analysis pipeline and variant interpretation tools were used for variant calling. Only non-synonymous single nucleotide variants (nsSNVs), nonsense variants, putative splice site (±10 bps) variants, insertions, duplications, and deletions represented by more than 20 sequence reads were considered for further analysis. In addition, variants with a minor allele frequency (MAF) >0.5% in the Exome Aggregation Consortium Database (ExAC) Version 0.3.1  were excluded from further investigation, with the exception of a few frequent variants in ABCA4 (i.e., c.2588G>C, c.5882G>A, and c.5603A>T [20-25]) that were selected separately.
Several criteria were taken into account to evaluate the potential pathogenicity of variants: 1) The variants had previously been reported to be pathogenic, 2) the variants were absent in the ExAC database or showed a low MAF (<0.5%), 3) the variants caused a loss-of-function (LOF) of the encoded protein, such as nonsense, canonical splice site, and frameshift mutations, and 4) missense variants were predicted to be damaging by in silico prediction algorithms. The pathogenicity prediction tools used for missense variants were PolyPhen-2, Sorting Intolerant From Tolerant (SIFT), PhyloP score, the Grantham score, Mutation Taster, and Combined Annotation Dependent Depletion (CADD) score assessment. For the selection of non-canonical splice site variants, in silico predictions were performed by using five algorithms (SpliceSiteFinder-like, MaxEntScan, NNSPLICE, GeneSplicer, and Human Splicing Finder) via Alamut Visual software version 2.7 [26–30], and Biosoftware (Interactive Biosoftware, Rouen, France), by comparing the splicing scores for wild-type and variant nucleotides.
Candidate variants were validated and tested for cosegregation within the families using Sanger sequencing. For this purpose, specific primers were designed for PCR amplification of fragments containing the identified candidate causal mutations in each patient. PCR amplicons were sequenced using Sanger sequencing on an ABI 3730 DNA analyzer (Cologne, Germany) with BigDye chemistry v3.1.
Fifty unrelated Iranian patients with non-syndromic IRD were included in this study, and their parents were first (34 families) or second cousins (16 families). All clinical information for the 50 families is summarized in Table 1. Among the 50 patients, 31 have RP, five have CRD, 11 have LCA, and three have STGD1.
One affected individual from each of the 50 families was subjected to targeted NGS of 108 known IRD-associated genes (Appendix 1). The averages of 1.2 million reads on target per sample were obtained using our capture panel technology, with an average coverage of 213 reads per MIP. Moreover, an average of 88% of targeted regions had 10X coverage or more, which was sufficient for accurate variant calling. The pipeline initially called an average of 532 single nucleotide variants and 64 insertions or deletions for each sample. In this study, putative pathogenic variants were identified in 36 index cases (Table 2), and we could not find the pathogenic variants for the remaining 14 families. All putative disease-associated variants were validated with conventional Sanger sequencing, and segregation analysis was performed for all 36 families with identified pathogenic variants. Homozygosity was observed for 32/36 patients (88%), and four patients were compound heterozygous.
Overall, we identified 36 unique pathogenic variants based on the low allele frequency or absence of variants in ExAC, their high evolutionary conservation, the type of the amino acid substitutions, and the high predicted impacts of an amino acid substitution on the structure and function of a human protein in 19 genes. Of these, 20 were novel with the remaining 16 previously reported as IRD-causing variants [31-45]. Furthermore, 14 out of the 50 families remained genetically unexplained (Figure 1). Thus, the sensitivity of the gene panel for detection rate was 72%. The unique variants comprised 15 missense variants, nine nonsense variants, three deletions or insertions leading to a frameshift, six canonical splice site variants, two in-frame deletion and duplications, and one start loss. Pathogenicity was interpreted in accordance with different predictions (Table 3). According to the prediction tools in this study, all variants were annotated as pathogenic except one missense variant in ABCA4 (c.6385A>G; p.(Ser2129Gly)) that is predicted to be benign by PolyPhen-2 and tolerated by SIFT. However, this variant was predicted to be disease causing by MutationTaster and a high CADD score. As shown in Appendix 1, this variant is situated at the penultimate position of exon 46 and is part of the splice donor site consensus sequence. The canonical splice site nucleotides are GC, and therefore, the corresponding splice site was recognized only by SpliceSiteFinder-like. It predicted a strength of 91.8 (on a scale from 0 to 100) for the wild-type sequence and 80.3 for the mutant c.6385A>G, which is considered a large decrease in splice strength. Accordingly, we included the p.? in the predicted protein change. In addition, this homozygous variant has not been reported in ExAC.
Although consanguineous marriages are common in the Iranian population , which makes the Iranian gene pool a valuable asset for genetic studies, little is known about inherited retinal degeneration in the Iranian community. Overall, 37.4% of Iranian marriages are consanguineous. Among them, 19.3% are first cousins and 18.1% second cousins . Thus far, three small studies on genetic causes of Iranian patients with IRD have been reported [41,48,49].
Compared to the multiple targeted gene panel tests for different subtypes of IRDs that have been developed in the past few years with a detection rate of approximately 50–70% , we found similar percentages of pathogenic variants using our panel testing. Haer-Wigman et al. showed that using an in silico gene panel (based on whole exome sequencing) that was performed for 266 Dutch patients with visual impairment, in 52% of the cases, the genetic cause was identified . However, in some studies the detection rate using panel testing was low. For instance, Fu et al. recruited 31 families with autosomal recessive RP and identified the pathogenic variant through a gene panel comprising 163 retinal disease genes. The authors achieved a detection rate of approximately 40% .
Variant c.6385A>G, apart from a predicted amino acid exchange, p.(Ser2129Gly), lowers the strength of a splice donor site of exon 46. A splice assay can shed light on its effect. Moreover, most of the variants detected in the patients are homozygous except four families that we identified as carrying compound heterozygous variants in RP1 (Gene ID 19888, OMIM 180100), ABCA4, and BBS2 (Gene ID 67378, OMIM 615981). The most frequently mutated gene was RPE65 (Gene ID 6121, OMIM 180069), mutated in 4/50 (8%) of the families (Figure 1). Sundaresan et al. reported that although the mutations in some genes such as RPE65 are a common cause of LCA in North America, they are rare in southern India . To determine whether mutations in RPE65 are a common cause of RP in the Iranian population, we need to screen a larger cohort of RP probands in the future.
Our genetic findings, in particular the recurrence for variants in CERKL (Gene ID 375298, OMIM 608381), RPE65, and RPGRIP1 (Gene ID 57096, OMIM 605446) will aid genetic testing for IRD in the Iranian population. Furthermore, different variants in one gene can cause the same phenotype as, for example, different homozygous missense variants in GUCY2D (Gene ID 3000, OMIM 600179) in two unrelated patients cause LCA. Similarly, various pathogenic variants in LRAT (Gene ID 9227, OMIM 604863) and CRB1 (Gene ID 23418, OMIM 604210 ) in unrelated patients cause RP. However, the same variant in one gene can cause different phenotypes, such as a homozygous frameshift variant in the CERKL gene that led to CRD and RP in two unrelated families. Another example of this category is a homozygous missense variant in RPGRIP1 that caused LCA in two unrelated patients and CRD in one patient. In addition, different variants in one gene can cause different phenotypes as exemplified by ABCA4 that causes STGD1 and autosomal recessive (arRP).
Mutations in genes associated with Bardet-Biedl syndrome (BBS), such as BBS1 (Gene ID 582, OMIM 209900) and BBS2, can also be found in non-syndromic arRP [54-56]. The variants within these two genes identified in this study are associated with non-syndromic RP as the probands did not show extraocular features.
We identified homozygous CRB1 variants in two RP probands. One of these missense mutations, p.(Thr745Met), was previously detected in three Iranian RP cases by Ghofrani et al. . Mutations in CRB1 have been shown to be responsible for 10% of LCA cases in northwestern Europe and 2.5% of arRP cases in the French population [10,57].
Although finding known and new mutations in known IRD-associated genes through cost-effective gene panel testing is important for patients who cannot afford the price of whole exome sequencing (WES) and whole genome sequencing (WGS), WES and WGS provide the opportunity to discover novel genes, as well as copy number variations (CNVs) and noncoding variants in IRD-associated genes [58-60]. The sequencing costs for this gene panel testing (MIP analysis), excluding the MIP synthesis costs and Sanger sequencing validation, were about €40 per sample, which is 10–20 times lower than the commercial price for WES.
Despite the high yield in this study, for 28% of the patients with IRDs, we still do not know the causal gene defects. The MIP design was based on the non-syndromic IRD-associated genes known in October 2013. In the meantime, another 60 non-syndromic IRD genes have been discovered that together may well explain another 10–15% of IRD cases. In conclusion, we demonstrated that this panel testing, employing MIPs, is a cost-effective targeted NGS-based method with a high detection rate for pathogenic variants in patients with IRDs.
Appendix 1. Splice site prediction scores for the ABCA4 c.6385A and c.6385G variants according to five algorithms in Alamut Visual.
We are grateful to the patients and their families for their participation in our study. We also thank Mina Bozorgzadeh Esfahani and Maryam Ghalyani for her help in this study to gather the families. We also thank the Medical Genetics Laboratory of Genome, Isfahan, Iran. This work was supported by the Algemene Nederlandse Vereniging ter Voorkoming van Blindheid and Landelijke Stichting voor Blinden en Slechtzienden that contributed through UitZicht 2014-13, together with the Rotterdamse Stichting Blindenbelangen, Stichting Blindenhulp and the Stichting tot Verbetering van het Lot der Blinden (to FPMC). The funding organizations had no role in the design or conduct of this research, and provided unrestricted grants.


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Will Clift’s favorite toy as a child was a huge set of wooden blocks, which he’d assemble into cantilevered structures, pushing them larger and larger until they came crashing down. As he grew up, sculpture remained his main passion, but was not his first career ambition. He earned B.S. and M.S. degrees from Stanford that combined psychology, business, and engineering, then worked as an environmental engineer for three years before committing to his art full-time in 2006.
In 2016, Stanford invited him back as Visiting Artist, during which time he developed several interdisciplinary projects with departments ranging from Dance Choreography, to Material Science, to Environmental Engineering. Later that same year, Clift won the prestigious International Visiting Artist prize through Australia’s Sculpture by the Sea exhibition, one of the most-visited outdoor sculpture exhibitions in the world. And in 2021 he was awarded the 2022 Prix de Henry Clews, a biennial art prize originating in France. As part of the Prix, he is spending from the fall of 2022 through the summer of 2023 developing new sculpture projects at the Chateau de La Napoule, in the town of Mandelieu-La Napoule, France.
While much of his early work was in wood, as the scale and complexity of his pieces has increased he has mastered a wide range of materials to keep up. Large-scale and site-specific works are now a primary focus, in materials ranging from steel, to carbon fiber composite, to ultra-high-performance concrete.
I explore gesture in sculpture through the interaction of form, gravity, and balance. This interaction is my medium, as much as any physical material.
My sculptures are abstract but evocative, tied to familiar forms. They explore the line between order and disorder, combining intersecting parts into a whole that stands in delicate equilibrium on a small foot. Each work is precarious, yet ultimately poised and stable, overcoming entropy. I use this narrow point of balance to connect viewers to something beyond the sculptural object itself. In each form are tension and poise, the suggestion of gesture or movement, the ephemeral moment between breathing in and out.
My training is a combination of engineering, the sciences, and the arts, and with my sculpture I aim to pull these disparate fields together. As I would have said in my days as an engineer, the point of balance is where potential energy transitions into kinetic energy, and a form narrowly balanced can express both.
Over the last 20 years I’ve mastered several traditional sculptural media, including wood, bronze, and steel, and have pioneered within the sculptural field several others, including carbon fiber composite and ultra-high-performance concrete. Each material has its strengths and limitations, and matching the material to the multi-faceted demands of a project is something I care a great deal about.


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Garden of Joy [Digipak] by Maria Muldaur.Maria Muldaur's ripe, sexy vocals have been delighting audiences ever since she started singing in Greenwich Village coffeehouses. As you may or may not know, her first recordings were made for Elektra Records in 1964 as part of the Even Dozen Jug Band, a group that included future icons John Sebastian (Lovin' Spoonful) and progressive bluegrass pioneer David Grisman, creator of Dawg Music.£6.27From New ZealandMSRP Previous price£10.99Free postage
Jr. Gone Wild - Simple Little Wish [New CD]Title: Simple Little Wish. Simple Little Wish. Artist: Jr. Gone Wild. Item Condition: New and unplayed. Format: CD. Label: Stony Plain Music. Dropping Like Flies.


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HUNTINGTON, W. Va., Feb. 20—The Huntington Herala‐Dispatch said it this morning with a picture: a panoramic view of the Ohio River stretching across page 1. Superimposed on the river was huge, black question mark.
Who spilled 70 tons of carbon tetrachloride into the Ohio River system, ford ing the inhabitants of river towns to boil their drinking water two days ago to ri? it of the potentially deadly chemical?
Was there ever any real danger?
And if there was, why weren't the valley's health officials notified of the dan. ger until it was almost over?
All of these questions—and especially the last—were being asked today as the 100‐mile‐long slick of carbon tetrachloride sped downstream, and as Federal officials said that the water from Huntington to Louisville, Ky., had again become safe to drink.
The incident of environmental examination “was over with before people knew it was happening,” conceded an official in the Federal Environmental Protection Agency's regional office in Chicago.
Actually, another E.P.A. official said, the agency began investigating the incident Feb. 6. But the public was not made aware of it until last Friday evening, 12 days later.
Meanwhile, the search for the source of the massive spill of carbon tetrachloride, which has been linked to cancer in laboratory experiments with rats, was continuing. The prime suspect, according to a source close to the investigation, is an FMC Corporation plant situated on West Virginia's Kanawha River at South Charleston. The Kanawha is a major tributary of the Ohio.
Suspicion has centered on FMC., the source said, because the company refused until last Friday to allow its discharges into the Kanawha to be sampled and inspected. Three other companies also produce carbon tetrachloride at Kanawha sites, and all three complied with the E.P.A.'s request for the sampling, according to the source.
The high levels of carbon tetrachloride became known in Cincinnati on Feb. 6, according to Daniel Snyder, an E.P.A. regional administrator in Philadelphia. Mr. Snyder said that carbon tetrachloride was found in quantities “in excess of 50 parts per billion in tap water” at Cincinnati. River communities from here to Louisville draw their drinking water from the river, purify it and store it for use.
But the carbon tetrachloride, a colorless toxic liquid, apparently slipped by Cincinnati's filtration system.
Fifty parts per billion is more than five times the normal amount of carbon tetrachloride in the Ohio River, Mr. Snyder said. He said also that there is “no unanimity” among scientists as to what levels of carbon tetrachloride are harmful tot health.
“You hear the number 50 [parts per billion] talked about, and the number 100 talked about,” he said.
On the basis of the Cincinnati discovery. Mr. Snyder said, the E.P.A. began taking samples of river water between Cincinnati and Parkersburg, W.Va.
“We thought we were looking at a fairly routine kind of enforcement survey,” Mr. Snyder said. “What we were looking for,” ho said, “was the possibility that somebody may have increased normal discharges. We never expected to find numbers indicative of a spill, and that's what we found.”
The samples of water were taken at 22 locations on Feb. 11 and 12, Mr. Snyder said. When asked why no warning was issued until Feb.18, he said it was because it took that long to analyze the results.
“You have to set up the lab equipment and calibrate it for accuracy,” he said. “so it makes sense to run a series of samples instead of one sample, so that you don't spend all your time setting up the equipment.” He said the samples were “batched” and delivered to the E.P.A.'s main national water laboratory in Cincinnati the weekend of Feb. 12 and 13.
The Cincinnati lab began early last week to analyze the samples at the maximum rate of “four or five a day,” Mr. Snyder said.
When all the results were assembled last Friday, he said, it was clear that there had been a massive spill. Here at Huntington, for example. the concentration of the chemical on Feb. 11 was 190 parts per billion in the river, and 100 to 130 parts per billion in treated drinking water.
The E.P.A. men advised riverbank dwellers to boil all their drinking water. Physicians were advised that any acute effects of carbon tetrachloride poisoning would show up as flu symptoms. The chemical is said to be particularly harmful to the kidney and liver. As of this afternoon, however, the environmental agency had received no reports of illness associated with the spill.
Meanwhile, the “sludge” of chemicals began moving downstream at four times the rate that the E.P.A. had expected.
By yesterday, carbon tetrachloride levels were said to be down to 34 parts per billion at Cincinnati, 8 at Portsmouth, Ohio, and 14 here. This morning, according to Mr. Snyder, the levels were measured at 20 at Louisville, and the slick had passed that city. Other E.P.A. officials said the slick was being steadily diluted as it moved toward the Mississippi. The E.P.A. has consequently lifted its water‐boiling recommendation.
Mr. Snyder said that the Federal agency suspects there was probably more than one spill. The first, he theorized, was reflected in the original sampling at Cincinnati. The second would have been reflected in the Feb. 11‐12 samplings.
On Feb. 7, according to the source close to the investigation, it had been determined by the Federal agency that only four plants could have released any carbon tetrachloride into the Ohio system.
When FMC refused to monitor its Kanawha River effluent, or to allow the E.P.A. to do so, the Federal agency went to court. Last Friday, FMC agreed in court to sample its river discharges voluntarily.

domain: chemistry


Childhood obesity, cancer, mental ill health and response to drugs therapy all present major challenges to the NHS for ethnic minority populations. These topics are being given priority in this year’s NHS Evidence update for ethnicity and health.
The NHS Evidence Collection (Ethnicity and Health) update will be taking place online from 19th to 23rd October (www.library.nhs.uk/ethnicity). The Collection, based at the University of Warwick and run in collaboration with De Montfort University, was formerly known as the Specialist Library for Ethnicity and Health.
In the first report, Dr Deborah Bird and Dr Monica Lakhanpaul from Leicester University give their overview of childhood obesity. They point out that UK obesity rates are significantly higher for South Asian children compared to white British children. However, a 2009 review of all the published evidence on interventions for treating obesity in children could not find any research which recorded ethnicity or considered its impact on successful intervention. Currently South Asian adults in the UK are six times more likely to suffer from conditions associated with obesity such as diabetes. Childhood obesity in South Asian population therefore represents a future time bomb for the NHS which needs to be addressed.
In another commentary, Paula Lloyd, Associate Director of the National Cancer Action Team points out that 30 years after collection of ethnic monitoring data was initiated by the NHS, the first analysis of cancer by ethnicity has been undertaken in England. She comments that the report published this year, “has for the first time confirmed increased rates in specific ethnic minority groups”. She also recommends immediate action since “this first national picture of how cancer affects minority ethnic populations raises a number of important issues for commissioners around the notion of awareness and detection and screening programmes”.
Differences in drug response between ethnic groups have long been acknowledged although little action has been taken by the NHS to date. Professor Larry Goodyer from Leicester School of Pharmacy and Tom Burnham from Guy’s Hospital, London point out that differences can affect the incidence of adverse effects or failure of therapy. In 2009, the Collection identified over 155 different drugs or classes of drug which are of immediate interest. However examination also showed “only 16 drug labels in the UK commented on the response to drugs in Asians”. In the USA the Food and Drug Administration (FDA) has now licensed specific drug combinations for use in African American patients with heart failure, but this lead has not been followed in the UK. Risks associated with differences in drug response between ethnic groups still need to be acknowledged and then addressed by the NHS.
In an update on mental health policy, Professor Kam Bhui from the Centre for Psychiatry, Wolfson Institute of Preventative Medicine, London comments that as the Delivering Race Equality programme in England comes to an end and is absorbed into a broader equalities programme, there is as yet no agreement on a separate race equality strand or policy for mental health. At the same time “there is evidence that integrated equalities and mental health policies, where these exist, have not successfully addressed ethnic inequalities”. With the National Service Framework for Mental Health coming to an end and New Horizons adopting a dramatically different approach with an emphasis on preventive actions, Prof Bhui argues that there is a danger that known inequalities will increase. The challenge is how best to “make use of the developing evidence base on ethnicity and mental health in order to guard against (and even reverse) any possible trends towards increased inequalities, in the light of the new public mental health agenda”.
Professor Ala Szczepura (Warwick Medical School) and Professor Mark Johnson (De Montfort University, Leicester) who are leads for the Collection have designed the 2009 annual evidence update to throw a spotlight on these areas of concern.
Professor Szczepura said: “As we collect and filter the evidence it has become increasingly clear that there is a need for more research combined with action by commissioners and service providers in the NHS to address emerging inequalities built into the health system”.
The NHS Evidence - ethnicity & health collection is a key way in which the NHS shows its commitment to improving the quality of healthcare to its black and minority ethnic patients. It was created by the collaborative Centre for Evidence in Ethnicity Health & Diversity (CEEHD) at the University of Warwick and De Montfort University Leicester.
The Collection was launched in October 2006, at the House of Commons Westminster, by the Secretary of State for Health. In 2009, the Collection became part of a new initiative NHS Evidence under the direction of the National Institute for Health & Clinical Excellence (NICE).
The team now intends to extend its work across Europe. Professor Manuel Carballo, of the Geneva-based International Centre for Migration and Health is highly supportive “About time too. We are fully supportive of these plans, which will also assist our objective of creating an international curriculum for culturally competent healthcare practitioners across Europe”.
For further information contact Professor Ala Szczepura, 02476 523985, firstname.lastname@example.org, alternatively contact Kelly Parkes-Harrison, Communications Officer, University of Warwick, 02476 150483, 07824 540863, email@example.com.


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Installation of metering pumps and piping installation considerationsFirst, to prevent the pipe from vibrating fluid inertial resistance
exhaust side, pump start moment, will have a ripple impact on pipeline. This is the unique phenomenon of reciprocating pumps, is due to the liquid in the pipe are caused by sudden acceleration. In order to combat this phenomenon, we request the discharge end inertial resistance (Pid) <1.0kgf/cm2 when Pid 1.0kgf/cm2 is reached, the pipeline will cause vibrations, will adversely affect the pump and its peripherals.
Solution: 1. install pulse dampers; 2. the increased diameter of the outlet pipe and shorten the length of the export pipeline.
excess supply, preventing excessive supply was due to the inertia of liquid flow in the pipeline, work affecting the check valve, the check valve failed, causing the flow rate of the pump is too large and unstable. When insufficient negative pressure suction side or pipe passing through long, are likely to produce this phenomenon. Therefore, we demand: measuring the differential pressure of the pump > inertial resistance to Pi (inlet port or outlet port is greater).
Solution: 1. install pulse dampers; 2. install back-pressure valve; 3. minimize the length of import and export pipelines;
third, preventing cavitation
If the unit loses (NPSHa) lack of metering pump may stop or cavitation damage. Therefore, we request the device loses, NPSHa> cavitation allowance required (NPSHr), NPSHa=Pa-Pv ± Phs-Pis* (* select larger or Pfs).
Pa: absolute pressure kg/cm2Pv of the liquid: liquid vapor pressure kg/cm2Phs: into the water height (height is level with the surface) the relative pressure (kg/cm2 into absorption taking "+" absorption absorption take on "-" Pis: into the water kg/cm2Pfs inertial resistance: into the water pipe resistance kg/cm2


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