Erin Patrick, Senior Program Officer, Fuel and Firewood Initiative, has worked in refugee policy and humanitarian response programs since 2001. She currently manages the Women’s Refugee Commission’s Fuel and Firewood Initiative, focused on ensuring that displaced women and girls have safe access to appropriate cooking fuel.
She led the Women’s Commission’s development and co-chairing – with the World Food Programme (WFP) and UN High Commissioner for Refugees – of the InterAgency Standing Committee Task Force on Safe Access to Firewood and alternative Energy in Humanitarian Settings (SAFE). The SAFE Task Force developed the first-ever global guidance documents for the UN system on the proper management of household energy collection, supply and use in humanitarian settings. Since the launch of the SAFE guidance in 2009, Erin has been conducting a series of workshops and trainings for agency staff worldwide and partnering with WFP to implement the guidance in a variety of countries. She is also responsible for developing the first Rapid Assessment Tool for household energy needs in humanitarian settings, which she field-tested in the immediate aftermath of the earthquake in Haiti.
Erin has worked for the Migration Policy Institute, Human Rights Watch, the Kettering Foundation and for CNN terrorism analyst Peter Bergen. She holds an MA with distinction from the Johns Hopkins University School of Advanced International Studies (SAIS) and a BA from Indiana University.


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Fertility hospitals are hospitals that specialize in the diagnosis and treatment of infertility. The first fertility hospital was established in 1977 by Dr. Bertold Wiesner, who was a gynecologist and obstetrician.
The goal of the our hospital is to help people with fertility problems get pregnant. We are best fertility hospital and offer many treatments including IVF, intrauterine insemination, surgery, and others. Our best Fertility hospitals in India is known for their high success rates when it comes to IVF treatments. We have the latest technology and they have enough space for patients. Some of our services are also offered at other types of hospitals or health care facilities, but it is important to find a fertility specialist for this type of care because they have the most experience with these issues. Here we have a good track record of success rates, and we specialise in this specific fertility treatments.
Frequently Asked Questions
Fertility is the natural capability to reproduce. A person’s fertility is affected by many things, such as age, lifestyle and environment. The most common thing that affects a person’s fertility is age. Age can affect a person’s fertility for many reasons, such as a decrease in hormone levels.
Fertility is the natural capability to reproduce. Fertility rates are calculated by measuring the number of births per 1000 people in a population. Fertility rates are an important indicator of how healthy a population is, with higher fertility rates indicating that there are more children being born and that the population is growing. The most common measure of fertility is the total fertility rate (TFR). This measures how many children a woman will have over her lifetime based on current patterns of age-specific fertility rates.
Infertility is a condition that affects one in six couples. With such a high number of people affected, you would think it would be more talked about and researched. But the opposite is true. There are many misconceptions about infertility, and as a result, many people don’t know how to get help or even what the problem really is.
The definition of infertility is not having a baby after trying for one year of unprotected sex (or six months if you’re over 35). It can be caused by things like: hormonal imbalances, blocked fallopian tubes, endometriosis, or problems with sperm production or movement.
The most common cause of infertility is male-factor infertility which accounts for about 40% of all cases. Female-factor infertility is the second most common cause which accounts for about 30% of all cases.
The causes of male infertility can be classified into two broad categories:
Obstruction: Obstruction of the passage of sperm from the testicles to the penis. This can be due to a blockage, such as a varicocele or an enlarged prostate.
Malformations: Malformed reproductive organs, such as an undescended testicle or a deformed penis or urethra.
The most common cause of infertility in males is low sperm count. This can be caused by a number of factors, including age, lifestyle, and health.
Low sperm count can also be caused by certain diseases or disorders that affect the testicles. These include:
In females, there are many causes of infertility. Some of the most common causes include:
Premature ovarian failure is a condition where the ovaries stop functioning before the age of 40. This happens when the eggs released by the ovaries are not able to mature and release. Premature ovarian failure and infertility are two different medical conditions that share some similarities but also have some key differences. Premature ovarian failure occurs when a woman’s ovaries stop functioning before the age of 40 and infertility is when a woman cannot conceive after unprotected sex for one year. Infertility is a condition in which a person cannot produce an egg or sperm, or both, to create an offspring.
The answer to this question is not straightforward. Stress has many different effects on the human body, and the reproductive system is no exception.
Stress can affect fertility in two ways: It can make it difficult for a woman to ovulate or it can make it difficult for her to become pregnant. The first way is called primary infertility, and the second way is called secondary infertility.
Primary infertility occurs when stress affects a woman’s ability to release eggs (ovulation). Secondary infertility occurs when stress affects a woman’s ability to become pregnant by reducing her chances of conceiving or carry a pregnancy to term.
Stress can be defined as a feeling of tension, anxiety, or worry. It is said that stress has the potential to cause infertility in both males and females.
Stress can affect fertility in both men and women. For men, stress can lead to erectile dysfunction or premature ejaculation, which will prevent them from becoming fertile. For women, stress can lead to infertility by affecting their menstrual cycle.
Infertility is defined as the inability to conceive after a year of unprotected intercourse. Infertility can be caused by many different factors such as:
MBBS, DCH, FELLOW NNF(NICU)
Neonatologist & Pediatrician
Director – Mother & Child Unit,
Neonatologist & Pediatrician
Director Gyane & Obstetrician
MBBS, MD Medicine
General And Critical Medician

domain: health


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The top showbiz news and headlines for the week ending September 11 including Jackson tribute concert canceled, EllenDeGeneres to join "American Idol," and Hugh Hefner files for... - 09.10.2009, ReutersFDP
28.03.2012 [Los Angeles Times] - 3 pm KABC The EllenDeGeneres Show Channing Tatum. 4 pm KNBC Anderson “American Idol” castoff; Niecy Nash. (N) 4 pm KTTV The Rosie Show Mackenzie Phillips; Jeff Lewis and Jenni Pulos. (N) 7 pm OWN Tavis Smiley Secretary of Labor Hilda Solis;
22.03.2012 [Vanguardia.com.mx] - Un gran jugador de americano”, le contestó a la presentadora EllenDegeneres cuando ésta le preguntó si tendría gemelos. Y cuando Simpson leyó un reportaje que decía que una persona expide flatulencias unas 15 veces al día, ella twiteó: “En promedio
22.03.2012 [Businessandleadership.com] - The broadcast last night of Dublin's St Patrick's Day celebrations on the EllenDeGeneres Show was worth more than €2m in advertising value, according to Tourism Ireland. An audience of almost 5 million American TV viewers saw images of Dublin and
27.03.2012 [Abbotsford Times] - Mission's Carly Rae Jepsen made her American TV debut Friday on The EllenDegeneres Show, as the protégé of the younger Canadian pop sensation Justin Bieber. The young crooner himself was apparently not announced as a guest on the show
02.11.2010 by Jason Shaw Yes, especially when Portia told Oprah of her deep pure love for her wife, the other American chat show queen - EllenDeGeneres! She also told how that deep emotion keeps her sane and saves her each and every day, as well as feeling ...
02.11.2010 by belle EllenDegeneres as Snooki's poof. Rachel Zoe as a Native American. Ciara as Strom. Shenae Grimes. Kim Kardashian as Little Red Riding Hood. Nicky Hilton as Supergirl and Paris Hilton as a Native American. Ashanti as a cat ...

domain: entertainment


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There are a lot of Bluetooth speakers in the market, from simple and minimalist ones to the more luxurious and expensive-looking ones. When it comes to design though, there aren’t that many that go out of the box so to speak so we see either circular, box-shaped, dome-shaped, spherical, and other common shapes. So when we see uniquely-designed ones, even if they’re still just in the concept stage, then it catches our attention.
Designer: Hyunjae Noh
The concept for the Saturn Bluetooth speaker is inspired by, you guessed it, the planet Saturn. It’s one of the more “unique” planets in a sense that it has countless rings surrounding it made from ice and rock particles. It also has a yellow-brown golden hue when viewed from earth because of gases like helium and hydrogen. The designer was able to adapt these qualities into a design for a speaker that would most likely stand out. It would look like a sculpture of the planet but once you start playing music from it, then it would be a conversation starter as well.
But it just doesn’t emulate the look of Saturn. There’s a functional purpose for the parts as well. There is an upper body, a lower body, and a singular ring. The last one is what you will use to adjust the volume of the music or podcast streaming from the speaker. Because there is an upper and lower part, the support between the two is there to minimize the vibration interference from the woofer, midrange, and tweeter as well as minimizing interaction between them. This means there should be better sound quality and accuracy of sound reproduction.
The 360 degree speaker placement means your sound can be distributed around the room. The multi-way system is also able to accurately separate low, mid, and high-frequency ranges. You get 10 hours of playback on a full wireless charge, so it means you can also bring it around with you if you don’t mind carrying around a planet.

domain: design


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Our fourth release came from Jack ‘Pola’ Higgins, a co founder of Soulvent, and one third of the label’s personnel. His debut release ‘Sound Killa’ blends new and old influences well – mixing warm liquid tones with an old school beat. The well rounded roller features a well-known jungle sample alongside surging drum progressions and rave-style piano chords.
Meanwhile ‘Little Do I Know’ is quite the change of pace. Featuring vocals provided by none other than Pola himself, it also features label mate Bryzone (Bryson). A stirring and atmospheric track, Pola blends melancholic chords with a gritty live drum sound to deliver a fitting B side to a beautifully balanced single.
These are two sophisticated pieces of work from producer and Pola, who has gained a nod of approval from the likes of Etherwood and Logistics, and the release began paving the way for a blossoming production partnership between himself and Harry Bryson.

domain: artistic


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SAN FRANCISCO — Pope John Paul II's planned trip here is stirring anger and anxiety within the city's homosexual community.
An Episcopal priest who is a gay-rights activist predicts huge demonstrations unless the pontiff cancels his visit.
A 350-member gay political group has adopted a resolution opposing the Pope's visit to San Francisco, one of eight cities on his Sept. 10-18 trip to six states. And a coalition task force is planning events to counter the Roman Catholic Church's official views on homosexuality and the role of women.
"The Pope has become possibly the most visible symbol in the world of oppression to gays and lesbians, and of homophobia. Having him here in San Francisco is like waving a red flag in front of a bull," said Richmond Young, chairman of the Political Action Committee of the Alice B. Toklas Lesbian-Gay Democratic Club.
A major statement issued in October by the Vatican restated and strengthened the church's condemnation of homosexual behavior and warned against association with pro-homosexual groups.
"Things have just started" in organizing opposition to the Pope's visit, Young said Friday. "I don't know if there will be any violence, but there is certainly going to be a lot of anger."
The club's resolution asks the mayor and Board of Supervisors of San Francisco not to extend an official welcome to the Pope nor to spend any public funds on his visit.
More organized opposition to the pontiff is expected, according to John Wahl, a San Francisco lawyer who is a member of the Stonewall Gay Democratic Club and chairman of the Papal Visit Task Force--a coalition of eight groups comprising gays, lesbians, abortion-rights groups, feminists and people who favor the ordination of women in the Catholic Church.
'We're Mad as Hell'
"We are preparing a significant, strong, even unforgettable reception for what really is a foreign prince coming to our country to preach against the freedoms many of us have fought for many years to achieve," Wahl said. "We are in no mood to meet this man. . . . If the Pope wants to be some kind of enemy, so be it. We'll take him on. . . . We're mad as hell."
Topics discussed by the task force at its first meeting last week included:
- Several demonstrations, at which members believe they can draw at least 100,000 people.
- Possible legal action to prohibit the use of city-owned Candlestick Park for the Pope's celebration of Mass on Sept. 18, based on an ordinance forbidding the city from doing business with groups that discriminate against gays.
- A letter to the Vatican warning the Pope of the adverse sentiment.
The Rev. Robert Cromey, rector of Trinity Episcopal Church, 50 of his parishioners and the church's board of directors recently signed a petition to San Francisco Mayor Dianne Feinstein, urging that she join him in asking the Pope to cancel his visit because it could "cause greater divisions between the homosexual and heterosexual communities in San Francisco."
"Many gay men and lesbian women I've talked to are offended and are sitting around thinking of things to do. I suspect there is going to be a lot more response to the Pope's position, which we call immoral because we think it leads to disruption, violence and gay-bashing," Cromey said.
"I don't think the mayor and police have any idea of the hostility and anger homosexual people have toward the Pope," Cromey, who is not gay, added. "I think people could get physically hurt in demonstrations and counter-demonstrations."
San Francisco is heavily Catholic, however, and support for the Pope is also likely to be high.
No Protest Planned
A spokesman for Dignity, a support group for homosexual Catholics, said that the organization was "outraged" at the guidelines recently issued by the Vatican that call homosexuality "an objective disorder" and "an intrinsic moral evil." But he said Dignity had no present plans to protest the Pope's visit.
"We want to be seen as the loyal opposition," he said. "But we will issue a vigorous and creative public statement during the Pope's stay in San Francisco offering him a prophetic Christian witness . . . and explaining our dissatisfaction with the papal statement" against homosexuality.
The Dignity spokesman, who spoke on condition that he not be named, said "a number of members" of the San Francisco chapter of Dignity had also signed Cromey's petition.
Bill Strawn, a spokesman for Feinstein, said the mayor had written Cromey that she "essentially disagreed completely" with his view that the Pope should not come to San Francisco.
"I feel San Francisco is a city of great tolerance. No one ideal or religion, in my view, should be denied to be heard," Strawn quoted Feinstein's letter as saying.
San Francisco Episcopal Bishop William Swing has also disassociated himself from Cromey's position.

domain: news


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Heart disease is the leading cause of death for both men and women in the United States and is often perceived as an “older person’s disease.” But now according to a first-of-its-kind study reported in Circulation: Journal of American Heart Association even the Now Generation can’t have a ‘whatever’ attitude about heart health.
Research shows that teenagers who consume a lot of added sugars in soft drinks and foods may have poor cholesterol profiles — which may possibly lead to heart disease in adulthood. (No worries I’ve got a Healthy Soda Recipe below 🙂
“Added sugars” are any caloric sweeteners (e.g. sugar, brown sugar, high fructose corn syrup, fructose, fruit juice, honey, maple syrup, cane sugar, organic cane juice, etc.) added to foods or beverages by the manufacturer during processing or by the consumer.
The National Health and Nutrition Survey (NHANES) of 2,157 teenagers (ages 12 to 18) found the average daily consumption of added sugars was 119 grams (28.3 tsp or 476 calories), accounting for 21.4 percent of their total energy. To put sugar content in perspective:
o 12 ounce can of fruit flavored drink or soda = 7-10 tsp of sugar
o brownie = 4 tsp sugar
o chicken nuggets = 3 tsp sugar
o plain slice of bread = 1-2 tsp sugar
So you can see how quickly it can add up. This is especially true since sweet things have lost their status as treats and are everyday foods.
Recently, the American Heart Association recommended a specific upper limit for added sugars intake, based on daily individual caloric needs the amount of energy the person expends, sex and age. For example, 1800 calories might be the appropriate amount for an average teenage girl ages 14-18, she would need no more than 100 calories from added sugars. An individual with a requirement of 2200 calories per day would drink or eat no more than 150 calories from added sugars.
Teens consuming the highest levels of added sugars had lower levels of high-density lipoprotein levels (HDL), the good cholesterol, and higher levels of triglycerides and low density lipoproteins (LDL), the bad cholesterol. Here are a few of the study highlights:
- Consuming high amounts of added sugars in soft drinks and foods in adolescence is associated with poor cholesterol profiles and poor diet quality, possibly leading to heart disease in adulthood.
- Teens who ate the highest levels of added sugars had lower good cholesterol levels and higher bad cholesterol and triglyceride levels than those with the lowest intake.
- Overweight or obese teens with the highest levels of sugars intake had increased signs of insulin resistance.
The good news for teens is that the chances of heart disease can be reduced when you take steps now to prevent and control factors that put people 25 and older at a greater risk. The research author Jean Welsh, MPH, PhD, R.N. suggests reading labels of the foods and drinks you consume and replacing sugary drinks with water since the largest contributor of added sugar was found to be from beverages.
Healthy diet and lifestyle are the main weapons you have to fight heart disease. The sooner you start the better and the easier. Adults have done a good job of making it seem harder than it really is. But the bottom line is the overall pattern of choices you make and your daily habits are what matter. So make them count!
HEALTHY SODA RECIPE
6 ounces sparkling water
4 ounces cran-apple juice, apple juice, cranberry juice, orange juice or pineapple juice
1 lime wedge
Serve cold and enjoy!!

domain: food


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A frustrated office worker thinks the murder of his boss is just a figment of his imagination - but it’s very real.
A warrior from another dimension fails in his attempt to kill a young Adolf Hitler.
Catch Metal Hurlant Chronicles on Mondays at 10 & 10:30 p.m.
Maybe the whole cryogenics rumors are true...
Download the TV Guide app for iPhone, iPad and Android!


Frank James is a “person of interest” in Tuesday’s Brooklyn Subway Shooting, which wounded over 20 people. At least ten individuals were hurt by gunshot, according to authorities, while another 13 were hurt by smoke inhalation or other means. Frank James, known as “Prophet of Truth 88,” released hundreds of disturbing films on his YouTube page, including threats against New York Mayor Eric Adams and references to subway atrocities. After the tapes were discovered and James was identified as a suspect, NYPD commissioner Keechant Sewell notified the media that security was increased for Mayor Adams.
A guy in a construction vest lobbed a smoke bomb onto the N train and opened fire, according to witnesses. The alleged shooter allegedly ran away when the train arrived at the 36th Street stop in Sunset Park. Subsequent investigation found that Frank James had driven to Brooklyn, New York, in a U-Haul cargo van he had hired in Philadelphia. The suspect’s car key was purportedly discovered at the subway shooting site.
Who is Frank James?
Police have identified 63-year-old Frank James as a “suspicious person” in the recent shooting on the Brooklyn Subway. His locations of residence are documented as Wisconsin and Philadelphia. It was found that James is a YouTuber with over 3,000 followers on his channel “Prophet of Truth 88.” His videos, which include repeated death threats on New York City Mayor Eric Adams, are filled with racist, political, and violent commentary.
Frank James: Prophet of Truth 88
According to Rolling Stone, Frank James has a Facebook group called Prophet of Truth 88, where he releases identical films to his YouTube site. Frank called himself a “victim” of Mayor Adams’ mental health programme and “full of hatred, rage, and bitterness” in one video. The individual disclosed further personal information, including his history as a patient at a New York Behavioral Health centre for treatment of mental illness. Frank James not only expressed a desire to kill other people but also stated that mental health institutions were rife with violence.
After being released from the mental institution, he said he intended to “murder” everyone. On March 1, Frank James released a video titled “I Told You So, ” which addressed subway crimes head-on. In earlier films, James made inflammatory remarks on race and ethnicities, such as African-Americans, Jews, Caucasians, and Latinos. In one video, he said “people of colour” were waiting to be “flushed down the drain by civilization” and predicted a battle between African-Americans and Caucasians. Catherine, Frank James’ sister, claimed she hadn’t spoken to him in years and that he “kept to himself.”
What happened to Frank James?
Police officials began a search for Frank James immediately after the Brooklyn Subway Shooting, even though they had not yet confirmed his identification as the shooter. According to the police report, the U-Haul related to the shooting included the man’s clothes and personal belongings. James Essig, chief of detectives for the New York Police Department, said that the force would try to track down James and investigate all possible links between him and the incident.


Reigning ACM® Entertainer of the Year, 15-time ACM Award winner and 55th ACM Awards® host Keith Urban, and international pop icon P!NK will perform the world television premiere of their new single, “One Too Many,” on the 55TH ACADEMY OF COUNTRY MUSIC AWARD, a night of heart and hits live from Nashville. The 55th ACM Awards will be broadcast live Wednesday, Sept. 16th (8pm, live ET/delayed PT) on the CBS Television Network, and available to stream live and on demand on CBS All Access.
— Keith Urban (@KeithUrban) September 14, 2020
For the first time in ACM Awards history, the show will take place in Nashville, broadcasting from three iconic Country Music venues: Grand Ole Opry House, Nashville’s historic Ryman Auditorium and The Bluebird Cafe. As previously announced, the 55th Academy of Country Music Awards will also feature performances by Jimmie Allen, Kelsea Ballerini, Gabby Barrett, Kane Brown, Luke Bryan, Eric Church, Luke Combs, Dan + Shay, Florida Georgia Line, Riley Green, Mickey Guyton, Miranda Lambert, Tim McGraw, Maren Morris, Old Dominion, Thomas Rhett featuring Jon Pardi, Blake Shelton featuring Gwen Stefani, Taylor Swift, Tenille Townes, Carrie Underwood, Morgan Wallen and Trisha Yearwood. Joining the all-star lineup are presenters Lauren Alaina, Lily Aldridge, Clint Black & Lisa Hartman Black, Bobby Bones, Cam, Darius Rucker and Runaway June.
For more Keith Urban information, go to www.keithurban.net or follow on facebook.com/keithurban, instagram.com/keithurban, youtube.com/keithurban.com and twitter.com/keithurban.
Keith Urban (ACM hosting) OC: …really fun. :30
“I’m really grateful that the ACMs are going ahead, ‘cause we need something right now. A lot of it will be done in different locations. I’m gonna be hosting from the Grand Ole Opry House, but I believe also we’re gonna cross over to the legendary Ryman Auditorium for some performances there. We’re also gonna be crossing over to the infamous Bluebird Café and doing some performances over there too. So, we’re really bringing in so much of Nashville, you know, and it’s gonna be really fun.”


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PRIMECAP Management Company was founded in September 1983 in Pasadena, California. It manages Vanguard’s PRIMECAP Fund, Vanguard Capital Opportunity Fund, and Vanguard PRIMECAP Core Fund. It also manages PRIMECAP ODYSSEY FUNDS. Since 1984, the Vanguard PRIMECAP Fund has gained an average of 14.5% as of Sept. 2008, while the S&P500 gained 11.6%. PRIMECAP was founded by Chairman and Chief Investment Officer Howard Schow, Vice Chairman Mitchell Milias, and President Theo Kolokotrones. As of Aug. 2008, the company has more than $60 billion under management.
PRIMECAP team evaluate securities based on their outlook over a three to five year time horizon, with the intention of holding them considerably longer if their fundamentals warrant it. They believe successful investment decisions rests in correctly appraising the relationship between the fundamental value of a company and the market price of its stock. A company may be valuable because of its free cash flow, its assets, or both; however, a company will be a superior investment only if it is purchased at the right price. PRIMECAP only invest their highest conviction ideas.
At this difficult time for a lot of value investors, PRIMECAP fares well relative to the market. For the 12 months ended 06/30/2008, PRIMECAP Odyssey Stock Fund lost 10.3%, Growth Fund lost 10.41%, Aggressive Growth Fund lost 16.31%, the S&P500 lost 13.12% during the same period. Since 2004, these three funds outperform the market by at least 2% a year.
PRIMECAP Management invests heavily in healthcare and technology stocks, their largest holdings are El Lily (LLY), Potash Corp. of Saskatchewan Inc. (POT), Novartis AG (NVS) etc. They initiated positions in C.H. Robinson Worldwide Inc. (CHRW), Honeywell International Inc. (HON) etc. This is their complete portfolio.
If you are a Premium Member and you have built your Personalized List of Gurus, PRIMECAP Management has not been added into your list. If you have not, PRIMECAP Management is added, and you can build your Personalized Personalized List of Gurus. If you are not a Premium Member, we invite you for a 7-day FREE Trial.

domain: finance


Lenovo, one of the world's largest electronics manufacturers and the proud owner of the Motorola brand, is expanding once again. The company announced that it would begin manufacturing both Lenovo and Motorola phones in a new factory in Chennai, India, starting with the low-price Moto E and Lenovo K3 Note models. According to the press release, 1500 employees have been hired across manufacturing, quality assurance, testing, and other departments.
The change is notable because in the last decade or so most smartphones have been manufactured almost exclusively in China, with a few exceptions for nearby regional companies (like Samsung in South Korea and Asus in Taiwan... though both only manufacture some models in their home countries). The vast majority of smartphones sold in India, even those made at the behest of Indian-owned companies, are manufactured in China by the company's own employees or intermediate manufacturers like Foxconn.
Lenovo isn't the first mobile manufacturer to open a factory specifically for India. Samsung has a manufacturing wing in the same Sriperambudur neighborhood as Lenovo, and it's already making mobile phones at another Indian plant. Chinese manufacturer Xiaomi began Indian production earlier this year. Some local phone manufacturers are also beginning to expand homeland production, such as Intex and Celkon. The presence of hundreds of millions of potential customers, cheaper distribution lines, and labor costs that are relatively competitive can do wonders for the bottom line. Google's own Android One line has focused on India as its first market. Expect to see other international phone makers expand into India soon.
It's worth mentioning that this Lenovo expansion comes just a week after the company announced it would be laying off 3,200 workers in various departments.
New Delhi, August 18, 2015: Lenovo today announced that it will start the local manufacturing of smartphones in Sriperambudur, Chennai. For the current financial year, Lenovo and Motorola will generate a capacity of six million units. The Moto E has already started rolling out from the plant and the K3 note will follow very soon.
“Lenovo is not new to manufacturing in India. We recognized the potential of India and we invested in PC manufacturing several years ago. Lenovo’s investment in the new manufacturing plant represents the potential we see in the Indian market and our long term commitment to our customers,” said Chen Xudong, president MBG Group, Lenovo and chairman Motorola Mobility Operating Board. “In the past ten years, our brand has grown manifold in India. We are excited to expand our presence and tap into India’s competent talent pool that will enable us to develop cutting-edge products for our customers across the world.”
The campus will house 1500 employees for manufacturing lines, quality assurance, product testing, etc. Both Lenovo and Motorola will have separate manufacturing lines at the same facility.
“The Indian Government’s thrust on ‘Make in India’ has opened up a plethora of opportunities for organizations looking to conduct business in India”, said Amar Babu, COO, Asia Pacific and chairman, Lenovo India. “Currently for smartphones, India is the third largest smartphone market in the world, according to IDC and we believe this an opportune time. Lenovo is transforming into a global consumer technology brand by differentiating itself on innovation and design. Today’s announcement reiterates India’s strategic importance in Lenovo’s global strategy and we are confident that this will propel Lenovo to its next phase of growth, diversifying beyond PCs into smart connected devices.”
The Lenovo and Motorola brands have seen huge success in India and have come back to manufacture in India in support of the ‘Make in India’ initiative. Both companies have started integrating the manufacturing and supply chain operations and are working towards to combining many back-end operations as well.


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Remembering Silvano Salvucci .
Feb. 19, 1958 – May 26 , 2021 .
Too much loved, to ever be forgotten
This musical tribute to Silvano was produced by his brother, Lou. As you listen to this performance by Lou, you will realize who inspired Silvano to make his special music with the Bliss i-Band!
Thank-you, Lou, for sharing this lovely memory of Silvano with us!


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Today I wanted to post about my thyroid health and my overall health. I see a really great doctor who has me on natural thyroid medicine. It has been a chore getting the dosage correct. In the meantime, I noticed that I am always so tired. Originally, I thought it was because of the thyroid but I ran across Dr. Berg’s YouTube channel
He talks about adrenal health and listed many of the symptoms that I was currently having. Friday, I went to my doctor’s and discussed with her some of what Dr. Berg had said. She verified that my blood work showed issues with my adrenal gland and my cortisol levels. She gave me a list of supplements that I needed to take, which are a lot.
Just so happens, today while working on my computer, Dr Berg ran an ad on the Adrenal Body Type package. It caught my attention because the supplements that he listed in his kit were the ones that my doctor recommended for me to take. He had an additional one to help with sleeping, an issue that I have regularly, that cinched it for me and I placed an order.
Here is what is coming in the kit:
A COMPLETE ADRENAL BODY TYPE KIT! (one Get Healthy Kit)
Your weight loss program is a get healthy plan:
STRATEGY: Get Healthy Kit. Your kit is designed to promote your metabolism and support your specific body type. With the Get Healthy Kit, you will receive the entire program, including:
|Gallbladder Formula and your Trace Minerals.|
|Gallbladder Formula – Supporting the gallbladder allows the liver to do its job and not work so hard. Gallbladder Formula has unique nutritional factors to get more out of the food you eat.|
|Dr. Berg’s Sleep Aid (Regular) – Formulated for The Adrenal Body Type to support healthy adrenal glands. By taking key nutrients to reduce your body stress a better quality rest can be achieved.|
|The Adrenal & Cortisol Relief – This product provides you with the essential nutrient factors to not only support healthy adrenal function but to support healthy cortisol levels. Cortisol is at the heart of all stress responses and this is the ultimate product to support stress. If you have a history of stress, both physical and mental or have indulged in years of stimulants (caffeine) or loss of sleep, then this product can help you greatly.|
|Trace Minerals – This product gives you plant based trace minerals to give the necessary factors for protein metabolism. Plant based minerals are 15,000 smaller than other minerals making them 100% absorbable.|
Another thing that he validated that my doctor said was to stop focusing on losing weight but to focus on getting healthy. There is something about validation from two different independent sources to really drive home the point. I am excited to get the kit and to work towards my health. I would like to be one of those that is not the norm when it comes to missing a thyroid. The norm is gaining 30 to 40 pounds when one loses a thyroid. That is depressing. For far for me, I am down 8 pound since losing my thyroid but I have a ways to go. I am not focusing on my weight but my health.
Well, that should do it for now.

domain: medical


For a while now, garment printing enthusiasts have been predicting that maybe Cricut infusible ink would render sublimation transfers obsolete. And yet for some reason, sublimation transfers refuse to go away.
Perhaps it’s because people have caught on to the conception that Cricut’s new line of infusible ink transfers is simply a pre-printed form of sublimation transfers. However, it is no surprise that Cricut has been reluctant to admit this.
In many ways, the two techniques resemble while still showing numerous significant distinctions. And before you decide on which technique to use, it’s important to familiarize yourself with the similarities and contrasting aspects of each.
Join me as I unravel this comparison between sublimation and infusible ink transfers.
The Similarities between Cricut Infusible Ink and Sublimation
The finished designs of both Cricut Infusible Ink and traditional sublimation are very identical, not surprisingly.
Both techniques involve heating the ink and turning it into gas particles which penetrate the substrate and bond with the polymer in the polyester. The ink then cools back to a solid form with the fibers of the base material, and becomes part of it forming the image.
This results in permanent images with no change to the feel of the fabric and zero obvious signs of wear, cheeping, flaking, peeling cosmetic defects.
In both cases, the images are bright and colorful with upscale clarity and details that come across well.
Another resemblance between the two methods of heat transfers is that both need a poly-based blank material with a polyester composition of at least 50%. The polymers in the polyester will bond with the infusible or sublimation ink to form a bright, fade-free image.
Both techniques are limited to white or light-colored blank materials. The inks used are usually translucent and rely on the background to give a base color and brightness to the final design. Therefore, white blanks and other light colors will produce the most vibrant and colorful designs.
You will also like to note that infusible ink sheets as well as printed sublimation transfer sheets appear dull and faded prior to transferring. But once transferred they both result in brilliant designs that are full of color.
Just like the design on infusible ink sheets, sublimation transfers must also be reversed before transferring to the base material.
Heat Press Required
It is also worth mentioning that each of the two techniques involves heat transfers that require heat application of about 385°F – 400°F (195°C) for 40-60 seconds.
Differences between Cricut Infusible Ink vs Sublimation
Although both procedures require a heat press, Cricut infusible ink transfers involve cutting and weeding which calls for a cutting machine.
Meanwhile, to carry out a sublimation transfer, you will need a sublimation printer to print the image onto sublimation transfer sheets.
Variety of Patterns and Colors
Cricut Infusible Ink sheets are only available in a limited number of pre-printed patterns and solid colors. Therefore, you need to cut your designs out of the fixed color choices and patterns of Infusible Ink sheets. You can only customize by cutting designs from the sheets, weeding them, and then pressing on to your blank materials at intervals.
On the other hand, sublimation ink comes in diverse colors, every drop of ink from the nozzles can be of different colors. Sublimation printers work by mixing base colors and using recipes from the design software to come up with any color you may have in mind. This allows you to print full-color pictures, shaped designs, and full patterned images.
Cricut Infusible ink sheets come with the ink embedded on a clear liner. You will need to cut and weed away the clear part to remain with the design.
On the contrary, sublimation paper is self-weeding. So only the printed areas will be transferred to the blank substrate when you press.
Cricut Infusible Ink vs Sublimation: The Summary
Cricut Infusible Ink
- Cricut infusible transfers are very durable. Because the transfer occurs at a molecular level within the fibers of the fabric, the images produced are permanent and free from fading, flaking, distortion, and cracking.
- There is no change to the feel of the fabric since the infusible ink chemically infuses into the fibers of the fabric.
- The colors in the final design are usually very bright and vibrant.
- The cost of the initial investment is low. Besides, the infusible ink transfer sheets, all you will need is a cutting machine and a heat press.
- The design can be layered to come up with a more sophisticated pattern and color combinations.
- You are limited on detail due to the need to cut and weed the transfer sheet.
- Infusible ink sheets come in fixed solid colors and patterns. This limits your freedom in matters of detailed text, intricate images, and full-color photos.
- Cricut infusible ink restricts you to poly-based blank items with a polyester count of at least 50% and only works on white or light-colored substrates.
When to use
If you are into sublimation but cannot afford a big up-front investment, Cricut Infusible Ink transfers are the ideal option for you. It is a relatively low-cost way of doing sublimation printing without the need for investing in costly sublimation printers.
Cricut printing is for you if you will be working with simple designs with little detail and solid colors. You can embed your infusible ink designs onto items you use every day such as t-shirts, bags, pillowcases, coasters and onesies, and non-fabric blanks like infusible key tags, mugs, ID cards, mousepads, key holders.
- Sublimation offers unlimited color options at no extra cost all thanks to the availability of ink in countless hues. Sublimated graphics, therefore, appear in vibrant full color, high-resolution with intricate images and superfine details. You enjoy more freedom to print your customized designs with infinite patterns and colors.
- Sublimation ink dries super fast. Therefore, you can fold for storage or wear the garment as soon as it leaves the press without the risk of smearing the ink.
- The design is permanent and fade-free. The ink bonds with polymers in the matrix of the base material and becomes part of it. So, the image produced is long-lasting and will not fade, crack, peel, or flake even when exposed to water, detergents, or heat.
- Sublimation is suitable for seam-to-seam printing. When heat is applied to the sublimation transfer paper, the ink sublimation to all portion of the print fabric including seams, buttonholes, hems, and other intricate shapes. That said, it is possible to apply the sublimation ink to the entire fabric of a garment.
- The garment printing technique is also economical if you will be doing small quantity runs. Of course, the upfront investment required to get into sublimation is bigger due to the cost of sublimation printers, heat press, and other material. Even so, once you’ve acquired the equipment, the price of sublimation transfer paper per sheet is much lower than the cost of transfer paper used in say Cricut infusible ink transfers. It is therefore cheaper to purchase sublimation transfer paper if you have all the necessary equipment.
- The entire sublimation process is simple and straightforward. Whether you are new to the game or an old hand, the process is a cake walk easy and does not require any special skills.
- The initial cost of buying the equipment is high. Even you are just getting started, the up-front investment can be enormous. The cost of a good sublimation printer can cost upwards of $500 while a heat press will require you to part with at least $250. The printer also requires specialty inks which can be costly.
- Sublimation printing restricts you to limited blank items with a polyester count of at least 50%. Also, you can only transfer sublimated designs onto white or light-colored sublimation blanks since there is no white sublimation ink.
When to use
Sublimation printing should be your go-to option if you have already invested in a sublimation printer. The price per sheet of the sublimation transfer paper is low so you can save a ton with the technique.
If you want limitless options in terms of colors, patterns, and intricate design, you shouldn’t look further than sublimation printing. Also, you will not have to undergo the trouble of cutting and weeding.
For everyday items that you will use and clean constantly such as sportswear, mousepads, and kitchenware, use sublimation printing. This is because the design will resist fading, distortion, and cracking.


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Scientific Games has been awarded a new four-year contract by the Dutch National Lottery to provide instant game scratch cards through the Scientific Games Enhanced Partnership, a performance-driven management programme used by more than 20 lotteries globally.
The agreement may be extended by the Dutch National Lottery for up to four additional years. The program generated more than 28 per cent growth in the lottery's scratch card retail sales during the previous contract period (2015-2019). Since SGEP services began in 2011, Dutch National Lottery's instant game retail sales increased 98 per cent.
Using data analytics and insights to responsibly maximise the lottery's performance, SGEP manages every aspect of the instant product portfolio including game design, manufacturing, inside sales, warehousing, distribution and retailer programmes.
Raffaele Fiorini, business director for the Dutch National Lottery's instant tickets, said: "After a decade of work refining our successful partnership, we are pleased to continue our collaboration with Scientific Games.
"While this announcement comes during a challenging global situation, we are confident our ongoing collaboration will continue our responsible growth trajectory of the instant ticket businessto provide maximum transfers to our beneficiaries."
Scientific Games has supplied the Dutch National Lottery (and its legacy companies) with scratch cards since 1994, moving to the SGEP program in 2010 for full product category management. Scientific Games also provides the lottery with sports betting technology and services.
John Schulz, senior vice president, lottery instant products for Scientific Games, said: "We are honoured that the Dutch National Lottery has entrusted Scientific Games with its instant scratch cards business and we are committed to using our more than 45 years of experience to continue developing its instant product portfolio to responsibly grow sales and profits."


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All images and links will lead to Amazon.com through the Amazon Associates program. All product descriptions also taken from amazon.com.
The Iron King by Julie Kagawa
Releases: February 1, 2010
Meghan Chase has a secret destiny—one she could never have imagined…
Something has always felt slightly off in Meghan’s life, ever since her father disappeared before her eyes when she was six. She has never quite fit in at school…or at home.
When a dark stranger begins watching her from afar, and her prankster best friend becomes strangely protective of her, Meghan senses that everything she’s known is about to change.
But she could never have guessed the truth—that she is the daughter of a mythical faery king and is a pawn in a deadly war. Now Meghan will learn just how far she’ll go to save someone she cares about, to stop a mysterious evil no faery creature dare face…and to find love with a young prince who might rather see her dead than let her touch his icy heart.
Rayne can’t wait to start her summer job at a remote country mansion, far from the crowded, noisy London she so desperately wants to escape. But the retreat soon turns into a nightmare — the mansion is creepy, the legends of ghosts keep Rayne up at night, and she doesn’t feel safe anywhere.
Can Rayne figure out why she’s so freaked — before she becomes a ghost story herself?
Zita is not an ordinary servant girl—she’s the thirteenth daughter of a king who wanted only sons. When she was born, Zita’s father banished her to the servants’ quarters to work in the kitchens, where she can only communicate with her royal sisters in secret.
Then, after Zita’s twelfth birthday, the princesses all fall mysteriously ill. The only clue is their strangely worn and tattered shoes. With the help of her friends—Breckin the stable boy, Babette the witch, and Milek the soldier—Zita follows her bewitched sisters into a magical world of endless dancing and dreams. But something more sinister is afoot—and unless Zita and her friends can break the curse, the twelve princesses will surely dance to their deaths.
A classic fairy tale with a bold twist, The Thirteenth Princess tells the unforgettable story of a magical castle, true love, spellbound princesses—and the young girl determined to save them all.
When a storm brings the dashing Prince Richard to her family’s farm, Violet falls in love at first sight. Richard also gives Violet his heart, but he knows his marriage is destined to be an affair of state, not of passion. For the king and queen have devised a contest to determine who will win their son’s hand in marriage.
To be reunited with her prince, Violet must compete against princesses from across the land. It will take all of her wits — and a little help from an unexpected source — if Violet is to demonstrate the depth of her character and become Richard’s bride.

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Wilson’s disease often remains undetected due to its numerous symptoms which emerge at different times, as well as its individual character. Conversely, Wilson’s disease can also be misdiagnosed as a result of misinterpreting the medical findings. To begin with, the autosomal recessive defect of the hepatic copper transporter ATP7B (chromosome 13q14.3; ATP7B; WND gene) (1,2) causes biochemical deviations followed by the fluctuating occurrence of hepatic and extrapyramidal symptoms (EPS) as well as the impairment of other organs (3-6).
Taking the clinical manifestation into account, primarily between age 5 and 45 (6), in some cases as early as age one or until age 70 (7-9), differential diagnostic considerations are required, which include Wilson’s disease. At the same time, a nosological classification of Wilson’s disease can be used for the allocation of typical and ruling out of atypical findings, to make a tentative diagnosis (10). In addition to starting treatment at an early stage, it is also necessary, from a therapeutic point of view, to make a correct diagnosis to justify treatment, which involves adverse reactions (5,11). In the case of the exclusion of an autosomal recessive disorder of the hepatic copper transporter ATP7B, the clarification of differential diagnoses based on the existing findings is paramount.
In this overview, classification and differential diagnostic consideration are conducted based on the findings. Significant biochemical parameters and clinical cardinal symptoms of Wilson’s disease are taken into account. Age onset as well as the typical spectrum of hepatic or neurological findings serves isolating relevant differential diagnoses.
Classification of Wilson’s disease
Wilson’s disease is characterized by various manifestations as a result of numerous qualitative and quantitative symptoms, which emerge at different times (10,12). Taking the individuality of each patient into consideration, it is a matter of additionally determining the essentials which are consistent in many patients.
Classification by age of onset
Until puberty, gastrointestinal symptoms with hepatic or haemolytic findings are predominant (6,12,13). Consequently, an indistinct elevation of transaminases and bilirubin, icteric flare-ups, signs of a virus—negative acute hepatitis as well as hepatosplenomegaly should lead to the suspicion (4). Acute liver failure is also possible. Haematologically, the occurrence of a Coombs-negative haemolysis and unclear anaemia, leukopenia as well as thrombocytopaenia, are suspicious (4,14).
Without an exact age limit and after overcoming undetected bland gastrointestinal findings, symptoms affecting the central nervous system appear from puberty onwards with dysarthric, extrapyramidal and mental manifestations (6,12,15-17). Laboratory-chemical involvement of the liver (transaminases, synthesis parameters albumin and coagulation factors, cholinesterase, ammonia), change in the sonographic liver texture and a Kayser-Fleischer ring (KFR) can support the suspicion (4,18).
Classification by cardinal symptoms in clinical forms of progression (clinical variants)
Based on the clinical and pathological-anatomical phenomena, Konovalov probably provided the most precise classification in his monograph published in 1960 (19). Following this, five clinical variants were distinguished (Table 1), modified according to Lössner et al. 1980 (15) and Bachmann et al. 1988 (20) based on clinical aspects.
Some authors additionally divide the mixed form into a dystonic and a choreatic form (1,23). Psychiatric symptoms are also variable and include personality changes, behavioural disorders to criminal activities, cognitive disorders, depression and schizophrenia (6,21,24,25). They correlate more with the occurrence of neurological symptoms than with the existence of hepatic symptoms (22,23). In nearly 10%, Wilson’s disease manifests with psychiatric symptoms (24,26). An exclusive psychiatric presentation of Wilson’s disease is also reported in literature (21,22). Oder et al.  recommend a classification of the neurological form of progression into three subgroups for this purpose based on extrapyramidal symptoms and cognitive as well as psychiatric disorders (27). On the other hand, only the (pragmatic simple) classification in neurological and non-neurological disease course is common in daily clinical practice.
A specific differential diagnosis can be made with an exact classification of Wilson’s disease based on the variable cardinal symptoms (10). Particularly in the case of unclear hepatic, extrapyramidal and psychiatric findings, Wilson’s disease must be included in differential diagnostic considerations at an early stage according to the knowledge of its clinical variants.
A quantitative assessment of the EPS (neurological score, Table 2) serves the documentation of the severity of the disease. Imaging results [cMRI, (18F)FDG-PET, 123J-Beta-CIT-SPECT and 123J-IBZM-SPECT], fine motor skills and electrophysiology support the classification in a neurological and non-neurological form of progression. They serve monitoring progression as well as defining differential diagnoses based on the profile of the diagnostic findings.
Differential diagnoses of Wilson’s disease related to findings
Copper metabolism disorders
Deviations in parameters of copper metabolism are not exclusively attributed to Wilson’s disease. Complex biochemical processes are involved in copper homoeostasis. Disruptions in these processes lead to separately described diseases contrary to the ATP7B defect. The following explanations regarding the physiology of copper regulation serve understanding them.
Discussion on standard values
Due to the mutation in the ATP7B gene, the balance of the key regulators for copper balance—the MNK and WND protein—is disrupted (28). The MNK protein (ATP7A, Menkes protein; located on the basal membrane of the small intestinal enterocytes) is responsible for intestinal copper absorption (29,30) and the WND protein (ATP7B; in hepatocytes) for the hepatobiliary excretion as well as copper uptake in the apoceruloplasmin in hepatocytes (31).
In the blood, reabsorbed copper binds loosely to albumin in relation of one atom per albumin molecule. In the process, special importance is attached to the histidine residue from the albumin for the complex formation with the copper atoms (32). Out of the amino acids in plasma, histidine has the highest affinity to copper (32) and transports it itself in small quantities as copper histidine (33). Furthermore, small quantities of copper are bound in the blood by transcuprein and other peptides (33). Ceruloplasmin, which is excreted into the serum, is formed with the covalent bond of 6–7 copper atoms in apoceruloplasmin (32). Approx. 95% of serum copper is transported to the other organs in this manner (34). There is only a small percentage of “free” serum copper.
The standard values in Table 3 apply as a means of orientation for intact ATPase 7B.
Given that ceruloplasmin represents the largest copper fraction in serum, the disruption of its synthesis due to a lack of copper uptake (ATPase 7B—defect) results in a severe decrease of the overall serum copper level. Merely marginal shortfalls of the reference range are not indicative of Wilson’s disease due to its broad spectrum. Free serum copper is higher because it is released from decomposing hepatocytes without a firm bond to other transport proteins. Another value is a matter of an (empirically) calculated value, which on its own is not very meaningful. This diagnostic finding can only be interpreted in a plausible manner in context with other findings.
Ceruloplasmin has a wide reference range and in the case of Wilson’s disease, is decreased to basal values (typically <0.05 g/L) [(36), own data]. The decrease of ceruloplasmin is not 100% sensitive or specific (36). Marginal decreases are often mistakenly considered an indicator for Wilson’s disease. However, these are alimentary, in the case of bile acid synthesis disorders or caused by kidney disorders or individually without pathological significance. Even in the case of heterozygous genetic carriers of the ATP7B mutation, there is still sufficient ceruloplasmin synthesis without the clinical manifestation of Wilson’s disease. Furthermore, aceruloplasminemia (see below) does not cause any symptoms related to Wilson’s disease (37). In conformance with the increase of free copper, daily renal excretion increases to >1 µmol/d. This parameter should be confirmed by being tested twice.
The liver copper content is considered pathological as of a dry weight >250 µg/g (12,38). A representative biopsy specimen is required for a definitive conclusion of the liver biopsy; if applicable, multiple biopsies as a result of non-homogeneous hepatic copper distribution must be conducted (5).
A distinctive pathological profile of the copper metabolism parameter can already be verified prior to the onset of hepatolenticular clinical cardinal symptoms based on the toxic effect of the copper. One single pathological finding with other normal values or merely marginal deviations is not plausible for Wilson’s disease. After clinical manifestation, the correlation to the cardinal symptoms (hepatopathy, EPS, KFR) must be tested, to support the validity of the diagnostic/laboratory tests (36).
Cellular enzymatic level
Bound to albumin, the copper is quickly transported to the liver and reaches the hepatocytes via an energy-dependent mechanism (hCtr1, high-affinity copper transporter) (31). Transport, excretion and storage, to maintain copper homoeostasis, are organized within the liver cells.
At the same time, glutathione is the most important cytosolic chelating agent; over 60% are in form of Cu(I)-GSH (14). Copper glutathione [Cu(I)-GSH] is the donator of copper to metallothionein and superoxide dismutase (31). Hepatic copper metallothionein serves as copper storage as well as copper supplier for other proteins (31). To prevent undesired toxic reactions triggered by copper ions, these are constantly escorted intracellularly by various chaperone proteins (chaperones such as HAH1, Cox17, CCS, Sco1/Sco2) (23,39,40).
Hepatic ATPase 7B acts as a central mechanism for copper homeostasis. It is an intracellular copper sensor with redistribution depending on the level (31). In the case of a low level of intracellular copper, the ATPase is located in the Golgi apparatus and communicates the copper uptake into enzymes containing copper, particularly in apoceruloplasmin (31,39). As soon as the copper level increases, it finds its way to the apical position, to ensure biliary copper excretion into the small ducts of the gall bladder (31,41). This complex function is disrupted by the mutations.
Two other intracellular proteins, XIAP (X-linked inhibitor of apoptosis, caspase inhibitor) and MURR1 (Copper Metabolism MURR1 Domain Protein 1, COMMD1), are involved in copper homeostasis (42,43). While MURR1 provokes vesicular compartmentalization and biliary excretion of copper (43), XIAP accelerates its proteasomal degradation through ubiquitination (42). The exact mechanism of the MURR1 effect is still unknown but an interaction with the ATP7B transporter is being discussed (44,45). MURR1 regulates the folding, stability and the proteasomal degradation of ATP7A, ATP7B as well as other proteins (45).
In regard to human pathogens, to date, the ATPases were known in this complex intracellular modulation. In 2012–2013, three new intracellular copper metabolism disorders were described; the MEDNIK syndrome, the Huppke-Brendel syndrome and chaperone deficiency CCS.
ATPases are enzymes (hydrolases) and simultaneously transport proteins, which use energy released through ATP hydrolysis, on a membrane (inside of a cell membrane, membrane-bound organelles) for active transport against a concentration gradient (46). They are substrate specific through a particular chemical and spatial structure and are distinguished in several types (ABC transporters, F-type, V-type, P-type, A-type, E-type among others) according to the substrate and occurrence in the cell or organisms (prokaryotes and/or eukaryotes, solely for bacteria or plants) (47). The formation of a phosphorylated intermediate is a characteristic feature of the P-type transporter, which also includes ATP7A and ATP7B (48).
The P-type ATPase 7B has substrate specificity for copper ions (47-51). Its structure is characterized by ATP binding sites, 8 transmembrane domains and amino-terminal by 6 copper-binding sequences (48,49). It is particularly found in the liver and kidneys, but to a small extent, also in the brain, lungs, placenta, skeletal muscle and pancreas (1,2,49-51). Its gene is located on the long arm of chromosome 13 (13q14-21-Locus) (52) and approx. 7.5 kilobases long. The encoded part for 1,411 amino acids is 4.3 kilobases allocated to 21 exons (33). Homozygous or compound heterozygous mutations lead to Wilson’s disease.
There is a strong correlation in the functionally significant regions between ATPase 7B and ATPase 7A, also a P-type ATPase with copper ion specificity (48,49,53,54). ATP7A is encoded x-chromosomal (Locus X 13.3). It is located in the intestine on the basal membrane of the enterocytes and responsible for copper absorption (23,49,51). Its defect causes Menkes disease (trichopoliodystrophy), which only occurs in boys (49). Disrupted copper-dependent enzymes in the CNS and connective tissue metabolism are responsible for the symptomology. Occipital horn syndrome (OHS; occurrence of occipital exostoses and calcifications) is considered a milder variant of the ATP7A defect (55) (Table 4).
Remarkably, the ATP7A-associated distal motor neuropathy (X-linked dHMN) does not have any of the clinical or biochemical abnormalities of Menkes disease or the OHS. It resembles Charcot-Marie-Tooth disease type 2. This shows that the ATP7A plays a significant role in maintaining motor neurons. The still unknown pathomechanism of the ATP7A-associated distal motor neuropathy differs from the one in Menkes disease and OHS (55).
From other ATPase—defects, DYT 12 and the Kufor-Rakeb syndrome (PARK 9) with Parkinson’s disease or extrapyramidal symptoms must be considered in differential diagnoses (Table 4).
It was assumed that Indian Childhood Cirrhosis (ICC) was endemic and unique in India. However, this disease has meanwhile been documented in children on non-Indian heritage (Non-Indian Childhood Cirrhosis, NICC) (65). An autosomal recessive defect of the Cirhin encoding CIRH1A gene was described as North American Indian Childhood Cirrhosis (NAIC) (67). Brewer also recognizes the analogy of ICC to Tyrolean Infantile Cirrhosis (TIC), an epidemic liver disease in children in Austria (3).
Adaptor proteins (AP) regulate the transport of transmembrane proteins and the clathrin-coated vesicles between Golgi apparatus, endosomes and plasma membrane. AP1 is responsible for normal ATP7A, ATP7B and clathrin function. A mutation in the AP1 gene—complex subunit sigma 1A (AP1S1), leads to a dysfunction of the ATP7A and ATP7B despite intact enzyme activities (69). Their mislocation results in dysfunctions in copper metabolism, a reduction of copper-dependent enzymes as well as a lack of copper transport. Patients with MEDNIK syndrome (acronym—see Table 4, autosomal recessive inheritance) have combined clinical and biochemical symptoms for Menkes disease as well as Wilson’s disease (68).
The autosomal recessive mutation of the copper chaperone CCS (for SOD1) is another dysfunction of proteins for copper metabolism. CCS is responsible for escorting copper in an intracellular manner and for its delivery to Cu/Zn superoxide dismutase (SOD1) (Table 4). A lack of CCS leads to a defect of the SOD1 with a lethal outcome (74).
Of the 2–4 mg of copper ingested daily with our food, 0.5–1.2 mg in total is reabsorbed in the upper segment of the small intestine; the rest leaves the body through our stool. As an integral part of at least 16 metalloproteins, copper has essential tasks, in particular in connective tissue metabolism, in the CNS and in haematopoiesis (75,76). Copper is also jointly responsible for enteral iron absorption (77).
Insufficient oral intake as well as malabsorption (e.g. as a result of bariatric surgery) are causes for a copper deficiency (78). An increased zinc uptake [through dietary supplements, denture adhesive cream (79)] also decreases the serum copper level (80). Taking valproic acid leads to a copper deficiency via a not yet clarified mechanism (81). A cause for copper deficiency cannot be found in approx. 20% of all patients; it is idiopathic.
Clinical manifestations of hypocupraemia are a sensorimotor polyneuropathy; damage to the optic nerve as well as the myelon with sensory ataxia and pyramidal tract signs (80,82,83). Blood work indicates microcytic hypochromic anaemia and there is cell dysplasia in the bone marrow (80,82,83). Anaemia, a low ceruloplasmin level as well as dysfunctions of the immune system (neutropenia), pigmentary abnormalities and disturbance of growth are also consequences of secondary iron deficiency (84). Moreover, osteoporosis as well as elevated glucose and cholesterol levels can occur.
A copper overload is rare, up to 10 mg/day are tolerated for longer periods of time. Larger doses of copper salts cause nausea, abdominal cramps and diarrhoea (85). High doses on a gram scale lead to liver and kidney damage, haemolysis, brain damage, coma and death (86,87).
Disorders in the formation of ceruloplasmin
Aceruloplasminemia and low ceruloplasmin
Ceruloplasmin (molecular weight of 151 kDa), an alpha-2-glycoprotein, is encoded on the long arm of chromosome 3 (CP gene, 3q23-q24) (33,34). It is primarily formed in the liver but also to a smaller extent in the brain and can transport up to 8 copper ions (Cu2+) per molecule. Approx. 95% of the serum copper is bound to ceruloplasmin and give it its bluish colour (88,89). In addition to the function as a copper transporter, it also has a copper-dependent oxidase activity (ferroxidase) (90). The iron oxidation of Fe2+ to Fe3+ enables its transport by transferrin. As an acute-phase protein, it acts as a strong antioxidant through inhibition of lipid peroxidation (88).
Aceruloplasminemia is a rare autosomal recessive neurodegenerative disease, which usually presents during late adulthood around age 50–60 (91). It belongs to the group of iron accumulation disorders (NBIA, Neurodegeneration with Brain Iron Accumulation) with iron accumulation in the brain, particularly in the basal ganglia and in the liver (92). There is a complete lack of ferroxidase activity in the case of the homozygous mutation (89). The serum indicates a low level of copper and iron with elevated ferritin. Renal copper excretion is normal (93). Neurologically, ataxia, dysarthria, hyperkinesia (tremor, chorea), dystonia as well as Parkinsonism accompanied by depression and cognitive disorders result (94). Anaemia, retinopathy, diabetes mellitus and in some cases, heart failure due to iron overload are internal characteristics (93). The prognosis is determined by heart failure.
Huppke-Brendel syndrome is an autosomal recessive defect of the SLC33A1 gene for an Acetyl-coA transporter. This leads to a dysfunction of posttranslational ceruloplasmin modification and its decreased secretion into the blood. Before reaching age one, this disease presents with developmental delay, hypotonia, hypacusis, cerebral atrophy, cataract and nystagmus without basal ganglia and liver involvement (95,96). Serum copper and ceruloplasmin levels are low (95,96). The prognosis is poor as there currently is no treatment (96).
The serum ceruloplasmin concentration is severely decreased in the case of Wilson’s disease and Menkes disease; also lower in the case of heterozygous trait carriers of Wilson’s disease (97). Homozygote causes a ceruloplasmin synthesis dysfunction in Wilson’s disease, so that there is inactive apoceruloplasmin without ferroxidase activity. On the other hand, the Menkes disease and OHS present a copper absorption disorder as cause for ceruloplasmin deficiency. Ceruloplasmin degradation also occurs in the case of hepatic insufficiency (hepatitis) and protein-losing enteropathy (97). Ceruloplasmin is physiologically low in infancy (98).
Exogenous causes of ceruloplasmin elevation are copper intoxication, zinc deficiency and taking hormonal contraceptives. Endogenously, ceruloplasmin reacts as an acute-phase protein in the case of inflammation (88) and to hormonal changes (pregnancy). Oestrogens can stimulate its formation (97). Elevations in the serum ceruloplasmin concentration are also reported in the case of lymphoma, Alzheimer’s disease and cholestasis. Clinical disorders caused by ceruloplasmin elevation itself are not described.
Differential diagnoses of typical clinical findings
Differential diagnoses of icterus and anaemia
If hepatic findings are made, in particular pertaining to icterus as well unclear anaemia, diseases with primary or possible manifestation in toddlers up to puberty are, in addition to Wilson’s disease, significant in regard to differential diagnoses (Table 5).
Amongst others, hemoglobinopathies, iron deficiency, lymphatic leukaemia, erythroblastopenia, glucose-6-phosphate dehydrogenase deficiency and autoimmune haemolytic disorders must be taken into consideration in infantile types of anaemia. The occurrence of different forms of anaemia varies greatly. In Europe, iron deficiency anaemia and thalassemia minor represent the majority of all causes for anaemia in children and adolescents (102).
Differential diagnoses of neurological and psychiatric symptoms with manifestation starting in puberty
Unclear symptoms associated with basal ganglia and the cerebellum must be analysed in differential diagnoses for the presence of Wilson’s disease, particularly before age 45, in exceptional cases even beyond that. Knowledge of the clinical forms of progression (clinical variants) of Wilson’s disease helps recognize deviations in clinical findings (10). Table 6 summarizes relevant neurological movement disorders at comparable ages of onset such as Wilson’s disease.
Particularly unclear cognitive disorders (e.g., worsening of school-based performance) should include the possibility of a primarily psychiatric manifestation of Wilson’s disease at puberty age (3,4). The psychopathological spectrum can include all ranges, so that a localization based on differential diagnoses is not possible a priori. An inclusion of extrapyramidal findings in the neurological status is a decisive factor.
Differential diagnoses of the KFR
The KFR is the macroscopically detectable phenomenon of copper deposition in the Descemet’s membrane of the cornea. They were described as earlier as 1902 by Kayser (106) and therefore, 10 years prior to the publication of progressive lenticular degeneration by Wilson (107). They appear on the edge of the cornea as a brown ring, which is not always closed. They are always mentioned when findings of Wilson’s disease are listed in textbooks and are considered a cardinal symptom (108). Nevertheless, there are numerous different aspects in literature. On the one hand, KFR belong to the initial symptoms (109), on the other hand, they are often not present in the early stages of the disease in children (105). In large populations of patients with Wilson’s disease with hepatic symptoms, the occurrence of KFR was only reported in 44–62% of patients (110,111) and they were usually not present in children with liver disease (112). Furthermore, they are more common in the case of the homozygous H1069Q mutation than in compound heterozygous patients at the time of diagnosis (113).
Initially, KFR was considered pathognomonic for Wilson’s disease, however, they were rarely found in other liver diseases such as primary biliary cholangitis, chronic cholestasis (114,115) or in children with neonatal cholestasis (116). In regard to differential diagnoses, corneal opacities caused by other diseases, such as galactosialidosis (117), are possible. Other authors also refer to this occurrence in “non-Wilson patients” as pseudo-KFR (115,118). Despite these aspects, KFR are considered a classical ophthalmological manifestation of Wilson’s disease, while the sunflower cataract caused by copper accumulation in the lens of the eye is rare (119,120). KFR can fade during decopperising therapy and disappear after years (121).
Differential diagnosis in heavy metal metabolism (manganese storage disease)
The recently recognized manganese storage disease is caused by an autosomal recessive mutation in the manganese transporter gene (SLC30A10) (122). It is considered the “new Wilson’s disease” with the manifestation of a generalized dystonia in childhood (age 2–14) and asymmetrical Parkinson’s disease with early postural instability before age 60 (123,124). The patients also develop liver cirrhosis and in doing so, “mirror” Wilson’s disease (92).
Paraclinical findings include polycythaemia, low ferritin, increased total iron-binding capacity and an elevated serum manganese level (122). The basal ganglia show hyperintense lesions on T1-weighted images (122). Therapeutically, calcium-disodium EDTA infusions are used to boost renal excretion of manganese (92,125). This leads to a good neurological improvement if treatment is started in a timely manner (122,125).
If a clinical tentative diagnosis for Wilson’s disease is made by allocating the current findings based on a classification scheme, considerations based on differential diagnoses must be taken into account until the genetic information has been ensured. Atypical symptoms as well as deviating progressions also require additional diagnosis. It must be taken into account, that a full presentation is not evident at the time of onset of the disease. As a result, differential diagnoses must be included in the respective clinical findings. An extensive understanding of copper metabolism and known disorders, in addition to Wilson’s disease, is significant, in particular for the interpretation of the paraclinical data.
As this overview shows, Wilson’s disease fits into a broad spectrum of internal and neurological disease patterns with icterus, anaemia and EPS. Recently discovered disease patterns pertaining to manganese and copper metabolism are relevant after ruling out an ATP7B mutation. On the one hand, starting treatment for Wilson’s disease early on is required but on the other hand, only a reliable diagnosis justifies treatment, which involves adverse reactions. Starting treatment at an early stage, avoiding wrong medication and the prognostic assessment are also significant for differential diagnoses.
Conflicts of Interest: The author has no conflicts of interest to declare.
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What would a city look like if it was built through an open-source process? That’s exactly what Raleigh’s Visual Art Exchange wants to find out with a new exhibit called IMBY, or In My Backyard.
Inspired by local and national debates between the YIMBY (yes in my backyard) and NIMBY (not in my backyard) camps, VAE staff realized that, often, the only voices heard about city development are those of the people who feel the strongest. The impact of that development, however, affects many, many more.
“We wanted to experiment with how creativity could further engage people in the process of planning a community, and how reaching a wider audience could create more equity in the process,” says Kyle Hazard, VAE’s exhibitions director. “The goal is to expose attendees to the challenges that surface when density, community, accessibility and growth all collide, and possibly find new, crowdsourced and more equitable ways to look at solutions to those challenges.”
The month-long, collaborative, experimental exhibit will be built completely by the public. Attendees will have the opportunity to build the community in which they would like to live, from scratch. Almost like a real-life SIM City, but with more creativity and flair, the gallery will start out with empty pedestals and a whole lot of cardboard. The city will grow from there.
“If, to build that community, they decide it is necessary to topple a building, move a community center or even move an entire neighborhood out of a particular area, [visitors] will have to physically pick up and move those resources, creating a more personal connection to development,” says Hazard of the public’s participation. Guests will be given prompts for things to include, such as roads, power and accessibility, and will occasionally be asked to draw disaster cards that introduce natural, medical, social or structural challenges to resolve.
According to Wake County government statistics, a total of 164 new residents move to Raleigh per week. With the inevitable growth, it’s becoming increasingly clear that residents will have to come together in real life and agree, or compromise, on how that will work for everyone.
“As a staff, we’re interested in seeing what the answer to our original question was—what does a publicly built, open-source community look like?,” Hazard says. “Then, we hope to engage people from the NIMBY and YIMBY camps to see how those attitudes affect how a city is developed.”
While VAE has invited the public into the gallery for collaborative projects before—to write concerns on toilet paper flushed away for the new year in January of 2017, for example, or a month-long, publicly built, giant collage project four years ago—this will be the first community city built in the gallery. Part interactive art installation, part game, and part community conversation VAE encourages people of all ages and backgrounds to come out and participate.
To get in on the action, visit the Visual Art Exchange between November 2 and 24 at 309 West Martin Street.
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The K&H Shoulder Sling Pet Carrier is the perfect carrier for those who love to take along their smaller furry friend.
This unique carrier allows pets to be carried in the front, providing for more interaction with them when out and about.
The comfortable shoulder strap is adjustable and a waist strap is included for stability.
Mesh windows and doorways allow pets to look out.
Two zippered doorways for convenience.
Attractive yet very durable.
Can also be buckled safely in a vehicle with the attached strap.
One-year limited warranty.

domain: pet


table top heater (stainless steel)SKU: #AZ.HLDS032.B
38-in tall when assembled, with a 5-ft heating radius, 11,000 BTU's with variable control and a piezo ignition.
For safe use, this heater requires a 24-36-in ceiling clearance and has a weight plate for added stability and both thermocouple and anti-tilt safety devices. It is fueled by a 1lb disposable propane tank, not included. CSA approved.
White-glove delivery not available on outdoor heaters.
- AZ.HLDS032.B table top heater (stainless steel)
- standard and 2-DAY shipping options available at checkout
- 21w 21d 38h
- 19 lbs
- in stock This item typically leaves the warehouse within 2-4 business days. Expedited or white glove delivery options may be available at checkout.
- some assembly required