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Our Uniqueness
Meet the Executive & the Board
Meet the Parents & Friends Association
Learn at KTC
Chagim, Commemorations & Celebrations
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Production at KTC
Every two years, The Girl's High School stages a production that involves every student in some way or another.
School productions are very important in the Chinuch (education) of a student. It has transformative powers that creates a metamorphosis in the student body. From the start of the year the corridors are filled with song, music, dance and drama. You can feel the sense of fun as well as confidence growing with every practice. There is a palpable feeling of Ahavas Yisroel and unity.
The production showcases the talents of the girls in the areas of song, dance and drama. We also have students dedicated to painting props, organising costumes, acting as stage crew, running technology and helping with sound and lights. Every student has some involvement. It brings out Middos, good character traits and promotes crucial social and executive skills. At the same time, there is an underlying message that resonates throughout the experience: talent is "gifted" to us by Hashem and it's up to us to develop and nurture it. Everyone has some talent and we need opportunities outside the classroom to allow students to discover their own.
Our own alumni and staff write the script and help train choir, drama girls and dancers. It is always such a pleasure to have alumni return and volunteer to help in all areas of the production.
Kesser Torah College is an Orthodox Jewish Chabad community school. We aim to provide a first class, child-centred Torah-true Jewish and general education for each individual student, within a nurturing and stimulating environment
Copyright Kesser Torah College 2018 | Website by Betsee


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Home » World News » People smugglers using TikTok to advertise deadly lorry journeys to UK for £20k
People smugglers using TikTok to advertise deadly lorry journeys to UK for £20k
Life-threatening journeys for migrants seeking to come to the UK are still being advertising on social media app TikTok.
Despite claims from social media companies that they would be cracking down on the posts, ads originating from Albania plugging "safe passage" via lorry are being advertised at more than £20,000 per family.
The investigation from The Mirror found 10 adverts, with one even promising a chance to meet the Queen.
Another claimed passengers could "ride alongside the driver" on routes from Belgium and Spain.
One user on the app claimed: "The last journey this year to meet the Queen in England. Secure journey inside the head of the lorry. 100% secure.
Another advert, posted last week, said: "Another journey to England on the head of the lorry – £24,000 sterling.
"Secure journey to England before Christmas.
"Get in touch with us quickly."
The discovery comes less than one week after the National Crime Agency said that TikTok, Facebook, Instagram, YouTube and Twitter had agreed to "greater collaboration against crime groups using the internet to recruit, communicate and advertise services to migrants".
Ex-border control officer Chris Hobbs said: "There is a responsibility for social media to do more. This could lead to a loss of life."
A spokesman for TikTok, which has now banned the accounts responsible for the adverts, said: "This has no place on our platform – Safety is our priority.
"We invest in people and technology to remove content of this nature."
The crackdown comes as news of 68 migrants including 3 babies were rescued from a boat in the English Channel after attempting a crossing in the early hours of Christmas Day.
All passengers aboard the vessel — who are reported to be from Afghanistan, Iraq and Iran — are now being processed in the UK.
One young girl could be heard among the people who were brought to Dover at around midnight on Christmas morning, according to agency reports.
The children found on board are now with social services.
A Home Office spokeswoman said: "Border Force has intercepted a number of boats containing migrants attempting to cross the Channel overnight and this morning, and has deployed resources to deal with these incidents."
For the latest breaking news and stories from across the globe from the Daily Star, sign up for our newsletter by clicking here.
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Posted on August 18, 2020 April 4, 2021 by romapodcast
You're listening to an Audio Guide to Ancient Rome. This episode is one in a series of short descriptions of monuments in the Roman Forum. In this episode I'm describing the Basilica Paulli.
Before the Basilica Paulli was built, this location had already served as the site of a basilica commissioned in 179 BCE by consul Marcus Fulvius Nobilior. That building replaced a series of butchers shops that previously occupied the site. Fulvius didn't see the project through to completion so, after his death, his colleague and contemporary Marcus Aemilius Lepidus ensured the work was finished. For the next 125 years the building sited here was known as the Basilica Fulvia after its original sponsor. This first version had a large and roughly rectangular main hall with 34 internal columns defining the inner apse – these were arranged in 4 columns at each end and an additional 13 on each side. Coins from the period show that it was two stories high with columns on the upper floor on the outside. The side of the Basilica that faced the Forum had a portico running along its length also supported by a set of columns. Under the portico were a set of alcoves that housed a row of new shops – these were referred to as the Tabernae Argentariae Novae which indicates that the shops were actually silversmiths, money changers and bankers.
A substantial refinement and upgrade of the Basilica was made by the Consul Lucius Aemilius Paullus in 55BCE using money he'd received as a bribe from Julius Caesar – the money had been given in return for political support while Caesar was vying for power with Pompey.
On this topic Plutarch wrote:
"Caesar began to lavish gifts upon all the public men out of the riches he had taken from the Gauls; he liberated Curio, the tribune, from his great debts and gave Paulus, then Consul, 1,500 talents with which he built the noble court of justice joining the Forum."
Taking 20 years to update, the project again outlived the sponsor so the end of the Basilica's refurbishment was overseen by Lucius Aemilius Paullus' son Lucius Aemilius Lepidus Paullus.
Unfortunately, 20 years after completion, a fire would start here in the Basilica Paulli that would sweep through the Forum, destroying many of the adjacent buildings – the devastation included the destruction of the Temple and accommodation for the Vestal Virgins. Fire-damaged fragments of high quality relief carvings from the Basilica have been found showing imagery depicting the foundation of Rome.
Given the scale of the damage and the nature of the buildings destroyed, Emperor Augustus oversaw the work to put things back in order taking the opportunity to refactor the layout and change the use of some of this public infrastructure.
As part of the overhaul, Augustus rebuilt the upper two floors and raised the height of the Basilica, he added stairs and significantly expanded the portico. Although the main part of the building was rededicated as the Basilica Pauli, the new front portico was dedicated to the Emperor's two grandsons and heirs Gauis and Lucius. This had two orders of arcades with pilasters and Doric semi-columns. Over the upper order an attic was constructed and decorated with carvings of plants and statues of barbarians. Carved remains of a very large white marble panel with a Latin dedication to Lucius have been found close by and can be seen on the southern corner of the Portico (that's the right side if you facing the Basilica while standing in from the Forum).
The Basilica's wooden roof, its Portico as well as the facade of the basilica were again completely destroyed by fire when Rome was sacked by Alaric the Visigoth in 410. If you look closely you can still see small green stains of bronze coins on the colored marble floor from the early fifth century that melted by the heat of this fire.
In the year 420 the basilica was rebuilt and given a new floor, the central part of the front porch was replaced by a new portico using columns of pink granite – after archaeological excavation three of these columns were re-erected and stand in a line facing the side of the Temple of Divine Julius.
An earthquake in 847 caused the final collapse of the remaining structure. That said, significant sections of the Basilica remained through to the 1500s as evidenced by artist sketches of that time. Unfortunately, readily-available high quality marble slabs and columns proved too tempting for some and the site was raided to aid in the construction of various renaissance palaces leaving us with the limited remains that you see today.


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Which Countries are Most Similar to Lesotho? 2.0
Jeff Jones September 26, 2021 September 26, 2021 country similarity index, lesotho
Similar to other English-speaking countries in Southern Africa
4 of the top 5 countries most similar to Lesotho were once colonies of Great Britain, with the exception being Namibia, which was a German colony, later ruled by South Africa. They all have English as one of their official languages. In addition all of these countries have a majority Protestant population. They also have similar infrastructure, since the top 5 all drive on the left and use 3′-6″ gauge railroad tracks.
The five least similar countries are all far more developed and have a higher standard of living. Their governments are also more democratic. The three least similar countries are located in East Asia. They are especially different because they do not use the Latin alphabet, do not traditionally follow Abrahamic religions, and are also much less religious. Wealthy countries on the Arabian Peninsula are also far different from Lesotho.
Top 10 Places Most Similar to Lesotho
Eswatini is another former colony of Great Britain that was planned to be incorporated into South Africa, but instead gained its independence. Still, both countries use the South African Rand as legal tender. Despite their close proximity to South Africa, their infrastructure is significantly less developed. Both countries primarily use Type M electrical outlets. They also primarily use hydropower to create electricity. However Lesotho is significantly more democratic than Eswatini.
Zimbabwe is another landlocked country that borders South Africa. The diets of both countries are quite alike. Both countries tend to grow and eat a lot of corn. In addition, the countries have a similar standard of living.
Zambia is similar to Zimbabwe. It is yet another landlocked former British colony on this list. One difference is that Zambia has fewer Catholics. However, a greater percentage of Zambia's land area is freshwater lakes. Its climate is also much hotter than Lesotho.
Botswana is another landlocked country that borders South Africa. The native languages of Lesotho and Botswana, Sesotho and Setswana, are closely related, and English is an official language of both countries. One big difference is that Lesotho has a more temperate climate, due to its high average elevation. It is also wetter and more mountainous.
Namibia is the only country that is not landlocked on this list. It is located between Botswana and the Atlantic Ocean. The South African Rand is legal tender in both countries. Both Namibia and Lesotho rely on hydropower to create energy. The South African Rand is legal tender in both countries as well. However, their agriculture is a lot different, since Namibia's climate is drier. Namibia mostly grows millet, while Lesotho mostly grows corn.
Malawi, 7. Kenya, 8. Uganda, 9. South Africa, 10. Tanzania
Top 10 Places Least Similar to Lesotho
South Korea is a densely populated East Asian country. Its infrastructure is extremely dissimilar from Lesotho, since it drives on the right, uses standard gauge railroad tracks, and Type C, F electrical outlets. One thing that they do have in common is that South Korea also has a significant Christian population. Still, its language and system of writing are completely different from Korean.
Taiwan is country that borders the Pacific Ocean on this list. Like South Korea, its infrastructure is much more developed than Lesotho. In addition, its laws are a lot different. Taiwan allows gay marriage and legalized prostitution. Also unlike Lesotho, it does not allow gambling. The countries also have extremely dissimilar demographics and culture. Taiwan's climate is also hotter than the more temperate climate of Lesotho.
Japan is an extremely densely populated island, in contrast to landlocked Lesotho. Not only is its geography significantly different, but also its demographics and culture. They use a different writing system and their religions are unrelated. However, Japan does share some similar infrastructure, since both countries drive on the left and use 3'6″ gauge railroad tracks. Still, Lesotho has a different electrical outlets that use a higher voltage than Japan.
Bahrain is a densely populated desert island located in the Persian Gulf. In contrast to landlocked Lesotho, most of its people is within a 15-minute drive from the beach. The country is also one of the wealthiest in the world. It is mostly Muslim. Due to a vast amount of migrant construction workers in the country, it has far more men than women.
Saudi Arabia is a predominately Muslim country in Asia. Although both countries have little vegetation, Saudi Arabia is much hotter and drier. The country creates most of its electricity using oil and natural gas, while Lesotho primarily uses hydropower. Its government is also an absolute monarchy and has more conservative laws than Lesotho.
United Arab Emirates, 7. Kuwait, 8. Qatar, 9. Finland, 10. Israel
Full Ranking of Countries and Territories Most Similar to Lesotho
botswana, countries like lesotho, country similarity, country similarity index, Eswatini, least similar, lesotho, most similar, namibia, similar countries, similarity index, swaziland, what countries are like lesotho, zambia, zimbabwe
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Home SportsBoxing Bombs away; Barrera, Ellis, and Rios in KO wins at Fantasy Springs
BoxingFeaturedSports
Bombs away; Barrera, Ellis, and Rios in KO wins at Fantasy Springs
by Gayle Falkenthal Dec 17, 2016
written by Gayle Falkenthal Dec 17, 2016
INDIO, California, December 16, 2016 – Fans had to ask themselves what might have happened if the version of Cuban light heavyweight Sullivan Barrera who showed up Friday night at the Fantasy Springs Casino had showed up last March against Andre Ward.
Barrera and Ukrainian Vyacheslav Shabranskyy (17-1, 14 KOs) delivered an all-action fight for the seven rounds it lasted, ending when referee Ray Corona stopped the fight at 2:05 of the round. Barrera (18-1, 13 KOs) scored knockdowns in the first, fifth and seventh rounds of the fight, resulting in Shabranskyy's first loss.
Shabranskyy has come back from the brink in previous fights, and it seemed early he might recover and do it again. He returned the favor by knocking down Barrera in the second round with a right hand of his own, staggering Barerra back as he fell to the canvas.
Sullivan Barrera (lright) said watching video of opponent Vyachaslav Shabranskyy helped him figure out his approach and score a knockout Friday. Photo: Ed Mulholland, HBO Latino
Barrera recovered, and as the two traded punches like much smaller men, Barrera delivered punches with far more accuracy, counterpunching as Shabranskyy tried to connect with jabs. After the bout, Barrera said his preparation watching video of Shabranskyy paid off.
"I watched video (of Shabranskyy) over and over. I knew when Slava popped his jab, he lunges, so I knew I could counter with my overhand right," said Barrera.
Counter he did, and never let Shabranskyy have a chance to catch his breath and recover. When he took the final right-hand flush to the face, it was over even though he got to his feet.
"Of course we would never expect this," said Slava Shabranskyy, obviously disappointed after the fight. "We will decide next steps after we get over this."
"With this win, I proved all the people who bad mouthed me wrong," said Barrera. "This win is for all the boxing fans outs there. I want to specifically thank my trainer, Derik Santos. He sat me down, we watched the tapes, and he said to me, 'Sullivan, this is what you have to do to get the win. This proves that my career in boxing is alive. I want a rematch with Andre Ward."
Sullivan Barrera celebrates after his victory Friday. Photo: Ed Mulholland, HBO Latino
Barrera's promoter, Kathy Duva of Main Events, was elated at Barrera's victory. After watching Ward beat Barrera and get a disputed win over Barrera's stablemate Sergey Kovalev, the win tonight was especially sweet. Duva said after the win, "Oh God yes, this is what it feels like. I mean, everyone hates to lose the way we did. That is something that has been pent up for weeks, I finally got to let it out," laughed Duva.
Barrera delivered exactly the sort of performance he needed to restore some luster to his career. Give credit perhaps to the home cooking now that Barrera trains at home in Miami with Santos.
Duva didn't rule out the possibility of pitting Barrera and Kovalev against each other at some point, though not right away. "Sergey Kovalev will be in a lot of great fights," said Duva.
"Speedy" Rashidi Ellis lived up to his nickname, winning by knockout at 1:19 of Round 1 over Eddie Gomez. Photo: Ed Mulholland, HBO Latino
Welterweights "Speedy" Rashidi Ellis (17-0, 12 KOs) of Lynn, Massachusetts and Eddie Gomez (19-2, 11 KOs) from Bronx, New York and became the co-main event due to the cancellation of the Orozco vs. Maldonado bout, and Ellis made the most of the showcase, running toward Gomez at the opening bell, firing off right hands, scoring a scorching knockdown barely a minute into the fight. Gomez got to his feet, but Ellis moved in and finished him off at 1:19 of the first round. "I'm so excited I can hardly talk," said Ellis. No need to worry, Ellis wins the IBF North American title and makes a statement about his future.
Ronny Rios dominated Roy Tapia in their featherweight bout with impressive bodywork scoring a sixth round TKO. Photo: HBO Latino/Ed Mulholland
Southern California featherweight Ronny Rios (27-1, 12 KOs) dominated a game but outgunned Roy Tapia (12-2-2, 6 KOs), stopping Tapia when referee Ray Corona and Tapia's corner stopped the fight after round six for a TKO win. Rios offered an impressive display of body punching followed by strategic strikes to the head from both sides. Rios was a significant step up in competition for the less experienced Tapia, and Rios appeared much bigger in the ring than Tapia.
Tapia was game and put in his best offensive effort before Rios's superior firepower took over. "It was a body shot in the first round that really affected me," Tapia. "After the fight, Ronny came up to me and told me to keep my head up, and to keep fighting. I'm going to listen to him."
"I was just in there having fun," said Rios. "I'm more aware of my surroundings – I could hear my coach, and relax my arms so much more. I was in the same position Roy is in now at one point in my career, and all I can say is that you learn so much more with a loss than you ever could with a win." Rios is now in good position to get the chance to fight for the vacant WBC super bantamweight title previously held by Japanese champion Hozumi Hasegawa, who recently retired.
Non-televised undercard results:
Ryan Martin of Chattanooga, Tennessee (18-0, 11 KOs) produced another strong performance to open the night with a stoppage of Yardley Suarez (19-6, 10 KOs) of Sacramento.
Promising lightweight prospect Ryan Martin of Chattanooga, Tennessee (18-0, 11 KOs) produced another strong performance to open the night with a stoppage of Yardley Suarez (19-6, 10 KOs) of Sacramento. Martin has a crowd pleasing, power punching style and a calm approach that will serve him well as his opposition gets tougher. "The moment I saw him go down, I knew that it was my time to go hard on him," said Martin. "It's always an exciting moment to remain undefeated, and I'm looking forward to more things to come."
Alexis Rocha (left) remained undefeated, knocking down Abraham Calderon twice on the way to a unanimous decision. Photo: Golden Boy Promotions
Alexis Rocha (6-0, 4 KOs) of Santa Ana, California had the upper hand in all four rounds over opponent Abraham Calderon (1-4) of Los Angeles, dropping him in the second and third rounds with snapping left hooks before getting the unanimous decision. Rocha, 19 and the younger brother of Ronny Rios who also won tonight. "He was a tough fighter, and even though his record wasn't spotless, he was never stopped before," said Rocha. "I was expecting a rough road, and I am happy with the two times I made him hit the floor. I'm a heavy welterweight, and I'm only 19 so I have a lot to learn."
Super lightweight Vergil Ortiz Jr. (3-0) of Dallas impressed fans landing a solid right cross to the head of Nestor Garcia of Mexico (0-2), scoring a one-punch knockout at 3:00 of the first round to remain undefeated.
Hometown favorite Javier Padilla (2-0, 1 KOs) of Indio scored a second-round knockout of Jose Mora (0-2) of Tijuana in their super bantamweight fight.
Gayle Lynn Falkenthal, APR, is President/Owner of the Falcon Valley Group in San Diego, California. She is also a serious boxing fan covering the Sweet Science for Communities. Read more Ringside Seat in Communities Digital News. Follow Gayle on Facebook and on Twitter @PRProSanDiego.
Please credit "Gayle Falkenthal for Communities Digital News" when quoting from or linking to this story.
Copyright © 2016 by Falcon Valley Group
boxingGayle FalkenthalRingside Seat
Gayle Falkenthal
Gayle Lynn Falkenthal, MS, APR, is President of the Falcon Valley Group, a San Diego based communications consulting firm. Falkenthal is a veteran award-winning broadcast and print journalist, editor, producer, talk host and commentator. She is an instructor at National University in San Diego, and previously taught in the School of Journalism & Media Studies at San Diego State University.
Boxing preview: Bernard Hopkins faces Father Time in 'The Final 1,' HBO Boxing Saturday
Ohio State terror attack and political correctness


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NYC's Success Academy Charter Schools Are Pushing Poor Students To Lofty Test Scores, But At What Cost?
Nick Chiles
In the latest skirmish over the national quest to raise the test scores of poor students of color, the case of New York's vast network of charter schools known as Success Academies highlights an essential question: Is an obsession with practice tests and test preparation before the state standardized tests good for students or bad for them?
If students outperform their peers on the tests by spending much of the year on grueling preparation sessions, is that a bastardization of the true meaning of education, or is it an acceptable response to the high-stakes testing that now faces most students in American schools?
These questions were probed in a New York Times profile of the Success Academy Charter Schools, the largest network of charters in the city. Publicly funded but privately operated, the network is run by former New York City councilwoman Eva Moskowitz. By next year Moskowitz will have 43 schools—a number that could increase to 100 if Gov. Andrew Cuomo has his way.
As the Times pointed out, that could make the Success network larger than the Buffalo school district, the second-largest in New York state.
The Times profile painted a picture of a network of schools where students are publicly ridiculed if their practice test scores are unacceptably low, toys and prizes are used as incentive to motivate students, teachers are closely monitored and held accountable if their students don't perform well, and teachers still in their 20s are promoted to school principal positions if their students do well on the tests.
The students' scores are off the charts compared to other low-income schools and parents are so eager to get in that this year the network said it received more than 22,000 applications for 2,688 seats.
While many parents are giddy at the results, it's the kind of learning environment and incentive structure that can drive educators crazy, making Success the center of constant controversy over its methods.
As noted by the Times, the critics of the academies say the high test scores are a "mirage" created, in part, by the inordinate test preparation.
Halley Potter, a fellow at the Century Foundation, a progressive policy organization, and the co-author of two books about charter schools, said of the impressive test scores: "Success Academy's strong test scores tell us that they have a strong model for producing good test scores," she told the Times, adding that there could be lessons in Success's practices for schools that are trying to improve their scores.
But while many of the current teachers were afraid to talk, the Times had no problem tracking down former teachers who lashed the school for creating an environment that was almost abusive.
Jasmine Araujo, 25, a former Teach for America teacher, quit after just half a year as a special-education teacher at Success Academy Harlem 3.
"I would cry almost every night thinking about the way I was treating these kids, and thinking that that's not the kind of teacher I wanted to be," said Araujo, who now teaches at a charter school in New Orleans.
Critics point to the school's exceedingly high turnover rate as evidence that the network's teaching environment was harmful.
Three of the Success schools actually had a turnover rate in the 2013-14 schoolyear of more than 50 percent, according to the latest school report cards, but Success officials said that these figures were inflated by the number of teachers who move from one Success school to another, or to nonteaching positions within the network.
According to the network's numbers, attrition last year was 17 percent, compared to 6.1 percent for the entire system.
The Times said most of the former teachers interviewed left not because of the workload, but because they disagreed with Success's punitive approach to education.
For example, one teacher complained when she was expected to announce all of her students' scores on practice tests by asking those who had scored a four to stand up, followed by those with a three and then those with a two. Though the teacher and her colleagues persuaded their supervisors not to make students with a score of one stand up, it was obvious when they were left conspicuously sitting down.
She said she was even told by a supervisor that when a student made a mistake, she should have torn up the paper in front of the student. She said students were not supposed to go to the restroom during practice tests and she heard a leader from another school praise the dedication of a child who had wet his pants rather than take a break.
"I dreaded going into work," the teacher, who now teaches in a public school, told the Times.
But in response to the critics, Moskowitz said she's just trying to bring middle-class standards into the school environment. She said their methods are putting their students on the same college track as children in wealthier neighborhoods who had better schools and money for extra help. She said the higher test scores will help Success students get into better middle schools and high schools.
"For affluent parents who are concerned about the test scores, they have an exit strategy — their exit strategy is to hire a private tutor," Moskowitz said.
No one criticizes those parents, but "when we support our students, we get criticized," she said.
"And I would argue that it's not fair that only the kids who can hire private tutors should do well."
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I had hope to escape and get up the mountain today and help with some track clearing and repair, allas! the rain came down all night and the project was canceled. So I will be spending the day with my paintbrush and drop sheet.


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No Animals Harmed in Making of "War Horse"
By Jennifer O'Connor
Domestication certainly hasn't benefited horses, as they've long been abused as beasts of burden and in other ways—as shown by our current battle to stop their export and slaughterfor meat. But the new movie War Horse makes a strong case that the bond between humans and horses transcends exploitation. Based on the book of the same name by Michael Morpurgo, War Horse follows the journey of a horse named Joey from birth to a World War I battlefield.
Unlike those involved in the making of We Bought a Zoo, the producers of War Horse took PETA's concerns about the use of animals on the set seriously and were responsive, open, and proactive. Director Steven Spielberg and producer Kathleen Kennedy—both horse lovers—took care to ensure that the horses used in the production of the film were not harmed.
(Spoiler alert: If you don't want to know how it was done, stop reading here.)
Computer-generated imagery was used in the most dangerous-looking scenes, a special track was built to help with the horses' footing, and breakaway ropes prevented tripping. In addition, the dramatic barbed wire scene was created using an elaborate system involving a harness, rubber "barbed wire," an animatronic horse, and a healthy dose of Hollywood magic. As one producer told PETA, "Great credit goes to the art department for making it look dangerous when it wasn't; everything was built to accommodate the horses."
War Horse's strong and moving anti-cruelty message is also sure to resonate with moviegoers and help them empathize with horses' plight. Hopefully, many will think long and hard before they patronize the modern-day horse "battlegrounds" created by the racing, rodeo, andcarriage industries. The movie may also prompt people to call their representatives to support the bill to ban American horses from being slaughtered in the U.S. and abroad.
PETA: P&G Helps Animals in Oil Spills, Harms Animals in Labs
CBS's "Let's Make a Deal" Exploits Animals
No Horses Die When Morrissey's in Town
HBO Cancels "Luck" After 3rd Horse Dies
NYC's Snowy Streets: No Cars, Just Horses
3rd Horse Dies on Set of HBO's "Luck"
2 Horses Killed During Filming of HBO's "Luck"
Horse Racing -- Money More Important than Horses' Health


The PP-R pipe at the new 75,000-sq.-ft. St. Johns County's health-services facility was utilized for its HVAC chilled- and condenser water system. Photo courtesy of Aquatherm.
When St. Johns County's old health and human services building — previously the Flagler West Hospital — in St. Augustine, Fla., reached the end of its useful life, the county commission "could've put $4.5 million worth of Band-Aids on the building or we could've invested in a brand-new facility. We chose the latter," St. Johns County Commissioner Rachael Bennett says.
Former St. Johns County Commissioner and now state Rep. Cyndi Stevenson called the 1960s structure "an energy hog," while a staff report called it "functionally obsolete." Even if brought up to code, the aged complex still would have needed major continual maintenance.
Instead, county commissioners cut the ribbon in February 2015 on the new relocated St. Johns County Health Center. The completed construction on the 75,000-sq.-ft. building cost about $12 million to build. The center houses at least five St. Johns County agencies: Mental Health Services, the Florida Department of Health, the Department of Children and Families, Veterans Services and the Family Integrity Program.
Health and human services centers typically assist the most vulnerable community members, and one of the many problems with this old structure was its inefficient HVAC system. According to the U.S. Environmental Protection Agency, building materials can have a major impact on air quality and can markedly affect occupants, especially the most susceptible of the population, such as children and the elderly. Careful material selection along with proper operation and maintenance can help improve air quality.
Jacksonville, Fla.-based McVeigh & Mangum Engineering (MME) partnered with PQH Architects to provide the total engineering and architectural designs for the new facility, with MME producing the mechanical, plumbing, electrical and structural designs for the project.
The building's HVAC system receives chilled water from two water-cooled chillers and two cooling towers. The chilled- and condenser-water systems originally were specified with steel and copper or polypropylene-random (PP-R) piping. Jacksonville-headquartered mechanical contractor AC General selected PP-R piping as an alternative material to steel because of its potential labor savings and natural insulation properties.
The PP-R piping system is fused via heat to form connections and bonds on both sides of a joint into a single, homogenous material without the use of chemicals, adhesives or mechanical connections, which eliminates systematic weaknesses and potential fail points in the pipe. The seamless heat-fusion connections, combined with the piping's resistance to corrosion and abrasion, help to ease leakage concerns.
According to Jeff Mock, P.E., a senior mechanical engineer who was with MME during the St. Johns project, Aquatherm piping systems were included in the bid because the potential labor and insulation savings. Additionally, MME had good experiences using Aquatherm PP-R piping for chilled-water systems on previous projects.
"Aquatherm had published labor rates and estimating software [the Aquatherm Quick Check Estimator] that allowed us to calculate labor savings pre-installation," AC Greneral Project Manager Marty Bryant said.
Lifespan and integrity also were key to the specification. The piping systems are repelling water from their surfaces, protecting the pipe walls from erosion and reducing leakage concerns. The smooth, chemically inert material prevents scaling and corrosion buildup so the piping systems' performance never suffers, even without chemical treatment.
Corrosion resistance — both on the inside and outside of the pipe — was a driving factor for allowing PP-R use on the project, Bryant notes. The local water quality is extremely hard on steel and copper piping and the St. Johns County Public Health Department service personnel wanted chilled- and condenser-water systems that would be as resistant to the aggressive water as possible.
"The quality of water is concerning, so we needed a piping solution that was corrosion-resistant and fit in our budget," Bryant concludes.
This article was originally titled "Cutting the ribbon" in the October 2016 print edition of PM Engineer.


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347 Quality Assurance / Safety jobs
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Florida International University is classified by Carnegie as a "R1: Doctoral Universities - Highest Research Activity" and recognized as a Carnegie Community Engaged university. It is a public research university with colleges and schools that offers bachelor's, master's and doctoral programs in fi...
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Electrical Engineer II
Viburnum, Missouri
Do you have at least 3 years of hands on experience as an Electrical Engineer? The Doe Run Company is seeking an Electrical Engineer II to plan, maintain, and coordinate electrical maintenance, upgrades, new installs and day-to-day jobs. This position provides electrical engineering support to minim...
Do you have at least 3 years of hands on experience as an Electrical Engineer? The Doe Run Company is seeking an Electrical Engineer II to...
Assistant/Associate/Professor in Aerospace Engineering
The Department of Mechanical Engineering at the University of Utah (https://mech.utah.edu/) invites applications for tenure-track faculty positions at any rank in its Aerospace Engineering program, with an anticipated Fall 2021 start date. Candidates with research related to any area of aerospace en...
The Department of Mechanical Engineering at the University of Utah (https://mech.utah.edu/) invites applications for tenure-track faculty...
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The Senior Project Engineer is a member of the Womack Systems Team reporting directly to the Director of Systems. The Senior Project Engineer is responsible for the development of initial system/component requirements and specifications; performing calculations (e. g. pressure drop, flow analyses, h...
The Senior Project Engineer is a member of the Womack Systems Team reporting directly to the Director of Systems. The Senior Project Engineer is...
Assistant Professor - Mechanical Engineering - Tenure Track
FACULTY POSITION ANNOUNCEMENT The Mechanical Engineering Department at the University of Arkansas is seeking outstanding candidates to fill a tenure-track Assistant Professor position starting in August 2021. The broad area of interest is Future Manufacturing. We are specifically looking for indiv...
FACULTY POSITION ANNOUNCEMENT The Mechanical Engineering Department at the University of Arkansas is seeking outstanding candidates to fill a...
Lucifer Lighting Company is a privately held San Antonio-based designer and manufacturer of precision-engineered architectural light fixtures for projects worldwide. You'll find our products everywhere from Wrigley Field to the Nike Headquarters. We're in the campuses of 4 of the 5 largest tech comp...
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Los Angeles, California Work Remotely
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The Production Manager is responsible for effective planning, creative development and management of the manufacturing departments including machining, assembly, and mechatronics production from conception to final installation. Requires innovation in identifying new content-rich feature and applica...
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Kinnos is a venture-backed company founded by three Columbia alumni with a mission to protect society from infections. We've created an award-winning and patented colorized disinfection technology called Highlight® that is revolutionizing how people use disinfectants. Highlight® is used by first res...
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Overview Open & closing dates 01/15/2021 to 01/22/2021 Service Competitive Pay scale & grade GS 14 Salary $122,530 to $159,286 per...
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The Young and the Restless' Bryton James Stars in New Film!
A new film was recently released titled, "The Intruder" which stars Bryton James who plays the role of Devon Hamilton on 'The Young and the Restless'. This film was directed and written by Gregori J. Martin, creator of The Bay and produced by LANY Entertainment. The film follows the story of a man named Michael Foster who invites a number of strange characters into his home following the death of his mother. Former daytime stars; Alla Korot and Brody Hutzler also star in the film, the film can be viewed on Amazon Prime according to Soap Opera Digest.
Soap Opera News: The Young and the Restless' Bryton James Stars in New Film!


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Raza Panjwani
Publications + Appearances
Hello! I'm Raza Panjwani, a recovering attorney and lover of odd trivia, and this is my personal website. You can also find me on LinkedIn, Twitter, and Mastodon.
Currently I'm catching up on my backlog of bought-but-unread books while thinking about what's next. Previously I led policy for the hardware design, development and manufacturing divisions of Reality Labs; regulatory strategy at Tidepool, a non-profit developing open source software to improve the lives of people with diabetes; public policy at Scotty Labs (acquired by DoorDash), an autonomous vehicle start-up in San Francisco; and was Policy Counsel at Public Knowledge, a Washington, DC-based public interest organization advocating for consumer rights in tech.
I like to take photos, and before I went to law school, I studied architecture and history. I support tinkering, the oxford comma, and the New York Mets (sigh).
You can find some things I've written and said here, and some things I've done or am doing on the Projects page.
© 2023 Raza Panjwani


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Miami Heat open NBA title defence with win
Sport Basketball Miami Heat open NBA title defence with win
6:03pm, Oct 30, 2013 Updated: 7:32pm, Oct 30
LeBron James scored 17 points as the Miami Heat spoiled Derrick Rose's return to the NBA by beating the Chicago Bulls 107-95 in the season-opener for both teams.
Chris Bosh scored 16 points, Shane Battier finished with 14 and Dwyane Wade and Mario Chalmers each scored 13 for the Heat, who got their 2013 NBA championship rings and raised their title banner in a pre-game ceremony at their home court.
Rose, the 2011 NBA Most Valuable Player, finished with 12 points in 34 minutes in his first game since a knee injury sidelined him in April 2012.
Carlos Boozer had 31 points and seven rebounds for Chicago, which fell behind by 21 points at halftime but got within eight points in the final minutes.
Elsewhere, the Indiana Pacers got 24 points from Paul George and 16 rebounds and seven blocks from Roy Hibbert to defeat the Orlando Magic 97-87.
The two-man tandem looked every bit as dominant in the season opener as they did leading the Pacers to the Eastern Conference finals in the playoffs last season.
George's buzzer-beating 3-pointer at the end of the third quarter gave Indiana a 69-64 lead and sparked the decisive 17-4 run to open the fourth.
Victor Oladipo, the No. 2 overall pick in the 2013 NBA draft, had 12 points and three turnovers for the Magic.


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Stamps in Gallery: 210
Home | New Additions | A | B | C | D | E | F | G | H | I | J | K | M | N | P | R | S | T | U | V | W |
All of the stamps shown are from my personal collection. They are not for sale. If you have any questions or information about a particular cancel, feel free to email me.
Clicking on an image thumbnail will pop up a full-size image.
Scott # 149
© and ™ 2011-2021, DBH. All rights reserved.


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Association of ADAMTS4 and ADAMTS5 polymorphisms with musculoskeletal degenerative diseases: a systematic review and meta-analysis
Jian-Zhong Huo, Xing-Hua Ji, Zhong-Yi Su, Peng Shang, Fei Gao
Bioscience Reports Nov 30, 2018, 38 (6) BSR20181619; DOI: 10.1042/BSR20181619
Jian-Zhong Huo
Department of Orthopedics, Shanxi Dayi Hospital, Taiyuan, Shanxi 030032, China
Xing-Hua Ji
Zhong-Yi Su
Fei Gao
Department of Endocrinology, the First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China
For correspondence: gaofei13935110660@hotmail.com
Objective: This meta-analysis and systematic review was performed with the aim of investigating the association between a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)4, AMDMTS5 polymorphisms and risk of musculoskeletal degenerative diseases.
Methods: PubMed, EMBASE, ISI Web of Science, Wanfang and CNKI were searched from their inception until May 2018 to identify eligible studies. Data from individual studies were extracted using a standardized data collection sheet. The estimate of association between ADAMTS4, AMDMTS5 polymorphisms and risk of musculoskeletal degenerative diseases was expressed as odds ratio (OR) along with its related 95% confidence interval (95%CI) under an allelic model of inheritance. Meta-analysis was conducted using RevMan 5.3 software. Subgroup-analyses by ethnicity and type of diseases were performed.
Results: Eight studies including ten cohorts were included in this meta-analysis. The meta-analyses results based on seven studies showed that rs226794 in ADAMTS5 gene was not associated with risk of musculoskeletal degenerative diseases (A vs. G: OR 1.07; 95%CI 0.97–1.19; P=0.16). Rs2830585 in ADAMTS5 was significantly associated with musculoskeletal degenerative diseases in only Asians (OR 1.41, 95%CI 1.18–1.68; P=0.0001), but not in Caucasians. Since only two of the collected studies referred to ADAMTS4, we did not perform meta-analysis for these comparisons.
Conclusion: Taken together, rs226794 and rs2830585 in ADAMTS5 gene were not associated with musculoskeletal degenerative diseases in overall population, but there seemed to be an ethnicity-dependent effect of rs2830585 in the risk of musculoskeletal degenerative diseases. Insufficient evidence was found to support the association of other single nucleotide polymorphisms and musculoskeletal degenerative diseases.
ADAMTS4
lumbar disc degeneration
meta analysis
single nucleotide polymorphisms
Musculoskeletal degenerative diseases are a diverse group of pathological conditions affecting bone, cartilage, joint and other connective tissues. They are typically characterized by severe chronic pain, stiffness, activity limitations and incapacity in patients' later life [1,2]. The incidence and prevalence of musculoskeletal degenerative diseases increase markedly with age, especially with the prolongation of human being lifespan over recent years [3–5]. Musculoskeletal degenerative diseases represent a great challenge to both patients and clinicians, and are becoming a serious public-health issue [6,7].
Osteoarthritis (OA) and intervertebral disc degeneration are two most common musculoskeletal degenerative diseases that share comparative similarities. The surfaces of joints are overlaid by a layer of articular cartilage covering the subchondral bone. Progressive damage of articular cartilage as with subchondral bone is the pivotal hallmark of musculoskeletal degenerative diseases. Articular cartilage consists of plenty of extracellular matrix (ECM) components that include macromolecules, collagen fibrils and large proteoglycanaggrecans [8]. Quite a small number of chondrocytes are embedded in ECM [9]. The chondrocytes can synthetize and catabolize ECM macromolecules, which correspondingly maintain the homeostasis of the extracellular microenvironment and the configuration of cartilage [9].
A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) in mammalian genomes contain a family of 19 secreted metalloproteinases [10,11]. All ADAMTSs belong to matrix-degrading enzymes. Regulating the structure and function of the ECM is the foremost action of the biology of ADAMTSs [11]. ADAMTS4 and ADAMTS5, also known as aggrecanase-1 and aggrecanase-2, are two members of ADAMTSs family and have been shown to degrade the cartilage proteoglycanaggrecan [12,13]. A series of studies have suggested that variants of genes encoding ECM degrading enzymes were related with OA, such as matrix metalloproteinase (MMP)-1 [14–18], MMP-3 [14,19,20] and MMP-9 [17]. Strong associations between MMP-3, MMP-9 polymorphisms and risk of lumbar disc degeneration (LDD) were also indicated [21,22]. As the earliest discovered and most efficient aggrecanases, ADAMTS4 and ADAMTS5 have received high attention in the development of musculoskeletal degenerative diseases [23].
A fully understanding of the risk factors, etiology and mechanism is significant to prevent and treat a disease. But the precise etiopathogenesis underlying musculoskeletal degenerative diseases remains unclear. Risk factors like genetics, age and joint biomechanics seem to all together result in triggering the diseases [24,25]. Mounting evidence has suggested that genetic factors play a critical role in the pathogenesis of musculoskeletal degenerative diseases [26]. So far, several studies have reported the relationship between ADAMTSs single nucleotide polymorphisms (SNPs) and musculoskeletal degenerative diseases, which have yielded inconsistent results. Therefore, we systematically reviewed the current body of evidence to summarize the association between ADAMTS4, ADAMTS5 polymorphisms and musculoskeletal degenerative diseases.
This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline [27].
Literature search strategy
Five online databases including PubMed, EMBASE, ISI Web of Science, Wanfang and CNKI were searched from their inception until May 2018 to identify eligible studies. Structured literature search strategy based on the combination of medical subject headings (MeSH) and free text terms was used to retrieve observational studies that analyzed the association between ADAMTSs and musculoskeletal degenerative disease, no language restriction was imposed on the literature search. The literature search was performed with the following terms: (Single Nucleotide Polymorphism or polymorphism or SNP or SNPs or 'Polymorphism, Single Nucleotide'[Mesh]) and ('ADAMTS4 Protein'[Mesh] or ADAMTS4 or Aggrecanase-1 or A Disintegrin And Metalloproteinase With Thrombospondin Motifs 4 Protein or 'ADAMTS5 Protein'[Mesh] or ADAMTS5 or Aggrecanase-2 or A Disintegrin And Metalloproteinase With Thrombospondin Motifs 5 Protein). A combination of related Chinese characters was used for literature search in Chinese academic databases: 'ADAMTS' and 'Duo Tai Xing'. Reference sections of the acquired studies were manually searched for additional eligible studies.
Inclusion criteria and exclusion criteria
We followed the PICOS principle to establish the eligibility criteria for the current meta-analysis. Studies satisfying the following criteria were included for review: (1) patients to be included should be diagnosed as musculoskeletal degenerative diseases, such as OA and LDD; (2) published or unpublished studies on the relationship between ADAMTS4 or ADAMTS5 polymorphisms and musculoskeletal degenerative diseases susceptibility; (3) control subjects should be defined as healthy subjects without history of musculoskeletal degenerative diseases; (4) available odds ratio (OR) and 95%CI under allelic comparison of individual loci; (5) observational studies (case–control or cohort studies) on humans.
Correspondingly, studies would be excluded if they met the following exclusion criteria: (1) animal studies, reviews, case reports, conference abstracts, as well as comments and editorials; (2) data that overlapped previous publications. If duplicated studies reporting overlapping data were identified, the most comprehensive one was included in the meta-analysis.
Two independent reviewers extracted detailed information according to a pre-specified data collection sheet, data extracted included: (1) surname of the first author; (2) year of publication; (3) variant locus; (4) country where the study was performed; (5) ethnicity of enrolled subjects; (6) diagnosis of cases; (7) sample size; (8) results of Hardy–Weinberg equilibrium (HWE) test; (9) major allele and minor allele distribution of case and control participants; (10) P value for the associations. Once encountering discrepancy during this process, two investigators re-inspected the article together and reached an agreement through discussion.
The Newcastle–Ottawa Scale (NOS) for the assessment of non-randomized studies was used to assess the methodological quality of case–control studies and cohort studies [28]. Three broad perspectives including selection of cases and controls, comparability of the groups and ascertainment of outcome of interest were assessed using the Star system (http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp). Higher score indicates higher methodological quality and the maximum score is 9 Stars. Two reviewers (J.H. and X.J.) independently assessed the methodological quality of included studies. The results of risk of bias assessment were compared afterwards. In case of discrepancies between two reviewers, the third reviewer (F.G.) was consulted.
The strength of association between ADAMTS4, ADAMTS5 polymorphisms and musculoskeletal degenerative diseases susceptibility was assessed through pooling ORs and the corresponding 95%CI of individual studies. The between-study heterogeneity was assessed using the Q-statistical test and I2 test, where P>0.1 and I2 < 50% indicate acceptable heterogeneity [29]. In our meta-analysis, patients diagnosed with different types of musculoskeletal degenerative diseases could be included. Therefore, we combined the OR of each study using a random-effect model regardless of the heterogeneity detected between included studies because random-effect model accommodates diversity between studies and is preferable in the presence or anticipation of interstudy variances [30,31].
The leave-one-out sensitivity analysis was performed by omitting each study in turn and re-evaluating the resulting effect on the overall effect. Egger's regression test and Begg's rank correlation test were used to estimate the publication bias (Stata version 12.0, Stata Corp LP, U.S.A.) [32]. Forest plots and funnel plots were generated using RevMan 5.3 software (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). In addition, stratified analyses were performed according to subtypes of musculoskeletal degenerative diseases and ethnicity of cases.
Functional predictions
In order to perform functional annotation of rs2830585 and rs26932893, we applied an in silico analysis using HaploReg 4.1 database (http://pubs.broadinstitute.org/mammals/haploreg/haploreg.php) [33]. The Genotype-Tissue Expression (GTEx) project is a combination of resource database and associated tissue bank to study the relationship between genetic variation and gene expression in human tissues (https://gtexportal.org/home/) [34]. GTEx was used to test if rs2830585 and rs26932893 in ADAMTS5 gene were associated with altered expression of ADAMTS5 in human tissues. Additionally, PROMO (http://alggen.lsi.upc.es/cgi-bin/promo_v3/promo/promoinit.cgi?dirDB=TF_8.3) was used to identify putative transcription factor binding sites in rs2830585 and rs26932893 [35].
Study selection
Combining the search results of all databases, a total of 78 potentially relevant articles were retrieved with 19 from PubMed, 27 from EMBASE, 23 from ISI Web of Science, 5 from Wanfang and 4 from CNKI. No additional articles were obtained through the manual search. After removing 34 records of duplicates, 44 articles remained for further screen. Another 35 articles were eliminated after screening for eligibility with titles and abstracts. Only 1 article was removed after evaluating the full text because of unavailable data [36]. Finally, 8 articles were deemed eligible and were subsequently incorporated into this systematic review [37–44]. The literature selection process was presented in Figure 1.
Figure 1 Flow diagram of literature search and screen
Study characteristics
All included studies were based on a case–control design. Seven studies [37,39–44] were performed among populations of Asian ancestry but Rodriguezs' [38] was among Caucasian ancestry with four different cohorts. Four of the included studies were about OA, and the others were about LDD. The OA was diagnosed according to the American College of Rheumatology criteria, and radiographic featured were assessed using the Kellgren–Lawrence score system. The diagnosis of LDD was made based upon the confirmation of MRI scanning. There were seven studies [37–39,41–43] looking at ADAMTS5, one looking at only ADAMTS4 [40], and one focusing on both of them [44]. The rs2830585 and rs226794 SNPs in ADAMTS5 were the mostly frequently investigated polymorphisms among these studies, consequently we combined the ORs from each individual study using an allele genetic model. The main characteristics of the 8 included studies were summarized in Tables 1 and 2. According to the NOS, our included studies gained an average of 6 Stars, the risk of bias for the included studies was summarized in Table 3.
Table 1 Main characteristics of included studies on ADAMTS5 polymorphisms
Table 3 Quality assessment of included studies
Association between ADAMTS5 and musculoskeletal degenerative diseases
Rs226794, rs2830585 and musculoskeletal degenerative diseases
For the reason that most of the included studies are lacking of available genotypes, we just analyze the allelic comparison of rs2830585 and rs226794, because the allele distributions in cases and controls could provide useful, direct summary statistics for the data. The data were analyzed by Chi-squared and I2 to detect the between-study heterogeneity. In this meta-analysis, the effect size of each included study was combined using random-effect model because there was an anticipated heterogeneity across study. The merged ORs suggested that for both rs2830585 and rs226794 polymorphisms, no pooled correlations with musculoskeletal degenerative diseases were identified under the allelic model when analyzing all of the relevant studies together. For rs2830585, four studies were pooled (C vs. T: OR 1.14; 95%CI 0.99–1.30; P=0.06. Figure 2), the result suggested no association between rs2830585 and musculoskeletal degenerative diseases. But there was a significant level of heterogeneity detected (P=0.002,
= 79%). For rs226794, summarized data was based on seven studies (A vs. G: OR 1.07; 95%CI 0.97–1.19; P=0.16, Figure 3) with a non-significant level of heterogeneity (P=0.89, I2 = 0).
Figure 2 Forest plot of rs2830585 in ADAMTS5 gene and risk of musculoskeletal degenerative diseases using a random effect model
Figure 3 Forest plot of rs26794 in ADAMTS5 gene and risk of musculoskeletal degenerative diseases using a random effect model
To test if there was an ethnicity-specific effect on these associations, subgroup analysis by ethnicity was performed for both polymorphisms (Table 4). For rs2830585 and musculoskeletal degenerative diseases, negative results were found in both Asian and Caucasian. However, we observed an ethnicity-dependent effect in rs2830585, rs2830585 was not associated with risk of musculoskeletal degenerative diseases in the overall population, but it was significantly associated with musculoskeletal degenerative diseases in Asian (OR 1.41, 95%CI 1.18–1.68; P=0.0001), this finding was further strengthened by low heterogeneity between studies among Asian populations (P=0.80, I2 = 0%). We also performed subgroup analysis according to the diagnosis of patients (OA or LDD), studies focusing on different kinds of musculoskeletal degenerative diseases were combined in different subgroups. Based on the results of subgroup analysis, rs226794 was not associated with risk of OA or LDD, neither was rs2830585 (Table 4).
Table 4 Subgroup analysis of rs226794, rs2830585 and risk of musculoskeletal degenerative diseases
The leave-one-out sensitivity analysis was carried out to evaluate the stability of the overall effect for both rs2830585 and rs226794, and the results confirmed the non-significant association between rs2830585, rs226794 and musculoskeletal degenerative diseases (detailed data not shown). The funnel plots for rs2830585 (Figure 4) and rs226794 (Figure 5) were both visually symmetrical, the results of Begg's test (rs2830585: z = 0.60, P=0.548; rs226794: z = 0.34, P=0.734) and Egger's test (rs2830585: t = 0.82, P=0.448; rs226794: t = −0.57, P=0.628) also indicated no statistically significant publication bias.
Figure 4 Funnel plot of rs2830585 in ADAMTS5 gene and risk of musculoskeletal degenerative diseases
Figure 5 Funnel plot of rs226794 in ADAMTS5 gene and risk of musculoskeletal degenerative diseases
Other polymorphisms of ADAMTS5 and musculoskeletal degenerative diseases
Since only few studies reported detailed data about the association between rs1974415, rs2132824, rs151065, rs162509 and risk of musculoskeletal degenerative diseases, these results were not combined using a meta-analysis, providing a narrative description as an alternative. Detailed data about these polymorphisms and risk of musculoskeletal degenerative diseases were summarized in Table 1.
Chen et al. [43] investigated the correlation of several SNPs about ADAMTS5 and OA among Chinese population. A linkage disequilibrium in SNPs of rsl51065-rs229077-rs56153501-rs2830585-rs58215296 was detected, and the haplotype of G-T-A-C-A of the SNPs was proportional to the susceptibility of OA (OR 1.874, 95%CI 1.019–3.446; P<0.05).
Jiang et al. [41] looked at rs162509 and lumbar spine pathologies through Chinese population. The G allele frequency of the case subjects was significantly higher than the control subjects (OR 1.38; 95%CI 1.13–1.69; P=0.001).
In Rajasekaran et al.'s study [39], rs162509 of ADAMTS5 were found to be significantly linked to the severity of disc degeneration (OR 1.281, P=0.04068). The study led by Gu et al. [42] looked at rs2380585 C/T and rs226794 G/A and OA occurred in cervical, lumber, knee and hand among Chinese population. In terms of rs226794, insignificantly statistical difference existed between OA and control participants under allelic and genotypic frequency comparison (P=0.261). With regard to rs2830585, T allele carrier seemed to have a lower risk for the cervical OA (OR 0.664, 95%CI 0.521, 0.847; P=0.001) and overall OA vulnerability (OR 0.701, 95%CI 0.569, 0.863; P=0.001).
Rodriguez et al.'s study [38] was conducted among European population from three countries (U.K., Spain and Greece). The initial study suggested that T allele of rs226794 might play a protective role towards OA susceptibility, while the initial finding was not replicated by additional studies. None of the remaining SNPs or haplotypes constructed with these SNPs presented to be significantly associated with OA susceptibility.
Association between ADAMTS4 polymorphisms and musculoskeletal degenerative diseases
Since only two of the collected studies referred to ADAMTS4, we did not perform meta-analysis for these comparisons. Liu et al. [40] genotyped five tag SNPs in and around ADAMTS4 gene, and four of them (rs11585858, rs41270041, rs4233367 and rs10908826) were further studied. Only rs4233367 presented significant difference under both allelic and genotypic comparisons between case and control subjects. The T allele was found to have a declined susceptibility to LDD (OR 0.69, 95%CI 0.50, 0.94; P=0.0166). Subjects with TT genotype also had significantly lower risk of LLD than subjects with CC genotype (OR 0.21, 95%CI 0.0461, 0.99; P=0.0374). Canbek et al.'s study [44] investigated rs226794 and rs2830585. For them, neither genotype nor allele distribution was observed to have an association with KOA. In addition, Canbek et al. [44] conducted stratification analysis based on gender, but still failed to find any positive association between KOA vulnerability and these SNPs.
In the GTEx database, no evidence was found to support the association between rs2830585, rs226794 and regulation of ADAMTS5 expression in any kind of human tissue (detailed data not shown). The effect of SNPs on expression from eQTL studies from HaploReg suggested that only rs2830585 was associated with altered expression of ADAMTS5 in human glioblastoma cell line U87MG, no promoter histone marks and enhancer histone marks were found in these variants (Figure 6A). According to the results of PROMO search, the predicted transcription factor binding sites remained unchanged in both polymorphisms (Figure 6B,C).
Figure 6 Functional predictions of rs2830585 and rs226794
(A) HaploReg view of rs2830585 and rs26794; (B) predicted transcription factor binding sites in rs2830585; (C) predicted transcription factor binding sites in rs226794.
Despite extensively studied, the etiology and pathogenesis of musculoskeletal disorders have not been entirely understood. A large body of studies has indicated that genetic susceptibility in collaboration with environmental effects contributes to the etiopathogenesis of musculoskeletal degenerative diseases [11,45,46]. In fact, according to some reports, genetic factors appear to be predominantly responsible for the development of musculoskeletal degenerative diseases such as OA and LDD, with environment playing a much less significant role [47–49]. The identification of variants conferring susceptibility to musculoskeletal degenerative diseases could help to develop individualized predictive model, and thus to anticipate the phenotype of musculoskeletal degenerative diseases in the future [50].
ADAMTS genes encode a series of secreted ADAMTS proteases which were known to regulate development, angiogenesis, coagulation, as well as homeostasis in the ECM [11]. Current studies have shown that variants within several ADAMTS genes are associated with musculoskeletal degenerative diseases like OA [51–53], LDD [39] and Achilles tendon pathology [54]. Several ADAMTSs have been discovered to be expressed in connective tissues [55]. Nevertheless, functional explorations of ADAMTSs have largely been limited to only a few specific members, exceptionally ADAMTS4 and ADAMTS5, which have been involved in the occurrence and progression of cartilage damage [56]. The remaining members are not prone to function since their low activity or even absence in the tissues, these members are not likely to play a critical role in musculoskeletal degenerative diseases [13]. Therefore, in our current study, we only focused on the variants within these two genes and the risk of musculoskeletal degenerative diseases.
ADAMTS4 and ADAMTS5 genes locate at chromosome 1q23 and 21q21.3, respectively, the corresponding proteases they encode share similar domain arrangement and comparable function [13]. Prasadam et al. [57] reported that irregular interplay between cartilage chondrocytes and subchondral bone osteoblasts significantly influence the critical features of both bone and cartilage by producing abnormal levels of ADAMTS4 and ADAMTS5. Both ADAMTS4 and ADAMTS5 have been recognized as biomarkers to assess the severity of early stage osteoarthritic cartilage damage in many in vivo and ex vivo experimental studies.
Rodriguez et al. [38] predicted the potential role of rs226794 and rs2830585 in musculoskeletal degenerative diseases using SIFT and PolyPhen, and they reported the potentially damaging effect of rs226794 but not that of rs2830585. However, with the application of SNPs3D they confirmed that both polymorphisms have potential deleterious effects on musculoskeletal degenerative diseases. The functional predictions of these two polymorphisms were based on screening of amino acid conservation, and the high degree of conservation of both polymorphisms is owing to their location in functional domains. Rs2830585 maps to the first of the two thrombospondin type I domain of ADAMTS5, while rs226794 maps to a functional domain of unknown function in exon 7. However, based on the findings of our present meta-analysis, rs2030585 and rs226794 were not associated with musculoskeletal degenerative diseases in the overall population. Insignificant results were also yielded in subgroup-analyses by types of diseases. The only statistically significant finding was that rs2830585 represented a risk factor for the development of musculoskeletal degenerative diseases in Asians (OR 1.14, 95%CI 1.18, 1.68; P=0.0001). There seemed to be an ethnicity-dependent effect in the association between rs2830585 and risk of musculoskeletal degenerative diseases, but whether the variation in ethnicity leads to different results needs to be confirmed by further studies within different ethnic backgrounds.
In order to confirm the negative findings of our present study, we performed functional predictions of rs226794 and rs2830585 using several online databases including GTEx, PROMO and HaploReg. We failed to find any evidence to support the hypotheses that rs226794 or rs2830585 could regulate the expression of ADAMTS5 in any kind of human tissues. The findings based on PROMO also suggested that predicted transcription factor binding sites remained unchanged in both polymorphisms. The HaploReg results further confirmed that no promoter or enhancer histone marks were associated with these variants. Taken together, reasonable confidence should be placed to the null findings of the association between ADAMTS5 polymorphisms and risk of degenerative musculoskeletal diseases.
During the past two decades, there has been a far-reaching transformation in the ability to distinguish genes that contribute to various diseases, so as to the number of novel genetic polymorphisms in relation to musculoskeletal degenerative diseases are surging. Unfortunately, under most circumstances, researchers have less interest to further study these previously reported SNPs. In addition, these studies indeed suffered from large heterogeneity that was caused by diverse ethnic origin of the participants, sex and age variation, as well as the difference of diagnostic criteria and so forth. Both the aforementioned factors made it impossible to perform a formal meta-analysis of these studies. In this meta-analysis and systematic review, we summarized the available literature about SNPs in ADAMTS4 and ASAMTS5 genes, thus providing an analysis of the correlation between these genetic polymorphisms and musculoskeletal degenerative diseases vulnerability. There are several genetic models that could be used in meta-analysis of association studies, such as recessive model, allele model, dominant model and co-dominant model. Although all these aforementioned models are valid methods for analysis of an association study, any such study should have a pre-specified analysis plan because applying all tests will definitely increase the probability of a false-positive result. We only synthesize the two SNPs with allelic comparison in this systematic review, because the allele distributions in cases and controls could provide useful and direct summary statistics for the data. For rs2830585 and rs226794, the merged ORs and 95%CIs did not appear to be associated with musculoskeletal degenerative diseases. However, the result could not represent the overall population because six of the eight studies were performed across Asian population. Studies with larger samples conducted in various populations are required to obtain a clear understanding of these possible associations. Another limitation shouldn't be ignored when interpreting the results was that there are several subtypes of OA and LDD. But a meta-analysis based on OA and LDD subtype could not be conducted because of the quantity limitation of currently available literature. Therefore, more well-designed clinical materials along with functional analyses are required to exactly elucidate the mechanisms of ADAMTS polymorphisms in the pathogenesis of musculoskeletal degenerative diseases.
In summary, our study elaborated the association of ADAMTS4, ADAMTS5 polymorphisms and risk of musculoskeletal degenerative diseases. Based upon the findings of our present study, rs226794 and rs2830585 in ADAMTS5 gene were not associated with musculoskeletal degenerative diseases in overall population, but there seemed to be an ethnicity-dependent effect of rs2830585 in the risk of musculoskeletal degenerative diseases since rs2830585 conferred a significantly higher risk of musculoskeletal degenerative diseases in Asians. Insufficient evidence was found to support the association of other SNPs and musculoskeletal degenerative diseases. Considering the limitations of our meta-analysis, additional studies with larger sample-size among other ethnicities are encouraged to elucidate the real effect of these polymorphisms and musculoskeletal degenerative diseases.
The authors declare that there are no competing interests associated with the manuscript.
Author Contribution
F.G. produced the idea of this study and had full access to all of the data in the study. F.G. takes responsibility for the integrity of the data and the accuracy of the data analysis. J.-Z.H. and X.-H.J. did the literature search, analyzed the data and drafted this paper. Z.-Y.S. designed the data collection tool and P.S. revised the manuscript. All authors read and approved the final manuscript.
The study was sponsored by a grant from the Shanxi Province Science and Technology Research Project [grant number 20150313012-1]. The funding source had no involvement in study design, data collection, data analysis and interpretation.
Abbreviations: ADAMTS, A disintegrin and metalloproteinase with thrombospondin motif; GTEx, Genotype-Tissue Expression; HWE, Hardy–Weinberg equilibrium; IVDD, intervertebral disc degeneration; LDD, lumbar disc degeneration; MeSH, Medical subject headings; MMP, matrix metalloproteinase; NOS, Newcastle–Ottawa Scale; NR, not reported; OA, osteoarthritis; OR, Odds ratio; SNP, single nucleotide polymorphism
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Bioscience Reports Dec 2018, 38 (6) BSR20181619; DOI: 10.1042/BSR20181619


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