After the success of our previous West Coast Trail hikes, we are offering it again to let more individuals with T1D experience this world-renowned hiking trail.
Step out of your comfort zone and onto the West Coast Trail with some of the most adventurous type 1s around, on one of the most grueling hiking trails in North America… and also one of the most rewarding!
Since leading this hike for the first time in 2012, ICD has led over 40 individuals to take on and complete this incredible trek. The West Coast Trail hike will take place on some very beautiful, yet challenging, hiking trails. We'll be hiking for 7 days and that means we'll be camping out too! Since we will be carrying all our supplies on our backs, it is VERY important to pack small and pack light! This is one of our rare programs where we will not be accepting everyone, the challenge is meant for fit and motivated participants with type 1 diabetes. We are happy to assist anyone who is interested to sort out if this is the right hike for you, and how to prepare to take on this challenge.
Where: The West Coast Trail adventure will take place on Vancouver Island, BC. This is quite a rigorous hike, and has a many unique features to experience over the course of 7 days of hiking.
What: Hiking, hiking, hiking and having fun! Cleaning off the mud with a nice splash in a river, ocean or bay may be accompanied by whale sightings, sea caves and sea lions, just to keep us motivated! Suspension bridges over gorgeous gorges, ladders up steep ravines, monstrous fallen trees turned into bridges and stair cases, ship wrecks, and hand-operated cable car crossings serve to navigate this trail, which was originally created to help survivors of ship wrecks get home. For the past 40 years, it has been a rare gem of hiking blisters and bliss, attracting people from around the world. We'll work as a team to get through this awesome adventure and take care of all the equipment, safety precautions and food prep for this trek. A bus ride for the return trip is included.
Be sure to check out pictures from our previous years' trips 2018 2017, 2016, 2014 and 2013!
Who: This trip is open to strong teens and adults who are type 1, physically fit, and can carry 30% of their body weight in a pack on their back. If you are willing to work hard and endure some physical difficulties to enjoy some amazing rewards, this trip is for you! We only have room for 8, so reserve your spot today!
Why: It has been said if someone can walk a mile in your shoes… well walking 75 km with others who understand diabetes just as much as you do and being inspired by your surroundings will be completely different. Our participants have overcome many challenges in their lives, diabetes being one of them, and have gone on to achieve greatness! This is an opportunity to do something extraordinary together.
Cost: $900 – Includes food, camping permits, group gear (tents, tracking, cooking supplies), ICD mentor/leadership, and transportation from the end of the trailhead back to the start. (Save $100 if you register before Jan 15th) The registration fee of $50 by Jan 15th will also secure the discount.
Since we will be carrying all of our supplies on our backs, it is VERY important to pack smart and pack light. We will provide gear lists as well as support you if you require gear rentals. Feel free to contact us if you have any questions surrounding gear rentals.
This program has amazing leaders! This trek is led by type 1 diabetics living full lives who love to mentor and share their skills and habits that have helped them to go after their wildest dreams and enjoy the 'normal' day-to-day parts of life. They have led more type 1 backpacking trips than anyone else in North America, not to mention the canoe trips, base camps, climbing programs, sport clinics and their own personal endeavours.


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« A couple of letters
Remembering Ted »
The seeds of the NEOCATECHUMENAL WAY were first sown in the Archdiocese of Lingayen-Dagupan in 1981 in the Parish of Saint Gabriel the Archangel in Bonuan Boquig. Since then, it has been born in other Catholic communities in the archdiocese – Bonuan Gueset, Calasiao, Calmay, Dagupan, Laoac, Lingayen, Mapandan Santa Barbara and San Jacinto. The Neocatechumenal Way has brought innumerable blessings to the Christian faithful in our archdiocese. It has profoundly changed many lukewarm lives. It has rebuilt many wounded families and has yielded many religious and priestly vocations for the vineyard of the Lord.
Yet, despite its positive effects such as those mentioned above, there are certain concerns about the direction the Neocatechumenate is leading to. Already during the time of my esteemed predecessor Archbishop Oscar Cruz, and in recent months, some questions have been raised by some respected members of the Catholic laity and a good number of our parish priests about the integration of the members of the Neocatechumenal communities in the mainstream of our Church life, their cooperation with the parish priests and their relationship with the Bishop.
The Statutes of the Neocatechumenal Way state these words: "The Neocatechumenal Way will seek to foster in its recipients a mature sense of belonging to the parish and to promote relations of profound communion and collaboration with the faithful and with other elements of the parish community." (Art. 6, n. 3)
Further, the Statutes enjoin that "the implementation of the Neocatechumenal Way must be coordinated with the proper function that the parish priest has in each parish community (cf. c. 519 of the Code of Canon Law), providing also with the collaboration of other presbyters, the pastoral care of those who are going through the Neocatechumenal Way. "(Art. 6, n.2) Similarly, the Statutes acknowledge that "the Neocatechumenate is realized, in communion with the parish priest and under his responsibility, by a team of catechists." (Art. 8, n. 4)
Furthermore, the Statutes declare that: "The Neo Catechumenal Way is at the service of the bishop as one of the forms of diocesan implementation of the Christian initiation and of ongoing formation in the faith." (Art. 1, n. 2)
In the weekly celebration of the Word prescribed by Article 11 of the Statutes, my attention was called to the lack of formation and preparation on the part of those entrusted to teach regarding the tenets of the Catholic Church as laid down in its Catechism as well as the meaning of the biblical readings proclaimed within the celebration. There seems to be a tendency towards fundamentalist interpretation of the Sacred Scriptures detached and, sometimes, even contrary to the documents of the Magisterium and the Catechism of the Church.
With respect to the preceding observation, the Statutes provide that "it pertains to the diocesan Bishop, as responsible for initiation, formation and Christian life in the local Church to watch over the implementation of the Neocatechumenal Way so that it may take place in conformity with what is established in Articles 1 and 2, respecting the doctrine and discipline of the Church." (Art. 26)
Respect for the Ordained
There is a prevailing sentiment of superiority among the community members on account of sheer membership in a Neocatechumenal community resulting in a disdainful attitude towards those who are not walking the Way or have stopped joining the meetings. Besides, disdainful and disrespectful remarks about my predecessor, about some priests and even about my own person, have been repeatedly heard from the catechists of the communities contrary to good manners, upright conduct, filial respect and Christian charity.
The President of the Pontifical Council for the Laity offered three guidelines for the Neocatechumenal communities when he presented the Holy See's approval of the movement: obedience to bishops, acknowledgement of the role of priests and fidelity to the liturgical texts of the Church. On the same occasion, Carmen Hernandez, co-founder of the movement, said: "What is important is NOT the Neocatechumenal Way, but the CHURCH." She continued by inviting the members of the movement to practice humility.
In January 2009, when the Neocatechumenal Way celebrated its fortieth year as a Catholic lay association, the Holy Father gave thanks to God for the fruits of the evangelical efforts of the Way. However, the Pope reminded them that the full realization of the work comes with docile adherence to the directives of the bishops and with communion with all the other components of the People of God. He encouraged them to work for unity — which makes of each community a living and well integrated joint in the mystical body of Christ.
We can veritably adopt as our own the observation of Augusto Faustini, writing to the Pope complaining about how the movement's founder, Kiko Arguello, "has established how you are, how you sit, how you pray, how you sing, how and what you play, how you confess, how you take Communion, how you read the Sacred Scriptures, making clear that anyone who does not do all that is lost in error." (Urquhart, The Pope's Armada, p. 250)
THEREFORE, considering the foregoing facts and statutory principles, by virtue of my authority as Archbishop of Lingayen-Dagupan, in order to guide and reorient the Neocatechumenal Way in this archdiocese, I hereby impose a moratorium on all initial catecheses in the Neocatechumenal Way within the archdiocese until the Episcopal Delegate, named below, recommends the lifting of this moratorium.
No new communities shall be opened and no new members may be initiated into the Neocatechumenal Way within the moratorium period starting on the Solemnity of Pentecost this year until the Solemnity of Pentecost in 2011.
Likewise, I order the reading, within the whole year, starting from the Solemnity of Pentecost this year until the Solemnity of Pentecost in 2011, of paragraphs 748 to 945 of the Catechism of the Catholic Church, pertaining to ecclesiology, the readings being spread out during the weekly celebrations of the Word of each Neocatechumenal community.
Moreover, I enjoin the recitation of the five mysteries of the Holy Rosary before the weekly celebration of the Word, starting on Pentecost Sunday, in adherence to the mandate of Article 14, number 4 of the Statutes;
In addition, effective today, I revoke the canonical mandate previously granted by the Archbishop of Lingayen-Dagupan to the incumbent itinerant catechist to teach the Catholic faith within this ecclesiastical jurisdiction.
Episcopal delegate
To put into effect the abovementioned directives, I hereby appoint FATHER MARIO DOMINIC SANCHEZ as my Episcopal delegate for the Neocatechumenal communities in the Archdiocese of Lingayen-Dagupan.
The Episcopal delegate is tasked with the following specific functions, namely: 1) to implement the strict observance of the directives contained in this communication with the faculty to impose canonical discipline in the name of the Archbishop when pastorally necessary; 2) to supervise all the convivences of the Neocatechumenal Way held in this ecclesiastical jurisdiction and to insure the regularity of confessions among its members in conformity with Article 14, n.1 of the Statutes; 3) to extend pastoral care and charity to the hurting members of the community who have stopped attending the meetings due to the scandalous conduct of the local leaders in the past and to render pastoral attention to the sick and elderly members who have been deemed unworthy to "walk the Way."
The Episcopal Delegate is also hereby directed to see to it that the manner of questioning that takes place during the scrutiny of members is done in accordance with the approved discipline of the Church, respecting the right to privacy and that it is carried out within the bounds of Christian charity. Finally, I instruct him to look into the accounting and administration of the financial donations made by the members of the Catholic faithful to the community and make a report thereof to me every three months.
Final admonition and appeal
I take this occasion to reaffirm my conviction that the Neocatechumenal Way, with its goal to bring people to fraternal communion and maturity of faith through the tripod of "Word of God-Liturgy-Community," is a gift of the Holy Spirit to the Church and society of our times.
Like all gifts, the Neocatechumenal Way must be cared for and protected from the effects of original sin in us. It must be shielded against the pride and arrogance of its leaders. Those who walk the Way must never be found lacking in charity and deviating from the path of truth.
Pastoral charity for the Catholic faithful who are members of this community moves me to take these steps to insure the stability of our faith and the purity of the teaching that the faithful are entitled to receive.
Let me conclude with these words of the Sacred Scriptures: "To the elders among you, I a fellow elder, a witness of Christ's sufferings and sharer in the glory that is to be revealed, make this appeal. God's flock is in your midst; give it a shepherd's care. Watch over it willingly as God would have you do, not lording over those assigned to you, so that when the chief shepherd appears, you will win for yourselves the unfading crown of glory." (1 Peter 5:1-4)
Peace be with you all! Amen!
From the Cathedral of St. John the Evangelist, Dagupan City, this 3rd day of May 2010.
+ SOCRATES B. VILLEGAS, DD
Archbishop of Lingayen-Dagupan
Source: http://www.lingayen-dagupan.org/ArchBishop/neocat.html

redpajama_set_name: RedPajamaCommonCrawl


Gorgeous flowers - both flowers and watercoloured ones!
How beautiful! What comes first--the watercolor or the ink?
This would make a gorgeous fabric design.
You have the WOW factor. Your post makes me want to see more!
You are such an amazing artist!!! This flowers are gorgeous!!!
I am learning so much from your watercolor course and I hope I will be able to draw and paint these flowers some day- Thanks Alisa!
Gorgeous color. I pinned your blog on Pinterest.
Your pages are so inspiring!


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Asrock CoreHT 252B HTPC Review
By Steven Walton on July 14, 2011
Unveiling the Asrock CoreHT
Taking Apart the CoreHT
Test System Specs
Memory Bandwidth Performance
Synthetic Application Performance
High Definition Playback
Encoding Performance
Gaming Performance
Low Quality Gaming Performance
Asrock had a hectic showing during this year's Taipei Computex, armed to the teeth with various new products including motherboards based on newfangled chipsets such as the Intel Z68 and AMD 990FX. Despite showcasing a bevy of boards, our interest was piqued by the latest entry in the company's long line of mini PCs.
Last year we examined the Vision 3D, the successor to the Core 100HT and Asrock's first mini PC to stray from the norm by dropping Intel's Atom processor for a much snappier Core Mobile chip. With significantly more CPU power, the results were impressive, but the Core 100HT still had one major weakness: Intel's HD Graphics.
To give you a quick rundown of Asrock's previous models, the Core 100HT used Intel's HM55 chipset and without the support of a discrete graphics card, it was forced to use the integrated graphics exclusively. Unsurprisingly, this resulted in by far the worst graphics performance we had seen in recent time from an Asrock mini PC.
Thankfully, Asrock got its act together with the Vision 3D, outfitting the system with Intel's Core Mobile processors (the flagship model carried a Core i5-560M). The company also kept the HM55 chipset but made one noteworthy change with the Vision 3D: the inclusion of an Nvidia GeForce GT425M discrete graphics card.
Granted, if you're serious about gaming, the GeForce GT425M doesn't have much to offer you. But it's good enough for casual gamers, as it provides the bare minimum for playable performance. The Vision 3D was a huge step forward in becoming the perfect HTPC in our opinion, as it allowed users to do a bit of everything.
In the end, we crowned Asrock's Vision 3D the ultimate small form factor computer and with that, we looked forward to what the company would deliver next. More than six months later, we now have the CoreHT Series, which promises to be the most powerful yet as it adopts the latest Sandy Bridge mobile processors.
The CoreHT Series includes three models that mostly vary based on the processor and the optical drive. The flagship is known as the 252B and it sports the Core i5 2520M along with a Blu-ray drive. The 231B gets a slower Core i3 2310M but keeps the Blu-ray drive, while the 231D is outfitted with the 2310M and a DVD drive.
Next Page Unveiling the Asrock CoreHT
User Comments: 8
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Looking at the 35% slump in the shares of DBS Group investors could be forgiven for wondering whether it's the same lender that perennially gets rated as one of the world's safest banks.
But that acclaim has meant little to investors in Singapore's largest bank as its shares have dropped from a high around SGD21 in July to just under SGD14, a selloff that looks overdone given DBS ( D05.SG ) is one of the better quality bank stocks in Asia. Sure, the lender faces some headwinds from slower economic growth and the specter of bad debts, but long term investors should consider accumulating shares in a bank Barron's Asia has written positively about over recent months.
Years of ultra-low interest rates have compressed margins, while Singapore's foundering housing market and lending to troubled commodities producers in Southeast Asia has pushed the stock down to its cheapest in five years. How much lower can DBS go? Not much, we reckon. As a whole, Singapore's banking sector is now among the most inexpensive in the region, cheaper than bank stocks in commodity-dependent markets like Indonesia and Malaysia.
Like lots of banks in Asia right now, DBS is struggling to grow earnings, but higher interest rates could provide a reprieve. The way Singapore manages its exchange rate means domestic interest rates track those in the U.S., though not necessarily in magnitude. The Fed's decision to hike rates for the first time in almost a decade should be good news for DBS. Banks like higher rates as it widens the spread between money collected from loan interest and that paid to depositors.
So if higher rates are good, why have DBS shares not rallied? Jaj Singh, an analyst at Nomura, says higher rates can be a double-edged sword. On one side, they're good for the bank's net interest margin – the spread between what it pays depositors and collects off loans. At the same time, they can stunt loan growth as customers are less likely to borrow if they have to pay more interest. Higher rates also risk adding additional stress to struggling borrowers.
Concerns over asset quality are overcooked. Non-performing loans mostly come from a couple of oil and gas loans in Southeast Asia. Historically, these loans are still in a very low range for DBS too. So defaults are unlikely to blow out. In Singapore, about half of the bank's loan book is tied to the housing market. Home prices in the city-state are falling, but the vast majority of Singaporeans buy properties to live in, not for investing. "Owners are unlikely to walk away" from their mortgage obligations, Singh says. It's worth mentioning Singapore's unemployment rate is only 2% - a historical low even by the Lion City's high standards.
China's weaker growth has also cast a pall over the stock. However, most of DBS's business in the world's second largest economy is short-term trade finance, while other lending is to foreign companies and state-owned enterprises. These borrowers are less likely to default.
The bottom line though is DBS needs higher rates to grow earnings and jolt its share price out of its stupor. China could be the source of some joy here. The depreciating yuan helps drag the Singapore dollar lower, given the Chinese currency has a hefty weighting in the basket to which the Singapore dollar is pegged. A falling Singapore dollar typically lifts the city's benchmark rates as investors seek compensation for holding the weakening currency. "Upward pressure on interest rates could strengthen significantly," reckons Nomura's Singh. On that note: A weaker local currency could also translate into a fatter bottom line when DBS exchanges its foreign earnings into Singapore dollars.
Brokers haven't given up on the shares, either. The average price target for the stock is SGD20 a share – about 40% higher than where the stock sits now. DBS also pays a pretty handsome 4.2% dividend, which is still well covered by earnings. It's also the cheapest stock among Singapore's big three banks at eight times forward earnings and we think it has better prospects.


"Excellent location and great value."
"Excellent location for the price."
"Old hotel that has seen better days."
"Toilet paper holder was broken."
Avoid it! Spend your money elsewhere.
It was better than staying at the Y.
"Recently remodeled" room means new headboard that bangs the wall whenever you roll over at night and a $50 Lowe's vanity in the bathroom, but don't fall for anything else. The tub was chipped, surround from the 70s, and the shower head held together with a paper towel roll and duct tape. Water pressure was low, temperature was tepid at best, even cold some mornings. They may have replaced the furniture but the linens looked original to the building and there was no such thing as a blackout curtain, something definitely required in the PNW summers. I called about the TV channels on the fritz but it turns out they don't have any satellite coverage, so you're stuck with fuzzy air (analog, not digital) channels. The elevator struggles to make it level with the floor before opening the door and the wifi is in the front lobby only, and slow. Don't expect to get any work done here, you'll be wandering the streets after your meeting like me, or hanging out in the library nearby for the WiFi. On the plus side, it didn't smell like smoke, though the carpet suggested that was an anomaly. I prepaid or I would've left for the W across the street, or at least a holiday inn somewhere. Definitely not worth your time or money, find somewhere else.
My headboard squeaked everytime I moved...was annoying. Only two electric plugs were working & between my daughter & I, charging smartphones & ipad was a problem.
For my standard this hotel is ok. No wifi is both a good and bad thing. I was not distracted by the internet. I felt like I rent a hotel in Europe. The hotel is next to the tunnel which connects to the airport, UW campus. This is good.
The bed stuff seemed not clean. I only feared of possibility of bedbugs. The sink was stuck because of many hairs in there. They should have cleaned it. Also the sink was leak.
Good location and very low price compared to competition.
Rooms very outdated and in poor condition. No air conditioning. Hallways in need of updating and repair. Bathroom wallpaper coming off. Old TV that hardly worked. Lobby furniture falling apart. With some investment and attention, this could be a much better hotel and get higher ratings and prices.
Location is only good about this hotel. However, don't stay there more than a night.
It was a bit shabby but as others have said- you get what you pay for. Shabby but clean, great location.
We got a very large room—looked like it was two former rooms that had been combined—for the price of a regular room. The location is fantastic and the staff was friendly. It's clearly an older hotel that hasn't had fancy upgrades, but if you need a place to stay in the heart of downtown, and all you're worried about is a good place to sleep at night, the Hotel Seattle works well.
Others have mentioned the water temperature, and we had the same problem. Fluctuated very wildly between warm, scalding, cooler, and back again. There were no screens on the three windows in our seventh-floor accommodations. Not a complaint, really, but it might make some people leery.
No parking at hotel. Hotel is old but I think hotel is trying to upgrade. Room had one outlet that worked. A very long extention cord went from one outlet along the side of the room to the opposite side of the room so the TV could be plugged in. Very dangerous.
Danny and Cris were great help.
Search for Hotel Seattle discounts in Seattle with KAYAK. Search for the cheapest hotel deal for Hotel Seattle in Seattle. KAYAK searches hundreds of travel sites to help you find and book the hotel deal at Hotel Seattle that suits you best. C$ 110 per night (Latest starting price for this hotel) - Save up to 35%.


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Multi-crop rotation offers benefits for livestock and crops
News News | Mar 23, 2019
Shauna Kopren, Freelance Contributor
Steers grazing pea-barley at the beginning of grazing. Photo courtesy of NDSU Dickinson Research Extension Center.
At the North Dakota State University Dickinson Research Extension Center, one focus is improving crop and beef cattle production efficiency. Douglas Landblom, a beef cattle specialist, has found that multi-crop rotations with beef cattle can increase efficiency while decreasing inputs.
Landblom's research consists of studying the comparison of spring wheat grown continuously on the same land compared to spring wheat grown in a multi-crop rotation consisting of spring wheat, dual cover crop, silage corn, field pea-barley mix and sunflowers. Yearling steers grazed three of the rotation crops and the deposited manure and urine contributed to soil organic matter, providing a food source for soil microorganisms.
According to Landblom, the principles of regenerative agriculture are based in the context of improving soil health. Systems like expanded crop rotations allow soil biota, microorganisms, and fungi the opportunity to function at a higher level of efficiency. "Managing crops in a way that gives soil organisms the food necessary to perform is extremely beneficial," says Landblom.
During the first few years of the multi-crop rotation study, both spring wheat yields were 40 and 41 bushels per acre. However, Landblom found that by discontinuing fertilizer application on the spring wheat rotation reduced the cost for fertilizer and, when combined with an increase in soil-derived nitrogen, resulted in a $15 per acre greater net return for spring wheat grown in the crop rotation that included livestock grazing.
"Increasing soil health results in greater biodiversity, while grazing reduces carbon dioxide emission, improves water cycles, and increases plant-available nitrogen," says Landblom. The research conducted by Larry Cihacek, Songul Senturklu, and Landblom found that for every one percent increase in field soil organic matter content there is potentially 16 pounds of nitrogen mineralized by soil microbes and available for plant growth.
"Replacing fertilizer with nitrogen produced by soil microbial processes is water-dependent," Landblom says. "Integrating crop and livestock systems increases soil organic matter and aggregation, which subsequently contribute to a soil's water-holding capacity and offers an opportunity to support better yields during moderate drought in semi-arid regions."
Winter crops like triticale, hairy vetch and winter rye seeded in the fall make excellent grazing crops the next spring for yearling steers, feeder heifers, cows and calves, or cull cows. Designing a grazing system that incorporates native range, when annual forages need time to grow, and a sequence of annual forages for grazing throughout the summer provides a measure of grazing flexibility.
Landblom found that yearling steers that grazed native range and multi-crop rotations gained 495 pounds after grazing 211 days. After that, the grazing steers were in the feedlot for 82 days and then slaughtered, "Feedlot average daily gain was 4.7 pounds per day and required 6.23 pounds of feed per pound of gain," Landblom says. "Compared to control steers that were finished in the feedlot, net return was greater for the extended forage grazing steers by $61 per steer."
In the past, producers have focused on the maximum yield that they can get from a field. However, Landblom explains that regenerative agricultural thinking still focuses on the need to produce, but also looks at more alternative ways to achieve maximum economic yield while also relying less on purchased inputs, like fuel, fertilizer, chemical, and labor, plus reducing environmental impact.
The multi-crop rotation was originally designed for grazing yearling steers, however, it can be manipulated for producers without livestock as well. Producers can substitute the appropriate crop such as grain corn for forage corn and the pea-barley mix produces excellent hay. In addition, the pea-barley mix can be replaced with low-water use legumes such as peas, lentils, canola, and chickpeas, which are known to be financially rewarding.
For producers that are interested in implementing an integrated crop and livestock system, Landblom suggests beginning with a plan that fits the available farm labor, machinery and infrastructure, and is agreeable with other farm members with a vested interest in the farm business. Additional consultation with property owners, lenders, tax consultants and spouses is also important to keep in mind whenever changes in a farm business plan are made.
Producers also need to determine the class of livestock and the way livestock will fit into their cropping system. "Begin with a goal to produce a sequence of crops that provide for a diversity of crop types using a combination of cool- and warm-season grasses and broadleaf crops for cash grain, oilseed and forage production," Landblom says. "I cannot over-emphasize the necessity for diversity, which can have a significant impact on soil fertility, weed, and pest management."
"Multi-crop diversity is very important, and every farm may have different goals and crop sequences to achieve those goals," Landblom says. It is important for producers to seek individuals with experience when first planning a multi-crop and grazing rotation. These individuals can help design a cropping system to fit specific farm objectives and also facilitate expertise for placement of crops within the cropping sequence.
"Experience has shown that producers who begin alternative production methods begin to see greater residual nitrogen the third or fourth year after initiation and, therefore, can begin reducing the amount of nitrogen fertilizer applied and subsequently increase their efficiency of the cropping and cattle systems while lowering their inputs," Landblom says.
For more information on the research done at the NDSU Dickinson Extension Center or to learn more about improving cattle production system efficiency contact Douglas Landblom at 701-456-1109, 701-690-8245, douglas.landblom@ndsu.edu.


Dave comedy shorts. 24 episodes (1 series) in 2018. Stars Andrew Maxwell, Dan Skinner, Beattie Edmondson, Dustin Demri-Burns and others.
Daily comedy shorts, to run across the 24 days in the lead up to Christmas. An exclusive comedy treat, Dave's Advent Calendar promises a festive insight into the finest minds in British comedy.


A gem of a venue, nestled within Loudoun County's green and rolling hills, Silverbrook Farm is a quaint bed and breakfast as well as a charming events space. From the main house to the barn to delightful gardens and other rustic dependencies, the property is full of romantic possibilities. Lovers can play a life-sized game of chess in the garden, or meander amongst the roses. A sprawling porch offers opportunity to relax in the rocking chairs for a few precious moments as lovely bucolic vistas spread towards the horizon.
The main house was originally constructed in the 1700s and exudes all the allure of a historic structure. Comprised of gorgeous stone, with wooden frame additions, it's easy to see why couples feel right at home on the property. Several ceremony sites are exclusive to the premises, the especial raised arbor a particular favorite.
Owned and operated by Dot Shetterly, Silverbrook Farm is an enchanting little secret, tucked away in the Virginian countryside. Read below as we explore the history, opportunities and possibilities Silverbrook offers, and begin to imagine yourself as a Silverbrook bride.
Meet Dot Shetterly, owner of the lovely, rural haven of Silverbrook Farm. Silverbrook is beautifully set amidst the rolling foothills of the Blue Ridge Mountains. Photo courtesy of Tom Lussier Photography.
Loudoun Weddings: What makes Silverbrook Farm a unique venue in Loudoun County?
Dot Shetterly: Silverbrook Farm is certainly a unique venue in Loudoun. We offer the residence, the lawn, the gardens, the barn, and a lovely tent site. But probably what makes us different is the flexibility we offer. We do only one wedding a week, which allows the bridal couple to come out any time during the week of their wedding to bring what they need for their special day. Rentals can come as early as Thursday and nothing has to be picked up until Monday. Decorating can be begun as early as Thursday and does not need to be taken down until Monday. The couple is encouraged to come out as often as they can from contract to wedding and bring friends and family. This makes for a very relaxed wedding day.
LW: What do couples say that they love best about Silverbrook Farm?
DS: Couples in many testimonials have said they love the positive energy at Silverbrook. They feel welcome from the first visit. By their wedding day, they feel it is their home away from home. They love the flexibility. They love the sereneness, the gardens, the views, and they refer to the barn as magical. As one bride said, "Silverbrook is the diamond in my tiara."
The arbor ceremony site. Photos courtesy of Genevieve Leiper Photography.
LW: How many ceremony locations does Silverbrook offer?
DS: The most popular ceremony site is the arbor with the raised platform in the garden. We also offer the boxwood garden, a tent site next to the barn, open fields and the barn itself, if weather dictates.
LW: Tell us about the reception location options couples have on the premises.
DS: The cocktail reception is usually held in the gardens and on the lawn. The dinner reception is most often held in the barn. If the number exceeds 125, there is a lovely space for a tent (with views of two mountains) next to the barn. The dinner is held there and folks come inside the barn for dancing.
For small weddings, we can accommodate up to 24 for a seated dinner in the residence or up to 60 for a cocktail reception. With both, we have room for ceremony and dancing, if desired.
Silverbrook Farm is a unique venue, offering brides and their grooms the opportunity to have a wedding that feels elegant, but homespun.
LW: What is the most magical moment you have experienced during a Silverbrook Farm wedding?
DS: There are so many magical moments, but the one that stands out the most was the releasing of the doves. The bride and groom each released a dove and they flew over the ceremony site, met and flew back to their home. Then the handler released several and they did the same. It was so great seeing them meet and then fly off.
LW: What Bed & Breakfast services are available for couples wedding at Silverbrook?
DS: As part of our wedding package, we offer a complimentary night's stay with a full country breakfast for the bride and groom.
A beautiful old stone façade graces the main house. Photos courtesy of Genevieve Leiper Photography.
LW: How many people can the inn accommodate, as far as overnight guests go?
DS: We have 3 suites, plus a handicapped bedroom. The number we accommodate depends upon the make-up of the group. Each suite has one bathroom so guests have to be willing to share a bath.
The bedroom that is handicapped accessible has its own bathroom, outfitted for the handicapped.
LW: Can you tell us about the history of the Silverbrook Farm property?
DS: The original part of the house was built circa 1765; the second wing circa 1790; the third wing circa 1870 and the fourth wing was built as our retirement wing in 1998. It has been owned by only two families since the mid 1700s: the Potts family and my family, the Florances. My family came in 1941 and it became a working dairy farm with 300 acres. When my father lost his health and could no longer farm, I bought the house and 37 acres in 1981. I started the B & B and wedding business nine years ago after my husband, Bob Shetterly, passed away.
The rustic barn at Silverbrook Farm is wonderfully nostalgic with beautiful opportunities for draping and exquisite lighting. Photos courtesy of Genevieve Leiper Photography.
LW: Tell us about one of your favorite events that has been held at this charming venue.
DS: Again, there are so many favorites, but the one that stands out in my mind is Holly's son, Alex's, wedding to Mallory. Alex booked two years in advance and I really got to know them during those two years. Of course, the flowers were the most beautiful ever. And the decorations and all the touches. But, what was the magical moment, was when Alex sang to Mallory during the reception. It was so touching that he would want to do that in front of God and everyone. Will always remember it.
LW: Are there any traditions specific to Silverbrook Farm that couples should partake in?
DS: We have an old southern tradition that I share with my clients. Part of me wants to share it with every bride and part of me wants to keep it for our Silverbrook brides. I am afraid if it gets too widespread that it will stop working for the brides at Silverbrook. o, this is just a teaser. No rain on the brides at Silverbrook.
Silverbrook brides enjoy tender moments with their grooms.
Visit Silverbrook Farm for more information.


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Freeland is a village and civil parish about  northeast of Witney in Oxfordshire. The 2021 Census recorded the parish population as 1,490.

History
Freeland village began as part of the parish of Eynsham. Its toponym is derived from the common Old English word , meaning a wood. In 1150 the Abbot of Eynsham granted land called terra de Frithe to one Nicholas of Leigh. "Frith Wood" later evolved into "Thrift Coppice" and by 1241 several people were living there. Freeland developed from a medieval freehold, probably on the site of Elm Farm.  The freehold farm was called Frithlands by the 16th century and had been joined by at least two other cottages before 1650.
 there were something less than a dozen cottages at Freeland by 1762.
 The enclosure of the parish of Eynsham was resisted by rioting in the north of the parish around Barnard Gate and Freeland in 1780 but was eventually carried out in 1784.

The Roslyn house was established in 1738 and reputed to have been a 19th-century pugilists' meeting place called the "Wrostling House". Freeland had several public houses by the later part of the 18th century and one called the Royal Oak was recorded in 1836. The New Inn was built by William Merry in 1842, sold to Morrells in 1846 and for most of the 19th century was Freeland's only public house. Since 1974 it has been called the Oxfordshire Yeoman. It is now controlled by Greene King Brewery. It is the only public house in Freeland.

Freeland Lodge was built for the Taunton family in 1807. Most of the land on the west side of Wroslyn Road belonged to the family and was made into a park for the Lodge. The Lodge is now Freeland House Nursing Home. The Taunton family had sold the Lodge by 1875–76, when Marion Taunton had St Mary's House built as a home for retired governesses. In 1952 a Church of England convent of the Community of Saint Clare moved to the house and in 1960 a Gothic Revival chapel designed by the architect Henry Gordon was added.

Freeland grew as a ribbon development along the Via Regia between Eynsham and Charlbury. By 1847 its community included seven farmers, two shopkeepers, a mason, a carpenter and the publican of the New Inn. Freeland's population peaked at 232 in 1881 but fell to 160 in 1891, presumably as a result of the agricultural depression. In 1932, when it was transferred from the civil parish of Eynsham to that of Hanborough, Freeland's population was 214. Freeland was made a separate civil parish in 1951, by which time its population had risen to 530. It then rose every decade, reaching 1,374 in 1981 and 1,490 in 2021.

Chapel, Church and School
The Wesleyan chapel was completed in 1807. It is now Freeland Methodist Church.  The Gothic Revival architect John Loughborough Pearson designed the Church of England parish church of Saint Mary the Virgin, parsonage and parish school.  The Taunton family paid for the church and parsonage to be built in 1869 and the school in 1871.  The church is high Victorian Gothic Revival, with stained glass and decoration by Clayton and Bell and 13th-century-style paintings of Jesus' Passion and Transfiguration.

Mears and Stainbank of the Whitechapel Bell Foundry cast four bells for St. Mary's in 1896. The same foundry cast a new treble and second bells in 2010, completing the present ring of six. The church clock was made and installed by Smiths of Derby in May 1898 and was dedicated to a Sarah Percival. In May 1969 the clock was taken down, reset and regilded by Judge Brothers of Oxford, and reinstalled by the local Breakspear family.  The parish is now part of the Benefice of Hanborough and Freeland.  The school, which was originally in an old stone house, next to the church on Wroslyn Road, moved to new premises in Parklands in 1964 and is now Freeland Church of England Primary School.

Amenities
Freeland's first village hall was a former Army hut opened in about 1920. The games fields were opened in 1958 and a new village hall was completed in the 1960s. The second village hall was demolished in 2010, a new one was built in its place and in September 2011 it was officially opened by Prime Minister and Witney MP, David Cameron. It has a main hall with a kitchen and storage rooms. A second phase of the building project (the Community Recreation Facility – CRF), with sports changing rooms and meeting room (the "Newell Room"), was opened by the Deputy Lieutenant of Oxfordshire, David Mason, in September 2013.  Freeland's one pub, The Oxfordshire Yeoman, is in Wroslyn Road opposite the village hall.

Freeland has a Football Club and a Cricket Club. Freeland Football club was founded in 1908. There is a gap in the history of the club, but recent activities are more recorded and are now documented at the club's website. The club's history is in the Witney and District League with at least one team in the league throughout the last 100 years. The club now has five teams. Freeland Firsts play in the W&DFA Premier Division and Freeland Reserves  play in W&DFA Second Division. There are also Freeland A and B teams and a Sunday League team. Freeland Firsts were Premier Division champions in the 2005–06 and 2006–07 seasons. Freeland Reserves were Oxfordshire Senior League Division 3 champions in the 2008–09 season with the First team gaining promotion after finishing second in division 2.  Freeland also has its own amateur orchestra.  Freeland Nurseries is a family-run independent plant nursery and garden centre in the walled garden of Freeland House. It has traded commercially since 1959.

References

Sources and further reading

External links

Freeland Village Website
The Society of Saint Francis: Community of Saint Clare
St Mary the Virgin parish church: Google 360° panorama of the interior of the nave
St Mary the Virgin parish church: Google 360° panorama of the interior of the chancel
Freeland Nurseries website

Civil parishes in Oxfordshire
Villages in Oxfordshire
West Oxfordshire District

redpajama_set_name: RedPajamaWikipedia


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Amir Ehsaei Named Special Agent in Charge of the Counterterrorism Division of the Los Angeles Field Office
Director Christopher Wray has named Amir Ehsaei as the special agent in charge (SAC) of the Counterterrorism Division of the Los Angeles Field Office. He most recently served as a section chief in the Human Resources Division at FBI Headquarters in Washington.
As the counterterrorism SAC, Mr. Ehsaei is responsible for counterterrorism investigations in Los Angeles, as well as much of Asia and Australia. He is also responsible for crisis response matters and the weapons of mass destruction program.
Mr. Ehsaei began his career as an FBI special agent in 2004. He was first assigned to the Joint Terrorism Task Force (JTTF) in the Los Angeles Field Office and moved to the Human Intelligence Squad in 2010. He was promoted later that year to supervisory special agent of a counterterrorism squad on the JTTF. Mr. Ehsaei deployed to Baghdad in 2010, leading an interagency team that interviewed members of a foreign terrorist organization.
In 2013, Mr. Ehsaei moved to the Inspection Division at Headquarters, where he served as an assistant inspector and team leader. He returned to Los Angeles in 2015 as the assistant special agent in charge (ASAC) of the Administrative Division and was named the ASAC for the Los Angeles JTTF in 2017.
Mr. Ehsaei was promoted to chief of the Employment Development and Selection Program Section of the Human Resources Division at Headquarters in 2018. As section chief, he oversaw the Leadership Selection Unit, the Office of Workforce Development, the Performance Appraisal Unit, and the Transfer Unit.
Prior to joining the FBI, Mr. Ehsaei was an attorney. He earned a bachelor's degree in chemistry from the University of Colorado and graduated with honors from the University of Miami School of Law. He is a member of the Florida and California State Bars. He is fluent in Farsi.
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Manga Manga News News
Blue Lock Gets Print Release In Summer 2022
By Varun Gupta
Kodansha USA has announced that Blue Lock by Muneyuki Kaneshiro and Yusuke Nomura will receive a print release in Summer 2022. The release is intended to coincide with the upcoming anime adaption of the manga, which is slated to premiere later this year. Kodansha USA's official announcement can be found below:
In celebration of the anime coming in 2022, Kodansha USA is excited to announce the print license acquisition of the fan-favorite manga series Blue Lock. Written by Muneyuki Kaneshiro (As the Gods Will: The Second Series), and illustrated by Yusuke Nomura (Dolly Kill Kill), Blue Lock is the heart-pounding soccer saga of a nation-wide competition to find the ace striker who will lead Japan to a World Cup victory. The first volume of Blue Lock in print is scheduled for Summer 2022, and will be distributed by Penguin Random House.
After a disastrous defeat at the 2018 World Cup, Japan's team struggles to regroup. But what's missing? An absolute Ace Striker, who can guide them to the win! The Football Association is hell-bent on creating a striker who hungers for goals and thirsts for victory, and who can be the decisive instrument in turning around a losing match … To do so, they've gathered 300 of Japan's best and brightest youth players. Who will emerge to lead the team … and will they be able to out-muscle and out-ego everyone who stands in their way?
Winner of the 45th Kodansha Manga Award in the shonen category in 2021, Blue Lock is currently available digitally in English, and can be read across a number of platforms including Bookwalker, comiXology, Kindle, Apple Books, Google Play, Nook, Kobo, izneo, MyAnimeList and more.
A long-awaited anime for Blue Lock was announced in August of 2021 from Eight Bit Animation Studio – the team responsible for the development of the That Time I Got Reincarnated as a Slime anime. The first season of the Blue Lock anime is set to debut later in 2022.
A free first chapter of Blue Lock is available to read right now at kodansha.us.
About Kodansha USA Publishing, LLC
A subsidiary of Kodansha, Japan's largest publisher, Kodansha USA Publishing is the English-language publisher of some of the world's most recognizable manga properties, including Katsuhiro Otomo's AKIRA and Naoko Takeuchi's Pretty Guardian Sailor Moon, along with a robust catalog of English-language Japanese novels, cookbooks, craft guides, historical and cultural literature, and more. Today, thanks to recent fan-favorite and critically acclaimed hits like Attack on Titan, Battle Angel Alita, Witch Hat Atelier, and the popular MONOGATARI novels, Kodansha USA Publishing is one of the best-selling manga publishers in the United States. Kodansha USA Publishing's print offerings are distributed by Penguin Random House Publisher Services, and their digital manga and select digital books are available across a number of digital comics, manga, and book vendors. For more information visit kodansha.us.
blue lockKodanshaMangamuneyuki kaneshiroNewsYusuke Nomura
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About The Author Varun Gupta
Varun Gupta is a BI Engineer that works in the entertainment industry. Throughout his entire life, Varun has had an immense love of animation and comics. An obsessive manga collector, he spends his free time attempting to read through his massive backlog of series, hoping to one day finish them all. Will he succeed in his perilous quest? Probably not, but at least he's having fun doing it!
Rainbow Days, Volume 1


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Commodities Market
Rural News
Australia, NZ split group games equally at Women's World Cup
1 December 2021, 7:11 pm ·2-min read
Australia United States Soccer
United States' Rose Lavelle chases the ball during the international women's soccer match between the United States and Australia in Newcastle, Australia, Tuesday, Nov. 30, 2021. (AP Photo/Mark Baker)
SYDNEY (AP) — Australia and New Zealand will each stage 24 games in the group stage when the countries host the Women's World Cup for the first time in 2023.
FIFA released further details of the schedule Wednesday after previously announcing that Auckland will stage the opening match on July 20 and the final will be at the Olympic stadium in Sydney on Aug. 20.
Australia's biggest city will also feature on the opening day with one of six group games at the newly renovated Sydney Football Stadium. The Olympic stadium is also hosting a round of 16 game, quarterfinal and semifinal before crowning the champion.
The 32-team tournament will be divided into eight four-team groups. New Zealand is in Group A and Australia in Group B but the other groups and teams won't be determined until qualifying is concluded and a draw is held.
The United States, which won the World Cup for the fourth time in France in 2019, is among the teams that have yet to qualify. The U.S. just completed a two-match friendly series against the Matildas in Australia as a dry run for the 2023 tournament, winning 3-0 in Sydney and drawing 1-1 in Newcastle.
Five Australian cities — Sydney, Perth, Melbourne, Brisbane and Adelaide — and four New Zealand cities — Auckland, Wellington, Dunedin and Hamilton, will host matches.
Australia will host 35 games and New Zealand 29.
The schedule favors the host countries — Australia will play every match in Australia if it wins Group B and keeps winning, New Zealand's only match outside New Zealand would be the final if it wins Group A and keeps winning.
Brisbane will host a quarterfinal and the third-place playoff. Other quarterfinal host cities are Sydney, Wellington and Auckland. Auckland's Eden Park will join Sydney as a venue for the other semifinal.
Match pairings and kickoff times will not be determined until the draw is held.
More AP soccer: https://apnews.com/hub/soccer and https://twitter.com/AP_Sports
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Union Pacific hauled in 24% more profit in the fourth quarter despite supply chain problems and weak auto production, but that is also compared with a period last year that included a one-time $278 million charge. Without last year's charge, the railroad's profit would have been up 8% over last year's adjusted results of $1.6 billion, or $2.36 per share. Union Pacific hauled 4% less freight in the fourth quarter as the computer chip shortage continued to hurt auto production and supply chain problems cribbed shipments of imported containers of goods.


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Science and Education /Customer Stories /iCommunity Customer Interviews & Case Studies /GLOBAL Clinical Study Demonstrates Value of Panomics-Based Drug Discovery Approach
GLOBAL Clinical Study Demonstrates Value of Panomics-Based Drug Discovery Approach
Integrating imaging, multiomic technologies, and big data uncovers novel diagnostic and therapeutic targets for common chronic diseases.
Szilard Voros, MD became interested in pharmaceutical research and development and entrepreneurial innovation while in cardiology training at the University of Virginia. He was working on cardiovascular imaging to support the development of ezetimibe, a first-in-class cholesterol-lowering drug. Dr. Voros later moved to the Piedmont Heart Institute in Atlanta, Georgia where he and his team developed novel ways to image and measure disease processes within different organs. They soon initiated separate projects to combine their imaging technologies with genomics, proteomics, and metabolomics, a multiomics approach that they now refer to as panomics.
In early 2011, it became clear to Dr. Voros that integrating all this data could improve the drug discovery and development process, as well as biomarker discovery and development, significantly. It could also provide physicians with information to understand the status of a patient's disease process and inform the most effective prevention and treatment. He founded the Global Genomics Group (G3) and set off to prove the potential of his panomics approach in a groundbreaking international clinical study, aptly named the Genetic Loci and the Burden of Atherosclerotic Lesions (GLOBAL) study.
Seven years, more than 7000 clinical subjects, and trillions of data points later, Dr. Voros has proved to be a visionary ahead of his time. G3 has succeeded in integrating imaging, panomics, and data analysis into a powerful drug discovery engine. The company has demonstrated the value of its novel approach, with the introduction of a new diagnostics and several drug candidates in development with pharmaceutical partners.
iCommunity spoke with Dr. Voros about how the G3 team developed and fine-tuned its panomics approach, the diagnostic and therapeutic projects that have resulted from it, and how Illumina products and systems are contributing to its success.
Szilard Voros, MD is Founder and Chief Executive Officer of G3.
Q: Why did you start G3?
Szilard Voros (SV): Part of the inspiration for G3 grew out of my frustration as a practicing physician. I was running a prevention cardiology program, seeing patients, and practicing evidence-based, guideline-driven medicine that focused on populations instead of individuals. It was discouraging. I didn't feel like I was positively impacting the quality of life for many of my patients. It was the 21st century and I felt like there had to be a better way.
During my early academic career, we developed new imaging approaches and technologies to support the identification of novel cardiovascular drugs. They were essentially phenotyping tools that provided specific and quantitative ways to identify and measure different aspects of disease. I founded the company and began to identify how we could integrate imaging data with panomics data, and use advanced analytics to analyze it all.
Q: What challenges did you face in creating G3?
SV: It was an enormous undertaking. Our idea was to bring all the different omics technologies together into a single company, as a single project, for a single objective. At the time, the field was incredibly siloed. There were genomics, proteomics, metabolomics, and metagenomics companies, but they didn't speak the same language. No one had ever tried to integrate any of those data sets. Conceptually, scientifically, and informatically, there wasn't a way to take all that information and translate it into a common vocabulary.
Q: What was the biggest unknown in establishing your process?
SV: The biggest unknown was how we were going to integrate the data informatically. We found that the solution was to use different approaches in a parallel, synergistic fashion. For example, we integrate genome-wide association studies (GWAS) with quantitative trait loci (QTL) analysis, and Mendelian randomization with Bayesian network analysis. It's an integrated approach that changes depending on the analysis objective.
Figure 1: Using a panomics approach, G3 captures and analyzes imaging, genomics, transcriptomics, methylomics, proteomics, and metabolomics/lipidomics data that totals up to several billion data points for each subject in the GLOBAL clinical study.
Q: What diseases are you focusing on?
SV: We're focusing on multifactorial, multigenic, common chronic diseases such as cardiovascular disease, fatty liver disease, diabetes, osteoporosis, and obesity. These diseases have a direct impact on human longevity. We're using our approach to understand, study, and impact the course of these diseases.
Q: What is the G3 approach?
SV: Our approach is based on three fundamental pillars. The first pillar is deep phenotyping using imaging to quantify different aspects of disease. The second pillar is panomic profiling where we analyze the DNA, RNA, proteins, lipids, and other small molecules in blood samples. The third pillar is to integrate the deep phenotyping and panomics data using a systems biology—driven bioinformatics. The data analysis step of the clinical study consists of integrating billions of data points for each subject. The goal is to translate and make sense of the data to inform development of new diagnostics and therapeutics.
"...we begin with genomic data and work to fill in the gaps with gene expression, proteomics, lipidomics, metabolomic, and the other omics."
Q: Why are you performing so many sequencing and omics studies on these samples?
SV: We wanted to solve the issue of missing heritability. When we started the company in 2011, there were twin studies in cardiovascular disease that demonstrated that roughly half of the disease risk is caused by genetic and inherited factors, and roughly half by the environment.1 We also knew that disease-associated variants could not explain more than 5–7% of cardiovascular disease phenotypes. In addition, 97% of disease-associated SNPs are not found in exomes, the genome regions that are translated into proteins.2 We started to think about how we could fill in those gaps and find the missing heritability in multifactorial diseases.
We realized that while genetic variants might increase someone's chances of developing a disease, they don't provide a picture over time of what is happening in the body. So that's why we begin with genomic data and work to fill in the gaps with gene expression, proteomics, lipidomics, metabolomic, and the other omics. It's the fundamental concept behind the company.
Q: Why did you decide to undertake such a large and ambitious clinical study?
SV: We realized that if we wanted to transform drug and biomarker discovery based on big data, we had to demonstrate the approach in a large clinical study. In 2013, we began enrollment for our GLOBAL study, an ambitious effort to prospectively collect samples from a global patient population. We knew that the study had to be large, with the statistical power needed to obtain useful data. Based on our calculations, the sample size was somewhere between 6500–7000. We ended up enrolling 7700–7800 patients at 48 clinical sites in nine countries on three continents. We believe that this is the largest and most comprehensive prospective study to collect multiomic data for the specific purpose of drug and biomarker discovery.
Q: How could a clinical trial of 8000 subjects have the statistical power necessary to detect variant associations?
SV: We're layering several omics measurements to understand the functional implications of each variant. Because the biological pathways converge onto each other, we're able to reduce the number of subjects needed to have the statistical power necessary to detect associations.
Q: What is the status of the clinical study?
SV: We completed enrollment in the GLOBAL clinical study in mid-2014. We've sequenced every gene in thousands of people and measured hundreds of thousands of intermediate biomarkers in the same subjects. We have all the raw data, images, and blood samples and are about halfway through the omics analysis. Theoretically, we'll be able to validate any target, for any disease, for which we have phenotype information. For the next few years, we'll be going through the data and identifying targets for the common chronic diseases that we're interested in.
"Bayesian analyses uncovered hierarchical panomic networks that converged onto the same biological pathway...with gene variance driving the networks, followed by RNA and protein networks."
Q: How many data points are you analyzing?
SV: For the imaging aspect, we took CAT scans of the chest, heart, and upper abdomen, with and without contrast. On each of the blood samples we performed whole-genome sequencing (WGS), assessed transcriptional events with RNA-Seq and microRNA analysis, and studied epigenetics with DNA methylation analysis. We also performed proteomics, lipidomics, and metabolomics studies to assess small molecules. It adds up to several billion data points for each subject in the trial (Figure 1).
Q: Given the number of analyses performed on each blood sample, how do you ensure data quality?
SV: From the beginning, we felt it was important to ensure data quality at the collection level. We take great care in how we treat those samples. After the blood is drawn, it is spun down and separated into 47 aliquots that are refrigerated within 70 minutes of the phlebotomy. We separate the aliquots into A and B samples, which are then shipped on different days, on different trucks or planes, to different states, for disaster recovery purposes.
When we have the blood samples in our biobanks, best-in-class service providers perform the different omics analyses, including Illumina Sequencing Services for WGS and Expression Analysis/IQVIA for RNA-Seq, miRNA-Seq, DNA methylation, protein, lipid, and small molecule/metabolite analysis.
Q: What scientific observations have you made?
SV: We have made a large number of scientific observations but at the highest level, there are two major insights. The first one revealed functional convergence, validating our concept. In one of our early analyses, we had one trillion data points in hundreds of patients and looked for pathways that lead to cardiovascular disease, nonalcoholic steatohepatitis (NASH), and osteoporosis. Bayesian analyses uncovered hierarchical panomic networks that converged onto the same biological pathway. They were just like we would expect based on the biological dogma with gene variance driving the networks, followed by RNA and protein networks. We also rediscovered known pathways, including the LDL pathway, one of the best known cardiovascular disease pathways.
Our second observation is a little more obscure. We looked across the genome for the top hits or strongest associations in each "omics" dataset for each disease state. Rather than being randomly distributed across the genome, we found the hits in clusters. We're starting to determine scientifically what the relevance of that is.
"...identified a potential target from the transcriptomic data. We were then able to use WGS data and performed genetic validation of the target based on LOF variants."
Q: Have you identified new targets using your panomics approach that have commercial potential?
SV: We were granted a patent on a diagnostic biomarker we identified for cardiovascular disease. It was derived from the mass spectrometry—driven metabolomics data. It's a very simple blood test that could be a gatekeeper to stress testing in patients who come to a physician's office with chest pain.
We were successful in identifying another target under a collaboration with a large pharmaceutical company. The unbiased Bayesian network analysis identified a potential target from the transcriptomic data. We were then able to use WGS data and performed genetic validation of the target based on loss-of-function (LOF) variants. Our pharmaceutical partner confirmed the NASH target in an in vitro setting.
We also identified a new biological pathway and drug target for cardiovascular and fatty liver disease. The pathway is an intersection of the two disease pathways. We're beginning development of a drug based on this target. The fact that we rediscovered known pathways using our panomics approach gives us confidence in the validity of this and several other new pathways that we've identified.
What's amazing is that these discoveries are based on data from just the first few thousand subjects that we've analyzed. We haven't even scratched the surface of all the data yet.
Q: Could the panomic approach introduce new concepts to drug development?
SV: The panomic approach accelerates the current time- and cost-intensive process of identifying and validating genetic variants. For example, GWAS identified the chromosome 9p21 locus associated with an increased risk of coronary artery calcification (CAD) events.3 It took almost 15 years to understand the functional aspects of those variants. One of the latest therapies in cardiovascular disease targets the PCSK9 protease. The initial observations were done on about 7000—9000 patients and it took many years to identify the target.
Our approach accelerates the identification of a variant's functional consequence in two ways. First, we're using WGS to look at each variant. As opposed to genotyping approaches that rely on previously identified variants, the variants we find using WGS are based on the difference in Cases and Controls in our own data set. We are not biased by previously performed studies. In fact, some of the important variants we identified for some of our novel targets were discovered this way.
Second, we are making several omics measurements to understand the functional implications of that variant. We've introduced the concept of omics quantitative trait loci (oQTL) where we perform quantitative analysis against gene expression, microRNAs, proteins, lipids, and metabolites for a single variant. With this data, we're able to gain the same insights based on a few hundred patients. For example, our NASH target was identified in just a few months after the data set had been collected and validation was completed at a high statistical significant level in < 500 patients.
Clinical studies are a significant financial investment for drug development. We believe that our panomic approach could reduce the amount of money required to develop new therapies.
"We believe that accurate WGS provides a significant incremental value over genotyping and whole-exome sequencing."
Q: What is the value of WGS in the panomics approach?
SV: We use WGS primarily for genetic target validation. However, we are often able to identify a potential target from the functional nonDNA data generated from our proteomics or gene expression studies. To validate it, we go to the WGS data and look at the gene that encodes that protein or receptor. We then identify the variants within that gene and look for LOF variants associated with the biomarker and phenotype of the disease. We used that approach in identifying the NASH target.
Q: How did you select your omics analysis partners?
SV: When we founded G3, we had two options. One was to buy all the equipment and perform omics measurements in our own lab, or outsource everything to best-in-class providers. After we completed our due diligence, it was clear that the right answer was to outsource.
We selected Illumina FastTrack Sequencing Services to be our WGS service provider. In my previous academic career, I used the iScan System and Infinium genotyping arrays to perform GWAS for cardiovascular disease. I knew that Illumina products were reliable and accurate and that the company provided good support. We believe that accurate WGS provides a significant incremental value over genotyping and whole-exome sequencing.
I had worked successfully with Expression Analysis/IQVIA prior to founding G3. We chose it to perform the other omics studies, some of which are with Illumina products. For example, Expression Analysis is performing RNA- and microRNA-Seq on the HiSeq 4000 System and DNA methylation analysis on the Human Methylation 450K BeadChip.
"The panomic approach accelerates the current time- and cost-intensive process of identifying and validating genetic variants."
Q: What are the next steps for G3?
SV: We're excited to see what the next few years bring. Just seven years into this journey, we have blood tests coming to market and several drug targets in development. Now that we've demonstrated the value of our panomics approach in cardiovascular, cardiometabolic, and liver disease, we'd like to apply it to other disease states. Alzheimer's disease is of particular interest. It is a multifactorial, multigenic common chronic disease and will require quantitative precision phenotyping, coupled with our panomics approach. We're seeking partners to study Alzheimer's disease and other dementias. We would like to take the same approach and apply it to neurodegenerative and musculoskeletal diseases. We would eventually like to initiate projects in oncology as well.
Q: How could the G3 approach impact health care?
SV: The 1990s and early 2000s were an era of population-based, guideline-driven medicine. We hope our approach is instrumental in transitioning to a molecular profile—driven, individualized approach. Our vision is that when physicians walk into an exam room in the future, our approach will enable them to review the patient's profile and molecular fingerprint, and prescribe a personalized therapy for the patient sitting across from them.
Learn more about how G3 is bringing all the omics together:
G3 Video
Learn more about the services, systems, and products mentioned in this article:
HiSeq 4000 System
iScan System
Methylation Microarrays
Illumina FastTrack Sequencing Services
Marenberg ME, Risch N, Berkman LF, et al. Genetic susceptibility to death from coronary heart disease in a study of twins. N Engl J Med. 1994; 330:1041-1046.
Maurano MT, Humbert R, Rynes E, et al. Systematic localization of common disease-associated variation in regulatory DNA. Science. 2012; 337:1190-1195.
McPherson R, Pertsemlidis A, Kavaslar N, et al. A common allele on chromosome 9 associated with coronary heart disease. Science. 2007;316:1488-1491.
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text:
2 Banning High students killed in crash on…
2 Banning High students killed in crash on Pacific Coast Highway in Wilmington
Two people were killed today when a passenger van and a small car collided on Pacific Coast Highway in Wilmington, firefighters said. (Chuck Bennett/Staff Photographer)
Lexi and and Eli Garcia who were killed Thurday afternoon in a car crash in Wilmington, CA. Jan. 29th 2015. (Photo via Instagram)
By Larry Altman | laltman32@gmail.com and Sandy Mazza | sandymazza@hotmail.com | Contributing Writer
PUBLISHED: January 29, 2015 at 7:25 p.m. | UPDATED: September 6, 2017 at 5:55 a.m.
Two Banning High School students were killed and two others were critically injured Thursday when their car lost control and veered into oncoming traffic while allegedly street racing on Pacific Coast Highway in Wilmington, authorities said.
Witnesses at the scene described the two killed as a sister and brother, Lexi and Eli Garcia. Police did not release names. Lexi was a senior, and her brother a sophomore.
Other witnesses who knew the victims said the compact red Honda contained an engine modified for street racing and that Lexi had little experience driving.
The crash occurred about 3:15 p.m., shortly after classes were dismissed for the day.
Witnesses told police that the Honda was possibly racing with another vehicle west on PCH between Marine and Island avenues when the it lost control and spun into eastbound traffic, Los Angeles police Lt. Darryl Martin said.
"At that time a van collided with the Honda, the Honda contained four occupants," Martin said. "Two are deceased, and two were transported to local hospitals."
The driver of the Vride.com van, a ride-sharing service, suffered minor injures and also was taken to a hospital. The van had no other occupants.
Martin said police have not identified the other vehicle in the race, or the driver.
About 100 people, including the victims' relatives, gathered at the crash site. Many of them were Banning High students who heard about the crash through social media. Police covered the red car with a yellow tarp because the bodies remained inside, awaiting coroner's workers.
Teens described the Garcia siblings as friendly students. Aileen Venegis, a Banning freshman, said she had recently talked to the boy.
"We talked about what we wanted to be when we grow up," Venegis said. "I want to be a professional basketball player, and he said he didn't know yet."
Venegis called Eli "very friendly, very social."
"He had a lot of style, very fresh in his Timberlands," she said.
Arturo Miranda said Lexi had just dropped off her boyfriend at a pizza shop where he works.
"They are saying she was racing, but she wasn't like that," he said.
The crash drew plenty of comments on social media. People expressed condolences and shock, while others were critical of street racing.
"How saddd & all because racing … ," one commenter said on the "Crime in Wilmington" blog. "A lot of people and specially those young ones think it's funny and fun to race. Prayers for the families."
Wrote another woman, "Omg I can't even imagine the devastation of the parents of these poor kids that were in this accident. Can u imagine how dreadful it feels? Ur thinking ur child is coming home from school safe and sound. And suddenly u find out they're dead. So so sad. My deepest condolences to all their families. May u RIP."
Larry Altman | Contributing Writer
Larry Altman has covered crime and court proceedings in Southern California since 1987. A graduate of Cal State Northridge, where he served as editor of the college newspaper, Altman has worked for the Daily Breeze since 1990. The Society of Professional Journalists named him a "Distinguished Journalist" in Los Angeles in 2006. Altman's work was featured twice on CBS' "48 Hours" and he appeared eight times with "Nancy Grace," who called him "dear." He has covered hundreds of homicides and many trials. Altman has crawled through a mausoleum to open a coffin, confronted husbands who killed their wives, wives who killed their husbands, and his coverage helped put a child molester and a murderer in prison. In his spare time, Altman is an avid Los Angeles Lakers and Dodgers fan, is the commissioner of a Fantasy Baseball league with several other current and former newspapermen, runs a real estate empire and likes to watch old movies on TCM.
laltman32@gmail.com
Follow Larry Altman	@larryaltman
Sandy Mazza | Freelancer
Sandy Mazza is a freelancer. She previously worked for Southern California News Group as a city reporter covering Carson and Hawthorne and specializing in features about Los Angeles' growing Silicon Beach tech, bioscience, and aerospace sectors.
sandymazza@hotmail.com
Follow Sandy Mazza	@SandyMazza
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