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This is an attempt to reason though the cascade of linked events which leads to the catastrophic multi-organ collapse in severe septic shock.
Organ system failure
The systemic inflammatory response (which forms a part of the definition of sepsis) results in organ system dysfunction.
The diagram below is merely a simplified way of looking at the pathogenesis of something this complex. Imagine what it would look like if it elaborated on the specific cytokine pathways, metabolic derangements, etc.
Lets try to reason through this.
Hypoxic respiratory failure
There is an increase in whole-body oxygen consumption, due to massive leucocyte activation as well as the increased metabolic rate of critical illness, as well as the increased metabolic rate associated with hyperthermia.
Not only that, but there may be a diffusion defect as the capillaries of the pulmonary circulation become leaky, and ARDS develops.
Hemodynamic collapse
The defining feature of septic shock, systemic vasodilation due to inflammatory mediators, results in decreased oxygen delivery to the whole body, exacerbating the dysfunction of the organs.
Septic cardiomyopathy
Thought to be due to impaired metabolite utilisation at a mitochondrial level, the cardiac dysfunction in sepsis results in biventricular failure.
Acute renal failure
As a result of decreased cardiac output, the renal function deteriorates, and oliguric renal failure becomes established. Not only that, but there is tubular dysfunction caused by the inflammatory cytokines, which is unrelated to the hypotension.
Hepatic dysfunction
Though the liver may not fail per se, there is typically a sepsis-associated rise in transaminases and bilirubin. Furthermore, the synthetic function is impaired, which contributes to the ensuing hypoalbuminaemia and coagulopathy.
Septic encephalopathy
Through mechanisms still poorly understood, severe sepsis results in a diffuse cerebral dysfunction which seems to worsen the prognosis. Cytokines, microvascular damage and impaired mitochondrial oxygen utilization have all been implicated.
Even in the absence of proper DIC, there is usually some degree of subclinical coagulopathy. There is simultaneously a depletion of coagulation factors and a decrease in their hepatic production.
An excellent resource for this topic are the chapters in Oh's Manual dealing with severe sepsis (ch 61, by A Raffaele de Gaudio) and with the immunocomrpomised host (ch 59, by Steve Wesselingh and Martyn A H French).
An older, yet similarly respectable source is Shoemaker (2005); Chapter 155 (Infections in the immunocompromised patient) by Andrew Githaiga, Magdaline Ndirangu and David L. Paterson covers this topic with great detail.


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Kris Meeke comes to Wales, looking to end his successful 2016 season on a high and take momentum into a full-time program with Citroën in 2017.
2016 Wales Rally GB
DMACK will be aiming for good results at their home rally at Wales Rally GB with Estonia's Ott Tänak, who retired from last year's rally in Flintshire.
Osian Pryce returns home at the 2016 Wales Rally GB after winning the 2016 Drive DMACK Fiesta Trophy last time out in Spain at Rally Catalunya.
Dani Sordo is hoping to add to his two podium finishes in the last three rounds when he tackles the British forests on Wales Rally GB
The supercars will be on show at the 2016 Cholmondeley Castle RallyFest, with some lucky people having a once in a lifetime experience in a supercar.
Former British Olympic skeleton racer Amy Williams will once again team up with Tony Jardine on the 2016 Wales Rally GB.
With the FIA World Rally Championship, Junior WRC series and DDFT all wrapped up, WRC2 remains up for grabs as we head in to the final stages of the 2016 season.
Kris Meeke is targeting a 'home' win for Citroën at the 2016 Wales Rally GB, as the Northern Irishman aims to become the first British winner in 16 years.
Brenig Reservoir played host to the countdown of the 2016 Wales Rally GB, which included North Wales' very own Elfyn Evans present at the media preview.
Plans for the 2016 Wales Rally GB National Rally have been announced today as Mike Faulkner is aiming for his third win in three years at this rally.
The legendary Group B rally cars will be honoured at the 2016 Wales Rally GB, 30 years after they were culled by the governing body at the time, FISA.
Thierry Neuville comes to Wales looking to continue his great run of consistency that has taken him to joint second in the standings.
Gus Greensmith: "This is the most exciting opportunity of my rallying career"
TCF catches up with Gus Greensmith as he heads in to the 2016 Wales Rally GB making the step up to R5 machinery.
The Dare to be Different campaign, which is designed to get females involved in motorsport will be holding an event at the 2016 Wales Rally GB.
We have two pairs of tickets to give away to the 2016 World Rally Championship Wales Rally GB, including access to RallyFest at Chomondely castle.
Live power stage coverage planned for British round of 2016 FIA World Rally Championship

subset: commoncrawl


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Gender Reveal Balloon
A fun way to celebrate! Pop this big 36" Confetti balloon to see what's inside...Pink or Blue??
Make sure to tell us in the notes what color you need! And, which style balloon: solid black, black w/white polka dots, black w/white question marks, or black with "Oh Baby" in white (you choose)
Inflation additional charge; please include phone number when ordering this item


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Compare mortgage rates from multiple lenders in one place. It's fast, free, and anonymous.
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Are Refinance Rates Higher Than Purchase Interest Rates 10 Years The maturity dates vary from one month to five years, but the most common ones are one year, 18 months or two years. The longer maturity dates typically offer higher interest rates as an incentive.Is A High Interest Rate Good Us Bank Fha Rates Latest News On Interest rate interest rate cut: Latest News, Photos, Videos on Interest. – Find Interest Rate Cut Latest News, Videos & Pictures on Interest Rate Cut and see latest updates, news, information from NDTV.COM. Explore more on Interest Rate Cut.FHA loan calculator – Consumer Banking | Personal. – 2019-04-05 · FHA loans offer an easier qualification requirements and favorable terms. Use our FHA loan calculator to estimate your monthly payments.The Effect of Interest Rates on Inflation and Recessions. A good example of this occurred between 1981 and 1982. Inflation was at 14% a year, and the Fed raised interest rates to 20%. This caused a severe recession, but it did put an end to the spiraling inflation that the country was seeing.
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Home Mortgage Rates Comparison 15 Year Mortgage Rates Refinance Calculator Current Mortgage Interest Rates | Wells Fargo – Use annual percentage rate APR, which includes fees and costs, to compare rates across lenders.Rates and APR below may include up to .50 in discount points as an upfront cost to borrowers. Select product to see detail. Use our Compare Home mortgage loans calculator for rates customized to your specific home financing need.We have identified more than 264 mortgage offers from banks and mortgage brokers across the country that may meet your needs. In order to track relevant mortgage rates and find the right home loan for your particular situation, we recommend using the filters below.This will allow you to search based on important criteria such as mortgage type, loan amount and loan duration.
. and lower than the 3.84 percent average for 5-year adjustable rate mortgages. By way of history, the record low for 30-year mortgages was in December 2012, at 3.31 percent. The record high was in.
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New Day Usa Mortgage Rates Interest Rate Vs Apr Calculator Interest Rate Vs Apr Calculator | Saglamtapu – How to Calculate APR vs. Interest Rate on a Loan – LendGenius – APR and interest rate are more closely related than either is with factor rate, so we'll discuss those two first before describing how a factor rate might come into play. What is an APR vs. interest rate? The interest rate is the annual cost of a loan to a borrower expressed as a percentage of the principal loan amount. easy.NewDay USA Launches New Reverse Mortgage Purchase Efforts – Reverse mortgage and Federal Housing Administration-focues lender NewDay USA this week announced it is making a new. The company's effort includes fixed rate and adjustable rate reverse mortgage.
Current Ten Year Mortgage Rates Available Locally. The following table shows current 10-year mortgage refinance rates available in Los Angeles. You can use the menus to select other loan durations, alter the loan amount. or change your location.


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Tops & Tees
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Swing – A New York Times Bestseller!
New York Times bestselling authors Kwame Alexander and Mary Rand Hess (Solo) tell this lyrical story about hope, courage, and love that speaks to anyone who's struggled to find their voice. And the surprise ending shines a spotlight on the issues related to our current social divide, challenging perspectives and inspiring everyone to make their voice heard.
When America is not so beautiful, or right, or just, it can be hard to know what to do. Best friends Walt and Noah decide to use their voices to grow more good in the world, but first they've got to find cool.
Walt is convinced junior year is their year, and he has a plan to help them woo the girls of their dreams and become amazing athletes. Never mind that he and Noah failed to make the high school baseball team yet again, and Noah's love interest since third grade, Sam, has him firmly in the friend zone. Noah soon finds himself navigating the worlds of jazz, batting cages, the strange advice of Walt's Dairy Queen-employed cousin, as well as Walt's "Hug Life" mentality. Status quo seems inevitable until Noah stumbles on a stash of old love letters. Each page contains the words he's always wanted to say to Sam, and he begins secretly creating artwork using the lines that speak his heart. But when his private artwork becomes public, Noah has a decision to make: continue his life in the dugout and possibly lose the girl forever, or take a swing and finally speak out?
At the same time, numerous American flags are being left around town. While some think it's a harmless prank and others see it as a form of peaceful protest, Noah can't shake the feeling something bigger is happening to his community. Especially after he witnesses events that hint divides and prejudices run deeper than he realized.
As the personal and social tensions increase around them, Noah and Walt must decide what is really true when it comes to love, friendship, sacrifice, and fate.
- Is written by New York Times bestselling authors Mary Rand Hess and Newbery Medal and Coretta Scott King Honor Book Award-winner Kwame Alexander
- Is a young adult fiction novel told through Kwame and Mary's one-of-a-kind free-verse poetry
- Is ripe with themes of hope, courage, and love
- Masterfully combines jazz, art, baseball, friendship, and love into what many are calling "Kwame's best book yet"
- Tackles some of the most painful social issues of today, including racial prejudice
"This important and recommended contemporary YA will inspire young people to find their own voices and take a swing at life. A must-have." –School Library Journal, starred review
"Despite the easy flow of verse, there is a density to this story with its multiple elements. Lively, moving, and heartfelt." –Kirkus, starred
"…this novel packs a punch into its shocking and extremely powerful ending straight from today's headlines." –Booklist
"…an unforgettable listening experience. This novel is particularly poignant in today's climate, and audio serves as superlative format to help readers immerse themselves in this story." Booklist, starred review for Swing audiobook
Swing Nominations, Awards, and Distinctions:
- Winner of Audiofile Earphones Award
- 2018 Nerdy Book Club Award Winner for Poetry
- 100 Best Books of Fall, Audible
- NCCBD 2019 Feature: Own Voices Novels for Poetry
- 2019 Amazing Audiobooks for Young Adults (YALSA)
- 2019 Teen Choice Book Awards (Nominee)


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The Container is a tapas and cocktail bar that draws inspiration from the elements of earth, air, water and fire. It is also one of two specially curated concepts – Aburiya Japanese Wagyu Yakiniku and The Container Wagyu Tapas & Bar which are located side by side, right next to the iconic Singapore River on Boat Quay, offering a comprehensive Japanese Wagyu experience.
In Hokkaido, wagyu farmers all have a second 'home'.
At the end of the day, they will gather in old, used containers which are converted into informal 'bars'.
It is at the bars where they share anecdotes about their day's work and their family (or how some miss theirs who live in other prefectures). They enjoy small plates of wagyu dishes, served up along with sake and beer. Sometimes, the farmers take turns to prepare their hometown wagyu specialities.
Laughing, bonding, over their stories. A place of camaraderie and friendship. This is a celebration of life. The Container is inspired by this experience.
78 & 79 Boat Quay
Tel: +65 6532 0365 Email: firstname.lastname@example.com


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Paddy Power Pays out More Than $1 Million on PSG vs Manchester United Bets
Players at Paddy Power have placed the right bet on Champions League's PSG vs Manchester United match, leaving the operator in a position to pay out more than $1 million in wagers amidst a pretty rough period of the year. Even though Paris Saint-Germain had an advantage over the English team since it had defeated it in the first leg of the competition with 2-0, Manchester United has found its way to triumph, and Paddy Power players were ready for it. Even though the operator wasn't expecting Manchester United's comeback, players were. Placing bets in favour of Manchester United, players have managed to put Paddy Power in a position to pay out over a million dollars.
The PSG vs Manchester United Match
Paris Saint-Germain has defeated United in the first of the two matches scoring two goals and leaving the English team with no goals whatsoever. With a clear advantage, PSG was the favourite to win. However, as many Paddy Power players anticipated, Manchester United was not ready to quit. Being down in points, Manchester United had to pull out the big guns and fight really hard to win the match. Thanks to the controversial final free kick by Marcus Rashford, Manchester United managed to win in the last second of the match. There was incidental contact, and after the referee reviewed it in the VAR, he gave the free-kick to Manchester United, which eventually led the team on the winning side. The free kick was deemed as the most controversial one in VAR history, and one that has left the entire football world stunned. But the one that was shocked the most was Paddy Power. Courtesy of the VAR call, the operator had to pay out $1.3 million in wagers.
Still Holding It
The operator has had a really rough year, mainly due to the 10% drop in sportsbook sales which eventually resulted in revenue drop. Due to punters winning the advantage, Paddy Power has experienced a 6% drop in revenue, and the four draws with 34 games weren't helpful either. The unbeaten records of Liverpool and Manchester City also filled players' pockets and emptied Paddy Power's. However, Paddy Power is still holding it. Thanks to the gaming sales which increased 26% on the strong US and European demand, the operator has seen an increase in revenue by 17%. The $622.43 million in revenue will compensate for the $1.3 million loss due to the single Paris Saint-Germain vs Manchester United match.


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BANDUNG. Monday (3/12). In order to provide temporary assistance to outpatients seeking treatment in Bandung, the Sukabumi city government in collaboration with Rumah Zakat rolled out the Rumah Singgah (shelter) program.
Sukabumi City Government Shelter House located on Jl. Mulyasari 1 no.7, Sukagalih Village, Sukajadi District, Bandung City is a program to provide temporary shelter for patients and families of poor outpatients from Sukabumi.
This program was officially signed on Monday (3/12) at the Bandung branch of Rumah Zakat office, Jl. Turangga no. 33, also attended by H. Achmad Fahmi as Mayor of Sukabumi and Mr. Nur Efendi as CEO of Rumah Zakat.
On this occasion the MoU was signed in the fields of Social, Health, education and humanity between the Sukabumi City Government and Rumah Zakat.
On the same day Mayor Sukabumi accompanied by CEO of Rumah Zakat also directly carried out ribbon scissors which marked the opening of the Shelter House and visiting patients who were already living in the shelter.
The shelter program is a work of 100 working days of the Mayor of Sukabumi. This is also one of the flagship programs of the Sukabumi City Government in the Social field.
"This program provides assistance in the form of temporary housing for outpatients, hoping that it can ease the burden on patients who must control treatment at the intended Hospital." Achmad Fahmi said as Mayor of Sukabumi.
And to take patients to the Hospital, the Shelter House has also been equipped with an Ambulance Car and the driver who is ready to deliver the patient.
He continued, with the launch of the Shelter House program, he hopes to be able to help the community, especially our citizens who are in Bandung, to be facilitated properly. "We are also grateful for the synergy of Rumah Zakat for this program." He concluded.
"We are grateful for the trust of the Sukabumi City Government to Rumah Zakat in this Shelter House program. Insya Allah, this is very beneficial for the community." Said Nur Efendi.
"Alhamdulillah, I am very grateful because now there is this shelter house, so at least it can reduce the cost of my husband's lodging during treatment in Bandung," said Astuti (39), wife of one of the beneficiaries.
Previously, Astuti and her husband Dedi Suhendi (47) had to rent a house every time they would go to the Cicendo Hospital. "Initially I stayed in my relative's house, but because the house was not too large and there were many family members, after a long time I didn't feel comfortable if I kept on going," Astuti added.
Astuti's husband, Dedi Suhendi, suffered from retinal disorders and loose nerves in his eyes. Until now, Dedi who lives in Sukabumi has done routine health checks at Cicendo Hospital Bandung for 25 times and eye surgeries three times.
Abdullah Thabit


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Alberta : visit by Consul General in Edmonton (Nov. 18-19th) [fr]
France-Alberta cooperations
On November 18th and 19th, Consul General, Philippe Sutter, met with several members of the provincial Government, to highlight France's support of cooperations in the fields of education, higher education, the French language, culture and environmental protection. He underlined the notable contributions of French companies to the economy of Alberta, including in the responsible and energy transition industries. He also presented France's competitive ecosystem.
Minister of Education, Adriana Lagrange, Consul General, Philippe Sutter, and representatives from the Embassy of France's Cultural and Education Cooperation Services, welcomed 9 French school Académies, an unprecedented number to date, and 14 provincial school districts to recognize the implementation of 5 current partnerships and to encourage more agreements. Our objective is to double the number currently in place in 2020.
A representative from Grenoble University continued the dialogue with University of Alberta's Campus Saint Jean on a double diploma, supervised by M. Pierre-Yves Mocquais, Dean of Campus Saint Jean. This would enable the training of more French teachers and make it easier to recruit French teachers from France.
Consul General also gave a talk during an international relations class at Campus Saint Jean.
Media Coverage
Consul General gave two interviews to the local media (in French) :
Radio Canada Alberta La Croisée.
Le Franco (to be published on Dec. 4th).
Etienne Farreyre, Cultural and Education Cooperation Attaché at the Embassy of France and Olivier Launay from Académie de Rouen also gave interviews. Watch the TV segment Radio Canada Alberta.


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me secure that I may not fear; it is but a delusion. 'Winch had these sad effects upon my soul; 1st, Strange and hard thoughts of God as of an enemy, Luke xix. 21; Gen. in. 5, as one that envied our good. 2dly, I judged all that God said of his love in his word to be but wind at best, or compliments or snares to entrap; and so made him a liar, 1 John v. 10, and by this means was made incapable to be taken with Christ's allurements in the gospel. 3dly, Hence I could neither love nor believe him, nor by any means be drawn to him, 1 Cor. xiii. 7, "Charity believeth all things." For how could I love him in whom I believed I had no other interest than that of a cruel judge ready to condemn, and watching for evil against me, and that when his "words were smoother than oil?" Psal. lv. 21; Zech. xi. 8. 4thly, I had no will to keep communion with him, was wearied of him. When the Israelites said, "We have no portion or inheritance in the son of Jesse," the next was, "Every man to his tents," and did quit him. Jer. iii. 19, "Thou shalt call me, My Father, and shalt not depart from me." 5thly, I was heartless or slight in duties, whereby he was honoured, and communion with him entertained; wanting love and hope, Jer. xviii. 12; Lam. i. 9; Luke xix. 21. Through unbelief my hands were weakened, and I departed from the living God. 6thly, Finding no satisfaction in God, which I could not do whilst these principles remained, I behoved to have it elsewhere in the creature. Jer. ii. 13, "Forsaking of God, the fountain of living waters, and hewing to ourselves broken cisterns," are joined. 7thly, Sermons did me no good, because not heard with faith, Heb. iv. 2, whereas, if I had believed and trusted in God, I should be strengthened with the joy of his salvation, Neh. viii. 10; Prov. xvii. 22; 2 Cor. ii. 7. § 2. Step 2. Notwithstanding of all this, I had hopes, that though as yet the Lord had not converted me, yet I might be converted, and therefore did not despair of it. Some secret thoughts in duties would drop in persuading me to hope, and some relish in duties. As likewise, since I was persuaded by a strong hand my sins were pardonable, and that the Lord possibly might pardon; this made me continue in the means. Satan therefore sought to beat me from this, or at least to make me remiss in them; and, knowing that palpable vanities would not do, (for I had been burned with that candle already,) therefore would compass this by making me close with an appearance of good, which he did thus: I studied stenography or short-writing, in the study of which, aiming at perfection In it, I was excessive, and so taken up altogether from any other thing, that I could scarce get the form of duties gone about two times a day. In end I resolved to give way, cheated with this, that, the sooner I acquired knowledge herein, I should the sooner have leisure to wait on God; but, however, this spirit of whoredom caused me to err, and took away my heart. This was the second mean of my decay.
§ 3. Step 3. When I was called home, through want of godly company, and dead formal society among which I lived, I was brought a further length of decay, even to omit duties almost altogether; contenting myself ordinarily with bed-prayers, and slight reading of Scripture and godly books. Several things had influence on this; the want of a convenient room, a prevailing spirit of sloth that would not break through difficulties, some false hopes that all would be well. Sometimes my heart would secretly despair, and prophesy things would never be better, and it is in vain to pray; through these tliings it came to pass that my heart turned altogether out of tune, and heeded not my work at all. Now had preachings and sermons no relish at all; then did I see that fulfilled, "He that followeth vain persons shall become poor," Prov. xxviii. 19; 1 Cor. xv. 33, " Evil company comipteth good manners."
§ 4. Step 4. Then, through want of the fear of God, and unwatchfulness, did I become vain and light in my conversation ; I followed lies and vanities; I carded, complied with sinfid customs, made no conscience of what company I came into, "inventing to myself instruments of musie," and seeking contentment from the creature. When company was away, my heart turned melancholy, but did not turn to God. I would pray when trysted with any disappointments; but still, through interruption, lost more ground than 1 gained, so as I went daily down the stream, and grew exceodinir hard-hearted. Spiritual duties were a weariness and a burden; and thus I was not only discouraged and remiss in duties, slighting them altogether, but grew very untender and carnal in my conversation.
§ 5. Whence a fifth step, which was, going to some relations to pass a visit, where there were many professors and much profession; but there I got a dead stroke, so as it is a wonder how ever I recovered; in a word, I turned desperate, and said, "There is no hope; I have loved idols, and after them I will go," Jer. ii. 25. The grounds of this despair were, 1st, A great and long account of sins that had run up upon me, which I thought would never be pardoned, Jer. ii. 28. 2dly, The terrible hard frame of my heart, and great deadness I was in, so that I thought I would never recover again, Jolm xi. 39; Ezek. xxxvii. 3, "Can these bones live?" Gen. xviii. 11, 12. 3dly, Some fruitless vain attempts I made to recover myself; my strength wasted in vain; and hence I said, "This evil is of the Lord, and remediless, what should I wait on him any more?" 2 Kings vi. 33. 4thly, The complaints, doubts, and discouragements of others, and their unsuitable walking up to their principles, who yet were eminent for godliness in the estimation of others; they went with bowed down backs, and raised an ill report to me of the Lord and his ways; and therefore were my hands weakened by these spies, Num. xiii. 30. 5thly, Their unloving carriage towards me, and keeping at a distance, and taunting me. At another time, seeking to join in with them, and to bear the burden of a good discourse lest it should die, I was put off with a taunt. It is true, my conversation at that time was not gospel-like; yet they had beams in their own eyes, and they should have dealt in greater meekness with me, and kythed love by a friendly reprehension. This turned me averse to them, and to their way. Ezek. xxxiv. 21, They pushed with horn and side, and this produced scattering. 6thly, I was but too much countenanced by others, and humoured and complied with; for I was given to foolish jesting, and they took but too much pleasure in this, and never once gave me a friendly warning or reproof, although my ways were
displeasing to them: "The soul that lacketh instruction shall die." 7thly, Satan was beating in strange tentations on my soul, sometimes telling me I was judicially hardened since I could not mourn for my sins, and that it was ever so since my terrors were removed. And then that place, Isa. vi. 10, came to my mind, "Make the heart of this people fat." Sometimes thinking my time was past, and my day gone, and that Christ had given his last knock, and that the door was shut. That place, Prov. i. 26, troubled me, "Because I called, and ye would not hear, therefore shall ye call, and I will not hear;" therefore, it is in vain now to cry or pray. Sometimes Satan said I had sinned the sin against the Holy Ghost, citing Heb. vi. 4. For it is true (was it suggested to me) thy blasphemies were not that sin, because thou didst that in unbelief, and not enlightened; but now thou hast been enlightened, and tasted of the powers of the world to come, and hast fallen away, and laid a new foundation from thy dead works for repentance, and therefore it is impossible to be renewed again; and this is the sin against the Holy Ghost. This raised not that terror in me which tentations of this kind were wont to do formerly; only made me heartless, and discouraged me. And then would Satan add, Dost thou not mark how unmoved thou art with this heavy message, which would cause any other to tremble but thyself? And why art thou not shaken? Because the Lord has hardened thee like Pharaoh, that thou canst not hearken; the sentence is past, and the stone is laid upon thy grave; and now all thy life is gone, thou art twice dead, and plucked up by the roots. With these thoughts I was dung from duties and their cheerful exercise; with pleasures, company, and want of inward and outward exercise, I was kept in my security and strong bonds.
§ 6. My sins were, 1st, Slighting and omitting of duties, public and private. 2dly, Vain and light conversation like the world; the show of my countenance witnessed against me. 3dly, Idle jesting, Eph. v. 4. 4thly, Breaking of the Sabbath with idleness and mine own words. 5thly, Following of the lusts of the flesh, and divers vanities. 6thly, Sensuality. 7thly, Doing no good, neither gloritying God, nor edifying others, nor profiting myself. 8thly, Haunting vain company, and not reproving them. 9thly, Sinful customs and recreations, though debated by some; such as healthing and playing at cards.
§ 7. Notwithstanding of this, the Lord upheld me by his right hand, and kept in the dying spunk, that all these waters could not quite extinguish it; I fell not totally away, nor was I utterly forsaken of God, Jer. v. 5. For these things remained; 1st, 1 was put out to pray, meditate, and read now and then; I was not dung altogether from duties; I did not show myself to have no knowledge at all, in not calling on God, Psal. xiv. 4. 2dly, There remained a secret and quiet hope things would be well, and a looking up to him; though cast down, yet not in despair, 2 Cor. iv. 8. 3dly, Love and affection to, and estimation of, the people of God, and delight in them, still remained, so as even then I loved them above others. 4thly, Dissatisfiedness with my present condition, groaning under and mourning when I remembered the days of old; this course was not pleasant, I was like a bone out of joint, these matters were not my element. 5thly, Some love to my first husband remained, and a preferring of the first course and life, even in its worst, before this, even as one prefers the day to the night; and often would I say that word, with Job, "O that it were with me as in months past, when the candle of the Lord shined upon my head!" Job xxix. 2, 3, 4. 6thly, I knew that it was ill with me; though I slept, yet I was not so dead as to be without sense or knowledge altogether.
§ 8. God's ends in this, for anything I can learn, were only to give further proof of his love, in renewing his kindness, in sparing me whilst in this condition, in preserving me from turning apostate, and, in his time, graciously reviving me again with much pains and long labour. 2dly, To keep me watchful in time coming, lest a worse thing befall me. 3dly, And to let me find the power of sin, and of my original corruption, more fully, 2 Chron. xxxii. 31. 4thly, To keep me humble for ever after it, that I may not open the mouth, Ezek. xvi. fi3.


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Delicious and paleo-friendly! A delightfully fresh and healthy twist on a classic burger stack using our organic paleo chuck & brisket beef burger patties.
Drizzle the mushrooms with 3 tbsp oil and season with salt and pepper on both sides. In a large frying pan, on medium low heat, cover with lid, cook mushroom for 5 minutes and turn them over, cover again for another 5 minutes until the mushrooms are tender.
Place onion ring and 3 tbsp oil in frying pan cook on medium heat for 3-5 minutes each side until onion are caramelised, season with sea salt
Heat the frying pan to medium heat, add two tablespoons of oil and cook the patties for 4 minutes both sides or to your liking.
Assemble burger with mushroom 'buns', pickles and vegetables.
Cut sweet potato into sticks and keep in cold water.
Drain sweet potato while heating frying oil to 180°C. Fry half of the potatoes at a time, for 6-8 minutes until golden. Alternatively potatoes can be tossed in a couple of tablespoons of oil and baked in oven on 230°C for 5-10 minutes.


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This afternoon we went down to check out the Young Thug #SlimeLand Pop-up Shop in Camden market. Young Thug is currently supporting Drake on his 'Boy Meets World' European tour. Why not make the most of it and give the UK fans a taste of the ATL merch, ey?
Speaking to a few people in the queue they were gassed about grabbing some Thugga merch . We could see the buzz from people's faces when they stepped out of the store with the freshest garms!
As we entered the store the DJ was mixing the hottest hip-hop and Thugga tunes with green smile dripping off his DJ deck followed by the trippy purple lighting of the whole shop gave us the real 'Slime Season' feel.
The collection features : T- Shirts (£25) – Short sleeve Slime, Lollipop , Thugger 'Lean' , 'Now my B*tch A Barbie, Woah' with a 'Slime Season' long sleeve all in a black colourway with the Skull tee in a white and red colourway. There was also a 'Black Thugga Skull' sweatshirt (£50) along with a denim 'Young Thug' stitched logo jacket (£150) in the collection. Other items in the collection included a black 'Y Thug' logo tote bag (£20), and 'Barbie, Woah' Snapback (£20).
Trying on the clothes, you could instantly feel that the clothes were made using good quality materials. The printing on the t-shirts was crisp and the fit of the tees were true to size. The denim jacket is made of heavy denim and the logo was stitched into the jacket as appose to being printed.
Make sure you check out the store, open Tomorrow & Sunday (4th & 5th Feb). Word is, Young Thug will be making an appearance tomorrow at some point so get down there early!
Check out the exclusive Young Thug clothing below!
Full address of pop up –
Camden Market
Chalk Farm Road
Stables Yard Entrance
Words – Amandeep Basi (@SignorBasi)


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Road closures for the next few months in the newest phase of the Town Creek Culvert construction project are affecting local businesses and resulting in traffic confusion in Uptown Greenville.
Director of Public Works, Kevin Mulligan, said Reade Circle and Cotanche Street will be closed for four months due to construction on the Town Creek Culvert.
The city of Greenville is working to open the pedestrian detour between Chico's and the West End of East Carolina University's main campus.
"They're looking to see what we can do to accelerate that so that part may only be a couple months and we're looking to open up that walkway where the speed humps are right now, that crosswalk, certainly sooner than the four months I just talked about," Mulligan said.
Construction is currently moving south along Reade Circle and Cotanche Street was closed on Monday. The section from the Chico's parking lot on Reade Street to the south of Fifth Street to the end of Cotanche Street will remain closed for four months.
After the end of January 2020, construction will move to the intersection of Evans Street. The Town Creek Culvert project is expected to be completed in the summer of 2020.
Yvonne Perry, operations manager at University Book Exchange (U.B.E.), said she believes their business may be affected slightly due to customers not being able to walk from dorms at West End on East Carolina University's campus to U.B.E.
Perry said students who live at West End, which is located directly in front of the construction area, will now have more difficulty accessing the Uptown area due to the closure of Reade Circle and Cotanche Street.
"That (road closures) I do think especially will affect the traffic that normally would walk to us," Perry said.
Perry said the amount of pedestrian traffic the store experiences varies depending on the seasons, but around this time of year, she said she believes traffic to the store is about 25% pedestrian and 75% by vehicle.
The best way to access U.B.E. and others around them, according to Perry, is by taking Evans Street to Fifth Street and accessing Cotanche Street from there.
"Evans Street is our lifeline right now," Perry said.
Perry said there is one barricade located in the road at Cotanche Street and Fifth Street but cars are still able to come down the street. She said this is causing confusion among drivers who were used to being able to drive down Cotanche Street the past month.
Perry said the confusion is apparent because drivers are now using U.B.E. and Chico's parking lot to turn around in so drivers do not run into the construction at Reade Circle.
"I've watched some of the traffic, and they are so confused," Perry said. "I feel that's the people who are trying to find their way around Uptown Greenville right now."
Perry said, although the closure is projected to last three to four months, she hopes people will continue to be patient and businesses will not be affected too drastically. She said U.B.E. understands this construction is for the improvement of Greenville.
Greer Jones, bartender at Club 519, said the sidewalk closures might be an inconvenience for pedestrian traffic in the future for their business, as well.
"A lot of our business is people walking here on foot, so the sidewalks around us being closed might end up hindering our business," Jones said.
Jones said she hopes the walkway closures will open sooner than the projected dates to help people access the Uptown area, but in the event the closures do last for three to four months, she believes residents will continue to find ways to walk and drive to the area.
A post on the City of Greenville's website said that Cotanche Street at Reade Circle was expected to close on Monday, Oct. 7.
The detour for Cotanche and will be on to East Tenth Street, Evans Street and East Fifth Street, the post said.


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By Sarah Wright
Santa Monica College's Two-Tier Trouble
If you follow the news even a little bit, you're probably aware that college students across the U.S. have been protesting quite a bit lately. Mostly, these protests have focused on financial issues relating to education, though in some cases the demonstrations have called attention to broader issues. Most recently, students have been protesting a radical new two-tier tuition plan at California's Santa Monica College. The plan, believed to be the first of its kind, would put in-demand classes at a higher tuition tier than other, less popular courses.
The justification for the plan is that demand has begun to far outstrip supply for popular and widely required courses in subjects like English, writing, science and math. Ordinarily, courses cost about $36 per credit hour, but the new system would price premium courses at a staggering $180 per credit hour. That's no small difference, and understandably, students were quite upset when the plan was first proposed. Santa Monica College students took to protesting in order to make their displeasure known. Unfortunately, the response to the protest got out of hand, with pepper spray and other tactics being used to the point that a small number of students were hospitalized in early April.
Controversy and Backpedaling
The publicity generated by these protests kicked off a bout of backpedaling by college authorities. The campus police were responsible for the pepper-spraying incident on April 5, which was a response to student protesters crashing a meeting of the school's Board of Trustees. Though college president Dr. Chui Tsang initially supported the officers responsible, he eventually announced a 'full investigation' of the incident. Additionally, he said that the college would reimburse students for medical bills for injuries suffered during the incident. In the aftermath, Santa Monica College's trustees called an emergency meeting to discuss the plan.
Many of the plan's original critics pointed to how inherently unfair it is to put popular classes at a financial premium - a plan that's particularly unexpected at a community college. But after the April 5 trustees' meeting, California Community Colleges Chancellor Jack Scott asked the college's administration to hold off on implementing the plan, citing the potential illegality of such a system. And indeed, at their emergency meeting on April 6, the trustees scrapped the plan. It's a good thing, too, not only due to the controversy, but also because the California attorney general's office announced that such two-tiered systems are illegal in that state.
Could It Happen Again?
So should you, the college student, be worried about this type of a plan being implemented in your school? In a word, I'd describe Santa Monica College's attempt to implement a two-tier tuition system as a disaster. The school received plenty of negative attention, and their plan was called out by top state legal officials as being illegal. That's hardly a strong endorsement for other colleges to attempt to do the same. Still, in such trying economic times, leaders at educational institutions are having to get creative. Hopefully, though, the creativity will focus less on creating an unfair system for students who are already likely struggling to pay for school.
Santa Monica College isn't the only institution seeking radical solutions to its budget problems. Some public universities are even considering going private.


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Icy and snowy roads present challenges for drivers in the winter months. Hazardous driving conditions can cause serious accidents, with extensive damages and injuries. To help protect against this, snow tires have long been recommended for drivers who live in snowy climates like New Hampshire. With the improvements in all-season tires, many drivers have begun to question if dedicated snow tires are really worth the time and expense.
Are Snow Tires Worthwhile?
When you purchase a new car, chances are it comes standard with all-season tires. These tires are designed to adapt to a broad range of road conditions. This ability to adapt comes at a cost – they are not ideal for the cold of winter, or the heat of summer. They're generally made of firm rubber that will stay consistent in most temperatures, with a moderate tread to give you a reasonably quiet and responsive ride year-round. While these are fine if you live in a climate without winter weather, they can pose a safety hazard when snow falls in places like New Hampshire.
What are Snow Tires?
Snow tires are like winter boots for your car. When the ground is slippery, most people pull out their trusty winter boots for added traction and safety. Winter tires offer similar protections for your vehicle. Snow tires are designed with deeper treads to grip into the snow and ice, making slipping on the road less likely. They are also available with studs that further help
Snow tires are made of
Are There Downsides to Snow Tires?
Snow tires are specifically designed for winter driving, which makes them less than ideal when the roads are clear. Snow tires are less responsive than all-weather or summer tires, giving you less precise handling and control. They also break down more
The main factor that gives people pause is the cost. Snow tires are an investment, with the initial purchase and also the cost – either in
Better Safety
The bottom line is snow tires provide a safer driving experience in winter weather. Studies have shown a 35% improvement in braking in slippery conditions when using snow tires instead of all-season tires. This improvement gives you a better breaking distance, helping you to avoid getting in a crash. Winter tires also help with cornering, helping to avoid a dangerous fishtail situation.
While all-weather tires are designed for a variety of situations, they simply cannot match the traction provided by snow tires on snow and ice. Whether it's getting out of the driveway or avoiding a pedestrian, snow tires will help you navigate the slippery roads better than your standard all-season tires.
Anyone who's driven in winter weather knows that when the snow starts falling in New Hampshire, the roads can get treacherous even for the most experienced drivers. While all-wheel and four-wheel drive, electronic stability, and other safety features can help your winter driving, your tires also play a critical role. Taking the time to switch to dedicated snow tires can dramatically improve your safety in winter weather. Stay safe!
This material is for informational purposes only. For an actual description of tire performance, please refer to the applicable vehicle owner's manual, or specific information provided by


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Power Spotlights
We develop European power markets
EEX is continuously expanding its range of products for the European power market in close cooperation with its customers. We aim at providing power trading for all major European markets along the whole curve.
On the subsequent pages, you will find an overview of our current initiatives.
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EEX German Power Future – the most liquid financial power future contract in Europe
EEX has introduced power products for the German and Austrian price zones in April 2017. Those products are based on the indices for these price zones as calculated by EPEX SPOT. Since then, the EEX German Power Future has firmly established itself as the benchmark product for European power along the whole curve.
© 2020 European Energy Exchange AG


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People have the right to defend themselves and their property from harm, but there are limits on how aggressive that defense can be. A person who causes serious injury to another may be charged with assault or battery even if the reason was some form of self-defense. Legally, the individual is allowed to use reasonable means to stop the possibility of harm but cannot continue aggression beyond that level. Charges may be filed and this person will need a skilled criminal defense lawyer for legal representation.
One example would be a fight that begins on the street or in a tavern. One person attacks the other by throwing a punch. The other can hit back but is expected to stop if the attacker gives up or falls down. Continuing to hit or kick the person at this point to cause further injury will most likely be considered assault and battery.
A second example would be the legal acceptance of a person doing physical harm to another in defense of property. Great bodily harm is not allowed unless there is personal danger to the household residents or someone else who is on the property.
True Self-Defense
A relatively clear case of self-defense would be if a household resident shoots a burglar who was carrying a firearm. Shooting an unarmed vandal who is spray-painting graffiti on a fence may lead to a charge of assault with a deadly weapon or homicide.
Imperfect Self-Defense
One type of defense is legally known as imperfect self-defense. It occurs when someone had an irrational fear of being harmed by someone and attacked before the other person could do anything violent. A lawyer would need to provide strong evidence for the client actually experiencing this fear and the reason for it. A woman who had been sexually assaulted in the past, for instance, might strike out violently at a stranger who groped her during a music festival.
Using self-defense as a legal strategy is fairly common. Nevertheless, the situations can be very complex as the prosecuting attorney seeks evidence that the individual overreacted. Skilled representation by a defense attorney is imperative.


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James G McLarnon*
The University of British Columbia, Vancouver British Columbia, V6T1W3, Canada
Received date September 21, 2016; Accepted date October 18, 2016; Published date October 25, 2016
Citation: McLarnon JG (2016) Chemokine Interleukin-8 (IL-8) in Alzheimer's and Other Neurodegenerative Diseases. J Alzheimers Dis Parkinsonism 6:273. doi:10.4172/2161-0460.1000273
Copyright: © 2016 McLarnon JG. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Visit for more related articles at Journal of Alzheimers Disease & Parkinsonism
Interleukin -8 (IL-8), a member of the CXC chemokine family, is well-documented as an important chemotactic signaling factor for recruitment of neutrophils to sites of infection and damage. However in neurodegenerative disease such as Alzheimer's disease (AD), it is the resident macrophage cells, microglia, which are primary responding cells to brain insult such as deposition of amyloid β peptide. IL-8 exhibits an autocrine interaction with microglia by inducing a recruitment of the cells to specific sites of inflammation and subsequent increased production of the chemokine from activated cells. This positive feedback process thus has the capacity to amplify and sustain inflammatory response and brain neuroinflammation. The net result is that a localized and enhanced inflammatory response is induced by accumulating activated microglia at sites of inflammation serving to exacerbate inflammatory reactivity in AD brain. Importantly, under certain conditions the chemotaxis and subsequent activation of microglia may be deleterious to bystander cells including neurons. This review summarizes work from selected studies concerning the involvement and contributions of IL-8 mobilization from activated microglia to brain neuroinflammation as documented in the neurodegenerative diseases Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD).
Chemotaxis; Interleukin-8; Activated microglia; Alzheimer's disease; Neurodegenerative disease; Neuroinflammation
Chemokine responses constitute an early and integral response from microglial cells to changes in parenchymal microenvironment in brain. The spatial localization and activation of the resident microglia comprises an immune response to brain insults. In theory, the process to mobilize microglia serves as a feedback mechanism to preserve homeostatic conditions in brain. In reality, under certain conditions including ones associated with disease, the inflammatory microenvironment arising from accumulated and reactive microglia may be detrimental to the viability of bystander cells including neurons.
The chemokine IL-8 is well known as an inflammatory factor which induces a chemotactic response involving infiltration of neutrophils through the blood-brain barrier [1]. However, in various neurodegenerative diseases mobilization of neutrophils in brain parenchyma may be highly restricted due to minimal permeability of the cells through BBB (for one exemption see below for recent findings showing neutrophil extravasation into brain in an animal model of Alzheimer's disease (AD)). Thus in neurodegenerative disease mobilized microglia constitute the primary cells which mediate chemotactic responses to brain insults and alterations in brain microenvironment [2]. Importantly, activated microglias are a potent secretory source of IL-8 and express CXCR2 receptor for the chemokine providing a positive feedback mechanism for sustained amplification of inflammatory response [3].
As noted, although chemotactic response could confer neuroprotection, considerable evidence has been presented to suggest that microglial activation in neurodegenerative disease is associated with excessive localized brain inflammation and neurotoxicity [4,5]. Much data regarding the proinflammatory activity of IL-8 in neurodegenerative disease has come from studies on Alzheimer's disease (AD) brain and these results provide a focus for this review. One reason for the more comprehensive results in AD is due to the more frequent use of in vitro studies on IL-8 cellular interactions which are relatively lacking in other neurodegenerative diseases. In particular, as discussed below the patterns of IL-8 mobilization and signaling associated with stimulation of microglia in culture have been detailed under conditions relevant to AD brain.
This review also considers evidence for IL-8-mediated chemotactic response in other neurodegenerative conditions including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD).
Evidence obtained from in vitro studies on cultured human microglia suggests that IL-8 may play a relatively important role in promoting pro-inflammatory reactivity in AD. In one study a comprehensive microarray analysis was carried out on expression of a broad spectrum of factors following amyloid-beta (Aβ) treatment of cortical human microglia [6]. In excess of 100 genes were tested following microglial exposure to a low dosage of peptide (full length Aβ1-42 at 2.5 μM) including a number of pro-inflammatory chemokines and cytokines. Overall, chemokine family members demonstrated the highest induced gene expression relative to other inflammatory mediators. Of these, the expression of IL-8 showed the largest extent of upregulation (in excess of 10-fold compared with unstimulated cells) of the genes analyzed.
The production of IL-8 has been examined in cultured microglia obtained post-mortem from AD and non-demented (ND) individuals [7]. Microglial cultured cells were isolated from tissue samples obtained from superior frontal gyrus for both groups. The adult cells were immunoreactive for a host of microglial markers including major histocompatibility complex class II marker. In addition, cultured cells demonstrated chemotactic responses in vitro induced by Aβ deposits. Cultured microglias were incubated with different levels of Aβ1- 42 (range 10 nM to 10 μM). For both diseased and control human microglia, exposure to peptide increased levels of IL-8 in a dosedependent manner. This work [7] also reported full length Aβ induced upregulation of other chemokines and proinflammatory cytokines indicating peptide stimulation of aged microglia was associated with a spectrum of inflammatory mediators.
The effects of incubation of human fetal microglia with full length Aβ peptide (5 μM Aβ1-42 for 8 h) was studied on expressions of IL-8 and a panel of pro-inflammatory cytokines cytokines IL-6, IL -1β and TNF-α [8]. In addition, the effects of adding IL-8 together with Aβ1-42 on expression of the inflammatory mediators were examined. Application of Aβ1-42 alone was found to significantly increase the expressions of IL-8 and the pro -inflammatory cytokines relative to controls (unstimulated cells and cells receiving reverse Aβ peptide (inactive form Aβ42-1) treatment). However, if IL-8 was applied together with Aβ1-42 the expression of IL-8 and the pro-inflammatory cytokines was further enhanced suggesting that the chemokine amplified inflammatory reactivity induced by peptide. This work also reported the production of the cytokines was significantly enhanced with IL-8 treatment of Aβ1-42–stimulated human microglia compared with peptide application alone. Interestingly, IL-8 priming of human microglia had no effect to alter levels of the anti-inflammatory cytokines IL-10 and TGFβ1.
The neurotoxic effects of IL-8 have been directly examined with chemokine treatment of neuronal cultures [9]. IL-8 application was found to induce neuronal death which was associated with changes in pro-apoptotic proteins and inflammatory mediators. In the latter case increased levels of the matrix metallo-proteinases MMP-2 and MMP-9 were implicated in neurotoxicity.
Several studies have examined levels of IL-8 in AD and control individuals. Cerebrospinal fluid levels of IL-8 were found significantly elevated in patients with mild cognitive impairment (MCI) and individuals diagnosed with AD compared with age -matched controls [10]. The increased IL-8 in MCI individuals was noteworthy in that MCI may serve as a progression to AD; indeed one-half of MCI patients developed AD within 3 years [10]. Interestingly, MCI individuals showed no changes in the intactness of blood-brain barrier (BBB) as demonstrated by permeability of the barrier to albumin and immunoglobulin.
A number of cytokines and chemokines have been analyzed in brain tissue extracts from genetic forms of AD [11]. The results showed that levels of IL-8 and monocyte chemo-attractant protein 1 (MCP-1) were significantly increased in brain tissue derived from AD patients relative to controls. A more recent work has also reported that levels of IL-8 were considerably elevated in AD patients compared to non-demented controls [12]. Importantly, the increased levels of IL-8 showed a correlation with a reduced performance on cell cognition tasks.
At present, pharmacological testing for modulation of IL-8 signaling in AD animal models has not been examined in detail. In one study, pharmacological inhibition of CXCR2 receptor was examined in vivo following Aβ1-42 injection into rat hippocampus [13]. This animal model showed elevated expression of IL-8 and CXCR2 in peptideinjected rats compared to animals receiving vehicle or reverse peptide. Blockade of CXCR2 was effective in reducing microgliosis and was found to be neuroprotective. It was suggested that the neuroprotection conferred from block of IL-8 receptor could be due to a reduced microglial production of oxidative species.
Recent work has raised the interesting possibility that neutrophil migration may be involved in inflammatory response in AD brain. Using transgenic AD models, the extravasation of neutrophils into brain parenchyma to areas of amyloid plaques has been demonstrated [14,15]. At this time it is not known how IL-8 signaling contributes to the patterns of neutrophil infiltration in the AD animal models.
Huntington's disease (HD)
Inflammation in HD is characterized by microglial activation and migration of cells in response to abnormal mutant protein [16]. The use of positron emission tomography (PET) has shown activation of microglia as an early event in the pathology of HD [17]. Microglial activation also demonstrated both temporal and spatial correlations with neuronal damage and dysfunction. Importantly, microglial activation and brain inflammation was associated with the severity in the progression of the disease [18]. Increased levels of IL-8 have been reported in HD brain [19] and in post-mortem samples from HD patients [20]. In the latter work, the chemokine was found elevated in cortex and cerebellum in addition to striatum. A transgenic porcine model, using fragments of human huntingtin protein, has been used as an animal model of HD. Elevated levels of IL-8 (and IL-1β) were found in transgenic animals [21] with activated microglia producing the increased levels of the chemokine. Since IL-8 was increased in serum, it was suggested that the chemokine could have utility as a biomarker for immunopathology in HD [22]. At present, the effects of pharmacological inhibition of IL-8 signaling pathways has not been reported in animal models of HD.
Amyotrophic lateral sclerosis (ALS)
Levels of IL-8 (and MCP-1) were considerably increased in cerebrospinal fluid (CSF) and serum from ALS patients compared to controls [23]. The expressions of both chemokines were higher in CSF relative to serum. The authors suggested that the elevation in IL-8 was mediated by activated microglia leading to a pro-inflammatory cascade in ALS brain. Levels of cytokines and chemokines have been measured in peripheral blood samples taken from ALS patients and controls [24]. A number of inflammatory mediators including IL-8 exhibited significant increases in blood from ALS individuals. Importantly, levels of IL-8 were found to be correlated with progression of the disease. The findings from this work suggested levels of IL-8 could serve as a systematic biomarker for severity of disease. Analysis of lumbar puncture of CSF samples from ALS and controls has also identified IL-8 as a candidate biomarker for progression of the disease [25]. In another study IL-8 levels in CSF were compared between sporadic ALS patients and individuals with non-inflammatory disease [26]. Amounts of the chemokine were found to be significantly elevated in the ALS patients relative to controls and considerably higher in males compared to females. The results from this work suggested a prominent role for IL-8 in mediating neuroinflammation in ALS brain.
Parkinson's disease (PD)
A number of reviews have provided evidence for roles of neuroinflammation in the pathogenesis of PD [27,28]. Activated microglias in the substantia nigra of PD patients have been implicated as cellular sources of inflammatory reactivity. At present, few studies have examined levels of IL-8 in PD brain. In one work serum levels of the chemokine were measured in individuals diagnosed with idiopathic PD and in controls [29]. The results showed IL-8 concentrations were doubled in diseased brain compared with control; this difference in levels of the chemokine was significant. However, a contrary finding has recently been reported. Levels of IL-8 and cytokine TNF-α were found reduced in serum from Indian PD patients relative to controls [30]. Overall, despite the relevance of neuroinflammation in the pathophysiology of PD, data is lacking on roles of IL-8 and other chemotactic factors in the progression of the disease.
Neuroinflammation is a critical component in the pathogenesis of neurodegenerative diseases. Evidence suggests that activated microglia serve as a primary source for a host of inflammatory mediators which in assemblage can lead to neurotoxicity in inflamed brain. Mobilization of chemokine factors is a response to changes in brain homeostatic conditions leading to localized accumulation of reactive microglia at target sites. In particular, levels of the chemokine IL -8 are significantly elevated in neurodegenerative disease. The putative roles of IL-8-mediated chemotactic responses in neuroinflammation have been most extensively examined in AD brain. Evidence from in vitro studies relevant to AD, use of AD animal models and analysis of IL-8 levels in human brain suggest that resident brain microglia are the primary cell both responding to, and producing, the chemokine. Thus autocrine responses to brain insults from activated microglia include increased levels of IL -8 which contribute to a positive feedback process amplifying and sustaining inflammatory reactivity in AD brain. Localized and chronic microglial activation in response to Aβ deposits is associated with sustained cellular production of a milieu of inflammatory mediators including pro-inflammatory cytokines, reactive oxygen species and matrix metalloproteinases which in assemblage can cause abnormalities to blood vessels and neurotoxicity. Pharmacological modulation of IL-8 signaling pathways, including inhibition of CXCR2 receptor in microglia, is suggested as a clinical strategy to reduce chemotactic-dependent inflammation and provide neuroprotection in neurodegenerative disease.
Grants from Pacific Alzheimer's Research Foundation, Canadian Alzheimer's Society and Canadian Institute for Health Research have provided support for research on AD carried out in my laboratory. Many individuals have contributed to the success of in vivo and in vitro studies relevant to AD with special thanks to Jae K Ryu and Hyun B Choi for their expertise.
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The company says that 85 percent of its new menu will feature some kind of seafood protein, and that it will add more lobster into dishes such as the Lobster Scampi Linguini.
The change comes during what has been a tumultuous year for the restaurant chain, which was sold to private equity firm Golden Gate Capital for $2.1 billion in July. Its previous owner, Darden Restaurants, said it was unloading Red Lobster so it could focus on a turnaround effort for its other flagship brand, Olive Garden.
Now that Red Lobster is privately owned, it is not known whether its sales or customer traffic have improved since the ownership change. But the brand was facing major challenges before the split. In its last quarter as part of Darden's stable, Red Lobster's sales at established restaurants were down 8.8 percent. Darden executives said a variety of factors led to the slide. Clarence Otis, Darden's chief executive, told investors earlier this year that Red Lobster's surge of promotions became confusing to diners, especially those who came to the restaurant for special occasions. Darden has also said that Red Lobster was struggling to make inroads with millennial diners and high-earners.
It appears the new menu is one of the first major efforts at the new Red Lobster to lure customers back to its 700 restaurants across the United States and Canada.
The company promises the new menu will have lobster options at a variety of price points. For casual diners, it has added a Lobster Tacos option; for special occasion diners, there's now a Roasted Maine Lobster Bake. Meanwhile, the company is ditching items that weren't selling especially well. In most cases, those are the dishes that were far away from the company's seafood focus, such as a wood-grilled pork chop and chicken with portobello wine sauce.
Red Lobster is also aiming to make its menu easier for diners to navigate. Previously, its menu came as five different pieces; now, there will be just two pieces. The menu previously came in a text-heavy format, but has been re-styled to feature plenty of photos of the dishes.
"We heard in testing it helps people explore and find new favorites, and it helps them decide they want to try something new," said Danielle Connor, Red Lobster' senior vice president of menu and strategy.


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Tag Archives: interviews
Where I'll Be: Multiverse Con 2019
I'm the Industry Guest of Honor at the inaugural Multiverse, an Atlanta-based fan-focused convention celebrating science fiction & fantasy in all media, this October. The other guests of honor are Seanan McGuire and John Picacio, and the full list of … Continue reading
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On Writing: Building Connections
I had a wonderful time talking to Shaun Duke and Jen Zink of the Skiffy and Fanty Show last week. The podcast is up here. If you enjoy it and use iTunes, show them a little love with a rating on there.
A reason the interview wa so enjoyable was that they asked really interesting, incisive questions about the stories in Near + Far, in that way a writer desires and dreads at the same time, where they're seeing some of your psyche's underpinnings shaping the stories that you create. I've been mulling over some of those questions since then, and was thinking about one on the bus home the other day.
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Posted in near+far Tagged connections, interviews, jen zink, shaun duke, skiffy and fanty, writing, writing F&SF 2 Comments
Interviewed by Genevieve Valentine
To me one of the inevitable things about the intrusion of the fantastic is that it makes us rethink the everyday in a way that may provoke a similar conflict in our souls. The very best stories sock us in the gut and leave us gasping with realization that we almost missed a cathartic moment. Continue reading
Posted in Writing Tagged genevieve valentine, interviews, writing Leave a comment


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CHICAGO – Like many of you, I have been perusing the digital platforms, looking for the appropriate binge shows that will provide a temporary bit of sanity. Amazon Prime, for example, offers the entire series of "30 Rock" (2006-13), the seminal NBC-TV series created by and featuring Tina Fey.
HollywoodChicago.com Hookup: 35 Pairs of Passes to 'Criminal' With Kevin Costner, Ryan ReynoldsSubmitted by HollywoodChicago.com on April 11, 2016 - 9:40am
CHICAGO – In the latest HollywoodChicago.com Hookup: Film, we have 35 pairs of advance-screening movie passes up for grabs to the new crime drama "Criminal" starring Kevin Costner and Ryan Reynolds!


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It is characteristic of fairy tales to state an existential dilemma briefly and pointedly. This permits the child to come to grips with the problem in its most essential form, where a more complex plot would confuse matters for him.
Quote ID: 00006
Bruno Bettelheim
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Recipes and articles by Katie Morford
10 Recipes to Keep You HealthyBreakfast, lunch, dinner and snack recipes to nourish your body (and your soul)! Our nutrition editor hand-picked each recipe to help you stay as healthy as possible.
Week 4 Challenge: One Simple ChangeDon't let the idea of changing your habits overwhelm you! Little changes eventually add up to BIG changes, and we're excited to walk you through a few of our favorite lifestyle tweaks to help you feel more energized and happy this year.
Winter Chicken Salad with Tangy Miso DressingThis Chopped Chicken Salad is easy to put together and filling enough to eat for dinner! Made with fennel, mandarin oranges, avocado, and a flavorful miso dressing, it's perfect for winter but also endlessly adaptable to the seasons.
Week 3 Challenge: Intuitive EatingHello, week 3! We're ready for you! Today we're talking about intuitive eating (and food journaling), and how it can help us be more mindful of our cravings and what our body needs.
Week 3 Healthy Meal PlanWelcome to your Week 3 Meal Plan! This week we take the guesswork out of what to make for dinner with healthy recipes that are sure to inspire and satisfy!
Mini Flourless Chocolate Olive Oil CakesThese Mini Flourless Chocolate Olive Oil Cakes are do delicious and decadent, you might be surprised to see healthy ingredients in the recipe. They're gluten-free (thanks to the almond flour!) and made with olive oil instead of butter. And the flavor? So rich and satisfying.
Week 2 Challenge: Snack Smarter!This month we're pleased to welcome Katie Morford as part of our January Reset Challenge! Katie is a San Francisco-based cookbook author and registered dietitian who writes the blog Mom's Kitchen Handbook. She'll chat healthy snacks with us today! When…
Week 2 Healthy Meal PlanUsher in week 2 of the January Challenge with these 5 days of healthy family dinner ideas! From Black Rice Grain Bowls to Spicy Turkey Burgers, everyone in the family will find something to love here!
Mediterranean Mezze PlatterA mezze platter is an easy, fun, and family-friendly dinner! Use the ingredients listed as a starting point, with room to swap in other dips, vegetables, or fruits depending on what's in season and what you have on hand.
Easy MuhammaraMuhammara is the dip that's been missing from your life! This slightly-spicy spread is made with roasted red peppers, walnuts, and a touch of pomegranate molasses. It's great spread on a sandwich or served as a dip for veggies!
Healthy Eating Meal Plan Wk 1: Half Plate ChallengeStart the New Year off with a healthy meal plan for the WHOLE family! This week's meal plan is full of tips to help you feel your best and recipes that will keep you and your family full, satisfied, and ready to take on the day!
Healthy Shepherd's PieThis Healthy Shepherd's Pie calls for olive oil instead of butter, extra-lean ground beef, lots of vegetables, and a cauliflower-potato mash topping for a lighter take on the classic that's still FULL of flavor!


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Manchester City 'excited' at meeting defending champions Porto in Europa League
Roberto Mancini believes Manchester City's Europa League tie against Porto is the "toughest draw" his side could have had and says the fixture would not look out of place in the Champions League.
City have been paired with the competition holders in one of three mouthwatering last-32 ties for the remaining British sides, with Manchester United facing Ajax and Stoke City being drawn against Valencia.
Porto secured the trophy last year under the guidance of André Villas-Boas, the current Chelsea manager, and will host Roberto Mancini's side in the first leg before a return fixture at the Etihad Stadium.
The Portuguese champions finished third in their Champions League group behind Apoel Nicosia and Zenit St Petersburg while City were knocked out after trailing behind Bayern


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This course teaches you how to apply wigs, hair preps, cleaning, maintaining, and styling human and synthetic hair wigs, on both lace front or costume wigs. The knowledge from this course will give you the confidence to break into the Wig business!
May 25-29, 2020
1 week
Class Tuition: $900
Kit Fee: $100
Total: $1,000
Register by May 20, 2020
Intro to Theatrical Wig Dressing (1 Week)


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Thread: How noisy the spindle motor?
27-07-2009 #1
Does any one know the noise rating of a Kress in dBa @ m?
Is it any quieter than your average 1kw router?
It must depend on speed ...
Where the Light was kept during the Dark Ages
27-07-2009 #2
I have a Kress 800 and at position 1 or 2 which equates to 10,000 to 12,000 revs it bearable to work alongside.
Above that it starts to get noisy and flat out at 6, around 30 thou it's close to a router.
John S.John S -
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