Over the course of many posts that I have written on Roman Catholicism, Reformation, and Karl Barth — and especially on all three combined — it has sometimes been asked (or disputed), by Catholics and Protestants alike, if these subjects really have anything to do with each other. What point is there in talking about reforming Roman Catholicism? With its view of the authority of its tradition, what chance could there ever be of change? How is Karl Barth relevant to this? Even if he is relevant, what kind of reforming influence could someone outside the Catholic Church, a Protestant no less, possibly have? I have come across no better response to these questions than that which Donald W. Norwood provides in the introduction to his book entitled Reforming Rome: Karl Barth and Vatican II. In what follows, Norwood addresses each of these questions in turn: Why reform? Why Barth? How a Protestant influence on the Catholic Church?
At the end of the fourteenth century it was obvious that the church needed reforming. In the Great Schism, which began in 1378 and was not resolved until 1415, there were at first two rival claimants to the Papacy, on in Rome and the other in Avignon and later a third elected at Pisa. The Council of Constance was convened to deal with the crisis. The conviction had been growing that the only way to reform the church and the papacy was to call a Council. There was talk of the need to reform the church "in head and members." It was said then, and is still being said today, that too much power is centralized in Rome.
If, as Roman Catholics claim, Peter was the first bishop of Rome though not officially listed as the first pope, he too needed reforming. The Gospels make no secret of this. Later in a famous incident at Antioch, Paul would confront Peter "to his face" because, in Paul's view, Peter was clearly in the wrong giving in to the so-called Judaizers and not sharing table fellowship with Gentiles…. The story would continue to be aired, however, whenever there was discussion of infallibility. Peter and his successors might be wrong….
Partly for historical reasons associated with conciliarism and the Reformation, "reform" remains a controversial issue for many, though not all, Roman Catholics. As noted earlier, Pope John XXIII's gut reaction to Congar's book on reform was to ask "is such a thing possible?" Possibly to calm the fears of traditionalists who would automatically reject all talk of "reform," he chose to speak of the Council's work as aggiornamento, a lovely Italian word that tends to be translated according to the whims of the Council's interpreters! He would be pleased to read in a Council document published after his death and quoted by John Paul II in Ut Unum Sint (1995) that "Christ summons the Church, as she goes her pilgrim way, to that continual reformation of which she always has need." To such an admission, churches in the Reformed tradition would respond with a cheer…ecclesia reformata sed semper reformanda!
According to Pope Pius XII, Barth was the greatest theologian since Thomas Aquinas. This judgment is often quoted, but…nobody seems to know where and when the pope said this. Suffice to say, it remains repeatable because perfectly plausible. Nor was Pius the only pope to appreciate Barth. It was obvious to Barth on his visit to Rome that Pope Paul VI had read some of his books…. Pope Benedict in his Commentary on Vatican II acknowledges Barth's influence on documents about Divine Revelation and the Church in the Modern World. Unlike the sixteenth-century Reformers who were confronted by popes who were for the most part theologically illiterate and inaccessible, Barth would have been able to have a serious theological discussion with Pius XII and his successors and did so with Paul VI and with Joseph Ratzinger, once a theology professor in Germany, later Pope Benedict XVI….
We must choose Barth for our partner because in him Protestantism has found for the first time its most completely consistent representative. He embodies a Protestantism that can only be reached by going back to its roots, its deepest sources: to Calvin and Luther…. We have in Barth, then, two crucial features: the most thorough and penetrating display of the Protestant view and the closest rapprochement with the Catholic….
How Can One Who Is Not a Roman Catholic Assist the Reform of Rome?
A short answer might be "with great difficulty!" But a longer and more carefully considered reply is that for most of the the twentieth century and, perhaps, still today it can be harder for a Roman Catholic theologian to promote reform. Rome resents dissent. Her bishops and theologians are expected to toe the line. Prior to Vatican II and continued in the long reign of Pope John Paul II and Cardinal Ratzinger, most of Rome's more radical and ecumenical theologians were at one time silenced or forced into exile…. Dissent was not possible within the Roman Catholic communion. It could not be prevented outside. No one, not even Hitler, could silence Karl Barth! And as I have noted already, a lot of prominent Roman Catholics including four popes, Pius XII, Paul VI, John Paul II, and Benedict XVI, came to appreciate that this "separated brother" had a gospel to proclaim. They listened.
What is more, by the time of Vatican II Rome was actually asking non-Roman Catholic theologians like Barth to contribute to the process that Pope John called aggiornamento…. A very distinguished group of non-Roman Catholic participant observers and Roman Catholic experts were actually being asked to help Roman Catholic bishops from all over the world take counsel together in the processes of bringing the church up to date, being reformed and renewed and moved toward the restoration of unity. Only those "inside" the Roman Catholic Church, and indeed, only the hierarchy of the pope and the bishops could decide what teachings or "reforms" should be promulgated and hopefully implemented, but those "outside" were being asked for their opinions. They helped the Roman Catholic Church to change.
So to recapitulate: Why reform? Because Roman Catholicism needs reformation as much today as it did in the sixteenth century (to say nothing of the centuries prior!). Those wanting to be faithful to the legacy of the Reformers cannot neglect to hope, pray, and work for this without betraying the very tradition that they purport to preserve. Why Barth? Because he occupies a unique place among Catholic and Protestant theologians alike in that he is regarded by many on both sides of the divide as one of the greatest doctors of the church universal and, for this reason, as the precursor of a way for rapprochement where possible and reform where necessary. How a Protestant influence on Catholicism? Because sparking reform (specifically theological reform) from the inside of the Catholic Church is extremely difficult (if not impossible), but inspiring reform from the outside is not inconceivable, as Barth's noted impact on Vatican II illustrates.
This is why I have written on these topics, and it is why I will continue to do so.
 Donald W. Norwood, Reforming Rome: Karl Barth and Vatican II (Grand Rapids; Cambridge: Eerdmans, 2015), pp.6-7, 11-12, 14-15, 23-24.


The Foundationism Ring was inspired by J. Michael Straczynski's concept of the religion of Foundationism (from Babylon 5), a quest for the common features of all religions. Any site which promotes the perennial philosophy is welcome. The photograph above, and on the navigation bar, is of actor, Richard Biggs (a.k.a. Dr. Stephen Franklin). Please note: Neither Mr. Straczynski nor Mr. Biggs have any connection with, nor have they endorsed, the Foundationism Ring.
This ring is dedicated to the proposition that religion is a laughing matter. There is nothing sacred.
All about Saint Chicken Adolfius Luva and the miracles he has performed. This webring is in memory of September 11th. "I'm proud to be an American where at least I know I'm free"
Explaining the new true way of living...Be the Duck!
This is where irreverence and spirituality meet. Some of these sites are sincerely spiritual, while others exist only to poke fun at religion and religiosity. You decide which is which.
War is bad. Satan is bad. Therefore war is Satan. Satan has green fingernails. My turtle has green fingernails. Therefore my turtle is Satan. Thus the violet of Jupiter is definitely religious and creative, while at the end of the scale the red of Mars is physical, violent and gross. Although the inner breath is a potent means of transformation, contacting it may be difficult at times. The surest refuge in the world is the freedom of our being.
This webring is dedicated to the benign and wise, all-knowing Leader. He is dedicated to the following principles: Non-breeding; Hating minivans; Drinking Beer; and being an all-around nuisance to religious fundamentalists. HUZZAH! Be well. Drink Beer.


"Stuffed" sweet potatoes with ground turkey and spinach. Not the prettiest, but nutritious and tasty. #januarywhole30 #cook90 and yes, I threw in a handful of dried cranberries because I didn't make the one I really wanted with apples, peppers, cranberries and bacon.
So fragrant and yummy. Tonight's #cook90 dinner is green Thai curry. I used #thaikitchen green curry paste and organic coconut milk (unsweetened) with 1/2 lb or so of chicken breast and a quick cheat of frozen stir fry veggies (#januarywhole30 compliant). Cooks up in about 30 minutes.
I'll come back and update the post with pictures and recipes.


529 members have decided to share their profiles only with other members of PatientsLikeMe.
Advice & Tips: I take ½ a pill only when I feel nervous, tense, etc.which amounts to maybe twice a month or less. Calming. No I moact on daily life because I don't take it daily. Don't want to become addicts.
Advice & Tips: For some reason (possibly a side effect of the Lyrica, possibly just fibro) I sometimes wake in the night with a burning desire to stretch everything, and when I stop stretching any muscle it insists of being stretched again. I writhe on the bed and it's torturous. The valium does wonders for getting my muscles to chill out and has the added benefit of helping me fall (back) asleep.
Advice & Tips: I take it when I need help with my suicidal ideation. It does help, but I have then tired afterward.


The beginnings of Avon can be traced back to 1886 when door-to-door salesman David McConnell decided to sell perfumes to New Yorkers instead of books. Now a leading global beauty company, Avon products are available in over 100 countries. The product line includes colour cosmetics, skin care, fragrance, and fashion and home products.


Misaquamicut Beach is one of Rhode Islands' largest beach attractions, it fills ups fast during summer months, drawing people from the local area and neighboring states. The soft sand has areas of pebbles; the waves are large which can be difficult for children or older adults although the entry to the water is easy with a mild descent.
Available on-site; price varies by time of day, weekday or weekend, and in-state of out of state, $14-$28. Electric vehicle charging is available.
A carry in/carry out beach with a concession stand is on-site. Additional food vendors are available within 5 minutes' driving.


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Q: Benefits from importing UIKit.UIViewController instead of importing the whole framework I have noticed that it is possible (in Xcode 12, at least) to do:
import UIKit.ViewController

class ViewController: UIViewController {}

Up until now I have always done import UIKit.
Does someone know which benefits one has from importing only the class? Does the app build/compile faster?
Thanks

redpajama_set_name: RedPajamaStackExchange


It has certainly been a long time since I have read a horror and this certainly didn't disappoint. It was a nice change from the chick – lit and other genres I seem to be reading recently. This was fast paced, edge of seat, gripping, and sometimes disturbing, but in my opinion it's not a good horror if you haven't got something sick, twisted and disturbing lurking around.
Obviously teen vampires and Dracula etc have been done to death but this was a whole new take on a vampire story. This is set in the time of werewolves and vampires in Transylvania. But definitely not in the traditional sense. Wonderfully written and didn't hang around, you were quickly transported to the next scene and character.
We are introduced to a lot of characters, each and every one of them very different and for that reason it is very difficult to single any of them out. With Anton, I felt there was always something bubbling beneath the surface. Milosh, I wasn't a fan of, but for me it's the sort of person he is. Irina, a bit sick and twisted, always trying to seduce the men in her life and others. Quintz, quite comical if you ask me and the list of characters goes on and on….
I really enjoyed this welcome change and would certainly recommend it to others that like reading horror. I'm looking forward to the next instalment and can't wait to pick it up. No spoilers as normal, but there's certainly one hell of a twist in it too!
I'm going to give this book a well deserved 4/5 rating.
Please do go and check out the other blogs on this tour for their amazing content!


In this section, you create an Amazon Lex bot (BookTrip).
On the Bots page, choose Create.
Leave the default bot name (BookTrip).
The console shows the BookTrip bot. On the Editor tab, review the details of the preconfigured intents (BookCar and BookHotel).
From the initial user input ("Book a hotel"), Amazon Lex infers the intent (BookHotel). The bot then uses the prompts preconfigured in this intent to elicit slot data from the user. After user provide all of the slot data, Amazon Lex returns a response back to the client with a message that includes all the user input as a message. The client displays the message in the response as shown.
Now you continue the conversation and try to book a car.
There is no user data validation at this time. For example, you can provide any city to book a hotel.
You are providing some of the same information again (destination, pick-up city, pick-up date, and return date) to book a car. In a dynamic conversation, your bot should initialize some of this information based on prior input user provided for booking hotel.
In this next section, you create a Lambda function to do some of the user data validation, and initialization using cross-intent information sharing via session attributes. Then you update the intent configuration by adding the Lambda function as code hook to perform initialization/validation of user input and fulfill intent.


In response to customer feedback and just in time for summer, Starbucks has added more protein, fruits and vegetables to the company's grab-and-go lunch menu. The top customer requests asked for protein-packed options, chicken and turkey raised without antibiotics, and more fruits and vegetables.
Inspired by the popular Protein Bistro Box, Starbucks now offers six Protein Boxes for customers to choose. The new Starbucks Protein Boxes are an excellent source of protein with at least 20 grams of protein per box and feature chicken and turkey raised without antibiotics and include at least one cup of fruits and vegetables combined.
Starbucks offers additional protein-rich food and beverage options in stores across the U.S.


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Home » Paranormal Investigations
Tag: Paranormal Investigations
Posted inHistorical Mysteries
Teddy Roosevelt's Bigfoot Sighting
The story of Teddy Roosevelt's alleged encounter with a Bigfoot-like creature has been passed down through generations, and it remains one of the most intriguing and debated cryptid sightings to date.
Teddy Roosevelt was an American statesman, conservationist, and writer who served as the 26th President of the United States from 1901 to 1909. He is well-known for his love of the outdoors, and his numerous hunting and camping trips throughout his life. One of the most famous and well-documented of these trips took place in the fall of 1903, when Roosevelt, along with a group of friends, embarked on a hunting expedition in the remote forests of Montana.
Teddy Roosevelt's Bigfoot Encounter
According to the legend of Teddy Roosevelt's Bigfoot Sighting, while on the hunting trip, Roosevelt and his party stumbled upon a large, ape-like creature. The creature, which Roosevelt described as being covered in dark fur and standing at least 7 feet tall, reportedly stared at the group for several minutes before running off into the woods.
The exact details of Teddy Roosevelt's Bigfoot sighting have been passed down through the years, with different accounts varying slightly. However, most accounts agree that the creature was first spotted by one of the guides in Roosevelt's party, who pointed it out to the others. Roosevelt himself reportedly described the creature as being "a monstrous creature, unlike anything I have ever seen before." The President and his party were said to have been shocked and amazed by the creature, with some members even claiming that it walked on two legs like a human.
The cryptid was said to have stared at the party for several minutes before turning and running away into the woods. Roosevelt and his companions reportedly followed the creature for a short distance, but it quickly disappeared into the dense forest. The President himself was said to have been so intrigued by the sighting that he ordered an immediate search for the creature, but it was never found.
Some accounts claim that Roosevelt and his party were able to get a good look at the creature, while others suggest that it was only visible for a brief moment before it disappeared into the woods. Some versions of the legend even suggest that the creature was able to elude the President and his party, despite their best efforts to track it. Regardless of the specifics, it is agreed that the encounter left a deep impression on all those involved, and that it was unlike anything they had ever encountered before.
The story of Teddy Roosevelt's Bigfoot sighting was not made public until many years later, when one of the members of the hunting party, a journalist named John L. Robinson, wrote about it in a magazine article. In the article, Robinson described the creature as being "a huge, dark, hairy beast," and stated that the President had ordered an immediate search for the creature in the wake of the encounter. The article generated a great deal of interest and speculation, and the story of Teddy Roosevelt's Bigfoot encounter quickly became a popular topic of discussion among cryptozoologists and skeptics alike.
The Debate over the Bigfoot Sighting
Despite the intriguing nature of Teddy Roosevelt's Bigfoot sighting, the existence of a Bigfoot-like creature in Montana remains a topic of debate among cryptozoologists and skeptics alike. Some argue that the creature could have been a bear or another known animal, while others believe that it was a genuine Bigfoot sighting.
Skeptics point out that there is no physical evidence to support the story, and that the creature could have easily been misidentified. They also point out that Roosevelt and his party were in the wilderness for several weeks, and it is possible that they may have been experiencing hallucinations or other symptoms of wilderness fatigue.
On the other hand, proponents of the Bigfoot theory argue that the fact that the story was related by a reputable and respected individual such as President Teddy Roosevelt lends credibility to the account. They also point out that the description of the creature, as well as the behavior and movements reported by the witnesses, align with what is known about Bigfoot from other reported sightings.
Another argument in favor of the Bigfoot theory is the fact that the area where the Teddy Roosevelt's Bigfoot sighting is said to have taken place, the remote forests of Montana, is known to be a hotspot for Bigfoot sightings. In fact, there have been numerous other reported sightings in the region over the years, further lending credence to the idea that a population of the creatures may exist in the area.
Conclusion to Teddy's Bigfoot Sighting
While the truth behind the legend of Teddy Roosevelt's Bigfoot sighting may never be fully known, the story continues to capture the imagination of people all over the world. It serves as a reminder that despite our modern technology and advancements, there are still vast wildernesses and unknown creatures that may exist beyond our current understanding. The possibility of the existence of such creatures sparks a sense of wonder and curiosity in us, leading to ongoing searches and investigations.
Even if the encounter did not truly take place, it serves as a reminder of the enduring human fascination with the unknown and the possibility that there may still be mysteries waiting to be discovered in the natural world. The legend of Teddy Roosevelt's Bigfoot sighting serves as a reminder that the world is not yet fully explored and that there are still many secrets to be uncovered. It is this sense of mystery and the unknown that keeps us searching for answers and fuels our curiosity about the world around us.
For more information on Teddy Roosevelt, see the Harvard collection.
Posted inParanormal Tutorials
Joining a Paranormal Research Group
How Manipulated UFO Evidence is Created
Ghost Hunting Bedford-Stuyvesant
Is Brooklyn Academy of Music Haunted?
by Anthony L January 4, 2023 January 11, 2023
Ghost Hunting Windsor Castle with the Royal Family
Inside The Haunted 'Ghost Towers' Of Ho Chi Minh City
Grand Canyon Ancient Underground City: Real or Hoax?
Types of UFOs
Understanding Hypnosis

redpajama_set_name: RedPajamaCommonCrawl


Park Avenue Clemenceau is one of the Singapore serviced apartments that enjoys an excellent location – strategically situated near the waterfront of the Singapore River. It is well connected by public transportation network and close to the main shopping belt, Orchard Road. The Fort Canning MRT Station (Downtown Line) and Clarke Quay MRT Station (North-East Line) are within walking distance.
This 150-serviced apartment comprises 94 one-bedroom units, 46 two-bedroom units, 2 three-bedroom units, as well as 2 four-bedroom units and 2 penthouse units.
The guests will enjoy the best in luxury living, curated to meet the needs of international travellers, and will indulge in modern comfort with a city view where every day brings new surprises in the most delightful ways. The vicinity offers a wide range of dining and entertainment options, a perfect choice for executives looking for long stay.


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Home / News / Exotics Month
Exotics Month
New SSC Supercar Leaked, Reveal Coming Later This Month
Nelson Ireson September 6, 2010
The Bugatti Veyron Super Sport has once again put the Volkswagen Group's French marque back at the top of the fastest production car charts with its recent 268-mph record, but within days Shelby Supercars (SSC) announced it would be once again gunning to top Bugatti. We already know that SSC's new model will be revealed this month, and now an image of what could possibly the world's next fastest production car has been leaked. SSC was quietly building some of the most extreme vehicles on earth until it leapt onto the global stage by topping the original Bugatti Veyron's record-setting...
Another Day, Another 2010 Ferrari 458 Italia Crashes
Warning--this is not a joke. Less than a week after reporting about the ninth wrecked 2010 Ferrari 458 Italia (the first on U.S. soil), comes news of yet another damaged example, this time in the Czech Republic. While the damage on this latest car is not as severe as previous incidents, it is still...
Viknesh Vijayenthiran August 24, 2010
First Drive: 2010 Aston Martin V12 Vantage
Coming straight out of a two-hour stint in the Ferrari 458 Italia and jumping into just about anything else, you expect to be...underwhelmed. Not so with the Aston Martin V12 Vantage. Though it takes a very different route, the big-engined baby Aston is, in its own way, even better. Take Aston...
Nelson Ireson August 19, 2010
2010 Aston Martin V12 Vantage First Drive Preview
We're saving the write-up for tomorrow, but we thought we'd share some photos from the drive with you today.
Guy Rents 2010 Ferrari 458 Italia, Then Crashes It
Only yesterday we reported that too many 2010 Ferrari 458 Italia supercars have been written off, either due to careless drivers crashing them or the cars themselves spontaneously combusting. We even saw one of the rare beauties suffering a crash just one day after leaving Ferrari's factory in...
Pebble 2010: Microbrands And Other Cars
There's more to see at Pebble than the Bugattis and Ferraris, though these representatives have few constituents. From the odd to the outstanding, and occasionally both at once, these cars represent the happy oddballs of one of the world's most important concourses. This 1958 Facel Vega Excellence...
Pebble 2010: A Fistful Of Ferraris
There are so many simply beautiful Ferraris at Pebble Beach it's hard to pick any as a favorite, but these are some that caught our eye.
Video: 2010 Ferrari 458 Italia Crashes One Day After Leaving Factory
In the short time that the new 2010 Ferrari 458 Italia has been on sale we've already managed to see at least one crashed example and hear about two other causalities, as well as see an additional two examples go up in flames. Now, we have a video showing yet another 458 Italia suffering from the...
August Is Exotics Month At Motor Authority
Get ready for a month of some of the hottest cars on the road.
Pebble 2010: Alfa Romeo, Fiat Don't Need No Stinkin' Ferraris
These Italian cars prove Ferrari isn't necessarily the master of the concours.
Pebble 2010: A Miller for the Ages
In a past life, I wrote about the Miller 91 that Car and Driver editor Karl Ludvigsen found in a dank barn in France, and brought to the U.S.--and later saw installed in the National History Museum. Today, it's another spectacular Miller that made its way to the 2010 Pebble Beach Concours...
Martin Padgett August 16, 2010
Pebble 2010: Morgan Eva GT Live Photos
Along with the Bugatti Veyron Super Sport, we've brought you all the details of the new Morgan EvaGT as they've trickled out over the Internet in the past few weeks. Today, at the 2010 Pebble Beach Concours' concept-car lawn, we were able to lens the tradition-breaking EvaGT for the first time...
Pebble 2010: Mercedes-Benz 500K
While Mercedes-Benz made a show of its own with a massive gathering of its 2010 SLS AMG sportscar, it also found a place of honor on the lawn at the 2010 Pebble Beach Concours d'Elegance with this near-perfect 1930s roadster. Shown for the first time at the 1934 Berlin Motor Show, this Mercedes-Benz 500K has all the hallmarks of a Pebble Beach champion, from elegant and perfect chromework, to a classic pedigree among the very finest. Though it didn't win the competition, the 500K drew constant crowds with its extravantly tapered shape and yards of linear chromework. The 500K--meaning a...
Pebble 2010: Ghia, In All Its Glory
Design studios rarely receive the kind of comprehensive museum treatment of established car brands. It's no easy thing to assemble a cohesive group of cars that eventually were sold by different car companies, each with a different purpose in mind. As one of the honored marques at this year's...
Pebble 2010: Bugatti Veyron Super Sport
We've told you all about the Bugatti Veyron Super Sport in previews earlier this month, but at today's 2010 Pebble Beach Concours d'Elegance, we grabbed our first live photos of the world's new record holder for production-car top speed. Bugatti introduced the car on Saturday at The Quail 2010...
Pebble 2010: 1937 Bugatti 57S Atlantic
The Bugatti 57S Atlantic was, in many ways, ahead of its time. Even now, over 70 years later, it features elements just beginning to make their way into the average passenger car, such as aluminum body panels. This example, on display this weekend at the 2010 Pebble Beach Concours d'Elegance...
Pebble 2010: 2011 Bentley Continental GTC And GTC Speed 80-11 Editions
The Bentley Continental range is starting to get a little long in the tooth, having been on sale in its current form since 2003. Despite this, Bentley is milking the most out of its Continental range for the 2011 model year, releasing two more special editions based on the Continental GTC and GTC...
All-Aluminum Morgan EvaGT Revealed
From the hydrogen-powered LIFEcar concept to the Aero SuperSports to its history of wood-framed cars, Morgan spans an incredible variety of technology and aims with its cars, all wrapped in a classically-styled package. For this month's 2010 Pebble Beach Concours d'Elegance, Morgan is turning its...
Quail 2010: Odds And Ends Gallery, Part Two
Who needs a reason to look at photos of collectible, unique, rare, or storied racing and sports cars? We sure don't. So we won't give you one this time around. If you've enjoyed these peeks through our lens of the many brilliant bits and pieces of the Quail gathering, hang on for a roundup of the best of the rest from Pebble Beach proper over the next few days--in addition to our ongoing live coverage from the event. Bonus points if you can name the cars from their detail shots.
Quail 2010: Odds And Ends Gallery, Part One
There are so many cars, so many objects of lust and art packed into California's central coast this weekend that it's simply too much to cover it all in detail. But ogling can be just as fun even if you don't know the name of the ogle-ee. Even this gallery contains just a sampling of the hundreds...
Pebble 2010: Picnicking On The Concept Lawn With Rolls-Royce
Back in July we brought you the full details on Rolls-Royce's bespoke picnic set for the Phantom, and today we snapped live photos of the car and kit in what may be their native environment: the concept lawn of the 2010 Pebble Beach Concours d'Elegance. The extramuros eating ensemble is even more...
Pebble 2010: Lotus Exos Type 125
The Lotus Exos Type 125 is a formula-style consumer track car.
Pebble 2010: McLaren MP4-12C Live Images
The McLaren MP4-12C made its North American debut this weekend in Pebble Beach, following it up with an appearance on the concept lawn at the lodge. Though cordoned off behind taunting white plastic chains on the putting green, we still managed to snag a few shots for your viewing pleasure. In case...
Quail 2010: Shelby Mustang Mania
With a frail Carroll Shelby at the helm, The Quail 2010 paid homage to some of the greatest Mustangs in history on Friday. And if you've never seen a 'Stang older than the 2011 BOSS 302 we brought you yesterday, the Quail's collection of pony cars provided an instant history lesson. Paired with...
Walter Röhrl walks us through the top 5 Porsche rally cars of all time
2020 Audi Q5 and A8 are ready to plug-in to America
Nissan celebrates every generation of Z sports car by gathering them on one track


In most tissues of the body, cellular ATP production predominantly occurs via mitochondrial oxidative phosphorylation of reduced intermediates, which are in turn derived from substrates such as glucose and fatty acids. In order to maintain ATP homeostasis, and therefore cellular function, the mitochondria require a constant supply of fuels and oxygen. In many disease states, or in healthy individuals at altitude, tissue oxygen levels fall and the cell must meet this hypoxic challenge to maintain energetics and limit oxidative stress. In humans at altitude and patients with respiratory disease, loss of skeletal muscle mitochondrial density is a consistent finding. Recent studies that have used cultured cells and genetic mouse models have elucidated a number of elegant adaptations that allow cells with a diminished mitochondrial population to function effectively in hypoxia. This article reviews these findings alongside studies of hypoxic human skeletal muscle, putting them into the context of whole-body physiology and acclimatization to high-altitude hypoxia. A number of current controversies are highlighted, which may eventually be resolved by a systems physiology approach that considers the time-or tissue-dependent nature of some adaptive responses. Future studies using high-throughput metabolomic, transcriptomic, and proteomic technologies to investigate hypoxic skeletal muscle in humans and animal models could resolve many of these controversies, and a case is therefore made for the integration of resulting data into computational models that account for factors such as duration and extent of hypoxic exposure, subjects' backgrounds, and whether data have been acquired from active or sedentary individuals. An integrated and more quantitative understanding of the body's metabolic response to hypoxia and the conditions under which adaptive processes occur could reveal much about the ways that tissues function in the very many disease states where hypoxia is a critical factor.
In oxidative tissues of the body, production of cellular energy, in the form of adenosine triphosphate (ATP), occurs primarily via the process of oxidative phosphorylation at the inner mitochondrial membrane. In order to sustain normal cellular function, therefore, the mitochondria require a constant supply of fuels and oxygen (Figure 1). In diseases where oxygen delivery to the peripheral tissues is impaired, through hypoxemia (for example, chronic obstructive pulmonary disease (COPD), cystic fibrosis), decreased oxygen carriage capacity (for example, anaemia), or decreased convective transport (for example, shock, heart failure), or in healthy individuals at altitude, a process of adaptation must occur to maintain cellular energy homeostasis. A compromise in cellular energetics can lead to more rapid fatigue in exercising skeletal muscle, since both crossbridge cycling at the sarcomere during contraction and calcium reuptake to the sarcoplasmic reticulum during relaxation are heavily dependent on ATP hydrolysis. Moreover, in cardiac muscle, energetic impairment has been associated with the pathogenesis of hypertrophic cardiomyopathy and sudden cardiac death .
Mitochondrial energy metabolism. Fatty acid β-oxidation and the TCA cycle produce NADH and FADH2, which are oxidized by complexes I and II, respectively, of the electron transport chain. Electrons are transferred through the chain to the final acceptor, O2. The free energy from electron transfer is used to pump H+ out of the mitochondria and generate an electrochemical gradient, ΔμH+, across the inner mitochondrial membrane. This gradient is the driving force for ATP synthesis via the ATP synthase.
The study of how healthy human subjects acclimatize to high altitude is a useful model in which to investigate hypoxic adaptation in the absence of the many confounding factors associated with hypoxic disease states and therapeutic interventions . Indeed, many common features have been noted between COPD in particular and altitude exposure, including similar patterns of muscle wasting, weight loss, and altered cellular metabolism [3, 4]. Individual variability in the process of hypoxic adaptation and performance has been identified in healthy individuals at altitude , and similar mechanisms may therefore underlie the observed variations in disease progression and outcome in patients where cellular hypoxia is an important feature, in particular severe respiratory and cardiac disease and critical illness .
Physiological adaptations that can improve oxygen delivery in hypoxic individuals are well documented and include increased ventilation rate and cardiac output, erythropoiesis, and possibly enhanced vascularization of tissues . At altitude, however, despite normal oxygen content and delivery up to 7,000 m above sea level , exercise capacity is dramatically reduced, and inter-individual variation in oxygen content does not correlate with exercise capacity . These findings support an important role for adaptive responses to a low arterial oxygen (O2) partial pressure at the tissue level. In the hypoxic myocyte, adaptations might aim to improve local O2 delivery by redistributing mitochondria within the cell to minimize O2 diffusion gradients; to limit ATP utilization by switching off non-essential cellular functions; or to enhance ATP synthesis.
The master regulator for many of the body's adaptive responses is hypoxia-inducible factor 1 (HIF-1), a heterodimeri transcription factor comprising HIF-1α and HIF-1β subunits . HIF-1α protein is continuously synthesized, and is predominantly regulated post-transcriptionally by the O2-dependent hydroxylation of two proline residues by the prolyl-hydroxylase enzymes (PHD1-3). Hydroxylation promotes binding of the von Hippel-Lindau protein (VHL), leading to ubiquitination and proteasomal degradation [9, 10]. HIF-1α protein is thus stabilized in low concentrations of O2, and accumulates spontaneously in the hypoxic cell . HIF-1β is constitutively present in the nucleus, and when dimerized with HIF-1α is able to bind to hypoxia response elements (HREs) in the regulatory region of a number of genes , thereby activating their transcription (Figure 2). The levels of HIF-target genes are therefore precisely controlled in response to cellular O2 concentrations, and include those associated with improving O2 delivery to muscle, such as vascular endothelial growth factor (VEGF) and erythropoietin (EPO) , and many metabolic enzymes or regulators of metabolism, including all glycolytic enzymes, pyruvate dehydrogenase kinase 1 (PDK1), and subunit 4-2 of mitochondrial cytochrome c oxidase (COX).
Mechanisms of hypoxic adaptation. (a) In normoxia, hypoxia inducible factor-1α (HIF-1α) is degraded, following O2-dependent hydroxylation by prolyl hydroxylase (PHD) enzymes. (b) In hypoxia, HIF-1α spontaneously accumulates and combines with HIF-1β in the nucleus to activate the transcription of hypoxia-responsive genes and driving a number of metabolic adaptations: (i) BNIP3 upregulation leads to mitochondrial autophagy; (ii) a subunit switch at cytochrome c oxidase (COX), complex IV of the electron transport chain, increases the efficiency of electron (e-) transfer, and attenuates reactive oxygen species (ROS) production; (iii) glycolytic enzymes and lactate dehydrogenase (LDH) are upregulated, increasing anaerobic ATP production and lactate; (iv) pyruvate dehydrogenase kinase (PDK) enzymes are upregulated, de-activating pyruvate dehydrogenase (PDH) and limiting the conversion of pyruvate to acetyl CoA.
Mitochondrial volume density is consistently and substantially decreased in the skeletal muscle of climbers acclimatizing to high altitude [12, 13], and was found to be lower in the muscles of Himalayan Sherpas than those of unacclimatized lowlanders . Prolonged exposure to altitude is also associated with accumulation of lipofuscin in skeletal muscle , a lipid peroxidation product that may be indicative of mitochondrial damage. Similarly, mitochondrial respiratory capacity is attenuated in the hearts of rats housed in hypoxia chambers , limiting total oxidative capacity. The primary mechanism driving the loss of mitochondrial density is likely to be mitochondrial autophagy, brought about by a HIF-1-dependent upregulation of the pro-apoptotic protein BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) , which localizes on mitochondrial membranes [11, 17] (Figure 2(i)). In rat hearts, BNIP3 levels were induced after one hour of hypoxia, and were found to integrate into the mitochondria of hypoxic ventricular myocytes, leading to mitochondrial defects associated with opening of the permeability transition pore, hence causing loss of inner membrane integrity .
A further mechanism that restricts mitochondrial respiration in response to hypoxia was elucidated in a renal cancer cell line, where HIF-1-dependent repression of c-Myc decreased expression of the downstream factor peroxisome proliferator-activated receptor γ co-activator-1β (PGC-1β) . PGC-1β, and its homolog, PGC-1α, are abundant in skeletal muscle and stimulate mitochondrial biogenesis via the activation of a number of transcriptional pathways [20, 21]. Overexpression of PGC-1α in mouse skeletal muscle leads to a proliferation of fatigue-resistant type I muscle fibers . Muscle wasting is common in patients with COPD, and studies have frequently reported a preferential loss of the mitochondrial-rich type I and type IIa fibers, with a sparing of glycolytic type IIb fibers , which have an enhanced capacity for anaerobic metabolism. In climbers at high altitude, a similar degree of muscle wasting also occurs , and has been thought to contribute towards an increased muscle capillary density, although increased vascularization has not always been reported . Unlike COPD patients, however, muscle wasting at altitude does not appear to be associated with the preferential loss of any particular fiber types . Moreover, although a switch in skeletal muscle fiber type towards more glycolytic fibers could theoretically be driven by decreased transcriptional activity of the PGC-1 cofactors, a measurement of decreased PGC-1α levels in a muscle biopsy could in fact be secondary to a loss of the type I fibers in which they are more highly expressed.
An additional related mechanism that might restrict mitochondrial biogenesis in hypoxic skeletal muscle at altitude involves the downregulation of protein synthesis in response to energy deprivation. The AMP-activated serine/threonine protein kinase (AMPK) is a molecular energy sensor that is activated when cellular ATP levels fall, for example, during stresses such as nutrient deprivation and hypoxia . Elevation of AMPK activity thereafter leads to modulation of multiple pathways in order to restore energetic homeostasis, typically involving suppression of biosynthesis and cell growth while stimulating ATP synthesis . One major downstream element negatively regulated by AMPK is the mammalian target-of-rapamycin (mTOR) pathway, which regulates cell growth via activation of protein synthesis , and, along with PGC-1α, is a necessary component of a transcriptional complex controlling mitochondrial oxidative function . In the skeletal muscle of lowlanders acclimatized to 4,559 m, levels of mTOR were decreased , possibly indicating a suppression of mitochondrial biogenesis via downregulation of PGC-1α transcriptional activity; however, the mechanism is almost certainly more complex than this since AMPK itself activates mitochondrial biogenesis by upregulating PGC-1α expression  in order to enhance skeletal muscle ATP production . It is probable, given the profound loss of mitochondrial density at altitude, that the suppression of biogenesis via mTOR downregulation is the more dominant of these stimuli in hypoxic skeletal muscle; however, the consequent effect on cellular energetics both at rest and during exercise remains to be determined.
It is likely that the loss of mitochondria in hypoxic skeletal muscle is an adaptive response, which aims to minimize production of harmful reactive O2 species (ROS) such as superoxide ( ). ROS can be produced by a number of means within the cell, including generation as a by-product during mitochondrial oxidative phosphorylation . The full reduction of O2 to water at complex IV of the electron transport chain, COX, requires the donation of four electrons. Donation of a single electron results in superoxide ( ) formation, whereas hydrogen peroxide (H2O2) can be formed following the donation of two electrons to O2 and its subsequent protonation. ROS are thus generated as intermediates during the sequential donation of electrons to O2, but can also arise in the hypoxic cell due to electron leak from a highly reduced respiratory chain, with complex III implicated as a major source of this leakage .
A role for ROS in hypoxic signaling and adaptation has been proposed, with oxidative stress increasing HIF stabilization in cells . The hypoxic mitochondrion might therefore bring about its own destruction via the resulting increase in autophagy, thereby maintaining sufficient O2 supply to the remaining mitochondrial population and thus minimizing ROS production. Correspondingly, PGC-1α activity appears to be tightly coupled to HIF-1 activity in skeletal muscle cells, with an increase in PGC-1α-driven mitochondrial biogenesis causing increased O2 consumption and intracellular hypoxia, leading to HIF-1 stabilization . By shifting the balance between the competing responses of mitochondrial biogenesis and mitochondria-specific autophagy, cellular mitochondrial density, and thus O2 demand, is closely matched to O2 supply.
A further HIF-1-mediated response to hypoxia that restores redox homeostasis occurs at COX, and might also improve cellular energetics. A switching of subunit 4 (COX4) at this complex occurs via the HIF-1-dependent transcription of a COX4-2 subtype, and a mitochondrial protease, LON, which degrades COX4-1 . This subunit switch increases the efficiency of electron donation to O2 at COX under hypoxic conditions, minimizing electron leakage and ROS production at complexes I and III  (Figure 2(ii)). This switch would have an additional energetic benefit, as increased proton pumping into the mitochondrial intermembrane space would arise from a decreased electron leak, and thus enhance the efficiency of ATP synthesis for a given O2 consumption.
Despite a loss of mitochondria, there is some evidence that successful acclimatization to high-altitude hypoxia over a period of several weeks can result in normal skeletal muscle energetics at rest and following an exercise challenge . The mechanisms by which a depleted mitochondrial population might be able to generate adequate quantities of high-energy phosphates to support normal cellular function are of direct relevance to basic and clinical physiology in a number of fields, including respiratory, cardiovascular, and fetal medicine; yet these mechanisms, which may involve enhanced function of the remaining mitochondria or increased non-mitochondrial ATP production, remain incompletely resolved.
A greater contribution of anaerobic glycolysis to ATP production, particularly during an exercise challenge, is a tempting solution to the problem of maintaining energy homeostasis in hypoxic skeletal muscle. Indeed, a number of genes encoding glycolytic enzymes, including aldolase, phosphoglycerate kinase 1, pyruvate kinase, phosphofructokinase, enolase, and lactate dehydrogenase, have HREs in their regulatory regions  (Figure 2(iii)). Furthermore, the glucose transporter, GLUT1, which mediates non-insulin-stimulated glucose uptake by heart and skeletal muscle, is upregulated in hypoxia in a HIF-dependent manner , and protein levels of both GLUT1 and the insulin-stimulated glucose transporter, GLUT4, were increased in hypoxic rat skeletal muscle, although mRNA levels were unchanged . Curiously, no HRE has been identified in the GLUT4 gene, although its expression patterns correlate with HIF-1 activity, perhaps suggesting that it is indirectly regulated by HIF-1α .
Measurement of metabolic enzyme activities in the skeletal muscle of rats housed in hypoxic-hypobaric chambers has suggested that shifts towards glycolysis are dependent on muscle type as well as activity levels . For example, altitude simulation increased hexokinase activity in soleus and plantaris, whereas lactate dehydrogenase activity increased in plantaris alone . In addition, decreased activity of the fatty acid β-oxidation enzyme hydroxyacyl-CoA dehydrogenase was seen in soleus, though not in plantaris , although this may be secondary to an overall loss of mitochondrial mass.
In addition to an enhanced capacity for glycolysis, an active shunting of pyruvate, the end-product of glycolysis, towards lactate production and away from oxidative metabolism in the mitochondrion appears to be upregulated in hypoxia. Induction of PDK1 by HIF-1 deactivates pyruvate dehydrogenase (PDH) [41, 42], preventing the conversion of pyruvate into acetyl-CoA (Figure 2(ii)). Two-dimensional difference in-gel electrophoresis (2D-DIGE) and mass spectrometry analysis of gastrocnemius muscle from chronically hypoxic rats showed downregulation of proteins involved in the tricarboxylic acid (TCA) cycle, ATP production, and electron transport, with upregulation of HIF-1α, glycolytic enzymes and PDK1 . This exclusion of pyruvate from mitochondrial oxidation occurs alongside a HIF-1-dependent upregulation of lactate dehydrogenase , which converts pyruvate to lactate. The transport of lactate out of the muscle cell is primarily mediated by the monocarboxylate transporters 1 and 4 (MCT1 and MCT4). MCT4, but not MCT1, was found to be upregulated in hypoxia via HIF-1 induction in a human uterus cancer cell line (HeLa) . Although skeletal muscle levels of neither MCT1 nor MCT4 increased in lowlanders acclimatized to 4,100 m , exercise in hypoxia increased muscle mRNA levels of MCT1 . Together with a decrease in mitochondrial density, these studies suggest an active Pasteur effect in which glycolytically derived lactate is expelled from the hypoxic cell . Human biopsy studies at altitude, however, have been less conclusive.
Increased activity of hexokinase was measured in vastus lateralis of human subjects after 3 weeks' residence at 4,300 m, yet decreased activity of phosphofructokinase was also noted, although this had also been recorded within 4 hours of arrival at altitude and may not form part of a longer-term adaptive response . A similar study, however, showed no change in activities of glycogen phosphorylase, hexokinase, lactate dehydrogenase, or malate dehydrogenase in vastus lateralis after 18 days at 4,300 m . Biopsies taken from climbers returning from ascents above 8,000 m, or undergoing simulated ascents over 8,000 m in a hypobaric chamber, showed decreased activities of mitochondrial enzymes , including citrate synthase [49, 50], succinate dehydrogenase , malate dehydrogenase , COX , and 3-hydroxyacyl-CoA dehydrogenase , although again, these changes may simply represent loss of mitochondrial mass. A dramatic decrease in hexokinase activity in sedentary subjects undergoing a simulated chamber ascent  contrasted with the same investigators' findings at 4,300 m , perhaps suggesting a combined effect of hypoxia and physical activity. Gel electrophoresis and mass spectrometry of vastus lateralis biopsies taken at sea level and after 7 to 9 days' exposure to 4,500 m, showed downregulation of TCA cycle and oxidative phosphorylation enzymes, but with no change in HIF-1α or PDK1 levels . Moreover, decreased levels of the protein synthesis marker mTOR suggested a global repression of transcription at this early stage of acclimatization, perhaps as part of a program to limit ATP consumption . Indeed, tissue hypoxia induces a specific pattern of chromatin modifications that appear to decrease transcriptional activity independent of HIF-1 regulation or cell type .
An apparent, and perhaps counterintuitive, blunting of glycolysis upon acclimatization to chronic hypoxia has also been suggested by the so-called 'lactate paradox' . Acute exposure to high altitude is accompanied by greater blood lactate levels ([Lab]) at any given submaximal exercise workload than in normoxia, although peak [Lab] remains unchanged. In subjects who have acclimatized to altitude over a period of more than 3 weeks, however, exercise at the same absolute workload and maximal exercise result in lower [Lab] compared with the same subjects exercising in the unacclimatized state . This phenomenon, initially seen as paradoxical, suggested that ATP production in chronic hypoxia is perhaps not dependent on increased anaerobic glycolysis but rather that mitochondrial ATP production becomes 'better tuned' to the hypoxic state. Recent studies, however, have suggested that the lactate paradox may only be a transient feature of hypoxic adaptation at altitude, disappearing in lowlanders over durations greater than 6 weeks at altitudes above 5,000 m [53, 54]. Moreover, a reduction in the capacity of muscles to produce lactate following acclimatization has not always been demonstrated .
Whether the lactate paradox arises from decreased muscle lactate production due to altered substrate preference, altered lactate handling via MCT1 and MCT4 at the muscle, or a better coupling of pyruvate production and oxidation at the mitochondria, remains to be resolved, along with a clear profile of the conditions under which it occurs. Intriguingly, metabolomic analysis of placentas from high-altitude births showed a blunting of lactate production following a labored delivery compared with sea-level placentas , suggesting that an analogous phenomenon to the lactate paradox may occur in tissues other than muscle in response to acute metabolic stress in chronic hypoxia.
One further possible solution to the problem of maintaining energetic homeostasis in chronic hypoxia might be to alter metabolic pathways to maximize the yield of ATP per mole of O2 consumed. As already discussed, an improvement in O2 efficiency could be achieved by minimizing electron leakage via COX subunit switching. A further increase in oxygen efficiency could be achieved via a switch in substrate preference towards more oxygen-efficient fuels (for example, glucose instead of fatty acids). For instance, stoichiometric calculations predict that complete oxidation of palmitate yields 8 to 11% less ATP per mole of O2 than that of glucose . A metabolic switch towards the exclusive oxidation of carbohydrate is, however, unlikely and unsustainable due to limited muscle and liver glycogen stores and a need to preserve glucose for the brain, which cannot oxidize fat.
In hypoxic epithelial cells, a dramatic reduction in levels of the fatty acid-activated transcription factor peroxisome proliferator-activated receptor (PPAR)α was mediated by HIF-1 . PPARα activation increases the expression of a number of proteins associated with fatty acid oxidation, and is therefore a mechanism for a metabolic shift towards fat metabolism . Downregulation of the PPARα gene regulatory pathway  and a number of PPARα target genes, including uncoupling protein 3 (UCP3), occurs in the hypoxic heart . In muscle fibers, however, it appears that the hypoxic response may be critically mediated by an upregulation of PPARα , which might promote anaerobic glycolysis by de-activating PDH via the upregulation of another pyruvate dehydrogenase kinase isoform, PDK4 . PPARα activation could, however, increase inefficient fatty acid oxidation. Indeed, lipid metabolism in liver, and fatty acid uptake and oxidation in skeletal muscle increased in rats exposed to 10.5% O2 for 3 months .
Furthermore, PPARα activation could activate mitochondrial uncoupling in hypoxic skeletal muscle by upregulation of UCP3, leading to relatively inefficient metabolism, and a recent study has shown that UCP3 is upregulated in hypoxic skeletal muscle via another PPARα-independent mechanism . Mitochondrial uncoupling by UCP3 can be activated by superoxide and may be an additional mechanism of antioxidant defense in the hypoxic cell , but at the cost of decreased metabolic efficiency, as protons re-enter the mitochondrial matrix independent of ATP synthesis. The regulation of mitochondrial efficiency, however, may occur independently of gene transcription mechanisms, and liver mitochondria from non-hypoxic acclimatized rats were found to have an improved phosphorylation efficiency and depressed uncoupling when respiration was measured under hypoxic conditions .
Whether changes in oxygen efficiency in the hypoxic mitochondrion translate into altered exercise economy at the whole-body level remains controversial. A number of studies from independent groups have reported improvements in exercise economy following acclimatization of between 3% and 10% (reviewed in ); however, other investigations have shown no change in economy . The choice of subjects and the varying methodologies of these studies may explain the discrepancies. For example, studies in which no changes in efficiency are shown have often reported data from highly trained athletes, who have high efficiency (and low UCP3 levels) at baseline . Clearly, more studies are required at the tissue level to characterize whether mitochondrial efficiency is altered in chronically hypoxic skeletal muscle, and the physiological significance of this.
The study of healthy humans at altitude has translational implications for many human diseases characterized by tissue hypoxia. In particular, parallels have been noted between muscle wasting and metabolic adaptation at altitude and in patients with COPD [3, 4]. While many facets of hypoxic adaptation, particularly those driven by HIF-1, have come to light over the past decade, much of this work has been carried out in cultured cells and animal models. The integrated response to hypoxic challenge in man is much less well understood and a number of controversies exist regarding the timings of such adaptations, the degree of the hypoxia in which they occur, and the tissue specificity of alterations in gene expression and metabolism.
The emergence of new technologies that enable relatively inexpensive, comprehensive and high-throughput analysis of gene expression, protein levels, and metabolic markers has the potential to contribute much to this area of research. Currently, very few investigators have applied these technologies to the study of humans at altitude and in hypoxia chambers, and only then under a limited number of hypoxic conditions and durations, and with small sample sizes. This may, at least in part, be due to the logistical difficulties of collecting and preserving biopsy samples in the high-altitude environment while preventing loss of oxygen-sensitive factors in the tissue. There is a clear need for technologists and high-altitude researchers to collaborate towards a resolution of these logistical difficulties in order to apply high-throughput analysis techniques to this area of research.
Such techniques can contribute much to our understanding of the adaptations in structure and function of cells, tissues, organs, and the whole organism in the hypoxic environment. While this review has focused primarily on the metabolic response of skeletal muscle to hypoxia, it is essential that the adaptations discussed are placed firmly within the context of the whole organism, and therefore the information generated by 'omics' technologies should, by necessity, form part of an integrative and quantitative physiological approach . The use of computational models, combining experimental and theoretical methods, greatly aids the understanding of complex biological systems and the response of such systems to stress ; for example, the integration of metabolomic and transcriptomic data with measures of exercise efficiency and gas exchange within such a model could reveal much about how metabolic adaptations drive changes in performance at high altitude. Moreover, this approach would be particularly beneficial to physiologists concerned with hypoxic adaptation, since a powerful model could incorporate data pertaining to differing degrees of hypoxia and time courses of exposure.
A strong case is therefore emerging for a coordinated approach in study design between the many groups currently involved in altitude research worldwide, and for an increased use of open access databases to disseminate findings. The potential for accumulating a significant body of genomic, proteomic, and metabolomic data from subjects at altitude is a tremendously exciting prospect, but also one that runs the risk of occurring in a haphazard manner. Inconsistencies in study design between different groups are all too abundant in this field, with differences in ascent profiles, durations of exposure, experimental details, and timings of physiological measurements and biopsy sampling, as well as variations in subjects' genetic backgrounds, ages, fitness levels, and pre-assessed ability to perform at altitude, often muddying the interpretation of results. In addition, while comparisons between sedentary subjects in hypoxic chambers and relatively active participants in the field have been revealing, the ability to infer biological responses that might be either common or specific to these particular stresses is limited if the study design and subject selection is not appropriately coordinated.
A final consideration concerns the logistical difficulties and significant financial cost of mounting large-scale research expeditions to altitude. The benefits of comprehensive, collaborative studies that bring together researchers with a wide range of expertise, both from the established altitude research community and from other research backgrounds, are clear and greatly outweigh the potential difficulties of conducting research in this way ; however, the frequency at which such studies can occur is inevitably limited. It is imperative, therefore, when planning field studies at altitude, that consideration is given to the particulars of how data generated by 'omic' technologies, as well as from physiological studies, can best be incorporated into accessible and universal models of hypoxic acclimatization. Such a coordinated approach could not only prove to be a powerful means of resolving the current controversies regarding metabolic adaptation at altitude, but could reveal much about the ways in which tissues respond to hypoxia in many disease states.
Andrew Murray is a Research Councils UK academic fellow and a lecturer in Integrative Mammalian Physiology at the University of Cambridge. He is also a member of the Caudwell Xtreme Everest Research Group.
The author wishes to thank Dr Mike Grocott, Professor Hugh Montgomery, Dr Denny Levett, Dr Daniel Martin, and other members of the Caudwell Xtreme Everest Research Group for many fascinating discussions on this topic.
AJM researched and wrote the manuscript.


2.6. Importance of colour, design and value of colour in clothing.
2.8. Individuality of pro-school children.
2.13. Role of clothing in the personality development of children.
2.14. Selection of materials for childrens dresses.
Test for Preference of design.
Test for preference of value of colour.
Tests for identification of style.
4.6.5. Parent questionaire for behavioural profile or temparament.
1.b. Difference in the self-concept of pre-school children for Individual income group.
5.b. Difference in the identification of garments for various occasions belonging to various income levels.
6.b. Difference in the Intensity of reaction belonging various income levels.
7.b. Difference in the reaction pattern belonging to various income levels.
5.1.18. Problems faced while purchasing childrens clothing.
5.3.7 Identification of dresses for various occasions.
5.4.4. Colour value preference and Self-concept.
6.1.12. Seeking opinion of the child while purchasing.
6.4.6. Colour and design preference by mother-child for childs dresses.
6.4.8. Intensity of reaction and preference of colour, design and colour value.
7.4 Implication of the study.


CSIR UGC NET Syllabus 2019 – The syllabus for CSIR includes topics which are required to be studied from the five subjects from that candidates can choose. The candidates who are going to appear for the examination must be familiar with CSIR UGC NET Syllabus 2019. CSIR UGC NET Syllabus 2019 includes all the important topics from different subjects- Chemical Sciences, Earth Sciences, Life Science, Mathematical Science, and Physical Science. CSIR UGC NET 2019 will be conducted two times tentatively in June and September. CSIR UGC NET 2019 will be conducted by Council of Scientific and Industrial Research to determine the eligibility of professors and lecturers in universities and colleges recognized under UGC and Junior Research Fellowship. Familiarity with CSIR UGC NET Syllabus 2019 will help the candidates for better preparation and in scoring good marks in the examination. This article of Get entrance imparts you all the relevant information regarding CSIR UGC NET Syllabus 2019, sectional syllabus, etc.
As per this topic, questions will be asked about earth, atmosphere, oceanic and planetary services. Following are the topics from which questions will be asked.
Earth Materials, Earth Processes, and Surface Features.
The syllabus for mathematical sciences will be divided into four sections. The following are brief list of units and topics covered in CSIR UGC NET Syllabus 2019 for mathematical sciences.
The syllabus for physical science exam is divided into parts core and advance. The topics which are included in both are enlisted below.
The above syllabus for examination is based on previous year's data. The exam is yet to be conducted. The candidates who will appear for the examination are advised to keep their eyeballs on syllabus for better preparation and result. The completion will likely increase this year.
This is all about CSIR UGC NET Syllabus 2019. If you still have any doubt or query then let us know in the comments section below.


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Glasgow's Tartan and Turbans event chooses sight loss charity as this year's beneficiary
Tartan and Turbans celebrates Scotland's diverse communities and culture and every year a different charity is nominated to raise funds for
Host Atta Yaqub
The Royal National Institute of Blind People (RNIB) has been chosen as the charity that this year's Tartan and Turbans event in Glasgow.
Scottish actor Atta Yaqub, star of the Ken Loach film 'Ae Fond Kiss', will be key speaker and presenter.
The charity is inviting businesses to sponsor its drive to produce more audio-books for people who are blind and partially sighted. Companies can buy a table at the event or donate money or a prize to the raffle.
Tartan and Turbans celebrates Scotland's diverse communities and culture. Every year a different charity is nominated to raise funds for. The event will be held at the Double Tree by Hilton in Glasgow.
Glasgow homeless charity needs help to get donation van on the move again
This fifth Tartan and Turbans event will consist of a three-course Burns supper as well as traditional Indian and Scottish dancing and a fashion show to showcase Scottish tartans and tartans from other cultures.
The Bhangra Beetles will be this year's live act, and auction-prizes will include a weekend test-drive of the new Tesla Model 6 hybrid car and two hours of story-telling from Glasgow-based author Michael Kerins.
In a call to potential sponsors and supporters, Jamila Shaikh of RNIB Scotland said: "We want to raise money to produce more 'talking' audio-books so that we can bring the gift of reading to more blind and partially sighted people in Scotland.
"Last year over 200 people attended Tartan and Turbans. Please help us make this year's event the biggest and best yet! We would very much like you to be part of this and there are plenty of ways to get involved.
Glasgow charity shop enjoys record year thanks to resurgence of vinyl record sales
"You can support our work by making a donation, and if you're a business we would love for you to join us at this event by buying a table and have your company name and logo as the centre piece on your table. Or, why not consider contributing by donating a prize to our raffle!
"It's a great way of getting your message out to a diverse range of groups in Scotland – and it's for a very worthwhile cause!"
Single tickets cost £40 for the February 10 event and a table of ten is £360. Please contact Jamila Shaikh on 07795 808 740 or email jamila.shaikh@rnib.org.uk .


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Q: WP7/8 is it possible to turn on Flash Light with PhotoCamera I have a Photo App with Flashmode support so i can decide to use autoFlash, no Flash or flash by every picture which is taken. But no i want to implement that the flash lights the scene to get a good view on QR-Codes for example.
So the user has to click on the flashmode button to switch the modes: Flashmode.Auto, FlashMode.On, FlashMode.Off and the new one "use Flash LED as a torch" ...
Is this possible in Windows Phone 7 / 8 ?
thx

A: In Windows Phone 8 you can do it natively, with AudioVideoCaptureDevice and the property VideoTorchMode=On.
On Windows Phone 7 you need to use Reflection and load "Microsoft.Phone.Media.Extended" library to get something like AudioVideoCaptureDevice and turn on the flash while you'r recording a video.
That could be useful for use the flashlight in WP7.
http://www.locked.nl/wp7-flashlight-getting-started

A: in xaml:
  <VideoBrush x:Name="PART_VideoBrush">
                            <VideoBrush.RelativeTransform>
                                <CompositeTransform x:Name="PART_VideoTransform" CenterX=".5"CenterY=".5"  />
                            </VideoBrush.RelativeTransform>
                        </VideoBrush>

in your code behind:
 PhotoCamera _cam = new PhotoCamera();
    this._cam.Initialized += _cam_Initialized;
  CameraVideoBrushExtensions.SetSource(this.PART_VideoBrush, this._cam);
                this.PART_VideoTransform.Rotation = 90.0;

 private void _cam_Initialized(object sender, CameraOperationCompletedEventArgs e)
        {
            this._cam.FlashMode = FlashMode.Off;           //FrashMode.ON,Auto, RedEyeReduction
        }


To dream about living in a camper signifies that you must press forward within some area of your life. You could be focusing too much on an aspect that should be ignored. You could also be showing a wish to become more self-assured and sovereign.


Immediately most people learn of touch sensitive faucets, they think its a brilliant idea. But then they imagine that they might have kids and pets around, and then they don't seem like such a good idea.
For instance, what if touches from these family members cause the faucet to go off unnecessarily? After all, these faucets require just a light touch to start running.
But, is there a reason to stay off touch sensitive faucets? Most people believe there is. But shouldn't the guys who design these systems have given thought to such issues, so that you can enjoy the amazing convenience of a touch less faucet regardless of whether you have kids of not?
Luckily, there is quite a bit of information on how touch sensitive faucets actually work, even in seemingly unsuitable situations.
Truth be told, no touch sensitive faucet is similar to another. For instance, top rated kitchen faucets in this category cannot be expected to deliver the same level of convenience as poorer quality alternatives. But how do you know which kitchen faucet is the best?
There is one simple trick that works most time – looking through customer reviews.
On Ebay, there are a number of touch sensitive faucets with lots of reviews and ratings that can give you a pretty good idea about the quality of the faucet on sale.
These concerns aside, some people think that splurging on a touch sensitive faucet is not a good financial decision. Others simply have a love for all things traditional, and a touch sensitive and battery-powered faucet doesn't make the cut.
Obviously, for a faucet to operate on touch sensitivity, it needs power. People are well aware of the volatile relationship between electricity and water, which makes the idea of an electricity powered faucet scary for some.
However, these devices run on a couple of 1.5 volt batteries, which is not dangerous by any standards. Additionally, the system that powers the faucet never gets into contact with water.
No good touch sensitive faucet will have this issue. Initially, these problems were present, but today, the technology has been refined considerably to ensure that the faucet only turns on when necessary.
That is why it is always a good idea to stick with top and proven brands when shopping for touch sensitive faucets to avoid running into these kinds of problems.
However, be careful with the installation of this appliance, since a solid contact with the sink would mean that the faucet will turn on when you touch the sink. But with proper insulation, no such problems will come up.
Some people fear that touch sensitive faucets will end up wasting a lot of water from being turned on too often by little kids.
On the contrary, a touch sensitive faucet is more appropriate for a home with kids, in part because children have easier access to water with these faucets. In fact, water is less likely to keep running because the faucet is easy to turn off for a kid.
This is not always the case with traditional faucets. However, these faucets are designed to turn off automatically after 3 to 5 minutes.
For these faucets, contact that lasts for more than few seconds counts as a grip, and that does not trigger any response. A touch is a brief contact.
Most pets are not capable of providing the brief touch needed to turn on a touch sensitive faucet, as their touch lasts for too long. In any case, these faucets automatically turn off after a few minutes, even when a pet happens to turn them on.
Most of the fears associated with touch sensitive faucets are unfounded. Actually concerns that these faucets are not ideal should are completely untrue. Children will have an easier time operating these faucets, and they can turn off automatically if left running. The same applies to pets. So, let nothing stop you from getting yourself a touch based faucet, it will be worth your while, regardless of the circumstances.


Clarity™ men's cufflinks with your sentimental item infused as a glass memory piece.
While associated with formal events, cuff links can be worn with more casual sport jacket and button shirt combinations as well as more formal suits or tuxedos as way of adding a playful, colorful, or, in this case, very personal accent to a masculine style. These cuff links can be ordered in either sterling silver or gold-plated with a specially crafted memory bead secured to the post. The links use a "bullet back" closure which is smooth in shape and rotates on a hinge for quick and easy wearing. Cuff links are about .6″ (15 mm) in diameter.
All content and images are © Copyright, Christina Cole. All rights reserved. Do not copy or publish content without written approval; thank you.


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CollectionMss 023 - Jan August Collection
Collection Mss 023 - Jan August Collection
Jan August Collection
1.5 linear feet; 1 document box and 1 record box
August, Jan
Jan was born Jan Augustoff in New York City, the youngest of five children. Jan's parents, having paid for music lessons for the four older siblings who lacked any musical aptitude, chose not to repeat the mistake with their youngest. Jan learned to play the piano by ear as a child; as an adult he learned to read and arrange music. He mastered the xylophone, vibraphone and Solovox as well as the piano. In 1946, his instrumental recording of "Misirlou," a Greek folk song, sold more than 1,000,000 records.
As a young man, Jan performed as a pianist with the Paul Specht Band in Greenwich Village nightclubs. In the 1930's, Paul Whiteman invited him to play in his orchestra; Jan also performed with Ferde Grofé. With the musical shift from jazz to swing in the 1940's, Jan returned to performing solo in clubs. His style attracted the attention of Irving Gwirtz of Diamond Records, who signed him to a recording contract. He received union scale wages of approximately $35 for his recording of "Bob-a-Loo" and "Misirlou"; the recording reached the Top Ten on the charts and launched his career.
Jan hosted and performed on radio, notably a 15-minute weekly broadcast on the Mutual Radio Network from 1947-1948. In 1948 and 1950, he appeared on "The Toast of the Town" and from 1949-1951 he accompanied singer Roberta Quinlan on her NBC variety show. Later he hosted "Jan August's Revere Camera Show". In 1949, he served as the subject of a 9-minute film short entitled "Audition for August" with Kitty Kallen. In the 1950's, Jan signed a recording contract with the Mercury label recording instrumental versions of popular hits laced with Latin rhythms. He also toured with his own orchestra in the United States and Canada. After arranging and recording more than 140 songs, Jan retired in 1967. He died of heart disease about a decade later.
Shortly before Jan's death, a musician performing under the name Jan August made the news in Florida, but it was an imposter.
The collection consists of menus, press clippings, photos and recordings from the career of arranger and composer Jan August.
The collection remains in its original order.
All material is open to the public without restriction. Copyright laws of the United States (Title 17, United States Code) govern the making of photocopies or other reproductions.
Some of the audio materials in the collection are on obsolete media. Access copies of these materials must be created prior to use. Consult the Library and Archives staff in advance of your visit to ensure access to these materials is available.
jan-august-collection.pdf
Received from June Appell, Jan August's granddaughter, on April 13, 2011.
Processing information: Minimally processed by Lisa Lobdell. Completed January 2012. Sound recordings will be separated from this collection and catalogued at a later time.
Citation: Jan August Papers, The Great American Songbook Foundation.
FInding aid created by Lisa Lobdell, January 2012.
AtoM description created by Ashlee James, November 2017.
August, Jan (Creator)


Dan Burn has admitted for the first time he would not have considered leaving Wigan Athletic for any club outside the Premier League.
The big centre-back, who is nearing a return to full fitness after breaking his foot in pre-season, signed for Brighton last month, before being loaned back to Wigan until January.
And he says it was only the lure of one more crack at the top flight that caused him to sever ties with a club he credits as having kickstarted his career.
"I think if it had been any other team in the Championship, I probably would have said 'no' because I'm so happy here," Burn told the Wigan Post.
"Fair play to the chairman and Gary Caldwell for bringing me here, because there weren't too many teams interested in me after Fulham released me (in 2016).
"For them to take that chance and then stick by me after a bit of a sticky start...I'll always be grateful – and hopefully I've repaid them since.
"But this is the Premier League, and I never thought I'd get ever back there.
Burn admits his guilt at leaving has been eased by the fine start Latics have made to the season in his absence.
And he's confident Paul Cook's men have it in them to establish themselves as a Championship outfit.
"I knew we wouldn't struggle this year, because of the quality across the board," he added.
"We've also got players not in the team who can come in and make a difference, as they did last week when Vaughany and Cal helped to change the Rotherham game.
"That gives the gaffer a headache when everybody's fit.


The country has a total land area of 490,000 square miles, and its population is approximately 11.3 million. Islam is the dominant religion and is practiced by more than 90 percent of the population. There also are small practicing communities of Christians and Baha'i. Christians, both Catholics and Protestants, account for less than 5 percent of the population but are active particularly in the region of Maradi, Dogondoutchi, Niamey, and other urban centers with expatriate populations. Christianity was the religion of French colonial institutions, and its followers include many local believers from the educated, the elite, and colonial families, as well as Africans from neighboring coastal countries; particularly Benin, Togo, and Ghana. Numbering only a few thousand, the Baha'i are located primarily in Niamey and in communities on the west side of the Niger River, bordering Burkina Faso. A small percentage of the population practices traditional indigenous religions. There is no information available regarding the number of atheists in the country.
Active Christian missionary organizations include Southern Baptists, Evangelical Baptists, Catholics, Assemblies of God, Seventh-day Adventists, Serving in Mission (SIM), and Jehovah's Witnesses.
The Constitution provides for freedom of religion, and the Government generally respects this right in practice. The Government at all levels strives to protect this right in full, and does not tolerate its abuse, either by governmental or private actors.
No religious group was subsidized; however, the Islamic Association, which acts as an official advisory committee on religious matters to the Government, conducted biweekly broadcasts on the government-controlled television station. Christian programming generally was broadcast only on special occasions, such as Christmas and Easter.
Religious organizations must register with the Interior Ministry. This registration is a formality, and there is no evidence that the Government favors any religion over another or that it ever has refused to register a religious organization. Approval is based on submission of required legal documents and the vetting of organization leaders. The Government must also authorize construction of any place of worship; however, there were no reports that the Government refused construction permits during the period covered by this report.
Foreign missionaries work freely, but their organizations must be registered officially as associations. In addition to proselytizing, most missionary groups generally offered development or humanitarian assistance. The Christian community in Galmi, Tahoua Department, housed a hospital and health center run by SIM missionaries. The hospital and health center have been in operation for more than 40 years.
Public school instruction is conducted in French, and there are also public bilingual schools conducted in French and Arabic. The government does not permit religious instruction in public schools.
Christmas, Easter Monday, and Muslim holy days are recognized as national holidays. It is not uncommon for Muslims and Christians to attend each other's festivities during these holidays.
Government policy and practice contributed to the generally free practice of religion; however, in the fall of 2001, the Government banned two Islamic organizations because they sent threatening letters to a foreign embassy. Despite the ban in 2002, the same organizations issued a tract calling for a jihad in which they denounced the secular state and advocated Shari'a law. The Government reaffirmed the ban and warned those who signed the tract to stop such actions. Later, in 2002, the Government arrested the leaders of both organizations and charged them with incitement to revolt. They were released in 2003, but their organizations remained banned at the end of the period covered by this report. No mainstream Islamic organizations or human rights organizations have challenged the legality of the bans.
The Constitution forbids political parties from having a doctrine based on any religious ideology.
The Government does not impose religious speech restrictions as long as there is no intent to disrespect public order, social peace, and national unity. In Spring 2004, during a regional polio vaccination campaign sponsored by the United Nations, seven Muslim preachers urged violent resistance to the campaign, claiming it was a plot by Westerners to sterilize Muslim children. In reaction, the Government temporarily detained the preachers on the grounds of inciting a riot. Nigerian Islamic associations and President Tandja publicly supported the campaign.
Some senior-level government employees are required to take religious oaths. The Constitution specifies that the President of the Republic, the Prime Minister, the President of the National Assembly, and the President of the Constitutional Court, must take an oath on a holy book of their own choosing. Members of the Constitutional Court, Independent National Election Commission, and High Council for Communications are also required to take religious oaths on a holy book of their own choosing.
The generally amicable relationship among religions in society contributed to religious freedom. There have been reports in the past of isolated instances where individual Muslims were not tolerant of the rights of members of minority religions to practice their faith; however, there were no reported cases of intolerance toward non-Islamic communities or religions during this reporting period.
In March 2003, Islamic organizations in Niamey held a rally to protest the war in Iraq and expressed solidarity with Iraqi citizens. No violence was reported.
In Spring 2004, Muslim preachers verbally protested a polio vaccination campaign, and the government intervened to limit their effect (see Section II).
The U.S. Government discusses religious freedom issues with the Government as part of its overall policy to promote human rights. The U.S. Embassy regularly emphasizes the importance of tolerance in its public statements and in meetings with government officials and members of civil society.
As part of the U.S. Embassy's continued outreach to the Muslim community, the U.S. Government funded an important cultural preservation project by supplying equipment and training to electronically preserve thousands of revered Islamic texts. The U.S. Government also funded a renowned American religious scholar to tour the country and lead discussions on Islam in America, prompting in-depth discussions and promoting a deeper appreciation of American society.
The U.S. Embassy hosted a series of Iftaar dinners during Ramadan, met with traditional Muslim leaders in Kiota and with Islamic leaders at the Islamic University in Say, enhanced existing relationships with Islamic journalists, and presented programs at French/Arabic bilingual schools. In March 2003, Embassy officials met with key Muslim leaders regarding the U.S. military operations in Iraq, in an effort to lessen any potential anti-Christian or anti-Western reactions.
The U.S. Embassy maintains good relationships with Protestant religious groups, most of which are long-term resident missionaries and well-known members of the American community. Embassy officials also have contact with the Catholic mission, the Baha'i community, and Islamic organizations.


While good guys are trying to secure their code from all possible attacks, hackers only need a small hole in the castle with their brilliant programming skills without constraint. Despite recent platform security options, hackers can exploit the vulnerable code due to common programing errors. So, here is the thumb rule to ensure you are really protecting your castle.
If you see a security flaw in your code, FIX it, just FIX it. Dont get caught thinking if there is anyone who would know this & could exploit it.
We will talk about buffer overflow attacks on applications & how we (as programmers) can minimize the risk by following security principles. This will be a 3 part series, and in the first session part we will discuss Stack Smashing in detail.
What is stack smashing and how a buffer overflow can be exploited to smash the stack?
What are compiler security options and how they can help?
Can a buffer overflow be exploited despite more secured platform options?
What are the coding guidelines to prevent stack smashing attacks?
Which tools can help me detect buffer overflow flaws in my code?


Buyer to abide by Copacabana Sec 2 deed restrictions. This lot 8 is for residential use only & driveway entry is via Copacabana Drive only. All lots require underground electric wiring. All Subdivision is private & has walkway to beach & no vehicular traffic..Prices, terms & property updates are subject to change without notice.


text:
Omicron's New Year's cocktail: Sorrow, fear, hope for 2022 | Health and Fitness
Students holds candles while participating in a demonstration to say goodbye to year 2021 and welcome in 2022, in Lahore, Pakistan, Friday, Dec. 31, 2021.
Indians, wearing face masks to help curb the spread of the coronavirus, hold the cutouts to welcome 2022 on New Year's Eve in Ahmedabad, India, Friday, Dec. 31, 2021.
Fireworks explode over the Sydney Opera House and Harbour Bridge as New Year's Eve celebrations begin in Sydney, Friday, Dec. 31, 2021.
Workers of a political party and others cheer in front of a huge kite to welcome 2022 on New Year's Eve in Ahmedabad, India, Friday, Dec. 31, 2021.
Pope Francis waves as he arrives to celebrate a new year's eve vespers Mass in St. Peter's Basilica at the Vatican, Friday, Dec. 31, 2021.
Nurses perform timed breathing exercises on a COVID-19 patient on a ventilator in the COVID-19 intensive care unit at the la Timone hospital in Marseille, southern France, Friday, Dec. 31, 2021. Paris region health authorities have instructed hospitals to cancel more non-urgent medical procedures to free up intensive-care beds for the growing influx of people gravely sick with COVID-19.
A security guard holds up a sign indicating that there is no countdown event at the famed Shibuya scramble crossing, a popular location for New Year's Eve gathering Friday, Dec. 31, 2021, in Tokyo as people gather to celebrate New Year's eve.
Nurses enjoy a new year's cake during a break in the COVID-19 intensive care unit at the la Timone hospital in Marseille, southern France, Friday, Dec. 31, 2021. Paris region health authorities have instructed hospitals to cancel more non-urgent medical procedures to free up intensive-care beds for the growing influx of people gravely sick with COVID-19.
Fireworks explode over the Chao Phraya River during New Year celebrations in Bangkok, Thailand, Saturday, Jan. 1, 2022,
A visitor wearing a face mask poses for a photo in front of an illuminated decorations on New Year's Eve in Seoul, South Korea, Friday, Dec. 31, 2021.
Attendees at an event that coincided with the New Year Eve cheer as fake snow from a foam machine is blown overhead in Beijing, China, Friday, Dec. 31, 2021.
A man looks at the decorations for the coming 2022 Year on New Year's Eve in Seoul, South Korea, Friday, Dec. 31, 2021.
The Smoke Squadron flies over a Copacabana Beach in Rio de Janeiro, Brazil on New Year's eve, Friday, Dec. 31, 2021. Residents and tourists prepare to party and watch a fireworks display marking the end of 2021.
A Palestinian woman takes photos of her children near the beach on the last day of the year and New Year's celebrations, in Gaza City, Friday, Dec. 31, 2021.
Crowds of people celebrate the New Year around the Christmas tree with the St. Sofia Cathedral in the background in Kyiv, Ukraine, Friday, Dec. 31, 2021. Despite of COVID-19 quarantine restrictions, a lot of Ukrainians enjoy outdoor New Year events, often ignoring protective measures.
People celebrate during a New Year's Eve concert in Hong Kong Saturday, Jan. 1, 2022.
Followers of the Yoruba religion give offerings to Yemanja, a deity celebrated by the African Yoruba religion, at a lake in downtown Brasilia, Brazil on New Year's Eve, Friday, Dec. 31, 2021. As the year winds down, Brazilian worshippers celebrate Yemanja, goddess of the sea, offering flowers and launching large and small boats into the water in exchange for blessings for the coming year.
People celebrate the New Year in Nikolskaya street near an empty Red Square due to pandemic restrictions during New Year celebrations in Moscow, Russia, Saturday, Jan. 1, 2022. Russia's state coronavirus task force has registered a total of about 10.5 million confirmed infections and 308,860 deaths, but the state statistics agency that uses broader criteria in its tallying system has reported nearly 626,000 virus-linked deaths in Russia since the start of the pandemic.
People celebrate during New Year's celebrations at Madrid's Puerta del Sol in downtown Madrid, Spain, early Saturday, Jan. 1, 2022.
People celebrate the New Year's Eve on the Champs Elysees avenue, in Paris, Friday, Dec. 31, 2021.
Party boats cruise over the river Main with only a few fireworks near the buildings of the banking district in Frankfurt, Germany, early Saturday, Jan. 1, 2022. Due to the coronavirus pandemic fireworks were not allowed.
Nurse Bess Tribout, center, pops champagne to celebrate the new year in the COVID-19 intensive care unit at the la Timone hospital in Marseille, southern France, Saturday, Jan. 1, 2022.
A man celebrates the start of the New Year, backdropped by fireworks exploding in the background over Copacabana Beach in Rio de Janeiro, Brazil, Saturday, Jan. 1, 2022.
Fireworks are set off at midnight during the Times Square New Year's Eve celebration, early Saturday, Jan. 1, 2022, in New York.
Derrick Westmorelandm of Houstonm and Alisha McCordm of Memphis, Tenn., pose with, from left, Melissa Dillon, Preeti Saha, Lydia Penn and Uli Auliani, all of Las Vegas, during the New Year's Eve party at the Fremont Street Experience in downtown Las Vegas on Friday, Dec. 31, 2021.
The Village People perform on New Year's Eve at the Fremont Street Experience in downtown Las Vegas Friday, Dec. 31, 2021.
Revelers celebrate on New Year's Eve at the Fremont Street Experience in downtown Las Vegas Friday, Dec. 31, 2021.
By JOHN LEICESTER and NICK PERRY – Associated Press
PARIS (AP) — Sorrow for the dead and dying, fear of more infections to come and hopes for an end to the coronavirus pandemic were — again — the bittersweet cocktail with which the world said good riddance to 2021 and ushered in 2022.
New Year's Eve, which used to be celebrated globally with a free-spirited wildness, felt instead like a case of deja vu, with the fast-spreading omicron variant again filling hospitals.
"We just need enjoyment," said Karen Page, 53, who was among the fed-up revelers venturing out in London. "We have just been in so long."
The mostly muted New Year's Eve celebrations around the world ushered in the fourth calendar year framed by the global pandemic. More than 285 million people have been infected by the coronavirus worldwide since late 2019 and more than 5 million have died.
In Paris, officials canceled the fireworks amid surging infections and reintroduced mandatory mask-wearing outdoors, an obligation followed by the majority of people who milled about on the Champs-Elysées as the final hours of 2021 ticked away.
In Berlin, police urged people not to gather near the Brandenburg Gate, where a concert was staged without a live audience. In Madrid, authorities allowed only 7,000 people into the city's Puerta del Sol downtown square, a venue traditionally hosting some 20,000 revelers.
Health & Fitnesscocktail, fear, fitness, health, hope, Omicrons, Sorrow, Years
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