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Free Throws Win and Lose National Championship
Another team coached by John Calipari was done in at that harmless strip of paint just 15 feet from the basket.
After shooting well from the free throw line much of the season, the kids from Kentucky wilted when it mattered most Monday night. Their inability to make one of the simplest shots in basketball was a big reason why the Wildcats lost 60-54 to Connecticut in the national championship game.
"Well, you could say that, but the way we started the game probably cost us the game," said Kentucky coach John Calipari, whose team found itself in an early 30-15 hole and never led.
Kentucky was 13 of 24 from the line and missed its final three attempts when the game was still in the balance. The last of them, a miss by Alex Poythress, would have cut the Wildcats' deficit to 56-53 with 3:47 remaining.
Instead, the lead swelled to six when DeAndre Daniels scored at the other end for UConn, and the Wildcats never had a chance to get within a single possession the rest of the way.
Making it all the more frustrating: UConn was 10 for 10 from the line.
Asked whether that decided the game, Kentucky's Aaron Harrison replied, "Maybe so."
So instead of Calipari's latest bunch of one-and-done stars cutting down the nets during "One Shining Moment," it was UConn joyously romping around the court inside AT&T Stadium, the confetti falling from the rafters as Kentucky players filed slowly toward the locker room.
Their free throw struggles recalled memories of the 2008 title game, when a Memphis team coached by Calipari struggled down the stretch against Kansas.
In that game, the Jayhawks fouled the poor-shooting Tigers when they had to rally late in regulation. Memphis responded by missing four of its final five free throws. And that was enough for Kansas to overcome its big deficit and ultimately win in regulation.
During that stretch before OT, Kansas made all of its shots, including its free throws. Asked whether it entered Calipari's mind, he replied flatly: "No."
UConn was just as maddeningly efficient as Kansas at the line, though, making the troubles of Kentucky all the more glaring: The Huskies never missed, and their final two free throws by Lasan Kromah with 25 seconds left sealed their fourth national championship.
James Young was 8 of 9 from the foul line for Kentucky, and finished with 20 points. But the rest of the team was 5 for 15, including lousy shooting from Julius Randle (4 of 7) and fellow big man Dakari Johnson, who was 1 of 4 the line.
It wasn't just the misses that hurt the Wildcats, either. It was their inability to get there.
Their best foul shooters, twin guards Aaron and Andrew Harrison, made it to the line only once, and Aaron missed. They were hounded all night by UConn guards Shabazz Napier and Ryan Boatright, who prevented them from getting to the rim as they had all tournament.
The Wildcats, who were seeking their ninth national championship, shot 68 percent from the line for the season. Only three times had they shot worse than they did in the national championship, twice overcoming the poor efforts to squeeze out victories.
None of those teams was UConn, though. And none of those games was for the national championship.
"Tough way to go out but at the same time, we proved a lot of people wrong," Johnson said. "We just had a great season and obviously we would have wanted to be on the other end the last game. We just had a tremendous season and we shouldn't feel down."
Courtesy of (AP)


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fishermen Painting
Medium: Oil on Canvas
Painted in (year): 2015
Category: original landscape paintings
TAGS: • Oil • Small (under 20 inch) • Impressionism • Landscape
Fishermen is an original, one-of-a-kind landscape painting signed by artist Daniel Penna. This piece of art was created in 2015 and the painter used oil on canvas. It measures 12" x 8" inch (30 x 20 cm) and is available for sale online for 350 USD.
Daniel Penna is an artist who was born in Sao Paulo, Brazil, in May of 1951. He has been a part of a number of different exhibitions, both solo and collective. His works are in countries all around the world, and it is from all across the world that he takes his inspirations as well. Daniel Penna primarily paints buildings and landscapes in his work with occasional religious symbology found throughout them. There seems to be a focus on churches and other such buildings in many of his paintings. One of the paintings by Daniel Penna even features Jesus, Mary and Joseph to suggest he is in fact painting from a place of religious feeling.

subset: commoncrawl


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9:00am PT by Lesley Goldberg
Robert Kirkman's 'Thief of Thieves' No. 2 Preview (Exclusive)
The Walking Dead creator Robert Kirkman expands his comic credits Wednesday when his newest entry, Thief of Thieves, hits comic shops.
The heist story about a thief who turns his back on his lifetime of crime in a bid to recapture his lost family life, appealed to Kirkman in a way similar to the double worlds of superheroes like Batman and Superman. In this world, Conrad Paulson -- aka Redmond -- is a master thief who exists in a criminal world filled with characters and has a secret identity of sorts that exists in his home life, where he has a family and does his own thing.
"I like the way that mirrors superhero stories in a big way and thought this kind of story would appeal to a comic book audience," Kirkman tells The Hollywood Reporter. "We're going to have our high adventure and cool criminal stuff and also have the more dramatic everyday life."
While the title leaves the zombie world behind, Kirkman says it was his experience in the writers' room of the AMC drama that inspired his storytelling approach for Thief of Thieves.
"Watching six brains craft a story and watching individual people pitch ideas and other people tear those ideas down to only the purest, most essential nuggets and then build up those up to something that's better than what ever the initial idea was is a really cool to tell stories," Kirkman says. "I'm trying to bring that approach into comics as well with this series. I'm working with a group of writers to craft these stories."
Thieves No. 1 was penned by Morning Glories' Nick Spencer and features a taste of what Redmond's criminal family is like, while Thief of Thieves No. 2 will offer insight into his personal life, including his ex-wife, Audrey. Check out the cover and three inside pages, in images exclusive to THR, from March's second issue.
Kirkman will also be on hand at Image Expo on Feb. 24-26 at the Oakland Convention Center, where the weekend panels will include Image's 20th anniversary, Comics on TV and The Talking Dead Live, with The Walking Dead's Steven Yeun. For more on Image Expo, go to Skybound.com.
Thief of Thieves No. 1 is on sale Wednesday, with issue No. 2 in stores in March. Will you read it?
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3.5 stars (out of 4)
The xx debuted in 2009 with a self-titled album that was something of a quiet-storm indie-rock success story – combining subtle touches of R&B rhythm and texture with sparse guitar and haunted vocal interplay. After sweeping to the 2010 Mercury Music Prize in the U.K., the London-based trio is back with "Coexist" (Young Turks).
As improbable as it may sound, "Coexist" is even more minimal and subtle than its predecessor. Single-note guitar lines twist around elegant counterpoint bass melodies. The low end is almost subliminal, felt more than heard. Jamie Smith's array of programmed rhythms stretch between hip-hop thump and Caribbean steel-drum chime. But just as often, the beats are invisible, leaving big chasms of silence where the tension between vocalists Oliver Sim and Romy Madley-Croft can simmer.
Their bedroom voices convey anxiety and longing. "My heart is beating in a different way," Sim murmurs in "Missing," while Madley-Croft's wordless harmonies hover ghost-like in the background. Fulfillment is always just out of reach. The sound conveys that sense of possibility slipping off into the shadows: guitar notes and drum beats surface briefly, then dissolve.
The melodies aren't quite as immediate as the best songs from the debut, but "Coexist" functions as a near-perfect mood piece. Because there are so few elements in each song, each reverberating guitar note, each tick of a hi-hat or whispered aside makes a bigger impact. It's an album designed to be heard through ear buds or head phones, a 37-minute cocoon for shut-ins.


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10 February 2014 • Campus Lecture • By Deborah (Malacky) Belonick • Photos by John Nieuwsma
In a presentation centering on Christian identity, Archimandrite Zacharias, [2]a monk of the Monastery of St. John the Baptist, Tolleshunt Knights by Maldon, Essex, England, inspired an audience of more than 100 people with what he termed "domestic theology"—that is, "simple things" in church life that bear profound consequences. Father Zacharias, a disciple of Father Sophrony (of blessed memory) who was a disciple of St. Silouan of Mount Athos, [2] emphasized the importance of each Christian becoming a living Temple of God, but in particular, priests.
"Our identity as members of the body of Christ is of far greater importance than any other identity," he began, "Many tragedies in the Church are due to the fact that we simply are not aware of our identity as members of Christ's body."
Father Zacharias noted several ways to acquire "traces of the presence of Christ in our hearts, so that we begin to build the Temple of God": invoking Jesus' name incessantly; bearing a humble and contrite spirit; never judging or condemning others; exchanging our lives for God's life in the Divine Liturgy; and daily hastening to meet the Coming Christ, living eschatalogically and awaiting the Age to Come. "All of these inscribe (that is, circumcise) our hearts with a trace of Jesus," he observed.
He also stressed the greater responsibility of priests, stating that they must "work in secret to fill their hearts with the Holy Spirit, in order to transmit a living word to the souls of the people they meet." "Priests are not just celebrants of sacraments," he said. "We are comforters of souls. Our destiny is to give a word to make people understand their identity within the wondrous body of Christ."
Hear Fr. Zacharias' entire presentation on Ancient Faith Radio. [3]


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Four weeks after being rushed to the hospital for a "possible overdose" or "delirium as a result from exhaustion," reality thing Daisy de la Hoya resurfaced in Atlantic City last night, looking er, healthy.
The "Daisy of Love" star -- and her raggedy weave -- hosted a party at The Pool at Harrah's Resort and Casino.
Way to get back on that horse, girl.
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Non-Wool Fabrics
Before we can determine the benefits of wool for men's suits, let's take a look at other fabrics and what they offer.
Linens- Men's suits made from linen are generally used for summer. Linen is lightweight and considered to be very stylish. On the downside, linen wrinkles and stains very easily. Linen is also a poor choice for travel, since you'll need to have this fabric pressed upon arriving at your destination.
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Even when blended with other materials, wool still maintains many of its advantages. Keep in mind, the blended fabrics may change some of the make-up of the suit, though. It may be less dirt resistant with the addition of another type of fabric. The cost of the suit may also be less with a wool blend.
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Many occasions demand people to wear formal attire. Occasions such as weddings, dances, and important meetings often make it mandatory to wear formal clothing. Formal clothing can be broken up into two categories - the white and the black. The category depends upon the type of occasion and time of the day you are supposed to attend the function or the occasion. Unless otherwise specified, formal clothing for men generally consists of a tuxedo and a black bow tie.
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Monsoon Magic – A railway trek to Dudhsagar Falls
The monsoon is slowly building to a peak, and this is the time to explore the magnificent Dudhsagar Falls on the Goa-Karnataka border. Three railfanners took, quite literally, the railroad less travelled to explore this route. For those unfamiliar with railfanners, they are to trains and railways what birdwatchers are to birds. They are enchanted with the minutest details of the railway -- from locomotives, stations and carriages to rakes, signals, cabooses... you name it. Over three days, these intrepid enthusiasts planned a unique "trek" to Dudhsagar Falls in the Western Ghats. They met at Hubli, Karnataka and boarded the Haripriya Express to Londa, and then hailed an auto-rickshaw to Castle Rock. From there they trekked along the jungle-fringed track, lashed by monsoon downpours, to Caranzol. The weather being unkind, the station master advised them to head back to Castle Rock or Londa for the night. On the second day, they went to Dudhsagar and spent the day at the falls, indulging their passion for trainspotting. They returned home the next day. These images, shot by the railfanning trio of HARISH KUMAR, RAGHUPATHY JAYARAMAN and BEN HUR, capture some of the excitement of an unforgettable monsoon trek along the railway.


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Tokyo • Nissan is going to inject extra energy into its product lineup with the announcement here that Nismo — a Japanese performance-tuning enterprise that has operated (until now) outside the Nissan family — will be embraced within the corporate structure.
Nismo has been tweaking Nissan products for 30 years and has become a very successful brand, especially here in Japan. For example, this past racing season, Nismo teams won every racing series it entered. Now, Nissan chairman and CEO Carlos Ghosn wants that DNA injected into his company's product lineup and is building the firm a new facility adjacent to Nissan's research and development operations to make that goal a reality.
To demonstrate what the closer relationship can do, Ghosn introduced the Nismo Juke concept, a hint of what future Nismo-massaged vehicles will look like. Ian Forsyth, Nissan Canada's director of corporate planning and business strategy, says plans for Nismo include a range of vehicles — and he adds that he is looking "real seriously" at putting the Juke version in his dealers' showrooms. Forsyth says the focus of Nismo will not just be tuner and performance parts, but complete vehicles such as the Juke concept. Such vehicles will be integrated into the product portfolio, taking performance and driver experience to new heights without going to the extreme, all-or-nothing level of Mercedes-Benz's AMG models, for example.
This approach is in tune with the changes made to the Juke, a sporty compact crossover that's already creating its own market segment with more than 232,000 units sold globally. Shinji Sasaki, chief designer in Nissan's global design centre and the creator of the current Maxima sedan, was charged with giving the production Juke some Nismo flavour. He says the changes made to the vehicle reflect the direction he will be taking with other Nismo versions of Nissan products. Specifically, Sasaki says exterior changes that improve a vehicle's aerodynamics and stability at speed will be one part of a Nismo makeover. Inside the cabin, controls, gauges, seats and other elements will be upgraded to make them more driver-oriented, enhancing the driving experience by adding a more sporty flair. And, naturally, engines will be tweaked to a higher level of performance.
In the case of the Nismo Juke concept, its aerodynamic efficiency — and overall look — has been improved with a body kit that includes a new grille pattern, revised lower fascias front and rear, wider fenders and side sill skirts. The tailgate spoiler has been modified by the addition of side elements to control airflow more efficiently, while the shape of the exterior mirrors has been altered to enhance aerodynamic performance and reduce front and rear lift without increasing drag.
The chassis has been lowered and stiffened using parts that will be available from an expanded Nismo parts catalogue. The new macho exterior is completed with the addition of stylish 19-inch alloy wheels. Nismo tuning experts have also worked some magic on the 1.6-litre direct-injection turbo gasoline engine, resulting in more power and higher response and performance. Inside, Sasaki points out several changes that better interact with the driver's senses. The tachometer, for example, has a gauge face and needle that are illuminated in red because, he says, "that instrument is very important to the driver."The look and feel of such items as the steering wheel, pedals, gauges, shifter knob and door trim have been redesigned to provide a greater sense of involvement for the driver. The special racing-style front seats are trimmed in soft charcoal suede with contrasting red stitching for a very sporty look.
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Nissan will continue to stay true to its roots, Palmer says, executing innovative products and design such as the Juke and the zero-emissions Leaf, while also building products that generate excitement, such as the scorching hot GT-R supercar. "I can't think of another Japanese automaker that could bring you both those types of vehicles, the Leaf and the GT-R."
And that commitment won't change, Palmer says. "Not while I'm in this chair. Nissan products will not be boring during my watch."
Pointing to the Nismo Juke, Palmer says it's an answer for customers looking for a vehicle that's beyond the norm. "It's energetic, distinctive and highly desirable."
Other Nissan introductions here also included a Nismo concept version of the Leaf, as well as a trio of futuristic exercises. The ESFlow is an electric two-seater that can accelerate to 100 kilometres an hour in less than five seconds. The Townpod EV is a look at future crossover design, with interior space features that will suit business or family needs. Finally, the PIVO3 is the latest generation of a series of small, electric concepts
This three-seater features a centre-positioned driver's seat, with the passenger seats located on either side. Its technological features include a system that lets the car find its own parking spot, then returns to pick you up when summoned by a smartphone. Mechanically, the PIVO3's four-wheel steering enables it to turn around in less than two metres — truly a boon for drivers having to cope with the intense traffic here.
Postmedia News


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Bring Your Own Custom Image for Emulation Mode Virtual Machines
The Oracle Cloud Infrastructure Compute service enables you to import your older operating systems to Oracle Cloud Infrastructure. You can import a wide range of new and legacy production operating systems, using the QCOW2 or VMDK formats, and then run them on Compute virtual machines (VMs) using emulated hardware.
If your custom image supports paravirtualized drivers, we recommend you use paravirtualized mode. Linux-based operating systems running the kernel version 3.4 or newer support paravirtualized drivers. See Bring Your Own Custom Image for Paravirtualized Mode Virtual Machines for more information.
The following table lists the operating systems that are supported for emulation mode VMs:
Image Name
Supported Versions
|4.5, 5.9, 5.11, 6.9
|4.0, 4.8, 5.11, 6.9
|Oracle Linux
|4.5, 4.8, 5.8, 5.11, 6.2, 6.5
|8, 9, 10, 11
|Windows Server
2008 R2 Standard, Enterprise, Datacenter
2012 Standard, Datacenter
2012 R2 Standard, Datacenter
2016 Standard, Datacenter
- Note
- Oracle Cloud Infrastructure has tested the operating systems listed in the previous table and will support customers in ensuring instances launched from these images and built according to the guidelines outlined in this topic are accessible using SSH or RDP.
- For operating systems and operating system versions not listed above Oracle Cloud Infrastructure will provide commercially reasonable support to customers in an effort to get instances launched from these images accessible via SSH or RDP.
- Support from Oracle Cloud Infrastructure in launching an instance from a custom operating system does not ensure that the operating system vendor will support the instance. Customers running Oracle Linux on Oracle Cloud Infrastructure automatically have access to Oracle Linux Premier Support, see Oracle Linux for more information.
Custom Image Requirements
Linux-based and Windows-based custom images imported for emulation mode VMs must meet the following requirements:
The image must be set up for BIOS boot.
The maximum image size is 300 GB.
Only one disk is supported, and it must be the boot drive with a valid MBR and boot loader. You can migrate additional data volumes after the image's boot volume has been imported.
The boot process must not require additional data volumes to be present for a successful boot.
The disk image cannot be encrypted.
The disk image must be a VMDK or QCOW2 file. VMDK files must be either the "single growable" (monolithicSparse) type or the "stream optimized" (streamOptimized) type, both of which will consist of a single VMDK file. All other VMDK formats such as those that use multiple files, split volumes, or contain snapshots, are not supported.
Existing network interfaces will not be recreated. Instead, a single network interface will be created after the import process is complete. You should use DHCP on this interface to discover the network settings.
Requirements Specific to Linux-Based Custom Images
The following requirements are only applicable to Linux-based custom images:
The boot loader should use LVM or UUID to locate the boot volume.
The network configuration should not hardcode the MAC address for the network interface.
For Linux-based instances, we recommend that you enable certificate-based SSH, however this is optional. If you want your image to automatically use ssh keys supplied from the User Data field when you launch an instance, you can install Cloud-Init when preparing the image. See Creating an Instance for more information about the User Data field.
Custom Image Import Process
The following is a high-level outline of the steps required to import custom images for emulation mode VMs.
Prepare the image for import. This includes enabling serial console access for all Linux-based custom images and configuring a network interface without a static MAC address and to support DHCP. For more information, see Preparing a Custom Linux Image for Import and Preparing a Custom Windows Image for Emulation Mode.
Export the image as VMDK or QCOW2 format using existing virtualization tools. See the tools documentation for your virtualization environment.
Upload the image to Oracle Cloud Infrastructure Object Storage. See Managing Objects and Overview of Object Storage for more information.
Import the image. See Importing Custom Images.


text:
FEV1 indicates forced expiratory volume in the first second of expiration.
Mean change of forced expiratory volume in the first second of expiration (FEV1). Error bars indicate 95% confidence intervals (CIs). The 168-day treatment difference was 0.02 L (95% CI, −0.05 to 0.08; P = .61). aOne placebo participant was missing an FEV1 measurement at day 28, but underwent subsequent measurements in the study and was included in the analysis.
Hazard ratio (0.50; 95% confidence interval, 0.31-0.79; P = .003) was from a Cox proportional hazards model.
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Saiman L, Anstead M, Mayer-Hamblett N, et al. Effect of Azithromycin on Pulmonary Function in Patients With Cystic Fibrosis Uninfected With Pseudomonas aeruginosa: A Randomized Controlled Trial. JAMA. 2010;303(17):1707–1715. doi:10.1001/jama.2010.563
© 2019
Context Azithromycin is recommended as therapy for cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa infection, but there has not been sufficient evidence to support the benefit of azithromycin in other patients with CF.
Objective To determine if azithromycin treatment improves lung function and reduces pulmonary exacerbations in pediatric CF patients uninfected with P aeruginosa.
Design, Setting, and Participants A multicenter, randomized, double-blind placebo-controlled trial was conducted from February 2007 to July 2009 at 40 CF care centers in the United States and Canada. Of the 324 participants screened, 260 were randomized and received study drug. Eligibility criteria included age of 6 to 18 years, a forced expiratory volume in the first second of expiration (FEV1) of at least 50% predicted, and negative respiratory tract cultures for P aeruginosa for at least 1 year. Randomization was stratified by age of 6 to 12 years vs 13 to 18 years and by CF center.
Intervention The active group (n = 131) received 250 mg (weight 18-35.9 kg) or 500 mg (weight ≥36 kg) of azithromycin 3 days per week (Monday, Wednesday, and Friday) for 168 days. The placebo group (n = 129) received identically packaged placebo tablets on the same schedule.
Main Outcome Measures The primary outcome was change in FEV1. Exploratory outcomes included additional pulmonary function end points, pulmonary exacerbations, changes in weight and height, new use of antibiotics, and hospitalizations. Changes in microbiology and adverse events were monitored.
Results The mean (SD) age of participants was 10.7 (3.17) years. The mean (SD) FEV1 at baseline and 168 days were 2.13 (0.85) L and 2.22 (0.86) L for the azithromycin group and 2.12 (0.85) L and 2.20 (0.88) L for the placebo group. The difference in the change in FEV1 between the azithromycin and placebo groups was 0.02 L (95% confidence interval [CI], −0.05 to 0.08; P = .61). None of the exploratory pulmonary function end points were statistically significant. Pulmonary exacerbations occurred in 21% of the azithromycin group and 39% of the placebo group. Participants in the azithromycin group had a 50% reduction in exacerbations (95% CI, 31%-79%) and an increase in body weight of 0.58 kg (95% CI, 0.14-1.02) compared with placebo participants. There were no significant differences between groups in height, use of intravenous or inhaled antibiotics, or hospitalizations. Participants in the azithromycin group had no increased risk of adverse events, but had less cough (−23% treatment difference; 95% CI, −33% to −11%) and less productive cough (−11% treatment difference; 95% CI, −19% to −3%) compared with placebo participants.
Conclusion In children and adolescents with CF uninfected with P aeruginosa, treatment with azithromycin for 24 weeks did not result in improved pulmonary function.
Trial Registration clinicaltrials.gov Identifier: NCT00431964
A vicious cycle of infection and inflammation causes progressive lung destruction and premature death in patients with cystic fibrosis (CF). Treatment strategies have therefore included both antimicrobial and anti-inflammatory agents.1,2 Over the past decade, there has been increasing evidence that azithromycin, an antibiotic with both antimicrobial and anti-inflammatory activity, benefits individuals with CF. Although the mechanism of action of azithromycin in CF is not understood, 4 randomized, placebo-controlled trials have been conducted (Australia, Great Britain, the United States, and France) in adults and children with CF, most of whom had chronic infection with Pseudomonas aeruginosa.3-6 These studies demonstrated that azithromycin was associated with reduced pulmonary exacerbations, increased weight gain, or both, and improved lung function. Thus, azithromycin is currently recommended as chronic therapy for CF patients infected with P aeruginosa.7,8 Although 2 previous studies did enroll some pediatric CF patients without P aeruginosa infection,4,6 the evidence to support the use of azithromycin in this CF population is incomplete.
We conducted a multicenter, randomized, double-blind, placebo-controlled trial in children and adolescents with CF who were uninfected with P aeruginosa. We sought to determine if azithromycin improved lung function, reduced pulmonary exacerbations, and was safe and well-tolerated in this population of individuals with CF.
The trial was conducted from February 2007 to July 2009 at 40 CF Foundation–accredited care centers—31 in the United States, 9 in Canada, and coordinated by the CF Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Hospital, Seattle, Washington. Institutional review boards and ethics committees at each participating center approved the study and each of the participants, their parent(s), or both voluntarily provided written consent to participate in the trial. When appropriate, assent was also obtained from children younger than 18 years of age.
Eligibility criteria included a documented diagnosis of CF; participant age of 6 to 18 years; weight of at least 18 kg; forced expiratory volume in the first second of expiration (FEV1) of at least 50% predicted9; and 2 or more negative respiratory cultures for P aeruginosa obtained at least 1 year prior to randomization, which could include a negative screening culture (performed 7-14 days prior to randomization).
Exclusion criteria included a positive respiratory tract culture for P aeruginosa in the year prior to screening or at screening; relative decrease in FEV1% of at least 20% predicted between screening and randomization; use of antibiotics or high-dose systemic steroids within 14 days of screening (defined as ≥1 mg/kg/d if participant's weight was <20 kg or ≥20 mg/d if participant's weight was ≥20 kg); initiation of dornase alfa, ibuprofen, aerosolized antibiotics, or hypertonic saline within 30 days of screening; a positive respiratory culture for Burkholderia cepacia complex or nontuberculous mycobacteria (NTM) within 1 year of screening or a positive sputum smear for acid fast bacillus at screening; or abnormal laboratory values for γ-glutamyltransferase phosphate, aspartate serum transferase, or alanine transferase at least 2 times the upper limit of normal, creatinine greater than 1.5 times upper limit of normal for age, or absolute neutrophil count of 1000 or less.
Ongoing treatment (>30 days) with dornase alfa, high-dose ibuprofen, aerosolized antibiotics, hypertonic saline, inhaled steroids, or bronchodilators were permitted during the trial.
Participants were randomized (1:1) to the azithromycin group or placebo group within strata defined by age group (6-12 years vs 13-18 years) and CF center. The University of South Florida (Tampa) generated randomization assignments via a centralized, secure randomization system. The data coordinating center, PPD Inc (Wilmington, North Carolina), distributed blinded study drug kits to the centers. All study personnel and participants were blinded to treatment assignment.
Azithromycin (250 mg) and placebo were supplied as identically packaged tablets. Participants who weighed 18-35.9 kg were instructed to take 1 tablet 3 times per week (Monday, Wednesday, and Friday) and participants weighing 36 kg or greater were instructed to take 2 tablets on the same time schedule. Study drug was discontinued if a participant had: (1) an allergic reaction thought to be due to study drug; (2) a serious life-threatening adverse event, not including hospitalization for a pulmonary exacerbation; (3) an adverse event considered intolerable by the participant or the site's study team; or (4) NTM grown from a sputum sample obtained at screening. The study protocol included provisions for a step-down dosing regimen for toxicity thought to be related to study drug, eg, gastrointestinal adverse effects. Compliance was monitored by the number of pills dispensed and returned.
Medical history, physical examination, and spirometry were obtained at the screening visit (14 days before randomization). Clinical evaluations, physical examinations and spirometry were performed at days 0 (randomization), 28, 84, and 168 (completion of therapy). Adverse events and concomitant medications were recorded during each visit and by phone calls conducted at days 56, 112, 140, and 196.
Respiratory tract specimens for microbiological assessment were obtained at screening, day 84, and at day 168. All participants were swabbed for oropharyngeal specimens at screening and day 168 and from participants who could not expectorate sputum at day 84. Additional sputum specimens were obtained from those participants who could spontaneously expectorate sputum at screening and at days 84 and 168.
Blood samples to monitor hematology, liver function, and creatinine levels were obtained at screening and at days 28 and 168.
The primary outcome of the study was to determine if azithromycin was associated with a change in FEV1 (liters) from day 0 to completion of therapy (day 168). Exploratory end points included changes in forced vital capacity (FVC [liters]) and forced midexpiratory flow rate (FEF 25%-75% [liters/s]), and changes in FEV1, FVC, and FEF 25% to 75% as a percentage of reference values (% predicted).9 Pulmonary function testing was performed in accordance with American Thoracic Society standards.10
Additional exploratory end points included time to first pulmonary exacerbation, proportion of participants experiencing an exacerbation, hospitalization rate, and initiation of new oral, intravenous, and/or inhaled antibiotics. Pulmonary exacerbations were defined a priori using previously described clinical criteria (eTable 1), with the exception that the duration of minor criteria symptoms was at least 3 days in the current trial.11 Treatment for pulmonary exacerbations was at the discretion of site investigators, but the signs and symptoms that prompted initiation of new antibiotics were collected to determine if the criteria for a pulmonary exacerbation were fulfilled. Exploratory end points also included changes in body weight, height, and body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]).
Safety outcomes included adverse events obtained by open-ended questions of participants; laboratory evaluations for elevated liver function enzymes, creatinine, or absolute neutrophil count, and changes in microbiology.
Standardized microbiologic evaluation of throat cultures, sputum cultures, or both for potential bacterial pathogens was performed by the Cystic Fibrosis Therapeutics Development Network Center for CF Microbiology, Seattle Children's Hospital, Seattle, Washington.5 Sputum was also cultured for NTM. Testing for macrolide-resistant Staphylococcus aureus and macrolide-resistant Haemophilus influenzae was performed according to current guidelines.12 Treatment-emergent pathogens were defined as new detection of a pathogen at day 168 from a participant in whom that pathogen was not detected at baseline.
We hypothesized that the difference between treatment groups for the primary efficacy end point (168-day change in FEV1) would be 0.08 L or greater, with an observed standard deviation of 0.215 in each group as noted in previous clinical trials.5,13 Thus, with a sample size of 150 per group, the study had 90% power to detect this proposed treatment effect. This corresponded to an estimated 4% to 6% difference in the relative change in FEV1 between treatment groups. However, enrollment was slower than expected and to complete the study within the predetermined study period, which reflected impending expiration of study drug and funding, the CF Foundation Therapeutics Development Network Coordinating Center principal investigators (L.S., M.A., L.C.L., and F.R.) and Cystic Fibrosis Foundation Therapeutics Inc elected to complete enrollment when approximately 260 participants were randomized. This decision was made independent of knowledge of interim study results and based on the estimation that a sample size of 130 per treatment group would provide 85% power to detect a 0.08-L difference between treatment groups with the assumptions used in the initial sample size planning.
Analyses were conducted by the CF Foundation Therapeutics Development Network Coordinating Center according to a prespecified analysis plan. The primary efficacy and safety analyses were performed with the modified intent-to-treat population, defined as all randomized participants who received at least 1 dose of study drug. For the primary efficacy analysis, we used a piece-wise, linear, repeated-measures regression model using generalized estimating equations with robust variance estimation.14,15 The regression parameters and their robust variance estimates were used to derive the model-based average change from baseline to day 168 for each treatment group, and compared using a .05 level of significance 2-sided t test with corresponding 95% confidence interval (CI). A piece-wise linear model with change point at day 28 was assumed a priori based on previous successful studies of therapies for CF, including azithromycin,5,13,16 in which an acute improvement in the active treatment group was observed by day 28 followed by a linear pattern of decline, improvement, or stabilization for the remainder of the treatment period (day 28 through day 168).
The 168-day change in exploratory pulmonary function measures was compared using 2-tailed sample t test, α = .05, and the relative change in FEV1 was calculated as:
[FEV1 at day 168 − FEV1 at day 0] × 100 [FEV1 at day 0]
Time to first exacerbation was assessed using Cox proportional hazards regression and graphically displayed using Kaplan-Meier estimates. Between-group comparisons of proportions were performed using χ2 tests or the Fisher exact test as appropriate, with corresponding 95% CI derived using the Newcombe-Wilson method.17 Differences between groups in the linear rate of change from baseline in height, weight, and BMI were estimated and tested using repeated measures regression with robust variance estimation.15
All secondary analyses were considered exploratory and thus no adjustments for multiple comparisons were performed. Diagnostics were performed as appropriate for all statistical models. P < .05 was considered statistically significant for all analyses, which were derived using either SAS version 9.1.3 (SAS Institute, Cary, North Carolina) or R statistical package version 2.9.1 (R Foundation for Statistical Computing, Vienna, Austria).
Safety outcomes were monitored throughout the study by a data monitoring committee from the CF Foundation data and safety monitoring board. One planned interim analysis to monitor patient safety was performed after half of the total number of randomized participants completed 3 months of study drug.
Of the 324 participants screened for this study, 263 (81%) were randomized; 131 were randomized to the azithromycin group and 132 were randomized to the placebo group. Overall, 131 participants in the azithromycin group and 129 participants in the placebo group received study drug (Figure 1). The median number of participants randomized per center was 6 (range, 2-14) across the 40 study centers that screened participants for eligibility. Three participants randomized to the placebo group did not receive study drug and were therefore not included in the modified intent-to-treat population. The baseline characteristics of participants were similar in the treatment groups, including the proportions of participants in each group using chronic concomitant medications (Table 1). Retention of participants was high, with only 5 and 3 participants withdrawing from the azithromycin and placebo groups, respectively (Figure 1). Excellent adherence was observed during the study; on average, 90% and 91% of the weekly dosages were used in the azithromycin and placebo groups, respectively.
The mean (SD) baseline and 168-day FEV1 was 2.13 (0.85) and 2.22 (0.86) L for the azithromycin group and 2.12 (0.85) and 2.20 (0.88) L for the placebo group. The primary end point analyses estimated a 0.02-L increase in the 168-day FEV1 change from baseline in the azithromycin group as compared with the placebo group, which was not statistically significant (95% CI, −0.05 to 0.08; P = .61; Figure 2). Similarly, there were no statistically significant treatment effects observed in the change in the exploratory pulmonary function end points (Table 2).
Compared with the placebo group, the azithromycin group had a 50% reduction in pulmonary exacerbations (95% CI, 31%-79%; P = .003; Figure 3). Overall, 28 of the 131 azithromycin participants (21%) and 50 of the 129 placebo participants (39%) experienced an exacerbation (−18% treatment effect; 95% CI, −28% to −6%; P = .003). The azithromycin group also had a −27% difference in the initiation of new oral antibiotics compared with the placebo group (65/131 [50%] vs 99/129 [77%], respectively; 95% CI, −38% to −16%; P < .001). During the study, few participants were treated with intravenous or newly initiated inhaled antibiotics, or both, and there were no significant differences between treatment groups. Intravenous antibiotics were initiated in 11 of 131 (8%) azithromycin participants vs 14 of 129 (11%) placebo participants (−3% treatment difference; 95% CI; −10% to 5%; P = .54), and inhaled antibiotics were newly initiated in 15 of 131 (11%) azithromycin participants vs 21 of 129 (16%) placebo participants (−5% treatment difference; 95% CI, −13% to 4%; P = .29). The percent of participants hospitalized was also comparable between the 2 groups with 12 of 131 (9%) in the azithromycin group vs 13 of 129 (10%) in the placebo group hospitalized (−1% treatment difference; 95% CI, −8% to 7%; P = .84).
During the 168-day study period, participants in the azithromycin group had a greater increase in weight (0.58 kg treatment difference; 95% CI, 0.14-1.02; P = .01) and in BMI (0.34 treatment difference; 95% CI, 0.15-0.52; P < .001) than participants in the placebo group. There was no significant difference in changes in height between the 2 groups (0.04-cm treatment difference; 95% CI; −0.41 to 0.33; P = .83).
Thirteen treatment-emergent, serious, adverse events occurred in the azithromycin group and 18 occurred in the placebo group; 12 of 131 azithromycin participants (9%) and 14 of 129 placebo participants (11%) experienced at least 1 serious adverse event (−2% treatment difference; 95% CI, −9% to 6%; P = .68). These events were consistent with CF-related complications. The differences in the incidence of combined nonserious and serious adverse events in the 2 treatment groups are shown in Table 3. The only adverse events that significantly differed between the 2 groups were cough (−23% treatment difference; 95% CI, −33 to −11; P < .001), and productive cough (−11% treatment difference; 95% CI, −19 to −3; P = .01); fewer participants in the azithromycin group experienced these events compared with those in the placebo group. Nausea, diarrhea, and wheezing occurred with similar frequency in the 2 groups. Nausea occurred in 11 of 131 (8%) azithromycin participants and in 12 of 129 (9%) placebo participants (−1% difference; 95% CI, −8% to 6%), diarrhea occurred in 6 of 131 (5%) azithromycin participants and in 11 of 129 (9%) placebo participants (−4% difference; 95% CI, −11% to 2%), and wheezing occurred in 10 of 131 (8%) azithromycin participants and in 9 of 129 (7%) placebo participants (1% difference; 95% CI, −6% to 7%). The majority of adverse events were described as mild to moderate by the investigators. There were no significant differences between treatment groups with respect to abnormal changes in laboratory parameters.
Dose modification of study drug occurred in 3 of 131 azithromycin participants (2%) and 6 of 129 placebo participants (5%). All individuals with dose modifications remained in the study including 2 azithromycin participants and 1 placebo participant who had dose modifications that resulted in permanent discontinuation of study drug.
At baseline, the microbiology profile was comparable between the 2 treatment groups (Table 4); 37 of 131 azithromycin participants (28%) and 46 of 128 placebo participants (36%) harbored macrolide-resistant S aureus. After randomization, 1 participant in the azithromycin group was found to be positive for P aeruginosa from the screening culture and withdrew from the study. One participant in the placebo group was positive for NTM and was discontinued from study drug, but remained in the study.
The only significant differences in treatment-emergent pathogens between treatment groups occurred with macrolide-resistant S aureus and H influenzae with 27% (95% CI, 14%-38%; P < .001) and 7% (95% CI, 2%-13%; P = .01) more emergence of these organisms, respectively, in azithromycin participants as compared with placebo participants. At baseline, 31 azithromycin and 23 placebo participants produced sputum and at the last day of the study period, 32 azithromycin and 19 placebo participants produced sputum for NTM culture. No participants in either treatment group had treatment-emergent NTM. There were no statistically significant differences between treatment groups in the eradication of the pathogens displayed in Table 4 (eTable 2).
This is, to our knowledge, the largest study conducted to date to examine the potential benefits of azithromycin in CF patients uninfected with P aeruginosa. In this study population of relatively healthy children and adolescents (mean FEV1% predicted 97%), azithromycin did not improve lung function, although detection of improvements in lung function could be limited in this study population with mild lung disease. However, analyses of exploratory end points demonstrated that when compared with the placebo group, the azithromycin group had a 50% reduction in pulmonary exacerbations, 27% reduction in the initiation of new oral antibiotics (other than azithromycin), 0.58-kg weight gain, and 0.34-unit increase in BMI. There were no differences in treatment groups in use of intravenous or inhaled antibiotics or hospitalizations.
Previous studies of azithromycin in CF have mainly focused on patients with P aeruginosa infection, although 2 trials included pediatric participants who were not chronically infected with P aeruginosa.4,6 While azithromycin was associated with a reduction in the number of pulmonary exacerbations, a reduction in the use of oral antibiotics, and/or an increase in time to exacerbation, these previous studies did not use a priori definitions for pulmonary exacerbations. However, there is no standardized definition for a pulmonary exacerbation, especially in patients with mild lung disease.18 Previous trials conducted in CF patients with moderate to severe lung disease have generally defined pulmonary exacerbations as those events requiring intravenous antibiotics as such exacerbations have been linked to mortality.19
The definition used for pulmonary exacerbations in the current study was developed by a working group of CF clinicians for use in an eradication trial of P aeruginosa recently conducted in children with CF aged 1 to 12 years.11 This definition uses clinical characteristics expected to delineate a pulmonary exacerbation in children with relatively mild lung disease, but has not been formally validated. Our observation that the azithromycin group had a reduction in the initiation of new oral antimicrobial agents, but not in the initiation of intravenous antibiotics, provides indirect support that this case definition successfully identified mild exacerbations. However, future studies are needed to further evaluate this case definition.
To date, the mechanism of action of azithromycin in CF remains uncertain. As suggested by previous clinical trials4-6 and confirmed in this trial, azithromycin does not eradicate CF pathogens. Earlier in vitro studies showed that azithromycin decreased expression of proinflammatory cytokines, but had a variable effect on anti-inflammatory cytokines and altered bacterial characteristics such as pili, flagella, exoproducts, and P aeruginosa quorum sensing.20,21 Azithromycin has been shown to reduce neutrophil recruitment in response to P aeruginosa infection in non CF animal models22 and to reduce neutrophilia and interleukin (IL)-8 in patients with bronchiolitis obliterans syndrome.23 In CF airway epithelial cells, azithromycin down-regulated IL-8 transcription and protein expression and reduced DNA binding of the IL-8 transcriptional regulators nuclear factor-κB (NF-κB) and activator protein-1 (AP-1).24 In ΔF508 homozygous CF mice, azithromycin has also been shown to reduce baseline inflammation as well as P aeruginosa lipopolysaccharide-induced inflammation.25 However, human data supporting the anti-inflammatory effects of azithromycin in CF are scarce. We previously demonstrated that levels of neutrophil elastase in sputum were stable in CF participants treated with azithromycin, but increased by 0.2 log10 μg/mL in CF participants treated with placebo, suggesting a potential anti-inflammatory effect.5 However, sputum levels of IL-8 did not differ between the 2 treatment groups. Future studies should continue to assess the mechanism of action of azithromcyin in patients with CF.
Azithromycin was well tolerated. There was no increase in serious or nonserious adverse events among participants receiving azithromycin. Specifically, nausea, diarrhea, or wheezing, which were observed more frequently in the azithromycin group in our previous trial,5 occurred with similar frequency in the azithromycin and placebo groups in the current trial and occurred in fewer than 10% of participants in either group. In contrast, cough and productive cough occurred less frequently in the azithromycin group, consistent with the reduction in pulmonary exacerbations as defined in this trial.
During the 6-month study period, azithromycin was not associated with significant changes in microbiology. There was no increase in treatment-emergent Gram-negative pathogens, including P aeruginosa, or in methicillin-resistant S aureus. However, treatment-emergent macrolide-resistant S aureus and macrolide-resistant nontypeable H influenzae were increased in the azithromycin group. This finding was expected as others have demonstrated macrolide-resistant S aureus26-28 as well as macrolide-resistant commensal flora29 associated with chronic azithromycin treatment in CF patients. The clinical implications of macrolide-resistant S aureus and nontypeable H influenzae in CF are unknown, but numerous alternative agents exist for these pathogens and macrolide antibiotics are not generally used to treat CF pulmonary exacerbations.
There are some potential limitations to this study. The generalizability of our findings may be limited because participants had mild lung disease. Participants could have been misclassified as uninfected with P aeruginosa because the majority only had oropharyngeal cultures obtained, although the negative predictive value of oropharyngeal swabs has been shown to be as high as 95%.30 We did not use serologic studies to assess P aeruginosa status. Treatment-emergent pathogens were only assessed at the end of the trial by the core microbiology laboratory and not assessed at other time points during the trial. Because few participants spontaneously expectorated sputum, this trial did not fully assess the risk of treatment-emergent NTM. Finally, changes in quality of life or patient-reported outcomes were not studied.
Among a group of children and adolescents with CF uninfected with P aeruginosa, treatment with azithromycin for 24 weeks, compared with placebo, did not result in improved pulmonary function. In the evaluation of exploratory end points, azithromycin was associated with a significant reduction in pulmonary exacerbations and a significant increase in weight gain. Further studies of azithromycin are warranted to further investigate its potential use in this population.
Corresponding Author: Lisa Saiman, MD, MPH, Columbia University, Department of Pediatrics, 650 W 168th St, PH 4 West, Room 420, New York, NY 10032 (firstname.lastname@example.com).
Author Contributions: Dr Saiman had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Saiman, Anstead, Mayer-Hamblett, Lands, Burns, Marshall, Ratjen.
Acquisition of data: Saiman, Anstead, Mayer-Hamblett, Lands, Hocevar-Trnka, Rose, Burns, Ratjen.
Analysis and interpretation of data: Saiman, Anstead, Mayer-Hamblett, Lands, Kloster, Hocevar-Trnka, Goss, Marshall, Ratjen.
Drafting of the manuscript: Saiman, Anstead, Mayer-Hamblett, Lands, Kloster, Hocevar-Trnka, Ratjen.
Critical revision of the manuscript for important intellectual content: Saiman, Anstead, Mayer-Hamblett, Lands, Goss, Rose, Burns, Marshall, Ratjen.
Statistical analysis: Mayer-Hamblett, Kloster.
Obtained funding: Saiman, Marshall.
Administrative, technical, or material support: Saiman, Hocevar-Trnka, Goss, Rose, Burns, Ratjen.
Study supervision: Saiman, Anstead, Lands, Rose, Marshall, Ratjen.
Safety monitoring and data review: Goss.
Financial Disclosures: Dr Saiman reports having served on advisory boards for Aridis, Bayer, Chiesi, Gilead, MPex, Novartis, Pfizer, SmithKlineBeecham, and Transave and receiving research funding (institutional) from Bayer, Chiesi, Johnson & Johnson, the National Institutes of Health, the Centers for Disease Control and Prevention, and CF Foundation Therapeutics, Inc. Dr Anstead reports receipt of funding (institutional) from CF Foundation Therapeutics, Inc. Dr Mayer-Hamblett reports receipt of funding (institutional) from CF Foundation Therapeutics, Inc and the National Institutes of Health. Dr Lands reports having served on advisory boards for Novartis and Solvay. Ms Kloster reports receipt of funding (institutional) from CF Foundation Therapeutics, Inc. Ms Hocevar-Trnka reports no disclosures. Dr Goss reports having served on an advisory board for Transave Inc without receiving financial reimbursement, receipt of research funding (institutional) from CF Foundation Therapeutics, Inc, the National Institutes of Health, Firlands Foundation, and Transave Inc, and SEER Pharmaceuticals for clinical trial participation. Dr Rose reports receipt of research funding from CF Foundation Therapeutics, Inc and the National Institutes of Health (National Center for Research Resources Clinical and Translational Science Award to the University of Washington). Dr Burns reports receipt of research funding (institutional) from Chiesi, Transave, Gilead, CF Foundation Therapeutics, Inc, and the National Institutes of Health. Dr Marshall reports having participated as an advisor to the executive study team and serving as a representative of CF Foundation Therapeutics, Inc. Dr Ratjen reports having served on advisory boards for AOP, Bayer, Boehringer/Ingelheim, Gilead, Inspire, MAP, Novartis, Pharmaxis, Roche, Vertex, and receipt of research funding (institutional) from Inspire, Novartis, Roche, CF Foundation Therapeutics, Inc, the National Institutes of Health, the Canadian CF Foundation, and the Canadian Institute of Health Research.
Funding/Support: This study was funded by CF Foundation Therapeutics, Inc. (CFFT). The CFFT Therapeutics Development Network (TDN) was funded by the CFFT to manage this trial on behalf of the study principal investigators (LS, MA, LCL, and FR) and the TDN Coordinating Center (CF Foundation Therapeutics Development Network Coordinating Center) was the regulatory sponsor of the study. The CF Foundation Therapeutics Development Network Coordinating Center leadership (NMH and LMR) participated on the executive committee for the study along with the principal investigators and participated in discussions and decisions pertaining to the study. Drug and placebo were supplied by Pfizer, Inc, which was not otherwise involved in any aspect of the study.
Role of Sponsor: CFFT did not participate in the design and conduct of the study; the collection, management, analysis, or interpretation of the data; nor the preparation, review, or approval of the manuscript.
AZ0004 Azithromycin Study Group Investigators: James D. Acton, MD, and Lorrie Duan, RN BSN (Cincinnati Children's Hospital); Ran D. Anbar, MD, and Valoree Suttmore, BS (SUNY Upstate Medical University); Michael Anstead, MD, and Barbara Owsley, RC (University of Kentucky); Philip Black, MD, and Candy Schmoll, RN, BSN (The Children's Mercy Hospital); Barbara Chatfield, MD, and Jane Vroom, BS (University of Utah); John Colombo, MD, and Deb Heimes, RC (UN Medical Center-Pediatric Pulmonary); A. George F. Davidson, MD, and Maggie McIlwaine, MCSP (BC Children's Hospital); Allen J. Dozor, MD, and Ingrid Gherson, MPH (New York Medical College); Albert Faro, MD, and Mary Boyle, RN, MSN (Washington University in St. Louis); Jonathan Finder, MD, and Judy Fulton, MPH, RD, LDN (Children's Hospital of Pittsburgh); Deborah Froh, MD, and Robin Kelly, RN (University of Virginia at Charlottesville Children's Hospital); Michelle S. Howenstine, MD, and Terry Barclay, RN, BSN (Riley Hospital for Children); Tom Kovesi, MD, and Anne Smith, RN (Children's Hospital of Eastern Ontario); Thomas Lahiri, MD, and Emily Keller, BS (Vermont Children's Hospital); Larry C. Lands, MD, PhD, and Jennifer Frei (Montreal Children's Hospital); Craig Lapin, MD, and Ginny Drapeau, BSN, RN (Connecticut Children's Medical Center); Brian Lyttle, MD, and Anne-Marie Lyttle, RN, (Brian Lyttle's private practice); Karen McCoy, MD, and Patricia Olson, RN (Nationwide Children's Hospital); Marcel Milot, MD, and Chantale Martineau, (CSSS de Chicoutimi); Kathryn S. Moffett, MD, and Sue Collins, MSN, RN (West Virginia University); Mark Montgomery, MD, FRCP(C), and Dianne MacLean, BS (Alberta Children's Hospital); Samya Z. Nasr, MD, and Dawn Kruse, CCRC (University of Michigan); Mary E. Noseworthy, MD, and Kimberley Manning (Janeway Children's Health & Rehabilitation Hospital); H. Worth Parker, MD, and Nicola Felicetti, RN (Dartmouth Hitchcock Medical Center); Linda Pedder, MD, and Rosamund Hennessey (McMaster Health Sciences Centre); Elizabeth Perkett, MD, Michelle Robinette, FNP-BC, and Cathy Tuzeneu, RN,BSN (Vanderbilt Children's Hospital); Adrienne Prestridge, MD, and Catherine Powers, RD, LDN (Children's Memorial Hospital); Diana R. Quintero, MD, and Brilliant Nimmer, BS (Children's Hospital of Wisconsin); Peggy J. Radford, MD, and Natalia Argel, BSN, RN-BC (Phoenix Children's Hospital); Felix Ratjen, MD, PhD, and Renee Jensen, RRT (The Hospital for Sick Children); Warren E. Regelmann, MD, and Patricia Grover, RN (University of Minnesota); Clement L. Ren, MD, and Marissa Dixon, BS (University of Rochester Medical Center); George Retsch-Bogart, MD, and Caroline O'Connor, BA (University of North Carolina at Chapel Hill); Eduardo Riff, MD, and Judy Marciel, MSN, RN (East Tennessee Children's Hospital, Pediatric Pulmonary & Respiratory Care); Ronald C. Rubenstein, MD, PhD, and Erin Hogge, BS-RRT (The Children's Hospital of Philadelphia); Lisa Saiman, MD, MPH, and John D'Agostino, RN (Columbia University); Michael Schechter, MD, MPH, and Jeannie Peabody, RN, BSN (Emory University); L. Terry Spencer, MD, and Summer Adams (Children's Hospital Boston); Dennis C. Stokes, MD, and Barbara Culbreath, RN, BSN (University of Tennessee LeBonheur Children's Medical Center); and Laurie Varlotta, MD, and Marcella Aramburo, BA (St. Christopher's Hospital for Children).
Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center (Project Office and Clinical Coordinating Center): Lynn Rose PhD, Chris Goss, MD, MSc, Terry Hough, MD, Jasna Hocevar-Trnka, MPH, Morty Cohen, RPh, Olena Boyarska, BS, Kimberly Gilmore, ND, Barbra Fogarty, and Lynne Larson, MS; Biostatistics and Clinical Data Management Unit (BCDM): Nicole Mayer-Hamblett, PhD, Margaret Kloster, MS, Ann Fowler, MA, Julie Fox, Barbara Mathewson, MS, Rohini Rao, MS, and Ilonka Evans, MS.
University of South FloridaDatabase Management and Randomization: Jeffrey Krischer, PhD, June Tran, MS, Franz Badias, BS, David Cuthbertson, MS, Bruce Gainer, MS, Michael Abbondondolo, MS, Jamie Malloy, MS, Veena Gowda, BS, Ken Young, BS, and Ping Xu, MPH.
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O.J. Mayo scored 28 points, Vince Carter hit a critical jumper in the final minute and the Dallas Mavericks beat the Portland Trail Blazers 105-99 on Wednesday night for coach Rick Carlisle's 500th career victory.
Mayo had 20 in the first half and was mostly quiet before getting two important baskets with Portland trying to rally late in the fourth quarter.
Carter put Dallas ahead 99-94 with a jumper just inside the 3-point line with the shot clock winding down.
LaMarcus Aldridge had 27 points and 10 rebounds a week after he beat the Mavericks at the buzzer in Portland.
(Copyright 2013 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.)


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Mayor Nagel and Chief Wood -Here is a response from Burlingame PD
I am writing in response to a traffic incident - a bicycle vs car collision - yesterday on Old Bayshore Road in Burlingame. While I was not involved in the incident, I am familiar with the details as the injured person - a Mr. Theo Cummings - is a good friend of mine and I often ride my bicycle on Old Bayshore with Mr. Cummings.
The facts are pretty straightforward, a VW Passat - license CA 5ULW165 made a right turn on Malcom Road off Old Bayshore without yielding the right of way to Mr. Cummings and the 3 cyclists following him who were going straight on Old Bayshore. This is commonly known as a "Right Hook" collision.
The response by Burlingame Forces was fine - perhaps over the top - one witness said "I counted 2 cop cars, 1 Fire Commanders car, 2 Fire Engines, and 1 Ambulance." Mr. Cummings was checked out by the Paramedics and will make a full recovery assuming the exam by the Urgent Care doctors was thorough and accurate. For this we can be thankful.
I was shocked however, to find that in an incident which could easily have cost Theo his life, that the Burlingame Police felt no need to cite the driver with even something as simple as "Failure to Yield". Personally, I would think reckless driving would be appropriate - he turned right in front of not one but four cyclists. Drivers with such little skill or care should be cited when they cause accidents - we have a "Points" system in California for a reason. In a time when red light cameras are being tuned to cite drivers who make a "California Stop" when turning right on red, a driver who causes a life threatening collision surely must be cited.
When I tell my friends about my commute route, I mention that I ride through the San Francisco Airport, and they express surprise. I tell them that the Airport is actually quite pleasant to ride through, and that the place I wish would disappear off the map entirely is Burlingame. While I do like visiting your downtown (accessed via the Caltrain), riding on Old Bayshore is quite annoying. Knowing that the Burlingame Police Force is unwilling to cite drivers who cause accidents inside your city, gives one even more pause.
The most insulting part of the entire experience, for my money, is this. A negligent driver had just run over Mr. Cummings, and a member of the Burlingame Police responded as such (I quote Mr. Cummings).
"The cop actually tried to suggest that we ride on back streets..."
Aside from the fact that this is blaming the victim, the accident happened on "Old Bayshore". Not on Highway 101. "Old Bayshore" is the back street. There was no excuse for this collision. It should have resulted in a citation.
Thank You
John Murphy San Francisco
Mr. Murphy,
Let me respond to this from the perspective of a cyclist and a police officer. Prior to moving the Coast, I regularly commuted from Fremont to Burlingame. I have continued to ride bikes, but I had to stop commuting as riding over Hwy 92 on a regular basis is too risky. I also understand the frustrations of having my right of way violated by cars and have had several close calls.
I am sorry for the frustration you are experiencing regarding your friend's injury and the lack of a citation being issued to the other driver. Unfortunately, police officers are not permitted to cite drivers at the scene of an accident unless they have been to an advanced accident investigation course. However, this does not mean the driver who causes a collision gets off without a blemished driving record. When an officer takes an accident report, he or she is almost always able to determine fault. This report is filed with the CHP who in turn delivers the accident findings to the DMV. The DMV then assigns a "point" to the party at fault's driver's license.
In reality this practice, from an enforcement perspective, is more efficient than issuing citations. If a citation is issued, the findings of a collision report are not shared with the DMV. The citation becomes the method of delivery to a person's driving record. Should this citation be contested in court, for a variety of reasons, the point may not be assigned to a person's driving record. Accident report findings cannot be contested. The DMV relies on the officer's "opinion" of who is at fault when assigning points.
In regards to the officer's comment suggesting cyclists should ride their bikes on the back road, I had the opportunity to overhear the officer discuss this at the police station. The officer rides his bicycle to work as well. Due to the number of bicycle collisions he has responded to over the years, and his own personal experience with riding bicycles, he merely meant to pass on advice with safety being first priority. We all know that bicycles have the same rights as cars. Unfortunately, when a bicycle is involved in a collision, the cyclist is almost always injured. Often times these injuries are serious or, as you mentioned, fatal.
Please feel free to call me if you have any questions.
Don Shepley
Acting Patrol Captain


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According to the Bureau of Labor Statistics, 21 states and the District of Columbia reported unemployment rate increases in November, while 15 states registered decreases and 14 states remained unchanged. Nationally, unemployment was at 9.8 percent in November.
Click ahead to see where your state may rank.
Updated Dec. 17, 2010


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That's the best part about Medicom is that you truely have no idea what they will do...
I"m just seeing this now. Wow, awesome set. Brent, I don't suppose you're planning on getting it? If it looks like there's an extra set I am totally in.
$700 for a master case - no.
Quote from: Morgbug on October 23, 2009, 07:26 PM$700 for a master case - no. Wuss.
Page created in 0.073 seconds with 18 queries.


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Active surveillance, or watchful waiting, involves actively monitoring the course of the disease with the expectation to intervene if the cancer progresses. Patients under active surveillance must commit to a regular schedule of follow-up, which includes a prostate exam and prostate-specific antigen (PSA), and which may include repeat prostate needle biopsies, especially if you're younger.
Your doctor may offer this choice if:
- You are older (less than a 20-year life expectancy) or have other health problems
- You are diagnosed with early-stage prostate cancer that seems to be slow growing
- Your Gleason score is 6 or less and your cancer is not detectable by rectal examination
The risks and potential side effects associated with treatment often outweigh the benefits in men with low and very low risk disease. The latest National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Oncology™ for Prostate Cancer recommend only active surveillance for those who meet the criteria for very low risk disease and have life expectancy less than 20 years.
Active surveillance avoids or delays the side effects of surgery and radiation, but this choice has risks. Rarely, it may reduce the chance to control cancer before it spreads. Also, it may be harder to cope with surgery and radiation therapy as you age. As with all treatment options, patients should discuss the pros and cons with their physicians.


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I wanted to include a couple of dishcloths with a family member's Christmas gift, so I found some pretty cotton yarn in my stash and started working away. I wanted to use sunny and bright colors that would be cheerful on the grayest winter day.
What I came up with is the Citrus Twist Dishcloth...
A fun little dishcloth with a lot of "a-peel". :-)
Citrus Twist Dishcloth
by Heather P.
100% cotton worsted weight yarn
G crochet hook
Stitches used:
ch - chain
sc - single crochet
hdc - half double crochet
dc - double crochet
sl st - slip stitch
Ch 32
Row 1: sc in 2nd ch from hook and in each ch across, ch 2, turn. (31 sts now and throughout.)
Row 2: dc in 1st st, sc in next st, *dc 2 times in next st, sk 1 st, sc in next st, repeat from * across to last two sts, sc in next st, dc in last st, ch 2, turn.
Row 3: dc in 1st st, hdc in the next st and in each st across, end row with a dc in the last st, ch 2, turn.
Row 4 and 5: Repeat row 3 (for a total of two additional rows).
Alternate Rows 2 and 3 until your cloth measures approx 6 1/2 inches (end with a Row 2).
Repeat Rows 3 - 5 (for a total of three additional rows).
Repeat Row 2, ch 1, turn.
sc across, ch 1 (do not turn work).
Round 1: sc evenly around cloth with (3 sc) in each corner, sl st in 1st sc, fasten off.
Round 2: Attach a complimentary color in any corner, sc evenly around cloth with (3 sc) in each corner, sl st in 1st sc, fasten off.
Weave in ends.


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This is the first of its kind site to fully dedicate the Tamil MP3 Songs with
Tamil Song Lyrics.
What is the rememdy for this? Our site! Yes our site enables the visitor to hear
the song as well as see the words of the Tamil song Lyrics. This enables the visitor
with greater joy of new Tamil MP3 music experience.
Just hear the Tamil song one or two times along with the Tamil Song's lyrics. That's
it. Automatically your mind will remember to recall the Tamil Song Lyrics again.
We strongly believe that, once the parents teaches the basic letters and words in
tamil language, the children who comes to this site, will definitely and easily
can pickup the tamil learning, just by listening to music while they watch the words
in real Tamil letters. Surely it will increase the learning curve at ease.
This sounds great! Isn't it?
We dedicate this site to all the people who loves to learn and speak tamil, one
of the ancient language, the entire world agrees.
Jai Hind!


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Apple is expected to introduce an iPhone 5 at its planned Sept. 12 event, and what follows, by any number of accounts, should be dramatic. JPMorgan Chase analyst Michael Feroli has suggested that the smartphone's arrival could actually boost the entire U.S. economy by up to half a percent. Topeka Capital analyst Brian White has predicted that its arrival will usher in the "biggest upgrade in consumer electronics history," while Jefferies' Peter Misek expects nothing short of the "biggest handset launch in history."
Certainly, then, Apple's new iPhone could also bring about a few feature phone converts. On the eve of Apple's announcement, the Pew Research Center released a study offering a snapshot of where we currently stand without it.
In Pew's Aug. 7 through Sept. 6 survey of 3,014 adults, it found that 45 percent of all American adults currently own a smartphone. Among young adults, those 18 to 29 years old, and all adults in households with incomes of $75,000 and higher, that figure rises considerably, to 66 percent and 68 percent, respectively.
"These latest figures show that smartphone ownership has increased from 35 percent in May 2011 to 45 percent," Pew said in the Sept. 11 report. More notably, it added, "There has been no change in smartphone ownership from figures ... in a survey at the beginning of the year."
Further reading
Apple's second-quarter iPhone sales failed to meet Wall Street expectations for only the second time in 39 quarters-which Apple CEO Tim Cook suggested could be due to consumers waiting for the iPhone 5-and Samsung earlier this month announced that it had sold more than 20 million Galaxy S III smartphones. Perhaps those who planned to buy one already have? If Apple's latest device can push the needle on smartphone user totals, Pew should know so by the end of the year.
NPD Group analyst Stephen Baker pointed out in a Sept. 11 blog post that Apple has already sated iPhone-hungry customers at Verizon Wireless and Sprint (T-Mobile's subscribers certainly remain hungry) and that "since blowing away all the weakened competition," it's now in the more challenging position of facing only the remaining, tougher competition.
But given's Pew's 45 percent figure, there are still users to convert. Who are they?
They're equally men and women. Pew found 46 percent of men to be smartphone owners, compared with 45 percent of women. Age is a far greater determinant of smartphone use: The younger the user group, the more likely to use smartphones. Among adults 30 to 49 years, 59 percent own smartphones, while that dips to 34 percent for the 50- to 64-year-old set and 11 percent for senior citizens.
Income and education, Pew found, also consistently affect smartphone ownership-the higher the household income or education level of respondents, the greater the percentage of smartphone owners among their peers.
Ethnically, Pew continued, Hispanics are the leading smartphone owners-49 percent, compared with 47 percent of black respondents and 42 percent of white.
Pew doesn't offer breakout information on users who identify themselves as Asian, because it says not enough of its survey participants do.
"For example, we usually get around 50 Asian-Americans in a standard tracking survey ... a group of that size has a margin of error of +/-16 percentage points, which is far too big to provide useful information," Aaron Smith, a senior research specialist at Pew explained to eWEEK in May, when we first inquired about this missing group. The responses of respondents who identify as Asian, Native American, mixed race or "other" do, however, get included in the overall numbers.
In a dated 2010 blog post, Smith went into a little more detail.
Interestingly, in a Sept. 11 Nielsen report on how Americans are consuming video across platforms, the firm found that, when mobile device use was broken down by ethnicity, Asians were the largest smartphone-using group of all-66 percent, compared with 56 percent of Hispanics, 55 percent of African-Americans and 45 percent of whites.
"Smartphones, with a penetration greater than that of DVRs and gaming consoles, said the report, are increasingly being used as vehicles for content delivery," reported Nielsen. "Today, nearly 36 million mobile phone owners in the U.S. watch video on their phones."
To Apple, that likely sounds like plenty of room for growth.


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PHOENIX (AP) — Jodi Arias will spend the weekend on suicide watch and return to court next week when jurors are expected to consider whether the death penalty should be an option for the former waitress' sentence.
Minutes after her conviction for killing a former boyfriend, Arias told a TV station she would "prefer to die sooner than later," complicating matters for defense lawyers who had hoped to spare her life during the penalty phase of the trial. The case was scheduled to resume Thursday, but court officials postponed it until Wednesday without any explanation.
The surprising interview with Fox affiliate KSAZ only added to the circus-like environment surrounding the trial, which has become a cable TV sensation with its graphic tales of sex, lies and violence. Since her arrest, Arias has repeatedly sought the spotlight, including TV interviews, 18 days on the witness stand before a global audience, jailhouse tweets and now the post-conviction comments.
She cannot choose the death penalty. It is up to the jury to make a sentencing recommendation, and the judge will then make the final decision.
If she were sentenced to death, she could decide not to appeal to speed up the process, but it could still take years to play out as she lives under punishing conditions on death row. The state Department of Corrections says Arizona death row inmates have little contact with the outside world and only get to leave their solitary cells for two hours a day, three times a week. They get three showers a week.
The panel of eight men and four women convicted Arias of first-degree murder Wednesday after about 15 hours of deliberations over four days. Testimony began in early January.
The so-called "aggravation" phase of the trial was expected to begin next week. When it does, jurors will deliberate one more time to determine whether the death penalty should be an option for sentencing Arias.
Prosecutor Juan Martinez must convince the panel that the murder was committed in an especially cruel, heinous and depraved manner. This phase will be a mini-trial of sorts, as both sides call witnesses to present testimony to jurors — the defense in an effort to spare Arias' life, the prosecution to at least have a shot at a death sentence.
If jurors find the killing fits the definition of cruel and heinous, the panel will recommend either life in prison or death.
If the panel finds no aggravating factors exist, jurors will be dismissed and the judge will determine whether Arias should spend the rest of her life in prison or be sentenced to 25 years with the possibility of release.
Arias admitted killing her onetime boyfriend Travis Alexander on June 4, 2008. She initially denied any involvement, then later blamed masked intruders. Two years after her arrest, she said it was self-defense when the victim attacked her after a day of sex.
Prosecutors said she planned the killing in a jealous rage as Alexander wanted to end their affair and was planning to take a trip to Mexico with another woman.
Phoenix criminal defense lawyer Dwane Cates said Arias has presented obstacle after obstacle for her defense attorneys, who are now just trying to save her life.
"Her defense counsel put four years of their lives into this," Cates said. "They're trying to do everything they can for her, and every problem they have in this case is caused by her.
"Every time she opens her mouth, she creates a new problem for the defense," Cates added.
He said prosecutor Juan Martinez will likely play for jurors the jailhouse interview from several years ago in which she said she wouldn't be convicted — along with the interview she did after her conviction.
"I would say, 'Ladies and gentlemen, she challenged you to convict her and you did. Now give her her wish and put her to death,'" Cates said.
Defendants convicted of crimes rarely do interviews right after convictions and before being sentenced, but Arias honored an earlier request that she talk to the Fox station in the event of a first-degree murder conviction.
The Maricopa County Sheriff's Office, which runs the jail system, has allowed Arias to do other media interviews and even put on a videotaped "American Idol"-style Christmas singing contest in which Arias took home the top prize.
The sheriff's office said no more interviews will be allowed with Arias now that she is on suicide watch.
During the next phase of the trial, prosecutors will likely call back to the witness stand the medical examiner who performed the autopsy, as well as the lead detective to explain for jurors how Alexander did not die quickly and likely suffered tremendous pain.
Arias stabbed and slashed Alexander nearly 30 times, shot him in the forehead and slit his throat from ear to ear, leaving the motivational speaker and businessman nearly decapitated before she dragged his mutilated body into his shower where friends found him about five days later.
Complicating things even more for her attorneys are Arias' own words. As she sat in jail awaiting trial several years ago, she made a bold prediction during an interview on the television show "Inside Edition."
"No jury will convict me," she said. Then she went before a camera Wednesday and made more news.
"Longevity runs in my family, and I don't want to spend the rest of my natural life in one place," a tearful Arias said. "I believe death is the ultimate freedom, and I'd rather have my freedom as soon as I can get it."


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Facilitated by Karen Cappello, MCC, BCC
Each month (excluding July and August) we have a chapter meeting that also includes an educational program. Chapter meeting locations will be announced with each event to accommodate statewide accessibility.
Join us at 5:30pm for a lightly-structured networking or getting-to-know-you exercise. Come with a new icebreaker or group communication technique you've learned or something you'd like to test out and you may be the randomly selected facilitator for that meeting! Don't worry, we have a pretty full toolbox if no one wants to volunteer. The regular program will begin promptly at 6pm.
Most of our programs are approved for CEUs. All chapter members are welcome and we also encourage guests to attend.