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Home › Our work › Adlens
Over 450 enquiries and a 79% reduction in cost per lead in just 30-days
Adlens commissioned Zest to prove that online channels were a viable source of leads for a new product range. This was to support a direct-to-consumer model that broke away from their traditional routes to market through third-party vendors that reduce margin.
We were asked to create and execute a strategy to generate leads through online channels to prove that it was a viable channel for future marketing.
We identified PPC as the best route to market, and deployed five landing pages to direct users to, each focused on driving data capture.
Our team tracked landing page performance to identify key drivers such as specific illnesses (diabetes, presbyopia) and general activity-based uses such as using computers as part of a day job. This gave crystal clear and attributable data to the client who could adjust their messaging and targeting appropriately. Our detailed tracking revealed insights about the client's audience, debunking previously held beliefs that the product was exclusively for 45+ age group. We found the best converting segment to be 45-54 but a younger demographic were enquiring on behalf of parents/grandparents due to our use of social media.
By monitoring activity by device closely, we were able to make tweaks to the campaign such as adding subtitles to a video so that the message was not lost on mobile users.
The results far exceeded our client's expectations. For a new product with absolutely no historical data to go on, we successfully generated 474 conversions within the short test period. In addition, we grew social following by 455%.
The test confirmed the viability of a direct-to-consumer business model and they are now investing heavily into a new website, using the learnings from this test to guide them.
leads generated within 30-days
growth in social following
reduction in Cost Per Lead over a 30-day period
"Results achieved were nothing short of staggering. Zest generated hundreds of leads in a very short space of time and provided insights into our customers and their online habits that we'll be able to use in future business decisions. We look forward to our continued work together."
Jason de Kauwe, Global Head of Digital Marketing, Adlens
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redpajama_set_name: RedPajamaCommonCrawl


The book contains all informations regarding RTO functioning, Traffic System, Safe Driving tips to all concerned to Motor Driving. The forms and performas of general use are also available. The only publication of this kind in India.
Form No. 25 (For Re-registration of Motor Vehicle) Form No.


Will a 300-year-old manuscript change Robert Grosseteste's story?
Will a 300-year-old manuscript change Robert Grosseteste's story?
As a church historian and academic theology co-ordinator at Bishop Grosseteste University in Lincoln, I have had the privilege of working alongside some of the world's finest Grosseteste scholars. Imagine my excitement when I received a phone call from an antiquarian in Spain who had discovered a 300-year-old manuscript about Lincoln's most important bishop.
Robert Grosseteste was an English statesman, scholastic philosopher, theologian, scientist and Bishop of Lincoln during a crucial period in the religious history of this country in terms of toleration.
My involvement with this project came about because I had just edited a book about Robert Grosseteste. This was a collection of essays by some of the world's finest Grosseteste scholars, it was called Robert Grosseteste, his thought and its Impact.
When this came out, it received quite a bit of attention: most importantly for me it received the attention of an antiquarian working at a Catholic seminary in Spain. He had there an old hand-written biography of Robert Grosseteste which had never been published.
After three centuries of collecting dust, he was anxious that it be brought to light. One afternoon I was sitting at my desk and the phone rang from Spain, telling me about this manuscript and asking me if I would be interested in editing it for publication.
I could hardly contain my excitement. It's certainly the most important thing that has happened to me in my academic career and it is the kind of thing that a scholar hopes might happen maybe just once in their lifetime.
I now have a digital version of the script which I have been working on. So far I have been able to ascertain that it was written in 1766 by an English Catholic Priest called Philip Perry.
He was in Spain because he was in charge of a seminary that trained English Catholic priests. At this time, they were forbidden to train in England.
The reason this document is so important is precisely because it is Catholic. Since the English Reformation Protestant scholars had written biographies of Grosseteste claiming him as one of their own.
Even though he lived five centuries before Protestantism, this was easy to do since he often argued with the popes of his time. There was even a story that his ghost appeared to Pope Innocent IV to berate him for being corrupt. According to the legend, the Lincoln Bishop hit the Pope in his side with his staff and shortly after he died.
Because of stories like this, authors such as the famous John Foxe, who wrote the incredibly popular book on martyrs called Acts and Monuments could claim that Grosseteste should be considered an English Protestant.
In the academic community we have always regretted that a Catholic reply to these claims never existed. In fact it did, all this time in Valladolid, Spain.
Philip Perry writes his 'Life of Grosseteste' primarily with the intention of claiming him back for the Catholics and this makes it both rare and fascinating. Like most histories that were written at this time, it is an argument.
That is effectively why the biography was never published, because in 1766 Catholics in this country were very close to emancipation and the leaders of their Church were very frightened that this biography would cause trouble and harm their cause. We also have letters from English bishops at this time telling the author to suppress his work.
Jack Cunningham has been working on translating a digital copy of the 330-year-old document.
I have been able to find out that there is only one other copy of this manuscript. It was brought to Britain by Perry's friend, and is currently housed in the Catholic Archives in Edinburgh.
The most exciting things about this manuscript's discovery are twofold. Firstly, not only does it tell us so much about Grosseteste, but it tells us so much about the author's time. The eighteenth century was a crucial period in the religious history of this country in terms of toleration. Laws were passed that gave greater freedom to Catholics at the same time as popular disturbances like the Gordon Riots were taking place against them. This biography and its suppression reflect all these tensions.
Secondly, it is important in the campaign to have Robert Grosseteste made into a saint. Some years ago, I wrote to the Vatican calling on them to recognise his great achievements by canonisation. It always frustrated me at the time that I had little evidence to support my claim. Well, in a coincidence that verges on the miraculous, it so happens that not only is Perry's biography the story of Grosseteste's life it is also a plea for his canonisation, and what's more an important Catholic scholar.
Perry makes a great case for Grosseteste. A case that was not allowed to be aired in the eighteenth century. I am more than delighted to be involved in ensuring that it is aired in the twenty first.
I am also delighted to be making available to the world, 300 years after its completion, a fascinating history of Lincoln's most important bishop and will be making the trip to Spain in the near future in order to finish the project.


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A next-level Tamil soundtrack packed with arm-waving choruses and syncopated beats.
Remo (Original Motion Picture Soundtrack) Anirudh Ravichander
Remo Nee Kadhalan
Senjitaley
Sirikkadhey
Anirudh Ravichander, Arjun Kanungo & Srinidhi Venkatesh
Meesa Beauty
Anirudh Ravichander & Richard
Daavuya
Anirudh Ravichander & Santhosh Narayanan
Tamilselvi
Anirudh Ravichander & Nakash Aziz
Come Closer (Sirikkadhey Reprise)
Anirudh Ravichander & Inno Genga
Released: 5 Sep 2016
℗ 2016 Sony Music Entertainment India Pvt. Ltd.
More By Anirudh Ravichander
Kaththi (Tamil) [Original Motion Picture Soundtrack]
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Cascade Aerospace Inc. announces that C-130 Hercules manufacturer Lockheed Martin recently executed an agreement that formalized Cascade as one of only two authorized Lockheed Martin C-130J Heavy Maintenance Centers (HMC) in the world. With this new designation, Cascade is now dual-qualified as both a C-130 Hercules Service Center and C-130J HMC, making Cascade a company of choice for Hercules operators around the world.
"Cascade has a long history of repair, overhaul and upgrades with military and commercial legacy C-130 Hercules aircraft," said Ben Boehm, Cascade Aerospace executive vice president and COO. "As the Optimized Weapons System Management prime for Canada's legacy Hercules fleet, Cascade is well-placed as a global leader in C-130 Hercules support."
This C-130J HMC designation is an integral project within the execution of the Air Capability Program – Tactical Industrial Regional Benefits commitment.
"With more than 1,400 C-130s operating in 70 countries, it is essential to have a global support network to keep these Hercules aircraft ready to support any mission — anytime, anywhere," said George Shultz, Lockheed Martin vice president and general manager, C-130 Programs. "The addition of Cascade Aerospace as the second-ever Lockheed Martin C-130J Heavy Maintenance Center not only strengthens this network, but greatly expands its capabilities as well. Cascade has long supported Canada's CC-130 fleet and this new designation ensures it will continue to be an essential partner for Hercules operators in Canada and beyond."
Currently, Cascade Aerospace is partnered with Lockheed Martin to support the Royal Canadian Air Force (RCAF) C-130J fleet under a 20-year contract and provides fleet management services directly to the RCAF for its legacy C-130 Hercules fleet. Cascade's recent signing of a contract with the Canadian Commercial Corporation (CCC) to undertake modernization and sustainment activities on two Mexican Air Force C-130K Hercules aircraft further solidifies Cascade's position within the international C-130 Hercules family.
About Lockheed Martin
Headquartered in Bethesda, Md., Lockheed Martin is a global security and aerospace company that employs approximately 115,000 people worldwide and is principally engaged in the research, design, development, manufacture, integration and sustainment of advanced technology systems, products and services. The Corporation's net sales for 2013 were $45.4 billion.
About Cascade Aerospace
Cascade Aerospace, an operating unit of IMP Aerospace & Defence, is a leading Canadian specialty aerospace & defence contractor that provides long-term integrated aircraft support programs and comprehensive program management, aircraft maintenance, modification, total fleet management, engineering & integrated logistics support to domestic & international military, government, OEM and commercial customers.
For additional information:
Kim Tamminga
Cascade Aerospace Inc.
Direct: +1-604-557-2716 x3050
Email: ktamminga@cascadeaerospace.com
Stephanie Stinn
Lockheed Martin Aeronautics
Email: stephanie.stinn@lmco.com


These webinars are a great way to discover Citi Bike beyond the bikes. Each session focuses on the NYC Better Bike Share Partnership's work in making bike share more accessible for all New Yorkers.
All webinars take place on the last Tuesday of the month at 2:00 PM. See below for exact dates and links to register!
The Better Bike Share Partnership aims to develop inclusive programs and policies to promote equity through bike share and increase the diversity of bike share riders to improve health and financial outcomes of NYC neighborhoods.
Citi Bike for Youth is one of the many programs of the BBSP. After a bike safety class ran by Bike New York, the program provides students, volunteers, and youth employees 16-24 years old with a year free of Citi Bike!
This webinar explores a variety of efforts in NYC being used to engage youth as early adopters of Citi Bike. From NYC pilot programs like Citi Bike to School and Citi Bike for Youth, we're finding better ways to connect young New Yorkers to bikes for transportation to school, work, and play.
Partners include: Department of Health, Department of Transportation, The Brown Bike Girl, Transportation Alternatives, People for Bikes, Bike New York, Transition High School, and El Barrio Bikes!
Learn how bike share can be used by both organizations and individuals as a valuable tool to increase savings. This webinar addresses how various membership options can support your clients, staff, and broader community. Hear from financial counseling professionals on how to translate transportation savings into other areas of your budget. The session also addresses how bike share can be used as an entry point for the unbanked, encouraging them to open a bank account and address credit issues impeding their financial health.


The traditional Omani diet of dates, milk, rice, brown bread, fish and vegetables has undergone considerable change, now resembling a Western diet that is high in calories, high glycaemic index carbohydrates, total fat and saturated, trans and omega 6 fatty acids, and low in omega-3 fatty acids and essential micronutrients. The available data on daily food intake and its impact on micro- and macro-nutrients are scanty in the Arab world. Obtaining these data is especially important in light of the growing prevalence of non-communicable diseases (NCDs) - cardiovascular diseases, diabetes, cancer and respiratory diseases - which now account for more than 60% of the global disease burden and mortality, and contribute to more than 50% of annual deaths in Arabian countries, including Oman. Moreover, obesity, an antecedent of NCDs, has reached epidemic proportions in the region. Since NCDs develop gradually during the course of the lifespan, various national and international committees on NCDs have recommended that children and young adults be the primary focus of any action plan that aims to prevent and control non-communicable diseases.
e) To investigate the impact of omega-3 fatty acids obtained from fish oil capsule on the red blood cell omega-3 fatty acids and plasma fat-soluble vitamins.
Children ages 9 and 10 years (n = 314) were recruited from three randomly selected schools in the Muscat Governorate. The schools were assigned to a fish, fish oil, or control group and the children were accordingly provided a lightly grilled oily fish, a re-esterified triacylglycerol fish oil capsule, or no fish for 12 weeks. Baseline body weight, height and body mass index were assessed and a non-fasting blood sample collected at baseline and after 12 weeks of intervention. Data on food intake were gathered using a 24-hour recall questionnaire; also collected were data on weight, height, blood pressure, triglycerides and fasting glucose. In addition, teachers completed the National Initiative for Children's Health Quality Vanderbilt Assessment Scales-Teacher Assessment Scale to assess the prevalence and sub-types of ADHD.
At baseline, a significant number of the children had low levels of vitamin D, and omega-3 fatty acids. The low levels of vitamin D and omega-3 fatty acids were ameliorated significantly by fish consumption and fish oil supplementation. In terms of weight, the prevalence of overweight or obesity for the total sample was 28.2% (10%, 46%) and 22.6% (8%, 38%). That is, about one fourth of the study subjects were overweight or obese. With regards to ADHD, the prevalence rate of PIS, PHIS and ADHDCIH among Omani school children was 7.3%, 3% and 8.8%, respectively.
After 12 weeks intervention, the children who received fish oil (54.1±17.5 nmol/L; p<0.001) and fish (49.2±17.4 nmol/L; p<0.05) had elevated levels of vitamin D than those who did not (42.3±17.5 nmol/L). The fish oil (1.2±0.70 μmol/L) and fish (1.20±0.7 μmol/L) groups also had higher concentrations of beta carotene than the placebo group (0.85±0.43 μmol/L; p<0.0001). Systolic and diastolic blood pressure (p=0.0001) and plasma triglycerides (p<0.05) but not HDL, LDL and total cholesterol (p>0.05) were lower in the fish oil group compared with those who were fed oily fish.
This study provides important and underreported data on nutrient intake levels by school children in Arab world. For the first time, these data will be available as a benchmark for future research and health programs in the region. A large number of boys and girls had diets that failed to provide the recommended levels of daily nutrients. This study also indicates that ADHD is relatively common among Omani school children; additional studies are needed to assess the generalisability of these findings.
Vitamin D deficiency is prevalent in Omani school children, but can be mitigated with omega-3 fatty acid supplementation. This study also provides evidence that Omani pre-adolescents have a low level n-3 fatty acid index that can be ameliorated by fish oil supplementation or consumption of oily fish. Hence, there is a need for a child-focused program of food fortification, school feeding programmes, targeted intervention with n-3 fatty acid enriched food products, family nutrition education and outdoor activities to alleviate the problem.


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Posted on January 7, 2016 by Fairborn Daily Herald
County moves ahead with courthouse project
By Nathan Pilling - npilling@civitasmedia.com
File photo The Greene County Courthouse will soon be receiving some infrastructure upgrades.
XENIA — Greene County Commissioners moved ahead with an infrastructure improvement project for the county courthouse at their regular meeting Dec. 29. Commissioners approved an approximately $127,500 contract with Palmer Conservation Consulting for the company to serve as the engineering consultant for the project.
In the project, which Greene County Services Director Carl Geisler has estimated will cost around $1.5 million, the courthouse will have its heating and air conditioning system upgraded. Geisler said the courthouse is currently served by steam radiator heat and approximately 35 residential-type air conditioning units.
"It's all very inefficient, very old," he said.
According to Geisler, the project will move the courthouse to a new, minimally intrusive, high efficiency system that "will save the taxpayers a significant amount of money in energy and deliver more comfort," he said.
According to Geisler, the project is slated to begin in summer 2016 with the hope that it will be completed with the system in operation by the fall. The courthouse will stay open while the work is being done.
"The courthouse is going to remained staffed and in operation during this process, which presents its own challenges, but we feel like it's totally feasible," Geisler said.
The project is part of a larger, estimated $5 million effort by the county to replace the aging central steam boiler system and other old units that serve four downtown-Xenia buildings owned by the county: the courthouse, the county jail, as well as government offices housed at 61 and 69 Greene St.
Project upgrades at the other sites would also center around replacing the old systems with modern heating, ventilating and air conditioning units. While funding and project plans have not been finalized at the other sites, the upgrades would likely follow on an annual basis, according to county officials.
http://aimmedianetwork.com/wp-content/uploads/sites/50/2016/01/web1_courthouse.jpgFile photo The Greene County Courthouse will soon be receiving some infrastructure upgrades.
By Nathan Pilling
npilling@civitasmedia.com
Reach Nathan Pilling at 937-502-4498 or on Twitter @XDGNatePilling.
Hi! A visitor to our site felt the following article might be of interest to you: County moves ahead with courthouse project. Here is a link to that story: https://www.fairborndailyherald.com/top-stories/5649/county-moves-ahead-with-courthouse-project


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Associated Press' ENPS automated news system now has an app for use with iPads and Android-based tablet PCs.
Called Tablet Story Viewer (TSV), the app is fully functional within the ENPS mobile client so all features are enabled. It will also work with iOS and Android smartphones as well.
TSV provides full copies of wire stories, updates them automatically and allows for story lists to be loaded and maintained. It will also allow access to other ENPS features such as contacts lists and messaging.
By providing a full copy of a story a TSV-enabled iPad or tablet PC can be a handheld script for on-air presenters.


Hi there and welcome to my first rules column, in which I will be highlighting and explaining some of the intricacies of the jiujitsu international competition ruleset. This edition, we will be looking at passing the guard.
Possibly the most common misconception about the rules that I see is when people demand points for side control. There are no points for side control. Ever. What there are points for (three, specifically) is passing the guard. For you to be able to pass someone's guard you have to be in someone's guard. So what does this mean? This means a takedown that lands you directly in side control only scores you points for a takedown, and no points for the position you land in. If someone is in turtle and stabilised and you push them over and take side control, you don't score any points. If you're on bottom in side control and you reverse your opponent and take them all the way over the top so you're on top in side control? You don't score any points at all, because you didn't pass their guard, and because you didn't sweep them (more on sweeps in a later edition of this column). Note that you don't have to pass a good guard to score points - if you are in side control, the person pushes you back into a terrible half guard, locks your foot, you pull it straight back again and end up back in side control? Great, you passed their guard, you score your points. For the sake of the rules, this includes situations like a leg drag. So if you sweep someone, come on top into a leg drag position, wait and then pass you will score the points for the guard pass.
In terms of competitive strategy, it's very common to allow someone to replace a very poor guard after a sweep that you can immediately pass to maximize your point scoring. If you sweep someone cleanly to side control from half guard you get two points. If you pause for a second in between their legs and then pass after, you will score two points for the pass and then three points for the guard pass, maximizing your potential points gain. So definitely an important thing to keep in mind when you're out there on the competition mats.


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About Axios Philadelphia
Axios Philadelphia is an Axios company.
Mike D'Onofrio
Jan 13, 2023 - News
First phase of South Philly's new Bellwether District to soon begin
A rendering of the Bellwether District in South Philadelphia facing southward. Courtesy of Hilco Redevelopment Partners
One of Philly's largest development projects is on the cusp of breaking ground.
What's happening: Hilco Redevelopment Partners (HRP) will begin the initial phase of its multibillion-dollar project in South Philly, dubbed the Bellwether District, in the coming months.
Go deeper (1 min. read)
Isaac Avilucea
Jan 9, 2023 - News
Sixers stadium plan faces new Chinatown opposition
The Fashion District shopping center where the Philadelphia 76ers hope to build a new arena. Photo: Matt Rourke/AP Photo
A faction of Philadelphia's Chinatown leaders is splintering off to form a new coalition aimed at blocking the 76ers' arena proposal.
Why it matters: The Chinatown community has a long history of fending off large-scale development projects, including a 2000 bid to build a new Phillies stadium at 12th and Vine Streets.
Philadelphia cracks down on Airbnbs and short-term rentals
Illustration: Shoshana Gordon/Axios
The new year brings new regulations for Philly's Airbnbs and other short-term rentals.
Why it matters: The rule changes are expected to reduce the number of vacation property rentals.
New Year's resolutions for Philadelphia in 2023
Illustration: Brendan Lynch/Axios
2022 is officially in the rear view, and we have high hopes for Philadelphia in 2023.
What's happening: The new year brings new resolutions, and Philly leaders have promised to address long-term challenges and make good on bold commitments. Here's how officials are hoping to improve the city this year.
Alexa Mencia
Nov 15, 2022 - Business
Abortion rights drew Pennsylvania voters to the polls
Data: #WeCount/Society of Family Planning; Map: Jacque Schrag/Axios
Abortion proved to be a big motivator for some Americans — and Pennsylvanians — in last week's midterms, the first election in the Keystone State since the U.S. Supreme Court overturned Roe v. Wade.
Driving the news: Josh Shapiro's victory has given abortion rights advocates a sense of relief that Pennsylvania's next governor won't roll back protections at the state level.
Screen Time with Fancy Brigade performance producer John Best
Photo illustration: Axios Visuals. Photo courtesy of John Best
John Best is bringing his Emmy Award-winning pedigree to the Fancy Brigade Association's annual Mummers performance.
State of play: Best was hired this year as the producer for 6ABC's broadcast of the association's finale inside the Pennsylvania Convention Center on New Year's Day.
Nov 4, 2022 - Business
How to call out if Philly wins the Fall Classic
Photo illustration: Allie Carl/Axios. Photo: Hunter Martin/Getty Images
Thought experiment: Let's say the Phillies take it all this weekend. People have a litttle too much fun. Enough that maybe Monday's a good day to stay home from work.
Just hypothesizing here, guys.
OK, but how might someone call out?
There's raw honesty:
"Look, boss, even if I come in, I'm telling you I'm gonna be about as productive as Houston's Alex Bregman was at the plate."
"I'm like the Phillies bullpen. I should get an extra day off for rest."
You play the sympathy card:
"I ate too many Schwarberfest hoagies and free tacos. Call a medic!"
"Sorry, boss. I stubbed a toe when I was 'Dancing on My Own.' Gotta get an X-ray."
Or just play the wild card:
"I was on my way in, but Lance McCullers Jr. is my Uber driver, so I had to make a quick run home."
"Someone stole my sign-in sheet, so I'mma head out."
Oct 12, 2022 - News
Philly's "eds and meds" economy
Illustration: Aïda Amer/Axios
Higher education institutions and hospitals power nearly 13% of all jobs in our regional economy, according to a new report from the Federal Reserve Bank of Philadelphia.
Driving the news: The fed's report, released last month, provides the first-ever nationwide economic assessment of the impact that "eds and meds," also known as anchor institutions, have on their communities.
The report includes a "Reliance Index" that calculates how dependent local economies are on these establishments.
Zoom in: Philadelphia — home to the University of Pennsylvania and its health system, Children's Hospital of Philadelphia, and Temple University — is among the most heavily reliant on eds and meds compared to its peer cities.
We rank fifth among peer regions when it comes to the overall impact that anchor institutions have on employment, trailing New York City and Chicago.
Why it matters: Higher ed and hospitals have wide-ranging economic effects on their hometowns.
They help stabilize communities through their large employment pools, typically resist economic shocks, spark innovation and attract talent.
Plus: These institutions remain anchored to their regions, whereas corporate headquarters or manufacturing facilities can pick up and relocate.
Yes, but: These industries are experiencing disruptions as a result of the pandemic and remote work, demographic changes and rising costs.
The result, the report says: "Regions that have reliably depended on anchor institutions, especially as other industries have moved out, may be looking at uncertain futures."
By the numbers: Eds and meds in the Philly region account for more than 495,000 employees and 8.4% of the region's income — or $33.8 billion — per the report.
What they're saying: Deborah Diamond, director of the Anchor Economy Initiative at the Philadelphia Federal Reserve, tells Axios that the city's meds and eds have led to the creation of companies in different industries, such as Spark Therapeutics, a gene therapy company.
Those spin-offs, she believes, have helped reduce the city's overall reliance on eds and meds.
They have "diversified our regional economy even further," she said.
Go deeper: Read the full report and use the online dashboard.
Get a free daily digest of the most important news in your backyard with Axios Philadelphia.


Anyone ever see this before?
Was it a particular map?
Was it right at the start of the round, or part way into it?
Anything else happen like revive, swap weapons etc that anyone noticed?
It's possible to select a different class to use next round once the round has started. You keep your current loadout and you'll have the next one at the start of the next round.


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Weather shelter for homeless to open tonight, Thursday due to upcoming storm
The National Weather Service has issued a Winter Storm Warning for the foothills down to the 2,000 foot elevation. Low snow levels and cold temperatures are predicted tonight through Friday morning. Sierra Roots, Salvation Army,...
Strong winter storm expected to hit Nevada County Wednesday
The first major winter storm of the year is expected to hit western Nevada County this week, with low snow and whiteout conditions at higher elevations. Multiple cold winter storm systems are expected to impact...
Multiple collisions, spin outs reported in Nevada County
Multiple vehicle collisions and spin outs were reported Thursday afternoon as snow dumped in Nevada County. Heavy traffic was reported along Highway 49 between Nevada City and Grass Valley after a silver SUV spun out...
Current highway conditions: Jan. 16, 2020
UPDATE 1:06 P.M.: State Route 49 Chains are required on all vehicles except 4-wheel-drive vehicles with snow tire on all four tires from Empire Street in Grass Valley to the west junction of SR 20....
Miro, K-9 patrol dog for state parks, suffers from disease that affects skeletal muscles
Nevada County's only K-9 dog patrolling regional state parks has been diagnosed with myasthenia gravis, a neuromuscular disease. Patrol dog Miro was released from UC Davis Veterinary Teaching Hospital and is recovering at home with...
THE UNION NOW: Live coverage from the newsroom
Live scanner feed here:Your browser does not support iFrames. Follow our live newsroom feed below!
Nevada City streets to stay one-way; City Council to conduct broader traffic study
The Nevada City Council is looking for ways to make the streets of the historic downtown area safer for pedestrians and traffic. The City Council decided last week to make Commercial and York streets permanently...
Nancy Pelosi and husband involved in some fishy business
Speaker of the House Nancy Pelosi's home district includes San Francisco. Star-Kist Tuna's headquarters is in San Francisco. Star-Kist is owned by Del Monte Foods and is a major contributor to Pelosi. Star-Kist is the...
Obituary of Janice Collins
Janice Ruth Maxey Collins passed away in her home on December 17, 2019. She was 73 years old. A private memorial service will be held by the family. Janice was born on April 16, 1946...
Nevada County's animal advocates collaborate to promote spay/neuter services
Nevada County's animal rescue groups would love to be out of work. The best way to accomplish the ultimate goal of no longer needing to find homes for unwanted pets is simple, advocates say: reduce...
Gov. Gavin Newsom begins tour of homelessness services in Grass Valley (VIDEOS)
Gov. Gavin Newsom on Monday kicked off his state-wide homelessness tour in Grass Valley, speaking to local officials, clients and volunteers while touring housing resource centers in the area, which the governor lauded as examples...
Nevada County Supervisors choose Heidi Hall as new chairwoman
The Nevada County Board of Supervisors on Tuesday unanimously chose District 1 Supervisor Heidi Hall as its new chairwoman and honored outgoing chairman, District 5 Supervisor Richard Anderson, with a plaque. "I want to thank...
Women's March this Saturday in Nevada City
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New webcams give live glimpses of downtown Nevada City
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Burger & Cream opens Grass Valley location
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School closure update: only Twin Ridges School District closed today
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The Union E-Edition
The Union NOW!
Putting the pieces back together: Holbrooke reopening hopeful for mid-year (VIDEO/PHOTO GALLERY)
Move fast and break things: New smash room opens in Grass Valley (VIDEO/PHOTO GALLERY)
Tiiiiiimber: Beetle kill trees come down in Condon Park (VIDEO/PHOTO GALLERY)
Grass Valley Planning Commission OKs Dorsey Marketplace, with conditions (VIDEO/PHOTO GALLERY)
'Uncharted territory': Why did Sierra Montessori Academy close its doors? (VIDEO/PHOTO GALLERY)
Alpine Meadows 25" 25" 108"
Boreal Mountain 13" 21" 78"
Donner Ski Ranch 0" 0" 34"
Northstar California 22" 22" 61"
Royal Gorge Cross Country 0" 0" 0"


Finished by the end of April! The Lewiston features a two story ceiling which stretches from the foyer to the living room. An upper-level balcony, which is visible from the lower level, offers a midway focal point. The kitchen is adjacent to the lofted living space and the dining room at the rear of the plan. It includes a large island, walk-in pantry, and wrap around counters. The master suite offers a vaulted bedroom, four piece master bath, and a spacious closet. Near the foyer is the laundry room, half-bath, and office or guest bedroom. On the upper level are two additional guest bedrooms and a shared bath with dual vanities. This is a fast track home. Photos are of same model but not actual home.


text:
Who's afraid of the nuclear wolf?
Who's afraid of the nuclear wolf?
By Ivo Vegter
Ivo Vegter is a columnist and the author of Extreme Environment, a book on environmental exaggeration and how it harms emerging economies. He writes on this and many other matters, from the perspective of individual liberty and free markets.
The tragedy unfolding in Japan has cast a sharp light on the safety or otherwise of nuclear power. However, using a rare accident as a reason to reject an entire technology is short-sighted. Hysteria serves no useful purpose.
At the risk of sounding callous about the loss of human life and property as a result of the devastating earthquake and tsunami in Japan, I'll follow the lead of the ecomentalists and address the consequences for nuclear power.
At the time of writing, the ultimate fate of the Daiichi nuclear reactors at Fukushima remains unclear. That has not stopped the ill-informed fear-mongering about nuclear meltdown on television, however.
For a superb discussion of exactly how the plants in question work, and why even a melt-down won't be likely to have the severe health and environmental consequences of Cherbnobyl, read this well-researched post: Why I am not worried about Japan's nuclear reactors.
Of course, this post could be wrong. A full meltdown could still occur, and it is possible that its containment could fail. The most recent news suggests that it's on the severe end of the accident scale, with at least some risk to the people and environment in the immediate area.
Even if meltdown is avoided, the situation is also very grave for the company that operates the plant, and the impact on the Japanese electricity supply will be felt for years.
Even in the unlikely event that significant amounts of persistent radioactive material is released into the environment, however, this still would not constitute a good argument against nuclear power.
For a start, consider the magnitude of the event that caused the damage at the reactors. There is no reasonable way to plan for catastrophes on this scale. Some damage at a nuclear plant pales beside the terrible toll the earthquake, tsunami and aftershocks have taken in terms of human life, limb and property.
If a tall building collapses in an earthquake, causing thousands of deaths, do we react by saying we shouldn't build tall buildings anymore? The rational response would be to revisit the structural engineering of such buildings, and make them as safe as possible in extreme circumstances.
This is exactly what was done at the Fukushima nuclear plants. Although the plants were forty years old, they had been designed to withstand an 8.2 magnitude quake, and are still more or less standing even after a quake five times as strong, plus a destructive tsunami to boot. That this is so is a testament to the safety of nuclear power, not to its inherent lack of safety. No doubt new measures will be installed, to protect other nuclear power stations from even worse natural catastrophes. For sure, modern plants built today will be orders of magnitude safer than even the robust reactors at Fukushima.
To assess risk, one needs two variables: the potential severity or cost of an incident, and the likelihood of it happening.
When a passenger airliner crashes, the incident is widely perceived to be very serious. Often, many people come to gruesome ends in such crashes, and the horror is splashed over the front pages and on TV screens for days. However, the actual incidence of crashes is low, thanks to many years of hard work to improve the engineering of aircraft. The upshot is the famous factoid that your chances of dying in an aircraft accident are much smaller than the odds of dying in a motor vehicle accident. In fact, even if you were to commute by plane every single day, instead of driving, you'd be about five times less likely to die in an accident.
That the magnitude of individual events is large does not make a good argument against flying.
The same goes for nuclear accidents. An explosive release of heavily radioactive material on the scale of Chernobyl is exceptionally rare. Unique, in fact. It was the consequence of an evil combination of human factors, including active recklessness. It would not be a stretch to blame it on communism, rather than on any fundamental safety issues with nuclear power.
Considerable disagreement exists about the long-term consequences of Chernobyl, largely thanks to a lack of adequate data. However, the most authoritative study on the subject, conducted in 2003 by the World Health Organisation, reflect considerably less severe consequences than the popular media had us believe.
That is not to dismiss such incidents, any more than one dismisses an aircraft crash as isolated and insignificant. From each case, we can (and ought to) learn, in order to improve safety in future.
However, to reject nuclear power as a reliable, clean and effective source of energy on the basis of a remarkably small number of incidents, only one of which had significant environmental or health consequences, is to throw out the baby with the bath water.
The owners of Fukushima will take a big hit, as will the Japanese population that depends on the energy it used to produce. This is incentive enough to invest significant money and effort into preventing a repeat of the scenario that is playing itself out this week.
A good argument against nuclear power would be based on cost-efficiency. Accidents, especially when they appear to be exaggerated by a media industry that thrives on the alarmism of sensational phrases like "nuclear meltdown", do not make a good argument.
Given the rarity of nuclear power plant incidents, and the even more rare examples of significantly harmful consequences, opposing nuclear power on the grounds of risk is as irrational as a fear of flying.
Far from being a rational, intelligent argument, nuclear fear is a reactionary political position that appeals to old Luddites, young radicals, superstitious fools and people who think the lottery is worth playing.
If we took such fears seriously, we wouldn't get out of bed in the mornings, for fear of tripping over the rug.
And now, instead of turning this natural disaster into an excuse to shout ill-informed slogans against nuclear power, can we please direct our attention to the many thousands of human victims? DM
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MADISON, N.J. and MIAMI, Fla. — Bausch + Lomb, the global eye health company, announced today a new research partnership with Cirle, Inc., a medical technology incubator, based in Miami, Fla.
The partnership brings together the experience and expertise of some of the world's leading eye health experts and medical researchers and Bausch + Lomb's global business and commercial capabilities. As a result, the two organizations will be better positioned to explore novel, early stage technologies and develop them into breakthrough innovations that fill previously unmet needs for the eye health community and the patients they serve.
The partnership with Bausch + Lomb's Pharmaceutical business will encompass a wide variety of cutting edge research projects including new compounds and technologies, and may ultimately be extended across Bausch + Lomb's Surgical and Vision Care divisions to include devices as well. Cirle has engaged leading eye health experts and engineers to contribute to this collaboration, in addition to working with the technology licensing group at the University of Miami Miller School of Medicine's Bascom Palmer Eye Institute. Dr. Awdeh is an assistant professor of ophthalmology and pathology and director of technology transfer at Bascom Palmer.
"The faculty at Bascom Palmer relentlessly pursues life-changing therapies. This partnership is a testimonial to the value of partnering between best-in-class organizations, including Bascom Palmer and Bausch + Lomb," said Jack Lord, M.D., chief operating officer and vice president for medical administration at the University of Miami Health System and University of Miami Miller School of Medicine.
Cirle is currently building a small, high-performance team of biomedical and chemical engineers, along with staff scientists, to pursue research and product development initiatives, including key efforts stemming from this collaboration. For more information, please email jobs@cirle.com.
Established in 2010, Cirle is a medical technology incubator based in Miami, Fla., focused on curing diseases that lead to blindness through the use of translational medical research and innovative technologies. The company develops and acquires early stage technologies and creates best-in-class partnerships for each of its projects. Cirle is currently focused exclusively on eye care-related technologies and has engaged leading eye health experts, engineers, and researchers, in addition to working with the technology licensing group at the University of Miami Miller School of Medicine's Bascom Palmer Eye Institute. For the past nine years, U.S. News and World Report has ranked Bascom Palmer Eye Institute as the nation's number one ophthalmology program.
Bausch + Lomb is one of the best-known and most respected healthcare companies in the world. Its core businesses include contact lenses and lens care products, ophthalmic surgical devices and instruments, and ophthalmic pharmaceuticals. Founded in 1853, the company is headquartered in Rochester, N.Y., and employs more than 11,000 people worldwide. Its products are available in more than 100 countries. More information is available at www.bausch.com.


text:
SingleNoiseModule = {}
setmetatable(SingleNoiseModule, { __index = Module })

function SingleNoiseModule:new()
	local instance = Module:new()

	instance.noise_a = nil
	instance.noise_b = nil
	instance.noise_c = nil
	instance.map_a = nil
	instance.map_b = nil
	instance.map_c = nil

	setmetatable(instance, self)
	self.__index = self

	return instance
end

function SingleNoiseModule:init(noise_manager)
	self.noise_a = noise_manager:get_noise_map(2, 0.3, 1, 120)
	self.noise_b = noise_manager:get_noise_map(4, 0.3, 1, 120)
	self.noise_c = noise_manager:get_noise_map(6, 0.3, 1, 120)
	self.noise_c = noise_manager:get_noise_map(8, 0.3, 1, 120)
end

function SingleNoiseModule:init_map(x, z)
	self.map_a = self.noise_a:get2dMap({ x = x, y = z })
	self.map_a = arrayutil.swapped_reindex2d(self.map_a, x, z)
	self.map_b = self.noise_b:get2dMap({ x = x, y = z })
	self.map_b = arrayutil.swapped_reindex2d(self.map_b, x, z)
	self.map_c = self.noise_c:get2dMap({ x = x, y = z })
	self.map_c = arrayutil.swapped_reindex2d(self.map_c, x, z)
end

function SingleNoiseModule:get(x, z, value, info, support)
	local val = 0
	val = val + self.map_a[x][z]
	val = val + self.map_b[x][z]
	val = val + self.map_c[x][z]
	val = val / 3

	return value + mathutil.round(val * 12), info
end

redpajama_set_name: RedPajamaGithub


You've probably noticed the new blogosphere widget at the bottom right hand side of this site since yesterday. It's not just for show – it actually does something! BlogRush is a blog syndication network which sends traffic to your blog by displaying your latest posts on other members' sites. If your blog gets 100 page views a day your headline will be displayed 100 times on other people's blogs.
Anyone who signs up under you also sends you part of their blog syndication traffic – up to 10 referrals deep!
This service is completely free. Sign up for BlogRush and watch your traffic skyrocket.
Just added it to my blog… let's see it it works.


text:
Q: Angular : How can I get parent component with child routes to react to URL changes (which include child route param changes)? This is my current route setup. (Note: ScheduleComponent is loaded by the main app when we want to see the Schedule screen)
ScheduleComponent has a <route-outlet> for the child routes.
const routes: Routes = [
  {
    path: '',
    component: ScheduleComponent,
    data: {
      screenName: 'schedule',
    },
    children: [
      { path: '', redirectTo: 'ABC', pathMatch: 'full' },
      {
        path: ':service',
        component: ScheduleTilesContainerComponent,
        data: {
          screenName: 'schedule',
        },
      },
      {
        path: ':service/:year/:month/:day',
        component: ScheduleTilesContainerComponent,
        data: {
          screenName: 'schedule',
        },
      },
    ],
  },
];

In ScheduleComponent I have:
// this._route: ActivatedRoute (in constructor)
this._route.params.subscribe((params: Params) => {
 console.log('Schedule params: ', params);
}

In ScheduleTilesContainerComponent I have:
// this._route: ActivatedRoute (in constructor)
this._route.params.subscribe((params: Params) => {
 console.log('Tiles Container params: ', params);
}

SCENARIO A:
When we put this in the browser: http://myserver.com/schedule
We see this in the console:
Schedule params: {}
Schedule params: {service: "ABC"}
TileContainer params: {service: "ABC"}

Then a user interaction triggers this:
this._router.navigate(['schedule/ABC/2020/03/25']);
Then we see in the browser address bar: http://myserver.com/schedule/ABC/2020/03/25
We see this in the console:
TileContainer params: {service: "ABC", year: "2020, month: "03", day: "25"}

Then a user interaction triggers this:
this._router.navigate(['schedule/ABC/2020/03/11']);
Then we see in the browser address bar: http://myserver.com/schedule/ABC/2020/03/11
We see this in the console:
TileContainer params: {service: "ABC", year: "2020, month: "03", day: "11"}

Question 1:  How come the ScheduleComponent is not seeing the params observable stream trigger when we navigate()?
Continuing...
Then I click the BACK button:
We see in the browser address bar: http://myserver.com/schedule/ABC/2020/03/25 (correct previous URL)
We see this in the console:
TileContainer params: {service: "ABC", year: "2020, month: "03", day: "25"}

Question 2:  How come the ScheduleComponent is not seeing the params observable stream trigger here as well? (it's probably the same issue)

SCENARIO B
HOWEVER, if THIS is the way we enter the screen, then the ScheduleComponent DOES get the param stream!
Put this into the browser directly: http://myserver.com/schedule/ABC/2020/03/25
Schedule params: {}
Schedule params: {service: "ABC", year: "2020, month: "03", day: "25"}
TileContainer params: {service: "ABC", year: "2020, month: "03", day: "25"}

Then a user interaction triggers this:
this._router.navigate(['schedule/ABC/2020/03/11']);
Schedule params: {service: "ABC", year: "2020, month: "03", day: "11"}
TileContainer params: {service: "ABC", year: "2020, month: "03", day: "11"}

If we click the BACK button the prev URL shows...
We this this in the console:
Schedule params: {service: "ABC", year: "2020, month: "03", day: "25"}
TileContainer params: {service: "ABC", year: "2020, month: "03", day: "25"}

Question 3: Why does the ScheduleComponent's param stream see this change?
Question 4: How can I get my ScheduleComponent to ALWAYS see the URL update?

redpajama_set_name: RedPajamaStackExchange


text:
BOA Welcomes Dorianne Laux as Judge of the 2012 A. Poulin, Jr. Poetry Prize!
[caption id="" align="alignleft" width="200" caption="author photo courtesy of doriannelaux.com"] [/caption] It's official! This year's A. Poulin, Jr. Poetry Prize will be judged by Dorianne Laux, BOA poet and author of five widely-circulated collections. Over the course of her literary career, Laux has received two Best American Poetry Prizes, a Pushcart Prize, two Fellowships from The National Endowment for the Arts, and a Guggenheim Fellowship. Her work has been selected for a variety of anthologies including the Best of APR, the Norton Anthology of Contemporary Poetry, and the Best of the Net, and has been translated into nine languages. Laux has also been teaching poetry since 1990, and continues to do so in the MFA program at North Carolina State University. It is truly an honor to have this year's contest judged by an author so esteemed in the world of literature. The winner, chosen by Laux, will receive A $1,500 Honorarium, paid in March 2013, and book publication by BOA Editions, Ltd. in March 2014, in The A. Poulin, Jr. New Poets of America Series. We're sure that Laux's decision will reaffirm BOA's tradition of bringing innovative, powerful poetry to the public. There's never been a better to time to get involved with BOA! Be sure to keep an eye out for contest updates and results! Major Works by Dorianne Laux The Book of Men (W.W. Norton, 2011) Facts about the Moon (W.W. Norton, 2007) Smoke (BOA Editions, 2000) What We Carry (BOA Editions, 1994) Awake (soon to be re-issued from Carnegie Mellon Press) For more about the A. Poulin, Jr. Poetry Prize, click here! To learn more about Dorianne Laux, including author information, updates, and upcoming appearances, please visit her official website. Laux will also be a featured poet at this year's Dine & Rhyme, one of the most anticipated BOA events of the year, on September 23. Mark your calendars now!


Cathedral of the Immaculate Conception, Albany, NY: Thinking about afterlife advancing could accomplish religious behavior as bodies age, University of Chicago advisers speculated. But could spritualty deepen from added years of absorption life's mysteries?
The west rose window was committed in 1977 in the attendance of Queen Elizabeth II and President Jimmy Carter.
Ceiling of the Washington National Cathedral.


text:
Гримучий газ (англ. fire-damp, нім. Knallgas n) — суміш двох об'ємів водню та одного об'єму кисню. При підпалюванні вибухає, в присутності губчатої платини горить. Воднево-кисневе полум'я має температуру до 2800 °C. Використовується для плавки кварцу, платини та інших речовин, різання та зварювання металів.

Література

Гази

redpajama_set_name: RedPajamaWikipedia


text:
GnRH antagonist rescue protocol combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome: a randomized controlled trial
Usama M. Fouda1Email author,
Ahmed M. Sayed1,
Hesham S. Elshaer1,
Bahaa Eldin M. Hammad1,
Mona M. Shaban1,
Khaled A. Elsetohy1 and
Mohamed A. Youssef1
© Fouda et al. 2016
Received: 3 April 2016
The aim of this study was to compare the efficacy of antagonist rescue protocol (replacing GnRH agonist with GnRH antagonist and reducing the dose of gonadotropins) combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome (OHSS) in patients pretreated with GnRH agonist long protocol who were at high risk for OHSS.
Two hundred and thirty six patients were randomized in a 1:1 ratio to the cabergoline group or the antagonist rescue combined with cabergoline group. Both groups received oral cabergoline (0.5 mg/day) for eight days beginning on the day of HCG administration. In the antagonist rescue combined with cabergoline group, when the leading follicle reached 16 mm, GnRH agonist (triptorelin) was replaced with GnRH antagonist (cetrorelix acetate) and the dose of HP-uFSH was reduced to 75 IU/day. HCG (5,000 IU/I.M) was administered when the serum estradiol level dropped below 3500 pg/ml. The study was open label and the outcome assessors (laboratory staff and the doctor who performed oocyte retrieval) were blind to treatment allocation.
The incidence of moderate/severe OHSS was significantly lower in the antagonist rescue combined with cabergoline group [5.08 % Vs 13.56 %, P value =0.025, OR = 0.342, 95 % CI, 0.129–0.906]. Four cycles were cancelled in the cabergoline group. There were no significant differences between the groups with respect to the number of retrieved oocytes, metaphase II oocytes, high quality embryos and fertilization rate. Moreover, the implantation and pregnancy rates were comparable between both groups.
GnRH antagonist rescue protocol combined with cabergoline is more effective than cabergoline alone in the prevention of OHSS.
Trial registration
Clinical trial.gov (NCT02461875).
IVF-ET
Ovarian hyperstimulation syndrome
GnRH antagonist
Ovarian hyperstimulation syndrome (OHSS) is the most dangerous iatrogenic complication associated with ovarian stimulation. Cystic enlargement of the ovaries, increased capillary permeability and fluid shift from the intravascular space into the third space are the main characteristics of OHSS [1].
Several strategies have been proposed to prevent or minimize the intensity of OHSS. Cycle cancellation, withholding gonadotropins administration and postponing human chorionic gonadotropin (HCG) injection till HCG drops to a safe level (coasting),antagonist rescue protocol, embryos freezing, minimal stimulation IVF, in vitro maturation of oocytes, metformin administration in patients with polycystic ovary syndrome, natural cycle IVF, triggering ovulation with a reduced dose of HCG or with GnRH agonist in GnRH antagonists stimulation cycle and administration of GnRH antagonist after oocyte retrieval have all been used. Apart from cycle cancelation, none of these strategies have been effective in the complete prevention of OHSS [1, 2].
The primary pathophysiological feature of OHSS is increased capillary permeability, which results in fluid shift to the third space. It appears that the main cause of increased capillary permeability is the release of vasoactive-angiogenic substances (interleukins, tumor necrosis factor (TNF) α, endothelin and vascular endothelial growth factor (VEGF)) from the ovaries in response to exogenous or endogenous HCG [1, 2]. Moreover, several authors suggested that the circulating peripheral blood mononuclear cells may be involved in the pathophysiology of OHSS. In vitro studies, revealed that HCG stimulates the production of IL8 and VEGF by monocytes [3]. Kosaka et al. [4] observed that peripheral blood mononuclear cells of patients with OHSS produce excessive amounts of VEGF. Several studies have revealed that VEGF is the primary vasoactive-angiogenic substance responsible for the development of OHSS. VEGF stimulates neovascularization and increased capillary permeability by interacting with VEGF receptor 2 (VEGFR-2). Gonadotropins stimulate the expression of VEGF and VEGFR-2 mRNA in granulosa cells and HCG (exogenous or endogenous) accentuates this expression [5, 6].
Recent animal and human studies have revealed that dopamine agonists antagonize VEGF dependent vascular permeability by inhibiting VEGFR-2 phosphorylation and signaling. The use of cabergoline (a dopamine receptor-2 agonist) in the prevention of OHSS has been investigated in several studies. Three meta-analyses have revealed that cabergoline reduces the incidence of moderate/severe OHSS without affecting implantation, pregnancy and miscarriage rates [2, 6, 7].
Antagonist rescue protocol (replacing GnRH agonist with GnRH antagonist and reducing the dose of gonadotropins) is another effective strategy for preventing OHSS. Several studies have shown that the antagonist rescue protocol causes a rapid reduction in the estradiol level, prevents cycle cancelation, and reduces the risk of moderate/severe OHSS [8, 9].
Recently, Rollene et al. [10] reported the use of cabergoline and GnRH antagonist (ganirelix) in the outpatient treatment of four patients with OHSS. Cabergoline combined with ganirelix resulted in rapid resolution of the clinical symptoms of OHSS. None of the patients required hospitalization.
The aim of this study was to compare the efficacy of antagonist rescue protocol combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome (OHSS) in patients pretreated with GnRH agonist long protocol who were at high risk for OHSS.
During the period between March 2013 and December 2015, this prospective, two arm, assessor blinded, randomized controlled trial was conducted at the assisted conception unit of Aljazeera (Al Gazeera) hospital, Giza, Egypt. The study protocol followed the CONSORT guidelines for reporting parallel group randomised trials [11]. This study included 236 patients who were stimulated using the long luteal GnRH agonist protocol and at high risk for developing OHSS [have more than 20 follicles (90 % of them less than 14 mm in mean diameter) and serum estradiol ≥ 3000 pg/ml] [9]. The exclusion criteria were an age less than 18 years or more than 37 years, endometriosis, presence of submucous or intramural myoma of more than 5 cm, recurrent abortion and a previous IVF-ET cycle. Patients with lung fibrosis, swelling or inflammation around the heart or lung, hypertension, liver disease, heart valve disease, or an allergy to cabergoline or ergot derivatives were also excluded from the study. The ethics committee of the hospital approved the study protocol [N-2-2013] and the patients provided informed consent before randomization. The study was registered at clinical trials.gov [NCT02461875].
Patients were randomized to the cabergoline group and the antagonist rescue combined with cabergoline group using a computer generated randomization list (obtained from http://graphpad.com/quickcalcs/randomN1.cfm) and sequentially numbered sealed envelopes containing allocation information written on a card. The randomization list and sealed envelopes were prepared by a statistician who was not involved in the allocation process. The sequentially numbered envelopes were opened by the study nurse and the patients were informed of their assigned group. The laboratory staff and the doctor who performed oocyte retrieval (Fouda U.M) were blinded to the treatment received.
All patients recruited to this study were stimulated using the long luteal GnRH agonist protocol [12]. Triptorelin (Decapeptyl, Ipsen, Slough, United Kingdom) at a daily dose of 0.1 mg/S.C was started one week before anticipated menstruation. In PCOS patients with oligomenorrhea or amenorrhea, medroxyprogesterone acetate tablets (Provera Pfizer, Inc., New York, NY) (5 mg twice daily) were administered orally for 5 days to induce withdrawal bleeding. Following withdrawal bleeding, the patients received a 3-week course of combined oral contraception pills (Gynera, Bayer-Shering, Pharma-AG, Germany) from day 2 of menstruation. Triptorelin (0.1 mg/day) was started from day 20 of the cycle. After confirmation of pituitary down regulation (serum E2 levels less than 50 pg/ml and endometrial thickness less than 5 mm) highly purified urinary FSH(HP-uFSH) (Fostimon, IBSA, Switzerland) was administered. The starting gonadotropins dose was determined according to the age, antral follicle count, basal FSH and E2 levels and body mass index. Follicular development was monitored by transvaginal ultrasonography and serum estradiol. The starting dose of gonadotropins was not adjusted during stimulation.
In cabergoline group, cabergoline (Dostinex; Pfizer, Italy) at a daily dose of 0.5 mg was administered orally at bed time for 8 days starting on the day of HCG administration. HCG (Pregnyl; N.V. Organon, Oss, Holland) at a dose of 5,000 IU/I.M was administered when three or more follicles ≥ 18 mm in diameter were detected by ultrasound examination.
In antagonist rescue combined with cabergoline group, when the leading follicle reached 16 mm, HP-uFSH was continued at a daily dose of 75 IU until and including the day of HCG administration. Triptorelin was discontinued and GnRH antagonist (Cetrorelix acetate)(Cetrotide; Serono International S.A., Geneva, Switzerland) 0.25 mg/S.C was administered daily until and including the day of HCG administration. Serum estradiol was measured daily and HCG (5,000 IU/I.M) was administered when the serum estradiol level dropped below 3500 pg/ml. Moreover, cabergoline (0.5 mg/day) was administered orally at bed time for 8 days starting on the day of HCG administration.
Oocyte retrieval was performed under deep sedation 36 ± 2 h after HCG administration. Two or three embryos were transferred 3 days after oocyte retrieval. Pregnancy test was performed two weeks after embryo transfer. Transvaginal ultrasound was performed five weeks after embryo transfer to detect the presence of intrauterine gestational sac.
The luteal phase was supported with progesterone vaginal pessaries (Prontogest, Marcyrl, Egypt) 400 mg twice daily, starting on the day of oocyte retrieval until 12 weeks gestation or negative B-subunit HCG. The occurrence and severity of OHSS was defined according to the classification described by Golan et al. [13]. The detection of ascites by ultrasound examination in patients with features with mild OHSS (enlarged ovaries (5–12 cm), abdominal discomfort, nausea, vomiting and diarrhea) indicated the occurrence of moderate OHSS. The presence of clinically evident ascites and/or hydrothorax, increased blood viscosity and coagulation abnormality indicated the occurrence of severe OHSS. Patients with severe OHSS were hospitalized. OHSS with an onset ≤ 10 days from oocyte retrieval was defined as early onset OHSS and OHSS with later onset was defined as late onset OHSS.
Clinical and ultrasound examinations were performed on the day of embryo transfer and after 4, 8 and 14 days to detect the occurrence of OHSS. All patients were instructed to contact us if they experienced difficulty in breathing, decreased urine volume, dizziness on standing, abdominal pain, enlargement of the abdomen and rapid weight gain.
The primary outcome measure was the incidence of moderate/severe OHSS and the secondary outcome measures were the number of retrieved oocytes, metaphase II oocytes, fertilization rate, implantation rate, miscarriage rate, clinical pregnancy rate (presence of intrauterine gestational sac detected by transvaginal ultrasound), and ongoing pregnancy rate (pregnancies continued beyond 20 weeks).
Sample size calculation
At the time of study design, a Cochrane review revealed that the incidence of moderate or severe OHSS in patients at high risk of developing OHSS treated with cabergoline was 16.95 % [2]. We considered that 11.95 % difference in the incidence of moderate/severe OHSS between the group of patients treated with cabergoline alone and the group of patients treated with the antagonist rescue protocol combined with cabergoline would be of clinical significance. To detect an 11.95 % difference in the incidence of moderate/severe OHSS between both groups, 107 patients would have to be recruited to each group of the study to achieve a study power of 80 % at a significance level of 0.05 (calculated on https//www.sealedenvelope.com/power/continuous-superiority). We expected that the dropout incidence would be 10 %; therefore, 118 patients were recruited to each arm of the study.
Statistical analysis was performed using student's t test and χ2 test, as appropriate. Fisher's exact test was used when the expected frequency was less than 5. A probability value (P value) less than 0.05 was considered statistically significant. All statistical calculations were performed using Excel version 7 (Microsoft, New York, NY, USA) and SPSS (SPSS, Chicago, IL, USA). Absolute risk reduction (95 % CI) and number needed to treat (95 % CI) were calculated on http://graphpad.com/quickcalcs/NNT1/. An intention to treat analysis and per protocol analysis were performed.
Between March 2013 and December 2015, 2458 IVF-ET cycles were performed in our institution. Among the 334 patients who were at high risk for OHSS, 88 patients did not meet the inclusion criteria and 10 patients declined to participate in the study. We enrolled 236 patients with 118 patients randomized to each arm of the study. The flow of the patients in the study is shown in Fig. 1.
The flow of the patients in the study
There were no significant differences between both groups with respect to age, body mass index (BMI), duration of infertility, cause of infertility, antral follicle count and baseline hormonal profile (Table 1).
Baseline characteristics of patients
Cabergoline group (n = 118)
Antagonist rescue combined with cabergoline group (n = 118)
Duration of infertility (years)
Type of infertility
• Primary
102/118(86.44 %)
97/118(82.2 %)
• Secondary
16/118(13.56 %)
Basal FSH (IU/L)
Antral follicle count
Patients with amenorrhea or oligomenorrhea
Cause of infertility
• Tubal Factor
• PCOS
• Unexplained
• Male Factor
• Two or more factors
PCOS polycystic ovary syndrome
Values are expressed as mean ± SD or n/n(%)
The serum estradiol level on the day of HCG administration was significantly higher in the cabergoline group than in the antagonist rescue combined with cabergoline group (5501 ± 1122 Vs. 2811 ± 399 pg/ml, P value < 0.001) (Table 2).
Outcome of ovarian stimulation
Duration of HP-uFSH Stimulation (days)
Total HP-uFSH ampoules (75U)
29.88 ± 6.8
Estradiol level on the HCG day (pg/ml)
5501 ± 1122
2811 ± 399
No. of retrieved oocytes
No. of metaphase II oocytes
No. of fertilized oocytes
Fertilization rate
1584/2003(79.08 %)
No. of high quality embryos
No. of embryos transferred
Cycles cancelled
4/118(3.39 %)
0/118(0 %)
Moderate or severe OHSS
Moderate OHSS
Severe OHSS
Early onset OHSS
Late onset OHSS
OHSS ovarian hyperstimulation syndrome
In the antagonist rescue combined with cabergoline group, the mean (SD) number of antagonist injections needed to reduce the estradiol level below 3500 pg/ml was 1.52(0.69). Seventy patients (59.32 %) required one GnRH antagonist dose, 35 patients (29.66 %) required two GnRH antagonist doses and 13 patients (11.02 %) required three GnRH antagonist doses to reduce the estradiol levels below 3500 pg/ml. The mean serum estradiol dropped by 34.56 % after the first 24 h of GnRH antagonist administration (5101 Vs. 3338 pg/ml). The drop in the serum estradiol level continued after the second and the third GnRH antagonist injections.
The incidence of moderate/severe OHSS was significantly lower in the antagonist rescue combined with cabergoline group [5.08 % Vs 13.56 %, P value =0.025, OR = 0.342, 95 % CI,0.129–0.906]. Absolute risk reduction was 8.48 % (95 % CI, 1.14 %–15.81 %) and number needed to treat was 12 (95 % CI, 6.3–88.1). Four patients in the cabergoline group had severe OHSS and none of the patients in the antagonist group had severe OHSS. Four cycles were cancelled in the cabergoline group and no cycles were cancelled in the antagonist rescue combined with cabergoline group (Table 2).
All patients in the antagonist rescue combined with cabergoline group received 75 IU/day of HP-uFSH when the leading follicle reached 16 mm and all patients in the cabergoline group received at least 150 IU/day of HP-uFSH during the stimulation period. The total gonadotropins dose administered till the leading follicle reached 16 mm was comparable between both groups [25.39 ± 5.64 Vs. 24.32 ± 6.62 ampules, P value = 0.184]. Conversely, the total gonadotropins dose administered after the leading follicle reached 16 mm was significantly lower in the antagonist rescue combined with cabergoline group (2.48 ± 0.64 Vs. 5.56 ± 1.92 ampules, P value < 0.001).
There were no significant differences in the number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, high quality embryos (grade 1 or 2) and fertilization rate between the two groups (Table 2). Moreover, the implantation rate and clinical and ongoing pregnancy rates were comparable between the two groups (Table 3). A case of ectopic pregnancy was reported in the antagonist rescue combined with cabergoline group.
Reproductive outcomes
Odd ratio (95 % CI)
Clinical pregnancy/started cycle
0.87[0.51–1.47]
Clinical pregnancy/transfer cycle
Ongoing pregnancy/started cycle
0.86[0.5–1.48]
Ongoing pregnancy/transfer cycle
0.9[0.52–1.56]
Implantation rate
Multiple pregnancy rate
7/42(16.67 %)
Spontaneous abortion rate
5/42(11.9 %)
Values are expressed as n/n (%) unless otherwise indicated
The data presented in this study revealed that GnRH antagonist rescue protocol combined with cabergoline minimized the risk of moderate/severe OHSS and prevented cycle cancelation without affecting the number of oocytes retrieved, quality of embryos and implantation and pregnancy rates in patients at high risk for OHSS who were pretreated with GnRH agonist long protocol. To our knowledge, this is the first randomized controlled study that evaluated the role of antagonist rescue protocol combined with cabergoline in minimizing the risk of OHSS.
The presence of a large number of growing follicles and rapidly rising estradiol level are associated with an increased likelihood of developing OHSS. The causative role of estradiol in inducing OHSS has not been proved. It seems that patients with a large number of growing follicle have a large mass of granulosa cells that produce excessive amounts of estradiol and chemical mediators that are responsible for OHSS [14]. Several authors have proposed several strategies, such as coasting and antagonist rescue protocol, to reduce estradiol levels in an effort to minimize the risk of OHSS [8, 9, 15, 16].
Coasting is one of the most commonly used preventive measures for OHSS. With this management strategy, gonadotropins administration is stopped, GnRH agonist administration is continued and HCG administration is delayed until estradiol drops to a safe level (≤3000 pg/ml). Withholding gonadotropins administration induces apoptosis of granulosa cells and therefore minimizes the production of estradiol and chemical mediators responsible for the development of OHSS [15, 16]. Previous studies revealed that the duration of coasting is an important predictor of IVF outcomes. It seems that prolonged complete deprivation of gonadotropins (>3 days) is associated with a decrease in the number of oocytes retrieved, implantation rate and clinical pregnancy rate [17, 18]. Antagonist rescue of agonist IVF cycles at risk of OHSS was first described by Gustafson et al. [8]. In a retrospective study including 87 patients down-regulated with GnRH agonist who were at risk of OHSS, GnRH agonist was switched to GnRH antagonist in patients who failed to response to reducing the dose of gonadotropins. HCG was administered when the serum estradiol level fell to a safe level (<3000 pg/ml). Antagonist rescue resulted in a rapid decline in the serum estradiol levels without adverse effects on embryo quality, the fertilization rate or the pregnancy rates. The incidence of moderate/severe OHSS was 4.6 % [8].
The exact mechanism by which GnRH antagonists induce a rapid decline in the estradiol level and reduce the risk of OHSS is not clear. Several studies have suggested that GnRH antagonists have a direct effect on the ovary mediated by interaction with the GnRH-I and GnRH-II receptors present on granulosa cells [19, 20]. Asimakopoulos et al. [21] reported that GnRH antagonists inhibit the production of VEGF from cultured human granulosa luteinized cells.
In a prospective randomized study, Aboulghar et al. [9] compared coasting with antagonist rescue protocol in a series of 192 patients pretreated with GnRH agonist long protocol who were at high risk for OHSS. None of the patients in either groups experienced severe OHSS. The duration of coasting was significantly longer than the duration of antagonist administration (2.81 ± 0.97 Vs. 1.74 ± 0.91 days; P < 0.001). Antagonist rescue protocol produced more high quality embryos and more oocytes. The rapid drop in the estradiol level with antagonist rescue protocol prevented prolonged deprivation of the growing follicles from gonadotropins which has a negative impact on the embryo quality and IVF-ET outcomes. Moreover, the administration of a low dose of gonadotropins (75 IU/day) in the antagonist rescue protocol group supported the function of granulosa cells and maintained the production of high quality embryos. Martinaz et al. [22] replaced GnRH agonist with GnRH antagonist in the early stages of ovarian stimulation (after 6 to 8 days of gonadotropins administration) in a series of 19 patients who were at high risk for OHSS (more than 10 follicles per ovary and/or serum estradiol > 900 pg/ml and the follicles expected to need 3 or more days to reach triggering criteria). The dose of gonadotropins was reduced and ovulation was triggered by rHCG in 14 patients and by a GnRH agonist bolus in 5 patients. The mean (SD) duration of antagonist administration was 4.8 ± 0.8 days. No oocytes were retrieved in one patient triggered with a GnRH agonist bolus. One patient had moderate OHSS. The authors suggested that early administration of GnRH antagonist could allow triggering of ovulation with GnRH agonist bolus which is associated with a lower risk of OHSS compared to triggering ovulation with HCG. Further studies are needed to determine for how long pituitary desensitization and unresponsiveness to GnRH bolus trigger persist after switching GnRH agonist to GnRH antagonist.
In a retrospective study, Hill et al. [23] replaced GnRH agonist with GnRH antagonist without reducing the dose of gonadotropins in 387 patients pretreated with microdose flare or long luteal agonist protocol who were at high risk of OHSS. In the majority of patients (98.45 %), one or two doses of GnRH antagonist were required to induced a rapid drop in the estradiol level. Antagonist rescue prevented cycle cancellation, as well as permitted continued gonadotropin administration and follicular development and maturation for an additional one to three days. The incidence of severe OHSS was 8 % and the cycle cancellation rate was 1.5 %.
The higher incidence of severe OHSS in the study by Hill et al. [23] (8 %) in comparison with our study (0 %) and the studies of Aboulghar et al. [9] (0 %), Martinez et al. [22] (0 %) and Gustafson et al. [8] (2.35 %) may be attributed to differences in the sample population or the treatment protocol. In the study by Hill et al. [23], antagonist administration was not accompanied with adjustment in the dose of gonadotropins, whereas the dose of gonadotropins was reduced in other studies [8, 9, 22]. Moreover, the duration of antagonist administration was longer in Martinaz et al. [22] study in comparison with the study by Hill et al. [23]. Further studies are needed to investigate the proper timing and duration of antagonist administration and the effect of reducing gonadotropins dose on the incidence of OHSS, the number of retrieved oocytes and the embryo quality.
Several studies revealed that the incidence of OHSS is lower in mild stimulation IVF cycles in comparison to conventional long agonist IVF cycles [24, 25]. Reducing gonadotropins dose seems to be effective in minimizing the risk of OHSS. Large follicles have higher sensitivity to gonadotropins compared to medium and small sized follicles, and therefore with reducing the dose of gonadotropins, large follicles continue to grow and small and medium sized follicles become atretic. The atresia of medium and small sized follicles minimizes the production of chemical mediators responsible for development of OHSS [26]. Moreover, reducing gonadotropins dose slows the rate of granulosa cells proliferation which produces the chemical mediators responsible for OHSS [27].
Antagonist rescue protocol and cabergoline minimize the risk of OHSS by two different mechanisms. Antagonist rescue protocol inhibits estradiol and VEGF production by the growing follicles and cabergoline blocks VEGF mediated increased capillary permeability [2, 21]. This means that cabergoline augments the effect antagonist rescue protocol.
In the current study, 5000 IU of HCG was used to trigger final oocyte maturation. The majority of studies revealed that the reproductive outcomes of IVF-ET cycles are comparable in women receiving 5000 IU or 10000 IU of HCG to trigger final oocyte maturation [28]. Several authors suggested that the administration of 5000 IU of HCG instead of 10000 IU of HCG may minimize the risk of OHSS in patients who have a high risk for OHSS [28, 29]. On the other hand, two small studies revealed that the administration of lower doses of HCG (≤5000 IU) does not reduce the incidence of OHSS in patients at high risk for OHSS [30, 31].
In the current study, the administration of 5000 IU of HCG instead of 10000 IU of HCG to trigger final oocyte maturation may have an additive effect in minimizing the risk of OHSS in both groups. However, because the same dose of HCG (5000 IU) was used to trigger final oocyte maturation in both groups, we do not think that the administration of 5000 IU of HCG instead of 10000 IU of HCG is responsible for the greater efficacy of antagonist rescue protocol combined with cabergoline in minimizing the risk of OHSS in comparison to cabergoline alone.
The main strength of this study is the prospective randomized controlled design. Our study has two limitations. First, the patients and the doctors were not blind to the treatment allocation. Second, it is not clear whether antagonist administration, HP-uFSH dose reduction to 75 IU/day or the combination of both is responsible for minimizing the risk of OHSS. Further studies are needed to clarify this point.
GnRH antagonist rescue protocol (replacing GnRH agonist with GnRH antagonist and reducing the dose of gonadotropins to 75 IU/day) combined with cabergoline is more effective than cabergoline alone in the prevention of OHSS in patients downregulated with GnRH agonist who are at high risk for OHSS.
The ethics committee of Aljazeera (Al Gazeera) hospital approved the study protocol [N-2-2013] and the patients provided informed consent before randomization.
BMI:
GnRH:
gonadotropin releasing hormone
HCG:
HP-uFSH:
highly purified urinary follicle stimulating hormone
IVF-ET:
in vitro fertilization embryo transfer
OHSS:
PCOS:
rHCG:
recombinant human chorionic gonadotropins
TNF:
tumor necrosis factor
VEGF:
vascular endothelial growth factor
There are no acknowledgements.
No funding sources.
All of the authors have made substantial contributions to conception and design, data collection, or data analysis and were involved in drafting the manuscript or revising it critically for important intellectual content. All authors have read and approved the final manuscript.
Usama M. Fouda, Ahmed M. Sayed, Hesham S. Elshaer, Bahaa Eldin M. Hammad, Mona M. Shaban, Khaled A. Elsetohy, Mohamed A. Youssef. All the authors are from the Department of Obstetrics and Gynecology, Faculty of medicine, Cairo University, Cairo, Egypt.
Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Kasr Al-Ainy Hospital, Al-Saraya Street, Cairo, Egypt
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New Zealand's emergency services responded to a Google Loon balloon.
A Google Loon balloon on a tranquil day.
Google's Loon project is all about good vibes—inclusiveness, world connectivity, access to information, etc. But the balloons themselves, which look sort of like airborne jellyfish, are a little out of place in the skies. And they're causing some freak-outs.
Last week, for example, a bystander in New Zealand mistook a Loon flying over New Zealand's South Island for a plane crash and called emergency services. According to the Wall Street Journal, the response included a rescue helicopter being sent out to survey the scene.
Google Loon balloons fly at double the altitude of commercial aircraft, and Google has been testing them around New Zealand, where they coordinate with air traffic control authorities. The rescue helicopter located the Loon, which had landed in the ocean, and identified it as a balloon, not a wrecked plane.
At least no power lines were hurt this time.