New coronavirus and cardiovascular disease are linked thanks to ACE2 enzyme and may respond to same treatments
Credit: Richard Siemens
(Edmonton, AB) A new blood test that reliably predicts outcomes for heart failure patients could lead to new diagnostics and treatments for COVID-19 patients as well, according to newly published research from cardiologists at the University of Alberta.
The researchers examined circulating angiotensin peptide levels in the blood of 110 people who were experiencing heart failure due to a heart attack or stroke at the University of Alberta Hospital emergency department and the Mazankowski Alberta Heart Institute in Edmonton. Angiotensin peptides are short proteins that regulate the cardiovascular system and are altered in patients with heart failure–and those with COVID-19.
The researchers found that a high ratio between beneficial peptides (angiotensin 1-7) and harmful peptides (angiotensin II) led to better outcomes, including a lower risk of death and shorter hospital stays, no matter how severe their symptoms were. It was determined that measuring levels of either type of peptide on its own did not provide enough information.
“What our study shows is that you have to look at both sides of it, so it’s a balance between the good guy and the bad guy,” said Gavin Oudit, a professor of cardiology, Canada Research Chair in Heart Failure and director of the Heart Function Clinic at the Mazankowski. “This is very relevant for heart failure because we can now target this pathway, but it also has implications for COVID-19 patients.”
Oudit recently published another paper explaining that the link between heart failure and COVID-19 is the key role played in each disease by the enzyme ACE2 (angiotensin-converting enzyme 2), which is produced in many parts of the body, including the heart, lungs, kidneys and gut. The enzyme protects the heart by increasing production of angiotensin 1-7 (the “good guy” peptide) and suppressing the renin-angiotensin system that produces angiotensin II (the “bad guy” peptide).
ACE2 has also been identified as the receptor for SARS-CoV-2, the virus that causes COVID-19 and has infected millions of people worldwide. Severe disease symptoms can include pneumonia, heart failure, neural problems and failure of other organs.
“This is why SARS-CoV-2 is such a problem,” Oudit said. “It’s evolved to bind to the right target.
“It picked the perfect receptor to bind to, this key enzyme that protects the cardiovascular system, the lungs, the kidneys, the gut and the central nervous system, and hence these are the type of symptoms our patients are having.
Oudit noted that cardiovascular disease is a key feature in patients with COVID-19, especially those who are hospitalized, are sicker and end up in intensive care units.
The test to determine the ratio between good and bad peptides in the cardiovascular system involves taking a single blood draw and analyzing it with a liquid chromatography-mass spectrometry technique that requires specialized instruments available in most analytic labs.
Oudit proposes the test should be used routinely to determine the risk of adverse outcomes in both heart failure and COVID-19 patients. A precision medicine approach could then be taken to target poor ratios and improve them with either traditional or new drug therapies.
He said the discovery of the ratio test highlights the bridge between cardiovascular disease and COVID-19 and the pivotal role ACE2 plays in both diseases.
“We are fortunate that we have the understanding of ACE2, and we have both the research and therapeutic tools to target this pathway for patients with heart failure, and also now patients with COVID-19,” he said. “The crisis is an opportunity to better help all of our patients.”
Oudit has been studying the role of ACE2 in heart failure for 20 years, but this research has been cited hundreds of times since the connection between ACE2 and COVID-19 was uncovered.
He explained that traditional heart failure treatments that block the bad peptides in the renin-angiotensin system–such as ACE inhibitors and angiotensin receptor blockers–might be beneficial for COVID-19 patients who experience similar symptoms. Clinical trials to determine their effectiveness are already underway in North America, Europe and China.
“In cardiovascular patients, the renin-angiotensin system makes the disease worse, so blocking the system has always been beneficial for patients with cardiovascular disease, including those with heart failure,” Oudit said.
He also suggested that new biologic therapies that boost the good peptides–synthetic human molecules such as recombinant human ACE2 or angiotensin 1-7 analogues–may also be beneficial for both cardiovascular and COVID-19 patients.
“We make large amounts of the human molecules that are shown to be pure and effective, and they can be given at high levels to replenish a system that’s relatively deficient in them,” he explained.
Oudit said trials giving peptide boosters to COVID-19 patients are starting in Europe, and his team intends to apply for Health Canada permission to study the effect of these treatments in both heart failure and COVID-19 patients as well.
Early on in the COVID-19 pandemic, medical researchers feared that boosting ACE2 in patients might make them more susceptible to the virus, but that has now been shown to be incorrect.
“We now know that whatever baseline ACE2 levels you have, whether you’re healthy or have cardiovascular disease, that’s more than enough for the virus to get into your body if you encounter the virus,” he said. “So changing the level with these drugs does not change your risk, and in fact it may actually improve your outcome.”
He explained that SARS-CoV-2 aids the harmful renin-angiotensin system by tying up the ACE2 regulator function, so the hope is that boosting ACE2 in COVID-19 patients can override that effect to better fight the disease.
“In heart failure patients, when your ACE2 is working well, your mortality is much lower, hospitalization is reduced,” he said. “Now we need to see the parallels in patients with COVID-19.”
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The research team included Kaiming Wang, an MSc candidate who was lead author on the papers published in Circulation: Heart Failure. The research was funded through the University of Alberta Hospital Foundation, Canadian Institutes of Health Research, Alberta Innovates and Heart and Stroke Foundation.
China's Birth Rate Plummets 10% To Lowest On Record
China's birthrate fell 10% last year to its lowest level on record, a significant drop in spite of extensive efforts by the CCP to encourage people to get busy.
The country had just 9.56 million births in 2022, the lowest figure since they began keeping records in 1949, according to a report by the National Health Commission.
The high costs of child care and education, growing unemployment and job insecurity as well as gender discrimination have all helped to deter many young couples from having more than one child or even having children at all. -NBC News
China's population also fell for the first time in six decades, dropping to 1.41 billion people - a demographic shift that's caused officials to worry that the country will 'get old before it gets rich' - with a slowing economy and declining tax receipts amid increases in government debt due to soaring health and welfare costs.
According to the report, the demographic downturn is largely thanks to China's one-child policy imposed between 1980 and 2015. Nearly 40% of Chinese babies last year were the second child of a married couple, while 15% were from families with three or more children.
The sharp decline in births comes despite Beijing's efforts to increase child care and provide other financial incentives. In May, President Xi Jinping presided over a panel to study the topic.
Not just China
As we noted in June, Japan's birth rate has also plummeted to a record low for the seventh straight year, with the number of babies born falling below 800,000 this year, health ministry data showed on June 2.
The number of newborns in Japan fell to 770,747 this year, down 40,875 from the previous year and the lowest since the country began record-keeping in 1899, Kyodo News reported, citing health ministry data.
Japan’s fertility rate—the average number of children born to a woman in her lifetime—fell from 1.30 in 2021 to 1.26 last year, equivalent to the previous low recorded in 2005. The number is far below the 2.07 rate necessary to sustain a stable population.
The decline in Japan’s birth rate is attributed to people delaying parenthood due to the economic impact brought on by the COVID-19 pandemic, as well as the prevailing trend among couples to delay marriage, according to the report.
The US birthrate has also been in decline, falling slightly in 2022 compared to 2021, with roughly 3.7 million babies born nationwide. It still hasn't recovered to pre-pandemic levels according to the CDC.
When the COVID pandemic led to widespread economic shutdowns and stay-at-home orders in the spring of 2020, many media outlets and pundits speculated this might lead to a baby boom. But it appears the opposite has happened: birth rates declined in many high-income countries amid the crisis, a new study shows.
Arnstein Aassve, a professor of social and political sciences at Bocconi University in Italy, and his colleagues looked at birth rates in 22 high-income countries, including the U.S., from 2016 through the beginning of 2021. They found that seven of these countries had statistically significant declines in birth rates in the final months of 2020 and first months of 2021, compared with the same period in previous years. Hungary, Italy, Spain and Portugal had some of the largest drops: reductions of 8.5, 9.1, 8.4 and 6.6 percent, respectively. The U.S. saw a decline of 3.8 percent, but this was not statistically significant—perhaps because the pandemic’s effects were more spread out in the country and because the study only had U.S. data through December 2020, Aassve says. The findings were published on Monday in the Proceedings of the National Academy of Sciences USA.
Birth rates fluctuate seasonally within a year, and many of the countries in the study had experienced falling rates for years before the pandemic. But the declines that began nine months after the World Health Organization declared a public health emergency on January 30, 2020, were even more stark. “We are very confident that the effect for those countries is real,” Aassve says. “Even though they might have had a bit of a mild downward trend [before], we’re pretty sure about the fact that there was an impact of the pandemic.”
Covid Accelerated the Existing Trend
Covid accelerated the already declining birth rates.
Given the 16-year lag between births and the civilian noninstitutional population coupled with the aging of the workforce there will be fewer and fewer workers supporting retired workers on Social Security.
Notice the relatively steep decline in the birth rate starting in 2008 and continuing through today.
That impact will start showing up in 2024 and last a minimum of 12 years.
How long depends on whether the birth rate picks up after Covid. I highly doubt the birth rate will pick up.
Deflationary and Inflationary Impacts
Inflationary: Shortage of workers increases wage pressures
Deflationary: Fewer workers support an increasing number of retirees
Deflationary: Older workers need more assistance, buy fewer things, travel less.
Deflationary: More government debt and deficits. Government spending has a negative impact on real GDP.
Welcome to TDR’s review of the Top 7 Cannabis Developments for the week of October 9. Aside from presenting a synopsis of news events, interviews and closing market prices for publicly-listed companies.
Trulieve Cannabis announced the filing of amended federal tax returns with refund claims for several of the company’s business entities for the years 2019, 2020, and 2021. In total, the company is claiming a refund of $143 million from taxes paid which the company believes it does not owe, although there is no guarantee of receipt.
Trulieve believes its determination is supported by legal interpretations that challenge the company’s tax liability under Section 280E of the Internal Revenue Code.
The Cannabist Company Holdings has delivered a notice of partial redemption to the holders of the company’s outstanding 13% senior secured notes due May 14, 2024. The Notice provides that the company will, on October 23, 2023, redeem US$25 million of the total US$38.2 million principal amount of the Notes currently outstanding.
On the Redemption Date, Holders of Notes will have a portion of their 13% Notes, in denominations of $1,000, redeemed effective as of the Redemption Date on a pro rata basis in accordance with the terms of the trust indenture between the company and Odyssey Trust Company dated May 14, 2020, as amended and supplemented.
Cannabis consumers who caught COVID-19 had significantly lower rates of intubation, respiratory failure and death than people who do not use marijuana, according a new study based on hospital data that was presented this week at the annual conference of The American College of Chest Physicians (CHEST) in Honolulu.
Marijuana Consumers Who Caught COVID Had 'Better Outcomes And Mortality' Than Nonusers, Study Finds: "The significant decrease in mortality and complications warrants further investigation of the association between marijuana use and COVID-19."https://t.co/0VvUvcHN0n
Authors analyzed records from 322,214 patients from the National Inpatient Sample, a government database that tracks hospital utilization and outcomes. Of those patients, 2,603—less than 1 percent—said they consumed cannabis.
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Chart Of The Week—Select MSOs Net Cash Flows After Interest Expense, CAPEX, Taxes And Debt Maturities
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Interview Of The Week: Jason Wild Speaks On The Eve Of TerrAscend’s Investor Day
TerrAscend (TSX: TSND) Chairman Jason Wild is here to share the latest developments in the industry, the recent news surrounding the house speaker in Washington, the upcoming ballot news in Florida and more.
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Georgia To Become First State Selling Medical Marijuana In Pharmacies
The U.S. Census Bureau has released its first report on state-level marijuana tax revenue data following what the agency calls “a complete canvass of all state agencies” going back to July 2021. In the 18-month period between then and the end of 2022, the data show, states collected more than $5.7 billion from licensed cannabis sales.
The US Census Bureau has released its first-ever set of data on state marijuana revenue—showing that cannabis sales generated more than $5.7 billion for public coffers during an 18-month period
The launch of the report, which the agency plans to update on a quarterly basis going forward, signals that at least some parts of the federal government are now beginning to treat the cannabis industry as a legitimate sector of the economy. The Census Bureau first announced in January 2021 that it would begin collecting marijuana tax figures for its quarterly summary of state and local government tax revenue. It also said it wants states to submit cannabis revenue data as part of annual reports as well.
In the news…
4Front Ventures has agreed to issue 1,283,425 subordinate voting share purchase warrants pursuant to an amendment to a previously entered promissory note purchase agreement. Pursuant to the Agreement, the lender has agreed to extend the maturity date of its loan, which has a principal amount of US$2,000,000, with a payment of an extension fee of C$65,000, which is payable in Warrants.
Aleafia Health announced that Red White & Bloom Brands Inc.has been selected as the successful bidder pursuant to the court-approved sale and investment solicitation process in connection with the previously announced proceedings of Aleafia and certain of its subsidiaries under the companies’ Creditors Arrangement Act.
BioHarvest Sciences announced that VINIA, its flagship nutraceutical product derived from red grape cells, has received its Canadian product license from Health Canada’s Natural and Non-Prescription Health Products Directorate.
California Governor vetoes cannabis cafe and marijuana labeling bills…
California Governor Vetoes Cannabis Cafe And Marijuana Labeling Bills, But Signs Others Into Law: The actions by Gov. Gavin Newsom are a mixed bag for the cannabis industry and consumers.https://t.co/58ORvVe5bT
Canopy Growthhas received EU GMP certification from RP Tuebingen, Regional Health Inspectorate of Baden-Wuerttemberg for the company’s cannabis cultivation facility in Kincardine, Ontario.
Cardiol Therapeuticsannounced positive study results from one of its international collaborating research centers demonstrating that subcutaneously administered cannabidiol, the active pharmaceutical ingredient in Cardiol’s novel CRD-38 subcutaneous formulation prevented increases in key cardiac inflammatory and remodelling markers in a model of heart failure.
Charlotte’s Web Holdingsannounced the appointment of Angela McElwee to its Board of Directors.
CLS Holdings USAannounced its financial results for the fiscal quarter ended August 31, 2023.
Colorado cannabis sales surpassed the $15 billion mark in August – a milestone since legal adult-use sales launched in the state in 2014.
Connecticut cannabis sales hit $25.2M in September 2023…
Connecticut cannabis sales hit $25.2M in September 2023
August 2023 Adult Use: $14,000,370.09 Medical: $10,938,272.39 August Total: $24,938,642.48
Cresco Labsannounced the launch of its Good News brand in the Commonwealth of Pennsylvania.
Curaleaf Holdingswill report its financial and operating results for the third quarter ended September 30, 2023 after market close on November 9, 2023.
Curaleaf Holdingshas filed its application to list the Company’s subordinate voting shares on the Toronto Stock Exchange.
Eurofins CDMO Alphora Inc.announced that it has received its Health Canada Cannabis Drug License issued within the Cannabis Act and Cannabis Regulations for its Oakville, Ontario operations in September 2023.
Goodness Growth Holdings and Grown Rogue International, Inc.have completed the issuance of warrants to purchase listed shares as previously announced on May 25, 2023.
Heritage Cannabis Holdingsannounced the procurement of an EU GMP certified extraction machine to be added to the existing fleet of extractors which will double the company’s hydrocarbon processing capacity.
iAnthus Capital Holdings announces that Robert Galvin will transition out of his role as Interim Chief Operating Officer of the Company, effective immediately.
IM Cannabis, a medical cannabis company with operations in Israel and Germany, releases message from the CEO about the Israel-Hamas War and announces the company, through its wholly-owned subsidiaries, IMC Holdings Ltd. and Rosen High Way Ltd., has secured C$1,390,000 in short-term debt.
IM Cannabisannounced that Uri Birenberg will join the company’s leadership team as Chief Financial Officer effective October 10, 2023.
Lead GOP Senate cosponsor of a bipartisan marijuana banking bill says a planned floor vote is on pause until he can ensure the legislation will later pass the Republican-controlled House, according to a cannabis financing executive who spoke with the senator this week.
Letter to Attorney General Garland and DEA Administrator Milgram urging halt to rescheduling process.
MariMed, Incannounced “Small Batch Exclusives,” a unique, limited-time program that gives customers the opportunity to purchase legendary flower strains.
MariMed Inc. retail footprint has once again expanded, as the company officially unveiled an adult-use Thrive dispensary in Casey, Illinois. This marks the fifth dispensary in operation within the state of Illinois and the 12th dispensary in MariMed’s expanding portfolio across five states.
Organigram Holdingshas obtained a receipt for a final short form base shelf prospectus filed with the securities commissions in each of the provinces and territories of Canada. A corresponding shelf registration statement on Form F-10 has been filed with the United States Securities and Exchange Commission (SEC File No. 333-274686) but is not yet effective.
RISE Dispensaries owned by Green Thumb Industries Inc.announced that RISE Dispensary Brandon, the Company’s 9th retail location in Florida, will open on October 14th.
SunStream Bancorpannounced a receivership court order granting the sale of certain assets of Greenpeak Industries Inc. and certain affiliated entities d.b.a. Skymint to Skymint Acquisition Co., a newly formed designee entity of Tropics LP. Tropics is a limited partnership fully owned by an affiliate of Sunstream, a joint venture sponsored by SNDL Inc.
The Cannabist Company Holdingswill report its financial results for the third quarter ended September 30, 2023 before U.S. financial markets open on Tuesday, November 14, 2023.
The Cannabist Companyto report third quarter 2023 results on November 14, 2023 before U.S. financial markets open.
Trulieve Cannabis announced the relocation of a medical cannabis dispensary in Melbourne, Florida.
Trulieve Cannabis has added $500,000 to a ballot initiative aimed at legalizing the recreational use of marijuana, bringing its total contributions to $39.55 million, according to a newly filed finance report.
Verano Holdingsannounced the opening of Zen Leaf Newington, the company’s second social equity joint venture location in Connecticut and fourth cannabis dispensary statewide, on October 13, following a ceremonial ribbon cutting at 9 a.m. local time.
Vext Sciencehas completed the previously announced non-brokered private placement of $11.5 million through the issuance of 67,647,058 common shares at a price of $0.17 per Common Share, including the full exercise of a $1.5 million over-allotment option.
Tier-1 cannabis multistate operator TerrAscend Corp. has made a notable splash in advance of Investor Day presentations at the Toronto Stock Exchange. The company has elevated forward-looking forecasts for net revenue and Adjusted EBITDA from ongoing operations for the entirety of 2023, signaling that business operations are exceeding previously-stated expectations.
For its full fiscal 2023, TerrAscend now expects net revenue and Adjusted EBITDA to register a minimum of $317 million and $63 million, respectively, versus previous a previous forecast of $305 million and $58 million. This represents year-over-year growth of 28% in net revenue and 62% in Adjusted EBITDA from continuing operations—both well above Tier-1 industry averages.
Furthermore, TerrAscend anticipates that its gross margin will surpass the 50% mark, and generate positive free cash flow from ongoing operations during the latter half of the year.
The House GOP’s pick for speaker, Steve Scalise, announced Thursday he will no longer seek the gavel as he confronted a likely insurmountable vote shortage. While Scalise had won a majority of votes in an internal GOP ballot a day earlier, he faced an ever-growing list of Republicans who vowed to support only his opponent, Rep. Jim Jordan, on the floor. The Ohio Republican is now expected to make another run for the position.
Scalise announced his decision on Thursday evening, following a conference meeting in which it became clear that he had no path to winning the 217 votes needed to ascend to the speakership.
House Republicans voted Friday to nominate conservative firebrand Jim Jordan for speaker of the House — the latest twist in a chaotic battle for speakership. Jordan, the chairman of the Judiciary Committee, received 124 votes — still more than 90 votes shy of the 217 he will need to grab the gavel in a vote on the House floor, according to members and aides who were the room. That floor vote has not yet been scheduled.
House Republicans voted Friday to nominate conservative firebrand Jim Jordan for speaker of the House — the latest twist in a chaotic battle for speakership. https://t.co/2EUUnHqpvg
Jordan had an opponent in the conference vote for speaker: Rep. Austin Scott, who filed to run for the top spot shortly before the vote went down. Scott received 81 votes in the candidate forum.
Jordan had earlier backed out of the speaker race, saying he would cast a vote for Rep. Steve Scalise after the majority leader earned the nomination is a similar closed-door session Wednesday. Scalise backed out Thursday night after he failed to secure the votes needed to become speaker.
Playgroups can be a lifeline for new parents. Run by volunteers, they give young children a space to explore and interact with others, and parents a chance to have a cup of tea and a chat.
This was certainly the case for me. Having low moments following the birth of my children, as one in five women may do, these playgroups helped me make connections with other parents and carers. They led to new friends for my children and provided a safe space to go on difficult days.
I witnessed first-hand the value of these groups, and the integral role volunteers fill in communities. But, according to charity Early Years Scotland, community-based playgroups are “struggling to survive” due to a decrease in volunteers.
Now, I’m researching the value of playgroups for families and communities, understanding what role they play in the first years of parenthood, and how that can contribute to community wellbeing and resilience.
Playgroups are also a place where parents can take a first step into volunteering, learning skills that can allow them to go on to take further leadership roles in their wider community. And playgroups can have economic benefits, if volunteers gain knowledge and confidence that they can take into paid employment.
During lockdown, inside group activities like playgroups were unavailable. But I saw volunteers innovating: moving outside and creating new spaces, such as the Scottish Buggy Club.
My own local playgroup moved to outdoor facilities at a local farm. Activity groups such as the charity group Fun Firstmoved online for their classes.
Now, the cost of living crisis is limiting opportunities for activities with children. As winter looms, more parents will be stuck inside with small children with nowhere to go. We know that single parents are particularly susceptible to social isolation.
We are at risk of losing community groups that create opportunities for their members to establish “thick networks”: collaborations between local people that create a welcoming and valuable local culture.
To help families, help volunteers
Recent policy initiatives from the Scottish and UK governments have focused on families. There is an effort in Scotland to focus on community-based responses to sustain community wellbeing.
But there have been complaints that resources are not being seen at a community level, where funding is decreasing and there is not enough support for volunteers.
In the short-term, solutions would include more resources to support volunteers – training, incentives and community funding, which will enhance their role and encourage volunteers to stay in their role for longer. But the decrease of volunteers is more fundamental that this.
Long-term strategies are needed if governments wish to rely on the services offered to local communities by the members of that community. These include encouraging businesses and industries to seriously consider the wealth of research that shows flexible working, job shares and four-day weeks are beneficial for the economy, productivity and wellbeing. With more time, more people could be able to help out in places like playgroups.
Finally, introducing a universal basic income, such as the participation income model – which requires that people contribute to their community in order to receive income – could help people to take on community and voluntary roles and instil a wider sense of wellbeing in the population.
Ruth Lightbody works for Glasgow Caledonian University. In 2023 she has been awarded funding from the British Academy/Leverhulme Small Research Grant to research playgroups and resilient and wellbeing communities.
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