The Conversation
Can at-home DNA tests predict how you’ll respond to your medications? Pharmacists explain the risks and benefits of pharmacogenetic testing
Can at-home DNA tests predict how you'll respond to your medications? Pharmacists explain the risks and benefits of pharmacogenetic testing
D3Damon/E+ via Getty Images
Kayla B. Rowe, University of Pittsburgh; Lucas Berenbrok, University of Pittsburgh, and Philip Empey, University of Pittsburgh
Have you ever wondered why certain medications don't seem to work as well for you as they do for others? This variability in drug response is what pharmacogenomic testing hopes to explain by looking at the genes within your DNA.
Pharmacogenomics, or PGx, is the study of how genes affect your response to medications. Genes are segments of DNA that serve as an instruction manual for cells to make proteins. Some of these proteins break down or transport certain medications through the body. Others are proteins that medications target to generate a desired effect.
As pharmacists who see patients who have stopped multiple medications because of side effects or ineffectiveness, we believe pharmacogenomic testing has the potential to help guide health care professionals to more precise dosing and prescribing.
How do PGx tests work?
PGx tests look for variations within the genes of your DNA to predict drug response. For instance, the presence of one genetic variant might predict that the specific protein it codes for is unable to break down a particular medication. This could potentially lead to increased drug levels in your body and an increased risk of side effects. The presence of another genetic variant might predict the opposite: It might predict that the protein it codes for is breaking down a medication more rapidly than expected, which may decrease the drug's effectiveness.
For example, citalopram is an antidepressant broken down by a protein called CYP2C19. Patients with genetic variants that code for a version of this protein with a reduced ability to break down the drug may have an increased risk of side effects.
Currently, there are over 80 medications with prescribing recommendations based on PGx results, including treatments for depression, cancer and heart disease. There are commercially available PGx tests that patients can have sent directly to their doorstep with or without the involvement of a health care professional. These direct-to-consumer PGx tests collect DNA from either a saliva sample or cheek swab that is then sent to the laboratory. Results can take anywhere from a few days to a few weeks depending on the company.
Some companies require a consultation with a health care provider, often a pharmacist or genetic counselor, who can facilitate a test order and discuss any medication changes once the results come back.
Limitations of PGx testing
PGx testing will not be able to predict how you will respond to all medications for several reasons.
First, most PGx tests do not look for every possible variant of every gene in the human genome. Instead, they look only at a limited number of genes and variants strongly linked to specific drugs. PGx tests can predict how you will respond only to medications associated with the genes it tests for.
Some drugs are broken down in very complicated pathways entailing multiple proteins and byproducts, and the usefulness of PGx testing for them remains unclear. For example, the antidepressant bupropion has three major pathways involved in its breakdown and forms three active byproducts that can interact with other drugs or body processes. This makes predicting how you will respond to the drug much more challenging because there is more than one variable involved. In many cases, there also isn't conclusive data to confidently predict the general function of a protein and how it would affect your response to a drug.
The applicability of PGx test results is additionally limited by a lack of diversity of study participants. Typically, populations of European ancestry are overrepresented in clinical trials. An ongoing research initiative by the National Institutes of Health called the All of Us Research Program aims to address this issue by collecting genetic samples from people of diverse backgrounds.
Another limitation of direct-to-consumer PGx tests is that they can predict drug response based only on your genetics. Lifestyle and environmental factors such as your age, liver or kidney function, tobacco use, drug interactions and other diseases can heavily influence how you may respond to medication. For example, leafy greens with high amounts of vitamin K can lower the effectiveness of the blood thinner warfarin. But PGx tests don't take these factors into account.
Finally, your PGx results may predict that you may respond to medications differently, but this does not guarantee that the medication won't have its intended effect. In other words, PGx testing is predictive rather than deterministic.
Risks of PGx testing
PGx testing carries the risk of not telling the whole story of drug response. If variations within the gene are not found, the testing company often assumes the proteins those genes code for function normally. Because of this assumption, someone carrying a rare or unknown variant may receive inaccurate results.
It may be tempting for some people to see their results and want to change their dose or discontinue their medications. However, this can be dangerous. Abruptly stopping some medications may cause withdrawal effects. Never change the way you take your medications without consulting your pharmacist and physician first.
Sharing your PGx test results with all the clinicians involved in your care can help prevent medication failure and improve safety. Pharmacists are increasingly trained in pharmacogenomics and can serve as a resource to address medication-related questions or concerns.
PGx tests that are not authorized by the Food and Drug Administration cannot be clinically interpreted and therefore cannot be used to inform prescribing. Results from these tests should not be added to your medical record.
Benefits of PGx testing
Direct-to-consumer PGx testing can empower patients to advocate for themselves and be an active participant in their health care by increasing access to and knowledge of their genetic information.
Patients' knowledge of their PGx genetic profile has the potential to improve treatment safety. For example, a 2023 study of over 6,000 patients in Europe found that those who used their PGx results to guide medication therapy were 30% less likely to experience adverse drug reactions.
Most PGx test results stay valid throughout a patient's life, and retesting is not needed unless additional genes or variants need to be evaluated. As more research on gene variants is conducted, prescribing recommendations may be updated.
Overall, genetic information from direct-to-consumer PGx tests can help you collaborate with health care professionals to select more effective medications with a lower risk of side effects.
Kayla B. Rowe, Fellow in Clinical Pharmacogenomics, University of Pittsburgh; Lucas Berenbrok, Associate Professor of Pharmacy and Therapeutics, University of Pittsburgh, and Philip Empey, Associate Professor of Pharmacogenomics, University of Pittsburgh
This article is republished from The Conversation under a Creative Commons license. Read the original article.
The Conversation
Chandrayaan-3’s measurements of sulfur open the doors for lunar science and exploration
Chandrayaan-3's measurements of sulfur open the doors for lunar science and exploration
(100 meters) and measured the chemistry of the lunar soil.
ISRO
Jeffrey Gillis-Davis, Arts & Sciences at Washington University in St. Louis
In an exciting milestone for lunar scientists around the globe, India's Chandrayaan-3 lander touched down 375 miles (600 km) from the south pole of the Moon on Aug. 23, 2023.
In just under 14 Earth days, Chandrayaan-3 provided scientists with valuable new data and further inspiration to explore the Moon. And the Indian Space Research Organization has shared these initial results with the world.
While the data from Chandrayaan-3's rover, named Pragyan, or “wisdom” in Sanskrit, showed the lunar soil contains expected elements such as iron, titanium, aluminum and calcium, it also showed an unexpected surprise – sulfur.
Planetary scientists like me have known that sulfur exists in lunar rocks and soils, but only at a very low concentration. These new measurements imply there may be a higher sulfur concentration than anticipated.
Pragyan has two instruments that analyze the elemental composition of the soil – an alpha particle X-ray spectrometer and a laser-induced breakdown spectrometer, or LIBS for short. Both of these instruments measured sulfur in the soil near the landing site.
Sulfur in soils near the Moon's poles might help astronauts live off the land one day, making these measurements an example of science that enables exploration.
Geology of the Moon
There are two main rock types on the Moon's surface – dark volcanic rock and the brighter highland rock. The brightness difference between these two materials forms the familiar “man in the moon” face or “rabbit picking rice” image to the naked eye.
Avrand6/Wikimedia Commons, CC BY-SA
Scientists measuring lunar rock and soil compositions in labs on Earth have found that materials from the dark volcanic plains tend to have more sulfur than the brighter highlands material.
Sulfur mainly comes from volcanic activity. Rocks deep in the Moon contain sulfur, and when these rocks melt, the sulfur becomes part of the magma. When the melted rock nears the surface, most of the sulfur in the magma becomes a gas that is released along with water vapor and carbon dioxide.
Some of the sulfur does stay in the magma and is retained within the rock after it cools. This process explains why sulfur is primarily associated with the Moon's dark volcanic rocks.
Chandrayaan-3's measurements of sulfur in soils are the first to occur on the Moon. The exact amount of sulfur cannot be determined until the data calibration is completed.
The uncalibrated data collected by the LIBS instrument on Pragyan suggests that the Moon's highland soils near the poles might have a higher sulfur concentration than highland soils from the equator and possibly even higher than the dark volcanic soils.
These initial results give planetary scientists like me who study the Moon new insights into how it works as a geologic system. But we'll still have to wait and see if the fully calibrated data from the Chandrayaan-3 team confirms an elevated sulfur concentration.
Atmospheric sulfur formation
The measurement of sulfur is interesting to scientists for at least two reasons. First, these findings indicate that the highland soils at the lunar poles could have fundamentally different compositions, compared with highland soils at the lunar equatorial regions. This compositional difference likely comes from the different environmental conditions between the two regions – the poles get less direct sunlight.
Second, these results suggest that there's somehow more sulfur in the polar regions. Sulfur concentrated here could have formed from the exceedingly thin lunar atmosphere.
The polar regions of the Moon receive less direct sunlight and, as a result, experience extremely low temperatures compared with the rest of the Moon. If the surface temperature falls, below -73 degrees C (-99 degrees F), then sulfur from the lunar atmosphere could collect on the surface in solid form – like frost on a window.
Sulfur at the poles could also have originated from ancient volcanic eruptions occurring on the lunar surface, or from meteorites containing sulfur that struck the surface and vaporized on impact.
Lunar sulfur as a resource
For long-lasting space missions, many agencies have thought about building some sort of base on the Moon. Astronauts and robots could travel from the south pole base to collect, process, store and use naturally occurring materials like sulfur on the Moon – a concept called in-situ resource utilization.
In-situ resource utilization means fewer trips back to Earth to get supplies and more time and energy spent exploring. Using sulfur as a resource, astronauts could build solar cells and batteries that use sulfur, mix up sulfur-based fertilizer and make sulfur-based concrete for construction.
Sulfur-based concrete actually has several benefits compared with the concrete normally used in building projects on Earth.
For one, sulfur-based concrete hardens and becomes strong within hours rather than weeks, and it's more resistant to wear. It also doesn't require water in the mixture, so astronauts could save their valuable water for drinking, crafting breathable oxygen and making rocket fuel.
NASA/GSFC/Arizona State University
While seven missions are currently operating on or around the Moon, the lunar south pole region hasn't been studied from the surface before, so Pragyan's new measurements will help planetary scientists understand the geologic history of the Moon. It'll also allow lunar scientists like me to ask new questions about how the Moon formed and evolved.
For now, the scientists at Indian Space Research Organization are busy processing and calibrating the data. On the lunar surface, Chandrayaan-3 is hibernating through the two-week-long lunar night, where temperatures will drop to -184 degrees F (-120 degrees C). The night will last until September 22.
There's no guarantee that the lander component of Chandrayaan-3, called Vikram, or Pragyan will survive the extremely low temperatures, but should Pragyan awaken, scientists can expect more valuable measurements.
Jeffrey Gillis-Davis, Research Professor of Physics, Arts & Sciences at Washington University in St. Louis
This article is republished from The Conversation under a Creative Commons license. Read the original article.
The Conversation
Spyware can infect your phone or computer via the ads you see online – report
Spyware can infect your phone or computer via the ads you see online – report
AP Photo/Julio Cortez
Claire Seungeun Lee, UMass Lowell
Each day, you leave digital traces of what you did, where you went, who you communicated with, what you bought, what you're thinking of buying, and much more. This mass of data serves as a library of clues for personalized ads, which are sent to you by a sophisticated network – an automated marketplace of advertisers, publishers and ad brokers that operates at lightning speed.
The ad networks are designed to shield your identity, but companies and governments are able to combine that information with other data, particularly phone location, to identify you and track your movements and online activity. More invasive yet is spyware – malicious software that a government agent, private investigator or criminal installs on someone's phone or computer without their knowledge or consent. Spyware lets the user see the contents of the target's device, including calls, texts, email and voicemail. Some forms of spyware can take control of a phone, including turning on its microphone and camera.
Now, according to an investigative report by the Israeli newspaper Haaretz, an Israeli technology company called Insanet has developed the means of delivering spyware via online ad networks, turning some targeted ads into Trojan horses. According to the report, there's no defense against the spyware, and the Israeli government has given Insanet approval to sell the technology.
Sneaking in unseen
Insanet's spyware, Sherlock, is not the first spyware that can be installed on a phone without the need to trick the phone's owner into clicking on a malicious link or downloading a malicious file. NSO's iPhone-hacking Pegasus, for instance, is one of the most controversial spyware tools to emerge in the past five years.
Pegasus relies on vulnerabilities in Apple's iOS, the iPhone operating system, to infiltrate a phone undetected. Apple issued a security update for the latest vulnerability on Sept. 7, 2023.
Eric Zeng, CC BY-ND
What sets Insanet's Sherlock apart from Pegasus is its exploitation of ad networks rather than vulnerabilities in phones. A Sherlock user creates an ad campaign that narrowly focuses on the target's demographic and location, and places a spyware-laden ad with an ad exchange. Once the ad is served to a web page that the target views, the spyware is secretly installed on the target's phone or computer.
Although it's too early to determine the full extent of Sherlock's capabilities and limitations, the Haaretz report found that it can infect Windows-based computers and Android phones as well as iPhones.
Spyware vs. malware
Ad networks have been used to deliver malicious software for years, a practice dubbed malvertising. In most cases, the malware is aimed at computers rather than phones, is indiscriminate, and is designed to lock a user's data as part of a ransomware attack or steal passwords to access online accounts or organizational networks. The ad networks constantly scan for malvertising and rapidly block it when detected.
Spyware, on the other hand, tends to be aimed at phones, is targeted at specific people or narrow categories of people, and is designed to clandestinely obtain sensitive information and monitor someone's activities. Once spyware infiltrates your system, it can record keystrokes, take screenshots and use various tracking mechanisms before transmitting your stolen data to the spyware's creator.
While its actual capabilities are still under investigation, the new Sherlock spyware is at least capable of infiltration, monitoring, data capture and data transmission, according to the Haaretz report.
Who's using spyware
From 2011 to 2023, at least 74 governments engaged in contracts with commercial companies to acquire spyware or digital forensics technology. National governments might deploy spyware for surveillance and gathering intelligence as well as combating crime and terrorism. Law enforcement agencies might similarly use spyware as part of investigative efforts, especially in cases involving cybercrime, organized crime or national security threats.
Companies might use spyware to monitor employees' computer activities, ostensibly to protect intellectual property, prevent data breaches or ensure compliance with company policies. Private investigators might use spyware to gather information and evidence for clients on legal or personal matters. Hackers and organized crime figures might use spyware to steal information to use in fraud or extortion schemes.
On top of the revelation that Israeli cybersecurity firms have developed a defense-proof technology that appropriates online advertising for civilian surveillance, a key concern is that Insanet's advanced spyware was legally authorized by the Israeli government for sale to a broader audience. This potentially puts virtually everyone at risk.
The silver lining is that Sherlock appears to be expensive to use. According to an internal company document cited in the Haaretz report, a single Sherlock infection costs a client of a company using the technology a hefty US$6.4 million.
Claire Seungeun Lee, Associate Professor of Criminology and Justice Studies, UMass Lowell
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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The Conversation
NASA’s Mars rovers could inspire a more ethical future for AI
Cracking down on slavery and human trafficking in NSW
shutterstock
Jennifer Burn, University of Technology Sydney
The NSW Community Relations Commission today released a report which found the NSW government is failing to adequately acknowledge or respond to reports of human trafficking and slavery.
While many in the community think of a trafficked person as a woman working in sexual servitude, the report found that human trafficking and slavery affects men, women and children.
Exploitation through trafficking and forced labour occurs in many industries including hospitality, agriculture and factory work. Some victims are criminally exploited in private homes; others are subjected to forced marriage.
Recent cases
Over the last few weeks and months, media reports of people experiencing such exploitation worldwide have put a spotlight on slavery, human trafficking and practices such as forced marriage and forced labour.
There were distressing reports of a high profile case in the United Kingdom where three women were allegedly held in slavery or slavery like-conditions for 30 years in an ordinary house in an ordinary residential area.
While the facts of the case are still unclear and highlight difficulties in understanding the dimension of abuse – particularly in private domestic settings – the police said that the women were controlled by “invisible handcuffs” demonstrating a “complicated and disturbing picture of emotional control”.
Back in Australia, the ABC reported in July on the case of a group of Filipino boxers who were trafficked to Sydney. It was alleged the boxers' passports were confiscated and they were prevented from leaving until their debts were paid off. They lived in substandard conditions in a small garage and were given food scraps for meals.
As a result of investigation, the Australian Federal Police charged three members of a family with people-trafficking offences. The case has not yet been heard.
In an earlier Australian case, a couple were charged and convicted of slavery offences involving the trafficking of a vulnerable Filipina woman to Australia to work in their takeaway food shop and as a domestic worker for their family. The woman worked in the family's takeaway food shop and the family's home in a Queensland country town every day for up to 18 hours a day.
After work, she returned to the family's home, cleaned and looked after the couple's three children and undertook other household duties. She was paid very little and was further abused. Eventually she escaped, leading to an investigation by police and charges and convictions of slavery offences.
Putting an end to slavery
New laws introduced by the Commonwealth earlier this year criminalise forced labour and forced marriage and boost the Australian legislative response to human trafficking, slavery and slavery-like practices.
People affected by trafficking and slavery must be supported in their recovery process and to achieve justice. As such, the NSW Community Relations Commission has recommended that the NSW attorney-general review the current Victims Rights and Support Act 2013 support scheme to include crimes related to human trafficking and slavery.
It also recommended the Commonwealth establish a national compensation scheme for victims of trafficking and slavery, recognising that such crimes are primarily Commonwealth offences.
AAP/Jenny Evans
The inquiry suggested the Department of Family and Community Services assess existing services and develop an action plan to co-ordinate services for people who have experienced trafficking and slavery. Non-residents in NSW are currently ineligible for housing support, for instance, so the inquiry asked Housing NSW to provide housing services for the small number of people who are ineligible for other forms of housing support and who are in desperate need of accommodation.
The inquiry also recommended a number of simple, practical measures. Visa applicants and entrants to Australia, for instance, should be provided with more information about the Australian legal system. They should also be given law enforcement contact details, information about the role of the Fair Work Ombudsman and a brief statement about Australian laws against slavery and trafficking, including forced marriage.
The inquiry noted the Commonwealth had initiated a community awareness program to boost general and specific awareness about human trafficking in slavery in Australian communities. Clearly, there is a role for NSW to work with the Commonwealth and to develop campaigns and information resources for the NSW community, in schools, and to be made available to vulnerable groups.
The inquiry also recommended the NSW government invest in more training of police, frontline government agency staff – especially in health and social services – to ensure we have the best chance of identifying trafficked and enslaved people in NSW and extending support to the trafficked person.
Responses to violence through human trafficking and slavery demand a multifaceted approach by governments and non-government agencies, and include the private sector. The inquiry sets out a pathway for NSW to co-ordinate and develop an effective state-based response to these abuses.
Jennifer Burn, Associate Professor, Faculty of Law and Director of Anti-Slavery Australia, University of Technology Sydney
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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