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Comment – Precision Medicine to Beat Antibiotic Resistance

Antibiotics from engineered bacteria

Antibiotic droplets emitted from engineered bacteria (University of Warwick)

20 Jan. 2019. One of the scarier public health threats today is the emergence of bacteria resistant to antibiotics now in use. As we’ve documented numerous times in Science & Enterprise, the problem is global and growing, affecting millions of people just here in the U.S. and spreading among a growing number of infectious diseases.

A strategy often used to fight infections in a patient is to find an appropriate antibiotic for the responsible bacterium. But as bacteria mutate and evolve to become resistant to today’s drugs, we’re running out of antibiotics to battle those infections, with drug makers in a never-ending race to stay one step ahead.

A story we published on Friday describes a promising technology applied to the problem, suggesting an alternative approach. Our story tells about a group at Johns Hopkins University in Baltimore using a hand-held DNA sequencing device to identify vulnerabilities in the bacterial genome, which clinicians can then use to prescribe an appropriate antibiotic. The device is made by Oxford Nanopore Technologies in the U.K., a company we’ve also reported on before.

While it’s easy to focus on genomic sequencing hardware that you hold in one hand and connect to a laptop computer, don’t lose sight of the change in treatment strategy enabled by the technology. The Johns Hopkins team used the portable sequencer with patients’ blood samples, testing for Klebsiella pneumoniae bacteria , a microbe becoming resistant to many current antibiotics. The tests identified vulnerabilities in the bacterial genome, offering targets for antibiotics, with results that show the technique reduces the time needed to spot those targets.

This change in approach is another example of precision medicine, but with a twist. Much of what we today call precision medicine identifies the molecular composition of patients, such as cancer-causing genetic mutations, in order to find appropriate treatments addressing those mutations. In this case, precision is applied to the bacterial genome, to find vulnerabilities making the microbe more susceptible to antibiotics, with those targets used to identify appropriate drugs.

This change in diagnosing infections could lead to a precision-medicine approach for antibiotic discovery and development. We’re seeing signs that strategy may be feasible. In October 2018, we reported on a lab at University of Warwick in the U.K. that created a new antibiotic derived from soil microbes identified through bioinformatics, followed by genome editing with Crispr. The Warwick researchers acknowledge it took some trial and error to get their results, but they believe automation and robotics can make the process more efficient.

And finding new antibiotics from soil microbes is hardly a far-fetched idea. As we reported in June 2018, a team from University of California in Berkeley and Berkeley National Lab identified a wide range of new microorganisms in Northern California soil samples, many of which having genetic similarities to current antibiotics. Thus the soil under our feet may be a rich source of yet undiscovered new antibiotics.

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The Growing Role of Tech in Your Business

– Contributed content –

Networked earth

(geralt, Pixabay)

21 Jan. 2019. If your business is like most, then it already has some incorporation of information technology. It’s helping us improve communication, make our core processes more efficient, and manage all sorts of data related to our customers. As the business grows, it’s only likely that its relationship with tech will continue to grow, as well. However, to make sure that tech remains a milestone in business and not a millstone, you have to make sure that you’re ready for the role it’s going to play.

State your purpose

There is a very wide variety of ways that tech can be used in the business. An internal network can be used to help teams collaborate and cooperate more effectively, from working on shared projects to making it easier to send resources from place to place. New software can be purchased to improve productivity and efficiency with the business’s core tasks. Servers can be implemented to help store and analyze large sets of data helping develop insights on the customer.

However, you need to figure out what tech is going to help you with your business goals first and foremost. Stick to one objective at a time, ensuring you have the budget and plan to see it through before you get too ambitious and risk spending more than you can or implementing tech that isn’t utilized as much as you expected it to be.

Lay out your road map

Technology is always changing, and you are likely to want to change it as time goes on. Whether this means a comprehensive change in the way you use it from top-to-bottom or simply scaling up the systems you use now, it pays to be prepared for that eventual change. A technology plan can help you plot out how those changes happen. It’s much like a business plan, looking at potential room for growth and how you’re going to achieve it, only it’s more specifically related to your tech.

With your tech comes a whole new responsibility to handle within the business, as well. An IT team is needed to not only fix errors and problems as they pop up, but to address questions of digital security, and to help you plan the further implementation and growth of new systems. As your reliance on tech grows, your IT team will also grow, and it becomes more likely you will need a leadership figure to serve as the bridge between you and that team. Interim CIO services can help you find the chief information officer that serves as that bridge, helping you see the benefits of having a leader of your IT team. Outsourcing is a cost-effective way to scaling the business until you’re ready to hire your own.

Make sure the team is with you

The most technologically savvy of your team are the most likely to see the benefits of new systems you’re implementing, first. But what about the rest of them? To them, it may pose a risk, introducing new demands to their jobs which they don’t have the skills for. Replacing them can be a lot costlier than simply taking the time to train them. IT skills training courses can help not only ensure your team can keep up with the pace of change but it can also serve as part of their professional development, helping them see the personal growth that can be a huge factor in retaining your employees.

Be aware of the risks

As your reliance on IT grows, it can become a bigger vulnerability and one you have to prepare for. Downtime as a result of power failure, internet failure, or equipment failure is a large one. Having backups for each source of downtime can help you get back on your feet all the sooner. However, the biggest risks are without a doubt data loss and data breaches. Investing in strong digital security for the business is essential. This means not only investing in the enterprise anti-malware software and digital protection services, but also investing the time to teach employees the risk of phishing scams, leaving their devices logged in and unattended, poor password management, and the like.

An effective plan, a purpose, the right team to manage it, thorough education of the rest of the team, and an awareness of the risks are all essential is tech is going to be playing a larger role in the business as it goes along. Don’t look for the tech revolution unless you’re prepared for it.

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What’s The Best Defense Against A Breach?

– Contributed content –

Hacker graphic

(TypographyImages, Pixabay)

20 Jan. 2019. Businesses are always under attack. If you’re having a good day and everything is running smoothly with no sign of trouble from outside threats, spare a thought for another company that is having the exact opposite day. Hackers are working around the clock to make new termites that will infiltrate your systems and breach all your precious data. This data is concerning, your customer’s addresses, their contact details, their profiles and accounts as well as even their financial details. This is just the tip of the iceberg of what hackers, viruses and malware are all trying to achieve.

In truth, malware is by far the most common form of attack. It’s a stealth bug that infests your entire network but lays dormant. Only when you do something specific will the bug activate and begin to take what it needs. It will do so quietly as to not bother you and make it known that it was present in your IT systems. So what are the best defenses against a breach?

Company discipline always

The most common way a business can become breached is by careless employees. Whether it’s an attack internally from people you have hired or just those that didn’t log out of their system when they went away leaving it exposed. The easiest way for viruses, malware and hackers to get into all your data is to be allowed in. Instruct employees that if they are away from their stations for no matter how long they should always log off. Incur penalties for those that aren’t doing so, so that everyone around them can perk up their ears and make sure they are following company codes of conduct.

No one gets away

In combat sports, they say a good defence is a good offense. When you are attacked by any kind of malware, virus or hacker then you should not let them get away with it. You will set an example and perhaps get your name in the media if you track the attack down and find out what really happened. Using a team that has IT consulting services which include cyber warfare you can allow them to see what the breach was about. They show that 43% of attacks are targeted at small businesses.

This is quite obviously because the enemy knows or thinks that small businesses don’t have the funds to protect themselves by either hiring a professional company or buying a service that the can use themselves. Even more shocking is the statistic that 60% of small businesses that are attacked actually go out of business just 6 months after the breach. Don’t allow yourself to become a victim, and punish those that do try to harm your business.

Security in the modern IT world just isn’t understandable to the average employee or business owner anymore. That’s why professionals at this game should be employed to keep a business safe instead of just buying what a normal consumer might buy for their home computer system. On the other hand, employees should be trained to never let their guard down either.

Editor’s note: The opinions in this post are the contributors and not those of Science & Enterprise. You’re encouraged to consult IT or security specialists to protect against threats faced by your organization.

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Infographic – Americans Affected by Gov’t Shutdown

Chart, survey of shutdown effects

Click on image for full-size view. (Statista)

19 Jan. 2019. The funding impasse shutting down parts of the U.S. government is now in its 29th day. As we reported in Science & Enterprise, the dispute is disrupting the conduct of science in the U.S. and affecting the work of many agencies, including the Food and Drug Administration.

Yesterday, our friends at Statista reported on a survey on how the shutdown is affecting people in the U.S., this weekend’s infographic. The results show 1 in 5 Americans (21%) are affected personally by the dispute. Those negative effects include not being able to use a government-provided service (8%), stopped from visiting a national park (7%), effects on their business (5%), not able to access a government web site (5%), and not able to apply for a passport (4%).

Nearly half of those polled (46%) report knowing someone affected by the shutdown. The survey, conducted by the Economist and market research company YouGov, queried some 1,500 Americans from 12 to 15 January.

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Hands Off! Robots in Modern Medicine

– Contributed content –


(skeeze, Pixabay)

19 Jan. 2019. The idea of going to a hospital and being dealt with by a robot is very sci-fi. Fortunately, health care hasn’t quite reached this point in most places, and friendly humans are what you’ll find behind the desks in your local surgery. Of course, though, once you get behind the curtain, there are far more machines than you might realize. With jobs ranging from managing pills to performing proper treatments, the array of technology in this field is always improving, and this makes it very exciting for business owners who are interested in all things cutting edge.

Measuring and packing

There are a lot of jobs which are handled in hospitals, pharmacies, and doctor’s offices which have the be incredibly precise. With a lot of essential treatments containing dangerous chemicals, it’s crucial that people are careful when they are preparing them for people to use. An IV Room can solve this problem for a medical business, providing a perfectly clean machine which will measure and dispense a wide range of different options. Of course, avoiding overdoses and contamination are important, but it is also worth thinking about the time this could save you, as this will be important to the whole thing, too.

Providing the tools

Despite the amount of time which goes in to the medical research, there will always be limitations when it comes to the human body, and this can get in the way of being able to do certain jobs. A surgeon, for example, can’t make their hands small enough to fit into every space. To overcome this issue, while also making the whole process a lot safer, surgery teams around the world have started using robots to carry out the procedures which are too small. Of course, there are other benefits to this sort of route. As one of the biggest, metal and plastic are both far easier to keep clean than skin, making these devices far less likely to cause infections than a human.

Long-term treatments

Finally, as the last area to consider, it’s time to think about the robots which are only designed to support one person throughout their lifespan. Having come a long way since traditional pacemakers, modern medical implants are becoming incredibly powerful, and are already able to handle complicated treatments on their own. In some cases, these devices can even dispense chemicals into the body. While this may seem risky, they will only do so after measuring your blood, and this is often far safer than having a human in charge of monitoring this side of your life.

With all of this in mind, you should have a much better idea of the robots being used in the field of medicine. A lot of people have no idea that they could be waiting to be seen by a machine when they visit their doctor, but this is something which is likely to change over time, slowly evolving and becoming more important to the industry. Of course, this isn’t a bad thing, though, especially if you find seeing people like this to be scary.

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Portable Sequencer Identifies Drug-Resistant Bacteria

Klebsiella pneumoniae

Klebsiella pneumoniae bacteria (

18 Jan. 2019. Researchers using a hand-held genomic sequencing device were able to identify targets for combating drug-resistant bacteria much faster than current methods. A team from Johns Hopkins University in Baltimore describes their techniques in the January 2019 issue of Antimicrobial Agents and Chemotherapy (paid subscription required).

The problem of infections from microbes becoming more resistant to current antibiotics is a global and growing public health issue. In the U.S., according to Centers for Disease Control and Prevention, at least 2 million people get an infection resistant to antibiotics each year, leading to some 23,000 deaths. World Health Organization says the kinds of infections becoming resistant to antibiotics is growing to include those from pneumonia, tuberculosis, blood poisoning, gonorrhea, and foodborne diseases.

A team from the lab of Johns Hopkins pathologist and microbiologist Patricia Simner is seeking faster ways of identifying the precise nature of infections, to provide patients with the best available treatments as soon as possible, since delays increase the chance for poor outcomes. “The current standard process of identifying appropriate treatment options for highly drug-resistant bacteria,” says pediatrics professor and first author Pranita Tamma in a university statement, “can take up to 96 hours from the time the lab receives samples, but our findings suggest that with the use of a rapid whole genome sequencing method, we might reduce that time to about one day less.”

The rapid whole genome sequencing method used by the researchers is a portable device called the Minion made by Oxford Nanopore Technologies in the U.K. The MinIon is a portable disease surveillance system that analyzes DNA from blood samples, returning results in as little as an hour, and operates as a plug-in peripheral on a laptop computer. The MinIon technology forces single strands of DNA through nanoscale pores, which makes it possible to analyze samples in real time.

The Johns Hopkins team sought to test the feasibility of a nanopore device to quickly spot genes that expose vulnerabilities in bacteria, thus offering targets for the right kind of antibiotics. To prove the concept, the researchers analyzed the whole genomes of Klebsiella pneumoniae, a gram-negative bacteria associated with pneumonia, bloodstream infections, wound or surgical site infections, and meningitis, particularly in health care settings. “Gram” refers to a classification for bacteria where the microbes either retain (gram-positive) or shed (gram-negative) a test stain on their protective cell coatings.

The team drew samples of Klebsiella pneumoniae bacteria from 40 patients at Johns Hopkins medical center. After establishing reference measures as baselines, the researchers analyzed the samples using 2 different methods: (1) genomic analysis of samples in real time, where the team could make judgements about susceptible genes while the analysis was underway, or (2) assembling the genome, then identifying target genes and mutations. The real-time method identified vulnerabilities in the genome in about 8 hours, but with an accuracy rate of 77 percent. The assembly method took a little longer — 14 hours — and with 92 percent accuracy. Both methods are faster than current techniques, by about an entire day.

“While we still need to wait 24 hours to get the culture to grow,” adds Simner, “we were able to cut time to identifying effective antibiotic therapy by at least 20 hours, compared to our current standard of care.” The researchers say more use of automation could reduce the analytical time even further.

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Engineered Microbe Blocks Ammonia Blood Poisoning

Ammonia molecule

Ammonia molecule (Ben Mills, Wikimedia Commons)

18 Jan. 2019. A genetically engineered bacterial strain is shown in tests with animals to stop ammonia poisons in the gut from reaching the blood stream, as well as be safe for humans in a clinical trial. Findings from the lab tests and clinical trial, conducted by biotechnology company Synlogic Inc. in Cambridge, Massachusetts, appear in the 16 January issue of Science Translational Medicine (paid subscription required).

A team led by Paul Miller, Synlogic’s chief scientist, is seeking better treatment options for hyperammonemia, a condition where the body’s metabolic system fails to clear ammonia from the gut, allowing ammonia to build up in the blood. The accumulation of ammonia often results in neurological disorders ranging from lethargy and irritability to seizures and Reye’s syndrome, swelling of the liver and brain. Treating hyperammonemia today usually involves managing its symptoms, although a liver transplant can sometimes correct the disorder.

Miller and colleagues tested a solution developed by Synlogic, an engineered form of Escherichia coli, or E. coli, bacteria in the gut that removes ammonia before it reaches the blood stream. While E. coli is often associated with food poisoning, the species includes many benign strains, including one called E. coli Nissle, a probiotic form used to treat colon inflammation, such as ulcerative colitis. Synlogic genetically engineers E. coli Nissle to perform another task: stop ammonia from building up in the colon. In this case, the modified E. coli Nissle bacteria absorb ammonia and convert it to arginine, an amino acid used by the body to produce proteins that dilate blood vessels, and marketed to treat conditions such as hypertension and erectile dysfunction.

Synlogic code-names its engineered microbe SYNB1020, which it tested in lab mice, monkeys, and humans. In lab mice bred to express a genetic condition that results in hyperammonemia, the researchers fed the animals a high-protein diet to produce high blood ammonia levels. Mice randomly assigned to receive feedings of SYNB1020 were found with lower ammonia levels in their blood, less liver damage, and longer survival times than other mice fed a deactivated substitute. The tests also show test mice tolerated feedings of SYNB1020, cleared it quickly from the gastrointestinal tract, and showed no signs of the engineered bacteria elsewhere in the body. Tests with lab monkeys show similar results in tolerating SYNB1020 and clearing it from the body.

The team then tested the safety of SYNB1020 in an early-stage clinical trial with 52 healthy volunteers. Participants were assigned to receive single, then multiple doses of SYNB1020 or a placebo for 14 days looking primarily for signs of adverse effects. The results show participants generally tolerated the daily doses of SYNB1020 with mild to moderate nausea or vomiting exhibited by some participants to higher doses. No serious adverse effects were reported.

The trial also checked for signs of SYNB1020 activity in the body. The results show recipients of SYNB1020 had traces of nitrate, an indicator of SYNB1020 in blood and urine samples, and arginine in fecal samples, while placebo recipients did not. Fecal samples from SYNB1020 recipients found no signs of of the bacteria after 14 days.

“These data demonstrate that we can engineer bacteria to carry out a specific function, deliver them to humans and that they perform as designed,” says Miller in a Synlogic statement. He adds, “The compelling data in this publication encouraged us to advance SYNB1020 into additional clinical studies and we look forward to presenting data from our trial, designed to evaluate the potential of SYNB1020 to lower ammonia in patients with cirrhosis, in mid-2019.”

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Want to Start Trading? Here’s How to Get Started

– Contributed content –

Calculator, pen, chart


18 Jan. 2019. While playing the lottery is commonly seen as gambling for the poor, trading with stocks is surely gambling for the rich. The misunderstanding here is, of course, that you don’t have to be particularly rich to get started. You just have to be willing to put in the effort to educate yourself a bit first.

Buying stocks is definitely a bit different from buying a simple lottery ticket although the outcome seems to be the same; you either win some or you lose some. Before you get started, it’s a good idea to go through some of the different options first and give you a few resources in terms of what to read up on.

Here is a handful of excellent tips to get you started with trading stocks and becoming a part of the ever-buzzing market.

First: Active or passive?

If you have ever discussed stock with someone before, you might have encountered two types of people: those who swear to only trading actively and those who would rather play it safe. First of all, it’s good to know that trading stocks actively simply means that you’re selling and buying according to a plan of your own, or that of your stock fund, rather than just following where the market is heading.

You could make a bit more, in other words, but you could also lose a bit more. Stock market experts have, in fact, concluded that those who stick to a long-term plan of trading stocks passively will make more money than those who trade actively, though, but whether or not you believe this is up to you.

Another point to this is that the more you know about trading stocks, the more you might be able to make by trading actively. Read up on everything, in other words, and consider doing a combination of both; keep you big savings in a passive index fund and reserve a part to gamble with actively.

If you choose to trace actively, it’s a good idea to have a plan in mind and always sticking with it. If you’ve told the system to sell after a 6% increase, in other words, this is what you should do.

Next: Are there other investment options?

Sure, being an active or passive trader on the stock market is definitely as basic as it gets. It’s still important to know about, however, and especially if you’re brand new to the market – but when you have mastered this, you can graduate to other investment options as well.

There are real estate investments, for example, and not just those where you need to save up for half a lifetime before you’re able to buy a place of your own. Become a part of the market as soon as possible instead by reading up on this commercial property investment advice. It’s a great way to get a foot into the real estate market and take advantage of the increase in prices.

And, if the prices should drop, you can always run over to the bank and take up a loan so that you can invest in an actual place. It’s a win-win situation, in other words, and it might help you to grow your fortune a bit faster.

Editor’s note: The opinions in this post are the contributor’s and not those of Science & Enterprise. Readers are encouraged to consult their personal financial advisors for guidance on appropriate investments.

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Sensor-Pill System Designed for Cancer Drugs

Proteus Discover system

Proteus Discover system — pill with sensor, patch, mobile app (Proteus Digital Health)

17 Jan. 2019. A system combining a tiny sensor with oral chemotherapy drugs aims to provide physicians with closer monitoring of cancer patients’ treatments and conditions. This digital medication initiative, a joint project of Proteus Digital Health Inc. in Redwood City, California, with University of Minnesota Health and Fairview Health Services in Minneapolis, was described today at the ASCO-GI 2019 Gastrointestinal Cancers Symposium in San Francisco.

Many cancer patients are asked to take powerful chemotherapy medications to treat the disease, in some cases formulated as oral drugs. In this case, the patients have colorectal cancer, and are taking the chemotherapy drug capecitabine in pill form. Instead of the usual capecitabine pills, however, patients are taking ingestible capsules containing the drug with a tiny electronic sensor, part of the Discover system made by Proteus Digital Health. The sensor, about the size of a grain of sand and made with biocompatible materials, is activated by fluids in the stomach. A signal reading patch is worn on the torso and tracks ingestion of the sensor-pill, as well as date/time and activity level, which sends signals to a mobile app providing immediate feedback to the individual taking the drug.

In addition, with the patient’s consent, the data captured by the app are shared with designated individuals, such as physician, pharmacist, or caregiver. The project includes a registry of cancer patients using the digital medicine system, receiving treatment at university medical centers and community clinics in urban centers and rural regions. Joining Proteus in the initiative is University of Minnesota Health and Fairview Health Services, a health care service provider in Minnesota with 20 cancer care centers in the Twin Cities and elsewhere in the state.

For the patients, the digital medicine system offers reminders to take their drugs, as well as a record of those medications. And for clinicians, the system provides a means for closer monitoring of cancer patients without the patients traveling to clinics for their medications. Paul Morales, infusion pharmacy manager at University of Minnesota health clinics says in a Proteus statement, “For pharmacists, it helps us identify patients who might be struggling to take their medication correctly and intervene, for example by giving them a call to explain how to safely move forward if they do miss a dose. For patients, it helps them feel in control as they take a more active role in managing their medication.”

Edward Greeno, director of  University of Minnesota Health’s oncology service adds that the system, “provides a much more direct connection to the patient. It creates a way for us to achieve a lot of things that happen when a patient is in the clinic for infusions without them coming in person.”

As reported by Science & Enterprise in November 2017, Food and Drug Administration then approved the first digital medication system, a Proteus Digital Health application to help people taking drugs for schizophrenia.

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Univ. Spin-Off Creates Concussion Detection App

Eye measurements

(Sakuie, Pixabay)

17 Jan. 2019. A start-up enterprise begun by students at Purdue University developed an iPhone app that detects mild brain injuries by measuring responses of eyes to light. The app, known as Reflex and released earlier this week, is the work of Brightlamp LLC in West Lafayette, Indiana.

The Reflex app measures size and reactions of the pupil in the eye to a beam of light, much like a pupillometer, a device used by neurologists. When a beam of light hits the eye, the pupil responds in a reflex known as pupillary light reflex, thus the name of the app. The light, after entering the pupil, stimulates the retina that sends electrical signals over the optic nerve to the brain. Pupils react predictably to the light beam, constricting then dilating, when there’s no damage to the eye or neurons, or nerve cells. If damage happens, however, when a concussion or other brain injury occurs, changes in the size of the pupil, speed of response, and time needed for recovery differ from normal.

Team doctors and athletic trainers will sometimes shine a penlight into the eyes of athletes on the sidelines to check for pupil reflexes, at best a rough indicator of possible nerve damage. The Reflex app, says Brightlamp is more precise and replicable, and just as easy to administer. The app sends a light beam into the eye, then records a video of the pupillary light reflex response. The test takes a few seconds.

The app measures the latency or delay in response, as well as tracking changes in the size of the pupil, speed of constriction and dilation, and recovery time. Variations in pupillary light reflex responses are correlated with concussion, but also fatigue and other neurological disorders including Alzheimer’s and Parkinson’s disease. The app is designed for trained clinicians, such as team doctors, who can export the data for future reference.

Brightcamp was founded in 2015 by Purdue chemistry and chemical engineering major Kurtis Sluss and management/finance major Michael Heims. “We give them an objective tool to monitor that,” says Sluss in a university statement. “That way they’re not second-guessing. Plus it gives them data they can reliably look back on and track progression over time.”

The Reflex app is now considered a Class 1 medical device by the Food and Drug Administration, indicating a low-risk diagnostic device, in line with other pupillometers. While the app is free from Apple, the company charges for monthly or annual subscriptions.

Brightcamp incubated at Purdue Foundry, the campus business accelerator, which also helped with gaining a patent for the technology. The founders eventually want to advance the device to provide more medical guidance, such as for youth sports coaches or parents who use the app with their children at home. But that type of device would likely require a higher classification from FDA and clinical trials.

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