Monthly Archives: March 2022

Vermont State Police investigators used advanced DNA sequencing techniques to identify a sample found as part of their investigation into the 2004 disappearance of a 17-year-old girl in the town of Montgomery, police said Friday.

But investigators say identifying the source of the DNA found near the abandoned car of Brianna Maitland does not mean they have identified a suspect in her disappearance.

"We are continuing our active efforts to investigate every lead associated with this case, and we constantly look for new technological advances to aid in our investigation," lead investigator Detective Sgt. Angela Baker said in a statement. "The use of genetic genealogy to identify the DNA found 18 years ago is just one example of how detectives continue to track down every potential lead in this case."

Brianna was last seen on the evening of March 19, 2004, when she left work at the Black Lantern Inn in Montgomery. She was headed to a friend's house where she was living, but she never arrived.

The next day, her 1985 Oldsmobile was located backed into an abandoned building about a mile from the restaurant. The now-identified DNA sample was later found near the car.

Police have said there is no evidence Brianna left the area willingly and they believe she was a victim of foul play.

The DNA collected from near Brianna's car was added to the FBI's DNA database and compared to samples from 11 people of interest in the case, but no match was found.

In the fall of 2020, the state police sent samples to Othram, a Texas-based forensic sequencing laboratorythat has set up afundraising pagefor the investigation.

After months of investigation, police were able to "locate, interview, and obtain DNA samples from possible donors."

Those DNA samples were sent to the Vermont Forensic Laboratory, which confirmed that DNA from one of the individuals matched the DNA found on the ground near Brianna's vehicle.

Anyone with tips or other information that might in any way be relevant to the investigation should contact Detective Baker atangela.baker@vermont.gov, or submit ananonymous tip online.

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DNA identified in search for Brianna Maitland, 17-year-old Vermont girl who went missing in 2004 - CBS News

Sample demographics

Twenty-five participants from across the UK were interviewed who were diagnosed with early-stage melanoma (Stages IAIIC) between 2011 and 2021 (see Table1 for a description of the cohort).

Views from participants regarding ctDNA monitoring for signs of early relapse and early treatment were grouped into two themes: (1) ctDNA monitoring would add service value and (2) test results provide opportunity and knowledge, with each theme including subthemes. All participant names have been replaced with pseudonyms.

The majority of participants did not know what ctDNA monitoring was or were unable to provide a definition. Upon providing participants with a simple definition of the new technology and blood test procedure, all of the participants described regular ctDNA monitoring as a good idea, as the new technology would be more scientific, would reduce the fear of the unknown and identify relapse early.

The majority of participants described skin check procedures as inconsistent in quality. They explained that at each appointment checks would be performed by a different healthcare professional, with some more thorough than others. They felt that skin checks are subject to human error and feared that changes could be missed. Consequently, participants believed that more could be done to provide them with a consistent marker of relapse:

Ive gone from having really detailed full body checks, lymph node checks, et cetera, every single one of the moles and I have a lot of them on my body being checked, to, okay, well check your lymph nodes, well look at the original site, are there any that youre worried about, type thing? (Fiona, 42, stage 1b, diagnosed in 2015)

When presented with the idea of a blood test to detect for early signs of relapse, all participants reacted positively, identifying ctDNA monitoring as the next step in melanoma care:

I think the treatment, as they stand at the moment, is all pretty visual. You know, on the whole, especially for stage 1 and 2, I think its virtually all visual, and things can get missed. Whereas, if youve got definite results, or likely results, from something like a blood test, I believe that to be more the way forward. (Harry, 49, stage 2b, diagnosed in 2017).

Compared to skin checks, they described a blood test as a more scientific measure, providing conclusive evidence of cancer recurrence. They explained that if ctDNA monitoring had been offered as part of their follow-up care, they would have been more reassured, describing the test as an extra safety measure or as one participant described another line of defence (Graeme, 34, stage 2a, diagnosed in 2021):

Id be over the moon if someone said to me, were going to put you on regular checks for x number of years as well as these visual skin checks. It feels more scientific. (Gill, 51, stage 1a, diagnosed in 2019)

As well as mitigating the effects of human error at skin checks, participants explained that blood test monitoring for early signs of relapse would be essential for providing internal evidence of change. Nevertheless, although deemed more conclusive than skin checks, all participants believed that ctDNA monitoring should not replace visual checks but be used alongside them for a belt and braces approach to care:

I just think its like a double check really isnt it, its like a belt and braces, youve got a visual and then youve got the internal and youve got something scientific that can be kind of highlighting you as early as possible. Especially if its being done every three months, thats so quick in terms of, if you start to see something then, you could do something quite preventable. (Yvonne, 47, stage 1b, diagnosed in 2019)

Participants described melanoma as a sneaky disease with no reliable means of knowing whether relapse would occur. This fear of the unknown was identified as anxiety-provoking and hard to live with post-diagnosis. However, the participants explained that a regular blood test would provide them with the confidence and peace of mind that they were being monitored for melanoma relapse more closely:

well certainly me with melanoma, you know, thats absolutely my biggest fear, is that its going to come back and Im not going to know about it, Im not going to know about it until, you know, Im so much further down the line so to speak. So, you know, if anything could detect something early and there could be early intervention then, you know, I would want to have it. (Lisa, 32, stage 2a, diagnosed in 2018)

They suggested that opting for this blood test would enable patients to feel more proactive about their care, reducing anxiety and enabling them to be forewarned about a potential relapse. Similarly, all participants felt that with regular blood tests, the anxieties regarding small changes to the skin and moles that occur between appointments could be better managed due to perceived additional surveillance:

say youre 1A and then finding a lymph node enlarged. That might happen in a second because you might find it and your mind does this massive jump, whereas if you were being monitored youd have a bit of logic. Youd be able to think well, I was monitored however long ago, this could be something else. I think it would just add a kind of reassurance that more than you poking and prodding your own body around. (Louise, 47, stage 1a, diagnosed in 2019)

The majority of participants viewed having regular blood tests for ctDNA monitoring could be useful as an early detection measure for relapse. Although the thought of relapse was difficult to consider, participants felt that a ctDNA test would provide them with the best opportunity to catch recurrence early before presentation with symptoms or radiological detection:

if it can detect something that mightthat wouldnt necessarily get picked up because obviously melanoma travels in the blood and unless youve got something, I dont know, maybe a mole or a lump, or something like that, you would never know until that. But obviously if this could pick that up beforehand then I think it would be a good thing. (Rebecca, 49, stage 1a, diagnosed in 2015)

In addition due to the radiation risks associated with computerising tomography (CT) scans, regular blood tests were deemed more favourable for some participants:

I think a blood test would be better than a scan, in levels of progression you would get your skin check, your blood check and then a scan would be the next step after that Id say. So it saves you having to have unnecessary exposure to radiation and things like that, which obviously is another cause of cancers. (Cathy, 34, stage 1a, diagnosed in 2019)

However, not all participants agreed that early treatment following the detection of ctDNA was appropriate, as a minority questioned whether treatment should be provided only after evidence of a tumour has been found via a CT scan, as they believed treatment prior to the identification of mass could be unnecessary:

Its hard, isnt it, because I think if youve actually got cancer and its there and you know its there, you want to do everything you can to get rid of it, dont you? [] But if its not actually come yet, do you really want treatment that could make you ill? (Jean, 63, stage 1a, diagnosed in 2017)

For the reassurance it would provide a number of participants explained that they would be happy to receive a ctDNA test for the rest of their lives, especially if the frequency of the blood test was manageable:

So if it was every few months, every three months or longer then Id probably be happy for it to go on for longer or indefinitely if need be. (Eric, 39, Stage 2a, diagnosed in 2018)

However, they understood that this might not be possible due to NHS funding, as well as the scientific rationale that the risk of recurrence decreases over time. For ctDNA monitoring to add the most value to patients, the majority explained that monitoring should be more frequent closer to diagnosis and reduced as the risk decreases, identifying a need for a risk-stratified approach:

I suppose it would depend how far after your diagnosis you were and what your dermatologist said were your chances of it recurring. So possibly the same as skin checks where its more frequent in the beginning and maybe spaces out as you get further away from it. (Louise, 47, stage 1a, diagnosed in 2019)

They described that three monthly for three years and 6 monthly for 2 years would be ideal as it would fit in with the existing care structure for stage two patients in the UK. Despite this ideal timeline, all participants stressed the importance of identifying ctDNA in the blood at the earliest opportunity. They, therefore, explained that if ctDNA can be identified earlier or later than three months then the frequency of blood tests should reflect this:

So it would depend on, I guess, the evidence for how likely you would expect to see changes. So if its once a year, six months, three months, I would say yes to whatever people gave me because it sounds like a preventable strategy kind of thing. (Yvonne, 47, stage 1b, diagnosed in 2019)

All participants described waiting and receiving test results as anxiety-provoking regardless of the outcome. They felt that being informed as to when to expect their ctDNA test results would improve anxiety. Notification of a negative test result would provide them with the reassurance to move on with life between tests. A positive test result, although worrying was viewed as an opportunity to access treatment early and receive better health outcomes.

All participants described waiting for test results as an anxious time and a result for a ctDNA blood test would be no exception. Participants identified that until results were received, there is constant speculation about the outcome, with some not being able to relax during the waiting period:

once you have a test for something youve always got it in the back of your mind until the results come in, so I wouldnt be totally on edge all the time, but it would be in [the] back of my head all the time. (Vanessa, 57, stage 2b, diagnosed in 2018)

With result anxiety in mind the majority of participants cited under two weeks as an appropriate time to receive notification of results. Others explained that waiting for their blood test result would depend on laboratory turnaround times in processing blood samples. However, no matter how long results would take, all participants explained that they would require notification of when to expect their results enabling them to manage their anxiety:

if they dont know what timeframe its going to be expected in, some peoples anxiety levels may be really, really high, straight from the off [] Whereas, if they know its not going to be expected for two weeks, a month, then they can at least get on with their lives, and not have it right at the forefront of their thoughts all the time. (Sam, 53, stage 1b, diagnosed in 2015).

Yet some identified that after attending for multiple blood tests receiving results would become routine and less worrying over time:

I dont think I would be particularly thinking about results coming through. I can imagine Id forget about it really over time and a letter or whatever it is would arrive every two months and I wouldnt be anticipating receiving it or anything like that. (Eric, 39, stage 2a, diagnosed in 2018).

When they considered how it would feel to receive ctDNA results, all participants said that they would be happy and trust their result if it were negative. All participants explained that they would want to be notified of a negative test result, as lack of notification would be unacceptable. They argued that they would not accept no news is good news but would instead worry and speculate about their result, with some being prepared to call services directly for confirmation:

I think, if I wasnt notified, Id be wondering if the letter is stuck in the post or if theres some problem at the hospital notifying, or there was an admin error. To have a negative result is much better than to be told if youre positive because it stops you worrying - I just want to check that that was okay and its just that you havent sent it out or I think I, personally, would still ring up about a few weeks later to say just want to check what results are on the file or Id bother my GP for it. (Gill, 51, stage 1a, diagnosed in 2019.)

Participants explained that a simple letter or text message notifying them of a negative result would provide them with peace of mind before their next appointment. Knowledge of a negative test result for ctDNA was viewed as something that could enable patients to move on with their lives between tests, providing them with time to enjoy life and worry less. Specifically, one participant explained that consistent notifications of negative test results would improve their state of mind regarding a potential relapse:

I think as well, the more times that happened [receiving a negative test result], so the further into those five years I got, I would become more and more reassured. You know, at three years, at four years, Id start to be probably quite optimistic. Because, again, I know that most melanoma reoccurs within the first two years. And I know that if you get to five years, you know, its quite a Its a very positive milestone (Graeme, 34, stage 2a, 2021)

However for a minority, the thought of there is always next time would be difficult to ignore, meaning any reassurance gained from a negative test result would be temporary. For example, one participant explained that the level of reassurance a negative test result would provide would depend on when the test was taken during their follow-up, with a negative ctDNA result at the beginning of monitoring being less significant than one received towards the end of follow-up:

I think it depends how long after youve been diagnosed that the test takes place, you know, where you are on your long term journey I suppose. If its, you know, a few months after I think youd be waiting for the next test for something, you know, youd be expecting something else to be happening next time in terms of spread. (Steph, 52, stage 2a, diagnosed in 2018)

Participants explained that a positive ctDNA blood test result would provide them with a chance to be treated early. Although a positive test result is not good news, they would be grateful that relapse was identified before cancer had time to progress and present visually:

Well, obviously thats [a positive result] going to cause a bit more anxiety, isnt it? But also at the same time there could be a bit of a relief there, you know, that its actually been caught rather than it not being picked up. So it can work either way, really. For me, if it was positive, Id rather know. That theres something going on, and maybe we can do something about it. (Jean, 63, stage 1a, diagnosed in 2017)

The majority of participants explained that they would soon deal with the initial shock of a positive test result and instead would concentrate their minds on what needed to be done to reduce the chances of cancer progressing:

Well, the first word that came to my mind was devastated, gutted. But, Id be like, right, okay, its been caught, before it can hopefully get anywhere, like if youre in regular testing? Id think, right, its been caught early, what are we going to do about it? (Cathy, 34, stage 1a, diagnosed in 2019)

As the majority would want to immediately know their management plan, they suggested that information material, such as leaflets and result letters state clearly what a positive test result would mean. Should a positive test result be delivered by letter, participants stressed the importance of having the opportunity to speak with a healthcare professional or have an appointment automatically arranged. Others believed that a positive test result and notification of needing treatment should be delivered in person to enable the patient to ask questions and be provided with the space and time they need to process the information with a healthcare professional present.

See original here:
Circulating tumour DNA monitoring and early treatment for relapse: views from patients with early-stage melanoma | British Journal of Cancer -...

If we want to find a potential multi-bagger, often there are underlying trends that can provide clues. Typically, we'll want to notice a trend of growing return on capital employed (ROCE) and alongside that, an expanding base of capital employed. This shows us that it's a compounding machine, able to continually reinvest its earnings back into the business and generate higher returns. With that in mind, the ROCE of ResMed (NYSE:RMD) looks great, so lets see what the trend can tell us.

For those that aren't sure what ROCE is, it measures the amount of pre-tax profits a company can generate from the capital employed in its business. To calculate this metric for ResMed, this is the formula:

Return on Capital Employed = Earnings Before Interest and Tax (EBIT) (Total Assets - Current Liabilities)

0.24 = US$976m (US$4.7b - US$621m) (Based on the trailing twelve months to December 2021).

Thus, ResMed has an ROCE of 24%. In absolute terms that's a great return and it's even better than the Medical Equipment industry average of 8.2%.

View our latest analysis for ResMed

Above you can see how the current ROCE for ResMed compares to its prior returns on capital, but there's only so much you can tell from the past. If you're interested, you can view the analysts predictions in our free report on analyst forecasts for the company.

ResMed is displaying some positive trends. The numbers show that in the last five years, the returns generated on capital employed have grown considerably to 24%. The company is effectively making more money per dollar of capital used, and it's worth noting that the amount of capital has increased too, by 56%. This can indicate that there's plenty of opportunities to invest capital internally and at ever higher rates, a combination that's common among multi-baggers.

To sum it up, ResMed has proven it can reinvest in the business and generate higher returns on that capital employed, which is terrific. Since the stock has returned a staggering 285% to shareholders over the last five years, it looks like investors are recognizing these changes. With that being said, we still think the promising fundamentals mean the company deserves some further due diligence.

On a final note, we've found 1 warning sign for ResMed that we think you should be aware of.

High returns are a key ingredient to strong performance, so check out our free list ofstocks earning high returns on equity with solid balance sheets.

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This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

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We Think ResMed (NYSE:RMD) Might Have The DNA Of A Multi-Bagger - Simply Wall St