packeted

Files are huge for sure (mine are like 25Gb x 3 of us) but Claude Science / Macbook Pro M5 Max knocked out my analyses in minutes using command line tools like bcftools and scripting. Honestly think this opens up WGS data to much easier analysis and refreshing those analyses in minutes as new discoveries are made.

Thanks for the kind words. Actually we got the trio whole genome sequencing through our neurologist/geneticist a couple of years ago. It was performed by a company called GeneDx. They interpreted the data at the time which is how we got to a diagnosis but knowing I'd want to dive in to it later I asked for the raw data. They provided it as the raw CRAM files and also the VCF (variant call files) which are a bit smaller. But each company has its own pipeline and for example uses different versions of the reference human genome which made working with the data quite hard for me and the people I enlisted. Claude Science seemed to make very easy work of it. Also to be clear, the question I was trying to answer was whether his mutation was likely passed down through my sperm or mom's egg - neither of us have the mutation in our own genomes. Turns out spontaneous (de novo) mutations are much more common in sperm because Spermatogonial stem cells have undergone many more cell divisions over their lives. Everyone has de novo mutations (70+), one of his just happens to be in an unlucky location.

GeneDx aren't direct to consumer so you'd need to get it ordered through a physician but there are some DTC options for example, Dante Labs, Nebula Genomics, Sequencing.com but I can't speak to the quality of their testing.

23andMe doesn't do whole genome or whole exome sequencing. They use a microarray technology that tests for about 650,000 single nucleotide polymorphisms. You can actually download the your raw data on 23andMe and do your own analysis or use a tool like promethease.

I'm an MD so I'm quite comfortable exploring this data and whatever it uncovers. Tools like Claude Science are going to put a lot of power in the hands of every day people, potentially outside the guidance of genetic counseling/docs, which many organizations in the past (including the FDA) have been hesitant to allow.

Marginally but the data manipulation is actually being done locally as the genome CRAM files are like 24Gb each.

I watched the announcement and gave it a spin as I'm a heavy user of cowork/code. So far I'm super impressed. I used it to analyze my whole genome sequencing data I have as my son has a rare genetic condition. I used it to answer a question I'd asked a few bioinformaticians to help me with but never got a satisfactory answer, it solved it in about a minute - whether his n-of-1 de novo, heterozygous single nucleotide mutation was likely passed down from mom or dad. It performed a read-backed phasing analysis on the data, identified a nearby SNP with overlapping coverage where mom was homozygous and dad was heterozygous. Identified my variant on his mutated allele so looks like it came from me..

It also crosschecked my data against AMCG Secondary Finding genes and ClinVar likely pathogenic/pathogenic variants and came back with identical results to my Natera Horizon carrier screening results.

I'd previously tried and failed to do this all with some ChatGPT guidance and subsequently hired a couple of bioinformatician post-docs at top tier universities via Upwork who had failed to give me satisfactory results.

And this is just getting started!

It's been a painstaking process of combing consolidator websites (eg. PetVet Care Centers, NVA) for practice names, verifying and adding them to a list over the course of over a year. I now get many people writing in to report practices that aren't on the list - admittedly it's not complete list as practices are still being acquired (although independents are now in the minority) and often the old practice branding is kept and the fact it's PE owned is hidden.

Thanks! Actually I did add the UK very recently but this is a good reminder to improve the UI to make it more obvious, if you go to https://www.privateequityvet.org/vet-list/map.html you can toggle between US and UK. I have over 2000 practices listed in the UK.

I'm working on a website that lists veterinary practices owned by private equity or large corporations to help people make more informed decisions about where they take their pets. It started as a small passion project after our dog (who was sideswiped by a car) died at the hands of a vet practice recently acquired by private equity. We were billed over $13k for 2 days of care where his diagnosis and the opportunity to treat it was missed, there was zero continuity of care, no medical leadership and predatory billing practices.

The site has become quite a hit and gets thousands of unique visitors each day. https://www.privateequityvet.org/vet-list

I'm looking forward to reading your book! Part of my expose of PE in the veterinary business can be found at https://www.privateequityvet.org

If anyone wants to see how private equity has transformed the veterinary industry check out www.privateequityvet.org/vet-list - over 7000 practices mapped across the US so far. Our dog died at the hands of a recently acquired PE practice :(

Wow, great work. This is the kind of citizen hackery we need in society :)

Auricle | Founding Biomechanical Engineer (Neurotech Medical Device) | ONSITE (Mountain View, CA) | Full-time | https://auricle.com

Auricle is developing a next-generation neurostimulation implant to restore hearing and the ability to understand speech in the millions of people who no longer benefit from acoustic amplification with hearing aids but who aren't prepared to take on the risks of a cochlear implant.

We're searching for a full-time engineer to join our founding team. Our device and prototypes are partly mechanical, electrical and software so we'll need someone who can wear multiple hats but is comfortable primarily in the mechanical domain as we execute on early clinical and pre-clinical studies.

Experience with rapid prototyping using 3D printing, CAD and bench models is a must. Experience of medical device development within a quality management system and developing pre-clinical models is highly valued. Bonus points for electrical engineering experience, programming experience (Python/Matlab) and a passion for auditory science. More than anything, we're looking for someone who will be highly motivated to help bring a complex but life changing device to patients.

We're a small team formed out of Stanford and backed by YC (W21), based out of Fogarty Innovation in Mountain View. The role is primarily in-person with very occasional travel to study sites and with some flexibility for hybrid work from time to time.

We're excited to hear from you! francis@auricle.com

Congratulations on the launch, this looks like a super useful product and I'll give it a try. I've been responsible for conducting hundreds of qualitative interviews over zoom in the past and while the insights were very useful, it took me months to execute. Scheduling and no shows were a massive pain and this has the potential to make it almost hands-off.

Auricle | Mechanical Engineer, Simulation Engineer | Mountain View, CA / Remote | Full-time & Internship | https://auricle.com

Auricle is a medical device company developing a breakthrough minimally-invasive neurostimulation implant to restore hearing in patients who no longer benefit from hearing aids but aren't prepared to make the jump to a cochlear implant. The company is a spin-out from Stanford and YC-backed. We're looking to fill two roles:

1) Our first full-time mechanical engineer to lead electrode design and surgical implantation. Experience with small-scale medical devices ideal, bonus points for experience with implantable devices. Role will be in-person in the Bay Area.

2) A simulation modeling engineer for a summer internship with potential for full-time role, will consider full-time to start for the right candidate. Experience with 3D modeling and Finite Element Analysis required, bonus points for experience with Sim4Life and/or NEURON. Role can be remote or in-person.

You'll be joining an early team working on a very exciting real-world application with a huge market opportunity ahead. Interested? Please contact Francis, Co-founder & CEO email: francis@auricle.com

Planet Money is looking for people who have had questionable experiences with BNPL providers, I'd take a look if you haven't already: https://www.npr.org/2022/02/10/1079837232/have-you-used-buy-...

That's exactly why Tesla are so good at what they do! I've had VW , BMW and Ford rental cars in the last year and they are literally stuck in the dark ages when it comes to on car entertainment and the things that just work and are very responsive in a Tesla.

Are google workspace accounts treated the same? I have several fill me domains hosted with Google duo curious if this behavior tracks over to their paid products

There are a few that I have listed on my website at https://franciswong.com/digital-health although since COVID some have been less active. Take a look at Docs and Hackers, UCSF Health Hub and Stanford's Center for Digital Health. Reach out if there's anything I can do to help!

I have the base model MBP 16 inch and I've been experiencing slow downs with laggy keyboard input, momentary freezes, etc. Battery life is also not as good as on my old MPB 13 and I don't use it for much more than browsing with many tabs. I've done plenty of troubleshooting and a reinstall but no luck.

I'm hoping that 10.15.3 which I installed yesterday will help remedy.

You can't beat free. SVB and others get you with free for x months but once their fees and "analysis fees" kick in it really gets quite expensive for a small bootstrapped business even with little activity on your account.

It's also incredible how far behind all banks are with simple things like being able to search your transactions over a decent amount of time.

Good luck and I genuinely hope the free and open to all model proves to be sustainable.

I wanted to read this article especially as I've been to Chateau de Chambord, but this website is the epitome of adverts ruining the browsing experience!

I recently listened to The Fountainhead by Ayn Rand and feel that it has changed the way I think. As an entrepreneur who has been in the trenches, I felt a lot of empathy for Roark's uncompromising ideals, his pursuit of excellence, his wanting to leave the world a better place with his work even if he wasn't able to claim credit and his continual battles with the status quo.

I want to love eBay but I can see why the board is so unhappy and the rot has been infiltrating the company for a long time.

Back in the 00's I was a PowerSeller, shifting over $20k a month. At first it was an incredible experience and I was selling high value items to people all over the world with high margins and almost always a great experience. I was long on eBay and became a shareholder, passing up on Amazon whose business seemed much less appealing to me at the time.

Then came along PayPal with their 3.5% uncapped fee, which on expensive items was significant. Buyers started expecting to be able to pay via PayPal and eBay stopped allowing trusted sellers to offer a small discount for paying by wire or cash. PayPal eventually became mandatory.

Later, eBay's fees went up significantly. Those along with PayPal's fees ate in to my margins and I eventually lost interest, packed up shop and sold my stock at about break-even.

While I continued to be an occasional buyer, I recently started selling a few items again. I was met with frequent time waster winning bidders and the same high fees that I remembered. My last sale was an iPhone X that went to Thailand, "covered" under PayPal's seller protection and sent with a shipping label printed directly from eBay's site. A few days after I had sent it, the buyer filed a dispute with PayPal saying he hadn't received it. PayPal almost immediately sided with the buyer with a boiler plate reply, removing the money from my account (including all fees) before the phone even had time to arrive. I sent an email to appeal which was met with a curt denial. I was almost $1500 out of pocket.

Don't even get me started on their site and mobile app - so much could be improved and way too many clicks to do anything meaningful. One of my last battles was spending 3 hours on the phone to try and resolve an account bug as I had transitioned from UK->US which seems to be an edge case they didn't finish working on.

It makes me sad because the idea behind eBay is fundamentally a fantastic one, you can still find great stuff on there and the prices are often much lower than Amazon (even more so with the recent coupons they must be burning through cash on). They still have the audience to make a global market place, although perhaps not for much longer.

Not very surprising, voice is a terrible interface for buying random products, even more so when you're talking to a dumb computer. It's what people used to have to do decades ago before e-commerce became widespread. That said I can see Alexa being used as a replacement for Amazon Dash style interactions for those who don't care to shop for price.

These guys are definitely predatory. I'm a bootstrapped startup founder and I think Prosper caught wind that I have some debt, most likely because I use Credit Karma who I'm sure must sell one's credit information. I now get weekly letters from Prosper and other companies offering high interest loans. Not cool.

Loved reading this! I just finished restored a 1912 house in Oakland made out of the same old growth west coast douglas fir - from the framing to the copious clear vertical grain and quarter sawn wainscoting, all stripped, sanded and refinished in a natural varnish. Great to see this kind of craftsmanship alive and well!

Would be very interested to hear whether this is actually a long-term fix to the problem. I have had this issue many times with my MBP non-TB model, usually resolved by some compressed air under the keys.

Awesome. I was playing Batman Arkham City yesterday and this is "Detective Mode" in the real life!

Though this was concerning the company who handle our home insurance, also a startup named Hippo, who are great. Thankfully not!

Why does Facebook need to give up any of this information to developers in the first place? Presumably these apps are part of the reason Facebook has the engagement it has? Or part of the reason for the user growth it has seen in the past?

Perhaps this will prompt Facebook to start cutting out third party developers and build more home grown social apps, leveraging the data it already has on what eye balls engage with. Maybe they'll only grant API access to large companies, eg. TripAdvisor, who they can hold accountable and would be worth investing the time to audit. Perhaps they will start their own internal Cambridge Analytica where no data sharing is even necessary, assuming they haven't already.

It's also interesting that there is barely a mention of all this in my news feed on Facebook and there have been no links to it as a trending story.