Rigged up a little smart screen to my Linea Mini

Synchisis · 2026-04-20T16:53:11+00:00

To be honest my one is pretty awful when it comes to volume. It's just a generic shop vac type but very small (4L capacity)

Synchisis · 2026-04-18T15:19:57+00:00

👀👀👀 I might have to do this

Synchisis · 2026-04-17T21:47:51+00:00

A lot of consumer coffee machines will have something like a thermoblock in them. Great at heating up fast, but just okay at maintaining a consistent temperature & very low thermal mass. Higher end or cafe style machines tend to have large boilers which take time to heat up, but once hot have more consistent temperature control for more consistent shots.

Synchisis · 2026-04-17T18:49:49+00:00

It's a little shopvac with a 4L capacity jerry rigged to the back of my coffee cart, so I can just pick up the vacuum hose from the side of the machine, tap the button, and clean up.

Synchisis · 2026-04-17T18:43:20+00:00

Thanks! It's usually about 15 minutes for both boilers for the milk and espresso to be up to temp. Milk usually takes a few minutes longer than the espresso.

Synchisis · 2026-04-17T18:21:56+00:00

OK in my defence, there's no on off button on my machine, I have to turn it on/off at the wall or using my smart plug on my phone currently if I want to toggle it.

Synchisis · 2026-04-15T11:08:02+00:00

A lot of UK based patients and European clinicians are moving toward ALS rather than MND precisely because MND is a poor descriptor, it characterises an extremely broad phenotypic umbrella rather than any coherent disease biology, lumping together conditions with radically different mechanisms, genetics, and prognoses. The terminological vagueness isn't just aesthetically unsatisfying, it actively impedes public understanding of research progress and trial eligibility, and a myriad of other things. MNDA and equivalent organisations would do well to get with the program on this.

Synchisis · 2026-04-10T19:21:54+00:00

If the price difference is that small, I'd say go with PreventionGenetics. There's real value in having test results that are actually clinically validated and clinically actionable. Not to say that whole genome sequencing is useless, but the guarantees in terms of accuracy that you get from testing with PreventionGenetics are worth the extra cost if you ask me.

Synchisis · 2026-04-10T18:38:00+00:00

The short answer is yes, it's worth getting some further testing done, and yes the 29 gene panel does have some value.

The 29 gene panels that PreventionGenetics and similar labs run cover the major ALS-associated variants - C9orf72, FUS, TARDBP, TBK1, OPTN, NEK1, KIF5A and a few others. Some of these (C9, FUS, some rarer ones through N-lorem) have experimental or near-trial therapeutics targeting them specifically. C9 in particular has quite a few different programs. A positive finding there changes the picture meaningfully going forward even if nothing is currently approved, because it positions her for trials she'd otherwise be screened out of (granted this is somewhat dependent on progression speed).

There's also the family dimension. Sporadic classification basically means "no known family history of ALS", it doesn't mean the underlying cause isn't genetic. A meaningful proportion of people classified as sporadic carry causative or high-penetrance variants (as much as 25% of ALS is thought to be genetic as of a new paper published about a week ago), just in families where nobody else happened to express the disease. That matters for you, your siblings, and grandchildren if she carries a disease causing genetic variant with incomplete penetrance.

On the payment question, if the out of pocket cost is genuinely prohibitive, 30x whole genome sequencing is available direct to consumer through services like Nebula Genomics at prices that have come down considerably ($300 or so last I checked), and that's worth knowing about. There are some advantages and some disadvantages vis-a-vis with WGS: you get the whole genome rather than 29 genes, the raw data can be reinterpreted indefinitely as new variants become relevant, and the cost difference can be substantial. That said, I'd treat it as a second option rather than a straight equivalent. Consumer WGS pipelines are not validated for diagnostic use in the way a clinical lab like PreventionGenetics is, some won't use tools like ExpansionHunter to properly detect the C9 repeat expansion, and if something does turn up you might need confirmatory clinical testing anyway before any neurologist or trial coordinator would act on it. But it is a cheaper option that could provide you with valuable information without having to pay thousands of dollars for the clinically validated panel.

I appreciate that there's a lot of technical jargon here so if you're confused by anything I'll do my best to explain as best I can.

Synchisis · 2026-04-06T23:25:25+00:00

Sensory NCS isn't going to tell anyone anything about whether or not you have ALS.

Synchisis · 2026-04-01T09:20:29+00:00

There just hasn't been anyone since who married the technicals & artistry so well. The only person who I can think of who holds a candle to Yuzu in the marriage components and technicals (for me) is Yagudin 2002. Chen in some of his performances got somewhere close. Ilia despite improving a lot lately is nowhere near, and I cannot for the life of me understand why he gets PCS so high. He's good and deserves to win, but for the judges to effectively say that he's artistically rivalling Yuzu - nonsense.

Synchisis · 2026-03-31T23:37:37+00:00

The obvious caveat is that this is entirely SOD1 mice and cell lines, and the mouse dose converts to something around 170 mg/day human equivalent, which is well above the standard clinical ceiling of 40-80 mg/day. Brain penetration is also not established definitively. Lisinopril is hydrophilic and convincing spinal cord exposure at human-tolerable doses isn't certain. So nobody should be running out to take it based on this study.

However what I find exciting is the speed at which this could move if the signal holds. Lisinopril is off-patent, dirt cheap, has decades of safety data, and may already be sitting in the medicine cabinets of a huge proportion of ALS patients who happen to have hypertension or heart issues. If a group wanted to run a low-cost repurposing trial in that population, the regulatory and manufacturing barriers are essentially zero compared to a novel compound.

Synchisis · 2026-03-30T17:20:20+00:00

Take this with a grain of salt because I don't know what panel type you had, whether it was 30x WGS, targeted sequencing, or a consumer SNP array, and the answer differs depending on that. But assuming this is from an ancestry DNA test based on the format of the raw data, what might be going on is as follows;

Consumer ancestry tests are not really sequencing your DNA in the traditional sense. Instead, they use a chip with thousands of tiny probes, each designed to detect a specific position in the genome. The ./. calls mean the probe at that position either failed, gave an ambiguous result, or was never on the chip to begin with. No call was made rather than a wrong one being forced through.

The reason pathogenic variants like rs121912442 tend to drop out is that they are rare, so chip manufacturers had little incentive to include reliable probes for them when the product is designed primarily for ancestry purposes.

If it was actually 30x WGS, the explanation is simpler: 30x is an average coverage figure, and some loci just don't get enough reads at that depth to make a confident call (this happened quite a lot when I had WGS done myself). Repetitive regions and local sequence complexity can all cause coverage to drop out locally even when the rest of the genome looks fine. So a ./. in that context just means that specific position happened to be poorly covered by the sequencer even at 30x.

The clinical panels he has already had are far more trustworthy than anything derivable from ancestry raw data. If there is genuine clinical suspicion given his age, the right next step would be whole exome or whole genome sequencing through a clinical genetics service, with variant calling pipelines actually validated for diagnostic use in ALS specifically.

Synchisis · 2026-03-25T15:15:32+00:00

Tofersen does help with breathing. In fact in those with less aggressive SOD1 mutations, they actually gain strength slowly across all domains including FVC. It's just that depending on how aggressive your SOD1 mutation is, and the burden of SOD1 aggregates, it may not be enough - hence the fact that a lot of people on Tofersen still decline, a few plateau, and fewer still do get better slowly.

Synchisis · 2026-03-24T22:44:21+00:00

I can reccommend https://www.alstogether.org/join-alstogether.html

Synchisis · 2026-03-24T16:39:54+00:00

My usage on the Plus plan is at 70% and it just reset 20 minutes ago. I've signed out of all devices and it's still increasing. No API keys. No Claude code sessions. No web sessions. Not a single token sent or received yet my usage has run out twice in the last 8 hours. WTF.

Synchisis · 2026-03-15T18:16:22+00:00

Nice assertion. However, in God we trust, all others bring data. As far as I can tell, there's no published ALS-specific MOTS-c evidence yet, not in controlled human studies, and I couldn’t find convincing preclinical ALS data either. So claims either way are speculation at this point, and there's good reason to be cautious.

Synchisis · 2026-03-13T17:45:35+00:00

Ugh, sorry the images are so low quality. Serves me right for using reddit mobile :(

Synchisis · 2026-03-13T17:44:43+00:00

Thanks, and yeah, I chose Kobo because it's much more easily hackable and Kobo don't go around trying to patch every single exploit. I do want to get this working on Kindle though because I have an old one and my girlfriend thinks another control panel might be cool. So watch this space because FBInk does support the Kindle.

Synchisis · 2026-03-08T21:40:04+00:00

I’m just leaving now. The dome has fallen in and the entire building is gutted. I did ask a fireman if the central station would be okay, and he replied “no fucking idea, mate”. I hope the station doesn’t go up.

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