Human Model · HM(t) at day 146
| Dimension | b_t | dS/dt | autocorr | recovery | observation model |
|---|---|---|---|---|---|
| Therapy response | 37 ± 7.8 | +0.36/d | 0.69 | 2 d | Imaging + tumour markers, interpolated · proxy · last read ≤ 14 d |
| Gastrointestinal function | 26 ± 8 | +1.03/d | 0.89 | — | Daily GI check-in · direct · today |
| Treatment toxicity | 14 ± 8.2 | +0.17/d | 0.39 | 14 d | Labs, interpolated between draws · proxy · last draw ≤ 7 d |
| Inflammatory activity | 22 ± 12.7 | +0.49/d | 0.31 | 2 d | CRP/ferritin + immune signature · inferred · weeks |
| Immune / metabolic | 48 ± 11 | +0.24/d | 0.2 | 3 d | Metabolic panel + wearable · inferred · weeks |
| Nutritional sufficiency | 61 ± 9.6 | -0.56/d | 0.69 | 1 d | Weight, albumin, food log · proxy · days |
| Adherence | 87 ± 5 | -0.28/d | 0.77 | 9 d | Dose + to-do completion · direct · today |
| Function / quality of life | 53 ± 5.3 | -0.22/d | 0.45 | 5 d | PRO items · direct · today |
High autocorrelation and slow recovery are early-warning signatures of a critical transition (Scheffer et al.), independent of the level.
- day 0baselineBaseline S10: NR phenotype; Poor metabolizer; butyrate 26
- day 3perturbationDaily walks resumed (3.3)
- day 41divergenceTrajectory diverged from the population model
- day 41noteTrajectory diverged from prediction
- day 65perturbationDietary drift (-2.6)
- day 93perturbationLow-HRV stretch (-2.7)
- day 111perturbationAlcohol on dosing days (-1.8)
Now: between basins, heading towards restoration.
Bile-acid diarrhoea on a low-butyrate ecology: reduced SCFA production leaves bile acids unconjugated after fat-rich meals; GI burden tracks fat intake with a one-day lag.
- Butyrate capacity 26/100
- Fat load → GI +4.2 next day
- —
- Faecal bile acids
- 7α-hydroxy-4-cholesten-3-one (C4)
- Rechallenge: 3 high-fat days under observation
Drug-exposure toxicity: pharmacokinetic over-exposure drives GI and systemic toxicity together; dietary and microbial factors are secondary.
- Poor metabolizer: exposure above modelled range
- GI autocorrelation 0.89 (slow recovery)
- Toxicity within range
- Trough drug level
- Dose-timing rechallenge (evening vs morning)
Behavioural spiral: symptomatic days cut adherence and sleep, which raise GI and stress, which cut adherence further; the biology is a follower, not the driver.
- Sleep quality worsening
- Adherence intact
- Dose-taking timestamps vs symptom timestamps
- Sleep-window rechallenge
Mucosal barrier loss: drug-induced epithelial injury amplified by a FUT2-dependent glycan deficit; histamine and inflammatory load add on top.
- DeepGene: Escherichia coli above range (LPS / zonulin)
- No FUT2 variant
- No histamine signal in the log
- Faecal calprotectin (would separate barrier from motility)
- Serum DAO / histamine
- Zonulin
No action started yet.
| Class | Action | Health | Info | Conf. | Risk | Burden | Cost | Utility |
|---|---|---|---|---|---|---|---|---|
| Observe | Continue passive collection, no perturbation A clean transition can be observed only without a new perturbation. | 0 | 0.15 | 0.05 | 0 | 0.05 | 0 | 0.03 |
| Measure | Faecal bile acids Discriminates T2 from its competitors (E?). | 0 | 0.45 | 0.2 | 0.02 | 0.25 | 0.2 | 0.01 |
| Maintain | Hold current regimen and content Protects nothing while the state deteriorates. | 0.05 | 0.05 | 0.05 | 0.05 | 0.05 | 0 | 0 |
| Test | 7α-hydroxy-4-cholesten-3-one (C4) Discriminates T2 from its competitors (E?). | 0 | 0.45 | 0.2 | 0.02 | 0.25 | 0.5 | -0.05 |
- DT-01 Not indicated for the current state.
- GI-04 Not indicated for the current state.
- HY-01 Not indicated for the current state.
- BR-03 Not indicated for the current state.
- AD-05 Not indicated for the current state.
- ME-01 Not indicated for the current state.
- NP-02 Not indicated for the current state.
- CR-01 Not indicated for the current state.
- SC-12 Not indicated for the current state.
- Biological identity Poor metabolizer; IL6, CYP2D6, MTHFRGermline panel, baseline0.86 (0.95·0.9·1)
- High-authority clinical Toxicity 14, response 37Labs / imaging, ≤ 14 d0.77 (0.9·1·0.85)
- Intervention response 0 within-patient responses recordedΔS after each action, accumulating0.68 (0.75·1·0.9)
- Deep biological state DeepGene retest day 90: damage 37/100, Shannon 2.77, butyrate 648 CPM, 2 opportunists above, 2 keystone absentSynthetic DeepGene metagenomics + host DNA, sample 969572-R (compositional proxy)0.43 (0.7·1·0.62)
- Dynamic state GI 26, sleep 5.6 h, HRV 40Companion + wearable, today0.18 (0.6·1·0.3)
- Exposure context Keep meals regular; three to four moderate portions spaced through the day; dosing per protocol; adherence 87%Food log + dose log, event-level0.1 (0.55·0.9·0.2)
P-03376 is on day 146 of ONX-7 (NR, baseline S10): response unstable, tolerance deteriorating, GI deteriorating. Over 14 days response moved +9 and GI +6; discontinuation risk is 25%. The state is between basins, heading towards restoration, after diverging from the model on day 41.
Biology sets the gain: IL6 high-expression variant, Poor metabolizer, Low butyrate capacity; butyrate capacity 26/100, diversity 3.0. Pushing it down: Escherichia coli 14.421% (LPS load) (-38.2), Low butyrate capacity (-34.1), Poor metabolizer (-24.8). Pulling it up: Protein (supports) (+22.6). From the daily log: protein -4.8 GI next day, fat +4.2 GI next day, caffeine +3.8 GI next day.
No action has been tried yet.
No action is indicated now; the trajectory is stable relative to similar patients.