Human Model · HM(t) at day 90
| Dimension | b_t | dS/dt | autocorr | recovery | observation model |
|---|---|---|---|---|---|
| Therapy response | 41 ± 10.1 | -0.64/d | 0.7 | 4 d | Imaging + tumour markers, interpolated · proxy · last read ≤ 14 d |
| Gastrointestinal function | 61 ± 7 | +0.12/d | 0.63 | 1 d | Daily GI check-in · direct · today |
| Treatment toxicity | 41 ± 7 | -0.01/d | -0.17 | 2 d | Labs, interpolated between draws · proxy · last draw ≤ 7 d |
| Inflammatory activity | 56 ± 12.6 | +0.15/d | 0.25 | 10 d | CRP/ferritin + immune signature · inferred · weeks |
| Immune / metabolic | 48 ± 11.4 | -0.42/d | 0.06 | 1 d | Metabolic panel + wearable · inferred · weeks |
| Nutritional sufficiency | 36 ± 8.6 | +0.22/d | 0.27 | 1 d | Weight, albumin, food log · proxy · days |
| Adherence | 57 ± 6.9 | -0.73/d | 0.85 | — | Dose + to-do completion · direct · today |
| Function / quality of life | 36 ± 6.7 | -0.5/d | 0.41 | 1 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 S14: EC-03 phenotype; Poor metabolizer; butyrate 28
- day 14perturbationDaily walks resumed (3.3)
- day 18perturbationDietary drift (-2.6)
- day 31recommendedNP-02 recommended
- day 32acceptedPatient accepted
- day 42responseGI symptom burden −15% vs expected
- day 48divergenceTrajectory diverged from the population model
- day 48noteTrajectory diverged from prediction
- day 48state changeTolerance state changed
- day 53recommendedGI-04 recommended
- day 54acceptedPatient accepted
- day 62responseGI symptom burden −22% vs expected
- day 68state changeTolerance state changed
Now: in the failing basin, heading towards failing.
Mucosal barrier loss: drug-induced epithelial injury amplified by a FUT2-dependent glycan deficit; histamine and inflammatory load add on top.
- FUT2 non-secretor genotype (barrier glycan deficit)
- DeepGene: host DNA fragmentation atypical
- DeepGene: tissue recycling 60
- Histamine load → GI +5.2 next day
- Inflammatory load 56
- GI-04 (barrier-support protocol) improved GI
- —
- Faecal calprotectin (would separate barrier from motility)
- Serum DAO / histamine
- Zonulin
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 28/100
- DeepGene: 6 keystone butyrate producers absent
- DeepGene: H2S above band
- Fat load → GI +6.5 next day
- Diversity 1.9
- —
- 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 0.62 (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.
- Adherence 57%
- Sleep and stress stable
- Dose-taking timestamps vs symptom timestamps
- Sleep-window rechallenge
| Action | pred ΔGI | obs ΔGI | ε | temporality | magnitude | dechallenge | rechallenge | cross-modal | confidence |
|---|---|---|---|---|---|---|---|---|---|
| NP-02 day 32 | -2 | 34 | +36 | ✗ | ✓ | n/a | n/a | ✗ | 18% |
| GI-04 day 54 | -16 | 1 | +17 | ✗ | ✗ | n/a | n/a | ✗ | 0% |
| Class | Action | Health | Info | Conf. | Risk | Burden | Cost | Utility |
|---|---|---|---|---|---|---|---|---|
| Escalate | CR-01 Clinician Review 100% of 6 similar improved. | 0.37 | 0.2 | 0.25 | 0.02 | 0.25 | 0.15 | 0.39 |
| Measure | Faecal calprotectin (would separate barrier from motility) Discriminates T1 from its competitors (E?). | 0 | 0.75 | 0.2 | 0.02 | 0.25 | 0.2 | 0.32 |
| Test | Serum DAO / histamine Discriminates T1 from its competitors (E?). | 0 | 0.75 | 0.2 | 0.02 | 0.25 | 0.5 | 0.27 |
| Escalate | ME-01 Monitoring Escalation 100% of 66 similar improved. | 0.22 | 0.2 | 0.25 | 0.08 | 0.1 | 0.15 | 0.26 |
| Treat | SC-12 Supportive Compound 67% of 45 similar improved. | 0.35 | 0.2 | 0.25 | 0.08 | 0.25 | 0.4 | 0.26 |
| Treat | HY-01 Hydration Protocol 0% of 0 similar improved. | 0.15 | 0.2 | 0.25 | 0.08 | 0.25 | 0.15 | 0.11 |
| Treat | BR-03 Behavioural Recommendation 0% of 0 similar improved. | 0.14 | 0.2 | 0.25 | 0.08 | 0.25 | 0.15 | 0.1 |
| 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 | 0.08 |
| Treat | AD-05 Adherence Support 0% of 0 similar improved. | 0.1 | 0.2 | 0.25 | 0.08 | 0.25 | 0.15 | 0.06 |
| Maintain | Hold current regimen and content Protects nothing while the state deteriorates. | 0.05 | 0.05 | 0.05 | 0.4 | 0.05 | 0 | -0.33 |
- GI-04 Not indicated for the current state.
- NP-02 Not indicated for the current state.
- DT-01 Dose-timing change requires investigator authorization in poor metabolizers (contraindication from I).
- Biological identity Poor metabolizer; FUT2, IL6, CYP2D6Germline panel, baseline0.86 (0.95·0.9·1)
- High-authority clinical Toxicity 41, response 41Labs / imaging, ≤ 14 d0.77 (0.9·1·0.85)
- Intervention response 2 within-patient responses recordedΔS after each action, accumulating0.68 (0.75·1·0.9)
- Deep biological state DeepGene retest day 90: damage 85/100, Shannon 1.64, butyrate 282 CPM, 3 opportunists above, 6 keystone absentSynthetic DeepGene metagenomics + host DNA, sample 909862-R (compositional proxy)0.63 (0.7·1·0.9)
- Dynamic state GI 61, sleep 6.9 h, HRV 46Companion + wearable, today0.18 (0.6·1·0.3)
- Exposure context Prepare a plain, low-fat pasta or rice meal and note how it feels afterwards; dosing per protocol; adherence 57%Food log + dose log, event-level0.1 (0.55·0.9·0.2)
P-01332 is on day 90 of NBL-101 (EC-03, baseline S14): response unstable, tolerance stable, GI unstable. Over 14 days response moved -14 and GI -2; discontinuation risk is 67%. The state is in the failing basin, heading towards failing, after diverging from the model on day 48.
Biology sets the gain: FUT2 non-secretor, IL6 high-expression variant, Poor metabolizer, Low butyrate capacity, Low microbial diversity, Baseline state S14, Cluster EC-03 (high response / high intolerance), Adherence < 60%; butyrate capacity 28/100, diversity 1.9. Pushing it down: Enterococcus faecium 16.88% (LPS load) (-28.5), Low butyrate capacity (-23.3), Dietary fat load (-20.5). Pulling it up: GI Support Protocol GI-04 (+28.4), Dietary Support Protocol NP-02 (+24.5). From the daily log: fat +6.5 GI next day, simple carbs +6 GI next day, histamine +5.2 GI next day.
Past actions: NP-02 on day 32 → improved (15%); GI-04 on day 54 → improved (22%).
Next: ME-01 — 100% of 284 similar trajectories improved, 83% probability here. This would be contradicted by a further GI rise within the onset window or falling adherence.