Human Model · HM(t) at day 112
| Dimension | b_t | dS/dt | autocorr | recovery | observation model |
|---|---|---|---|---|---|
| Therapy response | 44 ± 8 | -0.27/d | 0.69 | 11 d | Imaging + tumour markers, interpolated · proxy · last read ≤ 14 d |
| Gastrointestinal function | 54 ± 7.5 | +0.53/d | 0.77 | — | Daily GI check-in · direct · today |
| Treatment toxicity | 46 ± 9.6 | +0.21/d | 0.79 | 1 d | Labs, interpolated between draws · proxy · last draw ≤ 7 d |
| Inflammatory activity | 51 ± 11.6 | +0.39/d | 0.6 | 3 d | CRP/ferritin + immune signature · inferred · weeks |
| Immune / metabolic | 50 ± 10.5 | -0.14/d | 0.04 | 1 d | Metabolic panel + wearable · inferred · weeks |
| Nutritional sufficiency | 42 ± 8.8 | -0.38/d | 0.44 | 1 d | Weight, albumin, food log · proxy · days |
| Adherence | 43 ± 5 | -0.19/d | 0.7 | — | Dose + to-do completion · direct · today |
| Function / quality of life | 31 ± 5.1 | -0.24/d | 0.3 | 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 S06: EC-03 phenotype; Normal metabolizer; butyrate 28
- day 0perturbationAlcohol on dosing days (-1.8)
- day 2perturbationDietary drift (-2.6)
- day 31recommendedNP-02 recommended
- day 32acceptedPatient accepted
- day 42responseGI symptom burden −17% vs expected
- day 48state changeTolerance state changed
- day 50recommendedGI-04 recommended
- day 51acceptedPatient accepted
- day 53divergenceTrajectory diverged from the population model
- day 53noteTrajectory diverged from prediction
- day 59responseGI symptom burden −18% vs expected
- day 60perturbationDaily walks resumed (3.3)
- day 65state changeTolerance state changed
Now: between basins, heading towards failing.
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
- Fat load → GI +4.4 next day
- Diversity 2.1
- —
- Faecal bile acids
- 7α-hydroxy-4-cholesten-3-one (C4)
- Rechallenge: 3 high-fat days under observation
Mucosal barrier loss: drug-induced epithelial injury amplified by a FUT2-dependent glycan deficit; histamine and inflammatory load add on top.
- DeepGene: Klebsiella pneumoniae above range (LPS / zonulin)
- DeepGene: host DNA fragmentation atypical
- DeepGene: tissue recycling 64
- Inflammatory load 51
- GI-04 (barrier-support protocol) improved GI
- No FUT2 variant
- No histamine signal in the log
- Faecal calprotectin (would separate barrier from motility)
- Serum DAO / histamine
- Zonulin
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 43%
- Sleep quality worsening
- —
- Dose-taking timestamps vs symptom timestamps
- Sleep-window rechallenge
Drug-exposure toxicity: pharmacokinetic over-exposure drives GI and systemic toxicity together; dietary and microbial factors are secondary.
- Toxicity 46
- GI autocorrelation 0.83 (slow recovery)
- Normal metabolizer
- Trough drug level
- Dose-timing rechallenge (evening vs morning)
| Action | pred ΔGI | obs ΔGI | ε | temporality | magnitude | dechallenge | rechallenge | cross-modal | confidence |
|---|---|---|---|---|---|---|---|---|---|
| NP-02 day 32 | -2 | 22 | +24 | ✗ | ✓ | no | n/a | ✗ | 18% |
| GI-04 day 51 | -10 | 28 | +38 | ✗ | ✓ | no | n/a | ✗ | 18% |
| Class | Action | Health | Info | Conf. | Risk | Burden | Cost | Utility |
|---|---|---|---|---|---|---|---|---|
| Escalate | CR-01 Clinician Review 100% of 4 similar improved. | 0.37 | 0.2 | 0.25 | 0.02 | 0.25 | 0.15 | 0.39 |
| Measure | Faecal bile acids Discriminates T2 from its competitors (E?). | 0 | 0.75 | 0.2 | 0.02 | 0.25 | 0.2 | 0.32 |
| Test | 7α-hydroxy-4-cholesten-3-one (C4) Discriminates T2 from its competitors (E?). | 0 | 0.75 | 0.2 | 0.02 | 0.25 | 0.5 | 0.27 |
| Escalate | ME-01 Monitoring Escalation 100% of 67 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 | DT-01 Dosing / Timing Recommendation 0% of 0 similar improved. | 0.18 | 0.2 | 0.25 | 0.08 | 0.25 | 0.15 | 0.14 |
| 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.
- Biological identity Normal metabolizer; IL6, CYP2D6Germline panel, baseline0.86 (0.95·0.9·1)
- High-authority clinical Toxicity 46, response 44Labs / 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 1.63, butyrate 323 CPM, 4 opportunists above, 6 keystone absentSynthetic DeepGene metagenomics + host DNA, sample 910829-R (compositional proxy)0.55 (0.7·1·0.79)
- Dynamic state GI 54, sleep 5.6 h, HRV 30Companion + 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 43%Food log + dose log, event-level0.1 (0.55·0.9·0.2)
P-01438 is on day 112 of NBL-101 (EC-03, baseline S06): response declining, tolerance deteriorating, GI stable. Over 14 days response moved -8 and GI -2; discontinuation risk is 60%. The state is between basins, heading towards failing, after diverging from the model on day 53.
Biology sets the gain: IL6 high-expression variant, Low butyrate capacity, Low microbial diversity, Cluster EC-03 (high response / high intolerance), Adherence < 60%; butyrate capacity 28/100, diversity 2.1. Pushing it down: Enterococcus faecium 15.941% (LPS load) (-32.6), Low butyrate capacity (-27.5), 6 keystone species absent (-20.6). Pulling it up: Dietary Support Protocol NP-02 (+32.1), GI Support Protocol GI-04 (+30.5). From the daily log: fat +4.4 GI next day, simple carbs +3.4 GI next day, spicy +3.4 GI next day.
Past actions: NP-02 on day 32 → improved (17%); GI-04 on day 51 → improved (18%).
Next: ME-01 — 100% of 284 similar trajectories improved, 71% probability here. This would be contradicted by a further GI rise within the onset window or falling adherence.