Misalignment — shift work, jet lag, and the dysregulated setpoint

Circadian disease is a phase gap, not a stopped clock. A shift takes up to 12 cycles to close (PRC-bounded ~1 h/day), and during misalignment the gated cortisol rhythm's alignment to external demand falls monotonically (1.227923 → 0 → -1.364039): a well-formed rhythm at the wrong phase. One mechanism covers sleep-wake disorders, shift-work cardiometabolic disease, and IARC-2A night-shift cancer.

The disease axis is decoupling of the internal clock from external time. Re-entrainment is slow because the PRC bounds it, and the gated setpoint is dysregulated because it keeps a clean rhythm at the wrong external phase. The same mechanism underlies circadian sleep-wake disorders, shift-work cardiometabolic risk, and — through the shared Kramers oncology kernel — the IARC class 2A night-shift cancer association as a rate multiplier. The degradation sign is verified; absolute incidence stays open; rare monogenic forms belong to disease_wp.

The disease is a phase gap, not a broken clock

Circadian disease is not a stopped clock. The clock runs fine; it runs at the wrong phase relative to the external demand schedule. Impose a phase shift — the jet-lag / shift-work perturbation — and two things follow. First, re-entrainment takes time: because the PRC bounds re-alignment to ~1 hour per day, closing a gap of 2, 6, 12 hours takes that many cycles. A big shift is days of misalignment.

Cortisol peaks at the wrong external time

Second, during misalignment the gated setpoint is dysregulated. Project the gated cortisol rhythm onto the external demand schedule: aligned, it peaks with demand (healthy); misaligned, the peak slides off. The signed alignment falls monotonically as the phase gap grows — from 1.227923 (aligned, cortisol with demand) through 0 (orthogonal) to -1.364039 (antiphase, cortisol against demand, the worst case). The defended setpoint now fires at the wrong external time. That is the disease state: not an absent rhythm, but a well-formed rhythm at the wrong phase.

Three named diseases, one mechanism

This single mechanism underlies the package's major (non-rare) diseases. Circadian rhythm sleep-wake disorders (delayed/advanced phase, non-24h, shift-work disorder, jet lag) are the phenotype directly. Shift-work metabolic and cardiovascular disease is the chronic flattening of the gated metabolic and pressure setpoints. Night-shift cancer risk (IARC Group 2A) enters through the same oncology kernel the mechanical packages use: losing clock gating shrinks the effective barrier holding cellular setpoints and raises the Kramers crossing rate — circadian disruption is a rate multiplier, not a separate carcinogen. Rare and monogenic clock disorders (e.g. familial advanced sleep phase) are owned by disease_wp and enter here only as a cited parameter. The degradation sign is [V]; the shift-work relative risk is cited [L]; absolute incidence is [O].