/* CJC-1295 Online — Estilo Suico Cientifico (Swiss-scientific journal-supplement)
   Cool near-white ground, single neo-grotesque (Inter), JetBrains Mono for data tokens,
   cobalt #0047AB as single functional accent, hairline-only rules, systematic-repetition
   eyebrow primitive. */

:root {
  --primary: #0A0E1A;
  --primary-pure: #000000;
  --primary-50: #EEF0F4;
  --primary-900: #04060D;
  --secondary: #0047AB;
  --secondary-50: #E5EDF7;
  --secondary-100: #CCDAEF;
  --secondary-700: #003480;
  --secondary-900: #001F4F;
  --accent: #0047AB;
  --signal-verified: #1F6B4A;
  --signal-caution: #8B5A1A;
  --signal-danger: #8B0A0A;
  --neutral-50: #FAFBFC;
  --neutral-100: #F2F3F5;
  --neutral-200: #EFEFEF;
  --neutral-300: #DCDDE0;
  --neutral-400: #B5B7BC;
  --neutral-500: #6E7079;
  --neutral-700: #3F4148;
  --neutral-900: #0A0E1A;
  --bg: #FAFBFC;
  --surface: #FFFFFF;
  --surface-alt: #EFEFEF;
  --surface-callout: #F2F3F5;
  --text: #0A0E1A;
  --text-muted: #3F4148;
  --text-subtle: #6E7079;
  --rule-primary: #0A0E1A;
  --rule-secondary: #0047AB;
  --rule-hair: #DCDDE0;
  --rule-thin: #B5B7BC;
  --link: #0047AB;
  --link-hover: #003480;
  --focus-outline: #0047AB;
  --max-width: 74rem;
  --container-px: clamp(1rem, 3vw, 2.25rem);
  --font-display: 'Inter', 'Akzidenz-Grotesk', 'Helvetica Neue', Helvetica, Arial, sans-serif;
  --font-body: 'Inter', system-ui, -apple-system, 'Helvetica Neue', Helvetica, Arial, sans-serif;
  --font-mono: 'JetBrains Mono', 'IBM Plex Mono', ui-monospace, SFMono-Regular, 'SF Mono', Menlo, monospace;
}

/* Reset */
*, *::before, *::after { box-sizing: border-box; }
html { -webkit-text-size-adjust: 100%; }
body {
  margin: 0;
  font-family: var(--font-body);
  font-size: 1.0625rem;
  line-height: 1.62;
  color: var(--text);
  background: var(--bg);
  -webkit-font-smoothing: antialiased;
  -moz-osx-font-smoothing: grayscale;
}
img { max-width: 100%; height: auto; display: block; }
button { font: inherit; }
a { color: var(--link); text-decoration: underline; text-decoration-thickness: 1px; text-underline-offset: 3px; transition: color 180ms ease-out, text-decoration-thickness 180ms ease-out; }
a:hover { color: var(--link-hover); text-decoration-thickness: 1.5px; }
a:focus-visible { outline: 2.5px solid var(--focus-outline); outline-offset: 3px; }

/* Typography */
h1, h2, h3, h4 { font-family: var(--font-display); margin: 0; line-height: 1.12; }
h1 { font-size: clamp(2.25rem, 4.6vw, 3.5rem); font-weight: 700; letter-spacing: -0.022em; line-height: 1.08; }
h2 { font-size: clamp(1.625rem, 3.2vw, 2.25rem); font-weight: 600; letter-spacing: -0.015em; }
h3 { font-size: 1.25rem; font-weight: 500; letter-spacing: -0.005em; }
h4 { font-size: 1.0625rem; font-weight: 500; }
p { margin: 0 0 1.2em; }
ul, ol { margin: 0 0 1.2em; padding-left: 1.5em; }
li { margin-bottom: 0.4em; }
strong { font-weight: 700; }
sup { font-size: 0.75em; line-height: 0; vertical-align: super; }

.container { max-width: var(--max-width); margin: 0 auto; padding-left: var(--container-px); padding-right: var(--container-px); }

/* Eyebrow — systematic-repetition primitive */
.eyebrow {
  font-family: var(--font-mono);
  font-weight: 500;
  font-size: 0.75rem;
  letter-spacing: 0.18em;
  text-transform: uppercase;
  color: var(--accent);
  margin: 0 0 0.75rem;
}
.eyebrow-rule {
  display: block;
  width: 64px;
  height: 1px;
  background: var(--accent);
  margin: 0 0 1rem;
}

/* Mono utility */
.mono { font-family: var(--font-mono); font-weight: 500; }
code, .code-token {
  font-family: var(--font-mono);
  font-weight: 400;
  font-size: 0.9375rem;
  background: var(--neutral-100);
  border-radius: 2px;
  padding: 0.125rem 0.4rem;
}

/* Header / masthead */
.site-header {
  background: var(--bg);
  border-bottom: 1px solid var(--rule-primary);
}
.site-header .container {
  display: flex;
  flex-direction: column;
  gap: 0.5rem;
  padding-top: 1.25rem;
  padding-bottom: 1.25rem;
}
.masthead-top {
  display: flex;
  align-items: baseline;
  justify-content: space-between;
  gap: 1.5rem;
  flex-wrap: wrap;
}
.brand-lockup {
  display: inline-flex;
  align-items: baseline;
  gap: 0.4rem;
  text-decoration: none;
  color: var(--text);
}
.brand-lockup:hover { color: var(--text); }
.brand-name {
  font-family: var(--font-display);
  font-weight: 700;
  font-size: 1.25rem;
  letter-spacing: -0.02em;
}
.brand-modifier {
  font-family: var(--font-mono);
  font-size: 0.8125rem;
  color: var(--accent);
  font-weight: 500;
}
.edition-lockup {
  font-family: var(--font-mono);
  font-weight: 500;
  font-size: 0.6875rem;
  letter-spacing: 0.18em;
  text-transform: uppercase;
  color: var(--text-subtle);
  margin: 0;
}
.site-nav ul {
  list-style: none;
  padding: 0;
  margin: 0;
  display: flex;
  flex-wrap: wrap;
  gap: 1.5rem;
}
.site-nav a {
  font-family: var(--font-display);
  font-weight: 500;
  font-size: 0.9375rem;
  color: var(--text);
  text-decoration: none;
  padding-bottom: 4px;
  border-bottom: 1.5px solid transparent;
  transition: border-color 180ms ease-out, color 180ms ease-out;
}
.site-nav a:hover,
.site-nav a[aria-current="page"] { border-bottom-color: var(--accent); color: var(--text); }

/* Skip link */
.skip-link {
  position: absolute;
  left: -9999px;
  top: auto;
}
.skip-link:focus { left: 1rem; top: 1rem; background: var(--surface); padding: 0.5rem 1rem; border: 1.5px solid var(--accent); }

/* Hero */
.hero {
  padding-top: clamp(2.5rem, 6vw, 4rem);
  padding-bottom: clamp(2rem, 5vw, 3rem);
}
.hero-headline { max-width: 52ch; }
.hero-lede {
  max-width: 60ch;
  font-size: 1.1875rem;
  color: var(--text-muted);
  margin: 1.25rem 0 1.75rem;
}
.cta-row {
  display: flex;
  flex-wrap: wrap;
  gap: 0.75rem;
  margin: 1.5rem 0 0;
}

/* Data lockup */
.data-lockup {
  display: grid;
  grid-template-columns: repeat(1, minmax(0, 1fr));
  gap: 0;
  margin-top: 2rem;
  border-top: 1px solid var(--rule-hair);
  border-bottom: 1px solid var(--rule-hair);
}
.data-cell {
  padding: 1rem 1.25rem;
  border-bottom: 1px solid var(--rule-hair);
}
.data-cell:last-child { border-bottom: none; }
.data-cell-label {
  display: block;
  font-family: var(--font-display);
  font-weight: 500;
  font-size: 0.6875rem;
  letter-spacing: 0.18em;
  text-transform: uppercase;
  color: var(--text-subtle);
  margin-bottom: 0.35rem;
}
.data-cell-value {
  font-family: var(--font-mono);
  font-weight: 500;
  font-size: 1.0625rem;
  color: var(--text);
}
@media (min-width: 720px) {
  .data-lockup { grid-template-columns: repeat(4, minmax(0, 1fr)); border-bottom: 1px solid var(--rule-hair); }
  .data-cell { border-bottom: none; border-right: 1px solid var(--rule-hair); }
  .data-cell:last-child { border-right: none; }
}

/* Buttons */
.btn {
  display: inline-block;
  font-family: var(--font-display);
  font-weight: 500;
  font-size: 0.9375rem;
  letter-spacing: 0.02em;
  padding: 0.75rem 1.5rem;
  border-radius: 2px;
  text-decoration: none;
  border: 1px solid transparent;
  transition: background-color 180ms ease-out, color 180ms ease-out, border-color 180ms ease-out;
  cursor: pointer;
}
.btn-primary { background: var(--accent); color: #FFFFFF; border-color: var(--accent); }
.btn-primary:hover { background: var(--secondary-700); color: #FFFFFF; border-color: var(--secondary-700); text-decoration: none; }
.btn-primary:focus-visible { outline: 2px solid var(--accent); outline-offset: 5px; box-shadow: 0 0 0 5px #FFFFFF inset; }
.btn-secondary { background: transparent; color: var(--text); border-color: var(--text); }
.btn-secondary:hover { color: var(--accent); border-color: var(--accent); text-decoration: none; }

/* Sections */
main { display: block; }
.page-section {
  padding-top: clamp(2rem, 4vw, 3rem);
  padding-bottom: clamp(2rem, 4vw, 3rem);
  border-top: 1px solid var(--rule-hair);
}
.page-section:first-of-type { border-top: none; }
.page-section h2 { margin-bottom: 1.25rem; }
.page-section h3 { margin: 1.75rem 0 0.6rem; }

/* Figure */
.fig {
  margin: 1.75rem 0;
  border: 1px solid var(--rule-hair);
  border-radius: 2px;
  background: var(--surface);
}
.fig img { width: 100%; height: auto; display: block; border-radius: 2px 2px 0 0; }
.fig figcaption {
  border-top: 1px solid var(--rule-primary);
  padding: 0.85rem 1rem 1rem;
}
.fig-label {
  font-family: var(--font-mono);
  font-weight: 500;
  font-size: 0.75rem;
  letter-spacing: 0.16em;
  text-transform: uppercase;
  color: var(--text);
  margin: 0 0 0.35rem;
}
.fig-caption {
  font-family: var(--font-body);
  font-style: italic;
  font-size: 0.875rem;
  color: var(--text-muted);
  margin: 0;
}

/* Callout */
.callout {
  background: var(--surface-callout);
  border-left: 3px solid var(--accent);
  padding: 1rem 1.25rem 1rem 1.5rem;
  margin: 1.5rem 0;
  border-radius: 0 2px 2px 0;
}
.callout-eyebrow {
  font-family: var(--font-mono);
  font-weight: 500;
  font-size: 0.6875rem;
  letter-spacing: 0.18em;
  text-transform: uppercase;
  color: var(--accent);
  margin: 0 0 0.5rem;
}
.callout-verified { border-left-color: var(--signal-verified); }
.callout-verified .callout-eyebrow { color: var(--signal-verified); }
.callout-caution { border-left-color: var(--signal-caution); }
.callout-caution .callout-eyebrow { color: var(--signal-caution); }
.callout p:last-child { margin-bottom: 0; }

/* Pharmacokinetic compare block */
.pk-compare {
  display: grid;
  grid-template-columns: 1fr;
  gap: 0;
  margin: 2rem 0;
  border: 1px solid var(--rule-hair);
  border-radius: 2px;
}
.pk-card { padding: 1.5rem 1.5rem; background: var(--surface); }
.pk-card + .pk-card { border-top: 1px solid var(--accent); }
.pk-eyebrow {
  font-family: var(--font-mono);
  font-weight: 500;
  font-size: 0.6875rem;
  letter-spacing: 0.18em;
  text-transform: uppercase;
  margin: 0 0 0.5rem;
}
.pk-card.variant-a .pk-eyebrow { color: var(--accent); }
.pk-card.variant-b .pk-eyebrow { color: var(--secondary-700); }
.pk-card h3 { margin: 0 0 0.75rem; }
.pk-rows { margin: 0.5rem 0 1rem; padding: 0; list-style: none; }
.pk-rows li {
  display: grid;
  grid-template-columns: 9rem 1fr;
  gap: 0.75rem;
  padding: 0.4rem 0;
  border-bottom: 1px solid var(--rule-hair);
  font-size: 0.9375rem;
}
.pk-rows li:last-child { border-bottom: none; }
.pk-rows .pk-key {
  font-family: var(--font-display);
  font-weight: 500;
  font-size: 0.6875rem;
  letter-spacing: 0.16em;
  text-transform: uppercase;
  color: var(--text-subtle);
}
.pk-rows .pk-val { font-family: var(--font-mono); font-weight: 500; color: var(--text); }
@media (min-width: 820px) {
  .pk-compare { grid-template-columns: 1fr 1fr; }
  .pk-card + .pk-card { border-top: none; border-left: 1px solid var(--accent); }
}

/* Half-life chip */
.hl-chip {
  display: inline-block;
  font-family: var(--font-mono);
  font-weight: 500;
  font-size: 0.8125rem;
  padding: 0.125rem 0.5rem;
  border: 1px solid var(--accent);
  border-radius: 2px;
  color: var(--text);
  white-space: nowrap;
}

/* Inline citation marker */
.cite {
  font-family: var(--font-mono);
  font-weight: 500;
  font-size: 0.6875rem;
  color: var(--accent);
  text-decoration: none;
  vertical-align: super;
  line-height: 0;
  margin: 0 0.05em;
}
.cite:hover { color: var(--secondary-700); text-decoration: none; }

/* Tables */
table {
  width: 100%;
  border-collapse: collapse;
  border-top: 2px solid var(--rule-primary);
  border-bottom: 1px solid var(--rule-hair);
  margin: 1.5rem 0;
  font-size: 0.9375rem;
}
thead th {
  font-family: var(--font-display);
  font-weight: 500;
  font-size: 0.75rem;
  letter-spacing: 0.16em;
  text-transform: uppercase;
  text-align: left;
  padding: 0.75rem 1rem;
  border-bottom: 1px solid var(--accent);
  background: transparent;
}
tbody td {
  padding: 0.75rem 1rem;
  border-bottom: 1px solid var(--rule-hair);
  vertical-align: top;
}
tbody td.num, tbody td.id { font-family: var(--font-mono); }
tbody td.num { text-align: right; }

/* References list */
.references-list {
  list-style: none;
  padding: 0;
  margin: 0 0 2rem;
  counter-reset: ref;
  border-top: 2px solid var(--rule-primary);
}
.references-list li {
  counter-increment: ref;
  padding: 1rem 0 1rem 3rem;
  border-bottom: 1px solid var(--rule-hair);
  position: relative;
  font-size: 0.9375rem;
}
.references-list li::before {
  content: "[" counter(ref) "]";
  position: absolute;
  left: 0;
  top: 1rem;
  font-family: var(--font-mono);
  font-weight: 500;
  font-size: 0.8125rem;
  color: var(--accent);
}
.references-list .ref-meta {
  display: block;
  margin-top: 0.4rem;
  font-family: var(--font-mono);
  font-size: 0.8125rem;
  color: var(--text-subtle);
}
.references-list .ref-meta a { font-family: var(--font-mono); }

/* DataTables overrides — keep journal-supplement register */
table.dataTable thead th { background: transparent !important; border-bottom: 1px solid var(--accent) !important; }
table.dataTable tbody tr { background: transparent !important; }
table.dataTable tbody tr:hover > * { background: var(--neutral-100) !important; }
.dataTables_wrapper .dataTables_filter input,
.dataTables_wrapper .dt-search input {
  border: 1px solid var(--rule-hair);
  border-radius: 2px;
  padding: 0.4rem 0.65rem;
  font-family: var(--font-body);
  font-size: 0.9375rem;
  margin-left: 0.5rem;
}
.dataTables_wrapper .dataTables_length select,
.dataTables_wrapper .dt-length select {
  border: 1px solid var(--rule-hair);
  border-radius: 2px;
  padding: 0.3rem 0.5rem;
  font-family: var(--font-body);
}
.dataTables_wrapper .dataTables_info,
.dataTables_wrapper .dt-info { font-size: 0.8125rem; color: var(--text-subtle); padding-top: 1rem; }
.dataTables_wrapper .dataTables_paginate .paginate_button,
.dataTables_wrapper .dt-paging .dt-paging-button {
  font-family: var(--font-mono);
  font-size: 0.8125rem;
  padding: 0.25rem 0.65rem;
  border: 1px solid transparent;
  border-radius: 2px;
}
.dataTables_wrapper .dataTables_paginate .paginate_button.current,
.dataTables_wrapper .dt-paging .dt-paging-button.current { border-color: var(--accent) !important; color: var(--accent) !important; background: transparent !important; }

/* FAQ */
.faq-entry {
  padding: 1.25rem 0;
  border-bottom: 1px solid var(--rule-hair);
}
.faq-entry h3 { margin: 0 0 0.5rem; }
.faq-entry p { margin-bottom: 0.5rem; }

/* Side effect grid */
.fx-grid {
  list-style: none;
  padding: 0;
  margin: 1.5rem 0;
  display: grid;
  grid-template-columns: 1fr;
  gap: 1rem;
}
@media (min-width: 640px) { .fx-grid { grid-template-columns: 1fr 1fr; } }
@media (min-width: 960px) { .fx-grid { grid-template-columns: 1fr 1fr 1fr 1fr; } }
.fx-grid li {
  border: 1px solid var(--rule-hair);
  border-radius: 2px;
  padding: 1rem 1.1rem;
  background: var(--surface);
}
.fx-grid .fx-label {
  display: block;
  font-family: var(--font-mono);
  font-weight: 500;
  font-size: 0.6875rem;
  letter-spacing: 0.16em;
  text-transform: uppercase;
  color: var(--accent);
  margin-bottom: 0.35rem;
}
.fx-grid p { margin: 0; font-size: 0.9375rem; color: var(--text-muted); }

/* Contact form */
.contact-form {
  display: grid;
  gap: 1rem;
  max-width: 36rem;
  margin: 1.5rem 0;
}
.contact-form label {
  font-family: var(--font-display);
  font-weight: 500;
  font-size: 0.75rem;
  letter-spacing: 0.16em;
  text-transform: uppercase;
  color: var(--text);
  display: block;
  margin-bottom: 0.4rem;
}
.contact-form input,
.contact-form select,
.contact-form textarea {
  width: 100%;
  border: 1px solid var(--rule-hair);
  border-radius: 2px;
  padding: 0.65rem 0.75rem;
  font-family: var(--font-body);
  font-size: 0.9375rem;
  background: var(--surface);
  color: var(--text);
}
.contact-form textarea { min-height: 7rem; resize: vertical; }
.contact-form input:focus,
.contact-form select:focus,
.contact-form textarea:focus { outline: 2px solid var(--accent); outline-offset: 2px; border-color: var(--accent); }

/* Footer */
.site-footer {
  background: var(--bg);
  border-top: 1px solid var(--rule-primary);
  margin-top: clamp(3rem, 6vw, 5rem);
}
.site-footer .container {
  padding-top: 2.5rem;
  padding-bottom: 1.5rem;
}
.footer-grid {
  display: grid;
  grid-template-columns: 1fr;
  gap: 1.75rem;
  margin-bottom: 1.75rem;
}
@media (min-width: 760px) { .footer-grid { grid-template-columns: 1.4fr 1fr 1fr 1.1fr; } }
.footer-col h4 {
  font-family: var(--font-mono);
  font-weight: 500;
  font-size: 0.6875rem;
  letter-spacing: 0.18em;
  text-transform: uppercase;
  color: var(--text-subtle);
  margin: 0 0 0.75rem;
}
.footer-col ul { list-style: none; padding: 0; margin: 0; }
.footer-col li { margin-bottom: 0.45rem; font-size: 0.9375rem; }
.footer-col a { color: var(--text); text-decoration: none; border-bottom: 1px solid transparent; transition: border-color 180ms ease-out; }
.footer-col a:hover { border-bottom-color: var(--accent); color: var(--text); }
.footer-disclaimer {
  font-family: var(--font-body);
  font-style: italic;
  color: var(--text-muted);
  font-size: 0.9375rem;
  margin: 0.5rem 0 0;
  max-width: 32ch;
}
.footer-brand {
  font-family: var(--font-display);
  font-weight: 700;
  font-size: 1.0625rem;
  letter-spacing: -0.02em;
}
.footer-brand .brand-modifier { font-size: 0.8125rem; }
.footer-bottom {
  padding-top: 1.25rem;
  border-top: 1px solid var(--rule-hair);
  display: flex;
  flex-direction: column;
  gap: 0.5rem;
}
.footer-copyright {
  font-size: 0.8125rem;
  color: var(--text-subtle);
  margin: 0;
}
.footer-colophon {
  font-family: var(--font-mono);
  font-weight: 400;
  font-size: 0.6875rem;
  letter-spacing: 0.14em;
  text-transform: uppercase;
  color: var(--text-subtle);
  margin: 0;
}
.pk-quick li {
  display: flex;
  justify-content: space-between;
  gap: 0.5rem;
  font-family: var(--font-mono);
  font-size: 0.8125rem;
  padding: 0.25rem 0;
  border-bottom: 1px solid var(--rule-hair);
}
.pk-quick li:last-child { border-bottom: none; }
.pk-quick li a { font-family: var(--font-body); font-size: 0.875rem; }

/* 404 */
.not-found {
  padding-top: 4rem;
  padding-bottom: 4rem;
  text-align: left;
  max-width: 52ch;
}
.not-found .eyebrow { color: var(--signal-danger); }
.not-found .eyebrow-rule { background: var(--signal-danger); }

/* Tippy theme tweak */
.tippy-box[data-theme~='cjc-online'] {
  background: var(--surface);
  color: var(--text);
  border: 1px solid var(--rule-hair);
  border-left: 3px solid var(--accent);
  border-radius: 2px;
  font-family: var(--font-body);
  font-size: 0.875rem;
  line-height: 1.5;
  box-shadow: 0 1px 3px rgba(10,14,26,0.08);
  max-width: 380px !important;
  padding: 0;
}
.tippy-box[data-theme~='cjc-online'] .tippy-content { padding: 0.65rem 0.85rem; }
.tippy-box[data-theme~='cjc-online'] .tip-eyebrow {
  display: block;
  font-family: var(--font-mono);
  font-weight: 500;
  font-size: 0.625rem;
  letter-spacing: 0.18em;
  text-transform: uppercase;
  color: var(--accent);
  margin-bottom: 0.35rem;
}
.tippy-box[data-theme~='cjc-online'] .tip-citation { color: var(--text); display: block; margin-bottom: 0.35rem; }
.tippy-box[data-theme~='cjc-online'] .tip-meta { font-family: var(--font-mono); font-size: 0.75rem; color: var(--text-subtle); }
.tippy-box[data-theme~='cjc-online'] .tip-meta a { color: var(--accent); }

/* Reduced motion */
@media (prefers-reduced-motion: reduce) {
  *, *::before, *::after { transition-duration: 0ms !important; animation-duration: 0ms !important; }
}

/* Responsive */
@media (min-width: 1024px) {
  .site-header .container { flex-direction: row; align-items: center; justify-content: space-between; gap: 2rem; }
  .site-header .masthead-col { display: flex; flex-direction: column; gap: 0.25rem; }
}