@font-face {
  font-family: "Newsreader";
  src: url("assets/fonts/newsreader-latin.woff2") format("woff2");
  font-weight: 400 600;
  font-style: normal;
  font-display: swap;
}

@font-face {
  font-family: "IBM Plex Mono";
  src: url("assets/fonts/ibm-plex-mono-400-latin.woff2") format("woff2");
  font-weight: 400;
  font-style: normal;
  font-display: swap;
}

@font-face {
  font-family: "IBM Plex Mono";
  src: url("assets/fonts/ibm-plex-mono-500-latin.woff2") format("woff2");
  font-weight: 500;
  font-style: normal;
  font-display: swap;
}

:root {
  --paper: #e9eeec;
  --sheet: #f4f7f5;
  --ink: #16201e;
  --ink-2: #3b4a46;
  --ink-3: #5b6964;
  --rule: #c3cfca;
  --rule-strong: #9fb0aa;
  --pine: #14453c;
  --pine-deep: #0f2b25;
  --pine-soft: #2c6157;
  --wash: #d7e4df;
  --oxide: #8b3f2a;
  --oxide-wash: #f0e2dc;

  --serif: "Newsreader", ui-serif, Georgia, "Times New Roman", serif;
  --mono: "IBM Plex Mono", ui-monospace, SFMono-Regular, Menlo, monospace;
}

*,
*::before,
*::after {
  box-sizing: border-box;
}

html {
  background: var(--paper);
  color: var(--ink);
}

body {
  margin: 0;
  background: var(--paper);
  font-family: var(--serif);
  font-size: 17px;
  line-height: 1.55;
  font-optical-sizing: auto;
  -webkit-font-smoothing: antialiased;
  text-rendering: optimizeLegibility;
}

h1,
h2,
h3,
p,
figure,
ul,
ol {
  margin: 0;
}

a {
  color: var(--pine);
  text-underline-offset: 3px;
  text-decoration-thickness: 1px;
}

a:hover {
  color: var(--pine-soft);
}

:focus-visible {
  outline: 2px solid var(--pine);
  outline-offset: 3px;
}

::selection {
  background: var(--wash);
}

.wrap {
  width: 100%;
  max-width: 1320px;
  margin: 0 auto;
  padding-left: 40px;
  padding-right: 40px;
}

.skip {
  position: absolute;
  top: -100px;
  left: 16px;
  z-index: 10;
  padding: 8px 12px;
  background: var(--sheet);
  color: var(--ink);
  font-family: var(--mono);
  font-size: 12px;
}

.skip:focus {
  top: 12px;
}

.visually-hidden {
  position: absolute;
  width: 1px;
  height: 1px;
  padding: 0;
  margin: -1px;
  overflow: hidden;
  clip: rect(0, 0, 0, 0);
  white-space: nowrap;
  border: 0;
}

/* Cover ------------------------------------------------------------------ */

.cover {
  background: var(--pine-deep);
  color: var(--sheet);
}

.cover-top {
  display: flex;
  align-items: baseline;
  gap: 22px;
  padding-top: 22px;
}

.wordmark {
  color: var(--sheet);
  font-size: 29px;
  font-weight: 600;
  letter-spacing: -0.035em;
  line-height: 1;
  text-decoration: none;
}

.wordmark:hover {
  color: var(--sheet);
}

.cover-meta {
  font-family: var(--mono);
  font-size: 11px;
  color: #a9c0b8;
}

.cover-link {
  margin-left: auto;
  color: var(--wash);
  font-family: var(--mono);
  font-size: 11.5px;
  text-decoration: none;
  border-bottom: 1px solid #55746a;
  padding-bottom: 2px;
}

.cover-link:hover {
  color: var(--sheet);
  border-color: var(--sheet);
}

.cover-main {
  padding-top: 62px;
}

h1 {
  max-width: 1120px;
  font-size: clamp(3.5rem, 7.4vw, 7.1rem);
  font-weight: 500;
  line-height: 0.92;
  letter-spacing: -0.045em;
  text-wrap: balance;
}

.cover-sub {
  max-width: 54ch;
  margin-top: 24px;
  color: #c2d5cf;
  font-size: 18px;
  line-height: 1.5;
}

.cover-figure {
  padding-top: 26px;
  padding-bottom: 46px;
}

.figure-scroll {
  overflow-x: auto;
  overscroll-behavior-x: contain;
}

.forest {
  display: block;
  width: 100%;
  height: auto;
}

.forest-primary-band {
  fill: var(--sheet);
  opacity: 0.06;
}

.forest-label {
  fill: var(--sheet);
  font-family: var(--serif);
  font-size: 15px;
}

.forest-label-primary {
  font-weight: 600;
}

.forest-rule {
  stroke: #35534a;
  stroke-width: 1;
}

.forest-interval {
  stroke: #a9c0b8;
  stroke-width: 1.4;
}

.forest-interval-primary {
  stroke: var(--sheet);
  stroke-width: 2.2;
}

.forest-cap {
  stroke: #a9c0b8;
  stroke-width: 1.2;
}

.forest-cap-primary {
  stroke: var(--sheet);
  stroke-width: 1.8;
}

.forest-point {
  fill: #a9c0b8;
}

.forest-point-primary {
  fill: var(--sheet);
}

.forest-value {
  fill: #a9c0b8;
  font-family: var(--mono);
  font-size: 11px;
}

.forest-value-primary {
  fill: var(--sheet);
}

.forest-axis {
  stroke: #4c6a61;
  stroke-width: 1;
}

.forest-tick line {
  stroke: #4c6a61;
  stroke-width: 1;
}

.forest-tick text {
  fill: #a9c0b8;
  font-family: var(--mono);
  font-size: 11px;
}

figcaption {
  max-width: 80ch;
  margin-top: 8px;
  color: #a9c0b8;
  font-size: 12px;
  line-height: 1.45;
}

.cover-stats {
  display: grid;
  grid-template-columns: repeat(3, minmax(0, 1fr));
  margin-top: 28px;
  padding-top: 18px;
  border-top: 1px solid #35534a;
}

.cover-stat {
  padding-right: 28px;
}

.cover-stat + .cover-stat {
  padding-left: 28px;
  border-left: 1px solid #35534a;
}

.stat {
  display: block;
  font-family: var(--mono);
  font-size: clamp(1.7rem, 3vw, 2.6rem);
  font-weight: 500;
  line-height: 1;
  letter-spacing: -0.04em;
  color: var(--sheet);
}

.stat-label {
  display: block;
  margin-top: 7px;
  color: #a9c0b8;
  font-size: 12.5px;
  line-height: 1.35;
}

/* Sections --------------------------------------------------------------- */

main {
  background: var(--paper);
}

.section {
  padding-top: 56px;
  padding-bottom: 56px;
  border-bottom: 1px solid var(--rule);
}

.method-section {
  padding-top: 48px;
}

.section-head {
  display: flex;
  align-items: baseline;
  justify-content: space-between;
  gap: 32px;
  margin-bottom: 26px;
}

h2 {
  font-size: clamp(2.1rem, 3.6vw, 3.3rem);
  font-weight: 500;
  line-height: 0.98;
  letter-spacing: -0.035em;
}

.section-note {
  flex-shrink: 0;
  max-width: 42ch;
  color: var(--ink-3);
  font-family: var(--mono);
  font-size: 11.5px;
  line-height: 1.45;
  text-align: right;
}

/* Method ----------------------------------------------------------------- */

.steps {
  display: grid;
  grid-template-columns: repeat(4, minmax(0, 1fr));
  padding: 0;
  list-style: none;
  border-top: 1px solid var(--rule-strong);
}

.steps li {
  min-height: 152px;
  padding: 14px 26px 0 0;
  border-right: 1px solid var(--rule);
}

.steps li + li {
  padding-left: 26px;
}

.steps li:last-child {
  border-right: 0;
}

.step-number {
  display: block;
  color: var(--pine);
  font-family: var(--mono);
  font-size: 11px;
  line-height: 1;
}

.steps h3 {
  margin: 9px 0 6px;
  font-size: 18px;
  font-weight: 600;
  line-height: 1.2;
  letter-spacing: -0.015em;
}

.steps p {
  max-width: 30ch;
  color: var(--ink-2);
  font-size: 14px;
  line-height: 1.45;
}

.implementation {
  margin-top: 24px;
  color: var(--ink-3);
  font-family: var(--mono);
  font-size: 11px;
}

.implementation span {
  margin: 0 8px;
  color: var(--rule-strong);
}

/* Null sweep ------------------------------------------------------------- */

.split {
  display: grid;
  grid-template-columns: minmax(0, 1fr) 280px;
  gap: 48px;
  align-items: start;
}

.table-wrap {
  overflow-x: auto;
}

.matrix,
.data-table {
  width: 100%;
  border-collapse: collapse;
  font-variant-numeric: tabular-nums;
}

.matrix th,
.matrix td {
  padding: 11px 9px;
  border-bottom: 1px solid var(--rule);
  text-align: right;
}

.matrix thead th {
  color: var(--ink-3);
  font-family: var(--mono);
  font-size: 10.5px;
  font-weight: 400;
  line-height: 1.3;
  border-bottom-color: var(--rule-strong);
}

.matrix th:first-child {
  width: 34%;
  text-align: left;
}

.matrix tbody th {
  color: var(--ink);
  font-family: var(--serif);
  font-size: 14px;
  font-weight: 400;
  text-align: left;
}

.rate {
  background: rgba(20, 69, 60, calc(var(--r) * 0.3));
  color: var(--ink);
  font-family: var(--mono);
  font-size: 12.5px;
}

.rate-l1 {
  background: rgba(20, 69, 60, calc(var(--r) * 0.2));
}

.rate-watch {
  background: rgba(139, 63, 42, calc(var(--r) * 0.28));
}

.rate-inflated {
  background: rgba(139, 63, 42, calc(var(--r) * 0.4));
  font-weight: 500;
}

.mark {
  color: var(--oxide);
  font-family: var(--mono);
}

.caption {
  max-width: 74ch;
  margin-top: 10px;
  color: var(--ink-3);
  font-size: 11.5px;
  line-height: 1.5;
}

.callout {
  border-top: 2px solid var(--pine);
  padding-top: 14px;
}

.callout-big {
  color: var(--pine);
  font-family: var(--mono);
  font-size: clamp(2.6rem, 4.2vw, 4.2rem);
  font-weight: 400;
  line-height: 0.95;
  letter-spacing: -0.05em;
}

.callout-line {
  margin-top: 7px;
  font-size: 15px;
  line-height: 1.35;
}

.callout-small {
  margin-top: 14px;
  color: var(--ink-2);
  font-size: 12px;
  line-height: 1.4;
}

.width-block {
  margin-top: 46px;
  padding-top: 20px;
  border-top: 1px solid var(--rule-strong);
}

.width-head {
  display: flex;
  align-items: baseline;
  justify-content: space-between;
  gap: 30px;
  margin-bottom: 18px;
}

.width-head h3 {
  font-size: 18px;
  font-weight: 600;
  line-height: 1.2;
}

.width-head p {
  color: var(--ink-3);
  font-size: 12px;
  text-align: right;
}

.width-chart {
  display: grid;
  gap: 8px;
}

.width-row {
  display: grid;
  grid-template-columns: 180px minmax(0, 1fr) 48px;
  gap: 14px;
  align-items: center;
}

.width-label {
  font-size: 13px;
  line-height: 1.25;
}

.width-track {
  position: relative;
  height: 14px;
  border-left: 1px solid var(--rule-strong);
  border-right: 1px solid var(--rule-strong);
  background-image: linear-gradient(
    to right,
    transparent calc(50% - 0.5px),
    var(--rule) calc(50% - 0.5px),
    var(--rule) calc(50% + 0.5px),
    transparent calc(50% + 0.5px)
  );
}

.width-bar {
  display: block;
  width: var(--w);
  height: 100%;
  background: var(--pine);
  opacity: 0.85;
}

.width-value {
  color: var(--ink-2);
  font-family: var(--mono);
  font-size: 11.5px;
  text-align: right;
}

.width-axis {
  display: flex;
  justify-content: space-between;
  margin-top: 2px;
  margin-left: 194px;
  margin-right: 62px;
  color: var(--ink-3);
  font-family: var(--mono);
  font-size: 10px;
}

.margin-top {
  margin-top: 18px;
}

/* ACTG ------------------------------------------------------------------- */

.two-col {
  display: grid;
  grid-template-columns: minmax(0, 1.35fr) minmax(230px, 0.65fr);
  gap: 52px;
  align-items: start;
}

.data-table th,
.data-table td {
  padding: 12px 10px;
  border-bottom: 1px solid var(--rule);
  text-align: right;
}

.data-table thead th {
  padding-top: 0;
  color: var(--ink-3);
  font-family: var(--mono);
  font-size: 10.5px;
  font-weight: 400;
  border-bottom-color: var(--rule-strong);
}

.data-table th:first-child {
  text-align: left;
}

.data-table tbody th {
  color: var(--ink);
  font-family: var(--serif);
  font-size: 14px;
  font-weight: 400;
  text-align: left;
}

.data-table td {
  color: var(--ink);
  font-family: var(--mono);
  font-size: 12.5px;
  white-space: nowrap;
}

.primary-row th,
.primary-row td {
  background: var(--wash);
}

.primary-row th {
  font-weight: 600;
}

.neg-control {
  border-top: 2px solid var(--pine);
  padding-top: 14px;
}

.neg-control h3 {
  font-size: 16px;
  font-weight: 600;
}

.neg-sub {
  margin-top: 2px;
  color: var(--ink-3);
  font-size: 11.5px;
}

.neg-row {
  display: grid;
  grid-template-columns: 84px minmax(0, 1fr) 42px;
  gap: 10px;
  align-items: center;
  margin-top: 10px;
  font-size: 12px;
}

.neg-track {
  height: 10px;
  background: var(--rule);
}

.neg-bar {
  display: block;
  width: var(--w);
  height: 100%;
  background: var(--pine);
}

.neg-row b {
  font-family: var(--mono);
  font-size: 11.5px;
  font-weight: 500;
  text-align: right;
}

.neg-note {
  margin-top: 12px;
  color: var(--ink-3);
  font-size: 11.5px;
  line-height: 1.4;
}

.trial-note {
  max-width: 92ch;
  margin-top: 26px;
  padding-top: 14px;
  border-top: 1px solid var(--rule);
  color: var(--ink-2);
  font-size: 13.5px;
  line-height: 1.55;
}

.trial-note strong {
  color: var(--oxide);
  font-weight: 600;
}

/* TCGA ------------------------------------------------------------------- */

.auc {
  padding-top: 18px;
}

.auc-track {
  position: relative;
  height: 4px;
  margin: 54px 0 34px;
  background: var(--rule-strong);
}

.auc-mark {
  position: absolute;
  top: -5px;
  width: 1px;
  height: 14px;
  background: var(--ink);
}

.auc-mark::before {
  content: "";
  position: absolute;
  top: -4px;
  left: -4px;
  width: 9px;
  height: 9px;
  border-radius: 50%;
  background: var(--ink);
}

.auc-mark b {
  position: absolute;
  bottom: 20px;
  left: 0;
  transform: translateX(-50%);
  color: var(--ink);
  font-family: var(--mono);
  font-size: 12px;
  font-weight: 500;
  white-space: nowrap;
}

.auc-mark-primary {
  background: var(--pine);
}

.auc-mark-primary::before {
  background: var(--pine);
}

.auc-mark-primary b {
  color: var(--pine);
}

.auc-axis {
  display: flex;
  justify-content: space-between;
  color: var(--ink-3);
  font-family: var(--mono);
  font-size: 10px;
}

.auc-legend {
  display: flex;
  flex-wrap: wrap;
  gap: 8px 22px;
  margin-top: 16px;
  color: var(--ink-2);
  font-size: 12px;
}

.auc-legend span {
  display: inline-flex;
  align-items: center;
  gap: 7px;
}

.dot {
  display: inline-block;
  width: 8px;
  height: 8px;
  border-radius: 50%;
  background: var(--ink);
}

.dot-primary {
  background: var(--pine);
}

.expression-facts {
  display: grid;
  gap: 8px;
  padding-top: 12px;
  border-top: 1px solid var(--rule-strong);
  color: var(--ink-2);
  font-size: 13px;
  line-height: 1.4;
}

.expression-facts b {
  color: var(--ink);
  font-family: var(--mono);
  font-weight: 500;
}

/* Calculator ------------------------------------------------------------- */

.output-grid {
  display: grid;
  grid-template-columns: repeat(4, minmax(0, 1fr));
  border-top: 2px solid var(--pine);
  border-bottom: 1px solid var(--rule-strong);
}

.output {
  padding: 22px 24px 20px 0;
}

.output + .output {
  padding-left: 24px;
  border-left: 1px solid var(--rule);
}

.output-value {
  display: block;
  color: var(--pine);
  font-family: var(--mono);
  font-size: clamp(2rem, 3.4vw, 3.15rem);
  font-weight: 400;
  line-height: 1;
  letter-spacing: -0.045em;
}

.output-label {
  display: block;
  margin-top: 8px;
  color: var(--ink-2);
  font-size: 13px;
  line-height: 1.3;
}

.calculator-foot {
  display: flex;
  justify-content: space-between;
  gap: 34px;
  margin-top: 18px;
  color: var(--ink-2);
  font-size: 12.5px;
  line-height: 1.45;
}

.calculator-foot b {
  font-family: var(--mono);
  font-weight: 500;
}

.checks {
  margin-top: 5px;
  color: var(--ink-3);
  font-family: var(--mono);
  font-size: 10.5px;
  line-height: 1.5;
}

.downloads {
  display: flex;
  flex-wrap: wrap;
  gap: 18px;
  flex-shrink: 0;
  font-family: var(--mono);
  font-size: 11px;
}

.downloads a {
  color: var(--pine);
}

/* Limits and footer ------------------------------------------------------ */

.limits {
  padding-bottom: 64px;
}

.limits ul {
  display: grid;
  grid-template-columns: repeat(2, minmax(0, 1fr));
  gap: 0 48px;
  padding: 0;
  list-style: none;
  border-top: 1px solid var(--rule-strong);
}

.limits li {
  padding: 12px 0;
  border-bottom: 1px solid var(--rule);
  color: var(--ink-2);
  font-size: 13.5px;
  line-height: 1.45;
}

.footer {
  display: grid;
  grid-template-columns: minmax(0, 1fr) minmax(0, 1fr);
  gap: 16px 40px;
  padding-top: 32px;
  padding-bottom: 52px;
  border-top: 1px solid var(--rule-strong);
}

.footer-mark {
  font-size: 22px;
  font-weight: 600;
  letter-spacing: -0.03em;
  line-height: 1;
}

.footer p {
  margin-top: 5px;
  color: var(--ink-3);
  font-size: 12px;
  line-height: 1.45;
}

.footer-links {
  display: flex;
  flex-wrap: wrap;
  justify-content: flex-end;
  align-items: start;
  gap: 8px 20px;
  font-family: var(--mono);
  font-size: 11px;
}

.footer-links a {
  color: var(--ink-2);
  text-decoration: none;
  border-bottom: 1px solid var(--rule-strong);
  padding-bottom: 2px;
}

.footer-links a:hover {
  color: var(--pine);
  border-color: var(--pine);
}

.footer-note {
  grid-column: 1 / -1;
  margin-top: 8px;
}

/* Responsive ------------------------------------------------------------- */

@media (max-width: 1040px) {
  .steps {
    grid-template-columns: repeat(2, minmax(0, 1fr));
  }

  .steps li {
    min-height: 126px;
    border-bottom: 1px solid var(--rule);
  }

  .steps li:nth-child(2) {
    border-right: 0;
  }

  .steps li:nth-child(3),
  .steps li:nth-child(4) {
    border-bottom: 0;
  }

  .split {
    grid-template-columns: minmax(0, 1fr) 240px;
    gap: 34px;
  }

  .two-col {
    grid-template-columns: minmax(0, 1fr) 240px;
    gap: 34px;
  }

  .output {
    padding-right: 18px;
  }

  .output + .output {
    padding-left: 18px;
  }
}

@media (max-width: 820px) {
  .wrap {
    padding-left: 26px;
    padding-right: 26px;
  }

  .cover-main {
    padding-top: 48px;
  }

  .cover-figure {
    padding-bottom: 36px;
  }

  .figure-scroll {
    margin-right: -26px;
  }

  .forest {
    min-width: 760px;
  }

  .cover-stats {
    grid-template-columns: minmax(0, 1fr);
    gap: 0;
  }

  .cover-stat {
    display: flex;
    align-items: baseline;
    gap: 14px;
    padding: 11px 0;
  }

  .cover-stat + .cover-stat {
    padding-left: 0;
    border-top: 1px solid #35534a;
    border-left: 0;
  }

  .stat {
    min-width: 116px;
    font-size: 22px;
  }

  .stat-label {
    margin-top: 0;
  }

  .section-head {
    display: block;
  }

  .section-note {
    margin-top: 9px;
    text-align: left;
  }

  .split,
  .two-col {
    grid-template-columns: minmax(0, 1fr);
    gap: 30px;
  }

  .callout {
    max-width: 420px;
  }

  .width-head {
    display: block;
  }

  .width-head p {
    margin-top: 4px;
    text-align: left;
  }

  .output-grid {
    grid-template-columns: repeat(2, minmax(0, 1fr));
  }

  .output:nth-child(3) {
    border-top: 1px solid var(--rule);
  }

  .output:nth-child(3),
  .output:nth-child(4) {
    padding-top: 20px;
  }

  .calculator-foot {
    display: block;
  }

  .downloads {
    margin-top: 12px;
  }

  .footer {
    grid-template-columns: minmax(0, 1fr);
  }

  .footer-links {
    justify-content: flex-start;
  }
}

@media (max-width: 620px) {
  .wrap {
    padding-left: 20px;
    padding-right: 20px;
  }

  .cover-top {
    flex-wrap: wrap;
    gap: 8px 18px;
  }

  .cover-meta {
    width: 100%;
    order: 3;
  }

  .cover-link {
    margin-left: auto;
  }

  h1 {
    font-size: clamp(2.85rem, 13vw, 4.2rem);
  }

  .cover-sub {
    font-size: 16px;
  }

  .cover-figure {
    padding-left: 20px;
    padding-right: 20px;
  }

  .figure-scroll {
    margin-right: -20px;
  }

  .forest {
    min-width: 720px;
  }

  .steps {
    grid-template-columns: minmax(0, 1fr);
  }

  .steps li {
    min-height: 0;
    padding: 14px 0 18px;
    border-right: 0;
    border-bottom: 1px solid var(--rule);
  }

  .steps li + li {
    padding-left: 0;
  }

  .steps li:nth-child(3) {
    border-bottom: 1px solid var(--rule);
  }

  .steps h3 {
    margin-top: 7px;
  }

  .matrix th,
  .matrix td {
    padding: 9px 6px;
  }

  .matrix thead th {
    font-size: 9.5px;
  }

  .width-row {
    grid-template-columns: 116px minmax(0, 1fr) 42px;
    gap: 9px;
  }

  .width-axis {
    margin-left: 125px;
    margin-right: 51px;
  }

  .width-label {
    font-size: 12px;
  }

  .data-table th,
  .data-table td {
    padding: 10px 6px;
  }

  .data-table thead th {
    font-size: 9.5px;
  }

  .data-table tbody th {
    font-size: 13px;
  }

  .data-table td {
    font-size: 11.5px;
  }

  .output {
    padding-right: 12px;
  }

  .output + .output {
    padding-left: 12px;
  }

  .output-value {
    font-size: 26px;
  }

  .output-label {
    font-size: 12px;
  }

  .limits ul {
    grid-template-columns: minmax(0, 1fr);
  }
}

@media (prefers-reduced-motion: reduce) {
  *,
  *::before,
  *::after {
    scroll-behavior: auto !important;
  }
}

@media print {
  .cover {
    background: #fff;
    color: #000;
  }

  .cover-meta,
  .cover-link,
  .downloads,
  .footer-links {
    display: none;
  }

  .cover h1,
  .cover-sub,
  .stat,
  .stat-label,
  figcaption {
    color: #000;
  }

  .section {
    break-inside: avoid;
  }
}