Long Answer Question (LAQ): Down Syndrome

ls -la /home/daytona/workspace/ 2>/dev/null || mkdir -p /home/daytona/workspace

mkdir -p /home/daytona/workspace/down-syndrome && python3 -c "from reportlab.lib…

~/down-syndrome/generate_pdf.py

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.units import cm, mm
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, KeepTogether
)
from reportlab.platypus.flowables import HRFlowable
from reportlab.pdfbase import pdfmetrics
import urllib.request
import os

OUTPUT = "/home/daytona/workspace/down-syndrome/Down_Syndrome_LAQ.pdf"

# ── colour palette ────────────────────────────────────────────────────────────
BLUE_DARK  = colors.HexColor("#1a3a6b")
BLUE_MID   = colors.HexColor("#2563a8")
BLUE_LIGHT = colors.HexColor("#dbeafe")
TEAL       = colors.HexColor("#0f766e")
TEAL_LIGHT = colors.HexColor("#ccfbf1")
RED_DARK   = colors.HexColor("#991b1b")
RED_LIGHT  = colors.HexColor("#fee2e2")
YELLOW_BG  = colors.HexColor("#fefce8")
YELLOW_BD  = colors.HexColor("#ca8a04")
GREY_LINE  = colors.HexColor("#cbd5e1")
WHITE      = colors.white
BLACK      = colors.black

# ── document ──────────────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=1.8*cm, rightMargin=1.8*cm,
    topMargin=2*cm,    bottomMargin=2*cm,
    title="Down Syndrome – LAQ Reference",
    author="Orris Medical AI"
)
W, H = A4
CONTENT_W = W - 3.6*cm

# ── styles ────────────────────────────────────────────────────────────────────
base = getSampleStyleSheet()

def ps(name, parent="Normal", **kw):
    return ParagraphStyle(name, parent=base[parent], **kw)

TITLE    = ps("MyTitle",    "Title",
              fontSize=22, textColor=WHITE, alignment=TA_CENTER,
              spaceAfter=4, leading=28)
SUBTITLE = ps("MySub",      "Normal",
              fontSize=10, textColor=colors.HexColor("#bfdbfe"),
              alignment=TA_CENTER, spaceAfter=2)
REF_STYLE= ps("Ref",        "Normal",
              fontSize=7.5, textColor=colors.HexColor("#94a3b8"),
              alignment=TA_CENTER, spaceAfter=0)

H1       = ps("H1", "Heading1",
              fontSize=12, textColor=WHITE, leading=16,
              spaceBefore=10, spaceAfter=4,
              backColor=BLUE_DARK,
              leftIndent=-8, rightIndent=-8,
              borderPadding=(4,8,4,8))
H2       = ps("H2", "Heading2",
              fontSize=10, textColor=BLUE_DARK, leading=14,
              spaceBefore=8, spaceAfter=2,
              borderPadding=(2,0,2,0))
BODY     = ps("Body", "Normal",
              fontSize=9, leading=14, spaceAfter=3,
              alignment=TA_JUSTIFY)
BULLET   = ps("Bullet", "Normal",
              fontSize=9, leading=13, spaceAfter=2,
              leftIndent=14, firstLineIndent=-10)
SUB_BULL = ps("SubBull", "Normal",
              fontSize=8.5, leading=12, spaceAfter=1,
              leftIndent=26, firstLineIndent=-10,
              textColor=colors.HexColor("#374151"))
BOLD_B   = ps("BoldBody", "Normal",
              fontSize=9, leading=13, spaceAfter=2,
              fontName="Helvetica-Bold")
CAPTION  = ps("Caption", "Normal",
              fontSize=7.5, textColor=colors.HexColor("#6b7280"),
              alignment=TA_CENTER, spaceAfter=4)
KEYBOX   = ps("KeyBox", "Normal",
              fontSize=8.5, leading=12,
              backColor=TEAL_LIGHT,
              borderColor=TEAL, borderWidth=0.5, borderPadding=4)
WARN     = ps("Warn", "Normal",
              fontSize=8.5, leading=12,
              backColor=RED_LIGHT,
              borderColor=RED_DARK, borderWidth=0.5, borderPadding=4)
NOTE     = ps("Note", "Normal",
              fontSize=8.5, leading=12,
              backColor=YELLOW_BG,
              borderColor=YELLOW_BD, borderWidth=0.5, borderPadding=4)

def b(text): return f"<b>{text}</b>"
def i(text): return f"<i>{text}</i>"
def bi(text): return f"<b><i>{text}</i></b>"
def col(text, c): return f'<font color="{c}">{text}</font>'

# ── header banner ─────────────────────────────────────────────────────────────
def header_banner():
    banner_data = [[Paragraph(
        '<font color="white" size="22"><b>DOWN SYNDROME (TRISOMY 21)</b></font><br/>'
        '<font color="#bfdbfe" size="10">Long Answer Question – Pathology Quick Reference</font><br/>'
        '<font color="#94a3b8" size="8">Ref: Robbins &amp; Kumar Basic Pathology 11e | Robbins Cotran Pathologic Basis of Disease 10e | Harsh Mohan 7e</font>',
        ps("BannerP","Normal", alignment=TA_CENTER, leading=20))
    ]]
    t = Table(banner_data, colWidths=[CONTENT_W])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0),(-1,-1), BLUE_DARK),
        ("TOPPADDING",   (0,0),(-1,-1), 16),
        ("BOTTOMPADDING",(0,0),(-1,-1), 16),
        ("LEFTPADDING",  (0,0),(-1,-1), 12),
        ("RIGHTPADDING", (0,0),(-1,-1), 12),
        ("ROUNDEDCORNERS", (0,0),(-1,-1), [6,6,6,6]),
    ]))
    return t

# ── section heading ───────────────────────────────────────────────────────────
def section(num, title, color=BLUE_DARK):
    data = [[Paragraph(f'<font color="white" size="10"><b>{num}. {title.upper()}</b></font>',
                       ps("SH","Normal",alignment=TA_LEFT, leading=14))]]
    t = Table(data, colWidths=[CONTENT_W])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0),(-1,-1), color),
        ("TOPPADDING",   (0,0),(-1,-1), 5),
        ("BOTTOMPADDING",(0,0),(-1,-1), 5),
        ("LEFTPADDING",  (0,0),(-1,-1), 10),
        ("RIGHTPADDING", (0,0),(-1,-1), 10),
    ]))
    return t

def bullet(text, level=1):
    dot = "\u2022" if level == 1 else "\u25e6"
    indent = 14 if level==1 else 26
    fi     = -10
    style  = ps(f"bul{level}","Normal",
                fontSize=9, leading=13, spaceAfter=2,
                leftIndent=indent, firstLineIndent=fi)
    return Paragraph(f"{dot} {text}", style)

def hr(): return HRFlowable(width="100%", thickness=0.5, color=GREY_LINE, spaceAfter=4, spaceBefore=4)

# ── karyotype table ───────────────────────────────────────────────────────────
def karyotype_table():
    hdr = ["Type", "Karyotype", "Frequency", "Maternal Age Effect?"]
    rows = [
        ["Trisomy 21 (Meiotic non-disjunction)", "47, XX/XY, +21",               "~95%", "YES (strong)"],
        ["Robertsonian Translocation",            "46, XX/XY, der(14;21)(q10;q10), +21", "~4%", "NO"],
        ["Mosaicism (Mitotic non-disjunction)",   "46, XX / 47, XX, +21",         "~1%",  "NO"],
    ]
    col_w = [CONTENT_W*0.36, CONTENT_W*0.33, CONTENT_W*0.13, CONTENT_W*0.18]
    table_data = [
        [Paragraph(b(h), ps("TH","Normal",fontSize=8.5,textColor=WHITE,alignment=TA_CENTER)) for h in hdr]
    ] + [
        [Paragraph(c, ps("TD","Normal",fontSize=8.5,leading=12)) for c in row]
        for row in rows
    ]
    t = Table(table_data, colWidths=col_w, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), BLUE_MID),
        ("BACKGROUND", (0,1), (-1,1), BLUE_LIGHT),
        ("BACKGROUND", (0,2), (-1,2), WHITE),
        ("BACKGROUND", (0,3), (-1,3), BLUE_LIGHT),
        ("GRID",       (0,0), (-1,-1), 0.4, GREY_LINE),
        ("TOPPADDING",   (0,0),(-1,-1), 4),
        ("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",  (0,0),(-1,-1), 5),
        ("RIGHTPADDING", (0,0),(-1,-1), 5),
        ("VALIGN",     (0,0),(-1,-1),"MIDDLE"),
    ]))
    return t

# ── maternal age table ────────────────────────────────────────────────────────
def maternal_age_table():
    hdr = ["Maternal Age", "Risk of Down Syndrome"]
    rows = [
        ["< 20 years",    "1 in 1,550 live births"],
        ["25 years",      "1 in 1,300"],
        ["30 years",      "1 in 900"],
        ["35 years",      "1 in 365"],
        ["40 years",      "1 in 100"],
        ["> 45 years",    "1 in 25 live births"],
    ]
    col_w = [CONTENT_W*0.40, CONTENT_W*0.60]
    table_data = [
        [Paragraph(b(h), ps("TH2","Normal",fontSize=8.5,textColor=WHITE,alignment=TA_CENTER)) for h in hdr]
    ] + [
        [Paragraph(c, ps("TD2","Normal",fontSize=8.5,leading=12,
                          fontName="Helvetica-Bold" if i==5 else "Helvetica")) for c in row]
        for i, row in enumerate(rows)
    ]
    t = Table(table_data, colWidths=col_w, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), TEAL),
        ("BACKGROUND", (0,1), (-1,1), TEAL_LIGHT),
        ("BACKGROUND", (0,2), (-1,2), WHITE),
        ("BACKGROUND", (0,3), (-1,3), TEAL_LIGHT),
        ("BACKGROUND", (0,4), (-1,4), WHITE),
        ("BACKGROUND", (0,5), (-1,5), TEAL_LIGHT),
        ("BACKGROUND", (0,6), (-1,6), RED_LIGHT),
        ("GRID",       (0,0), (-1,-1), 0.4, GREY_LINE),
        ("TOPPADDING",   (0,0),(-1,-1), 4),
        ("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",  (0,0),(-1,-1), 8),
        ("VALIGN",     (0,0),(-1,-1),"MIDDLE"),
    ]))
    return t

# ── summary table ─────────────────────────────────────────────────────────────
def summary_table():
    rows = [
        ["Incidence",               "1 in 700 live births"],
        ["Chromosome",              "Trisomy 21 (extra chromosome 21)"],
        ["Most common karyotype",   "47, XX/XY, +21"],
        ["Main cause",              "Meiotic non-disjunction (95%)"],
        ["Maternal age effect",     "Strong – risk rises sharply after 35 years"],
        ["Hallmark facies",         "Flat face, epicanthic folds, upslanting palpebral fissures"],
        ["Intelligence",            "IQ 25–50 (most); near-normal in mosaics"],
        ["Most common cardiac defect","AVSD (43% of cardiac cases in DS)"],
        ["Leukemia risk",           "AML: 500x increased | ALL: 20x increased"],
        ["Alzheimer risk",          "~100% by >40 years (APP overexpression)"],
        ["Median age at death",     "~60 years (up from 25 years in 1983)"],
        ["Prenatal diagnosis",      "Nuchal translucency, cfDNA (NIPT), karyotype / FISH"],
    ]
    col_w = [CONTENT_W*0.38, CONTENT_W*0.62]
    table_data = [
        [Paragraph(b("Feature"), ps("SH","Normal",fontSize=8.5,textColor=WHITE,alignment=TA_CENTER)),
         Paragraph(b("Details"),  ps("SH","Normal",fontSize=8.5,textColor=WHITE,alignment=TA_CENTER))]
    ] + [
        [Paragraph(b(r[0]), ps("TK","Normal",fontSize=8.5,leading=12,textColor=BLUE_DARK)),
         Paragraph(r[1],    ps("TV","Normal",fontSize=8.5,leading=12))]
        for r in rows
    ]
    t = Table(table_data, colWidths=col_w, repeatRows=1)
    colors_alt = [BLUE_LIGHT if i%2==0 else WHITE for i in range(len(rows))]
    style = [
        ("BACKGROUND", (0,0), (-1,0), BLUE_DARK),
        ("GRID",       (0,0), (-1,-1), 0.4, GREY_LINE),
        ("TOPPADDING",   (0,0),(-1,-1), 4),
        ("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",  (0,0),(-1,-1), 6),
        ("RIGHTPADDING", (0,0),(-1,-1), 6),
        ("VALIGN",     (0,0),(-1,-1),"MIDDLE"),
    ]
    for i, c in enumerate(colors_alt):
        style.append(("BACKGROUND", (0,i+1),(-1,i+1), c))
    t.setStyle(TableStyle(style))
    return t

# ── cardiac defects table ─────────────────────────────────────────────────────
def cardiac_table():
    hdr = ["Cardiac Defect", "% of Cardiac Cases in DS"]
    rows = [
        ["Atrioventricular Septal Defect (AVSD)", "43% — MOST COMMON"],
        ["Ventricular Septal Defect (VSD)",        "32%"],
        ["Atrial Septal Defect (ASD)",             "19%"],
        ["Tetralogy of Fallot",                    "6%"],
    ]
    col_w = [CONTENT_W*0.60, CONTENT_W*0.40]
    table_data = [
        [Paragraph(b(h), ps("CH","Normal",fontSize=8.5,textColor=WHITE)) for h in hdr]
    ] + [
        [Paragraph(r[0], ps("CR","Normal",fontSize=8.5,leading=12,
                             fontName="Helvetica-Bold" if i==0 else "Helvetica")),
         Paragraph(r[1], ps("CR2","Normal",fontSize=8.5,leading=12,
                             textColor=RED_DARK if i==0 else BLACK,
                             fontName="Helvetica-Bold" if i==0 else "Helvetica"))]
        for i, r in enumerate(rows)
    ]
    t = Table(table_data, colWidths=col_w, repeatRows=1)
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,0), RED_DARK),
        ("BACKGROUND", (0,1), (-1,1), RED_LIGHT),
        ("BACKGROUND", (0,2), (-1,2), WHITE),
        ("BACKGROUND", (0,3), (-1,3), RED_LIGHT),
        ("BACKGROUND", (0,4), (-1,4), WHITE),
        ("GRID",       (0,0), (-1,-1), 0.4, GREY_LINE),
        ("TOPPADDING",   (0,0),(-1,-1), 4),
        ("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING",  (0,0),(-1,-1), 6),
        ("VALIGN",     (0,0),(-1,-1),"MIDDLE"),
    ]))
    return t

# ── build story ───────────────────────────────────────────────────────────────
story = []
SP = lambda n=1: Spacer(1, n*0.3*cm)

# TITLE BANNER
story.append(header_banner())
story.append(SP(2))

# 1. INTRODUCTION
story.append(KeepTogether([
    section(1, "Introduction / Definition"),
    SP(),
    Paragraph(
        "Down syndrome (Trisomy 21) is the <b>most common chromosomal disorder</b> and the leading "
        "genetic cause of intellectual disability in humans. First described by <b>John Langdon Down "
        "in 1866</b>, its chromosomal basis (an extra chromosome 21) was established by <b>Jerome "
        "Lejeune in 1959</b>. Incidence is approximately <b>1 in 700 live births</b>.",
        BODY),
    SP(),
]))

# 2. CYTOGENETICS
story.append(section(2, "Cytogenetics / Karyotypes"))
story.append(SP())
story.append(Paragraph(b("Three distinct mechanisms produce Down syndrome:"), BODY))
story.append(SP(0.5))
story.append(karyotype_table())
story.append(SP())

story.append(Paragraph(b("A. Trisomy 21 – Meiotic Non-disjunction (~95%)"), H2))
story.append(bullet(f"Failure of chromosome 21 to separate during {b('meiosis I or II')}, most often in the maternal ovum"))
story.append(bullet(f"In {b('95% of trisomy 21 cases')} the extra chromosome is of {b('maternal origin')}"))
story.append(bullet("Parents have a normal karyotype; condition is NOT familial"))
story.append(bullet(f"FISH with chromosome 21 probes shows {b('three fluorescent signals')}"))
story.append(SP(0.5))

story.append(Paragraph(b("B. Robertsonian Translocation (~4%)"), H2))
story.append(bullet(f"Long arm of chromosome 21 translocated to chromosome {b('14 or 22')}"))
story.append(bullet("Total chromosome count = 46, but there is triple gene dosage of Chr 21 material"))
story.append(bullet(f"{b('Frequently familial')} – carrier parent (usually mother) has Robertsonian translocation"))
story.append(bullet(f"Example maternal carrier karyotype: {i('45, XX, del(14;21)(q10;q10)')}"))
story.append(bullet(f"{b('Maternal age has NO effect')} in this type"))
story.append(SP(0.5))

story.append(Paragraph(b("C. Mosaicism – Mitotic Non-disjunction (~1%)"), H2))
story.append(bullet("Mitotic non-disjunction of Chr 21 during early embryogenesis"))
story.append(bullet(f"Mix of {b('46-chromosome')} and {b('47-chromosome')} cells"))
story.append(bullet(f"Features are {b('variably milder')}; intelligence may be near-normal"))
story.append(bullet(f"{b('Maternal age has NO effect')}"))
story.append(SP())

# 3. MATERNAL AGE
story.append(section(3, "Role of Maternal Age"))
story.append(SP())
story.append(Paragraph(
    "Maternal age has a <b>profound influence</b> on the incidence of trisomy 21 (applies to "
    "non-disjunction type only). The aging ovum becomes increasingly susceptible to non-disjunction "
    "by an as-yet unknown mechanism. <b>No paternal age effect</b> has been established.",
    BODY))
story.append(SP(0.5))
story.append(maternal_age_table())
story.append(SP())

# 4. PATHOGENESIS
story.append(section(4, "Pathogenesis / Molecular Basis"))
story.append(SP())
story.append(Paragraph(
    "Clinical features arise predominantly from <b>gene dosage effects</b> — extra copies of genes "
    "on chromosome 21 lead to overexpression of multiple gene products:",
    BODY))
story.append(SP(0.5))
story.append(bullet(f"{b('APP gene overexpression')} – Amyloid Precursor Protein on chr 21 is overexpressed; "
                    "excess amyloid-beta deposition drives early-onset Alzheimer disease"))
story.append(bullet(f"{b('Mitochondrial dysfunction')} – ~10% of overexpressed genes regulate mitochondrial "
                    "function; broken/swollen cristae, ROS generation, and apoptosis activation are seen"))
story.append(bullet(f"{b('Noncoding RNAs')} – chr 21 has highest density of lncRNAs; contributions to "
                    "phenotype under active investigation"))
story.append(bullet(f"{b('Immune dysregulation')} – T-cell function mainly affected; predisposes to "
                    "infections and autoimmunity"))
story.append(SP())

# 5. CLINICAL FEATURES
story.append(section(5, "Clinical Features"))
story.append(SP())
story.append(Paragraph(b("Facies (usually evident at birth):"), BOLD_B))
story.append(bullet(f"{b('Flat facial profile')}"))
story.append(bullet(f"{b('Oblique (upward slanting) palpebral fissures')} — mongoloid slant"))
story.append(bullet(f"{b('Epicanthic folds')} — vertical skin folds at inner canthus"))
story.append(bullet("Flat nasal bridge"))
story.append(bullet("Protruding tongue (macroglossia / hypotonia of tongue)"))
story.append(bullet("Small, low-set ears"))
story.append(bullet("Short neck with excess nuchal skin"))
story.append(SP(0.5))
story.append(Paragraph(b("Skull and Limbs:"), BOLD_B))
story.append(bullet(f"{b('Brachycephaly')} with flat occiput"))
story.append(bullet(f"{b('Simian crease')} (single palmar transverse crease) – ~50% of cases"))
story.append(bullet("Clinodactyly – incurved 5th finger"))
story.append(bullet("Sandal gap – wide space between 1st and 2nd toes"))
story.append(bullet("Short stature; short broad hands"))
story.append(bullet("Generalized hypotonia"))
story.append(SP(0.5))
story.append(Paragraph(b("Neurological:"), BOLD_B))
story.append(bullet(f"{b('Intellectual disability')} – IQ typically 25–50 (~80% of cases); range 25–70"))
story.append(bullet("Mosaics may have near-normal intelligence"))
story.append(SP())

# 6. COMPLICATIONS
story.append(section(6, "Complications and Associated Conditions"))
story.append(SP())

story.append(Paragraph(b("A. Congenital Heart Disease (~40% of patients) — Main cause of death in infancy:"), H2))
story.append(SP(0.3))
story.append(cardiac_table())
story.append(SP(0.5))

story.append(Paragraph(b("B. Leukemia"), H2))
story.append(bullet(f"{b('500-fold')} increased risk of Acute Myeloid Leukemia (AML) – especially {b('megakaryoblastic type (FAB M7)')}, ages 1–5 years"))
story.append(bullet(f"{b('20-fold')} increased risk of precursor B-cell Acute Lymphoblastic Leukemia (ALL)"))
story.append(bullet("AML in Down syndrome: increased chemosensitivity (especially to methotrexate), relatively favorable prognosis"))
story.append(SP(0.5))

story.append(Paragraph(b("C. Alzheimer Disease"), H2))
story.append(bullet(f"Virtually {b('ALL patients >40 years')} develop neuropathological changes of Alzheimer disease"))
story.append(bullet(f"Mechanism: {b('APP gene')} (chr 21) overexpression → excess amyloid-beta deposition → senile plaques and NFTs"))
story.append(SP(0.5))

story.append(Paragraph(b("D. Immune Defects"), H2))
story.append(bullet("Abnormal T-cell function → serious pulmonary infections"))
story.append(bullet("Increased susceptibility to thyroid autoimmunity (Hashimoto's thyroiditis)"))
story.append(SP(0.5))

story.append(Paragraph(b("E. Gastrointestinal Anomalies"), H2))
story.append(bullet("Esophageal and duodenal atresia ('double bubble' sign on X-ray)"))
story.append(bullet("Hirschsprung disease, small bowel atresias"))
story.append(SP(0.5))

story.append(Paragraph(b("F. Other Associations"), H2))
story.append(bullet("Eyes: Brushfield spots on iris, cataracts, refractive errors"))
story.append(bullet("Atlantoaxial instability (ligamentous laxity)"))
story.append(bullet("Hearing loss; cryptorchidism; hypospadias"))
story.append(SP())

# 7. PRENATAL DIAGNOSIS
story.append(section(7, "Prenatal Diagnosis"))
story.append(SP())
story.append(Paragraph(b("Biochemical Screening (Triple / Quadruple Test):"), BOLD_B))
story.append(bullet(f"{b('Decreased')}: maternal serum AFP (~25% lower), unconjugated estriol (uE3)"))
story.append(bullet(f"{b('Increased')}: beta-hCG, inhibin-A"))
story.append(SP(0.5))
story.append(Paragraph(b("Ultrasound Markers (1st trimester):"), BOLD_B))
story.append(bullet(f"{b('Increased nuchal translucency')} (>3 mm at 11–13 weeks) — most sensitive early marker"))
story.append(bullet("Absent / hypoplastic nasal bone"))
story.append(bullet("'Double bubble' sign on ultrasound (duodenal atresia)"))
story.append(SP(0.5))
story.append(Paragraph(b("Cell-Free Fetal DNA (cfDNA / NIPT):"), BOLD_B))
story.append(bullet("5–10% of total cell-free DNA in maternal blood is fetal in origin"))
story.append(bullet("Next-generation sequencing detects gene dosage imbalance of chr 21"))
story.append(bullet("High sensitivity and specificity – now standard non-invasive screening"))
story.append(SP(0.5))
story.append(Paragraph(b("Definitive Diagnosis:"), BOLD_B))
story.append(bullet("Amniocentesis (15–18 weeks) or Chorionic villus sampling (CVS, 10–12 weeks)"))
story.append(bullet("Karyotyping of fetal cells; FISH with chromosome 21 probes (three signals = trisomy 21)"))
story.append(SP())

# 8. PROGNOSIS
story.append(section(8, "Prognosis / Longevity"))
story.append(SP())
story.append(Paragraph(
    "Improved medical care has dramatically increased survival. Median age at death was "
    f"{b('25 years in 1983')}; currently the median age at death is {b('~60 years')} "
    "(Robbins & Kumar Basic Pathology, 11e). Cardiac surgery and better management of "
    "infections are the main contributors.",
    BODY))
story.append(SP())

# 9. SUMMARY TABLE
story.append(section(9, "Quick Reference Summary", color=TEAL))
story.append(SP())
story.append(summary_table())
story.append(SP(2))

# FOOTER NOTE
footer_data = [[
    Paragraph(
        '<font size="7.5" color="#64748b"><b>References:</b> Robbins &amp; Kumar Basic Pathology, '
        '11th ed., Ch. 4, pp. 125–126 | Robbins, Cotran &amp; Kumar Pathologic Basis of Disease, '
        '10th ed., Ch. 5, pp. 163–165 | Harsh Mohan Textbook of Pathology, 7th ed., Ch. 3, pp. 46–50'
        '<br/>Generated by Orris Medical AI – for educational purposes only.</font>',
        ps("Footer","Normal", alignment=TA_CENTER))
]]
ft = Table(footer_data, colWidths=[CONTENT_W])
ft.setStyle(TableStyle([
    ("BACKGROUND",    (0,0),(-1,-1), BLUE_LIGHT),
    ("TOPPADDING",    (0,0),(-1,-1), 8),
    ("BOTTOMPADDING", (0,0),(-1,-1), 8),
    ("LEFTPADDING",   (0,0),(-1,-1), 10),
    ("RIGHTPADDING",  (0,0),(-1,-1), 10),
]))
story.append(ft)

# ── build ─────────────────────────────────────────────────────────────────────
doc.build(story)
print(f"PDF generated: {OUTPUT}")

cd /home/daytona/workspace/down-syndrome && python3 generate_pdf.py 2>&1

ls -lh /home/daytona/workspace/down-syndrome/Down_Syndrome_LAQ.pdf