conclude it was almost certainly appendicitis, possibly from the treatments undertaken to improve fertility. Her replacement was Maria Anna of Neuburg, one of 12 children whose family reputation for fertility made them popular choices for royal marriages. Of her sisters, Maria Sophia married Peter II of Portugal, while Eleonore was the third wife of Emperor Leopold. Maria Anna was aunt to future emperors Joseph I and Charles VI, making her an ideal choice for the Austrian faction. Charles remained childless; by that time, he was almost certainly impotent, his autopsy later revealing he had only one atrophied testicle. As his health declined, internal struggles over the succession became increasingly bitter, leadership of the pro-French faction passing to Fernández de Portocarrero, Cardinal and Archbishop of Toledo. Under the influence of the 'Austrians,' in 1690 Spain joined the Grand Alliance in the Nine Years' War with France. It declared bankruptcy again in 1692 and by 1696, France occupied most of Catalonia; Mariana retained power with the support of German auxiliaries under Maria Anna's brother Charles Philip, many of whom were expelled after Mariana's death. She died on 16 May 1696 at the Uceda Palace in Madrid, at the age of sixty-one; the cause is thought to have been breast cancer. Issue As Queen of Spain from 1649 to 1665: Margaret Theresa (12 July 1651-12 March 1673), who married Leopold I, Holy Roman Emperor, in 1666. Maria Ambrosia de la Concepción (7–21 December 1655), died in infancy Philip Prospero, Prince of Asturias (28 November 1657-1 November 1661), died in childhood Ferdinand Thomas, Infante of Spain (21 December 1658-23 October 1659), died in infancy Charles II of Spain (6 November 1661-1 November 1700) Legacy In 1668, Mariana approved the establishment of a Jesuit mission under Diego Luis de San Vitores and Saint Pedro Calungsod on a series of islands the Spanish referred to as the Ladrones, which were renamed the Mariana Islands in her honour. The Portrait of Mariana of Austria painted by Diego Velázquez was commissioned by Philip and is the only known full-length painting of her. The original is in the Prado Museum in Madrid; a copy was sent to her father Ferdinand and is held by the Kunsthistorisches Museum in Vienna. Several other portraits of her were made, including Juan Bautista Martínez del Mazo's Queen Mariana of Spain in Mourning, 1666. She also appears as a detail in Velasquez' masterpiece Las