Independent studies by Ignaz Semmelweis in 1846 in Vienna and Oliver Wendell Holmes, Sr. in 1843 in Boston established a link between the hands of health care workers and the spread of hospital-acquired disease. The U.S. Centers for Disease Control and Prevention (CDC) state that "It is well documented that the most important measure for preventing the spread of pathogens is effective handwashing". In the developed world, hand washing is mandatory in most health care settings and required by many different regulators.