Circulating tumour DNA for clinicians: current and future clinical applications.

This review introduces clinicians to the basic concepts of the biology of circulating tumour DNA (ctDNA), which is required to understand clinical use of ctDNA technology. We provide an overview of how new technology has improved the sensitivity of ctDNA detection over the last decade and the available techniques for ctDNA analysis including whole-genome sequencing (WGS), targeted cancer-associated gene panels, and methylation analysis. We discuss the most recent evidence from clinical trials for ctDNA in patient care including precision treatment of advanced cancers, disease monitoring, improving adjuvant treatment, and screening for early detection of cancer. Finally, we outline how ctDNA is likely to directly impact radiologists, and identify further research required for ctDNA to progress into routine clinical application.

The evolutionary origins of Southeast Asian Ovalocytosis.

Southeast Asian Ovalocytosis (SAO) is a common red blood cell disorder that is maintained as a balanced polymorphism in human populations. In individuals heterozygous for the SAO-causing mutation there are minimal detrimental effects and well-documented protection from severe malaria caused by Plasmodium vivax and Plasmodium falciparum; however, the SAO-causing mutation is fully lethal in utero when homozygous. The present-day high frequency of SAO in Island Southeast Asia indicates the trait is maintained by strong heterozygote advantage. Our study elucidates the evolutionary origin of SAO by characterizing DNA sequence variation in a 9.5 kilobase region surrounding the causal mutation in the SLC4A1 gene. We find substantial haplotype diversity among SAO chromosomes and estimate the age of the trait to be approximately 10,005 years (95% CI: 4930-23,200 years). This date is far older than any other human malaria-resistance trait examined previously in Southeast Asia, and considerably pre-dates the widespread adoption of agriculture associated with the spread of speakers of Austronesian languages some 4000 years ago. Using a genealogy-based method we find no evidence of historical positive selection acting on SAO (s=0.0, 95% CI: 0.0-0.03), in sharp contrast to the strong present-day selection coefficient (e.g., 0.09) estimated from the frequency of this recessively lethal trait. This discrepancy may be due to a recent increase in malaria-driven selection pressure following the spread of agriculture, with SAO targeted as a standing variant by positive selection in malarial populations.

Improved medical understanding of human health.

The time has come to examine aspects of health and disease on a broader basis than immediate cause and effect. Recognition of the biological processes of adaptation shaped by natural selection has become a requirement for improved understanding of human health in the modern environment, and the time has come for its incorporation into medical teaching and clinical practice.

Family development theory.

This is the first in a series of columns which will discuss theories " borrowed " from other disciplines and used in clinical practice. In this article, Duvall and Terkleson 's theories of family development are examined for their clinical usefulness. Examples of their utility and limitations are included. Suggestions for ways in which clinical practice may direct further nursing research are suggested.

Health care in the Soviet Union.

More nurses today have the opportunity to visit other countries and broaden their ideas of health care and nursing. Several colleagues and I have prepared a series of three articles that describe visits to the Soviet Union, China and Africa by nurses participating in exchange tours conducted by Professional Seminar Consultants of Albuquerque, New Mexico. During these two-week trips, American nurses were able to observe health care facilities and talk to health care providers in other countries. Although short visits such as these are not able to provide in-depth understanding of the health care systems or cultures involved, they have provided provocative ideas about how our own health care system differs from others. In some instances, our health care system seems the better one, but in many instances we were able to gain insights from our observations that may help us improve our own system of nursing and health care. This is the first in a series of three articles reporting professional exchange tours between American nurses and nurses of other countries. In this article, the health care system of the Soviet Union is discussed and compared to the United States' system of health care. From this comparison come several insights into ways for improving health care delivery.