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.

Cooperative processes governing formation of small pentanuclear lanthanide(III) nanoclusters and energy transport within and between them.

Syntheses, lanthanide quantitative analyses, mass spectrometry and luminescence spectroscopy, and decay dynamics of crystals containing pentanuclear hetero-lanthanide(III) nanoclusters [(Ln'(5-x)Ln(x))(NO(3))(6)(mu(5)-OH)(mu(4)-L)(2)] (0 < or = x < or = 5), Ln' = Eu or Tb; Ln = La-Nd, Sm-Ho (hereafter Ln'(5-x) Ln(x)) were undertaken in search of information on factors governing self-assembly processes by which the clusters are formed and electronic interactions within and between them. The data obtained are consistent with the self-assembly of Ln'(5-x) Ln(x) nanoclusters being a concerted process featuring a profound expression of complementarity among mutually bridging [Ln(mu(4)-L](-) and [Ln(NO(3))(2)](+) components. The energy transport regime in crystals of Eu(5-x) Ln(x) is in the dynamic regime when x = 0 or Ln = La and, at 293 K, Ln = Dy, despite the presence of two crystallographically different Eu(3+) coordination environments which give rise to a doublet in the excitation and emission spectra of Eu(3+)((5)D(0)). The luminescence decay behavior of Eu(3+)((5)D(0)) in Eu(5-x) Ln(x) (Ln = Dy (for 77 K), Sm) is intermediate between the static and dynamic limits and reveals extensive electronic coupling among lanthanide ions, including many-body processes at relatively high Dy(3+) or Sm(3+) concentrations.

The effects of pentoxifylline on spinal cord blood flow after experimental spinal cord injury.

Previous clinical and experimental investigations have suggested that pentoxifylline, a methylxanthine, can improve cerebrovascular circulation and reduce cerebral edema in cerebrovascular disorders. Pentoxifylline's mechanism of action includes such rheologic effects as enhanced red cell deformability, alterations in leukocyte activation, and modification of coagulation parameters. The purpose of our investigation was to determine the effects of pentoxifylline in an experimental spinal cord injury model. A compression device was used to cause a reproducible spinal cord injury in adult female albino rats. Spinal cord blood flow was monitored using a laser Doppler flow meter pre- and postinjury for 4 hours. The experimental group (N = 7) was injected with pentoxifylline 10 minutes prior to injury. The control group (N = 5) received an identical protocol, except that this group was injected with an equal amount of saline. Results of this investigation revealed that pentoxifylline treatment significantly increased spinal cord blood flow. In the pentoxifylline-treated group, spinal cord blood flow was significantly higher from 120 to 240 minutes postinjury compared with that of the control group. We conclude that via its multiple physiologic effects, pentoxifylline significantly improves spinal cord blood flow in experimental spinal cord injury.

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.

The need for a new biological model in geratology.

Disease classes have hitherto been based on anatomical pathology and structural lesions belonging to an earlier ecological medical model involving classification. The diseases of ageing now coming to dominate clinical practice evolve across the clinical threshold in middle age parallel to changes occurring in the internal environment. The concept 'multiple pathology' used to describe the plural features of biological changes now requires new intellectual tools by which to understand overlap phenomena. Boolean algebra and Set Theory are proposed as the relevant enabling concepts, and their application to modern clinical practice is discussed.

Hypothesis: old people would benefit from a patient-held standardized primary health care record.

While many advances have been made in primary health care, for old people it has lagged behind other areas. The case is made for the adoption of a standard primary-care record for people aged over 70 years to be retained by the patient and attached behind the front door, where it would be available to ambulance crews, deputizing doctors and other community health workers. It would also be of value to the elderly patient when travelling or registering with a new doctor. Such a focus on information would facilitate communication between professional workers and increase productivity.