Can we really predict risk of cancer?

Background: Growing awareness of the potential to predict a person's future risk of cancer has resulted in the development of numerous algorithms. Such algorithms aim to improve the ability of policy makers, doctors and patients to make rational decisions about behaviour modification or surveillance, with the expectation that this activity will lead to overall benefit. There remains debate however, about whether accurate risk prediction is achievable for most cancers. Methods: We conducted a brief narrative review of the literature regarding the history and challenges of risk prediction, highlighting our own recent experiences in developing tools for oesophageal adenocarcinoma. Results and conclusions: While tools for predicting future risk of cardiovascular outcomes have been translated successfully to clinical practice, the experience with cancer risk prediction has been mixed. Models have now been developed and validated for predicting risk of melanoma and cancers of the breast, colo-rectum, lung, liver, oesophagus and prostate, and while several of these have adequate performance at the population-level, none to date have adequate discrimination for predicting risk in individual patients. Challenges of individual risk prediction for cancer are many, and include long latency, multiple risk factors of mostly small effect, and incomplete knowledge of the causal pathways.     

Can statin therapy really reduce the risk of Alzheimer's disease and slow its progression?

PURPOSE OF REVIEW: Statins are the most used cholesterol-lowering agents worldwide. Earlier studies suggested that they may have preventive effects in Alzheimer's disease. However, prospective studies have questioned this hypothesis. RECENT FINDINGS: Statins regulate beta-amyloid metabolism and microglial activation. Pathologically, patients with Alzheimer's disease have more severe atherosclerosis in cerebral arteries than do controls. Such lesions may cause cerebral hypoperfusion, a risk factor for dementia and cognitive decline. Although most population-based studies have failed to show a beneficial effect of statins in Alzheimer's disease, two randomized controlled trials suggested that statins slow cognitive decline in mild to moderate Alzheimer's disease. SUMMARY: There is still some hope that statins reduce the incidence of Alzheimer's disease and slow its progression. Large-scale randomized controlled trials of simvastatin and atorvastatin for mild to moderate Alzheimer's disease are underway, which might provide more conclusive results than earlier studies.     

Can the fall in Avon's sudden infant death rate be explained by changes in sleeping position?

OBJECTIVE--To examine the impact of changing practice with regard to infant sleeping position on mortality from the sudden infant death syndrome. DESIGN--A population based study of all infants dying suddenly and unexpectedly during February 1990 to July 1991, and two groups of controls; one comprising every 125th baby born to Avon residents and the other comprising pairs of infants matched to each index case for age, neighbourhood, and date of study. Information about sleeping position was collected at home visits soon after the index baby''s death or, for the population based controls, on several occasions in the first six months of life. The design was comparable to that of an earlier study of the same population. SETTING--County of Avon. SUBJECTS--35 infants who died suddenly and unexpectedly (32 of the sudden infant death syndrome), 70 matched controls, and 152 population based controls. RESULTS--The prevalence of prone sleeping in the matched controls was much lower than that found in an earlier study in Avon (28% (18/64) 1990-1 v 58% (76/131) 1987-9; p less than 0.001) and was comparable with the prevalence in population based controls (29%). This would be expected to lead to a reduction in the incidence of the sudden infant death syndrome to 2.0/1000 live births (95% confidence interval 1.8/1000 to 2.5/1000). The actual mortality fell from 3.5/1000 in 1987-9 to 1.7/1000. CONCLUSION--The fall in mortality can be almost entirely accounted for by the reduction in prone sleeping, suggesting a causal relation exists between them. Side and supine positions confer protection but the side position is unstable and the infant may roll prone. We therefore recommend supine as the safest sleeping position for babies.     

What really happens in the neutrophil phagosome?

Current viewpoints concerning the bactericidal mechanisms of neutrophils are reviewed from a perspective that emphasizes challenges presented by the inability to duplicate ex vivo the intracellular milieu. Among the challenges considered are the influences of confinement upon substrate availability and reaction dynamics, direct and indirect synergistic interactions between individual toxins, and bacterial responses to stressors. Approaches to gauging relative contributions of various oxidative and nonoxidative toxins within neutrophils using bacteria and bacterial mimics as intrinsic probes are also discussed.     

What really happened in the late Triassic?

Major extinctions occurred both in the sea and on land during the Late Triassic in two major phases, in the middle to late Carnian and, 12–17 Myr later, at the Triassic‐Jurassic boundary. Many recent reports have discounted the role of the earlier event, suggesting that it is (1) an artefact of a subsequent gap in the record, (2) a complex turnover phenomenon, or (3) local to Europe. These three views are disputed, with evidence from both the marine and terrestrial realms. New data on terrestrial tetrapods suggests that the late Carnian event was more important than the end‐Triassic event. For tetrapods, the end‐Triassic extinction was a whimper that was followed by the radiation of five families of dinosaurs and mammal‐like reptiles, while the late Carnian event saw the disappearance of nine diverse families, and subsequent radiation of 13 families of turtles, crocodilomorphs, pterosaurs, dinosaurs, lepidosaurs and mammals. Also, for many groups of marine animals, the Carnian event marked a more significant turning point in diversification than did the end‐Triassic event.     

Has the hippocampus really forgotten about space?

Several lines of evidence, including the discovery of place cells, have contributed to the notion that the hippocampus serves primarily to navigate the environment, as a repository of spatial memories, like a drawer full of charts; and that in some species it has exapted on this original one an episodic memory function. We argue that recent evidence questions the primacy of space, and points at memory load, whether spatial or not, as the challenge that mammalian hippocampal circuitry has evolved to meet.     

Did psychrophilic enzymes really win the challenge?

Organisms living in permanently cold environments, which actually represent the greatest proportion of our planet, display at low temperatures metabolic fluxes comparable to those exhibited by mesophilic organisms at moderate temperatures. They produce cold-evolved enzymes partially able to cope with the reduction in chemical reaction rates and the increased viscosity of the medium induced by low temperatures. In most cases, the adaptation is achieved through a reduction in the activation energy, leading to a high catalytic efficiency, which possibly originates from an increased flexibility of either a selected area of or the overall protein structure. This enhanced plasticity seems in return to be responsible for the weak thermal stability of cold enzymes. These particular properties render cold enzymes particularly useful in investigating the possible relationships existing between stability, flexibility, and specific activity and make them potentially unrivaled for numerous biotechnological tasks. In most cases, however, the adaptation appears to be far from being fully achieved.