Effect of regression to the mean on decision making in health care

Knowledge of regression to the mean can help with everything from interpreting test results to improving your career prospects. All healthcare professionals should be aware of its implication

Evidence for risk of bias in cluster randomised trials: review of recent trials published in three general medical journals

Objective To examine the prevalence of a risk of bias associated with the design and conduct of cluster randomised controlled trials among a sample of recently published studies. Design Retrospective review of cluster randomised trials published in the BMJ, Lancet, and New England Journal of Medicine from January 1997 to October 2002. Main outcome measures Prevalence of secure randomisation of clusters, identification of participants before randomisation (to avoid foreknowledge of allocation), differential recruitment between treatment arms, differential application of inclusion and exclusion criteria, and differential attrition. Results Of the 36 trials identified, 24 were published in the BMJ, I I in the Lancet, and a single trial in the New England journal of Medicine. At the cluster level, 15 (42%) trials provided evidence for secure allocation and 25 (69%) used stratified allocation. Few trials showed evidence of imbalance at the cluster level. However, some evidence of susceptibility to risk of bias at the individual level existed in 14 (39%) studies. Conclusions Some recently published cluster randomised trials may not have taken adequate precautions to guard against threats to the internal validity of their design

Population Genetics of Rare Variants and Complex Diseases

Identifying drivers of complex traits from the noisy signals of genetic variation obtained from high throughput genome sequencing technologies is a central challenge faced by human geneticists today. We hypothesize that the variants involved in complex diseases are likely to exhibit non-neutral evolutionary signatures. Uncovering the evolutionary history of all variants is therefore of intrinsic interest for complex disease research. However, doing so necessitates the simultaneous elucidation of the targets of natural selection and population-specific demographic history. Here we characterize the action of natural selection operating across complex disease categories, and use population genetic simulations to evaluate the expected patterns of genetic variation in large samples. We focus on populations that have experienced historical bottlenecks followed by explosive growth (consistent with most human populations), and describe the differences between evolutionarily deleterious mutations and those that are neutral. Genes associated with several complex disease categories exhibit stronger signatures of purifying selection than non-disease genes. In addition, loci identified through genome-wide association studies of complex traits also exhibit signatures consistent with being in regions recurrently targeted by purifying selection. Through simulations, we show that population bottlenecks and rapid growth enables deleterious rare variants to persist at low frequencies just as long as neutral variants, but low frequency and common variants tend to be much younger than neutral variants. This has resulted in a large proportion of modern-day rare alleles that have a deleterious effect on function, and that potentially contribute to disease susceptibility.Comment: 36 pages, 7 figure

New limits on variation of the fine-structure constant using atomic dysprosium

We report on the spectroscopy of radio-frequency transitions between nearly-degenerate, opposite-parity excited states in atomic dysprosium (Dy). Theoretical calculations predict that these states are very sensitive to variation of the fine-structure constant, $\alpha$, owing to large relativistic corrections of opposite sign for the opposite-parity levels. The near degeneracy reduces the relative precision necessary to place constraints on variation of $\alpha$ competitive with results obtained from the best atomic clocks in the world. Additionally, the existence of several abundant isotopes of Dy allows isotopic comparisons that suppress common-mode systematic errors. The frequencies of the 754-MHz transition in $^{164}$Dy and 235-MHz transition in $^{162}$Dy were measured over the span of two years. Linear variation of $\alpha$ is found to be $\dot{\alpha}/\alpha = (-5.8\pm6.9)\times10^{-17}$ yr$^{-1}$, consistent with zero. The same data are used to constrain the dimensionless parameter $k_\alpha$, characterizing a possible coupling of $\alpha$ to a changing gravitational potential. We find that $k_\alpha = (-5.5\pm5.2)\times10^{-7}$, essentially consistent with zero and the best constraint to date.Comment: 5 pages, 3 figure

Parable of two agencies, one of which randomizes

This article examines the design of evaluations in settings where there is a choice as to how an intervention is to be introduced and evaluated. It uses data from a supervision program for offenders on probation in the UK (Bruce and Hollin forthcoming) that had been indicated by a pilot evaluation in one probation area to merit wider-scale implementation and evaluation. For the remaining two probation areas in the region, a randomized controlled allocation of participants to conditions was recommended. One of the areas adopted a stepped wedge design, in which probation offices were randomly allocated sequentially to the program. The second area opted to launch the program across the whole area simultaneously, with a retrospective sample as control group. The article compares the results of implementation in each probation area and seeks to draw wider inferences about the management of program implementation and the randomized controlled designs appropriate for similar field studies. </jats:p