While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP-CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20-1.79, P=1.68x10-4). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92-1.18, P=0.49), 0.94 (95% CI: 0.84-1.05, P= 0.27), and 0.98 (95% CI: 0.85-1.12, P=0.75) respectively. A genetic risk score for 3-hydoxy-3-methylglutaryl-coenzyme A reductase (HMGCR) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR=0.69, 95% CI: 0.49-0.99, P=0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia.

Analytical expressions are derived for the longitudinal flow in a superhydrophobic microchannel where flat menisci in the Cassie state have partially invaded the grooves between no-slip blades. Using these solutions, the effective slip lengths are computed and compared with recent analytical results for unbounded shear flow over the same class of surfaces. Expressions for the first-order corrections to these effective slip lengths when the menisci are weakly curved are also derived. A mathematical connection to superhydrophobic channel flows where the flat menisci are still pinned to the tops of the pillars is also made, resulting in novel analytical expressions for those solutions too.

ObjectiveTo assess the cost-effectiveness of using cheap-but-noisy outcome measures, such as a short and simple questionnaire.BackgroundTo detect associations reliably, studies must avoid bias and random error. To reduce random error, we can increase the size of the study and increase the accuracy of the outcome measurement process. However, with fixed resources there is a trade-off between the number of participants a study can enrol and the amount of information that can be collected on each participant during data collection.MethodTo consider the effect on measurement error of using outcome scales with varying numbers of categories we define and calculate the Variance from Categorisation that would be expected from using a category midpoint; define the analytic conditions under-which such a measure is cost-effective; use meta-regression to estimate the impact of participant burden, defined as questionnaire length, on response rates; and develop an interactive web-app to allow researchers to explore the cost-effectiveness of using such a measure under plausible assumptions.ResultsCompared with no measurement, only having a few categories greatly reduced the Variance from Categorization. For example, scales with five categories reduce the variance by 96% for a uniform distribution. We additionally show that a simple measure will be more cost effective than a gold-standard measure if the relative increase in variance due to using it is less than the relative increase in cost from the gold standard, assuming it does not introduce bias in the measurement. We found an inverse power law relationship between participant burden and response rates such that a doubling the burden on participants reduces the response rate by around one third. Finally, we created an interactive web-app (https://benjiwoolf.shinyapps.io/cheapbutnoisymeasures/) to allow exploration of when using a cheap-but-noisy measure will be more cost-effective using realistic parameter.ConclusionCheap-but-noisy questionnaires containing just a few questions can be a cost effect way of maximising power. However, their use requires a judgment on the trade-off between the potential increase in risk information bias and the reduction in the potential of selection bias due to the expected higher response rates.Key Messages-A cheap-but-noisy outcome measure, like a short form questionnaire, is a more cost-effective method of maximising power than an error free gold standard when the percentage increase in noise from using the cheap-but-noisy measure is less than the relative difference in the cost of administering the two alternatives.-We have created an R-shiny app to facilitate the exploration of when this condition is met at https://benjiwoolf.shinyapps.io/cheapbutnoisymeasures/-Cheap-but-noisy outcome measures are more likely to introduce information bias than a gold standard, but may reduce selection bias because they reduce loss-to-follow-up. Researchers therefore need to form a judgement about the relative increase or decrease in bias before using a cheap-but-noisy measure.-We would encourage the development and validation of short form questionnaires to enable the use of high quality cheap-but-noisy outcome measures in randomised controlled trials.

Summary Theoretical evidence is given that it is possible for superhydrophobicity to enhance steady laminar convective heat transfer in pressure-driven flow along a circular pipe or tube with constant heat flux. Superhydrophobicity here refers to the presence of adiabatic no-shear zones in an otherwise solid no-slip boundary. Adding such adiabatic no-shear zones reduces not only hydrodynamic friction, leading to greater fluid volume fluxes for a given pressure gradient, but also reduces the solid surface area through which heat enters the fluid. This leads to a delicate trade-off between competing mechanisms so that the net effect on convective heat transfer along the pipe, as typically measured by a Nusselt number, is not obvious. Existing evidence in the literature suggests that superhydrophobicity always decreases the Nusselt number, and therefore compromises the net heat transfer. In this theoretical study, we confirm this to be generally true but, significantly, we identify a situation where the opposite occurs and the Nusselt number increases thereby enhancing convective heat transfer along the pipe.

At high surface Péclet numbers, it is common to associate the presence of surfactants with surface immobilization, where a free surface becomes indistinguishable from a no-slip surface. A different mechanism has recently been proposed for longitudinal shear flow along a unidirectional trench (Baier & Hardt, J. Fluid Mech., vol. 949, 2022, A34) wherein, at high Marangoni numbers, the meniscus spanning the finite-length trench becomes a constant-shear-stress surface due to contamination by incompressible surfactant. That model predicts recirculating interfacial flows on the meniscus, a phenomenon that has been observed experimentally (Song et al., Phys. Rev. Fluids, vol. 3, issue 3, 2018, 033303). By finding an explicit solution to the constant-shear-stress model at all protrusion angles and calculating the effective slip length for a dilute mattress of such surfactant-laden trenches, we show that those effective slip lengths are almost indistinguishable from those for a surface whose menisci have the same deflection but have been completely immobilized (i.e. they are no-slip surfaces). This means that, despite the presence of non-trivial recirculating vortical flows on the menisci, the aggregate slip characteristics of such surfaces are that they have been effectively immobilized. This surprising result underscores the need for caution in comparing theory with experiments based on effective slip properties alone.