Measures of effectiveness in medical research: Reporting both absolute and relative measures

Biomedical research, especially pharmaceutical research, has been criticised for engaging in practices that lead to over-estimations of the effectiveness of medical treatments. A central issue concerns the reporting of absolute and relative measures of medical effectiveness. In this paper we critically examine proposals made by Jacob Stegenga to (a) give priority to the reporting of absolute measures over relative measures, and (b) downgrade the measures of effectiveness (effect sizes) of the treatments tested in clinical trials (Stegenga, 2015a). After exposing significant flaws in a central case study used by Stegenga to bolster his first proposal (a), we go on to argue that neither of these proposals is defensible (a or b). We defend the practice, in line with the New England Journal of Medicine, of reporting both absolute and relative measures whenever feasible.     

John Wheeler’s Desert Island: The conservatism of non-empirical physics

This paper argues that non-empirical physics, as paradigmatically embodied by string theory, is a conservative research program, in spite of appearances. John Wheeler's 1950s research program of "daring conservatism" is identified as another non-empirical research program that checks all the same boxes as string theory. This case study is used to further analyze the connection between conservatism and a non-empirical approach. It is concluded that the prime difficulty of non-empirical physics is not that it involves unbridled speculation, but that the lack of empirical input prevents it from achieving revolutionary progress.     

拉伐尔喷嘴中气粉流的计算及喷嘴扩张段设计

根据作者关于拉伐尔喷嘴中气粉流行为的数学模型,采用确定喷嘴临界截面的压强检验法,对不同的粉气比 λ=0.1 ～0.9和不同的粉粒直径d_p=1～50 μm,讨论了对喷嘴扩张段的设计。计算表明,临界锥角随λ的增大而增大,且随粉粒直径d_p的减小而增大。     

Chiral supramolecular gold-cysteine nanoparticles: Chiroptical and nonlinear optical properties

Cysteine is a sulfur-containing amino acid that easily coordinates to soft metal ions and grafts to noble metal surfaces. We report a simple synthetic approach for the production of chiral gold-cysteine polymeric nanoparticles soluble in water. Conjugation of cysteine with gold in a polymeric way, leading to ~50 nm diameter nanoparticles, resulted in the generation of new characteristic circular dichroism (CD) signals in the region of 250–400 nm, whereas no CD signal changes were found with cysteine alone. We also investigate their nonlinear optical properties after two-photon absorption. Two-photon emission spectra and first hyper-polarizabilities, as obtained by the hyper-Rayleigh scattering technique, of these particles are presented.     

The importance of regional geology in the geological theories of Abraham Gottlob Werner: a contrary opinion

It has been and still is commonly believed by geologists and historians of geology alike that geological theory is an extrapolation from the empirical knowledge of the geology of a region. Abraham Gottlob Werner (1749–1817), whose theory concerning the origin of basalt and the minor role of volcanoes and the major role of water in the history of the earth's crust was eventually proven wrong in some respects, is usually cited as the prime example of a geologist who had not ventured beyond the confines of his native region, Saxony, and had developed a universal geological theory based almost entirely on his observations of that region. In this essay I show that the geology of Saxony played a relatively unimportant role in the development of Werner's universal geological theory; that he became a neptunist before he had closely examined the geology of Saxony; and that his explanation of the history of the earth's crust was as reasonable, if not more reasonable, than the explanations brought forth by those of his contemporaries who opposed his views.     

Substrate ambiguity among the nudix hydrolases: biologically significant, evolutionary remnant, or both?

Many members of the nudix hydrolase family exhibit considerable substrate multispecificity and ambiguity, which raises significant issues when assessing their functions in vivo and gives rise to errors in database annotation. Several display low antimutator activity when expressed in bacterial tester strains as well as some degree of activity in vitro towards mutagenic, oxidized nucleotides such as 8-oxo-dGTP. However, many of these show greater activity towards other nucleotides such as ADP-ribose or diadenosine tetraphosphate (Ap₄A). The antimutator activities have tended to gain prominence in the literature, whereas they may in fact represent the residual activity of an ancestral antimutator enzyme that has become secondary to the more recently evolved major activity after gene duplication. Whether any meaningful antimutagenic function has also been retained in vivo requires very careful assessment. Then again, other examples of substrate ambiguity may indicate as yet unexplored regulatory systems. For example, bacterial Ap₄A hydrolases also efficiently remove pyrophosphate from the 5′ termini of mRNAs, suggesting a potential role for Ap₄A in the control of bacterial mRNA turnover, while the ability of some eukaryotic mRNA decapping enzymes to degrade IDP and dIDP or diphosphoinositol polyphosphates (DIPs) may also be indicative of new regulatory networks in RNA metabolism. DIP phosphohydrolases also degrade diadenosine polyphosphates and inorganic polyphosphates, suggesting further avenues for investigation. This article uses these and other examples to highlight the need for a greater awareness of the possible significance of substrate ambiguity among the nudix hydrolases as well as the need to exert caution when interpreting incomplete analyses.