Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD

Energetic Materials and Atomic Force Microscopy: Structure and Kinetics

Understanding the structure and composition of energetic materials at the sub-micron level is imperative for the fundamental studies of hot-spot formation and structural composition of energetic materials. Using in situ high-temperature AFM we have observed the solid-solid phase transition of Octahydro-1,3,5,7,-tetrazocine, HMX, in real time. Massive surface reconstruction occurs during the 1st-order transition. The temperature induced increase in void space and surface roughness observed in the delta phase polymorph of HMX serve to increase the growth rate and volume of shock initiated hot spots and possibly reaction sensitivity. HMX exists in four solid phase polymorphs, labeled {alpha}, {beta}, {chi}, and {delta}. The phase conversion of the {beta} phase to the {delta} phase involves a major disruption of the crystal lattice. The energy required to bring about this change is a measurable quantity. Multiple thermal analysis techniques carried out simultaneously are preferable because the results are directly comparable. Thermal methods are dynamic techniques, where heating or cooling is applied to a sample, unless isothermal conditions are employed. Thermogravimetic Analysis, TGA, can be used to quantify decomposition components in a substance while Differential Thermal Analysis, DTA, can be used to measure the heat flow or the specific heat capacity, with respect to time and temperature. The advantage of TGA/DTA analysis is that the measurement of weight loss and heat flow are taken simultaneously and the observed events are directly related with respect to time and temperature. TGA/DTA experiments were performed to help us take a different look at the chemical nature of HMX and aid us in understanding the void formation process

The practicalities of using CFCs and SF6 for groundwater dating and tracing

Knowledge of groundwater residence time is important in understanding key issues in the evolution of water quality, whether this occurs due to water–rock interaction or simply by mixing or contamination. The build-up in the atmosphere of the trace gases chlorofluorocarbons (CFCs) and sulphur hexafluoride (SF6) from the middle of the last century offers a convenient way of dating waters up to ~60 yrs old. The gases are well-mixed in the atmosphere so their input functions are not area-specific as is the case with tritium. While any one of these trace gases can in principle provide a groundwater age, when two or more are measured on water samples the potential exists to distinguish between different modes of flow including piston flow, exponential flow and simple end-member mixing. As with all groundwater dating methods, caveats apply. Factors such as recharge temperature and elevation must be reasonably well-constrained. Primarily for SF6, the phenomenon of ‘excess air’ also requires consideration. Primarily for the CFCs, local sources of contamination need to be considered, as do redox conditions. For both SF6 and the CFCs, the nature and thickness of the unsaturated zone need to be factored into residence time calculations. However, as an inexpensive dating method, the trace gases can be applied to a wide range of groundwater problems where traditional age indicators might once have been used more sparingly. Examples include tracing flowlines, detecting small modern inputs in ‘old’ waters, and pollution risk assessment. In the future, with the main CFCs are already declining in the atmosphere, new anthropogenic trace gases are likely to take their place

Between family and friends: A longitudinal study of friendship choice

The increasing role for chosen friends is a key element in current debates on individualization and the transformation of intimacy. This paper describes the changes in friendship choices over time and demonstrates how life events subsequently impact on those choices. We primarily distinguish between kin and non-kin nominations of friends and how these may be related to the social and economic turbulence inherent in late modernity. Analyses of data from ten years of the British Household Panel Survey showed that kin nominations still form a significant proportion of all friends but increasingly so with age and over time as people age. Life events, such as divorce or death of a partner, have large effects on the likelihood of changes in friendship choices as did gender, age, marital status and social class. We frame these results in a discussion of the saliency and nature of friendship at stages of the life course and conclude that the case for a general secular shift to choosing non-kin friendships rather than kin-based friendship is not demonstrated. © London School of Economics and Political Science 2005