The science of clinical practice: disease diagnosis or patient prognosis? Evidence about "what is likely to happen" should shape clinical practice.

BACKGROUND: Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful. DISCUSSION: Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous 'yes' or 'no' is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient's future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome. SUMMARY: Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care

Crystal and melt inclusion timescales reveal the evolution of magma migration before eruption

Volatile element concentrations measured in melt inclusions are a key tool used to understand magma migration and degassing, although their original values may be affected by different re-equilibration processes. Additionally, the inclusion-bearing crystals can have a wide range of origins and ages, further complicating the interpretation of magmatic processes. To clarify some of these issues, here we combined olivine diffusion chronometry and melt inclusion data from the 2008 eruption of Llaima volcano (Chile). We found that magma intrusion occurred about 4 years before the eruption at a minimum depth of approximately 8 km. Magma migration and reaction became shallower with time, and about 6 months before the eruption magma reached 3–4 km depth. This can be linked to reported seismicity and ash emissions. Although some ambiguities of interpretation still remain, crystal zoning and melt inclusion studies allow a more complete understanding of magma ascent, degassing, and volcano monitoring data.NRF (Natl Research Foundation, S’pore)MOE (Min. of Education, S’pore)Published versio

The Impact of Oxygen on Metabolic Evolution: A Chemoinformatic Investigation

The appearance of planetary oxygen likely transformed the chemical and biochemical makeup of life and probably triggered episodes of organismal diversification. Here we use chemoinformatic methods to explore the impact of the rise of oxygen on metabolic evolution. We undertake a comprehensive comparative analysis of structures, chemical properties and chemical reactions of anaerobic and aerobic metabolites. The results indicate that aerobic metabolism has expanded the structural and chemical space of metabolites considerably, including the appearance of 130 novel molecular scaffolds. The molecular functions of these metabolites are mainly associated with derived aspects of cellular life, such as signal transfer, defense against biotic factors, and protection of organisms from oxidation. Moreover, aerobic metabolites are more hydrophobic and rigid than anaerobic compounds, suggesting they are better fit to modulate membrane functions and to serve as transmembrane signaling factors. Since higher organisms depend largely on sophisticated membrane-enabled functions and intercellular signaling systems, the metabolic developments brought about by oxygen benefit the diversity of cellular makeup and the complexity of cellular organization as well. These findings enhance our understanding of the molecular link between oxygen and evolution. They also show the significance of chemoinformatics in addressing basic biological questions

Impacts of chemical gradients on microbial community structure

Succession of redox processes is sometimes assumed to define a basic microbial community structure for ecosystems with oxygen gradients. In this paradigm, aerobic respiration, denitrification, fermentation and sulfate reduction proceed in a thermodynamically determined order, known as the ‘redox tower’. Here, we investigated whether redox sorting of microbial processes explains microbial community structure at low-oxygen concentrations. We subjected a diverse microbial community sampled from a coastal marine sediment to 100 days of tidal cycling in a laboratory chemostat. Oxygen gradients (both in space and time) led to the assembly of a microbial community dominated by populations that each performed aerobic and anaerobic metabolism in parallel. This was shown by metagenomics, transcriptomics, proteomics and stable isotope incubations. Effective oxygen consumption combined with the formation of microaggregates sustained the activity of oxygen-sensitive anaerobic enzymes, leading to braiding of unsorted redox processes, within and between populations. Analyses of available metagenomic data sets indicated that the same ecological strategies might also be successful in some natural ecosystems

Tracing the effects of high-pressure metasomatic fluids and seawater alteration in blueschist-facies overprinted eclogites: Implications for subduction channel processes

Eclogites from the Tian Shan high-pressure/low-temperature (HP/LT) metamorphic belt show evidence for successively increasing metasomatic alteration with increasing retrograde, blueschist-facies overprint. To constrain the source(s) of the metasomatizing fluid and to evaluate elemental and isotopic changes during this overprint, two sequences of eclogite-blueschist transitions were investigated: A layered transition from eclogite to blueschist (FTS 9–1 sequence) and blueschist-facies overprinted pillow metabasalts (FTS 4 samples). Geochemical trends based on the relationships of K, Ba, Rb and Th are consistent with HP metasomatism, but distinct from typical seafloor alteration trends. In contrast, oxygen isotope ratios in garnet (δ18OV-SMOW = 7.3–8.7‰) and omphacite (δ18OV-SMOW = 8.2–9.7‰) are similar to δ18OV-SMOW in bulk low-temperature altered oceanic crust (AOC), suggesting O isotopic preservation of a seafloor alteration signature. Carbonate crystallization related to the metasomatic overprint demonstrate CO2 mobility during subduction and potential C storage in HP metamorphic rocks. Carbon isotope ratios in the two sequences differ markedly: Disseminated calcite in the layered FTS 9–1 sequence has δ13CV-PDB = − 9.14 ± 0.19‰, whereas vein-forming ankerite in the pillow metabasalts has δ13CV-PDB = − 2.08 ± 0.12‰. The ankerite reflects an inorganic marine/hydrothermal signature, as observed in ophiolites, whereas the low δ13CV-PDB values from the calcite point to a contribution of organic carbon. The time when the metasomatic overprint occurred is estimated to be ~ 320 ± 11 Ma based on a Rb-Sr isochron age of six blueschist samples from the pillow metabasalts, which is in agreement with active subduction in this region. Initial (T = 320 Ma) 87Sr/86Sr ratios for all HP/LT rocks range from 0.7059 – 0.7085, and εNd320Ma varies from − 0.4 to + 10.9. Both eclogite-blueschist sequences have initial Sr isotope compositions (87Sr/86Sr ~ 0.707) that are significantly higher than those of typical oceanic mantle-derived basalts. They are thought to derive from a fluid that preserved the Sr isotopic signature of seawater by fluid-rock interaction with seawater-altered oceanic lithosphere in a subduction channel. Mixing models between eclogite and various fluids suggest that the contribution of a sediment-derived fluid was likely less than 20%. A fluid predominantly derived from seawater-altered oceanic lithosphere is also supported by the calculated O isotope composition of the fluids (10.2 – 11.2‰). It is thus evident that subduction channel fluids carry complex, mixed elemental and isotopic signatures, which reflect the composition of their source rocks modified by interaction with various other lithologies. Highlights ► Eclogites from the Tian Shan show blueschist-facies metasomatic overprint ► Fluid-induced metasomatism occurred at 320 ± 11 Ma ► Fluid predominantly derived from seawater-altered oceanic lithosphere ► Carbonates reflect C sequestration of mixture of organic and inorganic component

'Gut health': a new objective in medicine?

'Gut health' is a term increasingly used in the medical literature and by the food industry. It covers multiple positive aspects of the gastrointestinal (GI) tract, such as the effective digestion and absorption of food, the absence of GI illness, normal and stable intestinal microbiota, effective immune status and a state of well-being. From a scientific point of view, however, it is still extremely unclear exactly what gut health is, how it can be defined and how it can be measured. The GI barrier adjacent to the GI microbiota appears to be the key to understanding the complex mechanisms that maintain gut health. Any impairment of the GI barrier can increase the risk of developing infectious, inflammatory and functional GI diseases, as well as extraintestinal diseases such as immune-mediated and metabolic disorders. Less clear, however, is whether GI discomfort in general can also be related to GI barrier functions. In any case, methods of assessing, improving and maintaining gut health-related GI functions are of major interest in preventive medicine

Cold spells in the Nordic Seas during the early Eocene Greenhouse

Abstract The early Eocene (c. 56 - 48 million years ago) experienced some of the highest global temperatures in Earth’s history since the Mesozoic, with no polar ice. Reports of contradictory ice-rafted erratics and cold water glendonites in the higher latitudes have been largely dismissed due to ambiguity of the significance of these purported cold-climate indicators. Here we apply clumped isotope paleothermometry to a traditionally qualitative abiotic proxy, glendonite calcite, to generate quantitative temperature estimates for northern mid-latitude bottom waters. Our data show that the glendonites of the Danish Basin formed in waters below 5 °C, at water depths of &lt;300 m. Such near-freezing temperatures have not previously been reconstructed from proxy data for anywhere on the early Eocene Earth, and these data therefore suggest that regionalised cool episodes punctuated the background warmth of the early Eocene, likely linked to eruptive phases of the North Atlantic Igneous Province.</jats:p

Stepwise oxygenation of the Paleozoic atmosphere

Oxygen is essential for animal life, and while geochemical proxies have been instrumental in determining the broad evolutionary history of oxygen on Earth, much of our insight into Phanerozoic oxygen comes from biogeochemical modelling. The GEOCARBSULF model utilizes carbon and sulphur isotope records to produce the most detailed history of Phanerozoic atmospheric O2 currently available. However, its predictions for the Paleozoic disagree with geochemical proxies, and with non-isotope modelling. Here we show that GEOCARBSULF oversimplifies the geochemistry of sulphur isotope fractionation, returning unrealistic values for the O2 sourced from pyrite burial when oxygen is low. We rebuild the model from first principles, utilizing an improved numerical scheme, the latest carbon isotope data, and we replace the sulphur cycle equations in line with forwards modelling approaches. Our new model, GEOCARBSULFOR, produces a revised, highly-detailed prediction for Phanerozoic O2 that is consistent with available proxy data, and independently supports a Paleozoic Oxygenation Event, which likely contributed to the observed radiation of complex, diverse fauna at this time