Disease Progression Modelling in Chronic Obstructive Pulmonary Disease (COPD)

RATIONALE: The decades-long progression of Chronic Obstructive Pulmonary Disease (COPD) renders identifying different trajectories of disease progression challenging. OBJECTIVES: To identify subtypes of COPD patients with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference (SuStaIn)", and to evaluate the utility of SuStaIn for patient stratification in COPD. METHODS: We applied SuStaIn to cross-sectional CT imaging markers in 3698 GOLD1-4 patients and 3479 controls from the COPDGene study to identify COPD patient subtypes. We confirmed the identified subtypes and progression patterns using ECLIPSE data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data. MEASUREMENTS AND MAIN RESULTS: We identified two trajectories of disease progression in COPD: a "Tissue→Airway" subtype (n=2354, 70.4%) in which small airway dysfunction and emphysema precede large-airway wall abnormalities, and an "Airway→Tissue" subtype (n=988, 29.6%) in which large-airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV1/FVC decline (r=-0.16 (p<0.001) in the Tissue→Airway group; r=-0.14 (p=0.011) in the Airway→Tissue group). SuStaIn placed 30% of smokers with normal lung function at non-baseline stages suggesting imaging changes consistent with early COPD. Individuals with early changes were 2.5 times more likely to meet COPD diagnostic criteria at follow-up. CONCLUSIONS: We demonstrate two distinct patterns of disease progression in COPD using SuStaIn, likely representing different endotypes. One-third of healthy smokers have detectable imaging changes, suggesting a new biomarker of 'early COPD'

Preventing type 2 diabetes mellitus in Qatar by reducing obesity, smoking, and physical inactivity: mathematical modeling analyses.

BACKGROUND: The aim of this study was to estimate the impact of reducing the prevalence of obesity, smoking, and physical inactivity, and introducing physical activity as an explicit intervention, on the burden of type 2 diabetes mellitus (T2DM), using Qatar as an example. METHODS: A population-level mathematical model was adapted and expanded. The model was stratified by sex, age group, risk factor status, T2DM status, and intervention status, and parameterized by nationally representative data. Modeled interventions were introduced in 2016, reached targeted level by 2031, and then maintained up to 2050. Diverse intervention scenarios were assessed and compared with a counter-factual no intervention baseline scenario. RESULTS: T2DM prevalence increased from 16.7% in 2016 to 24.0% in 2050 in the baseline scenario. By 2050, through halting the rise or reducing obesity prevalence by 10-50%, T2DM prevalence was reduced by 7.8-33.7%, incidence by 8.4-38.9%, and related deaths by 2.1-13.2%. For smoking, through halting the rise or reducing smoking prevalence by 10-50%, T2DM prevalence was reduced by 0.5-2.8%, incidence by 0.5-3.2%, and related deaths by 0.1-0.7%. For physical inactivity, through halting the rise or reducing physical inactivity prevalence by 10-50%, T2DM prevalence was reduced by 0.5-6.9%, incidence by 0.5-7.9%, and related deaths by 0.2-2.8%. Introduction of physical activity with varying intensity at 25% coverage reduced T2DM prevalence by 3.3-9.2%, incidence by 4.2-11.5%, and related deaths by 1.9-5.2%. CONCLUSIONS: Major reductions in T2DM incidence could be accomplished by reducing obesity, while modest reductions could be accomplished by reducing smoking and physical inactivity, or by introducing physical activity as an intervention

Fuel cell technology for domestic built environment applications: state of-the-art review

Fuel cells produce heat when generating electricity, thus they are of particular interest for combined heat and power (CHP) and combined cooling heat and power (CCHP) applications, also known as tri-generation systems. CHP and tri-generation systems offer high energy conversion efficiency and hence the potential to reduce fuel costs and CO2 emissions. This article serves to provide a state-of-the-art review of fuel cell technology operating in the domestic built environment in CHP and tri-generation system applications. The review aims to carry out an assessment of the following topics: (1) the operational advantages fuel cells offer in CHP and tri-generation system configurations, specifically, compared to conventional combustion-based technologies such as Stirling engines, (2) how decarbonisation, running cost and energy security in the domestic built environment may be addressed through the use of fuel cell technology, and (3) what has been done to date and what needs to be done in the future. The article commences with a review of fuel cell technology, then moves on to examine fuel cell CHP systems operating in the domestic built environment, and finally explores fuel cell tri-generation systems in domestic built environment applications. The article concludes with an assessment of the present development of, and future challenges for, domestic fuel cells operating in CHP and tri-generation systems. As fuel cells are an emergent technology the article draws on a breadth of literature, data and experience, mostly from the United Kingdom, Germany, Japan, America and Australia. Fuel cells are a technology of the future here today, providing a change in the way heat and power are supplied to end users. Fuel cells operating in CHP and tri-generation systems in domestic built environment applications could finally provide the means by which energy generation can transfer from centralised to decentralised locales in a sustainable and effective manner

Measurements of Non-Wetting Phase Trapping Applied to Carbon Dioxide Storage

We measure the trapped non-wetting phase saturation as a function of the initial saturation in sand packs. The application of the work is for carbon dioxide (CO2) storage in aquifers where capillary trapping is a rapid and effective mechanism to render injected CO2 immobile. We used analogue fluids at ambient conditions. The trapped saturation initially rises linearly with initial saturation to a value of 0.11 for oil/water systems and 0.14 for gas/water systems. There then follows a region where the residual saturation is constant with further increases in initial saturation

Foldable structures made of hydrogel bilayers

We discuss self-folding of a thin sheet by using patterned hydrogel bilayers, which act as hinges connecting flat faces. Folding is actuated by heterogeneous swelling due to different crosslinking densities of the polymer network in the two layers. Our analysis is based on a dimensionally reduced plate model, obtained by applying a recently developed theory [1], which provides us with an explicit connection between (three-dimensional) material properties and the curvatures induced at the hinges. This connection offers a recipe for the fabrication and design of the bilayers, by providing the values of the cross-linking density of each layer that need to be imprinted during polymerization in order to produce a desired folded shape upon swelling

Novel PTH gene mutations causing isolated hypoparathyroidism

Context: PTH gene mutations represent a rare cause of familial isolated hypoparathyroidism (FIH). These defects can cause hypoparathyroidism with increased or decreased serum levels of PTH through 1) impaired PTH synthesis; 2) induction of parathyroid cell apoptosis; or 3) secretion of bioinactive PTH molecules. Eight pathogenic mutations of this gene have been described previously. Objective: Through describing two novel mutations of the PTH gene, we aim to extend the molecular basis for FIH and further refine the proposed mechanisms by which PTH mutations cause hypoparathyroidism. Design: Proband case reports with extended family analysis. Patients and Other Participants: The probands in both kindreds presented before 10-days-of-age with hypocalcemia and elevated phosphate levels. Proband A had low PTH levels, while these levels were elevated in Proband B. Proband B was initially diagnosed with pseudohypoparathyroidism. Interventions: Methylation analysis of CpG dinucleotides within three GNAS differentially methylated regions; Whole genome sequencing; and PTH infusion with analysis of nephrogenous cyclic AMP. Results: Proband A had a novel heterozygous sequence change in exon 2 of the PTH gene, c.46_47delinsAA (p.Ala16Lys) and Proband B had a novel homozygous nucleotide transition in PTH exon 3 (c.128G>A; p.G43E) that led to replacement of glycine by glutamic acid at position 12 of PTH 1-84. PTH 1-34 infusion demonstrated that renal responsiveness to PTH was intact and not antagonized by circulating bioinactive PTH. Conclusions: PTH gene mutations are uncommon causes of hypoparathyroidism, but can be misdiagnosed as disorders of gland development or receptor function if PTH levels are decreased or elevated, respectively. Genetic testing should be considered early in the diagnostic approach to these presentations

Dependence of quartz wettability on fluid density

Wettability is one of the most important parameters in multiphase flow through porous rocks. However, experimental measurements or theoretical predictions are difficult and open to large uncertainty. In this work we demonstrate that gas densities (which are much simpler to determine than wettability and typically well known) correlate remarkably well with wettability. This insight can significantly improve wettability predictions, thus derisking subsurface operations (e.g., CO2 geostorage or hydrocarbon recovery), and significantly enhance fundamental understanding of natural geological processes

Unified understanding of intrinsic and extrinsic controls of dissolved organic carbon reactivity in aquatic ecosystems

Despite our growing understanding of the global carbon cycle, scientific consensus on the drivers and mechanisms that control dissolved organic carbon (DOC) turnover in aquatic systems is lacking, hampered by the mismatch between research that approaches DOC reactivity from either intrinsic (inherent chemical properties) or extrinsic (environmental context) perspectives. Here we propose a conceptual view of DOC reactivity in which the combination of intrinsic and extrinsic factors controls turnover rates and determines which reactions will occur. We review three major types of reactions (biological, photochemical, and flocculation) from an intrinsic chemical perspective and further define the environmental features that modulate the expression of chemically inherent reactivity potential. Finally, we propose hypotheses of how extrinsic and intrinsic factors together shape patterns in DOC turnover across the land-to-ocean continuum, underscoring that there is no intrinsic DOC reactivity without environmental context. By acknowledging the intrinsic–extrinsic control duality, our framework intends to foster improved modeling of DOC reactivity and its impact on ecosystem services.publishedVersio