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- Smith, Richard J.H., et al.
(author)
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C3 glomerulopathy — understanding a rare complement-driven renal disease
- 2019
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In: Nature Reviews Nephrology. - : Springer Science and Business Media LLC. - 1759-5061 .- 1759-507X.
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Research review (peer-reviewed)abstract
- The C3 glomerulopathies are a group of rare kidney diseases characterized by complement dysregulation occurring in the fluid phase and in the glomerular microenvironment, which results in prominent complement C3 deposition in kidney biopsy samples. The two major subgroups of C3 glomerulopathy — dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) — have overlapping clinical and pathological features suggestive of a disease continuum. Dysregulation of the complement alternative pathway is fundamental to the manifestations of C3 glomerulopathy, although terminal pathway dysregulation is also common. Disease is driven by acquired factors in most patients — namely, autoantibodies that target the C3 or C5 convertases. These autoantibodies drive complement dysregulation by increasing the half-life of these vital but normally short-lived enzymes. Genetic variation in complement-related genes is a less frequent cause. No disease-specific treatments are available, although immunosuppressive agents and terminal complement pathway blockers are helpful in some patients. Unfortunately, no treatment is universally effective or curative. In aggregate, the limited data on renal transplantation point to a high risk of disease recurrence (both DDD and C3GN) in allograft recipients. Clinical trials are underway to test the efficacy of several first-generation drugs that target the alternative complement pathway.
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- Chatterjee, S., et al.
(author)
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Protein Paucimannosylation Is an Enriched N-Glycosylation Signature of Human Cancers
- 2019
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In: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 19:21-22
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Journal article (peer-reviewed)abstract
- While aberrant protein glycosylation is a recognized characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumorigenesis. This glycomics‐centric study investigates a possible link between protein paucimannosylation, an under‐studied class of human N‐glycosylation [Man1‐3GlcNAc2Fuc0‐1], and cancer. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non‐cancerous specimens are profiled from 467 published and unpublished PGC‐LC‐MS/MS N‐glycome datasets collected over a decade. PMGs, particularly Man2‐3GlcNAc2Fuc1, are prominent features of 29 cancer cell lines, but the PMG level varies dramatically across and within the cancer types (1.0–50.2%). Analyses of paired (tumor/non‐tumor) and stage‐stratified tissues demonstrate that PMGs are significantly enriched in tumor tissues from several cancer types including liver cancer (p = 0.0033) and colorectal cancer (p = 0.0017) and is elevated as a result of prostate cancer and chronic lymphocytic leukaemia progression (p < 0.05). Surface expression of paucimannosidic epitopes is demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N‐acetyl‐β‐hexosaminidase is indicated by quantitative proteomics. This intriguing association between protein paucimannosylation and human cancers warrants further exploration to detail the biosynthesis, cellular location(s), protein carriers, and functions of paucimannosylation in tumorigenesis and metastasis.
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- Goldberg, C., et al.
(author)
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Assessment of an energy-efficient aircraft concept from a techno-economic perspective
- 2018
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In: Applied Energy. - : Elsevier Ltd. - 0306-2619 .- 1872-9118. ; 221, s. 229-238
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Journal article (peer-reviewed)abstract
- An increase in environmental awareness in both the aviation industry and the wider global setting has led to large bodies of research dedicated to developing more sustainable technology with a lower environmental impact and lower energy usage. The goal of reducing environmental impact has necessitated research into revolutionary new technologies that have the potential to be significantly more energy efficient than their predecessors. However, for innovative technologies in any industry, there is a risk that adoption will be prohibitively expensive for commercial application. It is therefore important to model the economic factors of the new technology or policy at an early stage of development. This research demonstrates the application of a Techno-economic Environmental Risk Assessment framework that may be used to identify the economic impact of an energy-efficient aircraft concept and the impact that environmental policy would have on the viability of the concept. The framework has been applied to a case study aircraft designed to achieve an energy saving of 60% in comparison to a baseline 2005 entry-into-service aircraft. The model compares the green aircraft concept to a baseline conventional aircraft using a sensitivity analysis of the aircraft direct operating cost to changes in acquisition and maintenance cost. The research illustrates an economically viable region for the technology. Cost margins are identified where the increase in operating cost due to expensive novel technology is counterbalanced by the reduction in cost resulting from low energy consumption. Viability was found to be closely linked to fuel price, with a low fuel price limiting the viability of energy-efficient aviation technology. In contrast, a change in environmental taxation policy was found to be beneficial, with the introduction of carbon taxation incentivising the use of an environmentally optimised aircraft.
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- Nalianda, D. K., et al.
(author)
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Techno-economic viability assessments of greener propulsion technology under potential environmental regulatory policy scenarios
- 2015
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In: Applied Energy. - : Elsevier BV. - 0306-2619 .- 1872-9118. ; 157, s. 35-50
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Journal article (peer-reviewed)abstract
- Sustainability of the aviation industry, as any other industry, depends on the elasticity of demand for the product and profitability through minimising operating costs. Of paramount importance is assessing and understanding the interdependency and effects of environmentally optimised solutions and emission mitigation policies.This paper describes the development and application of assessment methodologies to better understand the effects of environmental taxation/energy policies aimed at environmental pollution reduction and the future potential economic impact they may have on the adaptation of "greener" novel technologies. These studies are undertaken using a Techno-economic Environmental Risk Assessment approach. The methodology demonstrated allows the assessment of the economic viability of new technologies compared to conventional technologies, for various CO2 emission taxation and fuel price scenarios. It considers relative increases in acquisition price and maintenance costs.A study undertaken as a 'proof of concept' compares a Counter Rotating Open Rotor aircraft with a conventional aircraft for short range operations. It indicates that at current fuel price and with no carbon taxation, a highly fuel efficient technology, such as the one considered, could be rendered economically unviable.The work goes on to demonstrate that in comparison to the conventional aircraft, any economic benefits that may be accrued from improvement in fuel consumption through such a technology, may well be negated through increases in acquisition price and maintenance costs. The work further demonstrates that if policy makers want to direct the industry towards greener propulsion solutions, then an increase in CO2 emission taxation may be appropriate.
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| 22. |
- Prasad, N., et al.
(author)
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Prescription Practices in Patients With Mild to Moderate CKD in India
- 2021
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In: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 6:9, s. 2455-2462
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Journal article (peer-reviewed)abstract
- Introduction: Patients with chronic kidney disease (CKD) require multiple medications. There is no information on prescription patterns or the use of evidence-based therapies for management of CKD from low-middle-income countries. Using baseline data from the Indian CKD (ICKD) cohort, we describe the drug prescription practices in patients with mild to moderate CKD. Methods: The ICKD study is a prospective, observational cohort study of mild to moderate kidney disease across 11 centers in India. We analyzed all the prescriptions captured at enrollment in the ICKD study. Drugs were categorized into 11 different groups. We provide descriptive data on prescription details and evaluate the appropriateness of medication use. Results: Complete prescription data were available in 3966 out of 4056 (97.8%) subjects enrolled in the ICKD database. Most patients had stage 3 CKD, 24.9% had diabetic kidney disease, 87% had hypertension, and 25.5% had moderate to severe proteinuria. Renin-angiotensin-aldosterone system blockers were prescribed in less than half (47.9%) and in 58.8% of patients with proteinuric CKD. Metformin was prescribed in 25.7% of diabetic subjects with CKD. Only 40.4% of patients were taking statins; 31.1% and 2.8% subjects with anemia were receiving iron and erythropoiesis-stimulating agents, respectively. Conclusion: This study highlights the missed opportunities for improving outcomes through appropriate prescriptions of drugs in patients with CKD. There is need for dissemination of evidence-based guidelines and institution of sustainable implementation practices for improving the overall health of patients with CKD. © 2021 International Society of Nephrology
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| 25. |
- Smith, JAB, et al.
(author)
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Three weeks of interrupting sitting lowers fasting glucose and glycemic variability, but not glucose tolerance, in free-living women and men with obesity
- 2021
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In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 321:2, s. E203-E216
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Journal article (peer-reviewed)abstract
- Under free-living conditions, breaking sitting modestly increased activity behavior. Breaking sitting was insufficient to modulate glucose tolerance or the skeletal muscle lipidome. Activity breaks reduced fasting blood glucose levels and daily glucose variation compared with baseline, with a tendency to also decrease fasting LDLc. This intervention may represent the minimal dose for breaking sedentary behavior, with larger volumes of activity possibly required to promote greater health benefits.
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| 26. |
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| 27. |
- Vuong, Lynda, et al.
(author)
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An orally active galectin-3 antagonist inhibits lung adenocarcinoma growth and augments response to PD-L1 blockade
- 2019
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In: Cancer Research. - 0008-5472. ; 79:7, s. 1480-1492
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Journal article (peer-reviewed)abstract
- A combination therapy approach is required to improve tumor immune infiltration and patient response to immune checkpoint inhibitors that target negative regulatory receptors. Galectin-3 is a β-galactoside-binding lectin that is highly expressed within the tumor microenvironment of aggressive cancers and whose expression correlates with poor survival particularly in patients with non-small cell lung cancer (NSCLC). To examine the role of galectin-3 inhibition in NSCLC, we tested the effects of galectin-3 depletion using genetic and pharmacologic approaches on syngeneic mouse lung adenocarcinoma and human lung adenocarcinoma xenografts. Galectin-3-/- mice developed significantly smaller and fewer tumors and metastases than syngeneic C57/ Bl6 wild-type mice. Macrophage ablation retarded tumor growth, whereas reconstitution with galectin-3-positive bone marrow restored tumor growth in galectin-3-/- mice, indicating that macrophages were a major driver of the antitumor response. Oral administration of a novel small molecule galectin-3 inhibitor GB1107 reduced human and mouse lung adenocarcinoma growth and blocked metastasis in the syngeneic model. Treatment with GB1107 increased tumor M1 macrophage polarization and CD8 + T-cell infiltration. Moreover, GB1107 potentiated the effects of a PD-L1 immune checkpoint inhibitor to increase expression of cytotoxic (IFNγ, granzyme B, perforin-1, Fas ligand) and apoptotic (cleaved caspase-3) effector molecules. In summary, galectin-3 is an important regulator of lung adenocarcinoma progression. The novel galectin-3 inhibitor presented could provide an effective, nontoxic monotherapy or be used in combination with immune checkpoint inhibitors to boost immune infiltration and responses in lung adenocarcinoma and potentially other aggressive cancers. Significance: A novel and orally active galectin-3 antagonist inhibits lung adenocarcinoma growth and metastasis and augments response to PD-L1 blockade.
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