Increased platelet reactivity in idiopathic pulmonary fibrosis is mediated by a plasma factor

Introduction Idiopathic Pulmonary Fibrosis (IPF) is a progressive, incurable fibrotic interstitial lung disease with a prognosis worse than many cancers. Its pathogenesis is poorly understood. Activated platelets can release pro-fibrotic mediators that have the potential to contribute to lung fibrosis. We determine platelet reactivity in subjects with IPF compared to age-matched controls. Methods Whole blood flow cytometry was used to measure platelet-monocyte aggregate formation, platelet P-selectin expression and platelet fibrinogen binding at basal levels and following stimulation with platelet agonists. A plasma swap approach was used to assess the effect of IPF plasma on control platelets. Results Subjects with IPF showed greater platelet reactivity than controls. Platelet P-selectin expression was significantly greater in IPF patients than controls following stimulation with 0.1 µM ADP (1.9% positive ±0.5 (mean ± SEM) versus 0.7%±0.1; p = 0.03), 1 µM ADP (9.8%±1.3 versus 3.3%±0.8; p<0.01) and 10 µM ADP (41.3%±4.2 versus 22.5%±2.6; p<0.01). Platelet fibrinogen binding was also increased, and platelet activation resulted in increased platelet-monocyte aggregate formation in IPF patients. Re-suspension of control platelets in plasma taken from subjects with IPF resulted in increased platelet activation compared to control plasma. Conclusions IPF patients exhibit increased platelet reactivity compared with controls. This hyperactivity may result from the plasma environment since control platelets exhibit increased activation when exposed to IPF plasma

Accessible decision support for sustainable energy systems in developing countries

With rising electricity demand through digitization and innovation, the urgency of climate change mitigation, and the recent geopolitical crisis, stakeholders in developing countries face the complex task to build reliable, affordable, and low-emission energy systems. Information inaccessibility, data unavailability, and scarce local expertise are major challenges for planning and transitioning to decentralized solutions. Motivated by the calls for more solution-oriented research regarding sustainability, we design, develop, and evaluate the web-based decision support system NESSI4Dweb+ that is tailored to the needs and capabilities of various stakeholders in developing countries. NESSI4Dweb+ is open access and considers location-specific circumstances to facilitate multi-energy planning. Its applicability is demonstrated with a case study of a representative rural village in southern Madagascar and evaluated through seven interviews with experts and stakeholders. We show that NESSI4Dweb+ can support the achievement of the United Nations Sustainable Development Goals and enable the very prerequisite of digitization: reliable electrification

Sustainable Energy System Planning in Developing Countries: Facilitating Load Profile Generation in Energy System Simulations

Successful energy system planning is dependent on detailed electricity demand information. Especially in developing countries, pre-generated load profiles are often unsuitable as appliance ownership and usage vary significantly across borders, between urban and rural areas, and on household and industry levels. Synthesizing load profiles is often hindered by the inaccessibility of tools due to cost barriers, global unavailability, or required technical knowledge. As currently, no easily accessible and usable tool is available during energy system planning in rural areas of developing countries, we incorporate the open-source load profile generator RAMP into our web-based energy system simulator NESSI4Dweb+ to provide an intuitive user interface. We conduct an applicability check with self-collected data from a guesthouse in Sri Lanka, analyzing the impact of load distribution and magnitude on the economic, environmental, and reliable energy supply, that validates the artifact's relevance and ability to empower local decision-makers

Sustainable Energy System Planning in Developing Countries: A Decision Support System Considering Variations Over Time

Planning energy systems is subject to changes in components’ health and installation costs, fossil fuel prices, and load demand. Especially in developing countries, electrical loads are reported to increase drastically after electrification. Improper sizing of the energy system’s components can lead to reduced environmental sustainability, decreased reliability, and long-term project failures. As no tools for energy system planning exist that aim at developing countries and sufficiently account for temporal variations, we modify the software NESSI4D in a design science cycle to provide the comprehensive decision support system NESSI4D+. We conduct an applicability check with a representative rural village in mountainous Nepal that validates NESSI4D+’s relevance and shows the importance of considering temporal variations for economically, ecologically, and socially long-term sustainable energy projects

Tool-based renewable energy system planning using survey data: A case study in rural Vietnam

Renewable energies provide effective sustainable development by raising living standards, accelerating economic growth, and mitigating pollution. However, specifically in developing countries, the lack of information, data, and local expertise challenges the design process and long-term success of renewable energy systems. Following the call for inter-disciplinary, solution-oriented research, this work uses a design science research-approach to facilitate multi-energy planning. The decision support system NESSI4D is developed, which considers site-specific economic, environmental, technological, and social factors and is tuned for stakeholder needs in developing countries. Following a step-by-step process model manual, the artifact’s applicability is demonstrated in a use case for a rural community in Thua Thien-Hue, Vietnam. Missing load data are synthesized from the TVSEP with the software RAMP. The results show that the implementation of renewable energy technologies only enables affordable, low-emission electrification with governmental financial incentives. Several sensitivity tests illustrate the impact of changing assumptions and highlight the importance of detailed analyses with highly specialized tools. The demonstrating use case validates the method’s relevance for research and practice towards the goals of effective sustainable development

Survivorship research for people with metastatic or advanced cancer: A time for action

Over recent decades, survival outcomes for people diagnosed with cancer have changed dramatically, with approximately 20% improvement in five-year relative survival rates in high-income countries including the United States and Australia. Regardless of regions, there is a decrease in overall cancer mortality rate of about 1% per year. Likewise, the cancer disease trajectory has changed. The traditional linear cancer trajectory in which a patient moves from cancer diagnosis through to a binary outcome (cure or death)—is no longer applicable and does not adequately describe the complexity of experience for many people. Indeed, the availability of targeted therapies and immunotherapies has meant that people diagnosed with cancers once rapidly fatal in the advanced or metastatic stages, such as prostate, breast, ovarian, melanoma, myeloma, and non-small cell lung cancer, are now being treated over relatively long periods of time with treatments that slow the progression of their cancer, prolong life and control cancer symptoms.1 However, despite the ability of these novel therapies to extend life, most patients with an advanced or metastatic cancer diagnosis will never be cured. For these patients, cancer is often a chronic and complex illness that is, often unpredictable and requires ongoing monitoring, treatment, care, and support

Diffuse Gastric Ganglioneuromatosis: Novel Presentation of PTEN

Gastrointestinal ganglioneuromatous proliferations are rare, most often found in the colon, and are three types: polypoid ganglioneuromas, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. We present a case of diffuse ganglioneuromatosis in the posterior gastric wall in a nine-year-old female. To our knowledge, this is the first reported case of diffuse ganglioneuromatosis located in the stomach. Only six cases of gastric ganglioneuromatous proliferations have previously been reported, two in English and none were diffuse ganglioneuromatosis. A diagnosis of diffuse ganglioneuromatosis is relevant for patient care because, unlike sporadic polypoid ganglioneuromas or ganglioneuromatous polyposis, most are syndromic. Diffuse ganglioneuromatosis is commonly associated with neurofibromatosis type 1, multiple endocrine neoplasia type 2b, and Cowden Syndrome, one of the phenotypes of PTEN hamartoma tumor syndrome. The patient had the noted gastric diffuse ganglioneuromatosis, as well as other major and minor criteria for Cowden syndrome. Genetic testing revealed a novel frameshift mutation in the PTEN gene in the patient, her father, paternal aunt, and the aunt’s son who is a paternal first cousin of the patient

Open access decision support for sustainable buildings and neighborhoods: The nano energy system simulator NESSI

The urgency of climate change mitigation, rising energy prices and geopolitical crises make a quick and efficient energy transition in the building sector imperative. Building owners, housing associations, and local governments need support in the complex task to build sustainable energy systems. Motivated by the calls for more solution-oriented, practice-focused research regarding climate change and guided by design science research principles, we address this need and design, develop, and evaluate the web-based decision support system NESSI. NESSI is an open-access energy system simulator with an intuitive user flow to facilitate multi-energy planning for buildings and neighborhoods. It calculates the technical, environmental, and economic effects of 14 energy-producing, consuming, and storing components of the electric and thermal infrastructure, considers time-dependent effects, and accounts for geographic as well as sectoral circumstances. Its applicability is demonstrated with the case of a single-family home in Hannover, Germany, and evaluated through twelve expert interviews