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Cirrhosis and age are key determinants of HCC risk in individuals with primary sclerosing cholangitis : A multicenter longitudinal cohort study
No full textBackground & Aims The risk of hepatocellular carcinoma (HCC) in primary sclerosing cholangitis (PSC) is unclear. Studies indicate a low risk for HCC questioning the rationale for current HCC surveillance guidelines. This study explores the risk of HCC in a longitudinal multicenter cohort with over 3.000 PSC-subjects. Approach & results Subjects with well characterized PSC (n=3.071) were followed at 12 university hospitals within the International PSC registry (IPSCR) collaboration for a total of 38,387 person-years. Incident HCC was registered. Subjects were followed from PSC-diagnosis until death, liver transplantation, diagnosis of hepatobiliary malignancy, or February 2024. Poisson regression was used to calculate incidence rate ratios for HCC for the total population and for subgroups of different ages and cirrhosis status. Thirty-nine subjects developed HCC after a mean time of 16.4 years (SD ±10.7) from PSC diagnosis. In 26 (66.7%) of HCC cases, cirrhosis was diagnosed before HCC. The mean age at HCC diagnosis was 55.6 years (±SD13.1 years) and 28 (71.8%) were male. HCC was associated with cirrhosis (IRR 10.8;95%CI=5.7-20.5) and age (IRR 1.05;95%CI=1.03-1.08). At the age 50, the incidence rate was 0.81 and 0.47 for cirrhotic men and women respectively. For non-cirrhotic subjects, the risk was low for both men and women and all age groups. Conclusion Hepatocellular carcinoma is relatively rare in patients with primary sclerosing cholangitis who do not have cirrhosis, especially in those under the age of 50. Our findings indicate that HCC monitoring for patients with PSC can be tailored, based on their age and cirrhosis status
From innovation to exnovation : insights from post-growth food enterprises in Australia
No full textThis study explores systemic barriers and enablers of post-growth food enterprises in Australia. We analyse three different case studies that offer alternative models of entrepreneurial approaches for achieving sustainability outcomes as a higher priority than economic growth. We identified three post-growth food enterprises that operate at different stages of the food supply chain. We found that these enterprises work towards various, interconnected, sustainability goals by embedding diverse principles into their organisational structure and operations. Their not-for-profit structure enables them to avoid trade-offs between financial extractivism and socio-ecological well-being goals. Additionally, we explored the systemic barriers faced by these enterprises, recognising that they are embedded in an economic system that favours and rewards the pursuit of economic growth. To navigate these barriers, the cases analysed adopted various innovative approaches, such as fostering alternative funding schemes, ways to acquire farmland and technology. While their bottom-up approaches are important, the inertia of dominant food systems impedes transitions to alternatives. We suggest that exnovation – the process of deliberately phasing out unsustainable practices – warrants more attention. For example, exnovating goals, policies, and performance metrics that prioritise economic growth at the expense of sustainability could play a crucial role in unlocking post-growth models. This study provides an orientation for further theoretical and empirical research about post-growth food systems transitions and stresses the value of engaging more with the wider political, economic, and legal foundations of transitions
Structure and morphology of vesicular dispersions based on novel glycophospholipids with various monosaccharide head groups
No full textGlycophospholipids combine the structural versatility of phospholipids and carbohydrates, but their potential as excipients and performance in other related applications remains largely unexplored due to their low natural abundance. We have synthesized four novel phosphatidyl saccharide conjugates with different carbohydrate head groups; glucose, galactose, fructose and xylose by using a Phospholipase D catalysed transphosphatidylation reaction. The combination of Small Angle X-ray Scattering (SAXS) and Cryogenic Transmission Electron Microscopy (cryo-TEM) data allowed us to characterize the dispersed glycophospholipid vesicles in excess water and under physiologically relevant solution conditions in terms of their morphology and structure. The different carbohydrate head group generated a large variability of the vesicle structures. Lipids conjugated with glucose and fructose self-assembled into unilamellar vesicles whereas galactose and xylose conjugated lipids formed multilamellar structures. Phosphatidylgalactose conjugated lipids formed a high number of stacked bilayers, while the phosphatidylxylose equivalent assembled into aggregates with only a few bilayers. These results highlight how carbohydrate hydroxyl spatial arrangements strongly influence lipid packing and self-assembly. The versatility of this glycophospholipid platform offers opportunities to generate biocompatible and biodegradable phospholipid excipients with properties that can be tailored for specific applications
Landscape of microRNA and target expression variation and covariation in single mouse embryonic stem cells
No full textmicroRNAs are small RNA molecules that can repress the expression of protein-coding genes post-transcriptionally. Previous studies have shown that microRNAs can also have alternative functions, including influencing target expression variation and covariation, but these observations have been limited to a few microRNAs. Here we systematically study microRNA alternative functions in mouse embryonic stem cells (mESCs) by genetically deleting Drosha, leading to global loss of microRNAs. We apply complementary single-cell RNA-seq methods to study the variation of the targets and the microRNAs themselves, and transcriptional inhibition to measure target half-lives. We find that microRNAs form four distinct coexpression groups across single cells. In particular, the mir-290 and the mir-182 genome clusters are abundantly, variably, and inversely expressed. Some cells have global biases toward specific miRNAs originating from either end of the hairpin precursor, suggesting the presence of unknown regulatory cofactors. We find that microRNAs generally increase variation and covariation of their targets at the RNA level, but we also find microRNAs such as miR-182 that appear to have opposite functions. In particular, microRNAs that are themselves variable in expression, such as miR-291a, are more likely to induce covariations. In summary, we apply genetic perturbation and multiomics to give the first global picture of microRNA dynamics at the single-cell level
Long-acting nitrate use before and after revascularization to evaluate angina in chronic coronary syndrome : a case-crossover study from SCAAR
No full textBACKGROUND: The ORBITA and ORBITA-2 trials have provided valuable insights into the effects of coronary revascularization in chronic coronary syndrome (CCS). However, uncertainties remain regarding the efficacy of revascularization on symptoms in large real-world populations. To evaluate the efficacy of revascularization, we used dispensed long-acting nitrates as a proxy for the presence of angina.METHODS: The Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was used to identify all patients with CCS and at least one stenosis ≥50% undergoing angiography between the 1st of January 2014 and the 16th of January 2020. Four groups were defined based on treatment strategy: coronary artery bypass graft (CABG) surgery, complete revascularization with percutaneous coronary intervention (PCI), incomplete revascularization with PCI, and no revascularization. As patients in these treatment arms are inherently different, we employed a case-crossover design where each patient served as their own control with data collected during two periods: 1 year before up until angiography and 1-2 years after. This study design inherently controls for time-invariant confounding. The primary outcome was the use of long-acting nitrates defined as a dispensed prescription during the studied periods. Conditional Poisson regression was used to analyse the data.FINDINGS: For this study, 15,955 patients were eligible. CABG, complete revascularization with PCI, and incomplete revascularization with PCI were associated with a decrease in dispensed prescriptions of long-acting nitrates (from 989/2218 [30.8%] to 156/3207 [4.9%]; risk-ratio (RR): 0.16 [95% confidence interval (CI): 0.13-0.19]), (from 1676/7525 [22.3%] to 966/7525 [12.8%]; RR: 0.58 [95% CI: 0.53-0.62]), and (from 601/2180 [27.6%] to 495/2180 [22.7%]; RR: 0.82 [95% CI: 0.73-0.93]), respectively. No difference was observed for no revascularization (from 864/3043 [28.4%] to 856/3043 [28.1%]; RR: 0.99 [95% CI: 0.90-1.09]).INTERPRETATION: Revascularization reduces the use of long-acting nitrates in patients with CCS, suggesting angina symptom improvement. CABG appears to provide a more significant effect than PCI, with complete PCI demonstrating greater effectiveness than incomplete revascularization.FUNDING: This work was supported by The Swedish Heart and Lung Foundation, ALF, Skane University Hospital funds, the Crafoord Foundation and the Swedish Medical Association
The relationship between experienced losses and damages, risk tolerance and livelihood thresholds in the East Gippsland, Australia, farming sector
No full textLosses and damages are residual impacts of climate change that occur despite mitigation and adaptation actions. Losses and damages are borderless, albeit experienced differently between and within countries. Although Australia is a high-income country, recent losses and damages have been particularly severe. Over the last eight years, farmers in East Gippsland, Victoria, have been severely affected by a prolonged drought, bushfires, and floods, with evidence emerging of the links between these events and anthropogenic climate change. Through a series of surveys and semi-structured interviews with farmers and agricultural governance actors in East Gippsland, this research explores the relationship between experienced losses and damages, risk tolerance and livelihood thresholds. East Gippsland farmers are undertaking adaptation, but are still experiencing significant economic and non-economic losses and damages. Farmers and sectoral governance actors portray a complex picture of high risk tolerance, which, together with livelihoods strongly linked to identities, values, and self-worth, translates into a low desire to leave the sector despite escalating losses and damages that are challenging livelihood viability. We suggest that farmers’ high risk tolerance may, at present, with limited structural adaptation action identified, be unsustainable in light of current and future climate change. However, the strong values associated with being a farmer and the apparent recognition of greater adaptation needs across scales provide a potentially conducive environment for change. Whether farmers choose to stay or leave the sector, there must be managed processes to enable people to decide without losing their dignity and incurring further losses and damages
Applications of COBOTS in manufacturing : a bibliometric analysis
No full textIn recent years, Collaborative Robots (Cobots) have gained traction. It is categorized as a special type of robot that is capable of working safely alongside humans. Cobots are used in a variety of industrial applications, including assembling, manufacturing, quality inspection, and packaging products. Cobots use smart technologies to work alongside humans, making work easier and more efficient. The presented research deeply explores the emerging field of human-robot collaboration, particularly focusing on Cobots and their integration into manufacturing, production planning, and control. It discusses the prevailing perceptions of Cobots while highlighting their potential benefits in enhancing workplace efficiency and safety. We explored the Scopus database in the initial phase and applied inclusion and exclusion criteria to obtain the relevant research articles. Next, a bibliometric analysis was performed via VosViewer and the R Package-Biblioshiny to investigate trends, patterns, and key research focus areas. This study reveals a growing interest in Cobots, emphasizing their applications in various industrial settings. Notable findings include distinctions between traditional robots and cobots, the evolution of Cobots technology, and prevalent research themes such as production control, planning, human-robot collaboration, and Industry 5.0. To conclude, the presented study discusses theoretical, practical implications, and future scope of research
