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Randomized trial studying metabolic outcomes and quality of life after adrenalectomy versus conservative management for mild autonomous cortisol secretion
No full textObjective: Evaluate the impact of adrenalectomy on metabolic parameters and quality of life (QoL) in patients with mild autonomous cortisol secretion (MACS). Method: A multicenter prospective randomized clinical trial compared adrenalectomy with conservative management. Metabolic parameters and QoL were assessed at baseline and after 2 years. Results: Forty-three MACS patients with a single adrenal adenoma were randomized to either adrenalectomy (n =21) or conservative management (n = 22). At baseline, 33 patients had hypertension, 13 had type 2 diabetes (T2D), 18 used statins, and nine patients had osteoporosis. After 2 years, normalization of cortisol levels post 1 mg dexamethasone suppression test was achieved in 19/21 adrenalectomy patients compared to 2/22 patients in the conservative group (P < 0.01). All adrenalectomy patients had a significant increase in ACTH and DHEA-S. Office blood pressure and daily defined doses of antihypertensives (DDD) improved in nine of 12 adrenalectomy patients versus four of 15 conservatively treated patients (P = 0.01). Using 24 h blood pressure and DDD, improvement rates were five of 11 in the adrenalectomy group and six of 15 in the conservative group (P = 0.78). Among patients without T2D, the 120 min glucose level during oral glucose tolerance test was lower in the adrenalectomy group (6.2 vs 7.3 mmol/L, P = 0.04), but within-group changes were not different (P = 0.76). There were no statistically significant differences in QoL between the two groups. Conclusion: Adrenalectomy showed trends toward improvement in office blood pressure and glucose metabolism in MACS, suggesting possible reduction in cardiovascular risk and metabolic complications. Clinical trials number: NCT01246739
Health and economic benefits of energy, urban planning, and food interventions that lower greenhouse gas emissions
No full textPublic health can be immediately and substantially improved by policies that also mitigate climate change over the longer term. However, implementation of these policies has been slowed at least in part by doubts and lack of awareness of these health co-benefits. To address this barrier to progress, we demonstrate how an illustrative set of interventions led to environmental, health, and economic benefits, in addition to mitigating climate change. These case studies include the closure of a coal coking plant near Pittsburgh, PA, USA, which was followed by substantial immediate and longer-term reductions in respiratory and cardiovascular health conditions in the affected local community; the health and economic benefits associated with the Barcelona, Spain Superblock program and, the air quality, health, and economic benefits from air pollution initiatives implemented in China. While improvements in air pollution are among the most obvious examples of the co-benefits achievable through climate-friendly interventions, others that reduce greenhouse gas emissions, such as the sustainable food systems in Sweden, forest conservation in Tanzania, and a plant-based food program in New York City, further illustrate how such initiatives can align with better nutrition, economic gains, and improved health. We conclude that more assessments of such interventions are needed internationally to more widely document their health and climate benefits and thereby motivate greater implementation of these interventions. Now is the time to showcase how we can improve the public's health and well-being, while also protecting our planet, the only home future generations will have
Evidence of Gaia Enceladus Experiencing at Least Two Passages around the Milky Way
No full textOne of the major recent breakthroughs has been the discovery of the last major merger to happen in the history of the Milky Way. Around 10 Gyr ago, the galaxy Gaia Enceladus with an estimated ∼10% of the Milky Way mass, fell into the potential of our Galaxy, bringing a large amount of stars that can be identified through their unique chemical and kinematic signatures. Simulations have long predicted that a galaxy of this size should experience several passages through the disk of the Milky Way before eventually being fully dispersed. For the first time, we present observational evidence to support this. We identify two subpopulations accreted from Gaia Enceladus: (1) stars that today have large kinematic energy, which originated from the outskirts of Gaia Enceladus and were accreted during early passages; (2) stars with low kinetic energy accreted at later passages, originating from the inner parts of Gaia Enceladus. Through the use of high-precision chemical abundances, crucially including new aluminum measurements, we show that in all observed abundance ratios ([Fe/H], [Al/Fe], [Mg/Fe], and [Mg/Ba]), stars with high energy show evidence of coming from a less chemically evolved outer region of Gaia Enceladus, compared to the stars with low energy. We therefore conclude that Gaia Enceladus experienced several passages before merging with the main body of our Galaxy. This discovery has wide implications for our understanding of this event and consolidates Gaia Enceladus as a benchmark for studying galaxy mergers and hierarchical galaxy formation in extraordinary detail
Sublytic Activity of a Pore-Forming Protein From Commensal Bacteria Causes Epigenetic Modulation of Tumour-Affiliated Protein Expression
No full textCytolysin A (ClyA) is a pore-forming protein from a strongly silenced gene in non-pathogenic Escherichia coli, including typical commensal isolates in the intestinal microbiome of healthy mammalian hosts. Upon overproduction, ClyA-expressing bacteria display a cytolytic phenotype. However, it remains unclear whether sublytic amounts of native ClyA play a role in commensal E. coli-host interactions in vivo. Here, we show that sublytic amounts of ClyA are released via outer membrane vesicles (OMVs) and affect host cells in a remarkable manner. OMVs isolated from ClyA+ E. coli were internalised into cultured colon cancer cells. The OMV-associated ClyA caused reduced levels of cancer-activating proteins such as H3K27me3, CXCR4, STAT3 and MDM2 via the EZH2/H3K27me3/microRNA 622/CXCR4 signalling axis. Our results demonstrate that sublytic amounts of ClyA in OMVs from non-pathogenic E. coli can influence the stability of the EZH2 protein, reducing its activity in epigenetic regulation, causing elevated level of the tumour suppressor protein p53
Deep Tissue Characterization by Ultrasound Optical Tomography Hybrid Monte Carlo Model
No full textWe propose analytical expressions for ultrasound optical tomography and verify them in Monte Carlo simulations. The proposed hybrid analytical-statistical Monte Carlo model enables quantitative reconstruction of up to 5-centimetre deep tissue absorption inhomogeneities
Social Representations of the Jihadist : A Study of an Emerging Identity in Street Culture
No full textOver the last two decades, the social identity of the jihadist has become a central part of street culture. Depictions of jihadists can be found in popular music, movies and media reports. Propaganda celebrating or condemning jihadism circulates online, and a significant number of individuals with a background in street crime have flirted with or converted to jihadism. Drawing on ethnographic fieldwork in Oslo, this article analyses how Muslims involved in street life and crime construct and relate to the social identity of the jihadist. The Durkheimian theory of representations is employed to show how the joint construction of this identity shapes the ways in which people on the street make sense of themselves, their enemies, and the actions they take towards jihadi extremism. In conclusion, we argue that the theory of representations, including the concepts of anchoring and objectification, should be incorporated into the analytical toolboxes of cultural criminology and narrative criminology to deepen our understanding of how meaning-making unfolds in cultural context
An ICF core set for designing cognitive web accessibility : a bridge between design and the implications of cognitive impairments
No full textAccessible design enables participation in the digital society for everyone. However, cognitive accessibility is not well established within the field of web design. The International Classification of Functioning, Disability and Health (ICF) provides a descriptive framework that relates health conditions to functioning and participation. ICF Core Sets are purposefully tailored shortlists of ICF categories for describing functioning. The aim of this study was to develop an ICF core set for cognitive web accessibility to be used by web designers. ICF categories with relevance for cognitive accessibility were extracted and linked to the guidelines in the standard for cognitive accessibility: ISO 21801-1, followed by interpretation of the meaning of the ICF categories in relation to cognitive accessibility. The latter was outlined as practical advice for designers on design considerations for cognitive accessibility. The analysis was performed by an iterative back-and-forth process between the lived experiences of persons with cognitive impairments, the ISO-standard and the ICF. The ICF core set comprises 46 ICF categories with design considerations for cognitive accessibility. The ICF core set is suggested to facilitate understanding of the challenges in digital design that users experience and provide strategies to address cognitive accessibility, and thereby improve design outcomes
Navigating uncertainty: Trauma quality improvement in urban India
No full textBackground and aimImproving the quality of health care is a global priority, yet many conventional quality improvement approaches, rooted in industrial models of standardisation and control, struggle to account for the uncertainty and complexity of clinical care. Trauma, defined as external injury and the body's physiological response, causes about 4.4 million deaths each year. The impact is greatest in low- and middle-income countries, where trauma is a leading cause of quality-related deaths. Trauma care involves time pressure, interdis- ciplinary teams, and high variability. This thesis investigates if, and how, a trauma quality improvement programme improves patient outcomes. The work is based on four em- pirical studies embedded in the Trauma Audit Filter Trial, a multicentre study evaluating a programme using audit filters and multidisciplinary case reviews in urban India. Audit filters are statements of agreed standards of care; when care deviates from these, the case is selected for review.Methods and resultsStudy I used a Delphi method to identify audit filters appropriate for the local context. Filters developed in other low- and middle-income countries were perceived as highly useful, and perceived usefulness was linked to medical relevance and feasibility.Study II, a prospective controlled interrupted time series trial, showed an 11% reduction in in-hospital mortality after programme implementation, while also highlighting confound- ing external factors and the limits of attributing causality in complex systems.Study III assessed the effect on health-related quality of life, showing that while survival improved, health-related quality of life slightly declined, likely because more severely in- jured patients survived, highlighting rehabilitation needs.Study IV used reflexive thematic analysis of interviews with participants in multidis- ciplinary review meetings to identify mechanisms through which the programme con- tributed to improvement. These included system-level awareness, shared understand- ing, navigation of hierarchical structures, and ethical sensitisation.ConclusionA trauma quality improvement programme based on case review and multidisciplinary discussion may reduce mortality in settings with a high burden of preventable deaths. Quality improvement in complex systems depends on structures that enable continuous learning, strengthen the forms of knowledge used in medical decision-making, and in- crease practitioners' understanding of the systems in which they work. Such approaches support better decision-making, enhance adaptability, and help identify and address ar- eas for improvement within local environments. This thesis contributes to understanding how quality improvement can lead to change in trauma care and may help inform the de- sign and implementation of similar programmes in other contexts. The knowledge gainedabout the mechanisms of improvement may also inform quality improvement efforts in other areas of health care
Characterization of five environmental phages infecting Escherichia coli K-12 isolated during a phage biology training course.
No full textPhage collections are essential tools for discovering and dissecting bacterial anti-phage defense systems. Here, we report the isolation, characterization, and annotated genome sequences of five environmental Escherichia coli-infecting phages, obtained during the 2023 Fundamentals of Basic and Applied Phage Biology course at Lund University. The phages were isolated using a motile E. coli K-12 BW25113 strain, whose motility is conferred by an IS5 insertion upstream of the flhDC operon, the master regulator of flagellar synthesis. The isolated Escherichia phages include Lubas (LuPh1) and Lucat (LuPh2) of the genus Tequatrovirus; Lupin (LuPh3) and Lucris (LuPh4) of the genus Tequintavirus; and Kompetensportalen (LuPh5) of the genus Chivirus. Transmission electron microscopy confirmed myovirus and siphovirus morphologies typical of these genera. Consistent with its classification in the flagellotropic Chivirus genus, LuPh5 did not infect a poorly motile BW25113 strain lacking the IS5 element upstream of flhDC, but did infect the motile laboratory Salmonella enterica subsp. enterica serovar Typhimurium strain 12023s. By testing a panel of eight previously described anti-phage defense systems, we found that LuPh1 and LuPh2 are inhibited by the toxin-antitoxin-chaperone CmdTAC system; LuPh5 is inhibited by both the restriction-modification system EcoRI and the abortive infection reverse transcriptase AbiK; and all five phages are sensitive to the hybrid artificial CmdTA-HigC system. Collectively, our findings expand the toolkit for probing phage-host interactions and underscore the pedagogical value of incorporating phage isolation into practical training for emerging researchers.IMPORTANCE Bacterial anti-phage defense systems are central to microbiology and have applications in biotechnology and medicine. Phage collections are key tools for uncovering and studying these systems. By isolating and characterizing five E. coli K12-infecting phages, including three newly identified species, this work expands resources for probing phage-host interactions. It also shows that hands-on phage isolation in educational settings can contribute meaningfully to both training and research
Extended Abstract : Probed Language-Based Assessments Using Spoken Language
No full textProbed language-based assessments, where individuals describe their states using open-ended responses analyzed with Artificial Intelligence, have shown great promise for written language. But emotions are also conveyed through spoken language which might provide further assessment power to this method. Participants (N=645) were randomly assigned to watch a video clip of a church, shopping mall, or park, then describe their emotions using written and spoken language and closed-ended rating scales. Results: Combining written and spoken language increases the convergence with the rating scales. Spoken language demonstrates higher accuracy in classifying which video clip participants saw (AUC=0.80), as compared with written language (AUC=0.69). Thus, spoken language can complement written language responses for assessing affect in communication research