Quantitative approaches for spatial metabolomics with isomer differentiation using surface sampling capillary electrophoresis mass spectrometry [Elektronisk resurs]

The importance of metabolites and their isomeric structures in biological function and dysfunction is increasingly recognized. However, achieving quantitative mapping of metabolites within tissue regions, particularly with isomeric specificity, remains an analytical challenge. This work presents the development of a quantitative surface sampling capillary electrophoresis method for spatial metabolomics with isomeric resolution. Five quantitation strategies were evaluated, with the optimal approach identified as sequential injection of metabolites directly from tissue alongside standards. This methodology was applied to a rat brain tissue section in a proof-of-principle study, enabling quantitative spatial analysis of metabolites, neurotransmitters, and isomeric species. Among the findings, the aromatic amino acids tyrosine, phenylalanine, and tryptophan exhibited the most dynamic distributions across four brain regions, while leucine and isoleucine demonstrated distinct spatial profiles, with leucine consistently being the more abundant isomer. This method offers a promising tool for advancing the understanding of spatially resolved biochemical processes underlying biological function and dysfunction.</p

Environmental dimensions of the ethics of antimicrobial resistance

Antimicrobial resistance (AMR) is a massive systemic, global threat to public health and the effectiveness of healthcare. The ethics of AMR comprises of ethical aspects of the phenomenon itself, understanding its significance for fundamental values, and of proposed actions to manage AMR, often linked to the concept of "one health". Most of this discussion has focused on rationalizing the use of antibiotics in human healthcare and farming. However, AMR has a sizeable environmental dimension that so far has mostly flown under the bioethical radar. This dimension encaptures the role of the environment as source for evolution of resistance as well as a transmission route, both spawned by the pollution of antibiotics and fecal matter from various sources. A bioethical analysis of AMR needs to take these dimensions into account, and doing so may potentially upset fundamental assumptions in both practical bioethics, health policy and their environmental counterparts. This chapter outlines the environmental dimensions of AMR, their bioethical significance, and some of the most obvious new ethical complexities and challenges for bioethical research made visible by such a broadening of the scope of the ethics of AMR

Rapid Traversal of Ultralarge Chemical Space using Machine Learning Guided Docking Screens [Elektronisk resurs]

The accelerating growth of make-on-demand chemical libraries provides unprecedented opportunities to identify starting points for drug discovery with virtual screening. However, these multi-billion-scale libraries are challenging to screen, even for the fastest structure-based docking methods. Here we explore a strategy that combines machine learning and molecular docking to enable rapid virtual screening of databases containing billions of compounds. In our workflow, a classification algorithm is trained to identify top-scoring compounds based on molecular docking of 1 million compounds to the target protein. The conformal prediction framework is then used to make selections from the multi-billion-scale library, reducing the number of compounds to be scored by docking. The CatBoost classifier showed an optimal balance between speed and accuracy and was used to adapt the workflow for screens of ultralarge libraries. Application to a library of 3.5 billion compounds demonstrated that our protocol can reduce the computational cost of structure-based virtual screening by more than 1,000-fold. Experimental testing of predictions identified ligands of G protein-coupled receptors and demonstrated that our approach enables discovery of compounds with multi-target activity tailored for therapeutic effect.</p

Can school closures decrease ethnic school segregation? [Elektronisk resurs] : Evidence from primary and lower secondary schools in Stockholm, Sweden

In recent decades, various cities in Sweden have implemented school closures as a desegregation strategy. Using simulation models calibrated with administrative data for all primary and lower secondary schools in Stockholm, Sweden, we assess the potential impact of school closure on ethnic school segregation. More specifically, we study how the characteristics of the school to be closed, the local opportunity structure for the displaced students, and the student reallocation criteria influence the effects of school closures on school segregation. Our findings show that the change in ethnic school segregation is highly dependent on reallocation criteria and local opportunity structures. Moreover, they demonstrate that the current practices associated with school closures in large urban areas (i.e., closing minority-dominated schools in minority-dominated neighborhoods) are likely to be ineffective in reducing school segregation, especially when students are reallocated to their nearest school or to schools whose composition resembles that of their former schools.</p

Swedish normative data and longitudinal effects of aging for older adults [Elektronisk resurs] : The Boston Naming Test 30-item and a short version of the Token Test

Naming ability and verbal comprehension are cognitive functions that may be affected both by normal aging and by disease. Neuropsychological testing is crucial to evaluate changes in language ability and reliable normative data for all ages are needed. We present clinically useful test norms, together with subsample analysis of longitudinal effects of aging, for two robust and well-known tests that evaluate naming ability and verbal comprehension where the present norms for older adults (aged 85 and older) are sparse or missing. Participants (n = 338) from a Swedish population-based study, the Elderly in Linkoping Screening Assessment, were cognitively evaluated with a cognitive screening battery at the age of 85 years and followed to the age of 93 years. Normative data at age 85 years were calculated from a sample (n = 207) that was determined as cognitively healthy after application of rigorous exclusion criteria. Effects of normal aging were investigated by analyzing follow-up performance at age 90 and 93 years for the subsample of cognitively healthy that completed the entire study. The evaluated tests in this study are Swedish versions of the Boston Naming Test 30-item Odd Version (BNT-30) and a short form of the Token Test, Part V (TokV). Analyzes of effects of aging showed that performance decreased with age for BNT-30, but not for TokV. Higher education was associated with better performance in both tests and men performed better than women on the BNT-30. Results also showed naming ability to be more sensitive to aging than verbal comprehension.</p

Mothers’ experiences of family life during COVID-19: a qualitative comparison between Sweden, the United Kingdom, and the United States

The COVID-19 pandemic amplified demands on parents regarding balancing childcare and working from home. How parents distribute responsibilities differs culturally, and governments undertook varied strategies to address COVID-19. Research indicates that the pandemic resulted in increased burden for mothers, but also that it created a novel situation in which parenting and working styles could be re-evaluated. However, Swedish mothers of toddlers and school-aged children were underrepresented in this research, and their voices can contribute to understanding how mothers in countries with different gender norms and lockdown statuses were affected. This study aimed to illuminate how mothers in a country with explicit commitment to gender equality in parenting and no lockdown (Sweden) experienced the pandemic, in contrast to mothers from countries that had lockdowns and different gender norms in parenting (the UK and US). Findings based on 193 mothers’ qualitative responses to open-ended questions indicated that mothers struggled with COVID-19 financial worries and concerns about family wellbeing. Support, both external and in coparenting, varied considerably among participants. Positives were reported, such as gratitude, closeness, and better quality of coparent interactions. We highlight the importance of considering emotional work, and the need to support parents both in times of crisis and beyond

Psychological prediction of stress-related hair stereoid hormone levels in young men : A person-centered approache

The aim was to: (1) identify individual profiles in young men regarding personality and cognitive appraisal style employing easy-to-use instruments, and (2) to explore how such profiles relate to biological stress indicators. The sample consisted of 173 male Lithuanian conscripts. An assessment was made after one month into their basic military training. Levels of cortisol, cortisone and testosterone were established through analysis of hair samples. Psychological assessments included the Big Five model of personality as well as cognitive appraisal style and perceived stress during the previous month of service. Four unique personality profiles were identified in a cluster analysis that differed significantly as theoretically expected on the Perceived Stress Scale. Statistically significant between-profile differences were found on cortisol and cortisone but not on testosterone. The personality profile with the highest scores on all three biological markers was characterized by high scores on Extraversion and Openness and low scores on Agreeableness. Second, three distinct cognitive appraisal style profiles emerged. They were related as theoretically expected to perceived stress, but they were unrelated to the hair steroid hormone concentration levels. Third, the combination of the most psychologically vulnerable personality profile, which included low scores on Emotional stability, and the most stressed cognitive appraisal style profile, yielded the clearest result and showed that it was possible to detect individuals with significantly higher stress-related hair steroid hormone levels using psychological instruments. Practical potential implications include identification of individuals who are most psychologically vulnerable and in need of close monitoring.</p

Designing digital solutions for sustainability: Navigating conflicting stakeholder requirements with dignity in mind

This teaching case examines the challenges of designing a digital solution to address complex sustainability problems. The case follows the vice president for innovation of a mid-sized European digital agency involved in a project dedicated to designing a digital application that connects climate-conscious investors, banks, and homeowners in need of loans for green house renovations. In this case, students need to navigate stakeholders’ conflicting needs and consider broader aspects of environmental, social, and economic sustainability in the design of digital applications. At the same time, this digital solution should seek to promote stakeholders’ dignity