Hållbar utveckling och i synnerhet hållbar stadsutveckling används idag som ett ledord för hur de flesta städer önskar utvecklas. Hållbarhetsindikatorer har etablerats som ett verktyg för att ...underlätta beslutsfattande åtgärder genom att förenkla, förtydliga och samla information. Tanken är att indikatorer ska styra och följa upp hållbarhetsarbetet men även fungera som ett verktyg för att kommunicera idéer, tankar och värderingar. I denna studie ämnar vi att beskriver hur hållbarhetsindikatorer kan bidra med att effektivisera hållbarhetsarbetet. Genom att undersöka hur tre svenska kommuner använder sig av indikatorer tillsammans med forskning inom området presenteras en slutsats som visar att det finns stora brister i de system som idag tillämpas. Litteraturen förespråkar ett fåtal indikatorer som bygger på både kvalitativa och kvantitativa värden där kommunikation blir centralt vilket går helt emot vad kommunerna gör. Nya indikatorsystem som bygger på deltagande där den tänkta målgruppen är i fokus skulle leda till en förståelse kring hållbarhetsmålen vilket är en förutsättning för att kunna nå dem. Indikatorerna ska underlätta beslutsfattande åtgärder där rollen som styrnings- och uppföljningsverktyg2blir central samtidigt som kommunikationen blir viktig i hållbarhetsarbetet. Som medborgare blir det svårt att påverka eller förstå hållbarhetsarbetet när det inte redovisas på ett begripligt sätt och när det är svårt att följa utvecklingen. Avslutningsvis presenteras en förstudie till ett projekt där ett förslag på hur en intern process vid framtagandet av ett nytt indikatorsystem skulle kunna gå till.
Sustainable development and in particular sustainable urban development are now catchphrases for how most cities wish to develop. Sustainability indicators have been established as a tool to facilitate decision-making measures to simplify, clarify and gather information. The idea is that indicators should control and follow through sustainability efforts but also serve as a tool to communicate ideas, thoughts and values. The aim of this study is to describe how sustainability indicators can help to streamline sustainability efforts. By looking at how three Swedish municipality use indicators along with research in the theoretical field a conclusion that shows that there are major weaknesses in the systems applied today is presented. The research advocates a few indicators based on both qualitative and quantitative values where communication is central which completely goes against what the municipalities are doing at the moment. New indicator systems based on participation where the intended audience is primary would lead to a broader understanding of sustainability goals, which is a requisite for achieving them. Indicators could facilitate decision-making where the role of management and monitoring will be key along with communication towards sustainability. As a citizen it is difficult to influence or understand sustainability projects when they are not presented in an understandable way and when it is difficult to monitor development. In the end of the study a preliminary project on how an internal process in developing a new indicator system is presented.
The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel ...tissue-specific transcriptional profiles and heterogeneity of CD127
ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2
and CRTH2
ILC2 with lung-specific signatures, which could be recapitulated by alarmin-exposure of circulating ILC2. Finally, we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells, revealing a subset of potentially immature ILCs with TCR-δ rearrangement. Our study provides a useful resource for in-depth understanding of ILC-mediated immunity in humans, with implications for disease.
Adoptive T-cell therapy (ACT) is a highly intensive immunotherapy regime that has yielded remarkable response rates and many durable responses in clinical trials in melanoma; however, 50-60% of the ...patients have no clinical benefit. Here, we searched for predictive biomarkers to ACT in melanoma. Whole exome- and transcriptome sequencing and neoantigen prediction were applied to pre-treatment samples from 27 patients recruited to a clinical phase I/II trial of ACT in stage IV melanoma. All patients had previously progressed on other immunotherapies. We report that clinical benefit is associated with significantly higher predicted neoantigen load. High mutation and predicted neoantigen load are significantly associated with improved progression-free and overall survival. Further, clinical benefit is associated with the expression of immune activation signatures including a high MHC-I antigen processing and presentation score. These results improve our understanding of mechanisms behind clinical benefit of ACT in melanoma.
Lung cancer is the worldwide leading cause of death from cancer. DNA methylation in gene promoter regions is a major mechanism of gene expression regulation that may promote tumorigenesis. However, ...whether clinically relevant subgroups based on DNA methylation patterns exist in lung cancer remains unclear.
Whole-genome DNA methylation analysis using 450K Illumina BeadArrays was performed on 12 normal lung tissues and 124 tumors, including 83 adenocarcinomas, 23 squamous cell carcinomas (SqCC), 1 adenosquamous cancer, 5 large cell carcinomas, 9 large cell neuroendocrine carcinomas (LCNEC), and 3 small-cell carcinomas (SCLC). Unsupervised bootstrap clustering was performed to identify DNA methylation subgroups, which were validated in 695 adenocarcinomas and 122 SqCCs. Subgroups were characterized by clinicopathologic factors, whole-exome sequencing data, and gene expression profiles.
Unsupervised analysis identified five DNA methylation subgroups (epitypes). One epitype was distinctly associated with neuroendocrine tumors (LCNEC and SCLC). For adenocarcinoma, remaining four epitypes were associated with unsupervised and supervised gene expression phenotypes, and differences in molecular features, including global hypomethylation, promoter hypermethylation, genomic instability, expression of proliferation-associated genes, and mutations in KRAS, TP53, KEAP1, SMARCA4, and STK11. Furthermore, these epitypes were associated with clinicopathologic features such as smoking history and patient outcome.
Our findings highlight one neuroendocrine and four adenocarcinoma epitypes associated with molecular and clinicopathologic characteristics, including patient outcome. This study demonstrates the possibility to further subgroup lung cancer, and more specifically adenocarcinomas, based on epigenetic/molecular classification that could lead to more accurate tumor classification, prognostication, and tailored patient therapy.
Esports are a rapidly growing phenomenon and understanding of factors underlying game performance are therefore of great interest. The present study investigated the influence of satisfaction of ...basic psychological needs (competence, autonomy, and relatedness), type of motivation (amotivation, external regulation, introjected regulation, identified regulation, integrated regulation, and intrinsic motivation), and number of matches played (time on task) on individuals’ performance on a matchmaking rating (MMR) in the video game Defence of the Ancients 2 (Dota 2). Collected data from 315 participants was included in the analyses. A web-based questionnaire was used to collect data and structural equation modelling (SEM) was performed to analyze the data. The results show that perceived competence and autonomy were the only significant predictors of MMR performance beyond matches played. Fulfillment of relatedness, as well as motivational factors, were not found to be predictors of MMR scores. The strong effect of matches played, used as proxy of time on task, emphasize the effect of time and practice as a critical aspect of video-game expertise.
To determine temporal trends in the incidence of cardiac arrest occurring in the ICU (ICU-CA) and its associated long-term mortality.
Retrospective observational study.
Swedish ICUs, between 2011 and ...2017.
Adult patients (≥18 yr old) recorded in the Swedish Intensive Care Registry (SIR).
None.
ICU-CA was defined as a first episode of cardiopulmonary resuscitation and/or defibrillation following an ICU admission, as recorded in SIR or the Swedish Cardiopulmonary Resuscitation Registry. Annual adjusted ICU-CA incidence trend (all admissions) was estimated using propensity score-weighted analysis. Six-month mortality trends (first admissions) were assessed using multivariable mixed-effects logistic regression. Analyses were adjusted for pre-admission characteristics (sex, age, socioeconomic status, comorbidities, medications, and healthcare utilization), illness severity on ICU admission, and admitting unit. We included 231,427 adult ICU admissions. Crude ICU-CA incidence was 16.1 per 1,000 admissions, with no significant annual trend in the propensity score-weighted analysis. Among 186,530 first admissions, crude 6-month mortality in ICU-CA patients was 74.7% (95% CI, 70.1-78.9) in 2011 and 68.8% (95% CI, 64.4-73.0) in 2017. When controlling for multiple potential confounders, the adjusted 6-month mortality odds of ICU-CA patients decreased by 6% per year (95% CI, 2-10). Patients admitted after out-of-hospital or in-hospital cardiac arrest had the highest ICU-CA incidence (136.1/1,000) and subsequent 6-month mortality (76.0% 95% CI, 73.6-78.4).
In our nationwide Swedish cohort, the adjusted incidence of ICU-CA remained unchanged between 2011 and 2017. More than two-thirds of patients with ICU-CA did not survive to 6 months following admission, but a slight improvement appears to have occurred over time.
The internal evolution of the Varuträsk rare-element pegmatite (Skellefte District, Northern Sweden) has been investigated using stable isotope (B, H, O) geochemistry of tourmaline and coexisting ...micas, feldspar and quartz. Varuträsk is a classic and typical example of highly fractionated LCT-type pegmatites, with a pronounced concentric zoning pattern composed of well-developed border, wall and intermediate zones and a quartz core. The pegmatite displays considerable rare-element enrichment, culminating in the formation of albite-lepidolite and pollucite units in the innermost zones. Major and trace element variations in tourmaline from the main pegmatite zones correlate well with the internal zoning pattern. Mineral compositions record an abrupt change in fractionation trends between the barren outer and intermediate zones and the inner, late-stage assemblages that carry rare-element mineralization. This change is also shown by the B-isotope variations of tourmaline. Early and mid-stage tourmalines record a systematic increase in δ11B from −14.6‰ to −6.2‰ which can be explained by closed-system melt-mineral isotope fractionation whereby crystallization of large amounts of muscovite preferentially removes 10B from the residual melt. In contrast, tourmaline from late-stage assemblages in the inner zones and cross-cutting veinlets shows a reversal in the B isotope trend, with a decrease in δ11B from −8‰ to −14.1‰. This reversal cannot be explained by mineral-melt isotope fractionation, but requires fluid-melt partitioning and partial fluid loss. Hydrogen isotope variations in mica support this model. The systematic increase in δD from −75‰ in the outer zones (muscovite) to −63‰ and −53‰ in the inner zones (Li-micas) cannot be explained by closed-system variations in temperature or melt-mica fractionation, but it is consistent with late fluid exsolution. Oxygen isotope compositions of tourmaline (δ18O from 9.7‰ to 11.6‰), quartz (13.3‰ to 14‰) and mica (10.3‰ to 11.3‰) show good agreement with equilibrium partitioning and yield temperatures in the range 450°C to 600°C. Combining this with the stability fields of Li-aluminosilicates petalite and spodumene indicates crystallization pressures of 2–3kbar. Taken together, the stable isotope and mineral chemistry data demonstrate that rare-element enrichment in the innermost fractionated assemblages in the Varuträsk pegmatite was associated with the transition from purely magmatic crystallization to conditions where a separate aqueous fluid phase became important.
•Rare-element enrichment in Varuträsk rare-element pegmatite related to fluid saturation.•Tourmaline δ11B increases during development of primary pegmatite zoning.•Increase in δ11B requires isotopic competition between mica and tourmaline.•Reversal in δ11B trend in late-stage pegmatite assemblages requires fluid separation.
Dopamine (DA) neurons of the midbrain are at risk to become affected by mitochondrial damage over time and mitochondrial defects have been frequently reported in Parkinson's disease (PD) patients. ...However, the causal contribution of adult-onset mitochondrial dysfunction to PD remains uncertain. Here, we developed a mouse model lacking Mitofusin 2 (MFN2), a key regulator of mitochondrial network homeostasis, in adult midbrain DA neurons. The knockout mice develop severe and progressive DA neuron-specific mitochondrial dysfunction resulting in neurodegeneration and parkinsonism. To gain further insights into pathophysiological events, we performed transcriptomic analyses of isolated DA neurons and found that mitochondrial dysfunction triggers an early onset immune response, which precedes mitochondrial swelling, mtDNA depletion, respiratory chain deficiency and cell death. Our experiments show that the immune response is an early pathological event when mitochondrial dysfunction is induced in adult midbrain DA neurons and that neuronal death may be promoted non-cell autonomously by the cross-talk and activation of surrounding glial cells.
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