| 1. |
- Biggs, Reinette, et al.
(författare)
-
Social-ecological change : insights from the Southern African Program on Ecosystem Change and Society
- 2022
-
Ingår i: Ecosystems and People. - : Informa UK Limited. - 2639-5908 .- 2639-5916. ; 18:1, s. 447-468
-
Tidskriftsartikel (refereegranskat)abstract
- Social-ecological systems (SES) research has emerged as an important area of sustainability science, informing and supporting pressing issues of transformation towards more sustainable, just and equitable futures. To date, much SES research has been done in or from the Global North, where the challenges and contexts for supporting sustainability transformations are substantially different from the Global South. This paper synthesises emerging insights on SES dynamics that can inform actions and advance research to support sustainability transformations specifically in the southern African context. The paper draws on work linked to members of the Southern African Program on Ecosystem Change and Society (SAPECS), a leading SES research network in the region, synthesizing key insights with respect to the five core themes of SAPECS: (i) transdisciplinary and engaged research, (ii) ecosystem services and human well-being, (iii) governance institutions and management practices, (iv) spatial relationships and cross-scale connections, and (v) regime shifts, traps and transformations. For each theme, we focus on insights that are particularly novel, interesting or important in the southern African context, and reflect on key research gaps and emerging frontiers for SES research in the region going forward. Such place-based insights are important for understanding the variation in SES dynamics around the world, and are crucial for informing a context-sensitive global agenda to foster sustainability transformations at local to global scales.
|
|
| 2. |
- Biggs, Reinette, et al.
(författare)
-
The Southern African Program on Ecosystem Change and Society : an emergent community of practice
- 2023
-
Ingår i: Ecosystems and People. - : Informa UK Limited. - 2639-5908 .- 2639-5916. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- Sustainability-focused research networks and communities of practice have emerged as a key response and strategy to build capacity and knowledge to support transformation towards more sustainable, just and equitable futures. This paper synthesises insights from the development of a community of practice on social-ecological systems (SES) research in southern Africa over the past decade, linked to the international Programme on Ecosystem Change and Society (PECS). This community consists of a network of researchers who carry out place-based SES research in the southern African region. They interact through various cross-cutting working groups and also host a variety of public colloquia and student and practitioner training events. Known as the Southern African Program on Ecosystem Change and Society (SAPECS), its core objectives are to: (1) derive new approaches and empirical insights on SES dynamics in the southern African context; (2) have a tangible impact by mainstreaming knowledge into policy and practice; and (3) grow the community of practice engaged in SES research and governance, including researchers, students and practitioners. This paper reflects on experiences in building the SAPECS community, with the aim of supporting the development of similar networks elsewhere in the world, particularly in the Global South.
|
|
| 3. |
- Bonagas, Nadilly, et al.
(författare)
-
Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
-
Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
-
Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
|
|
| 4. |
- Gineste, Charlotte, et al.
(författare)
-
Enzymatically dissociated muscle fibers display rapid dedifferentiation and impaired mitochondrial calcium control
- 2022
-
Ingår i: iScience. - : Elsevier. - 2589-0042. ; 25:12
-
Tidskriftsartikel (refereegranskat)abstract
- Cells rapidly lose their physiological phenotype upon disruption of their extracellular matrix (ECM)-intracellular cytoskeleton interactions. By comparing adult mouse skeletal muscle fibers, isolated either by mechanical dissection or by collagenase-induced ECM digestion, we investigated acute effects of ECM disruption on cellular and mitochondrial morphology, transcriptomic signatures, and Ca2+ handling. RNA-sequencing showed striking differences in gene expression patterns between the two isolation methods with enzymatically dissociated fibers resembling myopathic phenotypes. Mitochondrial appearance was grossly similar in the two groups, but 3D electron microscopy revealed shorter and less branched mitochondria following enzymatic dissociation. Repeated contractions resulted in a prolonged mitochondrial Ca2+ accumulation in enzymatically dissociated fibers, which was partially prevented by cyclophilin inhibitors. Of importance, muscle fibers of mice with severe mitochondrial myopathy show pathognomonic mitochondrial Ca2+ accumulation during repeated contractions and this accumulation was concealed with enzymatic dissociation, making this an ambiguous method in studies of native intracellular Ca2+ fluxes.
|
|
| 5. |
- Joelsson, Tanja, 1980-, et al.
(författare)
-
Vardagen i rörelse : en forsknings- och kunskapsöversikt om familjers vardagsmobilitet, social hållbarhet och mobilitetsrättvisa
- 2021
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med rapporten är att förstå vad social hållbarhet betyder i relation till resande, transporter och vardagliga förflyttningar. Av särskilt intresse är det resande som präglar vardagslivet för familjer i socialt utsatta områden. Till grund för rapporten ligger en forsknings- och kunskapsöversikt som berör befintlig forskning om vilken roll resande och transporter spelar i människors liv och hur det kan kopplas till makt, rättvisa och samhällsplanering. Rapporten visar att den tidigare forskningen om transporter, resande och resvanor inte tillräckligt belyser hur urbana områden med en hög andel låginkomsttagare med svag arbetsmarknadsanknytning organiserar och hanterar sin vardagsmobilitet. Forskning om ”transportfattigdom” belyser dock hur tillgång till och möjligheten att utnyttja befintliga transporter leder till ojämlikhet för personer med låg inkomst. Vardagslivets organisering där jobb, familjeliv, restid, och interaktion med institutioner kräver att familjer med en eller flera yrkesarbetande vuxna kan kontrollera sin tid. De studier som specifikt intresserat sig för familjers, barns och ungas resandepraktiker och vad det innebär för att kunna uppnå social hållbarhet, betonar närhet, trygghet och självständighet som viktiga faktorer för samhällsplaneringen. Begreppet mobilitetsrättvisa presenteras slutligen som ett fruktbart sammanhållet ramverk att arbeta med i kommande studier om familjers vardagliga mobilitet i socialt utsatta områden.
|
|
| 6. |
- Johansen, Karin, 1990-, et al.
(författare)
-
Laparoscopic distal pancreatectomy is more cost-effective than open resection: results from a Swedish randomized controlled trial
- 2023
-
Ingår i: HPB. - : ELSEVIER SCI LTD. - 1365-182X .- 1477-2574. ; 25:8, s. 972-979
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundLaparoscopic distal pancreatectomy is being implemented worldwide. The aim of this study was to perform a cost-effectiveness analysis from a health care perspective.MethodsThis cost-effectiveness analysis was based on the randomized controlled trial LAPOP, where 60 patients were randomized to open or laparoscopic distal pancreatectomy. For the follow-up of two years, resource use from a health care perspective was recorded, and health-related quality of life was assessed using the EQ-5D-5L. The per-patient mean cost and quality-adjusted life years (QALYs) were compared using nonparametric bootstrapping.ResultsFifty-six patients were included in the analysis. The mean health care costs were lower, €3863 (95% CI: -€8020 to €385), for the laparoscopic group. Postoperative quality of life improved with laparoscopic resection and resulted in a gain in QALYs of 0.08 (95% CI: −0.09 to 0.25). The laparoscopic group had lower costs and improved QALYs in 79% of bootstrap samples. With a cost-per-QALY threshold of €50 000, 95.4% of the bootstrap samples were in favour of laparoscopic resection.ConclusionLaparoscopic distal pancreatectomy is associated with numerically lower health care costs and improvements in QALYs compared with the open approach. The results support the ongoing transition from open to laparoscopic distal pancreatectomies.
|
|
| 7. |
- Lundgren, Linda, et al.
(författare)
-
Cost-effectiveness of gallbladder histopathology after cholecystectomy for benign disease
- 2020
-
Ingår i: BJS Open. - : JOHN WILEY & SONS LTD. - 2474-9842. ; 4:6, s. 1125-1136
-
Tidskriftsartikel (refereegranskat)abstract
- Background The prevalence of incidental gallbladder cancer is low when performing cholecystectomy for benign disease. The performance of routine or selective histological examination of the gallbladder is still a subject for discussion. The aim of this study was to assess the cost-effectiveness of these different approaches. Methods Four management strategies were evaluated using decision-analytical modelling: no histology, current selective histology as practised in Sweden, macroscopic selective histology, and routine histology. Healthcare costs and life-years were estimated for a lifetime perspective and combined into incremental cost-effectiveness ratios (ICERs) to assess the additional cost of achieving an additional life-year for each management strategy. Results In the analysis of the four strategies, current selective histology was ruled out due to a higher ICER compared with macroscopic selective histology, which showed better health outcomes (extended dominance). Comparison of routine histology with macroscopic selective histology resulted in a gain of 12 life-years and an incremental healthcare cost of approximately euro1 000 000 in a cohort of 10 000 patients, yielding an estimated ICER of euro76 508. When comparing a macroscopic selective strategy with no histological assessment, 50 life-years would be saved and the ICER was estimated to be euro20 708 in a cohort of 10 000 patients undergoing cholecystectomy. Conclusion A macroscopic selective strategy appears to be the most cost-effective approach.
|
|
| 8. |
- Pace, Andrea, et al.
(författare)
-
Determining medical decision-making capacity in brain tumor patients : why and how?
- 2020
-
Ingår i: Neuro-Oncology Practice. - : Oxford University Press. - 2054-2577 .- 2054-2585. ; 7:6, s. 599-612
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Brain tumor patients are at high risk of impaired medical decision-making capacity (MDC), which can be ethically challenging because it limits their ability to give informed consent to medical treatments or participation in research. The European Association of Neuro-Oncology Palliative Care Multidisciplinary Task Force performed a systematic review to identify relevant evidence with respect to MDC that could be used to give recommendations on how to cope with reduced MDC in brain tumor patients.Methods: A literature search in several electronic databases was conducted up to September 2019, including studies with brain tumor and other neurological patients. Information related to the following topics was extracted: tools to measure MDC, consent to treatment or research, predictive patient- and treatment-related factors, surrogate decision making, and interventions to improve MDC.Results: A total of 138 articles were deemed eligible. Several structured capacity-assessment instruments are available to aid clinical decision making. These instruments revealed a high incidence of impaired MDC both in brain tumors and other neurological diseases for treatment- and research-related decisions. Incapacity appeared to be mostly determined by the level of cognitive impairment. Surrogate decision making should be considered in case a patient lacks capacity, ensuring that the patient's "best interests" and wishes are guaranteed. Several methods are available that may help to enhance patients' consent capacity.Conclusions: Clinical recommendations on how to detect and manage reduced MDC in brain tumor patients were formulated, reflecting among others the timing of MDC assessments, methods to enhance patients' consent capacity, and alternative procedures, including surrogate consent.
|
|
| 9. |
- Willén, Linda, 1979-
(författare)
-
Factors influencing management and outcome in non-small cell lung cancer : the role of socioeconomic status, age, geographic region of origin and aspects of quality of life
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Yearly, 4,200 individuals in Sweden are diagnosed with lung cancer, of which 85 % are non-small cell lung cancer (NSCLC). The aims of this thesis were to investigate aspects of equality of care and outcomes in patients with NSCLC and to examine indicators of quality of life. All studies used data in Lung Cancer Database Sweden (LCBaSe), a research database generated by record linkages between the National Lung Cancer Register and other population-based registers. We identified 40,000 patients with NSCLC diagnosed between 2002 and 2016.Paper I examined influence of socioeconomic status. Patients with a high educational level were more often offered PET-CT, assessed in a multidisciplinary team setting, treated with stereotactic body radiotherapy and had better survival in early-, but not in late-stage disease.Paper II investigated elderly NSCLC patients. No difference in stage was seen in patients ≤ 84 years, nor in diagnostic intensity <80 years. Treatment intensity was adapted according to age. Survival differed across age groups in early-, but not late-stage disease.Paper III examined immigrants. We found evidence of a “healthy migrant effect”. There were only small differences in management and outcome. If anything, non-Nordic immigrants had better survival in early-stage disease. Paper IV assessed psychological impact following a NSCLC diagnosis. Higher rates of depression, anxiety, intoxication and suicide were seen in NSCLC patients compared to lung cancer free individuals. The risk of depression, anxiety and suicide decreased over time but the increased risk of intoxication remained throughout the follow-up period.In summary, we found equal access of care and only minor differences in patterns of management and outcomes according to socioeconomic status, age and geographic region of origin. New diagnostics and treatment modalities need to be quickly introduced to enable equal access across socioeconomic groups. A careful assessment of older patients is important to avoid age-biased clinical decision-making. A diagnosis of NSCLC impacts psychological aspects of quality of life and active measures to identify and treat depression and anxiety as well as to identify patients at risk of intoxication and suicide is necessary.
|
|
