| 51. |
- Walmsley, T., et al.
(författare)
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Characterizing the multi-dimensional reaction dynamics of dihalomethanes using XUV-induced Coulomb explosion imaging
- 2023
-
Ingår i: Journal of Chemical Physics. - 0021-9606. ; 159:14
-
Tidskriftsartikel (refereegranskat)abstract
- Site-selective probing of iodine 4d orbitals at 13.1 nm was used to characterize the photolysis of CH2I2 and CH2BrI initiated at 202.5 nm. Time-dependent fragment ion momenta were recorded using Coulomb explosion imaging mass spectrometry and used to determine the structural dynamics of the dissociating molecules. Correlations between these fragment momenta, as well as the onset times of electron transfer reactions between them, indicate that each molecule can undergo neutral three-body photolysis. For CH2I2, the structural evolution of the neutral molecule was simultaneously characterized along the C-I and I-C-I coordinates, demonstrating the sensitivity of these measurements to nuclear motion along multiple degrees of freedom.
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| 52. |
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| 53. |
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| 54. |
- Colleoni, M, et al.
(författare)
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Timing of CMF chemotherapy in combination with tamoxifen in postmenopausal women with breast cancer: role of endocrine responsiveness of the tumor.
- 2005
-
Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 0923-7534. ; 16:5, s. 716-25
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Controversy persists about whether chemotherapy benefits all breast cancer patients. PATIENTS AND METHODS: In the International Breast Cancer Study Group (IBCSG) trial VII, 1212 postmenopausal patients with node-positive disease were randomized to receive tamoxifen for 5 years or tamoxifen plus three concurrent courses of cyclophosphamide, methotrexate and 5-fluorouracil ('classical' CMF) chemotherapy, either early, delayed or both. In IBCSG trial IX, 1669 postmenopausal patients with node-negative disease were randomized to receive either tamoxifen alone or three courses of adjuvant classical CMF prior to tamoxifen. Results were assessed according to estrogen receptor (ER) content of the primary tumor. RESULTS: For patients with node-positive, ER-positive disease, adding CMF either early, delayed or both reduced the risk of relapse by 21% (P=0.06), 26% (P=0.02) and 25% (P=0.02), respectively, compared with tamoxifen alone. There was no difference in disease-free survival when CMF was given prior to tamoxifen in patients with node-negative, ER-positive tumors. CONCLUSIONS: CMF given concurrently (early, delayed or both) with tamoxifen was more effective than tamoxifen alone for patients with node-positive, endocrine-responsive breast cancer, supporting late administration of chemotherapy even after commencement of tamoxifen. In contrast, sequential CMF and tamoxifen for patients with node-negative, endocrine-responsive disease was ineffective.
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| 55. |
- Courseaux, A, et al.
(författare)
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Definition of the minimal MEN 1 candidate area based on a 5-Mb integrated map proximal to 11q13 : The european consortium on men1
- 1996
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 37:3, s. 345-353
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with a high penetrance characterized by tumors of the parathyroid glands, the endocrine pancreas, and the anterior pituitary. The MEN1 gene, a putative tumor suppressor gene, has been mapped to a 3- to 8-cM region in chromosome 11q13 but it remains elusive as yet. We have combined the efforts and resources from four laboratories to form the European Consortium on MEN1 with the aims of establishing the genetic and the physical maps of 11q13 and of further narrowing the MEN1 region. A 5-Mb integrated map of the region was established by fluorescence in situ hybridization on both metaphase chromosomes and DNA fibers, by hybridization to DNA from somatic cell hybrids containing various parts of human chromosome 11, by long-range restriction mapping, and by characterization of YACs and cosmids. Polymorphic markers were positioned and ordered by physical mapping and genetic linkage in 86 MEN1 families with 452 affected individuals. Two critical recombinants identified in two affected cases placed the MEN1 gene in an approximately 2-Mb region around PYGM, flanked by D11S1883 and D11S449.
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| 56. |
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| 57. |
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| 58. |
- Gornall, B. F., et al.
(författare)
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Measurement of quality of recovery using the QoR-40:a quantitative systematic review
- 2013
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912 .- 1471-6771. ; 111:2, s. 161-169
-
Forskningsöversikt (refereegranskat)abstract
- Background.Several rating scales have been developed to measure quality of recovery aftersurgery and anaesthesia, but the most extensively used is the QoR-40, a 40-itemquestionnaire that provides a global score and subscores across five dimensions: patientsupport, comfort, emotions, physical independence, and pain. It has been evaluated in avariety of settings, but its overall psychometric properties (validity, reliability, ease of use,and interpretation) and clinical utility are uncertain.Methods.We undertook a quantitative systematic review of studies evaluatingpsychometric properties of the QoR-40. Data were combined in meta-analyses usingrandom effects models. This resulted in a total sample of 3459 patients from 17 studiesoriginating in nine countries.Results.We confirmed content, construct, and convergent [pooled r¼0.58, 95% confidenceinterval (CI): 0.51–0.65] validity. Reliability was confirmed by excellent intraclass correlation(pooleda¼0.91, 95% CI: 0.88–0.93), test–retest reliability (pooled r¼0.90, 95% CI: 0.86–0.92), and inter-rater reliability (intraclass correlation¼0.86). The clinical utility of theQoR-40 instrument was supported by high patient recruitment into evaluation studies(97%), and an excellent completion and return rate (97%). The mean time to completethe QoR-40 was 5.1 (95% CI: 4.4–5.7) min.Conclusions.The QoR-40 is a widely used and extensively validated measure of quality ofrecovery. The QoR-40 is a suitable measure of postoperative quality of recovery in arange of clinical and research situations.Keywords:health status; meta-analysis; outcomes
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| 59. |
- Graham, C., et al.
(författare)
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The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke : Statistical and health economic analysis plan for the trials and for the individual patient data meta-analysis
- 2017
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Ingår i: Trials. - : BioMed Central Ltd.. - 1745-6215. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Small trials have suggested that fluoxetine may improve neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials which aim to determine whether the routine administration of fluoxetine (20 mg daily) for six months after an acute stroke improves patients' functional outcome. Methods/Design: The core protocol for the three trials has been published (Mead et al., Trials 20:369, 2015). The trials include patients aged 18 years and older with a clinical diagnosis of stroke and persisting focal neurological deficits at randomisation 2-15 days after stroke onset. Patients are randomised centrally via each trials' web-based randomisation system using a common minimisation algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for six months. The primary outcome measure is the modified Rankin scale (mRS) at six months. Secondary outcomes include: living circumstances; the Stroke Impact Scale; EuroQol (EQ5D-5 L); the vitality subscale of the 36-Item Short Form Health Survey (SF36); diagnosis of depression; adherence to medication; serious adverse events including death and recurrent stroke; and resource use at six and 12 months and the mRS at 12 months. Discussion: Minor variations have been tailored to the national setting in the UK (FOCUS), Australia, New Zealand and Vietnam (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned individual patient data meta-analysis of all three trials will provide the most precise estimate of the overall effect and establish whether any effects differ between trials or subgroups. This statistical analysis plan describes the core analyses for all three trials and that for the individual patient data meta-analysis. Recruitment and follow-up in the FOCUS trial is expected to be completed by the end of 2018. AFFINITY and EFFECTS are likely to complete follow-up in 2020.
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| 60. |
- Karlsson, Per, 1963, et al.
(författare)
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Patterns and risk factors for locoregional failures after mastectomy for breast cancer: an International Breast Cancer Study Group report
- 2012
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 23:11, s. 2852-2858
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Tidskriftsartikel (refereegranskat)abstract
- Rates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT). Local, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years. Ten-year cumulative incidence for chest wall recurrence of > 15% was seen in patients aged < 40 years (16.1%), with >= 4 positive nodes (16.5%) or 0-7 uninvolved nodes (15.1%); for supraclavicular failures > 10%: >= 4 positive nodes (10.2%); for axillary failures of > 5%: aged < 40 years (5.1%), unknown primary tumor size (5.2%), 0-7 uninvolved nodes (5.2%). In patients with 1-3 positive nodes, 10-year cumulative incidence for chest wall recurrence of > 15% were age < 40, peritumoral vessel invasion or 0-7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site. PMRT to the chest wall and supraclavicular fossa is supported in patients with >= 4 positive nodes. With 1-3 positive nodes, chest wall PMRT may be considered in patients aged < 40 years, with 0-7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axilla.
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| 61. |
- Maccari, Maria Elena, et al.
(författare)
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Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity.
- 2023
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Ingår i: The Journal of allergy and clinical immunology. - 1097-6825. ; 152:4
-
Tidskriftsartikel (refereegranskat)abstract
- Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking.This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS.Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs.The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS.APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.
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| 62. |
- Rabaglio, M, et al.
(författare)
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Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial.
- 2009
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 1569-8041. ; 20:9, s. 1489-98
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. METHODS: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. RESULTS: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. CONCLUSIONS: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.
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| 63. |
- Reintam Blaser, A., et al.
(författare)
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Incidence, diagnosis, management and outcome of acute mesenteric ischaemia: a prospective, multicentre observational study (AMESI Study)
- 2024
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Ingår i: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 28:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this multicentre prospective observational study was to identify the incidence, patient characteristics, diagnostic pathway, management and outcome of acute mesenteric ischaemia (AMI). Methods: All adult patients with clinical suspicion of AMI admitted or transferred to 32 participating hospitals from 06.06.2022 to 05.04.2023 were included. Participants who were subsequently shown not to have AMI or had localized intestinal gangrene due to strangulating bowel obstruction had only baseline and outcome data collected. Results: AMI occurred in 0.038% of adult admissions in participating acute care hospitals worldwide. From a total of 705 included patients, 418 patients had confirmed AMI. In 69% AMI was the primary reason for admission, while in 31% AMI occurred after having been admitted with another diagnosis. Median time from onset of symptoms to hospital admission in patients admitted due to AMI was 24 h (interquartile range 9-48h) and time from admission to diagnosis was 6h (1–12 h). Occlusive arterial AMI was diagnosed in 231 (55.3%), venous in 73 (17.5%), non-occlusive (NOMI) in 55 (13.2%), other type in 11 (2.6%) and the subtype could not be classified in 48 (11.5%) patients. Surgery was the initial management in 242 (58%) patients, of which 59 (24.4%) underwent revascularization. Endovascular revascularization alone was carried out in 54 (13%), conservative treatment in 76 (18%) and palliative care in 46 (11%) patients. From patients with occlusive arterial AMI, revascularization was undertaken in 104 (45%), with 40 (38%) of them in one site admitting selected patients. Overall in-hospital and 90-day mortality of AMI was 49% and 53.3%, respectively, and among subtypes was lowest for venous AMI (13.7% and 16.4%) and highest for NOMI (72.7% and 74.5%). There was a high variability between participating sites for most variables studied. Conclusions: The overall incidence of AMI and AMI subtypes varies worldwide, and case ascertainment is challenging. Pre-hospital delay in presentation was greater than delays after arriving at hospital. Surgery without revascularization was the most common management approach. Nearly half of the patients with AMI died during their index hospitalization. Together, these findings suggest a need for greater awareness of AMI, and better guidance in diagnosis and management. Trial registration: NCT05218863 (registered 19.01.2022).
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| 64. |
- Vuong, Lynda, et al.
(författare)
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An orally active galectin-3 antagonist inhibits lung adenocarcinoma growth and augments response to PD-L1 blockade
- 2019
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Ingår i: Cancer Research. - 0008-5472. ; 79:7, s. 1480-1492
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Tidskriftsartikel (refereegranskat)abstract
- A combination therapy approach is required to improve tumor immune infiltration and patient response to immune checkpoint inhibitors that target negative regulatory receptors. Galectin-3 is a β-galactoside-binding lectin that is highly expressed within the tumor microenvironment of aggressive cancers and whose expression correlates with poor survival particularly in patients with non-small cell lung cancer (NSCLC). To examine the role of galectin-3 inhibition in NSCLC, we tested the effects of galectin-3 depletion using genetic and pharmacologic approaches on syngeneic mouse lung adenocarcinoma and human lung adenocarcinoma xenografts. Galectin-3-/- mice developed significantly smaller and fewer tumors and metastases than syngeneic C57/ Bl6 wild-type mice. Macrophage ablation retarded tumor growth, whereas reconstitution with galectin-3-positive bone marrow restored tumor growth in galectin-3-/- mice, indicating that macrophages were a major driver of the antitumor response. Oral administration of a novel small molecule galectin-3 inhibitor GB1107 reduced human and mouse lung adenocarcinoma growth and blocked metastasis in the syngeneic model. Treatment with GB1107 increased tumor M1 macrophage polarization and CD8 + T-cell infiltration. Moreover, GB1107 potentiated the effects of a PD-L1 immune checkpoint inhibitor to increase expression of cytotoxic (IFNγ, granzyme B, perforin-1, Fas ligand) and apoptotic (cleaved caspase-3) effector molecules. In summary, galectin-3 is an important regulator of lung adenocarcinoma progression. The novel galectin-3 inhibitor presented could provide an effective, nontoxic monotherapy or be used in combination with immune checkpoint inhibitors to boost immune infiltration and responses in lung adenocarcinoma and potentially other aggressive cancers. Significance: A novel and orally active galectin-3 antagonist inhibits lung adenocarcinoma growth and metastasis and augments response to PD-L1 blockade.
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| 65. |
- Wallgren, Arne, 1940, et al.
(författare)
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Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII.
- 2003
-
Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X. ; 21:7, s. 1205-13
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies. PATIENTS AND METHODS: The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months' duration and/or tamoxifen. Median follow-up is 12 to 15.5 years. RESULTS: In women with node-negative disease, factors associated with increased risk of LRF were vascular invasion (VI) and tumor size greater than 2 cm for premenopausal and VI for postmenopausal patients. Of the 1,275 patients, 345 (27%) met criteria for the highest risk groups, and the 10-year cumulative incidences of LRF with or without distant metastases were 16% for premenopausal and 19% for postmenopausal women. For the node-positive cohort, number of nodes and tumor grade were factors for both menopausal groups, with additional prediction provided by VI for premenopausal and tumor size for postmenopausal patients. Of the 4,077 patients, 815 (20%) met criteria for the highest risk groups, and 10-year cumulative incidences were 35% for premenopausal and 34% for postmenopausal women. CONCLUSION: LRFs are a significant problem after mastectomy alone even for some patients with node-negative breast cancer, as well as after mastectomy and adjuvant treatment for some subgroups of patients with node-positive disease. In addition to number of positive lymph nodes, predictors of LRF include tumor-related factors, such as vascular invasion, higher grade, and larger size.
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| 66. |
- Barrio, Isabel C., et al.
(författare)
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Background invertebrate herbivory on dwarf birch (Betula glandulosa-nana complex) increases with temperature and precipitation across the tundra biome
- 2017
-
Ingår i: Polar Biology. - : Springer. - 0722-4060 .- 1432-2056. ; 40:11, s. 2265-2278
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Tidskriftsartikel (refereegranskat)abstract
- Chronic, low intensity herbivory by invertebrates, termed background herbivory, has been understudied in tundra, yet its impacts are likely to increase in a warmer Arctic. The magnitude of these changes is however hard to predict as we know little about the drivers of current levels of invertebrate herbivory in tundra. We assessed the intensity of invertebrate herbivory on a common tundra plant, the dwarf birch (Betula glandulosa-nana complex), and investigated its relationship to latitude and climate across the tundra biome. Leaf damage by defoliating, mining and gall-forming invertebrates was measured in samples collected from 192 sites at 56 locations. Our results indicate that invertebrate herbivory is nearly ubiquitous across the tundra biome but occurs at low intensity. On average, invertebrates damaged 11.2% of the leaves and removed 1.4% of total leaf area. The damage was mainly caused by external leaf feeders, and most damaged leaves were only slightly affected (12% leaf area lost). Foliar damage was consistently positively correlated with mid-summer (July) temperature and, to a lesser extent, precipitation in the year of data collection, irrespective of latitude. Our models predict that, on average, foliar losses to invertebrates on dwarf birch are likely to increase by 6-7% over the current levels with a 1 degrees C increase in summer temperatures. Our results show that invertebrate herbivory on dwarf birch is small in magnitude but given its prevalence and dependence on climatic variables, background invertebrate herbivory should be included in predictions of climate change impacts on tundra ecosystems.
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| 67. |
- Barrio, Isabel C., et al.
(författare)
-
Publisher Correction to : Background invertebrate herbivory on dwarf birch (Betula glandulosa-nana complex) increases with temperature and precipitation across the tundra biome (vol 40, pg 2265, 2017)
- 2018
-
Ingår i: Polar Biology. - : Springer. - 0722-4060 .- 1432-2056. ; 41:8, s. 1653-1654
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Tidskriftsartikel (refereegranskat)abstract
- The above mentioned article was originally scheduled for publication in the special issue on Ecology of Tundra Arthropods with guest editors Toke T. Hoye . Lauren E. Culler. Erroneously, the article was published in Polar Biology, Volume 40, Issue 11, November, 2017. The publisher sincerely apologizes to the guest editors and the authors for the inconvenience caused.
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| 68. |
- Berner, Logan T., et al.
(författare)
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The Arctic plant aboveground biomass synthesis dataset
- 2024
-
Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Plant biomass is a fundamental ecosystem attribute that is sensitive to rapid climatic changes occurring in the Arctic. Nevertheless, measuring plant biomass in the Arctic is logistically challenging and resource intensive. Lack of accessible field data hinders efforts to understand the amount, composition, distribution, and changes in plant biomass in these northern ecosystems. Here, we present The Arctic plant aboveground biomass synthesis dataset, which includes field measurements of lichen, bryophyte, herb, shrub, and/or tree aboveground biomass (g m−2) on 2,327 sample plots from 636 field sites in seven countries. We created the synthesis dataset by assembling and harmonizing 32 individual datasets. Aboveground biomass was primarily quantified by harvesting sample plots during mid- to late-summer, though tree and often tall shrub biomass were quantified using surveys and allometric models. Each biomass measurement is associated with metadata including sample date, location, method, data source, and other information. This unique dataset can be leveraged to monitor, map, and model plant biomass across the rapidly warming Arctic.
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| 69. |
- Borne, Kurtis D., et al.
(författare)
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Ultrafast electronic relaxation pathways of the molecular photoswitch quadricyclane
- 2024
-
Ingår i: NATURE CHEMISTRY. - 1755-4330 .- 1755-4349. ; 16, s. 499-505
-
Tidskriftsartikel (refereegranskat)abstract
- The light-induced ultrafast switching between molecular isomers norbornadiene and quadricyclane can reversibly store and release a substantial amount of chemical energy. Prior work observed signatures of ultrafast molecular dynamics in both isomers upon ultraviolet excitation but could not follow the electronic relaxation all the way back to the ground state experimentally. Here we study the electronic relaxation of quadricyclane after exciting in the ultraviolet (201 nanometres) using time-resolved gas-phase extreme ultraviolet photoelectron spectroscopy combined with non-adiabatic molecular dynamics simulations. We identify two competing pathways by which electronically excited quadricyclane molecules relax to the electronic ground state. The fast pathway (<100 femtoseconds) is distinguished by effective coupling to valence electronic states, while the slow pathway involves initial motions across Rydberg states and takes several hundred femtoseconds. Both pathways facilitate interconversion between the two isomers, albeit on different timescales, and we predict that the branching ratio of norbornadiene/quadricyclane products immediately after returning to the electronic ground state is approximately 3:2.
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| 70. |
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| 71. |
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| 72. |
- He, H. J., et al.
(författare)
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Multilaboratory Assessment of a New Reference Material for Quality Assurance of Cell-Free Tumor DNA Measurements
- 2019
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Ingår i: Journal of Molecular Diagnostics. - : Elsevier BV. - 1525-1578. ; 21:4, s. 658-676
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a multilaboratory assessment to determine the suitability of a new commercially available reference material with 40 cancer variants in a background of wild-type DNA at four different variant allele frequencies (VAFs): 2%, 0.50%, 0.125%, and 0%. The variants include single nucleotides, insertions, deletions, and two structural variations selected for their clinical importance and to challenge the performance of next-generation sequencing (NGS) methods. Fragmented DNA was formulated to simulate the size distribution of circulating wild-type and tumor DNA in a synthetic plasma matrix. DNA was extracted from these samples and characterized with different methods and multiple laboratories. The various extraction methods had differences in yield, perhaps because of differences in chemistry. Digital PCR assays were used to measure VAFs to compare results from different NGS methods. Comparable VAFs were observed across the different NGS methods. This multilaboratory assessment demonstrates that the new reference material is an appropriate tool to determine the analytical parameters of different measurement methods and to ensure their quality assurance.
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| 73. |
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| 74. |
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| 75. |
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| 76. |
- Pathak, S., et al.
(författare)
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Tracking the ultraviolet-induced photochemistry of thiophenone during and after ultrafast ring opening
- 2020
-
Ingår i: Nature Chemistry. - : Springer Science and Business Media LLC. - 1755-4330 .- 1755-4349. ; 12:9, s. 795-800
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Tidskriftsartikel (refereegranskat)abstract
- Photoinduced isomerization reactions lie at the heart of many chemical processes in nature. The mechanisms of such reactions are determined by a delicate interplay of coupled electronic and nuclear dynamics occurring on the femtosecond scale, followed by the slower redistribution of energy into different vibrational degrees of freedom. Here we apply time-resolved photoelectron spectroscopy with a seeded extreme ultraviolet free-electron laser to trace the ultrafast ring opening of gas-phase thiophenone molecules following ultraviolet photoexcitation. When combined with ab initio electronic structure and molecular dynamics calculations of the excited- and ground-state molecules, the results provide insights into both the electronic and nuclear dynamics of this fundamental class of reactions. The initial ring opening and non-adiabatic coupling to the electronic ground state are shown to be driven by ballistic S-C bond extension and to be complete within 350 fs. Theory and experiment also enable visualization of the rich ground-state dynamics that involve the formation of, and interconversion between, ring-opened isomers and the cyclic structure, as well as fragmentation over much longer timescales.
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| 77. |
- Phillips, K. A., et al.
(författare)
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Adjuvant ovarian function suppression and cognitive function in women with breast cancer
- 2016
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 114:9, s. 956-964
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Tidskriftsartikel (refereegranskat)abstract
- Background: To examine the effect on cognitive function of adjuvant ovarian function suppression (OFS) for breast cancer. Methods: The Suppression of Ovarian Function (SOFT) trial randomised premenopausal women with hormone receptor-positive breast cancer to 5 years adjuvant endocrine therapy with tamoxifen + OFS, exemestane + OFS or tamoxifen alone. The Co-SOFT substudy assessed objective cognitive function and patient reported outcomes at randomisation (T0), and 1 year later (T1); the primary endpoint was change in global cognitive function, measured by the composite objective cognitive function score. Data were compared for the pooled tamoxifen + OFS and exemestane + OFS groups vs the tamoxifen alone group using the Wilcoxon rank-sum test. Results: Of 86 participants, 74 underwent both T0 and T1 cognitive testing; 54 randomised to OFS+ either tamoxifen (28) or exemestane (26) and 20 randomised to tamoxifen alone. There was no significant difference in the changes in the composite cognitive function scores between the OFS+ tamoxifen or exemestane groups and the tamoxifen group (mean +/- s.d., -0.21 +/- 0.92 vs -0.04 +/- 0.49, respectively, P = 0.71, effect size = -0.20), regardless of prior chemotherapy status, and adjusting for baseline characteristics. Conclusions: The Co-SOFT study, although limited by small samples size, provides no evidence that adding OFS to adjuvant oral endocrine therapy substantially affects global cognitive function.
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| 78. |
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| 79. |
- Stray-Pedersen, Asbjorg, et al.
(författare)
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Primary immunodeficiency diseases : Genomic approaches delineate heterogeneous Mendelian disorders
- 2017
-
Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:1, s. 232-245
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.
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| 80. |
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| 81. |
- Ahrens, Richard, et al.
(författare)
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Intestinal Macrophage/Epithelial Cell-Derived CCL11/Eotaxin-1 Mediates Eosinophil Recruitment and Function in Pediatric Ulcerative Colitis
- 2008
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Ingår i: Journal of Immunology. - 0022-1767 .- 1550-6606. ; 181:10, s. 7390-7399
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Tidskriftsartikel (refereegranskat)abstract
- Clinical studies have demonstrated a link between the eosinophil-selective chemokines, eotaxins (eotaxin-1/CCL11 and eotaxin-2/CCL24), eosinophils, and the inflammatory bowel diseases, Crohn's disease and ulcerative colitis (UC). However, the cellular source and individual contribution of the eotaxins to colonic eosinophilic accumulation in inflammatory bowel diseases remain unclear. In this study we demonstrate, by gene array and quantitative PCR, elevated levels of eotaxin-1 mRNA in the rectosigmoid colon of pediatric UC patients. We show that elevated levels of eotaxin-1 mRNA positively correlated with rectosigmoid eosinophil numbers. Further, colonic eosinophils appeared to be degranulating, and the levels positively correlated with disease severity. Using the dextran sodium sulfate (DSS)-induced intestinal epithelial injury model, we show that DSS treatment of mice strongly induced colonic eotaxin-1 and eotaxin-2 expression and eosinophil levels. Analysis of eosinophil-deficient mice defined an effector role for eosinophils in disease pathology. DSS treatment of eotaxin-2(-/-) and eotaxin-1/2(-/-) mice demonstrated that eosinophil recruitment was dependent on eotaxin-1. In situ and immunofluorescence analysis-identified eotaxin-1 expression was restricted to intestinal F4/80(+)CD11b(+) macrophages in DSS-induced epithelia] injury and to CD68(+) intestinal macrophages and the basolateral compartment of intestinal epithelial cells in pediatric UC. These data demonstrate that intestinal macrophage and epithelial cell-derived eotaxin-1 plays a critical role in the regulation of eosinophil recruitment in colonic eosinophilic disease such as pediatric UC and provides a basis for targeting the eosinophil/eotaxin-1 axis in UC.
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| 82. |
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| 83. |
- Barrio, I. C., et al.
(författare)
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Biotic interactions mediate patterns of herbivore diversity in the Arctic
- 2016
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Ingår i: Global Ecology and Biogeography. - : Wiley-Blackwell. - 1466-822X .- 1466-8238. ; 25:9, s. 1108-1118
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Understanding the forces shaping biodiversity patterns, particularly for groups of organisms with key functional roles, will help predict the responses of ecosystems to environmental changes. Our aim was to evaluate the relative role of different drivers in shaping the diversity patterns of vertebrate herbivores, a group of organisms exerting a strong trophic influence in terrestrial Arctic ecosystems. This biome, traditionally perceived as homogeneous and low in biodiversity, includes wide variation in biotic and physical conditions and is currently undergoing major environmental change. Location: The Arctic (including the High Arctic, Low Arctic and Subarctic) MethodsWe compiled available data on vertebrate (birds and mammals) herbivore distribution at a pan-Arctic scale, and used eight variables that represent the most relevant hypotheses for explaining patterns of species richness. We used range maps rasterized on a 100kmx100km equal-area grid to analyse richness patterns of all vertebrate herbivore species combined, and birds and mammalian herbivores separately. Results: Overall, patterns of herbivore species richness in the Arctic were positively related to plant productivity (measured using the normalized difference vegetation index) and to the species richness of predators. Greater species richness of herbivores was also linked to areas with a higher mean annual temperature. Species richness of avian and mammalian herbivores were related to the distance from the coast, with the highest avian richness in coastal areas and mammalian richness peaking further inland. Main conclusions: Herbivore richness in the Arctic is most strongly linked to primary productivity and the species richness of predators. Our results suggest that biotic interactions, with either higher or lower trophic levels or both, can drive patterns of species richness at a biome-wide scale. Rapid ongoing environmental changes in the Arctic are likely to affect herbivore diversity through impacts on both primary productivity and changes in predator communities via range expansion of predators from lower latitudes.
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| 84. |
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| 85. |
- da Bandeira, Diana Sa, et al.
(författare)
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PDGFR beta(+) cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny
- 2022
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Ingår i: Cell Reports. - : CELL PRESS. - 2211-1247. ; 40:3
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cell (HSC) generation in the aorta-gonad-mesonephros region requires HSC specification signals from the surrounding microenvironment. In zebrafish, PDGF-B/PDGFR beta signaling controls hematopoietic stem/progenitor cell (HSPC) generation and is required in the HSC specification niche. Little is known about murine HSPC specification in vivo and whether PDGF-B/PDGFR beta is involved. Here, we show that PDGFR beta is expressed in distinct perivascular stromal cell layers surrounding the mid-gestation dorsal aorta, and its deletion impairs hematopoiesis. We demonstrate that PDGFR beta(+) cells play a dual role in murine hematopoiesis. They act in the aortic niche to support HSPCs, and in addition, PDGFR beta(+) embryonic precursors give rise to a subset of HSPCs that persist into adulthood. These findings provide crucial information for the controlled production of HSPCs in vitro.
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| 86. |
- Dennis, Martin, et al.
(författare)
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Effects of fluoxetine on functional outcomes after acute stroke (FOCUS) : a pragmatic, double-blind, randomised, controlled trial
- 2019
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 393:10168, s. 265-274
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Tidskriftsartikel (refereegranskat)abstract
- Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.Findings Between Sept 10,2012, and March 31,2017,3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99.3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0.951 [95% CI 0.839-1.079]; p=0.439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13.43%] patients vs 269 [17.21%]; difference 3.78% [95% CI 1.26-6.30]; p=0.0033), but they had more bone fractures (45 [2.88%] vs 23 [1.47%]; difference 1.41% [95% CI 0.38-2.43]; p=0.0070). There were no significant differences in any other event at 6 or 12 months.Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.
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| 87. |
- Dennis, Martin, et al.
(författare)
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Fluoxetine and Fractures After Stroke : Exploratory Analyses From the FOCUS Trial
- 2019
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Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 50:11, s. 3280-3282
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose- The FOCUS trial (Fluoxetine or Control Under Supervision) showed that fluoxetine did not improve modified Rankin Scale scores (mRS) but increased the risk of fractures. We aimed to describe the fractures, their impact on mRS and factors associated with fracture risk. Methods- A United Kingdom, multicenter, parallel-group, randomized, placebo-controlled trial. Patients ≥18 years with a clinical stroke and persisting deficit assessed 2 to 15 days after onset were eligible. Consenting patients were allocated fluoxetine 20 mg or matching placebo for 6 months. The primary outcome was the mRS at 6 months and secondary outcomes included fractures. Results- Sixty-five of 3127 (2.1%) patients had 67 fractures within 6 months of randomization; 43 assigned fluoxetine and 22 placebo. Fifty-nine (90.8%) had fallen and 26 (40%) had fractured their neck of femur. The effect of fluoxetine on mRS (common odds ratio =0.951) was not significantly altered by excluding fracture patients (common odds ratio =0.961). Cox proportional hazards modeling showed that only age >70 year (hazard ratio =1.97; 95% CI, 1.13-3.45; P=0.017), female sex (hazard ratio =2.13; 95% CI, 1.29-3.51; P=0.003), and fluoxetine (hazard ratio =2.00; 95% CI, 1.20-3.34; P=0.008) were independently associated with fractures. Conclusions- Most fractures resulted from falls. Although many fractures were serious, and likely to impair patients' function, the increased fracture risk did not explain the lack of observed effect of fluoxetine on mRS. Only increasing age, female sex, and fluoxetine were independent predictors of fractures. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN83290762.
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| 88. |
- Dennis, Martin, et al.
(författare)
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Fluoxetine to improve functional outcomes in patients after acute stroke : the FOCUS RCT
- 2020
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Ingår i: Health technology assessment (Winchester, England). - : National Institute for Health Research. - 2046-4924 .- 1366-5278. ; 24:22, s. 1-
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Rapport (refereegranskat)abstract
- BackgroundOur Cochrane review of selective serotonin inhibitors for stroke recovery indicated that fluoxetine may improve functional recovery, but the trials were small and most were at high risk of bias.ObjectivesThe Fluoxetine Or Control Under Supervision (FOCUS) trial tested the hypothesis that fluoxetine improves recovery after stroke.DesignThe FOCUS trial was a pragmatic, multicentre, parallel-group, individually randomised, placebo-controlled trial.SettingThis trial took place in 103 UK hospitals.ParticipantsPatients were eligible if they were aged ≥ 18 years, had a clinical stroke diagnosis, with focal neurological deficits, between 2 and 15 days after onset.InterventionsPatients were randomly allocated 20 mg of fluoxetine once per day or the matching placebo for 6 months via a web-based system using a minimisation algorithm.Main outcome measuresThe primary outcome was the modified Rankin Scale at 6 months. Patients, carers, health-care staff and the trial team were masked to treatment allocation. Outcome was assessed at 6 and 12 months after randomisation. Patients were analysed by their treatment allocation as specified in a published statistical analysis plan.ResultsBetween 10 September 2012 and 31 March 2017, we recruited 3127 patients, 1564 of whom were allocated fluoxetine and 1563 of whom were allocated placebo. The modified Rankin Scale score at 6 months was available for 1553 out of 1564 (99.3%) of those allocated fluoxetine and 1553 out of 1563 (99.4%) of those allocated placebo. The distribution across modified Rankin Scale categories at 6 months was similar in the two groups (common odds ratio adjusted for minimisation variables 0.951, 95% confidence interval 0.839 to 1.079; p = 0.439). Compared with placebo, patients who were allocated fluoxetine were less likely to develop a new episode of depression by 6 months [210 (13.0%) vs. 269 (16.9%), difference –3.78%, 95% confidence interval –1.26% to –6.30%; p = 0.003], but had more bone fractures [45 (2.9%) vs. 23 (1.5%), difference 1.41%, 95% confidence interval 0.38% to 2.43%; p = 0.007]. There were no statistically significant differences in any other recorded events at 6 or 12 months. Health economic analyses showed no differences between groups in health-related quality of life, hospital bed usage or health-care costs.LimitationsSome non-adherence to trial medication, lack of face-to-face assessment of neurological status at follow-up and lack of formal psychiatric diagnosis during follow-up.Conclusions20 mg of fluoxetine daily for 6 months after acute stroke did not improve patients’ functional outcome but decreased the occurrence of depression and increased the risk of fractures. These data inform decisions about using fluoxetine after stroke to improve functional outcome or to prevent or treat mood disorders. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) (Australasia/Vietnam) and Efficacy oF Fluoxetine – a randomisEd Controlled Trial in Stroke (EFFECTS) (Sweden) trials recruited an additional 2780 patients and will report their results in 2020. These three trials have an almost identical protocol, which was collaboratively developed. Our planned individual patient data meta-analysis will provide more precise estimates of the effects of fluoxetine after stroke and indicate whether or not effects vary depending on patients’ characteristics and health-care setting.
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| 89. |
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| 90. |
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| 91. |
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| 92. |
- Forbes, KM, et al.
(författare)
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Bombali Virus in Mops condylurus Bat, Kenya
- 2019
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Ingår i: Emerging infectious diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6059 .- 1080-6040. ; 25:5, s. 955-957
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Tidskriftsartikel (refereegranskat)
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| 93. |
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| 94. |
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| 95. |
- Forbes, Ruaridh, et al.
(författare)
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Time-resolved site-selective imaging of predissociation and charge transfer dynamics : The CH3I B-band
- 2020
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Ingår i: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 53:22
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Tidskriftsartikel (refereegranskat)abstract
- The predissociation dynamics of the 6s (B2E) Rydberg state of gas-phase CH3I were investigated by time-resolved Coulomb-explosion imaging using extreme ultraviolet (XUV) free-electron laser pulses. Inner-shell ionization at the iodine 4d edge was utilized to provide a site-specific probe of the ensuing dynamics. The combination of a velocity-map imaging (VMI) spectrometer coupled with the pixel imaging mass spectrometry (PImMS) camera permitted three-dimensional ionic fragment momenta to be recorded simultaneously for a wide range of iodine charge states. In accord with previous studies, initial excitation at 201.2 nm results in internal conversion and subsequent dissociation on the lower-lying A-state surface on a picosecond time scale. Examination of the time-dependent yield of low kinetic energy iodine fragments yields mechanistic insights into the predissociation and subsequent charge transfer following multiple ionization of the iodine products. The effect of charge transfer was observed through differing delay-dependencies of the various iodine charge states, from which critical internuclear distances for charge transfer could be inferred and compared to a classical over-the-barrier model. Time-dependent photofragment angular anisotropy parameters were extracted from the central slice of the Newton sphere, without Abel inversion, and highlight the effect of rotation of the parent molecule before dissociation, as observed in previous
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| 96. |
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| 97. |
- Gardiner, T., et al.
(författare)
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Trend analysis of greenhouse gases over Europe measured by a network of ground-based remote FTIR instruments
- 2008
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 8:22, s. 6719-6727
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the statistical analysis of annual trends in long term datasets of greenhouse gas measurements taken over ten or more years. The analysis technique employs a bootstrap resampling method to determine both the long-term and intra-annual variability of the datasets, together with the uncertainties on the trend values. The method has been applied to data from a European network of ground-based solar FTIR instruments to determine the trends in the tropospheric, stratospheric and total columns of ozone, nitrous oxide, carbon monoxide, methane, ethane and HCFC-22. The suitability of the method has been demonstrated through statistical validation of the technique, and comparison with ground-based in-situ measurements and 3-D atmospheric models.
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| 98. |
- Hagström, Åke, et al.
(författare)
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Havets usynlige liv
- 1996
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Rapport (övrigt vetenskapligt/konstnärligt)
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| 99. |
- Hilton, Emma N, et al.
(författare)
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Left-sided embryonic expression of the BCL-6 corepressor, BCOR, is required for vertebrate laterality determination.
- 2007
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 16:14, s. 1773-1782
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Tidskriftsartikel (refereegranskat)abstract
- Oculofaciocardiodental (OFCD) syndrome is an X-linked male lethal condition encompassing cardiac septal defects, as well as ocular and dental anomalies. The gene mutated in OFCD syndrome, the BCL-6 corepressor (BCOR), is part of a transcriptional repression complex whose transcriptional targets remain largely unknown. We reviewed cases of OFCD syndrome and identified patients exhibiting defective lateralization including dextrocardia, asplenia and intestinal malrotation, suggesting that BCOR is required in normal laterality determination. To study the function of BCOR, we used morpholino oligonucleotides (MOs) to knockdown expression of xtBcor in Xenopus tropicalis, thus creating an animal model for OFCD syndrome. The resulting tadpoles had cardiac and ocular features characteristic of OFCD syndrome. Reversed cardiac orientation and disorganized gut patterning were seen when MOs were injected into the left side of embryos, demonstrating a left-sided requirement for xtBcor in lateral determination in Xenopus. Ocular defects displayed no left-right bias and included anterior and posterior segment disorders such as microphthalmia and coloboma. Expression of xtPitx2c was shown to be downregulated when xtBcor was depleted. This identifies a pathway in which xtBcor is required for lateral specification, a process intrinsically linked to correct cardiac septal development.
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| 100. |
- Horstkotte, Tim, et al.
(författare)
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Human-animal agency in reindeer management : Sami herders' perspectives on vegetation dynamics under climate change
- 2017
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Ingår i: Ecosphere. - : WILEY. - 2150-8925 .- 2150-8925. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- Many primary livelihoods in Arctic and sub-Arctic regions experience accelerating effects of environmental change. The often close connection between indigenous peoples and their respective territories allows them to make detailed observations of how these changes transform the landscapes where they practice their daily activities. Here, we report Sami reindeer herders' observations based on their long-term inhabitance and use of contrasting pastoral landscapes in northern Fennoscandia. In particular, we focus on the capacity for various herd management regimes to prevent a potential transformation of open tundra vegetation to shrubland or woodland. Sami herders did not confirm a substantial, rapid, or large-scale transformation of treeless tundra areas into shrub-and/or woodlands. However, where they observe encroachment of open tundra landscapes, a range of factors was deemed responsible. These included abiotic conditions, anthropogenic influences, and the direct and indirect effects of reindeer. The advance of the mountain birch tree line was in some cases associated with reduced or discontinued grazing and firewood cutting, depending on the seasonal significance of these particular areas. Where the tree line has risen in elevation and/or latitude, herding practices have by necessity adapted to these changes. Exploiting the capacity of reindeer impacts on vegetation as a conservation tool offers time-tested adaptive strategies of ecosystem management to counteract a potential encroachment of the tundra by woody plants. However, novel solutions in environmental governance involve difficult trade-offs for ecologically sustainable, economically viable, and socially desirable management strategies.
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