Metas (Norway)

Understanding the interplay of environmental and anthropogenic drivers is essential to interpret past changes and anticipate future dynamics of marine fish stocks. Using Norwegian spring-spawning herring (NSSH) as a case study, we applied an iterative structured causal modelling framework combining causal knowledge analysis and inference—using structural equation models—to quantify the respective effects of climate and fisheries on stock biomass and catches. Initial simple models, grounded in prior ecological understanding, yielded implausible estimates when confronted with observational data, underscoring the necessity to treat data structure and content as integral to model design. We gradually incorporated multiple causal pathways, feedback loops, and confounders. Final models explained over 90% of observed variation in both biomass and catch and showed strong support for the roles of recruitment, prior biomass, and total allowable catch (TAC) advice. We found no causal effect of ocean climate variables (Relative Heat Content and Arctic Water Content) on year-to-year changes in NSSH biomass, nor of Spawning Stock Biomass on catches. Instead, catch levels were primarily governed by TAC advice and the degree of agreement between fishing nations. We conclude that reliable causal inference in ecological systems requires iterative model refinement, causal knowledge analysis, and explicit accounting for data structure. Adopting and transparently reporting this approach would benefit ecological studies used to support fisheries management.

Abstract BACKGROUND Brain metastasis is associated with poor prognosis, and median survival time from the time of diagnosis for cancer patients with brain metastases is only a few months. Brain metastases are estimated to occur in 20-40% of cancer patients. All solid tumors may spread to the brain, but the risk of developing brain metastases is higher in breast cancer, lung cancer and melanoma. Standard treatment of melanoma brain metastases (MBM) includes radiation therapy and surgery. In melanoma, the mitogen activated protein kinase (MAPK) and the phosphoinositide 3-kinase (PI3K) signaling pathways are often activated by genetic alterations. An activation mutation (BRAFV600E) in the MAPK pathway is commonly found in melanoma refractory to therapy. This mutation leads to increased proliferation and tumor cell survival. Previous studies show that BRAF-inhibitors block the increase in cell proliferation induced by the activated BRAF gene, however, many of the patients develop drug resistance within a few months. Objectives: In this project, we aimed to show that drugs targeting BRAF (vemurafenib) and PI3K pathways (buparlisib) used in combination effectively inhibit growth of treatment resistant MBM cells. MATERIAL AND METHODS Our research lab has previously developed human MBM cell lines, which have been made resistant towards vemurafenib treatment. To study the potential antitumoral effects of combined treatment we used these cells in several in vitro assays such as cell viability and proliferation, cell migration, colony forming assay, spheroid growth, apoptosis by IncuCyte and western blot to confirm effects on signaling pathways. RESULTS We found that combination treatment reduced the viability of resistant MBM cells, as well as their ability to proliferate. Further, the cells showed less ability to migrate after therapy. Altered cell morphology was also seen. Initial results show effects on colony formation and increased apoptosis after combined treatment. CONCLUSION A combination of MAPK and PI3K inhibitors effectively inhibits growth and viability of treatment resistant human MBM cells, compared to single drug treatment alone. The results support clinical use of combined therapy for melanoma patients with metastatic disease.

Abstract BACKGROUND Extraneural metastases of glioblastoma (GBM) are rare, reported incidence in literature is 0.4% to 2%. There is a lack in epidemiological data, and what little exists is outdated. The most commonly reported sites of metastases are bone, lymph node and lung. There is an insufficient understanding of the biological mechanism of metastasis, nevertheless, surgical intervention and peritoneal seeding through a ventriculoperitoneal shunt have been postulated as rational routes for the tumor cells. However, reports show metastasizing GBM in patients where neither of these procedures have been performed and therefore biological aspects should be elucidated. Previously, some few genomic studies have shown high mutational burden and that some mutations are only detected in the metastases, indicating clonal evolution. Commonly TP53, TERT, PTEN and CDKN2A/B have been revealed as shared mutations. MATERIAL AND METHODS A 55-year-old man presented with approximately 2 months of progressive headache and behavioral changes. Brain MRI revealed a left temporal lesion suspicious of GBM and no extracranial metastasis was detected. The patient underwent near total surgical resection and completed Stupp protocol. Nine months later, he was admitted to the local hospital with reduced general condition, tachypneic and lower back pain, but subsequent CT of thorax and abdomen revealed multiple pathological lesions in mediastinum, bones, lung, soft tissue, and mesentery. MRI confirmed the findings and a large soft tissue lesion at the level of the 6th thoracic vertebrae, was biopsied and showed metastasis from GBM. There was also local progression of the primary tumor in the brain. Treatment strategy was changed to a combination of lomustine, vincristine and bevacizumab. It was collected blood samples from the patient in respect of circulating tumor cells. A molecular characterization of the tumor samples was performed. RESULTS The primary tumor was MGMT promotor methylated, IDH-1/-2 wildtype, had no TERT promotor mutation, TP53 wildtype and ATRX was intact. The biopsy of the paravertebral lesion showed infiltration of a low differentiated, highly cellular tumor. Immunohistochemically the tumor cells were positive for GFAP, OLIG2 and S100. The molecular features revealed no mutation in BRAF or NTRK. Interestingly, PD-L1 was extremely upregulated, may indicating a potential benefit of immune-checkpoint inhibitors for extraneural metastases. A literature survey is done to find out any risk factors for metastasis. CONCLUSION We report a rare case of GBM with extensive extraneural metastases. This underlines the importance of comparing molecular biology, localization, and other patient and tumoral factors in order to identify any specific risk factor for metastasis. In turn, helping to stratify the follow up of this subgroup in the future.

Issues Closed Issue 1232 - Add link to documentation for VII L1b-reader. (PR 1236) Issue 1229 - FCI reader can read pixel_quality flags only after reading corresponding channel data (PR 1230) Issue 1215 - FCI reader fails to load composites due to metadata issues (PR 1216) Issue 1201 - Incorrect error message when some but not all readers found (PR 1202) Issue 1198 - Let NetCDF4FileHandler cache variable dimension names (PR 1199) Issue 1190 - Unknown dataset, solar_zenith_angle Issue 1172 - find_files_and_readers is slow (PR 1178) Issue 1171 - Add reading of pixel_quality variable to FCI FDHSI reader (PR 1177) Issue 1168 - Add more versatile options for masking datasets (PR 1175) Issue 1167 - saving sentinel-2 image as jpg Issue 1164 - Question about license Issue 1162 - abi_l2_nc reader unable to read MCMIP files Issue 1156 - dealing with 1D array output from data assimilation Issue 1154 - MERSI-2 250meters corrected refl. Issue 1153 - tropomi reader: scene attributes and data array attributes are different (PR 1155) Issue 1151 - amsr2 l1b reader also match amsr2 l2 products (PR 1152) Issue 1144 - Documentation bug: group_files keyword argument reader doc has sentence consisting of only the word "This" (PR 1147) Issue 1143 - save_datasets doesn't work for tropomi_l2 data (PR 1139) Issue 1132 - Add area definitions for the FCI FDHSI L1c grids (PR 1188) Issue 1050 - Return counts from avhrr_l1b_gaclac reader (PR 1051) Issue 1014 - The fci_l1c_fdhsi reader should proved the <code>platform_name</code> in the attributes (PR 1176) Issue 958 - Add a CMSAF reader (PR 720) Issue 680 - Expose <code>overviews</code> from Trollimage for saving (geo)tiff images In this release 23 issues were closed. Pull Requests Merged Bugs fixed PR 1230 - FCI: fix areadef when only pixel quality asked (1229, 1229) PR 1216 - Make combine_arrays understand non-numpy arrays (1215, 1215) PR 1213 - Remove invalid valid_range metadata from abi readers PR 1211 - Fix "rows_per_scan" not being available from VIIRS SDR readers PR 1202 - Fix bad error message when Scene was given a bad reader name (1201) PR 1195 - Fix accessing uncached root group variable when using NetCDF4FileHandler in caching mode (1195) PR 1170 - Fix cf writing of 3d arrays PR 1155 - Lowercase sensor of tropomi_l2 (1153) PR 1139 - Keep int type and fix scale_factor/dim bug in tropomi_l2 reader (1143) Features added PR 1227 - Delete kdtree after saving cache PR 1226 - Add a feature for handling scheduled_time in ahi_hsd reader. PR 1219 - Add VII L2 netCDF-reader. PR 1218 - Add VII L1b netCDF-reader. PR 1212 - Add file pattern for NWCSAF input file names to 'grib' reader (1212) PR 1199 - Cache dimension per variable (1198) PR 1189 - Add option to supply sunz-threshold applied in Pyspectral PR 1188 - Add areas for FCI (1132) PR 1186 - Fix SEVIRI native reader flipping PR 1185 - Add scanline acquisition times to hrit_jma PR 1183 - Add options for creating geotiff overviews PR 1181 - Add more explicit error message when string is passed to Scene.load PR 1180 - Migrate FCI tests to pytest PR 1178 - Optimize readers searching for matching filenames (1172) PR 1177 - Add support for reading pixel_quality ancillary variables, FCI reader no longer logs warnings (1171) PR 1176 - Provide platform_name in FCI L1C FDHSI reader. (1014) PR 1175 - Add more flexible masking (1168) PR 1173 - Check whether time dimension exists for timeseries PR 1169 - Implement remote file search PR 1165 - Add missing_ok option to find_files_and_readers (1165) PR 1163 - Add TROPOMI NO2 LEVEL2 composites PR 1161 - Add Effective_Pressure to NUCAPS reader PR 1152 - amsr2 reader for l2 ssw product (1151) PR 1142 - add filepatterns S-HSAF-h03B and S-HSAF-h05B to hsaf_grib.yaml PR 1141 - Add night lights composites for ABI, AHI and AMI PR 1135 - Fix reflectance and BT calibration in FCI FDHSI reader PR 1100 - Add support for GPM IMERG data PR 1051 - Return counts from satpy/avhrr_l1b_gaclac reader (1050) PR 983 - Add group method to MultiScene PR 812 - Add MOD06 support to 'modis_l2' reader (1200) PR 720 - CMSAF CLAAS v2. reader (958) Documentation changes PR 1223 - Add FCI Natural Color example page to sphinx docs PR 1203 - Add link to MTSAT sample data PR 1147 - Fix incomplete group_files docstring (1144) In this release 43 pull requests were closed.

Background:Ovarian cancer is the leading cause of death among cancers of the female genital tract, with poor outcomes despite chemotherapy. There was a persistent socioeconomic gradient in 1-year survival in England and Wales for more than 3 decades (1971–2001). Inequalities in 5-year survival persisted for more than 20 years but have been smaller for women diagnosed around 2000. We explored one possible explanation.Methods:We analysed data on 1406 women diagnosed with ovarian cancer during 1991–1998 and recruited to one of two randomised clinical trials. In the second International Collaborative Ovarian Neoplasm (ICON2) trial, women diagnosed between 1991 and 1996 were randomised to receive either the three-drug combination cyclophosphamide, doxorubicin and cisplatin (CAP) or single-agent carboplatin given at optimal dose. In the ICON3 trial, women diagnosed during 1995–1998 were randomised to receive either the same treatments as ICON2, or paclitaxel plus carboplatin.Relative survival at 1, 5 and 10 years was estimated for women in five categories of socioeconomic deprivation. The excess hazard of death over and above background mortality was estimated by fitting multivariable regression models with Poisson error structure and a dedicated link function in a generalised linear model framework, adjusting for the duration of follow-up and the confounding effects of age, Federation of Gynecology and Obstetrics (FIGO) stage and calendar period.Results:Unlike women with ovarian cancer in the general population, no statistically significant socioeconomic gradient was seen for women with ovarian cancer treated in the two randomised controlled trials. The deprivation gap in 1-year relative survival in the general population was statistically significant at −6.7% (95% CI (−8.1, −5.3)), compared with −3.6% (95% CI (−10.4, +3.2)) in the trial population.Conclusions:Although ovarian cancer survival is significantly lower among poor women than rich women in England and Wales, there was no evidence of an association between socioeconomic deprivation and survival among women with ovarian cancer who were treated and followed up consistently in two well-conducted randomised controlled trials. We conclude that the persistent socioeconomic gradient in survival among women with ovarian cancer, at least for 1-year survival, may be due to differences in access to treatment and standards of care.

La resolución de problemas en la enseñanza de las ciencias representa un recurso para afianzar la comprensión de los conceptos y hacerlos más significativos mediante ejemplos concretos. En este trabajo, empleamos este recurso para analizar algunas características de los alumnos con éxito académico cuando se enfrentan a la transposi¬ción de un modelo de enseñanza empleado en el estudio de las reacciones químicas en medio acuoso, durante varios semestres (Química Analítica). Los estudiantes deben aplicarlo al estudio de las reacciones químicas en otros disolventes. Evaluamos algunos factores que influyen en el proceso de transposición, principalmente en la participación de pares, el tiempo requerido para asi¬milar la explicación del profesor y el tiempo y la ayuda para reactivar los conocimientos. Finalmente se proponen algunas recomendaciones para ayudar a los estudiantes.