Due to the growing volume of remote sensing data and the low latency required for safe marine navigation, machine learning (ML) algorithms are being developed to accelerate sea ice chart generation, ...currently a manual interpretation task. However, the low signal-to-noise ratio of the freely available Sentinel-1 Synthetic Aperture Radar (SAR) imagery, the ambiguity of backscatter signals for ice types, and the scarcity of open-source high-resolution labelled data makes automating sea ice mapping challenging. We use Extreme Earth version 2, a high-resolution benchmark dataset generated for ML training and evaluation, to investigate the effectiveness of ML for automated sea ice mapping. Our customized pipeline combines ResNets and Atrous Spatial Pyramid Pooling for SAR image segmentation. We investigate the performance of our model for: i) binary classification of sea ice and open water in a segmentation framework; and ii) a multiclass segmentation of five sea ice types. For binary ice-water classification, models trained with our largest training set have weighted F1 scores all greater than 0.95 for January and July test scenes. Specifically, the median weighted F1 score was 0.98, indicating high performance for both months. By comparison, a competitive baseline U-Net has a weighted average F1 score of ranging from 0.92 to 0.94 (median 0.93) for July, and 0.97 to 0.98 (median 0.97) for January. Multiclass ice type classification is more challenging, and even though our models achieve 2% improvement in weighted F1 average compared to the baseline U-Net, test weighted F1 is generally between 0.6 and 0.80. Our approach can efficiently segment full SAR scenes in one run, is faster than the baseline U-Net, retains spatial resolution and dimension, and is more robust against noise compared to approaches that rely on patch classification.
The trajectory and orbit of the LL7 ordinary chondrite Dishchii'bikoh are derived from low‐light video observations of a fireball first detected at 10:56:26 UTC on June 2, 2016. Results show a ...relatively steep ~21° inclined orbit and a short 1.13 AU semimajor axis. Following entry in Earth's atmosphere, the meteor luminosity oscillated corresponding to a meteoroid spin rate of 2.28 ± 0.02 rotations per second. A large fragment broke off at 44 km altitude. Further down, mass was lost to dust during flares at altitudes of 34, 29, and 25 km. Surviving meteorites were detected by Doppler weather radar and several small 0.9–29 g meteorites were recovered under the radar reflection footprint. Based on cosmogenic radionuclides and ground‐based radiometric observations, the Dishchii'bikoh meteoroid was 80 ± 20 cm in diameter assuming the density was 3.5 g/cm3. The meteoroid's collisional history confirms that the unusual petrologic class of LL7 does not require a different parent body than three previously observed LL chondrite falls. Dishchii'bikoh was ejected 11 Ma ago from parent body material that has a 4471 ± 6 Ma U‐Pb age, the same as that of Chelyabinsk (4452 ± 21 Ma). The distribution of the four known pre‐impact LL chondrite orbits is best matched by dynamical modeling if the source of LL chondrites is in the inner asteroid belt in a low inclined orbit, with the highly inclined Dishchii'bikoh being the result of interactions with Earth before impacting.
Psychotherapy dropout is a common phenomenon in youth mental health, often due to dissatisfaction with treatment. However, little is known about the therapeutic processes that precede dropout due to ...dissatisfaction. This mixed-methods empirical case study aimed to explore the therapeutic process of a 12-session, prematurely ended therapy with a young person with depression in short-term psychoanalytic psychotherapy (STPP). The Adolescent Psychotherapy Q-set (APQ), an empirically validated process measure, was used as a framework for qualitative analysis exploring the therapy process over time. Analysis of APQ ratings of the 12 sessions found a productive patient-therapy dyad working collaboratively to understand the young person's experiences and emotions. Following an initial phase of the young person presenting as emotional and vulnerable, she became increasingly ambivalent about continuing in psychotherapy. A lively and argumentative period exploring the young person's ambivalence and increased sense of well-being culminated in eventual dropout. This study suggests that even in a strong, collaborative working relationship with an engaged young person, ambivalence around dependency and vulnerability can threaten treatment completion. Therapists' enhanced sensitivity to relevant processes that precede therapy dropout have the potential to improve engagement of young people in psychotherapy, which may optimise outcomes.
IMPORTANCE Genome-wide investigations provide systematic information regarding the neurobiology of psychiatric disorders. OBJECTIVE To identify biological pathways that contribute to risk for bipolar ...disorder (BP) using genes with consistent evidence for association in multiple genome-wide association studies (GWAS). DATA SOURCES Four independent data sets with individual genome-wide data available in July 2011 along with all data sets contributed to the Psychiatric Genomics Consortium Bipolar Group by May 2012. A prior meta-analysis was used as a source for brain gene expression data. STUDY SELECTION The 4 published GWAS were included in the initial sample. All independent BP data sets providing genome-wide data in the Psychiatric Genomics Consortium were included as a replication sample. DATA EXTRACTION AND SYNTHESIS We identified 966 genes that contained 2 or more variants associated with BP at P < .05 in 3 of 4 GWAS data sets (n = 12 127 5253 cases, 6874 controls). Simulations using 10 000 replicates of these data sets corrected for gene size and allowed the calculation of an empirical P value for each gene; empirically significant genes were entered into a pathway analysis. Each of these pathways was then tested in the replication sample (n = 8396 3507 cases, 4889 controls) using gene set enrichment analysis for single-nucleotide polymorphisms. The 226 genes were also compared with results from a meta-analysis of gene expression in the dorsolateral prefrontal cortex. MAIN OUTCOMES AND MEASURES Empirically significant genes and biological pathways. RESULTS Among 966 genes, 226 were empirically significant (P < .05). Seventeen pathways were overrepresented in analyses of the initial data set. Six of the 17 pathways were associated with BP in both the initial and replication samples: corticotropin-releasing hormone signaling, cardiac β-adrenergic signaling, phospholipase C signaling, glutamate receptor signaling, endothelin 1 signaling, and cardiac hypertrophy signaling. Among the 226 genes, 9 differed in expression in the dorsolateral prefrontal cortex in patients with BP: CACNA1C, DTNA, FOXP1, GNG2, ITPR2, LSAMP, NPAS3, NCOA2, and NTRK3. CONCLUSIONS AND RELEVANCE Pathways involved in the genetic predisposition to BP include hormonal regulation, calcium channels, second messenger systems, and glutamate signaling. Gene expression studies implicate neuronal development pathways as well. These results tend to reinforce specific hypotheses regarding BP neurobiology and may provide clues for new approaches to treatment and prevention.
ObjectivesWe sought to describe barriers and facilitators faced by three research projects aiming to link routinely-collected data across various sectors, to produce evidence to inform healthy public ...policy. We conducted these case studies as a part of a wider research project on cross-sectoral sharing and linkage of secondary data.
ApproachWe selected the case studies to cover a range of target populations and datasets. The chosen projects investigated (1) the health of care-experienced children; (2) the intersection of homelessness, justice involvement, drug use, and severe mental illness; (3) multi-morbidity among adults receiving social care. Information about timelines and governance processes was collected from lead investigators, including specific barriers and facilitators encountered, using a standardised pro forma and follow-up interviews. Thematic analysis was carried out by the research team, informed by themes identified in a parallel scoping review of existing literature on evidence use for healthy public policy and practice.
ResultsEach project involved between 6 and 11 agencies, with co-ordination across multiple institutions and geographies proving challenging. Due to challenges encountered, all projects had to amend their original geographical or demographic scope. Forty-four barriers and facilitators to sharing and linkage of cross-sectoral routinely-collected data for public health research were identified. These included but were not limited to: integration of current data in an ever-changing linkage landscape; the need for timely feedback in undertaking the study; standardisation of information governance processes; highlighting the resourcing and funding issues for data linkage projects; the need for data controllers to recognise the value of such projects; and issues relating to staff turnover and workload pressures.
ConclusionThe interconnected nature of barriers and facilitators identified by the case studies suggests the importance of a whole-systems approach to cross-sectoral linkage. While literature offers relatively few case studies of cross-sectoral linkage for health research, the value of their insight into the linkage landscape derived from real-life experience is substantial.
Single particle tracking (SPT) of transmembrane receptors in the plasma membrane often reveals heterogeneous diffusion. A thorough interpretation of the displacements requires an extensive analysis ...suited for discrimination of different motion types present in the data. Here the diffusion pattern of the homomeric α3-containing glycine receptor (GlyR) is analyzed in the membrane of HEK 293 cells. More specifically, the influence of the α3 RNA splice variants α3K and α3L on lateral membrane diffusion of the receptor is revealed in detail. Using a combination of ensemble and local SPT analysis, free and anomalous diffusion parameters are determined. The GlyR α3 free diffusion coefficient is found to be 0.13±0.01μm2/s and both receptor variants display confined motion. The confinement probability level and residence time are significantly elevated for the α3L variant compared to the α3K variant. Furthermore, for the α3L GlyR, the presence of directed motion was also established, with a velocity matching that of saltatory vesicular transport. These findings reveal that α3 GlyRs are prone to different types of anomalous diffusion and reinforce the role of RNA splicing in determining lateral membrane trafficking.
•The diffusion coefficient for free diffusion of the GlyR α3 is determined•Deviations from free diffusion are detected by local displacement analysis•α3-subunit RNA splicing effects on confined and directed motion are quantified•Quantitative anomalous diffusion properties are linked to biological processes
The spatio-temporal membrane behavior of glycine receptors (GlyRs) is known to be of influence on receptor homeostasis and functionality. In this work, an elaborate fluorimetric strategy was applied ...to study the GlyR α3K and L isoforms. Previously established differential clustering, desensitization and synaptic localization of these isoforms imply that membrane behavior is crucial in determining GlyR α3 physiology. Therefore diffusion and aggregation of homomeric α3 isoform-containing GlyRs were studied in HEK 293 cells. A unique combination of multiple diffraction-limited ensemble average methods and subdiffraction single particle techniques was used in order to achieve an integrated view of receptor properties. Static measurements of aggregation were performed with image correlation spectroscopy (ICS) and, single particle based, direct stochastic optical reconstruction microscopy (dSTORM). Receptor diffusion was measured by means of raster image correlation spectroscopy (RICS), temporal image correlation spectroscopy (TICS), fluorescence recovery after photobleaching (FRAP) and single particle tracking (SPT). The results show a significant difference in diffusion coefficient and cluster size between the isoforms. This reveals a positive correlation between desensitization and diffusion and disproves the notion that receptor aggregation is a universal mechanism for accelerated desensitization. The difference in diffusion coefficient between the clustering GlyR α3L and the non-clustering GlyR α3K cannot be explained by normal diffusion. SPT measurements indicate that the α3L receptors undergo transient trapping and directed motion, while the GlyR α3K displays mild hindered diffusion. These findings are suggestive of differential molecular interaction of the isoforms after incorporation in the membrane.
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► We monitored the differential membrane behavior of glycine receptor α3 isoforms. ► Both ensemble average and single particle fluorimetric techniques were applied. ► Aggregation and diffusion were quantified using fixed and live-cell measurements. ► Evidence for molecular interaction of isoforms after membrane insertion is revealed. ► Considerations for fluorimetric probing of membrane protein behavior are reported.
Acoustic dataloggers are used for monitoring the occurrence of cetaceans and can aid in fulfilling statutory monitoring requirements of protected species. Although useful for long-term monitoring, ...their spatial coverage is restricted, and for many devices the effective detection distance is not specified. A generalized additive mixed model (GAMM) was used to investigate the effects of (1) distance from datalogger, (2) animal behavior (feeding and traveling), and (3) group size on the detection probability of bottlenose dolphins (Tursiops truncatus) with autonomous dataloggers (C-PODs) validated with visual observations. The average probability of acoustic detection for minutes with a sighting was 0.59 and the maximum detection distance ranged from 1343-1779 m. Minutes with feeding activity had higher acoustic detection rates and longer average effective detection radius (EDR) than traveling ones. The detection probability for single dolphins was significantly higher than for groups, indicating that their acoustic behavior may differ from those of larger groups in the area, making them more detectable. The C-POD is effective at detecting dolphin presence but the effects of behavior and group size on detectability create challenges for estimating density from detections as higher detection rate of feeding dolphins could yield erroneously high density estimates in feeding areas.
Summary
Inhibition of the mitogen‐activated protein kinase (MAPK) pathway is a major advance in the treatment of metastatic melanoma. However, its therapeutic success is limited by the rapid ...emergence of drug resistance. The insulin‐like growth factor‐1 receptor (IGF‐1R) is overexpressed in melanomas developing resistance toward the BRAFV600 inhibitor vemurafenib. Here, we show that hyperactivation of BRAF enhances IGF‐1R expression. In addition, the phosphatase activity of PTEN as well as heterocellular contact to stromal cells increases IGF‐1R expression in melanoma cells and enhances resistance to vemurafenib. Interestingly, PTEN‐negative melanoma cells escape IGF‐1R blockade by decreased expression of the receptor, implicating that only in melanoma patients with PTEN‐positive tumors treatment with IGF‐1R inhibitors would be a suitable strategy to combat therapy resistance. Our data emphasize the crosstalk and therapeutic relevance of microenvironmental and tumor cell‐autonomous mechanisms in regulating IGF‐1R expression and by this sensitivity toward targeted therapies.
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