25 research outputs found
Dinamika beregov vostochnykh arkticheskikh morej Rossii: osnovnye faktory, zakonomernosti i tendentsii (Dynamics of the Russian east Arctic sea coast: Major factors, regularities and tendencies)
Climatic, geocryological, geological and hydrodynamic conditions and available data on Arctic coast dynamics are analyzed. The basic laws of ice-rich coast development in varied geocryological and climatic conditions are investigated. Functional connections of coastal destructive cryogenic processes activity with summer air temperature and storms recurrence are revealed. The forecast of ice-rich coast rate retreat for the Laptev Sea and East-Siberian Sea is executed in connection with prospective changes of climate in XXI century
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Na3FeH7 and Na3CoH6: Hydrogen-Rich First-Row Transition Metal Hydrides from High Pressure Synthesis
The formation of ternary hydrogen-rich hydrides involving the first-row transition metals TM = Fe and Co in high oxidation states is demonstrated from in situ synchrotron diffraction studies of reaction mixtures NaH-TM-H-2 at p approximate to 10 GPa. Na3FeH7 and Na3CoH6 feature pentagonal bipyramidal FeH73- and octahedral CoH63- 18-electron complexes, respectively. At high pressure, high temperature (300 &lt; T &lt;= 470 degrees C) conditions, metal atoms are arranged as in the face-centered cubic Heusler structure, and ab initio molecular dynamics simulations suggest that the complexes undergo reorientational dynamics. Upon cooling, subtle changes in the diffraction patterns evidence reversible and rapid phase transitions associated with ordering of the complexes. During decompression, Na3FeH7 and Na3CoH6 transform to tetragonal and orthorhombic low pressure forms, respectively, which can be retained at ambient pressure. The discovery of Na3FeH7 and Na3CoH6 establishes a consecutive series of homoleptic hydrogen-rich complexes for first-row transition metals from Cr to Ni.Funding Agencies|Swedish Government Strategic Research Area Grant in Materials Science on Functional Materials at Linkoping University [2009 00971]; Carl Tryggers Stiftelse (CTS) [16:198, 17:206]</p
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Delayed posttraumatic acute subdural hematoma in elderly patients on anticoagulation
To discuss delayed acute subdural hematoma (DASH), a relatively neglected entity, and to emphasize the potentially elevated risk for DASH among elderly, anticoagulated mild traumatic brain injury (TBI) patients.
The authors reviewed clinical and radiological data for four patients who had normal neurological examinations and normal computed tomographic scans after mild TBI, and who subsequently developed DASH and deteriorated rapidly.
The patients included two men and two women, aged 65 to 86 years, who presented to the emergency department after mild TBI between January 2002 and June 2004. All were treated with chronic anticoagulation or anti-aggregation therapy. They deteriorated owing to DASH from 9 hours to 3 days after TBI. Three of the four patients underwent craniotomy for evacuation of their hematomas. One patient, who suffered only focal neurological deficit, was treated conservatively, and her hematoma gradually resolved. Two patients died and two reached Glasgow Outcome Scores of 3 and 4 after extended inpatient rehabilitation.
A suspicion of DASH should be raised in elderly, anticoagulated, mild TBI patients, including those who present to the emergency department with Glasgow Coma Scores of 15 and normal computed tomographic scans after injury. Based on our experience, we recommend that elderly, anticoagulated mild TBI patients should be admitted for 24 to 48 hours of observation after injury
Physiological correlates and predictors of functional recovery after chiasmal decompression
Background: The intrinsic abilities and limits of the nervous system to repair itself after damage may be assessed using a model of optic chiasmal compression, before and after a corrective surgical procedure. Methods: Visual fields (VFs), multifocal visual evoked potentials (mfVEP), retinal nerve fiber layer (RNFL) thickness, and diffusion tensor imaging were used to evaluate a patient before and after removal of a meningioma compressing the chiasm. Normally sighted individuals served as controls. The advantage of each modality to document visual function and predict postoperative outcome (2-year follow-up) was evaluated. Results: Postsurgery visual recovery was best explained by critical mass of normally conducting fibers and not associated with average conduction amplitudes. Recovered VF was observed in quadrants in which more than 50% of fibers were identified, characterized by intact mfVEP latencies, but severely reduced amplitudes. Recovery was evident despite additional reduction of RNFL thickness and abnormal optic tract diffusivity. The critical mass of normally conducting fibers was also the best prognostic indicator for functional outcome 2 years later. Conclusions: Our results highlight the ability of the remaining normally conductive axons to predict visual recovery after decompression of the optic chiasm. The redundancy in anterior visual pathways may be explained, neuroanatomically, by overlapping receptive fields. [There is an errata for this article. It can be found in: Journal of neuro-ophthalmology 2016 Volume 36(1) p. 114 at DOI: 10.1097/WNO.0000000000000373]5 page(s
Variable respiration rates of incubated permafrost soil extracts from the Kolyma River lowlands, north-east Siberia
Thawing permafrost supplies dissolved organic carbon (DOC) to aquatic systems; however, the magnitude, variability and fate of this DOC is not well constrained. Our objective was to examine DOC respiration from seasonally thawed and near-surface (<1.5 m) permafrost soils collected from five locations in the Kolyma River Basin, north-east Russia. We measured soil organic carbon (OC) content, water-soluble macronutrients (DOC, NH4, PO4) and the heterotrophic respiration potentials of soil extract DOC in five-day laboratory incubations. DOC concentrations ranged from 2.8 to 27.9 mg L−1 (n = 14). Carbon respiration was 0.03–0.47 mg C (n = 16) and 8.7–31.4%, total DOC (n = 14). While DOC concentration was a function of soil OC concentration, we did not find a relationship between C respiration and soil OC or DOC concentrations. Respiration was highest in the top active layer, but varied widely among sites, and lowest at the bottom of the active layer. Respiration from yedoma varied across sites (0.04–0.47 mg C respired, 8.7–31.4% total DOC). Despite the small sample size, our study indicates near-surface soils and permafrost are spatially variable in terms of both soil OC content and C respiration rates, and also that OC contents do not predict C respiration rates. While a larger sample size would be useful to confirm these results at broader geographic scales, these initial results suggest that soil OC heterogeneity should be considered in efforts to determine the fate of soil OC released from permafrost-dominated terrestrial ecosystems to aquatic ecosystems following permafrost thaw
Permafrost Degradation and Its Hydrogeological Impacts
Under a warming climate, permafrost degradation has resulted in profound hydrogeological consequences. Here, we mainly review 240 recent relevant papers. Permafrost degradation has boosted groundwater storage and discharge to surface runoffs through improving hydraulic connectivity and reactivation of groundwater flow systems, resulting in reduced summer peaks, delayed autumn flow peaks, flattened annual hydrographs, and deepening and elongating flow paths. As a result of permafrost degradation, lowlands underlain by more continuous, colder, and thicker permafrost are getting wetter and uplands and mountain slopes, drier. However, additional contribution of melting ground ice to groundwater and stream-flows seems limited in most permafrost basins. As a result of permafrost degradation, the permafrost table and supra-permafrost water table are lowering; subaerial supra-permafrost taliks are forming; taliks are connecting and expanding; thermokarst activities are intensifying. These processes may profoundly impact on ecosystem structures and functions, terrestrial processes, surface and subsurface coupled flow systems, engineered infrastructures, and socioeconomic development. During the last 20 years, substantial and rapid progress has been made in many aspects in cryo-hydrogeology. However, these studies are still inadequate in desired spatiotemporal resolutions, multi-source data assimilation and integration, as well as cryo-hydrogeological modeling, particularly over rugged terrains in ice-rich, warm (>−1 °C) permafrost zones. Future research should be prioritized to the following aspects. First, we should better understand the concordant changes in processes, mechanisms, and trends for terrestrial processes, hydrometeorology, geocryology, hydrogeology, and ecohydrology in warm and thin permafrost regions. Second, we should aim towards revealing the physical and chemical mechanisms for the coupled processes of heat transfer and moisture migration in the vadose zone and expanding supra-permafrost taliks, towards the coupling of the hydrothermal dynamics of supra-, intra- and sub-permafrost waters, as well as that of water-resource changes and of hydrochemical and biogeochemical mechanisms for the coupled movements of solutes and pollutants in surface and subsurface waters as induced by warming and thawing permafrost. Third, we urgently need to establish and improve coupled predictive distributed cryo-hydrogeology models with optimized parameterization. In addition, we should also emphasize automatically, intelligently, and systematically monitoring, predicting, evaluating, and adapting to hydrogeological impacts from degrading permafrost at desired spatiotemporal scales. Systematic, in-depth, and predictive studies on and abilities for the hydrogeological impacts from degrading permafrost can greatly advance geocryology, cryo-hydrogeology, and cryo-ecohydrology and help better manage water, ecosystems, and land resources in permafrost regions in an adaptive and sustainable manner