Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Discourse of global governance: American hegemony in the post-Cold War era

10.1075/jlp.7.3.03lazJournal of Language and Politics72228-24

Semiosis, social change and governance: A critical semiotic analysis of a national campaign

1080/1035033032000152615Social Semiotics132201-22

Discover the power of femininity!

10.1080/14680770600990002Feminist Media Studies64505-51

ПАЛЕОГЕОГРАФІЧНІ УМОВИ УТВОРЕННЯ ВУГЛЕНОСНОЇ ТОВЩІ ЛЮБЕЛЬСЬКОГО РОДОВИЩА ЛЬВІВСЬКО-ВОЛИНСЬКОГО БАСЕЙНУ НА ОСНОВІ АНАЛІЗУ ЛІТОЛОГО-СТРАТИГРАФІЧНИХ РОЗРІЗІВ

 Determination of paleogeographical conditions for formation of coal-bearing formation of the Lyubelya field of the Lviv-Volyn Basin was conducted on the basis of the analysis of lithological-stratigraphical sections in area of the of the Lyubelya-3 plot. Studies of coal-bearing thickness wither the limits of the separate plot of the field will enable us to investigate in detail the evolution of the peat accumulation of the field in general and will help to interpret tectonic movements, to determine facies associations and to reproduce paleorelief.By lithological composition the studied thickness is mainly of aleurolite-argillite composition with some layers of sandstones, limestones and coal seams. Its accumulation occurred while alternating of marine shallow-water, near-shelf lagoon-bog and continental conditions. Smooth relief and humid tropical climate, the presence of boggy plots located on the open coast of the shallow sea contributed to the accumulation.In the studied territory, an intensive lowering of the south-western of the territory of the Lyubelya-3 plot in Serpukhovian time of the Lower Carboniferous is observed. Sufficient in flux of terrigenous material, creation of conditions for compensating sedimentation that promoted wide bogging of the locality and formatting of paleopeat deposits were connected with it. North-eastern and eastern parts of the plot underwent perceptible rising movements that is observed by the change in the lithological-facies of rocks.Obtained results confirm the common notions of paleogeographical conditions for the formation of coal-bearing thickness of the Lyubelya field of the Lviv-Volyn Basin. With common regressive trending and cyclic character of sedimentation the formation of relatively thick terrigenous polyfacial thickness with the layers of coal and limestone occurred. Common regressive trending caused by rising movements in the field of the Ukrainian crystalline shield led to receding of the sea in the south-western direction. In addition the gradual widening of continental situations of sedimentation and reducing of marine ones occurred. На основі аналізу літолого-стратиграфічних розрізів на площі ділянки Любельська №3 визначено палеогеографічні умови утворення відкладів вугленосної формації Любельського родовища Львівсько-Волинського басейну. Дослідження вугленосної товщі в межах окремої ділянки родовища дасть змогу докладно вивчити еволюцію торфовугленакопичення родовища загалом та допоможе інтерпретувати тектонічні рухи, з'ясувати фаціальні асоціації й відтворити палеорельеф.За літологічним складом досліджувана товща переважно алевроліт-аргілітового складу з окремими шарами пісковиків, вапняків і пластів вугілля. Накопичення її відбувалося під час чергування морських мілководних, пришельфових лагуно-болотних і континентальних умов. Торфонакопиченню сприяли згладжений рельєф і вологий тропічний клімат, наявність заболочених ділянок, розміщених на відкритому узбережжі неглибокого моря. У серпухівський час нижнього карбону спостерігається інтенсивне опускання південно-західної частини території ділянки Любельська №3. Із цим пов’язане чимале привнесення теригенного матеріалу, створення умов компенсованої седиментації, що сприяли широкому заболоченню місцевості та утворенню палеоторфовищ. Північно-східна і східна частини ділянки зазнала відчутних висхідних рухів, що спостерігається за зміною літолого-фаціальних типів порід.Отримані результати є підтвердженням загальних уявлень про палеогеографічні умови утворення вугленосної товщі Любельського родовища ЛВБ. За загальної регресивної спрямованості й циклічного характеру седиментації відбувалося формування порівняно потужних теригенних поліфаціальних товщ із пластами вугілля і вапняків. Загальна регресивна спрямованість, зумовлена висхідними рухами в області Українського кристалічного щита, приводила до відступання моря в південно-західному напрямку. Водночас відбувалося поступове розширення континентальних умов осадконакопичення й скорочення морських. 

Phytoplankton drives nitrite dynamics in the Gulf of Aqaba, Red Sea

This study focuses on the seasonal patterns of nitrite concentration changes and its relationship with phytoplankton activity that is mainly controlled by the alternation of the water column stratification and mixing. Within the euphotic zone during thermal summer stratification, nutrient depletion was severe, and no nitrite could be detected. However, during stratification nitrite was always associated with the nutriclines and formed a deep maximum at the bottom of the euphotic zone. By contrast, within the mixed water column during winter nitrite accumulated, closely following the development of phytoplankton biomass. In the Gulf of Aqaba, the maximum of nitrite accumulation occurred when winter mixing reached its greatest depth, which in turn was coincident with the height of the phytoplankton spring bloom. Thus, our field data suggest that the accumulation of nitrite is associated with nutrient-replete phytoplankton growth. This hypothesis was supported by nutrient enrichment bioassays performed concomitantly: Only when phytoplankton growth was stimulated by nutrient additions, nitrite accumulated in the water. In the bioassays, the time-course of nitrite accumulation closely followed the development of phytoplankton biomass during the incubation period. We therefore suggest that the accumulation of nitrite in the mixed water column during winter was due to the excretion by algal cells. Our field and experimental data show that between 10 to 15 % of the total amount of nitrogen introduced to the mixing water column is released as nitrite by phytoplankton. Further, our field and experimental data support the hypothesis that nitrite excretion by phytoplankton has a significant role in the formation of the DNM during stratification in summer. In the bioassays, phytoplankton cells did excrete nitrite even when ammonia was the nitrogen source. This gives evidence, that there is a so far unrecognised physiological pathway involved in nitrite excretion by phytoplankton cells

Implications of agricultural land use change to ecosystem services in the Ganges delta

Ecosystems provide the basis for human civilization and natural capital for green economy and sustainable development. Ecosystem services may range from crops, fish, freshwater to those that are harder to see such as erosion regulation, carbon sequestration, and pest control. Land use changes have been identified as the main sources of coastal and marine pollution in Bangladesh. This paper explores the temporal variation of agricultural land use change and its implications with ecosystem services in the Ganges delta. With time agricultural lands have been decreased and wetlands have been increased at a very high rate mainly due to the growing popularity of saltwater shrimp farming. In a span of 28 years, the agricultural lands have been reduced by approximately 50%, while the wetlands have been increased by over 500%. A large portion (nearly 40%) of the study area is covered by the Sundarbans which remained almost constant which can be attributed to the strict regulatory intervention to preserve the Sundarbans. The settlement & others land use type has also been increased to nearly 5%. There is a gradual uptrend of shrimp and fish production in the study area. The findings suggest that there are significant linkages between agricultural land use change and ecosystem services in the Ganges delta in Bangladesh. The continuous decline of agricultural land (due to salinization) and an increase of wetland have been attributed to the conversion of agricultural land into shrimp farming in the study area. Such land use change requires significant capital, therefore, only investors and wealthier land owners can get the higher profit from the land conversion while the poor people is left with the environmental consequences that affect their long-term lives and livelihood. An environmental management plan is proposed for sustainable land use in the Ganges delta in Banglades