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rgence of on-target resistance, which may provide guidance for clinical decision making.

Sequential postprogression plasma profiling revealed that increased lines of ALK inhibitors can accelerate the accumulation of ALK resistance mutations and may lead to treatment-refractory compound ALK mutations. The selection for optimal first-line TKI is very important to achieve a more efficacious long-term strategy and prevent the emergence of on-target resistance, which may provide guidance for clinical decision making.Mutigenerational studies are now of great interest in ecotoxicology and previous studies have shown the importance of conducting multigenerational studies when assessing radiation toxicity in fish. In our study, the first objective was to study the early life stages (embryo-larval stages) and critical functions such as reproduction (which are generally studied in the context of ecological risk assessment (ERA)), in order to assess the sensitivity of zebrafish to ionizing radiation. The second objective was to assess acquisition of phenotypic effects at select life stages over generations. To our knowledge, this was the first time that irradiation of zebrafish (0.05 and 5 mGy.h-1) up to generation F2 was maintained with the following two exposure conditions (1) recovery, only F0 genitors were irradiated and the progeny were placed in control condition, (2) irradiated condition, all generations were exposed. Multigenerational irradiation affected F1 parental reproductive capacity (reproductive success) mainly over the first reproductive cycle (104d) and larval survival rate. Unexpected yet significant effects on sex ratio were observed in F1 progeny after parental irradiation (mainly at 5 mGy.h-1). These effects were observed for both conditions -irradiated and recovery- suggesting transmitted effects from F0 genitors to offspring. All studied life stages were affected by ionizing radiation (IR), suggesting an alteration of vital physiological functions (reproduction and sexual determination). Such results highlight the hypothesis that IR affects population dynamics. In addition, the clear evidence of transmitted effects suggests worsening of effects at the population scale over generations. This approach is closer to environmental conditions to assess wild population fate, and thus highlights the importance of multigenerational studies to support ERA of ionizing radiation in fish.High-resolution STEM-EELS provides information about the composition of crystalline materials at the atomic scale, though a reliable quantitative chemical analysis is often hampered by zone axis conditions, where neighbouring atomic column intensities contribute to the signal at the probe position. In this work, we present a procedure to determine the concentration of two elements within equivalent atomic columns from EELS elemental maps - in our case barium and lanthanum within the A-sites of Ba1.1La1.9Fe2O7, a second order Ruddlesden-Popper phase. We took advantage of the large changes in the elemental distribution from column to column and introduced a technique, which substitutes inelastic scattering cross sections during the quantification step by using parameters obtained from the actual experiment. We considered channelling / de-channelling effects via inelastic multislice simulations and were thereby able to count occupancies in each atomic column. The EELS quantification results were then used as prior information during the Rietveld refinement in XRD measurements in order to differentiate between barium and lanthanum.Falls are common in daily life, often caused by trips and slips and, particularly in older adults, with serious consequences. Although arm movements play an important role in balance control, there is limited research into the role of arm movements during balance recovery after tripping in older adults. We investigated how older adults use their arms to recover from a trip and the difference in the effects of arm movements between fallers (n = 5) and non-fallers (n = 11). Sixteen older males and females (69.7 ± 2.3 years) walked along a walkway and were occasionally tripped over suddenly appearing obstacles. We analysed the first trip using a biomechanical model based on full-body kinematics and force-plate data to calculate whole body orientation during the trip and recovery phase. With this model, we simulated the effects of arm movements at foot-obstacle impact and during trip recovery on body orientation. Apart from an increase in sagittal plane forward body rotation at touchdown in fallers, we found no significant differences between fallers and non-fallers in the effects of arm movements on trip recovery. Like earlier studies in young adults, we found that arm movements during the recovery phase had most favourable effects in the transverse plane by delaying the transfer of angular momentum of the arms to the body, older adults rotated the tripped side more forward thereby allowing for a larger recovery step. Older adults that are prone to falling might improve their balance recovery after tripping by learning to prolong ongoing arm movements.Tendons are involved in multiple disorders and injuries, ranging from birth deformities to tendinopathies to acute ruptures. The ability to characterize embryonic tendon mechanical properties will enable elucidation of mechanisms responsible for functional tendon formation. In turn, an understanding of tendon development could inform approaches for adult and embryonic tendon tissue engineering and regenerative medicine. The chick embryo is a scientifically relevant model that we have been using to study Achilles (calcaneal) tendon development. Chick embryo calcaneal tendons are challenging to mechanically test due to small size and delicate nature, and difficulty distinguishing embryonic tendons from muscle and fibrocartilage using the naked eye. Here, we developed and implemented a "marking protocol" to identify and isolate calcaneal tendons at different stages of chick embryonic development. Mechanical testing of tendons isolated using the marking protocol revealed trends in mechanical property development that were not observed with tendons isolated by naked eye (eyeballing). Marked tendons exhibited non-linear increases in tensile modulus and ultimate tensile strength, whereas eyeballed tendons exhibited linear increases in the same properties, reflecting a need for the marking protocol. Furthermore, the tensile mechanical properties characterized for marked tendons are consistent with previously reported trends in cell length-scale mechanical properties measured using atomic force microscopy. This report establishes new methodology to enable tensile testing of chick embryo tendons and provides new information about embryonic tendon mechanical property development.There is meta-analytic evidence for the efficacy of cognitive training (CT) in Parkinson's disease (PD). We performed a randomized controlled trial where we found small positive effects of CT on executive function and processing speed in individuals with PD (ntotal = 140). In this study, we assessed the effects of CT on brain network connectivity and topology in a subsample of the full study population (nmri = 86). Participants were randomized into an online multi-domain CT and an active control condition and performed 24 sessions of either intervention in eight weeks. Resting-state functional MRI scans were acquired in addition to extensive clinical and neuropsychological assessments pre- and post-intervention. In line with our preregistered analysis plan (osf.io/3st82), we computed connectivity between 'cognitive' resting-state networks and computed topological outcomes at the whole-brain and sub-network level. We assessed group differences after the intervention with mixed-model analyses adjusting for baseline performance and analyzed the association between network and cognitive performance changes with repeated measures correlation analyses. The final analysis sample consisted of 71 participants (n CT = 37). After intervention there were no group differences on between-network connectivity and network topological outcomes. No associations between neural network and neuropsychological performance change were found. CT increased segregated network topology in a small sub-sample of cognitively intact participants. Post-hoc nodal analyses showed post-intervention enhanced connectivity of both the dorsal anterior cingulate cortex and dorsolateral prefrontal cortex in the CT group. The results suggest no large-scale brain network effects of eight-week computerized CT, but rather localized connectivity changes of key regions in cognitive function, that potentially reflect the specific effects of the intervention.Privately protected areas (PPAs) are internationally considered to be important policy implementation instruments to augment and strengthen protected area networks. However, there has been limited reflection on the performance of PPAs over time. This paper aims to identify key risks to the performance of PPAs as policy implementation instruments through the application of Theory of Change (ToC). Identifying and understanding these risks are important to allow for the evaluation and monitoring of PPA performance. The ToC method was applied to a specific PPA policy instrument namely, private nature reserves (PNRs) in the South African context. The research results produced 29 key assumptions translated into 29 key risks. These risk are critically discussed against existing South African and international literature. To test and refine the risks further it is recommended that they be applied to PPA case studies in different contexts.Globalization and income disparities have raised an urgent need to re-examine the environmental consequences of international trade. Using a global panel dataset covering 93 economies from 1980 to 2017, this paper explores the heterogeneous impacts of international trade on green productivity. Unlike previous studies that impose strict linear assumptions on functional forms, we adopt a newly developed partially linear functional-coefficient model to estimate the specific response functions of green productivity to imports and exports at different income levels, thus emphasizing the potential role of income heterogeneity. The results demonstrate that (1) imports and exports have different non-linear effects on green productivity; (2) imports do not significantly affect green productivity in lower-income countries (relative income level is less than 0.5), but imports increasingly promote green productivity in high-income countries; (3) exports hinder green productivity in extremely low-income countries (relative income level is less than 0.1), while gradually improving green productivity in high-income countries (relative income level is larger than 0.6); and (4) imports and exports promote green productivity more significantly by technological progress rather than efficiency improvements. The stimulus effect from induced technological progress is only observed in higher-income countries.Small hydropower (SHP) possesses significant economic, technical, and environmental advantages, and accounts for a large proportion of hydropower development in China. However, the concentrated, cascaded, and diversion-type development of SHP has resulted in long-distance dewatering of river sections, and inter-basin water transfers have led to severe exploitation of water resources and damage to river ecosystems. In this paper, the Datong River Basin, a secondary sub-basin of the Yellow River Basin in China, was selected as the illustrative case, which includes 22 hydropower projects (HPPs) and three inter-basin water diversion projects (WDPs). A nexus system model was established that used weighted multi-objective programming to consider three main objectives the water resources utilization (local water withdrawal and inter-basin water transfer), energy production (by cascaded HPPs), and riverine environmental conservation. The Tennant method was used to estimate the environmental flows (e-flows) at the cross-sections immediately downstream of the dam/sluice gate and immediately downstream of the hydropower plant of diversion-type HPPs.