Traditionally, groundwater and surface water flow models have been calibrated against two observation types: hydraulic heads and surface water discharge. It has repeatedly been demonstrated, however, ...that these classical observations do not contain sufficient information to calibrate flow models. To reduce the predictive uncertainty of flow models, the consideration of other observation types constitutes a promising way forward. Despite the ever‐increasing availability of other observation types, however, they are still unconventional when it comes to flow model calibration. By reviewing studies that included nonclassical observations in flow model calibration, benefits and challenges associated with their integration in flow model calibration were identified, and their information content was analyzed. While explicit simulation of mass transport processes in flow models poses challenges, even simplified approaches to integrate tracer concentrations yield significantly better calibration results than using only classical observations. For a majority of calibrated flow models, observations of tracer concentrations and of exchange fluxes were beneficial. Temperature observations improved the simulation of heat transport but often worsened all other model outcomes. Only when temperature observations were made within 2 m of the surface water‐groundwater interface did they have the potential to also improve flow and mass transport simulations. Surprisingly, many models were calibrated manually rather than with the widely available, mathematically robust and automated tools. There is a clear need for more systematic implementation of unconventional observations and automated flow model calibration as well as for more systematic quantification of the information content of unconventional observations.
Plain Language Summary
Traditionally, groundwater and surface water flow models, which are critical for water resources assessment, have been calibrated against only two classical observation types: groundwater levels and surface water discharge. In the past, it has repeatedly been demonstrated that these classical observations do not contain sufficient information to calibrate the parameters required for the simulation of groundwater and surface water flow systems. Owing to the rapid development of measurement techniques throughout the last three decades, however, many other observations of hydrological systems have become widely available. Despite this, observation types other than the classical ones are still unconventional when it comes to flow model calibration. The overall goal of this review is to identify optimal observation types and procedures for flow model calibration and hydrological predictions. We found that observations of tracer concentrations and exchange fluxes are beneficial for most flow models. Temperatures improve the simulation of heat transport but often worsen other flow model outcomes, unless temperatures are measured within 2 m of the surface water‐groundwater interface. We identified a need for more systematic implementation of unconventional observations in flow model calibration and for more systematic quantification of the information content of unconventional observations.
Key Points
The use and information content of diverse observations for groundwater model calibration are assessed
Most unconventional observations strongly improve the calibration of integrated groundwater flow models
Fluxes and tracer concentrations are of larger benefit for groundwater model calibration than temperature observations
This study used data from a 30-day diary study with 289 adults (age range 18-89 years) to model the effects of stressor pile-up on individuals' daily negative affect (NA) and positive affect (PA) and ...to test for age differences in these effects. Specifically, we developed a new approach to operationalize and model stressor pile-up and evaluated this approach using generalized mixed models, taking into account the gamma response distribution of the highly skewed daily NA data. Findings showed that pile-up of stressors over a 1-week period was significantly coupled with increases in individuals' daily NA above and beyond the effect of concurrent stressors. Findings also showed that the effects of stressor accumulation and concurrent stress were additive rather than multiplicative. Age interacted significantly with stressor accumulation so that a higher age was associated with less NA reactivity to stressor pile-up. Yet, we did not find such an age-related association for NA reactivity to concurrent daily stressors. Daily PA was not associated with daily stress or with stressor pile-up. The operational definition of stressor pile-up presented in this study contributes to the literature by providing a new approach to model the dynamic effects of stress, and by providing new ways of separating the effects of acute stressors from the effects of stressor pile-up. The age differences found in the present study suggest that older adults develop effective emotion regulation skills for handling stressor pile-up, but that they react to acute daily stressors in a similar way than younger adults.
A disintegrin and a metalloprotease (ADAM) 9 is a metzincin cell-surface protease involved in several biological processes such as myogenesis, fertilization, cell migration, inflammatory response, ...proliferation, and cell–cell interactions. ADAM9 has been found over-expressed in several solid tumors entities such as glioma, melanoma, prostate cancer, pancreatic ductal adenocarcinoma, gastric, breast, lung, and liver cancers. Immunohistochemical analyses highlight ADAM9 expression by actual cancer cells and associate its abundant presence with clinicopathological features such as shortened overall survival, poor tumor grade, de-differentiation, therapy resistance, and metastasis formation. In each of these tumors, ADAM9 may contribute to tumor biology via proteolytic or non-proteolytic mechanisms. For example, in liver cancer, ADAM9 has been found to shed MHC class I polypeptide-related sequence A, contributing towards the evasion of tumor immunity. ADAM9 may also contribute to tumor biology in non-proteolytic ways probably through interaction with different integrins. For example, in melanoma, the interaction between ADAM9 and β1 integrins facilitates tumor stroma cross talks, which then promotes invasion and metastasis via the activation of MMP1 and MMP2. In breast cancer, the interaction between β1 integrins on endothelial cells and ADAM9 on tumor cells facilitate tumor cell extravasation and invasion to distant sites. This review summarizes the present knowledge on ADAM9 in solid cancers, and the different mechanisms which it employ to drive tumor progression.
Indicators of objective functioning, such as everyday competence or sensory and sensorimotor functions, typically show pronounced declines in very old age. However, less is known about how very old ...adults perceive their abilities across multiple domains of health and functioning and to what extent changes in perceived functioning mirror changes in objective functioning. We compared changes in perceived versus objective health and functioning indicators among very old adults (n = 124; baseline age between 87 and 97 years, M = 90.56 years, SD = 2.92 years) across 11 measurement occasions, spanning approximately 5 years. Functioning was assessed by self-reports (subjective health, subjective movement ability, subjective vision, and number of perceived symptoms) and by objective and mostly performance-based tests (everyday competence, visual acuity, chair stand test, and grip strength). All objective measures exhibited a significant mean-level decline across 5 years, whereas most subjective indicators did not reveal significant mean-level changes. Interindividual variation in intraindividual change patterns was considerable in most domains. Correlations between trajectories of the different indicators were mostly weak, and predicting late-life changes in subjective functioning by time-varying objective functioning indicators accounted for only modest amounts of variance. Our findings suggest that there is a somewhat paradoxical pattern of discrepant late-life change trends in subjective versus objective indicators of health and functioning. We argue that a differentiated understanding of the fourth age is required and that common health definitions frequently applied to old and very old age need to be challenged.
Understanding the mixing between surface water and groundwater as well as groundwater travel times in vulnerable aquifers is crucial to sustaining a safe water supply. Age dating tracers used to ...infer apparent travel times typically refer to the entire groundwater sample. A groundwater sample, however, consists of a mixture of waters with a distribution of travel times. Age dating tracers only reflect the proportion of the water that is under the dating range of the used tracer, thus their interpretation is typically biased. Additionally, end‐member mixing models are subject to various sources of uncertainties, which are typically neglected. In this study, we introduce a new framework that untangles groundwater mixing ratios and travel times using a novel combination of in‐situ noble gas analyses. We applied this approach during a groundwater pumping test carried out in a pre‐alpine Swiss valley. First, we calculated transient mixing ratios between recently infiltrated river water and regional groundwater present in a wellfield, using helium‐4 concentrations combined with a Bayesian end‐member mixing model. Having identified the groundwater fraction of recently infiltrated river water (Frw) consequently allowed us to infer the travel times from the river to the wellfield, estimated based on radon‐222 activities of Frw. Furthermore, we compared tracer‐based estimates of Frw with results from a calibrated numerical model. We demonstrate (i) that partitioning of major water sources enables a meaningful interpretation of an age dating tracer of the water fraction of interest and (ii) that the streambed has a major control on the estimated travel times.
Key Points
We introduce a framework to estimate mean travel times of a groundwater fraction consisting of recently infiltrated river water (Frw)
We test the influence of temporally variable end‐member tracer concentrations on estimated mixing ratios
We demonstrate that the streambed has a major control on the travel times of Frw
Mutational inactivation of VHL is the earliest genetic event in the majority of clear cell renal cell carcinomas (ccRCC), leading to accumulation of the HIF-1α and HIF-2α transcription factors. While ...correlative studies of human ccRCC and functional studies using human ccRCC cell lines have implicated HIF-1α as an inhibitor and HIF-2α as a promoter of aggressive tumour behaviours, their roles in tumour onset have not been functionally addressed. Herein we show using an autochthonous ccRCC model that Hif1a is essential for tumour formation whereas Hif2a deletion has only minor effects on tumour initiation and growth. Both HIF-1α and HIF-2α are required for the clear cell phenotype. Transcriptomic and proteomic analyses reveal that HIF-1α regulates glycolysis while HIF-2α regulates genes associated with lipoprotein metabolism, ribosome biogenesis and E2F and MYC transcriptional activities. HIF-2α-deficient tumours are characterised by increased antigen presentation, interferon signalling and CD8
T cell infiltration and activation. Single copy loss of HIF1A or high levels of HIF2A mRNA expression correlate with altered immune microenvironments in human ccRCC. These studies reveal an oncogenic role of HIF-1α in ccRCC initiation and suggest that alterations in the balance of HIF-1α and HIF-2α activities can affect different aspects of ccRCC biology and disease aggressiveness.
Abstract
Background
Sleep and health perceptions, such as self-ratings of pain and health are closely linked. However, the temporal ordering of such associations is not well understood, and it ...remains unclear whether sleep quality and sleep duration show similar or differential associations with health perceptions.
Methods
We used ecological momentary assessment data from 123 young-old (66–69 years, 47% women) and 47 old-old adults (84–90 years, 60% women). Across 7 consecutive days, participants reported their sleep quality and sleep duration each morning and rated their momentary pain and health 6 times per day. We applied dynamic structural equation models to examine bidirectional links of morning reports of sleep quality and duration with daily levels of self-rated pain and health.
Results
In line with the hypotheses, results showed that when participants reported better sleep quality than what is typical for them, they reported less pain and better self-rated health on the day that followed. Longer sleep duration was not linked with subsequent pain or self-rated health. On days when people rated their health as better than usual, they reported better sleep quality but not longer sleep duration the following night. These associations were not moderated by age, gender, or chronic pain.
Conclusion
Findings suggest that in old age, sleep quality is more relevant for health perceptions than sleep duration. Associations between sleep quality and self-rated health seem to be bidirectional; daily pain was linked to prior but not subsequent sleep quality.
Fibroblast activation protein (FAP) is best known for its heightened expression in tumour stroma. This atypical serine protease has both dipeptidyl peptidase and endopeptidase activities, cleaving ...substrates at a post‐proline bond. FAP expression is difficult to detect in non‐diseased adult organs, but is greatly upregulated in sites of tissue remodelling, which include liver fibrosis, lung fibrosis, atherosclerosis, arthritis, tumours and embryonic tissues. Due to its restricted expression pattern and dual enzymatic activities, FAP is emerging as a unique therapeutic target. However, methods to exploit and target this protease are advancing more rapidly than knowledge of the fundamental biology of FAP. This review highlights this imbalance, emphasising the need to better define the substrate repertoire and expression patterns of FAP to elucidate its role in biological and pathological processes.
The Attitude Toward Own Aging Subscale (ATOA) is a frequently used measure of subjective aging. Although ATOA in midlife might assume a preparatory role for psychosocial adjustment in old age, ...research has been dominated by a focus on older adults. To enable a comparison of developmental trajectories of ATOA between middle-aged and young-old adults, we tested measurement invariance between age groups and over a 12-year study period. In addition, personality variables, health dimensions, and sociodemographic variables were investigated as predictors of developmental trajectories of ATOA. Data came from the Interdisciplinary Longitudinal Study of Adult Development (ILSE) with 2 birth cohorts (1930-1932: n = 500; 1950-1952: n = 501) followed over 12 years. Data analyses were conducted with confirmatory factor analysis for ordered-categorical variables and latent growth models. Support for the assumption of partial measurement invariance of ATOA was found in each age group, but not between age groups. Latent growth models revealed a steady decline in ATOA for young-old individuals, whereas ATOA trajectories in midlife were characterized by interindividual variation. Health variables predicted level of ATOA in the young-old. In midlife ATOA were shaped by a variety of factors. Future studies should be conducted with an awareness of differential item functioning of the ATOA scale across age groups. Furthermore, our results point to a greater modifiability of aging attitudes in middle-aged compared with young-old individuals, thus highlighting the importance of the midlife years in shaping developmental trajectories into old age.
Intermittent rivers and ephemeral streams (IRES) make up the majority of waterways in arid and semi‐arid regions. While the physical underpinnings of surface water‐groundwater (SW‐GW) flow systems ...are well understood, how ephemerality, hydraulic properties and vegetation interact along IRES is not clear, posing severe challenges to their sustainable management. This study sought to identify the controls for SW‐GW‐vegetation interactions along IRES. To this end, numerical experiments on a quasi‐hypothetical IRES cross‐section with an integrated surface‐subsurface hydrological model were undertaken. The influence of different degrees of ephemerality on infiltration and riverine transpiration was tested by varying the duration of no‐flow periods. The influence of hydraulic conductivity (K), moisture retention capacity, root density, and local rainfall was also explored. Experiments showed that infiltration is controlled by ephemerality and K, with infiltration decreasing rapidly with increasing ephemerality and decreasing K. Transpiration is influenced by a complex interplay between ephemerality, hydraulic properties, and vegetation. While transpiration is strongly controlled by the degree of ephemerality, the capacity of the subsurface to maintain variably saturated conditions can strongly attenuate the effects of ephemerality. A large moisture retention capacity of the subsurface can partly compensate for the reduced infiltration under increasing ephemerality. Transpiration can be as large under ephemeral as under perennial conditions, especially where water table fluctuations exhibit large amplitudes within the zone of high root density. Overall, the results provide important insights into the complex dynamics of IRES and highlight how changes in flow dynamics can have significant impacts beyond instream processes.
Plain Language Summary
Intermittent rivers and ephemeral streams (IRES) make up the majority of waterways in arid and semi‐arid regions. While the physics of surface water‐groundwater (SW‐GW) systems are well understood, how ephemerality, hydraulic properties and vegetation interact along IRES is not clear, posing severe challenges to their sustainable management. This study sought to identify the key mechanisms which control SW‐GW‐vegetation interactions along IRES through simulation experiments undertaken with a state‐of‐the‐art flow model. Simulation results revealed that infiltration of stream water is controlled by the degree of ephemerality and the hydraulic conductivity of the subsurface, with infiltration decreasing rapidly with an increase in ephemerality and decrease in hydraulic conductivity. Transpiration is influenced by a complex interplay between ephemerality, hydraulic properties and vegetation. The capacity of the subsurface to retain soil moisture can strongly attenuate the effects of ephemerality such that riverine transpiration may be as large under ephemeral as under perennial flow conditions, provided that water table fluctuations exhibit large amplitudes within the zone of high root density. Overall, the results provide important insights into the complex dynamics of IRES and highlight how changes in flow dynamics can have significant impacts beyond instream processes.
Key Points
Key controls for SW‐GW‐vegetation interactions along ephemeral streams were identified with integrated hydrological models
Streambed infiltration is controlled by ephemerality and hydraulic conductivity (K) and is largest under perennial streams
Transpiration is controlled by ephemerality, K, soil moisture and root density and can be as large in ephemeral as in perennial systems
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