CFPy-A Python Package for Pre- and Postprocessing of the Conduit Flow Process of MODFLOW.

The conduit flow process (CFP) for MODFLOW's groundwater flow model is an advanced approach for investigating complex groundwater systems, such as karst, with coupled discrete-continuum models. CFP represents laminar and turbulent flow in a discrete pipe network coupled to a matrix continuum. However, the preprocessing demand is comparatively high to generate the conduit network and is usually performed with graphical user interfaces. To overcome this limitation and allow a scalable, reproducible, and comprehensive workflow, existing and new routines were aggregated to a Python package named CFPy, to allow script-based modeling that harmonizes well with the available and widely used FloPy package. CFPy allows information about the location and geometry of the conduit network to be considered by user-specific approaches or by sophisticated methods such as stochastic conduit network generators. The latter allows the automatic generation of many model variants with differing conduit networks for advanced investigations like multi-model approaches in combination with automatic parameter estimation. Additional postprocessing routines provide powerful control and valuable insights for CFP applications. In this methods note, a general technical description of the approach is complemented with two examples that guide users and demonstrate the main capabilities of CFPy.

A data-driven approach for modelling Karst spring discharge using transfer function noise models.

Karst aquifers are important sources of fresh water on a global scale. The hydrological modelling of karst spring discharge, however, still poses a challenge. In this study we apply a transfer function noise (TFN) model in combination with a bucket-type recharge model to simulate karst spring discharge. The application of the noise model for the residual series has the advantage that it is more consistent with assumptions for optimization such as homoscedasticity and independence. In an earlier hydrological modeling study, named Karst Modeling Challenge (KMC; Jeannin et al., J Hydrol 600:126-508, 2021), several modelling approaches were compared for the Milandre Karst System in Switzerland. This serves as a benchmark and we apply the TFN model to KMC data, subsequently comparing the results to other models. Using different data-model-combinations, the most promising data-model-combination is identified in a three-step least-squares calibration. To quantify uncertainty, the Bayesian approach of Markov-chain Monte Carlo (MCMC) sampling is subsequently used with uniform priors for the previously identified best data-model combination. The MCMC maximum likelihood solution is used to simulate spring discharge for a previously unseen testing period, indicating a superior performance compared to all other models in the KMC. It is found that the model gives a physically feasible representation of the system, which is supported by field measurements. While the TFN model simulated rising limbs and flood recession especially well, medium and baseflow conditions were not represented as accurately. The TFN approach poses a well-performing data-driven alternative to other approaches that should be considered in future studies.

Estimating the Burden of Heat-Related Illness Morbidity Attributable to Anthropogenic Climate Change in North Carolina.

Climate change is known to increase the frequency and intensity of hot days (daily maximum temperature ≥30°C), both globally and locally. Exposure to extreme heat is associated with numerous adverse human health outcomes. This study estimated the burden of heat-related illness (HRI) attributable to anthropogenic climate change in North Carolina physiographic divisions (Coastal and Piedmont) during the summer months from 2011 to 2016. Additionally, assuming intermediate and high greenhouse gas emission scenarios, future HRI morbidity burden attributable to climate change was estimated. The association between daily maximum temperature and the rate of HRI was evaluated using the Generalized Additive Model. The rate of HRI assuming natural simulations (i.e., absence of greenhouse gas emissions) and future greenhouse gas emission scenarios were predicted to estimate the HRI attributable to climate change. Over 4 years (2011, 2012, 2014, and 2015), we observed a significant decrease in the rate of HRI assuming natural simulations compared to the observed. About 3 out of 20 HRI visits are attributable to anthropogenic climate change in Coastal (13.40% [IQR: -34.90,95.52]) and Piedmont (16.39% [IQR: -35.18,148.26]) regions. During the future periods, the median rate of HRI was significantly higher (78.65%: Coastal and 65.85%: Piedmont), assuming a higher emission scenario than the intermediate emission scenario. We observed significant associations between anthropogenic climate change and adverse human health outcomes. Our findings indicate the need for evidence-based public health interventions to protect human health from climate-related exposures, like extreme heat, while minimizing greenhouse gas emissions.

Microglia-mediated phagocytosis of apoptotic nuclei is impaired in the adult murine hippocampus after stroke.

Following stroke, neuronal death takes place both in the infarct region and in brain areas distal to the lesion site including the hippocampus. The hippocampus is critically involved in learning and memory processes and continuously generates new neurons. Dysregulation of adult neurogenesis may be associated with cognitive decline after a stroke lesion. In particular, proliferation of precursor cells and the formation of new neurons are increased after lesion. Within the first week, many new precursor cells die during development. How dying precursors are removed from the hippocampus and to what extent phagocytosis takes place after stroke is still not clear. Here, we evaluated the effect of a prefrontal stroke lesion on the phagocytic activity of microglia in the dentate gyrus (DG) of the hippocampus. Three-months-old C57BL/6J mice were injected once with the proliferation marker BrdU (250 mg/kg) 6 hr after a middle cerebral artery occlusion or sham surgery. The number of apoptotic cells and the phagocytic capacity of the microglia were evaluated by means of immunohistochemistry, confocal microscopy, and 3D-reconstructions. We found a transient but significant increase in the number of apoptotic cells in the DG early after stroke, associated with impaired removal by microglia. Interestingly, phagocytosis of newly generated precursor cells was not affected. Our study shows that a prefrontal stroke lesion affects phagocytosis of apoptotic cells in the DG, a region distal to the lesion core. Whether disturbed phagocytosis might contribute to inflammatory- and maladaptive processes including cognitive impairment following stroke needs to be further investigated.

Early Stroke Induces Long-Term Impairment of Adult Neurogenesis Accompanied by Hippocampal-Mediated Cognitive Decline.

Stroke increases neurogenesis in the adult dentate gyrus in the short term, however, long-term effects at the cellular and functional level are poorly understood. Here we evaluated the impact of an early stroke lesion on neurogenesis and cognitive function of the aging brain. We hypothesized that a stroke disturbs dentate neurogenesis during aging correlate with impaired flexible learning. To address this issue a stroke was induced in 3-month-old C57Bl/6 mice by a middle cerebral artery occlusion (MCAO). To verify long-term changes of adult neurogenesis the thymidine analogue BrdU (5-Bromo-2'-deoxyuridine) was administrated at different time points during aging. One and half months after BrdU injections learning and memory performance were assessed with a modified version of the Morris water maze (MWM) that includes the re-learning paradigm, as well as hippocampus-dependent and -independent search strategies. After MWM performance mice were transcardially perfused. To further evaluate in detail the stroke-mediated changes on stem- and progenitor cells as well as endogenous proliferation nestin-green-fluorescent protein (GFP) mice were used. Adult nestin-GFP mice received a retroviral vector injection in the hippocampus to evaluate changes in the neuronal morphology. At an age of 20 month the nestin-GFP mice were transcardially perfused after MWM performance and BrdU application 1.5 months later. The early stroke lesion significantly decreased neurogenesis in 7.5- and 9-month-old animals and also endogenous proliferation in the latter group. Furthermore, immature doublecortin (DCX)-positive neurons were reduced in 20-month-old nestin-GFP mice after lesion. All MCAO groups showed an impaired performance in the MWM and mostly relied on hippocampal-independent search strategies. These findings indicate that an early ischemic insult leads to a dramatical decline of neurogenesis during aging that correlates with a premature development of hippocampal-dependent deficits. Our study supports the notion that an early stroke might lead to long-term cognitive deficits as observed in human patients after lesion.

Adult hippocampal neurogenesis poststroke: More new granule cells but aberrant morphology and impaired spatial memory.

Stroke significantly stimulates neurogenesis in the adult dentate gyrus, though the functional role of this postlesional response is mostly unclear. Recent findings suggest that newborn neurons generated in the context of stroke may fail to correctly integrate into pre-existing networks. We hypothesized that increased neurogenesis in the dentate gyrus following stroke is associated with aberrant neurogenesis and impairment of hippocampus-dependent memory. To address these questions we used the middle cerebral artery occlusion model (MCAO) in mice. Animals were housed either under standard conditions or with free access to running wheels. Newborn granule cells were labelled with the thymidine analoque EdU and retroviral vectors. To assess memory performance, we employed a modified version of the Morris water maze (MWM) allowing differentiation between hippocampus dependent and independent learning strategies. Newborn neurons were morphologically analyzed using confocal microscopy and Neurolucida system at 7 weeks. We found that neurogenesis was significantly increased following MCAO. Animals with MCAO needed more time to localize the platform and employed less hippocampus-dependent search strategies in MWM versus controls. Confocal studies revealed an aberrant cell morphology with basal dendrites and an ectopic location (e.g. hilus) of new granule cells born in the ischemic brain. Running increased the number of new neurons but also enhanced aberrant neurogenesis. Running, did not improve the general performance in the MWM but slightly promoted the application of precise spatial search strategies. In conclusion, ischemic insults cause hippocampal-dependent memory deficits which are associated with aberrant neurogenesis in the dentate gyrus indicating ischemia-induced maladaptive plasticity in the hippocampus.