Imbalanced land-surface water budgets in a numerical weather prediction system

There has been a significant increase in the skill and resolution of numerical weather prediction models (NWPs) in recent decades, extending the time scales of useful weather predictions. The land-surface models (LSMs) of NWPs are often employed in hydrological applications, which raises the question of how hydrologically representative LSMs really are. In this paper, precipitation (P), evaporation (E) and runoff (R) from the European Centre for Medium-Range Weather Forecasts (ECMWF) global models were evaluated against observational products. The forecasts differ substantially from observed data for key hydrological variables. In addition, imbalanced surface water budgets, mostly caused by data assimilation, were found on both global (P-E) and basin scales (P-E-R), with the latter being more important. Modeled surface fluxes should be used with care in hydrological applications and further improvement in LSMs in terms of process descriptions, resolution and estimation of uncertainties is needed to accurately describe the land-surface water budgets

The Adverse Effects of Topical Photodynamic Therapy:a consensus review and approach to management

Background: Topical photodynamic therapy (PDT) is widely used to treat superficial nonmelanoma skin cancer and dysplasia, and is generally well tolerated. However, as with all treatments, adverse effects may occur and awareness may facilitate approaches to prevention and management. Objectives: To review the available evidence relating to the adverse effects of topical PDT, to help inform recommendations in updated clinical guidelines produced by the British Association of Dermatologists and British Photodermatology Group, and the efficacy of preventative and therapeutic approaches.Methods: This review summarizes the published evidence related to the adverse effects of topical PDT and attempts to interpret this evidence in the context of patient risk and management.Results: Pain and discomfort during PDT are acute adverse effects, which can be minimized through the use of modified and low-irradiance PDT regimens and do not therefore usually limit successful treatment delivery. Other adverse effects include the risk of contact allergy to photosensitizer prodrugs, although this is rare but should be kept in mind, particularly for patients who have received multiple PDT treatments to larger areas. There are no other significant documented longer-term risks and, to date, no evidence of cumulative toxicity or photocarcinogenic risk.Conclusions: Topical PDT is usually well tolerated, reinforcing the utility of this important therapeutic option in dermatology practice. The main acute adverse effect of pain can typically be minimized through preventative approaches of modified PDT regimens. Other adverse effects are uncommon and generally do not limit treatment delivery.</p

Uncovering the Electrochemical Interface of Low-Index Copper Surfaces in Deep Groundwater Environments

Using a combination of a sophisticated modeling protocol and well-established electrochemical techniques, we unravel the chemical composition of the low-index surfaces of copper in groundwater environments at different ion concentrations, pHs, and redox potentials. By carefully linking density functional theory (DFT) and cyclic voltammetry (CV), we are able to extract fundamental information on interfaces of broad significance. Herein, we focus on the case of groundwater found in deep geological environments of importance to the planned constructions of disposal repositories for spent nuclear fuel around the world. Within the error margins of DFT, we can assign adsorption structures and compositions to the current peaks of the CVs. It is found that among the groundwater ions of main interest (i.e. sulfide, bisulfide, sulfate, chloride and bicarbonate), sulfides (HS-, S2-) bind strongest to the surface, and are likely to dominate at the interfaces under the deep geological conditions relevant for repositories of spent nuclear fuel.</p

Simulation of the mechanical interlocking capacity of a rough bone implant surface during healing

Background: When an implant is inserted in the bone the healing process starts to osseointegrate the implant by creating new bone that interlocks with the implant. Biomechanical interlocking capacity is commonly evaluated in in vivo experiments. It would be beneficial to find a numerical method to evaluate the interlocking capacity of different surface structures with bone. In the present study, the theoretical interlocking capacity of three different surfaces after different healing times was evaluated by the means of explicit finite element analysis. Methods: The surface topographies of the three surfaces were measured with interferometry and were used to construct a 3D bone-implant model. The implant was subjected to a displacement until failure of the bone-to-implant interface and the maximum force represents the interlocking capacity. Results: The simulated ratios (test/control) seem to agree with the in vivo ratios of Halldin et al. for longer healing times. However the absolute removal torque values are underestimated and do not reach the biomechanical performance found in the study by Halldin et al. which might be a result of unknown mechanical properties of the interface. Conclusion: Finite element analysis is a promising method that might be used prior to an in vivo study to compare the load bearing capacity of the bone-to-implant interface of two surface topographies at longer healing times

Estrogen-Like Effects of Cadmium in Vivo Do Not Appear to be Mediated via the Classical Estrogen Receptor Transcriptional Pathway

Cadmium is a toxic metal classified as human carcinogen and ubiquitously found in our environment mainly from anthropogenic activities. Exposure to cadmium has been associated with increased risk of certain hormone-dependent cancers in humans, and the metal has been proposed to possess endocrine disruptive properties by mimicking the physiological actions of estrogens. However, the mechanisms behind these effects are unclear. The overall aim of this thesis was to provide mechanistic insights into the estrogenicity of cadmium that may have implications for the human health. To achieve this aim, investigations on the estrogen-like effects of cadmium as well as possible involvement of classical/non-classical estrogen receptor signaling was studied in mice, and these mechanisms were further scrutinized in cell-based models. Furthermore, associations of biomarker of cadmium exposure with endogenous circulating sex hormones were evaluated in a population-based study of women. Results presented here indicate that exposure to cadmium does not affect the genomic estrogen response in vivo in mice, suggesting that classical estrogen signaling is not targeted by cadmium. However, some estrogen-like effects were observed in cadmium exposed mice, i.e. significant thickening of uterine epithelia, in the absence of uterine weight increase, and activation of ERK1/2 MAPKs in the liver. This suggests the existence of alternative signaling pathways modulated by cadmium. In addition, exposure to a wide dose range of cadmium, dose-dependently increased the expression of the endogenous genes Mt1, Mt2, p53, c-fos, and Mdm2 in mouse liver, with p53 being the most sensitive gene. However, phosphorylation of ERK1/2 was already induced at the lowest exposure level (0.5µg/kg body weight), rendering ERK1/2 a more sensitive marker of exposure than any change in gene expression. Furthermore, in vivo findings suggest that cadmium-induced effects are markedly concentration dependent: low-level exposure activates protein-kinases whereas high-level exposure turns on cellular stress responses. The data from in vitro studies indicate that cadmium at regular human exposure levels activates protein-kinase signaling through Raf-MEK-ERK/MAPKs, and we identified EGFR and GPR30 as the mediating receptors. This cadmium-induced activation of protein-kinases further leads to a disturbance in Mdm2/p53 balance, with a significant increase in the Mdm2/p53 ratio in the presence of genotoxic compounds, which in turn suggest that cadmium may disrupt stress response to genotoxins. In 438 postmenopausal women, a positive association was observed between the concentrations of cadmium in blood and testosterone in serum, while an inverse association was observed with estradiol. This may suggest that cadmium affects steroidogenesis. In conclusion, data presented in this thesis collectively suggests that cadmium-induced estrogen-like effects do not involve classical estrogen receptor signaling but rather appear to be mediated via membrane-associated signaling. The activation/ transactivation of GPR30/EGFR-Raf-MEK-ERK/MAPKs and Mdm2 represent a general mechanism by which cadmium may exert its effects. Since EGFR, ERK and Mdm2 are all known key players in cancer promotion, cadmium-induced activation of these and disturbance in the estradiol/testosterone balance in women may have implications for the promotion/development of hormone-related cancers

GABA_A receptor availability is not altered In adults with autism spectrum disorder or in mouse models

Preliminary studies have suggested that γ-aminobutyric acid type A (GABAA) receptors, and potentially the GABAA α5 subtype, are deficient in autism spectrum disorder (ASD). However, prior studies have been confounded by the effects of medications, and these studies did not compare findings across different species. We measured both total GABAA and GABAA α5 receptor availability in two positron emission tomography imaging studies. We used the tracer [11C]flumazenil in 15 adults with ASD and in 15 control individuals without ASD and the tracer [11C]Ro15-4513 in 12 adults with ASD and in 16 control individuals without ASD. All participants were free of medications. We also performed autoradiography, using the same tracers, in three mouse models of ASD: the Cntnap2 knockout mouse, the Shank3 knockout mouse, and mice carrying a 16p11.2 deletion. We found no differences in GABAA receptor or GABAA α5 subunit availability in any brain region of adults with ASD compared to those without ASD. There were no differences in GABAA receptor or GABAA α5 subunit availability in any of the three mouse models. However, adults with ASD did display altered performance on a GABA-sensitive perceptual task. Our data suggest that GABAA receptor availability may be normal in adults with ASD, although GABA signaling may be functionally impaired

Ranking and rating bicycle helmet safety performance in oblique impacts using eight different brain injury models

Bicycle helmets are shown to offer protection against head injuries. Rating methods and test standards are used to evaluate different helmet designs and safety performance. Both strain-based injury criteria obtained from finite element brain injury models and metrics derived from global kinematic responses can be used to evaluate helmet safety performance. Little is known about how different injury models or injury metrics would rank and rate different helmets. The objective of this study was to determine how eight brain models and eight metrics based on global kinematics rank and rate a large number of bicycle helmets (n=17) subjected to oblique impacts. The results showed that the ranking and rating are influenced by the choice of model and metric. Kendall’s tau varied between 0.50 and 0.95 when the ranking was based on maximum principal strain from brain models. One specific helmet was rated as 2-star when using one brain model but as 4-star by another model. This could cause confusion for consumers rather than inform them of the relative safety performance of a helmet. Therefore, we suggest that the biomechanics community should create a norm or recommendation for future ranking and rating methods