Freshwater salinization is an emerging global problem impacting safe drinking water, ecosystem health and biodiversity, infrastructure corrosion, and food production. Freshwater salinization ...originates from diverse anthropogenic and geologic sources including road salts, human-accelerated weathering, sewage, urban construction, fertilizer, mine drainage, resource extraction, water softeners, saltwater intrusion, and evaporative concentration of ions due to hydrologic alterations and climate change. The complex interrelationships between salt ions and chemical, biological, and geologic parameters and consequences on the natural, social, and built environment are called Freshwater Salinization Syndrome (FSS). Here, we provide a comprehensive overview of salinization issues (past, present, and future), and we investigate drivers and solutions. We analyze the expanding global magnitude and scope of FSS including its discovery in humid regions, connections to human-accelerated weathering and mobilization of ‘chemical cocktails.’ We also present data illustrating: (1) increasing trends in salt ion concentrations in some of the world’s major freshwaters, including critical drinking water supplies; (2) decreasing trends in nutrient concentrations in rivers due to regulations but increasing trends in salinization, which have been due to lack of adequate management and regulations; (3) regional trends in atmospheric deposition of salt ions and storage of salt ions in soils and groundwater, and (4) applications of specific conductance as a proxy for tracking sources and concentrations of groups of elements in freshwaters. We prioritize FSS research needs related to better understanding: (1) effects of saltwater intrusion on ecosystem processes, (2) potential health risks from groundwater contamination of home wells, (3) potential risks to clean and safe drinking water sources, (4) economic and safety impacts of infrastructure corrosion, (5) alteration of biodiversity and ecosystem functions, and (6) application of high-frequency sensors in state-of-the art monitoring and management. We evaluate management solutions using a watershed approach spanning air, land, and water to explore variations in sources, fate and transport of different salt ions (
e.g.
monitoring of atmospheric deposition of ions, stormwater management, groundwater remediation, and managing road runoff). We also identify tradeoffs in management approaches such as unanticipated retention and release of chemical cocktails from urban stormwater management best management practices (BMPs) and unintended consequences of alternative deicers on water quality. Overall, we show that FSS has direct and indirect effects on mobilization of diverse chemical cocktails of ions, metals, nutrients, organics, and radionuclides in freshwaters with mounting impacts. Our comprehensive review suggests what could happen if FSS were not managed into the future and evaluates strategies for reducing increasing risks to clean and safe drinking water, human health, costly infrastructure, biodiversity, and critical ecosystem services.
Elevated relative regional cerebral blood volume (rCBV) reflects the increased microvascularity that is associated with brain tumors. The purpose of this study was to investigate the potential role ...of rCBV in the determination of recurrent/residual disease in patients with treated gliomas.
Thirty-one rCBV studies were performed in 19 patients with treated gliomas. All patients also had proton MR spectroscopy and conventional MR imaging. Regions of abnormality were identified on conventional MR images by two neuroradiologists and compared with rCBV and MR spectroscopic data. Metabolites and rCBV were quantified and compared in abnormal regions.
In high-grade tumors, rCBV values were proportional to choline in regions of tumor and nonviable tissue. Although the presence of residual/recurrent disease was often ambiguous on conventional MR images, the rCBV maps indicated regions of elevated vascularity in all low-grade tumors and in 12 of 17 grade IV lesions. Regions of elevated and low rCBV corresponded well with spectra, indicating tumor and nonviable tissue, respectively.
This study suggests that rCBV maps and MR spectroscopy are complementary techniques that may improve the detection of residual/recurrent tumor in patients with treated gliomas. Compared with the spectra, the rCBV maps may better reflect the heterogeneity of the tumor regions because of their higher resolution. The multiple markers of MR spectroscopy enable better discrimination between normal and abnormal tissue than do the rCBV maps.
The utility of three-dimensional (3-D) proton magnetic resonance spectroscopy (1H-MRS) imaging for detecting metabolic changes after brain tumor therapy was assessed in a serial study of 58 total ...examinations of 12 patients with glioblastoma multiforme (GBM) who received brachytherapy. Individual proton spectra from the 3-D array of spectra encompassing the lesion showed dramatic differences in spectral patterns indicative of radiation necrosis, recurrent or residual tumor, or normal brain. The 1H-MRS imaging data demonstrated significant differences between suspected residual or recurrent tumor and contrast-enhancing radiation-induced necrosis. Regions of abnormally high choline (Cho) levels, consistent with viable tumor, were detected beyond the regions of contrast enhancement for all 12 gliomas. Changes in the serial 1H-MRS imaging data were observed, reflecting an altered metabolism following treatment. These changes included the significant reduction in Cho levels after therapy, indicating the transformation of tumor to necrotic tissue. For patients who demonstrated subsequent clinical progression, an increase in Cho levels was observed in regions that previously appeared either normal or necrotic. Several patients showed regional variations in response to brachytherapy as evaluated by 1H-MRS imaging. This study demonstrates the potential of noninvasive 3-D 1H-MRS imaging to discriminate between the formation of contrast-enhancing radiation necrosis and residual or recurrent tumor following brachytherapy. This modality may also allow better definition of tumor extent prior to brachytherapy by detecting the presence of abnormnal metabolite levels in nonenhancing regions of solid tumor.
Before using blood-oxygen-level-dependent magnetic resonance imaging (BOLD MRI) during maternal hyperoxia as a method to detect individual placental dysfunction, it is necessary to understand ...spatiotemporal variations that represent normal placental function. We investigated the effect of maternal position and Braxton-Hicks contractions on estimates obtained from BOLD MRI of the placenta during maternal hyperoxia.
For 24 uncomplicated singleton pregnancies (gestational age 27–36 weeks), two separate BOLD MRI datasets were acquired, one in the supine and one in the left lateral maternal position. The maternal oxygenation was adjusted as 5 min of room air (21% O2), followed by 5 min of 100% FiO2. After datasets were corrected for signal non-uniformities and motion, global and regional BOLD signal changes in R2* and voxel-wise Time-To-Plateau (TTP) in the placenta were measured. The overall placental and uterine volume changes were determined across time to detect contractions.
In mothers without contractions, increases in global placental R2* in the supine position were larger compared to the left lateral position with maternal hyperoxia. Maternal position did not alter global TTP but did result in regional changes in TTP. 57% of the subjects had Braxton-Hicks contractions and 58% of these had global placental R2* decreases during the contraction.
Both maternal position and Braxton-Hicks contractions significantly affect global and regional changes in placental R2* and regional TTP. This suggests that both factors must be taken into account in analyses when comparing placental BOLD signals over time within and between individuals.
•Placental R2* increase with maternal hyperoxia is influenced by maternal position.•Maternal position affects the spatiotemporal distribution of placental BOLD signals.•Maternal position does not alter global TTP but results in regional changes in TTP.•Braxton-Hicks contractions can dominate R2* change even during maternal hyperoxia.•Braxton-Hicks contractions significantly affect regional changes in R2*.
Cancers commonly reactivate embryonic developmental pathways to promote the aggressive behavior of their cells, resulting in metastasis and poor patient outcome. While developmental pathways such as ...canonical Wnt signaling and epithelial-to-mesenchymal transition have received much attention, our understanding of the role of the planar cell polarity (PCP) pathway in tumor progression remains rudimentary. Protein components of PCP, including a subset that overlaps with the canonical Wnt pathway, partition in polarized epithelial cells along the planar axis and are required for the establishment and maintenance of lateral epithelial polarity. Significant insight into PCP regulation of developmental and cellular processes has come from analysis of the functions of the core PCP scaffolding proteins Vangl1 and Vangl2. In particular, studies on zebrafish and with Looptail (Lp) mice, which harbor point mutations in Vangl2 that alter its trafficking and localization, point to roles for the PCP pathway in maintaining cell polarization along both the apical-basal and planar axes as well as in collective cell motility and invasiveness. Recent findings have suggested that the Vangls can promote similar processes in tumor cells. Initial data-mining efforts suggest that VANGL1 and VANGL2 are dysregulated in human cancers, and estrogen receptor (ER)-positive breast cancer patients whose tumors exhibit elevated VANGL1 expression suffer from shortened overall survival. Overall, evidence is beginning to accumulate that the heightened cellular motility and invasiveness associated with PCP reactivation may contribute to the malignancy of some cancer subtypes.
The mechanical properties of bone estimated by micro-finite element (microFE) analysis on the basis of in vivo micro-MR images (microMRIs) of the distal extremities provide a new tool for direct ...assessment of the mechanical consequences of intervention. However, the accuracy of the method has not previously been investigated. Here, we compared microFE-derived mechanical parameters obtained from microMRIs at 160 microm isotropic voxel size now achievable in vivo with those derived from 25 microm isotropic (reference) microCT images of 30 cadaveric tibiae from 15 donors (4 females and 11 males, aged 55-84 years). Elastic and shear moduli estimated from 5mm(3) subvolumes of trabecular bone (TB) derived from microMRIs were significantly correlated with those derived from volume-matched reference microCT images (R(2)=0.60-0.67). Axial stiffness of whole-bone sections (including both cortical and trabecular compartments) derived from microMR-based models were highly correlated (R(2)=0.85) with those from high-resolution reference images. Further, microFE models generated from microCT images after downsampling to lower resolutions relevant to in vivo microMRI (100-160 microm) showed mechanical parameters to be strongly correlated (R(2)>0.93) with those derived at reference resolution (25 microm). Incorporation of grayscale image information into the microMR-based microFE model yielded slopes closer to unity than binarized models (1.07+/-0.15 vs. 0.71+/-0.11) when correlated with reference subregional elastic and shear moduli. This work suggests that elastic properties of distal tibia can be reliably estimated by microFE analysis from microMRIs obtainable at in vivo resolution.
Older patients in the intensive care unit are at greater risk of AKI; however, use of kidney replacement therapy in this population is poorly characterized. We describe the triggers and outcomes ...associated with kidney replacement therapy in older patients with AKI in the intensive care unit.
Our study was a prospective cohort study in 16 Canadian hospitals from September 2013 to November 2015. Patients were ≥65 years old, were critically ill, and had severe AKI; exclusion criteria were urgent kidney replacement therapy for a toxin and ESKD. We recorded triggers for kidney replacement therapy (primary exposure), reasons for not receiving kidney replacement therapy, 90-day mortality (primary outcome), and kidney recovery.
Of 499 patients, mean (SD) age was 75 (7) years old, Charlson comorbidity score was 3.0 (2.3), and median (interquartile range) Clinical Frailty Scale score was 4 (3-5). Most were receiving mechanical ventilation (64%;
=319) and vasoactive support (63%;
=314). Clinicians were willing to offer kidney replacement therapy to 361 (72%) patients, and 229 (46%) received kidney replacement therapy. Main triggers for kidney replacement therapy were oligoanuria, fluid overload, and acidemia, whereas main reasons for not receiving therapy were anticipated recovery (67%;
=181) and therapy not consistent with patient preferences for care (24%;
=66). Ninety-day mortality was similar in patients who did and did not receive kidney replacement therapy (50% versus 51%; adjusted hazard ratio, 0.78; 95% confidence interval, 0.58 to 1.06); however, decisions to offer kidney replacement therapy varied significantly by patient mix, acuity, and perceived benefit. There were no differences in health-related quality of life or rehospitalization among survivors.
Most older, critically ill patients with severe AKI were perceived as candidates for kidney replacement therapy, and approximately one half received therapy. Both willingness to offer kidney replacement therapy and reasons for not starting showed heterogeneity due to a range in patient-specific factors and clinician perceptions of benefit.