Transcranial direct current stimulation (tDCS) is being widely investigated in adults as a therapeutic modality for brain disorders involving abnormal cortical excitability or disordered network ...activity. Interest is also growing in studying tDCS in children. Limited empirical studies in children suggest that tDCS is well tolerated and may have a similar safety profile as in adults. However, in electrotherapy as in pharmacotherapy, dose selection in children requires special attention, and simple extrapolation from adult studies may be inadequate. Critical aspects of dose adjustment include 1) differences in neurophysiology and disease, and 2) variation in brain electric fields for a specified dose due to gross anatomical differences between children and adults. In this study, we used high-resolution MRI derived finite element modeling simulations of two healthy children, ages 8 years and 12 years, and three healthy adults with varying head size to compare differences in electric field intensity and distribution. Multiple conventional and high-definition tDCS montages were tested. Our results suggest that on average, children will be exposed to higher peak electrical fields for a given applied current intensity than adults, but there is likely to be overlap between adults with smaller head size and children. In addition, exposure is montage specific. Variations in peak electrical fields were seen between the two pediatric models, despite comparable head size, suggesting that the relationship between neuroanatomic factors and bioavailable current dose is not trivial. In conclusion, caution is advised in using higher tDCS doses in children until 1) further modeling studies in a larger group shed light on the range of exposure possible by applied dose and age and 2) further studies correlate bioavailable dose estimates from modeling studies with empirically tested physiologic effects, such as modulation of motor evoked potentials after stimulation.
Ecological theory suggests that habitat disturbance differentially influences distributions of habitat generalist and specialist species. While well-established for macroorganisms, this theory has ...rarely been explored for microorganisms. Here we tested these principles in permeable (sandy) sediments, ecosystems with much spatiotemporal variation in resource availability and physicochemical conditions. Microbial community composition and function were profiled in intertidal and subtidal sediments using 16S rRNA gene amplicon sequencing and metagenomics, yielding 135 metagenome-assembled genomes. Community composition and metabolic traits modestly varied with sediment depth and sampling date. Several taxa were highly abundant and prevalent in all samples, including within the orders Woeseiales and Flavobacteriales, and classified as habitat generalists; genome reconstructions indicate these taxa are highly metabolically flexible facultative anaerobes and adapt to resource variability by using different electron donors and acceptors. In contrast, obligately anaerobic taxa such as sulfate reducers and candidate lineage MBNT15 were less abundant overall and only thrived in more stable deeper sediments. We substantiated these findings by measuring three metabolic processes in these sediments; whereas the habitat generalist-associated processes of sulfide oxidation and fermentation occurred rapidly at all depths, the specialist-associated process of sulfate reduction was restricted to deeper sediments. A manipulative experiment also confirmed habitat generalists outcompete specialist taxa during simulated habitat disturbance. Together, these findings show metabolically flexible habitat generalists become dominant in highly dynamic environments, whereas metabolically constrained specialists are restricted to narrower niches. Thus, an ecological theory describing distribution patterns for macroorganisms likely extends to microorganisms. Such findings have broad ecological and biogeochemical ramifications.
The balance between estuarine denitrification and dissimilatory nitrate reduction to ammonium (DNRA) is critical for determining nitrogen loads received by oceans from inland waters. We aimed to ...determine the factors controlling the ratio between these processes and determining whether nitrogen was generally removed or recycled in estuaries. Rates of denitrification and DNRA with depth were measured in intact sediment cores in 11 estuaries along the coast of Victoria, Australia. The estuaries studied represent a range of biogeochemical conditions, land use, and catchment size. At a pore water profile scale, the ratio of denitrification to DNRA was well predicted by a multiple regression model with nitrate concentration in the overlying water, dissolved pore water iron, and ammonium as the predictor variables. Areal denitrification rates varied from 4 to 150 μmol · m−2 · hr−1, and DNRA rates varied from 2 to 30 μmol · m−2 · hr−1, with the ratio of denitrification to DNRA spanning a range from denitrification‐dominated (denitrification/DNRA = 8.4) to DNRA‐dominated (denitrification/DNRA = 0.3). DNRA dominated at sites with high iron pools and high organic carbon to nitrate ratios. We conclude that low nitrate and high Fe2+ availability generally enhances DNRA and drives an estuary toward being N recycling, rather than N removing.
Key Points
Dissolved iron and nitrate availability control the balance between denitrification and DNRA in estuaries
Denitrification and DNRA rates in estuaries are of the same order of magnitude
Most estuaries are slightly denitrification‐dominant
Denitrification (DNF) and dissimilatory nitrate reduction to ammonium (DNRA) are two competing nitrate reduction pathways that remove or recycle nitrogen, respectively. However, factors controlling ...the partitioning between these two pathways are manifold and our understanding of these factors is critical for the management of N loads in constructed wetlands. An important factor that controls DNRA in an aquatic ecosystem is the electron donor, commonly organic carbon (OC) or alternatively ferrous iron and sulfide. In this study, we investigated the role of natural organic carbon (NOC) and acetate at different OC/NO3− ratios and ferrous iron on the partitioning between DNF and DNRA using the 15N-tracer method in slurries from four constructed stormwater urban wetlands in Melbourne, Australia. The carbon and nitrate experiments revealed that DNF dominated at all OC/NO3− ratios. The higher DNF and DNRA rates observed after the addition of NOC indicates that nitrate reduction was enhanced more by NOC than acetate. Moreover, addition of NOC in slurries stimulated DNRA more than DNF. Interestingly, slurries amended with Fe2+ showed that Fe2+ had significant control on the balance between DNF and DNRA. From two out of four wetlands, a significant increase in DNRA rates (p < .05) at the cost of DNF in the presence of available Fe2+ suggests DNRA is coupled to Fe2+ oxidation. Rates of DNRA increased 1.5–3.5 times in the Fe2+ treatment compared to the control. Overall, our study provides direct evidence that DNRA is linked to Fe2+ oxidation in some wetland sediments and highlights the role of Fe2+ in controlling the partitioning between removal (DNF) and recycling (DNRA) of bioavailable N in stormwater urban constructed wetlands. In our study we also measured anammox and found that it was always <0.05% of total nitrate reduction in these sediments.
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•Natural organic carbon (NOC) and ferrous iron showed significant effect on the partitioning between DNF and DNRA.•Nitrate reduction was stimulated more by the addition of NOC than acetate.•NOC enhanced DNRA more than denitrification.•Fe2+ had a significant control on the balance between denitrification and DNRA.•There was a link between DNRA and Fe2+ oxidation in Fe2+ amended slurries.
•Both denitrification and DNRA decreased due to drying of sediments, but DNRA decreased more than denitrification.•Rates of both denitrification and DNRA increased with increasing temperature in ...slurries.•The relative increase in DNRA was more than denitrification with increasing temperature.
Constructed wetlands are increasingly used within urban areas to reduce pollutant runoff, including nitrogen. These environments are exposed to frequent wetting and drying events, and also increasing temperatures due to the heat island effect and seasonal variation. In this study, we have investigated the role of drying and rewetting of sediments and temperature on the partitioning of two nitrate reduction pathways: denitrification (DNF) and dissimilatory nitrate reduction to ammonium (DNRA) in four constructed urban stormwater wetlands in Melbourne, Australia. Our results suggest that both DNF and DNRA decreased due to drying of sediments, but DNRA decreased to a greater extent. Rates of DNRA from the drying-rewetting treatment decreased 5–90% compared to the control. Moreover, a concomitant increase in NH4+ fluxes and a slight change in sediment oxygen demand (SOD) suggest that oxic conditions arising from sediment drying was responsible for the decreased rates of DNF and DNRA. Rates of both DNF and DNRA increased with increasing temperature in slurries. The DNF:DNRA ratio suggests that the relative increase in DNRA was more than DNF with increasing temperature. The mean activation energy of DNF ranged from 41 ± 1 to 64 ± 4 kJ mol−1 and the corresponding temperature coefficient (Q10) values ranged from 1.3 to 2.4. In comparison, the mean activation energy of DNRA was higher and ranged from 50 ± 8 to 107 ± 14 kJ mol−1 with the corresponding Q10 values ranging from 1.2 to 3.4. Overall, our results suggest that drying and re-wetting of sediments decreases nitrate reduction and increases nitrogen retention, whereas increased temperature enhances the recycling of bioavailable nitrogen in wet sediments in constructed urban stormwater wetlands.
The microbial community composition and biogeochemical dynamics of coastal permeable (sand) sediments differs from cohesive (mud) sediments. Tide- and wave-driven hydrodynamic disturbance causes ...spatiotemporal variations in oxygen levels, which select for microbial generalists and disrupt redox cascades. In this work, we profiled microbial communities and biogeochemical dynamics in sediment profiles from three sites varying in their exposure to hydrodynamic disturbance. Strong variations in sediment geochemistry, biogeochemical activities, and microbial abundance, composition, and capabilities were observed between the sites. Most of these variations, except for microbial abundance and diversity, significantly correlated with the relative disturbance level of each sample. In line with previous findings, metabolically flexible habitat generalists (e.g., Flavobacteriaceae, Woeseaiceae, Rhodobacteraceae) dominated in all samples. However, we present evidence that aerobic specialists such as ammonia-oxidizing archaea (Nitrosopumilaceae) were more abundant and active in more disturbed samples, whereas bacteria capable of sulfate reduction (e.g., uncultured Desulfobacterales), dissimilatory nitrate reduction to ammonium (DNRA; e.g., Ignavibacteriaceae), and sulfide-dependent chemolithoautotrophy (e.g., Sulfurovaceae) were enriched and active in less disturbed samples. These findings are supported by insights from nine deeply sequenced metagenomes and 169 derived metagenome-assembled genomes. Altogether, these findings suggest that hydrodynamic disturbance is a critical factor controlling microbial community assembly and biogeochemical processes in coastal sediments. Moreover, they strengthen our understanding of the relationships between microbial composition and biogeochemical processes in these unique environments.
Those experiencing houselessness rely on obtaining food from community organizers and donations. Simultaneously, the houseless face disproportionally high rates of medical conditions that may be ...affected by diet including diabetes, hypertension, and hyperlipidemia. There is limited literature on the resources and barriers of the houseless community regarding optimal nutrition from an actionable perspective. Further, less data is available on how street medicine organizations may best impact the nutrition of the unhoused they serve. Elucidating this information will inform how organizational efforts may best support the nutrition of the houseless community.
In partnership with the medical student-run organization, Chicago Street Medicine, at Northwestern University Feinberg School of Medicine, twenty adults experiencing houselessness in Chicago, Illinois participated in the cross-sectional study. A 10-item survey was verbally administered to characterize the participants' daily food intake, food sources, barriers, resources, and nutritional preferences and needs. All data was directly transcribed into REDCap. Descriptive statistics were generated.
Individuals consumed a median of 2 snacks and meals per day (IQR: 1-3). No participant consumed adequate servings of every food group, with only one participant meeting the dietary intake requirements for one food group. Participants most often received their food from donations (n = 15), purchasing themselves (n = 11), food pantries (n = 4), and shelters (n = 3). Eleven of nineteen participants endorsed dental concerns as a major barrier to consuming certain foods. Twelve participants had access to a can opener and twelve could heat their meals on a stove or microwave. Seven had access to kitchen facilities where they may prepare a meal. Approximately half of participants had been counseled by a physician to maintain a particular diet, with most related to reducing sugar intake.
Most houseless participants were unable to acquire a balanced diet and often relied on organizational efforts to eat. Organizations should consider the chronic health conditions, dentition needs, and physical resources and barriers to optimal nutrition when obtaining food to distribute to the unhoused.
Dissolved oxygen (DO) is a key environmental variable that drives and feeds back with numerous processes. In the aquatic sediment that makes up the hyporheic zone, DO may exhibit pronounced spatial ...gradients and complex patterns which control the distribution of a series of redox processes. Yet, little is known regarding the dynamics of hyporheic zone DO, especially under transitional flow regimes. Considering the natural tendency of rivers to be highly responsive to external forcing, these temporal dynamics are potentially just as important and pronounced as the spatial gradients. Here we use laboratory flume experiments and multiphysics flow and reactive transport modeling to investigate surface flow controls on the depth of oxygen penetration in the bed as well as the area of oxygenated sediment. We show that the hyporheic zone DO conditions respond over time scales of hours‐to‐days when subjected to practically instantaneous surface flow perturbations. Additionally, the flume experiments demonstrate that hyporheic zone DO conditions respond faster to surface flow acceleration than to deceleration. Finally, we found that the morphology of the dissolved oxygen plume front depends on surface flow acceleration or deceleration. This study thus shows that the highly dynamic nature of typical streams and rivers drives equally dynamic redox conditions in the hyporheic zone. Because the redox conditions and their distribution within the hyporheic zone are important from biological, ecological, and contaminant perspectives, this hyporheic redox dynamism has the potential to impact system scale aquatic chemical cycles.
Plain Language Summary
The amount of dissolved oxygen (DO) in water is important both in rivers and their underlying sediment. River discharge is constantly changing, and since it is the river's flow which drives flow in the bed, the pronounced chemical and biological gradients within the riverbed may also be constantly changing. We used laboratory experiments and computational models to explore how fast the DO in the bed changes in response to changes in the river velocity. We found that small changes in river velocity created large changes in riverbed DO conditions. We also found that the riverbed DO conditions changed much slower than the river velocity, and that the riverbed response was faster when the river velocity increased and slower when the river decelerated. The shape of the high DO area in the riverbed depended on whether the river water was speeding up, slowing down, or steady. We observed short‐lived areas of low DO in what were mostly high DO zones, and vice versa, particularly when the river water was decelerating. This study thus showed that the riverbed is highly dynamic, subject to large changes in DO that can last much longer than the variations in the river flows that cause them.
Key Points
Experiments and models show that changes in channel water velocity lead to significant dynamic response in hyporheic zone dissolved oxygen
The hyporheic zone response time scale is much longer than the open channel perturbation time scale
Hyporheic response time scales and dissolved oxygen plume morphology exhibit hysteresis relative to channel velocity change
The Yarra River Estuary is a salt wedge estuary prone to hypoxia in the bottom waters during low flow periods. Rates of denitrification and dissimilatory nitrate reduction to ammonium (DNRA) were ...quantified using 15N in relation to oxygen, nitrate and available reductants. Denitrification was the dominant nitrate reduction pathway under all oxygen conditions, however, DNRA increased from <1% under hypoxic conditions (<50μmolL−1O2) to ∼18% of total nitrate reduction under oxygen saturation in the water column in intact core incubations. Microprofiles of nitrate reduction pathways in intact cores using diffusive equilibrium in thin layer (DET) gels showed significant rates of DNRA only occurred under oxic conditions in the presence of Fe2+. Cores incubated anoxically, developed free sulfide within the porewater, had very low concentrations of Fe2+ and low rates of DNRA. Slurry incubations with varying concentrations of NO3− showed that denitrifying bacteria had a higher affinity than nitrate ammonifying bacteria with Km values of 49 and 86μmolL−1 for denitrification and DNRA, respectively, however, this could not explain the change in the rates of DNRA relative to denitrification observed. Further slurry incubations to investigate the relationship between DNRA and Fe2+ oxidation were inconclusive and complicated by very high backgrounds of sorbed (HCl extractable) Fe2+. Addition of Fe2+ to the slurry did not stimulate denitrification compared to a control (no Fe2+ addition), however, there was a significant decrease in the Fe2+ concentration over the period where DNRA occurred in the Fe2+ addition treatment, and no significant decrease in the control treatment. The ratio of DNRA to Fe2+ consumption was 15±6 and 7±3 for the Fe2+ and control treatments, respectively. We suggest reduced rates of DNRA under anoxic conditions can be explained by the binding of Fe2+ with free sulfides and the formation of FeS removing available Fe2+ for DNRA.
The goal of therapy for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) ...are the most frequently used cytoreductive options for patients with ET and PV at high risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment-naïve, high-risk patients with ET/PV. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (P = .80) at 12 months. At 24 to 36 months, CR was 20% to 17% for HU and 29% to 33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, whereas grade 3/4 adverse events were more frequent with PEG (46% vs 28%). At 12 months of treatment, there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment, PEG was more effective in normalizing blood counts and reducing driver mutation burden, whereas HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk patients with ET/PV. This trial was registered at www.clinicaltrials.gov as #NCT01259856.
•Rates of thrombosis and progression were low in patients with ET/PV treated with either HU or IFN in this randomized study.•PEG was more effective in normalizing counts and reducing JAK2V617F VAF in PV whereas HU induced more HPRs in ET.
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