Spinal Muscular Atrophy Type 1 Survival Without New Pharmacotherapies: Two Treatment Paradigms.

OBJECTIVES: The aims of the study are to present noninvasive respiratory management outcomes using continuous noninvasive ventilatory support and mechanical in-exsufflation from infancy for spinal muscular atrophy type 1 and to consider bearing on new medical therapies. DESIGN: Noninvasive ventilatory support was begun for consecutively referred symptomatic infants with spinal muscular atrophy type 1 from 1 to 10 mos of age. Intercurrent episodes of respiratory failure were managed by intubation then extubation to continuous noninvasive ventilatory support and mechanical in-exsufflation despite failing ventilator weaning and extubation attempts. Intubations, tracheotomies, and survival were monitored. RESULTS: Of 153 patients with spinal muscular atrophy 1 consecutively referred since 1995, 37 became continuous noninvasive ventilatory support dependent, almost half before 10 yrs of age. Of the 37, 18 required continuous noninvasive ventilatory support for a mean 18.6 ± 3.3 yrs to a mean 25.3 (range, 18-30) yrs of age, dependent from as young as 4 mos of age with 0 to 40 ml of vital capacity. One of the 18 died from COVID-19 acute respiratory distress syndrome at age 24 after 23 yrs of continuous noninvasive ventilatory support. Extubation success rate of 85% per attempt (150/176) resulted in only one undergoing tracheotomy. CONCLUSIONS: Medical treatments begun during the first 6 wks of age convert spinal muscular atrophy 1 into spinal muscular atrophy 2 or 3 but cough flows remain inadequate to avoid many pneumonias that, once resolved by a treatment paradigm of extubation to continuous noninvasive ventilatory support and mechanical in-exsufflation, eliminates need to resort to tracheotomies.

Assessing surface and subsurface transport of neonicotinoid insecticides from no-till crop fields.

Increased use of neonicotinoid-coated crop seeds introduces greater amounts of insecticides into the environment, where they are vulnerable to transport. To understand the transport of neonicotinoids from agricultural fields, we planted maize (Zea mays L.) seeds coated with thiamethoxam in lysimeter plots in central Pennsylvania. Over the next year, we sampled water generated by rainfall and snowmelt and analyzed these samples with mass spectrometry for the neonicotinoids thiamethoxam and clothianidin (metabolite), which originated from the coated seeds. For surface and subsurface transport, thiamethoxam exhibited "first-flush" dynamics, with concentrations highest during the first events following planting and generally decreasing for the remainder of the study. The metabolite clothianidin, however, persisted throughout the study. The mass of thiamethoxam and clothianidin exported during the study period accounted for 1.09% of the mass applied, with more than 90% of the mass transported in subsurface flow and less than 10% in surface runoff. These results suggest that surface runoff, at least for our site, is a relatively small contributor to the overall fate and transport of these insecticides and that the delivery ratio (i.e., mass exported/mass applied) observed for these compounds is similar to those of other trace-level emerging contaminants known to negatively influence aquatic ecosystems.

Aeromonas hydrophila, Bacillus thuringiensis, Escherichia coli and Pseudomonas aeruginosa utilization of Ammonium-N, Nitrate-N and Urea-N in culture.

Agricultural drainage ditches represent a major source of nutrient pollution. Shifts in nitrogen source and use of animal manures have changed the bacterial composition both in species of bacteria and their abundance in agricultural ditches. This change affects how nitrogen is being cycled and potentially the final forms of available nutrients. In particular, animal manures often have bacteria such as Escherichia coli present, increasing the abundance of a bacterial species in ditches. Research has shown that the effect of different nitrogen sources is to change bacterial community composition (class, family). How this influences the role of an individual bacterial species is poorly understood. Thus, our question was how individual species would respond to different sources of nitrogen. We used Aeromonas hydrophila, Bacillus thuringiensis, Escherichia coli and Pseudomonas aeruginosa that are common in agricultural ditches and exposed them to different concentrations of nitrogen in cultures of 1 × 100 and 1 × 10-1 dilutions from a stock solution of bacteria. Nitrogen sources were ammonium chloride, sodium nitrate and urea. The results showed A. hydrophila and E. coli have strong similarities particularly with nitrate-N and urea-N utilization and the response was often correlated with the amount of nutrient added. P. aeruginosa while similar did not show any strong correlation with amount of nutrient added. B. thuringiensis was different from the other three bacteria in utilization or production. Research has provided insight into the role of some bacteria in nitrogen cycling and may be valuable in the future to developing management strategies to reduce nutrients.

Varying Influence of Dairy Manure Injection on Phosphorus Loss in Runoff over Four Years.

Surface application of manure on no-till farms can exacerbate P losses in runoff, contributing to the eutrophication of surface waters. We monitored 12 400-m field plots over 4 yr to compare P losses in surface runoff and lateral subsurface flow with shallow disk injection and broadcast application of dairy manure. Given the substantial variability in annual P losses, as well as a gradual, annual buildup of residual soil test P, significant differences in runoff P losses were detected in only 1 of 4 yr: in 2014, total P losses in runoff were 68% greater from broadcast manure plots than injected manure plots. Dissolved and particulate P were roughly even in their contribution to runoff. Even so, there were significant relationships between annual dissolved P losses and P in the soil surface, which pointed to soils as a regular source of P in runoff. Overall, results confirm the potential for injection to reduce P loss in runoff relative to broadcast application, but because in a few sampling dates injection resulted in greater losses, this study also highlights the importance of assessing mitigation benefits of manure application practices over longer timeframes.

Urea Release by Intermittently Saturated Sediments from a Coastal Agricultural Landscape.

Urea-N is linked to harmful algal blooms in lakes and estuaries, and urea-N-based fertilizers have been implicated as a source. However, the export of urea-N-based fertilizers appears unlikely, as high concentrations of urea-N are most commonly found in surface waters outside periods of fertilization. To evaluate possible autochthonous production of urea-N, we monitored urea-N released from drainage ditch sediments using mesocosms. Sediments from a cleaned (recently dredged) drainage ditch, uncleaned ditch, forested ditch, riparian wetland, and an autoclaved sand control were isolated in mesocosms and flooded for 72 h to quantify urea-N, NH-N, and NO-N in the floodwater. Sediments were flooded with different N-amended solutions (distilled HO, 1.5 mg L NH-N, 3.0 mg L NH-N, 2.6 mg L NO-N, or 5.1 mg L NO-N) and incubated at three water temperatures (16, 21, and 27°C). Urea-N concentrations in mesocosms representing uncleaned and cleaned drainage ditches were significantly greater than nonagricultural sediments and controls. While flooding sediments with N-enriched solution had no clear effect on urea-N, warmer (27°C) temperatures resulted in significantly higher urea-N. Data collected from field ditches that were flooded by a summer rainstorm showed increases in urea-N that mirrored the mesocosm experiment. We postulate that concentrations of urea-N in ditches that greatly exceed environmental thresholds are mediated by biological production in sediments and release to stagnant surface water. Storm-driven urea-N export from ditches could elevate the risk of harmful algal blooms downstream in receiving waters despite the dilution effect.

Estrogen Transport in Surface Runoff from Agricultural Fields Treated with Two Application Methods of Dairy Manure.

This study compares two methods of dairy manure application-surface broadcast and shallow disk injection-on the fate and transport of natural estrogens in surface runoff from 12 field plots in central Pennsylvania. Ten natural surface runoff events were sampled over a 9-mo period after fall manure application. Results show that the range of estrogen concentrations observed in surface runoff from the broadcast plots was several orders of magnitude higher (>5000 ng L) than the concentrations in runoff from the shallow disk injection plots (<10 ng L). Additionally, the transport dynamics differed, with the majority of the estrogen loads from the surface broadcast plots occurring during the first rainfall event after application, whereas the majority of the loads from the shallow disk injection plots occurred more than 6 mo later during a hail storm event. Total estrogen loads were, on average, two orders of magnitude lower for shallow disk injection compared with surface broadcast. Independent of the method of manure application, 17α-estradiol and estrone were preserved in the field for as long as 9 mo after application. Overall, injection of manure shows promise in reducing the potential for off-site losses of hormones from manure-amended soils.

A Protocol for Collecting and Constructing Soil Core Lysimeters.

Leaching of nutrients from land applied fertilizers and manure used in agriculture can lead to accelerated eutrophication of surface water. Because the landscape has complex and varied soil morphology, an accompanying disparity in flow paths for leachate through the soil macropore and matrix structure is present. The rate of flow through these paths is further affected by antecedent soil moisture. Lysimeters are used to quantify flow rate, volume of water and concentration of nutrients leaching downward through soils. While many lysimeter designs exist, accurately determining the volume of water and mass balance of nutrients is best accomplished with bounded lysimeters that leave the natural soil structure intact. Here we present a detailed method for the extraction and construction of soil core lysimeters equipped with soil moisture sensors at 5 cm and 25 cm depths. Lysimeters from four different Coastal Plain soils (Bojac, Evesboro, Quindocqua and Sassafras) were collected on the Delmarva Peninsula and moved to an indoor climate controlled facility. Soils were irrigated once weekly with the equivalent of 2 cm of rainfall to draw down soil nitrate-N concentrations. At the end of the draw down period, poultry litter was applied (162 kg TN ha(-1)) and leaching was resumed for an additional five weeks. Total recovery of applied irrigation water varied from 71% to 85%. Nitrate-N concentration varied over the course of the study from an average of 27.1 mg L(-1) before litter application to 40.3 mg L(-1) following litter application. While greatest flux of nutrients was measured in soils dominated by coarse sand (Sassafras) the greatest immediate flux occurred from the finest textured soil with pronounced macropore development (Quindocqua).

Persistence and Surface Transport of Urea-Nitrogen: A Rainfall Simulation Study.

Studies of harmful algal blooms and associated urea concentrations in the Chesapeake Bay and in coastal areas around the globe strongly suggest that elevated urea concentrations are associated with harmful algal blooms. The observed increased frequency and toxicity of these blooms in recent decades has been correlated with increased agricultural use of N inputs and increased use of urea as a preferred form of commercial N. This rainfall simulation study sought to assess the potential for different N fertilizers and manures to contribute to urea in runoff from a Coastal Plain soil on the Eastern Shore of Maryland. Under worst-case conditions, ~1% of urea-N applied as commercial fertilizer and surface-applied poultry litter was lost in runoff in a simulated rainfall event, roughly equivalent to a 1-yr return period rain storm in the study area, 12 h after application. Cumulative urea-N losses, including four subsequent weekly rainfall events, approached 1.7% from urea-N fertilizer containing a urease inhibitor. Urea-N loss from incorporated poultry litter was negligible, and losses from dairy manure were intermediate. These losses are likely confined to hydrological contributing areas that extend several meters from a drainage ditch or stream for storms with frequent recurrence intervals. Cumulative dissolved N losses in runoff (urea-N + ammonium-N + nitrate-N) as a proportion of total applied plant-available N were <5%, suggesting that most of the applied N was lost by other pathways or was immobilized in soil. Results also highlight the potential for simple management options, such as shallow incorporation or timing, to greatly reduce urea runoff losses.

Cardiopulmonary resuscitation interface adapted for postextubation continuous noninvasive ventilatory support.

The authors report that a new oral interface designed for cardiopulmonary resuscitation and use during anesthesia permitted the successful extubation of an "unweanable" 27-yr-old woman with nemaline rod myopathy to continuous noninvasive ventilatory support. She had failed two previous extubation attempts. Tracheotomy and institutional care were avoided as a result.

Efficacy of mechanical insufflation-exsufflation in extubating unweanable subjects with restrictive pulmonary disorders.

BACKGROUND: Subjects who do not pass ventilator weaning parameters but whose ambient air oxyhemoglobin saturation can be normalized by mechanical insufflation-exsufflation (MIE) can be extubated to continuous noninvasive ventilatory support (CNVS) with MIE used to maintain extubation. Our aim was to study MIE-associated changes in breathing tolerance, pulse oximetry, and vital capacity (VC) for consecutive unweanable subjects. METHODS: A retrospective chart review was performed for consecutively referred intubated subjects with single-organ (respiratory muscle) failure. At presentation, CO2 was normalized by adjusting ventilator settings and VC was measured (point 1). Then, MIE was used via the tube up to every h until oximetry remained ≥ 95% on ambient air and VC was remeasured (point 2) immediately before extubation. Subjects who could not meet ventilator weaning criteria and had no ventilator-free breathing ability upon extubation to CNVS were enrolled. Post-extubation, the MIE was used to maintain oximetry ≥ 95% in room air. VC and breathing tolerance were remeasured within 3 weeks (point 3). RESULTS: Ninety-seven of 98 subjects were successfully extubated despite 45 having been CNVS-dependent for 4 months to 18 y before being intubated. Sixty-nine of the 98 were intubated for 24.9 ± 22 (range 1-158) d and failed 0-6 (mean 1.7) extubation attempts before being transferred and successfully extubated in 2.24 ± 1.78 (range < 1-8) d to CNVS. VC increased by 270% (P < .001) from points 1 to 3. Weaning from CNVS to part-time NVS was achieved by all 52 subjects who had not been CNVS-dependent before intubation. One subject underwent tracheotomy. CONCLUSIONS: Many unweanable subjects can be extubated to CNVS and MIE. The latter can normalize O2 saturation, increase VC, and facilitate extubation.

Decanulation of patients with severe respiratory muscle insufficiency: efficacy of mechanical insufflation-exsufflation.

OBJECTIVE: Ventilator dependent patients with neuromuscular disorders and high level spinal cord injury have been extubated and decanulated to continuous noninvasive intermittent positive pressure ventilatory support after mechanical insufflation-exsufflation was used to achieve specific criteria for tube removal. The purpose of this study is to report changes in extent of need for ventilator use and in vital capacity related to mechanical insufflation-exsufflation used via tracheostomy tubes and post-decanulation via oronasal interfaces. METHODS: Upon presentation patients were placed on fiO2 21% and CO2 was normalized by adjusting ventilator settings as needed. The vital capacity (1st data point) and h/day of ventilator dependence were noted. Then mechanical insufflation-exsufflation was used via the tubes up to every 2 h until ambient air oxyhemoglobin saturation (SpO2) baseline remained ≥ 95% and other decanulation criteria were achieved. The vital capacity was re-measured (2nd data point) and the patient decanulated to continuous noninvasive intermittent positive pressure ventilatory support in ambient air as care providers used mechanical insufflation-exsufflation up to every 30 min to maintain SpO2 ≥ 95%. The vital capacity (3rd data point) and minimum hours/day of noninvasive intermittent positive pressure ventilatory support requirement during the next 3 weeks were recorded. RESULTS: The vital capacities of 61 tracheostomized ventilator users, 36 of whom were continuously dependent, increased significantly (p < 0.001) from presentation to immediately pre-decanulation and in the 3 weeks post-decanulation and all except one were successfully decanulated. CONCLUSION: Many ventilator users can be decanulated in outpatient clinics to continuous noninvasive intermittent positive pressure ventilatory support with mechanical insufflation-exsufflation used to increase vital capacity, SpO2, and autonomous ability to breathe.

Cuff deflation: rehabilitation in critical care.

This is a case series of rehabilitation failures that resulted in severe reactive depression from patients unnecessarily bereft of verbal communication by being left to breathe or be ventilated via tracheostomy tubes, with or without inflated cuffs, for months to years.

A protocol for conducting rainfall simulation to study soil runoff.

Rainfall is a driving force for the transport of environmental contaminants from agricultural soils to surficial water bodies via surface runoff. The objective of this study was to characterize the effects of antecedent soil moisture content on the fate and transport of surface applied commercial urea, a common form of nitrogen (N) fertilizer, following a rainfall event that occurs within 24 hr after fertilizer application. Although urea is assumed to be readily hydrolyzed to ammonium and therefore not often available for transport, recent studies suggest that urea can be transported from agricultural soils to coastal waters where it is implicated in harmful algal blooms. A rainfall simulator was used to apply a consistent rate of uniform rainfall across packed soil boxes that had been prewetted to different soil moisture contents. By controlling rainfall and soil physical characteristics, the effects of antecedent soil moisture on urea loss were isolated. Wetter soils exhibited shorter time from rainfall initiation to runoff initiation, greater total volume of runoff, higher urea concentrations in runoff, and greater mass loadings of urea in runoff. These results also demonstrate the importance of controlling for antecedent soil moisture content in studies designed to isolate other variables, such as soil physical or chemical characteristics, slope, soil cover, management, or rainfall characteristics. Because rainfall simulators are designed to deliver raindrops of similar size and velocity as natural rainfall, studies conducted under a standardized protocol can yield valuable data that, in turn, can be used to develop models for predicting the fate and transport of pollutants in runoff.

Using flue gas desulfurization gypsum to remove dissolved phosphorus from agricultural drainage waters.

High levels of accumulated phosphorus (P) in soils of the Delmarva Peninsula are a major source of dissolved P entering drainage ditches that empty into the Chesapeake Bay. The objective of this study was to design, construct, and monitor a within-ditch filter to remove dissolved P, thereby protecting receiving waters against P losses from upstream areas. In April 2007, 110 Mg of flue gas desulfurization (FGD) gypsum, a low-cost coal combustion product, was used as the reactive ingredient in a ditch filter. The ditch filter was monitored from 2007 to 2010, during which time 29 storm-induced flow events were characterized. For storm-induced flow, the event mean concentration efficiency for total dissolved P (TDP) removal for water passing through the gypsum bed was 73 ± 27% confidence interval (α = 0.05). The removal efficiency for storm-induced flow by the summation of load method was 65 ± 27% confidence interval (α = 0.05). Although chemically effective, the maximum observed hydraulic conductivity of FGD gypsum was 4 L s(-1), but it decreased over time to <1 L s(-1). When bypass flow and base flow were taken into consideration, the ditch filter removed approximately 22% of the TDP load over the 3.6-yr monitoring period. Due to maintenance and clean-out requirements, we conclude that ditch filtration using FGD gypsum is not practical at a farm scale. However, we propose an alternate design consisting of FGD gypsum-filled trenches parallel to the ditch to intercept and treat groundwater before it enters the ditch.

Vital capacity in spinal muscular atrophy.

OBJECTIVE: This work describes and correlates plateau/maximum observed vital capacity (VC) with spinal muscular atrophy (SMA) severity and prognosis for autonomous breathing. DESIGN: SMA severity was correlated with VC, onset, paradoxical breathing, age at definitive dependence on continuous mechanical ventilation (DDCV), and age at first respiratory hospitalization and gastrostomy. RESULTS: Ten severe SMA 1A patients with DDCV before 6 mos of age had maximum observed and plateau VC of 100 ml or less, with plateaus for six at 10.3 (range, 3-48) mos. Another 120 had typical SMA 1B defined by any three of the following: acute respiratory failure before 12 mos of age, gastrostomy before 12 mos of age, DDCV before 10 yrs of age, and VC not exceeding 200 ml, with plateaus for 15 at 26.4 (6-138) mos. Fifteen were with mild type 1C defined by three of the following: VC exceeding 200 ml, acute respiratory failure after 1 yr of age, gastrostomy after 1 yr of age, and no DDCV before 10 yrs of age and had a plateau/maximum observed mean VC of 409 (range, 200-1175) ml at 8.9 (range, 7-10) yrs of age. Of 88 patients with SMA 2 and paradoxical breathing (2A), 16 had a mean plateau/maximum observed VC of 758 (range, 460-2100) ml. DDCV with no autonomous breathing always followed plateauing of VC. Types 2B, 3, and 4 patients attained normal VC. Intergroup VC differences were significant (P < 0.05) for 1A, 1B, 1C, 2A, and 2B-4. When intubated and "unweanable," 50-ml VC signaled the ability for autonomous breathing 1 to 21 days after extubation. CONCLUSIONS: VC should be monitored from birth. It correlates with prognosis with SMA 1A VCs not exceeding 100 ml or 1B 200 ml. Patients who attained 200 ml at any time (milder 1C) retain some ability to breathe after 10 yrs of age.