Immunosuppression-Free Life after Pediatric Liver Transplant: A Case-Control Study from the Society of Pediatric Liver Transplant (SPLIT) Registry.

OBJECTIVE: To compare long-term outcomes of pediatric liver transplant (LT) recipients off immunosuppression (IS) with matched controls on IS using data from the Society of Pediatric Liver Transplant (SPLIT) registry. STUDY DESIGN: This was a retrospective case-control study. SPLIT participants <18 years of age, ≥4 years after isolated LT, and off IS for ≥1 year (cases) were age- and sex-matched 1:2 to patients with the same primary diagnosis and post-LT follow-up duration (controls). Primary outcomes included retransplantation, allograft rejection, IS comorbidities, and prevalence of SPLIT-derived composite ideal outcome (c-IO) achieved at the end of the follow-up period. Differences were compared using multiple linear regression for continuous outcomes and logistic regression for dichotomous data. RESULTS: The study cohort was composed of 33 cases (42.4% male, 60.6% biliary atresia, median age at LT of 0.7 [P25, P75, 0.5, 1.6] years, median IS withdrawal time of 9 [P25, P75, 6, 12] years after LT) and 66 age- and sex-matched controls. No cases required retransplantation. Cases and controls had similar growth parameters, laboratory values, calculated glomerular filtration rates, rates of post-transplant lymphoproliferative disease, graft rejection, and attainment of c-IO. CONCLUSIONS: No differences in allograft rejection rates, IS complications, or c-IO prevalence were seen between SPLIT patients off IS and age- and sex-matched controls remaining on IS. Discontinuation of IS most commonly occurred in the context of rigorously designed IS withdrawal trials. The available sample size was small, affecting generalizability to the broader pediatric LT population.

Recent Increase in Incidence of Severe Acute Hepatitis of Unknown Etiology in Children is Associated with Infection with Adenovirus and Other Nonhepatotropic Viruses.

OBJECTIVE: To evaluate whether the nature and severity of non-A-E severe acute hepatitis in children noted by the World Health Organization from late 2021 through early 2022 was indeed increased in 2021-2022 compared with prior years. STUDY DESIGN: We performed a single-center, retrospective study to track the etiology and outcomes of children with non-A-E severe acute hepatitis in 2021-2022 compared with the prior 3-year periods (2018-2019, 2019-2020, and 2020-2021). We queried electronic medical records of children ≤16 years of age with alanine or aspartate aminotransferase levels of >500 IU. Data were analyzed for the periods of October 1, 2021, to May 1, 2022, and compared with the same time periods in 2018-2021. RESULTS: Of 107 children meeting entry criteria, 82 cases occurred from October to May of 2018-2022. The average annual case number was 16.3 in 2018-2021 compared with a 2-fold increase (to 33) in 2021-2022 (P = .0054). Analyses of etiologies showed that this increase was associated with a higher number of children who tested positive for viruses (n = 16) when compared with the average of 3.7 for 2018-2021 (P = .018). Adenovirus (26.1%) and severe acute respiratory syndrome coronavirus-2 (10.3%) were the most frequently detected viruses in 2021-2022. Despite evidence of acute liver failure in 37.8% of children in the entire cohort and in 47% of those with viral infection, the overall survival rate was high at 91.4% and 88.9%, respectively. CONCLUSIONS: The number of children with severe acute hepatitis in our center increased from 2021 to May 2022, with a greater frequency of cases associated with adenovirus, yet transplant-free survival remains high.

Laboratory evaluations of biodegradable boric acid hydrogel baits for the control of Argentine ant (Hymenoptera: Formicidae).

Due to their mutualistic relationship with plant pests, the Argentine ant is considered a major pest in subtropical fruit orchards and vineyards. Besides insecticide sprays, liquid baiting has been demonstrated as an effective method to suppress the Argentine ant populations. To improve the economic feasibility of liquid baiting, hydrogel materials have been recently tested as a carrier for liquid baits containing various insecticidal active ingredients. Here, we tested boric acid as a toxicant in the aqueous sugar bait delivered in a biodegradable calcium alginate hydrogel. Laboratory tests demonstrated that boric acid (1%) liquid bait incorporated in the calcium alginate hydrogel effectively killed Argentine ant workers. Potassium sorbate (0.25%) added to the liquid bait as a preservative did not impact the efficacy of boric acid even though it significantly reduced the degree of swelling of the hydrogel beads in the bait solution. Testing with 2-month-old bait suggested that long-term storage might impact bait efficacy even with potassium sorbate preservative.

Sooty molds from the Jurassic of Patagonia, Argentina.

PREMISE: The sooty molds are a globally distributed ecological group of ascomycetes with epiphyllous, saprotrophic habit, comprising several phylogenetically distant taxa (i.e., members of the classes Dothideomycetes and Eurotiomycetes). Their fossil record extends almost continuously back to the early Cretaceous; however, they are hypothesized to have originated in the early Mesozoic. Here, we describe new specimens of sooty molds associated with conifer leaves from Jurassic hot spring deposits of Patagonia, Argentina. METHODS: Thin sections of chert samples from the La Matilde Formation, Deseado Massif (Santa Cruz, Argentina) were observed using light microscopy. RESULTS: The fungi occur on the surface and axils of leafy twigs with podocarpaceous affinities, forming dense subicula comprised by opaque moniliform hyphae. Additionally, several asexual and sexual reproductive structures are observed. On the basis of vegetative (i.e., dense subicula composed of moniliform hyphae; hyphae composed of opaque cells deeply constricted at the septa) and reproductive characters (i.e., poroconidial and sympodioconidial asexual stages and diverse spores), two morphotypes were identified with affinities within lineages of the subphylum Pezizomycotina that encompass the ecological group of sooty molds, and a third morphotype was within the phylum Ascomycota. CONCLUSIONS: This finding extends the fossil record of sooty molds to the Jurassic and their geographic fossil range to the South American continent. In particular, their association with podocarpaceous conifers is shown to be ancient, dating back to the Jurassic. This new record provides an additional reference point on the diversity of interactions that characterized Jurassic forests in Patagonia.

Development and Demonstration of Low-Impact IPM Strategy to Control Argentine Ants (Hymenoptera: Formicidae) in Urban Residential Settings.

Argentine ants are one of the most common nuisance pest ants treated by pest management professionals (PMPs) in southern and western urban residential areas of the United States. Two new technologies (spraying with a pheromone adjuvant and using a biodegradable hydrogel bait delivery method) were used to develop a unique low-impact integrated pest management (IPM) protocol for Argentine ants in urban residential settings. The IPM protocol included a one-time perimeter spray treatment with 0.03% fipronil (mixed with a pheromone adjuvant) at the beginning of the ant season to achieve a quick knockdown. The initial spray application was followed by a biodegradable hydrogel baiting with 1% boric acid as a maintenance treatment. This low-impact IPM protocol was compared with two other conventional methods: (1) one initial fipronil application and one pyrethroid spray application for maintenance, or (2) one initial fipronil application and one essential oil insecticide spray application for maintenance. Based on Argentine ant foraging activity, the protocols were compared for their control efficacy. Insecticide use information and treatment time were also recorded and compared among different treatment protocols. Our results provided empirical data to support the effectiveness and economic feasibility of the low-impact IPM protocol for managing Argentine ants in urban residential settings.

Biomolecules from Fossilized Hot Spring Sinters: Implications for the Search for Life on Mars.

Hot spring environments are commonly dominated by silica sinters that precipitate by the rapid cooling of silica-saturated fluids and the activity of microbial communities. However, the potential for preservation of organic traces of life in silica sinters back through time is not well understood. This is important for the exploration of early life on Earth and possibly Mars. Most previous studies have focused on physical preservation in samples <900 years old, with only a few focused on organic biomarkers. In this study, we investigate the organic geochemistry of hot spring samples from El Tatio, Chile and the Taupo Volcanic Zone, with ages varying from modern to ∼9.4 ka. Results show that all samples contain opaline silica and contain hydrocarbons that are indicative of a cyanobacterial origin. A ∼3 ka recrystallized, quartz-bearing sample also contains traces of cyanobacterial biomarkers. No aromatic compounds were detected in a ∼9.4 ka opal-A sample or in a modern sinter breccia sample. All other samples contain naphthalene, with one sample also containing other polyaromatic hydrocarbons. These aromatic hydrocarbons have a thermally mature distribution that is perhaps reflective of geothermal fluids migrating from deep, rather than surface, reservoirs. These data show that hot spring sinters can preserve biomolecules from the local microbial community, and that crystallinity rather than age may be the determining factor in their preservation. This research provides support for the exploration for biomolecules in opaline silica deposits on Mars.

The Case for Ancient Hot Springs in Gusev Crater, Mars.

The origin and age of opaline silica deposits discovered by the Spirit rover adjacent to the Home Plate feature in the Columbia Hills of Gusev crater remains debated, in part because of their proximity to sulfur-rich soils. Processes related to fumarolic activity and to hot springs and/or geysers are the leading candidates. Both processes are known to produce opaline silica on Earth, but with differences in composition, morphology, texture, and stratigraphy. Here, we incorporate new and existing observations of the Home Plate region with observations from field and laboratory work to address the competing hypotheses. The results, which include new evidence for a hot spring vent mound, demonstrate that a volcanic hydrothermal system manifesting both hot spring/geyser and fumarolic activity best explains the opaline silica rocks and proximal S-rich materials, respectively. The opaline silica rocks most likely are sinter deposits derived from hot spring activity. Stratigraphic evidence indicates that their deposition occurred before the emplacement of the volcaniclastic deposits comprising Home Plate and nearby ridges. Because sinter deposits throughout geologic history on Earth preserve evidence for microbial life, they are a key target in the search for ancient life on Mars.

Prospective Assessment of Ultrasound Shear Wave Elastography for Discriminating Biliary Atresia from other Causes of Neonatal Cholestasis.

OBJECTIVE: To prospectively assess the diagnostic performance of ultrasound shear wave elastography (SWE) and hepatobiliary laboratory biomarkers for discriminating biliary atresia from other causes of neonatal cholestasis. STUDY DESIGN: Forty-one patients <3 months of age with neonatal cholestasis (direct bilirubin >2 mg/dL) and possible biliary atresia were prospectively enrolled. Both 2-dimensional (2D) and point ultrasound SWE were performed prior to knowing the final diagnosis. Median 2D (8) and point (10) shear wave speed measurements were calculated for each subject and used for analyses. The Mann-Whitney U test was used to compare shear wave speed and laboratory measurements between patients with and without biliary atresia. Receiver operating characteristic curve analyses and multivariable logistic regression were used to evaluate diagnostic performance. RESULTS: Thirteen subjects (31.7%) were diagnosed with biliary atresia, and 28 subjects (68.3%) were diagnosed with other causes of neonatal cholestasis. Median age at the time of ultrasound SWE was 37 days. Median 2D (2.08 vs 1.49 m/s, P = .0001) and point (1.95 vs 1.21 m/s, P = .0014) ultrasound SWE measurements were significantly different between subjects with and without biliary atresia. Using a cut-off value of >1.84 m/s, 2D ultrasound SWE had a sensitivity = 92.3%, specificity = 78.6%, and area under the receiver operating characteristic curve (AuROC) of 0.89 (P < .0001). Using a cut-off value of >320 (U/L), gamma-glutamyl transferase (GGT) had a sensitivity = 100.0%, specificity = 77.8%, and AuROC of 0.85 (P < .0001). Multivariable logistic regression demonstrated an AuROC of 0.93 (P < .0001), with 2 significant covariates (2D ultrasound SWE [OR = 23.06, P = .01]; GGT [OR = 1.003, P = .036]). CONCLUSIONS: Ultrasound SWE and GGT can help discriminate biliary atresia from other causes of neonatal cholestasis.

Plastic Silica Conglomerate with an Extremophile Microbial Matrix in a Hot-Water Stream Paleoenvironment.

A new and unusual type of fossil, siliceous hot-spring deposit (sinter)-comprising monomictic, quartzose conglomerate encrusted with silicified microbial laminates-has been recognized in distal portions of Jurassic and Miocene paleo-geothermal fields of South and North America, respectively. The siliceous clasts are inferred to have originated as conduit-delivered hydrothermal silica gel, owing to their general plastic morphologies, which were then locally reworked and redistributed in geothermally influenced stream paleoenvironments. Today, hot-spring-fed streams and creeks, in places with silica-armored pavements, host microbial mats coating streambeds and/or growing over, and silicifying at, stream air-water interfaces, for example, in Yellowstone National Park (USA) and Waimangu Volcanic Valley (New Zealand). However, the modern deposits do not contain the plastically deformed silica cobbles evident in Mesozoic and Cenozoic examples described herein. Moreover, the fossil microbial laminates of this study are relatively dense and strongly coat the silica cobbles, suggesting the mats stabilized the clasts under fully submerged and hot, high-energy conditions. Thus, this new sinter facies, typically found a few kilometers from main spring-vent areas, is a perhaps unexpected extreme environment in which life took hold in hydrothermal-fluvial settings of the past, and may serve as an additional target in the search for fossil biosignatures of early Earth and possibly Mars.

Use of a Digital Modified Checklist for Autism in Toddlers - Revised with Follow-up to Improve Quality of Screening for Autism.

OBJECTIVES: To assess changes in quality of care for children at risk for autism spectrum disorders (ASD) due to process improvement and implementation of a digital screening form. STUDY DESIGN: The process of screening for ASD was studied in an academic primary care pediatrics clinic before and after implementation of a digital version of the Modified Checklist for Autism in Toddlers - Revised with Follow-up with automated risk assessment. Quality metrics included accuracy of documentation of screening results and appropriate action for positive screens (secondary screening or referral). Participating physicians completed pre- and postintervention surveys to measure changes in attitudes toward feasibility and value of screening for ASD. Evidence of change was evaluated with statistical process control charts and χ2 tests. RESULTS: Accurate documentation in the electronic health record of screening results increased from 54% to 92% (38% increase, 95% CI 14%-64%) and appropriate action for children screening positive increased from 25% to 85% (60% increase, 95% CI 35%-85%). A total of 90% of participating physicians agreed that the transition to a digital screening form improved their clinical assessment of autism risk. CONCLUSIONS: Implementation of a tablet-based digital version of the Modified Checklist for Autism in Toddlers - Revised with Follow-up led to improved quality of care for children at risk for ASD and increased acceptability of screening for ASD. Continued efforts towards improving the process of screening for ASD could facilitate rapid, early diagnosis of ASD and advance the accuracy of studies of the impact of screening.

Tracing Biosignature Preservation of Geothermally Silicified Microbial Textures into the Geological Record.

New Zealand and Argentine (Late Jurassic-Recent) siliceous hot-spring deposits (sinter) reveal preservation pathways of environmentally controlled, microbe-dominated sedimentary facies over geological time scales. Texturally distinctive, laminated to thinly layered, dense and vertically oriented, microtubular "palisade" fabric is common in low-temperature (<40°C) sinter-apron terraces. In modern hot springs, the dark green to brown, sheathed, photosynthetic cyanobacterium Calothrix spp. (family Rivulariaceae) constructs felted palisade mats in shallow terrace(tte) pools actively accreting opaline silica. The resulting stacked layers of silicified coarse filaments-a stromatolite-are highly porous and readily modified by postdepositional environmental perturbations, secondary silica infill, and diagenetic silica phase mineral transformations (opal-A to quartz). Fossil preservation quality is affected by relative timing of silicification, and later environmental and geological events. A systematic approach was used to characterize palisade fabric in sinters of different ages to refine tools for recognizing biosignatures in extreme environments and to track their long-term preservation pathways into the geological record. Molecular techniques, scanning electron microscopy, Raman spectrometry, X-ray powder diffraction, petrography, and lipid biomarker analyses were applied. Results indicate that microbial communities vary at the micron scale and that early and rapid silicification is paramount to long-term preservation, especially where minimal postdepositional disturbance follows fossilization. Overall, it appears that the most robust biomarkers of fossil microbial activity in hot-spring deposits are their characteristic macro- and microtextures and laser micro-Raman identified carbon. Studies of Phanerozoic geothermal deposits with mineralized microbial components are relevant analogs for Precambrian geobiology because early life is commonly preserved as microbial microfossils and biofilms in silica, some of it hydrothermal in origin. Yet the diagenetic "movie" has already been run. Hence, studying younger sinters of a range of ages provides an opportunity to "play it again" and follow the varied influences on biosignatures into the deep-time geological record.

High prevalence of renal dysfunction in long-term survivors after pediatric liver transplantation.

OBJECTIVE: To determine the prevalence and identify variables associated with renal dysfunction in long-term survivors of pediatric liver transplantation. STUDY DESIGN: Data from 117 patients who survived>or=3 years after liver transplantation were analyzed. Demographic and clinical information was obtained from chart review and from a clinical care database. The dependent variable was renal function as determined by measured glomerular filtration rate (mGFR). Univariate and multivariate analyses were performed to identify independent variables associated with renal dysfunction (mGFR<70 mL/min per 1.73 m2). RESULTS: The average time since liver transplant was 7.6+/-3.4 years (range, 3 to 14.6 years). When the last available mGFR for all patients was analyzed, renal dysfunction was present in 32%. In the univariate analysis, mGFR at 1 year after transplant, cyclosporine immunosuppression, and time since transplant were significant; the second two were strongly collinear. Using multiple logistic regression modeling excluding time since transplant, cyclosporine and mGFR at 1 year after transplant were strongly associated with renal dysfunction. CONCLUSIONS: Renal dysfunction is a common complication in children who survive liver transplantation. Our observations are of critical importance because children may live long enough to move from a stage of renal insufficiency characterized by asymptomatic decreased GFR to symptomatic end-stage renal disease.