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Biochars have the potential to reclaim mine-impacted soils; however, their variable physico-chemical properties incite speculation about their successful remediation performance. This investigation examined the capability of biochars produced from three different feedstocks along with a compost blend to improve switchgrass growth conditions in a mine-impacted soil by examining influences on soil pH, grass metal contents, and soil-extractable metal concentrations. Cadmium (Cd)- and zinc (Zn)-contaminated mine soil was collected from a site near Webb City, Missouri, USA-a location within the Tri-State Mining District. In a full factorial design, soil was treated with a 0%, 2.5%, and 5% ( w/w ) compost mixture (wood chips + beef cattle manure), and 0%, 2.5% and 5% of each biochar pyrolyzed from beef cattle manure, poultry litter, and lodgepole pine feedstocks. Switchgrass ( Panicum virgatum , 'Cave-In-Rock' variety) was grown in a greenhouse for 50 days and the mass of shoots (above-ground biomass) and roots was assessed, while soil pH, deionized H 2 O- and 0.01 M CaCl 2 -extractable Cd and Zn concentrations were measured. Poultry litter biochar and compost had the greatest ability to raise soil pH (from 4.40 to 6.61), beef cattle manure biochar and compost moderately raised pH (from 4.4 to 5.92), and lodgepole pine biochar and compost weakly raised pH (from 4.40 to 5.05). Soils treated with beef cattle manure biochar, poultry litter biochar significantly reduced deionized H 2 O- and 0.01 M CaCl 2 -extractable Cd and Zn concentrations, while lodgepole pine biochar-treated soils showed mixed results. Switchgrass shoot and root masses were greatest in soil treated with compost in combination with either beef cattle manure biochar or poultry litter biochar. Soils treated with 5% beef cattle manure biochar + 5% compost had greater reductions in total Cd and Zn concentrations measured in switchgrass shoots and roots compared to the other two treatments. The three biochars and compost mixtures applied to heavy metal, mine-impacted soil had considerable performance dissimilarities for improving switchgrass productivity. Switchgrass growth was noticeably improved after treatment with the compost in combination with biochar from beef cattle manure or poultry litter. This may be explained by the increased soil pH that promoted Zn and Cd precipitation and organic functional groups that reduced soil-available heavy metal concentrations. Our results imply that creating designer biochars is an important management component in developing successful mine-site phytostabilization programs.

Focusing laser light onto a very small target can produce the conditions for laboratory-scale nuclear fusion of hydrogen isotopes. The lack of accurate predictive models, which are essential for the design of high-performance laser-fusion experiments, is a major obstacle to achieving thermonuclear ignition. Here we report a statistical approach that was used to design and quantitatively predict the results of implosions of solid deuterium-tritium targets carried out with the 30-kilojoule OMEGA laser system, leading to tripling of the fusion yield to its highest value so far for direct-drive laser fusion. When scaled to the laser energies of the National Ignition Facility (1.9 megajoules), these targets are predicted to produce a fusion energy output of about 500 kilojoules-several times larger than the fusion yields currently achieved at that facility. This approach could guide the exploration of the vast parameter space of thermonuclear ignition conditions and enhance our understanding of laser-fusion physics.

Objective: The purpose of this study was to quantify the impact of a single lumbar spinal manipulation (SM) intervention on the leg movement performance of degenerative lumbar spinal stenosis (LSS) patients in a small-scale registered randomized clinical trial., Methods: Participants with LSS (n = 14) were tested at baseline for pain, lumbar range of motion, and behavioral or kinematic motor performance (using an established Fitts' Law foot-pointing task), then underwent covariate adaptive randomization to receive SM or no intervention. Postintervention all dependent measures were repeated. Experimenters were blinded to patient group allocation. University ethics board approval was attained., Results: For the primary outcome movement time, there was no significant difference between groups. As predicted by Fitts' Law, all participants had longer movement times as task difficulty increased. Secondary kinematic outcomes yielded no significant between-group differences. Consistent with Fitts' Law, kinematic measures changed significantly with task difficulty. Pairwise comparisons revealed the kinematic variables were more adversely affected by greater movement amplitudes than target size changes. No exploratory differences in pain or lumbar range of motion were observed., Conclusion: Changes in motor performance were not observed in this chronic pain population after a single SM intervention compared with a control group. Given the sample size, the study may have been underpowered to detect meaningful differences. Fitts' Law was observed for the lower extremity-pointing task for an LSS population and may provide an objective measure of motor performance., (Copyright © 2019. Published by Elsevier Inc.)

Context: Identifying high-value health care delivery for patients with clinically complex and high-cost conditions is important for future reimbursement models., Objectives: The objective of this study was to assess the Medicare reimbursement savings of an established palliative care homebound program., Methods: This is a retrospective cohort study involving 50 participants enrolled in a palliative care homebound program and 95 propensity-matched control patients at Mayo Clinic in Rochester, Minnesota, between September 1, 2012, and March 31, 2013. Total Medicare reimbursement was compared in the year before enrollment with the year after enrollment for participants and controls., Results: No significant differences were observed in demographic characteristics or prognostic indices between the two groups. Total Medicare reimbursement per program participant the year before program enrollment was $16,429 compared with $14,427 per control patient, resulting in $2004 higher charges per program patient. In 12 months after program enrollment, mean annual payment was $5783 per patient among participants and $22,031 per patient among the matched controls. In the second year, the intervention group had a decrease of $10,646 per patient; the control group had an increase of $7604 per patient. The difference between the participant group and control group was statistically significant (P < 0.001) and favored the palliative care homebound program enrollees by $18,251 (95% CI, $11,268-$25,234)., Conclusion: The Mayo Clinic Palliative Care Homebound Program reduced annual Medicare expenditures by $18,251 per program participant compared with matched control patients. This supports the role of home-based palliative medicine in delivering high-value care to high-risk older adults., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the impact of implementing bar-code medication administration (BCMA) technology on the rate of medication administration errors in the inpatient setting, specifically those that affect the patient and result in harm., Patients and Methods: Implementation of the new technology began in September 2008 in a staged rollout of 4 or 5 units at a time in 11 separate waves. All corresponding medication administrations and voluntarily reported medication-related adverse events from March 1, 2007, through September 30, 2013, were included for analyses. Adherence to the use of BCMA technology and the number of adverse events were tracked and compared across the preimplementation period through follow-up. Actual errors, not potential errors, were included in the analysis., Results: After the BCMA technology was introduced, reported medication administration errors decreased by 43.5%. More importantly, the rate of harmful medication errors decreased from 0.65 per 100,000 medications preintervention to 0.29 per 100,000 medications postintervention. This resulted in a 55.4% decrease in actual patient harm events. None of the errors at category E or higher was caused by BCMA factors., Conclusion: Consistent use of BCMA technology improves patient safety by decreasing the number of patients harmed by medication administration errors.

Background: Drug-resistant Gram-negative bacteria are a growing threat to children; thus new antibiotics are needed to treat infections caused by these pathogens. Ceftolozane/tazobactam is active against many Gram-negative pathogens and is approved for treatment of complicated intra-abdominal and urinary tract infections in adults, but has not been evaluated in children., Methods: This phase 1, noncomparative, open-label, multicenter study characterized the pharmacokinetics (by noncompartmental analysis), safety, and tolerability of single intravenous doses of ceftolozane/tazobactam in pediatric patients (birth [7 days postnatal] to < 18 years of age) with proven/suspected Gram-negative infection or receiving perioperative prophylaxis (clinicaltrials.gov NCT02266706). Patients were enrolled into 1 of 6 age groups to receive a single, age-based ceftolozane/tazobactam dose, with timed blood sample collection for determining plasma concentrations of ceftolozane and tazobactam. Safety and tolerability were also evaluated., Results: Thirty-seven patients received study drug; 34 were included in the pharmacokinetic population. Ceftolozane and tazobactam pharmacokinetic parameters were generally comparable for patients 3 months to < 18 years of age. Patients from birth (7 days postnatal) to < 3 months of age had lower clearance than older children, likely due to the immature renal function of these young infants. No deaths, study drug-related serious adverse events, or clinically significant laboratory abnormalities were observed after administration of ceftolozane/tazobactam., Conclusions: The doses evaluated in this study yielded ceftolozane/tazobactam exposure levels generally comparable with those in adults. Single doses of ceftolozane/tazobactam were well-tolerated, and no safety concerns were identified. These data informed pharmacokinetic/pharmacodynamic models to derive pediatric dose recommendations for phase 2 ceftolozane/tazobactam clinical trials.

The next-generation Magnetic Recoil Spectrometer, called MRSt, will provide time-resolved measurements of the deuterium-tritium-neutron spectrum from inertial confinement fusion implosions at the National Ignition Facility. These measurements will provide critical information about the time evolution of the fuel assembly, hot-spot formation, and nuclear burn. The absolute neutron spectrum in the energy range of 12-16 MeV will be measured with high accuracy (∼5%), unprecedented energy resolution (∼100 keV) and, for the first time ever, time resolution (∼20 ps). Crucial to the design of the system is a CD conversion foil for the production of recoil deuterons positioned as close to the implosion as possible. The foil-on-hohlraum technique has been demonstrated by placing a 1-mm-diameter, 40- μ m-thick CD foil on the hohlraum diagnostic band along the line-of-sight of the current time-integrated MRS system, which measured the recoil deuterons. In addition to providing validation of the foil-on-hohlraum technique for the MRSt design, substantial improvement of the MRS energy resolution has been demonstrated.

Reconstructing phylogenetic relationships at the micro- and macroevoutionary levels within the same tree is problematic because of the need to use different data types and analytical frameworks. We test the power of target enrichment to provide phylogenetic resolution based on DNA sequences from above species to within populations, using a large herbarium sampling and Euphorbia balsamifera (Euphorbiaceae) as a case study. Target enrichment with custom probes was combined with genome skimming (Hyb-Seq) to sequence 431 low-copy nuclear genes and partial plastome DNA. We used supermatrix, multispecies-coalescent approaches, and Bayesian dating to estimate phylogenetic relationships and divergence times. Euphorbia balsamifera, with a disjunct Rand Flora-type distribution at opposite sides of Africa, comprises three well-supported subspecies: western Sahelian sepium is sister to eastern African-southern Arabian adenensis and Macaronesian-southwest Moroccan balsamifera. Lineage divergence times support Late Miocene to Pleistocene diversification and climate-driven vicariance to explain the Rand Flora pattern. We show that probes designed using genomic resources from taxa not directly related to the focal group are effective in providing phylogenetic resolution at deep and shallow evolutionary levels. Low capture efficiency in herbarium samples increased the proportion of missing data but did not bias estimation of phylogenetic relationships or branch lengths., (© 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.)

It is important to understand molecular effects on plants exposed to compounds released from use of products containing engineered nanomaterials. Here, we present mRNA sequencing data on transcriptome impacts to Douglas-fir following 2 weeks of sublethal exposure to 30:1 diluted airborne emissions released from combustion of diesel fuel containing engineered CeO 2 nanoparticle catalysts (DECe). Our hypothesis was that chamber exposure to DECe would induce distinct transcriptome changes in seedling needles compared with responses to conventional diesel exhaust (DE) or filtered DECe Gas Phase. Significantly increased uptake/binding of Ce in needles of DECe treated seedlings was 2.7X above background levels and was associated with altered gene expression patterns. All 225 Blast2GO gene ontologies (GOs) enriched by up-regulated DECe transcripts were nested within GOs for DE, however, 29 of 31 enriched GOs for down-regulated DECe transcripts were unique. MapMan analysis also identified three pathways enriched with DECe down-regulated transcripts. There was prominent representation of genes with attenuated expression in transferase, transporter, RNA regulation and protein degradation GOs and pathways. CeO 2 nanoparticle additive decreased and shifted molecular impact of diesel emissions. Wide-spread use of such products and chronic environmental exposure to DECe may adversely affect plant physiology and development.

Biochar may be a tool for mine spoil remediation; however, its mechanisms for achieving this goal remain unclear. In this study, Miscanthus (Miscanthus giganteus) biochar was evaluated for its ability to reclaim acidic mine spoils (pH < 3) through reducing metal availability, improving soil microbial enzymatic activity, and initial growth of grass seedlings. Biochar was applied at 0, 1, 2.5 and 5% (w/w) along with lime/no lime and fertilizer additions. Blue Wildrye (Elymus glaucus cv. 'Elkton') was planted and later the shoots and roots were collected and metal concentrations determined. Afterwards, each pot was leached with deionized water, and the leachate analyzed for pH, electrical conductivity (EC), dissolved organic carbon (DOC) and soluble metal concentrations. After drying, the spoil was extracted with 0.01 M CaCl 2 and Mehlich 3 (M3) to determine extractable Al, Cu, and Zn concentrations. Additionally, microbial activity was measured using a fluorescent β-glucosidase and N-acetyl-β-d-glucosaminidase assay. Spoil treated with lime and biochar had significantly greater pH and EC values. Significantly greater β-glucosidase activity occurred only in the 5% biochar plus lime treatment, while N-acetyl-β-d-glucosaminidase activities were not altered. Metal concentrations in rye shoot and roots were mixed. Lime additions significantly reduced extractable metal concentrations. Increasing biochar rates alone significantly reduced leachate DOC concentrations, and subsequently reduced leachable metal concentrations. Surprisingly, miscanthus biochar, by itself, was limited at mitigation, but when combined with lime, the combination was capable of further reducing extractable metal concentrations and improving β-glucosidase enzyme activity., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The effects of cerium oxide nanoparticles (CeO 2 -NPs) on 15 N/ 14 N ratio (δ 15 N) in wheat and barley were investigated. Seedlings were exposed to 0 and 500 mg CeO 2 -NPs/L (Ce-0 and Ce-500, respectively) in hydroponic suspension supplied with NH 4 NO 3 , NH 4 + , or NO 3 - . N uptake and δ 15 N discrimination (i.e. differences in δ 15 N of plant and δ 15 N of N source) were measured. Results showed that N content and 15 N abundance decreased in wheat but increased in barley. Ce-500 only induced whole-plant δ 15 N discrimination (-1.48‰, P ≤ 0.10) with a simultaneous decrease (P ≤ 0.05) in whole-plant δ 15 N (-3.24‰) compared to Ce-0 (-2.74‰) in wheat in NH 4 + . Ce-500 decreased (P ≤ 0.01) root δ 15 N of wheat in NH 4 NO 3 and NH 4 + (3.23 and -2.25‰, respectively) compared to Ce-0 (4.96 and -1.27‰, respectively), but increased (P ≤ 0.05) root δ 15 N of wheat in NO 3 - (3.27‰) compared to Ce-0 (2.60‰). Synchrotron micro-XRF revealed the presence of CeO 2 -NPs in shoots of wheat and barley regardless of N source. Although the longer-term consequences of CeO 2 -NP exposure on N uptake and metabolism are unknown, the results clearly show the potential for ENMs to interfere with plant metabolism of critical plant nutrients such as N even when toxicity is not observed.

The transformation of cerium oxide nanoparticles (CeO 2 -NPs) in soil and its role in plant uptake is a critical knowledge gap in the literature. This study investigated the reduction and speciation of CeO 2 -NPs in barley ( Hordeum vulgare L.) cultivated in soil amended with 250 mg CeO 2 -NPs kg -1 soil. Synchrotron micro-X-ray fluorescence (μXRF) was employed for spatial localization and speciation of CeO 2 -NPs in thin sections of intact roots at the soil-root interface. Results revealed that Ce was largely localized in soil and at the root surface in nanoparticulate form (84-89%). However, a few hot spots on root surfaces revealed highly significant reduction (55-98%) of CeO 2 -NPs [Ce(IV)] to Ce(III) species. Interestingly, only roots in close proximity to hot spots showed Ce uptake which was largely CeO 2 (89-91%) with very little amount Ce(III) (9-10%). These results suggest that the reduction of CeO 2 -NPs to Ce(III) is needed to facilitate uptake of Ce.

Premise of the Study: Until recently, most phylogenetic studies of ferns were based on chloroplast genes. Evolutionary inferences based on these data can be incomplete because the characters are from a single linkage group and are uniparentally inherited. These limitations are particularly acute in studies of hybridization, which is prevalent in ferns; fern hybrids are common and ferns are able to hybridize across highly diverged lineages, up to 60 million years since divergence in one documented case. However, it not yet clear what effect such hybridization has on fern evolution, in part due to a paucity of available biparentally inherited (nuclear-encoded) markers., Methods: We designed oligonucleotide baits to capture 25 targeted, low-copy nuclear markers from a sample of 24 species spanning extant fern diversity., Results: Most loci were successfully sequenced from most accessions. Although the baits were designed from exon (transcript) data, we successfully captured intron sequences that should be useful for more focused phylogenetic studies. We present phylogenetic analyses of the new target sequence capture data and integrate these into a previous transcript-based data set., Discussion: We make our bait sequences available to the community as a resource for further studies of fern phylogeny.

Premise of the Study: Underutilized crops, such as breadfruit (Artocarpus altilis, Moraceae) have the potential to improve global food security. Humans have artificially selected many cultivars of breadfruit since its domestication began approximately 3500 years ago. The goal of this research was to identify transcriptomic signals of positive selection and to develop genomic resources that may facilitate the development of improved breadfruit cultivars in the future., Methods: A reference transcriptome of breadfruit was assembled de novo and annotated. Twenty-four transcriptomes of breadfruit and its wild relatives were generated and analyzed to reveal signals of positive selection that may have resulted from local adaptation or natural selection. Emphasis was placed on MADS-box genes, which are important because they often regulate fruiting timing and structures, and on carotenoid biosynthesis genes, which can impact the nutritional quality of the fruit., Key Results: Over 1000 genes showed signals of positive selection, and these genes were enriched for localization to plastids. Nucleotide sites and individuals under positive selection were discovered in MADS-box genes and carotenoid biosynthesis genes, with several sites located in cofactor or DNA-binding domains. A McDonald-Kreitman test comparing wild to cultivated samples revealed selection in one of the carotenoid biosynthesis genes, abscisic acid 8'-hydroxylase 3., Conclusions: This research highlights some of the many genes that may have been intentionally or unintentionally selected for during the human-mediated dispersal of breadfruit and stresses the importance of conserving a varied germplasm collection. It has revealed candidate genes for further study and produced new genomic resources for breadfruit., (© 2018 The Authors. American Journal of Botany is published by Wiley Periodicals, Inc. on behalf of the Botanical Society of America.)

The past decade has seen a major breakthrough in our ability to easily and inexpensively sequence genome-scale data from diverse lineages. The development of high-throughput sequencing and long-read technologies has ushered in the era of phylogenomics, where hundreds to thousands of nuclear genes and whole organellar genomes are routinely used to reconstruct evolutionary relationships. As a result, understanding which options are best suited for a particular set of questions can be difficult, especially for those just starting in the field. Here, we review the most recent advances in plant phylogenomic methods and make recommendations for project-dependent best practices and considerations. We focus on the costs and benefits of different approaches in regard to the information they provide researchers and the questions they can address. We also highlight unique challenges and opportunities in plant systems, such as polyploidy, reticulate evolution, and the use of herbarium materials, identifying optimal methodologies for each. Finally, we draw attention to lingering challenges in the field of plant phylogenomics, such as reusability of data sets, and look at some up-and-coming technologies that may help propel the field even further.

Background: In this article, we reflected on our experience of the cost of parenting a child with autism, including our ongoing search for educational and therapeutic intervention., Objectives: We aimed to give an academic insight into the state of autism education and care in South Africa as seen by us, with special attention to its cost and sustainability., Methods: Using evocative autoethnography as storied scholarship together with critical autism studies, we reflected on stories of the past 5 years since our son's diagnosis., Results: Our experiences agree with international studies that establish autism as the most expensive disability. In addition to the high costs of diagnosis, existing intervention and support approaches are unaffordable for the majority of South Africans. We recommend that teachers should be trained to participate in early screening and diagnosis, as well as co-therapists, to strengthen the implementation of inclusive education., Conclusion: The kind of autism intervention currently offered in South Africa is financially and socially unsustainable. Instead of positioning autism as an individual or family dilemma, it should be addressed as an educational and societal issue. Future research should explore cost-effective options for a developing country context, while promoting best practice within inclusive settings., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.

Premise of the Study: Untapped information about allele diversity within populations and individuals (i.e., heterozygosity) could improve phylogenetic resolution and accuracy. Many phylogenetic reconstructions ignore heterozygosity because it is difficult to assemble allele sequences and combine allele data across unlinked loci, and it is unclear how reconstruction methods accommodate variable sequences. We review the common methods of including heterozygosity in phylogenetic studies and present a novel method for assembling allele sequences from target-enriched Illumina sequencing libraries., Methods: We performed supermatrix phylogeny reconstruction and species tree estimation of Artocarpus based on three methods of accounting for heterozygous sequences: a consensus method based on de novo sequence assembly, the use of ambiguity characters, and a novel method for incorporating read information to phase alleles. We characterize the extent to which highly heterozygous sequences impeded phylogeny reconstruction and determine whether the use of allele sequences improves phylogenetic resolution or decreases topological uncertainty., Key Results: We show here that it is possible to infer phased alleles from target-enriched Illumina libraries. We find that highly heterozygous sequences do not contribute disproportionately to poor phylogenetic resolution and that the use of allele sequences for phylogeny reconstruction does not have a clear effect on phylogenetic resolution or topological consistency., Conclusions: We provide a framework for inferring phased alleles from target enrichment data and for assessing the contribution of allelic diversity to phylogenetic reconstruction. In our data set, the impact of allele phasing on phylogeny is minimal compared to the impact of using phylogenetic reconstruction methods that account for gene tree incongruence., (© 2018 Botanical Society of America.)

The assessment and monitoring of soil disturbance and its effect on soil quality (i.e., ability to support a range of ecosystem services) has been hindered due to the shortcomings of many traditional analytical techniques (e.g., soil enzyme activities, microbial incubations), including: high cost, long-term time investment and difficulties with data interpretation. Consequently, there is a critical need to develop a rapid and repeatable approach for quantifying changes in soil quality that will provide an assessment of the current status, condition and trend of natural and managed ecosystems. Here we report on a rapid, high-throughput approach to develop an ecological 'fingerprint' of a soil using Fourier transformed infrared (FTIR) spectroscopy and chemometric modeling, and its application to assess soil ecosystem status and trend. This methodology was applied in a highly disturbed forest ecosystem over a 19-year sampling period to detect changes in soil quality (detected via changes in spectral properties), resulting from changes in dynamic soil properties (e.g., soil organic matter, reactive mineralogy). Two chemometric statistical techniques (i.e., hierarchical clustering analysis and discriminate analysis of principal components) were evaluated for interpreting and quantifying similarities/dissimilarities between samples utilizing the entire FTIR spectra (i.e., fingerprint) from each sample. We found that this approach provided a means for clearly discriminating between degraded soils, soils in recovery and reference soils. Results from fingerprint FTIR analysis illustrate its power and potential for the monitoring and assessment of soil quality and soil landscape change.

Background Context: Emergent surgery for patients with a traumatic spinal cord injury (SCI) is seen as the gold standard in acute management. However, optimal treatment for those with the clinical diagnosis of central cord syndrome (CCS) is less clear, and classic definitions of CCS do not identify a unique population of patients., Purpose: The study aimed to test the authors' hypothesis that spine stability can identify a unique group of patients with regard to demographics, management, and outcomes, which classic CCS definitions do not., Study Design/setting: This is a prospective observational study., Patient Sample: The sample included participants with cervical SCI included in a prospective Canadian registry., Outcome Measures: The outcome measures were initial hospitalization length of stay, change in total motor score from admission to discharge, and in-hospital mortality., Methods: Patients with cervical SCI from a prospective Canadian SCI registry were grouped into stable and unstable spine cohorts. Bivariate analyses were used to identify differences in demographic, injury, management, and outcomes. Multivariate analysis was used to better understand the impact of spine stability on motor score improvement. No conflicts of interest were identified., Results: Compared with those with an unstable spine, patients with cervical SCI and a stable spine were older (58.8 vs. 44.1 years, p<.0001), more likely male (86.4% vs. 76.1%, p=.0059), and have more medical comorbidities. Patients with stable spine cervical SCI were more likely to have sustained their injury by a fall (67.4% vs. 34.9%, p<.0001), and have high cervical (C1-C4; 58.5% vs. 43.3%, p=.0009) and less severe neurologic injuries (ASIA Impairment Scale C or D; 81.3% vs. 47.5%, p<.0001). Those with stable spine injuries were less likely to have surgery (67.6% vs. 92.6%, p<.0001), had shorter in-hospital lengths of stay (median 84.0 vs. 100.5 days, p=.0062), and higher total motor score change (20.7 vs. 19.4 points, p=.0014). Multivariate modeling revealed that neurologic severity of injury and spine stability were significantly related to motor score improvement; patients with stable spine injuries had more motor score improvement., Conclusions: We propose that classification of stable cervical SCI is more clinically relevant than classic CCS classification as this group was found to be unique with regard to demographics, neurologic injury, management, and outcome, whereas classic CCS classifications do not . This classification can be used to assess optimal management in patients where it is less clear if and when surgery should be performed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Considerable progress has been made in ecological and evolutionary genetics with studies demonstrating how genes underlying plant and microbial traits can influence adaptation and even 'extend' to influence community structure and ecosystem level processes. Progress in this area is limited to model systems with deep genetic and genomic resources that often have negligible ecological impact or interest. Thus, important linkages between genetic adaptations and their consequences at organismal and ecological scales are often lacking. Here we introduce the Sphagnome Project, which incorporates genomics into a long-running history of Sphagnum research that has documented unparalleled contributions to peatland ecology, carbon sequestration, biogeochemistry, microbiome research, niche construction, and ecosystem engineering. The Sphagnome Project encompasses a genus-level sequencing effort that represents a new type of model system driven not only by genetic tractability, but by ecologically relevant questions and hypotheses., (© 2017 UT-Battelle New Phytologist © 2017 New Phytologist Trust.)

We followed soil C fluxes in a subalpine grassland system exposed to experimentally increased atmospheric N deposition for 7 years. Earlier we found that, different from the plant productivity response, the bulk soil C stock increase was highest at the medium, not the high N input as hypothesized. This implies that a smaller N-deposition rate has a greater potential to favor the biological greenhouse gas-sink. To help elucidate the mechanisms controlling those changes in SOC in response to N deposition, we produced four soil density fractions and analyzed soil organic C concentration [SOC], as well as δ 13 C signatures (δ 13 C SOC ) of SOC components. Soil respired CO 2 (δ 13 C CO2 ) was analyzed to better distinguish seasonal short term dynamics from N-deposition effects and to identify the predominant substrate of soil respiration. Both at the start of the experiment and after 7 years we found a strong, negative correlation between [SOC] and δ 13 C SOC of the soil density fractions in the control treatment, consistent with an advanced stage of microbial processing of SOC in fractions of higher density. During the experiment the [SOC] increased in the two lighter density fractions, but decreased in the two heavier fractions, suggesting a possible priming effect that accelerated decomposition of formerly recalcitrant (heavy) organic matter pools. The seasonal pattern of soil δ 13 C CO2 was affected by weather and canopy development, and δ 13 C CO2 values for the different N treatment levels indicated that soil respiration originated primarily from the lightest density fractions. Surprisingly, [SOC] increases were significantly higher under medium N deposition in the <1.8 fraction and in bulk soil, compared to the high N treatment. Analogously, the depletion of δ 13 C SOC was significantly higher in the medium compared to the high N treatment in the three lighter fractions. Thus, medium N deposition favored the highest C sequestration potential, compared to the low N control and the high N treatment. Clearly, our results show that it is inappropriate to use plant productivity N response as an indicator for shifts in SOC content in grassland ecosystems. Here, isotopic techniques illustrated why atmospheric N deposition of 14 kg N ha -1 yr -1 is below, and 54 kg N ha -1 yr -1 is above a threshold that tips the balance between new, assimilative gains and respiratory losses towards a net loss of [SOC] for certain soil fractions in the subalpine grassland.

We developed a rapid-test to screen for effects of biochar on seed germina- tion and soils. Crop seeds were placed in containers and covered with 15 g of soil with 1% biochar by weight. Two agricultural soils from South Carolina USA were used. Eighteen biochars were produced from six primary feedstocks [pine chips (PC), poultry litter (PL), swine solids (SS), switchgrass (SG); and two blends of PC and PL, 50% PC/50% PL (55), and 80% PC/20% PL (82)]. Each feedstock was pyrolyzed at 350, 500 and 700°C. There were few biochar effects on seed germination. Shoot dry weight was increased for carrot, cucumber, lettuce, oat, and tomato; primarily with biochars containing PL. Soil pH, electrical conductivity and extractable phosphorus primarily increased with PL, SS, 55, and 82 treatments for both soil types and across species. This method can be an early indicator of biochar effects on seed germination and soil health.

Familial Creutzfeldt-Jakob disease (fCJD) results from inheritance of mutations in the prion protein gene. Confirming fCJD diagnosis is essential for informing persons of their potential hereditary risk and for genetic counseling to support personal decisions for genetic testing and family planning. We describe a case of fCJD that was linked to a large cluster of African Americans with fCJD identified through a public health investigation, including 8 confirmed cases and 13 suspected cases involving 7 generations in 1 family. Genetic counseling is an important component of fCJD management for families coping with genetic prion diseases.

The extent of the association between temperature and heat-coded deaths, for which heat is the primary cause of death, remains largely unknown. We explored the association between temperature and heat-coded deaths and potential interactions with various demographic and environmental factors. A total of 335 heat-coded deaths that occurred in Oklahoma from 1990 through 2011 were identified using heat-related International Classification of Diseases codes, cause-of-death nomenclature, and narrative descriptions. Conditional logistic regression models examined the association between temperature and heat index on heat-coded deaths. Interaction by demographic factors (age, sex, marital status, living alone, outdoor/heavy labor occupations) and environmental factors (ozone, PM 10 , PM 2.5 ) was also explored. Temperatures ≥99 °F (the median value) were associated with approximately five times higher odds of a heat-coded death as compared to temperatures <99 °F (adjusted OR = 4.9, 95% CI 3.3, 7.2). The effect estimates were attenuated when exposure to heat was characterized by heat index. The interaction results suggest that effect of temperature on heat-coded deaths may depend on sex and occupation. For example, the odds of a heat-coded death among outdoor/heavy labor workers exposed to temperatures ≥99 °F was greater than expected based on the sum of the individual effects (observed OR = 14.0, 95% CI 2.7, 72.0; expected OR = 4.1 [2.8 + 2.3-1.0]). Our results highlight the extent of the association between temperature and heat-coded deaths and emphasize the need for a comprehensive, multisource definition of heat-coded deaths. Furthermore, based on the interaction results, we recommend that states implement or expand heat safety programs to protect vulnerable subpopulations, such as outdoor workers.

The soilborne pathogen Listeria monocytogenes frequently contaminates food products and food processing environments and is able to survive desiccation, high osmotic pressures, and starvation. However, little is known about how this pathogen survives starvation at 4°C. This study provides evidence that L. monocytogenes is able to survive total nutrient starvation for 4 weeks. L. monocytogenes strains EGD-e, Scott A, F2365, and HCC23 were starved individually in sterile water. Colony counts declined over 4 weeks, with Scott A declining the most rapidly. Transmission electron microscopy images revealed degradation of starving cell membranes and altered cytosols. Starving cells were subjected to the metabolic inhibitors fluoride, arsenite, 2,4-dinitrophenol, iodoacetate, and cyanide individually. Iodoacetate, which inhibits glyceraldehyde-3-phosphate dehydrogenase, completely reduced cultivable counts below the level of detection compared with the control starving cells; 2,4-dinitrophenol, which dissipates proton motive force, almost completely reduced cultivable counts. These results suggest that L. monocytogenes strains EGD-e, Scott A, F2365, and HCC23 are actively using part of the glycolysis pathway while starving. These results suggest that starving L. monocytogenes cells retain aspects of active metabolism.

Colorectal cancer originates within immunologically complex microenvironments. To date, the benefits of immunotherapy have been modest, except in neoantigen-laden mismatch repair-deficient tumors. Approaches to enhance tumor-infiltrating lymphocytes in the tumor bed may substantially augment clinical immunotherapy responses. In this article, we report that proteolysis of the tolerogenic matrix proteoglycan versican (VCAN) strongly correlated with CD8 + T cell infiltration in colorectal cancer, regardless of mismatch repair status. Tumors displaying active VCAN proteolysis and low total VCAN were associated with robust (10-fold) CD8 + T cell infiltration. Tumor-intrinsic WNT pathway activation was associated with CD8 + T cell exclusion and VCAN accumulation. In addition to regulating VCAN levels at the tumor site, VCAN proteolysis results in the generation of bioactive fragments with novel functions (VCAN-derived matrikines). Versikine, a VCAN-derived matrikine, enhanced the generation of CD103 + CD11c hi MHCII hi conventional dendritic cells (cDCs) from Flt3L-mobilized primary bone marrow-derived progenitors, suggesting that VCAN proteolysis may promote differentiation of tumor-seeding DC precursors toward IRF8- and BATF3-expressing cDCs. Intratumoral BATF3-dependent DCs are critical determinants for T cell antitumor immunity, effector T cell trafficking to the tumor site, and response to immunotherapies. Our findings provide a rationale for testing VCAN proteolysis as a predictive and/or prognostic immune biomarker and VCAN-derived matrikines as novel immunotherapy agents., (Copyright © 2017 by The American Association of Immunologists, Inc.)

The last 10-15 years have witnessed a revolution in treating multiple myeloma, an incurable cancer of Ab-producing plasma cells. Advances in myeloma therapy were ushered in by novel agents that remodel the myeloma immune microenvironment. The first generation of novel agents included immunomodulatory drugs (thalidomide analogs) and proteasome inhibitors that target crucial pathways that regulate immunity and inflammation, such as NF-κB. This paradigm continued with the recent regulatory approval of mAbs (elotuzumab, daratumumab) that impact both tumor cells and associated immune cells. Moreover, recent clinical data support checkpoint inhibition immunotherapy in myeloma. With the success of these agents has come the growing realization that the myeloid infiltrate in myeloma lesions-what we collectively call the myeloid-in-myeloma compartment-variably sustains or deters tumor cells by shaping the inflammatory milieu of the myeloma niche and by promoting or antagonizing immune-modulating therapies. The myeloid-in-myeloma compartment includes myeloma-associated macrophages and granulocytes, dendritic cells, and myeloid-derived-suppressor cells. These cell types reflect variable states of differentiation and activation of tumor-infiltrating cells derived from resident myeloid progenitors in the bone marrow-the canonical myeloma niche-or myeloid cells that seed both canonical and extramedullary, noncanonical niches. Myeloma-infiltrating myeloid cells engage in crosstalk with extracellular matrix components, stromal cells, and tumor cells. This complex regulation determines the composition, activation state, and maturation of the myeloid-in-myeloma compartment as well as the balance between immunogenic and tolerogenic inflammation in the niche. Redressing this balance may be a crucial determinant for the success of antimyeloma immunotherapies., (© Society for Leukocyte Biology.)

Parasitic diseases caused by kinetoplastid parasites of the genera Trypanosoma and Leishmania are an urgent public health crisis in the developing world. These closely related species possess a number of multimeric enzymes in highly conserved pathways involved in vital functions, such as redox homeostasis and nucleotide synthesis. Computational alanine scanning of these protein-protein interfaces has revealed a host of potentially ligandable sites on several established and emerging anti-parasitic drug targets. Analysis of interfaces with multiple clustered hotspots has suggested several potentially inhibitable protein-protein interactions that may have been overlooked by previous large-scale analyses focusing solely on secondary structure. These protein-protein interactions provide a promising lead for the development of new peptide and macrocycle inhibitors of these enzymes.

Inducible Cre-ERT recombinase technology is widely used for gene targeting studies. The second generation of inducible Cre-ERT recombinase, hemizygous B6.129S-Tg(UBC-cre/ERT2)1Ejb/J (hereafter abbreviated as Cre-ERT2), a fusion of a mutated estrogen receptor and Cre recombinase, was engineered to be more efficient and specific than the original Cre-ERT. The putative mechanism of selective Cre-mediated recombination is Cre sequestration in the cytoplasm in the basal state with translocation to the nucleus only in the presence of tamoxifen. We utilized both a reporter mouse (B6.129 (Cg)-Gt(ROSA)26Sor tm4(ACTB-tdTomato,-EGFP)Luo /J) and endothelin converting enzyme-1 floxed transgenic mouse line to evaluate Cre-ERT2 activity. We observed spontaneous Cre activity in both settings. Unintended Cre activity is a confounding factor that has a potentially large impact on data interpretation. Thus, it is important to consider background Cre activity in experimental design.

The unique physical and chemical properties of biochars make them promising materials for odor, gas, and nutrient sorption. Floating covers made from organic materials (biocovers) are one option for reducing odor and gas emissions from livestock manure lagoons. This study evaluated the potential of floating biochar covers to reduce odor and gas emissions while simultaneously sorbing nutrients from liquid dairy manure. This new approach has the potential to mitigate multiple environmental problems. Two biochars were tested: one made via gasification of Douglas fir chips at 650°C (FC650), and the other made from a mixture of Douglas fir [ (Mirb.) Franco] bark and center wood pyrolyzed at 600°C (HF600). The HF600 biocover reduced mean headspace ammonia concentration by 72 to 80%. No significant reduction was found with the FC650 biocover. Nutrient uptake ranged from 0.21 to 4.88 mg N g biochar and 0.64 to 2.70 mg P g biochar for the HF600 and FC650 biochars, respectively. Potassium ranged from a loss of 4.52 to a gain of 2.65 mg g biochar for the FC650 and HF600 biochars, respectively. The biochars also sorbed Ca, Mg, Na, Fe, Al, and Si. In a separate sensory evaluation, judges assessed odor offensiveness and odor threshold of five biocover treatments including four biochars applied over dairy manure. Reductions in mean odor offensiveness and mean odor threshold were observed in three treatments compared with the control. These results show that biochar covers hold promise as an effective practice for reducing odor and gas emissions while sorbing nutrients from liquid dairy manure., (Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

The endothelin (ET) system includes 3 small peptide hormones and a pair of G-protein-coupled receptors. This review first outlines the ET signaling pathway and ET metabolism. Next, it summarizes the role of ET1 signaling in craniofacial development. Then, it discusses observations relating ET signaling to osteoblastic and other osteosclerotic processes in cancer. Finally, it describes recent work in our laboratory that points to endothelin signaling as an upstream mediator of WNT signaling, promoting bone matrix synthesis and mineralization. It concludes with a statement of some remaining gaps in knowledge and proposals for future research., (Published by Elsevier Inc.)

Balancing economic, ecological, and social values has long been a challenge in the forests of the Pacific Northwest, where conflict over timber harvest and old-growth habitat on public lands has been contentious for the past several decades. The Northwest Forest Plan, adopted two decades ago to guide management on federal lands, is currently being revised as the region searches for a balance between sustainable timber yields and habitat for sensitive species. In addition, climate change imposes a high degree of uncertainty on future forest productivity, sustainability of timber harvest, wildfire risk, and species habitat. We evaluated the long-term, landscape-scale trade-offs among carbon (C) storage, timber yield, and old forest habitat given projected climate change and shifts in forest management policy across 2.1 million hectares of forests in the Oregon Coast Range. Projections highlight the divergence between private and public lands under business-as-usual forest management, where private industrial forests are heavily harvested and many public (especially federal) lands increase C and old forest over time but provide little timber. Three alternative management scenarios altering the amount and type of timber harvest show widely varying levels of ecosystem C and old-forest habitat. On federal lands, ecological forestry practices also allowed a simultaneous increase in old forest and natural early-seral habitat. The ecosystem C implications of shifts away from current practices were large, with current practices retaining up to 105 Tg more C than the alternative scenarios by the end of the century. Our results suggest climate change is likely to increase forest productivity by 30-41% and total ecosystem C storage by 11-15% over the next century as warmer winter temperatures allow greater forest productivity in cooler months. These gains in C storage are unlikely to be offset by wildfire under climate change, due to the legacy of management and effective fire suppression. Our scenarios of future conditions can inform policy makers, land managers, and the public about the potential effects of land management alternatives, climate change, and the trade-offs that are inherent to management and policy in the region., (© 2016 by the Ecological Society of America.)

Pathogenic mycobacteria trigger formation of organized granulomas. As granulomas mature, they induce angiogenesis and vascular permeability. Here, in a striking parallel to tumor pro-angiogenic signaling, we identify angiopoietin-2 (ANG-2) induction as an important component of vascular dysfunction during mycobacterial infection. Mycobacterial infection in humans and zebrafish results in robust induction of ANG-2 expression from macrophages and stromal cells. Using a small-molecule inhibitor closely related to one currently in clinical trials, we link ANG-2/TIE2 signaling to vascular permeability during mycobacterial infection. Targeting granuloma-induced vascular permeability via vascular endothelial-protein tyrosine phosphatase inhibition limits mycobacterial growth, suggesting a new strategy for host-directed therapies against tuberculosis., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Previously, our laboratory identified ECE-1 , encoding endothelin-converting enzyme-1 (ECE-1), as a positional candidate for a pleiotropic quantitative trait locus affecting femoral size, shape, and biomechanical performance. We hypothesized that endothelin-1 (ET-1) signaling promotes osteogenesis. Exposure of immortalized mouse osteoblast (TMOb) cells to big ET-1 increased mineralization. Following big ET-1 treatment, we measured the secretion of insulin-like-growth factor-1 (IGF1), dickkopf-homolog-1 protein 1 (DKK1), and sclerostin (SOST). In each case, big ET-1 signaling changed secretion in a manner that favored increased osteogenic activity. Treatment with ECE-1, endothelin receptor A (EDNRA), or WNT receptor antagonists inhibited the big ET-1-mediated increase in mineralization. In the presence of big ET-1, message levels of Runx2 , Igf1 , Dkk1, and Sost are uncoupled from protein production, suggesting posttranscriptional regulation. To evaluate the role of big ET-1 in normal bone physiology, we inhibited EDNRA signaling during mineralization in the absence of exogenous ET-1. EDNRA blockade reduced mineralization, decreased IGF1, and increased DKK1 and SOST secretion, responses opposite to those induced by exogenous big ET-1. Pharmacological and siRNA knockdown to inhibit ECE-1 reduced mineralization and IGF1 secretion with decreasing DKK1 and decreasing or stable SOST secretion, suggesting a further, unknown role of ECE-1 in osteoblast maturation. Previously we identified miR 126-3p as a potential ET-1-responsive regulator of SOST in murine cells. Overexpression of miR126-3p increased mineralization in TMOb cells and decreased SOST secretion. Osteoblasts express the ET-1 signaling pathway and ET-1 signaling is necessary for normal osteoblast differentiation and mineralization, acting through regulation of miRs that target osteogenic molecules., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: Observational research has shown that delayed presentation is associated with perforation in appendicitis. Many factors that affect the ability to present for evaluation are influenced by time of day (eg, child care, work, transportation, and office hours of primary care settings). Our objective was to evaluate for an association between care processes or clinical outcomes and presentation time of day., Methods: The study evaluated a prospective cohort of 7,548 adults undergoing appendectomy at 56 hospitals across Washington State. Relative to presentation time, patient characteristics, time to operation, imaging use, negative appendectomy, and perforation were compared using univariate and multivariate methodologies., Results: Overall, 63% of patients presented between noon and midnight. More men presented in the morning; however, race, insurance status, comorbid conditions, and white blood cell count did not differ by presentation time. Daytime presenters (6 am to 6 pm) were less likely to undergo imaging (94% vs 98%, P < .05) and had a nearly 50% decrease in median preoperative time (6.0 h vs 8.7 h, P < .001). Perforation significantly differed by time-of-day. Patients who presented during the workday (9 am to 3 pm) had a 30% increase in odds of perforation compared with patients presenting in the early morning/late night (adjusted odds ratio 1.29, 95% confidence interval, 1.05-1.59). Negative appendectomy did not vary by time-of-day., Conclusion: Most patients with appendicitis presented in the afternoon/evening. Socioeconomic characteristics did not vary with time-of-presentation. Patients who presented during the workday more often had perforated appendicitis compared with those who presented early morning or late night. Processes of care differed (both time-to-operation and imaging use). Time-of-day is associated with patient outcomes, process of care, and decisions to present for evaluation; this association has implications for the planning of the surgical workforce and efforts directed at quality improvement., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The intergenerational impact of engineered nanomaterials in plants is a key knowledge gap in the literature. A soil microcosm study was performed to assess the effects of multi-generational exposure of wheat ( Triticum aestivum L.) to cerium oxide nanoparticles (CeO 2 -NPs). Seeds from plants that were exposed to 0, 125, and 500 mg CeO 2 -NPs/kg soil (Ce-0, Ce-125 or Ce-500, respectively) in first generation (S1) were cultivated in factorial combinations of Ce-0, Ce-125 or Ce-500 to produce second generation (S2) plants. The factorial combinations for first/second generation treatments in Ce-125 were S1-Ce-0/S2-Ce-0, S1-Ce-0/S2-Ce-125, S1-Ce-125/S2-Ce-0 and S1-Ce-125/S2-Ce-125, and in Ce-500 were S1-Ce-0/S2-Ce-0, S1-Ce-0/S2-Ce-500, S1-Ce-500/S2-Ce-0 and S1-Ce-500/S2-Ce-500. Agronomic, elemental, isotopic, and synchrotron X-ray fluorescence (XRF) and X-ray absorption near-edge spectroscopy (XANES) data were collected on second generation plants. Results showed that plants treated during the first generation only with either Ce-125 or Ce-500 (e.g. S1-Ce-125/S2-Ce-0 or S1-Ce-500/S2-Ce-0) had reduced accumulation of Ce (61 or 50%), Fe (49 or 58%) and Mn (34 or 41%) in roots, and δ 15 N (11 or 8%) in grains compared to the plants not treated in both generations (i.e. S1-Ce-0/S2-Ce-0). Plants treated in both generations with Ce-125 (i.e. S1-Ce-125/S2-Ce-125) produced grains that had lower Mn, Ca, K, Mg and P relative to plants treated in the second generation only (i.e. S1-Ce-0/S2-Ce-125). In addition, synchrotron XRF elemental chemistry maps of soil/plant thin-sections revealed limited transformation of CeO 2 -NPs with no evidence of plant uptake or accumulation. The findings demonstrated that first generation exposure of wheat to CeO 2 -NPs affects the physiology and nutrient profile of the second generation plants. However, the lack of concentration-dependent responses indicate that complex physiological processes are involved which alter uptake and metabolism of CeO 2 -NPs in wheat.

Purpose of Review: The clinical benefits of vitamin D therapy have received substantial attention over the past decade. Recently, several trials looked to clarify the optimal vitamin D dose or serum level needed to promote human health. The purpose of this review is to highlight selected studies published since January 2015., Recent Findings: Several recent trials challenge whether serum vitamin D levels at least 30 ng/ml promote human health. In postmenopausal women with 25-hydroxyvitamin D [25(OH)D] levels 21 ± 3 ng/ml, high-dose vitamin D for 1 year increased calcium absorption by 1%, without changes in bone mineral density, physical function, or falls when compared with low-dose vitamin D and placebo. High-dose vitamin D increased risk of falling in 200 adults 78 ± 5 years old with baseline 25(OH)D levels of ∼19 ± 9 ng/ml. High-dose vitamin D in adults increased the number and duration of upper respiratory tract infections compared with placebo. Asthma patients achieving 25(OH)D levels more than 30 ng/ml during a trial experienced more respiratory infections than those not achieving such levels., Summary: Recent studies are congruent with the Institute of Medicine's conclusion that humans are vitamin D replete when their serum 25(OH)D levels are at least 20 ng/ml. Higher levels seem to promote falls and respiratory infections.

Mycobacterium tuberculosis infection in humans triggers formation of granulomas, which are tightly organized immune cell aggregates that are the central structure of tuberculosis. Infected and uninfected macrophages interdigitate, assuming an altered, flattened appearance. Although pathologists have described these changes for over a century, the molecular and cellular programs underlying this transition are unclear. Here, using the zebrafish-Mycobacterium marinum model, we found that mycobacterial granuloma formation is accompanied by macrophage induction of canonical epithelial molecules and structures. We identified fundamental macrophage reprogramming events that parallel E-cadherin-dependent mesenchymal-epithelial transitions. Macrophage-specific disruption of E-cadherin function resulted in disordered granuloma formation, enhanced immune cell access, decreased bacterial burden, and increased host survival, suggesting that the granuloma can also serve a bacteria-protective role. Granuloma macrophages in humans with tuberculosis were similarly transformed. Thus, during mycobacterial infection, granuloma macrophages are broadly reprogrammed by epithelial modules, and this reprogramming alters the trajectory of infection and the associated immune response., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Although echinocandins are generally well tolerated, there is little information on the frequency with which renal and hepatic adverse effects occur during use of micafungin or other parenteral antifungal (PAF) agents in clinical practice., Methods: MYCOS is a multicentre cohort study of adult and paediatric patients who received micafungin or other PAFs between 2005 and 2012 at seven tertiary care hospitals from six centres in the USA. PAF cohort controls were selected through propensity score (PS) matching to micafungin recipients using clinical characteristics, other treatments, procedures and hospital service where PAF treatment was initiated. Analysis was restricted to patients without chronic liver and kidney conditions at the time of cohort entry. Treatment-emergent hepatic and renal injury was documented by changes in liver enzymes or estimated glomerular filtration rate through 30 days following completion of PAF treatment. Comparisons were quantified using the HR from a proportional hazards analysis., Results: There were 2970 micafungin recipients PS matched to 6726 recipients of comparator PAFs. Balance was achieved in all baseline covariates between treatment groups. There were similar rates of hepatic injury (micafungin, 13 events per 100 patients and other PAF, 12 per 100; HR = 0.99; 95% CI 0.86-1.14) and lower rates of renal injury (micafungin, 63 events per 100 patients and other PAF, 65 per 100; HR = 0.93; 95% CI 0.87-0.99) for micafungin recipients versus PAF comparators., Conclusion: For a wide spectrum of underlying conditions, we observed no increase in liver injury by micafungin and possibly a reduced risk of renal dysfunction in comparison with other PAF medications., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Approximately 660 deaths occur annually in the United States associated with excess natural heat. A record heat wave in Oklahoma during 2011 generated increased interest concerning heat-related mortality among public health preparedness partners. We aimed to improve surveillance for heat-related mortality and better characterize heat-related deaths in Oklahoma during 1990-2011, and to enhance public health messaging during future heat emergencies., Methods: Heat-related deaths were identified by querying vital statistics (VS) and medical examiner (ME) data during 1990-2011. Case inclusion criteria were developed by using heat-related International Classification of Diseases codes, cause-of-death nomenclature, and ME investigation narrative. We calculated sensitivity and predictive value positive (PVP) for heat-related mortality surveillance by using VS and ME data and performed a descriptive analysis., Results: During the study period, 364 confirmed and probable heat-related deaths were identified when utilizing both data sets. ME reports had 87% sensitivity and 74% PVP; VS reports had 80% sensitivity and 52% PVP. Compared to Oklahoma's general population, decedents were disproportionately male (67% vs. 49%), aged ≥65 years (46% vs. 14%), and unmarried (78% vs. 47%). Higher rates of heat-related mortality were observed among Blacks. Of 95 decedents with available information, 91 (96%) did not use air conditioning., Conclusions: Linking ME and VS data sources together and using narrative description for case classification allows for improved case ascertainment and surveillance data quality. Males, Blacks, persons aged ≥65 years, unmarried persons, and those without air conditioning carry a disproportionate burden of the heat-related deaths in Oklahoma., (Published by Elsevier Inc.)

Ten agronomic plant species were exposed to different concentrations of nano-titanium dioxide (nTiO2 ) or nano-cerium oxide (nCeO2 ) (0 μg/mL, 250 μg/mL, 500 μg/mL, and 1000 μg/mL) to examine potential effects on germination and early seedling development. The authors modified a standard test protocol developed for soluble chemicals (OPPTS 850.4200) to determine if such an approach might be useful for screening engineered nanomaterials (ENMs) and whether there were differences in response across a range of commercially important plant species to 2 common metal oxide ENMs. Eight of 10 species responded to nTiO2 , and 5 species responded to nCeO2 . Overall, it appeared that early root growth may be a more sensitive indicator of potential effects from ENM exposure than germination. The observed effects did not always relate to the exposure concentration, indicating that mass-based concentration may not fully explain the developmental effects of these 2 ENMs. The results suggest that nTiO2 and nCeO2 have different effects on early plant growth of agronomic species, with unknown effects at later stages of the life cycle. In addition, standard germination tests, which are commonly used for toxicity screening of new materials, may not detect the subtle but potentially more important changes associated with early growth and development in terrestrial plants. Environ Toxicol Chem 2016;35:2223-2229. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America., (Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.)

Optimization of the potency and pharmacokinetic profile of 2,3,4-trisubstituted quinoline, 4, led to the discovery of two potent, selective, and orally bioavailable PI3Kδ inhibitors, 6a (AM-0687) and 7 (AM-1430). On the basis of their improved profile, these analogs were selected for in vivo pharmacodynamic (PD) and efficacy experiments in animal models of inflammation. The in vivo PD studies, which were carried out in a mouse pAKT inhibition animal model, confirmed the observed potency of 6a and 7 in biochemical and cellular assays. Efficacy experiments in a keyhole limpet hemocyanin model in rats demonstrated that administration of either 6a or 7 resulted in a strong dose-dependent reduction of IgG and IgM specific antibodies. The excellent in vitro and in vivo profiles of these analogs make them suitable for further development.

Systemic biologic therapy has become commonplace for the treatment of a variety of inflammatory dermatologic conditions, particularly psoriasis. Screening for latent tuberculosis infection (LTBI) is recommended prior to initiation of systemic biologic agents, and an interferon gamma release assays (IGRA) is often used as the screening modality. Annual screening for LTBI is also recommended for patients while on systemic biologic therapy, but the literature does not clearly support how often screening should be performed. In addition, serial testing with IGRAs, particularly among low-risk populations without any new tuberculosis (TB) exposures, has proven to be unreliable with frequent reversions and conversions. We propose that in low-incidence TB regions, repeat LTBI screening should only be considered for patients on systemic biologic therapy if any new TB exposures occurred since initial LTBI screening was performed prior to starting biologic therapy. This strategy aims to reduce false-positive LTBI testing that can expose patients to hazardous antibiotics and result in the unnecessary interruption of systemic biologic therapy.

Light nuclei were created during big-bang nucleosynthesis (BBN). Standard BBN theory, using rates inferred from accelerator-beam data, cannot explain high levels of ^{6}Li in low-metallicity stars. Using high-energy-density plasmas we measure the T(^{3}He,γ)^{6}Li reaction rate, a candidate for anomalously high ^{6}Li production; we find that the rate is too low to explain the observations, and different than values used in common BBN models. This is the first data directly relevant to BBN, and also the first use of laboratory plasmas, at comparable conditions to astrophysical systems, to address a problem in nuclear astrophysics.

Premise of the Study: We used moderately low-coverage (17×) whole-genome sequencing of Artocarpus camansi (Moraceae) to develop genomic resources for Artocarpus and Moraceae., Methods and Results: A de novo assembly of Illumina short reads (251,378,536 pairs, 2 × 100 bp) accounted for 93% of the predicted genome size. Predicted coding regions were used in a three-way orthology search with published genomes of Morus notabilis and Cannabis sativa. Phylogenetic markers for Moraceae were developed from 333 inferred single-copy exons. Ninety-eight putative MADS-box genes were identified. Analysis of all predicted coding regions resulted in preliminary annotation of 49,089 genes. An analysis of synonymous substitutions for pairs of orthologs (Ks analysis) in M. notabilis and A. camansi strongly suggested a lineage-specific whole-genome duplication in Artocarpus., Conclusions: This study substantially increases the genomic resources available for Artocarpus and Moraceae and demonstrates the value of low-coverage de novo assemblies for nonmodel organisms with moderately large genomes.

Premise of the Study: Using sequence data generated via target enrichment for phylogenetics requires reassembly of high-throughput sequence reads into loci, presenting a number of bioinformatics challenges. We developed HybPiper as a user-friendly platform for assembly of gene regions, extraction of exon and intron sequences, and identification of paralogous gene copies. We test HybPiper using baits designed to target 333 phylogenetic markers and 125 genes of functional significance in Artocarpus (Moraceae)., Methods and Results: HybPiper implements parallel execution of sequence assembly in three phases: read mapping, contig assembly, and target sequence extraction. The pipeline was able to recover nearly complete gene sequences for all genes in 22 species of Artocarpus. HybPiper also recovered more than 500 bp of nontargeted intron sequence in over half of the phylogenetic markers and identified paralogous gene copies in Artocarpus., Conclusions: HybPiper was designed for Linux and Mac OS X and is freely available at https://github.com/mossmatters/HybPiper.

The goal of this research was to investigate whether there has been a whole-genome duplication (WGD) in the ancestry of Sphagnum (peatmoss) or the class Sphagnopsida, and to determine if the timing of any such duplication(s) and patterns of paralog retention could help explain the rapid radiation and current ecological dominance of peatmosses. RNA sequencing (RNA-seq) data were generated for nine taxa in Sphagnopsida (Bryophyta). Analyses of frequency plots for synonymous substitutions per synonymous site (Ks ) between paralogous gene pairs and reconciliation of 578 gene trees were conducted to assess evidence of large-scale or genome-wide duplication events in each transcriptome. Both Ks frequency plots and gene tree-based analyses indicate multiple duplication events in the history of the Sphagnopsida. The most recent WGD event predates divergence of Sphagnum from the two other genera of Sphagnopsida. Duplicate retention is highly variable across species, which might be best explained by local adaptation. Our analyses indicate that the last WGD could have been an important factor underlying the diversification of peatmosses and facilitated their rise to ecological dominance in peatlands. The timing of the duplication events and their significance in the evolutionary history of peat mosses are discussed., (© 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.)