Network Analysis of Publicly Available RNA-seq Provides Insights into the Molecular Mechanisms of Plant Defense against Multiple Fungal Pathogens in Arabidopsis thaliana.

Fungal pathogens can have devastating effects on global crop production, leading to annual economic losses ranging from 10% to 23%. In light of climate change-related challenges, researchers anticipate an increase in fungal infections as a result of shifting environmental conditions. However, plants have developed intricate molecular mechanisms for effective defense against fungal attacks. Understanding these mechanisms is essential to the development of new strategies for protecting crops from multiple fungi threats. Public omics databases provide valuable resources for research on plant-pathogen interactions; however, integrating data from different studies can be challenging due to experimental variation. In this study, we aimed to identify the core genes that defend against the pathogenic fungi Colletotrichum higginsianum and Botrytis cinerea in Arabidopsis thaliana. Using a custom framework to control batch effects and construct Gene Co-expression Networks in publicly available RNA-seq dataset from infected A. thaliana plants, we successfully identified a gene module that was responsive to both pathogens. We also performed gene annotation to reveal the roles of previously unknown protein-coding genes in plant defenses against fungal infections. This research demonstrates the potential of publicly available RNA-seq data for identifying the core genes involved in defending against multiple fungal pathogens.

Fate of concomitant tricuspid regurgitation in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Owing to a lack of supportive data, tricuspid regurgitation (TR) is usually not addressed in patients undergoing coronary artery bypass grafting (CABG). Here we evaluated changes in TR degrees over time and its impact on survival in patients undergoing CABG. METHODS: We reviewed the data of 9726 patients who underwent isolated CABG between January 2000 and January 2021. According to preoperative TR severity, patients were stratified into nonsignificant (none to trivial, mild) and significant (moderate to severe) TR groups. We excluded patients who had undergone previous tricuspid valve surgery, pacemaker placement, and concomitant valve or ablative surgery. Propensity score matching and Cox proportional hazards models were used to identify associations between TR grade and the primary outcome of all-cause mortality. The secondary outcome was change in TR severity on the last echocardiogram. RESULTS: After propensity score matching, 380 patients in each group were identified. At baseline, 359 patients had moderate TR (94.5%) and 21 (5.5%) had severe TR. On the last follow-up echocardiogram, TR had improved in 40.5% of the patients in the significant TR group. Kaplan-Meier survival curves showed significantly lower survival in patients with significant preoperative TR compared to those with nonsignificant TR (P < .001). After adjusting for other confounders, survival was no worse in the patients with significant TR group (hazard ratio, 1.05; 95% confidence interval, 0.80-1.38; P = .70). CONCLUSIONS: Significant preoperative TR improved in 40.5% of patients after isolated CABG. After adjusting for other factors, significant TR did not affect long-term survival.

Impact of travel burden on the treatment of stage I and II breast cancer: A National Cancer Database analysis.

BACKGROUND: Although historic studies of state registries have demonstrated decreased radiation therapy use for patients with breast cancer living further away from radiation facilities, the association between travel distance and breast cancer treatment in a modern national cohort remains unknown. METHODS: Female patients with estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative pathologic stages I to II breast cancer were identified from the National Cancer Database (2018-2020) and dichotomized by distance ≤20 miles or >20 miles (75th percentile) from the treatment facility. The association between travel distance and type of surgery and treatment administered was analyzed by univariate and multivariate logistic regression and after 1:1 propensity matching. RESULTS: Of the 293,318 patients identified for inclusion, the median age was 63 years, and most patients (n = 190,567, 65%) lived ≤20 miles of the treatment facility. Patients with a travel burden >20 miles were more likely to receive a mastectomy (≤20 miles 30.4% vs >20 miles 34.0%, P < .001; odds ratio 1.14, P = .016), and less likely to receive radiation (≤20 miles 63.3% vs >20% miles 60.1%, P < .001; odds ratio 0.81, P < .001). These findings persisted after propensity score matching (n = 33,544 per cohort), with patients living further being more likely to undergo a mastectomy (≤20 miles 30.3% vs >20 miles 35.3%, P < .001) and less likely to receive radiation (≤ 20 miles 65.4% vs. >20 miles 58.5%, P < .001). CONCLUSION: Patients with hormone receptor-positive stage I to II breast cancer with a larger travel burden are more likely to receive a mastectomy and less likely to undergo radiation therapy to treat their disease.

Gene expression in African Americans, Puerto Ricans and Mexican Americans reveals ancestry-specific patterns of genetic architecture.

We explored ancestry-related differences in the genetic architecture of whole-blood gene expression using whole-genome and RNA sequencing data from 2,733 African Americans, Puerto Ricans and Mexican Americans. We found that heritability of gene expression significantly increased with greater proportions of African genetic ancestry and decreased with higher proportions of Indigenous American ancestry, reflecting the relationship between heterozygosity and genetic variance. Among heritable protein-coding genes, the prevalence of ancestry-specific expression quantitative trait loci (anc-eQTLs) was 30% in African ancestry and 8% for Indigenous American ancestry segments. Most anc-eQTLs (89%) were driven by population differences in allele frequency. Transcriptome-wide association analyses of multi-ancestry summary statistics for 28 traits identified 79% more gene-trait associations using transcriptome prediction models trained in our admixed population than models trained using data from the Genotype-Tissue Expression project. Our study highlights the importance of measuring gene expression across large and ancestrally diverse populations for enabling new discoveries and reducing disparities.

Etiologies of Acute Undifferentiated Febrile Illnesses in and near Iquitos from 1993 to 1999 in the Amazon River Basin of Peru.

The objective of this study was to determine the etiology of febrile illnesses among patients from October 1, 1993 through September 30, 1999, in the urban community of Iquitos in the Amazon River Basin of Peru. Epidemiological and clinical data as well as blood samples were obtained from consenting patients at hospitals, health clinics and private residences. Samples were tested for arboviruses in cell cultures and for IgM and IgG antibodies by ELISA. Blood smears were examined for malaria, and sera were tested for antibodies to Leptospira spp. by ELISA and microscopic agglutination. Among 6,607 febrile patients studied, dengue viruses caused 14.6% of the cases, and Venezuelan equine encephalitis virus caused 2.5%, Oropouche virus 1.0%, Mayaro virus 0.4%, and other arboviruses caused 0.2% of the cases. Also, 22.9% of 4,844 patients tested were positive for malaria, and of 400 samples tested, 9% had evidence of acute leptospirosis. Although the study was not designed to assess the importance of these pathogens as a cause of human morbidity in the total population, these results indicate that arboviruses, leptospirosis, and malaria were the cause of approximately 50% of the febrile cases. Although the arboviruses that were diagnosed can produce asymptomatic infections, our findings increased the overall understanding of the relative health burden of these infections, as well as baseline knowledge needed for designing and implementing further studies to better assess the health impact and threat of these pathogens in the Amazon Basin of Peru.

Clinical Performance and Surgeon Acceptability of a New Dual Mode Phacoemulsification System.

Purpose: The purpose of this first in-human study was to evaluate the overall clinical performance of the VERITAS™ Vision System in patients scheduled to undergo cataract extraction and to confirm overall surgeon acceptability. Patients and methods: This prospective, open-label multinational study included adults with cataracts scheduled for planned cataract extraction and posterior chamber IOL implantation. Standard small-incision phacoemulsification cataract surgery with the VERITAS Vision System was conducted. Surgeons completed a questionnaire regarding their clinical experience with the VERITAS Vision System for each patient following surgery and 1-day postoperative. Corneal clarity and adverse events (AEs) were assessed. Surgeon acceptability was scored on a 5-point scale, with acceptability considered favorable for scores of 4 and 5. Results: A total of 115 eyes (79 patients) were treated. The El Salvador site treated 41 patients (58 eyes), and the US site treated 38 patients (57 eyes). Overall, surgeons were satisfied with the clinical performance regardless of the cataract grade. The satisfaction with anterior chamber stability, post-occlusion surge, followability, holdability, cutting efficiency, usability, and overall satisfaction with the VERITAS Vision System was clinically favorable in ≥99% of cases. Overall satisfaction with the swivel handpiece, foot pedal, and enhanced ergonomics were clinically favorable in ≥97% of cases regardless of the cataract grade. Satisfaction with corneal clarity at same-day postoperative and 1-day postoperative, and 1-day overall clinical results of surgery with the VERITAS Vision System were clinically favorable in ≥94% of cases regardless of cataract grade. Conclusion: The new dual-mode phacoemulsification system with dual-durometer tubing, gas forced infusion, new swivel handpiece, and ergonomics improvements resulted in a high rate of user satisfaction with clinical performance and ergonomics. The VERITAS Vision System is safe and effective when used as indicated.

The potential epidemiologic, clinical, and economic impact of requiring schools to offer Physical Education (PE) classes in Mexico City.

BACKGROUND: Many schools have been cutting physical education (PE) classes due to budget constraints, which raises the question of whether policymakers should require schools to offer PE classes. Evidence suggests that PE classes can help address rising physical inactivity and obesity prevalence. However, it would be helpful to determine if requiring PE is cost-effective. METHODS: We developed an agent-based model of youth in Mexico City and the impact of all schools offering PE classes on changes in weight, weight-associated health conditions and the corresponding direct and indirect costs over their lifetime. RESULTS: If schools offer PE without meeting guidelines and instead followed currently observed class length and time active during class, overweight and obesity prevalence decreased by 1.3% (95% CI: 1.0%-1.6%) and was cost-effective from the third-party payer and societal perspectives ($5,058 per disability-adjusted life year [DALY] averted and $5,786/DALY averted, respectively, assuming PE cost $50.3 million). When all schools offered PE classes meeting international guidelines for PE classes, overweight and obesity prevalence decreased by 3.9% (95% CI: 3.7%-4.3%) in the cohort at the end of five years compared to no PE. Long-term, this averted 3,183 and 1,081 obesity-related health conditions and deaths, respectively and averted ≥$31.5 million in direct medical costs and ≥$39.7 million in societal costs, assuming PE classes cost ≤$50.3 million over the five-year period. PE classes could cost up to $185.5 million and $89.9 million over the course of five years and still remain cost-effective and cost saving respectively, from the societal perspective. CONCLUSION: Requiring PE in all schools could be cost-effective when PE class costs, on average, up to $10,340 per school annually. Further, the amount of time students are active during class is a driver of PE classes' value (e.g., it is cost saving when PE classes meet international guidelines) suggesting the need for specific recommendations.

Evidence of floral rewards in Brasiliorchis supports the convergent evolution of food-hairs in Maxillariinae.

PREMISE: Angiosperms distributed over a large geographical area may display considerable phenotypic variation that can be recognized at morphological and micromorphological levels. Here, we investigate the pollination biology and the presence of floral rewards in Brazilian populations of the widely distributed orchid, Brasiliorchis picta. Based on the new data presented here this study investigates the evolution of floral rewards in Maxillariinae, and tests for the occurrence of convergent evolution of food-hairs in this subtribe. METHODS: Micromorphological and histochemical analyses of the labellar tissues were conducted, together with chemical analysis of fragrance and experiments involving the use of chemical baits. The evolution of floral rewards in Maxillariinae were addressed. RESULTS: Microscopy revealed that B. picta offers food-hairs as a reward. Fragrance is produced by abaxially located labellar epidermal papillae. The main compound present in our samples (2-phenylethanol) also occurs in the aggregation pheromone produced by the mandible glands of pollinators, Meliponini bees. Our analyses indicate a high diversity of flower rewards and pollinators displayed by members of Maxillariinae, and support that edible trichomes evolved independently five times in the subtribe. CONCLUSIONS: The high diversity of floral rewards and pollinators displayed by members of Maxillariinae suggests that different pollinator pressures are involved in the evolution of this neotropical subtribe. In addition, the offering of food-hairs, which are generally infrequently encountered in Orchidaceae, arose by convergent evolution in Maxillariinae.

Phenotypic and Genotypic Characterization of Phytophthora infestans Isolates Associated with Tomato and Potato Crops in Colombia.

Late blight disease, caused by the plant pathogen Phytophthora infestans, is one of the major threats for tomato and potato crops. Monitoring the populations of P. infestans is important to determine if there are changes in the sensitivity to fungicides and host preference. In this study, microsatellite markers and mitochondrial haplotypes were used to assess the genotype of isolates of P. infestans collected from tomato and potato plants in Colombia. Furthermore, sensitivity to the three fungicides cymoxanil (penetrant fungicide), mefenoxam, and fluopicolide (systemic fungicides), and tomato-potato host preference, were evaluated. Mitochondrial haplotyping showed that isolates collected on tomato were from the genetic groups Ia and Ib, while isolates collected on potatoes belonged to group IIa. Microsatellite analyses showed that isolates from tomato form two groups, including the Ib mitochondrial haplotype (which is genetically close to the US-1 clonal lineage) and the Ia haplotype (related to the EC-3 lineage), whereas Colombian isolates from potato formed a separate group. Furthermore, differences in sensitivity to fungicides were observed. Eighty-one percent of the isolates tested were resistant to mefenoxam with an EC50 >10 µg ml-1. Forty-two percent of the isolates showed an intermediate resistance to cymoxanil. The EC50 values ranged between 1 and 10 µg ml-1. For fluopicolide, 90% of the isolates were sensitive, with EC50 <1 µg ml-1. Host preference assays showed that potato isolates infected both host species. Thus, isolates that infect potatoes may pose a risk for tomato crops nearby.

Altered fire regimes modify lizard communities in globally endangered Araucaria forests of the southern Andes.

Wildfire regimes are being altered in ecosystems worldwide. The density of reptiles responds to fires and changes to habitat structure. Some of the most vulnerable ecosystems to human-increased fire frequency are old-growth Araucaria araucana forests of the southern Andes. We investigated the effects of wildfires on the density and richness of a lizard community in these ecosystems, considering fire frequency and elapsed time since last fire. During the 2018/2019 southern summer season, we conducted 71 distance sampling transects to detect lizards in Araucaria forests of Chile in four fire "treatments": (1) unburned control, (2) long-term recovery, (3) short-term recovery, and (4) burned twice. We detected 713 lizards from 7 species. We found that the density and richness of lizards are impacted by wildfire frequency and time of recovery, mediated by the modification of habitat structure. The lizard community varied from a dominant arboreal species (L. pictus) in unburned and long-recovered stands, to a combination of ground-dwelling species (L. lemniscatus and L. araucaniensis) in areas affected by two fires. Araucaria forests provided key habitat features to forest reptiles after fires, but the persistence of these old-growth forests and associated biodiversity may be threatened given the increase in fire frequency.

Nectar secretion in a dry habitat: structure of the nectary in two endangered Mexican species of Barkeria (Orchidaceae).

Barkeria scandens and B. whartoniana are endangered, endemic taxa from Mexico. They are epiphytes adapted to dry habitats. Since these plants are xerophytic, their flowers were investigated for structural adaptations to nectar secretion. The flowers of both species are structurally similar, and contrary to most claims for the genus, have functional floral nectaries comprising a nectary chamber and a narrow tubular cuniculus. Nectar is present in both these structures, and contains sugars and lipid-like compounds. The nectary tissue is composed of a single-layered epidermis overlying 1-2 layers of subepidermal secretory parenchyma. The outer tangential wall of the epidermal cells is thick and multi-layered, whereas the cuticle, which often shows blistering, is lamellate and possesses micro-channels. Lipid-like material occurs both between the microfibrils of the cell wall and in the micro-channels. Robust secretory tissue, thick cell walls, and lipid-like nectar components limit nectar evaporation. Moreover, the rigidity of the nectary potentially makes it possible for red-flowered B. scandens to switch from entomophily to ornithophily.

In-silico study of the cardiac arrhythmogenic potential of biomaterial injection therapy.

Biomaterial injection is a novel therapy to treat ischemic heart failure (HF) that has shown to reduce remodeling and restore cardiac function in recent preclinical studies. While the effect of biomaterial injection in reducing mechanical wall stress has been recently demonstrated, the influence of biomaterials on the electrical behavior of treated hearts has not been elucidated. In this work, we developed computational models of swine hearts to study the electrophysiological vulnerability associated with biomaterial injection therapy. The propagation of action potentials on realistic biventricular geometries was simulated by numerically solving the monodomain electrophysiology equations on anatomically-detailed models of normal, HF untreated, and HF treated hearts. Heart geometries were constructed from high-resolution magnetic resonance images (MRI) where the healthy, peri-infarcted, infarcted and gel regions were identified, and the orientation of cardiac fibers was informed from diffusion-tensor MRI. Regional restitution properties in each case were evaluated by constructing a probability density function of the action potential duration (APD) at different cycle lengths. A comparative analysis of the ventricular fibrillation (VF) dynamics for every heart was carried out by measuring the number of filaments formed after wave braking. Our results suggest that biomaterial injection therapy does not affect the regional dispersion of repolarization when comparing untreated and treated failing hearts. Further, we found that the treated failing heart is more prone to sustain VF than the normal heart, and is at least as susceptible to sustained VF as the untreated failing heart. Moreover, we show that the main features of VF dynamics in a treated failing heart are not affected by the level of electrical conductivity of the biogel injectates. This work represents a novel proof-of-concept study demonstrating the feasibility of computer simulations of the heart in understanding the arrhythmic behavior in novel therapies for HF.

Corrosion Concerns? Trends in Metal-on-Polyethylene Total Hip Arthroplasty Revision Rates and Comparisons Against Ceramic-on-Polyethylene up to 10 Years of Follow-Up.

BACKGROUND: We compared the revision risk between metal-on-polyethylene (MOP) and ceramic-on-polyethylene (COP) total hip arthroplasty patients and evaluated temporal changes in short-term revision risks for MOP patients. METHODS: Primary MOP (n = 9480) and COP (n = 3620) total hip arthroplasties were evaluated from the Medicare data set (October 2005 to December 2015) for revision risk, with up to 10 years of follow-up using multivariate analysis. Temporal change in the short-term revision risk for MOP was evaluated (log-rank and Wilcoxon tests). RESULTS: Revision incidence was 3.8% for COP and 4.3% for MOP. MOP short-term revision risk did not change over time (P ≥ .844 at 1 year and .627 at 2 years). Dislocation was the most common reason for revision (MOP: 23.5%; COP: 24.8%). Overall adjusted revision risks were not different between MOP and COP up to 10 years of follow-up (P ≥ .181). CONCLUSIONS: Concerns with corrosion for metal heads do not appear to result in significantly elevated revision risk for MOP at up to 10 years. Corrosion does not appear as a primary reason for revision compared to other mechanisms.

Chronic subclinical mastitis reduces milk and components yield at the cow level.

We evaluated the effects of chronic subclinical mastitis (CSM) caused by different types of pathogens on milk yield and milk components at the cow level. A total of 388 Holstein cows had milk yield measured and were milk sampled three times at intervals of two weeks for determination of SCC and milk composition, and microbiological culture was performed. Cows were considered healthy if all three samples of SCC were ≤200 000 cells/ml and were culture-negative at the third milk sampling. Cows with one result of SCC > 200 000 cells/ml were considered to suffer non-chronic subclinical mastitis whereas cows with at least 2 out of 3 results of SCC > 200 000 cells/ml had CSM. These latter cows were further sorted according to culture results into chronic negative-culture or chronic positive-culture. This resulted in four udder health statuses: healthy, non-chronic, chronicNC or chronicPC. The milk and components yields were evaluated according to the udder health status and by pathogen using a linear mixed effects model. A total of 134 out of 388 cows (34.5%) were chronicPC, 57 cows (14.7%) were chronicNC, 78 cows (20.1%) were non-chronic and 119 cows (30.7%) were considered healthy, which resulted in a grand total of 1164 cow records included in the statistical model. The healthy cows produced more milk than each of the other groups (+2.1 to +5.7 kg/cow/day) and produced higher milk component yields than the chronicPC cows. The healthy cows produced more milk than cows with chronicPC caused by minor (+5.2 kg/cow/day) and major pathogens (+7.1 kg/cow/day) and losses varied from 5.8 to 11.8 kg/cow/day depending on the pathogen causing chronicPC mastitis. Chronic positive-culture cows had a reduction of at least 24.5% of milk yield and 22.4% of total solids yield.

Whole-Genome Sequencing Identifies Novel Functional Loci Associated with Lung Function in Puerto Rican Youth.

Rationale: Puerto Ricans have the highest childhood asthma prevalence in the United States (23.6%); however, the etiology is uncertain.Objectives: In this study, we sought to uncover the genetic architecture of lung function in Puerto Rican youth with and without asthma who were recruited from the island (n = 836).Methods: We used admixture-mapping and whole-genome sequencing data to discover genomic regions associated with lung function. Functional roles of the prioritized candidate SNPs were examined with chromatin immunoprecipitation sequencing, RNA sequencing, and expression quantitative trait loci data.Measurements and Main Results: We discovered a genomic region at 1q32 that was significantly associated with a 0.12-L decrease in the lung volume of exhaled air (95% confidence interval, -0.17 to -0.07; P = 6.62 × 10-8) with each allele of African ancestry. Within this region, two SNPs were expression quantitative trait loci of TMEM9 in nasal airway epithelial cells and MROH3P in esophagus mucosa. The minor alleles of these SNPs were associated with significantly decreased lung function and decreased TMEM9 gene expression. Another admixture-mapping peak was observed on chromosome 5q35.1, indicating that each Native American ancestry allele was associated with a 0.15-L increase in lung function (95% confidence interval, 0.08-0.21; P = 5.03 × 10-6). The region-based association tests identified four suggestive windows that harbored candidate rare variants associated with lung function.Conclusions: We identified common and rare genetic variants that may play a critical role in lung function among Puerto Rican youth. We independently validated an inflammatory pathway that could potentially be used to develop more targeted treatments and interventions for patients with asthma.

Impact of Alcohol Use Disorder Treatment on Clinical Outcomes Among Patients With Cirrhosis.

BACKGROUND AND AIMS: Despite the significant medical and economic consequences of coexisting alcohol use disorder (AUD) in patients with cirrhosis, little is known about AUD treatment patterns and their impact on clinical outcomes in this population. We aimed to characterize the use of and outcomes associated with AUD treatment in patients with cirrhosis. APPROACH AND RESULTS: This retrospective cohort study included Veterans with cirrhosis who received Veterans Health Administration care and had an index diagnosis of AUD between 2011 and 2015. We assessed the baseline factors associated with AUD treatment (pharmacotherapy or behavioral therapy) and clinical outcomes for 180 days following the first AUD diagnosis code within the study time frame. Among 93,612 Veterans with cirrhosis, we identified 35,682 with AUD, after excluding 2,671 who had prior diagnoses of AUD and recent treatment. Over 180 days following the index diagnosis of AUD, 5,088 (14%) received AUD treatment, including 4,461 (12%) who received behavioral therapy alone, 159 (0.4%) who received pharmacotherapy alone, and 468 (1%) who received both behavioral therapy and pharmacotherapy. In adjusted analyses, behavioral and/or pharmacotherapy-based AUD treatment was associated with a significant reduction in incident hepatic decompensation (6.5% vs. 11.6%, adjusted odds ratio [AOR], 0.63; 95% confidence interval [CI], 0.52, 0.76), a nonsignificant decrease in short-term all-cause mortality (2.6% vs. 3.9%, AOR, 0.79; 95% CI, 0.57, 1.08), and a significant decrease in long-term all-cause mortality (51% vs. 58%, AOR, 0.87; 95% CI, 0.80, 0.96). CONCLUSIONS: Most Veterans with cirrhosis and coexisting AUD did not receive behavioral therapy or pharmacotherapy treatment for AUD over a 6-month follow-up. The reductions in hepatic decompensation and mortality suggest that future studies should focus on delivering evidence-based AUD treatments to patients with coexisting AUD and cirrhosis.

Adenovirus-Associated Central Nervous System Disease in Children.

OBJECTIVE: To characterize the spectrum and salient clinical features of adenovirus-associated neurologic disease in immunocompetent children. STUDY DESIGN: Previously healthy children (aged 1 month-18 years) with central nervous system (CNS) disease associated with adenovirus infection were identified via the Encephalitis Registry (1996-2016) and Microbiology Database (2000-2016) at The Hospital for Sick Children, Toronto, and by systematic review of the literature. The data were pooled and analyzed to identify the spectrum of illness, clinical outcome, and risk factors for death or neurologic impairment. RESULTS: Neurologic complications associated with adenovirus infection in our institution included febrile seizures, encephalitis, acute disseminated encephalomyelitis, and aseptic meningitis. A total of 48 immunocompetent children with adenovirus-associated CNS disease were included in the pooled analysis-38 from the literature and 10 from our institution. In 85% of cases, the virus was detected in the respiratory or gastrointestinal tract, but not the cerebrospinal fluid. Eighteen of the 48 (38%) patients either died or suffered permanent neurologic sequelae. Predictors of adverse outcome included younger age, coagulopathy, the absence of meningismus, serotype 2 virus, and the presence of seizures. After multivariable adjustment, only seizures remained a significant risk factor. CONCLUSION: Adenovirus is a rare cause of CNS disease in immunocompetent children. Disease spectrum is variable, ranging from mild aspetic meningitis and fully reversible encephalopathy to severe, potentially fatal, acute necrotizing encephalopathy.

Extensive gene tree discordance and hemiplasy shaped the genomes of North American columnar cacti.

Few clades of plants have proven as difficult to classify as cacti. One explanation may be an unusually high level of convergent and parallel evolution (homoplasy). To evaluate support for this phylogenetic hypothesis at the molecular level, we sequenced the genomes of four cacti in the especially problematic tribe Pachycereeae, which contains most of the large columnar cacti of Mexico and adjacent areas, including the iconic saguaro cactus (Carnegiea gigantea) of the Sonoran Desert. We assembled a high-coverage draft genome for saguaro and lower coverage genomes for three other genera of tribe Pachycereeae (Pachycereus, Lophocereus, and Stenocereus) and a more distant outgroup cactus, Pereskia We used these to construct 4,436 orthologous gene alignments. Species tree inference consistently returned the same phylogeny, but gene tree discordance was high: 37% of gene trees having at least 90% bootstrap support conflicted with the species tree. Evidently, discordance is a product of long generation times and moderately large effective population sizes, leading to extensive incomplete lineage sorting (ILS). In the best supported gene trees, 58% of apparent homoplasy at amino sites in the species tree is due to gene tree-species tree discordance rather than parallel substitutions in the gene trees themselves, a phenomenon termed "hemiplasy." The high rate of genomic hemiplasy may contribute to apparent parallelisms in phenotypic traits, which could confound understanding of species relationships and character evolution in cacti.

Investing in New Technology in Pulmonary Medicine: Navigating the Tortuous Path to Success.

The introduction of new technologies offers the promise to advance medicine. This occurs alongside improved efforts to control costs of health care by hospital administrators, the Centers for Medicare & Medicaid Services' (CMS) pivot to value programs, and commercial payers' efforts to reduce reimbursement. These trends present a challenge for the pulmonologist, among others, who must navigate increasingly complex and highly scrutinized evaluation processes used to secure new technology (NT). Health-care providers are turning toward value assessments while simultaneously tasked with the mission of offering state of the art technologies and services. Pulmonologists desiring NT are thus faced with increased scrutiny in their evaluation of costs and clinical data to support investments. Consideration of this scrutiny and further evidence to temper the evaluation will improve the likelihood of adoption and patient access to clinically impactful technology. The identification of this evidence may provide a comprehensive view of the clinical and economic benefits of such technologies to both administrators and pulmonary clinicians. It is imperative that all parties involved in the decision process work collaboratively to deploy value added and clinically impactful technologies. Although a physician group might invest in such NT, the capital required often leads such decisions to a larger organization such as a hospital, health-care system, or privately owned entity. This article aims to provide a framework for pulmonary clinicians to better understand the processes that purchasers use to evaluate NT, the pressures that influence their consideration, and what resources may be leveraged toward success.