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Hybridization and introgression are complex evolutionary mechanisms that can increase species diversity and lead to speciation, but may also lead to species extinction. In this study, we tested the presence and genetic consequences of hybridization between the rare and Ecuadorian endemic O. loxensis van der Werff and the widespread O. infrafoveolata van der Werff (Lauraceae). Phenotypically, some trees are difficult to identify, and we expect that some might in fact be cryptic hybrids. Thus, we developed nuclear microsatellites to assess the existence of hybrids, as well as the patterns of genetic diversity and population structure in allopatric and sympatric populations. The results revealed high levels of genetic diversity, even in the rare O. loxensis , being usually significantly higher in sympatric than in allopatric populations. The Bayesian assignment of individuals into different genetic classes revealed a complex scenario with different hybrid generations occurring in all sympatric populations, but also in allopatric ones. The absence of some backcrossed hybrids suggests the existence of asymmetric gene flow, and that some hybrids might be more fitted than others might. The existence of current and past interspecific gene flow also explains the blurring of species boundaries in these species and could be linked to the high rates of species found in Ocotea .

Ecuador has a high diversity of orchids, but little is known about levels of genetic diversity for the great majority of species. Understanding how orchids might adapt to changes is crucial as deforestation and fragmentation of forest ecosystems threaten the survival of many epiphytic orchids that depend on other species, such as fungi and their host trees, for germination, growth, and establishment. Overcollection and the illegal trade are also major concerns for the survival of wild populations of orchids. Despite increasing awareness, effective interventions are often limited by a lack of data concerning the impacts that overexploitation might have. To fill this gap, we tested the effects of overcollection in the genetic diversity and structure of Masdevallia rosea, a narrow distributed epiphytic orchid historically collected in Ecuador, in comparison with the widely distributed Pleurothallis lilijae. Genotyping based on AFLPs showed reduced levels of diversity in wild populations but most especially in the overcollected, M. rosea. Overall, genetic admixture was high in P. lilijae segregating populations by altitude levels while fewer genetic groups were found in M. rosea. Genetic differentiation was low in both species. A spatial genetic structure was found in P. lilijae depending on altitude levels, while no spatial genetic structure was found in M. rosea. These results suggest different scenarios for the two species: while gene flow over long distance is possible in P. lilijae, the same seems to be unlikely in M. rosea possibly due to the low levels of individuals in the known populations. In situ and ex situ conservation strategies should be applied to protect the genetic pool in these epiphytic orchid species, and to promote the connectivity between wild populations. Adopting measures to reduce overexploitation and to understand the impacts of harvesting in wild populations are necessary to strengthen the legal trade of orchids., Competing Interests: The authors have declared that no competing interest exist., (Copyright: © 2023 Riofrío et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A single plant might be visited by many flower visitors but not all might act as pollinators. Legitimate pollinators might also differ considerably in their efficiency, limiting pollination success. Unsuitable climatic conditions such as rain also affect pollinator activity. However, in the evergreen rainforest there is no prolonged dry season and flowering occurs usually under rain. Here, we explore the dependence on pollinators and the efficiency of flower visitors for the fruiting success of 10 Andean rainforest orchids. All species were self-compatible but strictly pollinator-dependent. Overall, we found low levels of fruit set in control flowers while experimental geitonogamous and cross-pollinations increased fruit set, revealing extensive pollination limitation in all populations. Seed viability dropped considerably after self and geitonogamous pollinations suggesting the possibility of early-acting inbreeding depression. Even though we monitored flower visitors on an extensive survey, few visitors were seen in these species and even fewer acted as legitimate pollinators. Thus, even though orchid pollination might be extremely diversified, these results show that few visitors are pollinating these species, explaining the low levels of fruit set recorded in the area studied.

Background: Summary measures are used to quantify a hospital's quality of care by combining multiple metrics into a single score. We used Baby-MONITOR, a summary quality measure for NICUs, to evaluate quality by race and ethnicity across and within NICUs in the United States., Methods: Vermont Oxford Network members contributed data from 2015 to 2019 on infants from 25 to 29 weeks' gestation or of 401 to 1500 g birth weight who were inborn or transferred to the reporting hospital within 28 days of birth. Nine Baby-MONITOR measures were individually risk adjusted, standardized, equally weighted, and averaged to derive scores for African American, Hispanic, Asian American, and American Indian infants, compared with white infants., Results: This prospective cohort included 169 400 infants at 737 hospitals. Across NICUs, Hispanic and Asian American infants had higher Baby-MONITOR summary scores, compared with those of white infants. African American and American Indian infants scored lower on process measures, and all 4 minority groups scored higher on outcome measures. Within NICUs, the mean summary scores for African American, Hispanic, and Asian American NICU subsets were higher, compared with those of white infants in the same NICU. American Indian summary NICU scores were not different, on average., Conclusions: With Baby-MONITOR, we identified differences in NICU quality by race and ethnicity. However, the summary score masked within-measure quality gaps that raise unanswered questions about the relationships between race and ethnicity and processes and outcomes of care., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Edwards receives salary support from the Vermont Oxford Network. Ms Greenberg is an employee of the Vermont Oxford Network. Dr Horbar is chief executive officer, president, and chief scientific officer of the Vermont Oxford Network and an unpaid member of the Vermont Oxford Network Board of Trustees. The other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Seventeen European endemic plant species were considered extinct, but improved taxonomic and distribution knowledge as well as ex situ collecting activities brought them out of the extinct status. These species have now been reported into a conservation framework that may promote legal protection and in situ and ex situ conservation.

Objectives: Key validated clinical metrics are being used individually and in aggregate (Baby-MONITOR) to monitor the performance of neonatal intensive care units (NICUs). The degree to which perceptions of key components of safety culture, safety climate, and teamwork are related to aspects of NICU quality of care is poorly understood. The objective of this study was to test whether NICU performance on key clinical metrics correlates with caregiver perceptions of safety culture., Study Design: Cross-sectional study of 6253 very low-birth-weight infants in 44 NICUs. We measured clinical quality via the Baby-MONITOR and its nine risk-adjusted and standardized subcomponents (antenatal corticosteroids, hypothermia, pneumothorax, healthcare-associated infection, chronic lung disease, retinopathy screen, discharge on any human milk, growth velocity, and mortality). A voluntary sample of 2073 of 3294 eligible professional caregivers provided ratings of safety and teamwork climate using the Safety Attitudes Questionnaire. We examined NICU-level variation across clinical and safety culture ratings and conducted correlation analysis of these dimensions., Results: We found significant variation in clinical and safety culture metrics across NICUs. Neonatal intensive care unit teamwork and safety climate ratings were correlated with absence of healthcare-associated infection (r = 0.39 [P = 0.01] and r = 0.29 [P = 0.05], respectively). None of the other clinical metrics, individual or composite, were significantly correlated with teamwork or safety climate., Conclusions: Neonatal intensive care unit teamwork and safety climate were correlated with healthcare-associated infections but not with other quality metrics. Linkages to clinical measures of quality require additional research.

Apollo lunar samples reveal that the Moon generated its own global magnetosphere, lasting from ~4.25 to ~2.5 billion years (Ga) ago. At peak lunar magnetic intensity (4 Ga ago), the Moon was volcanically active, likely generating a very tenuous atmosphere, and, it is believed, was at a geocentric distance of ~18 Earth radii ( R E ). Solar storms strip a planet's atmosphere over time, and only a strong magnetosphere would be able to provide maximum protection. We present simplified magnetic dipole field modeling confined within a paraboloidal-shaped magnetopause to show how the expected Earth-Moon coupled magnetospheres provide a substantial buffer from the expected intense solar wind, reducing Earth's atmospheric loss to space., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Electromagnetic theory predicts spectral dependencies in extinction efficiency near a narrow absorption band for a particle with an index of refraction close to that of the medium in which it is immersed. These absorption band effects are anticipated in oceanographic beam-attenuation (beam-c) spectra, primarily due to the narrow red peak in absorption produced by the phytoplankton photopigment, chlorophyll a (Chl a ). Here we present a method to obtain Chl a absorption and size information by analyzing an eigendecomposition of hyperspectral beam-c residuals measured in marine surface waters by an automatic underway system. We find that three principal modes capture more than 99% of the variance in beam-c residuals at wavelengths near the Chl a red absorption peak. The spectral shapes of the eigenvectors resemble extinction efficiency residuals attributed to the absorption band effects. Projection of the eigenvectors onto the beam-c residuals produces a time series of amplitude functions with absolute values that are strongly correlated to concurrent Chl a absorption line height ( a L H ) measurements ( r values of 0.59 to 0.83) and hence provide a method to estimate Chl a absorption. Multiple linear regression of a L H on the amplitude functions enables an independent estimate of a L H , with RMSE of 3.19⋅10 -3 m -1 (3.3%) or log 10 -RMSE of 18.6%, and a raw-scale R 2 value of 0.90 based on the Tara Oceans Expedition data. Relationships between the amplitude functions and the beam-c exponential slopes are in agreement with theory relating beam-c to the particle size distribution. Compared to multispectral analysis of beam-c slope, hyperspectral analysis of absorption band effects is anticipated to be relatively insensitive to the addition of nonpigmented particles and to monodispersion.

Latent Dirichlet Allocation (LDA) is a topic model widely used in natural language processing and machine learning. Most approaches to training the model rely on iterative algorithms, which makes it difficult to run LDA on big corpora that are best analyzed in parallel and distributed computational environments. Indeed, current approaches to parallel inference either don't converge to the correct posterior or require storage of large dense matrices in memory. We present a novel sampler that overcomes both problems, and we show that this sampler is faster, both empirically and theoretically, than previous Gibbs samplers for LDA. We do so by employing a novel Pólya-urn-based approximation in the sparse partially collapsed sampler for LDA. We prove that the approximation error vanishes with data size, making our algorithm asymptotically exact, a property of importance for large-scale topic models. In addition, we show, via an explicit example, that-contrary to popular belief in the topic modeling literature-partially collapsed samplers can be more efficient than fully collapsed samplers. We conclude by comparing the performance of our algorithm with that of other approaches on well-known corpora.

Importance: Racial and ethnic minorities receive lower-quality health care than white non-Hispanic individuals in the United States. Where minority infants receive care and the role that may play in the quality of care received is unclear., Objective: To determine the extent of segregation and inequality of care of very low-birth-weight and very preterm infants across neonatal intensive care units (NICUs) in the United States., Design, Setting, and Participants: This cohort study of 743 NICUs in the Vermont Oxford Network included 117 982 black, Hispanic, Asian, and white infants born at 401 g to 1500 g or 22 to 29 weeks' gestation from January 2014 to December 2016. Analysis began January 2018., Main Outcomes and Measures: The NICU segregation index and NICU inequality index were calculated at the hospital level as the Gini coefficients associated with the Lorenz curves for black, Hispanic, and Asian infants compared with white infants, with NICUs ranked by proportion of white infants for the NICU segregation index and by composite Baby-MONITOR (Measure of Neonatal Intensive Care Outcomes Research) score for the NICU inequality index., Results: Infants (36 359 black [31%], 21 808 Hispanic [18%], 5920 Asian [5%], and 53 895 white [46%]) were segregated among the 743 NICUs by race and ethnicity (NICU segregation index: black: 0.50 [95% CI, 0.46-0.53], Hispanic: 0.58 [95% CI, 0.54-0.61], and Asian: 0.45 [95% CI, 0.40-0.50]). Compared with white infants, black infants were concentrated at NICUs with lower-quality scores, and Hispanic and Asian infants were concentrated at NICUs with higher-quality scores (NICU inequality index: black: 0.07 [95% CI, 0.02-0.13], Hispanic: -0.10 [95% CI, -0.17 to -0.04], and Asian: -0.26 [95% CI, -0.32 to -0.19]). There was marked variation among the census regions in weighted mean NICU quality scores (range: -0.69 to 0.85). Region of residence explained the observed inequality for Hispanic infants but not for black or Asian infants., Conclusions and Relevance: Black, Hispanic, and Asian infants were segregated across NICUs, reflecting the racial segregation of minority populations in the United States. There were large differences between geographic regions in NICU quality. After accounting for these differences, compared with white infants, Asian infants received care at higher-quality NICUs and black infants, at lower-quality NICUs. Explaining these patterns will require understanding the effects of sociodemographic factors and public policies on hospital quality, access, and choice for minority women and their infants.

Purpose: Kinesio tape (KT) is claimed to be able to facilitate muscle activation and promote muscle strength. Previous studies have proposed that placebo effect could be a major attributing factor. This study sought to compare the effects of facilitatory KT on muscle activity and performance between regular KT-users and non-users., Methods: Sixty participants, including 27 regular KT-users and 33 non-users, performed maximal grip assessment with and without facilitatory KT, which was applied to their wrist extensor muscles of the dominant forearm from the direction of origin to insertion at 75% of its maximal tension. Within-subject comparisons of normalized root mean square of the wrist extensors electromyographic activity, maximal grip strength, and perceived performance were conducted., Results: KT-users showed an increase in grip strength with application of facilitatory KT, when compared to tapeless condition (p = 0.030, Cohen's d = 0.16). Non-users demonstrated similar grip strength with and with KT application (p = 0.232). No significant differences were found in the muscle activity (p > 0.198) and perceived performance (p > 0.400) in both groups., Conclusions: Facilitatory KT promotes maximal grip strength only among regular KT users, but its effect is trivial. Interestingly, such effect is not related to any electrophysiological change in the KT applying muscle, which may indicate an indirect working mechanism leading to the increased grip strength.

The study of the drivers that shape spatial genetic structure across heterogeneous landscapes is one of the main approaches used to understand population dynamics and responses in changing environments. While the Isolation-by-Distance model (IBD) assumes that genetic differentiation increases among populations with geographical distance, the Isolation-by-Resistance model (IBR) also considers geographical barriers and other landscape features that impede gene flow. On the other hand, the Isolation-by-Environment model (IBE) explains genetic differentiation through environmental differences between populations. Although spatial genetic studies have increased significantly in recent years, plants from alpine ecosystems are highly underrepresented, even though they are great suitable systems to disentangle the role of the different factors that structure genetic variation across environmental gradients. Here, we studied the spatial genetic structure of the Mediterranean alpine specialist Silene ciliata across its southernmost distribution limit. We sampled three populations across an altitudinal gradient from 1850 to 2400 m, and we replicated this sample over three mountain ranges aligned across an E-W axis in the central part of the Iberian Peninsula. We genotyped 20 individuals per population based on eight microsatellite markers and used different landscape genetic tools to infer the role of topographic and environmental factors in shaping observed patterns along the altitudinal gradient. We found a significant genetic structure among the studied Silene ciliata populations which was related to the orography and E-W configuration of the mountain ranges. IBD pattern arose as the main factor shaping population genetic differentiation. Geographical barriers between mountain ranges also affected the spatial genetic structure (IBR pattern). Although environmental variables had a significant effect on population genetic diversity parameters, no IBE pattern was found on genetic structure. Our study reveals that IBD was the driver that best explained the genetic structure, whereas environmental factors also played a role in determining genetic diversity values of this dominant plant of Mediterranean alpine environments.

This study examined the effects of KT tape (KT) applied in an inhibitory manner on muscle activity, measured maximal grip strength, and perceived maximal grip strength in regular KT-users and non-users. This study was a single-blinded crossover study with sixty participants including 27 kT-users and 33 non-users. Participants underwent maximal grip strength tests with and without inhibitory KT applied across the wrist extensors. Muscle activity and maximal grip strength were measured, while perceived maximal grip strength was rated using a visual analogue scale. No significant interaction effect was found between taping conditions and participant KT-experience for muscle activity (F = 0.825, p = 0.367), measured grip strength (F = 1.018, p = 0.317) or perceived grip strength (F = 0.122, p = 0.728). No significant differences were observed in the EMG activity between taping conditions for either KT-users (p = 0.367) or non-users (p = 0.215). A similar trend was found in the measured grip strength (KT-users: p = 0.317; non-users: p = 0.294) and perceived grip strength (KT-users: p = 0.728; non-users: p = 0.063). KT applied in an inhibitory manner does not impede EMG activity, measured maximal grip strength, or perceived maximal grip strength in adults, regardless of their preconceived notions of KT., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Differences in NICU quality of care provided to very low birth weight (<1500 g) infants may contribute to the persistence of racial and/or ethnic disparity. An examination of such disparities in a population-based sample across multiple dimensions of care and outcomes is lacking., Methods: Prospective observational analysis of 18 616 very low birth weight infants in 134 California NICUs between January 1, 2010, and December 31, 2014. We assessed quality of care via the Baby-MONITOR, a composite indicator consisting of 9 process and outcome measures of quality. For each NICU, we calculated a risk-adjusted composite and individual component quality score for each race and/or ethnicity. We standardized each score to the overall population to compare quality of care between and within NICUs., Results: We found clinically and statistically significant racial and/or ethnic variation in quality of care between NICUs as well as within NICUs. Composite quality scores ranged by 5.26 standard units (range: -2.30 to 2.96). Adjustment of Baby-MONITOR scores by race and/or ethnicity had only minimal effect on comparative assessments of NICU performance. Among subcomponents of the Baby-MONITOR, non-Hispanic white infants scored higher on measures of process compared with African Americans and Hispanics. Compared with whites, African Americans scored higher on measures of outcome; Hispanics scored lower on 7 of the 9 Baby-MONITOR subcomponents., Conclusions: Significant racial and/or ethnic variation in quality of care exists between and within NICUs. Providing feedback of disparity scores to NICUs could serve as an important starting point for promoting improvement and reducing disparities., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

Traditionally, the use of genomic information for personalized medical decisions relies on prior discovery and validation of genotype-phenotype associations. This approach constrains care for patients presenting with undescribed problems. The National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) hypothesized that defining disease as maladaptation to an ecological niche allows delineation of a logical framework to diagnose and evaluate such patients. Herein, we present the philosophical bases, methodologies, and processes implemented by the NIH UDP. The NIH UDP incorporated use of the Human Phenotype Ontology, developed a genomic alignment strategy cognizant of parental genotypes, pursued agnostic biochemical analyses, implemented functional validation, and established virtual villages of global experts. This systematic approach provided a foundation for the diagnostic or non-diagnostic answers provided to patients and serves as a paradigm for scalable translational research.

Introduction: This article is not a traditional research report. It describes how conducting a specific set of benchmarking analyses led us to broader reflections on hospital benchmarking. We reexamined an issue that has received far less attention from researchers than in the past: How variations in the hospital admission threshold might affect hospital rankings. Considering this threshold made us reconsider what benchmarking is and what future benchmarking studies might be like. Although we recognize that some of our assertions are speculative, they are based on our reading of the literature and previous and ongoing data analyses being conducted in our research unit. We describe the benchmarking analyses that led to these reflections., Objectives: The Centers for Medicare and Medicaid Services' Hospital Compare Web site includes data on fee-for-service Medicare beneficiaries but does not control for severity of illness, which requires physiologic data now available in most electronic medical records.To address this limitation, we compared hospital processes and outcomes among Kaiser Permanente Northern California's (KPNC) Medicare Advantage beneficiaries and non-KPNC California Medicare beneficiaries between 2009 and 2010., Methods: We assigned a simulated severity of illness measure to each record and explored the effect of having the additional information on outcomes., Results: We found that if the admission severity of illness in non-KPNC hospitals increased, KPNC hospitals' mortality performance would appear worse; conversely, if admission severity at non-KPNC hospitals' decreased, KPNC hospitals' performance would appear better., Conclusion: Future hospital benchmarking should consider the impact of variation in admission thresholds.

The National Institutes of Health Undiagnosed Diseases Program (NIH UDP) applies translational research systematically to diagnose patients with undiagnosed diseases. The challenge is to implement an information system enabling scalable translational research. The authors hypothesized that similar complex problems are resolvable through process management and the distributed cognition of communities. The team, therefore, built the NIH UDP integrated collaboration system (UDPICS) to form virtual collaborative multidisciplinary research networks or communities. UDPICS supports these communities through integrated process management, ontology-based phenotyping, biospecimen management, cloud-based genomic analysis, and an electronic laboratory notebook. UDPICS provided a mechanism for efficient, transparent, and scalable translational research and thereby addressed many of the complex and diverse research and logistical problems of the NIH UDP. Full definition of the strengths and deficiencies of UDPICS will require formal qualitative and quantitative usability and process improvement measurement.

Purpose: Medical diagnosis and molecular or biochemical confirmation typically rely on the knowledge of the clinician. Although this is very difficult in extremely rare diseases, we hypothesized that the recording of patient phenotypes in Human Phenotype Ontology (HPO) terms and computationally ranking putative disease-associated sequence variants improves diagnosis, particularly for patients with atypical clinical profiles., Methods: Using simulated exomes and the National Institutes of Health Undiagnosed Diseases Program (UDP) patient cohort and associated exome sequence, we tested our hypothesis using Exomiser. Exomiser ranks candidate variants based on patient phenotype similarity to (i) known disease-gene phenotypes, (ii) model organism phenotypes of candidate orthologs, and (iii) phenotypes of protein-protein association neighbors., Results: Benchmarking showed Exomiser ranked the causal variant as the top hit in 97% of known disease-gene associations and ranked the correct seeded variant in up to 87% when detectable disease-gene associations were unavailable. Using UDP data, Exomiser ranked the causative variant(s) within the top 10 variants for 11 previously diagnosed variants and achieved a diagnosis for 4 of 23 cases undiagnosed by clinical evaluation., Conclusion: Structured phenotyping of patients and computational analysis are effective adjuncts for diagnosing patients with genetic disorders.Genet Med 18 6, 608-617.

Background: Regionalized care delivery purportedly optimizes care to vulnerable very low birth weight (VLBW; <1500 g) infants. However, a comprehensive assessment of quality of care delivery across different levels of NICUs has not been done., Methods: We conducted a cross-sectional analysis of 21,051 VLBW infants in 134 California NICUs. NICUs designated their level of care according to 2012 American Academy of Pediatrics guidelines. We assessed quality of care delivery via the Baby-MONITOR, a composite indicator, which combines 9 risk-adjusted measures of quality. Baby-MONITOR scores are measured as observed minus expected performance, expressed in standard units with a mean of 0 and an SD of 1., Results: Wide variation in Baby-MONITOR scores exists across California (mean [SD] 0.18 (1.14), range -2.26 to 3.39). However, level of care was not associated with overall quality scores. Subcomponent analysis revealed trends for higher performance of Level IV NICUs on several process measures, including antenatal steroids and any human milk feeding at discharge, but lower scores for several outcomes including any health care associated infection, pneumothorax, and growth velocity. No other health system or organizational factors including hospital ownership, neonatologist coverage, urban or rural location, and hospital teaching status, were significantly associated with Baby-MONITOR scores., Conclusions: The comprehensive assessment of the effect of level of care on quality reveals differential opportunities for improvement and allows monitoring of efforts to ensure that fragile VLBW infants receive care in appropriate facilities., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2016 by the American Academy of Pediatrics.)

The Undiagnosed Diseases Program (UDP) was started in 2008 with the goals of making diagnoses and facilitating related translational research. The individuals and families seen by the UDP are often unique and medically complex. Approximately 40% of UDP cases are pediatric. The Undiagnosed Diseases Program Integrated Collaboration System (UDPICS) was designed to create a collaborative workspace for researchers, clinicians and families. We describe our progress in developing the system to date, focusing on design rationale, challenges and issues that are likely to be common in the development of similar systems in the future.

Background: The absolute neutrophil count and the immature/total neutrophil ratio (I/T) provide information about the risk of early onset sepsis in newborns. However, it is not clear how to combine their potentially overlapping information into a single likelihood ratio., Methods: We obtained electronic records of blood cultures and of complete blood counts with manual differentials drawn <1 hour apart on 66,846 infants ≥ 34 weeks gestation and <72 hours of age born at Kaiser Permanente Northern California and Brigham and Women's Hospitals. We hypothesized that dividing the immature neutrophil count (I) by the total neutrophil count (T) squared (I/T) would provide a useful summary of the risk of infection. We evaluated the ability of the I/T to discriminate newborns with pathogenic bacteremia from other newborns tested using the area under the receiver operating characteristic curve (c)., Results: Discrimination of the I/T (c = 0.79; 95% confidence interval: 0.76-0.82) was similar to that of logistic models with indicator variables for each of 24 combinations of the absolute neutrophil count and the proportion of immature neutrophils (c = 0.80, 95% confidence interval: 0.77-0.83). Discrimination of the I/T improved with age, from 0.70 at <1 hour to 0.87 at ≥ 4 hours. However, 60% of I/T had likelihood ratios of 0.44-1.3, thus only minimally altering the pretest odds of disease., Conclusions: Calculating the I/T could enhance prediction of early onset sepsis, but the complete blood counts will remain helpful mainly when done at >4 hours of age and when the pretest probability of infection is close to the treatment threshold.

Background and Objectives: NICUs vary in the quality of care delivered to very low birth weight (VLBW) infants. NICU performance on 1 measure of quality only modestly predicts performance on others. Composite measurement of quality of care delivery may provide a more comprehensive assessment of quality. The objective of our study was to develop a robust composite indicator of quality of NICU care provided to VLBW infants that accurately discriminates performance among NICUs., Methods: We developed a composite indicator, Baby-MONITOR, based on 9 measures of quality chosen by a panel of experts. Measures were standardized, equally weighted, and averaged. We used the California Perinatal Quality Care Collaborative database to perform across-sectional analysis of care given to VLBW infants between 2004 and 2010. Performance on the Baby-MONITOR is not an absolute marker of quality but indicates overall performance relative to that of the other NICUs. We used sensitivity analyses to assess the robustness of the composite indicator, by varying assumptions and methods., Results: Our sample included 9023 VLBW infants in 22 California regional NICUs. We found significant variations within and between NICUs on measured components of the Baby-MONITOR. Risk-adjusted composite scores discriminated performance among this sample of NICUs. Sensitivity analysis that included different approaches to normalization, weighting, and aggregation of individual measures showed the Baby-MONITOR to be robust (r = 0.89-0.99)., Conclusions: The Baby-MONITOR may be a useful tool to comprehensively assess the quality of care delivered by NICUs., (Copyright © 2014 by the American Academy of Pediatrics.)

Background: Because of their fragmented nature, inselberg species are interesting biological models for studying the genetic consequences of disjoint populations. Inselbergs are commonly compared with oceanic islands, as most of them display a marked ecological isolation from the surrounding area. The isolation of these rock outcrops is reflected in the high number of recorded endemic species and the strong floristic differences between individual inselbergs and adjacent habitats. We examined the genetic connectivity of orchids Epidendrum cinnabarinum and E. secundum adapted to Neotropical inselbergs of northeastern Brazil. Our goals were to identify major genetic divergences or disjunctions across the range of the species and to investigate potential demographic and evolutionary mechanisms leading to lineage divergence in Neotropical mountain ecosystems., Results: Based on plastid markers, high genetic differentiation was found for E. cinnabarinum (FST = 0.644) and E. secundum (FST = 0.636). Haplotypes were not geographically structured in either taxon, suggesting that restricted gene flow and genetic drift may be significant factors influencing the diversification of these inselberg populations. Moreover, strong differentiation was found between populations over short spatial scales, indicating substantial periods of isolation among populations. For E. secundum, nuclear markers indicated higher gene flow by pollen than by seeds., Conclusions: The comparative approach adopted in this study contributed to the elucidation of patterns in both species. Our results confirm the ancient and highly isolated nature of inselberg populations. Both species showed similar patterns of genetic diversity and structure, highlighting the importance of seed-restricted gene flow and genetic drift as drivers of plant diversification in terrestrial islands such as inselbergs.

Background: Hybridization and polyploidy are central processes in evolution and speciation. These mechanisms often lead to complex patterns of genetic variation and the creation of novel genotypes, which may establish if they become isolated from gene flow. However, in the absence of reproductive isolation, species boundaries might easily be disrupted. Here, we used a combination of AFLPs, chloroplast DNA markers and flow cytometry to investigate the evolutionary outcomes of hybridization between two endemic Ecuadorian species of Epidendrum (E. madsenii and E. rhopalostele) in three hybrid zones. Postmating isolation was also quantified to determine the role of this barrier in restraining gene flow between hybrids and the parental species. In addition, future ecological niche models were constructed to predict the outcomes of hybridization between these species., Results: Our results confirmed the presence of hybrids in all hybrid zones, but revealed that a third parental species (E. falcisepalum) has contributed to one of the hybrid zones studied. Backcross genotypes were frequent in all hybrid zones, which was in accordance with the absence of strong reproductive barriers. The process of hybridization was highly asymmetric and followed in some cases by polyploidy. The projection of future niche models predicted a severe reduction in the area suitable for the occurrence of these species, although favorable conditions will still occur for the existence of the current hybrid zones., Conclusions: The recurrent process of hybridization has compromised the genetic integrity of the parental species. Most individuals of the parental species can no longer be considered as pure-bred individuals because most were classified as backcrossed hybrids. Novel genetic lineages occur in all hybrid zones implying that hybrids are fertile and can compete with the parental species. These results, together with the prediction of suitable conditions for the future occurrence of these hybrid zones, highlight the importance of conserving these geographic areas as sources of novel taxonomic entities.

Objective: To define a quantitative stratification algorithm for the risk of early-onset sepsis (EOS) in newborns ≥ 34 weeks' gestation., Methods: We conducted a retrospective nested case-control study that used split validation. Data collected on each infant included sepsis risk at birth based on objective maternal factors, demographics, specific clinical milestones, and vital signs during the first 24 hours after birth. Using a combination of recursive partitioning and logistic regression, we developed a risk classification scheme for EOS on the derivation dataset. This scheme was then applied to the validation dataset., Results: Using a base population of 608,014 live births ≥ 34 weeks' gestation at 14 hospitals between 1993 and 2007, we identified all 350 EOS cases <72 hours of age and frequency matched them by hospital and year of birth to 1063 controls. Using maternal and neonatal data, we defined a risk stratification scheme that divided the neonatal population into 3 groups: treat empirically (4.1% of all live births, 60.8% of all EOS cases, sepsis incidence of 8.4/1000 live births), observe and evaluate (11.1% of births, 23.4% of cases, 1.2/1000), and continued observation (84.8% of births, 15.7% of cases, incidence 0.11/1000)., Conclusions: It is possible to combine objective maternal data with evolving objective neonatal clinical findings to define more efficient strategies for the evaluation and treatment of EOS in term and late preterm infants. Judicious application of our scheme could result in decreased antibiotic treatment in 80,000 to 240,000 US newborns each year.

Objective: Using a comprehensive inpatient electronic medical record, we sought to develop a risk-adjustment methodology applicable to all hospitalized patients. Further, we assessed the impact of specific data elements on model discrimination, explanatory power, calibration, integrated discrimination improvement, net reclassification improvement, performance across different hospital units, and hospital rankings., Design: Retrospective cohort study using logistic regression with split validation., Participants: A total of 248,383 patients who experienced 391,584 hospitalizations between January 1, 2008 and August 31, 2011., Setting: Twenty-one hospitals in an integrated health care delivery system in Northern California., Results: Inpatient and 30-day mortality rates were 3.02% and 5.09%, respectively. In the validation dataset, the greatest improvement in discrimination (increase in c statistic) occurred with the introduction of laboratory data; however, subsequent addition of vital signs and end-of-life care directive data had significant effects on integrated discrimination improvement, net reclassification improvement, and hospital rankings. Use of longitudinally captured comorbidities did not improve model performance when compared with present-on-admission coding. Our final model for inpatient mortality, which included laboratory test results, vital signs, and care directives, had a c statistic of 0.883 and a pseudo-R of 0.295. Results for inpatient and 30-day mortality were virtually identical., Conclusions: Risk-adjustment of hospital mortality using comprehensive electronic medical records is feasible and permits one to develop statistical models that better reflect actual clinician experience. In addition, such models can be used to assess hospital performance across specific subpopulations, including patients admitted to intensive care.

Objective: To measure the influence of varying mortality time frames on performance rankings among regional neonatal intensive care units (NICUs) in a large state., Study Design: We performed a cross-sectional data analysis of very low birth weight infants receiving care at 24 level 3 NICUs. We tested the effect of 4 definitions of mortality: (1) death between admission and end of birth hospitalization or up to 366 days; (2) death between 12 hours of age and the end of birth hospitalization or up to 366 days; (3) death between admission and 28 days; and (4) death between 12 hours of age and 28 days. NICUs were ranked by quantifying their deviation from risk-adjusted expected mortality and dividing them into 3 tiers: top 6, bottom 6, and in between., Results: There was wide interinstitutional variation in risk-adjusted mortality for each definition (observed minus expected z-score range, -6.08 to 3.75). However, mortality-based NICU rankings and classification into performance tiers were very similar for all institutions in each of our time frames. Among all 4 definitions, NICU rank correlations were high (>0.91). Few NICUs changed relative to a neighboring tier with changes in definitions, and none changed by more than one tier., Conclusion: The time frame used to ascertain mortality had little effect on comparative NICU performance., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objectives: To examine whether high performance on one measure of quality is associated with high performance on others and to develop a data-driven explanatory model of neonatal intensive care unit (NICU) performance., Design: We conducted a cross-sectional data analysis of a statewide perinatal care database. Risk-adjusted NICU ranks were computed for each of 8 measures of quality selected based on expert input. Correlations across measures were tested using the Pearson correlation coefficient. Exploratory factor analysis was used to determine whether underlying factors were driving the correlations., Setting: Twenty-two regional NICUs in California., Patients: In total, 5445 very low-birth-weight infants cared for between January 1, 2004, and December 31, 2007., Main Outcomes Measures: Pneumothorax, growth velocity, health care-associated infection, antenatal corticosteroid use, hypothermia during the first hour of life, chronic lung disease, mortality in the NICU, and discharge on any human breast milk., Results: The NICUs varied substantially in their clinical performance across measures of quality. Of 28 unit-level correlations, 6 were significant (ρ < .05). Correlations between pairs of measures of quality of care were strong (ρ ≥ .5) for 1 pair, moderate (range, ρ ≥ .3 to ρ < .5) for 8 pairs, weak (range, ρ ≥ .1 to ρ < .3) for 5 pairs, and negligible (ρ < .1) for 14 pairs. Exploratory factor analysis revealed 4 underlying factors of quality in this sample. Pneumothorax, mortality in the NICU, and antenatal corticosteroid use loaded on factor 1; growth velocity and health care-associated infection loaded on factor 2; chronic lung disease loaded on factor 3; and discharge on any human breast milk loaded on factor 4., Conclusion: In this sample, the ability of individual measures of quality to explain overall quality of neonatal intensive care was modest.

Background: Ward patients who experience unplanned transfer to intensive care units have excess morbidity and mortality., Objective: To develop a predictive model for prediction of unplanned transfer from the medical-surgical ward to intensive care (or death on the ward in a patient who was "full code") using data from a comprehensive inpatient electronic medical record (EMR)., Design: Retrospective case-control study; unit of analysis was a 12-hour patient shift. Shifts where a patient experienced an unplanned transfer were event shifts; shifts without a transfer were comparison shifts. Hospitalization records were transformed into 12-hour shift records, with 10 randomly selected comparison shifts identified for each event shift. Analysis employed logistic regression and split validation., Setting: Integrated healthcare delivery system in Northern California., Patients: Hospitalized adults at 14 hospitals with comprehensive inpatient EMRs., Measurements: Predictors included vital signs, laboratory test results, severity of illness scores, longitudinal chronic illness burden scores, transpired hospital length of stay, and care directives. Patients were also given a retrospective, electronically (not manually assigned) Modified Early Warning Score, or MEWS(re). Outcomes were transfer to the intensive care unit (ICU) from the ward or transitional care unit, or death outside the ICU among patients who were "full code"., Results: We identified 4,036 events and 39,782 comparison shifts from a cohort of 102,422 patients' hospitalizations. The MEWS(re) had a c-statistic of 0.709 in the derivation and 0.698 in the validation dataset; corresponding values for the EMR-based model were 0.845 and 0.775., Limitations: Using these algorithms requires hospitals with comprehensive inpatient EMRs and longitudinal data., Conclusions: EMR-based detection of impending deterioration outside the ICU is feasible in integrated healthcare delivery systems., (Copyright © 2012 Society of Hospital Medicine.)

Methylene blue can be used as a stain for visualizing nucleic acids in polyacrylamide gel electrophoresis. However, its relatively low sensitivity and reversible binding make it a temporary stain that diffuses from the gel relatively fast. Here we describe a very simple method for fixing methylene blue bands in nucleic acid polyacrylamide gels. The procedure makes the methylene blue stain permanent and increases the visibility of the bands, also contributing to increasing the sensitivity of methylene blue., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To develop a quantitative model to estimate the probability of neonatal early-onset bacterial infection on the basis of maternal intrapartum risk factors., Methods: This was a nested case-control study of infants born at ≥34 weeks' gestation at 14 California and Massachusetts hospitals from 1993 to 2007. Case-subjects had culture-confirmed bacterial infection at <72 hours; controls were randomly selected, frequency-matched 3:1 according to year and birth hospital. We performed multivariate analyses and split validation to define a predictive model based only on information available in the immediate perinatal period., Results: We identified 350 case-subjects from a cohort of 608,014 live births. Highest intrapartum maternal temperature revealed a linear relationship with risk of infection below 100.5°F, above which the risk rose rapidly. Duration of rupture of membranes revealed a steadily increasing relationship with infection risk. Increased risk was associated with both late-preterm and postterm delivery. Risk associated with maternal group B Streptococcus colonization is diminished in the era of group B Streptococcus prophylaxis. Any form of intrapartum antibiotic given >4 hours before delivery was associated with decreased risk. Our model showed good discrimination and calibration (c statistic = 0.800 and Hosmer-Lemeshow P = .142 in the entire data set)., Conclusions: A predictive model based on information available in the immediate perinatal period performs better than algorithms based on risk-factor threshold values. This model establishes a prior probability for newborn sepsis, which could be combined with neonatal physical examination and laboratory values to establish a posterior probability to guide treatment decisions.

Background: A complete blood count (CBC) with white blood cell differential is commonly ordered to evaluate newborns at risk for sepsis., Objectives: To quantify how well components of the CBC predict sepsis in the first 72 hours after birth., Methods: For this retrospective cross-sectional study we identified 67 623 term and late-preterm (≥ 34 weeks gestation) newborns from 12 northern California Kaiser hospitals and 1 Boston, Massachusetts hospital who had a CBC and blood culture within 1 hour of each other at <72 hours of age. We compared CBC results among newborns whose blood cultures were and were not positive and quantified discrimination by using receiver operating characteristic curves and likelihood ratios., Results: Blood cultures of 245 infants (3.6 of 1000 tested newborns) were positive. Mean white blood cell (WBC) counts and mean absolute neutrophil counts (ANCs) were lower, and mean proportions of immature neutrophils were higher in newborns with infection; platelet counts did not differ. Discrimination improved with age in the first few hours, especially for WBC counts and ANCs (eg, the area under the receiver operating characteristic curve for WBC counts was 0.52 at <1 hour and 0.87 at ≥ 4 hours). Both WBC counts and ANCs were most informative when very low (eg, the likelihood ratio for ANC < 1000 was 115 at ≥ 4 hours). No test was very sensitive; the lowest likelihood ratio (for WBC count ≥ 20 000 at ≥ 4 hours) was 0.16., Conclusion: Optimal interpretation of the CBC requires using interval likelihood ratios for the newborn's age in hours.

Evolutionary consequences of natural hybridization between species may vary so drastically depending on spatial, genetic, and ecological factors that multiple approaches are required to uncover them. To unravel the evolutionary history of a controversial hybrid (Narcissus x perezlarae), here we use four approaches: DNA sequences from five regions (four organellar, one nuclear), cytological studies (chromosome counts and genome size), crossing experiments, and niche modeling. We conclude that (1) it actually consists of two different hybrid taxa, N.xperezlarae s.s. (N. cavanillesii x N. miniatus) and N.xalentejanus (N. cavanillesii x N. serotinus); (2) both have been formed several times independently, that is, polytopically; (3) N. cavanillesii was the mother progenitor in most hybridization events. We also address the origin of orphan hybrid populations of N.xperezlarae in eastern Spain, hundreds of kilometers away from N. cavanillesii. Although long-distance dispersal of already formed hybrids cannot be completely rejected, extirpation of N. cavanillesii via demographic competition is a more likely explanation. Low-reproductive barriers to fertilization by foreign pollen in N. cavanillesii, molecular footprints of the former presence of this species in the area, active asexual propagation by bulbs in N.xperezlarae, and overlapping ecological niches are consistent with the extirpation scenario.

Objective: To evaluate and compare the use of 6 different methods for calculating expected mortality rates and standardized mortality ratios (SMRs) when performing interhospital mortality rate comparisons., Design: Retrospective cohort study using actual and simulated hospitalization data to evaluate the use of (1) fixed-effects, (2) Generalized Linear Mixed Model, and (3) Bayesian (Markov Chain Monte Carlo-based) random-effects models on both aggregated and individual-level data to estimate SMRs by hospital., Setting: Seventeen hospitals in a large integrated health care delivery system., Main Outcome Measure: Inpatient mortality., Results: Results from the 6 different methods compared in this study were highly correlated both on log(SMR) values and hospital ranks (range, 0.91-1). All the methods had high specificity (>87%) for finding true underlying mortality effects. The fixed-effects models had higher overall sensitivity than the random-effects models. The individual-level random effects model had generally higher sensitivity than the aggregated random-effects models. All methods showed a high correlation with the true ranks., Discussion: When comparing mortality rates across hospitals, it is important to focus not only on the method used to measure patient sickness but also on the analytical technique used to estimate hospital-specific adjusted mortality rates. When an illness severity measure including detailed physiologic data was used, the simplest method we examined, a fixed-effects aggregate-level approach in common usage, out-performed the other methods when both specificity and sensitivity are considered. Use of a severity measure that correlates less well with mortality than the one we employed would be expected to reduce the sensitivity of all of the methods examined.

Objective: To determine if sorafenib is associated with an improved 4-month probability of progression-free survival, using radiographic and clinical criteria alone, in patients with metastatic castration-resistant prostate cancer. Secondary endpoints included pharmacokinetics, toxicity analysis and overall survival., Patients and Methods: The study was an open-label, phase II, two-stage design, focusing on the results from the second stage, as criteria for progression were modified after completing the first stage. Sorafenib was given at a dose of 400 mg orally twice daily in 28-day cycles. Clinical and laboratory assessments were done every 4 weeks, and radiographic scans were obtained every 8 weeks., Results: Twenty-four patients were accrued in the second stage; the median (range) age was 66 (49-85) years, the on-study prostate-specific antigen level was 68.45 (5.8-995) ng/mL, the Gleason score 8 (6-9) and Eastern Cooperative Oncology Group status 1 (in 17 patients). Of the 24 patients, 21 had previous chemotherapy with docetaxel. All patients had bony metastases, either alone (in 11) or with soft-tissue disease (in 13). One patient had a partial response; 10 patients had stable disease (median duration 18 weeks, range 15-48). At a median potential follow-up of 27.2 months, the median progression-free survival was 3.7 months and the median overall survival was 18.0 months. For the whole trial of 46 patients the median survival was 18.3 months. Most frequent toxicities included hand-foot skin reaction (grade 2 in nine patients, grade 3 in three), rash, abnormalities in liver function tests, and fatigue., Conclusions: Sorafenib has moderate activity as a second-line treatment for metastatic castration-resistant prostate cancer.

Insertional mutations leading to expansion of the octarepeat domain of the prion protein (PrP) are directly linked to prion disease. While normal PrP has four PHGGGWGQ octapeptide segments in its flexible N-terminal domain, expanded forms may have up to nine additional octapeptide inserts. The type of prion disease segregates with the degree of expansion. With up to four extra octarepeats, the average onset age is above 60 years, whereas five to nine extra octarepeats results in an average onset age between 30 and 40 years, a difference of almost three decades. In wild-type PrP, the octarepeat domain takes up copper (Cu(2+)) and is considered essential for in vivo function. Work from our lab demonstrates that the copper coordination mode depends on the precise ratio of Cu(2+) to protein. At low Cu(2+) levels, coordination involves histidine side chains from adjacent octarepeats, whereas at high levels each repeat takes up a single copper ion through interactions with the histidine side chain and neighboring backbone amides. Here we use both octarepeat constructs and recombinant PrP to examine how copper coordination modes are influenced by octarepeat expansion. We find that there is little change in affinity or coordination mode populations for octarepeat domains with up to seven segments (three inserts). However, domains with eight or nine total repeats (four or five inserts) become energetically arrested in the multi-histidine coordination mode, as dictated by higher copper uptake capacity and also by increased binding affinity. We next pooled all published cases of human prion disease resulting from octarepeat expansion and find remarkable agreement between the sudden length-dependent change in copper coordination and onset age. Together, these findings suggest that either loss of PrP copper-dependent function or loss of copper-mediated protection against PrP polymerization makes a significant contribution to early onset prion disease.

Objectives: To develop a risk-adjustment methodology that maximizes the use of automated physiology and diagnosis data from the time period preceding hospitalization., Design: : Retrospective cohort study using split-validation and logistic regression., Setting: Seventeen hospitals in a large integrated health care delivery system., Subjects: Patients (n = 259,699) hospitalized between January 2002 and June 2005., Main Outcome Measures: Inpatient and 30-day mortality., Results: Inpatient mortality was 3.50%; 30-day mortality was 4.06%. We tested logistic regression models in a randomly chosen derivation dataset consisting of 50% of the records and applied their coefficients to the validation dataset. The final model included sex, age, admission type, admission diagnosis, a Laboratory-based Acute Physiology Score (LAPS), and a COmorbidity Point Score (COPS). The LAPS integrates information from 14 laboratory tests obtained in the 24 hours preceding hospitalization into a single continuous variable. Using Diagnostic Cost Groups software, we categorized patients as having up to 40 different comorbidities based on outpatient and inpatient data from the 12 months preceding hospitalization. The COPS integrates information regarding these 41 comorbidities into a single continuous variable. Our best model for inpatient mortality had a c statistic of 0.88 in the validation dataset, whereas the c statistic for 30-day mortality was 0.86; both models had excellent calibration. Physiologic data accounted for a substantial proportion of the model's predictive ability., Conclusion: Efforts to support improvement of hospital outcomes can take advantage of risk-adjustment methods based on automated physiology and diagnosis data that are not confounded by information obtained after hospital admission.

Objective: To evaluate whether physiological trends and interaction terms could enhance predictive ability in a variant of the Richardson Score., Method: We conducted a retrospective cohort study using data from 2,222 newborns of 34 weeks or more gestation with respiratory distress. The outcome variable was assisted ventilation longer 3 days or death. Using logistic regression and split validation we fit models for a variant of the Richardson score (gestational age, worst PaO(2)/FIO(2) ratio, lowest MAP, and a single interaction variable relating the lowest pH and the highest PaCO(2)) as well as models incorporating variables for trends and additional interaction terms. We assessed discrimination using the c-statistic., Results: The 24-h Richardson score had a c-statistic of 0.83. In the validation dataset, adding pH trend significantly increased the c-statistic to 0.87. Adding PaO(2)/FIO(2) ratio trend increased the c-statistic to 0.86. Interactions with high significance were present in the data (e.g., adding all two-way interactions to our best trend model yielded a c-statistic of 0.92) but were unstably estimated with n = 2,222., Conclusions: Incorporating trend and interaction terms in severity scores can enhance predictive ability. These modeling strategies have been underutilized in severity scoring, but in an era of increasing electronic availability of detailed clinical data the incorporation of trend and interaction effects in severity scoring will become both feasible and desirable.

Natural hybrids between rare and common sympatric species are commonly eradicated to avoid the potential extinction of the rare species, although there is currently no clear predictive framework to quantify this risk. As hybrids can have intrinsic value as new evolutionary pathways, further knowledge on the factors controlling hybridization is needed. In this study we evaluated the role of pollination patterns in hybridization events in two sympatric populations of Narcissus cavanillesii and N. serotinus in Portugal. Narcissus cavanillesii is a rare species, while N. serotinus is widely distributed across the Mediterranean. The hybrid, N. ×perezlarae, is quite frequent in southeastern Spain but is scarce in Portugal. Reciprocal manual crossings confirmed compatibility between the two species, although hybridization was more successful when N. cavanillesii participated as female. Narcissus cavanillesii and N. serotinus only shared one pollinator, Megachile sp. (Hymenoptera), which had low visitation rates and high flower constancy. No single isolation mechanism was fully effective in preventing hybridization. Temporal displacement of flowering peaks, strong pollinator specificity, and high flower constancy in the shared pollinator all contributed to limiting hybridization in this site. In other sympatric occurrences, different phenological windows and pollination assemblages may allow greater frequency of the hybrid.

Apoptosis plays an essential role in T cell biology. Thymocytes expressing nonfunctional or autoreactive TCRs are eliminated by apoptosis during development. Apoptosis also leads to the deletion of expanded effector T cells during immune responses. The dysregulation of apoptosis in the immune system results in autoimmunity, tumorogenesis and immunodeficiency. Two major pathways lead to apoptosis: the intrinsic cell death pathway controlled by Bcl-2 family members and the extrinsic cell death pathway controlled by death receptor signaling. These two pathways work together to regulate T lymphocyte development and function.

Hypereosinophilic syndromes are defined by the presence of peripheral and bone marrow eosinophilia and by the infiltration of multiple organs by mature eosinophilic cells. Loffler's endocarditis is a condition in which mature eosinophils infiltrate and damage the endocardium and myocardium. Male adults who live in the tropics are the population predominantly affected by this condition. Typical clinical features include weight loss, fever, cough, rash, and congestive heart failure. In this article, we report the typical presentation of an unusual illness that occurred in 2 pediatric patients in different geographic locations. In addition, we believe that these are the youngest patients with Loffler's endocarditis reported.