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Evolutionary variation in the wing pigmentation of butterflies and moths offers striking examples of adaptation by crypsis and mimicry. The cortex locus has been independently mapped as the locus controlling color polymorphisms in 15 lepidopteran species, suggesting that it acts as a genomic hotspot for the diversification of wing patterns, but functional validation through protein-coding knockouts has proven difficult to obtain. Our study unveils the role of a long noncoding RNA (lncRNA) which we name ivory, transcribed from the cortex locus, in modulating color patterning in butterflies. Strikingly, ivory expression prefigures most melanic patterns during pupal development, suggesting an early developmental role in specifying scale identity. To test this, we generated CRISPR mosaic knock-outs in five nymphalid butterfly species and show that ivory mutagenesis yields transformations of dark pigmented scales into white or light-colored scales. Genotyping of Vanessa cardui germline mutants associates these phenotypes to small on-target deletions at the conserved first exon of ivory. In contrast, cortex germline mutant butterflies with confirmed null alleles lack any wing phenotype and exclude a color patterning role for this adjacent gene. Overall, these results show that a lncRNA gene acts as a master switch of color pattern specification and played key roles in the adaptive diversification of wing patterns in butterflies.
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Mariposas Diurnas , Pigmentación , ARN Largo no Codificante , Alas de Animales , Animales , Mariposas Diurnas/genética , Pigmentación/genética , Alas de Animales/anatomía & histología , Alas de Animales/crecimiento & desarrollo , ARN Largo no Codificante/genética , Fenotipo , Adaptación Fisiológica/genéticaRESUMEN
Butterfly color patterns provide visible and biodiverse phenotypic readouts of the patterning processes. Although the secreted ligand WntA has been shown to instruct the color pattern formation in butterflies, its mode of reception remains elusive. Butterfly genomes encode four homologs of the Frizzled-family of Wnt receptors. Here, we show that CRISPR mosaic knockouts of frizzled2 (fz2) phenocopy the color pattern effects of WntA loss of function in multiple nymphalids. Whereas WntA mosaic clones result in intermediate patterns of reduced size, fz2 clones are cell-autonomous, consistent with a morphogen function. Shifts in expression of WntA and fz2 in WntA crispant pupae show that they are under positive and negative feedback, respectively. Fz1 is required for Wnt-independent planar cell polarity in the wing epithelium. Fz3 and Fz4 show phenotypes consistent with Wnt competitive-antagonist functions in vein formation (Fz3 and Fz4), wing margin specification (Fz3), and color patterning in the Discalis and Marginal Band Systems (Fz4). Overall, these data show that the WntA/Frizzled2 morphogen-receptor pair forms a signaling axis that instructs butterfly color patterning and shed light on the functional diversity of insect Frizzled receptors.
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Mariposas Diurnas , Pigmentación , Animales , Pigmentación/genética , Mariposas Diurnas/genética , Mariposas Diurnas/metabolismo , Transducción de Señal/genética , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Alas de Animales/metabolismoRESUMEN
Mating cues evolve rapidly and can contribute to species formation and maintenance. However, little is known about how sexual signals diverge and how this variation integrates with other barrier loci to shape the genomic landscape of reproductive isolation. Here, we elucidate the genetic basis of ultraviolet (UV) iridescence, a courtship signal that differentiates the males of Colias eurytheme butterflies from a sister species, allowing females to avoid costly heterospecific matings. Anthropogenic range expansion of the two incipient species established a large zone of secondary contact across the eastern United States with strong signatures of genomic admixtures spanning all autosomes. In contrast, Z chromosomes are highly differentiated between the two species, supporting a disproportionate role of sex chromosomes in speciation known as the large-X (or large-Z) effect. Within this chromosome-wide reproductive barrier, linkage mapping indicates that cis-regulatory variation of bric a brac (bab) underlies the male UV-iridescence polymorphism between the two species. Bab is expressed in all non-UV scales, and butterflies of either species or sex acquire widespread ectopic iridescence following its CRISPR knockout, demonstrating that Bab functions as a suppressor of UV-scale differentiation that potentiates mating cue divergence. These results highlight how a genetic switch can regulate a premating signal and integrate with other reproductive barriers during intermediate phases of speciation.
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Mariposas Diurnas/genética , Mariposas Diurnas/efectos de la radiación , Genes de Cambio , Iridiscencia/genética , Azufre/química , Rayos Ultravioleta , Animales , Sistemas CRISPR-Cas/genética , Cromosomas/genética , Genes de Insecto , Sitios Genéticos , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Iridiscencia/efectos de la radiación , Masculino , Conducta Sexual Animal/fisiología , Especificidad de la Especie , Simpatría/genética , Alas de Animales/metabolismoRESUMEN
OBJECTIVES: To derive care targets and evaluate the impact of displaying them at the point of care on postoperative length of stay (LOS). STUDY DESIGN: A prospective cohort study using 2 years of historical controls within a freestanding, academic children's hospital. Patients undergoing benchmark cardiac surgery between May 4, 2014, and August 15, 2016 (preintervention) and September 6, 2016, to September 30, 2018 (postintervention) were included. The intervention consisted of displaying at the point of care targets for the timing of extubation, transfer from the intensive care unit (ICU), and hospital discharge. Family satisfaction, reintubation, and readmission rates were tracked. RESULTS: The postintervention cohort consisted of 219 consecutive patients. There was a reduction in variation for ICU (difference in SD -2.56, P < .01) and total LOS (difference in SD -2.84, P < .001). Patients stayed on average 0.97 fewer days (P < .001) in the ICU (median -1.01 [IQR -2.15, -0.39]), 0.7 fewer days (P < .001) on mechanical ventilation (median -0.54 [IQR -0.77, -0.50]), and 1.18 fewer days (P < .001) for the total LOS (median -2.25 [IQR -3.69, -0.15]). Log-transformed multivariable linear regression demonstrated the intervention to be associated with shorter ICU LOS (ß coefficient -0.19, SE 0.059, P < .001), total postoperative LOS (ß coefficient -0.12, SE 0.052, P = .02), and ventilator duration (ß coefficient -0.21, SE 0.048, P < .001). Balancing metrics did not differ after the intervention. CONCLUSIONS: Target-based care is a simple, novel intervention associated with reduced variation in LOS and absolute LOS across a diverse spectrum of complex cardiac surgeries.
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Benchmarking/métodos , Procedimientos Quirúrgicos Cardíacos , Cardiopatías Congénitas/cirugía , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Tiempo de Internación/tendencias , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Periodo Posoperatorio , Estudios Prospectivos , Factores de TiempoRESUMEN
OBJECTIVE: To evaluate the estimated labor costs and effectiveness of Ongoing Professional Practice Evaluation (OPPE) processes at identifying outlier performers in a large sample of providers across multiple health care systems and to extrapolate costs and effectiveness nationally. METHODS: Six hospital systems partnered to evaluate their labor expenses related to conducting OPPE. Estimates for mean labor hours and wages were created for the following: data analysts, medical staff office professionals, department physician leaders, and administrative assistants. The total number of outlier performers who were identified by OPPE metrics alone and that resulted in lack of renewal, limitation, or revoking of hospital privileges during the past annual OPPE cycle (2022) was recorded. National costs of OPPE were extrapolated. Literature review of the effect of OPPE on safety culture in radiology was performed. RESULTS: The evaluated systems had 12,854 privileged providers evaluated by OPPE. The total estimated annual recurring labor cost per provider was $50.20. Zero of 12,854 providers evaluated were identified as outlier performers solely through the OPPE process. The total estimated annual recurring cost of administering OPPE nationally was $78.54 million. In radiology over the past 15 years, the use of error rates based on score-based peer review as an OPPE metric has been perceived as punitive and had an adverse effect on safety culture. CONCLUSION: OPPE is expensive to administer, inefficient at identifying outlier performers, diverts human resources away from potentially more effective improvement work, and has been associated with an adverse impact on safety culture in radiology.
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Atención a la Salud , Médicos , Humanos , Hospitales , Práctica Profesional , Estudios LongitudinalesRESUMEN
Continuous color polymorphisms can serve as a tractable model for the genetic and developmental architecture of traits. Here we investigated continuous color variation in Colias eurytheme and Colias philodice, two species of sulphur butterflies that hybridize in sympatry. Using quantitative trait locus (QTL) analysis and high-throughput color quantification, we found two interacting large-effect loci affecting orange-to-yellow chromaticity. Knockouts of red Malpighian tubules (red), likely involved in endosomal maturation, result in depigmented wing scales. Additionally, the transcription factor bric-a-brac can act as a modulator of orange pigmentation. We also describe the QTL architecture of other continuously varying traits, together supporting a large-X effect model where the genetic control of species-defining traits is enriched on sex chromosomes. This study sheds light on the range of possible genetic architectures that can underpin a continuously varying trait and illustrates the power of using automated measurement to score phenotypes that are not always conspicuous to the human eye.
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Mariposas Diurnas , Animales , Humanos , Mariposas Diurnas/genética , Simpatría , Pigmentación/genética , Sitios de Carácter Cuantitativo/genética , Polimorfismo Genético , Alas de AnimalesRESUMEN
Social factors can be a determinate for multiple health outcomes. We evaluated the association of numerous social factors on rates of influenza nonvaccination in a large pediatric primary and subspecialty care system. Methods: During the 2019-2020 influenza vaccination season, we calculated the nonvaccination rate for a pediatric healthcare system with both subspecialty and primary care practices. We compared influenza vaccination rates for factors that might affect health equity (patient gender, language preference, health insurance payer category, race and ethnicity, and estimated median household income based on zip code analysis) by creating simultaneous 95% confidence intervals using the Wilson method with continuity correction and a Bonferroni adjustment for the number of categories compared. Results: The overall influenza nonvaccination rate was 58.0% (59,375 not vaccinated of 102,377). Statistically significant differences in nonvaccination rate were present for the following health equity indicators: Spanish (75.6%) and Chinese Dialects (78.0%) > English (55.9%) speaking; Hispanic (70.1%) > many other race and ethnicities; Asian (51%) < many other race and ethnicities; Commercial (53.5%) < Public (71.2%) or Self (81.4%) pay; and lower (67.6%-79.1%) > higher median household income (52.9%-56.4%). Conclusions: Non-English language preference, Hispanic ethnicity, public insurance, and lower median household income are associated with a decreased likelihood of influenza vaccination. We are using these data to inform our key drivers to improve influenza vaccination in our system.
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PURPOSE: Hospital-acquired venous thromboembolisms (HA-VTEs) are increasingly common in pediatric inpatients and associated with significant morbidity and cost. The Braden QD Scale was created to predict the risk of hospital-acquired pressure injury (HAPI) and is used broadly in children's hospitals. This study evaluated the ability of the Braden QD Total score to predict risk of HA-VTE at a quaternary children's hospital. METHODS: To analyze the predictive potential of the Braden QD Total score and subscores for HA-VTEs, the researchers performed univariate logistic regressions. The increase in a patient's odds of developing an HA-VTE for every 1-point increase in each Braden QD score was evaluated. Each model was evaluated using a 5-fold cross-validated area-under-the-curve of the corresponding receiver operating characteristic curve (AUROC). RESULTS: This study analyzed 27,689 pediatric inpatients. HA-VTE occurred in 135 patients. The odds of HA-VTE incidence increased by 29% (odds ratio 1.29, 95% confidence interval [CI] 1.25-1.34, p < 0.001) for every 1-point increase in a patient's Braden QD Total score. The AUROC was 0.81 (95% CI 0.77-0.85). CONCLUSION: The Braden QD Scale is a predictor for HA-VTE, outperforming its original intended use for predicting HAPI and performing similarly to other HA-VTE predictive models. As the Braden QD Total score is currently recorded in the electronic health records of many children's hospitals, it could be practically and easily implemented as a tool to predict which patients are at risk for HA-VTE.
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Hospitalización , Enfermedad Iatrogénica , Tromboembolia Venosa , Niño , Registros Electrónicos de Salud , Hospitales Pediátricos , Humanos , Pronóstico , Medición de Riesgo , Factores de Riesgo , Tromboembolia Venosa/diagnósticoRESUMEN
INTRODUCTION: According to the National Healthcare Safety Network (NHSN) definitions for Catheter-associated urinary tract infections (CAUTI) rates, determination of the number of urinary catheter days must occur by calculating the number of catheters in place "for each day of the month, at the same time of day" but does not define at what time of day this occurs. The purpose of this review was to determine if a data collection time of 11 am would yield a greater collection of urinary catheter days than that done at midnight. METHODS: During a 20-month period, the number of urinary catheter days was calculated using once-a-day electronic measurements to identify a urinary catheter presence. We used data collected at 11 am and collected at midnight (our historic default) in comparing the calculated urinary catheter days and resultant CAUTI rates. RESULTS: There were 7,548 patients who had a urinary tract catheter. The number of urinary catheter days captured using the 11 am collection time was 15,425, and using the midnight collection time was 10,234, resulting in a 50.7% increase. The CAUTI rate per 1,000 urinary catheter days calculated using the 11 am collection method was 0.58, and using the midnight collection method was 0.88, a reduced CAUTI rate of 33.6%. CONCLUSION: The data collection time can significantly impact the calculation of urinary catheter days and on calculated CAUTI rates. Variations in how healthcare systems define their denominator per current National Healthcare Safety Network policy may result in significant differences in reported rates.
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In Heliconius butterflies, wing colour pattern diversity and scale types are controlled by a few genes of large effect that regulate colour pattern switches between morphs and species across a large mimetic radiation. One of these genes, cortex, has been repeatedly associated with colour pattern evolution in butterflies. Here we carried out CRISPR knockouts in multiple Heliconius species and show that cortex is a major determinant of scale cell identity. Chromatin accessibility profiling and introgression scans identified cis-regulatory regions associated with discrete phenotypic switches. CRISPR perturbation of these regions in black hindwing genotypes recreated a yellow bar, revealing their spatially limited activity. In the H. melpomene/timareta lineage, the candidate CRE from yellow-barred phenotype morphs is interrupted by a transposable element, suggesting that cis-regulatory structural variation underlies these mimetic adaptations. Our work shows that cortex functionally controls scale colour fate and that its cis-regulatory regions control a phenotypic switch in a modular and pattern-specific fashion.
Heliconius butterflies have bright patterns on their wings that tell potential predators that they are toxic. As a result, predators learn to avoid eating them. Over time, unrelated species of butterflies have evolved similar patterns to avoid predation through a process known as Müllerian mimicry. Worldwide, there are over 180,000 species of butterflies and moths, most of which have different wing patterns. How do genes create this pattern diversity? And do butterflies use similar genes to create similar wing patterns? One of the genes involved in creating wing patterns is called cortex. This gene has a large region of DNA around it that does not code for proteins, but instead, controls whether cortex is on or off in different parts of the wing. Changes in this non-coding region can act like switches, turning regions of the wing into different colours and creating complex patterns, but it is unclear how these switches have evolved. Butterfly wings get their colour from tiny structures called scales, which each have their own unique set of pigments. In Heliconius butterflies, there are three types of scales: yellow/white scales, black scales, and red/orange/brown scales. Livraghi et al. used a DNA editing technique called CRISPR to find out whether the cortex gene affects scale type. First, Livraghi et al. confirmed that deleting cortex turned black and red scales yellow. Next, they used the same technique to manipulate the non-coding DNA around the cortex gene to see the effect on the wing pattern. This manipulation turned a black-winged butterfly into a butterfly with a yellow wing band, a pattern that occurs naturally in Heliconius butterflies. The next step was to find the mutation responsible for the appearance of yellow wing bands in nature. It turns out that a bit of extra genetic code, derived from so-called 'jumping genes', had inserted itself into the non-coding DNA around the cortex gene, 'flipping' the switch and leading to the appearance of the yellow scales. Genetic information contains the instructions to generate shape and form in most organisms. These instructions evolve over millions of years, creating everything from bacteria to blue whales. Butterfly wings are visual evidence of evolution, but the way their genes create new patterns isn't specific to butterflies. Understanding wing patterns can help researchers to learn how genetic switches control diversity across other species too.
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Mariposas Diurnas/genética , Pigmentos Biológicos/genética , Alas de Animales/fisiología , Animales , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Color , FenotipoRESUMEN
INTRODUCTION: Despite being a participating Solutions for Patient Safety (SPS) children's hospital and having attempted implementation of the SPS hospital-acquired pressure injuries (HAPIs) prevention bundle, our hospital remained at a HAPI rate that was 3 times the mean for SPS participating children's hospitals. This performance led to the launch of an enterprise-wide HAPI reduction initiative in our organization. The purpose of this article is to describe the improvement initiative, the key drivers, and the resulting decrease in the SPS-reportable HAPI rate. METHODS: We designed a hospital-wide HAPI reduction initiative with actions grouped into 3 key driver areas: standardization, data transparency, and accountability. We paused all individual hospital unit-based HAPI reduction initiatives. We calculated the rate of SPS-reportable HAPIs per 1,000 patient days during both the pre- and postimplementation phases and compared mean rates using a 2-sided t test assuming unequal variances. RESULTS: The mean SPS-reportable HAPI rate for the preimplementation phase was 0.3489, and the postimplementation phase was 0.0609. The difference in rates was statistically significant (P < 0.00032). This result equates to an 82.5% reduction in HAPI rate. CONCLUSIONS: Having an institutional pause and retooled initiative to reduce HAPI with key drivers in the areas of standardization, data transparency, and accountability had a statistically significant reduction in our organization's SPS-reportable HAPI rate.
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BACKGROUND: Pediatric patients undergoing cardiac surgeries are at an increased surgical site infection (SSI) risk, given prolonged cardiopulmonary bypasses and delayed sternal closures. At one institution, the majority of cardiac patients developed SSIs during prolonged recoveries in the cardiovascular intensive care unit (CVICU). Although guidelines have been published to reduce SSIs in the perioperative period, there have been few guidelines to reduce the risk during prolonged hospital recoveries. The aim of this project was to study a postoperative SSI reduction care bundle, with a goal of reducing cardiac SSIs by 50%, from 3.4 to 1.7 per 100 procedures. METHODS: This project was conducted at a quaternary, pediatric academic center with a 20-bed CVICU. Historical control data were recorded from January 2013 through May 2015 and intervention/sustainment data from June 2015 through March 2017. A multidisciplinary SSI reduction team developed five key drivers that led to implementation of 11 postoperative SSI reduction care elements. Statistical process control charts were used to measure process compliance, and Pearson's chi-square test was used to determine differences in SSI rates. RESULTS: Prior to implementation, there were 27 SSIs in 799 pediatric cardiac surgeries (3.4 SSIs per 100 surgeries). After the intervention, SSIs significantly decreased to 5 in 570 procedures (0.9 SSIs per 100 surgeries; pâ¯=â¯0.0045). CONCLUSION: This project describes five key drivers and 11 elements that were dedicated to reducing the risk of SSI during prolonged CVICU recoveries from pediatric cardiac surgery, with demonstrated sustainability.
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Procedimientos Quirúrgicos Cardíacos/métodos , Paquetes de Atención al Paciente/métodos , Cuidados Posoperatorios/normas , Mejoramiento de la Calidad/organización & administración , Infección de la Herida Quirúrgica/prevención & control , Centros Médicos Académicos , Adolescente , Niño , Preescolar , Femenino , Hospitales Pediátricos , Humanos , Lactante , Unidades de Cuidados Intensivos/normas , Paquetes de Atención al Paciente/enfermería , Mejoramiento de la Calidad/normas , Factores de Riesgo , Infección de la Herida Quirúrgica/enfermeríaRESUMEN
STUDY DESIGN: Retrospective study. OBJECTIVE: To evaluate the perioperative outcome of dual attending surgeon strategy for severe adolescent idiopathic scoliosis (AIS) patients with Cobb angle more than or equal to 90°. SUMMARY OF BACKGROUND DATA: The overall complication rate for AIS remains significant and is higher in severe scoliosis. Various operative strategies had been reported for severe scoliosis. However the role of dual attending surgeon strategy in improving the perioperative outcome in severe scoliosis has not been investigated. METHODS: The patients were stratified into two groups, Cobb angles 90° to 100° (Group 1) and more than 100° (Group 2). Demographic, intraoperative, preoperative, and postoperative day 2 data were collected. The main outcome measures were intraoperative blood loss, use of allogeneic blood transfusion, operative time, duration of hospital stay postsurgery, and documentation of any perioperative complications. RESULTS: Eighty-five patients were recruited. The mean age for the whole cohort was 16.2â±â5.2 years old. The mean age of Group 1 was 16.7â±â5.7 and Group 2 was 15.6â±â4.8 years old. The majority of the patients in both groups were Lenke 2 curves with the average Cobb angle of 93.9â±â3.0° in Group 1 and 114.2â±â10.2° in Group 2. The average operative time was 198.5â±â47.5âminutes with an average blood loss of 1699.5â±â939.3âmL. The allogeneic blood transfusion rate was 17.6%. The average length of stay postoperation was 71.6â±â22.5âhours. When comparing the patients between Group 1 and Group 2, the operating time, total blood loss, allogeneic transfusion rate showed significant intergroup differences. Five complications were documented (one intraoperative seizure, one massive blood loss, one intraoperative loss of somatosensory evoked potential (SSEP) signal, and two superficial wound breakdown). CONCLUSION: Dual attending surgeon strategy in severe AIS more than or equal to 90° demonstrated an average operative time of 199âminutes, intraoperative blood loss of 1.7âL, postoperative hospital stay of 71.6âhours, and a complication rate of 5.9% (5/85 patients). Curves with Cobb angle more than 100° lead to longer operating time, greater blood loss, and allogeneic transfusion rate. LEVEL OF EVIDENCE: 4.
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Cuerpo Médico de Hospitales/tendencias , Atención Perioperativa/tendencias , Escoliosis/cirugía , Fusión Vertebral/tendencias , Cirujanos/tendencias , Adolescente , Adulto , Pérdida de Sangre Quirúrgica/prevención & control , Transfusión Sanguínea/tendencias , Niño , Femenino , Humanos , Tiempo de Internación/tendencias , Masculino , Tempo Operativo , Atención Perioperativa/métodos , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Escoliosis/diagnóstico por imagen , Fusión Vertebral/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to compare the perioperative outcome of posterior spinal fusion (PSF) between overweight (OW) adolescent idiopathic scoliosis (AIS) patients and the healthy-weight (HW) patients using propensity score matching analysis. SUMMARY OF BACKGROUND DATA: Obesity was found to increase postoperative surgical complications compared with the nonobese group. In scoliosis correction surgery, association of OW and perioperative risks had been explored, but most studies were retrospective in nature. METHODS: From 374 patients, two comparable groups were matched using propensity score matching analysis with one-to-one nearest neighbor matching and a caliper of 0.2. There were 46 HW and OW patients in each group. The main outcome measures were intraoperative blood loss, use of allogeneic blood transfusion, operative time, duration of hospital stay post-surgery, total patient-controlled analgesia (PCA) morphine usage, perioperative complications, side bending flexibility (SBF), and correction rate (%). RESULTS: The mean age was 13.3â±â1.7 and 13.2â±â1.7 years for HW and OW groups, respectively. The majority of the patients were Lenke 1 curves; 32.6% (HW) and 26.1% (OW) with an average Cobb angle of 69.0â±â19.1° and 68.8â±â18.4° for each group, respectively. The two groups were comparable. The operation time was 145.2â±â42.2 and 154.4â±â48.3âminutes for HW and OW groups, respectively (Pâ>â0.05). The intraoperative blood loss was almost similar in both groups; 955.1â±â497.7âmL (HW group) and 1011.8â±â552.7âmL (OW group) (Pâ>â0.05). Total PCA morphine used was higher in OW group (30.4â±â22.7âmg) than in the HW group (16.2â±â11.3âmg). No complication was observed in HW group, while in OW group, one patient (2.2%) developed intraoperative seizure. CONCLUSION: OW AIS patients (≥85th percentile) had similar mean operative time, intraoperative blood loss, allogeneic transfusion rate, length of stay, and perioperative complications compared with HW AIS patients. LEVEL OF EVIDENCE: 3.