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OBJECTIVES: To identify and geolocate pediatric post-acute care (PAC) facilities in the United States. DESIGN: Cross-sectional survey using both online resources and telephone inquiry. SETTING: All 50 U.S. states surveyed from June 2022 to May 2023. Care sites identified via state regulatory agencies and the Centers for Medicare & Medicaid Services. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Number, size, and type of facility, scope of practice, and type of care provided. One thousand three hundred fifty-five facilities were surveyed; of these, 18.6% (252/1355) were pediatric-specific units or adult facilities accepting some pediatric patients. There were 109 pediatric-specific facilities identified within 39 U.S. states. Of these, 38 were freestanding with all accepting children with tracheostomies, 97.4% (37/38) accepting those requiring mechanical ventilation via tracheostomy, and 81.6% (31/38) accepting those requiring parenteral nutrition. The remaining 71 facilities were adult facilities with embedded pediatric units or children's hospitals with 88.7% (63/71), 54.9% (39/71), and 54.9% (39/71), accepting tracheostomies, mechanical ventilation via tracheostomy, and parenteral nutrition, respectively. Eleven states lacked any pediatric-specific PAC units or facilities. CONCLUSIONS: The distribution of pediatric PAC is sparse and uneven across the United States. We present an interactive map and database describing these facilities. These data offer a starting point for exploring the consequences of pediatric PAC supply.
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Atención Subaguda , Humanos , Estados Unidos , Estudios Transversales , Atención Subaguda/estadística & datos numéricos , Niño , Encuestas de Atención de la SaludRESUMEN
Importance: After the COVID-19 pandemic, there was a surge of pediatric respiratory syncytial virus (RSV) infections, but national data on hospitalization and intensive care unit use and advanced respiratory support modalities have not been reported. Objective: To analyze demographics, respiratory support modes, and clinical outcomes of children with RSV infections at tertiary pediatric hospitals from 2017 to 2023. Design, Setting, and Participants: This cross-sectional study evaluated children from 48 freestanding US children's hospitals registered in the Pediatric Health Information System (PHIS) database. Patients 5 years or younger with RSV from July 1, 2017, to June 30, 2023, were included. Each season was defined from July 1 to June 30. Prepandemic RSV seasons included 2017 to 2018, 2018 to 2019, and 2019 to 2020. The postpandemic season was delineated as 2022 to 2023. Exposure: Hospital presentation with RSV infection. Main Outcomes and Measures: Data on emergency department presentations, hospital or intensive care unit admission and length of stay, demographics, respiratory support use, mortality, and cardiopulmonary resuscitation were analyzed. Postpandemic season data were compared with prepandemic seasonal averages. Results: A total of 288â¯816 children aged 5 years or younger (median [IQR] age, 8.9 [3.3-21.5] months; 159â¯348 [55.2%] male) presented to 48 US children's hospitals with RSV from July 1, 2017, to June 30, 2023. Respiratory syncytial virus hospital presentations increased from 39â¯698 before the COVID-19 pandemic to 94â¯347 after the pandemic (P < .001), with 86.7% more hospitalizations than before the pandemic (50â¯619 vs 27â¯114; P < .001). In 2022 to 2023, children were older (median [IQR] age, 11.3 [4.1-26.6] months vs 6.8 [2.6-16.8] months; P < .001) and had fewer comorbidities (17.6% vs 21.8% of hospitalized patients; P < .001) than during prepandemic seasons. Advanced respiratory support use increased 70.1% in 2022 to 2023 (9094 vs 5340; P < .001), and children requiring high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV) were older than during prepandemic seasons (median [IQR] age for HFNC, 6.9 [2.7-16.0] months vs 4.6 [2.0-11.7] months; for NIV, 6.0 [2.1-16.5] months vs 4.3 [1.9-11.9] months). Comorbid conditions were less frequent after the pandemic across all respiratory support modalities (HFNC, 14.9% vs 19.1%, NIV, 22.0% vs 28.5%, invasive mechanical ventilation, 30.5% vs 38.0%; P < .001). Conclusions and Relevance: This cross-sectional study identified a postpandemic pediatric RSV surge that resulted in markedly increased hospital volumes and advanced respiratory support needs in older children with fewer comorbidities than prepandemic seasons. These clinical trends may inform novel vaccine allocation to reduce the overall burden during future RSV seasons.
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COVID-19 , Hospitalización , Infecciones por Virus Sincitial Respiratorio , Humanos , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/terapia , COVID-19/epidemiología , Estudios Transversales , Masculino , Lactante , Femenino , Preescolar , Hospitalización/estadística & datos numéricos , Estados Unidos/epidemiología , SARS-CoV-2 , Pandemias , Hospitales Pediátricos/estadística & datos numéricos , Recién Nacido , Respiración Artificial/estadística & datos numéricos , NiñoRESUMEN
BACKGROUND: After a stroke, poorly controlled blood pressure (BP) is associated with a higher risk of recurrent vascular events. Despite the importance of controlling BP to avert recurrent vascular events, fewer than half of stroke survivors in the United States achieve BP control. It is unclear to what extent insurance status affects BP levels after stroke. METHODS: We assessed BP control among adults with a history of stroke who participated in the National Health and Nutrition Examination Surveys from 1999 through 2016. The relationship between insurance type and BP level (low normal: <120/80 mmHg and normal: <140/90 mmHg) were evaluated using logistic regression before and after adjusting for sociodemographic characteristics and medical comorbidities for those <65 years and ≥ 65 years. RESULTS: Among 1646 adult stroke survivors (weighted n = 5,586,417), 30% had BP in the low normal range while 64% had BP in the normal range. Among 613 stroke survivors <65 years (weighted n = 2,396,980), only those with other government insurance (CHAMPVA, CHAMPUS/TRICARE) had better BP control than the uninsured (adjusted HR 2.68, 95% CI 0.99-7.25). Among 1033 participants ≥65 years (weighted n = 3,189,437), those with private insurance plus Medicare trended toward better normal BP compared to Medicare alone (adjusted HR 1.34, 95% CI 0.94-1.90). CONCLUSIONS: Only stroke survivors with CHAMPVA, CHAMPUS/TRICARE government insurance in the United States have lower odds of controlled BP compared to no insurance among those <65 years. Insurance alone does not improve BP control among stroke survivors.
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Presión Sanguínea , Accidente Cerebrovascular , Sobrevivientes , Humanos , Masculino , Femenino , Persona de Mediana Edad , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/economía , Estados Unidos/epidemiología , Anciano , Presión Sanguínea/fisiología , Sobrevivientes/estadística & datos numéricos , Hipertensión/epidemiología , Seguro de Salud/estadística & datos numéricos , Adulto , Encuestas Nutricionales , Cobertura del Seguro/estadística & datos numéricosRESUMEN
Accumulating evidence has implicated impaired extracellular matrix (ECM) clearance as a key factor in fibrotic disease. Despite decades of research elucidating the effectors of ECM clearance, relatively little is understood regarding the upstream regulation of this process. Collagen is the most abundant constituent of normal and fibrotic ECM in mammalian tissues. Its catabolism occurs through extracellular proteolysis and cell-mediated uptake of collagen fragments for intracellular degradation. Given the paucity of information regarding the regulation of this latter process, here we execute unbiased genome-wide screens to understand the molecular underpinnings of cell-mediated collagen clearance. Using this approach, we discover a mechanism through which collagen biosynthesis is sensed by cells internally and directly regulates clearance of extracellular collagen. The sensing mechanism appears to be dependent on endoplasmic reticulum-resident protein SEL1L and occurs via a noncanonical function of this protein. This pathway functions as a homeostatic negative feedback loop that limits collagen accumulation in tissues. In human fibrotic lung disease, the induction of this collagen clearance pathway by collagen synthesis is impaired, thereby contributing to the pathological accumulation of collagen in lung tissue. Thus, we describe cell-autonomous, rheostatic collagen clearance as an important pathway of tissue homeostasis.
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Colágeno , Matriz Extracelular , Animales , Humanos , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Fibrosis , Proteolisis , Pulmón/patología , Mamíferos/metabolismo , Proteínas/metabolismoRESUMEN
OBJECTIVE: Advances in management of congenital heart disease (CHD) have led to an increasing population of adults with CHD, many of whom require non-cardiac procedures. The objectives of this study were to describe the characteristics of these patients, their distribution among different hospital categories and the characteristics determining this distribution, and mortality rates following noncardiac procedures. METHODS: We retrospectively analysed 27 state inpatient databases. Encounters with CHD and non-cardiac procedures were included. The location of care was classified into two categories: hospitals with and without cardiac surgical programmes. Variables included were demographics, comorbidity index, mortality. Multivariable logistic regression was used to explore predictors for care in different locations. RESULTS: The cohort consisted of 12 944 encounters in 1206 hospitals. Most patients were cared for in hospitals with a cardiac surgical programme (78.1%). Patients presenting to hospitals with a cardiac surgical programme presented with higher comorbidity index (6 (IQR: 0-19) vs 2 (IQR: -3-14), p<0.001) than patients presenting to hospitals without a cardiac surgical programme. Mortality was higher in hospitals with cardiac surgical programmes compared with hospitals without cardiac surgical programmes (4.0% vs 2.3%, p<0.001). Factors associated with provision of care at a hospital with a cardiac surgical programme were comorbidity index (>7: OR 2.01 (95% CI 1.83 to 2.21), p<0.001; 2-7: OR 1.59 (95% CI 1.41 to 1.79), p<0.001) and age (18-44 years: OR 1.43 (95% CI 1.26 to 1.62), p<0.001; 45-64 years: OR 1.21 (95% CI 1.08 to 1.34), p<0.001). CONCLUSION: Adults with CHD undergoing non-cardiac procedures are mainly cared for in hospitals with a cardiac surgical programme and have greater comorbidities and higher mortality than those in centres without cardiac surgical programmes. Risk stratification and locoregional accessibility need further assessment to fully understand admission patterns.
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Cardiopatías Congénitas , Humanos , Adulto , Adolescente , Adulto Joven , Estudios Retrospectivos , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/terapia , Hospitalización , Hospitales , Pacientes InternosRESUMEN
Using the US EPA's Grants Reporting and Tracking System (GRTS), we test if completion of best management practices (BMPs) through the Clean Water Act Section (§)319 National Nonpoint Source Program was associated with a decreasing trend in total suspended solids (TSS) load (metric tons/year). The study area chosen had 21 completed projects in the Cuyahoga River watershed in northeastern Ohio from 2000 to 2018. The §319 projects ranged from dam removal, floodplain/wetland restoration to stormwater projects. There was an overall decreasing trend in TSS loads. We identified three phases of project implementation and completion, where phase 1 had ongoing projects, but none completed (2000-2004). The steepest decrease in loads, identified as phase 2 (2005-2011), was associated with completion of low-head dam modification and removal projects on the mainstem of the Cuyahoga River. A likely decreasing trend was associated with projects completed in the tributaries, such as natural channel design restoration and stormwater green infrastructure (phase 3). Pairing sediment reduction estimates from projects with the river's flow normalized TSS loading trend, we estimated that the §319 effort may account for a small fraction of the TSS load reduction. Other stream restoration projects (non-§319) have also been done in the Cuyahoga watershed by other organizations. However, trying to compile these other projects is challenging in larger watersheds having multiple municipalities, agencies, and nonprofits doing restoration without better coordinated record keeping and monitoring. While a decreasing trend in a pollutant load is a desirable water quality outcome, determining what contributed to that trend remains difficult.
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Understanding the interactions between SARS-CoV-2 and host cell machinery may reveal new targets to treat COVID-19. We focused on an interaction between the SARS-CoV-2 ORF3A accessory protein and the CLIC-like chloride channel-1 (CLCC1). We found that ORF3A partially co-localized with CLCC1 and that ORF3A and CLCC1 could be co-immunoprecipitated. Since CLCC1 plays a role in the unfolded protein response (UPR), we hypothesized that ORF3A may also play a role in the UPR. Indeed, ORF3A expression triggered a transcriptional UPR that was similar to knockdown of CLCC1. ORF3A expression in 293T cells induced cell death and this was rescued by the chemical chaperone taurodeoxycholic acid (TUDCA). Cells with CLCC1 knockdown were partially protected from ORF3A-mediated cell death. CLCC1 knockdown upregulated several of the homeostatic UPR targets induced by ORF3A expression, including HSPA6 and spliced XBP1, and these were not further upregulated by ORF3A. Our data suggest a model where CLCC1 silencing triggers a homeostatic UPR that prevents cell death due to ORF3A expression.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , COVID-19/genética , Canales de Cloruro/genética , Respuesta de Proteína Desplegada/genética , Muerte CelularRESUMEN
OBJECTIVES: We studied hospital utilization patterns among children with technology dependence (CTD). We hypothesized that increasing pediatric healthcare concentration requires those caring for CTD to selectively navigate healthcare systems and travel greater distances for care. METHODS: Using 2017 all-encounter datasets from 6 US states, we identified CTD visits defined by presence of a tracheostomy, gastrostomy, or intraventricular shunt. We calculated pediatric Hospital Capability Indices for hospitals and mapped distances between patient residence, nearest hospital, and encounter facility. RESULTS: Thirty-five percent of hospitals never saw CTD. Of 37 108 CTD encounters within the remaining 543 hospitals, most emergency visits (70.0%) and inpatient admissions (85.3%) occurred within 34 (6.3%) high capability centers. Only 11.7% of visits were to the closest facility, as CTD traveled almost 4 times further to receive care. When CTD bypassed nearer facilities, they were 10 times more likely to travel to high-capability centers (95% confidence interval: 9.43-10.8), but even those accessing low-capability facilities bypassed less capable, geographically closer hospitals. Transfer was more likely in nearest and low-capability facility encounters. CTD with Medicaid insurance, Black race, or from lower socioeconomic communities had lower odds of encounters at high-capability centers and of bypassing a closer institution than those with white race, private insurance, or from advantaged communities. CONCLUSIONS: Children with technology dependence routinely bypass closer hospitals to access care in facilities with higher pediatric capability. This access behavior leaves many hospitals unfamiliar with CTD, which results in greater travel but less transfers and may be influenced by sociodemographic factors.
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Atención a la Salud , Hospitalización , Estados Unidos , Niño , Humanos , Medicaid , Hospitales , Viaje , Accesibilidad a los Servicios de SaludRESUMEN
Epigenetic mechanisms regulate the multilineage differentiation capacity of hematopoietic stem cells (HSCs) into a variety of blood and immune cells. Mapping the chromatin dynamics of functionally defined cell populations will shed mechanistic insight into 2 major, unanswered questions in stem cell biology: how does epigenetic identity contribute to a cell type's lineage potential, and how do cascades of chromatin remodeling dictate ensuing fate decisions? Our recent work revealed evidence of multilineage gene priming in HSCs, where open cis-regulatory elements (CREs) exclusively shared between HSCs and unipotent lineage cells were enriched for DNA binding motifs of known lineage-specific transcription factors. Oligopotent progenitor populations operating between the HSCs and unipotent cells play essential roles in effecting hematopoietic homeostasis. To test the hypothesis that selective HSC-primed lineage-specific CREs remain accessible throughout differentiation, we used ATAC-seq to map the temporal dynamics of chromatin remodeling during progenitor differentiation. We observed epigenetic-driven clustering of oligopotent and unipotent progenitors into distinct erythromyeloid and lymphoid branches, with multipotent HSCs and MPPs associating with the erythromyeloid lineage. We mapped the dynamics of lineage-primed CREs throughout hematopoiesis and identified both unique and shared CREs as potential lineage reinforcement mechanisms at fate branch points. Additionally, quantification of genome-wide peak count and size revealed overall greater chromatin accessibility in HSCs, allowing us to identify HSC-unique peaks as putative regulators of self-renewal and multilineage potential. Finally, CRISPRi-mediated targeting of ATACseq-identified putative CREs in HSCs allowed us to demonstrate the functional role of selective CREs in lineage-specific gene expression. These findings provide insight into the regulation of stem cell multipotency and lineage commitment throughout hematopoiesis and serve as a resource to test functional drivers of hematopoietic lineage fate.
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Cromatina , Hematopoyesis , Cromatina/genética , Cromatina/metabolismo , Hematopoyesis/genética , Células Madre Hematopoyéticas/metabolismo , Diferenciación Celular/genética , Linaje de la Célula/genéticaRESUMEN
OBJECTIVE: To describe the relationship between neighborhood poverty and geographic access to pediatric inpatient care. METHODS: This is a retrospective, cross-sectional study using 2017-18 hospital and demographic data, as well as geographic data from the 2010 census. Acute care hospitals in 17 states were included, comprising approximately one-third of the national population. The main outcome was distance to capable pediatric hospital care by neighborhood Area Deprivation Index (ADI), both overall and by urbanicity. RESULTS: Median distance to pediatric hospital care increased linearly with poverty across ADI national deciles (Pearson coefficient of 0.986; P < .001). The most advantaged neighborhoods were a median of 2.5 miles from the nearest pediatric capable hospital (interquartile range [IQR] 1.2-5.6) while those in the most disadvantaged were a median of 13.8 miles away (IQR 3.3-35.9; P < .001). The nearest hospital admitted children in 51.17% (7927) of advantaged neighborhoods (lowest national ADI quintile) and only 26.02% (3729) of disadvantaged neighborhoods (highest national ADI quintile). The association between poverty and median distance to care was observed in rural, suburban, and urban census block groups (P < .001 for all trends). In suburban neighborhoods, children from the most disadvantaged neighborhoods were 3 times as likely as children from the most advantaged neighborhoods to live more than 20 miles from pediatric inpatient care (27.85%, 456,533 of children from bottom quintile neighborhoods vs 9.24%, 259,787 of children from top quintile neighborhoods, P < .001). CONCLUSIONS: Distances to capable pediatric hospital care are greater from poor than affluent neighborhoods. This carries potential implications for disparities in pediatric health outcomes.
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Hospitales Pediátricos , Características de la Residencia , Humanos , Niño , Estudios Retrospectivos , Estudios Transversales , Pobreza , Áreas de PobrezaRESUMEN
Accumulating evidence has implicated impaired extracellular matrix (ECM) clearance as a key factor in fibrotic disease. Despite decades of research elucidating the effectors of ECM clearance, relatively little is understood regarding the upstream regulation of this process. Collagen is the most abundant constituent of normal and fibrotic ECM in mammalian tissues. Its catabolism occurs through extracellular proteolysis and cell-mediated uptake of collagen fragments for intracellular degradation. Given the paucity of information regarding the regulation of this latter process, we executed unbiased genome-wide screens to understand the molecular underpinnings of cell-mediated collagen clearance. Using this approach, we discovered a previously unappreciated mechanism through which collagen biosynthesis is sensed by cells internally and directly regulates clearance of extracellular collagen. The sensing mechanism is dependent on endoplasmic reticulum-resident protein SEL1L and occurs via a noncanonical function of SEL1L. This pathway functions as a homeostatic negative feedback loop that limits collagen accumulation in tissues. In human fibrotic lung disease, the induction of this collagen clearance pathway by collagen synthesis is impaired, thereby contributing to the pathological accumulation of collagen in lung tissue. Thus cell-autonomous, rheostatic collagen clearance is a previously unidentified pathway of tissue homeostasis.
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This corrects the article DOI: 10.1103/PhysRevLett.129.165101.
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The dissipation of magnetized turbulence is an important paradigm for describing heating and energy transfer in astrophysical environments such as the solar corona and wind; however, the specific collisionless processes behind dissipation and heating remain relatively unconstrained by measurements. Remote sensing observations have suggested the presence of strong temperature anisotropy in the solar corona consistent with cyclotron resonant heating. In the solar wind, in situ magnetic field measurements reveal the presence of cyclotron waves, while measured ion velocity distribution functions have hinted at the active presence of cyclotron resonance. Here, we present Parker Solar Probe observations that connect the presence of ion-cyclotron waves directly to signatures of resonant damping in observed proton-velocity distributions using the framework of quasilinear theory. We show that the quasilinear evolution of the observed distribution functions should absorb the observed cyclotron wave population with a heating rate of 10^{-14} W/m^{3}, indicating significant heating of the solar wind.
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Background The type and location of hospitals where patients with congenital heart disease (CHD) undergo noncardiac procedures have not been investigated. This study aimed to describe (1) the characteristics of these patients, (2) the distribution of procedures among hospitals with and without a cardiac surgical program and travel distances, (3) the characteristics determining the distribution, and (4) mortality rates. Methods and Results This is a retrospective cohort analysis of inpatient data from the Center for Healthcare Information and Analysis of the Commonwealth of Massachusetts, Texas Healthcare Information Collection, and Health Care Cost and Utilization Project State Inpatient Database. Children <18 years old with CHD who underwent noncardiac procedures were included. Distances were calculated using the Haversine formula. Logistic regression was performed to evaluate the odds of a procedure at a hospital with a cardiac program. There were 7435 encounters at 235 hospitals analyzed. Most procedures (87.8%) occurred at hospitals with a cardiac program. Patients at a hospital without a cardiac program had simple CHD (72.4%) with <1% with single ventricle disease. At hospitals with a cardiac program, 56.8% had simple CHD, 35.4% complex CHD, and 7.8% single ventricle disease. The median distance traveled was 25.2 miles (interquartile range, 10.3-73.8 miles) to a hospital with a cardiac program and 14.6 miles (interquartile range, 6.2-37.4 miles) to a hospital without a cardiac program (P<0.001). Single ventricle disease (adjusted odds ratio [aOR], 16.25 [95% CI, 7.22-36.61]) and ≥6 chronic conditions (aOR, 1.81 [95% CI, 1.57-2.09]) were associated with performance at a hospital with a cardiac program. Mortality rate was 3.8%. Conclusions Patients with CHD are more likely to travel to a hospital with a cardiac program for noncardiac procedures than to a hospital without; especially patients with single ventricle disease, other complex CHD, and with ≥6 chronic conditions.
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Procedimientos Quirúrgicos Cardíacos , Cardiopatías Congénitas , Adolescente , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Niño , Bases de Datos Factuales , Hospitales , Humanos , Estudios RetrospectivosRESUMEN
White clover (Trifolium repens) is an allotetraploid pasture legume widely used in moist temperate climates, but its vulnerability to drought, grazing pressure and pests has restricted its wider use. A related species, Caucasian clover (Trifolium ambiguum), is a potential source of resistances to drought, cold, grazing pressure and pests that could potentially be transferred to white clover by interspecific hybridization. Although direct hybridization has been achieved with difficulty, the hybrids have not been easy to backcross for introgression breeding and no interspecific chromosome recombination has been demonstrated. The present work shows that interspecific recombination can be achieved by using Trifolium occidentale, one of the ancestral parents of T. repens, as a bridging species and that large white clover breeding populations carrying recombinant chromosomes can be generated. A 4x hybrid between T. ambiguum and T. occidentale was crossed with T. repens and then backcrossed for two generations. Five backcross hybrid plants with phenotypes appearing to combine traits from the parent species were selected for FISH-GISH analyses. Recombinant chromosome segments from T. ambiguum were found in all five plants, suggesting that recombination frequencies were significant and sufficient for introgression breeding. Despite early chromosome imbalances, the backcross populations were fertile and produced large numbers of seeds. These hybrids represent a major new resource for the breeding of novel resilient forms of white clover.
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BACKGROUND: Intermittent shortages of chemotherapeutics used to treat curable malignancies are a worldwide problem that increases patient mortality. Although multiple strategies have been proposed for managing these shortages (eg, prioritizing patients by age, scarce treatment efficacy per volume, alternative treatment efficacy difference), critical clinical dilemmas arise when selecting a management strategy and understanding its impact. PATIENTS AND METHODS: We developed a model to compare the impact of different allocation strategies on overall survival during intermittent chemotherapy shortages and tested it using vincristine, which was recently scarce for 9 months in the United States. Demographic and treatment data were abstracted from 1,689 previously treated patients in our tertiary-care system; alternatives were abstracted from NCCN Clinical Practice Guidelines in Oncology for each disease and survival probabilities from the studies cited therein. Modeled survival was validated using SEER data. Nine-month shortages were modeled for all possible supply levels. Pairwise differences in 3-year survival and risk reductions were calculated for each strategy compared with standard practice (first-come, first-served) for each 50-mg supply increment, as were supply thresholds above which each strategy maintained survival similar to scenarios without shortages. RESULTS: A strategy prioritizing by higher vincristine efficacy per volume and greater alternative treatment efficacy difference performed best, improving survival significantly (P<.01) across 86.5% of possible shortages (relative risk reduction, 8.3%; 99% CI, 8.0-8.5) compared with standard practice. This strategy also maintained survival rates similar to a model without shortages until supply fell below 72.2% of the amount required to treat all patients, compared with 94.3% for standard practice. CONCLUSIONS: During modeled vincristine shortages, prioritizing patients by higher efficacy per volume and alternative treatment efficacy difference significantly improved survival over standard practice. This approach can help optimize allocation as intermittent chemotherapy shortages continue to arise.
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Antineoplásicos , Neoplasias , Antineoplásicos/efectos adversos , Humanos , Neoplasias/tratamiento farmacológico , Tasa de Supervivencia , Estados Unidos , Vincristina/uso terapéuticoRESUMEN
OBJECTIVES: To characterize the prevalence, associations, management, and outcomes of supraventricular tachycardia (SVT) in neonates with congenital diaphragmatic hernia (CDH). DESIGN: Retrospective chart and cardiology code review within a cohort of patients with CDH was used to define a subpopulation with atrial arrhythmia. SVT mechanisms were confirmed by electrocardiogram analysis. Cox proportional hazard regression identified risk factors for SVT and association with clinical outcomes. SETTING: Medical Surgical ICU in a single, tertiary center, Boston Children's Hospital. PATIENTS: Eligible patients included neonates presenting with classic Bochdalek posterolateral CDH between 2005 and 2017, excluding newborns with Morgagni hernia or late diagnoses of CDH (>28 d). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: SVT arose in 25 of 232 neonates with CDH, (11%); 14 of 25 infants (56%) had recurrent SVT; atrioventricular node-dependent tachycardia was the most frequent mechanism (32%). The majority (71%) of SVT episodes received intervention. Nine patients (36%) received preventative antiarrhythmic medications. SVT was associated with lower Apgar score at 1 min, structural heart disease, larger defect size, extracorporeal membrane oxygenation (ECMO) support, and prostaglandin therapy for ductal patency as well as hospital stay greater than or equal to 8 weeks and use of supplemental oxygen at discharge. CONCLUSIONS: SVT can occur in neonates with CDH and frequently requires treatment. Odds of occurrence are increased with greater CDH disease severity, ECMO, and prostaglandin use. In unadjusted logistic regression analysis, SVT was associated with adverse hospital outcomes, underscoring the importance of recognition and management in this vulnerable population.
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Hernias Diafragmáticas Congénitas , Taquicardia Supraventricular , Niño , Hernias Diafragmáticas Congénitas/complicaciones , Hernias Diafragmáticas Congénitas/terapia , Humanos , Lactante , Recién Nacido , Prevalencia , Prostaglandinas , Estudios Retrospectivos , Taquicardia Supraventricular/epidemiología , Taquicardia Supraventricular/etiología , Taquicardia Supraventricular/terapiaRESUMEN
Upon fertilization, the mammalian embryo must switch from dependence on maternal transcripts to transcribing its own genome, and in mice this involves the transient up-regulation of MERVL transposons and MERVL-driven genes at the two-cell stage. The mechanisms and requirement for MERVL and two-cell (2C) gene up-regulation are poorly understood. Moreover, this MERVL-driven transcriptional program must be rapidly shut off to allow two-cell exit and developmental progression. Here, we report that robust ribosomal RNA (rRNA) synthesis and nucleolar maturation are essential for exit from the 2C state. 2C-like cells and two-cell embryos show similar immature nucleoli with altered structure and reduced rRNA output. We reveal that nucleolar disruption via blocking RNA polymerase I activity or preventing nucleolar phase separation enhances conversion to a 2C-like state in embryonic stem cells (ESCs) by detachment of the MERVL activator Dux from the nucleolar surface. In embryos, nucleolar disruption prevents proper nucleolar maturation and Dux silencing and leads to two- to four-cell arrest. Our findings reveal an intriguing link between rRNA synthesis, nucleolar maturation, and gene repression during early development.