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1.
Artigo em Inglês | MEDLINE | ID: mdl-33118669

RESUMO

OBJECTIVE: To compare the PCV at several timepoints following packed red blood cell (pRBC) administration to anemic dogs and to assess if underlying cause of anemia or regenerative status significantly affects these measurements. DESIGN: Prospective, observational study from November 2016 to October 2017. SETTING: A small animal emergency and specialty hospital. ANIMALS: Forty-six anemic client-owned dogs that received a total of 50 pRBC transfusions for management of anemia. INTERVENTIONS: Blood was collected, and a PCV was obtained prior to pRBC transfusion (T0), immediately after (T1), 30 minutes after (T2), 1 hour after (T3), 2 hours after (T4), and 4 hours after (T5) the transfusion. Underlying causes of anemia were classified as hemorrhage, hemolysis, and ineffective erythropoiesis. Dogs were also categorized in regard to regenerative status of anemia and the presence or absence of expected continued blood loss or destruction. MEASUREMENTS AND MAIN RESULTS: The mean PCV at T0 was 0.15 L/L (15%). After administration of a pRBC transfusion, the mean PCV at T1 was 0.28 L/L (28%). For all other timepoints (T2, T3, T4, and T5), the mean PCV was 0.27 L/L (27%). The PCV did not change significantly over time post-transfusion (P = 0.184), and no pairwise combinations of times differed significantly (paired t-tests; P > 0.05 for all). When dogs were categorized via regeneration status and continued blood loss or hemolysis, results were consistent. CONCLUSIONS: There was no significant change in PCV from the value obtained immediately after pRBC transfusion up to 4 hours post-transfusion in dogs with several different causes of anemia. These results suggest that obtaining a PCV immediately after administering a pRBC transfusion to an anemic dog may be just as reliable as obtaining a measurement 2 hours after the transfusion. This remains true for dogs with expected continued red blood cell loss or destruction.

2.
Plant J ; 103(4): 1263-1274, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32623778

RESUMO

Interactions between plant-parasitic nematodes and their hosts are mediated by effectors, i.e. secreted proteins that manipulate the plant to the benefit of the pathogen. To understand the role of effectors in host adaptation in nematodes, we analysed the transcriptome of Heterodera sacchari, a cyst nematode parasite of rice (Oryza sativa) and sugarcane (Saccharum officinarum). A multi-gene phylogenetic analysis showed that H. sacchari and the cereal cyst nematode Heterodera avenae share a common evolutionary origin and that they evolved to parasitise monocot plants from a common dicot-parasitic ancestor. We compared the effector repertoires of H. sacchari with those of the dicot parasites Heterodera glycines and Globodera rostochiensis to understand the consequences of this transition. While, in general, effector repertoires are similar between the species, comparing effectors and non-effectors of H. sacchari and G. rostochiensis shows that effectors have accumulated more mutations than non-effectors. Although most effectors show conserved spatiotemporal expression profiles and likely function, some H. sacchari effectors are adapted to monocots. This is exemplified by the plant-peptide hormone mimics, the CLAVATA3/EMBRYO SURROUNDING REGION-like (CLE) effectors. Peptide hormones encoded by H. sacchari CLE effectors are more similar to those from rice than those from other plants, or those from other plant-parasitic nematodes. We experimentally validated the functional significance of these observations by demonstrating that CLE peptides encoded by H. sacchari induce a short root phenotype in rice, whereas those from a related dicot parasite do not. These data provide a functional example of effector evolution that co-occurred with the transition from a dicot-parasitic to a monocot-parasitic lifestyle.

3.
Plant J ; 103(6): 2263-2278, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32593210

RESUMO

Potato tuber formation is a secondary developmental programme by which cells in the subapical stolon region divide and radially expand to further differentiate into starch-accumulating parenchyma. Although some details of the molecular pathway that signals tuberisation are known, important gaps in our knowledge persist. Here, the role of a member of the TERMINAL FLOWER 1/CENTRORADIALIS gene family (termed StCEN) in the negative control of tuberisation is demonstrated for what is thought to be the first time. It is shown that reduced expression of StCEN accelerates tuber formation whereas transgenic lines overexpressing this gene display delayed tuberisation and reduced tuber yield. Protein-protein interaction studies (yeast two-hybrid and bimolecular fluorescence complementation) demonstrate that StCEN binds components of the recently described tuberigen activation complex. Using transient transactivation assays, we show that the StSP6A tuberisation signal is an activation target of the tuberigen activation complex, and that co-expression of StCEN blocks activation of the StSP6A gene by StFD-Like-1. Transcriptomic analysis of transgenic lines misexpressing StCEN identifies early transcriptional events in tuber formation. These results demonstrate that StCEN suppresses tuberisation by directly antagonising the function of StSP6A in stolons, identifying StCEN as a breeding marker to improve tuber initiation and yield through the selection of genotypes with reduced StCEN expression.

4.
Curr Biol ; 30(3): 421-431.e2, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-31866369

RESUMO

The origin of trees and forests in the Mid Devonian (393-383 Ma) was a turning point in Earth history, marking permanent changes to terrestrial ecology, geochemical cycles, atmospheric CO2 levels, and climate. However, how all these factors interrelate remains largely unknown. From a fossil soil (palaeosol) in the Catskill region near Cairo NY, USA, we report evidence of the oldest forest (mid Givetian) yet identified worldwide. Similar to the famous site at Gilboa, NY, we find treefern-like Eospermatopteris (Cladoxylopsida). However, the environment at Cairo appears to have been periodically drier. Along with a single enigmatic root system potentially belonging to a very early rhizomorphic lycopsid, we see spectacularly extensive root systems here assigned to the lignophyte group containing the genus Archaeopteris. This group appears pivotal to the subsequent evolutionary history of forests due to possession of multiple advanced features and likely relationship to subsequently dominant seed plants. Here we show that Archaeopteris had a highly advanced root system essentially comparable to modern seed plants. This suggests a unique ecological role for the group involving greatly expanded energy and resource utilization, with consequent influence on global processes much greater than expected from tree size or rooting depth alone.

5.
BMJ Open ; 9(12): e030525, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31874871

RESUMO

OBJECTIVES: To understand complaint risk among mental health practitioners compared with physical health practitioners. DESIGN: Retrospective cohort study, using incidence rate ratios (IRRs) to analyse complaint risk and a multivariate regression model to identify predictors of complaints. SETTING: National study using complaints data from health regulators in Australia. PARTICIPANTS: All psychiatrists and psychologists ('mental health practitioners') and all physicians, optometrists, physiotherapists, osteopaths and chiropractors ('physical health practitioners') registered to practice in Australia between 2011 and 2016. OUTCOME MEASURES: Incidence rates, source and nature of complaints to regulators. RESULTS: In total, 7903 complaints were lodged with regulators over the 6-year period. Most complaints were lodged by patients and their families. Mental health practitioners had a complaint rate that was more than twice that of physical health practitioners (complaints per 1000 practice years: psychiatrists 119.1 vs physicians 48.0, p<0.001; psychologists 21.9 vs other allied health 7.5, p<0.001). Their risk of complaints was especially high in relation to reports, records, confidentiality, interpersonal behaviour, sexual boundary breaches and the mental health of the practitioner. Among mental health practitioners, male practitioners (psychiatrists IRR: 1.61, 95% CI 1.39 to 1.85; psychologists IRR: 1.85, 95% CI 1.65 to 2.07) and older practitioners (≥65 years compared with 36-45 years: psychiatrists IRR 2.37, 95% CI 1.95 to 2.89; psychologists IRR 1.78, 95% CI 1.47 to 2.14) were at increased risk of complaints. CONCLUSIONS: Mental health practitioners were more likely to be the subject of complaints than physical health practitioners. Areas of increased risk are related to professional ethics, communication skills and the health of mental health practitioners themselves. Further research could usefully explore whether addressing these risk factors through training, professional development and practitioner health initiatives may reduce the risk of complaints about mental health practitioners.

6.
J Exp Bot ; 70(20): 5703-5714, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31328229

RESUMO

For many potato cultivars, tuber yield is optimal at average daytime temperatures in the range 14-22 °C. Above this range, tuber yield is reduced for most cultivars. We previously reported that moderately elevated temperature increases steady-state expression of the core circadian clock gene TIMING OF CAB EXPRESSION 1 (StTOC1) in developing tubers, whereas expression of the StSP6A tuberization signal is reduced, along with tuber yield. In this study we provide evidence that StTOC1 links environmental signalling with potato tuberization by suppressing StSP6A autoactivation in the stolons. We show that transgenic lines silenced in StTOC1 expression exhibit enhanced StSP6A transcript levels and changes in gene expression in developing tubers that are indicative of an elevated sink strength. Nodal cuttings of StTOC1 antisense lines displayed increased tuber yields at moderately elevated temperatures, whereas tuber yield and StSP6A expression were reduced in StTOC1 overexpressor lines. Here we identify a number of StTOC1 binding partners and demonstrate that suppression of StSP6A expression is independent of StTOC1 complex formation with the potato homolog StPIF3. Down-regulation of StTOC1 thus provides a strategy to mitigate the effects of elevated temperature on tuber yield.


Assuntos
Proteínas de Plantas/metabolismo , Tubérculos/fisiologia , Solanum tuberosum/fisiologia , Relógios Circadianos/genética , Relógios Circadianos/fisiologia , Temperatura Alta , Proteínas de Plantas/genética , Tubérculos/genética , Solanum tuberosum/genética , Temperatura
7.
J Air Waste Manag Assoc ; 69(9): 1015-1022, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31199717

RESUMO

A low-cost air sensor package was used to monitor indoor air quality (IAQ) in a classroom at the Albany Middle School in the San Francisco Bay Area of California. A rapid increase in carbon dioxide (CO2) was observed in the classroom as soon as it is occupied. When the classroom is unoccupied, the CO2 levels decay slowly toward the outdoor background level. All high CO2 concentrations observed inside the classroom, above the outdoor background, was due to exhaling of the occupants. The CO2 concentrations generally exceed the recommended level of 1000 ppb towards the end of the school day. The exceedances and slow decay may suggest that the ventilation rate in this school is not sufficient. The particulate level in the classroom was low until a distant wildfire advected large amount of particulate matter to the San Francisco Bay Area. Very high (10-15 times compared to the background) particle numbers (per m3 of particles with diameter >0.3 µm) were observed in the classroom during the wildfire. These particles were relatively small (0.3-1.0 µm) and the filters (MERV 8) of the ventilation system were unable to filter them out. Therefore, the measurements made by low-cost particle counters can inform the school administrators of adverse IAQ during future wildfire (or other combustion) events. The particle number was independent of the occupation before and during the wildfire suggesting that all observed particles were infiltrated into the classroom from outside. Consistent with previous studies, no appreciable increase in the local ambient CO2 background was observed during this distant wildfire event. Implications: Low-cost air sensors are effective in monitoring indoor air quality in classrooms. The CO2 levels in classrooms are mainly generated indoors due to exhalation of occupants. Concentration of CO2 generally exceed the recommended level of 1000 ppb towards the end of the school day. In contrast, the particulate matter mostly comes from outdoors and small particles penetrate though the filters normally used at schools. Distant wildfires do not increase the local CO2 background appreciably, but significantly increase the particulate matter concentrations both indoors and outdoors. Further investigations are needed to assure that ventilation rates in classrooms are sufficiently health protective.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental/métodos , Instituições Acadêmicas , Incêndios Florestais , California , Monitoramento Ambiental/economia
8.
Eur J Clin Pharmacol ; 75(8): 1089-1097, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30937470

RESUMO

BACKGROUND AND OBJECTIVES: Dosing of vancomycin in pediatric patients undergoing continuous venous-venous hemodiafiltration (CVVHDF) is challenging. Characterization of vancomycin pharmacokinetics can assist with dosing and attainment of goal serum concentrations. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Patients less than 19 years of age who received vancomycin and had post-dose vancomycin concentrations while undergoing CVVHDF were identified. Data collection included the following: patient demographics, vancomycin dosing and serum concentrations, CVVHDF variables, serum creatinine (SCR), blood urea nitrogen (BUN), albumin, hematocrit, and urine output. Fat-free mass was calculated. Data were summarized with descriptive statistical methods, and population pharmacokinetic analysis was performed with NONMEM 7.2 and PDx-Pop 5.2. Simulation was performed to identify dosing regimens with the highest percentage of goal serum concentration < 20 mg/L and AUC0-24:MIC ≥ 400 attainment. RESULTS: A total of 138 patients met study criteria (45.6% male, median age 4.9 years (IQR (1.0, 14.5))). Mean vancomycin dose was 14.3 ± 1.6 mg/kg/dose (19.5 ± 3.0 mg/kg/dose by FFM). Patients had a median of six (IQR 2, 12) vancomycin serum concentrations sampled 13.6 ± 8.4 h after the dose, and the mean vancomycin serum concentration was 11.3 ± 3.4 mg/L. Vancomycin pharmacokinetics were characterized by a two-compartment model with allometric scaling on fat-free mass and significant covariates of SCR, BUN, dialysate flow rate, and ultrafiltration rate on clearance. Simulation identified doses of 40-50 mg/kg/day that divided every 8-12 h had the highest percentage of patients with a serum concentration < 20 mg/L and an AUC0-24:MIC ≥ 400. CONCLUSIONS: Vancomycin pharmacokinetics are characterized by fat-free mass, serum creatinine, blood urea nitrogen, dialysate flow rate, and ultrafiltration rate in the pediatric CVVHDF population. Dosing of 40-50 mg/kg/day on fat-free mass divided every 8-12 h with frequent vancomycin serum sampling is recommended.


Assuntos
Antibacterianos/farmacocinética , Terapia de Substituição Renal Contínua , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/farmacocinética , Adolescente , Antibacterianos/administração & dosagem , Área Sob a Curva , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Taxa de Depuração Metabólica , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia , Vancomicina/administração & dosagem
9.
J Pediatr Pharmacol Ther ; 24(2): 107-116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019403

RESUMO

OBJECTIVE: Vancomycin is often used in the pediatric cardiac surgical population, but few pharmacokinetic data are available to guide dosing. METHODS: A retrospective, population pharmacokinetic study was performed for patients <19 years of age initiated on vancomycin after cardiac surgery in the cardiac intensive care unit from 2011-2016 in our institution. Patient data were summarized by using descriptive statistical methods, and population pharmacokinetic analysis was performed by using NONMEM. Simulation was performed to determine a dosing strategy that most frequently obtained an AUC0-24:MIC (minimum inhibitory concentration) ratio of >400. RESULTS: A total of 261 patients (281 cardiac surgical procedures, cardiopulmonary bypass 82.3%) met inclusion criteria (60.1% male, median age 0.31 [IQR, 0.07-0.77] years). Vancomycin (14.5 ± 1.7 mg/kg/dose) was administered at median postoperative day 9 (IQR, 4-14), with a mean serum concentration of 11.5 ± 5.5 mg/L at 8.9 ± 3.8 hours after a dose. Population pharmacokinetic analysis demonstrated that a 1-compartment proportional error model with allometrically scaled weight best fit the data, with creatinine clearance and postmenstrual age as significant covariates. Simulation identified that a dosing regimen of 20 mg/kg/dose every 8 hours was most likely to achieve an AUC0-24:MIC ratio > 400 at a mean trough serum concentration of 12.9 ± 3.2 mg/L. CONCLUSIONS: Vancomycin dosing in the postoperative pediatric cardiac surgical population should incorporate postmenstrual age and creatinine clearance. A vancomycin dose of 20 mg/kg every 8 hours is a reasonable empiric strategy.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30745380

RESUMO

The most appropriate vancomycin dosing strategy in pediatric patients weighing ≥70 kg (weight based versus non-weight based) to achieve an area under the concentration-time curve (AUC) of ≥400 mg·liter/h and a trough concentration of <20 mg/liter is not known. Population pharmacokinetic analysis determined that dosing of vancomycin should be weight based using fat-free mass, with appropriate adjustment for kidney dysfunction.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Vancomicina/administração & dosagem , Vancomicina/farmacocinética , Adolescente , Área Sob a Curva , Peso Corporal , Criança , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana
12.
Artigo em Inglês | MEDLINE | ID: mdl-30718247

RESUMO

This retrospective study included pediatric intensive care unit patients receiving continuous veno-venous hemodiafiltration (CVVHDF) being treated with cefepime. The free drug concentration above one time the MIC (fT>1×MIC) and four times a presumed MIC (fT>4×MIC) of 8 µg/ml were calculated. Four patients received doses ranging from 48 to 64 mg/kg of body weight every 6 to 12 h. Three patients achieved 100% fT>1×MIC, with the fourth patient achieving 98% fT>1×MIC. Therapeutic drug monitoring should be considered for critically ill patients receiving cefepime on CVVHDF.


Assuntos
Antibacterianos/farmacocinética , Cefepima/farmacocinética , Terapia de Substituição Renal Contínua , Lesão Renal Aguda/terapia , Antibacterianos/uso terapêutico , Cefepima/uso terapêutico , Pré-Escolar , Estado Terminal/terapia , Monitoramento de Medicamentos , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Estudos Retrospectivos
13.
J Patient Saf ; 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30480651

RESUMO

OBJECTIVE: The aim of the study was to describe the sources of notifications of concern ("notifications") regarding the health, performance, and conduct of health practitioners from 14 registered professions in Australia. METHODS: This retrospective cohort study analyzed 43,256 notifications lodged with the Australian Health Practitioner Regulation Agency and the Health Professional Councils Authority between 2011 and 2016. We used descriptive statistical analysis to describe the characteristics of these notifications, including their source, issue and domain, and subject. RESULTS: Patients and their relatives lodged more than three-quarters (78%) of notifications regarding clinical performance, including diagnosis, treatment, and communication. Fellow practitioners were a common source of notifications about advertising and titles. Self-reports commonly related to health impairments, such as mental illness or substance use. Other agencies played a role in reporting concerns about prescribing or supply of medicines. CONCLUSIONS: Various actors in the healthcare system play different roles in sketching the picture of healthcare quality and safety that notifications present to regulators. Improved understanding of which sources are most likely to raise which concerns may enhance regulators' ability to identify and respond to patient safety risks.

14.
PLoS One ; 13(10): e0202439, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30281600

RESUMO

INTRODUCTION: Vancomycin associated acute kidney injury (vAKI) is a well known complication in pediatric patients. Identification and characterization of the incidence and risk factors for vAKI in the pediatric population would assist clinicians in potentially preventing or mitigating vAKI. METHODS AND MATERIALS: A 6 year retrospective cohort study was designed. Patients were included if they were < 19 years of age, received vancomycin as inpatients, and had a baseline SCr and one other SCr drawn during and up to 72 hours after the discontinuation of vancomycin. Data collection included patient demographics, vancomycin doses and length of therapy, vancomycin serum concentrations, and concomitant medications. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to characterize acute kidney injury. Descriptive statistical methods were used and ordinal logistic regression was employed to determine variables significantly associated with vAKI. RESULTS: A total of 7,095 patients met study criteria (55.4% male, median age 4.1 years (IQR 0.67-11.2 years)). Mechanical ventilation was used in 7.9% (n = 563) and mortality was 4.9% (n = 344). A total of 153 concomitant medications were identified. A median of 5 (IQR 3-7) SCr values were obtained and median SCr prior to vancomycin was 0.39 (IQR 0.28-0.57) mg/dL (CrCl 134±58 mL/min/1.73m2). Vancomycin was administered for a median of 2 (IQR 1-3) days (14.9±1.6 mg/kg/dose). vAKI was present in 12.2% (n = 862: KDIGO stage 1 (8.30%, n = 589), KDIGO stage 2 (1.94%, n = 138) KDIGO stage 3 (1.89%, n = 134)). Mean vancomycin serum concentration at 6-8 hours after a dose for patients with vAKI (10.7±8.9 mg/L) was significantly, but not clinically different for patients with no vAKI (7.5±6.3 mg/L). (p<0.05) Ordinal logistic regression identified total dose of vancomycin, vancomycin administration in the intensive care unit, and concomitant medication administration as significant for vAKI. In particular, concomitant administration of several different medications, including nafcillin, clindamycin, and acetazolamide, were noted for strong associations with vAKI. (p<0.05). CONCLUSIONS: Moderate to severe acute kidney injury due to vancomycin is infrequent in children and associated with concomitant medication use and total dose of vancomycin. Serum vancomycin concentrations are not useful predictors of vAKI in the pediatric population.


Assuntos
Lesão Renal Aguda/terapia , Rim/efeitos dos fármacos , Vancomicina/toxicidade , Acetazolamida/administração & dosagem , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/mortalidade , Lesão Renal Aguda/patologia , Criança , Pré-Escolar , Clindamicina/administração & dosagem , Feminino , Mortalidade Hospitalar , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Rim/lesões , Rim/patologia , Modelos Logísticos , Masculino , Nafcilina/administração & dosagem , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , Vancomicina/sangue
16.
Pediatr Crit Care Med ; 19(10): 973-980, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30063652

RESUMO

OBJECTIVES: Describe the pharmacokinetics of vancomycin in pediatric patients undergoing extracorporeal membrane oxygenation and provide dosing recommendations to attain an area under the curve for 24 hours greater than 400 in this population. DESIGN: Retrospective, population pharmacokinetic analysis. SETTING: PICU of a large tertiary care children's hospital. INTERVENTIONS: Population pharmacokinetic analysis and simulation were performed with NONMEM v7.3 (Icon, PLC, Dublin, Ireland). PATIENTS: Patients less than 19 years old who received IV vancomycin and had serum vancomycin concentration monitoring while undergoing extracorporeal membrane oxygenation from January 1, 2011, to June 30, 2017. MEASUREMENTS AND MAIN RESULTS: A total of 93 patients met study criteria (male 51%, median age 0.64 yr [interquartile range 0.07-6.7 yr]). Mean estimated creatinine clearance was 65 ± 47 mL/min/1.73 m. Patients received 1,116 vancomycin doses (14.6 ± 1.9 mg/kg/dose) and had 433 vancomycin serum concentrations (13.6 ± 6.9 mg/L) at 13.2 ± 10.7 hours after a dose. A two-compartment pharmacokinetic model with allometrically scaled weight on clearance (0.75) and volumes of distribution (1) was developed. Serum creatinine, postmenstrual age were significant covariates for clearance, patient age for central volume of distribution, and albumin for peripheral volume of distribution. Simulation identified a doses of 25-30 mg/kg/dose every 12-24 hours as having the highest percentage of patients with an area under the curve for 24 hours greater than 400 with the highest percentage trough concentrations in the less than 15 mg/L range. CONCLUSIONS: A vancomycin dose of 25-30 mg/kg/dose every 12-24 hours with serum concentration monitoring is a reasonable empiric dosing strategy to obtain an area under the curve for 24 hours greater than 400 in pediatric extracorporeal membrane oxygenation patients.


Assuntos
Antibacterianos/farmacocinética , Oxigenação por Membrana Extracorpórea/métodos , Vancomicina/farmacocinética , Administração Intravenosa , Adolescente , Antibacterianos/administração & dosagem , Criança , Pré-Escolar , Estado Terminal/terapia , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Taxa de Depuração Metabólica , Estudos Retrospectivos , Vancomicina/administração & dosagem , Vancomicina/sangue
17.
Ther Drug Monit ; 40(5): 581-588, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29957666

RESUMO

BACKGROUND: Gentamicin pharmacokinetics may be altered in pediatric patients undergoing extracorporeal membrane oxygenation (ECMO). Description of gentamicin pharmacokinetics and relevant variables can improve dosing. METHODS: A retrospective population pharmacokinetic study was designed, and pediatric patients who received gentamicin while undergoing ECMO therapy over a period of 6 1/2 years were included. Data collection included the following: patient demographics, serum creatinine, albumin, hematocrit, gentamicin dosing and serum concentrations, urine output, and ECMO circuit parameters. Descriptive statistics were used to characterize the patient population. Population pharmacokinetic analysis was performed with NONMEM, and simulation was performed to identify empiric doses to achieve therapeutic serum concentrations. RESULTS: A total of 37 patients met study criteria (75.7% male patients), with a median age of 0.17 [interquartile range (IQR) 0.12-0.82] years. Primary indications for ECMO included the following: congenital diaphragmatic hernia (n = 17), persistent pulmonary hypertension (n = 5), and septic shock (n = 4). Patients received a total of 117 gentamicin doses [median 1.8 (IQR 1.4-2.9) mg/kg/dose] and had 125 serum concentrations measured at a median of 22.8 (IQR 15.8-25.5) hours after a dose. Population pharmacokinetic analysis identified a 2-compartment model with additive error as the best fit. Covariates included the following: allometrically scaled fat-free mass on clearance, central and peripheral volume of distribution (VDcentral and VDperipheral), and intercompartmental clearance; serum creatinine on clearance; ultrafiltration rate on central volume of distribution. Simulation identified dosage of 4-5 mg/kg/dose every 24 hours for neonates and infants as an acceptable empiric dosing regimen. Children and adolescents had elevated trough concentrations when dosed according to traditional dosing methods. CONCLUSIONS: Fat-free mass should be used to dose gentamicin in pediatric ECMO patients. Serum creatinine is a marker of gentamicin clearance and should be used to adjust gentamicin dosing in pediatric ECMO patients.


Assuntos
Oxigenação por Membrana Extracorpórea , Gentamicinas/farmacocinética , Creatinina/sangue , Feminino , Gentamicinas/sangue , Gentamicinas/urina , Hematócrito , Humanos , Lactente , Masculino , Estudos Retrospectivos , Albumina Sérica/metabolismo , Fatores de Tempo
18.
Nat Commun ; 9(1): 660, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29440736

RESUMO

Efforts to estimate the physical and economic impacts of future climate change face substantial challenges. To enrich the currently popular approaches to impact analysis-which involve evaluation of a damage function or multi-model comparisons based on a limited number of standardized scenarios-we propose integrating a geospatially resolved physical representation of impacts into a coupled human-Earth system modeling framework. Large internationally coordinated exercises cannot easily respond to new policy targets and the implementation of standard scenarios across models, institutions and research communities can yield inconsistent estimates. Here, we argue for a shift toward the use of a self-consistent integrated modeling framework to assess climate impacts, and discuss ways the integrated assessment modeling community can move in this direction. We then demonstrate the capabilities of such a modeling framework by conducting a multi-sectoral assessment of climate impacts under a range of consistent and integrated economic and climate scenarios that are responsive to new policies and business expectations.

19.
Proc Natl Acad Sci U S A ; 115(10): E2274-E2283, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29463716

RESUMO

Establishing the timescale of early land plant evolution is essential for testing hypotheses on the coevolution of land plants and Earth's System. The sparseness of early land plant megafossils and stratigraphic controls on their distribution make the fossil record an unreliable guide, leaving only the molecular clock. However, the application of molecular clock methodology is challenged by the current impasse in attempts to resolve the evolutionary relationships among the living bryophytes and tracheophytes. Here, we establish a timescale for early land plant evolution that integrates over topological uncertainty by exploring the impact of competing hypotheses on bryophyte-tracheophyte relationships, among other variables, on divergence time estimation. We codify 37 fossil calibrations for Viridiplantae following best practice. We apply these calibrations in a Bayesian relaxed molecular clock analysis of a phylogenomic dataset encompassing the diversity of Embryophyta and their relatives within Viridiplantae. Topology and dataset sizes have little impact on age estimates, with greater differences among alternative clock models and calibration strategies. For all analyses, a Cambrian origin of Embryophyta is recovered with highest probability. The estimated ages for crown tracheophytes range from Late Ordovician to late Silurian. This timescale implies an early establishment of terrestrial ecosystems by land plants that is in close accord with recent estimates for the origin of terrestrial animal lineages. Biogeochemical models that are constrained by the fossil record of early land plants, or attempt to explain their impact, must consider the implications of a much earlier, middle Cambrian-Early Ordovician, origin.


Assuntos
Evolução Biológica , Plantas/genética , Biodiversidade , Ecossistema , Fósseis/história , História Antiga , Filogenia , Plantas/classificação , Fatores de Tempo
20.
Curr Biol ; 28(5): 733-745.e2, 2018 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-29456145

RESUMO

The evolutionary emergence of land plant body plans transformed the planet. However, our understanding of this formative episode is mired in the uncertainty associated with the phylogenetic relationships among bryophytes (hornworts, liverworts, and mosses) and tracheophytes (vascular plants). Here we attempt to clarify this problem by analyzing a large transcriptomic dataset with models that allow for compositional heterogeneity between sites. Zygnematophyceae is resolved as sister to land plants, but we obtain several distinct relationships between bryophytes and tracheophytes. Concatenated sequence analyses that can explicitly accommodate site-specific compositional heterogeneity give more support for a mosses-liverworts clade, "Setaphyta," as the sister to all other land plants, and weak support for hornworts as the sister to all other land plants. Bryophyte monophyly is supported by gene concatenation analyses using models explicitly accommodating lineage-specific compositional heterogeneity and analyses of gene trees. Both maximum-likelihood analyses that compare the fit of each gene tree to proposed species trees and Bayesian supertree estimation based on gene trees support bryophyte monophyly. Of the 15 distinct rooted relationships for embryophytes, we reject all but three hypotheses, which differ only in the position of hornworts. Our results imply that the ancestral embryophyte was more complex than has been envisaged based on topologies recognizing liverworts as the sister lineage to all other embryophytes. This requires many phenotypic character losses and transformations in the liverwort lineage, diminishes inconsistency between phylogeny and the fossil record, and prompts re-evaluation of the phylogenetic affinity of early land plant fossils, the majority of which are considered stem tracheophytes.


Assuntos
Evolução Biológica , Embriófitas/anatomia & histologia , Embriófitas/genética , Filogenia
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