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Interactions between microorganisms and frugivorous insects can modulate fruit rot disease epidemiology. Insect feeding and/or oviposition wounds may create opportunities for fungal infection. Passive and active dispersal of fungal inoculums by adult insects also increases disease incidence. In fall-bearing raspberries and blackberries, such vectoring interactions could increase crop damage from the invasive pestiferous vinegar fly Drosophila suzukii (spotted-wing drosophila). Periods of peak D. suzukii activity are known to overlap with several species of primary fruit rot pathogen, particularly Botrytis cinerea and Cladosporium cladosporioides, and previous work indicates that larvae co-occur with and feed on various filamentous fungi at low rates. To further our understanding of the epidemiological consequences that may emerge from these associations, we surveyed the filamentous fungal community associated with adult D. suzukii, isolating and molecularly identifying fungi externally and internally (indicating feeding) from field-collected adults over 3 years. We isolated and identified 37 unique genera of fungi in total, including known raspberry pathogens. Most fungi were detected infrequently, and flies acquired and carried fungi externally at higher richness, frequency, and density relative to internally. In a worst-case scenario laboratory vectoring assay, D. suzukii adults were able to transfer B. cinerea and C. cladosporioides to sterile media at 0, 24, 48, and 72 h after exposure to sporulating cultures in Petri dishes. These results collectively suggest an adventitious vectoring association between D. suzukii and fruit rot fungi that has the potential to alter caneberry disease dynamics.
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Drosophila , Rubus , Animais , Feminino , Doenças das Plantas , Rubus/microbiologia , Larva , Frutas/microbiologia , Controle de Insetos/métodosRESUMO
The Early Pliocene is a crucial time period in carnivoran evolution. Holarctic carnivoran faunas suffered a turnover event at the Miocene-Pliocene boundary. This event is also observed in Africa but its onset is later and the process more drawn-out. Kanapoi is one of the earliest faunas in Africa to show evidence of a fauna that is more typical Pliocene than Miocene in character. The taxa recovered from Kanapoi are: Torolutra sp., Enhydriodon (2 species), Genetta sp., Helogale sp., Homotherium sp., Dinofelis petteri, Felis sp., and Parahyaena howelli. Analysis of the broader carnivoran context of which Kanapoi is an example shows that all these taxa are characteristic of Plio-Pleistocene African faunas, rather than Miocene ones. While some are still extant and some went extinct in the Early Pleistocene, P. howelli is unique in both originating and going extinct in the Early Pliocene.
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Biodiversidade , Evolução Biológica , Carnívoros , Animais , Fósseis , Quênia , PaleontologiaRESUMO
OBJECTIVES: Rapid bedside assessment of left ventricular (LV) function can aid in the evaluation of the critically ill patient and guide clinical management. Our primary hypothesis was that mitral valve E-point septal separation measurements would correlate with contemporaneous fractional shortening measurements of LV systolic function when performed by emergency physicians. Our secondary hypothesis was that E-point septal separation as a continuous variable would predict fractional shortening using a linear regression model. METHODS: We studied a prospective convenience sample of patients undergoing a sequence of LV systolic function measurements during a 3-month period at a suburban academic emergency department with a census of 114,000 patients. The sample included adult emergency department patients who were determined by the treating emergency physician to have 1 or more clinical indications for bedside LV systolic function assessment. Investigators performed bedside M-mode cardiac sonographic measurements of fractional shortening and E-point septal separation using the parasternal long-axis window. The sequence of LV systolic function measurements was randomized. RESULTS: A total of 103 patients were enrolled. The Pearson correlation coefficient for E-point septal separation and fractional shortening measurements was -0.59 (P< .0001). Linear regression analysis performed for E-point septal separation with fractional shortening as the dependent variable yielded an R2 value of 0.35. CONCLUSIONS: E-point septal separation and fractional shortening measurements had a moderate negative correlation. E-point septal separation, when used as a continuous variable in a linear regression model, did not reliably predict fractional shortening.
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Septos Cardíacos/diagnóstico por imagem , Septos Cardíacos/fisiopatologia , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Função Ventricular Esquerda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Emergências , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sístole , Ultrassonografia , Adulto JovemRESUMO
Continuing education programs that increase nursing knowledge and collaboration are needed across urban and rural settings. A survey was distributed to determine interest in nursing grand rounds and preferred educational modalities at two unaffiliated hospitals. Results revealed that nurses from the urban and rural hospitals were interested in nursing grand rounds as a recorded online offering, thus providing valuable information used to develop a nursing grand rounds program.
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Educação Continuada em Enfermagem , Hospitais Rurais , Hospitais Urbanos , Avaliação em Enfermagem , Recursos Humanos de Enfermagem Hospitalar/psicologia , Centros Médicos Acadêmicos , Adulto , Atitude do Pessoal de Saúde , Competência Clínica/estatística & dados numéricos , Estudos Transversais , Emprego/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Meio-Oeste dos Estados Unidos , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Especialidades de Enfermagem/estatística & dados numéricos , Inquéritos e Questionários , Visitas de Preceptoria/métodos , Recursos HumanosRESUMO
INTRODUCTION: Key measures in preventing spread of the virus that causes coronavirus disease 2019 (COVID-19) are social distancing and stay-at-home mandates. These measures along with other stressors have the potential to increase incidences of intimate partner violence (IPV), sexual assault, and child maltreatment. METHODS: We performed a retrospective review of county police dispatches, emergency department (ED) visits, Sexual Assault Nurse Examiner (SANE) consults, Domestic Violence Healthcare Project (DVHP) team consults, and Child Protection Team consults at a large, tertiary, Level I trauma center. We queried International Classification of Diseases Revision 10 codes most specific to IPV, sexual assault, and child maltreatment from March-October 2020 compared to 2019. Similarly, the number of consults performed by SANE, DVHP, and our Child Protection Team were collected. We compared all ED visits and consultations to total ED visits for the reviewed time period. Finally, the total number of calls and referrals to a child advocacy center and resource call line for victims were recorded during this timeframe. RESULTS: Police dispatches for IPV-related assaults increased by 266 reports from 2019 to 2020 (P = 0.015). Emergency department visits related to IPV increased from 0.11% of visits in 2019 to 0.15% in 2020 (P = 0.032), and DVHP consults increased from 0.31% in 2019 to 0.48% in 2020 of ED visits in the first three months (P < 0.001). Child maltreatment visits increased from 0.47% of visits in 2019 to 0.81% of visits in 2020 (P = 0.028), and a higher percentage of patients required Child Protection team consults from 1% in 2019 to 1.6% in 2020 (P = 0.004). Sexual assault-related visits and SANE consults both showed a small increase that was not statistically significant. Fewer calls and referrals were made to our child advocacy center and resource call line, decreasing by 99 referrals and 252 calls, respectively. CONCLUSION: Despite decreased ED volumes throughout the pandemic, we observed an increase in police dispatches, ED visits, and utilization of hospital consult services related to IPV and child maltreatment following the initiation of stay-at-home orders. However, use of community resources, such as the local child advocacy center, declined.
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COVID-19 , Maus-Tratos Infantis , Violência Doméstica , Violência por Parceiro Íntimo , Delitos Sexuais , COVID-19/epidemiologia , Criança , Violência Doméstica/prevenção & controle , Serviço Hospitalar de Emergência , HumanosRESUMO
The Early Pleistocene was a critical time period in the evolution of eastern African mammal faunas, but fossil assemblages sampling this interval are poorly known from Ethiopia's Afar Depression. Field work by the Hadar Research Project in the Busidima Formation exposures (~2.7-0.8 Ma) of Hadar in the lower Awash Valley, resulted in the recovery of an early Homo maxilla (A.L. 666-1) with associated stone tools and fauna from the Maka'amitalu basin in the 1990s. These assemblages are dated to ~2.35 Ma by the Bouroukie Tuff 3 (BKT-3). Continued work by the Hadar Research Project over the last two decades has greatly expanded the faunal collection. Here, we provide a comprehensive account of the Maka'amitalu large mammals (Artiodactyla, Carnivora, Perissodactyla, Primates, and Proboscidea) and discuss their paleoecological and biochronological significance. The size of the Maka'amitalu assemblage is small compared to those from the Hadar Formation (3.45-2.95 Ma) and Ledi-Geraru (2.8-2.6 Ma) but includes at least 20 taxa. Bovids, suids, and Theropithecus are common in terms of both species richness and abundance, whereas carnivorans, equids, and megaherbivores are rare. While the taxonomic composition of the Maka'amitalu fauna indicates significant species turnover from the Hadar Formation and Ledi-Geraru deposits, turnover seems to have occurred at a constant rate through time as taxonomic dissimilarity between adjacent fossil assemblages is strongly predicted by their age difference. A similar pattern characterizes functional ecological turnover, with only subtle changes in dietary proportions, body size proportions, and bovid abundances across the composite lower Awash sequence. Biochronological comparisons with other sites in eastern Africa suggest that the taxa recovered from the Maka'amitalu are broadly consistent with the reported age of the BKT-3 tuff. Considering the age of BKT-3 and biochronology, a range of 2.4-1.9 Ma is most likely for the faunal assemblage.
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Hominidae , Mamífero Proboscídeo , Theropithecus , Bovinos , Animais , Suínos , Etiópia , Meio Ambiente , Fósseis , Mamíferos , PerissodáctilosRESUMO
Drosophila suzukii (Matsumura) has spread rapidly, challenging berry and cherry crop production due to its ability to lay eggs into ripening fruit. To prevent infestation by this pest, insecticides are applied during fruit ripening and harvest. We field-tested the Rapid Assessment Protocol for IDentification of resistance in D. suzukii (RAPID) on seventy-eight populations collected across eight U.S. states in 2017 and 2018. Exposure to LC50 rates of malathion, methomyl, spinetoram, spinosad, and zeta-cypermethrin led to average female fly mortality of 25.0% in 2017, and after adjusting concentrations the average was 39.9% in 2018. Using LC99 × 2 discriminating concentrations in 2017 and LC90 × 8 rates in 2018, average female mortalities were 93.3% and 98.5%, respectively, indicating high overall susceptibility. However, using these high concentrations we found 32.0% of assays with survival of some female flies in 2017 and 27.8% in 2018. The adjustment in discriminating dose from 2017 to 2018 also reduced the proportion of assays with <90% survival from 17.6 to 2.9%. Populations with low mortality when exposed to spinosad were identified using this assay, triggering more detailed follow-up bioassays that identified resistant populations collected in California coastal region berry crops. Widespread evaluations of this method and subsequent validation in California, Michigan, and Georgia in 2019-2021 show that it provides a quick and low-cost method to identify populations of D. suzukii that warrant more detailed testing. Our results also provide evidence that important insecticide classes remain effective in most U.S. regions of fruit production.
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Inseticidas , Animais , Produtos Agrícolas , Drosophila , Feminino , Frutas , Controle de Insetos/métodos , Inseticidas/farmacologia , Malation/farmacologia , Metomil/farmacologia , Estados UnidosRESUMO
BACKGROUND: Geriatric trauma populations respond differently than younger trauma populations. Critical care ultrasound (CCUS) can guide resuscitation, and it has been shown to decrease intravenous fluid (IVF), lower time until operation, and lower mortality in trauma. Critical care ultrasound-guided resuscitation has not yet been studied in geriatric trauma. We hypothesized that incorporation of CCUS would decrease amount of IVF administered, decrease time to initiation of vasopressors, and decrease end organ dysfunction. METHODS: A PRE-CCUS geriatric trauma group between January 2015 and October 2016 was resuscitated per standard practice. A POST-CCUS group between January 2017 and December 2018 was resuscitated based on CCUS performed by trained intensivist upon admission to the intensive care unit and 6 hours after initial ultrasound. The PRE-CCUS and POST-CCUS groups underwent propensity score matching, yielding 60 enrollees in each arm. Retrospective review was conducted for demographics, clinical outcomes, and primary endpoints, including amount of IVF in the first 48 hours, duration to initiation of vasopressor use, and end organ dysfunction. Wilcoxon two-sample, χ2 tests, and κ statistics were performed to check associations between groups. RESULTS: There was no statistical difference between PRE-CCUS and POST-CCUS demographics and Injury Severity Scores. Intravenous fluid within 48 hours decreased from median [interquartile range] of 4941 mL [4019 mL] in the PRE-CCUS to 2633 mL [3671 mL] in the POST-CCUS (p = 0.0003). There was no significant difference between the two groups in time to initiation of vasopressors, vasopressor duration, lactate clearance, intensive care unit length of stay, or hospital length of stay. There was a significant decrease in ventilator days, with 26.7% PRE-CCUS with ventilation longer than 2 days, and only 6.7% POST-CCUS requiring ventilation longer than 2 days (p = 0.0033). CONCLUSION: Critical care ultrasound can be a useful addition to geriatric resuscitation. The POST-CCUS received less IV fluid and had decreased ventilator days. While mortality, lactate clearance, complications, and hospital stay were not statistically different, there was a perception that CCUS was a useful adjunct for assessing volume status and cardiac function. LEVEL OF EVIDENCE: Therapeutic, level II.
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Cuidados Críticos/métodos , Hidratação/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , Ressuscitação/estatística & dados numéricos , Ferimentos e Lesões/terapia , Idoso , Idoso de 80 Anos ou mais , Cuidados Críticos/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Humanos , Infusões Intravenosas/estatística & dados numéricos , Escala de Gravidade do Ferimento , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Ressuscitação/métodos , Estudos Retrospectivos , Ultrassonografia/métodos , Ultrassonografia/estatística & dados numéricos , Ferimentos e Lesões/diagnósticoRESUMO
Spotted-wing drosophila, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), a vinegar fly of Asian origin, has emerged as a devastating pest of small and stone fruits throughout the United States. Tolerance for larvae is extremely low in fresh market fruit, and management is primarily achieved through repeated applications of broad-spectrum insecticides. These applications are neither economically nor environmentally sustainable, and can limit markets due to insecticide residue restrictions, cause outbreaks of secondary pests, and select for insecticide resistance. Sustainable integrated pest management programs include cultural control tactics and various nonchemical approaches for reducing pest populations that may be useful for managing D. suzukii. This review describes the current state of knowledge and implementation for different cultural controls including preventative tactics such as crop selection and exclusion as well as strategies to reduce habitat favorability (pruning; mulching; irrigation), alter resource availability (harvest frequency; sanitation), and lower suitability of fruit postharvest (cooling; irradiation). Because climate, horticultural practices, crop, and market underlie the efficacy, feasibility, and affordability of cultural control tactics, the potential of these tactics for D. suzukii management is discussed across different production systems.
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OBJECTIVE: To measure prevalence of discordance between electrical activity recorded by electrocardiography (ECG) and myocardial activity visualized by echocardiography (echo) in patients presenting after cardiac arrest and to compare survival outcomes in cohorts defined by ECG and echo. METHODS: This is a secondary analysis of a previously published prospective study at twenty hospitals. Patients presenting after out-of-hospital arrest were included. The cardiac electrical activity was defined by ECG and contemporaneous myocardial activity was defined by bedside echo. Myocardial activity by echo was classified as myocardial asystole--the absence of myocardial movement, pulseless myocardial activity (PMA)--visible myocardial movement but no pulse, and myocardial fibrillation--visualized fibrillation. Primary outcome was the prevalence of discordance between electrical activity and myocardial activity. RESULTS: 793 patients and 1943 pauses in CPR were included. 28.6% of CPR pauses demonstrated a difference in electrical activity (ECG) and myocardial activity (echo), 5.0% with asystole (ECG) and PMA (echo), and 22.1% with PEA (ECG) and myocardial asystole (echo). Twenty-five percent of the 32 pauses in CPR with a shockable rhythm by echo demonstrated a non-shockable rhythm by ECG and were not defibrillated. Survival for patients with PMA (echo) was 29.1% (95%CI-23.9-34.9) compared to those with PEA (ECG) (21.4%, 95%CI-17.7-25.6). CONCLUSION: Patients in cardiac arrest commonly demonstrate different electrical (ECG) and myocardial activity (echo). Further research is needed to better define cardiac activity during cardiac arrest and to explore outcome between groups defined by electrical and myocardial activity.
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Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Ecocardiografia , Cardioversão Elétrica , Eletrocardiografia , Humanos , Parada Cardíaca Extra-Hospitalar/diagnóstico por imagem , Parada Cardíaca Extra-Hospitalar/terapia , Estudos ProspectivosRESUMO
Spray coverage may influence the efficacy of insecticides targeting the invasive vinegar fly Drosophila suzukii (Matsumura), a primary pest of raspberries and blackberries. In commercially managed caneberries, spray coverage is typically lowest in the inner and lower plant canopy, regions that overlap with higher levels of adult D. suzukii activity. To understand how spray coverage of fruit impacts efficacy against D. suzukii, laboratory bioassays were conducted using raspberries. In laboratory bioassays, higher spray coverage did not impact larval infestation rates but did increase adult mortality, indicating that flies can avoid a lethal dose of insecticide when applications do not achieve adequate coverage. We also evaluated how carrier water volume impacts spray coverage patterns throughout the canopy of raspberry and blackberry plants using both airblast and CO2 backpack sprayers. Increasing carrier water volume generally improved spray coverage in the lower plant canopy. However, effects in the upper plant canopy were inconsistent and varied between sprayer types. In addition to carrier water volume, other approaches, including adjusting the pesticide sprayer equipment used and/or sprayer calibration, should also be explored to improve coverage. Growers should evaluate spray coverage in their caneberries to identify and troubleshoot coverage issues. Results from this study indicate that taking the time to optimize this aspect of pesticide application may improve chemical management of D. suzukii and will likely also improve control of other important caneberry pests.
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Inseticidas , Rubus , Animais , Drosophila , Fazendas , Frutas , Controle de InsetosRESUMO
The striped cucumber beetle, Acalymma vittatum (Fabricius), is an important pest of cucurbit production in the eastern United States, where most commercial producers rely on insecticides to control this pest species. Biological control provides an alternative to insecticide use, but for A. vittatum, top-down control has not been well developed. In the northeastern United States, two parasitoid species, Celatoria setosa (Coquillett) (Diptera: Tachinidae) and Centistes diabroticae (Gahan) (Hymenoptera: Braconidae) have been reported from A. vittatum, but their distribution is poorly known. To determine whether these parasitoid species are attacking A. vittatum in Pennsylvania and the amount of mortality they provide, we characterized the parasitoid dynamics in two distinct efforts. First, we reared parasitoids from beetles captured at two research farms. Second, we focused on one of these farms and dissected beetles to quantify both parasitoid and parasite species attacking A. vittatum. Both efforts confirmed Cl. setosa and Cn. diabroticae, and parasitism rates varied widely between locations and among years (4-60%). Unexpectedly, our dissections revealed that a potentially undescribed nematode species (Howardula sp.) as the most common parasite in the community. We also discovered gregarine protists. Despite being smaller than females, males were more commonly attacked by parasitic species, but we detected no relationship between the size of beetles and abundance of parasitic species in A. vittatum. This work provides a baseline understanding of the parasitoid and parasite community attacking A. vittatum and advances opportunities for conservation biological control using these natural-enemy species.
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Besouros , Cucumis sativus , Inseticidas , Nematoides , Animais , Feminino , Masculino , Pennsylvania , Controle Biológico de VetoresRESUMO
Larval Drosophila encounter and feed on a diverse microbial community within fruit. In particular, free-living yeast microbes provide a source of dietary protein critical for development. However, successional changes to the fruit microbial community may alter host quality through impacts on relative protein content or yeast community composition. For many species of Drosophila, fitness benefits from yeast feeding vary between individual yeast species, indicating differences in yeast nutritional quality. To better understand these associations, we evaluated how five species of yeast impacted feeding preference and development in larval Drosophila suzukii. Larvae exhibited a strong attraction to the yeast Hanseniaspora uvarum in pairwise yeast feeding assays. However, larvae also performed most poorly on diets containing H. uvarum, a mismatch in preference and performance that suggests differences in yeast nutritional quality are not the primary factor driving larval feeding behavior. Together, these results demonstrate that yeast plays a critical role in D. suzukii's ecology and that larvae may have developed specific yeast associations. Further inquiry, including systematic comparisons of Drosophila larval yeast associations more broadly, will be necessary to understand patterns of microbial resource use in larvae of D. suzukii and other frugivorous species.
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Drosophila/crescimento & desenvolvimento , Comportamento Alimentar/fisiologia , Larva/crescimento & desenvolvimento , Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Animais , Frutas/crescimento & desenvolvimento , Microbiota , Leveduras/química , Leveduras/metabolismoRESUMO
An otherwise healthy nine-year-old female who spoke only French presented with abdominal pain, vomiting, intermittent fevers, fatigue, and headache. She then quickly became febrile and altered requiring intubation. When treating a healthy child, the physician may initially develop a differential that includes common illnesses. Yet, as emergency medicine providers, we must be thinking about the "zebras" in order to not miss potentially deadly, curable diseases.
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BACKGROUND: In January 2015, the Centers for Disease Control and Prevention (CDC)/National Health Safety Network (NHSN) changed the definition of catheter-associated urinary tract infection (CAUTI). We evaluated the outcomes of a robust CAUTI prevention program when we performed surveillance using the old definition (before 2015) versus the new definition (after 2015). This is the first study to evaluate how the change in CDC/NHSN definitions affected the outcomes of a CAUTI reduction program. METHODS: Baseline was from January 2012 to September 2014; the intervention period was from October 2014 to February 2016. Staff nurses were trained to be liaisons of infection prevention (Link Nurses) with clearly defined CAUTI prevention goals and with ongoing monthly activities. CAUTI incidence per 1000 catheter days was compared between the baseline and intervention periods, using the 2 definitions. RESULTS: With the new definition, CAUTIs decreased by 33%, from 2.69 to 1.81 cases per 1000 catheter days (incidence rate ratio [IRR] = 0.67; 95% confidence interval [CI]: 0.48-0.93; P < .016). With the old definition, CAUTIs increased by 12%, from 3.38 to 3.80 cases per 1000 catheter days (IRR = 1.12; 95% CI: 0.88-1.43; P = .348). CONCLUSION: We aggressively targeted CAUTI prevention, but a reduction was observed only with the new definition. Our findings stress the importance of having a reasonably accurate surveillance definition to monitor infection prevention initiatives.
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Infecções Relacionadas a Cateter/prevenção & controle , Infecções Urinárias/prevenção & controle , Infecções Relacionadas a Cateter/diagnóstico , Humanos , Papel do Profissional de Enfermagem , Berçários Hospitalares , Terminologia como Assunto , Atenção Terciária à Saúde , Cateteres Urinários/efeitos adversos , Infecções Urinárias/diagnósticoRESUMO
Magnet hospitals understand that healthcare providers no longer work with a homogeneous stakeholder population (including healthcare professionals, employees, and patients); thus, organizations must ensure that their practices accommodate the patients and employees of today and tomorrow. Although the medical center did not pursue its Magnet status goal, it is on the path to transforming its culture into a culturally competent environment. Such an environment allows the organization to be better poised for success when the time is right to, once again, pursue Magnet designation.
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Diversidade Cultural , Tomada de Decisões Gerenciais , Relações Hospital-Paciente , Hospitais Urbanos/organização & administração , Gestão da Qualidade Total/métodos , Benchmarking , Área Programática de Saúde , Competência Clínica , Relações Comunidade-Instituição , Etnicidade , Conselho Diretor , Hospitais com Fins Lucrativos/organização & administração , Hospitais Urbanos/normas , Humanos , Sistemas Multi-Institucionais , Estudos de Casos Organizacionais , Objetivos Organizacionais , Recursos Humanos em Hospital/educação , Tradução , VirginiaRESUMO
Objective. To develop predictive computational models forecasting the academic performance of students in the didactic-rich portion of a doctor of pharmacy (PharmD) curriculum as admission-assisting tools. Methods. All PharmD candidates over three admission cycles were divided into two groups: those who completed the PharmD program with a GPA ≥ 3; and the remaining candidates. Random Forest machine learning technique was used to develop a binary classification model based on 11 pre-admission parameters. Results. Robust and externally predictive models were developed that had particularly high overall accuracy of 77% for candidates with high or low academic performance. These multivariate models were highly accurate in predicting these groups to those obtained using undergraduate GPA and composite PCAT scores only. Conclusion. The models developed in this study can be used to improve the admission process as preliminary filters and thus quickly identify candidates who are likely to be successful in the PharmD curriculum.
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Logro , Tomada de Decisões Assistida por Computador , Técnicas de Apoio para a Decisão , Educação de Pós-Graduação em Farmácia , Aprendizado de Máquina , Critérios de Admissão Escolar , Avaliação Educacional , Escolaridade , Previsões/métodos , Humanos , Faculdades de Farmácia/normas , Estudantes de FarmáciaRESUMO
Purpose: CD19, a B-cell lineage-specific marker, is highly represented in B-cell malignancies and an attractive target for therapeutic interventions. MGD011 is a CD19 x CD3 DART bispecific protein designed to redirect T lymphocytes to eliminate CD19-expressing cells. MGD011 has been engineered with a modified human Fc domain for improved pharmacokinetic (PK) properties and designed to cross-react with the corresponding antigens in cynomolgus monkeys. Here, we report on the preclinical activity, safety and PK properties of MGD011.Experimental Design: The activity of MGD011 was evaluated in several in vitro and in vivo models. PK, safety and pharmacodynamic activity was also assessed in dose-escalation and repeat-dose studies of MGD011 administered once weekly in cynomolgus monkeys.Results: MGD011 mediated killing of human B-cell lymphoma lines by human or cynomolgus monkey PBMCs as well as autologous B-cell depletion in PBMCs from both species. MGD011-mediated killing was accompanied by target-dependent T-cell activation and expansion, cytokine release and upregulation of perforin and granzyme B. MGD011 demonstrated antitumor activity against localized and disseminated lymphoma xenografts reconstituted with human PBMCs. In cynomolgus monkeys, MGD011 displayed a terminal half-life of 6.7 days; once weekly intravenous infusion of MGD011 at doses up to 100 µg/kg, the highest dose tested, was well tolerated and resulted in dose-dependent, durable decreases in circulating B cells accompanied by profound reductions of B lymphocytes in lymphoid organs.Conclusions: The preclinical activity, safety and PK profile support clinical investigation of MGD011 as a therapeutic candidate for the treatment of B-cell malignancies. Clin Cancer Res; 23(6); 1506-18. ©2016 AACR.
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Anticorpos Biespecíficos/administração & dosagem , Antígenos CD19/imunologia , Linfoma de Células B/tratamento farmacológico , Linfócitos T/imunologia , Animais , Anticorpos Biespecíficos/imunologia , Antígenos CD19/uso terapêutico , Humanos , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Macaca fascicularis , Camundongos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: Our objective was to determine whether organized or disorganized cardiac activity is associated with increased survival in patients who present in pulseless electrical activity (PEA) treated with either 1) standard advanced cardiac life support (ACLS) medications or 2) other interventions. METHODS: This was a secondary analysis of a prospective, multi-center observational study utilizing ultrasound in out-of-hospital or inemergency department PEA arrest. Bedside ultrasound was performed as ACLS protocol started and during pulse checks. Only cases with visible cardiac activity on ultrasound were included in the present analysis. Cardiac activity was categorized as disorganized (agonal twitching) or organized (contractions with changes in ventricular dimensions). Patients were categorized as receiving either standard bolus ACLS medications or alternative medications during the resuscitation (continuous adrenergic agents, thrombolytics, others). The primary outcome was survival to hospital admission. The secondary outcome was return of spontaneous circulation (ROSC). Multivariate modeling was performed to assess association between survival to hospital admission in patients with intravenous adrenergic agents and cardiac activity. RESULTS: In our cohort of 225 patients in PEA cardiac arrest with cardiac activity on ultrasound, the overall survival rate was higher in patients with organized cardiac activity than with disorganized cardiac activity. PEA cardiac arrest patients with organized cardiac activity treated with standard ACLS interventions demonstrated improved survival to hospital admission compared to those with disorganized activity (37.7% (95%CI 24.8-50.2%) versus 17.9% (95%CI 10.9-28%). PEA cardiac arrest patients with organized cardiac activity who received continuous adrenergic agents during the resuscitation and prior to ROSC demonstrated higher survival to hospital admission 45.5% (95%CI 26.9-65.4%) and ROSC 90.9% (95%CI 71.0-98.7%) compared to those with disorganized cardiac activity who received continuous adrenergic agents during the resuscitation 0% (95%CI 0-23.0%) and 47.1% (95%CI 26-69%). Regression analysis demonstrates an association between increased survival in patients receiving intravenous adrenergic agents and organized cardiac activity. CONCLUSION: Survival in patients following PEA arrest is higher in patients with organized cardiac activity. The initiation of continuous adrenergic agents during PEA was associated with improved survival to hospital admission in patients with organized cardiac activity on bedside ultrasound, but this improvement was not seen in patients in PEA with disorganized cardiac activity. Bedside ultrasound may identify a subset of patients that respond differently to ACLS interventions.