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Clinical adoption of an artificial intelligence-enabled imaging tool requires critical appraisal of its life cycle from development to implementation by using a systematic, standardized, and objective approach that can verify both its technical and clinical efficacy. Toward this concerted effort, the ASFNR/ASNR Artificial Intelligence Workshop Technology Working Group is proposing a hierarchal evaluation system based on the quality, type, and amount of scientific evidence that the artificial intelligence-enabled tool can demonstrate for each component of its life cycle. The current proposal is modeled after the levels of evidence in medicine, with the uppermost level of the hierarchy showing the strongest evidence for potential impact on patient care and health care outcomes. The intended goal of establishing an evidence-based evaluation system is to encourage transparency, foster an understanding of the creation of artificial intelligence tools and the artificial intelligence decision-making process, and to report the relevant data on the efficacy of artificial intelligence tools that are developed. The proposed system is an essential step in working toward a more formalized, clinically validated, and regulated framework for the safe and effective deployment of artificial intelligence imaging applications that will be used in clinical practice.
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Inteligencia Artificial , Diagnóstico por Imagen , HumanosRESUMEN
BACKGROUND AND PURPOSE: Prioritizing reading of noncontrast head CT examinations through an automated triage system may improve time to care for patients with acute neuroradiologic findings. We present a natural language-processing approach for labeling findings in noncontrast head CT reports, which permits creation of a large, labeled dataset of head CT images for development of emergent-finding detection and reading-prioritization algorithms. MATERIALS AND METHODS: In this retrospective study, 1002 clinical radiology reports from noncontrast head CTs collected between 2008 and 2013 were manually labeled across 12 common neuroradiologic finding categories. Each report was then encoded using an n-gram model of unigrams, bigrams, and trigrams. A logistic regression model was then trained to label each report for every common finding. Models were trained and assessed using a combination of L2 regularization and 5-fold cross-validation. RESULTS: Model performance was strongest for the fracture, hemorrhage, herniation, mass effect, pneumocephalus, postoperative status, and volume loss models in which the area under the receiver operating characteristic curve exceeded 0.95. Performance was relatively weaker for the edema, hydrocephalus, infarct, tumor, and white-matter disease models (area under the receiver operating characteristic curve > 0.85). Analysis of coefficients revealed finding-specific words among the top coefficients in each model. Class output probabilities were found to be a useful indicator of predictive error on individual report examples in higher-performing models. CONCLUSIONS: Combining logistic regression with n-gram encoding is a robust approach to labeling common findings in noncontrast head CT reports.
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Cabeza , Procesamiento de Lenguaje Natural , Algoritmos , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND AND PURPOSE: Glioblastoma is an aggressive brain tumor, with no validated prognostic biomarkers for survival before surgical resection. Although recent approaches have demonstrated the prognostic ability of tumor habitat (constituting necrotic core, enhancing lesion, T2/FLAIR hyperintensity subcompartments) derived radiomic features for glioblastoma survival on treatment-naive MR imaging scans, radiomic features are known to be sensitive to MR imaging acquisitions across sites and scanners. In this study, we sought to identify the radiomic features that are both stable across sites and discriminatory of poor and improved progression-free survival in glioblastoma tumors. MATERIALS AND METHODS: We used 150 treatment-naive glioblastoma MR imaging scans (Gadolinium-T1w, T2w, FLAIR) obtained from 5 sites. For every tumor subcompartment (enhancing tumor, peritumoral FLAIR-hyperintensities, necrosis), a total of 316 three-dimensional radiomic features were extracted. The training cohort constituted studies from 4 sites (n = 93) to select the most stable and discriminatory radiomic features for every tumor subcompartment. These features were used on a hold-out cohort (n = 57) to evaluate their ability to discriminate patients with poor survival from those with improved survival. RESULTS: Incorporating the most stable and discriminatory features within a linear discriminant analysis classifier yielded areas under the curve of 0.71, 0.73, and 0.76 on the test set for distinguishing poor and improved survival compared with discriminatory features alone (areas under the curve of 0.65, 0.54, 0.62) from the necrotic core, enhancing tumor, and peritumoral T2/FLAIR hyperintensity, respectively. CONCLUSIONS: Incorporating stable and discriminatory radiomic features extracted from tumors and associated habitats across multisite MR imaging sequences may yield robust prognostic classifiers of patient survival in glioblastoma tumors.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/patología , Supervivencia sin Progresión , Estudios Retrospectivos , Neoplasias Encefálicas/patología , Pronóstico , Imagen por Resonancia Magnética/métodosRESUMEN
Introduction Video consultation involves the live interaction between the doctor and the patient remotely. Prior to the Covid-19 pandemic, the majority of video consultations in primary care were provided by GPs who were not the individual's own GP, which presented safety and continuity issues. This study aims to determine GPs' attitudes to the use of video consultation for their own patients. Methods This was a qualitative study involving semi-structured interviews. Participants were purposively recruited through use of a GP tutor as a key informant and guided by a sampling framework to include those with and without previous video consultation experience. Braun and Clarke thematic analysis was used. Results Participants included eight GPs, half of whom had previously worked with video consultation. Four themes emerged: impact on the consultation, the potential role, and the potential threat to current practice and technology and logistics. There were optimistic and cautious observations within all themes. Conclusion With the increased use of video consultation, Irish General Practice is in a unique position to frame the future its use. The provision of this modality to one's own patients may provide benefit while mitigating some of the pitfalls but would not entirely avoid the potential dangers of video consultation.
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COVID-19 , Medicina General , Médicos Generales , Telemedicina , Actitud del Personal de Salud , Humanos , Pandemias , Relaciones Médico-Paciente , Investigación Cualitativa , Derivación y ConsultaRESUMEN
Hog production takes place mostly in large concentrated animal feeding operations (CAFOs) where waste is managed by storing in lagoons prior to land application of lagoon liquid. Salmonella, including antibiotic-resistant Salmonella, have been found in the farm environment and lagoons. The objective of this research was to determine whether Salmonella resistant to clinically relevant antibiotics were present in wastewaters and surface waters from hog CAFOs. Samples of hog waste and on farm environmental waters were analysed for Salmonella, which were tested for antimicrobial susceptibility. The highest percentage of resistant isolates were found in raw waste flushed from hog houses and in lagoon wastewater; few resistant isolates were found in on-farm surface water. Resistance to sulphamethoxazole was most common, mostly in waste samples and less commonly in surface water, followed by chloramphenicol and ampicillin. No resistance to cephalosporin or fluoroquinolones was found. Resistance to clinically relevant antibiotics was commonly found in Salmonella from hog waste but was less extensive in farm surface waters. Management of wastes from hog CAFOs should be designed to further reduce the risk of human exposures resulting from environmental contamination with Salmonella. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests antibiotic-resistant Salmonella were common in hog wastes and present in environmental waters associated with hog CAFOs. Low levels of antibiotic-resistant Salmonella in on-farm stream waters suggest surface waters could have been contaminated, potentially serving as a mechanism of off-farm transport. Since the study, there have been multiple economic, regulatory and practice changes at the federal, state and industry level. These include regulation of antibiotic use and animal waste treatment, vertical integration in the industry and changes in antibiotic use practice. This study is a useful historical baseline against which current antibiotic resistance trends can be measured.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Salmonella/genética , Aguas Residuales/microbiología , Ampicilina/farmacología , Alimentación Animal/microbiología , Animales , Cloranfenicol/farmacología , Granjas , Humanos , Ríos , Salmonella/efectos de los fármacos , Salmonella/aislamiento & purificación , Sulfametoxazol/farmacología , Porcinos/microbiología , Enfermedades de los Porcinos/microbiologíaRESUMEN
Alternative sanitation options are needed for effective waste management in low-income countries where centralized, large-scale waste treatment is not easily achievable. A newly designed solar concentrator technology utilizes solar thermal energy to treat feces contained in drums. This pilot study assessed the efficacy of the new design to inactivate microbes in 13 treatment drums under field conditions in Kenya. Three-quarters of the drums contained <1000â¯E. coli/g of total solids following 6â¯h of solar thermal treatment and inactivation of thermotolerant C. perfringens spores ranged from <1.8 to >5.0â¯log10. Nearly all (94%) samples collected from treatment drums achieved thermophilic temperatures (>50⯰C) during the treatment period, however this alone did not ensure samples met the WHO E. coli guideline; higher, sustained thermophilic temperatures tended to be more effective in reaching this guideline. The newly designed solar concentrator was capable of inactivating thermotolerant, environmentally-stable microorganisms as, or possibly more, efficiently than a previous design. Additional data are needed to better characterize how temperature, time, and other parameters affect the ability of the solar concentrator to inactivate microbes in feces.
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Cuartos de Baño , Eliminación de Residuos Líquidos/métodos , Microbiología del Agua , Heces , Calor , Kenia , Proyectos Piloto , Pobreza , Saneamiento/métodos , Aguas del Alcantarillado , Esporas BacterianasRESUMEN
Functional MR imaging is being performed with increasing frequency in the typical neuroradiology practice; however, many readers of these studies have only a limited knowledge of the functional anatomy of the brain. This text will delineate the locations, anatomic boundaries, and functions of the cortical regions of the brain most commonly encountered in clinical practice-specifically, the regions involved in movement and language.
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Mapeo Encefálico/métodos , Encéfalo/anatomía & histología , Imagen por Resonancia Magnética/métodos , Femenino , Humanos , Lenguaje , Masculino , Persona de Mediana Edad , MovimientoRESUMEN
BACKGROUND AND PURPOSE: Differentiating pseudoprogression, a radiation-induced treatment effect, from tumor progression on imaging is a substantial challenge in glioblastoma management. Unfortunately, guidelines set by the Response Assessment in Neuro-Oncology criteria are based solely on bidirectional diametric measurements of enhancement observed on T1WI and T2WI/FLAIR scans. We hypothesized that quantitative 3D shape features of the enhancing lesion on T1WI, and T2WI/FLAIR hyperintensities (together called the lesion habitat) can more comprehensively capture pathophysiologic differences across pseudoprogression and tumor recurrence, not appreciable on diametric measurements alone. MATERIALS AND METHODS: A total of 105 glioblastoma studies from 2 institutions were analyzed, consisting of a training (n = 59) and an independent test (n = 46) cohort. For every study, expert delineation of the lesion habitat (T1WI enhancing lesion and T2WI/FLAIR hyperintense perilesional region) was obtained, followed by extraction of 30 shape features capturing 14 "global" contour characteristics and 16 "local" curvature measures for every habitat region. Feature selection was used to identify most discriminative features on the training cohort, which were evaluated on the test cohort using a support vector machine classifier. RESULTS: The top 2 most discriminative features were identified as local features capturing total curvature of the enhancing lesion and curvedness of the T2WI/FLAIR hyperintense perilesional region. Using top features from the training cohort (training accuracy = 91.5%), we obtained an accuracy of 90.2% on the test set in distinguishing pseudoprogression from tumor progression. CONCLUSIONS: Our preliminary results suggest that 3D shape attributes from the lesion habitat can differentially express across pseudoprogression and tumor progression and could be used to distinguish these radiographically similar pathologies.
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Neoplasias Encefálicas/diagnóstico por imagen , Glioblastoma/diagnóstico por imagen , Imagenología Tridimensional/métodos , Neuroimagen/métodos , Traumatismos por Radiación/diagnóstico por imagen , Adulto , Anciano , Neoplasias Encefálicas/patología , Estudios de Cohortes , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Glioblastoma/patología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Traumatismos por Radiación/patología , Estudios Retrospectivos , Máquina de Vectores de SoporteRESUMEN
In 2015, a typhoid fever outbreak began in downtown Kampala, Uganda, and spread into adjacent districts. In response, an environmental survey of drinking water source types was conducted in areas of the city with high case numbers. A total of 122 samples was collected from 12 source types and tested for Escherichia coli, free chlorine, and conductivity. An additional 37 grab samples from seven source types and 16 paired large volume (20 liter) samples from wells and springs were also collected and tested for the presence of Salmonella enterica serovar Typhi. Escherichia coli was detected in 60% of kaveras (drinking water sold in plastic bags) and 80% of refilled water bottles; free chlorine was not detected in either source type. Most jerry cans (68%) contained E. coli and had free chlorine residuals below the WHO-recommended level of 0.5 mg/liter during outbreaks. Elevated conductivity readings for kaveras, refilled water bottles, and jerry cans (compared to treated surface water supplied by the water utility) suggested that they likely contained untreated groundwater. All unprotected springs and wells and more than 60% of protected springs contained E. coli Water samples collected from the water utility were found to have acceptable free chlorine levels and no detectable E. coli While S Typhi was not detected in water samples, Salmonella spp. were detected in samples from two unprotected springs, one protected spring, and one refilled water bottle. These data provided clear evidence that unregulated vended water and groundwater represented a risk for typhoid transmission.IMPORTANCE Despite the high incidence of typhoid fever globally, relatively few outbreak investigations incorporate drinking water testing. During waterborne disease outbreaks, measurement of physical-chemical parameters, such as free chlorine residual and electrical conductivity, and of microbiological parameters, such as the presence of E. coli or the implicated etiologic agent, in drinking water samples can identify contaminated sources. This investigation indicated that unregulated vended water and groundwater sources were contaminated and were therefore a risk to consumers during the 2015 typhoid fever outbreak in Kampala. Identification of contaminated drinking water sources and sources that do not contain adequate disinfectant levels can lead to rapid targeted interventions.
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Agua Potable/microbiología , Agua Subterránea/microbiología , Salmonella typhi/aislamiento & purificación , Fiebre Tifoidea/microbiología , Brotes de Enfermedades , Ambiente , Humanos , Salmonella typhi/clasificación , Salmonella typhi/genética , Fiebre Tifoidea/epidemiología , Uganda/epidemiología , Contaminación del Agua , Abastecimiento de AguaRESUMEN
Cryptosporidium, a parasite known to cause large drinking and recreational water outbreaks, is tolerant of chlorine concentrations used for drinking water treatment. Human laboratory-based surveillance for enteric pathogens detected a cryptosporidiosis outbreak in Baker City, Oregon during July 2013 associated with municipal drinking water. Objectives of the investigation were to confirm the outbreak source and assess outbreak extent. The watershed was inspected and city water was tested for contamination. To determine the community attack rate, a standardized questionnaire was administered to randomly sampled households. Weighted attack rates and confidence intervals (CIs) were calculated. Water samples tested positive for Cryptosporidium species; a Cryptosporidium parvum subtype common in cattle was detected in human stool specimens. Cattle were observed grazing along watershed borders; cattle faeces were observed within watershed barriers. The city water treatment facility chlorinated, but did not filter, water. The community attack rate was 28·3% (95% CI 22·1-33·6), sickening an estimated 2780 persons. Watershed contamination by cattle probably caused this outbreak; water treatments effective against Cryptosporidium were not in place. This outbreak highlights vulnerability of drinking water systems to pathogen contamination and underscores the need for communities to invest in system improvements to maintain multiple barriers to drinking water contamination.
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Criptosporidiosis/epidemiología , Cryptosporidium/fisiología , Diarrea/epidemiología , Brotes de Enfermedades , Agua Potable/parasitología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Criptosporidiosis/parasitología , Criptosporidiosis/prevención & control , Diarrea/parasitología , Diarrea/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oregon/epidemiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The incidence of recreational water-associated outbreaks in the United States has significantly increased, driven, at least in part, by outbreaks both caused by Cryptosporidium and associated with treated recreational water venues. Because of the parasite's extreme chlorine tolerance, transmission can occur even in well-maintained treated recreational water venues (e.g. pools) and a focal cryptosporidiosis outbreak can evolve into a community-wide outbreak associated with multiple recreational water venues and settings (e.g. childcare facilities). In August 2004 in Auglaize County, Ohio, multiple cryptosporidiosis cases were identified and anecdotally linked to pool A. Within 5 days of the first case being reported, pool A was hyperchlorinated to achieve 99·9% Cryptosporidium inactivition. A case-control study was launched to epidemiologically ascertain the outbreak source 11 days later. A total of 150 confirmed and probable cases were identified; the temporal distribution of illness onset was peaked, indicating a point-source exposure. Cryptosporidiosis was significantly associated with swimming in pool A (matched odds ratio 121·7, 95% confidence interval 27·4-∞) but not with another venue or setting. The findings of this investigation suggest that proactive implementation of control measures, when increased Cryptosporidium transmission is detected but before an outbreak source is epidemiologically ascertained, might prevent a focal cryptosporidiosis outbreak from evolving into a community-wide outbreak.
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Criptosporidiosis/epidemiología , Criptosporidiosis/prevención & control , Cryptosporidium/aislamiento & purificación , Transmisión de Enfermedad Infecciosa/prevención & control , Agua Dulce/parasitología , Control de Infecciones/métodos , Piscinas , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Criptosporidiosis/transmisión , Femenino , Halogenación , Humanos , Lactante , Masculino , Persona de Mediana Edad , Ohio/epidemiología , Adulto JovenRESUMEN
OBJECTIVES: To identify and describe the most critical strategic and operational contributors to the successful implementation of clinical information technologies, as deployed within a moderate sized system of U.S. community hospitals. BACKGROUND AND SETTING: CHRISTUS Health is a multi-state system comprised of more than 350 services and 60 hospitals with over 9 000 physicians. The Santa Rosa region of CHRISTUS Health, located in greater San Antonio, Texas is comprised of three adult community hospital facilities and one Children's hospital each with bed capacities of 142-180. Computerized Patient Order Entry (CPOE) was first implemented in 2012 within a complex market environment. The Santa Rosa region has 2 417 credentialed physicians and 263 mid-level allied health professionals. METHODS: This report focuses on the seven most valuable strategies deployed by the Health Informatics team in a large four hospital CHRISTUS region to achieve strong CPOE adoption and critical success lessons learned. The findings are placed within the context of the literature describing best practices in health information technology implementation. RESULTS: While the elements described involved discrete de novo process generation to support implementation and operations, collectively they represent the creation of a new customer-centric service culture in our Health Informatics team, which has served as a foundation for ensuring strong clinical information technology adoption beyond CPOE. CONCLUSION: The seven success factors described are not limited in their value to and impact on CPOE adoption, but generalize to - and can advance success in - varied other clinical information technology implementations across diverse hospitals. A number of these factors are supported by reports in the literature of other institutions' successful implementations of CPOE and other clinical information technologies, and while not prescriptive to other settings, may be adapted to yield value elsewhere.
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Sistemas de Entrada de Órdenes Médicas , Evaluación de Resultado en la Atención de Salud , Contratos , Hospitales/estadística & datos numéricos , Humanos , Sistemas de Entrada de Órdenes Médicas/organización & administración , Sistemas de Entrada de Órdenes Médicas/estadística & datos numéricos , Médicos/legislación & jurisprudencia , Médicos/estadística & datos numéricosRESUMEN
Paediatric lacerations presenting to emergency departments are a common cause of referral to surgical specialties in the UK. LAT gel (lidocaine, adrenaline, and tetracaine) is a safe and effective topical anaesthetic that can aid with the closure of uncomplicated lacerations, particularly in the paediatric trauma setting. The benefits to both the patient and management in terms of the avoidance of a general anaesthetic and the freeing up of hospital resources (e.g. beds, staffing, emergency theatre) make it an invaluable tool in the arsenal of the emergency department. The authors describe a reliable method of anaesthetizing lacerations with LAT gel and question its underuse within the emergency departments in the South West region of the UK.
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Anestésicos Locales/administración & dosificación , Laceraciones/cirugía , Niño , Desbridamiento , Combinación de Medicamentos , Servicio de Urgencia en Hospital , Epinefrina/administración & dosificación , Geles , Humanos , Lidocaína/administración & dosificación , Dimensión del Dolor , Tetracaína/administración & dosificación , Resultado del Tratamiento , Reino Unido , Cicatrización de Heridas/efectos de los fármacosRESUMEN
A prominent hydrogen-related infrared absorption peak seen in many types of diamonds at 3107 cm(-1) has been the subject of investigation for many years. It is present in natural type-Ia material and can be introduced by heat-treating synthetic or CVD diamond. Based upon the most recent experimental data, it is thought that the defect giving rise to this vibrational mode is vacancy-related and is likely to contain nitrogen. Using first-principles simulations we present a VN3H model for the originating centre that simultaneously satisfies the different experimental observations including the strain response.
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Diamante/química , Hidrógeno/química , Simulación por Computador , Cristalización , Teoría Cuántica , Espectrofotometría InfrarrojaRESUMEN
In June 2011, a cluster of suspected cases of Guillain-Barré syndrome (GBS), which can follow Campylobacter jejuni infection, was identified in San Luis Río Colorado (SLRC), Sonora, Mexico and Yuma County, Arizona, USA. An outbreak investigation identified 26 patients (18 from Sonora, eight from Arizona) with onset of GBS 4 May-21 July 2011, exceeding the expected number of cases (n = 1-2). Twenty-one (81%) patients reported antecedent diarrhoea, and 61% of 18 patients tested were seropositive for C. jejuni IgM antibodies. In a case-control study matched on age group, sex, ethnicity, and neighbourhood of residence, all Arizona GBS patients travelled to SLRC during the exposure period vs. 45% of matched controls (matched odds ratio 8·1, 95% confidence interval 1·5-∞). Exposure information and an environmental assessment suggested that GBS cases resulted from a large outbreak of C. jejuni infection from inadequately disinfected tap water in SLRC. Binational collaboration was essential in investigating this cross-border GBS outbreak, the first in mainland North America since 1976.
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Infecciones por Campylobacter/complicaciones , Infecciones por Campylobacter/epidemiología , Campylobacter jejuni/aislamiento & purificación , Brotes de Enfermedades , Síndrome de Guillain-Barré/epidemiología , Síndrome de Guillain-Barré/microbiología , Anticuerpos Antibacterianos/sangre , Arizona/epidemiología , Infecciones por Campylobacter/transmisión , Estudios de Casos y Controles , Microbiología de Alimentos , Humanos , México/epidemiología , Vigilancia en Salud Pública , Estudios Retrospectivos , Microbiología del AguaRESUMEN
Dolphin shows and dolphin interaction programs are two types of education programs within zoological institutions used to educate visitors about dolphins and the marine environment. The current study examined the short- and long-term effects of these programs on visitors' conservation-related knowledge, attitude, and behavior. Participants of both dolphin shows and interaction programs demonstrated a significant short-term increase in knowledge, attitudes, and behavioral intentions. Three months following the experience, participants of both dolphin shows and interaction programs retained the knowledge learned during their experience and reported engaging in more conservation-related behaviors. Additionally, the number of dolphin shows attended in the past was a significant predictor of recent conservation-related behavior suggesting that repetition of these types of experiences may be important in inspiring people to conservation action. These results suggest that both dolphin shows and dolphin interaction programs can be an important part of a conservation education program for visitors of zoological facilities.
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Animales de Zoológico , Conducta Animal/fisiología , Conservación de los Recursos Naturales/estadística & datos numéricos , Delfines/fisiología , Zoología/educación , Adulto , Animales , Actitud , Humanos , Análisis de Regresión , Encuestas y Cuestionarios , Estados UnidosRESUMEN
In July and August 2007, a giardiasis outbreak affected attendees of a private recreational camp in California. Twenty-six persons had laboratory-confirmed giardiasis; another 24 had giardiasis-like illness with no stool test. A retrospective cohort study determined that showering was associated with illness (adjusted odds ratio 3·1, 95% confidence interval 1·1-9·3). Two days before the outbreak began, the camp had installed a slow-sand water filtration system that included unsterilized sand. Review of historical water-quality data identified substantially elevated total coliform and turbidity levels in sand-filtered spring water used for showering during the suspected exposure period. Unfiltered spring water tested at the same time had acceptable coliform and turbidity levels, implicating the filtration system as the most likely contamination source. To prevent waterborne illness, slow-sand water filtration systems should use sterilized sand, and slow-sand-filtered water should not be used for any purpose where inadvertent ingestion could occur until testing confirms its potability.
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Brotes de Enfermedades , Filtración/métodos , Giardiasis/epidemiología , Purificación del Agua/métodos , Agua/parasitología , Adolescente , Adulto , California/epidemiología , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
We have recently described the N-terminal RAS association domain family of genes, RASSF7-10. Previously, we cloned the N-terminal RASSF10 gene and demonstrated frequent methylation of the associated 5'-CpG island in acute lymphoblastic leukemia. To characterize RASSF10 gene expression, we demonstrate that in developing Xenopus embryos, RASSF10 shows a very striking pattern in the rhombencephalon (hind brain). It is also expressed in other parts of the brain and other organs. Due to the well-defined expression pattern in the brain of Xenopus embryos, we analyzed the methylation status of the RASSF10-associated 5'-CpG island in astrocytic gliomas. RASSF10 was frequently methylated in WHO grade II-III astrocytomas and WHO grade IV primary glioblastomas (67.5%), but was unmethylated in grade I astrocytomas and in DNA from age matched control brain samples. RASSF10 gene expression both at the mRNA and protein levels could be switched back on in methylated glioma cell lines after treatment with 5-aza-2'-deoxycytidine. In secondary glioblastomas (sGBM), RASSF10 methylation was an independent prognostic factor associated with worst progression-free survival and overall survival and occurred at an early stage in their development. In cell culture experiments, overexpression of RASSF10 mediated a reduction in the colony forming ability of two RASSF10-methylated glioma cell lines. Conversely, RNAi-mediated knockdown of RASSF10-stimulated anchorage-independent growth of U87 glioma cells, increased their viability and caused an increase in the cells' proliferative ability. We generated and characterized a RASSF10-specific antibody and demonstrated for the first time that RASSF10 subcellular localization is cell-cycle dependent with RASSF10 colocalizing to centrosomes and associated microtubules during mitosis. This is the first report demonstrating that RASSF10 can act as a tumor suppressor gene and is frequently methylated in gliomas and can potentially be developed into a prognostic marker for sGBM.
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Neoplasias Encefálicas/genética , Metilación de ADN/genética , Silenciador del Gen , Genes Supresores de Tumor , Glioblastoma/genética , Proteínas Supresoras de Tumor/genética , Animales , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/mortalidad , Línea Celular Tumoral , Supervivencia sin Enfermedad , Electroforesis en Gel de Poliacrilamida , Femenino , Glioblastoma/mortalidad , Humanos , Inmunohistoquímica , Hibridación in Situ , Isocitrato Deshidrogenasa/genética , Estimación de Kaplan-Meier , Masculino , Mutación , Reacción en Cadena de la Polimerasa , Modelos de Riesgos Proporcionales , XenopusRESUMEN
Giardiasis is a common waterborne gastrointestinal illness. In 2007, a community giardiasis outbreak occurred in New Hampshire, USA. We conducted a cohort study to identify risk factors for giardiasis, and stool and environmental samples were analysed. Consuming tap water was significantly associated with illness (risk ratio 4.7, 95% confidence interval 1.5-14.4). Drinking-water samples were coliform-contaminated and a suspect Giardia cyst was identified in a home water filter. One well was coliform-contaminated, and testing indicated that it was potentially under the influence of surface water. The well was located 12.5 m from a Giardia-contaminated brook, although the genotype differed from clinical specimens. Local water regulations require well placement at least 15 m from surface water. This outbreak, which caused illness in 31 persons, represents the largest community drinking-water-associated giardiasis outbreak in the USA in 10 years. Adherence to well placement regulations might have prevented this outbreak.