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Focusing on British Columbia during the mid-twentieth century, this article illuminates how North American medical, public-health, and law-enforcement professionals used the "reservoir" metaphor in efforts to control venereal disease (VD). It traces the transition from a pre-Second-World-War paradigm of VD eradication - what I call an epidemio-logic - focused on the single reservoir of female sex workers, to one concerned with several groups, including the White "male homosexual." The article also demonstrates how conceptualizing VD control in terms of human reservoirs led to analogical reasoning, improvements and setbacks to disease-control efforts, shifting understandings of infection risks, and changes to the built urban environment.
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Trabajadores Sexuales , Enfermedades de Transmisión Sexual , Humanos , Femenino , Masculino , Metáfora , Antropología Médica , América del NorteRESUMEN
AIM: A new definition of sepsis released by an international task-force has introduced the concept of quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA). This study aimed to measure the proportion of patients who fulfilled qSOFA criteria during a Rapid Response Team (RRT) review and to assess their associated outcomes. METHODS: We conducted a prospective study of adult RRT reviews over a one month period between 6th June and 10th July 2016 in a large tertiary hospital in Melbourne Australia RESULTS: Over a one-month period, there were 282 RRT reviews, 258 of which were included. One hundred out of 258 (38.8%) RRT review patients fulfilled qSOFA criteria. qSOFA positive patients were more likely to be admitted to the intensive care unit (29% vs 18%, P=0.04), to have repeat RRT reviews (27% vs 13%; p=0.007) and die in hospital (31% vs 10%, P<0.001). qSOFA positive patients with suspected infection were more likely to be admitted to the intensive care unit compared to patients with infection alone (37% vs 15%, P=0.002). Eleven of 42 patients (26%) who had infection and qSOFA died whilst in hospital, compared to 8/55 (15%) of patients with infection alone (P=0.2). CONCLUSION: Adult patients who are qSOFA positive at the time of their RRT review are at increased risk of in-hospital mortality. The assessment of qSOFA may be a useful triage tool during a RRT review.
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Mortalidad Hospitalaria , Unidades de Cuidados Intensivos/estadística & datos numéricos , Puntuaciones en la Disfunción de Órganos , Sepsis/diagnóstico , Anciano , Anciano de 80 o más Años , Femenino , Equipo Hospitalario de Respuesta Rápida/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Estudios Prospectivos , Sepsis/mortalidad , Sepsis/fisiopatología , Sepsis/terapia , Índice de Severidad de la EnfermedadRESUMEN
The emergence of HIV-1 group M subtype B in North American men who have sex with men was a key turning point in the HIV/AIDS pandemic. Phylogenetic studies have suggested cryptic subtype B circulation in the United States (US) throughout the 1970s and an even older presence in the Caribbean. However, these temporal and geographical inferences, based upon partial HIV-1 genomes that postdate the recognition of AIDS in 1981, remain contentious and the earliest movements of the virus within the US are unknown. We serologically screened >2,000 1970s serum samples and developed a highly sensitive approach for recovering viral RNA from degraded archival samples. Here, we report eight coding-complete genomes from US serum samples from 1978-1979-eight of the nine oldest HIV-1 group M genomes to date. This early, full-genome 'snapshot' reveals that the US HIV-1 epidemic exhibited extensive genetic diversity in the 1970s but also provides strong evidence for its emergence from a pre-existing Caribbean epidemic. Bayesian phylogenetic analyses estimate the jump to the US at around 1970 and place the ancestral US virus in New York City with 0.99 posterior probability support, strongly suggesting this was the crucial hub of early US HIV/AIDS diversification. Logistic growth coalescent models reveal epidemic doubling times of 0.86 and 1.12 years for the US and Caribbean, respectively, suggesting rapid early expansion in each location. Comparisons with more recent data reveal many of these insights to be unattainable without archival, full-genome sequences. We also recovered the HIV-1 genome from the individual known as 'Patient 0' (ref. 5) and found neither biological nor historical evidence that he was the primary case in the US or for subtype B as a whole. We discuss the genesis and persistence of this belief in the light of these evolutionary insights.
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Síndrome de Inmunodeficiencia Adquirida/historia , Síndrome de Inmunodeficiencia Adquirida/virología , Genoma Viral/genética , VIH-1/clasificación , VIH-1/genética , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Teorema de Bayes , VIH-1/aislamiento & purificación , Historia del Siglo XX , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Masculino , Ciudad de Nueva York/epidemiología , América del Norte/epidemiología , ARN Viral/análisis , ARN Viral/genética , ARN Viral/aislamiento & purificación , Análisis de Secuencia de ADN , Análisis Espacio-TemporalRESUMEN
AIMS: To gauge clinical opinion about the current system and possible changes as well as providing a forum for education about Non-Invasive Prenatal Testing (NIPT). METHODS: A series of workshops for doctors and midwives, supported by the National Screening Unit of the Ministry of Health and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists, were held in the main centres of New Zealand. Following a brief education session, a structured evaluation of current screening and future possibilities was undertaken by questionnaire. RESULTS: One hundred and eight maternity carers participated in 5 workshops. Over 40% identified barriers to current screening. More than 60% would support NIPT in the first trimester. The majority of carers provided their own counselling support for women. CONCLUSIONS: The survey has shown general enthusiasm for the introduction of publically funded NIPT into prenatal screening in New Zealand. Barriers to utilisation of the current system have been identified and enhancements to screening performance with guidelines around conditions to be screened for would be supported.
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Aneuploidia , Actitud del Personal de Salud , Trastornos de los Cromosomas/diagnóstico , Pruebas de Detección del Suero Materno , Ultrasonografía Prenatal , Biomarcadores/sangre , Femenino , Humanos , Nueva Zelanda , Embarazo , Primer Trimestre del Embarazo/sangre , Encuestas y CuestionariosRESUMEN
BACKGROUND: Medical Emergency Teams (METs) involve specialist staff who respond to acutely deteriorating ward patients. There is little literature describing the scope of practice and training of MET responders. PURPOSE: To describe and discuss an education and training program for Intensive Care Unit (ICU) nurses who function in a high capability teaching hospital MET. FINDINGS: The program is overseen and coordinated by four senior nurses. Applicants require at least three years experience working as an ICU nurse in a level 3 tertiary ICU. Each program participant is allocated a mentor and must complete the program within six months. Induction involves attending lectures outlining expected roles, responsibilities and appropriate conduct during MET calls. A course handbook outlines a series of competencies including checking of the MET trolley, assisting endo-tracheal intubation, commencement of non-invasive ventilation and high flow oxygen. Each participant attends the first five MET calls under supervision. A series of case scenarios are discussed and reviewed and an oral examination on two such cases is undertaken prior to completion of the program. Throughout, candidates are trained in their expected roles and responsibilities during MET calls, follow-up of at-risk and deteriorating patients, emergency calls in the mental health precinct, and assisting with procedures outside of the ICU. Emphasis is placed on both technical and non-technical skills. CONCLUSIONS: We have provided a framework for the development of a MET nurse training program. The applicability of this program to other settings and effects of this program on patient outcomes remain unknown.
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Enfermería de Cuidados Críticos/educación , Capacitación en Servicio , Personal de Enfermería en Hospital/educación , Australia , Cuidados Críticos , Curriculum , Hospitales de Enseñanza , Humanos , Rol de la Enfermera , Grupo de Atención al Paciente , UniversidadesRESUMEN
OBJECTIVES: To assess tasks completed by intensive care medical emergency team nurses. RESEARCH DESIGN: Prospective observational study. SETTING: Australian teaching hospital. MAIN OUTCOME MEASURES: Nursing-related technical and non-technical tasks and level of self-reported confidence and competence. RESULTS: Amongst 400 calls, triggers and nursing tasks were captured in 93.5% and 77.3% of cases, respectively. The median patient age was 73 years. The four most common triggers were hypotension (22.0%), tachycardia (21.1%), low SpO2 (17.4%), and altered conscious state (10.1%). Non-technical skills included investigation review (33.7%), history acquisition (18.4%), contribution to the management plan (40.5%) and explanation to bedside nurses (78.3%), doctors (13.6%), allied health (3.9%) or patient/relative (39.5%). Technical tasks included examining the circulation (32%), conscious state (29.4%), and chest (26.5%). Additional tasks included adjusting oxygen (23.9%), humidification (8.4%), non-invasive ventilation (6.5%), performing an ECG (22%), and administrating fluid as a bolus (17.5%) or maintenance (16, 5.2%), or medication as a statim dose (16.8%) or infusion (5.2%). Self-reported competence and confidence appeared to be high overall amongst our MET nurses. CONCLUSION: Our findings provide important information on the tasks completed by Medical Emergency Team nurses and will guide future training.
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Equipo Hospitalario de Respuesta Rápida , Hospitales de Enseñanza , Rol de la Enfermera , Centros de Atención Terciaria , Trabajo , Anciano , Anciano de 80 o más Años , Actitud del Personal de Salud , Australia , Competencia Clínica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Autoimagen , Recursos HumanosRESUMEN
This article contextualizes the production and reception of And the Band Played On, Randy Shilts's popular history of the initial recognition of the American AIDS epidemic. Published over twenty-five years ago, the book and its most notorious character, "Patient Zero," are in particular need of a critical historical treatment. The article presents a more balanced consideration-a "patient's view"-of Gaétan Dugas's experience of the early years of AIDS. I oppose the assertion that Dugas, the so-called Patient Zero, ignored incontrovertible information about the condition and was intent on spreading his infection. Instead I argue that scientific ideas in 1982 and 1983 about AIDS and the transmissibility of a causative agent were later portrayed to be more self-evident than they were at the time. The article also traces how Shilts's highly selective-and highly readable-characterization of Dugas rapidly became embedded in discussions about the need to criminalize the reckless transmission of HIV.
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Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/historia , Epidemias/historia , Síndrome de Inmunodeficiencia Adquirida/transmisión , Síndrome de Inmunodeficiencia Adquirida/virología , Canadá/epidemiología , Conocimientos, Actitudes y Práctica en Salud , Historia del Siglo XX , Prioridad del Paciente , Estados Unidos/epidemiologíaRESUMEN
Accurate focusing is a critical challenge of whole slide imaging, primarily due to inherent tissue topography variability. Traditional line scanning and tile-based scanning systems are limited in their ability to acquire a high degree of focus points while still maintaining high throughput. This review examines limitations with first-generation whole slide scanning systems and explores a novel approach that employs continuous autofocus, referred to as independent dual sensor scanning. This "second-generation" concept decouples image acquisition from focusing, allowing for rapid scanning while maintaining continuous accurate focus. The technical concepts, merits, and limitations of this method are explained and compared to that of a traditional whole slide scanning system.
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CONTEXT: Whole slide imaging (WSI) for digital pathology involves the rapid automated acquisition of multiple high-power fields from a microscope slide containing a tissue specimen. Capturing each field in the correct focal plane is essential to create high-quality digital images. Others have described a novel focusing method which reduces the number of focal planes required to generate accurate focus. However, this method was not applied dynamically in an automated WSI system under continuous motion. AIMS: This report measures the accuracy of this method when applied in a rapid continuous scan mode using a dual sensor WSI system with interleaved acquisition of images. METHODS: We acquired over 400 tiles in a "stop and go" scan mode, surveying the entire z depth in each tile and used this as ground truth. We compared this ground truth focal height to the focal height determined using a rapid 3-point focus algorithm applied dynamically in a continuous scanning mode. RESULTS: Our data showed the average focal height error of 0.30 (±0.27) µm compared to ground truth, which is well within the system's depth of field. On a tile by tile assessment, approximately 95% of the tiles were within the system's depth of field. Further, this method was six times faster than acquiring tiles compared to the same method in a non-continuous scan mode. CONCLUSIONS: The data indicates that the method employed can yield a significant improvement in scan speed while maintaining highly accurate autofocusing.
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Image focus quality is of utmost importance in digital microscopes because the pathologist cannot accurately characterize the tissue state without focused images. We propose to train a classifier to measure the focus quality of microscopy scans based on an extensive set of image features. However, classifiers rely heavily on the quality and quantity of the training data, and collecting annotated data is tedious and expensive. We therefore propose a new method to automatically generate large amounts of training data using image stacks. Our experiments demonstrate that a classifier trained with the image stacks performs comparably with one trained with manually annotated data. The classifier is able to accurately detect out-of-focus regions, provide focus quality feedback to the user, and identify potential problems of the microscopy design.
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Algoritmos , Inteligencia Artificial , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Microscopía/métodos , Reconocimiento de Normas Patrones Automatizadas/métodos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Direct analysis of samples using atmospheric pressure ionization (API) provides a more rapid method for analysis of volatile and semivolatile compounds than vacuum solids probe methods and can be accomplished on commercial API mass spectrometers. With only a simple modification to either an electrospray (ESI) or atmospheric pressure chemical ionization (APCI) source, solid as well as liquid samples can be analyzed in seconds. The method acts as a fast solids/liquid probe introduction as well as an alternative to the new direct analysis in real time (DART) and desorption electrospray ionization (DESI) methods for many compound types. Vaporization of materials occurs in the hot nitrogen gas stream flowing from an ESI or APCI probe. Ionization of the thermally induced vapors occurs by corona discharge under standard APCI conditions. Accurate mass and mass-selected fragmentation are demonstrated as is the ability to obtain ions from biological tissue, currency, and other objects placed in the path of the hot nitrogen stream.
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Presión Atmosférica , Cromatografía Liquida/instrumentación , Cromatografía Liquida/métodos , Espectrometría de Masa por Ionización de Electrospray/instrumentación , Espectrometría de Masa por Ionización de Electrospray/métodosRESUMEN
Modification of commercial LC/MS instrumentation to allow both atmospheric pressure (AP) LC/MS and GC/MS is described. Advantages of this additional capability versus LC/MS alone include higher chromatographic resolution in the GC versus LC mode, greater peak capacity for complex mixture analysis, higher sensitivity for a variety of volatile compounds, and the ability to observe compounds of low polarity that are not readily observed in LC/MS. Advantages over conventional GC/MS include the ability to use higher carrier gas flow and shorter columns for passing less volatile materials through the gas chromatograph, selective ionization, and rapid switching between positive and negative ion modes. Other advantages include application of the enhanced capabilities of LC/MS instrumentation to GC/MS analyses such as cone voltage fragmentation, MS(n), high mass resolution, and accurate mass measurement. Limitations of APGC/MS include the inability to observe saturated hydrocarbon and certain other highly nonpolar compounds and less odd-electron fragmentation for computer aided library searching. For some analyses, the limitation related to ionization of highly nonpolar compounds is advantageous, as is the simplified mass spectrum and easy molecular weight identification that results from less fragmentation observed in the AP ionization mode.
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Cromatografía Líquida de Alta Presión/instrumentación , Mezclas Complejas/análisis , Cromatografía de Gases y Espectrometría de Masas/instrumentación , Espectrometría de Masa por Ionización de Electrospray/instrumentación , Cromatografía Líquida de Alta Presión/métodos , Diseño de Equipo , Análisis de Falla de Equipo , Cromatografía de Gases y Espectrometría de Masas/métodos , Espectrometría de Masa por Ionización de Electrospray/métodos , Integración de SistemasRESUMEN
Methods were developed to quantify the amount of perfluorooctanoic acid (PFOA) extracted from textile and carpet samples through contact with water, methanol, and sweat and saliva simulants using LC/MS/MS. The limit of quantitation (LOQ) for samples extracted in water and sweat simulant is 1 ppb (ng PFOA (g sample)(-1)) while the limits of quantitation for samples extracted in saliva simulant and methanol were 3 ppb and 2.5 ppb, respectively. Method validation results are provided for a polyester control textile sample that was extracted in water on two different days by different analysts, which gave an overall recovery of 103% and standard deviation of 5.3% for 30 analyses. However, for routine application of these methods to a large number of sample sets differing in chemical and physical compositions, a complete validation for each sample type is not practical or possible since control samples for fortifications are often not available. Instead, suitable analytical methods and acceptance criteria are described which ensure accurate PFOA quantitation in each of the solvent extract types. During routine use of these methods, post-extraction spike recoveries for the different sample types and solvents are 100 +/- 15% using a dual isotopically labeled (13)C-PFOA internal standard to correct for matrix effects. A comparison of extraction solvent versus time using a wrist action shaker for textile and carpet samples demonstrates that the total extractable amount of PFOA is similar for each of the solvent types. However, as expected the rate of extraction in water and simulants is significantly less than that of methanol. Finally, a comparison of 2 h and 24 h wrist action shaker extractions with a 1.5 h pressurized fluid extraction (PFE) in methanol reveals that the 24 h wrist action shaker yields the highest results. The 2 h wrist action shaker results are similar to those of the 1.5 h PFE extraction.
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Caprilatos/análisis , Pisos y Cubiertas de Piso , Fluorocarburos/análisis , Textiles , Humanos , Espectrometría de Masas/métodos , Metanol/química , Saliva/química , Solventes , Sudor/química , Agua/químicaRESUMEN
Conformational coupling with the inositol 1,4,5-trisphosphate (IP3) receptor has been suggested as a possible mechanism of activation of TRPC3 channels and a region in the C terminus of TRPC3 has been shown to interact with the IP3 receptor as well as calmodulin (calmodulin/IP3 receptor-binding (CIRB) region). Here we show that internal deletion of 20 amino acids corresponding to the highly conserved CIRB region results in the loss of diacylglycerol and agonist-mediated channel activation in HEK293 cells. By using confocal microscopy to examine the cellular localization of Topaz fluorescent protein fusion constructs, we demonstrate that this loss in activity is caused by faulty targeting of CIRB-deleted mutants to intracellular compartments. Wild type TRPC3 and mutants lacking a C-terminal predicted coiled coil region downstream of CIRB were targeted to the plasma membrane correctly in HEK293 cells and exhibited TRPC3-mediated calcium entry in response to agonist activation. Mutation of conserved YQ and MKR motifs to alanine within the CIRB region in TRPC3-Topaz, which would be expected to interfere with IP3 receptor and/or calmodulin binding, had no effect on channel function or targeting. Additionally, TRPC3 targets to the plasma membrane of DT40 cells lacking all three IP3 receptors and forms functional ion channels. These findings indicate that the previously identified CIRB region of TRPC3 is involved in its targeting to the plasma membrane by a mechanism that does not involve interaction with IP3 receptors.
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Canales de Calcio/metabolismo , Canales Iónicos/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Secuencia de Aminoácidos , Animales , Calcio/metabolismo , Calmodulina/metabolismo , Carbacol/farmacología , Línea Celular , Pollos , Agonistas Colinérgicos/farmacología , Secuencia Conservada , Diglicéridos/metabolismo , Citometría de Flujo , Eliminación de Gen , Humanos , Receptores de Inositol 1,4,5-Trifosfato , Cinética , Microscopía Confocal , Datos de Secuencia Molecular , Mutación , Plásmidos/metabolismo , Conformación Proteica , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Homología de Secuencia de Aminoácido , Canales Catiónicos TRPC , Factores de Tiempo , TransfecciónRESUMEN
Canonical transient receptor potential 3 (TRPC3) is a receptor-activated, calcium permeant, non-selective cation channel. TRPC3 has been shown to interact physically with the N-terminal domain of the inositol 1,4,5-trisphosphate receptor, consistent with a "conformational coupling" mechanism for its activation. Here we show that low concentrations of agonists that fail to produce levels of inositol 1,4,5-trisphosphate sufficient to induce Ca(2+) release from intracellular stores substantially activate TRPC3. By several experimental approaches, we demonstrate that neither inositol 1,4,5-trisphosphate nor G proteins are required for TRPC3 activation. However, diacylglycerols were sufficient to activate TRPC3 in a protein kinase C-independent manner. Surface receptor agonists and exogenously applied diacylglycerols were not additive in activating TRPC3. In addition, inhibition of metabolism of diacylglycerol slowed the reversal of receptor-dependent TRPC3 activation. We conclude that receptor-mediated activation of phospholipase C in intact cells activates TRPC3 via diacylglycerol production, independently of G proteins, protein kinase C, or inositol 1,4,5-trisphosphate.
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Canales de Calcio/fisiología , Calcio/metabolismo , Canales de Calcio/efectos de los fármacos , Células Cultivadas , Diglicéridos/metabolismo , Diglicéridos/farmacología , Factor de Crecimiento Epidérmico/farmacología , Subunidades alfa de la Proteína de Unión al GTP Gq-G11 , Proteínas de Unión al GTP Heterotriméricas/fisiología , Humanos , Inositol 1,4,5-Trifosfato/farmacología , Receptores de Inositol 1,4,5-Trifosfato , Cloruro de Metacolina/farmacología , Proteína Quinasa C/fisiología , Receptores Citoplasmáticos y Nucleares/fisiología , Canales Catiónicos TRPC , Fosfolipasas de Tipo C/metabolismoRESUMEN
Capacitative calcium entry or store-operated calcium entry in nonexcitable cells is a process whereby the activation of calcium influx across the plasma membrane is signaled by depletion of intracellular calcium stores. Transient receptor potential (TRP) proteins have been proposed as candidates for store-operated calcium channels. Human TRPC3 (hTRPC3), an extensively studied member of the TRP family, is activated through a phospholipase C-dependent mechanism, not by store depletion, when expressed in HEK293 cells. However, store depletion by thapsigargin is sufficient to activate hTRPC3 channels when expressed in DT40 avian B-lymphocytes. To gain further insights into the differences between hTRPC3 channels generated in these two expression systems and further understand the role of hTRPC3 in capacitative calcium entry, we examined the effect of two well characterized inhibitors of capacitative calcium entry, Gd3+ and 2-aminoethoxydiphenyl borane (2APB). We confirmed that in both DT40 cells and HEK293 cells, 1 microm Gd3+ or 30 microm 2APB completely blocked calcium entry due to receptor activation or store depletion. In HEK293 cells, 1 microm Gd3+ did not block receptor-activated hTRPC3-mediated cation entry, whereas 2APB had a partial (approximately 60%) inhibitory effect. Interestingly, store-operated hTRPC3-mediated cation entry in DT40 cells was also partially inhibited by 2APB, whereas 1 microm Gd3+ completely blocked store-operated hTRPC3 activity in these cells. Furthermore, the sensitivity of store-operated hTRPC3 channels to Gd3+ in DT40 cells was similar to the endogenous store-operated channels, with essentially 100% block of activity at concentrations as low as 0.1 microm. Finally, Gd3+ has a rapid inhibitory effect when added to fully developed hTRPC3-mediated calcium entry, suggesting a direct action of Gd3+ on hTRPC3 channels. The distinct action of these inhibitors on hTRPC3-mediated cation entry in these two cell types may result from their different modes of activation and may also reflect differences in basic channel structure.