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BACKGROUND: Little is known about the potential benefits or harms of statins on physical function among people with HIV (PWH). METHODS: REPRIEVE was a double-blind randomized controlled trial evaluating pitavastatin for primary prevention of major adverse cardiovascular events (MACE) in PWH. Time to complete ten chair rises, 4-meter gait speed, grip strength, and a modified short physical performance test were assessed annually for up to 5 years in the ancillary study PREPARE and analyzed using linear mixed models. FINDINGS: Of 602 PWH, 52% were randomized to pitavastatin and 48% to placebo. Median age was 51 years; 18% were female at birth; 2% transgender; 40% Black, and 18% Hispanic. Median PREPARE follow-up was 4.7 (4.3, 5.0) years. Muscle symptoms (grade ≥3 or treatment-limiting) occurred in 5% of both groups. There was no evidence of decline in chair rise rate in either treatment group, and no difference in the pitavastatin group compared to placebo (estimated difference -0.10 [95% CI: -0.30, 0.10] rises/min/year; p=0.31). Small declines over time were observed in other physical function tests in both treatment groups, with no apparent differences between groups. INTERPRETATION: We observed minimal declines in physical function over 5 years of follow-up among middle-aged PWH, with no differences among PWH randomized to pitavastatin compared to placebo. This finding, combined with low prevalence of myalgias, supports the long-term safety of statin therapy on physical function, when used for primary prevention of MACE among PWH.
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The International Union for Conservation of Nature's Red List of Threatened Species (IUCN Red List) is the world's most comprehensive information source on the global conservation status of species. Governmental agencies and conservation organizations increasingly rely on IUCN Red List assessments to develop conservation policies and priorities. Funding agencies use the assessments as evaluation criteria, and researchers use meta-analysis of red-list data to address fundamental and applied conservation science questions. However, the circa 143,000 IUCN assessments represent a fraction of the world's biodiversity and are biased in regional and organismal coverage. These biases may affect conservation priorities, funding, and uses of these data to understand global patterns. Isolated oceanic islands are characterized by high endemicity, but the unique biodiversity of many islands is experiencing high extinction rates. The archipelago of Hawaii has one of the highest levels of endemism of any floristic region; 90% of its 1367 native vascular plant taxa are classified as endemic. We used the IUCN's assessment of the complete single-island endemic (SIE) vascular plant flora of Kauai, Hawaii, to assess the proportion and drivers of decline of threatened plants in an oceanic island setting. We compared the IUCN assessments with federal, state, and other local assessments of Kauai species or taxa of conservation concern. Finally, we conducted a preliminary assessment for all 1044 native vascular plants of Hawaii based on IUCN criterion B by estimating area of occupancy, extent of occurrence, and number of locations to determine whether the pattern found for the SIE vascular flora of Kauai is comparable to the native vascular flora of the Hawaiian Islands. We compared our results with patterns observed for assessments of other floras. According to IUCN, 256 SIE vascular plant taxa are threatened with extinction and 5% are already extinct. This is the highest extinction risk reported for any flora to date. The preliminary assessment of the native vascular flora of Hawaii showed that 72% (753 taxa) is threatened. The flora of Hawaii may be one of the world's most threatened; thus, increased and novel conservation measures in the state and on other remote oceanic islands are urgently needed.
La Lista Roja de la Unión Internacional para la Conservación de la Naturaleza (Lista Roja UICN) es la fuente más completa a nivel mundial de información sobre el estado de conservación de las especies. Las agencias gubernamentales y las organizaciones para la conservación dependen cada vez más de las valoraciones en esta lista para desarrollar sus políticas y prioridades de conservación; también los organismos de financiamiento usan las valoraciones como criterios de evaluación y los investigadores aplican metaanálisis a los datos de la lista para abordar preguntas fundamentales y aplicadas a las ciencias de la conservación. Sin embargo, las casi 143,000 valoraciones de la UICN representan sólo una fracción de la biodiversidad mundial y están sesgadas en cuanto a la cobertura regional y de organismos. Estos sesgos pueden afectar a las prioridades de conservación, al financiamiento y al uso de estos datos para entender los patrones globales. Las islas oceánicas aisladas se caracterizan por un alto endemismo, aunque la biodiversidad única de muchas de estas islas está experimentando un índice elevado de extinciones. El archipiélago de Hawái tiene uno de los niveles más altos de endemismo de cualquier región florística con el 90% de los 1,367 taxones nativos de flora vascular clasificado como endémico. Usamos las valoraciones de la UICN para todas las plantas vasculares endémicas de una sola isla (ESI) en Kauai, Hawái, para evaluar la proporción y los impulsores de la declinación de plantas amenazadas en el entorno de una isla oceánica. Comparamos las valoraciones de la UICN con las federales, estatales y otras valoraciones locales de las especies o taxones de Kauai que son de importancia para la conservación. Por último, realizamos una valoración preliminar para las 1,044 especies de plantas vasculares nativas de Hawái con base en el criterio B de la UICN mediante la estimación del área de ocupación, la extensión de la ocurrencia y el número de localidades para determinar si el patrón hallado para la flora vascular ESI de Kauai es comparable con la flora vascular nativa de las islas hawaianas. Comparamos nuestros resultados con los patrones observados en las valoraciones de otras floras. De acuerdo con la UICN, el 95% de los taxones de plantas vasculares ESI de Kauai están amenazadas y el 5% ya se encuentra extinto. A la fecha, este es el riesgo de extinción más alto reportado para cualquier flora. La valoración preliminar de la flora vascular nativa de Hawái mostró que el 72% (753 taxones) se encuentra amenazado. La flora de Hawái puede ser una de las más amenazadas a nivel mundial; por lo tanto, se necesitan urgentemente medidas novedosas e incrementadas en el estado y en otras islas oceánicas remotas.
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Conservación de los Recursos Naturales , Especies en Peligro de Extinción , Animales , Biodiversidad , Conservación de los Recursos Naturales/métodos , Extinción Biológica , Hawaii , PlantasRESUMEN
Ultraviolet-C (UVC) radiation can effectively inactivate pathogens on surfaces and in the air. Due to the potential for harm to skin and eyes, human exposure to UVC should be limited within the guideline exposure limits produced by the International Commission on Non-Ionising Radiation Protection (ICNIRP) or the American Conference of Governmental Industrial Hygienists (ACGIHs). Both organisations state an effective spectrally weighted limit of 3 mJ cm-2, although the spectral weighting factors of the two organisations diverged following a revision of the ACGIH guidelines in 2022. Using existing published human exposure data, the effective spectrally weighted radiant exposure was calculated for both unfiltered and filtered (to reduce UV emissions above 230 nm) krypton chloride (KrCl*) excimer lamps. The effective radiant exposure of the filtered KrCl* lamp was greater than 3 mJ cm-2when applying ICNIRP or either of the revised ACGIH spectral weightings. This indicates that both guidelines are appropriately conservative for this specific lamp. However, the effective radiant exposure of the unfiltered KrCl* lamp was as low as 1 mJ cm-2with the revised ACGIH weighting function that can be applied to the skin if the eyes are protected. Erythema has therefore been directly observed in a clinical study at an exposure within the revised ACGIH guideline limits. Extrapolating this information means that a mild sunburn could be induced in Fitzpatrick skin types I and II if that particular ACGIH weighting function were applied and an individual received an effective exposure of 3 mJ cm-2. Whilst it is improbable that such an effect would be seen in current deployment of KrCl* lamp technology, it does highlight the need for further research into skin sensitivity and irradiance-time reciprocity for UVC wavelengths.
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Criptón , Exposición Profesional , Humanos , Cloruros , Rayos Ultravioleta , Piel/efectos de la radiación , Exposición Profesional/análisisRESUMEN
PREMISE: Expanded phylogenetic analyses of the Hawaiian silversword alliance (Argyroxiphium, Dubautia, Wilkesia; Compositae) were undertaken to assess evolutionary and biogeographic informativeness of cytonuclear discordance and any biases in evolutionary directionality of ecological transitions within this prominent example of adaptive radiation. METHODS: Samples spanning the geographic and ecological distributions of all recognized taxa were included in phylogenetic and biogeographic analyses of nuclear ribosomal DNA (nrDNA) and cpDNA sequences. Bayesian model testing approaches were used to model ecological evolution and the evolution of nuclear chromosomal arrangements while accounting for phylogenetic uncertainty. RESULTS: Cytonuclear discordance detected previously appears to reflect chloroplast capture, at least in part, with nrDNA trees being largely congruent with nuclear chromosomal structural data and fine-scale taxonomy. Comparison of biogeographic histories estimated from the posterior distributions of nrDNA and cpDNA trees, including inferred chloroplast-capture events, provides additional resolution of dispersal history, including a back-dispersal to Maui Nui from Hawai'i. A newly resolved major nrDNA clade of endemic Kaua'i taxa that mostly were described as new-to-science since the 1980s strengthens the earlier hypothesis that diversification on Kaua'i has not waned since the island began to decline in area through subsidence and erosion. Bias in habitat shifts was estimated, with transitions from dry-to-mesic or -wet and from wet-to-mesic or -bog habitats dominating diversification of the silversword alliance from a dry-adapted tarweed ancestor. CONCLUSIONS: The habitat-transition biases estimated here may indicate more limited pathways of ecological evolution than proposed previously for an adaptive radiation involving such major ecological shifts.
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Asteraceae , Teorema de Bayes , Ecosistema , Evolución Molecular , Hawaii , FilogeniaRESUMEN
It is possible to enhance topical drug delivery by pretreatment of the skin with ablative fractional lasers (AFLs). However, the parameters to use for a given AFL to achieve the desired depth of ablation or the desired therapeutic or cosmetic outcome are hard to predict. This leaves open the real possibility of overapplication or underapplication of laser energy to the skin. In this study, we developed a numerical model consisting of a Monte Carlo radiative transfer (MCRT) code coupled to a heat transfer and tissue damage algorithm. The simulation is designed to predict the depth effects of AFL on the skin, verified with in vitro experiments in porcine skin via optical coherence tomography (OCT) imaging. Ex vivo porcine skin is irradiated with increasing energies (50-400 mJ/pixel) from a CO2 AFL. The depth of microscopic treatment zones is measured and compared with our numerical model. The data from the OCT images and MCRT model complement each other well. Nonablative thermal effects on surrounding tissue are also discussed. This model, therefore, provides an initial step toward a predictive determination of the effects of AFL on the skin. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.
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Terapia por Láser , Láseres de Gas , Animales , Sistemas de Liberación de Medicamentos , Rayos Láser , Láseres de Gas/uso terapéutico , Método de Montecarlo , Piel , Porcinos , Tomografía de Coherencia ÓpticaRESUMEN
IMPORTANCE: There has been limited research on patients with ST-segment elevation myocardial infarction (STEMI) and COVID-19. OBJECTIVE: To compare characteristics, treatment, and outcomes of patients with STEMI with vs without COVID-19 infection. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of consecutive adult patients admitted between January 2019 and December 2020 (end of follow-up in January 2021) with out-of-hospital or in-hospital STEMI at 509 US centers in the Vizient Clinical Database (N = 80â¯449). EXPOSURES: Active COVID-19 infection present during the same encounter. MAIN OUTCOMES AND MEASURES: The primary outcome was in-hospital mortality. Patients were propensity matched on the likelihood of COVID-19 diagnosis. In the main analysis, patients with COVID-19 were compared with those without COVID-19 during the previous calendar year. RESULTS: The out-of-hospital STEMI group included 76â¯434 patients (551 with COVID-19 vs 2755 without COVID-19 after matching) from 370 centers (64.1% aged 51-74 years; 70.3% men). The in-hospital STEMI group included 4015 patients (252 with COVID-19 vs 756 without COVID-19 after matching) from 353 centers (58.3% aged 51-74 years; 60.7% men). In patients with out-of-hospital STEMI, there was no significant difference in the likelihood of undergoing primary percutaneous coronary intervention by COVID-19 status; patients with in-hospital STEMI and COVID-19 were significantly less likely to undergo invasive diagnostic or therapeutic coronary procedures than those without COVID-19. Among patients with out-of-hospital STEMI and COVID-19 vs out-of-hospital STEMI without COVID-19, the rates of in-hospital mortality were 15.2% vs 11.2% (absolute difference, 4.1% [95% CI, 1.1%-7.0%]; P = .007). Among patients with in-hospital STEMI and COVID-19 vs in-hospital STEMI without COVID-19, the rates of in-hospital mortality were 78.5% vs 46.1% (absolute difference, 32.4% [95% CI, 29.0%-35.9%]; P < .001). CONCLUSIONS AND RELEVANCE: Among patients with out-of-hospital or in-hospital STEMI, a concomitant diagnosis of COVID-19 was significantly associated with higher rates of in-hospital mortality compared with patients without a diagnosis of COVID-19 from the past year. Further research is required to understand the potential mechanisms underlying this association.
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COVID-19/complicaciones , Mortalidad Hospitalaria , Hospitalización , Infarto del Miocardio con Elevación del ST/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paro Cardíaco Extrahospitalario , Puntaje de Propensión , Estudios Retrospectivos , Infarto del Miocardio con Elevación del ST/complicaciones , Estados Unidos/epidemiologíaRESUMEN
The dichloromethane extract from leaves of Melicope barbigera (Rutaceae), endemic to the Hawaiian island of Kaua'i, yielded four new and three previously known acetophenones and 2H-chromenes, all found for the first time in M. barbigera. The structures of the new compounds obtained from the dichloromethane extract after purification by chromatographic methods were unambiguously elucidated by spectroscopic analyses including 1D/2D NMR spectroscopy and HRESIMS. The absolute configuration was determined by modified Mosher's method. Compounds 2, 4 and the mixture of 6 and 7 exhibited moderate cytotoxic activities against the human ovarian cancer cell line A2780 with IC50 values of 30.0 and 75.7 µM for 2 and 4, respectively, in a nuclear shrinkage cytotoxicity assay.
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Acetofenonas/química , Benzopiranos/química , Hojas de la Planta/química , Rutaceae/química , Acetofenonas/farmacología , Benzopiranos/farmacología , Línea Celular Tumoral , Femenino , Hawaii , Humanos , Espectroscopía de Resonancia Magnética/métodos , Cloruro de Metileno/química , Neoplasias Ováricas/tratamiento farmacológicoRESUMEN
The infrageneric relationships and taxonomy of the largest fern genus, Asplenium (Aspleniaceae), have remained poorly understood. Previous studies have focused mainly on specific species complexes involving a few or dozens of species only, or have achieved a large taxon sampling but only one plastid marker was used. In the present study, DNA sequences from six plastid markers (atpB, rbcL, rps4, rps4-trnS, trnL and trnL-F) of 1030 accessions (616 of them newly sequenced here) representing c. 420 species of Asplenium (60% of estimated species diversity), 16 species of Hymenasplenium, three Diplaziopsidaceae, and four Rhachidosoraceae were used to produce the largest genus-level phylogeny yet for ferns. Our major results include: (i) Asplenium as broadly circumscribed is monophyletic based on our inclusion of representatives of 32 of 38 named segregate genera; (ii) 11 major clades in Asplenium are identified, and their relationships are mostly well-resolved and strongly supported; (iii) numerous species, unsampled in previous studies, suggest new relationships and numerous cryptic species and species complexes in Asplenium; and (iv) the accrued molecular evidence provides an essential foundation for further investigations of complex patterns of geographical diversification, speciation and reticulate evolution in this family.
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BACKGROUND: High mitotic activity is associated with the genesis and progression of many cancers. Small molecule inhibitors of mitotic apparatus proteins are now being developed and evaluated clinically as anticancer agents. With clinical trials of several of these experimental compounds underway, it is important to understand the molecular mechanisms that determine high mitotic activity, identify tumor subtypes that carry molecular aberrations that confer high mitotic activity, and to develop molecular markers that distinguish which tumors will be most responsive to mitotic apparatus inhibitors. METHODS: We identified a coordinately regulated mitotic apparatus network by analyzing gene expression profiles for 53 malignant and non-malignant human breast cancer cell lines and two separate primary breast tumor datasets. We defined the mitotic network activity index (MNAI) as the sum of the transcriptional levels of the 54 coordinately regulated mitotic apparatus genes. The effect of those genes on cell growth was evaluated by small interfering RNA (siRNA). RESULTS: High MNAI was enriched in basal-like breast tumors and was associated with reduced survival duration and preferential sensitivity to inhibitors of the mitotic apparatus proteins, polo-like kinase, centromere associated protein E and aurora kinase designated GSK462364, GSK923295 and GSK1070916, respectively. Co-amplification of regions of chromosomes 8q24, 10p15-p12, 12p13, and 17q24-q25 was associated with the transcriptional upregulation of this network of 54 mitotic apparatus genes, and we identify transcription factors that localize to these regions and putatively regulate mitotic activity. Knockdown of the mitotic network by siRNA identified 22 genes that might be considered as additional therapeutic targets for this clinically relevant patient subgroup. CONCLUSIONS: We define a molecular signature which may guide therapeutic approaches for tumors with high mitotic network activity.
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Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes/genética , Genoma Humano/genética , Mitosis/efectos de los fármacos , Aurora Quinasas/antagonistas & inhibidores , Aurora Quinasas/genética , Aurora Quinasas/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Proteínas Cromosómicas no Histona/antagonistas & inhibidores , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Femenino , Amplificación de Genes , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes/efectos de los fármacos , Humanos , Estimación de Kaplan-Meier , Mitosis/genética , Pronóstico , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Interferencia de ARN , Bibliotecas de Moléculas Pequeñas/farmacología , Resultado del Tratamiento , Quinasa Tipo Polo 1RESUMEN
The wide geographical distribution of many fern species is related to their high dispersal ability. However, very limited studies surveyed biological traits that could contribute to colonization success after dispersal. In this study, we applied phylogenetic approaches to infer historical biogeography of the fern genus Deparia (Athyriaceae, Eupolypods II). Because polyploids are suggested to have better colonization abilities and are abundant in Deparia, we also examined whether polyploidy could be correlated to long-distance dispersal events and whether polyploidy could play a role in these dispersals/establishment and range expansion. Maximum likelihood and Bayesian phylogenetic reconstructions were based on a four-region combined cpDNA dataset (rps16-matK IGS, trnL-L-F, matK and rbcL; a total of 4252 characters) generated from 50 ingroup (ca. 80% of the species diversity) and 13 outgroup taxa. Using the same sequence alignment and maximum likelihood trees, we carried out molecular dating analyses. The resulting chronogram was used to reconstruct ancestral distribution using the DEC model and ancestral ploidy level using ChromEvol. We found that Deparia originated around 27.7Ma in continental Asia/East Asia. A vicariant speciation might account for the disjunctive distribution of East Asia-northeast North America. There were multiple independent long-distance dispersals to Africa/Madagascar (at least once), Southeast Asia (at least once), south Pacific islands (at least twice), Australia/New Guinea/New Zealand (at least once), and the Hawaiian Islands (at least once). In particular, the long-distance dispersal to the Hawaiian Islands was associated with polyploidization, and the dispersal rate was slightly higher in the polyploids than in diploids. Moreover, we found five species showing recent infraspecific range expansions, all of which took place concurrently with polyploidization. In conclusion, our study provides the first investigation using phylogenetic and biogeographic analyses trying to explore the link between historical biogeography and ploidy evolution in a fern genus and our results imply that polyploids might be better colonizers than diploids.
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Helechos/clasificación , África , Asia , Australia , Teorema de Bayes , Biodiversidad , Criptocromos/clasificación , Criptocromos/genética , Criptocromos/metabolismo , ADN de Cloroplastos/química , ADN de Cloroplastos/genética , ADN de Cloroplastos/metabolismo , Helechos/genética , Hawaii , América del Norte , Filogenia , Filogeografía , Poliploidía , Análisis de Secuencia de ADNRESUMEN
The various benefits of light sheet microscopy have made it a widely used modality for capturing three-dimensional images. It is mostly used for fluorescence imaging, but recently another technique called light sheet tomography solely relying on scattering was presented. The method was successfully applied to imaging of plant roots in transparent soil, but is limited when it comes to more turbid samples. This study presents a polarised light sheet tomography system and its advantages when imaging in highly scattering turbid media. The experimental configuration is guided by Monte Carlo radiation transfer methods, which model the propagation of a polarised light sheet in the sample. Images of both reflecting and absorbing phantoms in a complex collagenous matrix were acquired, and the results for different polarisation configurations are compared. Focus scanning methods were then used to reduce noise and produce three-dimensional reconstructions of absorbing targets.
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BACKGROUND: Guidelines from the Infectious Diseases Society of America/The American Thoracic Society (IDSA/ATS) provide recommendations for diagnosis and treatment of ventilator-associated pneumonia (VAP). However, the mere presence of guidelines is rarely sufficient to promote widespread adoption and uptake. Using the Systems Engineering Initiative for Patient Safety (SEIPS) model framework, we undertook a study to understand barriers and facilitators to the adoption of the IDSA/ATS guidelines. METHODS: We conducted surveys and focus group discussions of different health care providers involved in the management of VAP. The setting was medical-surgical ICUs at a tertiary academic hospital and a large multispecialty rural hospital in Wisconsin, USA. RESULTS: Overall, we found that 55 % of participants indicated that they were aware of the IDSA/ATS guideline. The top ranked barriers to VAP management included: 1) having multiple physician groups managing VAP, 2) variation in VAP management by differing ICU services, 3) physicians and level of training, and 4) renal failure complicating doses of antibiotics. Facilitators to VAP management included presence of multidisciplinary rounds that include nurses, pharmacist and respiratory therapists, and awareness of the IDSA/ATS guideline. This awareness was associated with receiving effective training on management of VAP, keeping up to date on nosocomial infection literature, and belief that performing a bronchoscopy to diagnose VAP would help with expeditious diagnosis of VAP. CONCLUSIONS: Findings from our study complement existing studies by identifying perceptions of the many different types of healthcare workers in ICU settings. These findings have implications for antibiotic stewardship teams, clinicians, and organizational leaders.
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Actitud del Personal de Salud , Adhesión a Directriz/estadística & datos numéricos , Unidades de Cuidados Intensivos/normas , Neumonía Asociada al Ventilador/diagnóstico , Neumonía Asociada al Ventilador/terapia , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Grupos Focales , Encuestas de Atención de la Salud , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , WisconsinRESUMEN
The ability to make a diagnosis early and appropriately is paramount for the survival of the critically ill ICU patient. Along with the myriad physical examination and imaging modalities available, biomarkers provide a window on the disease process. Herein we review hepatic biomarkers in the context of the critical care patient.
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Biomarcadores/metabolismo , Cuidados Críticos/métodos , Hepatopatías/metabolismo , HumanosRESUMEN
This document was developed through the collaborative efforts of the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations. Under the auspices of these societies, a multidisciplinary, multi-institutional task force was convened, incorporating expertise in critical care medicine, organ donor management, and transplantation. Members of the task force were divided into 13 subcommittees, each focused on one of the following general or organ-specific areas: death determination using neurologic criteria, donation after circulatory death determination, authorization process, general contraindications to donation, hemodynamic management, endocrine dysfunction and hormone replacement therapy, pediatric donor management, cardiac donation, lung donation, liver donation, kidney donation, small bowel donation, and pancreas donation. Subcommittees were charged with generating a series of management-related questions related to their topic. For each question, subcommittees provided a summary of relevant literature and specific recommendations. The specific recommendations were approved by all members of the task force and then assembled into a complete document. Because the available literature was overwhelmingly comprised of observational studies and case series, representing low-quality evidence, a decision was made that the document would assume the form of a consensus statement rather than a formally graded guideline. The goal of this document is to provide critical care practitioners with essential information and practical recommendations related to management of the potential organ donor, based on the available literature and expert consensus.
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Unidades de Cuidados Intensivos/organización & administración , Guías de Práctica Clínica como Asunto , Donantes de Tejidos , Obtención de Tejidos y Órganos/organización & administración , Muerte , Humanos , Unidades de Cuidados Intensivos/normas , Derechos del Paciente , Sociedades Médicas , Obtención de Tejidos y Órganos/normas , Estados UnidosAsunto(s)
Desinfección , Eritema , ADN , Eritema/inducido químicamente , Voluntarios Sanos , Humanos , Mutágenos , Proyectos Piloto , PielRESUMEN
Breast cancers are comprised of molecularly distinct subtypes that may respond differently to pathway-targeted therapies now under development. Collections of breast cancer cell lines mirror many of the molecular subtypes and pathways found in tumors, suggesting that treatment of cell lines with candidate therapeutic compounds can guide identification of associations between molecular subtypes, pathways, and drug response. In a test of 77 therapeutic compounds, nearly all drugs showed differential responses across these cell lines, and approximately one third showed subtype-, pathway-, and/or genomic aberration-specific responses. These observations suggest mechanisms of response and resistance and may inform efforts to develop molecular assays that predict clinical response.
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Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Neoplasias de la Mama/genética , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Dosificación de Gen/genética , Humanos , Modelos Biológicos , Transducción de Señal/genética , Transcripción Genética/efectos de los fármacosRESUMEN
The ability to accurately measure and assess current and potential health care system capacities is an issue of local and national significance. Recent joint statements by the Institute of Medicine and the Agency for Healthcare Research and Quality have emphasized the need to apply industrial and systems engineering principles to improving health care quality and patient safety outcomes. To address this need, a decision support tool was developed for planning and budgeting of current and future bed capacity, and evaluating potential process improvement efforts. The Strategic Bed Analysis Model (StratBAM) is a discrete-event simulation model created after a thorough analysis of patient flow and data from Geisinger Health System's (GHS) electronic health records. Key inputs include: timing, quantity and category of patient arrivals and discharges; unit-level length of care; patient paths; and projected patient volume and length of stay. Key outputs include: admission wait time by arrival source and receiving unit, and occupancy rates. Electronic health records were used to estimate parameters for probability distributions and to build empirical distributions for unit-level length of care and for patient paths. Validation of the simulation model against GHS operational data confirmed its ability to model real-world data consistently and accurately. StratBAM was successfully used to evaluate the system impact of forecasted patient volumes and length of stay in terms of patient wait times, occupancy rates, and cost. The model is generalizable and can be appropriately scaled for larger and smaller health care settings.
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Simulación por Computador , Eficiencia Organizacional , Administración Hospitalaria , Capacidad de Camas en Hospitales/estadística & datos numéricos , Modelos Estadísticos , Vías Clínicas/estadística & datos numéricos , Técnicas de Apoyo para la Decisión , Hospitalización/estadística & datos numéricos , Humanos , Tiempo de Internación , Reproducibilidad de los Resultados , Factores de Tiempo , Estados Unidos , Listas de EsperaRESUMEN
OBJECTIVES: Guidelines have recommended that risk stratification be performed in patients diagnosed with an acute pulmonary embolism (PE). No study has described the use of risk stratification in routine clinical practice. The purpose of this study was to measure the frequency and impact of risk stratification on treatment decisions and outcomes in patients admitted with acute PE. METHODS: A retrospective cohort study was conducted of all of the patients admitted with acute PE at two Geisinger community-based teaching hospitals between 2006 and 2011. Baseline demographics, vital signs, and relevant clinical variables were recorded. The Pulmonary Embolism Severity Index was calculated for each patient. Risk stratification was defined as the measurement of either a biomarker or an echocardiogram within 24 hours of admission. The outcomes measured were short-term adverse events (in-hospital mortality or need for intensive care) and 30-day mortality. RESULTS: The mean age for the study cohort (n = 889) was 61 ± 17 years and 52% were men. Overall, 59% of study subjects were risk stratified. The frequency of risk stratification did not change over time. Risk stratification was associated with assignment to a higher acuity of care and increased use of thrombolysis and inferior vena cava filter placement. When controlling for severity of illness, risk stratification was a significant predictor of worsened short-term adverse outcome (odds ratio 3.43, 95% confidence interval 1.75-6.74, P < 0.001) but was not associated with improved 30-day mortality (odds ratio 1.14, 95% confidence interval 0.66-1.95, P = 0.64). CONCLUSIONS: Risk stratification is frequently performed in patients admitted with acute PE and has had a stable prevalence during a 5-year period. The use of risk stratification in acute PE is associated with assignment to higher levels of care and with more advanced treatments. Despite more intense treatment, risk stratification does not improve either short-term outcomes or 30-day mortality.
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Biomarcadores/sangre , Péptido Natriurético Encefálico/sangre , Embolia Pulmonar/diagnóstico , Troponina/sangre , Enfermedad Aguda , Anciano , Estudios de Cohortes , Toma de Decisiones , Electrocardiografía , Femenino , Mortalidad Hospitalaria , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Embolia Pulmonar/sangre , Embolia Pulmonar/mortalidad , Estudios Retrospectivos , Medición de Riesgo/métodos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Estados UnidosRESUMEN
Cyrtandraobliquifolia K.R. Wood & W.L. Wagner (Gesneriaceae), a new shrub species known only from Kaua'i, Hawaiian Islands, is described and illustrated with notes on its distribution, ecology, and conservation status. The new species is morphologically most similar to Cyrtandrawawrae C.B. Clarke but differs by its unique combination of oblique, non-peltate, auriculate leaf bases, more deeply divided calyx lobes, inflorescence with fewer flowers and lacking profusely umbellate cymes. Cyrtandraobliquifolia is known from only two localities which have undergone severe habitat degradation from landslides and invasive plants and animals and is determined to be Critically Endangered (CR) when evaluated under IUCN criteria.
RESUMEN
Far-UVC, from filtered Krypton-Chloride lamps, is promising for reducing airborne transmission of disease. While significant research has been undertaken to investigate skin safety of these lamps, less work has been undertaken on eye safety. There is limited data on human eye safety or discomfort from the deployment of this germicidal technology. In this pilot study, immediate and delayed eye discomfort were assessed in a simulated office environment with deployment of Krypton-Chloride lamps, located on the ceiling and directed downwards into the occupied room. Discomfort was assessed immediately postexposure and several days after exposure using validated, Standard Patient Evaluation Eye Dryness (SPEED) and Ocular Surface Disease Index (OSDI) questionnaires. Our results show no significant eye discomfort or adverse effects from the deployment of Far-UVC in this simulated office environment, even when lamps were operated continuously with participants receiving head exposures of up to 50 mJ cm-2 . In addition, a statistically significant reduction in bacteria and fungi of 52% was observed. Far-UVC in this simulated office environment did not cause any clinically significant eye discomfort and was effective at reducing pathogens in the room. These results contribute an important step to further investigation of the interaction of Far-UVC with the human eye.