House Calls by Mobile Integrated Health Paramedics for Patients with Heart Failure: A Feasibility Study.

Background: Early readmissions following hospital discharge for heart failure (HF) remain a major concern. Among the various strategies designed to reduce readmissions, home evaluations have been observed to have a favorable impact. We assessed the feasibility of integrating community paramedics into the outpatient management of HF patients. Methods: Selected paramedics completed an educational HF curriculum. These Mobile Integrated Health Paramedics (MIHP) performed scheduled home visits 2- and 15-days post-discharge for patients with Stage C HF (Phase I) and patients with Stage D HF (Phase II). Facilitated by a Call Center, a process was created for performing urgent MIHP house calls within 60 minutes of a medical provider’s request. A HF specialist, with an on-call emergency department command physician, could order an intravenous diuretic during home visits. During each phase of the study the incidence of 30-day HF readmissions, 30-day all-cause readmissions, emergency room evaluations, unplanned office encounters, as well as any adverse events were prospectively documented. Results: Collaborative relationships between our hospital network and local EMS organizations were created. There were 82 MIHP home visits. Eight patients received urgent home evaluations within 60 minutes post-request, 1 requiring transport to an ED. The incidence of all-cause 30-day readmissions in 20 Stage C and 20 Stage D patients was 15% and 40%, respectively. There were no adverse events attributable to the MIHP house calls. Conclusions: It is feasible to integrate MIHPs into the outpatient management of HF. Signals of effectiveness for reducing early readmissions were observed. Obstacles to creating an effective paramedic “House Calls” program were identified. A randomized trial is required to assess the value of this care process and its impact on early readmissions in patients with Stage C and Stage D HF

The late Pleistocene Sacarosa tephra-fall deposit, Misti Volcano, Arequipa, Peru: its magma, eruption, and implications for past and future activity

Entre 38.5 ka cal BP y 32.4 ka cal BP el volcán Misti generó una erupción dacítica con Indice de Explosividad Volcánica 5 que emplazo el depósito de caída de tefra “Sacarosa”. La presencia de fenocristales de biotita, el tamaño fino de sus granos, escasos líticos y la abundancia de cristales libres caracterizan el depósito en los lugares muestreados. El magma tuvo una temperatura de ~ 800 °C, el cual ascendió rápidamente de ~ 10 km de profundidad y resultó en una erupción Pliniana que tuvo una tasa de descarga de masa de 7.7 × 106– 4.1 × 107 kg/s, y deposito alrededor de 3 km3 de tefra dentro de decenas de horas. El depósito tiene dos capas con espesores casi similares, separados por un contacto difuso y con una capa superior que se caracteriza por contener granos un poco más gruesos y ser un poco menos sorteado que la capa inferior. La capa superior gruesa indica condiciones culminantes o un menor grado de fragmentación durante la última mitad de la erupción. Fuertes vientos distribuyeron el depósito al suroeste del Misti cubriendo al menos 800 km2, incluyendo la actual ciudad de Arequipa donde el depósito de tefra tiene hasta 100 cm de espesor. El depósito “Sacarosa” es el primero entre los depósitos de la etapa Cayma (un grupo distintivo de unidades félsicas que contienen biotita) que es descrito detalladamente y con su erupción caracterizada. Varios depósitos de la etapa Cayma fueron generados por erupciones explosivas voluminosas similares a la erupción “Sacarosa”, representando un intervalo de ~ 8.9–15.5 ky de poderosas erupciones. Una erupción tan explosiva hoy amenazaría a los más de 1,100,000 habitantes de Arequipa, muchos de ellos viven dentro del área de distribución del depósito “Sacarosa”

Phage-Mediated Acquisition of a Type III Secreted Effector Protein Boosts Growth of Salmonella by Nitrate Respiration

Information on how emerging pathogens can invade and persist and spread within host populations remains sparse. In the 1980s, a multidrug-resistant Salmonella enterica serotype Typhimurium clone lysogenized by a bacteriophage carrying the sopE virulence gene caused an epidemic among cattle and humans in Europe. Here we show that phage-mediated horizontal transfer of the sopE gene enhances the production of host-derived nitrate, an energetically highly valuable electron acceptor, in a mouse colitis model. In turn, nitrate fuels a bloom of S. Typhimurium in the gut lumen through anaerobic nitrate respiration while suppressing genes for the utilization of energetically inferior electron acceptors such as tetrathionate. Through this mechanism, horizontal transfer of sopE can enhance the fitness of S. Typhimurium, resulting in its significantly increased abundance in the feces

Characterisation of riverine dissolved organic matter using a complementary suite of chromatographic and mass spectrometric methods

Dissolved organic matter (DOM) plays a fundamental role in nutrient cycling dynamics in riverine systems. Recent research has confirmed that the concentration of riverine DOM is not the only factor regulating its functional significance; the need to define the chemical composition of DOM is a priority. Past studies of riverine DOM rested on bulk quantification, however technological advancements have meant there has been a shift towards analytical methods which allow the characterisation of DOM either at compound class or more recently molecular level. However, it is important to consider that all analytical methods only consider a defined analytical window. Thus, herein, we explore the use of a hierarchy of methods which can be used in combination for the investigation of a wide range of DOM chemistries. By using these methods to investigate the DOM composition of a range of streams draining catchments of contrasting environmental character, a wide range of compounds were identified across a range of polarities and molecular weight, thereby extending the analytical window. Through the elucidation of the DOM character in stream samples, information can be collected about likely the sources of DOM. The identification of individual key compounds within the DOM pool is a key step in the design of robust and informative bioassay experiments, used to understand in-stream ecosystem responses. This is critical if we are to assess the role of DOM as a bioavailable nutrient resource and/or ecotoxicological factor in freshwater

Deconvolution of Images from BLAST 2005: Insight into the K3-50 and IC 5146 Star-Forming Regions

We present an implementation of the iterative flux-conserving Lucy-Richardson (L-R) deconvolution method of image restoration for maps produced by the Balloon-borne Large Aperture Submillimeter Telescope (BLAST). We have analyzed its performance and convergence extensively through simulations and cross-correlations of the deconvolved images with available highresolution maps. We present new science results from two BLAST surveys, in the Galactic regions K3-50 and IC 5146, further demonstrating the benefits of performing this deconvolution. We have resolved three clumps within a radius of 4.'5 inside the star-forming molecular cloud containing K3-50. Combining the well-resolved dust emission map with available multi-wavelength data, we have constrained the Spectral Energy Distributions (SEDs) of five clumps to obtain masses (M), bolometric luminosities (L), and dust temperatures (T). The L-M diagram has been used as a diagnostic tool to estimate the evolutionary stages of the clumps. There are close relationships between dust continuum emission and both 21-cm radio continuum and 12CO molecular line emission. The restored extended large scale structures in the Northern Streamer of IC 5146 have a strong spatial correlation with both SCUBA and high resolution extinction images. A dust temperature of 12 K has been obtained for the central filament. We report physical properties of ten compact sources, including six associated protostars, by fitting SEDs to multi-wavelength data. All of these compact sources are still quite cold (typical temperature below ~ 16 K) and are above the critical Bonner-Ebert mass. They have associated low-power Young Stellar Objects (YSOs). Further evidence for starless clumps has also been found in the IC 5146 region.Comment: 13 pages, 12 Figures, 3 Table

La erupción subpliniana del volcán Misti ocurrida hace 33,700 años que emplazó el depósito de caída de tefra “sacarosa”

El volcán Misti, es uno de los ocho volcanes activos del sur peruano, cuyo cráter está localizado a 17 km al NE del centro de la ciudad de Arequipa, donde viven aproximadamente un millón de habitantes. Durante los últimos 40 mil años, el volcán Misti ha presentado una actividad predominantemente explosiva ligados al crecimiento y colapso de domos, erupciones vulcanianas, plinianas y subplinianas depositando corrientes de densidad piroclástica y caídas de tefra (Thouret et al., 2001). En este periodo el Misti registró una erupción que dejó un depósito de caída de tefra con una granulometría fina homogénea en Arequipa denominado como caída “Sacarosa”, datada en este estudio en ~33 700 años AP. Este depósito aflora al Oeste y SO del volcán Misti en los distritos Mariano Melgar, Alto Selva Alegre, Cayma, Cerro Colorado y Yura. El depósito “Sacarosa” presenta buen sorteo y gradación inversa, con una matriz rica en fenocristales libres de plagioclasa (90%), biotita y anfíbol. Las pómez son angulosas a subangulosas de color blanquecina. Además, el depósito presenta escasos fragmentos líticos lávicos oxidados (< 1%) en las zonas proximales, a 11 km del volcán donde tiene un espesor de 1.25 m. En la zona medial a 15 km del cráter, el espesor del depósito tiene 0.78 m y en la zona distal a 25 km del cráter el depósito tiene entre 18 y 20 cm de espesor, resultando así un eje de dispersión hacia el SO del volcán Misti. La pómez del depósito “Sacarosa” es de composición dacítica (65 wt% SiO2). La erupción generó una columna eruptiva de ~22 km de altura, y tuvo un volumen de 0.5 – 1.5 km3, siendo catalogada como una erupción de tipo subpliniana de VEI 4

Estudio preliminar de la erupción del volcán Misti ocurrida hace 33,600 años AP que emplazo el depósito de caída de tefra “Sacarosa” en Arequipa

El volcán Misti (5822 msnm), es uno de los siete volcanes activos del sur peruano, cuyo cráter está localizado a 17 km al noreste del centro de la ciudad de Arequipa, donde radican aproximadamente un millón de habitantes (INEI, 2016). Dicho volcán actualmente presenta emisiones de gases en el interior del cráter que indica que el volcán está en un continuo proceso de desgasificación. A través del estudio de uno de los depósitos emplazados por una erupción del Misti ocurrida hace ~30000 años AP, conocido como “Sacarosa” nosotros deseamos comprender mejor el comportamiento pasado del volcán para contribuir a la prevención y mitigación de riesgo volcánico en Arequipa, esto en caso de una posible reactivación del volcán Misti

The Vaginal Microbiome: Disease, Genetics and the Environment

The vagina is an interactive interface between the host and the environment. Its surface is covered by a protective epithelium colonized by bacteria and other microorganisms. The ectocervix is nonsterile, whereas the endocervix and the upper genital tract are assumed to be sterile in healthy women. Therefore, the cervix serves a pivotal role as a gatekeeper to protect the upper genital tract from microbial invasion and subsequent reproductive pathology. Microorganisms that cross this barrier can cause preterm labor, pelvic inflammatory disease, and other gynecologic and reproductive disorders. Homeostasis of the microbiome in the vagina and ectocervix plays a paramount role in reproductive health. Depending on its composition, the microbiome may protect the vagina from infectious or non-infectious diseases, or it may enhance its susceptibility to them. Because of the nature of this organ, and the fact that it is continuously colonized by bacteria from birth to death, it is virtually certain that this rich environment evolved in concert with its microbial flora. Specific interactions dictated by the genetics of both the host and microbes are likely responsible for maintaining both the environment and the microbiome. However, the genetic basis of these interactions in both the host and the bacterial colonizers is currently unknown. _Lactobacillus_ species are associated with vaginal health, but the role of these species in the maintenance of health is not yet well defined. Similarly, other species, including those representing minor components of the overall flora, undoubtedly influence the ability of potential pathogens to thrive and cause disease. Gross alterations in the vaginal microbiome are frequently observed in women with bacterial vaginosis, but the exact etiology of this disorder is still unknown. There are also implications for vaginal flora in non-infectious conditions such as pregnancy, pre-term labor and birth, and possibly fertility and other aspects of women&#x2019;s health. Conversely, the role of environmental factors in the maintenance of a healthy vaginal microbiome is largely unknown. To explore these issues, we have proposed to address the following questions:&#xd;&#xa;&#xd;&#xa;*1.&#x9;Do the genes of the host contribute to the composition of the vaginal microbiome?* We hypothesize that genes of both host and bacteria have important impacts on the vaginal microbiome. We are addressing this question by examining the vaginal microbiomes of mono- and dizygotic twin pairs selected from the over 170,000 twin pairs in the Mid-Atlantic Twin Registry (MATR). Subsequent studies, beyond the scope of the current project, may investigate which host genes impact the microbial flora and how they do so.&#xd;&#xa;*2.&#x9;What changes in the microbiome are associated with common non-infectious pathological states of the host?* We hypothesize that altered physiological (e.g., pregnancy) and pathologic (e.g., immune suppression) conditions, or environmental exposures (e.g., antibiotics) predictably alter the vaginal microbiome. Conversely, certain vaginal microbiome characteristics are thought to contribute to a woman&#x2019;s risk for outcomes such as preterm delivery. We are addressing this question by recruiting study participants from the ~40,000 annual clinical visits to women&#x2019;s clinics of the VCU Health System.&#xd;&#xa;*3.&#x9;What changes in the vaginal microbiome are associated with relevant infectious diseases and conditions?* We hypothesize that susceptibility to infectious disease (e.g. HPV, _Chlamydia_ infection, vaginitis, vaginosis, etc.) is impacted by the vaginal microbiome. In turn, these infectious conditions clearly can affect the ability of other bacteria to colonize and cause pathology. Again, we are exploring these issues by recruiting participants from visitors to women&#x2019;s clinics in the VCU Health System.&#xd;&#xa;&#xd;&#xa;Three kinds of sequence data are generated in this project: i) rDNA sequences from vaginal microbes; ii) whole metagenome shotgun sequences from vaginal samples; and iii) whole genome shotgun sequences of bacterial clones selected from vaginal samples. The study includes samples from three vaginal sites: mid-vaginal, cervical, and introital. The data sets also include buccal and perianal samples from all twin participants. Samples from these additional sites are used to test the hypothesis of a per continuum spread of bacteria in relation to vaginal health. An extended set of clinical metadata associated with these sequences are deposited with dbGAP. We have currently collected over 4,400 samples from ~100 twins and over 450 clinical participants. We have analyzed and deposited data for 480 rDNA samples, eight whole metagenome shotgun samples, and over 50 complete bacterial genomes. These data are available to accredited investigators according to NIH and Human Microbiome Project (HMP) guidelines. The bacterial clones are deposited in the Biodefense and Emerging Infections Research Resources Repository (&#x22;http://www.beiresources.org/&#x22;:http://www.beiresources.org/). &#xd;&#xa;&#xd;&#xa;In addition to the extensive sequence data obtained in this study, we are collecting metadata associated with each of the study participants. Thus, participants are asked to complete an extensive health history questionnaire at the time samples are collected. Selected clinical data associated with the visit are also obtained, and relevant information is collected from the medical records when available. This data is maintained securely in a HIPAA-compliant data system as required by VCU&#x2019;s Institutional Review Board (IRB). The preponderance of these data (i.e., that judged appropriate by NIH staff and VCU&#x2019;s IRB are deposited at dbGAP (&#x22;http://www.ncbi.nlm.nih.gov/gap&#x22;:http://www.ncbi.nlm.nih.gov/gap). Selected fields of this data have been identified by NIH staff as &#x2018;too sensitive&#x2019; and are not available in dbGAP. Individuals requiring access to these data fields are asked to contact the PI of this project or NIH Program Staff. &#xd;&#xa

Treatment of Severe Swallowing Dysfunction in Systemic Sclerosis with IVIG: Role of Antimuscarinic Antibodies

Oropharyngeal and esophageal dysmotility can cause serious clinical complications such as aspiration pneumonia, cachexia, and sarcopenia, with a resulting increase in mortality and disability. The current standard of care for the treatment of SSc-associated swallowing dysfunction is mainly supportive, although severe cases are usually refractory to conventional management. Recent studies have shown that the abnormal production of functional autoantibodies such as anti-cholinergic muscarinic receptor III antibodies may participate in the pathogenesis of SSc-associated gastrointestinal dysmotility and may provide a novel target for therapeutic intervention. We describe two patients with severe and rapid onset of SSc-associated severe swallowing dysfunction and esophageal dysmotility who had failed standard of care therapy, requiring complete enteral and parenteral nutrition. Both patients were positive for the presence of circulating antimuscarinic III receptor antibodies. They were treated with IVIG at a dose of 2 g/Kg/month divided in two consecutive days, for six months. Following IVIG therapy, both patients markedly improved their symptoms as shown by a reduction in their UCLA2.0 score, and achieved an improvement of esophageal motility documented radiologically. Both patients resumed oral feeding and had their feeding tubes removed within the treatment period. None of the patients developed severe adverse events attributable to IVIG, except for low-grade fever during IVIG infusion in one of the cases. These results provide support for the role of functional autoantibodies in the development of SSc-associated gastrointestinal dysfunction

IL-1α Signaling Is Critical for Leukocyte Recruitment after Pulmonary Aspergillus fumigatus Challenge

Aspergillus fumigatus is a mold that causes severe pulmonary infections. Our knowledge of how A. fumigatus growth is controlled in the respiratory tract is developing, but still limited. Alveolar macrophages, lung resident macrophages, and airway epithelial cells constitute the first lines of defense against inhaled A. fumigatus conidia. Subsequently, neutrophils and inflammatory CCR2+ monocytes are recruited to the respiratory tract to prevent fungal growth. However, the mechanism of neutrophil and macrophage recruitment to the respiratory tract after A. fumigatus exposure remains an area of ongoing investigation. Here we show that A. fumigatus pulmonary challenge induces expression of the inflammasome-dependent cytokines IL-1β and IL-18 within the first 12 hours, while IL-1α expression continually increases over at least the first 48 hours. Strikingly, Il1r1-deficient mice are highly susceptible to pulmonary A. fumigatus challenge exemplified by robust fungal proliferation in the lung parenchyma. Enhanced susceptibility of Il1r1-deficient mice correlated with defects in leukocyte recruitment and anti-fungal activity. Importantly, IL-1α rather than IL-1β was crucial for optimal leukocyte recruitment. IL-1α signaling enhanced the production of CXCL1. Moreover, CCR2+ monocytes are required for optimal early IL-1α and CXCL1 expression in the lungs, as selective depletion of these cells resulted in their diminished expression, which in turn regulated the early accumulation of neutrophils in the lung after A. fumigatus challenge. Enhancement of pulmonary neutrophil recruitment and anti-fungal activity by CXCL1 treatment could limit fungal growth in the absence of IL-1α signaling. In contrast to the role of IL-1α in neutrophil recruitment, the inflammasome and IL-1β were only essential for optimal activation of anti-fungal activity of macrophages. As such, Pycard-deficient mice are mildly susceptible to A. fumigatus infection. Taken together, our data reveal central, non-redundant roles for IL-1α and IL-1β in controlling A. fumigatus infection in the murine lung