The coming-of-age of the hygiene hypothesis

The hygiene hypothesis, as originally proposed, postulated an inverse relation between the incidence of infectious diseases in early life and the subsequent development of allergies and asthma. New evidence from epidemiological, biological and genetic studies has significantly enlarged the scope of the hypothesis. It now appears probable that environmental 'danger' signals regulate the pattern of immune responses in early life. Microbial burden in general, and not any single acute infectious illness, is the main source of these signals. The latter interact with a sensitive and complex receptor system, and genetic variations in this receptor system may be an important determinant of inherited susceptibility to asthma and allergies

Mometasone or Tiotropium in Mild Asthma with a Low Sputum Eosinophil Level

Background: In many patients with mild, persistent asthma, the percentage of eosinophils in sputum is less than 2% (low eosinophil level). The appropriate treatment for these patients is unknown. Methods In this 42-week, double-blind, crossover trial, we assigned 295 patients who were at least 12 years of age and who had mild, persistent asthma to receive mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist), or placebo. The patients were categorized according to the sputum eosinophil level (= 2%). The primary outcome was the response to mometasone as compared with placebo and to tiotropium as compared with placebo among patients with a low sputum eosinophil level who had a prespecified differential response to one of the trial agents. The response was determined according to a hierarchical composite outcome that incorporated treatment failure, asthma control days, and the forced expiratory volume in 1 second; a two-sided P value of less than 0.025 denoted statistical significance. A secondary outcome was a comparison of results in patients with a high sputum eosinophil level and those with a low level. Results: A total of 73% of the patients had a low eosinophil level; of these patients, 59% had a differential response to a trial agent. However, there was no significant difference in the response to mometasone or tiotropium, as compared with placebo. Among the patients with a low eosinophil level who had a differential treatment response, 57% (95% confidence interval [CI], 48 to 66) had a better response to mometasone, and 43% (95% CI, 34 to 52) had a better response to placebo (P=0.14). In contrast 60% (95% CI, 51 to 68) had a better response to tiotropium, whereas 40% (95% CI, 32 to 49) had a better response to placebo (P=0.029). Among patients with a high eosinophil level, the response to mometasone was significantly better than the response to placebo (74% vs. 26%) but the response to tiotropium was not (57% vs. 43%). Conclusions: The majority of patients with mild, persistent asthma had a low sputum eosinophil level and had no significant difference in their response to either mometasone or tiotropium as compared with placebo. These data provide equipoise for a clinically directive trial to compare an inhaled glucocorticoid with other treatments in patients with a low eosinophil level. (Funded by the National Heart, Lung, and Blood Institute; SIENA ClinicalTrials.gov number, .) In this trial involving patients with mild, persistent asthma, there was no significant difference in therapeutic effect between an inhaled glucocorticoid (mometasone) and placebo in patients with a low sputum eosinophil level (<2%), which was reported in nearly three quarters of the patients.National Heart, Lung, and Blood Institute6 month embargo; published online: 19 May 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Spatial and seasonal abundance of sand seatrout (Cynoscion arenarius) and silver seatrout (C. nothus) off the coast of Texas, determined with twenty years of data (1987–200

Sand seatrout (Cynoscion arenarius) and silver seatrout (C. nothus) are both found within the immediate offshore areas of the Gulf of Mexico, especially around Texas; however information is limited on how much distributional overlap really occurs between these species. In order to investigate spatial and seasonal differences between species, we analyzed twenty years of bay and offshore trawl data collected by biologists of the Coastal Fisheries Division, Texas Parks and Wildlife Department. Sand seatrout and silver seatrout were distributed differently among offshore sampling areas, and salinity and water depth appeared to correlate with their distribution. Additionally, within the northernmost sampling area of the gulf waters, water depth correlated significantly with the presence of silver seatrout, which were found at deeper depths than sand seatrout. There was also an overall significant decrease in silver seatrout abundance during the summer season, when temperatures were at their highest, and this decrease may have indicated a migration farther offshore. Sand seatrout abundance had an inverse relationship with salinity and water depth offshore. In addition, sand seatrout abundance was highest in bays with direct passes to the gulf and correlated with corresponding abundance in offshore areas. These data highlight the seasonal and spatial differences in abundance between sand and silver seatrout and relate these differences to the hydrological and geological features found along the Texas coastline

Field host range of Apanteles opuntiarum (Hymenoptera: Braconidae) in Argentina, a potential biocontrol agent of Cactoblastis cactorum (Lepidoptera: Pyralidae) in North America

Field exploration in Argentina for cactophagous lepidopteran hosts parasitized by the recently described braconid parasitoid Apanteles opuntiarum Martínez & Berta (Hymenoptera: Braconidae) revealed a host range restricted to Cactoblastis cactorum (Berg) (Lepidoptera: Pyralidae) and C. doddi. Field collections of cactophagous larvae parasitized by the congeneric and sympatric parasitoid A. alexanderi included the host species C. bucyrus, Sigelgaita nr. chilensis, Tucumania sp., Tucumania tapiacola and Salambona sp. If a narrow host range for A.opuntiarum is confirmed in quarantine with North American cactus-feeding species, then this parasitoid could be released as a biological control agent for C. cactorum with little or no risk to non-target species.Las exploraciones de campo en Argentina de larvas hospedadoras cactófagas parasitadas por Apanteles opuntiarum Martínez & Berta (Hymenoptera: Braconidae), un bracónido recientemente descripto, revelaron un espectro de hospedadores restringido a Cactoblastis cac­torum (Berg) (Lepidoptera: Pyralidae) y C. doddi. Las colecciones de campo de larvas cactófagas parasitadas por la especie congenérica y simpátrica A. alexanderi identificaron a C. bucyrus, Sigelgaita nr. chi­lensis, Tucumania sp., Tucumania tapiacola y Salambona sp. como es­pecies hospedadoras. Si se confirma en cuarentena el estrecho rango de hospedadores de A. opuntiarum sobre especies norteamericanas que se alimentan de cactus, podría ser liberado como agente de con­trol biológico de C. cactorum, con bajo riesgo o ninguno a especies no blanco.Fil: Varone, Laura. Fundación para el Estudio de Especies Invasivas; ArgentinaFil: Logarzo, Guillermo Alejandro. Fundación para el Estudio de Especies Invasivas; ArgentinaFil: Martinez, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales ; ArgentinaFil: Navarro, Fernando. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Superior de Entomología; ArgentinaFil: Carpenter, James E.. United States Department of Agriculture; Estados UnidosFil: Hight, Stephen D.. United States Department of Agriculture; Estados Unido

The Association Between Rate and Severity of Exacerbations in Chronic Obstructive Pulmonary Disease: An Application of a Joint Frailty-Logistic Model.

Exacerbations are a hallmark of chronic obstructive pulmonary disease (COPD). Evidence suggests the presence of substantial between-individual variability (heterogeneity) in exacerbation rates. The question of whether individuals vary in their tendency towards experiencing severe (versus mild) exacerbations, or whether there is an association between exacerbation rate and severity, has not yet been studied. We used data from the MACRO Study, a 1-year randomized trial of the use of azithromycin for prevention of COPD exacerbations (United States and Canada, 2006-2010; n = 1,107, mean age = 65.2 years, 59.1% male). A parametric frailty model was combined with a logistic regression model, with bivariate random effects capturing heterogeneity in rate and severity. The average rate of exacerbation was 1.53 episodes/year, with 95% of subjects having a model-estimated rate of 0.47-4.22 episodes/year. The overall ratio of severe exacerbations to total exacerbations was 0.22, with 95% of subjects having a model-estimated ratio of 0.04-0.60. We did not confirm an association between exacerbation rate and severity (P = 0.099). A unified model, implemented in standard software, could estimate joint heterogeneity in COPD exacerbation rate and severity and can have applications in similar contexts where inference on event time and intensity is considered. We provide SAS code (SAS Institute, Inc., Cary, North Carolina) and a simulated data set to facilitate further uses of this method

The Programmer's Assistant: Conversational Interaction with a Large Language Model for Software Development

Large language models (LLMs) have recently been applied in software engineering to perform tasks such as translating code between programming languages, generating code from natural language, and autocompleting code as it is being written. When used within development tools, these systems typically treat each model invocation independently from all previous invocations, and only a specific limited functionality is exposed within the user interface. This approach to user interaction misses an opportunity for users to more deeply engage with the model by having the context of their previous interactions, as well as the context of their code, inform the model's responses. We developed a prototype system -- the Programmer's Assistant -- in order to explore the utility of conversational interactions grounded in code, as well as software engineers' receptiveness to the idea of conversing with, rather than invoking, a code-fluent LLM. Through an evaluation with 42 participants with varied levels of programming experience, we found that our system was capable of conducting extended, multi-turn discussions, and that it enabled additional knowledge and capabilities beyond code generation to emerge from the LLM. Despite skeptical initial expectations for conversational programming assistance, participants were impressed by the breadth of the assistant's capabilities, the quality of its responses, and its potential for improving their productivity. Our work demonstrates the unique potential of conversational interactions with LLMs for co-creative processes like software development.Comment: 43 pages, 3 figures. To be published in IUI 202

Magmatic and tectonic extension at the Chile Ridge: Evidence for mantle controls on ridge segmentation

We use data from an extensive multibeam bathymetry survey of the Chile Ridge to study tectonomagmatic processes at the ridge axis. Specifically, we investigate how abyssal hills evolve from axial faults, how variations in magmatic extension influence morphology and faulting along the spreading axis, and how these variations correlate with ridge segmentation. The bathymetry data are used to estimate the fraction of plate separation accommodated by normal faulting, and the remaining fraction of extension, M, is attributed primarily to magmatic accretion. Results show that M ranges from 0.85 to 0.96, systematically increasing from first-order and second-order ridge segment offsets toward segment centers as the depth of ridge axis shoals relative to the flanking highs of the axial valley. Fault spacing, however, does not correlate with ridge geometry, morphology, or M along the Chile Ridge, which suggests the observed increase in tectonic strain toward segment ends is achieved through increased slip on approximately equally spaced faults. Variations in M along the segments follow variations in petrologic indicators of mantle melt fraction, both showing a preferred length scale of 50620 km that persists even along much longer ridge segments. In comparison, mean M and axial relief fail to show significant correlations with distance offsetting the segments. These two findings suggest a form of magmatic segmentation that is partially decoupled from the geometry of the plate boundary. We hypothesize this magmatic segmentation arises from cells of buoyantly upwelling mantle that influence tectonic segmentation from the mantle, up

Stage-Specific Sampling by Pattern Recognition Receptors during Candida albicans Phagocytosis

Candida albicans is a medically important pathogen, and recognition by innate immune cells is critical for its clearance. Although a number of pattern recognition receptors have been shown to be involved in recognition and phagocytosis of this fungus, the relative role of these receptors has not been formally examined. In this paper, we have investigated the contribution of the mannose receptor, Dectin-1, and complement receptor 3; and we have demonstrated that Dectin-1 is the main non-opsonic receptor involved in fungal uptake. However, both Dectin-1 and complement receptor 3 were found to accumulate at the site of uptake, while mannose receptor accumulated on C. albicans phagosomes at later stages. These results suggest a potential role for MR in phagosome sampling; and, accordingly, MR deficiency led to a reduction in TNF-α and MCP-1 production in response to C. albicans uptake. Our data suggest that pattern recognition receptors sample the fungal phagosome in a sequential fashion

Surgery and radioembolization of liver tumors

Surgical resection is considered the curative treatment par excellence for patients with primary or metastatic liver tumors. However, less than 40% of them are candidates for surgery, either due to nonmodifiable factors (comorbidities, age, liver dysfunction. . .), or to the invasion or proximity of the tumor to the main vascular requirements, the lack of a future liver remnant (FLR) adequate to maintain postoperative liver function, or criteria oftumor size and number. In these lastfactors, hepatic radioembolization has been shown to play a role as a presurgical tool, either by hypertrophy of the FLR or by reducing tumor size that manages to reduce tumor staging (term known as downstaging ¨ ¨ ). To these is added a third factor, which is its ability to apply the test oftime, which makes it possible to identify those patients who present progression of the disease in a short period of time (both locally and at distance), avoiding a unnecessary surgery. This paper aims to review RE as a tool to facilitate liver surgery, both through the experience of our center and the available scientific evidence.La resección quirúrgica se considera eltratamiento curativo por excelencia para los pacientes con tumores hepáticos primarios o metastásicos. Sin embargo, menos del 40% de ellos son candidatos a cirugía, ya sea por factores no modificables (comorbilidades, edad, disfunción hepática. . .), como por la invasión o proximidad del tumor a los principales pedículos vasculares, la falta de un futuro remanente hepático (FRH) adecuado para mantener una función hepática postoperatoria, o criterios de tamano˜ y numero tumoral. En estos últimos factores, la radioembolización hepática ha mostrado tener un papel como herramienta prequirúrgica, ya sea mediante la hipertrofia del FRH o mediante la reducción del tamano˜ tumoral que consigue disminuir la estadificación tumoral (término conocido como “downstaging”). A estos se suma un tercer factor, que es su capacidad de aplicar el test del tiempo, que permite identificar aquellos pacientes que presenten en un plazo corto de tiempo progresión de la enfermedad (tanto a nivel local como a distancia), evitándoles una cirugía innecesaria. En este trabajo se pretende hacer una revisión de la RE como herramienta facilitadora de la cirugía hepática, tanto a través de la experiencia de nuestro centro como de la evidencia científica disponible

Vegetation Changes Following Biosolids Applications at an Old Boer Lovegrass Pasture in Northern Sonora, México

Short grass prairies (Bouteloua-Aristida) are the main vegetation type in northern Sonora, México, however, factors such as land fragmentation, overgrazing, severe droughts and lack of infrastructure in most ranches poor grazing management has caused land degradation. Boer lovegrass (Eragrostis curvula var. conferta) is an introduced species planted to increase productivity on deteriorated rangelands. Forage production with Boer lovegrass increases two to three fold as compared to native grasses after range seeding but productivity declines as stands become old. Biosolids have been recognized as a useful soil amendment and source of nitrogen, phosphorus, organic matter and other nutrients, which can enhance soil physical properties as well as plant yield (US Environmental Protection Agency 1999, Kinney et al. 2006). These organic compounds of human origins may play an important role in rangelands increasing soil fertility, however data do not exist to justify its use in México. This study was conducted to evaluate forage responses of old Boer lovegrass stands to biosolids applications