Influenza And Asthma Hospitalizations In Nyc From 2002-2012

INTRODUCTION: The literature has focused primarily on rhinoviruses as the major determinant of asthma exacerbations. The association between other respiratory viruses such as influenza and asthma exacerbations is not well characterized and further understanding can better inform prevention strategies to reduce influenza-related asthma. OBJECTIVES: The primary objective of this study is to determine whether asthma hospitalizations of children and adults in the five boroughs of New York City is correlated with influenza hospitalizations temporally and spatially and whether these correlations differ by county or age. METHODS: A times series regression analysis was performed using influenza hospitalizations as the explanatory series and and asthma hospitalizations as the outcome series. A cross correlation function was computed to determine the temporal correlations between the two time series. A measure similar to traditional attributable risks was calculated across age groups and boroughs to assess differences in influenza-related asthma hospitalizations. Additionally, times series analysis was stratified by age and boroughs to examine the significance of influenza and asthma correlations across strata. RESULTS: A seasonal ARIMA (1,0,0)x(0,1,1)12 model was the final model for our data and yielded a significant positive correlation between asthma and influenza hospitalizations. After stratification by age, individuals 18 and older had significant correlations between influenza and asthma whereas there was no significant temporal correlation found in children 17 years or younger. Attributable risk percentages for adults (18-44, 45-64, 65+) increased with increasing age (2.9%, 3.4%, 4%, respectively). Positive significant correlations between asthma and influenza were found in the Bronx, Brooklyn, and Manhattan. Attributable risk percentages by borough identified the Bronx and Manhattan as the highest risk areas (2.6% and 2.5%). CONCLUSION: Significant positive correlations between influenza and asthma hospitalizations were identified in this study. Influenza prevention strategies should emphasize older age groups. Environmental pollutants may interact with influenza to exacerbate asthma. Further research needs to be performed to understand the nature of interaction between environmental pollutants and respiratory viruses in effecting asthma and other respiratory-related outcomes

From Metagenomics to Pangenomics: Characterization of Dairy Worker Microbiomes and Development of Novel Statistical Methodology

Thesis (Ph.D.)--University of Washington, 2022The complex interplay between routine antibiotic use and zoonotic pathogen presence makes livestock farming environments unique nexuses for the potential emergence of zoonotic diseases and/or antibiotic resistant bacteria and their resistance genes. Livestock can further facilitate transmission and emergence by serving as intermediary or amplifying hosts in which pathogens and antibiotic resistant bacteria and their genes can evolve and spill over into humans. As such, we were interested in understanding differences in the dairy worker microbiota that may arise due to exposure to livestock farming environments to evaluate potential risks of these environments in facilitating global dissemination of zoonotic disease, antibiotic resistant bacteria and antibiotic resistance genes. We used culture independent methods that go beyond the traditional single pathogen approach to conduct comparisons between the gut microbiota and resistome of dairy workers and of community controls as well as to interrogate functional differences in commensal genomes recovered from both groups. To enable our study of functional differences, we first addressed methodological limitations with novel statistical methods for pangenomics. We developed happi, a statistical method for modeling gene presence that accounts for differential genome quality factors (e.g., mean coverage). We evaluated happi's performance using simulated and shotgun sequencing data and found that happi is accurate and robust even in scenarios when genome quality is correlated with the main covariate of interest. happi can furthermore be broadly applied to functional comparisons of genomes of other microorganisms beyond bacteria, and used in functional comparisons of metagenomes to adjust for differential quality (e.g., sequencing depths) of metagenomes. Using happi to facilitate our functional comparisons, we conducted a metagenomics and pangenomics investigation of the effects of occupational exposure to dairy farm environments on metagenome differences in taxonomy, diversity and gene presence (i.e., co-abundant gene groups (CAGs), antibiotic resistance genes (ARGs), and virulence factors) and on functional differences of gut commensal bacteria genomes in dairy workers and community controls. A major strength of our study was the multi-level interrogation of dairy worker and community control microbiomes. Our cross-sectional study examining differences in microbial genes and genomes from dairy workers and community controls observed several patterns for further investigation including greater abundance of tetracycline resistance genes and higher occurrence of cephamycin resistance genes in dairy workers' metagenomes; evidence of commensal organism association with plasmid-mediated tetracycline resistance genes found in both dairy workers and community controls; and lower average gene and genome diversity in dairy workers' metagenomes compared to community controls. These findings point towards possible avenues for future research to better understand the impact of exposure to zoonotic pathogens, antibiotic resistant organisms, and ARGs on the microbiome and resistome of livestock workers and others with close animal contact

happi: a hierarchical approach to pangenomics inference

Abstract Recovering metagenome-assembled genomes (MAGs) from shotgun sequencing data is an increasingly common task in microbiome studies, as MAGs provide deeper insight into the functional potential of both culturable and non-culturable microorganisms. However, metagenome-assembled genomes vary in quality and may contain omissions and contamination. These errors present challenges for detecting genes and comparing gene enrichment across sample types. To address this, we propose happi, an approach to testing hypotheses about gene enrichment that accounts for genome quality. We illustrate the advantages of happi over existing approaches using published Saccharibacteria MAGs, Streptococcus thermophilus MAGs, and via simulation

One Health Relationships Between Human, Animal, and Environmental Microbiomes: A Mini-Review

The One Health concept stresses the ecological relationships between human, animal, and environmental health. Much of the One Health literature to date has examined the transfer of pathogens from animals (e.g., emerging zoonoses) and the environment to humans. The recent rapid development of technology to perform high throughput DNA sequencing has expanded this view to include the study of entire microbial communities. Applying the One Health approach to the microbiome allows for consideration of both pathogenic and non-pathogenic microbial transfer between humans, animals, and the environment. We review recent research studies of such transmission, the molecular and statistical methods being used, and the implications of such microbiome relationships for human health. Our review identified evidence that the environmental microbiome as well as the microbiome of animals in close contact can affect both the human microbiome and human health outcomes. Such microbiome transfer can take place in the household as well as the workplace setting. Urbanization of built environments leads to changes in the environmental microbiome which could be a factor in human health. While affected by environmental exposures, the human microbiome also can modulate the response to environmental factors through effects on metabolic and immune function. Better understanding of these microbiome interactions between humans, animals, and the shared environment will require continued development of improved statistical and ecological modeling approaches. Such enhanced understanding could lead to innovative interventions to prevent and manage a variety of human health and disease states

Behavioral thermoregulation of northern elephant seal (Mirounga angustirostris) adults and pups in a breeding colony at Piedras Blancas, California

Our study tested the hypothesis that the Northern elephant seal (NES) Mirounga angustirostris uses coloration for thermoregulation on land. The NES comes ashore every winter to breed and—being adapted to living in cold seas for most of the year—on shore they may be faced with over-heating from higher temperatures and direct solar radiation. Their large size and thick blubber give adult NES’s low surface area to volume ratios and a layer of thermal insulation which are advantageous for conserving heat in cold seas but disadvantageous for dissipating it on land. However, they are very dark on the back and pale beneath, which could allow them to absorb or reflect heat by adjusting orientation to the sun. Pups are born with no blubber but are uniformly black, which could allow them to absorb heat from the sun over the entire body surface. We found that pups did tend to stay exposed to sunlight in cooler hours and shaded by their mothers’ shadows in warmer ones. In adults we found that females exposed their reflective bellies to the sun more than males at all times and that both sexes were significantly more likely to orient the belly toward the sun during warmer hours compared to cooler ones

Behavioral thermoregulation of northern elephant seal (Mirounga angustirostris) adults and pups in a breeding colony at Piedras Blancas, California

Our study tested the hypothesis that the Northern elephant seal (NES) Mirounga angustirostris uses coloration for thermoregulation on land. The NES comes ashore every winter to breed and—being adapted to living in cold seas for most of the year—on shore they may be faced with over-heating from higher temperatures and direct solar radiation. Their large size and thick blubber give adult NES’s low surface area to volume ratios and a layer of thermal insulation which are advantageous for conserving heat in cold seas but disadvantageous for dissipating it on land. However, they are very dark on the back and pale beneath, which could allow them to absorb or reflect heat by adjusting orientation to the sun. Pups are born with no blubber but are uniformly black, which could allow them to absorb heat from the sun over the entire body surface. We found that pups did tend to stay exposed to sunlight in cooler hours and shaded by their mothers’ shadows in warmer ones. In adults we found that females exposed their reflective bellies to the sun more than males at all times and that both sexes were significantly more likely to orient the belly toward the sun during warmer hours compared to cooler ones

Synthesis of nitro-aryl functionalised 4-amino-1,8-naphthalimides and their evaluation as fluorescent hypoxia sensors

Fluorescent sensors are a vital research tool, enabling the study of intricate cellular processes in a sensitive manner. The design and synthesis of responsive and targeted probes is necessary to allow such processes to be interrogated in the cellular environment. This remains a challenge, and requires methods for functionalisation of fluorophores with multiple appendages for sensing and targeting groups. Methods to synthesise more structurally complex derivatives of fluorophores will expand their potential scope. Most known 4-amino-1,8-naphthalimides are only functionalised at imide and 4-positions, and structural modifications at additional positions will increase the breadth of their utility as responsive sensors. Here we evaluate methods for the incorporation of a hypoxia sensing group to 4-amino-1,8-naphthalimide. We developed an intermediate that allowed us to incorporate a sensing group, targeting group, and ICT donor to the naphthalimide core in a modular fashion. Synthetic strategies for attaching the hypoxia sensing group and how they affected the fluorescence of the naphthalimide were evaluated by photophysical characterisation and time-dependent density functional theory. We then rationally designed an extracellular hypoxia probe that could selectively image the hypoxic and necrotic region of tumour spheroids. Our results demonstrate the versatility of the naphthalimide scaffold and expand its utility. This approach to probe design will enable the flexible, efficient generation of selective, targeted fluorescent sensors for various biological purposes

Prospective Evaluation of Severe Skin Toxicity and Pain During Postmastectomy Radiation Therapy

Purpose: To prospectively capture acute toxicities and pain associated with postmastectomy radiation therapy (PMRT), to analyze patient and treatment risk factors for severe side effects. Methods and Materials: Women referred for PMRT were prospectively enrolled and assessed weekly during and after radiation therapy. The endpoint included severe National Cancer Institute Common Terminology Criteria for Adverse Effects grade 3 moist desquamation, other skin symptoms, and pain. Results: Of 257 patients, 73 (28.4%) experienced extensive moist desquamation, 84 (32.7%) Common Terminology Criteria for Adverse Effects skin toxicity grade 3, and 57 (22.2%) a pain impacting on daily life activities. Among symptoms only grade 3 moist desquamation was significantly associated with severe pain (P Conclusions: The present cohort study suggests excessive radiation toxicity after PMRT. Among factors associated with an increase of toxicity are smoking habits and the use of skin bolus. (C) 2015 Elsevier Inc