Virome Data Explorer: A web resource to longitudinally explore respiratory viral infections, their interactions with other pathogens and host transcriptomic changes in over 100 people.

Viral respiratory infections are an important public health concern due to their prevalence, transmissibility, and potential to cause serious disease. Disease severity is the product of several factors beyond the presence of the infectious agent, including specific host immune responses, host genetic makeup, and bacterial coinfections. To understand these interactions within natural infections, we designed a longitudinal cohort study actively surveilling respiratory viruses over the course of 19 months (2016 to 2018) in a diverse cohort in New York City. We integrated the molecular characterization of 800+ nasopharyngeal samples with clinical data from 104 participants. Transcriptomic data enabled the identification of respiratory pathogens in nasopharyngeal samples, the characterization of markers of immune response, the identification of signatures associated with symptom severity, individual viruses, and bacterial coinfections. Specific results include a rapid restoration of baseline conditions after infection, significant transcriptomic differences between symptomatic and asymptomatic infections, and qualitatively similar responses across different viruses. We created an interactive computational resource (Virome Data Explorer) to facilitate access to the data and visualization of analytical results.

Respiratory viruses in pediatric emergency department patients and their family members.

BACKGROUND: Respiratory viral infections account for a substantial fraction of pediatric emergency department (ED) visits. We examined the epidemiological patterns of seven common respiratory viruses in children presenting to EDs with influenza-like illness (ILI). Additionally, we examined the co-occurrence of viral infections in the accompanying adults and risk factors associated with the acquisition of these viruses. METHODS: Nasopharyngeal swab were collected from children seeking medical care for ILI and their accompanying adults (Total N = 1315). Study sites included New York Presbyterian, Bellevue, and Tisch hospitals in New York City. PCR using a respiratory viral panel was conducted, and data on symptoms and medical history were collected. RESULTS: Respiratory viruses were detected in 399 children (62.25%) and 118 (17.5%) accompanying adults. The most frequent pathogen detected was human rhinovirus (HRV) (28.81%). Co-infection rates were 14.79% in children and 8.47% in adults. Respiratory syncytial virus (RSV) and parainfluenza infections occurred more often in younger children. Influenza and HRV occurred more often in older children. Influenza and coronavirus were mostly isolated in winter and spring, RSV in fall and winter and HRV in fall and spring. Children with HRV were more likely to have history of asthma. Adults with the same virus as their child often accompanied ≤ 2-year-old-positive children and were more likely to be symptomatic compared to adults with different viruses. CONCLUSIONS: Respiratory viruses, while presenting the same suite of symptoms, possess distinct seasonal cycles and affect individuals differently based on a number of identifiable factors, including age and history of asthma.

Active surveillance documents rates of clinical care seeking due to respiratory illness.

BACKGROUND: Respiratory viral infections are a leading cause of disease worldwide. However, the overall community prevalence of infections has not been properly assessed, as standard surveillance is typically acquired passively among individuals seeking clinical care. METHODS: We conducted a prospective cohort study in which participants provided daily diaries and weekly nasopharyngeal specimens that were tested for respiratory viruses. These data were used to analyze healthcare seeking behavior, compared with cross-sectional ED data and NYC surveillance reports, and used to evaluate biases of medically attended ILI as signal for population respiratory disease and infection. RESULTS: The likelihood of seeking medical attention was virus-dependent: higher for influenza and metapneumovirus (19%-20%), lower for coronavirus and RSV (4%), and 71% of individuals with self-reported ILI did not seek care and half of medically attended symptomatic manifestations did not meet the criteria for ILI. Only 5% of cohort respiratory virus infections and 21% of influenza infections were medically attended and classifiable as ILI. We estimated 1 ILI event per person/year but multiple respiratory infections per year. CONCLUSION: Standard, healthcare-based respiratory surveillance has multiple limitations. Specifically, ILI is an incomplete metric for quantifying respiratory disease, viral respiratory infection, and influenza infection. The prevalence of respiratory viruses, as reported by standard, healthcare-based surveillance, is skewed toward viruses producing more severe symptoms. Active, longitudinal studies are a helpful supplement to standard surveillance, can improve understanding of the overall circulation and burden of respiratory viruses, and can aid development of more robust measures for controlling the spread of these pathogens.

Voluhemins, new inhibitors of sterol O-acyltransferase, produced by Volutella citrinella BF-0440.

New compounds, designated voluhemins A (1) and B (2), are isolated from the culture broth of the fungal strain Volutella citrinella BF-0440 along with structurally related known NK12838 (3). Spectroscopic data, including 1D and 2D NMR, elucidated their structures. Compounds 1-3 have a common indoline-diterpene core and two additional isoprenyl moieties. Compounds 1 and 3 contain a hemiaminal unit, while 2 is O-methylated 1. Their inhibitory activities toward sterol O-acyltransferase (SOAT) 1 and 2 isozymes in SOAT1- and SOAT2-expressing Chinese hamster ovary (CHO) cells show that 2 selectively inhibits the SOAT2 isozyme.

The Future of Careers at the Intersection of Climate Change and Public Health: What Can Job Postings and an Employer Survey Tell Us?

Climate change is acknowledged to be a major risk to public health. Skills and competencies related to climate change are becoming a part of the curriculum at schools of public health and are now a competency required by schools in Europe and Australia. However, it is unclear whether graduates of public health programs focusing on climate change are in demand in the current job market. The authors analyzed current job postings, 16 years worth of job postings on a public health job board, and survey responses from prospective employers. The current job market appears small but there is evidence from job postings that it may be growing, and 91.7% of survey respondents believe the need for public health professionals with training in climate change may grow in the next 5-10 years. Current employers value skills/competencies such as the knowledge of climate mitigation/adaptation, climate-health justice, direct/indirect and downstream effects of climate on health, health impact assessment, risk assessment, pollution-health consequences and causes, Geographic Information System (GIS) mapping, communication/writing, finance/economics, policy analysis, systems thinking, and interdisciplinary understanding. Ensuring that competencies align with current and future needs is a key aspect of curriculum development. At the same time, we recognize that while we attempt to predict future workforce needs with historical data or surveys, the disruptive reality created by climate change cannot be modeled from prior trends, and we must therefore adopt new paradigms of education for the emerging future.

Longitudinal active sampling for respiratory viral infections across age groups.

BACKGROUND: Respiratory viral infections are a major cause of morbidity and mortality worldwide. However, their characterization is incomplete because prevalence estimates are based on syndromic surveillance data. Here, we address this shortcoming through the analysis of infection rates among individuals tested regularly for respiratory viral infections, irrespective of their symptoms. METHODS: We carried out longitudinal sampling and analysis among 214 individuals enrolled at multiple New York City locations from fall 2016 to spring 2018. We combined personal information with weekly nasal swab collection to investigate the prevalence of 18 respiratory viruses among different age groups and to assess risk factors associated with infection susceptibility. RESULTS: 17.5% of samples were positive for respiratory viruses. Some viruses circulated predominantly during winter, whereas others were found year round. Rhinovirus and coronavirus were most frequently detected. Children registered the highest positivity rates, and adults with daily contacts with children experienced significantly more infections than their counterparts without children. CONCLUSION: Respiratory viral infections are widespread among the general population with the majority of individuals presenting multiple infections per year. The observations identify children as the principal source of respiratory infections. These findings motivate further active surveillance and analysis of differences in pathogenicity among respiratory viruses.

Collaborative efforts to forecast seasonal influenza in the United States, 2015-2016.

Since 2013, the Centers for Disease Control and Prevention (CDC) has hosted an annual influenza season forecasting challenge. The 2015-2016 challenge consisted of weekly probabilistic forecasts of multiple targets, including fourteen models submitted by eleven teams. Forecast skill was evaluated using a modified logarithmic score. We averaged submitted forecasts into a mean ensemble model and compared them against predictions based on historical trends. Forecast skill was highest for seasonal peak intensity and short-term forecasts, while forecast skill for timing of season onset and peak week was generally low. Higher forecast skill was associated with team participation in previous influenza forecasting challenges and utilization of ensemble forecasting techniques. The mean ensemble consistently performed well and outperformed historical trend predictions. CDC and contributing teams will continue to advance influenza forecasting and work to improve the accuracy and reliability of forecasts to facilitate increased incorporation into public health response efforts.

Asymptomatic Shedding of Respiratory Virus among an Ambulatory Population across Seasons.

Most observation of human respiratory virus carriage is derived from medical surveillance; however, the infections documented by this surveillance represent only a symptomatic fraction of the total infected population. As the role of asymptomatic infection in respiratory virus transmission is still largely unknown and rates of asymptomatic shedding are not well constrained, it is important to obtain more-precise estimates through alternative sampling methods. We actively recruited participants from among visitors to a New York City tourist attraction. Nasopharyngeal swabs, demographics, and survey information on symptoms, medical history, and recent travel were obtained from 2,685 adults over two seasonal arms. We used multiplex PCR to test swab specimens for a selection of common respiratory viruses. A total of 6.2% of samples (168 individuals) tested positive for at least one virus, with 5.6% testing positive in the summer arm and 7.0% testing positive in the winter arm. Of these, 85 (50.6%) were positive for human rhinovirus (HRV), 65 (38.7%) for coronavirus (CoV), and 18 (10.2%) for other viruses (including adenovirus, human metapneumovirus, influenza virus, and parainfluenza virus). Depending on the definition of symptomatic infection, 65% to 97% of infections were classified as asymptomatic. The best-fit model for prediction of positivity across all viruses included a symptom severity score, Hispanic ethnicity data, and age category, though there were slight differences across the seasonal arms. Though having symptoms is predictive of virus positivity, there are high levels of asymptomatic respiratory virus shedding among the members of an ambulatory population in New York City.IMPORTANCE Respiratory viruses are common in human populations, causing significant levels of morbidity. Understanding the distribution of these viruses is critical for designing control methods. However, most data available are from medical records and thus predominantly represent symptomatic infections. Estimates for asymptomatic prevalence are sparse and span a broad range. In this study, we aimed to measure more precisely the proportion of infections that are asymptomatic in a general, ambulatory adult population. We recruited participants from a New York City tourist attraction and administered nasal swabs, testing them for adenovirus, coronavirus, human metapneumovirus, rhinovirus, influenza virus, respiratory syncytial virus, and parainfluenza virus. At recruitment, participants completed surveys on demographics and symptomology. Analysis of these data indicated that over 6% of participants tested positive for shedding of respiratory virus. While participants who tested positive were more likely to report symptoms than those who did not, over half of participants who tested positive were asymptomatic.

Evaluation of mechanistic and statistical methods in forecasting influenza-like illness.

A variety of mechanistic and statistical methods to forecast seasonal influenza have been proposed and are in use; however, the effects of various data issues and design choices (statistical versus mechanistic methods, for example) on the accuracy of these approaches have not been thoroughly assessed. Here, we compare the accuracy of three forecasting approaches-a mechanistic method, a weighted average of two statistical methods and a super-ensemble of eight statistical and mechanistic models-in predicting seven outbreak characteristics of seasonal influenza during the 2016-2017 season at the national and 10 regional levels in the USA. For each of these approaches, we report the effects of real time under- and over-reporting in surveillance systems, use of non-surveillance proxies of influenza activity and manual override of model predictions on forecast quality. Our results suggest that a meta-ensemble of statistical and mechanistic methods has better overall accuracy than the individual methods. Supplementing surveillance data with proxy estimates generally improves the quality of forecasts and transient reporting errors degrade the performance of all three approaches considerably. The improvement in quality from ad hoc and post-forecast changes suggests that domain experts continue to possess information that is not being sufficiently captured by current forecasting approaches.

Influenza forecast optimization when using different surveillance data types and geographic scale.

BACKGROUND: Advance warning of influenza incidence levels from skillful forecasts could help public health officials and healthcare providers implement more timely preparedness and intervention measures to combat outbreaks. Compared to influenza predictions generated at regional and national levels, those generated at finer scales could offer greater value in determining locally appropriate measures; however, to date, the various influenza surveillance data that are collected by state and county departments of health have not been well utilized in influenza prediction. OBJECTIVES: To assess whether an influenza forecast model system can be optimized to generate accurate forecasts using novel surveillance data streams. METHODS: Here, we generate retrospective influenza forecasts with a dynamic, compartmental model-inference system using surveillance data for influenza-like illness (ILI), laboratory-confirmed cases, and pneumonia and influenza mortality at state and county levels. We evaluate how specification of 3 system inputs-scaling, observational error variance (OEV), and filter divergence (lambda)-affects forecast accuracy. RESULTS: In retrospective forecasts, and across data types, there were no clear optimal combinations for the 3 system inputs; however, scaling was most critical to forecast accuracy, whereas OEV and lambda were not. CONCLUSIONS: Forecasts using new data streams should be tested to determine an appropriate scaling value using historical data and analyzed for forecast accuracy.

Asymptomatic Summertime Shedding of Respiratory Viruses.

To determine rates of both symptomatic and asymptomatic infection among ambulatory adults, we collected nasopharyngeal swab specimens, demographic characteristics, and survey information from 1477 adult visitors to a New York City tourist attraction during April-July 2016. Multiplex polymerase chain reaction analysis was used to identify specimens positive for common respiratory viruses. A total of 7.2% of samples tested positive for respiratory viruses; among positive samples, 71.0% contained rhinovirus, and 21.5% contained coronavirus. Influenza virus, respiratory syncytial virus, and parainfluenza virus were also detected. Depending on symptomatologic definition, 57.7%-93.3% of positive samples were asymptomatic. These findings indicate that significant levels of asymptomatic respiratory viral shedding exist during summer among the ambulatory adult population.

Iridium-catalysed hydrosilylation of cyclopropanes via regioselective carbon-carbon bond cleavage.

While cyclopropanes have been explored as synthetically valuable building blocks, their transformation without conjugated substituents or directly substituted heteroatoms remains challenging. The current study describes the iridium-catalysed ring-opening hydrosilylation of cyclopropanes. A nitrogen-based directing group was found to control the reactivity of iridium active species as well as the regiochemistry of carbon-carbon bond cleavage and hydrosilylation.

Acceleration Effects of Phosphine Ligands on the Rhodium-Catalyzed Dehydrogenative Silylation and Germylation of Unactivated C(sp(3))-H Bonds.

The current work describes the marked rate of acceleration caused by phosphine ligands on the rhodium-catalyzed dehydrogenative silylation and germylation of unactivated C(sp(3))-H bonds. The reactivity was affected by the steric and electronic nature of the phosphine ligands. The use of the bulky and electron-rich diphosphine ligand (R)-DTBM-SEGPHOS was highly effective to yield the dehydrogenative silylation products selectively in the presence of a hydrogen acceptor. An appropriate choice of C2-symmetric chiral diphosphine ligand enables the asymmetric dehydrogenative silylation via the enantioselective desymmetrization of the C(sp(3))-H bond. The unprecedented catalytic germylation of C(sp(3))-H bonds with dehydrogenation was also examined with the combination of the rhodium complex and a wide bite angle diphosphine ligand to provide the corresponding 2,3-dihydrobenzo[b]germoles in good yield.

Effectiveness of a Multifaceted Community-Based Promotion Strategy on Use of GetHealthyHarlem.org, a Local Community Health Education Website.

The use of health communication extends beyond simply promoting or disseminating a particular product or proposed behavior change; it involves the systematic and strategic integration and execution of evidence-based, theory-driven, and community engagement strategies. Much like in public health intervention design based on health behavior theory, health communication seeks to encourage the target audience to make a positive behavior change through core concepts such as understanding and specifying the target audience, tailoring messages based on audience segmentation, and continually conducting evaluation of specific and overarching goals. While our first article "Development of a Culturally Relevant Consumer Health Information Website for Harlem, New York" focused on the design, development, and initial implementation of GetHealthyHarlem.org between 2004 and 2009, this article delves into the process of promoting the website to increase its use and then evaluating use among website visitors. Just as for the development of the website, we used community-based participatory research methods, health behavior theory, and health communication strategies to systemically develop and execute a health communication plan with the goals of increasing awareness of GetHealthyHarlem.org in Harlem, driving online traffic, and having the community recognize it as a respected community resource dedicated to improving health in Harlem.

Global health impacts of future aviation emissions under alternative control scenarios.

There is strong evidence of an association between fine particulate matter less than 2.5 µm (PM2.5) in aerodynamic diameter and adverse health outcomes. This study analyzes the global excess mortality attributable to the aviation sector in the present (2006) and in the future (three 2050 scenarios) using the integrated exposure response model that was also used in the 2010 Global Burden of Disease assessment. The PM2.5 concentrations for the present and future scenarios were calculated using aviation emission inventories developed by the Volpe National Transportation Systems Center and a global chemistry-climate model. We found that while excess mortality due to the aviation sector emissions is greater in 2050 compared to 2006, improved fuel policies (technology and operations improvements yielding smaller increases in fuel burn compared to 2006, and conversion to fully sustainable fuels) in 2050 could lead to 72% fewer deaths for adults 25 years and older than a 2050 scenario with no fuel improvements. Among the four health outcomes examined, ischemic heart disease was the greatest cause of death. Our results suggest that implementation of improved fuel policies can have substantial human health benefits.

Health impacts of heat in a changing climate: how can emerging science inform urban adaptation planning?

Extreme heat is one of the most important global causes of weather-related mortality, and climate change is leading to more frequent and intense heat waves. Recent epidemiologic findings on heat-related health impacts have reinforced our understanding of mortality impacts of extreme heat and have shown a range of impacts on morbidity outcomes including cardiovascular, respiratory and mental health responses. Evidence is also emerging on temporal trends towards decreasing exposure-response, probably reflecting autonomous population adaptation. Many cities are actively engaged in the development of heat adaptation plans to reduce future health impacts. Epidemiologic research into the evolution of local heat-health responses over time can greatly aid adaptation planning for heat, prevention of adverse health outcomes among vulnerable populations, as well as evaluation of new interventions. Such research will be facilitated by the formation of research partnerships involving epidemiologists, climate scientists, and local stakeholders.

Development of a culturally relevant consumer health information website for Harlem, New York.

The process of creating a geographically tailored health information website with ongoing feedback from community members is one of inquiry and discovery, frustration and triumph, and development and reevaluation. This article reviews the development and implementation of GetHealthyHarlem.org, a health literacy level-appropriate consumer health information website tailored to consumers in Harlem, New York City. From 2004 to 2009, the Harlem Health Promotion Center, one of 37 Prevention Research Centers in the United States, sought to determine the use and seeking of online health information in Harlem, New York City in order to further explore the possibility of providing online health information to this community. Specifically, this article details how we sought to identify gaps, concerns, and uses of online health information and health care seeking in this local, predominantly racial and ethnic minority population. We review how we identified and addressed the multitude of variables that play a role in determining the degree of success in finding and using online health information, and include discussions about the genesis of the website and our successes and challenges in the development and implementation stages.

Neurotropin® relieves oxaliplatin-induced neuropathy via Gi protein-coupled receptors in the monoaminergic descending pain inhibitory system.

AIMS: Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic peripheral neuropathies. We previously reported that repeated administration of neurotropin prevents oxaliplatin-induced mechanical allodynia by inhibiting axonal degeneration in rats. In the present study, we investigated the analgesic effect of a single administration of neurotropin on oxaliplatin-induced neuropathy in rats. MAIN METHODS: Oxaliplatin (4mg/kg) was administered intraperitoneally twice a week for 4weeks. Cold hyperalgesia was assessed using the acetone test and mechanical allodynia was evaluated using the von Frey test. KEY FINDINGS: Repeated injection of oxaliplatin induced cold hyperalgesia on day 5 and mechanical allodynia on day 28. A single administration of neurotropin transiently relieved both pain behaviors. The analgesic effect of neurotropin was inhibited by pretreatment with 5-HT1A, 5-HT2, 5-HT3, and α2 receptor antagonists and by monoamine depletion. Moreover, the analgesic effect of neurotropin was abolished by intrathecal injection of pertussis toxin, a Gi protein inhibitor. SIGNIFICANCE: These results suggest that neurotropin is effective in relieving oxaliplatin-induced neuropathy, and that Gi protein-coupled receptors in the monoaminergic descending pain inhibitory system may be involved in the analgesic effect of neurotropin. Neurotropin may have clinical potential for the treatment of oxaliplatin-induced neuropathies.

[Reading poems to oneself affects emotional state and level of distraction].

Bibliotherapy has occasionally been used as a counseling technique. However, most reports are basically single-case studies and the psychological effect of this approach remains unclear. Two experiments using 96 healthy college volunteers were conducted to determine how the reading of emotionally positive, negative, or neutral passages affect one's mood and level of distraction. Study 1 revealed that participants felt more relaxed after reading positive poems with either personal or social content than after reading negativie ones, and they felt least refreshed and calm after reading negative poems with personal content. Study 2 showed that participants reported less depressed feelings, both after reading an excerpt from an explanatory leaflet and after a controlled rest period. These results were discussed in terms of the mood congruence effect. Future research may evaluate the effects of reading novels, manga, and life teachings on self-narratives and views of life in normal and clinical populations.