Overdispersion in COVID-19 increases the effectiveness of limiting nonrepetitive contacts for transmission control.

Increasing evidence indicates that superspreading plays a dominant role in COVID-19 transmission. Recent estimates suggest that the dispersion parameter k for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is on the order of 0.1, which corresponds to about 10% of cases being the source of 80% of infections. To investigate how overdispersion might affect the outcome of various mitigation strategies, we developed an agent-based model with a social network that allows transmission through contact in three sectors: "close" (a small, unchanging group of mutual contacts as might be found in a household), "regular" (a larger, unchanging group as might be found in a workplace or school), and "random" (drawn from the entire model population and not repeated regularly). We assigned individual infectivity from a gamma distribution with dispersion parameter k We found that when k was low (i.e., greater heterogeneity, more superspreading events), reducing random sector contacts had a far greater impact on the epidemic trajectory than did reducing regular contacts; when k was high (i.e., less heterogeneity, no superspreading events), that difference disappeared. These results suggest that overdispersion of COVID-19 transmission gives the virus an Achilles' heel: Reducing contacts between people who do not regularly meet would substantially reduce the pandemic, while reducing repeated contacts in defined social groups would be less effective.

Mercury in Neotropical birds: a synthesis and prospectus on 13 years of exposure data.

Environmental mercury (Hg) contamination of the global tropics outpaces our understanding of its consequences for biodiversity. Knowledge gaps of pollution exposure could obscure conservation threats in the Neotropics: a region that supports over half of the world's species, but faces ongoing land-use change and Hg emission via artisanal and small-scale gold mining (ASGM). Due to their global distribution and sensitivity to pollution, birds provide a valuable opportunity as bioindicators to assess how accelerating Hg emissions impact an ecosystem's ability to support biodiversity, and ultimately, global health. We present the largest database on Neotropical bird Hg concentrations (n = 2316) and establish exposure baselines for 322 bird species spanning nine countries across Central America, South America, and the West Indies. Patterns of avian Hg exposure in the Neotropics broadly align with those in temperate regions: consistent bioaccumulation across functional groups and high spatiotemporal variation. Bird species occupying higher trophic positions and aquatic habitats exhibited elevated Hg concentrations that have been previously associated with reductions in reproductive success. Notably, bird Hg concentrations were over four times higher at sites impacted by ASGM activities and differed by season for certain trophic niches. We developed this synthesis via a collaborative research network, the Tropical Research for Avian Conservation and Ecotoxicology (TRACE) Initiative, which exemplifies inclusive, equitable, and international data-sharing. While our findings signal an urgent need to assess sampling biases, mechanisms, and consequences of Hg exposure to tropical avian communities, the TRACE Initiative provides a meaningful framework to achieve such goals. Ultimately, our collective efforts support and inform local, scientific, and government entities, including Parties of the United Nations Minamata Convention on Mercury, as we continue working together to understand how Hg pollution impacts biodiversity conservation, ecosystem function, and public health in the tropics.

RESúMEN: La contaminación ambiental por mercurio (Hg) en los trópicos supera nuestra comprensión de sus consecuencias para la biodiversidad. Los vacíos de conocimiento que existen sobre la exposición a la contaminación podrían ocultar las amenazas para la conservación en el Neotrópico: una región que alberga a más de la mitad de las especies del mundo, pero que enfrenta una continua intensificación de las emisiones de Hg y del cambio de uso del suelo por el avance de la minería de oro artesanal y de pequeña escala (MAPE). Debido a su distribución global y su sensibilidad a la contaminación, las aves brindan una oportunidad valiosa como bioindicadores para evaluar cómo las emisiones de Hg afectan la capacidad de un ecosistema para sustentar la biodiversidad y, en última instancia, la salud global. Presentamos la más grande base de datos sobre concentraciones de Hg en aves Neotropicales (n = 2,316) para establecer una línea base para los niveles de exposición a Hg en 322 especies de aves de nueve países de América Central, América del Sur, y el Caribe. Encontramos patrones de las concentraciones de Hg en aves de los trópicos que se asemejan a los de las regiones templadas: mostrando una bioacumulación consistente a través de grupos funcionales y una alta variación espaciotemporal. Las especies de aves que ocupan posiciones más altas en la cadena trófica y en hábitats acuáticos registraron concentraciones elevadas de Hg que podrían tener efectos negativos en su éxito reproductivo. Es importante resaltar que las concentraciones de Hg en las aves de los sitios afectados por la MAPE fueron cuatro veces más altas que las de los sitios control y además difirió por temporada para ciertos nichos tróficos. Desarrollamos esta síntesis a través de una red de investigación colaborativa, la Iniciativa de Investigación Tropical para la Conservación y Ecotoxicología Aviar (TRACE), que ejemplifica un intercambio de datos inclusivo, equitativo e internacional. Si bien nuestros hallazgos sugieren una necesidad urgente de evaluar los sesgos en el muestreo, los mecanismos, y las consecuencias de la exposición al Hg en las comunidades de aves tropicales, la Iniciativa TRACE proporciona un marco para abordar estos objetivos. Nuestro esfuerzo colectivo tiene como propósito respaldar y brindar información a las entidades locales, científicas, y gubernamentales, incluyendo las Partes de la Convención de Minamata de las Naciones Unidas sobre el Mercurio, mientras continuamos trabajando juntos para comprender cómo la contaminación por Hg en los trópicos puede afectar la salud pública, el funcionamiento de los ecosistemas, y la conservación de la biodiversidad. Total mercury (THg) concentrations (µg/g) and sample sizes of birds across Central America, South America, and the West Indies from 2007­2023. Point size and color are arranged in order of increasing THg concentration and hexagonal grid cells are colored in terms of increasing sample size.

Intraoperative vasopressors in head and neck free flap reconstruction.

INTRODUCTION: Historically, there were concerns vasopressors impair free flap outcomes, but recent studies suggest vasopressors are safe. Here we investigate this controversy by (1) evaluating vasopressors' effect on head and neck free-flap survival and surgical complications, and (2) performing soft tissue and bony subset analysis. PATIENTS AND METHODS: Post hoc analysis was performed of a single-blinded, prospective, randomized clinical trial at a tertiary care academic medical center involving patients ≥18 years old undergoing head and neck free flap reconstruction over a 16-month period. Patients were excluded if factors prevented accurate FloTrac™ use. Patients were randomized to traditional volume-based support, or goal-directed support including vasopressor use. Primary data was obtained by study personnel through intraoperative data recording and postoperative medical record review. RESULTS: Forty-one and 38 patients were randomized to traditional and pressor-based algorithms, respectively. Flap survival was 95% (75/79). There was no significant difference between the pressor-based and traditional protocols' flap failure (1/38 [3%] vs. 3/41 [7%], RR 0.36, 95% CI of RR 0.04-3.31, p = .63) or flap-related complications (12/38 [32%] vs. 18/41 [44%], RR 0.72, 95% CI 0.40-1.29, p = .36) Soft tissue flaps had surgical complication rates of 12/30 (40%) and 9/27 (33%) for traditional and pressor-based protocols, respectively. Bony flaps had surgical complication rates of 6/11 (55%), and 3/11 (27%) for traditional and pressor-based protocols, respectively. CONCLUSIONS: Intraoperative goal-directed vasopressor administration during head and neck free flap reconstruction does not appear to increase the rate of flap complications or failures.

Estimating the population-level impact of vaccines using synthetic controls.

When a new vaccine is introduced, it is critical to monitor trends in disease rates to ensure that the vaccine is effective and to quantify its impact. However, estimates from observational studies can be confounded by unrelated changes in healthcare utilization, changes in the underlying health of the population, or changes in reporting. Other diseases are often used to detect and adjust for these changes, but choosing an appropriate control disease a priori is a major challenge. The "synthetic controls" (causal impact) method, which was originally developed for website analytics and social sciences, provides an appealing solution. With this approach, potential comparison time series are combined into a composite and are used to generate a counterfactual estimate, which can be compared with the time series of interest after the intervention. We sought to estimate changes in hospitalizations for all-cause pneumonia associated with the introduction of pneumococcal conjugate vaccines (PCVs) in five countries in the Americas. Using synthetic controls, we found a substantial decline in hospitalizations for all-cause pneumonia in infants in all five countries (average of 20%), whereas estimates for young and middle-aged adults varied by country and were potentially influenced by the 2009 influenza pandemic. In contrast to previous reports, we did not detect a decline in all-cause pneumonia in older adults in any country. Synthetic controls promise to increase the accuracy of studies of vaccine impact and to increase comparability of results between populations compared with alternative approaches.

Challenges in Estimating the Impact of Vaccination with Sparse Data.

BACKGROUND: The synthetic control model is a powerful tool to quantify the population-level impact of vaccines because it can adjust for trends unrelated to vaccination using a composite of control diseases. Because vaccine impact studies are often conducted using smaller, subnational datasets, we evaluated the performance of synthetic control models with sparse time series data. To obtain more robust estimates of vaccine impacts from noisy time series, we proposed a possible alternative approach, STL+PCA method (seasonal-trend decomposition plus principal component analysis), which first extracts smoothed trends from the control time series and uses them to adjust the outcome. METHODS: Using both the synthetic control and STL+PCA models, we estimated the impact of 10-valent pneumococcal conjugate vaccine on pneumonia hospitalizations among cases <12 months and 80+ years of age during 2004-2014 at the subnational level in Brazil. We compared the performance of these models using simulation analyses. RESULTS: The synthetic control model was able to adjust for trends unrelated to 10-valent pneumococcal conjugate vaccine in larger states but not in smaller states. Simulation analyses showed that the estimates obtained with the synthetic control approach were biased when there were fewer cases, and only 4% of simulations had credible intervals covering the true estimate. In contrast, the STL+PCA analysis had 90% lower bias and had 95% of simulations, with credible intervals covering the true estimate. CONCLUSIONS: Estimates from the synthetic control model might be biased when data are sparse. The STL+PCA model provides more accurate evaluations of vaccine impact in smaller populations.

Using Clinical Research Networks to Assess Severity of an Emerging Influenza Pandemic.

Background: Early clinical severity assessments during the 2009 influenza A H1N1 pandemic (pH1N1) overestimated clinical severity due to selection bias and other factors. We retrospectively investigated how to use data from the International Network for Strategic Initiatives in Global HIV Trials, a global clinical influenza research network, to make more accurate case fatality ratio (CFR) estimates early in a future pandemic, an essential part of pandemic response. Methods: We estimated the CFR of medically attended influenza (CFRMA) as the product of probability of hospitalization given confirmed outpatient influenza and the probability of death given hospitalization with confirmed influenza for the pandemic (2009-2011) and post-pandemic (2012-2015) periods. We used literature survey results on health-seeking behavior to convert that estimate to CFR among all infected persons (CFRAR). Results: During the pandemic period, 5.0% (3.1%-6.9%) of 561 pH1N1-positive outpatients were hospitalized. Of 282 pH1N1-positive inpatients, 8.5% (5.7%-12.6%) died. CFRMA for pH1N1 was 0.4% (0.2%-0.6%) in the pandemic period 2009-2011 but declined 5-fold in young adults during the post-pandemic period compared to the level of seasonal influenza in the post-pandemic period 2012-2015. CFR for influenza-negative patients did not change over time. We estimated the 2009 pandemic CFRAR to be 0.025%, 16-fold lower than CFRMA. Conclusions: Data from a clinical research network yielded accurate pandemic severity estimates, including increased severity among younger people. Going forward, clinical research networks with a global presence and standardized protocols would substantially aid rapid assessment of clinical severity. Clinical Trials Registration: NCT01056354 and NCT01056185

Using Feathers to Evaluate Adverse Effects of Metals on Northern Bobwhites (Colinus virginianus) in Texas.

Northern bobwhites (Colinus virginianus) have been declining across the range of the species primarily due to habitat loss and habitat fragmentation. There is increasing concern regarding effects related to elevated environmental contaminants, including pesticides and metals. Elevated concentrations of some metals are known to have adverse effects on reproduction, development, and survival in birds; however, little research has been conducted on metal exposure in wild bobwhites. We analyzed metal concentrations in the feathers of 60 bobwhites from 3 ecoregions in Texas and evaluated differences between age-class, gender, and location with the objective of determining if bobwhites in Texas are at increased risk of exposure to elevated metal concentrations. We found feather Pb concentrations above the established effect threshold of 4.0 µg/g dry weight at which sublethal and reproductive effects have been reported in birds. More than 25% (n = 16) of the samples analyzed had Pb concentrations above the effect threshold, including four that were five times above the threshold. We also observed slightly elevated feather Cd concentrations, above 0.1 µg/g dry weight, in 17% (n = 11) of the bobwhites analyzed. On average, juvenile bobwhites had higher concentrations of Ba, Co, Fe, Mn, Sr, and V compared to adults (p < 0.05). Additionally, concentrations of Al, Be, Co, Fe, Hg, Ni, Se, Sr, and Tl differed significantly between sampling locations, indicating a potential relationship between metal levels and local agricultural practices. The results of our study indicate a potential risk of sublethal effects of Pb and to a lesser extent Cd in bobwhites in Texas.

Impact of Pneumococcal Conjugate Vaccines on Pneumonia Hospitalizations in High- and Low-Income Subpopulations in Brazil.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used to evaluate the impact. Data from middle-income countries that have both low- and high-income subpopulations can provide a proxy measure for the impact of the vaccine in low-income countries. METHODS: We evaluated the impact of PCV10 on hospitalizations for all-cause pneumonia in Brazil, a middle-income country with localities that span a broad range of human development index (HDI) levels. We used complementary time series and spatiotemporal methods (synthetic controls and hierarchical Bayesian spatial regression) to test whether the decline in pneumonia hospitalizations associated with vaccine introduction varied across the socioeconomic spectrum. RESULTS: We found that the declines in all-cause pneumonia hospitalizations in children and young and middle-aged adults did not vary substantially across low and high HDI subpopulations. Moreover, the estimated declines seen in infants and young adults were associated with higher levels of uptake of the vaccine at a local level. CONCLUSIONS: These results suggest that PCVs have an important impact on hospitalizations for all-cause pneumonia in both low- and high-income populations.

Bayesian Model Averaging with Change Points to Assess the Impact of Vaccination and Public Health Interventions.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) prevent invasive pneumococcal disease and pneumonia. However, some low-and middle-income countries have yet to introduce PCV into their immunization programs due, in part, to lack of certainty about the potential impact. Assessing PCV benefits is challenging because specific data on pneumococcal disease are often lacking, and it can be difficult to separate the effects of factors other than the vaccine that could also affect pneumococcal disease rates. METHODS: We assess PCV impact by combining Bayesian model averaging with change-point models to estimate the timing and magnitude of vaccine-associated changes, while controlling for seasonality and other covariates. We applied our approach to monthly time series of age-stratified hospitalizations related to pneumococcal infection in children younger 5 years of age in the United States, Brazil, and Chile. RESULTS: Our method accurately detected changes in data in which we knew true and noteworthy changes occurred, i.e., in simulated data and for invasive pneumococcal disease. Moreover, 24 months after the vaccine introduction, we detected reductions of 14%, 9%, and 9% in the United States, Brazil, and Chile, respectively, in all-cause pneumonia (ACP) hospitalizations for age group 0 to <1 years of age. CONCLUSIONS: Our approach provides a flexible and sensitive method to detect changes in disease incidence that occur after the introduction of a vaccine or other intervention, while avoiding biases that exist in current approaches to time-trend analyses.

Model estimates of the burden of outpatient visits attributable to influenza in the United States.

BACKGROUND: Although many studies have modelled the national burdens of hospitalizations and deaths due to influenza, few studies have considered the outpatient burden. To fill this gap for the United States (US), we applied traditional statistical modelling approaches to time series derived from large medical claims databases held in the private sector. METHODS: We accessed ICD-9-coded office visit data extracted from Truven Health Analytics' MarketScan Commercial database covering about one third of the US population <65 years during 2001-2009, and Medicare Supplemental data covering about one fifth of US seniors 65+ during 2006-2009. We extracted weekly time series of visits due to respiratory diagnoses, otitis media (OM), and urinary tract infections (UTI), a "negative control". We used multiple linear regression modelling to estimate age-specific influenza-related excess in office visits. RESULTS: In the <65 year age group, in the 8 pre-pandemic seasons studied and for the broadest defined respiratory outcome, the model attributed an average of ~14.5 M (Standard deviation [SD] across seasons 3.9 million) office visits to influenza (rate of 5,581/100,000 population). Of these, ~80 % of visits occurred in the 5-17 and 18-49 age group. In school children aged 5-17 year olds and adult 18-64 year age groups the majority of visits were due to influenza B, while A/H3N2 explained most visits in children <5 year olds. The model further attributed ~2.2 M OM visits (SD across seasons 790,000) annually to influenza, of which 86 % of these occurred in children <18 years; this indicates that 6.4 % of all infants <2 years and 4.9 % of all toddlers aged 2-4 years in the US have an influenza-attributable outpatient visit with an OM diagnosis. In seniors 65 years and older, our model attributed ~0.7 M (SD across seasons 351,000) respiratory visits to influenza (rate of 1,887/100,000 population). The model identified no significant excess UTI (negative control) visits in most seasons. CONCLUSIONS: This is to our knowledge a first study of the outpatient burden of influenza in the US in a large database. The model estimated that 10 % of all children <18 years and 4 % of the entire population <65 years seek outpatient care for respiratory illness attributable to influenza annually. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02019732 .

Modelling estimates of age-specific influenza-related hospitalisation and mortality in the United Kingdom.

BACKGROUND: Influenza is rarely confirmed with laboratory testing and accurate assessment of the overall burden of influenza is difficult. We used statistical modelling methods to generate updated, granular estimates of the number/rate of influenza-attributable hospitalisations and deaths in the United Kingdom. Such data are needed on a continuing basis to inform on cost-benefit analyses of treatment interventions, including vaccination. METHODS: Weekly age specific data on hospital admissions (1997-2009) and on deaths (1997-2009) were obtained from national databases. Virology reports (1996-2009) of influenza and respiratory syncytial virus detections were provided by Public Health England. We used an expanded set of ICD-codes to estimate the burden of illness attributable to influenza which we refer to as 'respiratory disease broadly defined'. These codes were chosen to optimise the balance between sensitivity and specificity. A multiple linear regression model controlled for respiratory syncytial virus circulation, with stratification by age and the presence of comorbid risk status (conditions associated with severe influenza outcomes). RESULTS: In the United Kingdom there were 28,516 hospitalisations and 7163 deaths estimated to be attributable to influenza respiratory disease in a mean season, with marked variability between seasons. The highest incidence rates of influenza-attributable hospitalisations and deaths were observed in adults aged 75+ years (252/100,000 and 131/100,000 population, respectively). Influenza B hospitalisations were highest among 5-17 year olds (12/100,000 population). Of all estimated influenza respiratory deaths in 75+ year olds, 50 % occurred out of hospital, and 25 % in 50-64 year olds. Rates of hospitalisations and death due to influenza-attributable respiratory disease were increased in adults identified as at-risk. CONCLUSIONS: Our study points to a substantial but highly variable seasonal influenza burden in all age groups, particularly affecting 75+ year olds. Effective influenza prevention or early intervention with anti-viral treatment in this age group may substantially impact the disease burden and associated healthcare costs. The high burden of influenza B hospitalisation among 5-17 year olds supports current United Kingdom vaccine policy to extend quadrivalent seasonal influenza vaccination to this age group. TRIAL REGISTRATION: ClinicalTrial.gov, NCT01520935.

Trace Elements in Sea Ducks of the Alaskan Arctic Coast: Patterns of Variation Among Species, Sexes, and Ages.

Climate change and increasing industrialization in the Arctic call for the collection of reference data for assessing changes in contaminant levels. For migratory birds, measuring and interpreting changes in trace element burdens on Arctic breeding areas require insights into factors such as sex, body size, or wintering area that may modify patterns independently of local exposure. In the Alaskan Arctic, we determined levels of trace elements in liver and kidney of common eiders (Somateria mollissima) and long-tailed ducks (Clangula hyemalis) from the Prudhoe Bay oil field and of king eiders (S. spectabilis) and threatened spectacled eiders (S. fischeri) and Steller's eiders (Polystica stelleri) from near the town of Barrow. Small-bodied Steller's eiders and long-tailed ducks from different locations had similarly low levels of selenium (Se), cadmium (Cd), and copper (Cu), perhaps reflecting high mass-specific rates of metabolic depuration during long spring migrations through areas of low exposure. In larger species, Se, Cd, and Cu concentrations were higher in adults than juveniles suggesting that these elements were acquired in nonbreeding marine habitats. Adult male spectacled eiders had exceptionally high Se, Cd, and Cu compared with adult females, possibly because of depuration into eggs and longer female occupancy of nonmarine habitats. Adult female common eiders and juvenile long-tailed ducks at Prudhoe Bay had high and variable levels of Pb, potentially due to local exposure. Explanations for substantial variations in Hg levels were not apparent. Further research into reasons for differing element levels among species and sexes will help clarify the sources, pathways, and risks of exposure.

Tracking Metal Pollution in Lake Chapala: Concentrations in Water, Sediments, and Fish.

We measured concentrations of selected metals (Al, Ba, Cu, Mn, Hg, Sr, V, and Zn) in water, sediments, and fish from Lake Chapala and a reference site to evaluate potential negative effects on wildlife, particularly fish-eating birds. Fish metal concentrations ranged from 0.05 µg/g wet weight (ww) for Al and Cu to 64.70 µg/g ww for Sr. There was a positive and significant correlation between fish length and metals particularly for Ba, Cu, Mn, and Zn in Lake Chapala (p < 0.05). However, there were no significant correlations between metal concentrations and δ(15)N values in fish indicating no biomagnification through the food web. Overall, metal concentrations in water, sediments, and fish were similar to and in some cases below those reported for Lake Chapala over the last 20 years. Also, metal concentrations were below those that could be of concern for negative effects on fish and wildlife of Lake Chapala.

Modelling estimates of the burden of Respiratory Syncytial virus infection in adults and the elderly in the United Kingdom.

BACKGROUND: Growing evidence suggests respiratory syncytial virus (RSV) is an important cause of respiratory disease in adults. However, the adult burden remains largely uncharacterized as most RSV studies focus on children, and population-based studies with laboratory-confirmation of infection are difficult to implement. Indirect modelling methods, long used for influenza, can further our understanding of RSV burden by circumventing some limitations of traditional surveillance studies that rely on direct linkage of individual-level exposure and outcome data. METHODS: Multiple linear time-series regression was used to estimate RSV burden in the United Kingdom (UK) between 1995 and 2009 among the total population and adults in terms of general practice (GP) episodes (counted as first consultation ≥28 days following any previous consultation for same diagnosis/diagnostic group), hospitalisations, and deaths for respiratory disease, using data from Public Health England weekly influenza/RSV surveillance, Clinical Practice Research Datalink, Hospital Episode Statistics, and Office of National Statistics. The main outcome considered all ICD-listed respiratory diseases and, for GP episodes, related symptoms. Estimates were adjusted for non-specific seasonal drivers of disease using secular cyclical terms and stratified by age and risk group (according to chronic conditions indicating severe influenza risk as per UK recommendations for influenza vaccination). Trial registration NCT01706302 . Registered 11 October 2012. RESULTS: Among adults aged 18+ years an estimated 487,247 GP episodes, 17,799 hospitalisations, and 8,482 deaths were attributable to RSV per average season. Of these, 175,070 GP episodes (36 %), 14,039 hospitalisations (79 %) and 7,915 deaths (93 %) were in persons aged 65+ years. High- versus low-risk elderly were two-fold more likely to have a RSV-related GP episode or death and four-fold more likely be hospitalised for RSV. In most seasons since 2001, more GP episodes, hospitalisations and deaths were attributable to RSV in adults than to influenza. CONCLUSION: RSV is associated with a substantial disease burden in adults comparable to influenza, with most of the hospitalisation and mortality burden in the elderly. Treatment options and measures to prevent RSV could have a major impact on the burden of RSV respiratory disease in adults, especially the elderly.

Accumulation and hazard assessment of mercury to waterbirds at Lake Chapala, Mexico.

Lake Chapala is the largest tropical lake in Mexico. The objectives of this study were to determine bioaccumulation of Hg in fish and to evaluate the potential impacts of Hg in the diet of aquatic birds, particularly the American white pelican (AWPE), in Lake Chapala. Hg concentrations in three fish species ranged from 0.021 to 0.568 µg/g wet weight. Mercury in fish was positively and significantly correlated with total fish length (R2=0.44, P<0.05). The δ15N values in fish were significantly correlated with Hg concentrations in Chapala and the San Antonio Reservoir (R2=0.69, P<0.001 and R2=0.40, P<0.001, respectively). However, Hg concentrations in bird feathers were not significantly different between years, among locations, or among species. Hg concentrations in fish from Lake Chapala were within values reported in many parts of the world. The Hg (mean range of 2.75 to 4.54 µg/g dw) and δD (mean range of -62‰ to -11‰) values in bird feathers suggested a wide pattern of exposure for highly migratory AWPE and egrets, although birds with lower δD values in feathers appeared to have greater concentrations of Hg than those with higher δD values. Contaminant exposure in aquatic birds in Chapala during the breeding season should be monitored next to better determine the potential effects of Hg on resident aquatic birds.

Comprehensive quality of life outcomes for pediatric patients undergoing endoscopic sinus surgery.

BACKGROUND: Limited quality of life data exist for pediatric chronic rhinosinusitis (CRS) patients undergoing endoscopic sinus surgery (ESS). Further exploration of the following areas will enhance understanding and support clinical decision-making: baseline and post-ESS general and disease-specific quality of life, parent vs. child report, and correlation of nasal endoscopy to sinus CT scores. METHODOLOGY: A prospective cohort study evaluated CRS patients age 5-18 undergoing ESS. Surveys were completed at two timepoints: (1) pre-ESS and (2) 30-90 days post-ESS, with parents completing general (PedsQLTM) and CRS-specific (SNOT-16 and SN-5) quality of life surveys and children completing PedsQLTM and SNOT-16 surveys. Preoperative Lund-Kennedy nasal endoscopy and Lund-Mackay sinus CT scores were calculated. Where appropriate, outcomes were stratified by cystic fibrosis status. RESULTS: Impaired preoperative general quality of life was evidenced by parent proxy-report of PedsQLTM scores in 10 cystic fibrosis and 11 non-CF patients. ESS was associated with decreased sinus symptoms at 1-3 months postoperatively with SN-5 change scores of -1.85 and -2.2, in CF and non-CF patients, respectively. Parents reported worse CRS symptoms via higher preoperative SNOT-16 scores than their children did. Nasal endoscopy and sinus CT scores correlated with a Spearman correlation coefficient of 0.51. Scores not reaching statistical significance included CF-related CRS SNOT-16 change scores and PedsQLTM general quality of life change scores. CONCLUSION: In pediatric patients with CRS electing ESS, general quality of life is impaired preoperatively and sinus symptoms improve significantly 1-3 months after sinus surgery. Parents report statistically worse CRS symptom scores than their children do. Nasal endoscopy scores in this cohort correlated with sinus CT scores.

Alteration of epigenetic methyl and acetyl marks by postnatal chromium(VI) exposure causes apoptotic changes in the ovary of the F1 offspring.

Hexavalent chromium, Cr(VI), is a heavy metal endocrine disruptor used widely in various industries worldwide and is considered a reproductive toxicant. Our previous studies demonstrated that lactational exposure to Cr(VI) caused follicular atresia, disrupted steroid hormone biosynthesis and signaling, and delayed puberty. However, the underlying mechanism was unknown. The current study investigated the effects of Cr(VI) exposure (25 ppm) during postnatal days 1-21 via dam's milk on epigenetic alterations in the ovary of F1 offspring. Data indicated that Cr(VI) disrupted follicle development and caused apoptosis by increasing DNMT3a /3b and histone methyl marks (H3K27me3 and H3K9me3) along with decreasing histone acetylation marks (H3K9ac and H3K27ac). Our study demonstrates that exposure to Cr(VI) causes changes in the epigenetic marks, partially contributing to the transcriptional repression of genes regulating ovarian development, cell proliferation (PCNA), cell survival (BCL-XL and BCL-2), and activation of genes regulating apoptosis (AIF and cleaved caspase-3), resulting in follicular atresia. The current study suggests a role for epigenetics in Cr(VI)-induced ovotoxicity and infertility.

Global mortality estimates for the 2009 Influenza Pandemic from the GLaMOR project: a modeling study.

BACKGROUND: Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortality burden through statistical modeling of mortality data from multiple countries. METHODS AND FINDINGS: We obtained weekly virology and underlying cause-of-death mortality time series for 2005-2009 for 20 countries covering ∼35% of the world population. We applied a multivariate linear regression model to estimate pandemic respiratory mortality in each collaborating country. We then used these results plus ten country indicators in a multiple imputation model to project the mortality burden in all world countries. Between 123,000 and 203,000 pandemic respiratory deaths were estimated globally for the last 9 mo of 2009. The majority (62%-85%) were attributed to persons under 65 y of age. We observed a striking regional heterogeneity, with almost 20-fold higher mortality in some countries in the Americas than in Europe. The model attributed 148,000-249,000 respiratory deaths to influenza in an average pre-pandemic season, with only 19% in persons <65 y. Limitations include lack of representation of low-income countries among single-country estimates and an inability to study subsequent pandemic waves (2010-2012). CONCLUSIONS: We estimate that 2009 global pandemic respiratory mortality was ∼10-fold higher than the World Health Organization's laboratory-confirmed mortality count. Although the pandemic mortality estimate was similar in magnitude to that of seasonal influenza, a marked shift toward mortality among persons <65 y of age occurred, so that many more life-years were lost. The burden varied greatly among countries, corroborating early reports of far greater pandemic severity in the Americas than in Australia, New Zealand, and Europe. A collaborative network to collect and analyze mortality and hospitalization surveillance data is needed to rapidly establish the severity of future pandemics. Please see later in the article for the Editors' Summary.

Major depressive disorder among older African Americans, Caribbean blacks, and non-Hispanic whites: secondary analysis of the National Survey of American Life.

BACKGROUND: Previous epidemiological and clinical research on mental disorders has treated Blacks as a homogenous group and yet Blacks of Caribbean descent and African Americans differ with respect to ethnicity, national heritage, living circumstances, and immigration status. The purpose of this article is to examine the prevalence of major depressive disorder (MDD) among African Americans, Caribbean Blacks, and non-Hispanic whites aged 50 and older with data on psychiatric and physical comorbidity, mental illness severity, and service use. METHODS: Secondary analysis of data from the National Survey of American Life, a national household probability sample of African Americans, Caribbean Blacks, and non-Hispanic Whites in the United States, were used (n = 1,950). The response rate was 72.3%. RESULTS: Controlling for age, the lifetime prevalence rate of MDD was 12.1% and the 12-month rate was 5.2%. Older Whites and Caribbean Blacks had significantly higher lifetime prevalence than African Americans but 12-month rates were similar across the three groups. Rates of co-occurring psychiatric disorders and physical conditions were high and were similar for African Americans, Caribbean Blacks, and Whites. Most older adults had either moderate or severe 12-month MDD and most talked to at least one professional, most frequently a family doctor, psychiatrist, or other mental health professional. CONCLUSION: MDD among older adults is highly prevalent, often associated with other psychiatric disorders or chronic physical conditions, and is associated with high overall mental illness severity. Differences among older Blacks highlight the need for further research on this population to ensure appropriate treatment is being provided to these groups.

Comparison of adverse events and hospital length of stay associated with various amphotericin B formulations: sequential conventional amphotericin b/lipid versus lipid-only therapy for the treatment of invasive fungal infections in hospitalized patients.

PURPOSE: Patients with invasive fungal infections are often treated initially with conventional amphotericin B deoxycholate (CAB), followed by a switch to lipid-based formulations of amphotericin B (LF-AMB). Our study examined adverse events and hospital length of stay (LOS) among adults who received LF-AMB exclusively or CAB followed by LF-AMB (CAB/LF-AMB). METHODS: Data were extracted from the Cerner Health Facts database. The study included adults with evidence of infection by Aspergillus, Candida, or Cryptococcus in addition to either renal insufficiency, a clinical condition suggesting intolerance to CAB, or CAB exposure within 90 days of admission. Nephrotoxicity was defined as a serum creatinine (SCr) level exceeding a 100% increase from baseline and an absolute level above 1.2 mg/dL. We used a hierarchical mixed-effect logistic regression model with nephrotoxicity as the outcome for the multivariate analysis. RESULTS: The study included 327 LF-AMB and 81 CAB/LF-AMB patients with similar demographics and baseline SCr values. The mean pre-to-post percentage increase in SCr levels was greater for CAB/LF-AMB (122.9%) compared with LF-AMB (62.2%) (P < 0.001). The multivariate-adjusted odds ratio of nephrotoxicity was 5.93, for a 95% confidence interval of 2.92 to 12.05 (P < 0.001) for CAB/LF-AMB compared with LF-AMB. Hypokalemia, hypomagnesemia, and infusion-related reactions were more frequent with CAB/LF-AMB. Compared with the LF-AMB group, the CAB/LF-AMB patients had a longer post-amphotericin B LOS (24.1 days vs. 15.7 days, respectively; P < 0.001), with a marginal effect of 4.5 days longer for those receiving CAB/LF-AMB (P = 0.016). CONCLUSION: In this retrospective study, we noted a significantly longer post-amphotericin B LOS and a greater frequency of adverse events, including nephrotoxicity, for patients whose initial treatment was CAB and who were switched to LF-AMB, compared with patients who received LF-AMB only.