Potential pandemic risk of circulating swine H1N2 influenza viruses.

Influenza A viruses in swine have considerable genetic diversity and continue to pose a pandemic threat to humans due to a potential lack of population level immunity. Here we describe a pipeline to characterize and triage influenza viruses for their pandemic risk and examine the pandemic potential of two widespread swine origin viruses. Our analysis reveals that a panel of human sera collected from healthy adults in 2020 has no cross-reactive neutralizing antibodies against a α-H1 clade strain (α-swH1N2) but do against a γ-H1 clade strain. The α-swH1N2 virus replicates efficiently in human airway cultures and exhibits phenotypic signatures similar to the human H1N1 pandemic strain from 2009 (H1N1pdm09). Furthermore, α-swH1N2 is capable of efficient airborne transmission to both naïve ferrets and ferrets with prior seasonal influenza immunity. Ferrets with H1N1pdm09 pre-existing immunity show reduced α-swH1N2 viral shedding and less severe disease signs. Despite this, H1N1pdm09-immune ferrets that became infected via the air can still onward transmit α-swH1N2 with an efficiency of 50%. These results indicate that this α-swH1N2 strain has a higher pandemic potential, but a moderate level of impact since there is reduced replication fitness and pathology in animals with prior immunity.

Pediatric Tuberculosis: A Review of Evidence-Based Best Practices for Clinicians and Health Care Providers.

Advances in pediatric TB care are promising, the result of decades of advocacy, operational and clinical trials research, and political will by national and local TB programs in high-burden countries. However, implementation challenges remain in linking policy to practice and scaling up innovations for prevention, diagnosis, and treatment of TB in children, especially in resource-limited settings. There is both need and opportunity to strengthen clinician confidence in making a TB diagnosis and managing the various manifestations of TB in children, which can facilitate the translation of evidence to action and expand access to new tools and strategies to address TB in this population. This review aims to summarize existing guidance and best practices for clinicians and health care providers in low-resource, TB-endemic settings and identify resources with more detailed and actionable information for decision-making along the clinical cascade to prevent, find, and cure TB in children.

Performance of established disease severity scores in predicting severe outcomes among adults hospitalized with influenza-FluSurv-NET, 2017-2018.

Background: Influenza is a substantial cause of annual morbidity and mortality; however, correctly identifying those patients at increased risk for severe disease is often challenging. Several severity indices have been developed; however, these scores have not been validated for use in patients with influenza. We evaluated the discrimination of three clinical disease severity scores in predicting severe influenza-associated outcomes. Methods: We used data from the Influenza Hospitalization Surveillance Network to assess outcomes of patients hospitalized with influenza in the United States during the 2017-2018 influenza season. We computed patient scores at admission for three widely used disease severity scores: CURB-65, Quick Sepsis-Related Organ Failure Assessment (qSOFA), and the Pneumonia Severity Index (PSI). We then grouped patients with severe outcomes into four severity tiers, ranging from ICU admission to death, and calculated receiver operating characteristic (ROC) curves for each severity index in predicting these tiers of severe outcomes. Results: Among 8252 patients included in this study, we found that all tested severity scores had higher discrimination for more severe outcomes, including death, and poorer discrimination for less severe outcomes, such as ICU admission. We observed the highest discrimination for PSI against in-hospital mortality, at 0.78. Conclusions: We observed low to moderate discrimination of all three scores in predicting severe outcomes among adults hospitalized with influenza. Given the substantial annual burden of influenza disease in the United States, identifying a prediction index for severe outcomes in adults requiring hospitalization with influenza would be beneficial for patient triage and clinical decision-making.

Whole-Slide Imaging, Mutual Information Registration for Multiplex Immunohistochemistry and Immunofluorescence.

Multiplex immunohistochemistry/immunofluorescence (mIHC/mIF) is a developing technology that facilitates the evaluation of multiple, simultaneous protein expressions at single-cell resolution while preserving tissue architecture. These approaches have shown great potential for biomarker discovery, yet many challenges remain. Importantly, streamlined cross-registration of multiplex immunofluorescence images with additional imaging modalities and immunohistochemistry (IHC) can help increase the plex and/or improve the quality of the data generated by potentiating downstream processes such as cell segmentation. To address this problem, a fully automated process was designed to perform a hierarchical, parallelizable, and deformable registration of multiplexed digital whole-slide images (WSIs). We generalized the calculation of mutual information as a registration criterion to an arbitrary number of dimensions, making it well suited for multiplexed imaging. We also used the self-information of a given IF channel as a criterion to select the optimal channels to use for registration. Additionally, as precise labeling of cellular membranes in situ is essential for robust cell segmentation, a pan-membrane immunohistochemical staining method was developed for incorporation into mIF panels or for use as an IHC followed by cross-registration. In this study, we demonstrate this process by registering whole-slide 6-plex/7-color mIF images with whole-slide brightfield mIHC images, including a CD3 and a pan-membrane stain. Our algorithm, WSI, mutual information registration (WSIMIR), performed highly accurate registration allowing the retrospective generation of an 8-plex/9-color, WSI, and outperformed 2 alternative automated methods for cross-registration by Jaccard index and Dice similarity coefficient (WSIMIR vs automated WARPY, P < .01 and P < .01, respectively, vs HALO + transformix, P = .083 and P = .049, respectively). Furthermore, the addition of a pan-membrane IHC stain cross-registered to an mIF panel facilitated improved automated cell segmentation across mIF WSIs, as measured by significantly increased correct detections, Jaccard index (0.78 vs 0.65), and Dice similarity coefficient (0.88 vs 0.79).

Social trust, cultural trust, and the will to sacrifice for environmental protections.

Because environmental problems are characterized by uncertainty and free-riding fears, trust that others will reciprocate one's own efforts to alleviate them are likely an important predictor of willingness to support environmental protections. Drawing on cross-disciplinary theory and research, I argue that whether individuals' social trust translates into willingness to sacrifice for environmental protections depends both on their own social trust and a culture of trust. I test this proposition using cross-national data from the International Social Survey Programme's Environment III survey. In societies characterized by a culture of high trust, those individuals reporting high social trust are considerably more willing to support environmental protections in these ways. However, in those characterized by a culture of low social trust environments, the relationship between high trust and willingness is dampened. The findings highlight that while there is a positive relationship between social trust and willingness, this relationship likely depends on cultural trust.

Targeting Bladder Urothelial Carcinoma with pHLIP-ICG and Inhibition of Urothelial Cancer Cell Proliferation by pHLIP-amanitin.

Acidity is a useful biomarker for the targeting of metabolically active-cells in tumors. pH Low Insertion Peptides (pHLIPs) sense the pH at the surfaces of tumor cells and can facilitate intracellular delivery of cell-permeable and cell-impermeable cargo molecules. In this study we have shown the targeting of malignant lesions in human bladders by fluorescent pHLIP agents, intracellular delivery of amanitin toxin by pHLIP for the inhibition of urothelial cancer cell proliferation, and enhanced potency of pHLIP-amanitin for cancer cells with 17p loss, a mutation frequently present in urothelial cancers. Twenty-eight ex-vivo bladder specimens, from patients undergoing robotic assisted laparoscopic radical cystectomy for bladder cancer, were treated via intravesical incubation for 15-60 minutes with pHLIP conjugated to indocyanine green (ICG) or IR-800 near infrared fluorescent (NIRF) dyes at concentrations of 4-8 µM. White light cystoscopy identified 47/58 (81%) and NIRF pHLIP cystoscopy identified 57/58 (98.3%) of malignant lesions of different subtypes and stages selected for histopathological processing. pHLIP NIRF imaging improved diagnosis by 17.3% (p < 0.05). All carcinoma-in-situ cases missed by white light cystoscopy were targeted by pHLIP agents and were diagnosed by NIRF imaging. We also investigated the interactions of pHLIP-amanitin with urothelial cancer cells of different grades. pHLIP-amanitin produced concentration- and pH-dependent inhibition of the proliferation of urothelial cancer cells treated for 2 hrs at concentrations up to 4 µM. A 3-4x enhanced cytotoxicity of pHLIP-amanitin was observed for cells with a 17p loss after 2 hrs of treatment at pH6. Potentially, pHLIP technology may improve the management of urothelial cancers, including imaging of malignant lesions using pHLIP-ICG for diagnosis and surgery, and the use of pHLIP-amanitin for treatment of superficial bladder cancers via intravesical instillation.

Immune correlates of protection following Rift Valley fever virus vaccination.

Rift Valley fever virus (RVFV) is a hemorrhagic fever virus with the potential for significant economic and public health impact. Vaccination with an attenuated strain, DelNSsRVFV, provides protection from an otherwise lethal RVFV challenge, but mechanistic determinants of protection are undefined. In this study, a murine model was used to assess the contributions of humoral and cellular immunity to DelNSsRVFV-mediated protection. Vaccinated mice depleted of T cells were protected against subsequent challenge, and passive transfer of immune serum from vaccinated animals to naïve animals was also protective, demonstrating that T cells were dispensable in the presence of humoral immunity and that humoral immunity alone was sufficient. Animals depleted of B cells and then vaccinated were protected against challenge. Total splenocytes, but not T cells alone, B cells alone, or B + T cells harvested from vaccinated animals and then transferred to naïve animals were sufficient to confer protection, suggesting that multiple cellular interactions were required for effective cellular immunity. Together, these data indicate that humoral immunity is sufficient to confer vaccine-mediated protection and suggests that cellular immunity plays a role in protection that requires the interaction of various cellular components.

Comparative analysis of human immune responses following SARS-CoV-2 vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S.

SARS-CoV-2 vaccines BNT162b2, mRNA-1273, and Ad26.COV2.S received emergency use authorization by the U.S. Food and Drug Administration in 2020/2021. Individuals being vaccinated were invited to participate in a prospective longitudinal comparative study of immune responses elicited by the three vaccines. In this observational cohort study, immune responses were evaluated using a SARS-CoV-2 spike protein receptor-binding domain ELISA, SARS-CoV-2 virus neutralization assays and an IFN- γ ELISPOT assay at various times over six months following initial vaccination. mRNA-based vaccines elicited higher magnitude humoral responses than Ad26.COV2.S; mRNA-1273 elicited the most durable humoral response, and all humoral responses waned over time. Neutralizing antibodies against the Delta variant were of lower magnitude than the wild-type strain for all three vaccines. mRNA-1273 initially elicited the greatest magnitude of T cell response, but this declined by 6 months. Declining immunity over time supports the use of booster dosing, especially in the setting of emerging variants.

Genetic diversity of collaborative cross mice enables identification of novel rift valley fever virus encephalitis model.

Rift Valley fever (RVF) is an arboviral disease of humans and livestock responsible for severe economic and human health impacts. In humans, RVF spans a variety of clinical manifestations, ranging from an acute flu-like illness to severe forms of disease, including late-onset encephalitis. The large variations in human RVF disease are inadequately represented by current murine models, which overwhelmingly die of early-onset hepatitis. Existing mouse models of RVF encephalitis are either immunosuppressed, display an inconsistent phenotype, or develop encephalitis only when challenged via intranasal or aerosol exposure. In this study, the genetically defined recombinant inbred mouse resource known as the Collaborative Cross (CC) was used to identify mice with additional RVF disease phenotypes when challenged via a peripheral foot-pad route to mimic mosquito-bite exposure. Wild-type Rift Valley fever virus (RVFV) challenge of 20 CC strains revealed three distinct disease phenotypes: early-onset hepatitis, mixed phenotype, and late-onset encephalitis. Strain CC057/Unc, with the most divergent phenotype, which died of late-onset encephalitis at a median of 11 days post-infection, is the first mouse strain to develop consistent encephalitis following peripheral challenge. CC057/Unc mice were directly compared to C57BL/6 mice, which uniformly succumb to hepatitis within 2-4 days of infection. Encephalitic disease in CC057/Unc mice was characterized by high viral RNA loads in brain tissue, accompanied by clearance of viral RNA from the periphery, low ALT levels, lymphopenia, and neutrophilia. In contrast, C57BL/6 mice succumbed from hepatitis at 3 days post-infection with high viral RNA loads in the liver, viremia, high ALT levels, lymphopenia, and thrombocytopenia. The identification of a strain of CC mice as an RVFV encephalitis model will allow for future investigation into the pathogenesis and treatment of RVF encephalitic disease and indicates that genetic background makes a major contribution to RVF disease variation.

A Cross-Sectional Study of SARS-CoV-2 Seroprevalence between Fall 2020 and February 2021 in Allegheny County, Western Pennsylvania, USA.

Seroprevalence studies are important for understanding the dynamics of local virus transmission and evaluating community immunity. To assess the seroprevalence for SARS-CoV-2 in Allegheny County, an urban/suburban county in Western PA, 393 human blood samples collected in Fall 2020 and February 2021 were examined for spike protein receptor-binding domain (RBD) and nucleocapsid protein (N) antibodies. All RBD-positive samples were evaluated for virus-specific neutralization activity. Our results showed a seroprevalence of 5.5% by RBD ELISA, 4.5% by N ELISA, and 2.5% for both in Fall 2020, which increased to 24.7% by RBD ELISA, 14.9% by N ELISA, and 12.9% for both in February 2021. Neutralization titer was significantly correlated with RBD titer but not with N titer. Using these two assays, we were able to distinguish infected from vaccinated individuals. In the February cohort, higher median income and white race were associated with serological findings consistent with vaccination. This study demonstrates a 4.5-fold increase in SARS-CoV-2 seroprevalence from Fall 2020 to February 2021 in Allegheny County, PA, due to increased incidence of both natural disease and vaccination. Future seroprevalence studies will need to include the effect of vaccination on assay results and incorporate non-vaccine antigens in serological assessments.

Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade.

Next-generation tissue-based biomarkers for immunotherapy will likely include the simultaneous analysis of multiple cell types and their spatial interactions, as well as distinct expression patterns of immunoregulatory molecules. Here, we introduce a comprehensive platform for multispectral imaging and mapping of multiple parameters in tumor tissue sections with high-fidelity single-cell resolution. Image analysis and data handling components were drawn from the field of astronomy. Using this "AstroPath" whole-slide platform and only six markers, we identified key features in pretreatment melanoma specimens that predicted response to anti-programmed cell death-1 (PD-1)-based therapy, including CD163+PD-L1- myeloid cells and CD8+FoxP3+PD-1low/mid T cells. These features were combined to stratify long-term survival after anti-PD-1 blockade. This signature was validated in an independent cohort of patients with melanoma from a different institution.

Relative and Absolute Effectiveness of High-Dose and Standard-Dose Influenza Vaccine Against Influenza-Related Hospitalization Among Older Adults-United States, 2015-2017.

BACKGROUND: Seasonal influenza causes substantial morbidity and mortality in older adults. High-dose inactivated influenza vaccine (HD-IIV), with increased antigen content compared to standard-dose influenza vaccines (SD-IIV), is licensed for use in people aged ≥65 years. We sought to evaluate the effectiveness of HD-IIV and SD-IIV for prevention of influenza-associated hospitalizations. METHODS: Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at 8 hospitals in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015-2016 and 2016-2017 influenza seasons. Enrolled patients were tested for influenza, and receipt of influenza vaccine by type was recorded. Effectiveness of SD-IIV and HD-IIV was estimated using a test-negative design (comparing odds of influenza among vaccinated and unvaccinated patients). Relative effectiveness of SD-IIV and HD-IIV was estimated using logistic regression. RESULTS: Among 1487 enrolled patients aged ≥65 years, 1107 (74%) were vaccinated; 622 (56%) received HD-IIV, and 485 (44%) received SD-IIV. Overall, 277 (19%) tested positive for influenza, including 98 (16%) who received HD-IIV, 87 (18%) who received SD-IIV, and 92 (24%) who were unvaccinated. After adjusting for confounding variables, effectiveness of SD-IIV was 6% (95% confidence interval [CI] -42%, 38%) and that of HD-IIV was 32% (95% CI -3%, 54%), for a relative effectiveness of HD-IIV versus SD-IIV of 27% (95% CI -1%, 48%). CONCLUSIONS: During 2 US influenza seasons, vaccine effectiveness was low to moderate for prevention of influenza hospitalization among adults aged ≥65 years. High-dose vaccine offered greater effectiveness. None of these findings were statistically significant.

Association between extent of resection on survival in adult brainstem high-grade glioma patients.

BACKGROUND: Brainstem high-grade gliomas (HGG) are rare lesions with aggressive behavior that pose significant treatment challenges. The operative use of brainstem safe entry zones has made such lesions surgically accessible, though the benefits of aggressive resection have been unclear. This study aimed to clarify the survival in adult patients. METHODS: We utilized the SEER database (1973-2015) to analyze the association between survival and demographic data, tumor characteristics, and treatment factors in adult patients with brainstem HGGs. Patients without surgical intervention were excluded. Overall survival (OS) was analyzed using univariable and multivariable Cox regression. RESULTS: Our dataset included a total of 502 brainstem HGG patients of which only those who had undergone surgical intervention were included in the analysis, totaling 103. Mean age was 42.4 ± 14.1 years with 57.2% (n = 59) male. Median OS of the entire cohort was 11.0 months. Median OS for patients receiving biopsy, subtotal resection, and gross total resection were 8, 11, and 16 months, respectively. Age, extent of resection, and radiation therapy were selected into the multivariable model. A significant decrease in survival was seen in older patients, 50-60 years (HR = 2.77, p = 0.002) and ≥ 60 years (HR = 5.30, p < 0.001), compared to younger patients (18-30 years). Partial resection (HR = 0.32, p = 0.006) and GTR (HR = 0.24, p < 0.001) sustained survival benefits compared to patients with biopsy only. Patients receiving postoperative radiation demonstrated no survival benefit (HR = 1.57, p = 0.161) in multivariable regression. CONCLUSIONS: While survival of brainstem HGG patients remains poor, for surgically accessible HGGs, STR and GTR were associated with a three and fourfold increase in overall survival when compared to biopsy only.

Socioeconomic Status and Diet Quality in College Students.

OBJECTIVE: To investigate the existence and trajectory of diet disparities among college students from different socioeconomic statuses (SESs). METHODS: A random sample of freshman and sophomore students was invited to participate in an online survey on eating behaviors. Ordinary least squares regressions were fit to 148 complete responses to examine the association between family income ≤200% of the federal poverty level and overall, healthy, and unhealthy food consumption. RESULTS: Low-SES students reported eating significantly more unhealthy food during their freshman year than their non-low-SES peers. This difference is not statistically significant for second-year students and robust to on-campus spending power. CONCLUSIONS AND IMPLICATIONS: Disparities in diets for students from different socioeconomic backgrounds that were observed in the freshman year of college were absent in the sophomore year. Awareness of these disparities and trend is important to broadly promote healthy eating.

Influenza virus-related critical illness: prevention, diagnosis, treatment.

Annual seasonal influenza epidemics of variable severity result in significant morbidity and mortality in the United States (U.S.) and worldwide. In temperate climate countries, including the U.S., influenza activity peaks during the winter months. Annual influenza vaccination is recommended for all persons in the U.S. aged 6 months and older, and among those at increased risk for influenza-related complications in other parts of the world (e.g. young children, elderly). Observational studies have reported effectiveness of influenza vaccination to reduce the risks of severe disease requiring hospitalization, intensive care unit admission, and death. A diagnosis of influenza should be considered in critically ill patients admitted with complications such as exacerbation of underlying chronic comorbidities, community-acquired pneumonia, and respiratory failure during influenza season. Molecular tests are recommended for influenza testing of respiratory specimens in hospitalized patients. Antigen detection assays are not recommended in critically ill patients because of lower sensitivity; negative results of these tests should not be used to make clinical decisions, and respiratory specimens should be tested for influenza by molecular assays. Because critically ill patients with lower respiratory tract disease may have cleared influenza virus in the upper respiratory tract, but have prolonged influenza viral replication in the lower respiratory tract, an endotracheal aspirate (preferentially) or bronchoalveolar lavage fluid specimen (if collected for other diagnostic purposes) should be tested by molecular assay for detection of influenza viruses.Observational studies have reported that antiviral treatment of critically ill adult influenza patients with a neuraminidase inhibitor is associated with survival benefit. Since earlier initiation of antiviral treatment is associated with the greatest clinical benefit, standard-dose oseltamivir (75 mg twice daily in adults) for enteric administration is recommended as soon as possible as it is well absorbed in critically ill patients. Based upon observational data that suggest harms, adjunctive corticosteroid treatment is currently not recommended for children or adults hospitalized with influenza, including critically ill patients, unless clinically indicated for another reason, such as treatment of asthma or COPD exacerbation, or septic shock. A number of pharmaceutical agents are in development for treatment of severe influenza.

Interim Estimates of 2018-19 Seasonal Influenza Vaccine Effectiveness - United States, February 2019.

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (https://www.cdc.gov/flu/protect/whoshouldvax.htm). Effectiveness of seasonal influenza vaccine varies by season. During each influenza season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent laboratory-confirmed influenza associated with medically attended acute respiratory illness (ARI). This interim report uses data from 3,254 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during November 23, 2018-February 2, 2019. During this period, overall adjusted vaccine effectiveness against all influenza virus infection associated with medically attended ARI was 47% (95% confidence interval [CI] = 34%-57%). For children aged 6 months-17 years, overall vaccine effectiveness was 61% (44%-73%). Seventy-four percent of influenza A infections for which subtype information was available were caused by A(H1N1)pdm09 viruses. Vaccine effectiveness was estimated to be 46% (30%-58%) against illness caused by influenza A(H1N1)pdm09 viruses. CDC recommends that health care providers continue to administer influenza vaccine because influenza activity is ongoing and the vaccine can still prevent illness, hospitalization, and death associated with currently circulating influenza viruses, or other influenza viruses that might circulate later in the season. During the 2017-18 influenza season, in which influenza A(H3N2) predominated, vaccination was estimated to prevent 7.1 million illnesses, 3.7 million medical visits, 109,000 hospitalizations, and 8,000 deaths (1). Vaccination can also reduce the severity of influenza-associated illness (2). Persons aged ≥6 months who have not yet been vaccinated this season should be vaccinated.

Pediatric influenza and illness severity: what is known and what questions remain?

PURPOSE OF REVIEW: Influenza causes a range of illnesses in children, from uncomplicated self-limited illness to severe disease and death. This review provides an update on the severity and burden of influenza in US children over recent seasons. RECENT FINDINGS: The 2017-2018 influenza season was widespread and severe across all ages, including children. Disease severity is influenced by influenza virologic characteristics and host factors, as well as public health interventions such as influenza vaccination and antiviral treatment. In recent influenza A (H3N2)-predominant seasons (2016-2017 and 2017-2018), influenza vaccination effectiveness was higher in younger children compared with older children and adolescents, although the reasons for this are unclear. Interestingly, even in seasons when influenza A (H3N2) viruses predominate, influenza A (H1N1)pdm09 and B viruses can play a large role in severe pediatric disease. Although children less than 5 years of age and those with underlying medical conditions are at increased risk for severe disease, influenza-associated hospitalizations and deaths occur every season in healthy children. SUMMARY: Influenza causes a substantial burden of outpatient visits, hospitalizations, and deaths among children. Ongoing research is important to better characterize factors that contribute to influenza severity, and to identify strategies to improve the impact of influenza vaccination and treatment.

Improving Influenza Testing and Treatment in Hospitalized Children.

OBJECTIVES: National guidelines recommend influenza testing for children hospitalized with influenza-like illness (ILI) during influenza season and treatment of those with confirmed influenza. Using quality improvement methods, we sought to increase influenza testing and treatment of children admitted to our hospital medicine service with ILI from 65% to 90% during the 2014-2015 influenza season. METHODS: We targeted several key drivers using multiple plan-do-study-act cycles. Interventions included awareness modules, biweekly flyers, and failure tracking. ILI admissions (fever plus respiratory symptoms) were reviewed weekly once surveillance data revealed elevated influenza activity. Appropriate testing and treatment of ILI was defined as influenza testing and/or treatment within 24 hours of admission unless a known cause other than influenza was present. We used statistical process control charts to track progress using established quality improvement methods. Appropriate testing and treatment was also assessed in the 2016-2017 influenza season by using similar methods, although no new interventions were introduced. RESULTS: For the 2014-2015 season, appropriate testing and treatment increased from a baseline mean of 65% to 91% within 3 months. For the 2016-2017 season, appropriate testing and treatment remained at a mean of 80% throughout the influenza season. CONCLUSIONS: Appropriate influenza testing and treatment increased to 90% in children with ILI during the 2014-2015 season. Improvements were sustained in a subsequent influenza season. Our initiative improved recognition of influenza and likely increased treatment opportunities. Future work should be focused on wider implementation and further reducing variation.

Institutionalized collective action and the relationship between beliefs about environmental problems and environmental actions: A cross-national analysis.

How do institutions affect the relationship between an individual's beliefs and their actions? Institutionalized strategies are routine ways of addressing problems that become taken-for-granted in a society. Environmental problems constitute a collective action problem in that personal consumption often conflicts with collective interests. I test whether beliefs about environmental problems have a different impact on a person's pro-environmental behaviors, depending on how addressing collective action problems is institutionalized in their society. In particular, I use level of welfare targeting as an observable, organizational difference among societies that reflects different institutionalized strategies for addressing a prominent collective action problem. I use multilevel models on data from the 2010 International Social Survey Programme (ISSP) and measures of welfare targeting from the Organization for Economic Cooperation and Development (OECD) to answer this question. I find that in societies where the institutionalized strategy for dealing with inequality is highly targeted, individuals' beliefs that these problems are important, real, and whether they can do something about them have a greater impact on their actions. The results suggest individuals generalize taken-for-granted strategies of assuring collective welfare to implement their individual beliefs about the environment, making institutional environments important moderators of the strength of the belief-action relationship.