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Asthma affects 25 million people in the United States, and its prevalence is increasing. Access to care and adherence to prescribed asthma-treatment programs remain the principal formidable challenges for asthma management. Telemedicine offers substantial opportunities for improved asthma care of patients across the full range of socioeconomic strata. Ever-improving digital tools for asthma assessment and treatment are key components of telemedicine platforms for asthma management. These include a variety of remote patient-monitoring devices, digital inhaler systems, and mobile-health applications that facilitate ongoing assessment and adherence to treatment protocols. Digital tools for monitoring treatment focus on tracking medication use, inhalation technique, and physiological markers such as peak-flow rate and pulse-oximetry. Telemedicine visits allow for elements of assessment via video, approximating or duplicating many aspects of in-person visits, such as evaluating a patient's general appearance, breathing effort, and cough. Challenges remain in ensuring equitable access to these technologies, especially in rural and low-income areas, and in maintaining patient privacy and data security in digital platforms., Competing Interests: RSC receives grant support from the Consortium for Food Allergy Research (CoFAR), National Institute of Allergy and Infectious Disease (NIAID), Food Allergy Research & Education (FARE), and is an advisory board member for Alladapt Immunotherapeutics, Novartis, Intrommune Therapeutics, Phylaxis, and Genentech. SS reports grants from NIH, Regeneron, DBV Technologies, Aimmune, Novartis, CoFAR, and FARE. She is an Advisory member at Genentech and DBV Technologies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interes., (© 2024 Bocian, Chin, Rodriguez, Collins, Sindher and Chinthrajah.)

A significant percentage of bridges in the United States are serving beyond their 50-year design life, and many of them are in poor condition, making them vulnerable to fatigue cracks that can result in catastrophic failure. However, current fatigue crack inspection practice based on human vision is time-consuming, labor intensive, and prone to error. We present a novel human-centered bridge inspection methodology to enhance the efficiency and accuracy of fatigue crack detection by employing advanced technologies including computer vision and augmented reality (AR). In particular, a computer vision-based algorithm is developed to enable near-real-time fatigue crack detection by analyzing structural surface motion in a short video recorded by a moving camera of the AR headset. The approach monitors structural surfaces by tracking feature points and measuring variations in distances between feature point pairs to recognize the motion pattern associated with the crack opening and closing. Measuring distance changes between feature points, as opposed to their displacement changes before this improvement, eliminates the need of camera motion compensation and enables reliable and computationally efficient fatigue crack detection using the nonstationary AR headset. In addition, an AR environment is created and integrated with the computer vision algorithm. The crack detection results are transmitted to the AR headset worn by the bridge inspector, where they are converted into holograms and anchored on the bridge surface in the 3D real-world environment. The AR environment also provides virtual menus to support human-in-the-loop decision-making to determine optimal crack detection parameters. This human-centered approach with improved visualization and human-machine collaboration aids the inspector in making well-informed decisions in the field in a near-real-time fashion. The proposed crack detection method is comprehensively assessed using two laboratory test setups for both in-plane and out-of-plane fatigue cracks. Finally, using the integrated AR environment, a human-centered bridge inspection is conducted to demonstrate the efficacy and potential of the proposed methodology.

This paper describes the use of wireless smart sensors for examining the underlying mechanism for the wind-induced vibration of high-mast illumination pole (HMIP) structures. HMIPs are tall, slender structures with low inherent damping. Video recordings of multiple HMIPs showed considerable vibrations of these HMIPs under wind loading in the state of Kansas. The HMIPs experienced cyclic large-amplitude displacements at the top, which can produce high-stress demand and lead to fatigue cracking at the bottom of the pole. In this study, the natural frequencies of the HMIP were assessed using pluck tests and finite element modeling, and the recorded vibration frequencies were obtained through computer vision-based video analysis. Meanwhile, a 30.48 m tall HMIP with three LED luminaires made of galvanized steel located in Wakeeney, Kansas, was selected for long-term vibration monitoring using wireless smart sensors to investigate the underlying mechanism for the excessive wind-induced vibrations. Data analysis with the long-term monitoring data indicates that while vortex-induced vibration occurs frequently at relatively low amplitude, buffeting-induced vibration was the leading cause of the excessive vibrations of the monitored HMIP. The findings provide crucial information to guide the design of vibration mitigation strategies for these HMIP structures.

Analyzing vast textual data and summarizing key information from electronic health records imposes a substantial burden on how clinicians allocate their time. Although large language models (LLMs) have shown promise in natural language processing (NLP) tasks, their effectiveness on a diverse range of clinical summarization tasks remains unproven. Here we applied adaptation methods to eight LLMs, spanning four distinct clinical summarization tasks: radiology reports, patient questions, progress notes and doctor-patient dialogue. Quantitative assessments with syntactic, semantic and conceptual NLP metrics reveal trade-offs between models and adaptation methods. A clinical reader study with 10 physicians evaluated summary completeness, correctness and conciseness; in most cases, summaries from our best-adapted LLMs were deemed either equivalent (45%) or superior (36%) compared with summaries from medical experts. The ensuing safety analysis highlights challenges faced by both LLMs and medical experts, as we connect errors to potential medical harm and categorize types of fabricated information. Our research provides evidence of LLMs outperforming medical experts in clinical text summarization across multiple tasks. This suggests that integrating LLMs into clinical workflows could alleviate documentation burden, allowing clinicians to focus more on patient care., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective : To describe pregnancy-related mortality among Hispanic people by place of origin (country or region of Hispanic ancestry), 2009-2018. Materials and Methods : We conducted a cross-sectional descriptive study of pregnancy-related deaths among Hispanic people, stratified by place of origin (Central or South America, Cuba, Dominican Republic, Mexico, Puerto Rico, Other and Unknown Hispanic), using Pregnancy Mortality Surveillance System data, 2009-2018. We describe distributions of pregnancy-related deaths and pregnancy-related mortality ratios (number of pregnancy-related deaths per 100,000 live births) overall and by place of origin for select demographic and clinical characteristics. Results : For 2009-2018, the overall pregnancy-related mortality ratio among Hispanic people was 11.5 pregnancy-related deaths per 100,000 live births (95% confidence intervals [CI]: 10.8-12.2). In general, pregnancy-related mortality ratios were higher among older age groups ( i.e. , 35 years and older) and lower among those with higher educational attainment ( i.e. , college degree or higher). Approximately two in five pregnancy-related deaths among Hispanic people occurred on the day of delivery through 6 days postpartum. Place of origin-specific pregnancy-related mortality ratios ranged from 9.6 (95% CI: 5.8-15.0) among people of Cuban origin to 15.3 (95% CI: 12.4-18.3) among people of Puerto Rican origin. Hemorrhage and infection were the most frequent causes of pregnancy-related deaths overall among Hispanic people. People of Puerto Rican origin had a higher proportion of deaths because of cardiomyopathy. Conclusions : We identified differences in pregnancy-related mortality by place of origin among Hispanic people that can help inform prevention of pregnancy-related deaths.

Sifting through vast textual data and summarizing key information from electronic health records (EHR) imposes a substantial burden on how clinicians allocate their time. Although large language models (LLMs) have shown immense promise in natural language processing (NLP) tasks, their efficacy on a diverse range of clinical summarization tasks has not yet been rigorously demonstrated. In this work, we apply domain adaptation methods to eight LLMs, spanning six datasets and four distinct clinical summarization tasks: radiology reports, patient questions, progress notes, and doctor-patient dialogue. Our thorough quantitative assessment reveals trade-offs between models and adaptation methods in addition to instances where recent advances in LLMs may not improve results. Further, in a clinical reader study with ten physicians, we show that summaries from our best-adapted LLMs are preferable to human summaries in terms of completeness and correctness. Our ensuing qualitative analysis highlights challenges faced by both LLMs and human experts. Lastly, we correlate traditional quantitative NLP metrics with reader study scores to enhance our understanding of how these metrics align with physician preferences. Our research marks the first evidence of LLMs outperforming human experts in clinical text summarization across multiple tasks. This implies that integrating LLMs into clinical workflows could alleviate documentation burden, empowering clinicians to focus more on personalized patient care and the inherently human aspects of medicine.

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data., (© 2023. The Author(s).)

The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., "If you do not practice these steps, you can endanger yourself and others") or potential gains (e.g., "If you practice these steps, you can protect yourself and others")? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions., Competing Interests: Conflict of InterestThe authors declare no conflict of interest., (© The Society for Affective Science 2022.)

The atmospheric concentration of methane has more than doubled since the start of the Industrial Revolution. Methane is the second-most-abundant greenhouse gas created by human activities and a major driver of climate change. This APS-Optica report provides a technical assessment of the current state of monitoring U.S. methane emissions from oil and gas operations, which accounts for roughly 30% of U.S. anthropogenic methane emissions. The report identifies current technological and policy gaps and makes recommendations for the federal government in three key areas: methane emissions detection, reliable and systematized data and models to support mitigation measures, and effective regulation.

There is increasing understanding, globally, that climate change and increased pollution will have a profound and mostly harmful effect on human health. This review brings together international experts to describe both the direct (such as heat waves) and indirect (such as vector-borne disease incidence) health impacts of climate change. These impacts vary depending on vulnerability (i.e., existing diseases) and the international, economic, political, and environmental context. This unique review also expands on these issues to address a third category of potential longer-term impacts on global health: famine, population dislocation, and environmental justice and education. This scholarly resource explores these issues fully, linking them to global health in urban and rural settings in developed and developing countries. The review finishes with a practical discussion of action that health professionals around the world in our field can yet take., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Competing Interests: Competing Interests The authors declare no competing interests.

Background: One key aspect of a learning health system (LHS) is utilizing data generated during care delivery to inform clinical care. However, institutional guidelines that utilize observational data are rare and require months to create, making current processes impractical for more urgent scenarios such as those posed by the COVID-19 pandemic. There exists a need to rapidly analyze institutional data to drive guideline creation where evidence from randomized control trials are unavailable., Objectives: This article provides a background on the current state of observational data generation in institutional guideline creation and details our institution's experience in creating a novel workflow to (1) demonstrate the value of such a workflow, (2) demonstrate a real-world example, and (3) discuss difficulties encountered and future directions., Methods: Utilizing a multidisciplinary team of database specialists, clinicians, and informaticists, we created a workflow for identifying and translating a clinical need into a queryable format in our clinical data warehouse, creating data summaries and feeding this information back into clinical guideline creation., Results: Clinical questions posed by the hospital medicine division were answered in a rapid time frame and informed creation of institutional guidelines for the care of patients with COVID-19. The cost of setting up a workflow, answering the questions, and producing data summaries required around 300 hours of effort and $300,000 USD., Conclusion: A key component of an LHS is the ability to learn from data generated during care delivery. There are rare examples in the literature and we demonstrate one such example along with proposed thoughts of ideal multidisciplinary team formation and deployment., Competing Interests: N.H.S. is a co-founder of Atropos Health. A.C. is an advisor to Atropos Health. None of the other authors have conflicts of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Numerous biomaterial scaffolds have been developed which provide architectures to support the proliferation of mammalian cells. Scaffolds derived from plant components have been utilized in several tissue engineering applications, including the production of cultured meats. Bread crumb is a common ingredient employed as a texturizer and filler in existing manufacturing processes for the production of animal meat products. Though an unconventional choice as a scaffolding material, we developed a yeast-free "soda bread" with controllable porosity and mechanical properties which is stable over several weeks in culture with fibroblasts, myoblasts and pre-osteoblasts. All cells were able to proliferate throughout the three-dimensional scaffolds, depositing extra-cellular matrix while exhibiting low stress and high viability. Importantly, myoblasts were also able to differentiate into myotubes, a key step required for the culture of skeletal muscle tissue. The results suggest opportunities for the dual-use possibility of utilizing existing texturizer and filler components in future lab grown meat products, however this will of course require further validation. Regardless, the bread-derived scaffolds presented here are simply produced, inherently edible and support muscle tissue engineering, qualities which highlight their utility in the production of future meat products., (Copyright © 2021. Published by Elsevier Ltd.)

Background: It is unclear whether asthma and its allergic phenotype are risk factors for hospitalization or severe disease from SARS-CoV-2., Methods: All patients over 28 days old testing positive for SARS-CoV-2 between March 1 and September 30, 2020, were retrospectively identified and characterized through electronic analysis at Stanford. A sub-cohort was followed prospectively to evaluate long-term COVID-19 symptoms., Results: 168,190 patients underwent SARS-CoV-2 testing, and 6,976 (4.15%) tested positive. In a multivariate analysis, asthma was not an independent risk factor for hospitalization (OR 1.12 [95% CI 0.86, 1.45], p = .40). Among SARS-CoV-2-positive asthmatics, allergic asthma lowered the risk of hospitalization and had a protective effect compared with non-allergic asthma (OR 0.52 [0.28, 0.91], p = .026); there was no association between baseline medication use as characterized by GINA and hospitalization risk. Patients with severe COVID-19 disease had lower eosinophil levels during hospitalization compared with patients with mild or asymptomatic disease, independent of asthma status (p = .0014). In a patient sub-cohort followed longitudinally, asthmatics and non-asthmatics had similar time to resolution of COVID-19 symptoms, particularly lower respiratory symptoms., Conclusions: Asthma is not a risk factor for more severe COVID-19 disease. Allergic asthmatics were half as likely to be hospitalized with COVID-19 compared with non-allergic asthmatics. Lower levels of eosinophil counts (allergic biomarkers) were associated with a more severe COVID-19 disease trajectory. Recovery was similar among asthmatics and non-asthmatics with over 50% of patients reporting ongoing lower respiratory symptoms 3 months post-infection., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 12 May 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.c.4878591.v1., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Inhibitory control is a key executive function and has been studied extensively using the stop signal task. By applying a simple race model that posits an independent race between a GO process responsible for initiation of responses and a STOP process responsible for inhibition of responses, one can estimate how long it takes an individual to inhibit an ongoing response, the stop signal reaction time. Here, we examined how stop signal reaction time can be affected by working memory. Participants engaged in a dual task; they completed a stop signal task under low and high working memory load conditions. Working memory capacity was also measured. We found that the STOP process was lengthened in the high, compared to the low, working memory load condition, as evidenced by differences in stop signal reaction time. The GO process was unaffected and working memory capacity could not account for differences across the load conditions. These results indicate that inhibitory control can be influenced by placing demands on working memory.

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

This study highlights the role of local communities in creating culturally rooted health information resources based on comparative effectiveness research (CER), depicting the role of culture in creating entry points for building community-grounded communication structures for evidence-based health knowledge. We report the results from running a year-long culture-centered campaign that was carried out among African American communities in two counties, Lake and Marion County, in Indiana addressing basic evidence-based knowledge on four areas of cardiovascular disease (CVD). Campaign effectiveness was tested through an experimental design with post-test knowledge of CER among African Americans in these counties compared to CER knowledge among African Americans in a comparable control county (Allen). Our campaign, based on the principles of the culture-centered approach (CCA), increased community CER knowledge in the experimental communities relative to a community that did not receive the culturally centered health information campaign. The CCA-based campaign developed by community members and distributed through the mass media, community wide channels such as health fairs and church meetings, postcards, and face-to-face interventions explaining the postcards improved CER knowledge in specific areas (ACE-I/ARBs, atrial fibrillation, and renal artery stenosis) in the CCA communities as compared to the control community.

American Foulbrood (AFB) is a deadly bacterial disease affecting pupal and larval honey bees. AFB is caused by the endospore-forming bacterium Paenibacillus larvae (PL). Propolis, which contains a variety of organic compounds, is a product of bee foraging and is a resinous substance derived from botanical substances found primarily in trees. Several compounds from the class of caffeic acid esters, which are commonly found in propolis, have been shown to have antibacterial activity against PL. In this study, six different caffeic acid esters were synthesized, purified, spectroscopically analyzed, and tested for their activity against PL to determine the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs). Caffeic acid isopropenyl ester (CAIE), caffeic acid benzyl ester (CABE), and caffeic acid phenethyl ester (CAPE) were the most effective in inhibiting PL growth and killing PL cell with MICs and MBCs of 125 µg/mL when used individually, and a MIC and MBC of 31.25 µg/mL for each compound alone when CAIE, CABE, and CAPE are used in combination against PL. These compounds inhibited bacterial growth through a bactericidal effect, which revealed cell killing but no lysis of PL cells after 18 h. Incubation with CAIE, CABE, and CAPE at their MICs significantly increased reactive oxygen species levels and significantly changed glutathione levels within PL cells. Caffeic acid esters are potent bactericidal compounds against PL and eliminate bacterial growth through an oxidative stress mechanism.

The substantia nigra pars compacta (SNpc) is a discrete region of the brain that exhibits a dark pigment, neuromelanin (NM), a biomaterial with unique properties and the subject of ongoing research pertaining to neurodegenerative conditions like Parkinson's disease (PD). Obtaining human tissue to isolate this pigment is costly and labor intensive, making it necessary to find alternatives to model the biochemical interaction of NM and its implications on PD. To address this limitation, we modified our established silk 3D brain tissue model to emulate key characteristics of the SNpc by using a structural analogue of NM to examine the effects of the material on dopaminergic neurons using Lund's human mesencephalon (LUHMES) cells. We utilized a sepia-melanin, squid ink, derived NM analogue (NM-sim) to chelate ferric iron, and this iron-neuromelanin precipitate (Fe-NM) was purified and characterized. We then exposed LUHMES dopaminergic cells to the NM-sim, Fe-NM-sim, and control vehicle within 3D silk protein scaffolds. The presence of both NM-sim and Fe-NM-sim in the scaffolds negatively impacted spontaneous electrical activity from the LUMES networks, as evidenced by changes in local field potential (LFP) electrophysiological recordings. Furthermore, the Fe-NM-sim precipitate generated peroxides, depleted nutrients/antioxidants, and increased protein oxidation by carbonylation in sustained (>2 weeks) 3D cultures, thereby contributing to cell dysfunction. The results suggest that this 3D tissue engineered brain-like model may provide useful readouts related to PD neuro-toxicology research.

Objective: The study identified important stressors associated with depressive symptoms in college students across the subgroups of gender and domestic/international status, and compared between-group differences across stress levels., Participants: Data were collected from 631 undergraduate students from October 2014 to March 2015., Methods: Participants completed an online survey containing measures of stressors (Student-Stress-Survey), depressive symptoms (CES-D scale), and demographics., Results: The mean CES-D score (16.24) of sample indicated high depressive symptoms. International students reported higher depressive symptoms than domestic students and students identifying as female showed higher depression symptoms than male. Eight most frequently occurring stressors experienced by over 50% of the sample were identified as important; differences in stress levels across gender and domestic/international status were discussed., Conclusions: This renewed look reinforced that tailored and sustained efforts are needed to address the continued prevalence of different stressors and associated depressive symptoms faced by college students on US campuses.

The present study used data from the Minnesota Longitudinal Study of Risk and Adaptation (MLSRA) to investigate how multiple dimensions of childhood abuse and neglect predict romantic relationship functioning in adulthood. Several dimensions of abuse and neglect (any experience, type, chronicity, co-occurrence, and perpetrator) were rated prospectively from birth through age 17.5 years. Multimethod assessments of relational competence and violence in romantic relationships were conducted repeatedly from ages 20 to 32 years. As expected, experiencing childhood abuse and neglect was associated with lower romantic competence and more relational violence in adulthood. Follow-up analyses indicated that lower romantic competence was specifically associated with physical abuse, maternal perpetration, chronicity, and co-occurrence, whereas more relational violence was uniquely associated with nonparental perpetration. We discuss these novel prospective findings in the context of theory and research on antecedents of romantic relationship functioning.

Electrophysiology is a powerful tool to examine cellular functions, but the use of the techniques remains challenging outside of physiology and neuroscience fields. We aim to provide a practical methods guide for electrophysiological recordings to nonexperts in the field to help with the utility of these important research tools. We focus on two techniques that are critical in the context of tissue engineering, whole-cell patch clamp recording for assessing cellular functions and extracellular field potential recording for evaluating network activities. Specific examples are presented to demonstrate how the techniques were applied to tissue engineering studies.

Across the life course, African Americans bear an unequal burden of disease compared to other racial groups. In spite of the widespread acknowledgment of racial health disparities, the voices of African Americans, their articulations of health and their local etiologies of health disparities are limited. In this article, we highlight the important role of communication scholarship to understand the everyday enactment of health disparities. Drawing upon the culture-centered approach (CCA) to co-construct narratives of health with African Americans residents of Lake County, Indiana, we explore the presence of stress in the everyday narratives of health. These narratives voice the social and structural sources of stress, and articulate resistive coping strategies embedded in relationship to structures.

Methane emissions contribute to global warming, damage public health and reduce the yield of agricultural and forest ecosystems. Quantifying these damages to the planetary commons by calculating the social cost of methane (SCM) facilitates more comprehensive cost-benefit analyses of methane emissions control measures and is the first step to potentially incorporating them into the marketplace. Use of a broad measure of social welfare is also an attractive alternative or supplement to emission metrics focused on a temperature target in a given year as it incentivizes action to provide benefits over a broader range of impacts and timescales. Calculating the SCM using consistent temporal treatment of physical and economic processes and incorporating climate- and air quality-related impacts, we find large SCM values, e.g. ∼$2400 per ton and ∼$3600 per ton with 5% and 3% discount rates respectively. These values are ∼100 and 50 times greater than corresponding social costs for carbon dioxide. Our results suggest that ∼110 of 140 Mt of identified methane abatement via scaling up existing technology and policy options provide societal benefits that outweigh implementation costs. Within the energy sector, renewables compare far better against use of natural gas in electricity generation when incorporating these social costs for methane. In the agricultural sector, changes in livestock management practices, promoting healthy diets including reduced beef and dairy consumption, and reductions in food waste have been promoted as ways to mitigate emissions, and these are shown here to indeed have the potential to provide large societal benefits (∼$50-150 billion per year). Examining recent trends in methane and carbon dioxide, we find that increases in methane emissions may have offset much of the societal benefits from a slowdown in the growth rate of carbon dioxide emissions. The results indicate that efforts to reduce methane emissions via policies spanning a wide range of technical, regulatory and behavioural options provide benefits at little or negative net cost. Recognition of the full SCM, which has typically been undervalued, may help catalyze actions to reduce emissions and thereby provide a broad set of societal benefits.

Mild hyperthermia generated using high intensity focused ultrasound (HIFU) and microbubbles (MBs) can improve tumor drug delivery from non-thermosensitive liposomes (NTSLs) and low temperature sensitive liposomes (LTSLs). However, MB and HIFU are limited by the half-life of the contrast agent and challenges in accurate control of large volume tumor hyperthermia for longer duration (>30min.). The objectives of this study were to: 1) synthesize and characterized long-circulating echogenic nanobubble encapsulated LTSLs (ELTSLs) and NTSLs (ENTSLs), 2) evaluate in vivo drug release following short duration (~20min each) HIFU treatments administered sequentially over an hour in a large volume of mouse xenograft colon tumor, and 3) determine the impact of the HIFU/nanobubble combination on intratumoral drug distribution. LTSLs and NTSLs containing doxorubicin (Dox) were co-loaded with a nanobubble contrast agent (perfluoropentane, PFP) using a one-step sonoporation method to create ELTSLs and ENTSLs, which then were characterized for size, release in a physiological buffer, and ability to encapsulate PFP. For the HIFU group, mild hyperthermia (40-42°C) was completed within 90min after liposome infusion administered sequentially in three regions of the tumor. Fluorescence microscopy and high performance liquid chromatography analysis were performed to determine the spatial distribution and concentration of Dox in the treated regions. PFP encapsulation within ELTSLs and ENTSLs did not impact size or caused premature drug release in physiological buffer. As time progressed, the delivery of Dox decreased in HIFU-treated tumors with ELTSLs, but this phenomenon was absent in the LTSL, NTSL, and ENTSL groups. Most importantly, PFP encapsulation improved Dox penetration in the tumor periphery and core and did not impact the distribution of Dox in non-tumor organs/tissues. Data from this study suggest that short duration and sequential HIFU treatment could have significant benefits and that its action can be potentiated by nanobubble agents to result in improved drug penetration., (Copyright © 2016 Elsevier B.V. All rights reserved.)

College is a time when young adults establish lifestyle habits. This research examines how personalization and limited resources might be balanced most effectively when designing incentives to shift college students' intentions toward positive dietary changes. A randomized 2 × 2 experiment (Coaching/Coupons × Fruits and Vegetables/Low Fat) was conducted, where respondents were exposed to virtual interventions and asked pre- and post-intervention about their intent to eat healthy. Results suggest that interventions may incentivize students, but are dependent on student characteristics. On-campus students and students with more knowledge about healthy diets were more likely to increase their intent when offered coaching; students living off campus and those with less knowledge resonated with coupons. On- and off-campus students differed in their positive responses to eating fruits and vegetables versus low fat foods, respectively. Younger students may be more susceptible to interventions. Findings may be useful in designing meaningful incentives for college students., (© The Author(s) 2016.)

Background: To achieve a measles free world, effective communication must be part of all elimination plans. The choice of communication approaches must be evidence based, locally appropriate, interactive and community owned. In this article, we document the innovative approach of using house visits supported by a web-enabled mobile phone application to create a real-time platform for adaptive management of supplemental measles immunization days in Kenya., Methods: One thousand nine hundred and fifty-two Red Cross volunteers were recruited, trained and deployed to conduct house-to-house canvassing in 11 urban districts of Kenya. Three days before the campaigns, volunteers conducted house visits with a uniform approach and package of messages. All house visits were documented using a web-enabled mobile phone application (episurveyor®) that in real-time relayed information collected to all campaign management levels. During the campaigns, volunteers reported daily immunizations to their co-ordinators. Post-campaign house visits were also conducted within 4 days, to verify immunization of eligible children, assess information sources and detect adverse events following immunization., Results: Fifty-six per cent of the 164 643 households visited said that they had heard about the planned 2012 measles vaccination campaign 1-3 days before start dates. Twenty-five per cent of households were likely to miss the measles supplemental dose if they had not been reassured by the house visit. Pre- and post-campaign reasons for refusal showed that targeted communication reduced misconceptions, fear of injections and trust in herbal remedies. Daily reporting of immunizations using mobile phones informed changes in service delivery plans for better immunization coverage. House visits were more remembered (70%) as sources of information compared with traditional mass awareness channels like megaphones (41%) and radio (37%)., Conclusions: In high-density settlements, house-to-house visits are easy and more penetrative compared with traditional media approaches. Using mobile phones to document campaign processes and outputs provides real time evidence for service delivery planning to improve immunization coverage., (Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2014; all rights reserved.)

The climatic impact of CO2 and other greenhouse gases is usually quantified in terms of radiative forcing, calculated as the difference between estimates of the Earth's radiation field from pre-industrial and present-day concentrations of these gases. Radiative transfer models calculate that the increase in CO2 since 1750 corresponds to a global annual-mean radiative forcing at the tropopause of 1.82 ± 0.19 W m(-2) (ref. 2). However, despite widespread scientific discussion and modelling of the climate impacts of well-mixed greenhouse gases, there is little direct observational evidence of the radiative impact of increasing atmospheric CO2. Here we present observationally based evidence of clear-sky CO2 surface radiative forcing that is directly attributable to the increase, between 2000 and 2010, of 22 parts per million atmospheric CO2. The time series of this forcing at the two locations-the Southern Great Plains and the North Slope of Alaska-are derived from Atmospheric Emitted Radiance Interferometer spectra together with ancillary measurements and thoroughly corroborated radiative transfer calculations. The time series both show statistically significant trends of 0.2 W m(-2) per decade (with respective uncertainties of ±0.06 W m(-2) per decade and ±0.07 W m(-2) per decade) and have seasonal ranges of 0.1-0.2 W m(-2). This is approximately ten per cent of the trend in downwelling longwave radiation. These results confirm theoretical predictions of the atmospheric greenhouse effect due to anthropogenic emissions, and provide empirical evidence of how rising CO2 levels, mediated by temporal variations due to photosynthesis and respiration, are affecting the surface energy balance.

In this study, we drew on prospective, longitudinal data to investigate the long-term predictive significance of the quality of early parent-child relationship experiences for adults' sympathetic nervous system (SNS) activity during conflict discussions with their romantic partners. Maternal sensitivity was repeatedly assessed across childhood via direct observations of mother-child interactions. When the children in the study became adults (34-37 years old), electrodermal activity-an index of SNS arousal and a psychophysiological marker of behavioral inhibition-was recorded for 37 participants while at rest and while they attempted to resolve conflicts in their romantic relationships. Individuals who had experienced less sensitive maternal caregiving during childhood had greater increases in electrodermal activity during conflict discussions with their adult partners, relative to resting conditions. This longitudinal association was not accounted for by observed or self-reported romantic-relationship quality, gender, ethnicity, or early socioeconomic factors., (© The Author(s) 2015.)

This study drew on prospective, longitudinal data to test the hypothesis that the intergenerational transmission of positive parenting is mediated by competence in subsequent relationships with peers and romantic partners. Interview-based ratings of supportive parenting were completed with a sample of 113 individuals (46% male) followed from birth to age 32. Results indicated that supportive parenting during adulthood was predicted by observed maternal sensitivity during the first 3 years of life, even after controlling for adults' age at first childbirth and adults' socioeconomic status and educational attainment at the time of the second generation parenting assessments. Moreover, the intergenerational association in parenting was mediated by later competence in relationships with peers and romantic partners. In particular, sensitive caregiving in infancy and early childhood predicted teachers' rankings of children's social competence with peers during childhood and adolescence, which in turn forecasted later interview ratings of romantic relationship competence during young adulthood, which in turn predicted supportive parenting in adulthood. Findings are discussed with respect to current theory and research on the intergenerational transmission of parenting.

Fingolimod treatment initiation is associated with a transient slowing of heart rate and atrioventricular conduction. This report presents first-dose fingolimod effects (0.5mg or 1.25mg) on cardiac parameters using phase 3 FREEDOMS, FREEDOMS II and TRANSFORMS pooled study data (n=3635 patients). Vital signs were recorded hourly for ≥6h; 12-lead electrocardiogram (ECG) was obtained at baseline and at 6h post-dose. Clinical events were graded at the first-dose administrator׳s discretion. At screening, on day 1 and at month 3, 1073 patients underwent 24-h ambulatory electrocardiogram monitoring. A transient decrease in mean measured heart rate occurred 4-5h after the first dose, with a maximum reduction of 8 (fingolimod 0.5mg) and 11 beats per minute (fingolimod 1.25mg) below baseline. Symptomatic bradycardia at treatment initiation was reported in 0.6% (fingolimod 0.5mg) and 2.1% (fingolimod 1.25mg) of patients; events were typically mild or moderate in severity, and most resolved spontaneously. Atrioventricular (AV) conduction delays were observed in a few patients (Wenckebach (Mobitz type I) second-degree AV block, fingolimod 0.5mg, 0.2%; 1.25mg, 1%: 2:1 AV block fingolimod, 0.5mg, 0%; 1.25mg, 0.2% on ECG 6-h post-dose). These were usually well tolerated and first occurred within 6h of dosing. Consistent with its effects on atrial myocytes, fingolimod treatment initiation induced a transient slowing of heart rate and AV conduction. However, symptomatic bradycardia and second-degree AV block were uncommon and did not require intervention., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Fingolimod 0.5mg once daily is the first approved oral therapy for relapsing multiple sclerosis (MS)., Objective: To report integrated long-term safety data from phase 2/3 fingolimod studies., Methods: Descriptive safety data are reported from the FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study, a 24-month, randomized, double-blind study comparing fingolimod 0.5mg and 1.25mg with placebo, and an All Studies group (patients who received fingolimod 0.5mg (n=1640) or 1.25-0.5mg (n=1776) in phase 2/3 studies and associated extensions). Relevant post-marketing experience, up to December 2011, is included., Results: The incidence of adverse events (AEs) and serious AEs (SAEs) was similar with fingolimod and placebo in FREEDOMS. In the All Studies group, fingolimod 0.5mg was associated with transient, rarely symptomatic (0.5%), bradycardia and second-degree atrioventricular block on treatment initiation, minor blood pressure increases, frequent (9%) but generally asymptomatic liver enzyme elevations, and macular oedema (0.4%). The incidences of infections (including serious and herpes infections), malignancies, SAEs and treatment discontinuations due to AEs were similar with fingolimod 0.5mg and placebo., Conclusion: The safety profile of fingolimod has been well characterized in this large combined trial population. Although infrequent SAEs can occur, there is no increased risk of infections, malignancies or serious cardiovascular events versus placebo., (Copyright © 2014. Published by Elsevier B.V.)

Background: Reduction in peripheral blood lymphocytes is an expected pharmacodynamic outcome of fingolimod therapy., Objective: The objective of this article is to evaluate lymphocyte dynamics during and after fingolimod therapy and assess the relationship between lymphocyte counts and infections., Methods: Lymphocyte counts and their relationship with infections were evaluated in three multiple sclerosis (MS) populations: (Group A) FREEDOMS phase 3 core study group (n = 1272); (Group B) All Studies group (one phase 2 and two phase 3 studies, plus their extensions; n = 2315); and (Group C) Follow-up group (after fingolimod discontinuation; n = 538)., Results: Administration of fingolimod 0.5 mg led to reductions in lymphocyte counts to a steady-state of 24%-30% of baseline values within two weeks, which remained stable while on therapy. Following fingolimod discontinuation, average counts exceeded the lower limit of normal range within six to eight weeks, and were 80% of baseline values by three months. In Group A, infection rates per patient-year were 1.4 with placebo and 1.0 in fingolimod-treated patients who had the lowest lymphocyte counts (< 0.2 × 10(9)/l). No evidence was seen for an increase in serious or opportunistic infections., Conclusions: Fingolimod induces a rapid and reversible reduction in lymphocyte counts without an increase in infections relative to placebo. Because fingolimod reduces blood lymphocyte counts via redistribution in secondary lymphoid organs, peripheral blood lymphocyte counts cannot be utilized to evaluate the lymphocyte subset status of a patient.

Objective: To report outcomes of pregnancies that occurred during the fingolimod clinical development program., Methods: Pregnancy outcomes from phase II, phase III, and phase IV clinical studies (with optional extensions) were reported by clinical trial investigators. Fingolimod exposure in utero was defined as fingolimod treatment at the time of conception or in the 6 weeks before conception., Results: As of October 31, 2011, 89 pregnancies were reported in completed or ongoing clinical studies, with 74 in fingolimod treatment arms. Of 66 pregnancies with in utero exposure to fingolimod, there were 28 live births, 9 spontaneous abortions, 24 elective abortions, 4 ongoing pregnancies, and 1 pregnancy with an unknown outcome (patient lost to follow-up). Two infants were born with malformations: 1 with congenital unilateral posteromedial bowing of the tibia and 1 with acrania. Elective abortions were performed for 1 case each of tetralogy of Fallot, spontaneous intrauterine death, and failure of fetal development. There were 5 cases (7.6%; 95% confidence interval 3%-17%) of abnormal fetal development in the 66 pregnancies that had in utero exposure to fingolimod. In all 5 cases, fetal exposure to the drug took place in the first trimester of pregnancy., Conclusions: The number of patients becoming pregnant during fingolimod therapy remains small and does not permit firm conclusions to be drawn about fetal safety of fingolimod in humans. Given the known risks of teratogenicity in animals and the present data, women of childbearing potential should use effective contraception during fingolimod therapy and for 2 months after discontinuation.

Background: Longitudinal research has demonstrated that individual differences in attachment security show only modest continuity from infancy to adulthood. Recent findings based on retrospective reports suggest that individuals' genetic variation may moderate the developmental associations between early attachment-relevant relationship experiences and adult attachment security. The purpose of this study was to use a prospective, longitudinal design to investigate genetic contributions to continuity and changes in attachment security from infancy to young adulthood in a higher risk sample., Methods: Infant attachment security was assessed using the Strange Situation Procedure at 12 and 18 months. Adults' general attachment representations were assessed using the Adult Attachment Interview at ages 19 and 26. Romantic attachment representations were assessed with the Current Relationship Interview (CRI) at ages 20-21 and ages 26-28. Individuals were genotyped for variants within the oxytocin receptor (OXTR), dopamine D4 receptor (DRD4), and serotonin transporter linked polymorphic region (5-HTTLPR)., Results: The continuity of attachment security from infancy into young adulthood was consistently moderated by OXTR genetic variation. Infant attachment security predicted the security of adults' general and romantic attachment representations only for individuals with the OXTR G/G genotype. This interaction was significant when predicting adult attachment security as measured by the Adult Attachment Interview at ages 19 and 26 and the CRI at ages 26-28. Dopamine D4 receptor and 5-HTTLPR genetic variation did not consistently moderate the longitudinal associations between attachment security during infancy and adulthood., Conclusions: This study provides initial longitudinal evidence for genetic contributions to continuity and change in attachment security from infancy to young adulthood. Genetic variation related to the oxytocin system may moderate the stability of attachment security across development., (© 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.)

This study tests a model of young adult romantic quality as a moderator of the effects of early caregiving on anxious-depressed symptoms over a 9-year period in adulthood. Participants (n = 93) were a subsample from a longitudinal study of risk and adaptation. Quality of early caregiving was measured using observational data collected at five points in the first 4 years of life. Young adult romantic relationship quality was assessed from interviews with participants at age 23. Self-report anxious-depressed symptoms were measured at ages 23, 26, and 32. The results indicated that romantic quality moderated early caregiving to predict symptom levels across this period, with evidence for inoculation, amplification, and compensation effects. A discriminant analysis examining young adult work competence as a moderator provided further evidence for the distinctiveness of romantic relationships in changing the association between early caregiving and adult internalizing symptoms.

Purpose: To report outcomes of ophthalmic evaluations in clinical studies of patients receiving fingolimod (Gilenya; Novartis Pharma AG, Basel, Switzerland) for multiple sclerosis (MS)., Design: Analysis done on pooled safety data (N = 2615, all studies group) from 3 double-masked, randomized, parallel-group clinical trials (phase 2 core and extension >5 years, and phase 3 FREEDOMS and TRANSFORMS core and extension studies)., Participants: Patients aged 18 to 55 years (18-60 years in phase 2 study) diagnosed with relapsing-remitting MS were included. Patients with diabetes mellitus or macular edema (ME) at screening were excluded., Intervention: Participants received fingolimod (0.5/1.25 mg), placebo, or interferon beta for the respective study durations. Ophthalmic examination included detailed eye history (at screening), visual acuity (VA) assessment, dilated ophthalmoscopy, optical coherence tomography (OCT), and fluorescein angiography (FA)., Main Outcome Measures: Extensive ophthalmic monitoring was performed for all patients. While being studied, patients with abnormal findings on dilated ophthalmoscopy and OCT compatible with ME were further studied by FA. All locally diagnosed ME cases were centrally reviewed by the retina specialist (M.A.Z.) on the Data and Safety Monitoring Board., Results: Among 2615 patients assessed, 19 confirmed ME cases were observed in fingolimod-treated groups (0.5 mg: n = 4, 0.3%; 1.25 mg: n = 15, 1.2%). Most patients (n = 13, 68%) presented with blurred vision, decreased VA, or eye pain. Macular edema was diagnosed within 3 to 4 months of treatment initiation in most cases (n = 13, 68%); 2 patients had late onset (>12 months) ME. Of the 19 patients with ME, 5 (26%), all treated with fingolimod 1.25 mg, had a history of uveitis compared with 26 (1%) in the all studies group. In most cases (n = 16, 84%), ME resolved after discontinuing the study drug. Eleven patients required topical anti-inflammatory medications. No patient had further vision deterioration., Conclusions: Fingolimod 0.5 mg is associated with a low incidence of ME in MS studies. Patients with a history of uveitis may be at an increased risk of developing ME. An ophthalmic examination before initiating fingolimod therapy and regular follow-up eye examinations during fingolimod therapy are recommended., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: Recent epidemiological and longitudinal studies indicate that attachment relationships may be a significant predictor of physical health in adulthood. This study is among the few to prospectively link attachment classifications assessed in infancy to physical health outcomes 30 years later in adulthood, controlling for various health-related confounds., Methods: Participants were 163 individuals involved in a 32-year longitudinal study of risk and adaptation who have been followed since birth. Attachment classifications were assessed at ages 12 and 18 months using the Ainsworth Strange Situation Procedure. Stability of attachment security was derived from these assessments. At age 32, participants completed a questionnaire asking about the presence of or treatment for current physical illnesses., Results: Binary logistic regression analyses controlling for health-related confounds at age 32 indicated that individuals who were insecurely attached (i.e., anxious-resistant or anxious-avoidant) during infancy were more likely to report an inflammation-based illness in adulthood than those classified as securely attached during infancy. There also was a trend whereby individuals classified as anxious-resistant reported more nonspecific symptoms in adulthood than those classified as either anxious-avoidant or secure. Individuals who were continuously insecure during infancy were more likely to report all types of physical illness in adulthood., Conclusion: These findings reveal the lasting effect of early interpersonal relationships on physical health and suggests that infancy may be a fruitful point for prevention efforts. The widespread influence that attachment has on endogenous and exogenous health-related processes may make it particularly potent in the prevention of later physical health problems., (2013 APA, all rights reserved)

The St. Elizabeth strain of Plasmodium vivax originated in the South Carolina State Hospital instead of the St. Elizabeth Hospital in Washington, DC.

The Extended Parallel Process Model (EPPM) posits that an effective fear appeal includes both threat and efficacy components; however, research has not addressed whether there is an optimal threat-to-efficacy ratio. It is possible that varying levels of threat and efficacy in a persuasive message could yield different effects on attitudes, beliefs, and behaviors. In a laboratory experiment, women (n = 442) were exposed to human papilloma virus (HPV) prevention messages containing one of six threat-to-efficacy ratios and one of two message frames (messages emphasizing the connection between HPV and cervical cancer or HPV and genital warts). Multiple mediation analysis revealed that a 1-to-1 ratio of threat to efficacy was most effective at increasing prevention intentions, primarily because it caused more fear and risk susceptibility than other message ratios. Response efficacy significantly mediated the relationship between message framing and intentions, such that participants exposed to a genital warts message reported significantly higher intentions, and this association can be explained in part through response efficacy. Implications for future theoretical research as well as campaigns and intervention research are discussed.

The patient presented below gives us the opportunity to discuss challenges in the diagnosis of drug-induced liver injury in an era of increasing awareness of hepatitis E., (Copyright © 2012 American Association for the Study of Liver Diseases.)

To test proposals regarding the hierarchical organization of adult attachment, this study examined developmental origins of generalized and romantic attachment representations and their concurrent associations with romantic functioning. Participants (N=112) in a 35-year prospective study completed the Adult Attachment Interview (AAI) and Current Relationship Interview (CRI). Two-way analysis of variance tested interactive associations of AAI and CRI security with infant attachment, early parenting quality, preschool ego resiliency, adolescent friendship quality, and adult romantic functioning. Both representations were associated with earlier parenting and core attachment-related romantic behavior, but romantic representations had distinctive links to ego resiliency and relationship-specific romantic behaviors. Attachment representations were independent and did not interactively predict romantic functioning, suggesting that they confer somewhat distinctive benefits for romantic functioning., (© 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.)

According to a recent evolutionary life history model of development proposed by Ellis, Figueredo, Brumbach, and Schlomer (2009), growing up in harsh versus unpredictable environments should have unique effects on life history strategies in adulthood. Using data from the Minnesota Longitudinal Study of Risk and Adaptation, we tested how harshness and unpredictability experienced in early childhood (age 0-5) versus in later childhood (age 6-16) uniquely predicted sexual and risky behavior at age 23. Findings showed that the strongest predictor of both sexual and risky behavior was an unpredictable environment between ages 0 and 5. Individuals exposed to more unpredictable, rapidly changing environments during the first 5 years of life displayed a faster life history strategy at age 23 by having more sexual partners, engaging in more aggressive and delinquent behaviors, and being more likely to be associated with criminal activities. In contrast, exposure to either harsh environments or experiencing unpredictability in later childhood (age 6-16) was, for the most part, not significantly related to these outcomes at age 23. Viewed together, these findings show that unpredictable rather than merely harsh childhood environments exert unique effects on risky behavior later in life consistent with a faster life history strategy. The findings also suggest that there is a developmentally sensitive period for assessing environmental unpredictability during the first 5 years of life.

Background: High rates of typhoid fever in children in urban settings in Asia have led to focus on childhood immunization in Asian cities, but not in Africa, where data, mostly from rural areas, have shown low disease incidence. We set out to compare incidence of typhoid fever in a densely populated urban slum and a rural community in Kenya, hypothesizing higher rates in the urban area, given crowding and suboptimal access to safe water, sanitation and hygiene., Methods: During 2007-9, we conducted population-based surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural area in western Kenya. Participants had free access to study clinics; field workers visited their homes biweekly to collect information about acute illnesses. In clinic, blood cultures were processed from patients with fever or pneumonia. Crude and adjusted incidence rates were calculated., Results: In the urban site, the overall crude incidence of Salmonella enterica serovar Typhi (S. Typhi) bacteremia was 247 cases per 100,000 person-years of observation (pyo) with highest rates in children 5-9 years old (596 per 100,000 pyo) and 2-4 years old (521 per 100,000 pyo). Crude overall incidence in Lwak was 29 cases per 100,000 pyo with low rates in children 2-4 and 5-9 years old (28 and 18 cases per 100,000 pyo, respectively). Adjusted incidence rates were highest in 2-4 year old urban children (2,243 per 100,000 pyo) which were >15-fold higher than rates in the rural site for the same age group. Nearly 75% of S. Typhi isolates were multi-drug resistant., Conclusions: This systematic urban slum and rural comparison showed dramatically higher typhoid incidence among urban children <10 years old with rates similar to those from Asian urban slums. The findings have potential policy implications for use of typhoid vaccines in increasingly urban Africa.

Long interspersed element-1 (LINE-1 or L1) retrotransposons account for nearly 17% of human genomic DNA and represent a major evolutionary force that has reshaped the structure and function of the human genome. However, questions remain concerning both the frequency and the developmental timing of L1 retrotransposition in vivo and whether the mobility of these retroelements commonly results in insertional and post-insertional mechanisms of genomic injury. Cells exhibiting high rates of L1 retrotransposition might be especially at risk for such injury. We assessed L1 mRNA expression and L1 retrotransposition in two biologically relevant cell types, human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), as well as in control parental human dermal fibroblasts (HDFs). Full-length L1 mRNA and the L1 open reading frame 1-encoded protein (ORF1p) were readily detected in hESCs and iPSCs, but not in HDFs. Sequencing analysis proved the expression of human-specific L1 element mRNAs in iPSCs. Bisulfite sequencing revealed that the increased L1 expression observed in iPSCs correlates with an overall decrease in CpG methylation in the L1 promoter region. Finally, retrotransposition of an engineered human L1 element was ~10-fold more efficient in iPSCs than in parental HDFs. These findings indicate that somatic cell reprogramming is associated with marked increases in L1 expression and perhaps increases in endogenous L1 retrotransposition, which could potentially impact the genomic integrity of the resultant iPSCs.