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The criminal legal system in the USA drives an incarceration rate that is the highest on the planet, with disparities by class and race among its signature features1–3. During the first year of the coronavirus disease 2019 (COVID-19) pandemic, the number of incarcerated people in the USA decreased by at least 17%—the largest, fastest reduction in prison population in American history4. Here we ask how this reduction influenced the racial composition of US prisons and consider possible mechanisms for these dynamics. Using an original dataset curated from public sources on prison demographics across all 50 states and the District of Columbia, we show that incarcerated white people benefited disproportionately from the decrease in the US prison population and that the fraction of incarcerated Black and Latino people sharply increased. This pattern of increased racial disparity exists across prison systems in nearly every state and reverses a decade-long trend before 2020 and the onset of COVID-19, when the proportion of incarcerated white people was increasing amid declining numbers of incarcerated Black people5. Although a variety of factors underlie these trends, we find that racial inequities in average sentence length are a major contributor. Ultimately, this study reveals how disruptions caused by COVID-19 exacerbated racial inequalities in the criminal legal system, and highlights key forces that sustain mass incarceration. To advance opportunities for data-driven social science, we publicly released the data associated with this study at Zenodo6.

We present molecular-frame high-harmonic spectroscopic measurements of the spectral intensity and group delay of carbon dioxide. Using four different driving wavelengths and a range of intensities at each wavelength for high-harmonic generation, we observe a well-characterized minimum in the harmonic emission that exhibits both a wavelength and intensity dependence. Using the intensity dependence at each driving wavelength, we classify the minimum as due to either a structural two-center interference or dynamic multichannel interference, consistent with previous literature. By additionally measuring the group delay at each driving wavelength and intensity, we find that the sign of the group delay excursion across the interference is an acute probe of the interference mechanism. The experimental results are confirmed by ab initio time-dependent density functional theory calculations of both the spectral intensity and the phase of the harmonic emission.

Domestic travel creates a serious risk of spreading COVID-19, including novel strains of the virus. Motivating potential travelers to take precautions is critical, especially for those at higher risk for severe illness. To provide an evidence base for communication efforts, we examined the experiences and views of travelers during the summer of 2020 through a telephone survey of 1,968 US adults, conducted in English and Spanish, July 2 through July 16, 2020. The survey found that more than one-quarter (28%) of adults had traveled domestically in the prior 30 days, most commonly for "vacation" (43%), and less than half wore masks (46%) or practiced social distancing (47%) "all of the time." Although high-risk adults were significantly less likely to travel than non-high-risk adults (23% vs 31%; P < .001), they were no more likely to take precautions. Many travelers did not wear a mask or practice social distancing because they felt such actions were unnecessary (eg, they were outside or with friends and family). Although a substantial share of travelers (43% to 53%) trusted public health agencies "a great deal" for information about reducing risks while traveling, more travelers (73%) trusted their own healthcare providers. Findings suggest that outreach may be improved by partnering with providers to emphasize the benefits of layering precautions and provide targeted education to high-risk individuals. Messages that are empathetic to the need to reduce stress and convey how precautions can protect loved ones may be particularly resonant after more than a year of pandemic-related restrictions.

Background The first documented human leptospirosis cases in the U.S. Virgin Islands (USVI) occurred following 2017 Hurricanes Irma and Maria. We conducted a representative serosurvey in USVI to estimate the seroprevalence and distribution of human leptospirosis and evaluate local risk factors associated with seropositivity. Methodology/Principal findings A stratified, two-stage cluster sampling design was used and consisted of three island strata and random selection of census blocks and then households. All eligible members of selected households were invited to participate (≥5 years old, resided in USVI ≥6 months and ≥6 months/year). Household and individual-level questionnaires were completed, and serum collected from each enrolled individual. Microscopic agglutination test serology was conducted, and bivariate and logistic regression analyses completed to identify risk factors for seropositivity. In March 2019, 1,161 individuals were enrolled from 918 households in St. Croix, St. Thomas, and St. John. The territory-wide weighted seroprevalence was 4.0% (95% CI:2.3–5.7). Characteristics/exposures independently associated with seropositivity using logistic regression included contact with cows (OR: 39.5; 95% CI: 9.0–172.7), seeing rodents/rodent evidence or contact with rodents (OR: 2.6; 95% CI: 1.1–5.9), and increasing age (OR: 1.02; 95% CI: 1.002–1.04); full or partial Caucasian/White race was negatively correlated with seropositivity (OR: 0.02, 95% CI: 0.04–0.7). Bivariate analysis showed self-reported jaundice since the 2017 hurricanes (pRR: 5.7; 95% CI: 1.0–33.4) was associated with seropositivity and using a cover/lid on cisterns/rainwater collection containers (pRR: 0.3; 95% CI: 0.08–0.8) was protective against seropositivity. Conclusions/Significance Leptospirosis seropositivity of 4% across USVI demonstrates an important human disease that was previously unrecognized and emphasizes the importance of continued leptospirosis surveillance and investigation. Local risk factors identified may help guide future human and animal leptospirosis studies in USVI, strengthen leptospirosis public health surveillance and treatment timeliness, and inform targeted education, prevention, and control efforts.

We present a dataset of approximately 5.5 million subtest scores from over 750,000 adults who completed the NeuroCognitive Performance Test (NCPT; Lumos Labs, Inc.), a validated, self-administered cognitive test accessed via web browser. The dataset includes assessment scores from eight test batteries consisting of 5-11 subtests that collectively span several cognitive domains including working memory, visual attention, and abstract reasoning. In addition to the raw scores and normative data from each subtest, the dataset includes basic demographic information from each participant (age, gender, and educational background). The scale and diversity of the dataset provides an unprecedented opportunity for researchers to investigate population-level variability in cognitive abilities and their relation to demographic factors. To facilitate reuse of this dataset by other researchers, we provide a Python module that supports several common preprocessing steps.

Primate vision is characterized by constant, sequential processing and selection of visual targets to fixate. Although expected reward is known to influence both processing and selection of visual targets, similarities and differences between these effects remains unclear mainly because they have been measured in separate tasks. Using a novel paradigm, we simultaneously measured the effects of reward outcomes and expected reward on target selection and sensitivity to visual motion in monkeys. Monkeys freely chose between two visual targets and received a juice reward with varying probability for eye movements made to either of them. Targets were stationary apertures of drifting gratings, causing the endpoints of eye movements to these targets to be systematically biased in the direction of motion. We used this motion-induced bias as a measure of sensitivity to visual motion on each trial. We then performed different analyses to explore effects of objective and subjective reward values on choice and sensitivity to visual motion in order to find similarities and differences between reward effects on these two processes. Specifically, we used different reinforcement learning models to fit choice behavior and estimate subjective reward values based on the integration of reward outcomes over multiple trials. Moreover, to compare the effects of subjective reward value on choice and sensitivity to motion directly, we considered correlations between each of these variables and integrated reward outcomes on a wide range of timescales. We found that in addition to choice, sensitivity to visual motion was also influenced by subjective reward value, even though the motion was irrelevant for receiving reward. Unlike choice, however, sensitivity to visual motion was not affected by objective measures of reward value. Moreover, choice was determined by the difference in subjective reward values of the two options whereas sensitivity to motion was influenced by the sum of values. Finally, models that best predicted visual processing and choice used sets of estimated reward values based on different types of reward integration and timescales. Together, our results demonstrate separable influences of reward on visual processing and choice, and point to the presence of multiple brain circuits for integration of reward outcomes.

The flexibility to learn diverse tasks is a hallmark of human cognition. To improve our understanding of individual differences and dynamics of learning across tasks, we analyse the latent structure of learning trajectories from 36,297 individuals as they learned 51 different tasks on the Lumosity online cognitive training platform. Through a data-driven modelling approach using probabilistic dimensionality reduction, we investigate covariation across learning trajectories with few assumptions about learning curve form or relationships between tasks. Modelling results show substantial covariation across tasks, such that an entirely unobserved learning trajectory can be predicted by observing trajectories on other tasks. The latent learning factors from the model include a general ability factor that is expressed mostly at later stages of practice and additional task-specific factors that carry information capable of accounting for manually defined task features and task domains such as attention, spatial processing, language and math.

The embodied cognition hypothesis postulates that human cognition is fundamentally grounded in our experience of interacting with the physical world (Barsalou in Behav Brain Sci 22:577–609, 1999). Research has shown bi-directional associations between physical action and the processes of understanding language: language comprehension seems to activate implied visual and motor components (Zwaan and Taylor in J Exp Psychol Gen 135(1):1–11, 2006), and action behavior seems to facilitate the comprehension of associated action-language (Beilock et al. in Proc Natl Acad Sci USA 105:13269–13273, 2008). Although numerous research studies have reported a link between action and language comprehension, the exact nature of their association remains subject to debate (Chatterjee in Lang Cognit 2:79–116, 2010). Moreover, the role of action in the production of language is under-explored, as are general language production processes in Austronesian languages. The endangered Austronesian language Truku provides typological patterns that are both under-examined in psycholinguistic research and informative for questions of language production. Truku allows flexibility in the relative location of verbs versus arguments in sentence production, and uses a symmetrical voice system that marks the prominence of different participants in an event. Working with native speakers of Truku, we tested whether performing physical motions immediately affects the conceptual saliency of the components represented in a to-be-described event in ways that guide speakers’ visual attention and shape their utterance formulation. More specifically, we investigated whether speakers’ engagement as an agent or patient in a non-speech physical action affects initial eye-fixations on agent versus patient participants in a visual scene, as well as word order and grammatical voice choices in the speakers’ descriptions of simple transitive events. The results revealed significant effects of physical action on the relative location and prominence of agents in subsequent sentence formulation, and on online patterns of eye fixations. These results provide further support for language-action connections in cognitive processing, and shed light on the cross-linguistic patterns of sentence production.

Background: Ten years ago, the U.S. Surgeon General’s Call to Action to Support Breastfeeding made recommendations for childcare settings, including: (1) accommodating and supporting breastfeeding families; and (2) adopting national guidelines on breastfeeding support in childcare settings. Research Aims: To (1) describe the existing breastfeeding friendly childcare designation programs in the United States; and (2) describe how states are accommodating breastfeeding families in childcare settings. Method: The study design was cross-sectional, prospective thematic description of existing publicly available documents. A search of state breastfeeding coalitions was conducted to assess the number of states with breastfeeding friendly childcare designation programs. A definitive yes-or-no answer regarding whether each state had a program was obtained from all 50 states. For states with programs, designation materials were analyzed using thematic analysis and the framework method to compare designation components. Results: Fifteen states had evidence of breastfeeding friendly childcare designation programs and similarities exist across designation program components. Four standards were common to all 15 programs: written policy on breastfeeding, suitable space within the center where mothers can breastfeed or express their milk, educational materials, and resources on breastfeeding available to parents. Most states required self-assessment to achieve designation status. Conclusion: Research is needed to enable evidence-based programs and decision-making regarding components and processes. Federal funding should support these programs’ mission, including funding research to assess how and in what circumstances these programs are improving breastfeeding-related outcomes and supporting breastfeeding families.

Switching from tenofovir disoproxil fumarate (TDF)- to tenofovir alafenamide (TAF)-containing antiretroviral therapy may negatively influence weight, cholesterol, and atherosclerotic cardiovascular disease risk. The extent of these changes and their association with TAF remain unclear.This retrospective cohort evaluated metabolic changes in virologically suppressed patients with HIV infection who switched from TDF to TAF without switching other antiretroviral therapy medications. Adult patients on TDF and with no HIV viral load values200 copies/mL for ≥2 years prior to and following a TAF switch were included. Weight and other variables were collected for 2 years before and after the switch. Longitudinal linear mixed-effects models evaluated changes at 1 and 2 years after the switch.In the unadjusted analysis, there were increases in weight, BMI, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, fasting glucose, and atherosclerotic cardiovascular disease risk scores 2 years after switching to TAF (each p ≤ 0.03). However, only increases in total and low-density lipoprotein cholesterol were associated with TAF and were significantly different from expected changes predicted in the adjusted longitudinal models.Despite observing significant unadjusted metabolic changes after switching to TAF, only changes in cholesterol were associated with TAF and were different from changes expected in time-trend adjusted models.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with few effective treatment options. We found a highly significant correlation between pregnancy-associated plasma protein (PAPP)-A expression in IPF lung tissue and disease severity as measured by various pulmonary and physical function tests. PAPP-A is a metalloproteinase that enhances local insulin-like growth factor (IGF) activity. We used primary cultures of normal adult human lung fibroblasts (NHLF) to test the hypothesis that PAPP-A plays an important role in the development of pulmonary fibrosis. Treatment of NHLF with pro-fibrotic transforming growth factor (TGF)-β stimulated marked increases in IGF-I mRNA expression (>20-fold) and measurable IGF-I levels in 72-h conditioned medium (CM). TGF-β treatment also increased PAPP-A levels in CM fourfold (p = 0.004) and proteolytic activity ~2-fold. There was an indirect effect of TGF-β to stimulate signaling through the PI3K/Akt pathway, which was significantly inhibited by both IGF-I-inactivating and PAPP-A inhibitory antibodies. Induction of senescence in NHLF increased PAPP-A levels in CM 10-fold (p = 0.006) with attendant increased proteolytic activity. Thus, PAPP-A is a novel component of the senescent lung fibroblast secretome. In addition, NHLF secreted extracellular vehicles (EVs) with surface-bound active PAPP-A that were increased fivefold with senescence. Regulation of PAPP-A and IGF signaling by TGF-β and cell senescence suggests an interactive cellular mechanism underlying the resistance to apoptosis and the progression of fibrosis in IPF. Furthermore, PAPP-A-associated EVs may be a means of pro-fibrotic, pro-senescent communication with other cells in the lung and, thus, a potential therapeutic target for IPF.

This study examines how individual pragmatic skills, and more specifically, empathy, influences language processing when a temporary lexical ambiguity can be resolved via intonation. We designed a visual-world eye-tracking experiment in which participants could anticipate a referent before disambiguating lexical information became available, by inferring either a contrast meaning or a confirmatory meaning from the intonation contour alone. Our results show that individual empathy skills determine how listeners deal with the meaning alternatives of an ambiguous referent, and the way they use intonational meaning to disambiguate the referent. Listeners with better pragmatic skills (higher empathy) were sensitive to intonation cues when forming sound-meaning associations during the unfolding of an ambiguous referent, and showed higher sensitivity to all the alternative interpretations of that ambiguous referent. Less pragmatically skilled listeners showed weaker processing of intonational meaning because they needed subsequent disambiguating material to select a referent and showed less sensitivity to the set of alternative interpretations. Overall, our results call for taking into account individual pragmatic differences in the study of intonational meaning processing and sentence comprehension in general.

BACKGROUND: Seasonal influenza vaccination rates among pregnant women remain well below the Healthy People 2020 target of 80%. Obstetrician–gynecologist (OB/GYN) recommendations are a critical means of encouraging pregnant women to get vaccinated, but there are limited data about their views. MATERIALS AND METHODS: A nationally representative survey of 506 practicing OB/GYNs was completed between October 26, 2015, and May 8, 2016. Analyses included univariate distributions and comparisons based on age, size of practice, and academic affiliation using all-pairs, dependent t-tests. RESULTS: A majority of OB/GYNs report they ‘‘strongly recommend’’ seasonal influenza vaccination for their pregnant patients in the first (79%) or second and third trimesters (81%). Among those who do not strongly recommend the flu vaccine in the first trimester, many say this is because of their own concerns (28%) or their patients’ concerns (44%) about safety. Older OB/GYNs, those in smaller practices, and those without academic affiliation were less likely to recommend the vaccine and more likely to have safety concerns. For example, 72% of those age 60+ strongly recommended the vaccine in the second and third trimester, compared with 86% of those ages 30–44 and 83% of those ages 45–59 ( p < 0.05 for all comparisons). CONCLUSIONS: OB/GYNs across the country largely support seasonal flu vaccination among pregnant women. Nonetheless, safety is a concern for them and their patients. Outreach to support clinician decisions and conversations with pregnant patients may be most needed among older physicians, those in smaller practices, and those without academic affiliation.

Cellular senescence is characterized by an irreversible cell cycle arrest and a pro‐inflammatory senescence‐associated secretory phenotype (SASP), which is a major contributor to aging and age‐related diseases. Clearance of senescent cells has been shown to improve brain function in mouse models of neurodegenerative diseases. However, it is still unknown whether senescent cell clearance alleviates cognitive dysfunction during the aging process. To investigate this, we first conducted single‐nuclei and single‐cell RNA‐seq in the hippocampus from young and aged mice. We observed an age‐dependent increase in p16Ink4a senescent cells, which was more pronounced in microglia and oligodendrocyte progenitor cells and characterized by a SASP. We then aged INK‐ATTAC mice, in which p16Ink4a‐positive senescent cells can be genetically eliminated upon treatment with the drug AP20187 and treated them either with AP20187 or with the senolytic cocktail Dasatinib and Quercetin. We observed that both strategies resulted in a decrease in p16Ink4a exclusively in the microglial population, resulting in reduced microglial activation and reduced expression of SASP factors. Importantly, both approaches significantly improved cognitive function in aged mice. Our data provide proof‐of‐concept for senolytic interventions' being a potential therapeutic avenue for alleviating age‐associated cognitive impairment., Senescence is a major contributor to aging and age‐related diseases. However, it is still unknown whether senolytics impact on cognitive function during the aging process. We found that both pharmacogenetic clearance of p16Ink4a senescent cells or treatment with senolytic cocktail Dasatinib and Quercetin, reduced senescent microglia in the hippocampus and improved cognitive function in aged mice.

Bilateral oophorectomy in premenopausal women is a unique condition causing the abrupt and premature loss of ovarian hormones, primarily estrogen. Bilateral oophorectomy causes an alteration of several fundamental aging processes at the cellular, tissue, organ, and system levels, leading to multimorbidity, frailty, and reduced survival. However, many questions remain unanswered.

We report an analysis of experts’ picturebook recommendations and rationales for read-alouds. Such recommendations are important as experts provide book suggestions to teachers. In this investigati...

The accelerator for the Diagnostics Neutral Beam (DNB) beam source is composed of a multi-aperture grid system with three water cooled grids made from Oxygen free Copper. To achieve the focusing requirements at the distance of > 20 m, the grid segments are designed with two stage angles (0.222° and 0.665°) from the centerline in the horizontal direction. The configuration of this kind of ‘angled segment’ includes the water cooling channels milled in the angular form, subsequently closed by copper electrodeposition, providing the angles on front and back surface and then drilling of apertures on the angular plane. The long beam path and low energy beam demands the tight tolerances on each of these mechanical features and therefore demands the high degree of manufacturing controls on each of the processes. To unveil the challenges those could appear during the production of such grid, a 1:1 prototype of the most complex type of grid has been manufactured. This paper shall present the technical data generated out of manufacturing of this prototype, summarizing the recommendations for real grid production on: optimization of the sequence of manufacturing, effect of each of the operations, post-manufacturing handling and identifying the measurement techniques. The experience gathered here provides a recipe for the best manufacturing practices for the accelerators of NB system for ITER and upcoming devices.

Fifty percent of middle schools and 35% of high schools in Hillsborough County, Florida, serve students at high-risk for teen birth and sexually transmitted infections. This study assessed the desired type of sexual health education (SHE), content, and support for SHE from residents in the districts. Descriptive and bivariate statistics were used to analyze 314 survey phone interviews with adults, and thematic analysis was used to analyze eight focus groups with 104 youth living in the high-risk school districts. Survey results showed strong community support for comprehensive SHE with human anatomy and reproduction and HIV and sexually transmitted disease as the most supported contents for both middle (93%, 98%) and high school (93%, 97%). However, 38% of adults surveyed agreed that providing information about how to obtain and use contraception would cause teens to be more sexually active. Themes from the focus groups included an acknowledgement of a teen pregnancy problem and perils, support for comprehensive SHE, and a lack of contraception knowledge. In conclusion, adults and youth expressed support and need for comprehensive SHE in their schools. As a link between the community and schools, Hillsborough County school boards have a responsibility to convey such support.

Certain English intonational contours facilitate a conversational implicature that a relevant alternative to the stated proposition does not hold true. We evaluated how frequently and how quickly naïve participants achieved such pragmatically enriched meanings when their attention had not already been drawn to a set of alternatives. Sentences with L+H* L-H% intonational contours, along with broad focus affirmative and negative counterparts, were tested in a pair of experiments. Experiment 1 revealed that most interpretations of the L+H* L-H% sentences evidenced the expected implicature, but a substantial number did not. Experiment 2 mapped the activation levels across time for the asserted state and a contradictory/implicated alternative for the same three sentence types, using a picture-naming paradigm. The results revealed that lexical negation produced a contrast in activation levels between the two alternatives at an earlier time point than the L+H* L-H% contour, and that the relative activation of the two states shifted over time for L+H* L-H% sentences, such that an intonationally implicated alternative was highly activated at a time point when the activation for the asserted meaning had declined. These results further our understanding of the pragmatic processes involved in the interpretation of negation and intonation.

The spatial phase and direction of extreme-ultraviolet light are controlled by an all-optical modulator based on argon gas. It works by using an infrared pulse to control the spatial and spectral phase of the free induction decay in the gas system.

This study examines how individual pragmatic skills, and more specifically, empathy, influences language processing when a temporary lexical ambiguity can be resolved via intonation. We designed a visual-world eye-tracking experiment in which participants could anticipate a referent before disambiguating lexical information became available, by inferring either a contrast meaning or a confirmatory meaning from the intonation contour alone. Our results show that individual empathy skills determine how listeners deal with the meaning alternatives of an ambiguous referent, and the way they use intonational meaning to disambiguate the referent. Listeners with better pragmatic skills (higher empathy) were sensitive to intonation cues when forming sound-meaning associations during the unfolding of an ambiguous referent, and showed higher sensitivity to all the alternative interpretations of that ambiguous referent. Less pragmatically skilled listeners showed weaker processing of intonational meaning because they needed subsequent disambiguating material to select a referent and showed less sensitivity to the set of alternative interpretations. Overall, our results call for taking into account individual pragmatic differences in the study of intonational meaning processing and sentence comprehension in general.

Adipose tissue inflammation and dysfunction are associated with obesity‐related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug‐inducible “suicide” genes driven by the p16Ink4a promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra‐abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity‐related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity‐related metabolic dysfunction and its complications.

Aging and obesity increase multimorbidity and disability risk, and determining interventions for reversing healthspan decline is a critical public health priority. Exercise and time‐restricted feeding (TRF) benefit multiple health parameters when initiated in early life, but their efficacy and safety when initiated at older ages are uncertain. Here, we tested the effects of exercise versus TRF in diet‐induced obese, aged mice from 20 to 24 months of age. We characterized healthspan across key domains: body composition, physical, metabolic, and cardiovascular function, activity of daily living (ADL) behavior, and pathology. We demonstrate that both exercise and TRF improved aspects of body composition. Exercise uniquely benefited physical function, and TRF uniquely benefited metabolism, ADL behavior, and circulating indicators of liver pathology. No adverse outcomes were observed in exercised mice, but in contrast, lean mass and cardiovascular maladaptations were observed following TRF. Through a composite index of benefits and risks, we conclude the net healthspan benefits afforded by exercise are more favorable than those of TRF. Extrapolating to obese older adults, exercise is a safe and effective option for healthspan improvement, but additional comprehensive studies are warranted before recommending TRF.

Summary While reports suggest a single dose of senolytics may improve vasomotor function, the structural and functional impact of long‐term senolytic treatment is unknown. To determine whether long‐term senolytic treatment improves vasomotor function, vascular stiffness, and intimal plaque size and composition in aged or hypercholesterolemic mice with established disease. Senolytic treatment (intermittent treatment with Dasatinib + Quercetin via oral gavage) resulted in significant reductions in senescent cell markers (TAF + cells) in the medial layer of aorta from aged and hypercholesterolemic mice, but not in intimal atherosclerotic plaques. While senolytic treatment significantly improved vasomotor function (isolated organ chamber baths) in both groups of mice, this was due to increases in nitric oxide bioavailability in aged mice and increases in sensitivity to NO donors in hypercholesterolemic mice. Genetic clearance of senescent cells in aged normocholesterolemic INK‐ATTAC mice phenocopied changes elicited by D+Q. Senolytics tended to reduce aortic calcification (alizarin red) and osteogenic signaling (qRT–PCR, immunohistochemistry) in aged mice, but both were significantly reduced by senolytic treatment in hypercholesterolemic mice. Intimal plaque fibrosis (picrosirius red) was not changed appreciably by chronic senolytic treatment. This is the first study to demonstrate that chronic clearance of senescent cells improves established vascular phenotypes associated with aging and chronic hypercholesterolemia, and may be a viable therapeutic intervention to reduce morbidity and mortality from cardiovascular diseases.

Strong-field laser excitation of solids can produce extremely nonlinear electronic and optical behaviour. As recently demonstrated, this includes the generation of high harmonics extending into the vacuum-ultraviolet and extreme-ultraviolet regions of the electromagnetic spectrum. High harmonic generation is shown to occur fundamentally differently in solids and in dilute atomic gases. How the microscopic mechanisms in the solid and the gas differ remains a topic of intense debate. Here we report a direct comparison of high harmonic generation in the solid and gas phases of argon and krypton. Owing to the weak van der Waals interaction, rare (noble)-gas solids are a near-ideal medium in which to study the role of high density and periodicity in the generation process. We find that the high harmonic generation spectra from the rare-gas solids exhibit multiple plateaus extending well beyond the atomic limit of the corresponding gas-phase harmonics measured under similar conditions. The appearance of multiple plateaus indicates strong interband couplings involving multiple single-particle bands. We also compare the dependence of the solid and gas harmonic yield on laser ellipticity and find that they are similar, suggesting the importance of electron-hole recollision in these solids. This implies that gas-phase methods such as polarization gating for attosecond pulse generation and orbital tomography could be realized in solids.

High-harmonic generation was used to probe the spectral intensity and phase of the recombination-dipole matrix element of methyl chloride (CH3Cl), revealing a Cooper minimum (CM) analogous to the 3p CM previously reported in argon. The CM structure altered the spectral response and group delay (GD) of the emitted harmonics, and was revealed only through careful removal of all additional contributors to the GD. In characterizing the GD dispersion, also known as the “attochirp” we additionally present the most complete validation to date of the commonly used strong-field approximation for calculating the GD, demonstrating the correct intensity scaling and extending its usefulness to simple molecules.

Background Excessive weight gain in patients living with HIV (PLWH) can have considerable health-related consequences. Recent observational studies suggest that patients initiating or switching to integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) may experience weight gain. The prevalence and extent of weight gain as well as the presence of other metabolic changes following switches to INSTI-based ART remain unclear. Methods This retrospective study evaluated changes in weight, body mass index (BMI), cholesterol and hemoglobin A1C in virologically suppressed PLWH who switched from non-INSTI to INSTI-based ART at a single academic medical center from May 2015 to December 2017. Adult patients on non-INSTI-based ART for ≥1 year before switching to INSTI-based regimens were included. Body weight, BMI, cholesterol and A1C values were collected for the year prior to and 18 months following the switch. The unadjusted distributions of pre- and post-switch values were compared with the Wilcoxon signed-rank test and predictors of weight gain were determined with simple linear regression. Results A total of 90 patients met criteria for analysis (Table 1). In unadjusted analyses, there were significant increases in weight and BMI (each P ≤ 0.001, Table 2), but not cholesterol or A1C values following switches to INSTI-based ART (Table 3). On average, patient weight increased by 2.2 kg after switching, though 26% of patients gained ≥4.5 kg. Patients switching from non-nucleoside reverse transcriptase inhibitors vs. protease inhibitors had numerically greater mean increases in weight (Table 3). A similar trend occurred for those switching to elvitegravir as opposed to dolutegravir. In the linear regression model, neither pre-switch nor post-switch ART components were identified as predictors for weight gain. This was also true for differences in gender, race, and pre-switch BMI. Increasing age was protective against weight gain in the model. Conclusion Weight gain in patients switching to INSTI-based ART observed in this analysis did not correspond to changes in cholesterol or glycemic control. Some patients receiving INSTIs in this sample gained substantial amounts of weight. The mechanisms and risk factors for substantial weight gain require further study. Disclosures All authors: No reported disclosures.

The ventro-lateral pulvinar is reciprocally connected with the visual areas of the ventral stream that are important for object recognition. To understand the mechanisms of attentive stimulus processing in this pulvinar-cortex loop, we investigated the interactions between the pulvinar, area V4, and IT cortex in a spatial-attention task. Sensory processing and the influence of attention in the pulvinar appeared to reflect its cortical inputs. However, pulvinar deactivation led to a reduction of attentional effects on firing rates and gamma synchrony in V4, a reduction of sensory-evoked responses and overall gamma coherence within V4, and severe behavioral deficits in the affected portion of the visual field. Conversely, pulvinar deactivation caused an increase in low-frequency cortical oscillations, often associated with inattention or sleep. Thus, cortical interactions with the ventro-lateral pulvinar are necessary for normal attention and sensory processing and for maintaining the cortex in an active state. The pulvinar is often proposed to modulate cortical processing with attention. Zhou et al. find that beyond any role in attention, the pulvinar input to cortex seems necessary to maintain the cortex in an active state., National Institutes of Health (U.S.) (Grant R01 EY017292)

Objectives To determine the potential impact of a brief human immunodeficiency virus (HIV) educational intervention delivered by a pharmacist during a provider visit on patient knowledge and retention in HIV care. Methods This study was performed in an HIV clinic at a large medical centre in Philadelphia. Patients had been attending the clinic for at least 1 year and were receiving antiretroviral therapy (ART). Participants were randomized to standard care (SC) or SC plus a 10-min educational presentation (EP). Participants were followed over their next two scheduled visits. All participants received a baseline and end of study knowledge assessment. EP patients also received a knowledge assessment immediately following the presentation. A participant answering all assessment questions correctly was considered to have perfect knowledge. Participant retention in care was measured by attendance at provider visits, completion of laboratory work and adherence to ART. Key findings Forty-five patients were enrolled; 24 received the EP. At baseline, two-thirds of participants (31/45) had nonperfect knowledge and most had nonperfect retention (31/45). Among those with nonperfect baseline knowledge, most had nonperfect retention (23/31, P = 0.042). Following education, perfect knowledge improved in the intervention group (5/24 at baseline versus 16/24 post-EP, P = 0.002) and maintained through study completion. EP patients were more likely to have perfect retention compared with SC patients at study visit two (17/24 versus 5/21, P = 0.002) and study completion (16/24 versus 5/21, P = 0.026). Conclusion Brief education delivered by a pharmacist may improve patient knowledge and retention in HIV care.

As the disease spread, the scale of the epidemic required a multi-faceted public health response., Over the span of a few weeks during July and August 2014, events in West Africa changed perceptions of Ebola virus disease (EVD) from an exotic tropical disease to a priority for global health security. We describe observations during that time of a field team from the Centers for Disease Control and Prevention and personnel of the Liberian Ministry of Health and Social Welfare. We outline the early epidemiology of EVD within Liberia, including the practical limitations on surveillance and the effect on the country’s health care system, such as infections among health care workers. During this time, priorities included strengthening EVD surveillance; establishing safe settings for EVD patient care (and considering alternative isolation and care models when Ebola Treatment Units were overwhelmed); improving infection control practices; establishing an incident management system; and working with Liberian airport authorities to implement EVD screening of departing passengers.

People speak metaphorically about abstract concepts—for instance, a person can be “full of love” or “have a lot of love to give.” Over the past decade, research has begun to focus on how metaphors are processed during language comprehension. Much of this work suggests that understanding a metaphorical expression involves activating brain and body systems involved in perception and motor control. However, no research to date has asked whether the same is true while speakers produce language. We address this gap using a sentence production task. Its results demonstrate that visually activating a concrete source domain can trigger the use of metaphorical language drawn from that same concrete domain, even in sentences that are thematically unrelated to the primes, a metaphorical priming effect. This effect suggests that conceptual metaphors play a part in language production. It also shows that activation in the perceptual system that is not part of an intended message can nevertheless influence sentence formulation.

Senescent cells have the capacity to both effect and limit fibrosis. Senotherapeutics target senescent cells to improve aging conditions. Here, we review the contexts in which senescent cells mediate wound healing and fibrotic pathology and the potential utility of senotherapeutic drugs for treatment of fibrotic disease. Multi-action and temporal considerations influence deleterious versus beneficial actions of senescent cells. Acutely generated senescent cells can limit proliferation, and the senescence-associated secretory phenotype (SASP) contains factors that can facilitate tissue repair. Long-lived senescent cells that evade clearance or are generated outside of programmed remodeling can deplete the progenitor pool to exhaust regenerative capacity and through the SASP, stimulate continual activation, leading to disorganized tissue architecture, fibrotic damage, sterile inflammation, and induction of bystander senescence. Senescent cells contribute to fibrotic pathogenesis in multiple tissues, including the liver, kidney, and lung. Senotherapeutics may be a viable strategy for treatment of a range of fibrotic conditions.

The commenter’s key argument is that Diamond Lake’s problem is strictly one of biomass, i.e., introduction of the invasive Tui Chub fish. There are a few things to note in that respect. The Tui Chub is a bait fish. It is a lower-order prey fish for higher-order trout/salmonid species. Tui Chub is zooplanktivorous. Since the Tui Chub feed on zooplankton, if they themselves are prey for other species (or are being “culled” by artificial means), and there is no other entity to feed on the plankton and algae, the result would be a mass of plankton/algae bloom (i.e., harmful algal blooms (HABs)). This would lead to anoxic conditions in the euphotic zone, which puts even more stress on the higher-order trout/salmonid species. Our work found that the biological community (i.e., invertebrates and fish) are lagging indicators (i.e., response indicators).

Despite living in difficult and socially disorganized conditions, some individuals displaced by disasters and living in FEMA parks can be remarkably resilient to depression. We conceptualize resilience as emerging from a combination of situational advantages that accrue for some residents but not for others. We assess whether situational advantages lead to resilience, either in isolation or in combination with one another, in two parts. First, we used a delimited person-centered analysis (PCA) to identify advantages present among the most resilient and absent among the least resilient FEMA park residents. Second, we used fuzzy-set analysis (FSA) to systematically uncover advantageous individual-level conditions that were consistent among resilient individuals using the full sample of FEMA park respondents. Implications for sociological theory and disaster mental health research are discussed.

Low bone mineral density is common among persons with human immunodeficiency virus (HIV) infection, and studies reporting increased fracture rates in this patient population are emerging. The causes of low bone mineral density, osteoporosis, and fractures in persons with HIV are likely multifactorial, involving traditional risk factors, HIV infection, and exposure to antiretroviral treatment. Specific antiretrovirals such as tenofovir may cause a greater loss of bone mineral density compared with other agents and have recently been linked to an increased risk for fracture. As a result, recent treatment guidelines suggest that clinicians consider avoiding tenofovir as initial therapy in postmenopausal women. Evaluating bone mineral density and vitamin D status in persons with HIV may be important steps in identifying those requiring pharmacotherapy; however, the appropriate timing for bone mineral density and vitamin D screening is uncertain, as is the appropriate method of replacing vitamin D in HIV-positive patients who are deficient. Further study is necessary to definitively determine the approach to evaluating bone health and managing low bone mineral density and vitamin D deficiency in patients with HIV infection.

This study investigates how syntactic and semantic load factors impact sentence comprehension and BOLD signal under moderate hypoglycemia. A dual session, whole brain fMRI study was conducted on 16 healthy participants using the glucose clamp technique. In one session, they experienced insulin-induced hypoglycemia (plasma glucose at ∼50mg/dL); in the other, plasma glucose was maintained at euglycemic levels (∼100mg/dL). During scans subjects were presented with sentences of contrasting syntactic (embedding vs. conjunction) and semantic (reversibility vs. irreversibility) load. Semantic factors dominated the overall load effects on both performance (p