Historical Lessons on Vaccine Hesitancy: Smallpox, Polio, and Measles, and Implications for COVID-19.

Vaccine hesitancy continues to pose a formidable obstacle to increasing national COVID-19 vaccination rates in the US, but this is not the first time that American vaccination efforts have confronted resistance and apathy. This study examines the history of US vaccination efforts against smallpox, polio, and measles, highlighting persistent drivers of vaccine hesitancy as well as factors that helped overcome it. The research reveals that logistical barriers, negative portrayals in the media, and fears about safety stymied inoculation efforts as early as the 18th century and continue to do so. However, vaccine hesitancy has been markedly diminished when trusted community leaders have guided efforts, when ordinary citizens have felt personally invested in the success of the vaccine, and when vaccination efforts have been tied to broader projects to improve public health and social cohesion. Deliberately cultivating such factors could be an effective strategy for lessening opposition today, when COVID-19's distinctive characteristics make addressing vaccine hesitancy more urgent than it has ever been.

Epistaxis in people with hereditary haemorrhagic telangiectasia: surgical management and psychological impact.

From the emergency management of acute epistaxis to the surgical procedures for chronic epistaxis, this article covers the options available to control the archetypal symptom of hereditary haemorrhagic telangiectasia while exploring the psychological effect such a disease has on the patient.

Cultivating a communities of practice for colorectal cancer screening in northern Canada.

BACKGROUND: Knowledge management systems such as a Communities of Practice (CoP) can improve healthcare processes but are challenging in complex multidisciplinary systems, and guidance on methods to establish a CoP are needed. This case illustrates the use of early stakeholder engagement and Nominal Group Technique (NGT) to cultivate a CoP in a complex multidisciplinary system: colorectal cancer screening in northern Canada. METHODS: Stakeholders in the Northwest Territories, Canada were recruited and co-designed a workshop with authors to introduce CoP concepts and identify priorities. At the workshop NGT was used to identify and prioritize gaps in process, practice, and evidence for the CoP to focus on. An anonymous polling system was used to obtain workshop participants' feedback on the process. RESULTS: The co-design process integrated stakeholders' perspectives in developing a workshop. Using NGT, the gap analysis identified 23 areas of focus for the CoP, among which, the highest priorities were identified: communication between clinicians and with patients, and identification of screening eligibility in the electronic medical record. Participants found the process to be useful, educational, and interesting. There was unanimous interest in moving forward with developing a CoP. CONCLUSION: A co-designed workshop and NGT were useful in laying the foundation for a CoP in a complex multidisciplinary environment. POLICY STATEMENT: This case shows the utility of a co-designed workshop and NGT in starting a CoP: a knowledge management system that would provide critical insight into colorectal cancer screening policies for the region.

Multiwavelength Light Curves of Two Remarkable Sagittarius A* Flares.

Sgr A*, the supermassive black hole (SMBH) at the center of our Milky Way Galaxy, is known to be a variable source of X-ray, near-infrared (NIR), and submillimeter radiation and therefore a prime candidate to study the electromagnetic radiation generated by mass accretion flow onto a black hole and/or a related jet. Disentangling the power source and emission mechanisms of this variability is a central challenge to our understanding of accretion flows around SMBHs. Simultaneous multiwavelength observations of the flux variations and their time correlations can play an important role in obtaining a better understanding of possible emission mechanisms and their origin. This paper presents observations of two flares that both apparently violate the previously established patterns in the relative timing of submillimeter/NIR/X-ray flares from Sgr A*. One of these events provides the first evidence of coeval structure between NIR and submillimeter flux increases, while the second event is the first example of the sequence of submillimeter/X-ray/NIR flux increases all occurring within ~1 hr. Each of these two events appears to upend assumptions that have been the basis of some analytic models of flaring in Sgr A*. However, it cannot be ruled out that these events, even though unusual, were just coincidental. These observations demonstrate that we do not fully understand the origin of the multiwavelength variability of Sgr A* and show that there is a continued and important need for long-term, coordinated, and precise multiwavelength observations of Sgr A* to characterize the full range of variability behavior.

Simultaneous X-Ray and Infrared Observations of Sagittarius A*'s Variability.

Emission from Saggitarius A* is highly variable at both X-ray and infrared (IR) wavelengths. Observations over the last ~20 yr have revealed X-ray flares that rise above a quiescent thermal background about once per day, while faint X-ray flares from Sgr A* are undetectable below the constant thermal emission. In contrast, the IR emission of Sgr A* is observed to be continuously variable. Recently, simultaneous observations have indicated a rise in IR flux density around the same time as every distinct X-ray flare, while the opposite is not always true (peaks in the IR emission may not be coincident with an X-ray flare). Characterizing the behavior of these simultaneous X-ray/IR events and measuring any time lag between them can constrain models of Sgr A*'s accretion flow and the flare emission mechanism. Using 100+ hours of data from a coordinated campaign between the Spitzer Space Telescope and the Chandra X-ray Observatory, we present results of the longest simultaneous IR and X-ray observations of Sgr A* taken to date. The cross-correlation between the IR and X-ray light curves in this unprecedented data set, which includes four modest X-ray/IR flares, indicates that flaring in the X-ray may lead the IR by approximately 10-20 min with 68% confidence. However, the 99.7% confidence interval on the time-lag also includes zero, i.e., the flaring remains statistically consistent with simultaneity. Long-duration and simultaneous multi-wavelength observations of additional bright flares will improve our ability to constrain the flare timing characteristics and emission mechanisms, and must be a priority for Galactic Center observing campaigns.

Exploring psychosocial predictors of STI testing in University students.

BACKGROUND: To explore university students' Sexually Transmitted Infection (STI) testing knowledge, psychosocial and demographic predictors of past STI testing behaviour, intentions to have an STI test, and high risk sexual behaviour, to inform interventions promoting STI testing in this population. METHODS: A cross-sectional, quantitative online survey was conducted in March 2016, recruiting university students from North East Scotland via an all-student email. The anonymous questionnaire assessed student demographics (e.g. sex, ethnicity, age), STI testing behaviours, sexual risk behaviours, knowledge and five psychological constructs thought to be predictive of STI testing from theory and past research: attitudes, perceived susceptibility to STIs, social norms, social fear and self-efficacy. RESULTS: The sample contained 1294 sexually active students (response rate 10%) aged 18-63, mean age = 23.61 (SD 6.39), 888 (69%) were female. Amongst participants, knowledge of STIs and testing was relatively high, and students held generally favourable attitudes. 52% reported ever having an STI test, 13% intended to have one in the next month; 16% reported unprotected sex with more than one 'casual' partner in the last six months. Being female, older, a postgraduate, longer UK residence, STI knowledge, perceived susceptibility, subjective norms, attitudes and self-efficacy all positively predicted past STI testing behaviour (p < 0.01). Perceived susceptibility to STIs and social norms positively predicted intentions to have an STI test in the next month (p < 0.05); perceived susceptibility also predicted past high-risk sexual behaviour (p < 0.01). CONCLUSIONS: Several psychosocial predictors of past STI testing, of high-risk sexual behaviour and future STI intentions were identified. Health promotion STI testing interventions could focus on male students and target knowledge, attitude change, and increasing perceived susceptibility to STIs, social norms and self-efficacy towards STI-testing.

Variability Timescale and Spectral Index of Sgr A* in the Near Infrared: Approximate Bayesian Computation Analysis of the Variability of the Closest Supermassive Black Hole.

Sagittarius A* (Sgr A*) is the variable radio, near-infrared (NIR), and X-ray source associated with accretion onto the Galactic center black hole. We present an analysis of the most comprehensive NIR variability data set of Sgr A* to date: eight 24 hr epochs of continuous monitoring of Sgr A* at 4.5 µm with the IRAC instrument on the Spitzer Space Telescope, 93 epochs of 2.18 µm data from Naos Conica at the Very Large Telescope, and 30 epochs of 2.12 µm data from the NIRC2 camera at the Keck Observatory, in total 94,929 measurements. A new approximate Bayesian computation method for fitting the first-order structure function extracts information beyond current fast Fourier transformation (FFT) methods of power spectral density (PSD) estimation. With a combined fit of the data of all three observatories, the characteristic coherence timescale of Sgr A* is τ b = 243 - 57 + 82 minutes (90% credible interval). The PSD has no detectable features on timescales down to 8.5 minutes (95% credible level), which is the ISCO orbital frequency for a dimensionless spin parameter a = 0.92. One light curve measured simultaneously at 2.12 and 4.5 µm during a low flux-density phase gave a spectral index α s = 1.6 ± 0.1 ( F ν ∝ ν - α s ) . This value implies that the Sgr A* NIR color becomes bluer during higher flux-density phases. The probability densities of flux densities of the combined data sets are best fit by log-normal distributions. Based on these distributions, the Sgr A* spectral energy distribution is consistent with synchrotron radiation from a non-thermal electron population from below 20 GHz through the NIR.

Young Stellar Objects in the Massive Star-forming Regions W51 and W43.

We present the results of our investigation of the star-forming complexes W51 and W43, two of the brightest in the first Galactic quadrant. In order to determine the young stellar object (YSO) populations in W51 and W43 we used color-magnitude relations based on Spitzer mid-infrared and 2MASS/UKIDSS near-infrared data. We identified 302 Class I YSOs and 1178 Class II/transition disk candidates in W51, and 917 Class I YSOs and 5187 Class II/transition disk candidates in W43. We also identified tens of groups of YSOs in both regions using the Minimal Spanning Tree (MST) method. We found similar cluster densities in both regions, even though Spitzer was not able to probe the densest part of W43. By using the Class II/I ratios, we traced the relative ages within the regions and, based on the morphology of the clusters, we argue that several sites of star formation are independent of one another in terms of their ages and physical conditions. We used spectral energy distribution-fitting to identify the massive YSO (MYSO) candidates since they play a vital role in the star formation process, and then examined them to see if they are related to any massive star formation tracers such as UCH II regions, masers, or dense fragments. We identified 17 MYSO candidates in W51, and 14 in W43, respectively, and found that groups of YSOs hosting MYSO candidates are positionally associated with H II regions in W51, though we do not see any MYSO candidates associated with previously identified massive dense fragments in W43.

Dispersal of Amblyseius swirskii (Acari: Phytoseiidae) on High-Tunnel Bell Peppers in Presence or Absence of Polyphagotarsonemus latus (Acari: Tarsonemidae).

Amblyseius swirskiiAthias-Henriot (Acari: Phytoseiidae) is a predatory mite used to control thrips (Thysanoptera), whiteflies (Bemisia tabaci Genn., Hemiptera: Aleyrodidae), and broad mites (BMs) (Polyphagotarsonemus latus Banks, Acari: Tarsonemidae). Dispersal of A. swirskii, using the ornamental pepper "Explosive Ember" as a banker plant was evaluated for control of BMs in high-tunnel peppers. Open-canopy plants (5 weeks old) versus closed-canopy plants (10-weeks old) were used to evaluate the effect of plant connectedness in A. swirskii dispersal, in the presence (two females per plant) and absence of BMs. Plots consisted of a single central banker plant and four bell peppers extending linearly north and south. Sets of all treatments were destructively sampled 1, 4, and 7 days after releasing A. swirskii Within 24 h, A. swirskii dispersed four plants away from the banker plants (1 m), regardless of the state of the canopy. Canopy connectedness did increase the presence of A. swirskii on the crop plants. Predatory mite numbers on closed-canopy treatments doubled within the 7-day sampling period, whereas no significant increase was observed on open-canopy treatments. The presence of BMs had no significant effect on the movement of A. swirskii The results suggest further experiments with A. swirskii and banker plants for control of BMs is warranted.

Transmission of Squash vein yellowing virus to and From Cucurbit Weeds and Effects on Sweetpotato Whitefly (Hemiptera: Aleyrodidae) Behavior.

Since 2003, growers of Florida watermelon [Citrullus lanatus (Thunb.) Matsum. and Nakai] have periodically suffered large losses from a disease caused by Squash vein yellowing virus (SqVYV), which is transmitted by the whitefly Middle East-Asia Minor 1 (MEAM1), formerly Bemisia tabaci (Gennadius) biotype B. Common cucurbit weeds like balsam apple (Momordica charantia L.) and smellmelon [Cucumis melo var. dudaim (L.) Naud.] are natural hosts of SqVYV, and creeping cucumber (Melothria pendula L.) is an experimental host. Study objectives were to compare these weeds and 'Mickylee' watermelon as sources of inoculum for SqVYV via MEAM1 transmission, to determine weed susceptibility to SqVYV, and to evaluate whitefly settling and oviposition behaviors on infected vs. mock-inoculated (inoculated with buffer only) creeping cucumber leaves. We found that the lowest percentage of watermelon recipient plants was infected when balsam apple was used as a source of inoculum. Watermelon was more susceptible to infection than balsam apple or smellmelon. However, all weed species were equally susceptible to SqVYV when inoculated by whitefly. For the first 5 h after release, whiteflies had no preference to settle on infected vs. mock-inoculated creeping cucumber leaves. After 24 h, whiteflies preferred to settle on mock-inoculated leaves, and more eggs were laid on mock-inoculated creeping cucumber leaves than on SqVYV-infected leaves. The transmission experiments (source of inoculum and susceptibility) show these weed species as potential inoculum sources of the virus. The changing settling preference of whiteflies from infected to mock-inoculated plants could lead to rapid spread of virus in the agroecosystem.

Acute Toxicity and Sublethal Effects of Fenpyroximate to Amblyseius swirskii (Acari: Phytoseiidae).

Knowledge about the effects of pesticides on biological control agents is required in order to successfully implement integrated pest management programs. The predatory mite Amblyseius swirskii Athias-Henriot has been used to control thrips, whiteflies, and broad mites in vegetable production; however, effects of fenpyroximate, an acaricide and insecticide used in vegetable crops, on A. swirskii have not been evaluated. The effect of four residual concentrations of fenpyroximate on A. swirskii females was measured under laboratory conditions including its effect on their fecundity and larval survival. Fresh residues of fenpyroximate were significantly toxic to adult females and larvae. Mortality increased and fecundity decreased as the concentration (0.026-0.208 ml/50 ml of water) and time after treatment (24-120 h) increased. Fifty percent of the larvae survived on the two lower concentrations (0.026 and 0.052 ml/50 ml of water) after 120 h.

Genome-wide QTL mapping of saltwater tolerance in sibling species of Anopheles (malaria vector) mosquitoes.

Although freshwater (FW) is the ancestral habitat for larval mosquitoes, multiple species independently evolved the ability to survive in saltwater (SW). Here, we use quantitative trait locus (QTL) mapping to investigate the genetic architecture of osmoregulation in Anopheles mosquitoes, vectors of human malaria. We analyzed 1134 backcross progeny from a cross between the obligate FW species An. coluzzii, and its closely related euryhaline sibling species An. merus. Tests of 2387 markers with Bayesian interval mapping and machine learning (random forests) yielded six genomic regions associated with SW tolerance. Overlap in QTL regions from both approaches enhances confidence in QTL identification. Evidence exists for synergistic as well as disruptive epistasis among loci. Intriguingly, one QTL region containing ion transporters spans the 2Rop chromosomal inversion that distinguishes these species. Rather than a simple trait controlled by one or a few loci, our data are most consistent with a complex, polygenic mode of inheritance.

New insecticides for management of tomato yellow leaf curl, a virus vectored by the silverleaf whitefly, Bemisia tabaci.

Greenhouse studies using a randomized complete block design were carried out to evaluate the effect of six insecticides on transmission of Tomato yellow leaf curl virus (TYLCV) by the silverleaf whitefly, Bemisia tabaci biotype B Gennadius (Hemiptera: Aleyrodidae) to tomato, Lycopersicon esculentum (Miller) (Solanales: Solanaceae), seedlings that were inoculated with whiteflies from a TYLCV colony in cages 3, 7, or 14 d after treatment with insecticide. The purpose was to reveal differences in residual efficacy of four materials that are nearing registration for use on tomato-cyazypyr, flupyradifurone, pyrafluquinazon, and sulfoxaflor-and to compare them with two established insecticides, pymetrozine and a zeta-cypermethrin/bifenthrin combination. Differences in efficacy were expected because these six materials represent five distinct modes of action and both contact and systemic materials. Percentage of tomato seedlings expressing virus symptoms tended to be lowest in seedlings treated with flupyradifurone. The zeta-cypermethrin/bifenthrin insecticide demonstrated comparable efficacy to flupyradifurone in some trials at 3 and 7 d after treatment inoculations, but not the 14 d after treatment inoculation. Pyrafluquinazon was not statistically different from cyazypyr or sulfoxaflor in percentage of plants with virus symptoms in any trial. Percentage virus in the cyazypyr and sulfoxaflor treatments was not statistically different in the 3 and 7 d after treatment inoculations. Among seedlings treated with insecticide, percentage with virus symptoms tended to be highest in the seedlings treated with pymetrozine.

Associations between accelerometer-derived physical activity and regional adiposity in young men and women.

OBJECTIVE: Empirical evidence supports an inverse relationship between physical activity (PA) and adiposity, but studies using detailed measures of both are scarce. The relationship between regional adiposity and accelerometer-derived PA in men and women are described. DESIGN AND METHODS: Cross-sectional analysis included 253 participants from a weight loss study limited to ages 20-45 years and BMI 25-39.9 kg m(-2) . PA data were collected with accelerometers and expressed as total accelerometer counts and average amount of time per day accumulated in different intensity levels [sedentary, light-, and moderate-to-vigorous intensity PA (MVPA)]. Accumulation of time spent above 100 counts was expressed as total active time. Computed tomography (CT) was used to measure abdominal and adipose tissue (AT). Multivariate linear regression analyses were used to assess the relationship between regional adiposity (dependent variable) and the various PA levels (independent variable), and were executed separately for men and women, adjusting for wear time, age, race, education, and BMI. RESULTS: Among males, light activity was inversely associated with total AT (ß = -0.19; P = 0.02) as well as visceral AT (VAT) (ß = -0.30; P = 0.03). Among females sedentary time was positively associated with VAT (ß = 0.11; P = 0.04) and total active time was inversely associated with VAT (ß = -0.12; P = 0.04). CONCLUSIONS: Findings from this study suggest that PA intensity level may influence regional adiposity differently in men and women. Additional research is needed in larger samples to clarify the difference in these associations by sex, create recommendations for the frequency, duration and intensity of PA needed to target fat deposits, and determine if these recommendations should differ by sex.

Rapid evolution of sex frequency and dormancy as hydroperiod adaptations.

Dormancy can serve as an adaptation to persist in variable habitats and often is coupled with sex. In cyclically parthenogenetic rotifers, an asexual phase enables rapid population growth, whereas sex results in diapausing embryos capable of tolerating desiccation. Few studies have experimentally tested whether sex-dormancy associations in temporary waters reflect evolution in response to the short hydroperiod selecting for diapause ability. Here, we demonstrate evolution of higher propensity for sex and dormancy in ephemeral rotifer cultures mimicking temporary ponds, and lower propensity in permanent cultures. Results are consistent with rapid evolution, with evolutionary changes occurring in a short timeframe (385 days, ≤ 84 generations). We also provide insight into mechanisms for rapid evolution in basal metazoans, discussing potential roles of new mutations, recombination and clonal selection.

Swallowing problems and dementia in acute hospital settings: practical guidance for the management of dysphagia.

There is little evidence to support tube feeding in advanced dementia although it is still frequently used in acute hospital settings. Patients present with complex problems and are often unable to make decisions about their healthcare needs. Multidisciplinary teams may be challenged by the difficult ethical decisions they are required to make in the best interests of their patients. This paper guides decision making in the management of patients with dementia and dysphagia in the acute hospital setting. A structured approach to information gathering, assessment and management is outlined with practical application of recent published guidelines and research evidence, which ensures appropriate individualised care.

Effects of moderate hypothermia on IL-1 beta-induced leukocyte rolling and adhesion in pial microcirculation of mice and on proinflammatory gene expression in human cerebral endothelial cells.

SUMMARY: Although the neuroprotective effects of hypothermia have been known for a long time, the molecular correlates of this neuroprotection are poorly understood. In this study, the authors investigated how hypothermia affects inflammatory responses in the brain elicited by systemic injection of IL-1 beta. Leukocyte rolling and adhesion were quantified in pial venules (20 to 50 microm) of C57/Bl6 mice 4 hours after intraperitoneal injection of IL-1 beta (5 microg/kg) using an open cranial window and intravital microscopy. Animals were subjected to moderate hypothermia (32 degrees C) or normothermia (37 degrees C) for 1 or 4 hours after IL-1 beta injection. Significant increases in leukocyte rolling and adhesion were observed in IL-1 beta-injected animals as compared with sham controls. Whereas 1-hour hypothermia did not affect IL-1 beta-induced leukocyte rolling and adhesion, 4-hour hypothermia caused a reduction in both rolling and adhesion. Molecular mechanisms of hypothermic effects were investigated in cultured human cerebral endothelial cells exposed to IL-1 beta (50 U/mL) for 4 hours at 37 degrees C or 32 degrees C followed by 18 hours at 37 degrees C. Human cerebral endothelial cells exposed to IL-1 beta at 32 degrees C showed attenuated NF-kappa B activation determined by the Luciferase yellow reporter gene assay and reduced expression of IL-8 and IL-1 beta measured by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. Intracellular adhesion molecule-1 was induced to similar levels (threefold over control) at both temperatures. The expression of CD18 on neutrophils in vitro was not affected by either IL-1 beta or hypothermia. These findings suggest that mechanisms by which hypothermia reduces leukocyte rolling and adhesion include suppression of inflammatory gene transcription in brain endothelial cells.

The regulation of DNA vaccines.

The framework for regulating DNA vaccines has been in place since the first clinical trial was initiated in the mid-1990s. American and European regulatory guidance has evolved on the basis of insights provided by ongoing preclinical and clinical studies. These include analyses of the safety of DNA vaccines in normal volunteers, and recent data concerning the tissue distribution, persistence, and integration potential of DNA plasmids.

Effect of silver reflective mulch and a summer squash trap crop on densities of immature Bemisia argentifolii (Homoptera: Aleyrodidae) on organic bean.

Polyethylene mulch with a reflective silver stripe and a yellow summer squash, Cucurbita pepo L., trap crop were tested alone and in combination as tactics to reduce densities of Bemisia argentifolii Bellows & Perring eggs and nymphs, and incidence of bean golden mosaic geminivirus on snap bean, Phaseolus vulgaris L. Egg densities were consistently higher on squash than on bean, but egg densities and virus incidence were not lower on bean grown with squash than on bean grown in monoculture. Silver reflective mulch reduced egg densities compared with bean grown on bare ground during the first week after crop emergence for 2 of the 3 yr that the study was conducted. However, egg suppression by silver mulch was not enhanced by the presence of a squash trap crop when both tactics were combined. The obstacles to suppressing B. argentifolii through the use of trap crops are discussed.

A standardized method for measuring intracranial arterial stenosis.

BACKGROUND AND PURPOSE: Atherosclerosis of the major intracranial arteries is an important cause of ischemic stroke. We established measurement criteria to assess percent stenosis of a major intracranial artery (carotid, middle cerebral, vertebral, basilar) and determined the interobserver/intraobserver agreements and interclass/intraclass correlations of these measurements. METHODS: We defined percent stenosis of an intracranial artery as follows: percent stenosis = [(1 - (D(stenosis)/D(normal)))] x 100, where D(stenosis) = the diameter of the artery at the site of the most severe stenosis and D(normal) = the diameter of the proximal normal artery. If the proximal segment was diseased, contingency sites were chosen to measure D(normal): distal artery (second choice), feeding artery (third choice). Using a hand-held digital caliper, three neuroradiologists independently measured D(stenosis) and D(normal) of 24 stenotic intracranial arteries. Each observer repeated the readings 4 weeks later. We determined how frequently two observers' measurements of percent stenosis of each of the 24 diseased arteries differed by 10% or less. RESULTS: Among the three pairs of observers, interobserver agreements were 88% (observer 1 versus observer 2), 79% (observer 1 versus observer 3), 75% (observer 2 versus observer 3) for the first reading and were 75% (observer 1 versus observer 2), 100% (observer 1 versus observer 3), and 71% (observer 2 versus observer 3) for the second reading. Intraobserver agreement for each of the observers was 88%, 83%, and 100%. Interclass correlation was 85% (first reading) and 87% (second reading). Intraclass correlation was 92% (first and second readings combined). CONCLUSION: This method shows good interobserver and intraobserver agreements for the measurement of intracranial stenosis of a major artery. If validated in subsequent studies, this method may serve as a standard for the measurement of percent stenosis of an intracranial artery.