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IntroductionExposure to media content can shape public opinions about tobacco. In early September 2019, the outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) became headline news in the United States.MethodsIn August and September 2019, we conducted two cross-sectional online surveys with current and former smokers assessing attitudes and beliefs about e-cigarettes. Study one (n = 865) was collected before the EVALI outbreak was widely covered and study two (n = 344) was collected after the outbreak had become nation-wide news. We examined differences in perceptions and beliefs between time points.ResultsE-cigarette harm perceptions increased between study one (mean = 2.67) and study two (mean = 2.90, p < .05). Ever-users of e-cigarettes largely account for this change. Endorsement of the belief that e-cigarettes were risky and more likely to cause lung damage compared to cigarettes increased between studies (p < .05). Seventy eight percent of participants at study two were aware of the vaping illness story. Being aware of the story was associated with more endorsement of the belief that e-cigarettes were risky to use, but not that using e-cigarettes would make the participant more likely to get damaged lungs.DiscussionWhen the stories about the health and safety of tobacco products dominate the public information environment, it presents an opportunity to change beliefs that are frequently targeted by paid health campaigns. Changes in participant's perceptions of e-cigarettes were associated with coverage of this large news story, underscoring the importance of working to ensure that coverage is a scientifically accurate as possible.

SARS-CoV-2 viral attachment and entry into host cells is mediated by a direct interaction between viral spike glycoproteins and membrane bound angiotensin-converting enzyme 2 (ACE2). The receptor binding motif (RBM), located within the S1 subunit of the spike protein, incorporates the majority of known ACE2 contact residues responsible for high affinity binding and associated virulence. Observation of existing crystal structures of the SARS-CoV-2 receptor binding domain (SRBD)-ACE2 interface, combined with peptide array screening, allowed us to define a series of linear native RBM-derived peptides that were selected as potential antiviral decoy sequences with the aim of directly binding ACE2 and attenuating viral cell entry. RBM1 (16mer): S443KVGGNYNYLYRLFRK458, RBM2A (25mer): E484GFNCYFPLQSYGFQPTNGVGYQPY508, RBM2B (20mer): F456NCYFPLQSYGFQPTNGVGY505 and RBM2A-Sc (25mer): NYGLQGSPFGYQETPYPFCNFVQYG. Data from fluorescence polarisation experiments suggested direct binding between RBM peptides and ACE2, with binding affinities ranging from the high nM to low μM range (Kd = 0.207-1.206 μM). However, the RBM peptides demonstrated only modest effects in preventing SRBD internalisation and showed no antiviral activity in a spike protein trimer neutralisation assay. The RBM peptides also failed to suppress S1-protein mediated inflammation in an endogenously expressing ACE2 human cell line. We conclude that linear native RBM-derived peptides are unable to outcompete viral spike protein for binding to ACE2 and therefore represent a suboptimal approach to inhibiting SARS-CoV-2 viral cell entry. These findings reinforce the notion that larger biologics (such as soluble ACE2, 'miniproteins', nanobodies and antibodies) are likely better suited as SARS-CoV-2 cell-entry inhibitors than short-sequence linear peptides.

Saccharomyces cerevisiae is the primary yeast species responsible for most fermentations in winemaking. However, other yeasts, including Saccharomyces uvarum, have occasionally been found conducting commercial fermentations around the world. S. uvarum is typically associated with white wine fermentations in cool-climate wine regions, and has been identified as the dominant yeast in fermentations from France, Hungary, northern Italy, and, recently, Canada. However, little is known about how the origin and genetic diversity of the Canadian S. uvarum population relates to strains from other parts of the world. In this study, a highly diverse S. uvarum population was found dominating uninoculated commercial fermentations of Chardonnay grapes sourced from two different vineyards. Most of the strains identified were found to be genetically distinct from S. uvarum strains isolated globally. Of the 106 strains of S. uvarum identified in this study, four played a dominant role in the fermentations, with some strains predominating in the fermentations from one vineyard over the other. Furthermore, two of these dominant strains were previously identified as dominant strains in uninoculated Chardonnay fermentations at the same winery two years earlier, suggesting the presence of a winery-resident population of indigenous S. uvarum. This research provides valuable insight into the diversity and persistence of non-commercial S. uvarum strains in North America, and a stepping stone for future work into the enological potential of an alternative Saccharomyces yeast species.

BackgroundIn the state of Bihar, India a multi-faceted quality improvement nurse-mentoring program was implemented to improve provider skills in normal and complicated deliveries. The objective of this analysis was to examine changes in diagnosis and management of postpartum hemorrhage (PPH) of the mother and intrapartum asphyxia of the infant in primary care facilities in Bihar, during the program.MethodsDuring the program, mentor pairs visited each facility for one week, covering four facilities over a four-week period and returned for subsequent week-long visits once every month for seven to nine consecutive months. Between- and within-facility comparisons were made using a quasi-experimental and a longitudinal design over time, respectively, to measure change due to the intervention. The proportions of PPH and intrapartum asphyxia among all births as well as the proportions of PPH and intrapartum asphyxia cases that were effectively managed were examined. Zero-inflated negative binomial models and marginal structural methodology were used to assess change in diagnosis and management of complications after accounting for clustering of deliveries within facilities as well as time varying confounding.ResultsThis analysis included 55,938 deliveries from 320 facilities. About 2% of all deliveries, were complicated with PPH and 3% with intrapartum asphyxia. Between-facility comparisons across phases demonstrated diagnosis was always higher in the final week of intervention (PPH: 2.5-5.4%, intrapartum asphyxia: 4.2-5.6%) relative to the first week (PPH: 1.2-2.1%, intrapartum asphyxia: 0.7-3.3%). Within-facility comparisons showed PPH diagnosis increased from week 1 through 5 (from 1.6% to 4.4%), after which it decreased through week 7 (3.1%). A similar trend was observed for intrapartum asphyxia. For both outcomes, the proportion of diagnosed cases where selected evidence-based practices were used for management either remained stable or increased over time.ConclusionsThe nurse-mentoring program appears to have built providers' capacity to identify PPH and intrapartum asphyxia cases but diagnosis levels are still not on par with levels observed in Southeast Asia and globally.

Access to therapeutic oxygen remains a challenge in the effort to reduce pneumonia mortality among children in low- and middle-income countries. The use of oxygen concentrators is common, but their effectiveness in delivering uninterrupted oxygen is gated by reliability of the power grid. Often cylinders are employed to provide continuous coverage, but these can present other logistical challenges. In this study, we examined the use of a novel, low-pressure oxygen storage system to capture excess oxygen from a concentrator to be delivered to patients during an outage. A prototype was built and tested in a non-clinical trial in Jinja, Uganda. The trial was carried out at Jinja Regional Referral Hospital over a 75-day period. The flow rate of the unit was adjusted once per week between 0.5 and 5 liters per minute. Over the trial period, 1284 power failure episodes with a mean duration of 3.1 minutes (range 0.08 to 1720 minutes) were recorded. The low-pressure system was able to deliver oxygen over 56% of the 4,295 power outage minutes and cover over 99% of power outage events over the course of the study. These results demonstrate the technical feasibility of a method to extend oxygen availability and provide a basis for clinical trials.

BACKGROUND:Globally, there were 2.7 million neonatal deaths in 2015. Significant mortality reduction could be achieved by improving care in low- and middle-income countries (LMIC), where the majority of deaths occur. Determining the physical readiness of facilities to identify and manage complications is an essential component of strategies to reduce neonatal mortality. METHODS:We developed clinical cascades for 6 common neonatal conditions then utilized these to assess 23 health facilities in Kenya and Uganda at 2 time-points in 2016 and 2017. We calculated changes in resource availability over time by facility using McNemar's test. We estimated mean readiness and loss of readiness for the 6 conditions and 3 stages of care (identification, treatment, monitoring-modifying treatment). We estimated overall mean readiness and readiness loss across all conditions and stages. Finally, we compared readiness of facilities with a newborn special care unit (NSCU) to those without using the two-sample test of proportions. RESULTS:The cascade model estimated mean readiness of 26.3-26.6% across the 3 stages for all conditions. Mean readiness ranged from 11.6% (respiratory distress-apnea) to 47.8% (essential newborn care) across both time-points. The model estimated overall mean readiness loss of 30.4-31.9%. There was mild to moderate variability in the timing of readiness loss, with the majority occurring in the identification stage. Overall mean readiness was higher among facilities with a NSCU (36.8%) compared to those without (20.0%). CONCLUSION:The cascade model provides a novel approach to quantitatively assess physical readiness for neonatal care. Among 23 facilities in Kenya and Uganda, we identified a consistent pattern of 30-32% readiness loss across cascades and stages. This aggregate measure could be used to monitor and compare readiness at the facility-, health system-, or national-level. Estimates of readiness and loss of readiness may help guide strategies to improve care, prioritize resources, and promote neonatal survival in LMICs.

INTRODUCTION:US law requires disclosure of quantities of toxic chemicals (constituents) in cigarette smoke by brand and sub-brand. This information may drive smokers to switch to cigarettes with lower chemical quantities, under the misperception that doing so can reduce health risk. We sought to understand past brand-switching behavior and whether learning about specific chemicals in cigarette smoke increases susceptibility to brand switching. METHODS:Participants were US adult smokers surveyed by phone (n = 1,151, probability sample) and online (n = 1,561, convenience sample). Surveys assessed whether smokers had ever switched cigarette brands or styles to reduce health risk and about likelihood of switching if the smoker learned their brand had more of a specific chemical than other cigarettes. Chemicals presented were nicotine, carbon monoxide, lead, formaldehyde, arsenic, and ammonia. RESULTS:Past brand switching to reduce health risk was common among smokers (43% in phone survey, 28% in online survey). Smokers who were female, over 25, and current "light" cigarette users were more likely to have switched brands to reduce health risks (all p < .05). Overall, 61-92% of smokers were susceptible to brand switching based on information about particular chemicals. In both samples, lead, formaldehyde, arsenic, and ammonia led to more susceptibility to switch than nicotine (all p < .05). CONCLUSIONS:Many US smokers have switched brands or styles to reduce health risks. The majority said they might or would definitely switch brands if they learned their cigarettes had more of a toxic chemical than other brands. Brand switching is a probable unintended consequence of communications that show differences in smoke chemicals between brands.

The composition of the scientific workforce shapes the direction of scientific research, directly through the selection of questions to investigate, and indirectly through its influence on the training of future scientists. In most fields, however, complete census information is difficult to obtain, complicating efforts to study workforce dynamics and the effects of policy. This is particularly true in computer science, which lacks a single, all-encompassing directory or professional organization. A full census of computer science would serve many purposes, not the least of which is a better understanding of the trends and causes of unequal representation in computing. Previous academic census efforts have relied on narrow or biased samples, or on professional society membership rolls. A full census can be constructed directly from online departmental faculty directories, but doing so by hand is expensive and time-consuming. Here, we introduce a topical web crawler for automating the collection of faculty information from web-based department rosters, and demonstrate the resulting system on the 205 PhD-granting computer science departments in the U.S. and Canada. This method can quickly construct a complete census of the field, and achieve over 99% precision and recall. We conclude by comparing the resulting 2017 census to a hand-curated 2011 census to quantify turnover and retention in computer science, in general and for female faculty in particular, demonstrating the types of analysis made possible by automated census construction.

International trade of the invasive South African clawed frog (Xenopus laevis), a subclinical carrier of the fungal pathogen Batrachochytrium dendrobatis (Bd) has been proposed as a major means of introduction of Bd into naïve, susceptible amphibian populations. The historical presence of Bd in the indigenous African population of Xenopus is well documented. However, there are no reports documenting the presence of Bd in wild Xenopus populations in the US, particularly in California where introduced populations are well-established after intentional or accidental release. In this report, a survey was conducted on 178 archived specimens of 6 species of Xenopus collected in Africa from 1871-2000 and on 23 archived specimens (all wild-caught Xenopus laevis) collected in California, USA between 2001 and 2010. The overall prevalence rate of Bd in the tested Xenopus was 2.8%. The earliest positive specimen was X. borealis collected in Kenya in 1934. The overall prevalence of Bd in the X. laevis collected in California was 13% with 2 positive specimens from 2001 and one positive specimen from 2003. The positive Xenopus (3/23) collected in California were collected in 2001 (2/3) and 2003 (1/3). These data document the presence of Bd-infected wild Xenopus laevis in California. The findings reported here support the prevailing hypothesis that Bd was present as a stable, endemic infection in Xenopus populations in Africa prior to their worldwide distribution likely via international live-amphibian trade.

There is no consensus on optimal use of radiotherapy following radical prostatectomy. The purpose of this study was to describe opinions of urologists and radiation oncologists regarding adjuvant and salvage radiotherapy following radical prostatectomy.Urologists and genitourinary radiation oncologists were solicited to participate in an online survey. Respondent characteristics included demographics, training, practice setting, patient volume/experience, and access to radiotherapy. Participant practice patterns and attitudes towards use of adjuvant and salvage radiotherapy in standardized clinical scenarios were assessed.One hundred and forty-six staff physicians participated in the survey (104 urologists and 42 genitourinary radiation oncologists). Overall, high Gleason score (Gleason 7 vs. 6, RR 1.37 95% CI 1.19-1.56, p

Pax3 is a developmental transcription factor that is required for neural tube and neural crest development. We previously showed that inactivating the p53 tumor suppressor protein prevents neural tube and cardiac neural crest defects in Pax3-mutant mouse embryos. This demonstrates that Pax3 regulates these processes by blocking p53 function. Here we investigated the mechanism by which Pax3 blocks p53 function.We employed murine embryonic stem cell (ESC)-derived neuronal precursors as a cell culture model of embryonic neuroepithelium or neural crest. Pax3 reduced p53 protein stability, but had no effect on p53 mRNA levels or the rate of p53 synthesis. Full length Pax3 as well as fragments that contained either the DNA-binding paired box or the homeodomain, expressed as GST or FLAG fusion proteins, physically associated with p53 and Mdm2 both in vitro and in vivo. In contrast, Splotch Pax3, which causes neural tube and neural crest defects in homozygous embryos, bound weakly, or not at all, to p53 or Mdm2. The paired domain and homeodomain each stimulated Mdm2-mediated ubiquitination of p53 and p53 degradation in the absence of the Pax3 transcription regulatory domains, whereas Splotch Pax3 did not stimulate p53 ubiquitination or degradation.Pax3 inactivates p53 function by stimulating its ubiquitination and degradation. This process utilizes the Pax3 paired domain and homeodomain but is independent of DNA-binding and transcription regulation. Because inactivating p53 is the only required Pax3 function during neural tube closure and cardiac neural crest development, and inactivating p53 does not require Pax3-dependent transcription regulation, this indicates that Pax3 is not required to function as a transcription factor during neural tube closure and cardiac neural crest development. These findings further suggest novel explanations for PAX3 functions in human diseases, such as in neural crest-derived cancers and Waardenburg syndrome types 1 and 3.

Association studies are a promising way to uncover the genetic basis of complex traits in wild populations. Data on population stratification, linkage disequilibrium and distribution of variant effect-sizes for different trait-types are required to predict study success but are lacking for most taxa. We quantified and investigated the impacts of these key variables in a large-scale association study of a strongly selected trait of medical importance: pyrethroid resistance in the African malaria vector Anopheles gambiae.We genotyped ≈1500 resistance-phenotyped wild mosquitoes from Ghana and Cameroon using a 1536-SNP array enriched for candidate insecticide resistance gene SNPs. Three factors greatly impacted study power. (1) Population stratification, which was attributable to co-occurrence of molecular forms (M and S), and cryptic within-form stratification necessitating both a partitioned analysis and genomic control. (2) All SNPs of substantial effect (odds ratio, OR>2) were rare (minor allele frequency, MAF

The susceptibility status of Anopheles funestus to insecticides remains largely unknown in most parts of Africa because of the difficulty in rearing field-caught mosquitoes of this malaria vector. Here we report the susceptibility status of the An. funestus population from Tororo district in Uganda and a preliminary characterisation of the putative resistance mechanisms involved.A new forced egg laying technique used in this study significantly increased the numbers of field-caught females laying eggs and generated more than 4000 F1 adults. WHO bioassays indicated that An. funestus in Tororo is resistant to pyrethroids (62% mortality after 1 h exposure to 0.75% permethrin and 28% mortality to 0.05% deltamethrin). Suspected DDT resistance was also observed with 82% mortality. However this population is fully susceptible to bendiocarb (carbamate), malathion (organophosphate) and dieldrin with 100% mortality observed after exposure to each of these insecticides. Sequencing of a fragment of the sodium channel gene containing the 1014 codon conferring pyrethroid/DDT resistance in An. gambiae did not detect the L1014F kdr mutation but a correlation between haplotypes and resistance phenotype was observed indicating that mutations in other exons may be conferring the knockdown resistance in this species. Biochemical assays suggest that resistance in this population is mediated by metabolic resistance with elevated level of GSTs, P450s and pNPA compared to a susceptible strain of Anopheles gambiae. RT-PCR further confirmed the involvement of P450s with a 12-fold over-expression of CYP6P9b in the Tororo population compared to the fully susceptible laboratory colony FANG.This study represents the first report of pyrethroid/DDT resistance in An. funestus from East Africa. With resistance already reported in southern and West Africa, this indicates that resistance in An. funestus may be more widespread than previously assumed and therefore this should be taken into account for the implementation and management of vector control programs in Africa.

Although Anopheles funestus is difficult to rear, it is crucial to analyse field populations of this malaria vector in order to successfully characterise mechanisms of insecticide resistance observed in this species in Africa. In this study we carried out a large-scale field collection and rearing of An. funestus from Mozambique in order to analyse its susceptibility status to insecticides and to broadly characterise the main resistance mechanisms involved in natural populations.3,000 F(1) adults were obtained through larval rearing. WHO susceptibility assays indicated a very high resistance to pyrethroids with no mortality recorded after 1 h 30 min exposure and less than 50% mortality at 3 h 30 min. Resistance to the carbamate, bendiocarb was also noted, with 70% mortality after 1h exposure. In contrast, no DDT resistance was observed, indicating that no kdr-type resistance was involved. The sequencing of the acetylcholinesterase gene indicated the absence of the G119S and F455W mutations associated with carbamate and organophosphate resistance. This could explain the absence of malathion resistance in this population. Both biochemical assays and quantitative PCR implicated up-regulated P450 genes in pyrethroid resistance, with GSTs playing a secondary role. The carbamate resistance observed in this population is probably conferred by the observed altered AChE with esterases also involved.The high level of pyrethroid resistance in this population despite the cessation of pyrethroid use for IRS in 1999 is a serious concern for resistance management strategies such as rotational use of insecticides. As DDT has now been re-introduced for IRS, susceptibility to DDT needs to be closely monitored to prevent the appearance and spread of resistance to this insecticide.