Search

The harm caused by cigarette smoking is overwhelmingly due to byproducts of tobacco combustion. Electronic Nicotine Delivery Systems (ENDS) provide nicotine to users without combustion, and may support tobacco harm reduction among cigarette smokers who would not otherwise quit in the near term. Analyses of Wave 5 of the Population Assessment of Tobacco and Health (PATH) Study compared biomarkers of exposure (BOE) levels for nicotine, 3 metals, 2 tobacco-specific nitrosamines and 14 smoking-related volatile organic compounds in 151 exclusive ENDS users, 1341 exclusive cigarette smokers, 115 dual users (cigarettes and ENDS), and 1846 past 30-day nonusers of tobacco, adjusting for demographics. Nicotine exposure in ENDS users and dual users did not significantly differ from smokers. Among ENDS users, 16 of 18 other BOEs were significantly lower than smokers’; 9 BOEs were not significantly different from nonusers. Among dual users smoking

BackgroundIn diploid organisms, phasing is the problem of assigning the heterozygous variants to one of two haplotypes. Reads from PacBio HiFi sequencing provide long, accurate observations that can be used as the basis for both calling and phasing variants. HiFi reads also excel at calling larger classes of variation such as structural variants. However, current phasing tools typically only phase small variants, leaving larger structural variants unphased.MethodsWe developed HiPhase, a tool that jointly phases SNVs, indels, and structural variants. The main benefits of HiPhase are 1) dual mode allele assignment for detecting structural variants, 2) a novel application of the A*-algorithm to phasing, and 3) logic allowing phase blocks to span breaks caused by alignment issues around reference gaps and homozygous deletions.ResultsIn our assessment, HiPhase produced an average phase block NG50 of 493 kb with 933 switchflip errors and fully phased 95.2% of genes, improving over the current state of the art. Additionally, HiPhase jointly phases SNVs, indels, and structural variants and includes innate multi-threading, statistics gathering, and concurrent phased alignment output generation.Availabilityhttps://github.com/PacificBiosciences/HiPhase

This article reads Buṭrus al-Bustānī’s 1861 translation of Daniel Defoe's 1719 Robinson Crusoe into Arabic in Beirut alongside Karl Marx's contemporaneous critique of the popularity of Robinsonades among British political economists. Al-Bustānī’s translation of Robinson Crusoe sought to synch Arabic up with a global age of double-column bookkeeping, the telegraph, the steamship, and the newspaper, and in turn supplant the Indian Ocean stories of Sindbad the Sailor among Beirut's merchants. The latter story cycle constitutes Arabic literary capital appropriated, enumerated, and rendered exchangeable by the new novel form in the serialized English press of the mercantilist era. In Capital, Vol. 1, in the chapter “The Fetishism of Commodities and the Secret Thereof,” Marx represents Robinson not as a well-armed slave trader, but rather as endowed with only a watch (unbeknownst to Defoe), paper, pen, and ink. With these tools Marx's Robinson enacts the theory of value in the time of factory labor and the incomplete abolition of slavery. Al-Bustānī—like Faraḥ Anṭūn forty years later—confronts this unevenly syncopated, up-to-the-minute temporality in Arabic, as imperial finance reshapes the resources of the Eastern Mediterranean and migrant laborers depart its shores to work in textile mills in Argentina, Brazil, and the United States.

The attainment of professional competencies leads to essential skills for successful and employable veterinarians. However, the inclusion of professional competencies in veterinary curricula is often underdeveloped, and it is sometimes less appreciated by students than the science/technical skill curricula. The aim of this study was to better understand students’ motivation within professional competency courses (PC courses) by (a) comparing students’ motivational perceptions in PC courses to those in science/technical skill courses (ST courses), (b) determining the extent to which students’ motivational perceptions predict their course effort, and (c) identifying teaching strategies that could be used to improve PC courses. Participants included students from eight courses enrolled in their first or second year of a veterinary college at a large land-grant university in the United States. A partially mixed concurrent dominant status research design was used to collect quantitative and qualitative data. Students completed closed- and open-ended survey items regarding their effort and the motivational climate in their courses. Compared to ST courses, students put forth less effort in PC courses; rated PC courses lower on empowerment, usefulness, and interest; and had higher success expectancies in PC courses. Although students’ perceptions of empowerment, usefulness, interest, and caring were significantly correlated with their effort, interest was the most significant predictor of effort in both PC and ST courses. Based on students’ responses to the open-ended questions, specific motivational strategies are recommended to increase students’ effort in PC courses, such as intentionally implementing strategies to increase students’ interest and perceptions of usefulness and empowerment.

Between November and December 2021, the first ever recorded outbreak of enteroinvasive Escherichia coli in Denmark occurred at national scale. We describe the investigation of this outbreak, which was initially recognised in early December 2021. A total of 88 cases (58 female; 30 male) with a median age of 52 years (range: 0–91) were detected by PCR-based diagnostic methods. Case ascertainment was complicated by current culture-free diagnostic procedures, with only 34 cases confirmed by culture, serotyping and whole genome sequencing. Isolates from cases grouped into two serotypes (O136:H7 and O96:H19), which was supported by whole-genome-sequence-phylogeny, also yielding two clusters. Interviews of 42 cases and traceback investigation pointed towards consumption of ready-to-eat salads as the outbreak cause. While the ready-to-eat salads comprised different vegetables, imported spring onions were the only common ingredient and thus the likely source. Environmental investigations failed to recover outbreak strains. This report highlights the value of fast typing (here O-typing) to confirm cases in an outbreak situation. Timely communication and data sharing are also important, and were facilitated by the national collaboration between relevant laboratories, the public health institute and the veterinary and food administration. High hygiene standards for imported fresh vegetables intended for ready-to-eat products are essential.

In cooperative species, human-induced rapid environmental change may threaten cost–benefit tradeoffs of group behavioral strategies that evolved in past environments. Capacity for behavioral flexibility can increase population viability in novel environments. Whether the partitioning of individual responsibilities within social groups is fixed or flexible across populations is poorly understood, despite its relevance for predicting responses to global change at the population and species levels and designing successful conservation programs. We leveraged bio-logging data from two populations of fish-eating killer whales (Orcinus orca) to quantify patterns of fine-scale foraging movements and their relationships with demography. We reveal striking interpopulation differences in patterns of individual foraging behavior. Females from the endangered Southern Resident (SRKW) population captured less prey and spent less time pursuing prey than SRKW males or Northern Resident (NRKW) females, whereas NRKW females captured more prey than NRKW males. The presence of a calf (≤3 years) reduced the number of prey captured by adult females from both populations, but disproportionately so for SRKW. SRKW adult males with a living mother captured more prey than those whose mother had died, whereas the opposite was true for NRKW adult males. Across populations, males foraged in deeper areas than females, and SRKW captured prey deeper than NRKW. These population-level differences in patterns of individual foraging behavior challenge the existing paradigm that females are the disproportionate foragers in gregarious resident killer whales, and demonstrate considerable variation in the foraging strategies across populations of an apex marine predator experiencing different environmental stressors.

BackgroundUnrecognised changes in a hospitalised patient’s clinical course may lead to a preventable adverse event. Early warning systems (EWS) use patient data, such as vital signs, nursing assessments and laboratory values, to aid in the detection of early clinical deterioration. In 2018, an EWS programme was deployed at an academic hospital that consisted of a commercially available EWS algorithm and a centralised virtual nurse team to monitor alerts. Our objective was to understand the nursing perspective on the use of an EWS programme with centralised monitoring.MethodsWe conducted and audio-recorded semistructured focus groups during nurse staff meetings on six inpatient units, stratified by alert frequency (high: >100 alerts/month; medium: 50–100 alerts/month; low: ResultsWe conducted 28 focus groups with 227 bedside nurses across all shifts. We identified six principal themes: (1) Alert timeliness, nurses reported being aware of the patient’s deterioration before the EWS alert, (2) Lack of accuracy, nurses perceived most alerts as false positives, (3) Workflow interruptions caused by EWS alerts, (4) Questions of actionability of alerts, nurses were often uncertain about next steps, (5) Concerns around an underappreciation of core nursing skills via reliance on the EWS programme and (6) The opportunity cost of deploying the EWS programme.ConclusionThis qualitative study of nurses demonstrates the importance of earning user trust, ensuring timeliness and outlining actionable next steps when implementing an EWS. Careful attention to user workflow is required to maximise EWS impact on improving hospital quality and patient safety.

Successful use of biomedical forms of HIV risk-reduction may have predisposed many gay and bisexual men (GBM) to vaccination against COVID-19, which may, in turn, affect their sexual behavior. A total of 622 Australian GBM provided weekly data on COVID-19 vaccination history and sexual behaviour between 17 January 2021 and 22 June 2021. We identify factors associated with COVID-19 vaccination, and compare sexual behavior before and since vaccination. Mean age was 47.3 years (SD 14.0). At least one-dose vaccination coverage had reached 57.2%, and 61.3% reported that the majority of their friends intended to be vaccinated. Vaccinated men reported a mean of 1.11 (SD 2.10) weekly non-relationship sex partners before vaccination and 1.62 (SD 3.42) partners following vaccination. GBM demonstrated high confidence in COVID-19 vaccines. Their sexual activity increased following vaccination suggesting that greater sexual freedom may be a specific motivation for vaccine uptake among some men.

Motivationgene co-expression networks have been widely applied to identify critical genes and pathways for neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. Now, with the advent of single-cell RNA-sequencing, we have the opportunity to create cell-type specific gene co-expression networks. However, single-cell RNA-sequencing data is characterized by its sparsity, amongst some other issues raised by this new type of data.ResultsWe present scCoExpNets, a framework for the discovery and analysis of cell-type specific gene coexpression networks (GCNs) from single-cell RNA-seq data. We propose a new strategy to address the problem of sparsity, named iterative pseudo-cell identification. It consists of adding the gene expression of pairs of cells that belong to the same individual and the same cell-type while the number of cells is over 200, thus creating multiple matrices and multiple scGCNs for the same cell-type, all of them seen as alternative and complementary views of the same phenomena. We applied this new tool on a snRNA-seq dataset human post-mortem substantia nigra pars compacta tissue of 13 controls and 14 Parkinson’s disease (PD) cases (18 males and 9 females) with 30-99 years. We show that one of the hypotheses that support the selective vulnerability of dopaminergic neurons in PD, the iron accumulation, is sustained in our dopaminergic neurons network models. Moreover, after successive pseudo-celluling iterations, the gene groups sustaining this hypothesis remain intact. At the same time, this pseudo-celulling strategy also allows us to discover genes whose grouping changes considerably throughout the iterations and provides new insights. Finally, since some of our models were correlated with diagnosis and age at the same time, we also developed our own framework to create covariate-specific GCNs, called CovCoExpNets. We applied this new software to our snRNA-seq dataset and we identified 11 age-specific genes and 5 diagnosis-specific genes which do not overlap.Availability and implementationThe CoExpNets implementations are available as R packages: scCoExpNets for creating single-cell GCNs and CovCoExpNets for creating covariate-specific GCNs. Users can either download the development version via githubhttps://github.com/aliciagp/scCoExpNetsandhttps://github.com/aliciagp/CovCoExpNetsContactalicia.gomez1@um.esSupplementary informationsupplementary data is available online.

SUMMARYTemperature affects elastic rock properties but is less-studied and thus less-understood than pressure and stress. Thermal effects on dispersion are experimentally observed herein from seismic to ultrasonic frequencies: Young’s moduli and Poisson’s ratios plus P- and S-wave velocities are determined by forced oscillation (FO) from 1 to 144 Hz and by pulse transmission at 500 kHz. Despite being the dominant sedimentary rock type, shales receive less experimental attention than sandstones and carbonates. To our knowledge, no other FO studies on shale at above ambient temperatures exist. Temperature fluctuations are enforced by two temperature cycles from 20 via 40 to 60 °C and vice versa. Measured rock properties are initially irreversible but become reversible with increasing number of heating and cooling segments. Rock property sensitivity to temperature is likewise reduced. It is revealed that dispersion shifts towards higher frequencies with increasing temperature (reversible if decreased), Young’s moduli and P-wave velocity maxima occur at 40 °C for frequencies below 56 Hz, and S-wave velocities remain unchanged with temperature (if the first heating segment is neglected) at seismic frequencies. In comparison, ultrasonic P- and S-wave velocities are found to decrease with increasing temperatures. Behavioural differences between seismic and ultrasonic properties are attributed to decreasing fluid viscosity with temperature. We hypothesize that our ultrasonic recordings coincide with the transition-phase separating the low- and high-frequency regimes while our seismic recordings are within the low-frequency regime.

The traditional, triangular yield-line method used by most departments of transportation for analyzing concrete traffic barriers and bridge rails has been largely unchanged since 1978. Testing of concrete barriers since this time has indicated that the triangular yield-line method is not qualitatively representative of observed damage patterns and is overconservative. Further, the conversion from NCHRP Report 350 to the crash test criteria from the Manual for Assessing Safety Hardware (MASH) will result in increases to lateral impact loads; therefore, overconservative analysis practices may result in many concrete barriers being unnecessarily deemed inadequate. In this research, alternative analysis methods for concrete barriers were extracted from an extensive literature review of concrete barrier investigations. These methods were applied to a sample of eight concrete barriers to demonstrate and compare their effects on capacity estimates. Alternative methods included trapezoidal yield-line mechanisms, effects of impact heights lower than the top of the barrier, punching shear evaluation, and consideration of expected material strengths. Capacity estimates of the selected barriers were increased by an average of 47 percent when alternative methods were cumulatively applied. Although the traditional method does not consider punching shear, the capacity of one of the eight barriers was controlled by punching shear rather than by yield-line flexure. With the alternative methods applied, seven of the eight barriers were deemed adequate relative to the increased lateral loads corresponding to MASH criteria for Test Levels 2 through 5. By contrast, if analyzed according to the traditional method, three of the eight barriers would have been deemed insufficient considering MASH loads.

Regret describes recognizing alternative actions could have led to better outcomes. It remains unclear whether regret derives from generalized mistake appraisal or instead comprises dissociable, action-specific processes. Using a neuroeconomic task, we found that mice were sensitive to fundamentally distinct types of regret following exposure to chronic social defeat stress or manipulations of CREB, a transcription factor implicated in stress action. Bias to make compensatory decisions after rejecting high-value offers (regret type I) was unique to stress-susceptible mice. Bias following the converse operation, accepting low-value offers (regret type II), was enhanced in stress-resilient mice and absent in stress-susceptible mice. CREB function in either the prefrontal cortex or nucleus accumbens was required to suppress regret type I but bidirectionally regulated regret type II. We provide insight into how maladaptive stress response traits relate to distinct forms of counterfactual thinking, which could steer therapy for mood disorders, such as depression, toward circuit-specific computations through a careful description of decision narrative.

Patient education and resources that address barriers to health literacy to improve understanding in pancreatic cancer are limited. We evaluated the impact and outcomes benefits of Animated Pancreas Patient (APP) cancer educational modules (APP website and YouTube).A retrospective study of APP metrics and utilization data from September 2013 to February 2021 was conducted. We evaluated audience reach and calculated top views by media type (animation/expert video/patient video/slideshow) and top retention videos from the modules.During the study period, APP had 4,551,079 views worldwide of which 2,757,064 unique visitors or 60% were from the United States. Of these, 54% were patients, 17% were family members or caregivers, 16% were health care providers, and 13% were other. The most popular topic viewed among the animations was "Understanding Clinical Trials" (n = 182,217), and the most common expert video viewed was "What are the different stages of pancreatic cancer?" (n = 15,357).Pancreatic cancer patient education using APP's visual formats of learning demonstrated a wide reach and had a significant impact on improved understanding among patients, families, and caregivers. Continued efforts should be made to provide patient resources that address health literacy, better quality of life and improved health outcomes in pancreatic cancer.

Background: Salmonella enterica is among the major burdens for public health at global level. Typing of salmonellae below the species level is fundamental for different purposes, but traditional methods are expensive, technically demanding, and time-consuming, and therefore limited to reference centers. Fourier transform infrared (FTIR) spectroscopy is an alternative method for bacterial typing, successfully applied for classification at different infra-species levels.Aim: This study aimed to address the challenge of subtyping Salmonella enterica at O-serogroup level by using FTIR spectroscopy. We applied machine learning to develop a novel approach for S. enterica typing, using the FTIR-based IR Biotyper® system (IRBT; Bruker Daltonics GmbH & Co. KG, Germany). We investigated a multicentric collection of isolates, and we compared the novel approach with classical serotyping-based and molecular methods.Methods: A total of 958 well characterized Salmonella isolates (25 serogroups, 138 serovars), collected in 11 different centers (in Europe and Japan), from clinical, environmental and food samples were included in this study and analyzed by IRBT. Infrared absorption spectra were acquired from water-ethanol bacterial suspensions, from culture isolates grown on seven different agar media. In the first part of the study, the discriminatory potential of the IRBT system was evaluated by comparison with reference typing method/s. In the second part of the study, the artificial intelligence capabilities of the IRBT software were applied to develop a classifier for Salmonella isolates at serogroup level. Different machine learning algorithms were investigated (artificial neural networks and support vector machine). A subset of 88 pre-characterized isolates (corresponding to 25 serogroups and 53 serovars) were included in the training set. The remaining 870 samples were used as validation set. The classifiers were evaluated in terms of accuracy, error rate and failed classification rate.Results: The classifier that provided the highest accuracy in the cross-validation was selected to be tested with four external testing sets. Considering all the testing sites, accuracy ranged from 97.0% to 99.2% for non-selective media, and from 94.7% to 96.4% for selective media.Conclusions: The IRBT system proved to be a very promising, user-friendly, and cost-effective tool for Salmonella typing at serogroup level. The application of machine learning algorithms proved to enable a novel approach for typing, which relies on automated analysis and result interpretation, and it is therefore free of potential human biases. The system demonstrated a high robustness and adaptability to routine workflows, without the need of highly trained personnel, and proving to be suitable to be applied with isolates grown on different agar media, both selective and unselective. Further tests with currently circulating clinical, food and environmental isolates would be necessary before implementing it as a potentially stand-alone standard method for routine use.

Variants of uncertain significance (VUS) are a common result of diagnostic genetic testing and can be difficult to manage with potential misinterpretation and downstream costs, including time investment by clinicians. We investigated the rate of VUS reported on diagnostic testing via multi-gene panels (MGPs) and exome and genome sequencing (ES/GS) to measure the magnitude of uncertain results and explore ways to reduce their potentially detrimental impact. We collected data from over 1.5 million genetic tests from 19 clinical laboratories across the United States and Canada from during 2020-2021. We found a lower rate of inconclusive results due to VUS on ES/GS tests compared to MGPs (22.5% vs. 32.6%; p

The complex nature of the transcriptional networks underlying addictive behaviors suggests intricate cooperation between diverse gene regulation mechanisms that go beyond canonical activity-dependent pathways. Here we implicate in this process a novel nuclear receptor transcription factor, Retinoid X Receptor Alpha (RXRα), which we identified bioinformatically as associated with addiction-like behaviors. In the nucleus accumbens (NAc) of male and female mice, we show that, while its own expression remains unaltered after cocaine exposure, RXRα controls plasticity- and addiction-relevant transcriptional programs in both dopamine receptor D1- and D2-expressing medium spiny neurons, which in turn modulate intrinsic excitability and synaptic activity of these NAc cell types. Behaviorally, bidirectional viral and pharmacological manipulation of RXRα regulates drug reward sensitivity in both non-operant and operant paradigms. Together, this study demonstrates a key role for NAc RXRα in promoting drug addiction, and paves the way for future studies of rexinoid signaling in psychiatric disease states.

Cretaceous shales from the emerging gas province of the Rovuma basin are examined using well‐log data from two exploration wells. The P‐wave acoustic impedance (AIp) data were estimated, and then brittleness and ductility were assessed within the framework of the Reuss–Voigt limits for acoustic impedance. We then predicted the shale consolidation using a weighting function (Wc) which varies between 0 for the case of grains in suspension (the Reuss limit) and 1 for the case of consolidated rock or cemented shale (the Voigt limit). At the Reuss limit, the formation AIp is highly sensitive to pressure while at the Voigt limit the formation AIp is insensitive to pressure. For the wells in this study, most data plot close to the lower bound with Wc 58°C. These differences in the development and rate of chemical diagenesis in the same formation are likely due to contrasts in the rate of burial and have important implications for future seismic exploration studies.

Mary Robinson’s Lyrical Tales (1800) has long been understood as a retort to William Wordsworth and Samuel Taylor Coleridge’s first edition of Lyrical Ballads (1798) and has long been admired for i...

Objectives: We assessed adult never smokers' trajectories of smoking over 12 months after a first-time JUUL Starter Kit (JSK) purchase. Methods: Adult (≥ 21) never smokers (N = 3853) who purchased a JSK were recruited into an observational naturalistic study. Analyses distinguished those who had previously used ENDS (NS+E, N = 2848) from those who had not (NS-NE, N = 1005). Participants were invited to complete follow-up assessments at 1, 2, 3, 6, 9, and 12 months. "Smoking" was defined as any past-30-day smoking ("even a puff"). Results: Past-30-day smoking was reported by 5.01% of NS+E at month one, and 7.56% at month 12; for NS-NE, these were 10.23% and 12.35%. In both groups, < 5% reported smoking at both 9 and 12 months. Across follow-ups, 25%-49% of those reporting having smoked then said they were now smoking "not at all"; the remainder reported low frequency (10-12 days-per-month) and quantity (2-4 cigarettes-per-day) of smoking. Past-30-day use of JUUL remained at ≥ 80% across follow-ups. Each additional day-per-month of JUUL use decreased the odds of smoking by 1%. Conclusions: Some adult never smokers who purchased a JSK reported smoking during the suceeding year; smoking was light and intermittent. Participants who used JUUL more frequently were less likely to smoke.