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Cryo-soft-X-ray tomography is being increasingly used in biological research to study the morphology of cellular compartments and how they change in response to different stimuli, such as viral infections. Segmentation of these compartments is limited by time-consuming manual tools or machine learning algorithms that require extensive time and effort to train. Here we describe Contour, a new, easy-to-use, highly automated segmentation tool that enables accelerated segmentation of tomograms to delineate distinct cellular compartments. Using Contour, cellular structures can be segmented based on their projection intensity and geometrical width by applying a threshold range to the image and excluding noise smaller in width than the cellular compartments of interest. This method is less laborious and less prone to errors from human judgement than current tools that require features to be manually traced, and it does not require training datasets as would machine-learning driven segmentation. We show that high-contrast compartments such as mitochondria, lipid droplets, and features at the cell surface can be easily segmented with this technique in the context of investigating herpes simplex virus 1 infection. Contour can extract geometric measurements from 3D segmented volumes, providing a new method to quantitate cryo-soft-X-ray tomography data. Contour can be freely downloaded at github.com/kamallouisnahas/Contour.
The coronavirus disease 2019 (COVID-19) pandemic has challenged the ability of Emergency Medical Services (EMS) providers to maintain personal safety during the treatment and transport of patients potentially infected. Increased rates of COVID-19 infection in EMS providers after patient care exposure, and notably after performing aerosol-generating procedures (AGPs), have been reported. With an already strained workforce seeing rising call volumes and increased risk for AGP-requiring patient presentations, development of novel devices for the protection of EMS providers is of great importance.
Based on the concept of a negative pressure room, the AerosolVE BioDome is designed to encapsulate the patient and contain aerosolized infectious particles produced during AGPs, making the cabin of an EMS vehicle safer for providers. The objective of this study was to determine the efficacy and safety of the tent in mitigating simulated infectious particle spread in varied EMS transport platforms during AGP utilization.
Methods:
Fifteen healthy volunteers were enrolled and distributed amongst three EMS vehicles: a ground ambulance, an aeromedical-configured helicopter, and an aeromedical-configured jet. Sodium chloride particles were used to simulate infectious particles and particle counts were obtained in numerous locations close to the tent and around the patient compartment. Counts near the tent were compared to ambient air with and without use of AGPs (non-rebreather mask, continuous positive airway pressure [CPAP] mask, and high-flow nasal cannula [HFNC]).
Results:
For all transport platforms, with the tent fan off, the particle generator alone, and with all AGPs produced particle counts inside the tent significantly higher than ambient particle counts (P <.0001). With the tent fan powered on, particle counts near the tent, where EMS providers are expected to be located, showed no significant elevation compared to baseline ambient particle counts during the use of the particle generator alone or with use of any of the AGPs across all transport platforms.
Conclusion:
Development of devices to improve safety for EMS providers to allow for use of all available therapies to treat patients while reducing risk of communicable respiratory disease transmission is of paramount importance. The AerosolVE BioDome demonstrated efficacy in creating a negative pressure environment and workspace around the patient and provided significant filtration of simulated respiratory droplets, thus making the confined space of transport vehicles potentially safer for EMS personnel.
Economic incentives are in widespread use to stimulate the development of the electric vehicle industry. However, the distributional effects of such incentives have been subject to little empirical inquiry. This study examines how California’s electric vehicle rebate program impacts different income groups financially. Two effects are considered: the income distribution of rebate beneficiaries and the income distribution of the rebate payers. The results reveal that the overall net financial impacts of the electric vehicle rebate program are regressive: the benefit distribution is highly regressive while the cost distribution is slightly progressive. Recent efforts to improve the fairness of the rebate program do not alter our findings. Policy implications are discussed.
The coronavirus disease 2019 (COVID-19) pandemic has created challenges in maintaining the safety of prehospital providers caring for patients. Reports have shown increased rates of Emergency Medical Services (EMS) provider infection with COVID-19 after patient care exposure, especially while utilizing aerosol-generating procedures (AGPs). Given the increased risk and rising call volumes for AGP-necessitating complaints, development of novel devices for the protection of EMS clinicians is of great importance.
Drawn from the concept of the powered air purifying respirator (PAPR), the AerosolVE helmet creates a personal negative pressure space to contain aerosolized infectious particles produced by patients, making the cabin of an EMS vehicle safer for providers. The helmet was developed initially for use in hospitals and could be of significant use in the prehospital setting. The objective of this study was to determine the efficacy and safety of the helmet in mitigating simulated infectious particle spread in varied EMS transport platforms during AGP utilization.
Methods:
Fifteen healthy volunteers were enrolled and distributed amongst three EMS vehicles: a ground ambulance, a medical helicopter, and a medical jet. Sodium chloride particles were used to simulate infectious particles, and particle counts were obtained in numerous locations close to the helmet and around the patient compartment. Counts near the helmet were compared to ambient air with and without use of AGPs (non-rebreather mask [NRB], continuous positive airway pressure mask [CPAP], and high-flow nasal cannula [HFNC]).
Results:
Without the helmet fan on, the particle generator alone and with all AGPs produced particle counts inside the helmet significantly higher than ambient particle counts. With the fan on, there was no significant difference in particle counts around the helmet compared to baseline ambient particle counts. Particle counts at the filter exit averaged less than one despite markedly higher particle counts inside the helmet.
Conclusion:
Given the risk to EMS providers by communicable respiratory diseases, development of devices to improve safety while still enabling use of respiratory therapies is of paramount importance. The AerosolVE helmet demonstrated efficacy in creating a negative pressure environment and provided significant filtration of simulated respiratory droplets, thus making the confined space of transport vehicles potentially safer for EMS personnel.
Online peer support platforms have been shown to provide a supportive space that can enhance social connectedness and personal empowerment. Some studies have analysed forum messages, showing that users describe a range of advantages, and some disadvantages to their use. However, the direct examination of users’ experiences of such platforms is rare and may be particularly informative for enhancing their helpfulness. This study aimed to understand users’ experiences of the Support, Hope and Recovery Online Network (SHaRON), an online cognitive behavioural therapy-based peer support platform for adults with mild to moderate anxiety or depression. Platform users (n = 88) completed a survey on their use of different platform features, feelings about using the platform, and overall experience. Responses were analysed descriptively and using thematic analysis. Results indicated that most features were generally well used, with the exception of private messaging. Many participants described feeling well supported and finding the information and resources helpful; the majority of recent users (81%) rated it as helpful overall. However, some participants described feeling uncomfortable about posting messages, and others did not find the platform helpful and gave suggestions for improvements. Around half had not used the platform in the past 3 months, for different reasons including feeling better or forgetting about it. Some described that simply knowing it was there was helpful, even without regular use. The findings highlight what is arguably a broader range of user experiences than observed in previous studies, which may have important implications for the enhancement of SHaRON and other platforms.
Key learning aims
(1) To understand what an online peer support platform is and how this can be used to support users’ mental health.
(2) To learn how users described their experience of the SHaRON platform.
(3) To understand the benefits that online peer support may provide.
(4) To consider what users found helpful and unhelpful, and how this might inform the further development of these platforms.
Background: Visual impairment exists for an estimated 70% of individuals who have experienced a stroke. Identification and remediation of visual impairments can improve overall function and perceived quality of life. Our project aims to improve visual assessment and timely intervention for patients with post-stroke visual impairment (PSVI). Methods: We conducted a quality improvement initiative to create a standardized screening and referral process for patients with PSVI to access an orthoptist. Post-stroke visual impairment was assessed by way of the Visual Screen Assessment (VISA) tool, administered by an occupational therapist. Patients filled out a VFQ-25 questionnaire before and after orthoptic assessment and intervention. The VFQ-25 is a validated post-stroke survey assessing a patient’s perceived quality of life. Differences between pre- and post-orthoptic assessment scores will be evaluated. Results: Data collection currently ongoing.The benefits of a standardized screen for PSVI, standardized referral to, and experience with an orthoptist assessment will be determined. Learnings gained will also inform how we can expand the program to benefit a wider demographic of patients. Conclusions: The data gathered and the subsequent analysis will be instrumental in guiding ongoing improvement initiatives for patients with PSVI.
Large truncated spherical near-field systems with conductive or absorbing floors are typically used in the measurement of the performances of vehicle-installed antennas. The main advantage of conductive floor systems is the ease of accommodation of the vehicle under test, but their performances are affected by the interaction with the reflecting ground floor. Instead, absorbing-based systems emulating free-space conditions minimize the effect of the interaction with the floor, but generally require longer setup times, especially at lower frequencies (70–400 MHz), where bulky absorbers are typically used to improve reflectivity levels. Considering scaled measurements of a vehicle model, the performances of these two typical implementations are analyzed in the 84–1500 MHz range and compared to free-space measurements. Absorbers with different dimensions and reflectivity have been installed in the scaled measurement setup, and measured data have been investigated with proper post-processing to verify the applicability to realistic systems. Figures of merit of interest for automotive applications, like gain and partial radiated powers, have been compared to free-space to evaluate the impact of different scenarios.
High levels of early emotionality (of either negative or positive valence) are hypothesized to be important precursors to early psychopathology, with attention-deficit/hyperactivity disorder (ADHD) a prime early target. The positive and negative affect domains are prime examples of Research Domain Criteria (RDoC) concepts that may enrich a multilevel mechanistic map of psychopathology risk. Utilizing both variable-centered and person-centered approaches, the current study examined whether levels and trajectories of infant negative and positive emotionality, considered either in isolation or together, predicted children's ADHD symptoms at 4 to 8 years of age. In variable-centered analyses, higher levels of infant negative affect (at as early as 3 months of age) were associated with childhood ADHD symptoms. Findings for positive affect failed to reach statistical threshold. Results from person-centered trajectory analyses suggest that additional information is gained by simultaneously considering the trajectories of positive and negative emotionality. Specifically, only when exhibiting moderate, stable or low levels of positive affect did negative affect and its trajectory relate to child ADHD symptoms. These findings add to a growing literature that suggests that infant negative emotionality is a promising early life marker of future ADHD risk and suggest secondarily that moderation by positive affectivity warrants more consideration.
We compared the rates of hospital-onset secondary bacterial infections in patients with coronavirus disease 2019 (COVID-19) with rates in patients with influenza and controls, and we investigated reports of increased incidence of Enterococcus infections in patients with COVID-19.
Design:
Retrospective cohort study.
Setting:
An academic quaternary-care hospital in San Francisco, California.
Patients:
Patients admitted between October 1, 2019, and October 1, 2020, with a positive SARS-CoV-2 PCR (N = 314) or influenza PCR (N = 82) within 2 weeks of admission were compared with inpatients without positive SARS-CoV-2 or influenza tests during the study period (N = 14,332).
Methods:
National Healthcare Safety Network definitions were used to identify infection-related ventilator-associated complications (IVACs), probable ventilator-associated pneumonia (PVAP), bloodstream infections (BSIs), and catheter-associated urinary tract infections (CAUTIs). A multiple logistic regression model was used to control for likely confounders.
Results:
COVID-19 patients had significantly higher rates of IVAC and PVAP compared to controls, with adjusted odds ratios of 4.7 (95% confidence interval [CI], 1.7–13.9) and 10.4 (95 % CI, 2.1–52.1), respectively. COVID-19 patients had higher incidence of BSI due to Enterococcus but not BSI generally, and whole-genome sequencing of Enterococcus isolates demonstrated that nosocomial transmission did not explain the increased rate. Subanalyses of patients admitted to the intensive care unit and patients who required mechanical ventilation revealed similar findings.
Conclusions:
COVID-19 is associated with an increased risk of IVAC, PVAP, and Enterococcus BSI compared with hospitalized controls, which is not fully explained by factors such as immunosuppressive treatments and duration of mechanical ventilation. The mechanism underlying increased rates of Enterococcus BSI in COVID-19 patients requires further investigation.
Recent X-ray observations by Jiang et al. have identified an active galactic nucleus (AGN) in the bulgeless spiral galaxy NGC 3319, located just
$14.3\pm 1.1$
Mpc away, and suggest the presence of an intermediate-mass black hole (IMBH;
$10^2\leq M_\bullet/\textrm{M}_{\odot}\leq 10^5$
) if the Eddington ratios are as high as 3 to
$3\times10^{-3}$
. In an effort to refine the black hole mass for this (currently) rare class of object, we have explored multiple black hole mass scaling relations, such as those involving the (not previously used) velocity dispersion, logarithmic spiral arm pitch angle, total galaxy stellar mass, nuclear star cluster mass, rotational velocity, and colour of NGC 3319, to obtain 10 mass estimates, of differing accuracy. We have calculated a mass of
$3.14_{-2.20}^{+7.02}\times10^4\,\textrm{M}_\odot$
, with a confidence of 84% that it is
$\leq $
$10^5\,\textrm{M}_\odot$
, based on the combined probability density function from seven of these individual estimates. Our conservative approach excluded two black hole mass estimates (via the nuclear star cluster mass and the fundamental plane of black hole activity—which only applies to black holes with low accretion rates) that were upper limits of
${\sim}10^5\,{\textrm M}_{\odot}$
, and it did not use the
$M_\bullet$
–
$L_{\textrm 2-10\,\textrm{keV}}$
relation’s prediction of
$\sim$
$10^5\,{\textrm M}_{\odot}$
. This target provides an exceptional opportunity to study an IMBH in AGN mode and advance our demographic knowledge of black holes. Furthermore, we introduce our novel method of meta-analysis as a beneficial technique for identifying new IMBH candidates by quantifying the probability that a galaxy possesses an IMBH.
The primary aim of this study was to assess the epidemiology of carbapenem-resistant Acinetobacter baumannii (CRAB) for 9 months following a regional outbreak with this organism. We also aimed to determine the differential positivity rate from different body sites and characterize the longitudinal changes of surveillance test results among CRAB patients.
Design:
Observational study.
Setting:
A 607-bed tertiary-care teaching hospital in Milwaukee, Wisconsin.
Patients:
Any patient admitted from postacute care facilities and any patient housed in the same inpatient unit as a positive CRAB patient.
Methods:
Participants underwent CRAB surveillance cultures from tracheostomy secretions, skin, and stool from December 5, 2018, to September 6, 2019. Cultures were performed using a validated, qualitative culture method, and final bacterial identification was performed using mass spectrometry.
Results:
In total, 682 patients were tested for CRAB, of whom 16 (2.3%) were positive. Of the 16 CRAB-positive patients, 14 (87.5%) were residents from postacute care facilities and 11 (68.8%) were African American. Among positive patients, the positivity rates by body site were 38% (6 of 16) for tracheal aspirations, 56% (9 of 16) for skin, and 82% (13 of 16) for stool.
Conclusions:
Residents from postacute care facilities were more frequently colonized by CRAB than patients admitted from home. Stool had the highest yield for identification of CRAB.
Various host and parasite factors interact to determine the outcome of infection. We investigated the effects of two factors on the within-host dynamics of malaria in mice: initial infectious dose and co-infection with a helminth that limits the availability of red blood cells (RBCs). Using a statistical, time-series approach to model the within-host ‘epidemiology’ of malaria, we found that increasing initial dose reduced the time to peak cell-to-cell parasite propagation, but also reduced its magnitude, while helminth co-infection delayed peak cell-to-cell propagation, except at the highest malaria doses. Using a mechanistic model of within-host infection dynamics, we identified dose-dependence in parameters describing host responses to malaria infection and uncovered a plausible explanation of the observed differences in single vs co-infections. Specifically, in co-infections, our model predicted a higher background death rate of RBCs. However, at the highest dose, when intraspecific competition between malaria parasites would be highest, these effects of co-infection were not observed. Such interactions between initial dose and co-infection, although difficult to predict a priori, are key to understanding variation in the severity of disease experienced by hosts and could inform studies of malaria transmission dynamics in nature, where co-infection and low doses are the norm.
Since the 2010s, a number of scholars have explicitly worked with the term ‘interpersonal pragmatics’ in order to zoom in on the relational and interpersonal side of communication. The purpose of the chapter is to demonstrate how the research interest on the interpersonal and relational is inspired by (im)politeness, identity construction and communication studies in order to tackle questions about pragmatic variation and interpersonal effects. Interpersonal pragmatics does not propagate a particular methodology nor only one theory but is conceptualized as a perspective on the interpersonal side of language and communication. The chapter draws on and points to a number of earlier chapters dealing with key concepts for this field, such as (im)politeness, relational work, face, identity construction, roles and the social and historical embeddedness of communication. Key themes within interpersonal pragmatics are, among others, negotiations of agreement and disagreement, negotiations of (clashes of) norms and understandings of self and other in particular social contexts.
To describe interfacility transfer communication (IFTC) methods for notification of multidrug-resistant organism (MDRO) status in a diverse sample of acute-care hospitals.
Design:
Cross-sectional survey.
Participants:
Hospitals within the Society for Healthcare Epidemiology of America (SHEA) Research Network (SRN).
Methods:
SRN members completed an electronic survey on protocols and methods for IFTC. We assessed differences in IFTC frequency, barriers, and perceived benefit by presence of an IFTC protocol.
Results:
Among 136 hospital representatives who were sent the survey, 54 (40%) responded, of whom 72% reported having an IFTC protocol in place. The presence of a protocol did not differ significantly by hospital size, academic affiliation, or international status. Of those with IFTC protocols, 44% reported consistent notification of MDRO status (>75% of the time) to receiving facilities, as opposed to 13% from those with no IFTC protocol (P = .04). Respondents from hospitals with IFTC protocols reported significantly fewer barriers to communication compared to those without (2.8 vs 4.3; P = .03). Overall, however, most respondents (56%) reported a lack of standardization in communication. Presence of an IFTC protocol did not affect whether respondents perceived IFTC protocols as having a significant impact on infection prevention or antimicrobial stewardship.
Conclusions:
Most respondents reported having an IFTC protocol, which was associated with reduced communication barriers at transfer. Standardization of protocols and clarity about expectations for sending and receipt of information related to MDRO status may facilitate IFTC and promote appropriate and timely infection prevention practices.
Olanzapine effectively treats schizophrenia and bipolar I disorder (BD-I); however, its use is hindered by significant weight gain. A combination of olanzapine and samidorphan (OLZ/SAM) is in development to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain through opioid-receptor blockade. Here, we summarize OLZ/SAM clinical data.
Methods
The OLZ/SAM development program consists of 18 phase 1–3 clinical studies evaluating antipsychotic and weight mitigation efficacy of OLZ/SAM, along with pharmacokinetics, safety, and tolerability. Safety evaluation also included metabolic laboratory assessments.
Results
OLZ/SAM significantly improved psychotic symptoms (measured by Positive and Negative Syndrome Scale); improvements were similar to that observed with olanzapine vs placebo. OLZ/SAM resulted in significantly less weight gain than olanzapine. Additionally, 2 long-term phase 3 extension studies confirmed the durability of antipsychotic effect, as well as stabilization of weight and metabolic parameters in those continuing treatment. Supporting the potential use of OLZ/SAM in BD-I, OLZ/SAM or olanzapine resulted in bioequivalent olanzapine plasma concentrations, and OLZ/SAM did not affect lithium or valproate pharmacokinetics. OLZ/SAM treatment had no clinically relevant effects on ECG parameters (including QTc interval). OLZ/SAM and olanzapine safety were similar, except for reduced weight gain with OLZ/SAM; no additional safety risks were identified.
Conclusion
Data across 18 OLZ/SAM studies in >1600 subjects support an antipsychotic efficacy and safety profile for OLZ/SAM that is similar to olanzapine, with significantly less weight gain than olanzapine. OLZ/SAM is a potential new treatment for schizophrenia and BD-I patients needing efficacious long-term treatment with reduced risk of weight gain.
To examine associations between diet and risk of developing gastro-oesophageal reflux disease (GERD).
Design:
Prospective cohort with a median follow-up of 15·8 years. Baseline diet was measured using a FFQ. GERD was defined as self-reported current or history of daily heartburn or acid regurgitation beginning at least 2 years after baseline. Sex-specific logistic regressions were performed to estimate OR for GERD associated with diet quality scores and intakes of nutrients, food groups and individual foods and beverages. The effect of substituting saturated fat for monounsaturated or polyunsaturated fat on GERD risk was examined.
Setting:
Melbourne, Australia.
Participants:
A cohort of 20 926 participants (62 % women) aged 40–59 years at recruitment between 1990 and 1994.
Results:
For men, total fat intake was associated with increased risk of GERD (OR 1·05 per 5 g/d; 95 % CI 1·01, 1·09; P = 0·016), whereas total carbohydrate (OR 0·89 per 30 g/d; 95 % CI 0·82, 0·98; P = 0·010) and starch intakes (OR 0·84 per 30 g/d; 95 % CI 0·75, 0·94; P = 0·005) were associated with reduced risk. Nutrients were not associated with risk for women. For both sexes, substituting saturated fat for polyunsaturated or monounsaturated fat did not change risk. For both sexes, fish, chicken, cruciferous vegetables and carbonated beverages were associated with increased risk, whereas total fruit and citrus were associated with reduced risk. No association was observed with diet quality scores.
Conclusions:
Diet is a possible risk factor for GERD, but food considered as triggers of GERD symptoms might not necessarily contribute to disease development. Potential differential associations for men and women warrant further investigation.
Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems.
Methods
The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse (‘baseline’) and the longitudinal Vietnam Era Twin Study of Aging (‘follow-up’). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)].
Results
Total depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07–1.57), erectile dysfunction (OR 1.32, 95% CI 1.10–1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04–1.53), and sleep apnea (OR 1.40, 95% CI 1.13–1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09–1.60).
Conclusions
A history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.