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Background: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery. Design: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (e.g., severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The two independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the two co-primary outcomes. Summary: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery. Population Health Research Institute

Little is known about how nursing care at the end of a child's life impacts long-term parental bereavement. We aimed to explain, contextualize, and examine comparisons between quantitative trends in children's end-of-life care and parents' qualitative perceptions. We used a mixed methods design, combining quantitative data from the RESTORE clinical trial with qualitative interviews with bereaved parents. Patients who died during RESTORE were included in quantitative analyses. A subset of their parents was interviewed 7 to 11 years later. The quantitative analyses included 104 children. Eight parents were interviewed; 4 had a child die after cancer, and 4 had a child die after a complex chronic illness. Quantitatively, patients' pain and sedation scores were generally comfortable. Children died with multiple invasive devices in place. Parents' descriptions of their child's comfort and critical care requirements differed by illness trajectory (cancer, complex chronic illness). Parents' memories of their child's suffering aligned with peaks in clinical scores, rather than averages. Invasive devices and equipment altered parents' ability to make meaningful final memories with the dying child. Pediatric intensive care clinicians may need to broaden how they attend to dying children's pain and corresponding parental distress, as parents' memories of their dying child's suffering persist for years.

River corridors are fundamental components of the Earth system, and their biogeochemistry can be heavily influenced by processes in subsurface zones immediately below the riverbed, referred to as the hyporheic zone. Within the hyporheic zone, organic matter (OM) fuels microbial respiration, and OM chemistry heavily influences aerobic and anaerobic biogeochemical processes. The link between OM chemistry and respiration has been hypothesized to be mediated by OM molecular diversity, whereby respiration is predicted to decrease with increasing diversity. Here we test the specific prediction that aerobic respiration rates will decrease with increases in the number of unique organic molecules (i.e., OM molecular richness, as a measure of diversity). We use publicly available data across the United States from crowdsourced samples taken by the Worldwide Hydrobiogeochemical Observation Network for Dynamic River Systems (WHONDRS) consortium. Our continental-scale analyses rejected the hypothesis of a direct limitation of respiration by OM molecular richness. In turn, we found that organic carbon (OC) concentration imposes a primary constraint over hyporheic zone respiration, with additional potential influences of OM richness. We specifically observed respiration rates to decrease nonlinearly with the ratio of OM richness to OC concentration. This relationship took the form of a constraint space with respiration rates in most systems falling below the constraint boundary. A similar, but slightly weaker, constraint boundary was observed when relating respiration rate to the inverse of OC concentration. These results indicate that maximum respiration rates may be governed primarily by OC concentration, with secondary influences from OM richness. Our results also show that other variables often suppress respiration rates below the maximum associated with the richness-to-concentration ratio. An important focus of future research will identify physical (e.g., sediment grain size), chemical (e.g., nutrient concentrations), and/or biological (e.g., microbial biomass) factors that suppress hyporheic zone respiration below the constraint boundaries observed here.

As much as half or more of deep partial-thickness burn wounds develop hypertrophic scarring and contracture. Once formed, treatments are only minimally effective. Pirfenidone (Pf), indicated for treatment of idiopathic pulmonary fibrosis, is an anti-inflammatory and anti-fibrotic small molecule that potentially can be repurposed as a preventative against scarring in burn wounds. We present a drug-in-matrix patch with a soft skin adhesive (SSA) wound-contacting layer for multi-day drug delivery of Pf into burn wounds at the point of injury. Our patch construction consists of an SSA adhesive layer (Liveo™ MG7-9850, Dupont, Wilmington, DE, USA) for wound fixation, an acrylic co-polymer drug matrix (DURO-TAK 87-2852, Henkel, Düsseldorf, Germany) as the drug (Pf) reservoir, and an outermost protective polyurethane backing. By employing a drug-in-matrix patch design, Pf can be loaded as high as 2 mg/cm2. Compared to the acrylic co-polymer adhesive patch preparations and commercial films, adding an SSA layer markedly reduces skin stripping observed under scanning electron microscopy (SEM). Moreover, the addition of varying SSA thicknesses did not interfere with the in vitro release kinetics or drug permeation in ex vivo porcine skin. The Pf patch can be easily applied onto and removed from deep partial-thickness burn wounds on Duroc pigs. Continuous multi-day dosing of Pf by the patches (>200 μg/cm2/day) reduced proinflammatory biomarkers in porcine burn wounds. Pf patches produced by the manual laboratory-scale process showed excellent stability, maintaining intact physical patch properties and in vitro biological activity for up to one year under long-term (25 °C at 60% RH) and 6 months under accelerated (40 °C at 75% RH) test conditions. To manufacture our wound safe-and-extended-release patch, we present scale-up processes using a machine-driven automated roll-to-roll pilot scale coater.

FOXJ1 is expressed in ciliated cells of the airways, testis, oviduct, central nervous system and the embryonic left–right organizer. Ablation or targeted mutation of Foxj1 in mice, zebrafish and frogs results in loss of ciliary motility and/or reduced length and number of motile cilia, affecting the establishment of the left–right axis. In humans, heterozygous pathogenic variants in FOXJ1 cause ciliopathy leading to situs inversus, obstructive hydrocephalus and chronic airway disease. Here, we report a novel truncating FOXJ1 variant (c.784_799dup; p.Glu267Glyfs*12) identified by clinical exome sequencing from a patient with isolated congenital heart defects (CHD) which included atrial and ventricular septal defects, double outlet right ventricle (DORV) and transposition of the great arteries. Functional experiments show that FOXJ1 c.784_799dup; p.Glu267Glyfs*12, unlike FOXJ1, fails to induce ectopic cilia in frog epidermis in vivo or to activate the ADGB promoter, a downstream target of FOXJ1 in cilia, in transactivation assays in vitro. Variant analysis of patients with heterotaxy or heterotaxy-related CHD indicates that pathogenic variants in FOXJ1 are an infrequent cause of heterotaxy. Finally, we characterize embryonic-stage CHD in Foxj1 loss-of-function mice, demonstrating randomized heart looping. Abnormal heart looping includes reversed looping (dextrocardia), ventral looping and no looping/single ventricle hearts. Complex CHDs revealed by histological analysis include atrioventricular septal defects, DORV, single ventricle defects as well as abnormal position of the great arteries. These results indicate that pathogenic variants in FOXJ1 can cause isolated CHD.

Objectives: The use of neuromuscular blocking agents (NMBAs) in pediatric acute respiratory distress syndrome (PARDS) is common but unsupported by efficacy data. We sought to compare the outcomes between patients with moderate-to-severe PARDS receiving continuous NMBA during the first 48 hours of endotracheal intubation (early NMBA) and those without.Design: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial, a pediatric multicenter cluster randomized trial of sedation.Setting: Thirty-one PICUs in the United States.Patients: Children 2 weeks to 17 years receiving invasive mechanical ventilation (MV) for moderate-to-severe PARDS (i.e., oxygenation index >= 8 and bilateral infiltrates on chest radiograph on days 0-1 of endotracheal intubation).Interventions: NMBA for the entire duration of days 1 and 2 after intubation.Measurements and Main Results: Among 1,182 RESTORE patients with moderate-to-severe PARDS, 196 (17%) received early NMBA for a median of 50.0% ventilator days (interquartile range, 33.3-60.7%). The propensity score model predicting the probability of receiving early NMBA included high-frequency oscillatory ventilation on days 0-2 (odds ratio [OR], 7.61; 95% CI, 4.75-12.21) and severe PARDS on days 0-1 (OR, 2.16; 95% CI, 1.50-3.12). After adjusting for risk category, early use of NMBA was associated with a longer duration of MV (hazard ratio, 0.57; 95% CI, 0.48-0.68; p < 0.0001), but not with mortality (OR, 1.62; 95% CI, 0.92-2.85; p = 0.096) compared with no early use of NMBA. Other outcomes including cognitive, functional, and physical impairment at 6 months post-PICU discharge were similar. Outcomes did not differ when comparing high versus low NMBA usage sites or when patients were stratified by baseline PaO2/FIO2 less than 150.Conclusions: Early NMBA use was associated with a longer duration of MV. This propensity score analysis underscores the need for a randomized controlled trial in pediatrics.

In this study, gadolinium (Gd) doped MgAl layered double hydroxides (LDHs) were synthesized via a ‘bottom-up’ method and fully characterized by X-ray diffraction, infrared spectroscopy and relaxivity measurements. Two cytotoxic agents were then intercalated via ion-exchange. X-ray diffraction patterns exhibit expanded interlayer spacings as a result of successful drug intercalation. Infrared spectra also showed characteristic peaks of the incorporated methotrexate (MTX) or 5-fluorouracil (5-FU). The LDHs were found to be highly stable under physiological conditions, while in acidic conditions a small proportion of Gd was freed into the immersion medium. Dissolution tests revealed that both 5FU and MTX were rapidly released from the LDH carrier. The longitudinal relaxivity of Gd-LDHs remains largely stable during drug release over 24 h, and was higher in acidic environments. Overall, the drug-loaded Gd-LDH systems prepared in this study could serve as pH-sensitive theranostic platforms for MRI-guided anti-cancer therapy.

High-resolution mass spectrometry techniques are widely used in the environmental sciences to characterize natural organic matter and, when utilizing these instruments, researchers must make multiple decisions regarding sample pre-treatment and the instrument ionization mode. To identify how these choices alter organic matter characterization and resulting conclusions, we analyzed a collection of 17 riverine samples from East River, CO (USA) under four PPL-based Solid Phase Extraction (SPE) treatment and electrospray ionization polarity (

The Russian invasion of Ukraine on February 24, 2022, has displaced more than a quarter of the population. Assessing disease burdens among displaced people is instrumental in informing global public health and humanitarian aid efforts. We estimated the disease burden in Ukrainians displaced both within Ukraine and to other countries by combining a spatiotemporal model of forcible displacement with age- and gender-specific estimates of cardiovascular disease (CVD), diabetes, cancer, HIV, and tuberculosis (TB) in each of Ukraine’s 629 raions (i.e., districts). Among displaced Ukrainians as of May 13, we estimated that more than 2.63 million have CVDs, at least 615,000 have diabetes, and over 98,500 have cancer. In addition, more than 86,000 forcibly displaced individuals are living with HIV, and approximately 13,500 have TB. We estimated that the disease prevalence among refugees was lower than the national disease prevalence before the invasion. Accounting for internal displacement and healthcare facilities impacted by the conflict, we estimated that the number of people per hospital has increased by more than two-fold in some areas. As regional healthcare systems come under increasing strain, these estimates can inform the allocation of critical resources under shifting disease burdens.

We report a novel magnetically-facilitated approach to produce 1-D ‘nano-necklace’ arrays composed of 0-D magnetic nanoparticles, which are assembled and coated with an oxide layer to produce semi-flexible core@shell type...

Aims The aim of this study was to investigate whether wear and backside deformation of polyethylene (PE) tibial inserts may influence the cement cover of tibial trays of explanted total knee arthroplasties (TKAs). Methods At our retrieval centre, we measured changes in the wear and deformation of PE inserts using coordinate measuring machines and light microscopy. The amount of cement cover on the backside of tibial trays was quantified as a percentage of the total surface. The study involved data from the explanted fixed-bearing components of four widely used contemporary designs of TKA (Attune, NexGen, Press Fit Condylar (PFC), and Triathlon), revised for any indication, and we compared them with components that used previous generations of PE. Regression modelling was used to identify variables related to the amount of cement cover on the retrieved trays. Results A total of 114 explanted fixed-bearing TKAs were examined. This included 76 used with contemporary PE inserts which were compared with 15 used with older generation PEs. The Attune and NexGen (central locking) trays were found to have significantly less cement cover than Triathlon and PFC trays (peripheral locking group) (p = 0.001). The median planicity values of the PE inserts used with central locking trays were significantly greater than of those with peripheral locking inserts (205 vs 85 microns; p < 0.001). Attune and NexGen inserts had a characteristic pattern of backside deformation, with the outer edges of the PE deviating inferiorly, leaving the PE margins as the primary areas of articulation. Conclusion Explanted TKAs with central locking mechanisms were significantly more likely to debond from the cement mantle. The PE inserts of these designs showed characteristic patterns of deformation, which appeared to relate to the manufacturing process and may be exacerbated in vivo. This pattern of deformation was associated with PE wear occurring at the outer edges of the articulation, potentially increasing the frictional torque generated at this interface. Cite this article: Bone Joint J 2021;103-B(12):1791–1801.

To report a rare case of infusion port site tumor seeding of choroidal melanoma after pars plana vitrectomy-assisted biopsy and successful treatment with second plaque brachytherapy.Observational case report with clinical data and diagnostic images.A 55-year-old Caucasian woman diagnosed with choroidal melanoma of the left eye was found to have a second intraocular tumor thirty months after plaque brachytherapy and pars plana vitrectomy-assisted tumor biopsy. The second melanoma developed at the 5 o'clock vitrectomy infusion port site. The tumor regressed after plaque brachytherapy and the patient has not developed systemic metastasis five years after diagnosis of intraocular seeding.Intraocular seeding into the infusion port site, although rare, may be encountered after pars plana vitrectomy-assisted biopsy of choroidal melanoma.

Major changes in North Atlantic zooplankton communities in recent decades have been linked to climate change but the roles of environmental drivers are often complex. High temporal resolution data is required to disentangle the natural seasonal drivers from additional sources of variability in highly heterogeneous marine systems. Here, physical and plankton abundance data spanning 2003–2017 from a weekly long-term monitoring site on the west coast of Scotland were used to investigate the cause of an increasing decline to approximately -80± 5% in annual average total zooplankton abundance from 2011 to 2017. Generalized additive mixed models (GAMMs), with an autoregressive correlation structure, were used to examine seasonal and inter-annual trends in zooplankton abundance and their relationship with environmental variables. Substantial declines were detected across all dominant taxa, with ∼ 30–70% of the declines in abundance explained by a concurrent negative trend in salinity, alongside the seasonal cycle, with the additional significance of food availability found for some taxa. Temperature was found to drive seasonal variation but not the long-term trends in the zooplankton community. The reduction in salinity had the largest effect on several important taxa. Salinity changes could partly be explained by locally higher freshwater run-off driven by precipitation as well as potential links to changes in offshore water masses. The results highlight that changes in salinity, caused by either freshwater input (expected from climate predictions) or fresher offshore water masses, may adversely impact coastal zooplankton communities and the predators that depend on them.

Background There is limited information available on the impact of moderate asthma exacerbations, often called “asthma attacks” (i.e., those not requiring hospitalisation or treatment with systemic corticosteroids) on patients’ lives. This multi-country qualitative study explored the patient experience of these events. Methods Semi-structured concept elicitation interviews were conducted in the USA and Germany with adult patients with asthma who had experienced a moderate asthma exacerbation in the prior 30 days. Physicians with experience in managing patients with asthma were also interviewed. Interviews explored patients’ experience of symptoms and impact of moderate exacerbations and associated exacerbation triggers and treatment patterns. Physicians were also asked about their interpretation of a clinical definition and treatment of a moderate exacerbation. Results Twenty-eight patient (n = 20 in the USA, n = 8 in Germany) and six physician (n = 3 in the USA, n = 3 in Germany) interviews were conducted. During their moderate exacerbation, all patients reported experiencing shortness of breath, which many considered to be severe and the most bothersome symptom. Wheezing was also reported by all patients and considered severe by two thirds of patients. Most patients also reported coughing and chest tightness. All or almost all patients reported that moderate exacerbation caused fatigue/tiredness and impacted their physical functioning, emotional functioning, activities of daily living and work/school life. Most patients reported using rescue or maintenance inhalers to alleviate symptoms of the exacerbation. Conceptual saturation (i.e., the point at which no new concepts are likely to emerge with continued data collection) was achieved. Findings were used to develop a patient-focused conceptual model of the experience of moderate asthma exacerbations, outlining concepts related to triggers, symptoms, impact, and treatment from the patient perspective. Physician data was consistent with patient reports and complemented the conceptual model. Conclusions Findings from concept elicitation interviews highlight the increased frequency, duration and severity of asthma symptoms and increased rescue medication use during moderate asthma exacerbations compared with the typical daily asthma experience, which have a substantial impact on patients’ lives.

The variability induced by precipitable water vapour (PWV) can heavily affect the accuracy of time-series photometric measurements gathered from the ground, especially in the near-infrared. We present here a novel method of modelling and mitigating this variability, as well as open-sourcing the developed tool -- Umbrella. In this study, we evaluate the extent to which the photometry in three common bandpasses (r', i', z'), and SPECULOOS' primary bandpass (I+z'), are photometrically affected by PWV variability. In this selection of bandpasses, the I+z' bandpass was found to be most sensitive to PWV variability, followed by z', i', and r'. The correction was evaluated on global light curves of nearby late M- and L-type stars observed by SPECULOOS' Southern Observatory (SSO) with the I+z' bandpass, using PWV measurements from the LHATPRO and local temperature/humidity sensors. A median reduction in RMS of 1.1% was observed for variability shorter than the expected transit duration for SSO's targets. On timescales longer than the expected transit duration, where long-term variability may be induced, a median reduction in RMS of 53.8% was observed for the same method of correction., Accepted for publication in MNRAS, 10 pages, 7 figures, 3 tables

Prevention of musculoskeletal disorders (MSD) often involves a participatory rrgonomics (PE) program. The paper compares the PE approach with occupational health and safety management system (OHSMS). The PE literature did not speak to many elements of OHSMS. It is expected that paying attention to management system frameworks could make prevention of MSD activities more effective and sustainable.

Among business ethicists, Adam Smith is widely viewed as the defender of an amoral if not anti-moral economics in which individuals’ pursuit of their private self-interest is converted by an ‘invisible hand’ into shared economic prosperity. This is often justified by reference to a select few quotations from The Wealth of Nations. We use new empirical methods to investigate what Smith actually had to say, firstly about the relationship between free market institutions and individuals’ moral virtues, and secondly about the further relationship between virtues and societal flourishing. We show with more quantitative precision than traditional scholarship that the invisible hand reading dramatically misrepresents both the nuance and the sum of Smith’s analysis. Smith paid a great deal of attention to a flourishing society’s dependence on virtues, including the non-self-regarding virtues of justice and benevolence, and he worried also about their fragility in the face of the changed incentives and social conditions of commercial society.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and has caused significant medical/socioeconomic impacts. Other than vaccination, effective public health measures, including contact tracing, isolation, and quarantine, is critical for deterring viral transmission, preventing infection progression and resuming normal activities. Viral transmission is affected by many factors, but the viral load and vitality could be among the most important ones. Although in vitro studies have indicated that the amount of virus isolated from infected individuals affects the successful rate of virus isolation, whether the viral load carried at the individual level would determine the transmissibility was unknown. We examined whether the cycle threshold (Ct) value, a measurement of viral load by RT-PCR assay, could differentiate the spreaders from the non-spreaders in a population of college students. Our results indicate that while at the population level the Ct value is lower, suggesting a higher viral load, in the symptomatic spreaders than that in the asymptomatic non-spreaders, there is a significant overlap in the Ct values between the two groups. Thus, Ct value, or the viral load, at the individual level could not predict the transmissibility. Instead, a sensitive method to detect the presence of virus is needed to identify asymptomatic individuals who may carry a low viral load but can still be infectious.

To report 6 cases of diffuse choroidal hemangioma (DCH) in children treated with iodine-125 plaque brachytherapy at a single tertiary care center.Retrospective case series.Six pediatric patients diagnosed with DCH were included in the study. Pre-plaque visual acuity (VA) ranged from 20/150 to no light perception (NLP). All patients had extensive serous retinal detachment at presentation. An iodine-125 radioactive plaque was placed on the affected eye to administer a dose of 34.2-42.1 Gy to the tumor apex over a median of 4 days. Tumor regression and subretinal fluid resolution were observed in all eyes within 17 months of treatment. Visual acuity improved in 2 patients. Radiation-induced cataract and subretinal fibrosis were documented in 1 case, and 1 patient developed radiation retinopathy. No patients developed neovascular glaucoma within a follow-up range of 12-65 months.Iodine-125 plaque radiotherapy is an effective option for DCH, although there is a risk for radiation-induced complications.

BackgroundDiagnostic testing has been pivotal in detecting SARS-CoV-2 infections and reducing transmission through the isolation of positive cases. We quantified the value of implementing frequent, rapid antigen (RA) testing in the workplace to identify screening programs that are cost-effective.MethodsTo project the number of cases, hospitalizations, and deaths under alternative screening programs, we adapted an agent-based model of COVID-19 transmission and parameterized it with the demographics of Ontario, Canada, incorporating vaccination and waning of immunity. Taking into account healthcare costs and productivity losses associated with each program, we calculated the incremental cost-effectiveness ratio (ICER) with quality-adjusted life year (QALY) as the measure of effect. Considering RT-PCR testing of only severe cases as the baseline scenario, we estimated the incremental net monetary benefits (iNMB) of the screening programs with varying durations and initiation times, as well as different booster coverages of working adults.ResultsAssuming a willingness-to-pay threshold of CDN$30,000 per QALY loss averted, twice weekly workplace screening was cost-effective only if the program started early during a surge. In most scenarios, the iNMB of RA screening without a confirmatory RT-PCR or RA test was comparable or higher than the iNMB for programs with a confirmatory test for RA-positive cases. When the program started early with a duration of at least 16 weeks and no confirmatory testing, the iNMB exceeded CDN$1.1 million per 100,000 population. Increasing booster coverage of working adults improved the iNMB of RA screening.ConclusionsOur findings indicate that frequent RA testing starting very early in a surge, without a confirmatory test, is a preferred screening program for the detection of asymptomatic infections in workplaces.

Rapid antigen (RA) tests are being increasingly employed to detect SARS-CoV-2 infections in quarantine and surveillance. Prior research has focused on RT-PCR testing, a single RA test, or generic diagnostic characteristics of RA tests in assessing testing strategies.We have conducted a comparative analysis of the post-quarantine transmission, the effective reproduction number during serial testing, and the false-positive rates for 18 RA tests with emergency use authorization from The United States Food and Drug Administration and an RT-PCR test. To quantify the extent of transmission, we developed an analytical mathematical framework informed by COVID-19 infectiousness, test specificity, and temporal diagnostic sensitivity data.We demonstrate that the relative effectiveness of RA tests and RT-PCR testing in reducing post-quarantine transmission depends on the quarantine duration and the turnaround time of testing results. For quarantines of two days or shorter, conducting a RA test on exit from quarantine reduces onward transmission more than a single RT-PCR test (with a 24-h delay) conducted upon exit. Applied to a complementary approach of performing serial testing at a specified frequency paired with isolation of positives, we have shown that RA tests outperform RT-PCR with a 24-h delay. The results from our modeling framework are consistent with quarantine and serial testing data collected from a remote industry setting.These RA test-specific results are an important component of the tool set for policy decision-making, and demonstrate that judicious selection of an appropriate RA test can supply a viable alternative to RT-PCR in efforts to control the spread of disease.Previous research on SARS-CoV-2 infection has determined optimal timing for testing in quarantine and the utility of different frequencies of testing for infection surveillance using RT-PCR and generalized rapid antigen tests. However, these strategies can depend on the specific rapid antigen test used. By examining 18 rapid antigen tests, we demonstrate that a single rapid antigen test performs better than RT-PCR when quarantines are two days or less in duration. In the context of infection surveillance, the ability of a rapid antigen test to provide results quickly counteracts its lower sensitivity with potentially more false positives. Our findings indicate that rapid antigen tests can be a suitable alternative to RT-PCR for application in quarantine and infection surveillance.

Quarantine and serial testing strategies for a disease depend principally on its incubation period and infectiousness profile. In the context of COVID-19, these primary public health tools must be modulated with successive SARS CoV-2 variants of concern that dominate transmission. Our analysis shows that (1) vaccination status of an individual makes little difference to the determination of the appropriate quarantine duration of an infected case, whereas vaccination coverage of the population can have a substantial effect on this duration, (2) successive variants can challenge disease control efforts by their earlier and increased transmission in the disease time course relative to prior variants, and (3) sufficient vaccine boosting of a population substantially aids the suppression of local transmission through frequent serial testing. For instance, with Omicron, increasing immunity through vaccination and boosters—for instance with 100% of the population is fully immunized and at least 24% having received a third dose—can reduce quarantine durations by up to 2 d, as well as substantially aid in the repression of outbreaks through serial testing. Our analysis highlights the paramount importance of maintaining high population immunity, preferably by booster uptake, and the role of quarantine and testing to control the spread of SARS CoV-2.

Peracetic acid is a disinfection agent used in medical and food processing facilities, and occupational exposures have been documented. To facilitate characterization of daily occupational exposures, the current work describes the development of a personal sampling technique to quantify the peracetic acid concentration in air samples. Peracetic acid atmospheres were generated in 100 L Teflon chambers, and samples were collected on 350 mg XAD-7 solid sorbent tubes for 4 h at a flow rate of 250 mL/min using a personal sampling pump. Indirect measurement of peracetic acid was achieved by desorption from the sorbent and subsequent treatment with cyclohexene to initiate an epoxidation reaction, formally known as the Prilezhaev reaction. The epoxidation product, cyclohexene oxide, was quantified by gas chromatography–mass spectrometry. The reaction enabled quantification of peracetic acid with high specificity over the common co-contaminants hydrogen peroxide and acetic acid, which were introduced in 10-fold and 100-fold excess to challenge the reaction. The technique also demonstrated an overall estimate of bias and precision of 11 and 8%, respectively, and a limit of detection of 60 ppbv was estimated. Preliminary storage experiments indicate that unreacted peracetic acid is stable on the sorbent tubes for 72 h when stored at −20 °C following collection. Overall, the specificity of the reaction and capability to sample for longer time periods than current methods, in addition to the use of safer personal sampling materials, demonstrate the utility of this technique for peracetic acid measurement in air.

We report on infrared to visible Zeeman absorption spectroscopy and parameterised crystal-field modelling of Nd3+ centres in Y2SiO5 through the use of experimentally inferred crystal-field energy levels and Zeeman directional electronic g values. We demonstrate that good agreement between the calculated and experimental crystal-field energy levels as well as directional Zeeman g values along all three crystallographic axes can be obtained. Further, we demonstrate that the addition of correlation crystal field effects successfully account for discrepancies that arise between the calculated and experimental values relevant to the 2H 11 / 2 (2) multiplet in a one-electron crystal field model.

Background Many patients with hand osteoarthritis (HOA) experience reduced health-related quality of life. This study sought to better understand the disease and treatment experience of individuals with HOA, explore any differences in experiences between erosive and non-erosive HOA sub-types, and evaluate content validity of the Michigan Hand Outcomes Questionnaire (MHQ) in HOA. Methods Thirty subjects from the United States (n = 15 erosive HOA; n = 15 non-erosive HOA) participated in semi-structured interviews: concept elicitation explored symptoms/impacts important to patients; cognitive interviews assessed understanding and relevance of the MHQ. A sub-sample participated in real-time data capture (RTDC) activities via a smartphone/tablet app over 7 days. Verbatim transcripts were coded using Atlas.ti software and thematically analyzed. Concept saturation and MHQ content validity were evaluated. Results Most participants reported experiencing pain, swelling and stiffness, symptoms that most commonly had a direct impact on physical functioning. Substantial impacts on activities of daily living, emotional functioning, sleep and work were also reported. RTDC findings corroborated concept elicitation findings. There were no notable differences between erosive and non-erosive HOA, except nodules were reported more frequently in erosive disease. Most participants used analgesic treatments, but effects were short-lived. Pain was the symptom most frequently reported as most bothersome and important to treat. Concept saturation was achieved. MHQ items and instructions were well understood and relevant to most participants; stiffness and swelling were reported as important symptoms not included in the MHQ. Conclusions This study characterizes key symptoms of HOA which are burdensome for patients and not well controlled by current therapies, highlighting an unmet treatment need. Although the study is limited by a small sample size that may not be representative of the broader erosive and non-erosive HOA population, concept saturation was achieved, and our findings suggest that disease experience is similar for patients with erosive and non-erosive HOA. Evaluation of stiffness and swelling items in conjunction with the MHQ may enhance relevance and improve measurement precision to assess important domains of HQRoL in an HOA population.

Background Global vaccine development efforts have been accelerated in response to the devastating coronavirus disease 2019 (COVID-19) pandemic. We evaluated the impact of a 2-dose COVID-19 vaccination campaign on reducing incidence, hospitalizations, and deaths in the United States. Methods We developed an agent-based model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and parameterized it with US demographics and age-specific COVID-19 outcomes. Healthcare workers and high-risk individuals were prioritized for vaccination, whereas children under 18 years of age were not vaccinated. We considered a vaccine efficacy of 95% against disease following 2 doses administered 21 days apart achieving 40% vaccine coverage of the overall population within 284 days. We varied vaccine efficacy against infection and specified 10% preexisting population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current nonpharmaceutical interventions in the United States. Results Vaccination reduced the overall attack rate to 4.6% (95% credible interval [CrI]: 4.3%–5.0%) from 9.0% (95% CrI: 8.4%–9.4%) without vaccination, over 300 days. The highest relative reduction (54%–62%) was observed among individuals aged 65 and older. Vaccination markedly reduced adverse outcomes, with non-intensive care unit (ICU) hospitalizations, ICU hospitalizations, and deaths decreasing by 63.5% (95% CrI: 60.3%–66.7%), 65.6% (95% CrI: 62.2%–68.6%), and 69.3% (95% CrI: 65.5%–73.1%), respectively, across the same period. Conclusions Our results indicate that vaccination can have a substantial impact on mitigating COVID-19 outbreaks, even with limited protection against infection. However, continued compliance with nonpharmaceutical interventions is essential to achieve this impact.

Rationale: Racial disparities in pain management have been previously reported for children receiving emergency care. Objectives: To determine whether patient race or ethnicity is associated with the broader goal of pain management and sedation among pediatric patients mechanically ventilated for acute respiratory failure. Methods: Planned secondary analysis of RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure). RESTORE, a cluster-randomized clinical trial conducted in 31 U.S. pediatric intensive care units, compared protocolized sedation management (intervention arm) with usual care (control arm). Participants included 2,271 children identified as non-Hispanic white (white, n = 1,233), non-Hispanic Black (Black, n = 502), or Hispanic of any race (Hispanic, n = 536). Results: Within each treatment arm, neither opioid nor benzodiazepine selection, nor cumulative dosing, differed significantly among race and ethnicity groups. Black patients experienced fewer days with an episode of pain (compared with white patients in the control arm and with Hispanic patients in the intervention arm) and experienced less iatrogenic withdrawal syndrome (compared with white patients in either arm or with Hispanic patients in the intervention arm). The percentage of days awake and calm while intubated was not significantly different in pairwise comparisons by race and ethnicity groups in either the control arm (median: white, 75%; Black, 71%; Hispanic, 75%) or the intervention arm (white, 86%; Black, 88%; Hispanic, 85%). Conclusions: Across multiple measures, our study found scattered differences in sedation management among critically ill Black, Hispanic, and white children that did not consistently favor any group. However, racial disparities related to implicit bias cannot be completely ruled out. Clinical trial registered with clinicaltrials.gov (NCT 00814099).

PurposeWe used Andersen's Behavioral Model in a cross-sectional study to determine the factors associated with utilization of the emergency department (ED), controlling for whether an adolescent has a developmental disability (DD) and one or more oral complications (toothaches, decayed teeth, bleeding gums, eating or swallowing problems).MethodsData from the 2016–2019 National Survey of Children's Health (NSCH) was used for this secondary data analysis study. We used frequencies and percentages to describe the sample characteristics. Chi-square tests were used for bivariate analyses. Multivariable logistic regression modeling was conducted to predict ED visits by adolescents aged 10–17 controlling for predisposing, enabling, and need variables.ResultsThe sample consisted of 68,942 adolescents who were primarily male, non-Hispanic White, and born in the U.S. Parents reported that 69% of the adolescents had neither a DD nor an oral complication; 10% had no DD but experienced one or more oral complication; 16% had a DD but no oral complication; and 5% had both DDs and one or more oral complication. Adolescents with both a DD and an oral complication reported the highest level of ED visits at 33%, compared to 14% of adolescents with neither DD nor oral complication. Regression analysis showed that adolescents with a DD and oral complication (OR: 2.0, 95% CI: 1.64–2.54, p < 0.0001), and those with DDs but no oral complications (OR: 1.45, 95% CI: 1.25–1.68, p < 0.0001) were at higher odds of having an ED visit compared to those with neither a DD nor an oral complication. Not having a Medical Home increased the likelihood of ED visits by 14% (p = 0.02). Those with private insurance (OR: 0.63, 95% CI: 0.53–0.75, p < 0.0001) and those from a family where the highest level of education was some college and above (OR: 0.85, 95% CI: 0.73–0.98, p = 0.03) were less likely than their counterparts to have had an ED visit.ConclusionAdolescents with DDs and oral complications utilize ED visits more frequently than those with neither DDs nor oral complications. Integrating the dental and medical health systems and incorporating concepts of a Patient-Centered Medical Home could improve overall health care and reduce ED visits for adolescents.

Transcatheter aortic valve replacement (TAVR) first received FDA approval for high-risk surgical patients in 2011 and has been approved for low-risk surgical patients since 2019. It is now the most common type of aortic valve replacement, and its use continues to accelerate. Computer modeling and simulation (CM&S) is a tool to aid in TAVR device design, regulatory approval, and indication in patient-specific care. This study introduces a computational fluid-structure interaction (FSI) model of TAVR with Medtronic’s CoreValve Evolut R device using the immersed finite element-difference (IFED) method. We perform dynamic simulations of crimping and deployment of the Evolut R, as well as device behavior across the cardiac cycle in a patient-specific aortic root anatomy reconstructed from computed tomography (CT) image data. These IFED simulations, which incorporate biomechanics models fit to experimental tensile test data, automatically capture the contact within the device and between the self-expanding stent and native anatomy. Further, we apply realistic driving and loading conditions based on clinical measurements of human ventricular and aortic pressures and flow rates to demonstrate that our Evolut R model supports a physiological diastolic pressure load and provides informative clinical performance predictions.

The authors describe a challenging case of unilateral retinoblastoma in a patient referred for xanthocoria. A 3-year-old boy was referred for unilateral xanthocoria and disordered retinal vasculature, suggestive of Coats disease. Further investigation revealed diffuse subretinal tumor seeding and areas of calcification, consistent with retinoblastoma. Enucleation was performed and histopathology confirmed exophytic retinoblastoma. This case highlights that xanthocoria, although often encountered in patients with Coats disease, can sometimes be associated with retinoblastoma. As such, retinoblastoma should be considered in the differential diagnosis for children with both leukocoria and xanthocoria. [ J Pediatr Ophthalmol Strabismus. 2022;59(X):e32–e34.]

This paper introduces a sharp-interface approach to simulating fluid-structure interaction involving flexible bodies described by general nonlinear material models and across a broad range of mass density ratios. This new flexible-body immersed Lagrangian-Eulerian (ILE) approach incorporates the geometrical and domain solution flexibility of the immersed boundary (IB) method with an accuracy comparable to body-fitted approaches that sharply resolve flows and stresses up to the fluid-structure interface. Unlike many IB methods, our ILE formulation uses distinct momentum equations for the fluid and solid subregions with a Dirichlet-Neumann coupling strategy that connects fluid and solid subproblems through simple interface conditions. We use a penalty method involving two representations of the fluid-structure interface. These two representations are connected by approximate Lagrange multiplier forces that impose kinematic interface conditions. This approach also enables the use of multi-rate time stepping, which allows us to take different time step sizes for the fluid and structure subproblems. Our fluid solver relies on an immersed interface method for discrete surfaces to impose stress jump conditions along complex interfaces. The dynamics of the volumetric structural mesh are determined using a standard finite element approach to large-deformation nonlinear elasticity via a nearly incompressible solid mechanics formulation. This formulation also readily accommodates compressible structures for cases in which part of the solid boundary does not contact the incompressible fluid. Comparisons are made with computational and experimental benchmarks. We also demonstrate the capabilities of this methodology by applying it to model the transport and capture of a cylindrical blood clot in an inferior vena cava filter.

Purpose: The aim of this study was to describe 2 patients with intraocular lens (IOL) and lens capsule spread of iridociliary melanoma. Methods: Two pseudophakic patients with iridociliary body melanoma that spread onto the surface of their IOL and remaining lens capsule were included. Their eyes were enucleated and the histopathologic features were evaluated. Results: Case 1 was an 82-year-old woman with diffuse primary iridociliary melanoma affecting the iris, lens capsule, IOL surface, and ciliary body. Case 2 was a 68-year-old female who developed melanoma recurrence in the anterior segment after plaque brachytherapy for iridociliary melanoma. The melanoma in both cases grew as a pigmented membrane onto the surface of the IOL. Conclusions: IOL and lens capsule spread of iridociliary melanoma can occur primarily or develop secondarily after plaque brachytherapy of a pseudophakic eye. Since the extent of the melanoma may be uncertain and there is a high likelihood of glaucoma, enucleation is a reasonable option.

A 46-year-old patient with previously documented Ebola virus persistence in his ocular fluid, associated with severe panuveitis, developed a visually significant cataract. A multidisciplinary approach was taken to prevent and control infection. Ebola virus persistence was assessed before and during the operation to provide safe, vision-restorative phacoemulsification surgery.

Significance An individual’s decision to vaccinate can be motivated by both self-interest and prosociality, making it difficult to delineate the contribution of prosociality to vaccination uptake. A silent polio epidemic in Israel in which the primary purpose of vaccination was to avert transmission to the general community provides a unique case study through which we quantify, using game-theoretical models, the contribution of prosociality to vaccination decisions. We find that prosociality was a significant driver to rapidly achieving a high coverage of polio vaccination. To further boost coverage, public health communication efforts should be directed toward allaying fears about vaccine risks. Our approach is useful for enhancing participation in diverse disease control measures, Regions with insufficient vaccination have hindered worldwide poliomyelitis eradication, as they are vulnerable to sporadic outbreaks through reintroduction of the disease. Despite Israel’s having been declared polio-free in 1988, a routine sewage surveillance program detected polio in 2013. To curtail transmission, the Israel Ministry of Health launched a vaccine campaign to vaccinate children—who had only received the inactivated polio vaccine—with the oral polio vaccine (OPV). Determining the degree of prosocial motivation in vaccination behavior is challenging because vaccination typically provides direct benefits to the individual as well as indirect benefits to the community by curtailing transmission. However, the Israel OPV campaign provides a unique and excellent opportunity to quantify and model prosocial vaccination as its primary objective was to avert transmission. Using primary survey data and a game-theoretical model, we examine and quantify prosocial behavior during the OPV campaign. We found that the observed vaccination behavior in the Israeli OPV campaign is attributable to prosocial behavior and heterogeneous perceived risk of paralysis based on the individual’s comprehension of the prosocial nature of the campaign. We also found that the benefit of increasing comprehension of the prosocial nature of the campaign would be limited if even 24% of the population acts primarily from self-interest, as greater vaccination coverage provides no personal utility to them. Our results suggest that to improve coverage, communication efforts should also focus on alleviating perceived fears surrounding the vaccine.

Existing distance metric learning methods require optimisation to learn a feature space to transform data—this makes them computationally expensive in large datasets. In classification tasks, they make use of class information to learn an appropriate feature space. In this paper, we present a simple supervised dissimilarity measure which does not require learning or optimisation. It uses class information to measure dissimilarity of two data instances in the input space directly. It is a supervised version of an existing data-dependent dissimilarity measure called $$m_\mathrm{e}$$ . Our empirical results in k-NN and LVQ classification tasks show that the proposed simple supervised dissimilarity measure generally produces predictive accuracy better than or at least as good as existing state-of-the-art supervised and unsupervised dissimilarity measures.

Age-related hearing impairment (ARHI) is very common in older adults and has major impact on quality of life. The heritability of ARHI has been estimated to be around 50%. The present study aimed to estimate heritability and environmental contributions to liability of ARHI and the extent to which a polygenic risk score (PRS) derived from a recent genome-wide association study of questionnaire items regarding hearing loss using the UK Biobank is predictive of hearing loss in other samples. We examined (1) a sample from TwinsUK who have had hearing ability measured by pure-tone audiogram and the speech-to-noise ratio test as well as questionnaire measures that are comparable with the UK Biobank questionnaire items and (2) European and non-European samples from the UK Biobank which were not part of the original GWAS. Results indicated that the questionnaire items were over 50% heritable in TwinsUK and comparable with the objective hearing measures. In addition, we found very high genetic correlation (0.30–0.84) between the questionnaire responses and objective hearing measures in the TwinsUK sample. Finally, PRS computed from weighted UK Biobank GWAS results were predictive of both questionnaire and objective measures of hearing loss in the TwinsUK sample, as well as questionnaire-measured hearing loss in Europeans but not non-European subpopulations. These results demonstrate the utility of questionnaire-based methods in genetic association studies of hearing loss in adults and highlight the differences in genetic predisposition to ARHI by ethnic background.