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OBJECTIVES:. Respiratory failure secondary to COVID-19 is associated with morbidity and mortality. Current anti-inflammatory therapies are effective but are given systemically and have significant side effects. Furosemide has anti-inflammatory properties, can be administered by inhalation, and is inexpensive. We investigated the efficacy of nebulized furosemide as an adjunctive therapy for COVID-19 respiratory failure. DESIGN:. A double-blind, randomized, placebo-controlled trial. SETTING:. Multicenter ICU study. PATIENTS:. Adults requiring invasive mechanical ventilation secondary to COVID-19. INTERVENTION:. Patients were randomized within 48 hours of intubation to receive inhaled furosemide or placebo until day 28, death, or liberation from mechanical ventilation. MEASUREMENTS AND MAIN RESULTS:. The study was stopped early due to waning incidence of COVID-19; 39 patients were available for analysis with mean ± sd age of 70.5 (10.8) years, Acute Physiology and Chronic Health Evaluation II 26.1 (7.8) and Fio2 60.0% (21.9). Baseline characteristics were similar between the groups. For the primary outcome of change in Pao2/Fio2 ratio between day 1 and day 6, it was +31.4 (83.5) in the furosemide arm versus +20.1 (92.8) in the control (p = 0.58). For secondary outcomes, furosemide versus control: 60-day mortality was 48% versus 71% (p = 0.20), hospital stay was 25.6 (21.9) versus 27.4 (25.0) days, p = 0.94 and VFD was 6.0 (9.1) versus 3.1 (7.1), p value of equals to 0.28. A post hoc analysis of the hierarchical composite outcome, alive and ventilator-free favored furosemide. There were no adverse events. CONCLUSIONS:. In this trial of inhaled furosemide for COVID-19 respiratory failure, differences in Pao2/Fio2 ratio to day 6 and other clinical outcomes were not significantly different, although the trial was underpowered due to early termination. Given the favorable profile of inhaled furosemide, further study is warranted in disease states where acute pulmonary inflammation contributes to the underlying pathophysiology.

Background: Acute kidney injury (AKI) resulting in kidney replacement therapy is rising among critically ill adults. Long-term kidney replacement therapy and critical illness are independently linked to acute and prolonged cognitive impairment, and structural brain pathology. Poor regional cerebral oxygenation (rSO 2 ) may be a contributing factor. Objective: To assess the feasibility of testing the association between intradialytic rSO 2 and acute and long-term neurological outcomes. Design: Longitudinal observational study. Setting and Participants: We enrolled patients initiating continuous kidney replacement therapy or intermittent hemodialysis in the Kingston Health Sciences Centre (KHSC) Intensive Care Unit (ICU). Measurements and Methods: rSO 2 was monitored during the first 72 hours of continuous kidney replacement therapy or throughout each intermittent hemodialysis session. We measured acute neurological impairment by daily delirium screening and long-term neurocognitive outcomes using the Kinarm robot, Repeatable Battery for the Assessment of Neuropsychological Status, and brain magnetic resonance imaging. Results: Of 484 ICU patients, 26 met the screening criteria. Two declined, and 13 met at least one exclusion criteria. Eleven patients were enrolled. Eight died in ICU, one died 2 months after discharge, and one declined follow-up. Data capture rates were high: rSO 2 /vitals (91.3%), and delirium screening and demographics (100%). Longitudinal testing was completed in 50% (1 of 2) of survivors. Limitations: Enrollment was low due to a variety of factors, limiting our ability to evaluate long-term outcomes. Conclusion: rSO 2 and delirium data collection is feasible in critically ill patients undergoing kidney replacement therapy; high mortality limits follow-up.

The Indo-Pacific legume genus Serianthes was recently placed in the Archidendron clade (sensu Koenen et al. 2020), a subclade of the mimosoid clade in subfamily Caesalpinioideae, which also includes Acacia, Archidendron, Archidendropsis, Falcataria, Pararchidendron, Paraserianthes and Wallaceodendron. Serianthes comprises ca. 18 species, five subspecies and two varieties that are characterised by bipinnately compound leaves with alternate sessile leaflets, branched axillary corymbiform panicles and woody indehiscent pods. Generic relationships, as well as species relationships within genera in the Archidendron clade, remain uncertain. While the sister relationship between Serianthes and the genus Falcataria is strongly supported by molecular data, the distinction between Serianthes and the monotypic genus Wallaceodendron has been questioned, based on their similar flower and fruit morphologies. We combined three gene-enriched hybrid capture DNA sequence datasets (generated from the 964 mimobaits v1 probe set, the expanded 997 mimobaits v2 probe set and the GoFlag angiosperm 408 probe set) and used their overlapping markers (77 loci of the target exonic and flanking regions) to test the monophyly of Serianthes and to investigate generic relationships within the Archidendron clade using 55 ingoid plus two outgroup taxa. We show that Serianthes is monophyletic, confirm the Serianthes + Falcataria sister relationship to Wallaceodendron and recognise this combined clade as the Serianthes clade within the Archidendron clade. We also evaluated the use of overlapping loci across datasets in combination with concordance analyses to test generic relationships and further investigate previously unresolved relationships across the wider ingoid clade. Concordance analysis revealed limited gene tree conflicts near the tips of the Archidendron clade, but increased discordance at the base of the clade, which could be attributed to rapid lineage divergence (radiation) and/or incomplete lineage sorting.

With high equilibrium temperatures and tidally locked rotation, ultra-hot Jupiters (UHJs) are unique laboratories within which to probe extreme atmospheric physics and chemistry. In this paper, we present high-resolution dayside spectroscopy of the UHJ WASP-189 b obtained with the new Gemini High-resolution Optical SpecTrograph (GHOST) at the Gemini South Observatory. The observations, which cover 3 hr of post-eclipse orbital phases, were obtained during the instrument’s System Verification run. We detect the planet’s atmosphere via the Doppler cross-correlation technique, and recover a detection of neutral iron in the planet’s dayside atmosphere at a significance of 7.5 σ in the red arm of the data, verifying the presence of a thermal inversion. We also investigate the presence of other species in the atmosphere and discuss the implications of model injection/recovery tests. These results represent the first atmospheric characterization of an exoplanet with GHOST’s high-resolution mode, and demonstrate the potential of this new instrument in detecting and studying ultra-hot exoplanet atmospheres.

Abstract The size/volume of the brain’s ventricles is essential in diagnosing and treating many neurological disorders, with various forms of hydrocephalus being some of the most common. Initial ventricular size and changes, if any, in response to disease progression or therapeutic intervention are monitored by serial imaging methods. Significant variance in ventricular size is readily noted, but small incremental changes can be challenging to appreciate. We have previously reported using artificial intelligence to determine ventricular volume. The values obtained were compared with those calculated using the inaccurate manual segmentation as the “gold standard”. This document introduces a strategy to measure ventricular volumes where manual segmentation is not employed to validate the estimations. Instead, we created 3D printed models that mimic the lateral ventricles and measured those 3D models’ volume with a tuned water displacement device. The 3D models are placed in a gel and taken to the magnetic resonance scanner. Images extracted from the phantoms are fed to an artificial intelligence-based algorithm. The volumes yielded by the automation must equal those yielded by water displacement to assert validation. Then, we provide certified volumes for subjects in the age range (1–114) months old and two hydrocephalus patients.

IntroductionSepsis is a result of initial over-activation of the immune system in response to an infection or trauma that results in reduced blood flow and life-threatening end-organ damage, followed by suppression of the immune system that prevents proper clearance of the infection or trauma. Because of this, therapies that not only limit the activation of the immune system early on, but also improve blood flow to crucial organs and reactivate the immune system in late-stage sepsis, may be effective treatments. The tyrosine kinase FES may fulfill this role. FES is present in immune cells and serves to limit immune system activation. We hypothesize that by enhancing FES in early sepsis and inhibiting its effects in late sepsis, the severity and outcome of septic illness can be improved.Methods and analysisIn vitro and in vivo modeling will be performed to determine the degree of inflammatory signaling, cytokine production, and neutrophil extracellular trap (NET) formation that occurs in wild-type (WT) and FES knockout (FES-/-) mice. Clinically available treatments known to enhance or inhibit FES expression (lorlatinib and decitabine, respectively), will be used to explore the impact of early vs. late FES modulation on outcomes in WT mice. Bioinformatic analysis will be performed to examine FES expression levels in RNA transcriptomic data from sepsis patient cohorts, and correlate FES expression data with clinical outcomes (diagnosis of sepsis, illness severity, hospital length-of-stay).Ethics and disseminationEthics approval pending from the Queen’s University Health Sciences & Affiliated Teaching Hospitals Research Ethics Board. Results will be disseminated through scientific publications and through lay summaries to patients and families.

Abstract Farmer wildlife management practices are critical to conserve biodiversity and ecosystem functions across intensively used agricultural landscapes. Policies and initiatives aimed at encouraging these practices have generally focused on economic incentives, with limited effectiveness. Farmer identity theory addresses the emergence of norms, values and perceptions in farm management and can contribute to the development of policies and initiatives that engage more effectively with farmers and farming communities. Here we evaluate linkages between farmer identity and wildlife habitat management practices in the intensively farmed US state of Iowa. We conducted an exploratory factor analysis using data from a survey of over 1,300 Iowa farmers that asked their opinions on what constitutes ‘a good farmer’. We use logistic regression to model relationships between farmer identity factor scores and contextual variables against participation in a set of habitat management practices. Four ‘good farmer’ identity types were identified and labelled as productivist, soil conservationist, wildlife conservationist and civic‐minded. Logistic regression results indicated that these farmer identity types have highly divergent responses to wildlife habitat management practices among Iowa farmers. Recreational factors may supplement identity and are also influential towards habitat production on farms. We conclude that farmer identity theory offers a critical link between social and ecological processes on Iowa farms. The research presented here quantitatively associates farmer identity theory with wildlife habitat management, increasing our understanding of how wildlife habitat practices and individual‐level farmer identities interact. A free Plain Language Summary can be found within the Supporting Information of this article.

OBJECTIVES:. High-frequency data streams of vital signs may be used to generate individualized hemodynamic targets for critically ill patients. Central to this precision medicine approach to resuscitation is our ability to screen these data streams for errors and artifacts. However, there is no consensus on the best method for data cleaning. Our goal was to determine whether an error-checking algorithm developed for intraoperative use could be applied to high volumes of arterial line data in an ICU population. DESIGN:. Multicenter observational study. SETTING:. ICUs across Ontario, Canada. PATIENTS:. Nested cohort of ICU patients with shock and/or respiratory failure requiring invasive mechanical ventilation. INTERVENTIONS:. High-frequency blood pressure data was analyzed. Systolic, diastolic, and mean arterial pressure minute averages were calculated. For manual analysis, a trained researcher retrospectively reviewed mean arterial pressure data, removing values that were deemed nonphysiological. The algorithm was implemented and identified artifactual data. MEASUREMENTS AND MAIN RESULTS:. Arterial line data was extracted from 15 patients. A trained researcher manually reviewed 40,798 minute-by-minute data points, then subsequently analyzed them with the algorithm. Manual review resulted in the identification of 119 artifacts (0.29%). The optimized algorithm identified 116 (97%) of these artifacts. Five hundred thirty-seven data points were erroneously removed or modified. Compared with manual review, the modified algorithm incorporating absolute thresholds of greater than 30 and less than 200 mm Hg had 97.5% sensitivity, 98.7% specificity, and a Matthew correlation coefficient of 0.41. CONCLUSIONS:. The error-checking algorithm had high sensitivity and specificity in detecting arterial line blood pressure artifacts compared with manual data cleaning. Given the growing use of large datasets and machine learning in critical care research, methods to validate the quality of high-frequency data is important to optimize algorithm performance and prevent spurious associations based on artifactual data.

Background: Neurocognitive impairment is a common finding across the spectrum of kidney disease and carries important consequences for quality of life. We previously demonstrated that robotic technology can identify neurocognitive impairments not readily detectable by traditional testing in patients with acute kidney injury (AKI) and chronic kidney disease (CKD). Objective: The present study aimed to assess whether these quantifiable deficits in neurocognition differ based on a diagnosis of AKI, CKD, or kidney failure. Design: This was a cross-sectional analysis of participants previously enrolled in an observational study. Setting: Patients were enrolled at a tertiary academic hospital, Kingston Health Sciences Centre, Kingston, ON, Canada. Patients: Adults with AKI, CKD, or kidney failure. Measurements: Each participant underwent robotic neurocognitive assessment using the Kinarm: an interactive robotic device that uses a series of behavioral tasks involving movement of the upper limbs to precisely quantify neurocognitive impairment across a variety of neurocognitive domains. Methods: Multilevel modeling was used to determine the effect of Kinarm task type, kidney diagnostic group (AKI vs CKD vs kidney failure), and the interaction between the two, on neurocognitive performance. Results: A total of 104 participants within 1 year of an AKI event or with CKD category G3-5 were enrolled. We found that across all of the kidney diagnostic groups, participants performed worst on the Kinarm tasks of Reverse Visually Guided Reaching ( b = 0.64 [95% confidence interval = 0.42, 0.85]), Visually Guided Reaching ( b = 0.28 [0.07, 0.49]), and Trail Making ( b = 0.50 [0.28, 0.72]), relative to all other tasks. There were no significant differences in average performance across tasks based on kidney diagnostic group. However, diagnostic group and neurocognitive task type interacted to determine performance, such that patients with AKI performed worse than those with either CKD or kidney failure on the Reverse Visually Guided Reaching task. Limitations: Kinarm assessment was performed at a single time point, and the sample size itself was small, which may lead to the risk of a false-positive association despite the use of multilevel modeling. Our sample size also did not permit inclusion of the underlying etiology of kidney impairment as a covariate in our analyses, which may have also influenced neurocognitive function. Conclusions: In this study that utilized the Kinarm to assess neurocognitive function, patients with AKI demonstrated significantly worse neurocognitive functioning than patients with CKD or kidney failure on a task measuring executive function and visuomotor control.

Phylogenomic data increase the possibilities of resolving the evolutionary and systematic relationships among taxa. This is especially valuable in groups with few and homoplasious morphological characters, in which systematic and taxonomical delimitations have been traditionally difficult. Such is the case of several lineages within Bryophyta, like Orthotrichaceae, the second most diverse family of mosses. Members of tribe Orthotricheae are common in temperate and cold regions, as well as in high tropical mountains. In extratropical areas, they represent one of the main components of epiphytic communities, both in dry and oceanic or hyperoceanic conditions. The epiphytic environment is considered a hostile one for plant development, mainly due to its low capacity of moisture retention. Thus, the diversification of the Orthotrichaceae in this environment could be seen as striking. Over the last two decades, great taxonomic and systematic progresses have led to a rearrangement at the generic level in this tribe, providing a new framework to link environment to patterns of diversification. Here, we use nuclear loci targeted with the GoFlag 408 enrichment probe set to generate a well-sampled phylogeny with well-supported suprageneric taxa and increasing the phylogenetic resolution within the two recognized subtribes. Specifically, we show that several genera with Ulota-like morphology jointly constitute an independent lineage. Within this lineage, the recently described Atlantichella from Macaronesia and Western Europe appears as the sister group of Ulota bellii from Zealandia. This latter species is here segregated in the new genus Rehubryum. Assessment of the ecological and biogeographical affinities of the species within the phylogenetic framework suggests that niche adaptation (including climate and substrate) may be a key evolutionary driver that shaped the high diversification of Orthotricheae.

Abstract Introduction Immunological dysfunction is common in critically ill patients but its clinical significance and the optimal method to measure it are unknown. The level of tumor necrosis factor alpha (TNF-α) after ex-vivo whole blood stimulation with lipopolysaccharide (LPS) has been proposed as a possible method to quantify immunological function. We hypothesized that in a cohort of critically ill patients, those with a lower post-stimulation TNF-α level would have increased rates of nosocomial infections (NIs) and worse clinical outcomes. Methods A secondary analysis of a phase 2 randomized, multi-centre, double-blinded placebo-controlled trial. As there was no difference between treatment and control arms in outcomes and NI rate, all the patients were analyzed as one cohort. On enrolment, day 4, 7, and weekly until day 28, whole blood was incubated with LPS ex-vivo and subsequent TNF-α level was measured. Patients were grouped in tertiles according to delta and peak TNF-α level. The primary outcome was the association between NIs and tertiles of TNF-α level post LPS stimulation; secondary outcomes included ICU and 90-day mortality, and ICU and hospital length of stay. Results Data was available for 201 patients. Neither the post LPS stimulation delta TNF-α group nor the peak TNF-α post-stimulation group were associated with the development of NIs or clinical outcomes. Patients in the highest tertile for post LPS stimulation delta TNF-α compared to the lowest tertile were younger [61.1 years ± 15.7 vs. 68.6 years ± 12.8 standard deviations (SD) in the lowest tertile], had lower acuity of illness (APACHE II 25.0 ± 9.7 vs. 26.7 ± 6.1) and had lower baseline TNF-α (9.9 pg/mL ± 19.0 vs. 31.0 pg/mL ± 68.5). When grouped according to peak post-stimulation TNF-α levels, patients in the highest tertile had higher serum TNF-α at baseline (21.3 pg/mL ± 66.7 compared to 6.5 pg/mL ± 9.0 in the lowest tertile). Conclusion In this prospective multicenter study, ex-vivo stimulated TNF-α level was not associated with the occurrence of NIs or clinical outcomes. Further study is required to better ascertain whether TNF levels and ex-vivo stimulation can be used to characterize immune function in critical illness and if other assays might be better suited to this task.

Abstract Background Previous phylogenetic studies that include the four recognized species of Gallus have resulted in a number of distinct topologies, with little agreement. Several factors could lead to the failure to converge on a consistent topology, including introgression, incomplete lineage sorting, different data types, or insufficient data. Methods We generated three novel whole genome assemblies for Gallus species, which we combined with data from the published genomes of Gallus gallus and Bambusicola thoracicus (a member of the sister genus to Gallus). To determine why previous studies have failed to converge on a single topology, we extracted large numbers of orthologous exons, introns, ultra-conserved elements, and conserved non-exonic elements from the genome assemblies. This provided more than 32 million base pairs of data that we used for concatenated maximum likelihood and multispecies coalescent analyses of Gallus. Results All of our analyses, regardless of data type, yielded a single, well-supported topology. We found some evidence for ancient introgression involving specific Gallus lineages as well as modest data type effects that had an impact on support and branch length estimates in specific analyses. However, the estimated gene tree spectra for all data types had a relatively good fit to their expectation given the multispecies coalescent. Conclusions Overall, our data suggest that conflicts among previous studies probably reflect the use of smaller datasets (both in terms of number of sites and of loci) in those analyses. Our results demonstrate the importance of sampling large numbers of loci, each of which has a sufficient number of sites to provide robust estimates of gene trees. Low-coverage whole genome sequencing, as we did here, represents a cost-effective means to generate the very large data sets that include multiple data types that enabled us to obtain a robust estimate of Gallus phylogeny.

Background: Transcatheter aortic valve implantation (TAVI) is a routine procedure that is often performed on older adults that are high-risk patients with severe aortic stenosis. Patients after TAVI may experience neurological complications. However, there is a lack of objective neurological testing available for patients undergoing cardiac surgery. Objective: This brief communication seeks to explore the use of robotic technology to quantify distinctive patterns of visuospatial, sensorimotor, and cognitive functioning in patients undergoing TAVI. Methods: Patients undergoing TAVI were recruited for this prospective observational study. Prior to their procedure, study participants performed four robotic reaching tasks using the Kinarm robotic system. Patients repeated the assessment three months after their TAVI procedure. Significant changes in overall task score and parameters were determined. Results: Ten patients were recruited and included in this brief report. In a simple reaching task, patients show significant improvement in performance post-TAVI. However, patients do not improve nor worsen in a complex reaching task after TAVI. Similarly, patients demonstrate impairments in both trail making tasks before and after their TAVI procedure. Conclusions: This study captures the variability in neurological functioning in older patients undergoing TAVI. Robotic technology and quantified assessment procedures can be extremely valuable for detecting perioperative neurological impairments in this patient population.

We report on a chemo-dynamical analysis of SPLUS J142445.34−254247.1 (SPLUS J1424−2542), an extremely metal-poor halo star enhanced in elements formed by the rapid neutron-capture process ( r -process). This star was first selected as a metal-poor candidate from its narrowband S-PLUS photometry and followed up spectroscopically in medium resolution with Gemini-South/GMOS, which confirmed its low-metallicity status. High-resolution spectroscopy was gathered with GHOST at Gemini-South, allowing for the determination of the chemical abundances for 36 elements, from carbon to thorium. At [Fe/H] = −3.39, SPLUS J1424−2542 is one of the lowest-metallicity stars with measured Th and has the highest $\mathrm{log}\epsilon (\mathrm{Th}/\mathrm{Eu})$ observed to date, making it part of the “actinide-boost” category of r -process–enhanced stars. The analysis presented here suggests that the gas cloud from which SPLUS J1424−2542 formed must have been enriched by at least two progenitor populations. The light-element ( Z ≤ 30) abundance pattern is consistent with the yields from a supernova explosion of metal-free stars with 11.3–13.4 M _⊙ , and the heavy-element ( Z ≥ 38) abundance pattern can be reproduced by the yields from a neutron star merger (1.66 M _⊙ and 1.27 M _⊙ ) event. A kinematical analysis also reveals that SPLUS J1424−2542 is a low-mass, old halo star with a likely in situ origin, not associated with any known early merger events in the Milky Way.

This study describes an automatic technique to accurately determine the maximum head circumference (MHC) measurement from MRI studies within the Picture Archiving and Communications System, and can automatically add this measurement to the final radiology report. Participants were selected through a retrospective chart review of patients referred to the neurosurgery clinic. Forty-nine pediatric patients with ages ranging from 5 months to 11 years were included in the study. We created 14 printed ring structures to mirror the head circumference values at various ages along the x-axis of the Nellhaus chart. The 3D-printed structures were used to create MRI phantoms. Analytical obtainment of circumference values from the 3D objects and phantom images allowed for a fair estimation and correction of errors on the image-based-measuring instrument. Then, standard manual MHC measurements were performed and compared to values obtained from the patients' MRI T1 images using the tuned instrument proposed in this document. A T-test revealed no statistical difference between the manual assessments and the ones obtained by the automation p = 0.357, α = 0.05. This automatic application augments the more error-prone manual MHC measurement, and can add a numerical value to the final radiology report as a standard application.

Studies have pointed to a positive relationship between farmers' active engagement in watershed management (WM) and soil and water conservation practice adoption. If farmers' involvement in WM leads to more conservation, what predicts WM participation? This study seeks to answer that question through binomial logistic regression analysis of data from a survey of 6,006 Iowa farmers conducted to support the implementation of the Iowa Nutrient Reduction Strategy (NRS). Results indicate that public and private sector information sources, awareness of and attitudes regarding nutrient loss reduction strategies, farm contiguity to water bodies, and cost-share and technical assistance were positive predictors of farmers' engagement in WM, while lower agronomic self-efficacy, farm press as an information source, greater age, and higher farm sales were negative. Findings point to several potential actions to improve farmer involvement in WM: (1) more effectively engage with the farm press to disseminate information about the benefits of WM, (2) increase outreach to larger-scale farmers, and (3) focus on nutrient loss management capacity building. Further, a continued emphasis on awareness and attitudes related to the NRS and related actions, such as watershed management, may guide efforts to recruit farmers into watershed groups to help improve soil and water conservation outcomes.

The U.S. Midwest is a major producer of grain, meat, dairy, eggs, and other major agricultural commodities. It has also been increasingly impacted by climate change-related extreme weather over the last decade as droughts, extreme rains, floods, and, most recently, a severe derecho have damaged crops, livestock, and livelihoods. Climate and agricultural scientists and other stakeholders are concerned that without major shifts away from degrading practices toward regenerative systems, long-term sustainability will be compromised. We used cumulative logistic regression to analyze data from a 2020 survey of 1,059 Iowa farmers to examine (1) how farmers are adapting to increasingly variable and extreme weather-related to climate change and (2) whether selected factors were associated with different kinds of adaptive (e.g., increased use of cover crops) or potentially maladaptive (e.g., increased use of pesticides) actions. Our results found that many farmers have been taking adaptive and maladaptive actions. Stewardship ethics, attitudes toward adaptive action, and integration in conservation-related networks were consistent, positive predictors of increases in adaptive practices. On the other hand, faith in crop insurance as a coping strategy, farm scale, and other factors were associated with some maladaptive actions, with several positive predictors of adaptation also being positive predictors of maladaptation, use of pesticides and drainage in particular. This research contributes to the growing literature on climate risk management and adaptation in agricultural landscapes by providing empirical evidence of the factors related to farmers' adaptive and maladaptive actions.

BackgroundKinarm Standard Tests (KSTs) is a suite of upper limb tasks to assess sensory, motor, and cognitive functions, which produces granular performance data that reflect spatial and temporal aspects of behavior (>100 variables per individual). We have previously used principal component analysis (PCA) to reduce the dimensionality of multivariate data using the Kinarm End-Point Lab (EP). Here, we performed PCA using data from the Kinarm Exoskeleton Lab (EXO), and determined agreement of PCA results across EP and EXO platforms in healthy participants. We additionally examined whether further dimensionality reduction was possible by using PCA across behavioral tasks.MethodsHealthy participants were assessed using the Kinarm EXO (N = 469) and EP (N = 170–200). Four behavioral tasks (six assessments in total) were performed that quantified arm sensory and motor function, including position sense [Arm Position Matching (APM)] and three motor tasks [Visually Guided Reaching (VGR), Object Hit (OH), and Object Hit and Avoid (OHA)]. The number of components to include per task was determined from scree plots and parallel analysis, and rotation type (orthogonal vs. oblique) was decided on a per-task basis. To assess agreement, we compared principal components (PCs) across platforms using distance correlation. We additionally considered inter-task interactions in EXO data by performing PCA across all six behavioral assessments.ResultsBy applying PCA on a per task basis to data collected using the EXO, the number of behavioral parameters were substantially reduced by 58–75% while accounting for 76–87% of the variance. These results compared well to the EP analysis, and we found good-to-excellent agreement values (0.75–0.99) between PCs from the EXO and those from the EP. Finally, we were able to reduce the dimensionality of the EXO data across tasks down to 16 components out of a total of 76 behavioral parameters, which represents a reduction of 79% while accounting for 73% of the total variance.ConclusionPCA of Kinarm robotic assessment appears to capture similar relationships between kinematic features in healthy individuals and is agnostic to the robotic platform used for collection. Further work is needed to investigate the use of PCA-based data reduction for the characterization of neurological deficits in clinical populations.

Abstract Background To maintain adequate oxygen delivery to tissue, resuscitation of critically ill patients is guided by assessing surrogate markers of perfusion. As there is no direct indicator of cerebral perfusion used in routine critical care, identifying an accurate strategy to monitor brain perfusion is paramount. Near-infrared spectroscopy (NIRS) is a non-invasive technique to quantify regional cerebral oxygenation (rSO2) that has been used for decades during cardiac surgery which has led to targeted algorithms to optimize rSO2 being developed. However, these targeted algorithms do not exist during critical care, as the physiological determinants of rSO2 during critical illness remain poorly understood. Materials and methods This prospective observational study was an exploratory analysis of a nested cohort of patients within the CONFOCAL study (NCT02344043) who received high-fidelity vital sign monitoring. Adult patients (≥ 18 years) admitted

Abstract Background Evidence is mounting that patient-reported experience can provide a valuable indicator of the quality of healthcare services. However, little is known about the relationship between the experiences of people with severe mental illness and the quality of care they receive. We conducted a study to examine the relationship between patient-reported experience and the quality of care provided to people with schizophrenia. Methods We calculated a composite global rating of quality of care for people with schizophrenia using data from an audit of 64 mental health providers. We then examined associations between these ratings and mean patient satisfaction and patient-rated outcome using data from a survey of 5608 schizophrenic patients treated in these services. Results Global rating of quality of care was positively correlated with patient-rated outcome (r = 0.33; p = 0.01) but not with patient satisfaction (r = 0.21, p = 0.10). Patient-rated outcome was also positively correlated with patient involvement (r = 0.26, p = 0.04) and the quality of prescribing practice (r = 0.31, p = 0.02). High patient satisfaction scores were significantly associated with the extent of use of care plans within each organisation (r = 0.27, p = 0.03). Conclusions Among people with schizophrenia, patient-rated outcome provides a better guide to the quality of care than patient-rated satisfaction. Greater use of patient-reported outcome measures should be made when assessing the quality of care provided to people with psychosis.

PREMISE New sequencing technologies facilitate the generation of large‐scale molecular data sets for constructing the plant tree of life. We describe a new probe set for target enrichment sequencing to generate nuclear sequence data to build phylogenetic trees with any flagellate land plants, including hornworts, liverworts, mosses, lycophytes, ferns, and all gymnosperms. METHODS We leveraged existing transcriptome and genome sequence data to design the GoFlag 451 probes, a set of 56,989 probes for target enrichment sequencing of 451 exons that are found in 248 single‐copy or low‐copy nuclear genes across flagellate plant lineages. RESULTS Our results indicate that target enrichment using the GoFlag451 probe set can provide large nuclear data sets that can be used to resolve relationships among both distantly and closely related taxa across the flagellate land plants. We also describe the GoFlag 408 probes, an optimized probe set covering 408 of the 451 exons from the GoFlag 451 probe set that is commercialized by RAPiD Genomics. CONCLUSIONS A target enrichment approach using the new probe set provides a relatively low‐cost solution to obtain large‐scale nuclear sequence data for inferring phylogenetic relationships across flagellate land plants.

Abstract Background The KINARM robot produces a granular dataset of participant performance metrics associated with proprioceptive, motor, visuospatial, and executive function. This comprehensive battery includes several behavioral tasks that each generate 9 to 20 metrics of performance. Therefore, the entire battery of tasks generates well over 100 metrics per participant, which can make clinical interpretation challenging. Therefore, we sought to reduce these multivariate data by applying principal component analysis (PCA) to increase interpretability while minimizing information loss. Methods Healthy right-hand dominant participants were assessed using a bilateral KINARM end-point robot. Subjects (Ns = 101–208) were assessed using 6 behavioral tasks and automated software generated 9 to 20 metrics related to the spatial and temporal aspects of subject performance. Data from these metrics were converted to Z-scores prior to PCA. The number of components was determined from scree plots and parallel analysis, with interpretability considered as a qualitative criterion. Rotation type (orthogonal vs oblique) was decided on a per task basis. Results The KINARM performance data, per task, was substantially reduced (range 67–79%), while still accounting for a large amount of variance (range 70–82%). The number of KINARM parameters reduced to 3 components for 5 out of 6 tasks and to 5 components for the sixth task. Many components were comprised of KINARM parameters with high loadings and only some cross loadings were observed, which demonstrates a strong separation of components. Conclusions Complex participant data produced by the KINARM robot can be reduced into a small number of interpretable components by using PCA. Future applications of PCA may offer potential insight into specific patterns of sensorimotor impairment among patient populations.

Abstract Background Wearable devices generate signals detecting activity, sleep, and heart rate, all of which could enable detailed and near-continuous characterization of recovery following critical illness. Methods To determine the feasibility of using a wrist-worn personal fitness tracker among patients recovering from critical illness, we conducted a prospective observational study of a convenience sample of 50 stable ICU patients. We assessed device wearability, the extent of data capture, sensitivity and specificity for detecting heart rate excursions, and correlations with questionnaire-derived sleep quality measures. Results Wearable devices were worn over a 24-h period, with excellent capture of data. While specificity for the detection of tachycardia was high (98.8%), sensitivity was low to moderate (69.5%). There was a moderate correlation between wearable-derived sleep duration and questionnaire-derived sleep quality (r = 0.33, P = 0.03). Devices were well-tolerated and demonstrated no degradation in quality of data acquisition over time. Conclusions We found that wearable devices could be worn by patients recovering from critical illness and could generate useful data for the majority of patients with little adverse effect. Further development and study are needed to better define and enhance the role of wearables in the monitoring of post-ICU recovery. Trial registration Clinicaltrials.gov, NCT02527408

This article explores patterns in teachers' reported correction of student language use in speech and writing. The authors use the concept of language correction in student writing and student speech as a proxy for prescriptive approaches to teaching about language. By conducting a large-scale survey of all language and literacy teachers from preschool through 12th grade across an entire state, the authors were able to identify patterns in teachers' approaches to teaching about language that smaller case studies and nuanced qualitative studies have not yet documented. They examine differences in teachers' self-reported correction of student language use across teacher characteristics and contexts such as grade levels taught, regions of the state, years of teaching experience, and whether teachers had taken a linguistics class. The authors identified marked differences in how elementary and secondary teachers report correcting student writing and speech. They found a small but significant difference in the impact of taking a linguistics class depending on grades taught. They note small but significant differences between reported correction of language for teachers in urban and rural contexts. They discuss implications for professional development on teaching about language targeted to the needs of teachers based on grade level, context, and experience.

We report a first measurement for ultrahigh energy cosmic rays of the correlation between the depth of shower maximum and the signal in the water Cherenkov stations of air-showers registered simultaneously by the fluorescence and the surface detectors of the Pierre Auger Observatory. Such a correlation measurement is a unique feature of a hybrid air-shower observatory with sensitivity to both the electromagnetic and muonic components. It allows an accurate determination of the spread of primary masses in the cosmic-ray flux. Up till now, constraints on the spread of primary masses have been dominated by systematic uncertainties. The present correlation measurement is not affected by systematics in the measurement of the depth of shower maximum or the signal in the water Cherenkov stations. The analysis relies on general characteristics of air showers and is thus robust also with respect to uncertainties in hadronic event generators. The observed correlation in the energy range around the ‘ankle’ at lg⁡(E/eV)=18.5–19.0 differs significantly from expectations for pure primary cosmic-ray compositions. A light composition made up of proton and helium only is equally inconsistent with observations. The data are explained well by a mixed composition including nuclei with mass A>4. Scenarios such as the proton dip model, with almost pure compositions, are thus disfavored as the sole explanation of the ultrahigh-energy cosmic-ray flux at Earth. Keywords: Pierre Auger Observatory, Cosmic rays, Mass composition, Ankle

Entrenched compartmentalisation of curriculum subjects and 'teaching to the test' can leave students with limited understanding of the nature and interaction of disciplines. The necessity of developing future teachers' epistemic insight (EI) and equipping them with strategies to address the gaps between subjects has been pushed to the fore by challenges that emerged during the pandemic. This article examines the extent to which epistemic insight is understood by Initial Teacher Education tutors and features in their programmes as well as their recommendations for increasing the inclusion of multidisciplinary approaches in education, based on qualitative and quantitative research. While initial findings revealed a poor understanding of EI, its importance was broadly acknowledged, and the follow-up survey revealed progress in the form of greater engagement with and inclusion of EI by tutors in teacher education. This research was done in the context of a new inspection framework distinguishing substantive and disciplinary knowledge.

Background: Approximately 24,000 Ontarians live in remote Indigenous communities with no road access. These communities are a subset of Nishnawbe Aski Nation (NAN), a political grouping of 49 First Nations communities in Northern Ontario, Canada. Limited information is available regarding the status of emergency care in these communities. Objective: We aimed to understand emergency response systems, services, and training in remote NAN communities. Design: We used an environmental scan approach to compile information from multiple sources including community-based participatory research. This included the analysis of data collected from key informant interviews (n=10) with First Nations community health leaders and a multi-stakeholder roundtable meeting (n=33) in October 2013. Results: Qualitative analysis of the interview data revealed four issues related to emergency response systems and training: (1) inequity in response capacity and services, (2) lack of formalised dispatch systems, (3) turnover and burnout in volunteer emergency services, and (4) challenges related to first aid training. Roundtable stakeholders supported the development of a community-based emergency care system to address gaps. Conclusions: Existing first response, paramedical, and ambulance service models do not meet the unique geographical, epidemiological and cultural needs in most NAN communities. Sustainable, context-appropriate, and culturally relevant emergency care systems are needed.

Phylogenetic trees can reveal the origins of endosymbiotic lineages of bacteria and detect patterns of co-evolution with their hosts. Although taxon sampling can greatly affect phylogenetic and co-evolutionary inference, most hypotheses of endosymbiont relationships are based on few available bacterial sequences. Here we examined how different sampling strategies of Gammaproteobacteria sequences affect estimates of the number of endosymbiont lineages in parasitic sucking lice (Insecta: Phthirapatera: Anoplura). We estimated the number of louse endosymbiont lineages using both newly obtained and previously sequenced 16S rDNA bacterial sequences and more than 42,000 16S rDNA sequences from other Gammaproteobacteria. We also performed parametric and nonparametric bootstrapping experiments to examine the effects of phylogenetic error and uncertainty on these estimates. Sampling of 16S rDNA sequences affects the estimates of endosymbiont diversity in sucking lice until we reach a threshold of genetic diversity, the size of which depends on the sampling strategy. Sampling by maximizing the diversity of 16S rDNA sequences is more efficient than randomly sampling available 16S rDNA sequences. Although simulation results validate estimates of multiple endosymbiont lineages in sucking lice, the bootstrap results suggest that the precise number of endosymbiont origins is still uncertain.

Investigators from Ruth Children's Hospital, Haifa, and Schneider Medical Center, Petah Tikuah, Israel, evaluated the long-term motor and neurocognitive outcome of 43 children hospitalized during 2002-2012 with acute disseminated encephalomyelitis (ADEM), and identified prognostic risk factors.

Investigators from Child Neurology and Pediatrics, University of Texas Health Science Center, Houston, report extrapyramidal symptoms in a 13-year-old boy with a psychiatric history of schizophrenia, bipolar disorder, ADHD, and autism, responsive to combination risperidone, oxcarbazepine, and MPH.

Investigators from Teikyo University School of Medicine, Tokyo, Japan, evaluated the clinical features, prognosis, and prophylaxis of cyclic vomiting syndrome and the relationship between the syndrome and levels of adrenocorticotropic/antidiuretic hormones (ACTH/ADH).

A Task Force established by the Brazil Ministry of Health investigated the possible association of microcephaly with Zika virus infection during pregnancy and a registry for microcephaly cases among women suspected to have had Zika virus infection during pregnancy.

Over the past 30 years, Pediatric Neurology Briefs (PNB) has been published monthly as a continuing education service designed to expedite and facilitate review of current medical literature concerning pediatric neurology.

Investigators from hospitals in Brazil tested verbal fluency in 20 adolescent patients, ages ranged from 11 to 16 years (mean 13.8 years), with Sydenham chorea compared with 20 patients with rheumatic fever without chorea and 20 healthy controls, matched for age and gender.

Investigators at the Karol Marcinkowski University of Medical Sciences, Poznan, Poland, analyzed the records of 194 children diagnosed with Epstein-Barr virus infection and having the viral capsid antigen IgM antibody.

Investigators from the Boston Children's Hospital recorded pattern-reversal visual evoked potentials (VEPs) in Mecp2 heterozygous female mice and in 34 girls with Rett syndrome (RTT).

Investigators from Hospital Sant Joan de Deu, Barcelona, Spain, studied the relationship between the etiology of refractory childhood epilepsy, CSF neurotransmitters, pterins, and amino acids, and response to a ketogenic diet in 60 patients with refractory epilepsy, 83% focal and 52% idiopathic.

Investigators from the Division of Developmental Medicine and Clinical Research Center, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, studied the relationship between the timing of Attention Deficit Hyperactivity Disorder (ADHD) diagnosis in children with Autism Spectrum Disorder (ASD) and the age at ASD diagnosis.