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Pompe disease results from lysosomal acid α-glucosidase deficiency, which leads to cardiomyopathy in all infantile-onset and occasional late-onset patients. Cardiac assessment is important for its diagnosis and management. This article presents unpublished cardiac findings, concomitant medications, and cardiac efficacy and safety outcomes from the ADVANCE study; trajectories of patients with abnormal left ventricular mass z score at enrolment; and post hoc analyses of on-treatment left ventricular mass and systolic blood pressure z scores by disease phenotype, GAA genotype, and “fraction of life” (defined as the fraction of life on pre-study 160 L production-scale alglucosidase alfa). ADVANCE evaluated 52 weeks’ treatment with 4000 L production-scale alglucosidase alfa in ≥1-year-old United States of America patients with Pompe disease previously receiving 160 L production-scale alglucosidase alfa. M-mode echocardiography and 12-lead electrocardiography were performed at enrolment and Week 52. Sixty-seven patients had complete left ventricular mass z scores, decreasing at Week 52 (infantile-onset patients, change −0.8 ± 1.83; 95% confidence interval −1.3 to −0.2; all patients, change −0.5 ± 1.71; 95% confidence interval −1.0 to −0.1). Patients with “fraction of life” <0.79 had left ventricular mass z score decreasing (enrolment: +0.1 ± 3.0; Week 52: −1.1 ± 2.0); those with “fraction of life” ≥0.79 remained stable (enrolment: −0.9 ± 1.5; Week 52: −0.9 ± 1.4). Systolic blood pressure z scores were stable from enrolment to Week 52, and no cohort developed systemic hypertension. Eight patients had Wolff–Parkinson–White syndrome. Cardiac hypertrophy and dysrhythmia in ADVANCE patients at or before enrolment were typical of Pompe disease. Four-thousand L alglucosidase alfa therapy maintained fractional shortening, left ventricular posterior and septal end-diastolic thicknesses, and improved left ventricular mass z score.
Social Media Statement: Post hoc analyses of the ADVANCE study cohort of 113 children support ongoing cardiac monitoring and concomitant management of children with Pompe disease on long-term alglucosidase alfa to functionally improve cardiomyopathy and/or dysrhythmia.
To determine the utility of the Sofia SARS rapid antigen fluorescent immunoassay (FIA) to guide hospital-bed placement of patients being admitted through the emergency department (ED).
Cross-sectional analysis of a clinical quality improvement study.
This study was conducted in 2 community hospitals in Maryland from September 21, 2020, to December 3, 2020. In total, 2,887 patients simultaneously received the Sofia SARS rapid antigen FIA and SARS-CoV-2 RT-PCR assays on admission through the ED.
Rapid antigen results and symptom assessment guided initial patient placement while confirmatory RT-PCR was pending. The sensitivity, specificity, positive predictive values, and negative predictive values of the rapid antigen assay were calculated relative to RT-PCR, overall and separately for symptomatic and asymptomatic patients. Assay sensitivity was compared to RT-PCR cycle threshold (Ct) values. Assay turnaround times were compared. Clinical characteristics of RT-PCR–positive patients and potential exposures from false-negative antigen assays were evaluated.
For all patients, overall agreement was 97.9%; sensitivity was 76.6% (95% confidence interval [CI], 71%–82%), and specificity was 99.7% (95% CI, 99%–100%). We detected no differences in performance between asymptomatic and symptomatic individuals. As RT-PCR Ct increased, the sensitivity of the antigen assay decreased. The mean turnaround time for the antigen assay was 1.2 hours (95% CI, 1.0–1.3) and for RT-PCR it was 20.1 hours (95% CI, 18.9–40.3) (P < .001). No transmission from antigen-negative/RT-PCR–positive patients was identified.
Although not a replacement for RT-PCR for detection of all SARS-CoV-2 infections, the Sofia SARS antigen FIA has clinical utility for potential initial timely patient placement.
The escalating evolution of weed species resistant to acetolactase synthase (ALS)-inhibitor herbicides makes alternative weed control strategies necessary for field crops that are dependent on this herbicide group. A fully integrated strategy that combined increased crop seeding rates (2X or 4X recommended), mechanical weed control with a minimum-tillage rotary hoe, and reduced-rate non–ALS inhibitor herbicides was compared with herbicides, rotary hoe, and seeding rates alone as a method of controlling ALS inhibitor–tolerant Indian mustard as a model weed. The full-rate herbicide treatment had the lowest weed biomass (98% reduction) and the highest yield of all treatments in 3 of 4 site-years, regardless of seeding rate. The fully integrated treatment at the 4X seeding rate had weed suppression rates equal to the full herbicide treatment at the recommended seeding rate. The fully integrated and reduced-rate herbicide treatments at the 4X seeding rate reduced weed biomass by 89% and 83%, respectively, compared with the control at the recommended seeding rate. The rotary hoe treatment alone resulted in poor weed control (≤38%), even at the highest seeding rate. Fully integrated and reduced-rate herbicide treatments at 2X and 4X seeding rates had yields equal to those of the full herbicide treatment at the recommended seeding rate. Partially or fully integrated weed control strategies that combine increased crop seeding rates and reduced-rate non–ALS inhibitor herbicides, with or without the use of a rotary hoe, can control weeds resistant to ALS-inhibitor herbicides, while maintaining crop yields similar to those achieved with full-rate herbicides. However, combining increased seeding rate, reduced-rate herbicides, and mechanical rotary hoe treatment into a fully integrated strategy maximized weed control, while reducing reliance on and selection pressure against any single weed control tactic.
Concern over the development of herbicide-resistant weeds has led to interest in integrated weed management systems that reduce selection pressure by utilizing mechanical and cultural weed control practices in addition to herbicides. Increasing crop seeding rate increases crop competitive ability and thus can enhance herbicide efficacy. However, it is unknown how increasing the seeding rate affects an herbicide’s efficacy. The objective of this study was to examine the interaction between increasing seeding rate and herbicide dose to control weeds. To meet this objective, the herbicide fluthiacet-methyl was applied to field-grown lentil, with Indian mustard, a proxy for wild mustard, used as a model weed. The experiment was a factorial design with four lentil seeding rates and seven herbicide rates. Overall the herbicide dose response was altered by changing lentil seeding rate. Increasing lentil seeding rate decreased the weed biomass production when herbicides were not applied. In two of the four site-years, increasing lentil seeding rate lowered the herbicide ED50, the dose required to result in a 50% reduction in weed biomass. Increasing the crop seeding rate altered the dose response to provide greater weed control at lower herbicide rates compared with normal crop seeding rates. Increased seeding rates also resulted in higher and more stable crop seed yields across a wider range of herbicide dosages. These results suggest that dose–response models can be used to evaluate the efficacy of other weed management practices that can interact with herbicide performance.
The recently developed three-dimensional electron microscopic (EM) method of serial block-face scanning electron microscopy (SBEM) has rapidly established itself as a powerful imaging approach. Volume EM imaging with this scanning electron microscopy (SEM) method requires intense staining of biological specimens with heavy metals to allow sufficient back-scatter electron signal and also to render specimens sufficiently conductive to control charging artifacts. These more extreme heavy metal staining protocols render specimens light opaque and make it much more difficult to track and identify regions of interest (ROIs) for the SBEM imaging process than for a typical thin section transmission electron microscopy correlative light and electron microscopy study. We present a strategy employing X-ray microscopy (XRM) both for tracking ROIs and for increasing the efficiency of the workflow used for typical projects undertaken with SBEM. XRM was found to reveal an impressive level of detail in tissue heavily stained for SBEM imaging, allowing for the identification of tissue landmarks that can be subsequently used to guide data collection in the SEM. Furthermore, specific labeling of individual cells using diaminobenzidine is detectable in XRM volumes. We demonstrate that tungsten carbide particles or upconverting nanophosphor particles can be used as fiducial markers to further increase the precision and efficiency of SBEM imaging.
To validate the utility of a previously published scoring model (Italian) to identify patients infected with community-onset extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-EKP) and develop a new model (Duke) based on local epidemiology.
This case-control study included patients 18 years of age or more admitted to Duke University Hospital between January 1, 2008, and December 31, 2010, with culture-confirmed infection due to an ESBL-EKP (cases). Uninfected controls were matched to cases (3 : 1). The Italian model was applied to our patient population for validation. The Duke model was developed through logistic-regression-based prediction scores calculated on variables independently associated with ESBL-EKP isolation. Sensitivities and specificities at various point cutoffs were determined, and determination of the area under the receiver operating characteristic curve (ROC AUC) was performed.
A total of 123 cases and 375 controls were identified. Adjusted odds ratios and 95% confidence intervals for variables previously identified in the Italian model were as follows: hospitalization (3.20 [1.62–6.55]), transfer (4.31 [2.15–8.78]), urinary catheterization (5.92 [3.09–11.60]), β-lactam and/or fluoroquinolone therapy (3.76 [2.06–6.95]), age 70 years or more (1.55 [0.79–3.01]), and Charlson Comorbidity Score of 4 or above (1.06 [0.55–2.01]). Sensitivity and specificity were, respectively, more than or equal to 95% and less than or equal to 47% for scores 3 or below and were less than or equal to 50% and more than or equal to 96% for scores 8 or above. The ROC AUC was 0.88. Variables identified in the Duke model were as follows: hospitalization (2.63 [1.32–5.41]), transfer (5.30 [2.67–10.71]), urinary catheterization (6.89 [3.62–13.38]), β-lactam and/or fluoroquinolone therapy (3.47 [1.91–6.41]), and immunosuppression (2.34 [1.14–4.80]). Sensitivity and specificity were, respectively, more than or equal to 94% and less than or equal to 65% for scores 3 or below and were less than or equal to 58% and more than or equal to 95% for scores 8 or above. The ROC AUC was 0.89.
While the previously reported model was an excellent predictor of community-onset ESBL-EKP infection, models utilizing factors based on local epidemiology may be associated with improved performance.
Motivated by complex multi-fluid geometries currently being explored in fibre-device manufacturing, we study capillary instabilities in concentric cylindrical flows of fluids with arbitrary viscosities, thicknesses, densities, and surface tensions in both the Stokes regime and for the full Navier–Stokes problem. Generalizing previous work by Tomotika (), Stone & Brenner (, equal viscosities) and others, we present a full linear stability analysis of the growth modes and rates, reducing the system to a linear generalized eigenproblem in the Stokes case. Furthermore, we demonstrate by Plateau-style geometrical arguments that only axisymmetric instabilities need be considered. We show that the case is already sufficient to obtain several interesting phenomena: limiting cases of thin shells or low shell viscosity that reduce to problems, and a system with competing breakup processes at very different length scales. The latter is demonstrated with full three-dimensional Stokes-flow simulations. Many cases remain to be explored, and as a first step we discuss two illustrative cases, an alternating-layer structure and a geometry with a continuously varying viscosity.
The spread of many invasive plants is facilitated through seed dispersal by frugivorous animals. The effectiveness of various frugivores as dispersers of the seeds of Melia azedarach, a highly invasive alien tree species, was evaluated in South Africa in savanna and bushveld vegetation. During 264 h of observation, seven bird species and one bat species were recorded foraging on fruiting trees of M. azedarach. The most common visitors were the dark-capped bulbul (Pycnonotus barbatus) followed by Wahlberg's epauletted fruit bat (Epomophorus wahlbergi), but both species dropped nearly as many seeds as they dispersed. Knysna turaco (Tauraco corythaix) dispersed the highest number of fruits per minute, but occurred in low abundance in our study sites. Seed germination differed significantly between de-pulped fruits and untreated fruits after 2 mo, but was similar after 4 mo. Germination success did not differ between animal-handled and hand-depulped fruits. In contrast to the high germination success in the greenhouse, seedlings showed very low recruitment in the field. Thus, M. azedarach seems likely to benefit from frugivores (particularly dark-capped bulbul and Wahlberg's epauletted fruit bat) dispersing seeds to suitable microsites.
The model developed by Forbes (1987) of how body fat mass (FM) and fat-free mass (FFM) change during periods of weight loss or gain (Δ body weight (BW)) assumed that they change in relationship to a constant C = 10·4, where ΔFFM/ΔBW = 10·4/(10·4+FM). Forbes derived C based on aggregated, cross-sectional data from a small sample of women. The objective of the present study was to reanalyse the relationship described by Forbes and to explore whether this relationship is consistent across ethnicity and sex groups using cross-sectional data from a large sample of white and African-American men and women. Baseline data from white and African-American men and women aged 18–60 years, who participated in a clinical study at the Pennington Biomedical Research Center since 2001 and who underwent dual-energy X-ray absorptiometry scans, were available for analysis. To overcome differences in BMI distributions among the ethnicity-by-sex groups, a stratified random sample of participants was selected within each group such that numbers in each BMI category ( < 25, 25–29·9, 30–34·9, 35–39·9, 40+ kg/m2) were proportional to those within the group with the smallest sample size, yielding a sample of 1953 individuals. Linear regression models assessed the FM–FFM relationship across the four ethnicity-by-sex groups. The FM–FFM relationship varied little by ethnicity (P = 0·57) or by sex (P = 0·26). The constant describing the FM–FFM relationship was estimated to be 9·7 (95 % CI 9·0, 10·3). In conclusion, results from our large, biethnic sample of men and women found a FM–FFM relationship very close to that originally described by Forbes, absent of significant variability by ethnicity or sex.