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We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult and pediatric patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015-2022. Of 30,824 reported CDI cases, 94.9% (29,250/30,824) were among adult (73.2% HA; 26.8% CA) and 5.1% (1,574/30,824) pediatric (77.6% HA; 22.4% CA) patients. During the study period, adult HA CDI rates decreased by 19.9% and CA CDI rates remained stable; pediatric HA CDI rates decreased by 29.6% and CA CDI decreased by 58.3%. Ribotype (RT) 106 was most common among both groups and replaced RT027 as the predominant strain type. RT027 was most associated with adult patients, HA acquisition, severe CDI, and severe outcomes. Moxifloxacin resistance was higher in adult than pediatric cases; clindamycin and rifampin resistance rates were similar between groups. Continued national surveillance is integral to understanding the epidemiology of adult and pediatric CDI in Canada and informing prevention efforts.

Background: The molecular and epidemiological landscape of C. difficile infection (CDI) has evolved markedly in the last decade; however, limited information is available contrasting differences between adult and pediatric populations. We describe a multicenter study evaluating healthcare-associated (HA) and community-associated (CA) adult and pediatric-CDI identified in the Canadian Nosocomial Infection Surveillance Program (CNISP) network from 2015 to 2022. Methods: Hospitalized patients with CDI were identified from up to 84 hospitals between 2015–2022 using standardized case definitions. Cases were confirmed by PCR, cultured, and further characterized using ribotyping and E-test. We used two-tailed tests for significance (p≤0.05). Results: Of 30,817 cases reported, 29,245 were adult cases [HA-CDI (73.2%), CA-CDI (26.8%)] and 1,572 were pediatric cases [HA-CDI (77.7%), CA-CDI (22.3%)]. From 2015 to 2022, HA-CDI rates decreased 19.7% (p=0.007) and 29.4% (p=0.004) in adult and pediatric populations, respectively (Figure 1). CA-CDI rates remained relatively stable in the adult population (p=0.797), while decreasing 60.7% in the pediatric population (p=0.013). Median ages of adult and pediatric patients were 70 (interquartile range (IQR), 58–80) and seven (IQR, 3–13) years, respectively. Thirty-day all-cause mortality was significantly higher among adult vs. Pediatric CDI patients (11.0% vs 1.4%, p < 0.0001). No significant differences in other severe outcomes were found. Ribotyping and susceptibility data were available for 4,620 samples: 3,558 adult (77.0%) and 1,062 pediatric (23.0%). The predominant adult and pediatric ribotypes (RT) were 106 (12.2/16.2%), 027 (11.4/3.2%), and 014 (8.8/8.2%). Overall, RT027 prevalence significantly decreased from 17.9% in 2015 to 3.2% in 2022 (p=0.003), while RT106 increased from 8.5% to 14.4%. Resistance rates among adult and pediatric isolates were similar for all antimicrobials tested except moxifloxacin (16.2% vs. 6.2%, p < 0.0001, respectively). Adult moxifloxacin resistance decreased from 30% to 6.3% from 2015 to 2022 (p=0.006). Adults with moxifloxacin-resistant CDI were older (median: 74 vs. 69 years, p < 0.001) and had higher thirty-day all-cause mortality (13% vs. 9.8%, p=0.041) and recurrence (10% vs. 5.7%, p < 0.001) compared to those with moxifloxacin non-resistant CDI, while these trends were not observed in pediatric patients. Among RT027 strains, moxifloxacin resistance decreased from 91.0% in 2015 to 7.1% in 2022. There was one metronidazole-resistant pediatric sample in 2018 and no resistance to vancomycin or tigecycline in either population. Conclusion: We have found differences in the epidemiological and molecular characteristics of adult and pediatric CDI, with higher thirty-day all-cause mortality among adults. Overall, RT106 has replaced RT027 as the predominant ribotype with a concomitant decrease in fluoroquinolone resistance.

The purpose of this study is to explore the pre-decision processes that led to approval of local stipends for teachers who completed National Board certification in two South Carolina school districts. Specifically, in the two school districts chosen for analysis, the researcher desires to conduct a case study of these processes to determine the conditions under which a policy was approved to award stipends to National Board certified teachers. Recognizing the finite status of resources and how vital the effective allocations of these limited funds are to the educational process, understanding the decision-making process utilized to distribute resources and variables that influenced the process are critical to the concept of resource allocation. The significance of this study is deeply rooted in the practical utilization of the NBPTS certification process by local schools districts. Over one hundred million dollars have been allocated to the NBPTS by the federal government and many state legislatures have committed vast resources to support what they believe is an effort to improve teaching and learning in American classrooms. Critics have recognized a different purpose in utilization of the NBPTS process at the local level, specifically driven by the perceptions and actions of local policy makers. Local districts have been accused of using national certification as a means to raise teacher pay; thereby, they cement their position and ability to compete for teachers in the labor market. If local districts are using NBPTS certification primarily as an avenue to permit accomplished teachers to earn more, then the NBPTS purpose of improving teaching and learning in the classroom is not the main objective in local implementation. Considering the high percentage of policy actors within this group (65%) that recognized an organizational emphasis on programs that enhance student achievement, there appeared to be inconsistency between the organizational emphasis of student achievement and the perceived impact of the decision to grant local stipends to National Board certified teachers.

Landlords need help interpreting the eviction moratorium and applying it correctly; tenants need protection against wrongful eviction, homelessness.

Malignant glioma is the most common and lethal primary brain tumour, with dismal survival rates and no effective treatment. We examined the safety and activity of NSC-CRAd-S-pk7, an engineered oncolytic adenovirus delivered by neural stem cells (NSCs), in patients with newly diagnosed high-grade glioma. This was a first-in-human, open-label, phase 1, dose-escalation trial done to determine the maximal tolerated dose of NSC-CRAd-S-pk7, following a 3 + 3 design. Patients with newly diagnosed, histologically confirmed, high-grade gliomas (WHO grade III or IV) were recruited. After neurosurgical resection, NSC-CRAd-S-pk7 was injected into the walls of the resection cavity. The first patient cohort received a dose starting at 6·25 × 1010 viral particles administered by 5·00 × 107 NSCs, the second cohort a dose of 1·25 × 1011 viral particles administered by 1·00 × 108 NSCs, and the third cohort a dose of 1·875 × 1011 viral particles administered by 1·50 × 108 NSCs. No further dose escalation was planned. Within 10–14 days, treatment with temozolomide and radiotherapy was initiated. Primary endpoints were safety and toxicity profile and the maximum tolerated dose for a future phase 2 trial. All analyses were done in all patients who were included in the trial and received the study treatment and were not excluded from the study. Recruitment is complete and the trial is finished. The trial is registered with ClinicalTrials.gov, NCT03072134. Between April 24, 2017, and Nov 13, 2019, 12 patients with newly diagnosed, malignant gliomas were recruited and included in the safety analysis. Histopathological evaluation identified 11 (92%) of 12 patients with glioblastoma and one (8%) of 12 patients with anaplastic astrocytoma. The median follow-up was 18 months (IQR 14–22). One patient receiving 1·50 × 108 NSCs loading 1·875 × 1011 viral particles developed viral meningitis (grade 3) due to the inadvertent injection of NSC-CRAd-S-pk7 into the lateral ventricle. Otherwise, treatment was safe as no formal dose-limiting toxicity was reached, so 1·50 × 108 NSCs loading 1·875 × 1011 viral particles was recommended as a phase 2 trial dose. There were no treatment-related deaths. The median progression-free survival was 9·1 months (95% CI 8·5–not reached) and median overall survival was 18·4 months (15·7–not reached). NSC-CRAd-S-pk7 treatment was feasible and safe. Our immunological and histopathological findings support continued investigation of NSC-CRAd-S-pk7 in a phase 2/3 clinical trial. US National Institutes of Health.

Severe spinal cord injury (SCI) leads to skeletal muscle atrophy and adipose tissue infiltration in the skeletal muscle, which can result in compromised muscle mechanical output and lead to health-related complications. In this study, we developed a novel automatic 3-D approach for volumetric segmentation and quantitative assessment of thigh Magnetic Resonance Imaging (MRI) volumes in individuals with chronic SCI as well as non-disabled individuals. In this framework, subcutaneous adipose tissue, inter-muscular adipose tissue and total muscle tissue are segmented using linear combination of discrete Gaussians algorithm. Also, three thigh muscle groups were segmented utilizing the proposed 3-D Joint Markov Gibbs Random Field model that integrates first order appearance model, spatial information, and shape model to localize the muscle groups. The accuracy of the automatic segmentation method was tested both on SCI (N = 16) and on non-disabled (N = 14) individuals, showing an overall 0.93±0.06 accuracy for adipose tissue and muscle compartments segmentation based on Dice Similarity Coefficient. The proposed framework for muscle compartment segmentation showed an overall higher accuracy compared to ANTs and STAPLE, two previously validated atlas-based segmentation methods. Also, the framework proposed in this study showed similar Dice accuracy and better Hausdorff distance measure to that obtained using DeepMedic Convolutional Neural Network structure, a well-known deep learning network for 3-D medical image segmentation. The automatic segmentation method proposed in this study can provide fast and accurate quantification of adipose and muscle tissues, which have important health and functional implications in the SCI population.

A user-friendly ImageJ plugin enables the application and training of U-Nets for deep-learning-based image segmentation, detection and classification tasks with minimal labeling requirements.

Environmental enteric dysfunction (EED) is a subclinical condition of intestinal inflammation, barrier dysfunction and malabsorption associated with growth faltering in children living in poverty. This study explores association of altered duodenal permeability (lactulose, rhamnose and their ratio) with higher burden of enteropathogen in the duodenal aspirate, altered histopathological findings and higher morbidity (diarrhea) that is collectively associated with linear growth faltering in children living in EED endemic setting. In a longitudinal birth cohort, 51 controls (WHZ > 0, HAZ > −1.0) and 63 cases (WHZ< -2.0, refractory to nutritional intervention) were recruited. Anthropometry and morbidity were recorded on monthly bases up to 24 months of age. Dual sugar assay of urine collected after oral administration of lactulose and rhamnose was assessed in 96 children from both the groups. Duodenal histopathology (n = 63) and enteropathogen analysis of aspirate via Taqman array card (n = 60) was assessed in only cases. Giardia was the most frequent pathogen and was associated with raised L:R ratio (p = 0.068). Gastric microscopy was more sensitive than duodenal aspirate in H . pylori detection. Microscopically confirmed H . pylori negatively correlated with HAZ at 24 months (r = −0.313, p = 0.013). Regarding histopathological parameters, goblet cell reduction significantly correlated with decline in dual sugar excretion (p< 0.05). Between cases and controls, there were no significant differences in the median (25 th , 75 th percentile) of urinary concentrations (μg/ml) of lactulose [27.0 (11.50, 59.50) for cases vs. 38.0 (12.0, 61.0) for controls], rhamnose [66.0 (28.0, 178.0) vs. 86.5 (29.5, 190.5)] and L:R ratio [0.47 (0.24, 0.90) vs. 0.51 (0.31, 0.71)] respectively. In multivariable regression model, 31% of variability in HAZ at 24 months of age among cases and controls was explained by final model including dual sugars. In conclusion, enteropathogen burden is associated with altered histopathological features and intestinal permeability. In cases and controls living in settings of endemic enteropathy, intestinal permeability test may predict linear growth. However, for adoption as a screening tool for EED, further validation is required due to its complex intestinal pathophysiology.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry starts with membrane attachment and ends with spike (S) protein—catalyzed membrane fusion depending on two cleavage steps, namely, one usually by furin in producing cells and the second by TMPRSS2 on target cells. Endosomal cathepsins can carry out both. Using real-time three-dimensional single-virion tracking, we show that fusion and genome penetration require virion exposure to an acidic milieu of pH 6.2 to 6.8, even when furin and TMPRSS2 cleavages have occurred. We detect the sequential steps of S1-fragment dissociation, fusion, and content release from the cell surface in TMPRRS2-overexpressing cells only when exposed to acidic pH. We define a key role of an acidic environment for successful infection, found in endosomal compartments and at the surface of TMPRSS2-expressing cells in the acidic milieu of the nasal cavity.

To progress from the laboratory to commercial applications, it will be necessary to develop industrially scalable methods to produce large quantities of defect-free graphene. Here we show that high-shear mixing of graphite in suitable stabilizing liquids results in large-scale exfoliation to give dispersions of graphene nanosheets. X-ray photoelectron spectroscopy and Raman spectroscopy show the exfoliated flakes to be unoxidized and free of basal-plane defects. We have developed a simple model that shows exfoliation to occur once the local shear rate exceeds 10 4 s −1 . By fully characterizing the scaling behaviour of the graphene production rate, we show that exfoliation can be achieved in liquid volumes from hundreds of millilitres up to hundreds of litres and beyond. The graphene produced by this method performs well in applications from composites to conductive coatings. This method can be applied to exfoliate BN, MoS 2 and a range of other layered crystals. Methods to achieve large-scale production of defect-free graphene are needed to enable the commercial development of graphene-based devices. It is now shown that high-shear mixing is an effective way to exfoliate graphene and other two-dimensional materials in liquid volumes up to hundreds of litres.