The objective of this study was to report on the development of neuroinvasive West Nile virus (WNV) infection in the context of anti-CD20 monotherapy for multiple sclerosis (MS).
This is a case ...series study.
In 2021-2022, we observed 4 cases of neuroinvasive WNV infection in our patient population of 2009 patients with MS on ocrelizumab, compared with a total of 46 cases of neuroinvasive WNV infection reported in Pennsylvania and 40 in New Jersey. Odds were 258 times that of the general population (95% confidence interval 97-691), χ
< 0.0001). All were women aged 41-61 years with variable disease duration, level of disability, and duration of anti-CD20 therapy. All presented in summer/early fall with fever, headache, and encephalopathy consistent with meningoencephalitis. Three patients had acute cerebellitis. Two had anterior nerve root involvement progressing to quadriparesis, and 1 developed refractory nonconvulsive status epilepticus. All required intubation and experienced significant morbidity. All had CSF pleocytosis. Two patients were WNV IgM positive in both the serum and CSF, 1 patient had positive serum IgM and CSF metagenomic next-generation sequencing (mNGS), while 1 had positive CSF mNGS with negative serum and CSF antibodies.
Neuroinvasive WNV infection can develop with anti-CD20 monotherapy in the absence of additional immunosuppression. WNV serologies may be negative in the setting of anti-CD20 treatment; in the appropriate clinical context, one should consider direct detection methods such as PCR or mNGS-based testing.
In the United States, beginning teacher retention rates are extraordinarily low; only 50% of teachers remain in the classroom after five years. In particular, the State of Arizona has been recruiting ...significant numbers of teachers from out of state and attempting to retain them with minimal success. This persistent problem has led the neediest of students to have teachers with lower levels of professional experience, leaving those students with continually lower achievement gains. Drawing on integrated action research and grounded theory methodology, this study’s took place in a large kindergarten to eighth grade elementary school district located in a high-poverty neighborhood in Arizona. The study invited six new teachers in their first year of teaching to explore innovative strategies to increase these teachers’ retention in the profession. The ultimate goal was to understand how such support might alter a beginning teacher’s perceptions of their own persistence and resilience in dealing with the challenges of first-year teaching, thereby reducing beginning teacher attrition. The study finds that teachers must be nurtured and cared for in order for them to fully devote their time and energy to effectively care for the students in their classroom. Increasing self-awareness and resiliency has the potential to create a ripple effect to retain more beginning teachers, as they become more likely to persevere, ask for help, connect with others, and achieve a healthy life/work balance while positively impacting students and their community.
Abstract
INTRODUCTION
Recent discoveries have provided valuable insight into the genomic landscape of pediatric low grade gliomas (LGGs) at diagnosis, facilitating molecularly targeted treatment. ...However, little is known about their temporal and therapy-related genomic heterogeneity. An adequate understanding of the evolution of pediatric LGGs’ genomic profiles over time is critically important in guiding decisions about targeted therapeutics and diagnostic biopsy at recurrence.
METHODS
Fluorescence in situ hybridization, mutation-specific immunohistochemistry, and exome analyses were performed on paired tumor samples from primary diagnostic and subsequent surgeries.
RESULTS
101 tumor samples from 48 patients (43 with 2 specimens, 5 with 3 specimens) from 3 institutions underwent testing. BRAF fusion and BRAFV600E status were conserved in 100% and 97% of paired specimens, respectively. No loss or gain of IDH1 mutations or FGFR1, NTRK2, MYB, or MYBL1 rearrangements were detected over time. Histologic diagnosis remained the same in all tumors, with no acquired H3K27M mutations or malignant transformation. CDKN2A deletions were acquired in 7 patients (including 3 who received chemotherapy 2 with temozolomide and 1 who received radiation), and were associated with a trend toward shorter time to progression (median: 5.5 vs. 13.0 months p=0.08).
CONCLUSIONS
Most targetable genetic alterations in pediatric LGGs, including BRAF alterations, are conserved at recurrence and following chemotherapy or radiation. However, CDKN2A deletion acquisition was demonstrated and may define a higher risk group. Given potential for targeted therapies for tumors acquiring CDKN2A deletions, performing a biopsy at recurrence may be indicated in certain patients, especially those with rapid progression.
Low-background lead for radiation measurement shielding is often assayed for 210Pb to ensure acceptable backgrounds. Samples of lead assayed with a germanium spectrometer calibrated for ...bremsstrahlung-based assay of 210Pb provide a view into the 210Pb content of commercial lead in the U.S. (other than stockpiled Doe Run lead). Results suggest that the loss of lead smelting in the U.S. has eliminated the traditional supply of “low background” lead (~30Bqkg−1), and indicate current commercial supplies contain roughly an order of magnitude higher 210Pb levels.
•Samples representative of U.S. commercial lead supplies assayed for 210Pb.•End of U.S. lead smelting has impacted availability of low-background lead.•Recycled lead supplies may contain an order of magnitude more 210Pb.
What is already known about this topic? COVID-19 has disproportionately affected Black or African American and Hispanic communities. What is added by this report? Among persons vaccinated during ...March 29–April 6, 2021, compared with December 14, 2020–January 3, 2021, in North Carolina, the proportion who were Black nearly doubled, and the share of vaccine doses administered to Hispanic persons doubled during this period, approaching the proportion of the state population for these groups aged ≥16 years. What are the implications for public health practice? To promote equitable vaccination coverage, public health officials could consider using U.S. Census tract-level mapping to guide vaccine allocation, promote shared accountability for equitable distribution of vaccines with providers through data sharing, and facilitate community partnerships to support vaccine access.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Approximately 50% of the risk for the development of testicular germ cell tumors (TGCTs) is estimated to be heritable, but no mendelian TGCT predisposition genes have yet been identified. It is ...hypothesized that inherited pathogenic DNA repair gene (DRG) alterations may drive susceptibility to TGCTs.
To systematically evaluate the enrichment of germline pathogenic variants in the mendelian cancer predisposition DRGs in patients with TGCTs vs healthy controls.
A case-control enrichment analysis was performed from January 2016 to May 2018 to screen for 48 DRGs in 205 unselected men with TGCT and 27 173 ancestry-matched cancer-free individuals from the Exome Aggregation Consortium cohort in the discovery stage. Significant findings were selectively replicated in independent cohorts of 448 unselected men with TGCTs and 442 population-matched controls, as well as 231 high-risk men with TGCTs and 3090 ancestry-matched controls. Statistical analysis took place from January to May 2018.
Gene-level enrichment analysis of germline pathogenic variants in individuals with TGCTs relative to cancer-free controls.
Among 205 unselected men with TGCTs (mean SD age, 33.04 9.67 years), 22 pathogenic germline DRG variants, one-third of which were in CHEK2 (OMIM 604373), were identified in 20 men (9.8%; 95% CI, 6.1%-14.7%). Unselected men with TGCTs were approximately 4 times more likely to carry germline loss-of-function CHEK2 variants compared with cancer-free individuals from the Exome Aggregation Consortium cohort (odds ratio OR, 3.87; 95% CI, 1.65-8.86; nominal P = .006; q = 0.018). Similar enrichment was also seen in an independent cohort of 448 unselected Croatian men with TGCTs (mean SD age, 31.98 8.11 years) vs 442 unselected Croatian men without TGCTs (at least 50 years of age at time of sample collection) (OR, >1.4; P = .03) and 231 high-risk men with TGCTs (mean SD age, 31.54 9.24 years) vs 3090 men (all older than 50 years) from the Penn Medicine Biobank (OR, 6.30; 95% CI, 2.34-17.31; P = .001). The low-penetrance CHEK2 variant (p.Ile157Thr) was found to be a Croatian founder TGCT risk variant (OR, 3.93; 95% CI, 1.53-9.95; P = .002). Individuals with the pathogenic CHEK2 loss-of-function variants developed TGCTs 6 years earlier than individuals with CHEK2 wild-type alleles (5.95 years; 95% CI, 1.48-10.42; P = .009).
This multicenter case-control analysis of men with or without TGCTs provides evidence for CHEK2 as a novel moderate-penetrance TGCT susceptibility gene, with potential clinical utility. In addition to highlighting DNA-repair deficiency as a potential mechanism driving TGCT susceptibility, this analysis also provides new avenues to explore management strategies and biological investigations for high-risk individuals.
The C-4 dark matter experiment Bonicalzi, R.M.; Collar, J.I.; Colaresi, J. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
06/2013, Letnik:
712
Journal Article
Recenzirano
Odprti dostop
We describe the experimental design of C-4, an expansion of the CoGeNT dark matter search to four identical detectors each approximately three times the mass of the p-type point contact germanium ...diode presently taking data at the Soudan Underground Laboratory. Expected reductions of radioactive backgrounds and energy threshold are discussed, including an estimate of the additional sensitivity to low-mass dark matter candidates to be obtained with this search.
This ethnographic case study examined the experiences of African American students within an urban school detracking reform initiative, which was intended to replace tracking practices through the ...institution of small schools. Over the course of a year, the researchers interviewed administrators, teachers, and students while gathering observational data from classrooms to explore the political nature of the reform and its impact on how students were viewed and treated by their teachers. Although this school reorganization aimed to expand opportunities for African American students, ultimately the data illustrated that restructuring efforts failed to change teachers’ attitudes and academic expectations, thereby denying students equitable educations. We found colorblindness to be a key factor that informed teachers’ persistent low expectations for students of color that reproduced tracking practices and inequitable opportunity structures in the smaller schools, thereby reinforcing the former stereotypes of low achievement for those students. This study calls for educators to challenge the racial ideologies of academic achievement, vis-a-vis teachers’ colorblind expectations, through political, normative, and technical dimensions of change to actualize educational equity in urban schools.
A new ultra-low-background proportional counter was recently developed with an internal volume of 100cm3 and has been characterized at pressures from 1–10atm with P-10 (90% Ar, 10% methane) gas. This ...design, along with a counting system providing event digitization and passive and active shielding, has been developed to complement a new shallow underground laboratory (30m water-equivalent). Backgrounds and low-level reference materials have been measured, and system sensitivity for 37Ar has been calculated.
•A new PNNL shallow underground laboratory is operational.•A low-background gas proportional counting system for argon has been prepared.•First background data has been collected relevant to an Ar-37 signature.•First calibration measurements of a low-level standard have been made.•Detector response to Ar-37 has been calculated and Ar-37 sensitivity projected.
Argon-37 is an important environmental signature of an underground nuclear explosion. Producing and quantifying low-level 37Ar standards is an important step in the development of sensitive field ...measurement instruments for use during an On-Site Inspection, a key provision of the Comprehensive Nuclear-Test-Ban Treaty. This paper describes progress at Pacific Northwest National Laboratory (PNNL) in the development of a process to generate and quantify low-level 37Ar standard material, which can then be used to calibrate sensitive field systems at activities consistent with soil background levels. The 37Ar used for our work was generated using a laboratory-scale, high-energy neutron source to irradiate powdered samples of calcium carbonate. Small aliquots of 37Ar were then extracted from the head space of the irradiated samples. The specific activity of the head space samples, mixed with P10 (90% stable argon:10% methane by mole fraction) count gas, is then derived using the accepted Length-Compensated Internal-Source Proportional Counting method. Due to the low activity of the samples, a set of three Ultra-Low Background Proportional-Counters designed and fabricated at PNNL from radio-pure electroformed copper was used to make the measurements in PNNL’s shallow underground counting laboratory. Very low background levels (<10 counts/day) have been observed in the spectral region near the 37Ar emission feature at 2.8 keV. Two separate samples from the same irradiation were measured. The first sample was counted for 12 days beginning 28 days after irradiation, the second sample was counted for 24 days beginning 70 days after irradiation (the half-life of 37Ar is 35.0 days). Both sets of measurements were analyzed and yielded very similar results for the starting activity (~0.1 Bq) and activity concentration (0.15 mBq/ccSTP argon) after P10 count gas was added. A detailed uncertainty model was developed based on the ISO Guide to the Expression of Uncertainty in Measurement. This paper presents a discussion of the measurement analysis, along with assumptions and uncertainty estimates.
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