Highlights • Insulin resistance was increased in individuals with AD and PD compared to healthy elderly subjects. • AD subjects exhibited more severe metabolic dysfunction than PD subjects. • ...Within-group assessments showed a significant relationship between gray matter volume and insulin resistance. • Both the brain region and directionality of the relationship between metabolism and brain volume was unique in each group.
The relationship between the quantity of iodine and cesium present in the fuel-sheath gap region and the amount of stable fission gas released from the fuel matrix has been investigated for typical ...natural UO
2
Canada deuterium uranium power reactor fuels. Two leaching techniques were employed to determine the fuel-sheath gap inventories of cesium and iodine, and their respective release fractions were derived from these. The
I37
Cs/Xe and
134
Cs/Xe release ratios were close to one over nearly three orders of magnitude of release fraction. Limited data suggest that
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I may show similar behavior. The experiments were performed in support of the safety assessment of irradiated fuel disposal and may have further application to fuel storage and reactor safety studies.
García-Verdugo et al. (2017) recently tested the loss of dispersal ability hypothesis in a wind-dispersed shrub from Southern Europe. Although the hypothesis has guided research for over 150 years, ...García-Verdugo et al. (2017) results failed to substantiate its central prediction—the loss of seed dispersal potential in island populations. Here, I highlight several additional limitations of the hypothesis. First, García-Verdugo et al. (2017) results are not unusual. Empirical support for the hypothesis is equivocal. Second, when reduced dispersal potential is documented, it may often evolve as a passive by-product of selection for large seeds, for reasons that are wholly unrelated to their dispersal. Third, the hypothesis does not readily apply to all plant dispersal modes, particularly plants that produce fleshy fruits. These issues advocate a fresh approach to the study of how selection shapes the evolution of dispersal potential on islands.
Diagnosing primary central nervous system lymphoma (PCNSL) frequently requires neurosurgical biopsy due to nonspecific radiologic features and the low yield of cerebrospinal fluid (CSF) studies. We ...characterized the clinical evaluation of suspected PCNSL (N = 1007 patients) and designed a rapid multiplexed genotyping assay for MYD88, TERT promoter, IDH1/2, H3F3A, and BRAF mutations to facilitate the diagnosis of PCNSL from CSF and detect other neoplasms in the differential diagnosis. Among 159 patients with confirmed PCNSL, the median time to secure a diagnosis of PCNSL was 10 days, with a range of 0 to 617 days. Permanent histopathology confirmed PCNSL in 142 of 152 biopsies (93.4%), whereas CSF analyses were diagnostic in only 15/113 samplings (13.3%). Among 86 archived clinical specimens, our targeted genotyping assay accurately detected hematologic malignancies with 57.6% sensitivity and 100% specificity (95% confidence interval CI: 44.1% to 70.4% and 87.2% to 100%, respectively). MYD88 and TERT promoter mutations were prospectively identified in DNA extracts of CSF obtained from patients with PCNSL and glioblastoma, respectively, within 80 minutes. Across 132 specimens, hallmark mutations indicating the presence of malignancy were detected with 65.8% sensitivity and 100% specificity (95% CI: 56.2%-74.5% and 83.9%-100%, respectively). This targeted genotyping approach offers a rapid, scalable adjunct to reduce diagnostic and treatment delays in PCNSL.
•Nonspecific radiographic and CSF findings result in delayed diagnosis and treatment when PCNSL is suspected.•Integrating a rapid genotyping assay into workup of PCNSL can potentially resolve treatment delays and obviate neurosurgical sampling.
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The psychology of natural history Burns, K.C.; Low, Jason
Trends in ecology & evolution (Amsterdam),
December 2022, 2022-12-00, 20221201, Letnik:
37, Številka:
12
Journal Article
Recenzirano
Natural history observations are an integral part of ecology and evolution. However, they can be underappreciated because they operate independent of the scientific method. Here, we illustrate that ...the science of natural history has its own methodology based on a well-known psychological paradigm that describes how the human mind learns.
The APOBEC3 family of antiviral DNA cytosine deaminases is implicated as the second largest source of mutation in cancer. This mutational process may be a causal driver or inconsequential passenger ...to the overall tumor phenotype. We show that human APOBEC3A expression in murine colon and liver tissues increases tumorigenesis. All other APOBEC3 family members, including APOBEC3B, fail to promote liver tumor formation. Tumor DNA sequences from APOBEC3A-expressing animals display hallmark APOBEC signature mutations in TCA/T motifs. Bioinformatic comparisons of the observed APOBEC3A mutation signature in murine tumors, previously reported APOBEC3A and APOBEC3B mutation signatures in yeast, and reanalyzed APOBEC mutation signatures in human tumor datasets support cause-and-effect relationships for APOBEC3A-catalyzed deamination and mutagenesis in driving multiple human cancers.
IMPORTANCE: Although most critically ill patients receive invasive mechanical ventilation (IMV), few studies have characterized how IMV is discontinued in practice. OBJECTIVE: To describe practice ...variation in IMV discontinuation internationally, associations between initial discontinuation events and outcomes, and factors associated with the use of select discontinuation strategies and failed initial spontaneous breathing trials (SBTs). DESIGN, SETTING, AND PARTICIPANTS: Prospective, multinational, observational study of critically ill adults who received IMV for at least 24 hours from 142 intensive care units (ICUs) in 19 countries within 6 regions (27 in Canada, 23 in India, 22 in the UK, 26 in Europe, 21 in Australia/New Zealand, and 23 in the US). EXPOSURES: Receiving IMV. MAIN OUTCOMES AND MEASURES: Primary analyses characterized types of initial IMV discontinuation events (extubation, SBT, or tracheostomy) and associations with clinical outcomes (including duration of ventilation, ICU and hospital mortality, and ICU and hospital length of stay). Secondary analyses examined the associations between SBT outcome and SBT timing and clinical outcomes. RESULTS: Among 1868 patients (median interquartile range age, 61.8 48.9-73.1 years; 1173 62.8% men) 424 (22.7%) underwent direct extubation, 930 (49.8%) had an initial SBT (761 81.8% successful), 150 (8.0%) underwent direct tracheostomy, and 364 (19.5%) died before a weaning attempt. Across regions, there was variation in the use of written directives to guide care, daily screening, SBT techniques, ventilator modes, and the roles played by clinicians involved in weaning. Compared with initial direct extubation, patients who had an initial SBT had higher ICU mortality (20 4.7% vs 96 10.3%; absolute difference, 5.6% 95% CI, 2.6%-8.6%), longer duration of ventilation (median of 2.9 vs 4.1 days; absolute difference, 1.2 days 95% CI, 0.7-1.6), and longer ICU stay (median of 6.7 vs 8.1 days; absolute difference, 1.4 days 95% CI, 0.8-2.4). Patients whose initial SBT failed (vs passed) had higher ICU mortality (29 17.2% vs 67 8.8%; absolute difference, 8.4% 95% CI, 2.0%-14.7%), longer duration of ventilation (median of 6.1 vs 3.5 days; absolute difference, 2.6 days 95% CI, 1.6-3.6), and longer ICU stay (median of 10.6 vs 7.7 days; absolute difference, 2.8 days 95% CI, 1.1-5.2). Compared with patients who underwent early initial SBTs, patients who underwent late initial SBTs (>2.3 days after intubation) had longer duration of ventilation (median of 2.1 vs 6.1 days; absolute difference, 4.0 days 95% CI, 3.7-4.5), longer ICU stay (median of 5.9 vs 10.8 days; absolute difference, 4.9 days 95% CI, 4.0-6.3), and longer hospital stay (median of 14.3 vs 22.8 days; absolute difference, 8.5 days 95% CI, 6.0-11.0). CONCLUSIONS AND RELEVANCE: In this observational study of invasive mechanical ventilation discontinuation in 142 ICUs in Canada, India, the UK, Europe, Australia/New Zealand, and the US from 2013 to 2016, weaning practices varied internationally. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03955874
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