Laws for Pauses Gilden, David L.; Mezaraups, Taylor M.
Journal of experimental psychology. Learning, memory, and cognition,
01/2022, Letnik:
48, Številka:
1
Journal Article
Recenzirano
It is shown that a particular class of pauses taken in both read and composed speech obey allometric laws such that mean pause length predicts body size. The pauses in this class have durations that ...roughly span 250 ms to 1,000 ms and are taken to mark grammatical and prosodic boundaries. A theory of pause allometry is developed based on the observation that these pauses are expressive, they give speech momentum and rhythm, and most importantly, their durations reflect temporal discrimination-they are not produced by articulatory constraints. The theory is formulated in terms of a leaky integrator differential equation that is intended to model the sense of time passage that occurs during relatively brief pauses. The theory predicts that if the decay time scale associated with the leakage term includes body size as a parameter, then allometry will be observed generally in the amount of silence people deploy in pause behavior. A second study tested the theory on a class of long pauses defined by being terminated by a speech gesture indicating speaker recognition that the pause was indeed long. These long pauses were also found to obey allometry. The exponents derived from power law models of mean pause duration in both studies were found to be significantly larger than those associated with allometries of body energy expenditure. These findings provide a new meaning to the embodiment of cognition.
IMPORTANCE: Clostridium difficile is a major cause of health care–associated infection, but disagreement between diagnostic tests is an ongoing barrier to clinical decision making and public health ...reporting. Molecular tests are increasingly used to diagnose C difficile infection (CDI), but many molecular test-positive patients lack toxins that historically defined disease, making it unclear if they need treatment. OBJECTIVE: To determine the natural history and need for treatment of patients who are toxin immunoassay negative and polymerase chain reaction (PCR) positive (Tox−/PCR+) for CDI. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study at a single academic medical center among 1416 hospitalized adults tested for C difficile toxins 72 hours or longer after admission between December 1, 2010, and October 20, 2012. The analysis was conducted in stages with revisions from April 27, 2013, to January 13, 2015. MAIN OUTCOMES AND MEASURES: Patients undergoing C difficile testing were grouped by US Food and Drug Administration–approved toxin and PCR tests as Tox+/PCR+, Tox−/PCR+, or Tox−/PCR−. Toxin results were reported clinically. Polymerase chain reaction results were not reported. The main study outcomes were duration of diarrhea during up to 14 days of treatment, rate of CDI-related complications (ie, colectomy, megacolon, or intensive care unit care) and CDI-related death within 30 days. RESULTS: Twenty-one percent (293 of 1416) of hospitalized adults tested for C difficile were positive by PCR, but 44.7% (131 of 293) had toxins detected by the clinical toxin test. At baseline, Tox−/PCR+ patients had lower C difficile bacterial load and less antibiotic exposure, fecal inflammation, and diarrhea than Tox+/PCR+ patients (P < .001 for all). The median duration of diarrhea was shorter in Tox−/PCR+ patients (2 days; interquartile range, 1-4 days) than in Tox+/PCR+ patients (3 days; interquartile range, 1-6 days) (P = .003) and was similar to that in Tox−/PCR− patients (2 days; interquartile range, 1-3 days), despite minimal empirical treatment of Tox−/PCR+ patients. No CDI-related complications occurred in Tox−/PCR+ patients vs 10 complications in Tox+/PCR+ patients (0% vs 7.6%, P < .001). One Tox−/PCR+ patient had recurrent CDI as a contributing factor to death within 30 days vs 11 CDI-related deaths in Tox+/PCR+ patients (0.6% vs 8.4%, P = .001). CONCLUSIONS AND RELEVANCE: Among hospitalized adults with suspected CDI, virtually all CDI-related complications and deaths occurred in patients with positive toxin immunoassay test results. Patients with a positive molecular test result and a negative toxin immunoassay test result had outcomes that were comparable to patients without C difficile by either method. Exclusive reliance on molecular tests for CDI diagnosis without tests for toxins or host response is likely to result in overdiagnosis, overtreatment, and increased health care costs.
Treatment options for the management of breast cancer are still inadequate. This inadequacy is attributed to the lack of effective targeted medications, often resulting in the recurrence of ...metastatic disorders. Cumulative evidence suggests that epidermal growth factor receptor (EGFR-TK) and cyclin-dependent kinases-9 (CDK-9) overexpression correlates with worse overall survival in breast cancer patients. Pyranopyrazole and pyrazolone are privileged options for the development of anticancer agents. Inspired by this proven scientific fact, we report here the synthesis of two new series of suggested anticancer molecules incorporating both heterocycles together with their characterization by IR,
1
H NMR,
13
C NMR,
13
C NMR-DEPT, and X-ray diffraction methods. An attempt to get the pyranopyrazole-gold complexes was conducted but unexpectedly yielded benzylidene-2,4-dihydro-3H-pyrazol-3-one instead. This unexpected result was confirmed by X-ray crystallographic analysis. All newly synthesized compounds were assessed for their anti-proliferative activity against two different human breast cancer cells, and the obtained results were compared with the reference drug Staurosporine. The target compounds revealed variable cytotoxicity with IC
50
at a low micromolar range with superior selectivity indices. Target enzyme EGFR-TK and CDK-9 assays showed that compounds 22 and 23 effectively inhibited both biological targets with IC
50
values of 0.143 and 0.121 µM, respectively. Molecular docking experiments and molecular dynamics simulation were also conducted to further rationalize the in vitro obtained results.
Communicated by Ramaswamy H. Sarma
•Five different NDV displayed variable pathogenicity and transmissibility.•The chicken-origin viruses were pathogenic and transmissible at low doses.•The wild bird-origin viruses required a high dose ...to infect chickens.•Regardless of dose, the wild bird-origin NDV did not transmit bird to bird.•Our data may explain why wild bird-origin viruses are rarely found in poultry.
Five, class II, virulent Newcastle disease virus (vNDV) isolates of different genotypes from different host species were evaluated for their ability to infect, cause disease, and transmit to naïve chickens. Groups of five birds received a low, medium, or high dose, by the oculonasal route, of one of the following vNDV: three chicken-origin, one cormorant-origin, and one pigeon-origin. Three naïve birds were added to each group at two days post-inoculation (DPI) to evaluate transmission. Virus shedding was quantified from swabs (2/4/7 DPI), and seroconversion was evaluated at 14 DPI. All inoculated and contact birds in the chicken-origin vNDV groups succumbed to infection, displaying clinical signs typical of Newcastle disease and shed virus titers above 6 log10 EID50/ml. Birds receiving a high and medium dose of the cormorant virus showed primarily neurological clinical signs with 80% and 60% mortality, respectively. The chickens showing clinical disease shed virus at titers below 4 log10 EID50/ml, and the remaining bird in the high dose group seroconverted with a high HI titer. For the pigeon-origin virus, no clinical signs were observed in any of the birds, but all 5 chickens in the high challenge dose and one bird in the medium challenge group shed virus at mean titers of 3.1 and 2.2 log10 EID50/ml, respectively. Overall, the chicken-origin viruses infected chickens and efficiently transmitted to naïve birds, while the cormorant- and pigeon-origin viruses infected chickens only at the higher doses and did not transmit to other birds.
Context:
Adrenocortical carcinoma (ACC) is a rare and lethal malignancy with a poorly defined etiology, and the molecular genetics of ACC are incompletely understood.
Objective:
To utilize ...whole-exome sequencing for genetic characterization of the underlying somatic mutations and copy number alterations present in ACC.
Design:
Screening for somatic mutation events and copy number alterations (CNAs) was performed by comparative analysis of tumors and matched normal samples from 41 patients with ACC.
Results:
In total, 966 nonsynonymous somatic mutations were detected, including 40 tumors with a mean of 16 mutations per sample and one tumor with 314 mutations. Somatic mutations in ACC-associated genes included TP53 (8/41 tumors, 19.5%) and CTNNB1 (4/41, 9.8%). Genes with potential disease-causing mutations included GNAS, NF2, and RB1, and recurrently mutated genes with unknown roles in tumorigenesis comprised CDC27, SCN7A, and SDK1. Recurrent CNAs included amplification at 5p15.33 including TERT (6/41, 14.6%) and homozygous deletion at 22q12.1 including the Wnt repressors ZNRF3 and KREMEN1 (4/41 9.8% and 3/41, 7.3%, respectively). Somatic mutations in ACC-established genes and recurrent ZNRF3 and TERT loci CNAs were mutually exclusive in the majority of cases. Moreover, gene ontology identified Wnt signaling as the most frequently mutated pathway in ACCs.
Conclusions:
These findings highlight the importance of Wnt pathway dysregulation in ACC and corroborate the finding of homozygous deletion of Wnt repressors ZNRF3 and KREMEN1. Overall, mutations in either TP53 or CTNNB1 as well as focal CNAs at the ZNRF3 or TERT loci denote mutually exclusive events, suggesting separate mechanisms underlying the development of these tumors.
Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7-10% of the general population. ...Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased drug prescriptions and visits to health care providers, as well as the morbidity from the pain itself and the inciting disease. Despite challenges, progress in the understanding of the pathophysiology of neuropathic pain is spurring the development of new diagnostic procedures and personalized interventions, which emphasize the need for a multidisciplinary approach to the management of neuropathic pain.
The intestinal extracellular matrix (ECM) helps maintain appropriate tissue barrier function and regulate host-microbial interactions. Chondroitin sulfate- and dermatan sulfate-glycosaminoglycans ...(CS/DS-GAGs) are integral components of the intestinal ECM, and alterations in CS/DS-GAGs have been shown to significantly influence biological functions. Although pathologic ECM remodeling is implicated in inflammatory bowel disease (IBD), it is unknown whether changes in the intestinal CS/DS-GAG composition are also linked to IBD in humans. Our aim was to characterize changes in the intestinal ECM CS/DS-GAG composition in intestinal biopsy samples from patients with IBD using mass spectrometry. We characterized intestinal CS/DS-GAGs in 69 pediatric and young adult patients (n = 13 control, n = 32 active IBD, n = 24 IBD in remission) and 6 adult patients. Here, we report that patients with active IBD exhibit a significant decrease in the relative abundance of CS/DS isomers associated with matrix stability (CS-A and DS) compared to controls, while isomers implicated in matrix instability and inflammation (CS-C and CS-E) were significantly increased. This imbalance of intestinal CS/DS isomers was restored among patients in clinical remission. Moreover, the abundance of pro-stabilizing CS/DS isomers negatively correlated with clinical disease activity scores, whereas both pro-inflammatory CS-C and CS-E content positively correlated with disease activity scores. Thus, pediatric patients with active IBD exhibited increased pro-inflammatory and decreased pro-stabilizing CS/DS isomer composition, and future studies are needed to determine whether changes in the CS/DS-GAG composition play a pathogenic role in IBD.
For millennia, healing and psychoactive plants have been part of the medicinal and ceremonial fabric of elaborate rituals and everyday religious practices throughout Mesoamerica. Despite the ...essential nature of these ritual practices to the societal framework of past cultures, a clear understanding of the ceremonial life of the ancient Maya remains stubbornly elusive. Here we record the discovery of a special ritual deposit, likely wrapped in a bundle, located beneath the end field of a Late Preclassic ballcourt in the Helena complex of the Maya city of Yaxnohcah. This discovery was made possible by the application of environmental DNA technology. Plants identified through this analytical process included Ipomoea corymbosa (xtabentun in Mayan), Capsicum sp. (chili pepper or ic in Mayan), Hampea trilobata (jool), and Oxandra lanceolata (chilcahuite). All four plants have recognized medicinal properties. Two of the plants, jool and chilcahuite, are involved in artifact manufacture that have ceremonial connections while chili peppers and xtabentun have been associated with divination rituals. Xtabentun (known to the Aztecs as ololiuhqui) produces highly efficacious hallucinogenic compounds and is reported here from Maya archaeological contexts for the first time.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AIM: To determine whether extinction risk assessments based on biological collections and using Criterion B of the IUCN Red List Criteria reflect in part an accurate measure of species rarity and ...thus extinction risk. LOCATION: Madagascar. METHODS: We calculate the extent of occurrence (EOO) and area of occupancy (AOO) for orchids using herbarium specimen data. Correlations were made against range, occupancy, extinction risk, number of specimens and the date of description. We calculated the average increase in range per species specimen, correlated this against the date of description and determined significance of the observed EOO accumulation using randomization tests. RESULTS: Significant negative correlations were found between date of description and all measures of range, occupancy and associated Red List Categories and number of specimens, as well as between the average range accumulation per specimen and date of description. Seventy‐five percentage of species’ observed EOO accumulations significantly differed from random. Maximum deviations between observed EOO accumulations and those derived from random sampling were always significantly positive. For most species, this occurred more frequently during the first half of the accumulation sequence. MAIN CONCLUSIONS: Species described more recently have smaller ranges and occupancies, fewer specimens and greater perceived extinction risk status. Levels of geographic uniqueness of collections are higher in species described more recently. Awareness of a species range increased faster than random, particularly in the first half of the sampling process, suggesting that newly discovered or yet to be discovered species are rare and likely have a higher risk of extinction. For many species, biological collections represent the sum of our knowledge. While data may be limited, such species should be listed in an appropriate Red List Category in accordance with the IUCN Red List Guidelines rather than as Data Deficient.
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