The experiences associated with remembering, including metamemory feelings about the act of remembering and attempts at remembering, are not often integrated into general accounts of memory. For example, David Rubin (2022) proposes a unified, three-dimensional conceptual space for mapping memory states, a map that does not systematically specify metamemory feelings. Drawing on Rubin's model, we define a distinct role for metamemory in relation to first-order memory content. We propose a fourth dimension for the model and support the proposal with conceptual, neurocognitive, and clinical lines of reasoning. We use the modified model to illustrate several cases, and show how it helps to conceptualize a new category of memory state: autonoetic knowing, exemplified by déjà vu. We also caution not to assume that memory experience is directly correlated with or caused by memory content, an assumption Tulving (1989) labeled the doctrine of concordance.
In this study, the photocatalytic N2 immobilization performance of NaNbO3 is enhanced via oxygen vacancy introduction and Pt loading. The designed Pt-loaded NaNbO3 with rich oxygen defects (Pt/O-NaNbO3) is synthesized by combining ion-exchange and photodeposition methods. Characterization result indicates that the O-NaNbO3 has hollow microcube morphology and higher surface area than NaNbO3. The introduced oxygen defects greatly affect the energy band structure. The band gap is slightly narrowed and the conduction band is raised, allowing O-NaNbO3 to generate electrons with strong reducibility. Moreover, the oxygen defects reduced the work function of NaNbO3, leading to increased charge separation in the bulk phase. The loaded Pt nanoparticles can further increase the surface charge separation via the formed Schottky barriers between Pt and O-NaNbO3, which was thought to be the primary cause of the increased photocatalytic activity. Additionally, the oxygen vacancies and metal Pt also contribute to the adsorption and activation of N2. Under the combined effect of the above changes, Pt/O-NaNbO3 presents much higher photoactivity than NaNbO3. The optimized NH3 production rate reaches 293.3 μmol/L g-1h-1 under simulated solar light, which is approximately 2.2 and 20.2 times higher than that of O-NaNbO3 and NaNbO3, respectively. This research offers a successful illustration of how to improve photocatalytic N2 fixation and may shed some light on how to design and construct efficient photocatalysts by combining several techniques.
Insomnia is one of the most common and burdensome disorders in adults. We compared and ranked insomnia medication on the basis of their efficacy and tolerability. We performed a systematic review and network meta-analysis of placebo-controlled or head-to-head randomized controlled trials for primary insomnia in adults comparing 20 drugs. We searched eight databases and seven trial registers from inception to March 1st, 2022. Primary outcomes included sleep latency (SL), awake time after sleep onset (WASO) and discontinuation for adverse events (AED), and secondary outcomes included total sleep time (TST), sleep efficiency (SE), sleep quality (SQ) and adverse events (ADE). Pooled standardized mean differences or odds ratios with 95% credible intervals were estimated using pairwise and network meta-analysis with random-effects. Differences among trial findings were explored in subgroup and sensitivity analyses. Confidence in evidence was assessed using GRADE. The PROSPERO registered number is CRD42020182144. We identified 22,538 records and included 69 studies (17,319 patients). Orexin receptor antagonists (ORAs) are more efficacious than benzodiazepine-like drugs (Z-drugs) and placebo for WASO and SE, and better than melatonin receptor agonists (MRAs) for SL, WASO and SE. ORAs ranked the best in SL (SUCRA value: 0.84), WASO (0.93), TST (0.86) and SE (0.96). Lemborexant and daridorexant (two ORAs) showed greater efficacy than placebo for SL, WASO, and TST, with good tolerability. Z-drugs were more efficacious than placebo for SL, WASO, TST and SE, but with higher risk to safety. Zaleplon and eszopiclone had better efficacy than placebo for TST and SQ respectively. MRAs may also be efficacious for sleep-onset insomnia with good safety. However, the long-term adverse effects of all medications are unclear. Insomnia medications differ in their efficacy and tolerability. ORAs have superior efficacy and tolerability. These findings should aid clinicians in matching risk/benefits of drugs available in their countries to insomnia symptoms.
Resident heat exposure (RHE) is becoming more severe in the coming decades owing to rapid urbanization and climate change. Urban ecological land (UEL) provides important ecosystem services, such as mitigating the urban heat islands effect. However, the impacts of UEL on RHE remain poorly understood. This study quantifies the effects of UEL and its interaction with the natural-anthropogenic environment on RHE in the Guangdong-Hong Kong-Macao Greater Bay Area, a mega-urban agglomeration in China. The results showed a tight spatial–temporal coupling between the UEL and RHE: UEL transitioned from degradation-fragmentation in 2000–2010 to recovery-agglomeration in 2010–2020, while the RHE distribution evolved from intensification-expansion-inequity to mitigation-contraction-equity. The average explanatory power (q value) of UEL and its structure on RHE also increased by 75.99% and 70.79%, respectively. UEL patch diversity gradually dominated the RHE distribution, and the spatial marginal effect of UEL dominance increased by 234.97%. Moreover, RHE shifted from being dominated by UEL and anthropogenic heat emissions interactions to being jointly driven by UEL and natural-anthropogenic factors (especially the interaction of patch fragmentation with topography and built-up land expansion). The results of this study provide valuable information for nature-based (i.e., UEL) landscape planning and management to develop “human-centric” RHE mitigation strategies.
Mutant protein kinase A catalytic subunit (PKAc) drives adrenal Cushing’s syndrome, though its signaling interactions remain unclear. This protocol details steps to use live-cell proximity labeling to identify subcellular compartments and proteins closely associated with variants of PKAc in human adrenal cells. We include instructions for clonal cell line generation, live biotin labeling of proximal proteins, isolation of biotinylated proteins, and sample processing for proteomic analysis using the biotin ligase miniTurbo with wild-type and mutant PKAc.¹,² For complete details on the use and execution of this protocol, please refer to Omar et al. (2022).
Epigenetic repression has been linked to the regulation of different cell states. In this study, we focus on the influence of this repression, mainly by H3K27me3, over gene expression in muscle cells, which may affect mineral content, a phenotype that is relevant to muscle function and beef quality. Based on the inverse relationship between H3K27me3 and gene expression (i.e., epigenetic repression) and on contrasting sample groups, we computationally predicted regulatory genes that affect muscle mineral content. To this end, we applied the TRIAGE predictive method followed by a rank product analysis. This methodology can predict regulatory genes that might be affected by repressive epigenetic regulation related to mineral concentration. Annotation of orthologous genes, between human and bovine, enabled our investigation of gene expression in the Longissimus thoracis muscle of Bos indicus cattle. The animals under study had a contrasting mineral content in their muscle cells. We identified candidate regulatory genes influenced by repressive epigenetic mechanisms, linking histone modification to mineral content in beef samples. The discovered candidate genes take part in multiple biological pathways, i.e., impulse transmission, cell signalling, immunological, and developmental pathways. Some of these genes were previously associated with mineral content or regulatory mechanisms. Our findings indicate that epigenetic repression can partially explain the gene expression profiles observed in muscle samples with contrasting mineral content through the candidate regulators here identified.
Background: Sex-related steroid hormones and proteins may contribute to the sex differences in the characteristics and health consequences of alcohol use disorder. This study aimed to examine the associations between alcohol dependence (AD) and sex-related hormones/proteins using a population-based dataset. Methods: We retrieved serum total testosterone (TT) and estradiol (TE2), sex hormone binding globulin (SHBG), and albumin levels along with clinical data from the UK Biobank. Hormone/protein levels were compared between AD (lifetime AD and/or related diagnoses; 2218 males; 682 females) and control (no aforementioned diagnoses and AUDIT<8; 198,058 males; 250,830 females) groups with sex-dependent linear regression models adjusting for age and body mass index. Moderation and mediation analyses were performed to test whether SHBG was a moderator and/or mediator between hormones and AD or current drinking. Results: AD males had higher TT, TE2, and SHBG levels but lower bioavailable testosterone, bioavailable estradiol, and albumin levels than controls (padjusted<0.001). After adjusting for menopause, AD females had higher TT and lower albumin levels than controls (padjusted<0.001). These differences remained after accounting for current drinking frequency (p < 0.001). SHBG moderated TT's effect on AD in males (pinteraction<0.001). SHBG was a positive mediator between TT and AD in both sexes and between TE2 and AD in males (p < 0.001), but a negative mediator between TT and current drinking in controls (both sexes) and AD males (p < 0.001). Conclusions: Testosterone and estradiol levels are altered in males and females with AD distinctly regardless of current drinking frequency. SHBG may play a critical role in these associations.
This chapter highlights the role of institutional coaches in supporting community college transformational reform efforts, such as guided pathways. The history of coaching support for student success is explored along with a description of a national network of state intermediaries supporting the work of coaches focused on campus‐level change. Specific examples of how coaching creates a culture of student success innovation and support is provided from three states.
Background and Objectives: Research suggests LGBT populations have unique healthcare challenges. The purpose of this study was to understand contextual factors, including minority stress and social resources, associated with the healthcare utilization of LGBT middle-aged and older adults. Research Design and Methods: Using data from the Caring and Aging With Pride: National Health, Aging, and Sexuality/Gender Study (NHAS; N = 2,560), multiple logistic regression investigated associations between minority stress (i.e., internalized stigma, LGBT identity disclosure) and healthcare utilization (i.e., health screenings, emergency room use, routine checkups, regular provider). We also examined the moderating effect of social resources (i.e., social network size, social support, LGBT community belonging) in these associations. Results: Internalized stigma was negatively associated with having a routine checkup in the previous year. LGBT identity disclosure was positively associated with having a health screening within the past 3 years. Social support moderated the association between LGBT identity disclosure and health screenings. Discussion and Implications: Health and human service professionals and their clients should be educated about the ways that LGBT identity disclosure can impact healthcare utilization. Providers should consistently assess the social support of their aging LGBT clients and inform them about the potential risk of low social support in healthcare utilization.
Background Melioidosis is a neglected tropical infection caused by the environmental saprophyte Burkholderia pseudomallei. Methods We conducted a prospective, observational study at nine hospitals in northeastern Thailand, a hyperendemic melioidosis zone, to define current characteristics of melioidosis patients and quantify outcomes over one year. Findings 2574 individuals hospitalised with culture-confirmed melioidosis were screened and 1352 patients were analysed. The median age was 55 years, 975 (72%) were male and 951 (70%) had diabetes. 561 (42%) patients presented with lung infection, 1042 (77%) were bacteraemic, 442 (33%) received vasopressors/inotropes and 547 (40%) received mechanical ventilation. 1307 (97%) received an intravenous antibiotic against B. pseudomallei. 335/1354 (25%) patients died within one month and 448/1331 (34%) of patients died within one year. Most patients had risk factors for melioidosis, but patients without identified risk factors did not have a reduced risk of death. Of patients discharged alive, most received oral trimethoprim-sulfamethoxazole, which was associated with decreased risk of post-discharge death; 235/970 (24%) were readmitted, and 874/1015 (86%) survived to one year. Recurrent infection was detected in 17/1018 patients (2%). Patients with risk factors other than diabetes had increased risk of death and increased risk of hospital readmission. Interpretation In northeastern Thailand patients with melioidosis experience high rates of bacteraemia, organ failure and death. Most patients discharged alive survive one year although all-cause readmission is common. Recurrent disease is rare. Strategies that emphasize prevention, rapid diagnosis and intensification of early clinical management are likely to have greatest impact in this and other resource-restricted regions. Funding US NIH/NIAID U01AI115520.
The aim of this case report is to demonstrate a case of primary thyroid hemangioma in a 62-year-old female who presented with a painless neck mass, treated with right hemithyroidectomy and diagnosed by surgical biopsy. Thyroid hemangiomas are rare, benign lesions which present a diagnostic challenge given the lack of specific imaging findings and clinical manifestations associated with them. However, accurate recognition of these lesions is important and can facilitate conservative, rather than surgical, management strategies. In this report, we discuss a case in a patient whose laboratory assessment raised concern for a thyroid paraganglioma, leading to surgical resection of what was ultimately a benign thyroid hemangioma. We also review the pathophysiology, clinical manifestations, differential diagnostic considerations, and imaging characteristics of thyroid hemangiomas across multiple modalities and discuss strategies for accurately diagnosing these lesions.
Coronary artery perforation is one of the most common and feared complications of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We evaluated the utility of the recently presented OPEN-CLEAN (Coronary artery bypass graft, Length of occlusion, Ejection fraction, Age, calcificatioN) perforation score in an independent multicenter CTO PCI dataset. Of the 2,270 patients who underwent CTO PCI at 7 centers, 150 (6.6%) suffered coronary artery perforation. Patients with perforations were older (69 ± 10 vs 65 ± 10, p <0.001), more likely to be women (89% vs 82%, p = 0.010), more likely to have history of previous coronary artery bypass graft (38% vs 20%, p <0.001), and unfavorable angiographic characteristics such as blunt stump (64% vs 42%, p <0.001), proximal cap ambiguity (51% vs 33%, p <0.001), and moderate-severe calcification (57% vs 43%, p = 0.001). Technical success was lower in patients with perforations (69% vs 85%, p <0.001). The area under the receiver operating characteristic curve of the OPEN-CLEAN perforation risk model was 0.74 (95% confidence interval 0.68 to 0.79), with good calibration (Hosmer–Lemeshow p = 0.72). We found that the CTO PCI perforation risk increased with higher OPEN-CLEAN scores: 3.5% (score 0 to 1), 3.1% (score 2), 5.3% (score 3), 7.1% (score 4), 11.5% (score 5), 19.8% (score 6 to 7). In conclusion, given its good performance and ease of preprocedural calculation, the OPEN-CLEAN perforation score appears to be useful for quantifying the perforation risk for patients who underwent CTO PCI.
The discovery of early Levallois stone-tool technology at 170 ka at Guanyindong cave, Southwest China, has raised questions about the validity and characters of Levallois strategy at this site. To address these questions, we present a detailed technological analysis that primarily focuses on the Levallois cores, along with Levallois flakes and by-products. These analysis include analytical descriptions, technological illustrations, worldwide inter-site comparisons, and quantitative analysis, providing extended and substantial evidence of the usage of Levallois strategy at Guanyindong cave, and indicating highly technological variability and likely convergent technological evolution during Late Middle Pleistocene in East Asia.
Precisely measuring the Earth’s changing surface on decadal to centennial time scales is critical for many science and engineering applications, yet long-term records of quantitative landscape change are often temporally and geographically sparse. Archives of scanned historical aerial photographs provide an opportunity to augment these records with accurate elevation measurements that capture the historical state of the Earth surface. Structure from Motion (SfM) photogrammetry workflows produce high-quality digital elevation models (DEMs) and orthoimage mosaics from these historical images, but time-intensive tasks like manual image preprocessing (e.g., fiducial marker identification) and ground control point (GCP) selection impede processing at scale. We developed an automated method to process historical images and generate self-consistent time series of high-resolution (0.5–2 m) DEMs and orthomosaics, without manual GCP selection. The method relies on SfM to correct camera interior and exterior orientation and a robust multi-stage co-registration approach using modern reference terrain datasets for geolocation refinement. We demonstrate the method using scanned images from the North American Glacier Aerial Photography (NAGAP) archive collected between 1967 and 1997. We present results for two sites with variable photo acquisition geometry and overlap — Mount Baker and South Cascade Glacier in Washington State, USA. The automated method corrects initial camera position errors of several kilometers and produces accurately georeferenced, high-resolution DEMs and orthoimages, regardless of camera configuration, acquisition geometry, terrain characteristics, and reference DEM properties. The average RMS reprojection error following bundle adjustment optimization was 0.67 px (0.15 m) for the 261 images contributing to 10 final DEM mosaics between 1970 and 1992 at Mount Baker, and 0.65 px (0.13 m) for the 243 images contributing to 18 individual DEMs between 1967 and 1997 at South Cascade Glacier. The relative accuracy of elevation values in the historical time series stacks was 0.68 m at Mount Baker and 0.37 m at South Cascade Glacier. Our products have reduced systematic error and improved accuracy compared to DEM products generated using SfM with manual GCP selection. Final elevation change measurement precision was ∼0.7–1.0 m over a 30-year period, enabling the study of processes with rates as low as ∼1-3 cm/yr. Our results demonstrate the potential of this scalable method to rapidly process archives of historical imagery and deliver new quantitative insights on long-term geodetic change and Earth surface processes.
Background The impact of the COVID-19 vaccination campaign in the US has been hampered by a substantial geographical heterogeneity of the vaccination coverage. Several studies have proposed vaccination hesitancy as a key driver of the vaccination uptake disparities. However, the impact of other important structural determinants such as local disparities in healthcare capacity is virtually unknown. Methods In this cross-sectional study, we conducted causal inference and geospatial analyses to assess the impact of healthcare capacity on the vaccination coverage disparity in the US. We evaluated the causal relationship between the healthcare system capacity of 2417 US counties and their COVID-19 vaccination rate. We also conducted geospatial analyses using spatial scan statistics to identify areas with low vaccination rates. Findings We found a causal effect of the constraints in the healthcare capacity of a county and its low-vaccination uptake. Counties with higher constraints in their healthcare capacity were more probable to have COVID-19 vaccination rates ≤50, with 35% higher constraints in low-vaccinated areas (vaccination rates ≤ 50) compared to high-vaccinated areas (vaccination rates > 50). We also found that COVID-19 vaccination in the US exhibits a distinct spatial structure with defined “vaccination coldspots”. Interpretation We found that the healthcare capacity of a county is an important determinant of low vaccine uptake. Our study highlights that even in high-income nations, internal disparities in healthcare capacity play an important role in the health outcomes of the nation. Therefore, strengthening the funding and infrastructure of the healthcare system, particularly in rural underserved areas, should be intensified to help vulnerable communities. Funding None.
Where competition suppresses tree growth, mortality of adjacent trees can release the surviving individuals, leading to a growth increase. However, primary forests are complicated systems, where trees interact in both competitive and facilitative ways mediated by their size, species, and the broad ecological context in which they grow. Thus, the magnitude and even direction of growth responses to the mortality of nearby trees may vary, which has implications for our understanding of community-and ecosystem-level dynamics following mortality events. Unfortunately, although many studies focus on the impacts of light availability and general crowding on tree growth, we know relatively little about the effects of naturally occurring mortality events on the growth of neighboring trees. To address this issue, we used 40 years of data from 15 permanent forest-monitoring plots in Mt Rainier old-growth forests, comparing observed to expected radial growth of individual trees following the death of their nearest neighbor. Although we found evidence of a general growth-release response, this was not universal among all trees, with small trees in particular exhibiting growth suppression (rather than release) following neighboring tree mortality. In addition to small size, growth-suppression was more likely if the dead neighbor was the same species, consistent with facilitative effects as mediated through belowground networks. At the stand level, the average growth release after nearest neighbor mortality was greatest in low-density stands with large trees, with elevation and community composition also playing a role. Decades more monitoring could reveal how long growth release (or suppression) is sustained by individual trees following neighboring mortality events, as well as potential response lags and the role of species identity in determining whether interactions with neighbors are competitive or facilitative. Nonetheless, our results suggest that although mature trees have competitive effects on their larger neighbors, they also have an important role in supporting the ingrowth of small trees. More broadly, we demonstrate that the nature of interactions between individual neighboring trees is highly context dependent.
Objective: Women with HIV (WWH) have heightened heart failure risk. Plasma OPN (osteopontin) is a powerful predictor of heart failure outcomes in the general population. Limited data exist on relationships between plasma OPN and surrogates of HIV-associated heart failure risk. Design: Prospective, cross-sectional. Methods: We analyzed relationships between plasma OPN and cardiac structure/function (assessed using cardiovascular magnetic resonance imaging) and immune activation (biomarkers and flow cytometry) among 20 WWH and 14 women without HIV (WWOH). Results: Plasma OPN did not differ between groups. Among WWH, plasma OPN related directly to the markers of cardiac fibrosis, growth differentiation factor-15 (ρ = 0.51, P = 0.02) and soluble interleukin 1 receptor-like 1 (ρ = 0.45, P = 0.0459). Among WWH (but not among WWOH or the whole group), plasma OPN related directly to both myocardial fibrosis (ρ = 0.49, P = 0.03) and myocardial steatosis (ρ = 0.46, P = 0.0487). Among the whole group and WWH (and not among WWOH), plasma OPN related directly to the surface expression of C-X3-C motif chemokine receptor 1 (CX3CR1) on nonclassical (CD14-CD16+) monocytes (whole group: ρ = 0.36, P = 0.04; WWH: ρ = 0.46, P = 0.04). Further, among WWH and WWOH (and not among the whole group), plasma OPN related directly to the surface expression of CC motif chemokine receptor 2 (CCR2) on inflammatory (CD14+CD16+) monocytes (WWH: ρ = 0.54, P = 0.01; WWOH: ρ = 0.60, P = 0.03), and in WWH, this held even after controlling for HIV-specific parameters. Conclusion: Among WWH, plasma OPN, a powerful predictor of heart failure outcomes, related to myocardial fibrosis and steatosis and the expression of CCR2 and CX3CR1 on select monocyte subpopulations. OPN may play a role in heart failure pathogenesis among WWH. Clinicaltrialsgov registration: NCT02874703.
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