Purpose
Intracranial pressure (ICP) > 20 mmHg is associated with worse outcomes in children. The gold standard for monitoring ICP is invasive, has complications such as bleeding and infection, and ...may not be available in resource limited areas. Ultrasound of the optic nerve sheath diameter (ONSD) has been studied as a noninvasive way to evaluate for elevated ICP in adults. Its utility in pediatrics remains unclear.
Methods
A prospective study was performed in a pediatric intensive care unit in children ≤ 18 years old. ONSD ultrasound was performed using a 13–6 MHz linear probe with the patient’s invasively measured ICP simultaneously recorded. Linear mixed effects models were used to evaluate the association between ONSD and ICP.
Results
One hundred thirty-six measurements were obtained from 16 patients. ONSD was not significantly associated with ICP (
p
= 0.51). A ROC curve assessing ONSD to determine elevated ICP > 20 mmHg had an area under the curve of 0.52 (95%CI = 0.32–0.72). There was no difference in measurements obtained between the left and right ONSD at the same time (
p
= 0.82).
Conclusions
In conclusion, this study demonstrated no association between ONSD measurement and invasively monitored ICP in critically ill children.
Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits ...evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19.
From the late 1970s through the early 1990s, a minority conservative faction took over the Southern Baptist Convention (SBC). This project seeks to answer the questions of how a fringe minority ...within the nation’s largest Protestant denomination could undertake such a feat and why they chose to do so. The framework through which this work analyzes these questions is one of competing worldviews that emerged within the SBC in response to decades of societal shifts and denominational transformations in the post-World War II era. To place the events of the Southern Baptist “crisis” within this framework, this study seeks to refute the prevailing notion put forth in earlier works that the takeover was an in-house event, driven purely by doctrinal disputes between conservative Southern Baptists and SBC leadership. Illustrating the differences between rhetoric and action on both sides of this intra-denominational conflict, this work seeks to provide perspective to the narrative of the Southern Baptist “crisis” by asserting that the worldviews guiding the opposing factions diverged not only on doctrine, but culture and politics as well. Placing the events of the “crisis” within the context of broader worldviews, this project highlights and examines the intertwined nature of religion, culture, and politics in modern American society.
Noninvasive detection of Alzheimer's disease (AD) with high specificity and sensitivity can greatly facilitate identification of at-risk populations for earlier, more effective intervention. AD ...patients exhibit a myriad of retinal pathologies, including hallmark amyloid β-protein (Aβ) deposits.
Burden, distribution, cellular layer, and structure of retinal Aβ plaques were analyzed in flat mounts and cross sections of definite AD patients and controls (n = 37). In a proof-of-concept retinal imaging trial (n = 16), amyloid probe curcumin formulation was determined and protocol was established for retinal amyloid imaging in live patients.
Histological examination uncovered classical and neuritic-like Aβ deposits with increased retinal Aβ42 plaques (4.7-fold; P = 0.0063) and neuronal loss (P = 0.0023) in AD patients versus matched controls. Retinal Aβ plaque mirrored brain pathology, especially in the primary visual cortex (P = 0.0097 to P = 0.0018; Pearson's r = 0.84-0.91). Retinal deposits often associated with blood vessels and occurred in hot spot peripheral regions of the superior quadrant and innermost retinal layers. Transmission electron microscopy revealed retinal Aβ assembled into protofibrils and fibrils. Moreover, the ability to image retinal amyloid deposits with solid-lipid curcumin and a modified scanning laser ophthalmoscope was demonstrated in live patients. A fully automated calculation of the retinal amyloid index (RAI), a quantitative measure of increased curcumin fluorescence, was constructed. Analysis of RAI scores showed a 2.1-fold increase in AD patients versus controls (P = 0.0031).
The geometric distribution and increased burden of retinal amyloid pathology in AD, together with the feasibility to noninvasively detect discrete retinal amyloid deposits in living patients, may lead to a practical approach for large-scale AD diagnosis and monitoring.
National Institute on Aging award (AG044897) and The Saban and The Marciano Family Foundations.
High-throughput proteomics allows researchers to simultaneously explore the roles of thousands of biomarkers in the pathophysiology of diabetes. We conducted proteomic association studies of incident ...type 2 diabetes and physiologic responses to an intravenous glucose tolerance test (IVGTT) to identify novel protein contributors to glucose homeostasis and diabetes risk. We tested 4,776 SomaScan proteins measured in relation to 18-year incident diabetes risk in participants from the Cardiovascular Health Study (N = 2,631) and IVGTT-derived measures in participants from the HERITAGE Family Study (N = 752). We characterize 51 proteins that were associated with longitudinal diabetes risk, using their respective 39, 9, and 8 concurrent associations with insulin sensitivity index (SI), acute insulin response to glucose (AIRG), and glucose effectiveness (SG). Twelve of the 51 diabetes associations appear to be novel, including β-glucuronidase, which was associated with increased diabetes risk and lower SG, suggesting an alternative pathway to insulin for glucose disposal; and plexin-B2, which also was associated with increased diabetes risk, but with lower AIRG, and not with SI, indicating a mechanism related instead to pancreatic dysfunction. Other novel protein associations included alcohol dehydrogenase-1C, fructose-bisphosphate aldolase-B, sorbitol dehydrogenase with elevated type 2 diabetes risk, and a leucine-rich repeat containing protein-15 and myocilin with decreased risk.
Plasma proteins are associated with the risk of incident diabetes in older adults independent of various demographic, lifestyle, and biochemical risk factors. These same proteins are associated with subtle differences in measures of glucose homeostasis earlier in life. Proteins that are associated with lower insulin sensitivity in individuals without diabetes tend to be associated with appropriate compensatory mechanisms, such as a stronger acute insulin response or higher glucose effectiveness. Proteins that are associated with future diabetes risk, but not with insulin insensitivity, tend to be associated with lower glucose effectiveness and/or impaired acute insulin response.
Tubulointerstitial fibrosis is common with ageing and strongly prognostic for ESRD but is poorly captured by eGFR or urine albumin to creatinine ratio (ACR). Higher urine levels of procollagen type ...III N-terminal propeptide (PIIINP) mark the severity of tubulointerstitial fibrosis in biopsy studies, but the association of urine PIIINP with CKD progression is unknown. Among community-living persons aged ≥65 years, we measured PIIINP in spot urine specimens from the 1996 to 1997 Cardiovascular Health Study visit among individuals with CKD progression (30% decline in eGFR over 9 years, n=192) or incident ESRD (n=54) during follow-up, and in 958 randomly selected participants. We evaluated associations of urine PIIINP with CKD progression and incident ESRD. Associations of urine PIIINP with cardiovascular disease, heart failure, and death were evaluated as secondary end points. At baseline, mean age (±SD) was 78±5 years, mean eGFR was 63±18 ml/min per 1.73 m(2), and median urine PIIINP was 2.6 (interquartile range, 1.4-4.2) μg/L. In a case-control study (192 participants, 231 controls), each doubling of urine PIIINP associated with 22% higher odds of CKD progression (adjusted odds ratio, 1.22; 95% confidence interval, 1.00 to 1.49). Higher urine PIIINP level was also associated with incident ESRD, but results were not significant in fully adjusted models. In a prospective study among the 958 randomly selected participants, higher urine PIIINP was significantly associated with death, but not with incident cardiovascular disease or heart failure. These data suggest higher urine PIIINP levels associate with CKD progression independently of eGFR and ACR in older individuals.
Inflammation is believed to play a role in prostate cancer (PCa) etiology, but it is unclear whether inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) associate with PCa risk in ...older men. Using Cox regression, we assessed the relationship between baseline concentrations of CRP and IL-6 and the subsequent PCa risk in the Cardiovascular Health Study, a population-based cohort study of mostly European American men of ages >64 years (n = 2,234; mean follow-up = 8.7 years; 215 incident PCa cases). We also tested associations between CRP and IL-6 tagSNPs and PCa risk, focusing on SNPs that are known to associate with circulating CRP and/or IL-6. Neither CRP nor IL-6 blood concentrations was associated with PCa risk. The C allele of IL-6 SNP rs1800795 (-174), a known functional variant, was associated with increased risk in a dominant model (HR = 1.44; 95% CI = 1.03-2.01; p = 0.03), but was not statistically significant after accounting for multiple tests (permutation p = 0.21). Our results suggest that circulating CRP and IL-6 do not influence PCa risk. SNPs at the CRP locus are not associated with PCa risk in this cohort, while the association between rs1800795 and PCa risk warrants further investigation.
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The resonance properties, frequency and half-band-half-width, of a quartz crystal microbalance (QCM) immersed in concentrated suspensions of 16.2 vol% TiO2 are shown to be a function ...of pH. The overall QCM response is dependent on the complex interactions between the QCM sensor and overlying particle suspension. Atomic force microscopy confirms pH dependent interaction forces between the QCM sensor (gold-coated) and a TiO2 particle: a strong attraction is measured between pH 4–4.5, and the interaction becomes increasingly repulsive at all pH > 6.5. Yield stress measurements of the concentrated TiO2 suspensions also confirm the changing particle-particle interaction strength as the pH is adjusted from acidic to basic conditions. For the chosen system, the total potential energy of interaction (VT) between the sensor-suspension (Au-TiO2) is comparatively stronger than the particle-particle (TiO2-TiO2) interaction; hence the QCM responds to changes in VT sensor-suspension, as verified by the calculated interaction energy between two dissimilar surfaces (Hogg-Healy-Fuerstenau (HHF) theory), and not the suspension yield stress. Slight deviation between the measured QCM responses and the theoretical sphere-plate interaction strength is shown over a narrow pH range and likely corresponds to strengthening particle-particle interactions. Although the suspensions exhibit significant yield strengths, the QCM response can be suitably described by the sensor-suspension contact mechanics of inertial loading. Combined with our previous study 1, the current study confirms the suspension yield strength can only be measured when VT sensor-suspension is attractive and comparatively weaker than VT particle-particle.
Along-strike variation in scarp morphology reflects differences in a fault's geomorphic and structural development and can thus indicate fault rupture history and mechanical segmentation. Parameters ...that define scarp morphology (height, width, slope) are typically measured or calculated manually. The time-consuming manual approach reduces the density and objectivity of measurements and can lead to oversight of small-scale morphological variations that occur at a resolution impractical to capture. Furthermore, inconsistencies in the manual approach may also lead to unknown discrepancies and uncertainties between, and also within, individual fault scarp studies. Here, we aim to improve the efficiency, transparency and uniformity of calculating scarp morphological parameters by developing a semi-automated Scarp PARameTer Algorithm (SPARTA). We compare our findings against a traditional, manual analysis and assess the performance of the algorithm using a range of digital elevation model (DEM) resolutions. We then apply our new algorithm to a 12 m resolution TanDEM-X DEM for four southern Malawi fault scarps, located at the southern end of the East African Rift system: the Bilila–Mtakataka fault (BMF) and three previously unreported scarps – Thyolo, Muona and Malombe. All but Muona exhibit first-order structural segmentation at their surface. By using a 5 m resolution DEM derived from high-resolution (50 cm pixel−1) Pleiades stereo-satellite imagery for the Bilila–Mtakataka fault scarp, we quantify secondary structural segmentation. Our scarp height calculations from all four fault scarps suggest that if each scarp was formed by a single, complete rupture, the slip–length ratio for each earthquake exceeds the maximum typical value observed in historical normal faulting earthquakes around the world. The high slip–length ratios therefore imply that the Malawi fault scarps likely formed in multiple earthquakes. The scarp height distribution implies the structural segments of both the BMF and Thyolo fault have merged via rupture of discrete faults (hard links) through several earthquake cycles, and the segments of the Malombe fault have connected via distributed deformation zones (soft links). For all faults studied here, the length of earthquake ruptures may therefore exceed the length of each segment. Thus, our findings shed new light on the seismic hazard in southern Malawi, indicating evidence for a number of large (Mw 7–8) prehistoric earthquakes, as well as providing a new semi-automated methodology (SPARTA) for calculating scarp morphological parameters, which can be used on other fault scarps to infer structural development.
Premature atrial contractions (PACs) are frequently observed on electrocardiograms and are associated with increased risks of atrial fibrillation (AF), stroke, and mortality. In this study, we aimed ...to identify genetic susceptibility loci for PAC frequency. We performed a genome-wide association study meta-analysis with PAC frequency obtained from ambulatory cardiac monitoring in 4,831 individuals of European ancestry. We identified a genome-wide significant locus at the SCN5A gene. The lead variant, rs7373862, located in an intron of SCN5A, was associated with an increase of 0.12 95% CI 0.08–0.16 standard deviations of the normalized PAC frequency per risk allele. Among genetic variants previously associated with AF, there was a significant enrichment in concordance of effect for PAC frequency (n = 73/106, p = 5.1 × 10−5). However, several AF risk loci, including PITX2, were not associated with PAC frequency. These findings suggest the existence of both shared and distinct genetic mechanisms for PAC frequency and AF.
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•Variants in SCN5A are associated with premature atrial contractions (PAC) frequency•Other atrial fibrillation (AF) risk variants are also associated with PAC frequency•Both shared and distinct genetic mechanisms exist for PAC frequency and AF
Clinical genetics; Cardiovascular medicine; Human genetics; Genomics
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