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IntroductionIn a nested case-control study, we examined how cerebral perfusion relates to cognitive status and amyloid in the oldest-old (i.e., 90 years of age and older).MethodsStudy participants included 113 dementia-free older adults (76 cognitively normal [CN]; 37 cognitively impaired, no dementia [CIND]) from the 90+ Study (mean age = 92.9, SD = 2.4). We quantified regional perfusion from arterial spin labeling-MRI (magnetic resonance imaging) and amyloid deposition from florbetapir-positron emission tomography (PET) in a region comprising the posterior cingulate and precuneus (PCC+PCu), and additionally quantified perfusion in other regions important for cognitive decline (medial temporal lobe, inferior parietal lobe, and orbitofrontal cortex).ResultsParticipants with CIND displayed lower perfusion in the PCC+PCu relative to participants who were CN, but there was no statistically significant difference between the groups in amyloid burden in this region. In addition, participants with CIND exhibited lower inferior parietal and higher orbitofrontal perfusion.DiscussionCerebral perfusion is related to cognitive status in the oldest-old independent of amyloidosis.HighlightsCerebral perfusion and amyloid positron emission tomography (PET) were measured in older adults: 90 years of age and older. Perfusion but not amyloid differed between cognitively impaired and normal groups. Frontal and parietal regions linked to cognitive decline had altered perfusion. Perfusion is related to cognitive status in the oldest-old independent of amyloid.

This paper presents a novel approach to teaching how vaccines work in the body, and introduces a community outreach project and activity we piloted with youth. Our Nuestra Ciencia program addresses scientific misconceptions among bilingual elementary school children in engaging and scientifically accurate ways. Utilizing analogies and storytelling, one of our lessons simplifies the complex microbiology concept of the mechanism of action of vaccines. We underscore the issue with conveying this concept through accurate visuals, supported by our research that revealed that less than 1% of cartoons available online accurately depict how vaccines work. The analogy we developed and showcase in this paper employs relatable characters: the virus as a robber, the immune system as a superhero, and the vaccine as a "most wanted" poster. The activities include a skit and storyboard session, enabling students to act out the analogy and create their own imaginative scenarios. By targeting young learners, this lesson aims to prevent long-standing misconceptions and empower future generations to make informed decisions about vaccination. Nuestra Ciencia offers a promising model for combating vaccine hesitancy and promoting public health through effective science communication.

Blood pressure variability (BPV) is emerging as an important risk factor across numerous disease states, including cerebrovascular and neurodegenerative disease in older adults. However, there is no current consensus regarding specific use cases for the numerous available BPV metrics. There is also little published data supporting the ability to reliably measure BPV across metrics in older adults. The present study derived BPV metrics from continuous beat-to-beat blood pressure monitoring data. Two sequential 7 min waveforms were analyzed. Absolute and relative reliability testing was performed. Differences between antihypertensive medication users and non-users on BPV metric reliability was also assessed. All sequence and dispersion based BPV metrics displayed good test-retest reliability. A measure of BP instability displayed only moderate reliability. Systolic and diastolic average real variability displayed the highest levels of reliability at ICC = 0.87 and 0.82 respectively. Additionally, systolic average real variability was the most reliable metric in both the antihypertensive use group, and the no antihypertensive use group. In conclusion, beat-to-beat dispersion and sequence-based metrics of BPV can be reliably obtained in older adults using noninvasive continuous blood pressure monitoring. Average real variability may be the most reliable and specific beat-to-beat blood pressure variability metric due to its decreased susceptibility to outliers and low frequency blood pressure oscillations.

OBJECTIVE: Rathke cleft cysts (RCCs) are benign, epithelial-lined sellar lesions that arise from remnants of the craniopharyngeal duct. Due to their rarity in the pediatric population, data are limited regarding the natural history and optimal management of growing or symptomatic RCCs. We present our institutional experience with the surgical management of RCCs. METHODS: We performed a retrospective study of consecutive RCC patients ≤ 18 years old treated surgically at our institution between 2006 and 2022. RESULTS: Overall, 567 patients with a diagnosis of pituitary mass or cyst were identified. Of these, 31 had a histopathological diagnosis of RCC, 58% female and 42% male. The mean age was 13.2 ± 4.2 years. Presenting symptoms included headache (58%), visual changes (32%), and endocrinopathies or growth delay (26%); 13% were identified incidentally and subsequently demonstrated growth on serial imaging. Six percent presented with symptomatic intralesional hemorrhage. Surgical approach was transsphenoidal for 90% of patients and orbitozygomatic for 10%. Preoperative headaches resolved in 61% of patients and preoperative visual deficits improvement in 55% after surgery. New pituitary axis deficits were seen in 9.7% of patients. Only two complications occurred from a first-time surgery: one cerebrospinal fluid leak requiring lumbar drain placement, and one case of epistaxis requiring cauterization. No patients experienced new visual or neurological deficits. Patients were followed postoperatively with serial imaging at a mean follow-up was 62.9 ± 58.4 months. Recurrence requiring reoperation occurred in 32% of patients. Five-year progression-free survival was 47.9%. Except for one patient with multiple neurological deficits from a concurrent tectal glioma, all patients had a modified Rankin Scale score of 0 or 1 (good outcome) at last follow-up. CONCLUSION: Due to their secretory epithelium, pediatric RCCs may demonstrate rapid growth and can cause symptoms due to local mass effect. Surgical management of symptomatic or growing pediatric RCCs via cyst fenestration or partial resection of the cyst wall can be performed safely, with good neurologic outcomes. There is a nontrivial risk of endocrinologic injury, and long-term follow up is needed due to high recurrence rates.

BackgroundBlood pressure variability is increasingly linked with cerebrovascular disease and Alzheimer's disease, independent of mean blood pressure levels. Elevated blood pressure variability is also associated with attenuated cerebrovascular reactivity, which may have implications for functional hyperemia underpinning brain network connectivity. It remains unclear whether blood pressure variability is related to functional network connectivity. We examined relationships between beat-to-beat blood pressure variability and functional connectivity in brain networks vulnerable to aging and Alzheimer's disease.Methods53 community-dwelling older adults (mean [SD] age = 69.9 [7.5] years, 62.3% female) without history of dementia or clinical stroke underwent continuous blood pressure monitoring and resting state fMRI scan. Blood pressure variability was calculated as variability independent of mean. Functional connectivity was determined by resting state fMRI for several brain networks: default, salience, dorsal attention, fronto-parietal, and language. Multiple linear regression examined relationships between short-term blood pressure variability and functional network connectivity.ResultsElevated short-term blood pressure variability was associated with lower functional connectivity in the default network (systolic: standardized ß = -0.30 [95% CI -0.59, -0.01], p = .04). There were no significant associations between blood pressure variability and connectivity in other functional networks or between mean blood pressure and functional connectivity in any network.DiscussionOlder adults with elevated short-term blood pressure variability exhibit lower resting state functional connectivity in the default network. Findings support the role of blood pressure variability in neurovascular dysfunction and Alzheimer's disease. Blood pressure variability may represent an understudied early vascular risk factor for neurovascular dysfunction relevant to Alzheimer's disease, with potential therapeutic implications.

In Canada, recent advances towards reconciliation have introduced new collaborations between Indigenous and non-Indigenous governments, including for species-at-risk recovery planning. During these collaborations, Indigenous Knowledge (IK) is often requested, however, clear expectations of what IK is being sought and how diverse knowledge systems will be woven to produce tangible benefits to species recovery are often limited. Here, we provide a case study of a two-stage process to identify and collect IK components that can aid whudzih (caribou) recovery planning. First, we surveyed non-Indigenous government professionals involved in caribou initiatives to specify what IK would benefit recovery planning. Responses were used to guide the development of semi-structured interview questions. Interviews were conducted with knowledge holders from Lhtako Dene, a Southern Dakelh Nation in British Columbia, Canada with historic socioecological ties to caribou. Responses of government professionals highlighted 24 topics for caribou recovery, and interviews with Lhtako Dene knowledge holders revealed strong linkages between ecological and social information types. In some cases, the IK requested was not available from knowledge holders. Collaborations for caribou recovery would benefit from clarity on expectations and outcomes of IK sharing. We suggest that structured processes that respectfully facilitate IK requests and collection become commonplace in species recovery planning.

Building on Jack Richard's interest in vocabulary, this paper looks at the importance of morphology (how words are formed) in language learning and teaching. It describes why knowledge of morphology is important, and how it affects vocabulary learning. It provides clear guidelines on what word parts to focus on, how much time to spend on word parts and what a teacher (and learners) should do about word parts. Morphological knowledge involving derivational affixes becomes particularly important when learners know the first 2000-3000 words of English. One of the major activities for developing morphological awareness is cutting words into parts and relating the meanings of the parts to the meaning of the whole word. Teachers should help learners develop morphological awareness, train learners in word part strategies, and help learners to learn frequent word parts. The paper includes activities to achieve these goals in the classroom, as well as links that provide material for classroom use.

We show that there are finite distributive lattices that are not the congruence lattice of any finite semidistributive lattice. For \(0 \leq k \leq 2\), the distributive lattice \((\mathbf{B}_k)_{++} = \mathbf{2} + \mathbf{B}_k\), where \(\mathbf{B}_k\) denotes the boolean lattice with \(k\) atoms, is not the congruence lattice of any finite semidistributive lattice. Neither can these lattices be a filter in the congruence lattice of a finite semidistributive lattice. However, each \((\mathbf{B}_k)_{++}\) with \(k \geq 3\) is the congruence lattice of a finite semidistributive lattice, say \(\mathbf{L}_k\). These lattices \(\mathbf{L}_k\) cannot be bounded (in the sense of McKenzie), as no \((\mathbf{B}_k)_{++}\) \((k \geq 0)\) is the congruence lattice of a finite bounded lattice. A companion paper shows that every \((\mathbf{B}_k)_{++}\) \((k \geq 0)\) can be represented as the congruence lattice of an infinite semidistributive lattice. We also find sufficient conditions for a finite distributive lattice to be representable as the congruence lattice of a finite bounded (and hence semidistributive) lattice.

People learn new words in narrative contexts. Little is known about the influence of the emotional valence of the text on word learning. In a pre-registered experiment, we investigated whether emotional narrative context shapes word learning. English adults (N = 76) read 30 novel adjectives embedded in 60 short narratives (20 positive, 20 negative, and 20 neutral valence). Post-tests assessed learning (immediate and 24 hours later) and examined whether the valence of the novel words can be inferred from contextual valence. Compared to the neutral context, emotional contexts (both positive and negative) facilitated word form learning in the immediate post-tests, but only negative emotion words were recognized better 24 hours later. Furthermore, the valence of the context was reflected in the word meanings participants generated for each novel word. These findings are discussed with reference to theories of affective embodiment and its implications for supporting the learning of abstract concepts.

This study assessed whether the effect of vascular risk on cerebral blood flow (CBF) varies by gene dose of apolipoprotein (APOE) ε4 alleles. 144 older adults without dementia from the Alzheimers Disease Neuroimaging Initiative underwent arterial spin labeling and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure (BP) assessment. Vascular risk was assessed using pulse pressure (systolic BP - diastolic BP). CBF was examined in six AD-vulnerable regions: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regressions tested the interaction between APOE ε4 dose and pulse pressure on CBF in each region, adjusting for age, sex, cognitive classification, antihypertensive medication use, FDG-PET, reference CBF region, and AD biomarker positivity. There was a significant interaction between pulse pressure and APOE ɛ4 dose on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex, such that higher pulse pressure was associated with lower CBF only among ε4 homozygous participants. These findings demonstrate that the association between pulse pressure and regional CBF differs by APOE ε4 dose, suggesting that targeting modifiable vascular risk factors may be particularly important for those genetically at risk for AD.

Abstract In this study we present a replication method to determine surface roughness and to identify surface features when a sample cannot be directly analyzed by conventional techniques. As a demonstration, this method was applied to an unused spent nuclear fuel dry storage canister to determine variation across different surface features. In this study, an initial material down-selection was performed to determine the best molding agent and determined that non-modified Polytek PlatSil23-75 provided the most accurate representation of the surface while providing good usability. Other materials that were considered include Polygel Brush-On 35 polyurethane rubber (with and without Pol-ease 2300 release agent), Polytek PlatSil73-25 silicone rubber (with and without PlatThix thickening agent and Pol-ease 2300 release agent), and Express STD vinylpolysiloxane impression putty. The ability of PlatSil73-25 to create an accurate surface replica was evaluated by creating surface molds of several locations on surface roughness standards representing ISO grade surfaces N3, N5, N7, and N8. Overall, the molds were able to accurately reproduce the expected roughness average (Ra) values, but systematically over-estimated the peak-valley maximum roughness (Rz) values. Using a 3D printed sample cell, several locations across the stainless steel spent nuclear fuel canister were sampled to determine the surface roughness. These measurements provided information regarding variability in normal surface roughness across the canister as well as a detailed evaluation on specific surface features (e.g., welds, grind marks, etc.). The results of these measurements can support development of dry storage canister ageing management programs, as surface roughness is an important factor for surface dust deposition and accumulation. This method can be applied more broadly to different surfaces beyond stainless steel to provide rapid, accurate surface replications for analytical evaluation by profilometry.

Abstract Limited data from Asia are available on long-term effects of pneumococcal conjugate vaccine introduction on pneumococcal carriage. Here we assess the impact of 13-valent pneumococcal conjugate vaccine (PCV13) introduction on nasopharyngeal pneumococcal carriage prevalence, density and antimicrobial resistance. Cross-sectional carriage surveys were conducted pre-PCV13 (2015) and post-PCV13 introduction (2017 and 2022). Pneumococci were detected and quantified by real-time PCR from nasopharyngeal swabs. DNA microarray was used for molecular serotyping and to infer genetic lineage (Global Pneumococcal Sequence Cluster). The study included 1461 infants (5–8 weeks old) and 1489 toddlers (12–23 months old) enrolled from family health clinics. We show a reduction in PCV13 serotype carriage (with non-PCV13 serotype replacement) and a reduction in the proportion of samples containing resistance genes in toddlers six years post-PCV13 introduction. We observed an increase in pneumococcal nasopharyngeal density. Serotype 15 A, the most prevalent non-vaccine-serotype in 2022, was comprised predominantly of GPSC904;9. Reductions in PCV13 serotype carriage will likely result in pneumococcal disease reduction. It is important for ongoing surveillance to monitor serotype changes to potentially inform new vaccine development.

Abstract Blood pressure variability (BPV) is emerging as an important risk factor across numerous disease states, including cerebrovascular and neurodegenerative disease in older adults. However, there is no current consensus regarding specific use cases for the numerous available BPV metrics. There is also little published data supporting the ability to reliably measure BPV across metrics in older adults. The present study derived BPV metrics from continuous beat-to-beat blood pressure monitoring data. Two sequential 7 min waveforms were analyzed. Absolute and relative reliability testing was performed. Differences between antihypertensive medication users and non-users on BPV metric reliability was also assessed. All sequence and dispersion based BPV metrics displayed good test–retest reliability. A measure of BP instability displayed only moderate reliability. Systolic and diastolic average real variability displayed the highest levels of reliability at ICC = 0.87 and 0.82 respectively. Additionally, systolic average real variability was the most reliable metric in both the antihypertensive use group, and the no antihypertensive use group. In conclusion, beat-to-beat dispersion and sequence-based metrics of BPV can be reliably obtained in older adults using noninvasive continuous blood pressure monitoring. Average real variability may be the most reliable and specific beat-to-beat blood pressure variability metric due to its decreased susceptibility to outliers and low frequency blood pressure oscillations.

Emotion is closely associated with language, but we know very little about how children express emotion in their own writing. We used a large-scale, cross-sectional, and data-driven approach to investigate emotional expression via writing in children of different ages, and whether it varies for boys and girls. We first used a lexicon-based bag-of-words approach to identify emotional content in a large corpus of stories (N>100,000) written by 7- to 13-year-old children. Generalized Additive Models were then used to model changes in sentiment across age and gender. Two other machine learning approaches (BERT and TextBlob) validated and extended these analyses, converging on the finding that positive sentiments in children's writing decrease with age. These findings echo reports from previous studies showing a decrease in mood and an increased use of negative emotion words with age. We also found that stories by girls contained more positive sentiments than stories by boys. Our study shows the utility of large-scale data-driven approaches to reveal the content and nature of children's writing. Future experimental work should build on these observations to understand the likely complex relationships between written language and emotion, and how these change over development.

Dilation of perivascular spaces (PVS) in the brain may indicate poor fluid drainage due to the accumulation of perivascular cell debris, waste, and proteins, including amyloid-beta (Aβ). No prior study has assessed whether plasma Aβ levels are related to PVS in older adults without dementia. Independently living older adults (N = 56, mean age = 68.2 years; Standard deviation (SD) = 6.5; 30.4% male) free of dementia or clinical stroke were recruited from the community and underwent brain MRI and venipuncture. PVS were qualitatively scored and dichotomized to low PVS burden (scores 0-1,) or high PVS burden (score>1). Plasma was assayed using a Quanterix Simoa Kit to quantify Aβ42 and Aβ40 levels. A significant difference was observed in plasma Aβ42/Aβ40 ratio between low and high PVS burden, controlling for age (F[1, 53] = 5.59, p = 0.022, η2 = 0.10), with lower Aβ42/Aβ40 ratio in the high PVS burden group. Dilation of PVS is associated with a lower plasma Aβ42/Aβ40 ratio, which may indicate higher cortical amyloid deposition. Future longitudinal studies examining PVS changes, and the pathogenesis of AD are warranted.

We present data from the Heart Rate Variability and Emotion Regulation (HRV-ER) randomized clinical trial testing effects of HRV biofeedback. Younger (N = 121) and older (N = 72) participants completed baseline magnetic resonance imaging (MRI) including T1-weighted, resting and emotion regulation task functional MRI (fMRI), pulsed continuous arterial spin labeling (PCASL), and proton magnetic resonance spectroscopy (1H MRS). During fMRI scans, physiological measures (blood pressure, pulse, respiration, and end-tidal CO2) were continuously acquired. Participants were randomized to either increase heart rate oscillations or decrease heart rate oscillations during daily sessions. After 5 weeks of HRV biofeedback, they repeated the baseline measurements in addition to new measures (ultimatum game fMRI, training mimicking during blood oxygen level dependent (BOLD) and PCASL fMRI). Participants also wore a wristband sensor to estimate sleep time. Psychological assessment comprised three cognitive tests and ten questionnaires related to emotional well-being. A subset (N = 104) provided plasma samples pre- and post-intervention that were assayed for amyloid and tau. Data is publicly available via the OpenNeuro data sharing platform.