Heightened hurricane surge risk in northwest Florida revealed from climatological-hydrodynamic modeling and paleorecord reconstruction

Historical tropical cyclone (TC) and storm surge records are often too limited to quantify the risk to local populations. Paleohurricane sediment records uncover long-term TC activity, but interpreting these records can be difficult and can introduce significant uncertainties. Here we compare and combine climatological-hydrodynamic modeling (including a method to account for storm size uncertainty), historical observations, and paleohurricane records to investigate local surge risk, using Apalachee Bay in northwest Florida as an example. The modeling reveals relatively high risk, with 100 year, 500 year, and “worst case” surges estimated to be about 6.3 m, 8.3 m, and 11.3 m, respectively, at Bald Point (a paleorecord site) and about 7.4 m, 9.7 m, and 13.3 m, respectively, at St. Marks (the head of the Bay), supporting the inference from paleorecords that Apalachee Bay has frequently suffered severe inundation for thousands of years. Both the synthetic database and paleorecords contain a much higher frequency of extreme events than the historical record; the mean return period of surges greater than 5 m is about 40 years based on synthetic modeling and paleoreconstruction, whereas it is about 400 years based on historical storm analysis. Apalachee Bay surge risk is determined by storms of broad characteristics, varies spatially over the area, and is affected by coastally trapped Kelvin waves, all of which are important features to consider when accessing the risk and interpreting paleohurricane records. In particular, neglecting size uncertainty may induce great underestimation in surge risk, as the size distribution is positively skewed. While the most extreme surges were generated by the uppermost storm intensities, medium intensity storms (categories 1–3) can produce large to extreme surges, due to their larger inner core sizes. For Apalachee Bay, the storms that induced localized barrier breaching and limited sediment transport (overwash regime; surge between 3 and 5 m) are most likely to be category 2 or 3 storms, and the storms that inundated the entire barrier and deposited significantly more coarse materials (inundation regime; surge > 5 m) are most likely to be category 3 or 4 storms.United States. National Oceanic and Atmospheric Administration (Grant NA11OAR4310101)National Science Foundation (U.S.) (Grant OCE-0903020)National Science Foundation (U.S.) (Grant OCE-1250506

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker

Soluble TREM2 in CSF and its association with other biomarkers and cognition in autosomal-dominant Alzheimer's disease: a longitudinal observational study

BACKGROUND: Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression of Alzheimer's disease. Although studies in animal models suggest that TREM2 is protective against Alzheimer's pathology, its effect on tau pathology and its potential beneficial role in people with Alzheimer's disease is still unclear. Our aim was to study associations between the dynamics of soluble TREM2, as a biomarker of TREM2 signalling, and amyloid β (Aβ) deposition, tau-related pathology, neuroimaging markers, and cognitive decline, during the progression of autosomal dominant Alzheimer's disease. METHODS: We did a longitudinal analysis of data from the Dominantly Inherited Alzheimer Network (DIAN) observational study, which includes families with a history of autosomal dominant Alzheimer's disease. Participants aged over 18 years who were enrolled in DIAN between Jan 1, 2009, and July 31, 2019, were categorised as either carriers of pathogenic variants in PSEN1, PSEN2, and APP genes (n=155) or non-carriers (n=93). We measured amounts of cleaved soluble TREM2 using a novel immunoassay in CSF samples obtained every 2 years from participants who were asymptomatic (Clinical Dementia Rating [CDR]=0) and annually for those who were symptomatic (CDR>0). CSF concentrations of Aβ40, Aβ42, total tau (t-tau), and tau phosphorylated on threonine 181 (p-tau) were measured by validated immunoassays. Predefined neuroimaging measurements were total cortical uptake of Pittsburgh compound B PET (PiB-PET), cortical thickness in the precuneus ascertained by MRI, and hippocampal volume determined by MRI. Cognition was measured using a validated cognitive composite (including DIAN word list test, logical memory delayed recall, digit symbol coding test [total score], and minimental status examination). We based our statistical analysis on univariate and bivariate linear mixed effects models. FINDINGS: In carriers of pathogenic variants, a high amyloid burden at baseline, represented by low CSF Aβ42 (β=–4·28 × 10^{–2} [SE 0·013], p=0·0012), but not high cortical uptake in PiB-PET (β=–5·51 × 10^{–3} [0·011], p=0·63), was the only predictor of an augmented annual rate of subsequent increase in soluble TREM2. Augmented annual rates of increase in soluble TREM2 were associated with a diminished rate of decrease in amyloid deposition, as measured by Aβ42 in CSF (r=0·56 [0·22], p=0·011), in presymptomatic carriers of pathogenic variants, and with diminished annual rate of increase in PiB-PET (r=–0·67 [0·25], p=0·0060) in symptomatic carriers of pathogenic variants. Presymptomatic carriers of pathogenic variants with annual rates of increase in soluble TREM2 lower than the median showed a correlation between enhanced annual rates of increase in p-tau in CSF and augmented annual rates of increase in PiB-PET signal (r=0·45 [0·21], p=0·035), that was not observed in those with rates of increase in soluble TREM2 higher than the median. Furthermore, presymptomatic carriers of pathogenic variants with rates of increase in soluble TREM2 above or below the median had opposite associations between Aβ42 in CSF and PiB-PET uptake when assessed longitudinally. Augmented annual rates of increase in soluble TREM2 in presymptomatic carriers of pathogenic variants correlated with decreased cortical shrinkage in the precuneus (r=0·46 [0·22]), p=0·040) and diminished cognitive decline (r=0·67 [0·22], p=0·0020). INTERPRETATION: Our findings in autosomal dominant Alzheimer's disease position the TREM2 response within the amyloid cascade immediately after the first pathological changes in Aβ aggregation and further support the role of TREM2 on Aβ plaque deposition and compaction. Furthermore, these findings underpin a beneficial effect of TREM2 on Aβ deposition, Aβ-dependent tau pathology, cortical shrinkage, and cognitive decline. Soluble TREM2 could, therefore, be a key marker for clinical trial design and interpretation. Efforts to develop TREM2-boosting therapies are ongoing

Amyloid and Tau Pathology Associations With Personality Traits, Neuropsychiatric Symptoms, and Cognitive Lifestyle in the Preclinical Phases of Sporadic and Autosomal Dominant Alzheimer's Disease

Background: Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods: A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results: In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions: In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression

Amyloid and tau pathology associations with personality traits, neuropsychiatric symptoms, and cognitive lifestyle in the preclinical phases of sporadic and autosomal dominant Alzheimer’s disease

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

HIV in Rural Vermont

Through our Health Sciences capstone, we are serving as public health interns at the Pride Center of Vermont. The Pride Center provides sexual health education materials, activities, a wide range of resources, and a safe space for the LGBTQ+ community. The main demographic that this community center works with is within Chittenden county. An estimated 5% of adult Vermonters identify as lesbian, gay, bisexual, or transgender. People aged 18-24 are most likely to identify as LGBTQ+ and about 8% of high school students identify as lesbian, gay, or bisexual (Vermont State Health Assessment, 2018). The majority of services for the LGBTQ+ community in Vermont are located in the greater Burlington area. An issue of focus for The Pride Center is to increase access to services for rural communities in Vermont, with a focus on people living with HIV however they lack major funding. Knowing this, we will assess the rates of HIV in rural areas of Vermont in addition to taking an inventory of current efforts locally and best practices in the literature on reaching rural populations. By the conclusion of our internships, we formulate a proposal for the Pride Center of Vermont on how to successfully expand into rural areas of Vermont. We would like to present at the 2019 Student Research Conference on our service learning research. Sources: -http://www.healthvermont.gov/sites/default/files/documents/pdf/ID_HIV_2016VermontHIVEpiProfile.pdf Vermont State Health Assessment, 201

A method to estimate the longshore sediment transport at ebb‐tidal deltas based on their volumetric growth: application to the Guadiana (Spain–Portugal border)

Current techniques assessing longshore sediment transport rates have large uncertainties, pleading for the development of alternative and complementary approaches. The present study proposes a method to estimate the decadal average rate of longshore transport at modern ebb-tidal deltas based on a sediment budget analysis of the outer shoal growth. This transport is obtained as the balance of the other contributions to the shoal with the total sediment input rate obtained from an inverse application of the inlet reservoir model. The method is applied to the Guadiana ebb-tidal delta, yielding an average longshore sediment transport rate (~85 000 m3 year(-1)) in good agreement with expectations for the region. It is exemplified that this decadal averaged rate can be used to improve longshore sediment transport expressions in order to study its variability over shorter time scales. At the Guadiana, the yearly longshore sediment transport from the improved formula ranges from ~25 000 m(3) (westward) to ~245 000 m(3) (eastward) and is related to the North Atlantic Oscillation index. Overall, the proposed method constitutes an alternative tool to constrain the average longshore sediment transport rate over decades in the vicinity of tidal inlets. It is applicable to ebb-tidal deltas where the outer shoal growth (from an early to a mature stage) is well documented by bathymetric maps, and where the main transport pathways towards the outer shoal can be specified. (c) 2019 John Wiley & Sons, Ltd. (c) 2019 John Wiley & Sons, Ltd.info:eu-repo/semantics/publishedVersio