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The Great Basin is home to a variety of avian species but as anthropogenic change continues, land cover change in this region may displace some species. We quantified the amount of land cover change in the Great Basin region between 2001 and 2019, analyzed distribution data derived from the eBird Status and Trends database for 19 raptor species (orders Accipitriformes and Falconiformes), and identified each species' land cover occurrence patterns. We discovered that 15 of the raptor species investigated had land cover type as a top-10 predictor for occupancy. We also observed a large percent change in total cover of water, deciduous forest, mixed forest, shrublands, and grasslands land cover types. The raptor species with land cover in their top-10 predictor list could thus potentially be affected by these land cover change trends. While the complexity of land cover associations are nuanced, we identify patterns of land cover change over almost 2 decades in the Great Basin and reveal species that may be impacted by continued landscape change. These findings can provide crucial information for both habitat management and species conservation. El Great Basin (en el occidente de los Estados Unidos) es hábitat para una variedad de especies de aves, aunque el cambio antropogénico sostenido en la cobertura del suelo en esta región podría desplazar a algunas especies. Cuantificamos la suma de cambio en la cobertura del suelo en la región del Great Basin entre 2001–2019, analizamos la distribución derivada de la base de datos eBird Status and Trends para 19 especies de rapaces (órdenes Accipitriformes y Falconiformes) e identificamos los patrones de presencia por cobertura de cada especie. Descubrimos que 15 de especies de rapaces que investigamos tenían la cobertura del suelo como una de las 10 principales variables de ocupación. También observamos un gran porcentaje de cambio en la superficie total de los tipos de cobertura agua, bosque deciduo, bosque mixto, matorral y pradera. Las especies de rapaces con cobertura del suelo en su lista de las 10 principales variables predictivas podrían ser potencialmente afectadas por esas tendencias en cambio de la cobertura del suelo. Si bien la complejidad de las asociaciones de cobertura del suelo es ambigua, identificamos patrones de cambio de cobertura a lo largo de cerca de 2 décadas en el Great Basin y revelan especies que podrían estar impactadas por un continuo cambio en el paisaje. Estos hallazgos proveen información crucial para el manejo de hábitat y la conservación de especies. Palabras clave: aves de presa, cambio antropogénico, cambio de uso del suelo, ciencia comunitaria, desertificación.

The Great Basin is home to a variety of avian species but as anthropogenic change continues, land cover change in this region may displace some species. We quantified the amount of land cover change in the Great Basin region between 2001 and 2019, analyzed distribution data derived from the eBird Status and Trends database for 19 raptor species (orders Accipitriformes and Falconiformes), and identified each species' land cover occurrence patterns. Wc discovered that 15 of the raptor species investigated had land cover type as a top-10 predictor lor occupancy. We also observed a large percent change in total cover of water, deciduous forest, mixed forest, shrublands, and grasslands land cover types. The raptor species with land cover in their top-10 predictor list could thus potentially be affected by these land cover change trends. While the complexity of land cover associations are nuanced, we identify patterns of land cover change over almost 2 decades in the Great Basin and reveal species that may be impacted by continued landscape change. These findings can provide crucial information for both habitat management and species conservation. Received 23 February 2021. Accepted 8 June 2022.

The Harvard Aging Brain Study (HABS) is a longitudinal observational study on the differences between \"normal\" aging and preclinical AD. Sixteen HABS participants have undergone brain donation. We evaluate to what extent PET biomarkers predict neuropathologic assessments. Neuropathologic assessments of amyloid-β plaques (Thal phase/A score), tau neurofibrillary tangles (Braak NFT stage/B score) and neuritic plaques (CERAD NP score/C score) were compared with antemortem PET. For amyloid-β PET (PiB), the frontal, lateral temporal, parietal, and retrosplenial cortices (FLR) distribution volume ratio (DVR) and spatial extent (EXT) were calculated. For tau PET (flortaucipir, FTP), the whole temporal, temporal allocortex (MTL), and temporal neocortex (NEO-T) standardized uptake value ratios (SUVRs) were calculated, using bilateral and lateralized regions (left or right, whichever is greater). PET-neuropathologic correlations were measured with Spearman's ρ. PiB FLR DVR and EXT correlate significantly with A (ρ=0.81, p = 0.00029 and ρ=0.73, p = 0.0020) and C score (ρ=0.73, p = 0.0019 and ρ=0.77, p = 0.00087). Two cases had unusually low FTP SUVRs and high B scores (Cases #14 and #16, Table 1). Initially no FTP SUVR correlated significantly with B score. After removing the aforementioned outliers, whole temporal and NEO-T SUVR correlated significantly with B score (both ρ=0.76, p = 0.017, n = 9). After additionally removing an MTL-sparing case (spared at the time of PET acquisition, Case #8), MTL SUVR correlated significantly with B score (ρ=0.78, p = 0.021, n = 8). Lateralizing SUVRs strengthened correlations with B score for whole temporal (ρ=0.86, p = 0.0031, n = 9) and MTL (ρ=0.87, p = 0.0054, n = 8). Amyloid-β PET metrics correlated with amyloid-β plaque spatial distribution and density, while tau PET metrics correlated with tau NFT spatial distribution only after removing outliers. These outliers suggest that PET-neuropathologic discrepancies arise with tau PET more so than amyloid-β PET, and were driven by: primary age-related tauopathy, Braak NFT stage III; amyloid-β-driven tau spread (\"ca-tau-strophe\") between imaging and death; and variability and asymmetry in tau accumulation. In conclusion, individualized tau PET metrics that respect the heterogeneity in tauopathy may be better able to predict neuropathologic assessments.

The Harvard Aging Brain Study (HABS) is a longitudinal observational study on the differences between \"normal\" aging and preclinical AD. Sixteen HABS participants have undergone brain donation. We evaluate to what extent PET biomarkers predict neuropathologic assessments. Neuropathologic assessments of amyloid-β plaques (Thal phase/A score), tau neurofibrillary tangles (Braak NFT stage/B score) and neuritic plaques (CERAD NP score/C score) were compared with antemortem PET. For amyloid-β PET (PiB), the frontal, lateral temporal, parietal, and retrosplenial cortices (FLR) distribution volume ratio (DVR) and spatial extent (EXT) were calculated. For tau PET (flortaucipir, FTP), the whole temporal, temporal allocortex (MTL), and temporal neocortex (NEO-T) standardized uptake value ratios (SUVRs) were calculated, using bilateral and lateralized regions (left or right, whichever is greater). PET-neuropathologic correlations were measured with Spearman's ρ. PiB FLR DVR and EXT correlate significantly with A (ρ=0.81, p = 0.00029 and ρ=0.73, p = 0.0020) and C score (ρ=0.73, p = 0.0019 and ρ=0.77, p = 0.00087). Two cases had unusually low FTP SUVRs and high B scores (Cases #14 and #16, Table 1). Initially no FTP SUVR correlated significantly with B score. After removing the aforementioned outliers, whole temporal and NEO-T SUVR correlated significantly with B score (both ρ=0.76, p = 0.017, n = 9). After additionally removing an MTL-sparing case (spared at the time of PET acquisition, Case #8), MTL SUVR correlated significantly with B score (ρ=0.78, p = 0.021, n = 8). Lateralizing SUVRs strengthened correlations with B score for whole temporal (ρ=0.86, p = 0.0031, n = 9) and MTL (ρ=0.87, p = 0.0054, n = 8). Amyloid-β PET metrics correlated with amyloid-β plaque spatial distribution and density, while tau PET metrics correlated with tau NFT spatial distribution only after removing outliers. These outliers suggest that PET-neuropathologic discrepancies arise with tau PET more so than amyloid-β PET, and were driven by: primary age-related tauopathy, Braak NFT stage III; amyloid-β-driven tau spread (\"ca-tau-strophe\") between imaging and death; and variability and asymmetry in tau accumulation. In conclusion, individualized tau PET metrics that respect the heterogeneity in tauopathy may be better able to predict neuropathologic assessments.

Background The Harvard Aging Brain Study (HABS) is a longitudinal observational study on the differences between “normal” aging and preclinical AD. Sixteen HABS participants have undergone brain donation. We evaluate to what extent PET biomarkers predict neuropathologic assessments. Method Neuropathologic assessments of amyloid‐β plaques (Thal phase/A score), tau neurofibrillary tangles (Braak NFT stage/B score) and neuritic plaques (CERAD NP score/C score) were compared with antemortem PET. For amyloid‐β PET (PiB), the frontal, lateral temporal, parietal, and retrosplenial cortices (FLR) distribution volume ratio (DVR) and spatial extent (EXT) were calculated. For tau PET (flortaucipir, FTP), the whole temporal, temporal allocortex (MTL), and temporal neocortex (NEO‐T) standardized uptake value ratios (SUVRs) were calculated, using bilateral and lateralized regions (left or right, whichever is greater). PET‐neuropathologic correlations were measured with Spearman’s ρ. Result PiB FLR DVR and EXT correlate significantly with A (ρ=0.81, p = 0.00029 and ρ=0.73, p = 0.0020) and C score (ρ=0.73, p = 0.0019 and ρ=0.77, p = 0.00087). Two cases had unusually low FTP SUVRs and high B scores (Cases #14 and #16, Table 1). Initially no FTP SUVR correlated significantly with B score. After removing the aforementioned outliers, whole temporal and NEO‐T SUVR correlated significantly with B score (both ρ=0.76, p = 0.017, n = 9). After additionally removing an MTL‐sparing case (spared at the time of PET acquisition, Case #8), MTL SUVR correlated significantly with B score (ρ=0.78, p = 0.021, n = 8). Lateralizing SUVRs strengthened correlations with B score for whole temporal (ρ=0.86, p = 0.0031, n = 9) and MTL (ρ=0.87, p = 0.0054, n = 8). Conclusion Amyloid‐β PET metrics correlated with amyloid‐β plaque spatial distribution and density, while tau PET metrics correlated with tau NFT spatial distribution only after removing outliers. These outliers suggest that PET‐neuropathologic discrepancies arise with tau PET more so than amyloid‐β PET, and were driven by: primary age‐related tauopathy, Braak NFT stage III; amyloid‐β‐driven tau spread (“ca‐tau‐strophe”) between imaging and death; and variability and asymmetry in tau accumulation. In conclusion, individualized tau PET metrics that respect the heterogeneity in tauopathy may be better able to predict neuropathologic assessments.

Background The Harvard Aging Brain Study (HABS) is a longitudinal observational study on the differences between “normal” aging and preclinical AD. Sixteen HABS participants have undergone brain donation. We evaluate to what extent PET biomarkers predict neuropathologic assessments. Method Neuropathologic assessments of amyloid‐β plaques (Thal phase/A score), tau neurofibrillary tangles (Braak NFT stage/B score) and neuritic plaques (CERAD NP score/C score) were compared with antemortem PET. For amyloid‐β PET (PiB), the frontal, lateral temporal, parietal, and retrosplenial cortices (FLR) distribution volume ratio (DVR) and spatial extent (EXT) were calculated. For tau PET (flortaucipir, FTP), the whole temporal, temporal allocortex (MTL), and temporal neocortex (NEO‐T) standardized uptake value ratios (SUVRs) were calculated, using bilateral and lateralized regions (left or right, whichever is greater). PET‐neuropathologic correlations were measured with Spearman's ρ. Result PiB FLR DVR and EXT correlate significantly with A (ρ=0.81, p = 0.00029 and ρ=0.73, p = 0.0020) and C score (ρ=0.73, p = 0.0019 and ρ=0.77, p = 0.00087). Two cases had unusually low FTP SUVRs and high B scores (Cases #14 and #16, Table 1). Initially no FTP SUVR correlated significantly with B score. After removing the aforementioned outliers, whole temporal and NEO‐T SUVR correlated significantly with B score (both ρ=0.76, p = 0.017, n = 9). After additionally removing an MTL‐sparing case (spared at the time of PET acquisition, Case #8), MTL SUVR correlated significantly with B score (ρ=0.78, p = 0.021, n = 8). Lateralizing SUVRs strengthened correlations with B score for whole temporal (ρ=0.86, p = 0.0031, n = 9) and MTL (ρ=0.87, p = 0.0054, n = 8). Conclusion Amyloid‐β PET metrics correlated with amyloid‐β plaque spatial distribution and density, while tau PET metrics correlated with tau NFT spatial distribution only after removing outliers. These outliers suggest that PET‐neuropathologic discrepancies arise with tau PET more so than amyloid‐β PET, and were driven by: primary age‐related tauopathy, Braak NFT stage III; amyloid‐β‐driven tau spread (“ca‐tau‐strophe”) between imaging and death; and variability and asymmetry in tau accumulation. In conclusion, individualized tau PET metrics that respect the heterogeneity in tauopathy may be better able to predict neuropathologic assessments.

A single-nucleotide polymorphism (SNP) in exon 4 results in expression of either arginine (72R) or proline (72P) at codon 72 of p53. We demonstrate that the in vitro response of cells exposed to anticancer agents is strongly influenced by this SNP in wild-type p53. In inducible systems and in cells expressing the endogenous protein, expression of 72P wild-type p53 results in a predominant G1 arrest, with only a minor apoptosis, at drug concentrations causing extensive apoptosis in cells expressing the 72R wild-type variant. The superior apoptosis-inducing activity of the 72R form correlates with more efficient induction of specific apoptosis-associated genes, and is maximal in the presence of serine 46 (S46). In vivo , the outcome of chemo-radiotherapy of squamous carcinomas is more favourable in cancers retaining a wild-type 72R allele, such cases having higher response rates and longer survival than those with wild-type 72P. Together, these results reveal that this SNP is an important determinant of response to anticancer agents in cells expressing wild-type p53. Analysis of complete p53 genotype (mutation and SNP) merits detailed investigation as a simple means for prediction of treatment response and survival in clinical oncology.

INTRODUCTION Alzheimer's disease (AD) biomarkers are assessed on their ability to detect AD pathophysiology in vivo, with confirmation of AD neuropathology only at autopsy. METHODS Positron emission tomography (PET), plasma, and cognitive AD biomarkers were compared to AD neuropathology in Harvard Aging Brain Study participants (10 cognitively unimpaired; 6 mild cognitive impairment). Different PET methods were evaluated, for example, standardized uptake volume ratio (SUVR), distribution volume ratio (DVR), spatial extent (EXT), and partial‐volume correction (PVC). RESULTS Amyloid beta (Aβ)–PET (11C‐Pittsburgh compound B [PiB]), tau‐PET (18F‐flortaucipir [FTP]), and plasma tau phosphorylated at threonine 217 (p‐tau217) correlate with Aβ plaques (A‐score), Braak tau neurofibrillary tangle (NFT) stage (B‐score), and neuritic plaques (C‐score), whereas plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and cognitive measures did not; although digital Clock Drawing Test (dCDT) latency features did, in an exploratory comparison. Correlations were stronger for Aβ‐PET DVR and Aβ‐PET EXT (than SUVR with/without PVC) and tau‐PET SUVR (composite reference and PVC). DISCUSSION These findings support the innovative use of imaging, plasma, and digital cognitive tools for detecting AD pathophysiology in a largely cognitively unimpaired population. Highlights Amyloid beta–positron emission tomography (Aβ‐PET), tau‐PET imaging, and plasma tau phosphorylated at threonine 217 (p‐tau217) correlate with ABC scores Correlations were larger for Aβ‐PET distribution volume ratio (DVR) and tau‐PET standardized uptake volume ratio (SUVR; composite reference, partial volume correction [PVC]) Digital Clock Drawing Test latency features correlate with A‐ and Cscores Standard cognitive measures mostly did not correlate with ABC scores Plasma glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) biomarkers did not correlate with ABC scores

IntroductionProcess evaluation provides insight into how interventions are delivered across varying contexts and why interventions work in some contexts and not in others. This manuscript outlines the protocol for a process evaluation embedded in a hybrid type 1 effectiveness-implementation randomised clinical trial of incremental-start haemodialysis (HD) versus conventional HD delivered to patients starting chronic dialysis (the TwoPlus Study). The trial will simultaneously assess the effectiveness of incremental-start HD in real-world settings and the implementation strategies needed to successfully integrate this intervention into routine practice. This manuscript describes the rationale and methods used to capture how incremental-start HD is implemented across settings and the factors influencing its implementation success or failure within this trial.Methods and analysisWe will use the Consolidated Framework for Implementation Research (CFIR) and the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) frameworks to inform process evaluation. Mixed methods include surveys conducted with treating providers (physicians) and dialysis personnel (nurses and dialysis administrators); semi-structured interviews with patient participants, caregivers of patient participants, treating providers (physicians and advanced practice practitioners), dialysis personnel (nurses, dieticians and social workers); and focus group meetings with study investigators and stakeholder partners. Data will be collected on the following implementation determinants: (a) organisational readiness to change, intervention acceptability and appropriateness; (b) inner setting characteristics underlying barriers and facilitators to the adoption of HD intervention at the enrollment centres; (c) external factors that mediate implementation; (d) adoption; (e) reach; (f) fidelity, to assess adherence to serial timed urine collection and HD treatment schedule; and (g) sustainability, to assess barriers and facilitators to maintaining intervention. Qualitative and quantitative data will be analysed iteratively and triangulated following a convergent parallel and pragmatic approach. Mixed methods analysis will use qualitative data to lend insight to quantitative findings. Process evaluation is important to understand factors influencing trial outcomes and identify potential contextual barriers and facilitators for the potential implementation of incremental-start HD into usual workflows in varied outpatient dialysis clinics and clinical practices. The process evaluation will help interpret and contextualise the trial clinical outcomes’ findings.Ethics and disseminationThe study protocol was approved by the Wake Forest University School of Medicine Institutional Review Board (IRB). Findings from this study will be disseminated through peer-reviewed journals and scientific conferences.Trial registration numberNCT05828823.