Effects of rising amyloidβ levels on hippocampal synaptic transmission, microglial response and cognition in APPSwe/PSEN1M146V transgenic mice

Background: Progression of Alzheimer's disease is thought initially to depend on rising amyloidβ and its synaptic interactions. Transgenic mice (TASTPM; APPSwe/PSEN1M146V) show altered synaptic transmission, compatible with increased physiological function of amyloidβ, before plaques are detected. Recently, the importance of microglia has become apparent in the human disease. Similarly, TASTPM show a close association of plaque load with upregulated microglial genes. Methods: CA1 Synaptic transmission and plasticity were investigated using in vitro electrophysiology. Migroglial relationship to plaques was examined with immunohistochemistry. Behaviour was assessed with a forced-alternation T-maze, open field, light/dark box and elevated plus maze. Findings: The most striking finding is the increase in microglial numbers in TASTPM, which, like synaptic changes, begins before plaques are detected. Further increases and a reactive phenotype occur later, concurrent with development of larger plaques. Long-term potentiation is initially enhanced at pre-plaque stages but decrements with the initial appearance of plaques. Finally, despite altered plasticity, TASTPM have little cognitive deficit, even with a heavy plaque load, although they show altered non-cognitive behaviours. Interpretation: The pre-plaque synaptic changes and microglial proliferation are presumably related to low, non-toxic amyloidβ levels in the general neuropil and not directly associated with plaques. However, as plaques grow, microglia proliferate further, clustering around plaques and becoming phagocytic. Like in humans, even when plaque load is heavy, without development of neurofibrillary tangles and neurodegeneration, these alterations do not result in cognitive deficits. Behaviours are seen that could be consistent with pre-diagnosis changes in the human condition

US SOLAS Science Report

The article of record may be found at https://doi.org/10.1575/1912/27821The Surface Ocean – Lower Atmosphere Study (SOLAS) (http://www.solas-int.org/) is an international research initiative focused on understanding the key biogeochemical-physical interactions and feedbacks between the ocean and atmosphere that are critical elements of climate and global biogeochemical cycles. Following the release of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016), the Ocean-Atmosphere Interaction Committee (OAIC) was formed as a subcommittee of the Ocean Carbon and Biogeochemistry (OCB) Scientific Steering Committee to coordinate US SOLAS efforts and activities, facilitate interactions among atmospheric and ocean scientists, and strengthen US contributions to international SOLAS. In October 2019, with support from OCB, the OAIC convened an open community workshop, Ocean-Atmosphere Interactions: Scoping directions for new research with the goal of fostering new collaborations and identifying knowledge gaps and high-priority science questions to formulate a US SOLAS Science Plan. Based on presentations and discussions at the workshop, the OAIC and workshop participants have developed this US SOLAS Science Plan. The first part of the workshop and this Science Plan were purposefully designed around the five themes of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016) to provide a common set of research priorities and ensure a more cohesive US contribution to international SOLAS.This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G).This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G)

US SOLAS Science Report

The Surface Ocean – Lower Atmosphere Study (SOLAS) (http://www.solas-int.org/) is an international research initiative focused on understanding the key biogeochemical-physical interactions and feedbacks between the ocean and atmosphere that are critical elements of climate and global biogeochemical cycles. Following the release of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016), the Ocean-Atmosphere Interaction Committee (OAIC) was formed as a subcommittee of the Ocean Carbon and Biogeochemistry (OCB) Scientific Steering Committee to coordinate US SOLAS efforts and activities, facilitate interactions among atmospheric and ocean scientists, and strengthen US contributions to international SOLAS. In October 2019, with support from OCB, the OAIC convened an open community workshop, Ocean-Atmosphere Interactions: Scoping directions for new research with the goal of fostering new collaborations and identifying knowledge gaps and high-priority science questions to formulate a US SOLAS Science Plan. Based on presentations and discussions at the workshop, the OAIC and workshop participants have developed this US SOLAS Science Plan. The first part of the workshop and this Science Plan were purposefully designed around the five themes of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016) to provide a common set of research priorities and ensure a more cohesive US contribution to international SOLAS.This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G)

Discrepancy between radiological and pathological size of renal masses

<p>Abstract</p> <p>Background</p> <p>Tumor size is a critical variable in staging for renal cell carcinoma. Clinicians rely on radiological estimates of pathological tumor size to guide patient counseling regarding prognosis, choice of treatment strategy and entry into clinical trials. If there is a discrepancy between radiological and pathological measurements of renal tumor size, this could have implications for clinical practice. Our study aimed to compare the radiological size of solid renal tumors on computed tomography (CT) to the pathological size in an Australian population.</p> <p>Methods</p> <p>We identified 157 patients in the Westmead Renal Tumor Database, for whom data was available for both radiological tumor size on CT and pathological tumor size. The paired Student's <it>t</it>-test was used to compare the mean radiological tumor size and the mean pathological tumor size. Statistical significance was defined as <it>P </it>< 0.05. We also identified all cases in which post-operative down-staging or up-staging occurred due to discrepancy between radiological and pathological tumor sizes. Additionally, we examined the relationship between Fuhrman grade and radiological tumor size and pathological T stage.</p> <p>Results</p> <p>Overall, the mean radiological tumor size on CT was 58.3 mm and the mean pathological size was 55.2 mm. On average, CT overestimated pathological size by 3.1 mm (<it>P </it>= 0.012). CT overestimated pathological tumor size in 92 (58.6%) patients, underestimated in 44 (28.0%) patients and equaled pathological size in 21 (31.4%) patients. Among the 122 patients with pT1 or pT2 tumors, there was a discrepancy between clinical and pathological staging in 35 (29%) patients. Of these, 21 (17%) patients were down-staged post-operatively and 14 (11.5%) were up-staged. Fuhrman grade correlated positively with radiological tumor size (<it>P </it>= 0.039) and pathological tumor stage (<it>P </it>= 0.003).</p> <p>Conclusions</p> <p>There was a statistically significant but small difference (3.1 mm) between mean radiological and mean pathological tumor size, but this is of uncertain clinical significance. For some patients, the difference leads to a discrepancy between clinical and pathological staging, which may have implications for pre-operative patient counseling regarding prognosis and management.</p

Ideas and Perspectives: A Strategic Assessment of Methane and Nitrous Oxide Measurements In the Marine Environment

In the current era of rapid climate change, accurate characterization of climate-relevant gas dynamics-namely production, consumption, and net emissions-is required for all biomes, especially those ecosystems most susceptible to the impact of change. Marine environments include regions that act as net sources or sinks for numerous climateactive trace gases including methane (CH4) and nitrous oxide (N2O). The temporal and spatial distributions of CH4 and N2O are controlled by the interaction of complex biogeochemical and physical processes. To evaluate and quantify how these mechanisms affect marine CH4 and N2O cycling requires a combination of traditional scientific disciplines including oceanography, microbiology, and numerical modeling. Fundamental to these efforts is ensuring that the datasets produced by independent scientists are comparable and interoperable. Equally critical is transparent communication within the research community about the technical improvements required to increase our collective understanding of marine CH4 and N2O. A workshop sponsored by Ocean Carbon and Biogeochemistry (OCB) was organized to enhance dialogue and collaborations pertaining to marine CH4 and N2O. Here, we summarize the outcomes from the workshop to describe the challenges and opportunities for near-future CH4 and N2O research in the marine environment

Multidimensional Signals and Analytic Flexibility: Estimating Degrees of Freedom in Human-Speech Analyses

Recent empirical studies have highlighted the large degree of analytic flexibility in data analysis that can lead to substantially different conclusions based on the same data set. Thus, researchers have expressed their concerns that these researcher degrees of freedom might facilitate bias and can lead to claims that do not stand the test of time. Even greater flexibility is to be expected in fields in which the primary data lend themselves to a variety of possible operationalizations. The multidimensional, temporally extended nature of speech constitutes an ideal testing ground for assessing the variability in analytic approaches, which derives not only from aspects of statistical modeling but also from decisions regarding the quantification of the measured behavior. In this study, we gave the same speech-production data set to 46 teams of researchers and asked them to answer the same research question, resulting in substantial variability in reported effect sizes and their interpretation. Using Bayesian meta-analytic tools, we further found little to no evidence that the observed variability can be explained by analysts’ prior beliefs, expertise, or the perceived quality of their analyses. In light of this idiosyncratic variability, we recommend that researchers more transparently share details of their analysis, strengthen the link between theoretical construct and quantitative system, and calibrate their (un)certainty in their conclusions

COPDGene® 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease

Background:Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. Methods:Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. Results:Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics. Conclusions:A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop