Cognitively Normal Women With Alzheimer’s Disease Proteinopathy Show Relative Preservation of Memory but Not of Hippocampal Volume

Background: We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes. Methods: We assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer’s disease (AD) proteinopathy (CSF Aß/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes. Results: Amyloid-positive (Aβ/P-tau+) CN women (women with preclinical AD) showed memory equivalent to amyloid-negative (Aβ/P-tau−) CN women. In contrast, Aβ/P-tau+ CN men (men with preclinical AD) showed poorer memory than Aβ/P-tau− CN men. Symptomatic groups showed no sex differences in effect of AD proteinopathy on memory. There was no interactive effect of sex, diagnosis, and Aβ/P-tau on other measures of cognition or on hippocampal volume. Conclusions: CN women show relatively preserved verbal memory, but not general cognitive reserve or preserved hippocampal volume in the presence of Aβ/P-tau+. Results have implications for diagnosing AD in women, and for clinical trials

Closing the compliance gap in marine protected areas with human behavioural sciences

Advocates, practitioners and policy-makers continue to use and advocate for marine protected areas (MPAs) to meet global ocean protection targets. Yet many of the worlds MPAs, and especially no-take MPAs, are plagued by poaching and ineffective governance. Using a global dataset on coral reefs as an example, we quantify the potential ecological gains of governing MPAs to increase compliance, which we call the ‘compliance gap’. Using ecological simulations based on model posteriors of joint Bayesian hierarchical models, we demonstrate how increased compliance in no-take MPAs could nearly double target fish biomass (91% increases in median fish biomass), and result in a 292% higher likelihood of encountering top predators. Achieving these gains and closing the compliance gap necessitates a substantial shift in approach and practice to go beyond optimizing enforcement, and towards governing for compliance. This will require engaging and integrating a broad suite of actors, principles, and practices across three key domains: (i)) harnessing social influence, (ii) integrating equity principles, and (iii) aligning incentives through market-based instruments. Empowering and shaping communication between actor groups (e.g., between fishers, practitioners, and policy-makers) using theoretically underpinned approaches from the behavioural sciences is one of the most essential, but often underserved aspects of governing MPAs. We therefore close by highlighting how this cross-cutting tool could be further integrated in governance to bolster high levels of compliance in MPAs

The K2 & TESS Synergy II: Revisiting 26 systems in the TESS Primary Mission

The legacy of NASA's K2 mission has provided hundreds of transiting exoplanets that can be revisited by new and future facilities for further characterization, with a particular focus on studying the atmospheres of these systems. However, the majority of K2-discovered exoplanets have typical uncertainties on future times of transit within the next decade of greater than four hours, making observations less practical for many upcoming facilities. Fortunately, NASA's Transiting exoplanet Survey Satellite (TESS) mission is reobserving most of the sky, providing the opportunity to update the ephemerides for $\sim$300 K2 systems. In the second paper of this series, we reanalyze 26 single-planet, K2-discovered systems that were observed in the TESS primary mission by globally fitting their K2 and TESS lightcurves (including extended mission data where available), along with any archival radial velocity measurements. As a result of the faintness of the K2 sample, 13 systems studied here do not have transits detectable by TESS. In those cases, we re-fit the K2 lightcurve and provide updated system parameters. For the 23 systems with $M_* \gtrsim 0.6 M_\odot$, we determine the host star parameters using a combination of Gaia parallaxes, Spectral Energy Distribution (SED) fits, and MESA Isochrones and Stellar Tracks (MIST) stellar evolution models. Given the expectation of future TESS extended missions, efforts like the K2 & TESS Synergy project will ensure the accessibility of transiting planets for future characterization while leading to a self-consistent catalog of stellar and planetary parameters for future population efforts.Comment: Accepted for publication in ApJ. 29 pages, 9 figures, 12 table

Higher-dose sitagliptin and the risk of congestive heart failure in older adults with CKD

Background and objectives Sitagliptin, a dipeptidylpeptidase-4 inhibitor, is commonlyprescribed to patientswith type 2 diabetes. As this drug is primarily eliminated by the kidney, a reduced dose is recommended for patients with CKD. Some evidence suggests that sitagliptin is associated with a higher risk of congestive heart failure, particularly at higher doses.Wecompare the 1-year risk of death or hospitalizationwith congestive heart failure in patients with CKD newly prescribed sitagliptin at \u3c50 versus ≤50 mg/d. Design, setting, participants, & measurements This population-based cohort study included older adults (\u3e66 years) with type 2 diabetes and an eGFR\u3c45 ml/min per 1.73 m2 (but not receiving dialysis) who were newly prescribed sitagliptin between 2010 and 2017 in Ontario, Canada. We used inverse probability of treatment weighting on the basis of propensity scores to balance baseline characteristics. The primary composite outcome was death or hospitalization with congestive heart failure. Secondary outcomes included hospitalization with pancreatitis or hypoglycemia, all-cause hospitalization, and glycemic control. Weighted hazard ratios were obtained using Cox proportional hazards regression, and 95%confidence intervalswere obtained using bootstrap variance estimators. Results Of 9215 patients, 6518 started sitagliptin at \u3e50 mg/d, and 2697 started sitagliptin at ≤50 mg/d. The 1-year risk of death or hospitalization with congestive heart failure did not differ significantly between groups (79 versus 126 events per 1000 person-years; weighted hazard ratio, 0.88; 95% confidence interval, 0.67 to 1.14); hospitalization with pancreatitis (weighted hazard ratio, 0.98; 95% confidence interval, 0.32 to 3.03) and hypoglycemia (weighted hazard ratio, 1.10; 95% confidence interval, 0.64 to 1.90) also did not differ significantly between groups. Patients starting sitagliptin at \u3e50 mg/d had lower mean glycated hemoglobin concentrations (weighted between-group difference, 20.12%; 95% confidence interval, 20.19 to 20.06) and a lower risk of allcause hospitalization (weighted hazard ratio, 0.81; 95% confidence interval, 0.66 to 0.98). Conclusions The risk of death or congestive heart failure was not higher in older adults with CKD starting sitagliptin at \u3e50 versus ≤50 mg/d

Oral polio vaccine response in the MAL-ED birth cohort study: Considerations for polio eradication strategies

Background: Immunization programs have leveraged decades of research to maximize oral polio vaccine (OPV) response. Moving toward global poliovirus eradication, the WHO recommended phased OPV-to-IPV replacement on schedules in 2012. Using the MAL-ED prospective birth cohort data, we evaluated the influence of early life exposures impacting OPV immunization by measuring OPV response for serotypes 1 and 3.Methods: Polio neutralizing antibody assays were conducted at 7 and 15 months of age for serotypes 1 and 3. Analyses were conducted on children receiving ≥3 OPV doses (n = 1449). History of vaccination, feeding patterns, physical growth, home environment, diarrhea, enteropathogen detection, and gut inflammation were examined as risk factors for non-response [Log2(titer) \u3c 3] and Log2(titer) by serotype using multivariate regression.Findings: Serotype 1 seroconversion was significantly higher than serotype 3 (96.6% vs. 89.6%, 15 months). Model results indicate serotypes 1 and 3 failure was minimized following four and six OPV doses, respectively; however, enteropathogen detection and poor socioeconomic conditions attenuated response in both serotypes. At three months of age, bacterial detection in stool reduced serotype 1 and 3 Log2 titers by 0.34 (95% CI 0.14–0.54) and 0.53 (95% CI 0.29–0.77), respectively, and increased odds of serotype 3 failure by 3.0 (95% CI 1.6–5.8). Our socioeconomic index, consisting of Water, Assets, Maternal education, and Income (WAMI), was associated with a 0.79 (95% CI 0.15–1.43) and 1.23 (95% CI 0.34–2.12) higher serotype 1 and 3 Log2 titer, respectively, and a 0.04 (95% CI 0.002–0.40) lower odds of serotype 3 failure. Introduction of solids, transferrin receptor, and underweight were differentially associated with serotype response. Other factors, including diarrheal frequency and breastfeeding practices, were not associated with OPV response.Interpretation: Under real-world conditions, improved vaccination coverage and socio-environmental conditions, and reducing early life bacterial exposures are key to improving OPV response and should inform polio eradication strategies

Effects of Impact and Target Parameters on the Results of a Kinetic Impactor: Predictions for the Double Asteroid Redirection Test (DART) Mission

The Double Asteroid Redirection Test (DART) spacecraft will impact into the asteroid Dimorphos on 2022 September 26 as a test of the kinetic impactor technique for planetary defense. The efficiency of the deflection following a kinetic impactor can be represented using the momentum enhancement factor, β, which is dependent on factors such as impact geometry and the specific target material properties. Currently, very little is known about Dimorphos and its material properties, which introduces uncertainty in the results of the deflection efficiency observables, including crater formation, ejecta distribution, and β. The DART Impact Modeling Working Group (IWG) is responsible for using impact simulations to better understand the results of the DART impact. Pre-impact simulation studies also provide considerable insight into how different properties and impact scenarios affect momentum enhancement following a kinetic impact. This insight provides a basis for predicting the effects of the DART impact and the first understanding of how to interpret results following the encounter. Following the DART impact, the knowledge gained from these studies will inform the initial simulations that will recreate the impact conditions, including providing estimates for potential material properties of Dimorphos and β resulting from DART’s impact. This paper summarizes, at a high level, what has been learned from the IWG simulations and experiments in preparation for the DART impact. While unknown, estimates for reasonable potential material properties of Dimorphos provide predictions for β of 1–5, depending on end-member cases in the strength regime

HD 219134 Revisited: Planet d Transit Upper Limit and Planet f Transit Nondetection with ASTERIA and TESS

HD 219134 is a K3V dwarf star with six reported radial-velocity discovered planets. The two innermost planets b and c show transits, raising the possibility of this system to be the nearest (6.53 pc), brightest (V = 5.57) example of a star with a compact multiple transiting planet system. Ground-based searches for transits of planets beyond b and c are not feasible because of the infrequent transits, long transit duration (~5 hr), shallow transit depths (<1%), and large transit time uncertainty (~half a day). We use the space-based telescopes the Arcsecond Space Telescope Enabling Research in Astrophysics (ASTERIA) and the Transiting Exoplanet Survey Satellite (TESS) to search for transits of planets f (P = 22.717 days and M sin i = 7.3 ± 0.04M_⊕) and d (P = 46.859 days and M sin i = 16.7 ± 0.64M_⊕). ASTERIA was a technology demonstration CubeSat with an opportunity for science in an extended program. ASTERIA observations of HD 219134 were designed to cover the 3σ transit windows for planets f and d via repeated visits over many months. While TESS has much higher sensitivity and more continuous time coverage than ASTERIA, only the HD 219134 f transit window fell within the TESS survey's observations. Our TESS photometric results definitively rule out planetary transits for HD 219134 f. We do not detect the Neptune-mass HD 219134 d transits and our ASTERIA data are sensitive to planets as small as 3.6 R_⊕. We provide TESS updated transit times and periods for HD 219134 b and c, which are designated TOI 1469.01 and 1469.02 respectively

Genomic and epigenetic evidence for oxytocin receptor deficiency in autism

<p>Abstract</p> <p>Background</p> <p>Autism comprises a spectrum of behavioral and cognitive disturbances of childhood development and is known to be highly heritable. Although numerous approaches have been used to identify genes implicated in the development of autism, less than 10% of autism cases have been attributed to single gene disorders.</p> <p>Methods</p> <p>We describe the use of high-resolution genome-wide tilepath microarrays and comparative genomic hybridization to identify copy number variants within 119 probands from multiplex autism families. We next carried out DNA methylation analysis by bisulfite sequencing in a proband and his family, expanding this analysis to methylation analysis of peripheral blood and temporal cortex DNA of autism cases and matched controls from independent datasets. We also assessed oxytocin receptor (OXTR) gene expression within the temporal cortex tissue by quantitative real-time polymerase chain reaction (PCR).</p> <p>Results</p> <p>Our analysis revealed a genomic deletion containing the oxytocin receptor gene, <it>OXTR </it>(MIM accession no.: 167055), previously implicated in autism, was present in an autism proband and his mother who exhibits symptoms of obsessive-compulsive disorder. The proband's affected sibling did not harbor this deletion but instead may exhibit epigenetic misregulation of this gene through aberrant gene silencing by DNA methylation. Further DNA methylation analysis of the CpG island known to regulate <it>OXTR </it>expression identified several CpG dinucleotides that show independent statistically significant increases in the DNA methylation status in the peripheral blood cells and temporal cortex in independent datasets of individuals with autism as compared to control samples. Associated with the increase in methylation of these CpG dinucleotides is our finding that <it>OXTR </it>mRNA showed decreased expression in the temporal cortex tissue of autism cases matched for age and sex compared to controls.</p> <p>Conclusion</p> <p>Together, these data provide further evidence for the role of OXTR and the oxytocin signaling pathway in the etiology of autism and, for the first time, implicate the epigenetic regulation of <it>OXTR </it>in the development of the disorder.</p> <p>See the related commentary by Gurrieri and Neri: <url>http://www.biomedcentral.com/1741-7015/7/63</url></p

Gaussian mixture model classification of odontocetes in the Southern California Bight and the Gulf of California

A method for the automatic classification of free-ranging delphinid vocalizations is presented. The vocalizations of short-beaked and long-beaked commo

The khmer software package: enabling efficient nucleotide sequence analysis [version 1; referees: 2 approved, 1 approved with reservations]

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/