Who Needs Good Neighbours?

Abstract: Due to the increasing spatial dispersion of social networks, the association between neighbor relationships and quality of life has become more uncertain. Our analysis used instrumental variable modelling to reduce bias associated with residual confounding and reverse causation, in order to provide a more reliable examination of the effect of interaction with neighbors on subjective well-being than previous work. While the frames of reference for individuals’ socializing may have shifted outside the neighborhood, our analysis provides robust evidence that interaction with neighbors still matters a great deal for subjective well-being. A further important question to ask is if neighboring does affect well-being, then are there certain groups in society for whom contact with neighbors matters more? Our analysis suggests that there are, namely for those in a relationship, unemployed or retired. This means that while fostering contact with neighbors has the potential to significantly improve individual well-being, such policy efforts are likely to matter a good deal more in neighborhoods with relatively large numbers of geographically constrained social groups, such as the elderly and the unemployed. Key words: subjective well-being, neighborly interaction, social capita

Imbalance in the response of pre- and post-synaptic components to amyloidopathy

Alzheimer’s disease (AD)-associated synaptic dysfunction drives the progression of pathology from its earliest stages. Aβ species, both soluble and in plaque deposits, have been causally related to the progressive, structural and functional impairments observed in AD. It is, however, still unclear how Aβ plaques develop over time and how they progressively affect local synapse density and turnover. Here we observed, in a mouse model of AD, that Aβ plaques grow faster in the earlier stages of the disease and if their initial area is > 500 µm2; this may be due to deposition occurring in the cloud part of the plaque. In addition, synaptic turnover is higher in the presence of amyloid pathology and this is paralleled by a reduction in pre- but not post-synaptic densities. Plaque proximity does not appear to have an impact on synaptic dynamics. These observations indicate an imbalance in the response of the pre- and post-synaptic terminals and that therapeutics, alongside targeting the underlying pathology, need to address changes in synapse dynamics

Comparing biological markers of Alzheimer\u27s disease across blood fraction and platforms: Comparing apples to oranges

Introduction: This study investigated the comparability of potential Alzheimer\u27s disease (AD) biomarkers across blood fractions and assay platforms. Methods: Nonfasting serum and plasma samples from 300 participants (150 AD patients and 150 controls) were analyzed. Proteomic markers were obtained via electrochemiluminescence or Luminex technology. Comparisons were conducted via Pearson correlations. The relative importance of proteins within an AD diagnostic profile was examined using random forest importance plots. Results: On the Meso Scale Discovery multiplex platform, 10 of the 21 markers shared \u3e50% of the variance across blood fractions (serum amyloid A R2 = 0.99, interleukin (IL)10 R2 = 0.95, fatty acid-binding protein (FABP) R2 = 0.94, I309 R2 = 0.94, IL-5 R2 = 0.94, IL-6 R2 = 0.94, eotaxin3 R2 = 0.91, IL-18 R2 = 0.87, soluble tumor necrosis factor receptor 1 R2 = 0.85, and pancreatic polypeptide R2 = 0.81). When examining protein concentrations across platforms, only five markers shared \u3e50% of the variance (beta 2 microglobulin R2 = 0.92, IL-18 R2 = 0.80, factor VII R2 = 0.78, CRP R2 = 0.74, and FABP R2 = 0.70). Discussion: The current findings highlight the importance of considering blood fractions and assay platforms when searching for AD relevant biomarkers

Matrix-Bound Nanovesicles: The Effects of Isolation Method upon Yield, Purity, and Function

Identification of matrix-bound nanovesicles (MBV) as ubiquitous components of the extracellular matrix (ECM) raises questions regarding their biologic functions and their potential theranostic application. Unlike liquid-phase extracellular vesicles (e.g., exosomes), MBV are tightly bound to the ECM, which makes their isolation and harvesting more challenging. The indiscriminate use of different methods to harvest MBV can alter or disrupt their structural and/or functional integrity. The objective of the present study was to compare the effect of various MBV harvesting methods upon yield, purity, and biologic activity. Combinations of four methods to solubilize the ECM (collagenase [COL], liberase [LIB], or proteinase K [PK] and nonenzymatic elution with potassium chloride) and four isolation methods (ultracentrifugation, ultrafiltration [UF], density barrier, and size exclusion chromatography [SEC]) were used to isolate MBV from urinary bladder-derived ECM. All combinations of solubilization and isolation methods allowed for the harvesting of MBV, however, distinct differences were noted. The highest yield, purity, cellular uptake, and biologic activity were seen with MBV isolated by a combination of liberase or collagenase followed by SEC. The combination of proteinase K and UF was shown to have detrimental effects on bioactivity. The results show the importance of selecting appropriate MBV harvesting methods for the characterization and evaluation of MBV and for analysis of their potential theranostic application

The detection rate of early UV emission from supernovae: A dedicated GALEX/PTF survey and calibrated theoretical estimates

The radius and surface composition of an exploding massive star,as well as the explosion energy per unit mass, can be measured using early UV observations of core collapse supernovae (SNe). We present the first results from a simultaneous GALEX/PTF search for early UV emission from SNe. Six Type II SNe and one Type II superluminous SN (SLSN-II) are clearly detected in the GALEX NUV data. We compare our detection rate with theoretical estimates based on early, shock-cooling UV light curves calculated from models that fit existing Swift and GALEX observations well, combined with volumetric SN rates. We find that our observations are in good agreement with calculated rates assuming that red supergiants (RSGs) explode with fiducial radii of 500 solar, explosion energies of 10^51 erg, and ejecta masses of 10 solar masses. Exploding blue supergiants and Wolf-Rayet stars are poorly constrained. We describe how such observations can be used to derive the progenitor radius, surface composition and explosion energy per unit mass of such SN events, and we demonstrate why UV observations are critical for such measurements. We use the fiducial RSG parameters to estimate the detection rate of SNe during the shock-cooling phase (<1d after explosion) for several ground-based surveys (PTF, ZTF, and LSST). We show that the proposed wide-field UV explorer ULTRASAT mission, is expected to find >100 SNe per year (~0.5 SN per deg^2), independent of host galaxy extinction, down to an NUV detection limit of 21.5 mag AB. Our pilot GALEX/PTF project thus convincingly demonstrates that a dedicated, systematic SN survey at the NUV band is a compelling method to study how massive stars end their life.Comment: See additional information including animations on http://www.weizmann.ac.il/astrophysics/ultrasa

The hemodynamic tolerability and feasibility of sustained low efficiency dialysis in the management of critically ill patients with acute kidney injury

<p>Abstract</p> <p>Background</p> <p>Minimization of hemodynamic instability during renal replacement therapy (RRT) in patients with acute kidney injury (AKI) is often challenging. We examined the relative hemodynamic tolerability of sustained low efficiency dialysis (SLED) and continuous renal replacement therapy (CRRT) in critically ill patients with AKI. We also compared the feasibility of SLED administration with that of CRRT and intermittent hemodialysis (IHD).</p> <p>Methods</p> <p>This cohort study encompassed four critical care units within a single university-affiliated medical centre. 77 consecutive critically ill patients with AKI who were treated with CRRT (n = 30), SLED (n = 13) or IHD (n = 34) and completed at least two RRT sessions were included in the study. Overall, 223 RRT sessions were analyzed. Hemodynamic instability during a given session was defined as the composite of a > 20% reduction in mean arterial pressure or any escalation in pressor requirements. Treatment feasibility was evaluated based on the fraction of the prescribed therapy time that was delivered. An interrupted session was designated if < 90% of the prescribed time was administered. Generalized estimating equations were used to compare the hemodynamic tolerability of SLED vs CRRT while accounting for within-patient clustering of repeated sessions and key confounders.</p> <p>Results</p> <p>Hemodynamic instability occurred during 22 (56.4%) SLED and 43 (50.0%) CRRT sessions (p = 0.51). In a multivariable analysis that accounted for clustering of multiple sessions within the same patient, the odds ratio for hemodynamic instability with SLED was 1.20 (95% CI 0.58-2.47), as compared to CRRT. Session interruption occurred in 16 (16.3), 30 (34.9) and 11 (28.2) of IHD, CRRT and SLED therapies, respectively.</p> <p>Conclusions</p> <p>In critically ill patients with AKI, the administration of SLED is feasible and provides comparable hemodynamic control to CRRT.</p

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

The Zwicky Transient Facility Census of the Local Universe. I. Systematic Search for Calcium-rich Gap Transients Reveals Three Related Spectroscopic Subclasses

Using the Zwicky Transient Facility alert stream, we are conducting a large spectroscopic campaign to construct a complete, volume-limited sample of transients brighter than 20 mag, and coincident within 100" of galaxies in the Census of the Local Universe catalog. We describe the experiment design and spectroscopic completeness from the first 16 months of operations, which have classified 754 supernovae. We present results from a systematic search for calcium-rich gap transients in the sample of 22 low-luminosity (peak absolute magnitude M > −17), hydrogen-poor events found in the experiment. We report the detection of eight new events, and constrain their volumetric rate to ≳ 15% ± 5% of the SN Ia rate. Combining this sample with 10 previously known events, we find a likely continuum of spectroscopic properties ranging from events with SN Ia–like features (Ca-Ia objects) to those with SN Ib/c–like features (Ca-Ib/c objects) at peak light. Within the Ca-Ib/c events, we find two populations distinguished by their red (g − r ≈ 1.5 mag) or green (g - r ≈ 0.5 mag) colors at the r-band peak, wherein redder events show strong line blanketing features and slower light curves (similar to Ca-Ia objects), weaker He lines, and lower [Ca ii]/[O i] in the nebular phase. We find that all together the spectroscopic continuum, volumetric rates, and striking old environments are consistent with the explosive burning of He shells on low-mass white dwarfs. We suggest that Ca-Ia and red Ca-Ib/c objects arise from the double detonation of He shells, while green Ca-Ib/c objects are consistent with low-efficiency burning scenarios like detonations in low-density shells or deflagrations