Three-Phase Co-assembly: In Situ Incorporation of Nanoparticles into Tunable, Highly Ordered, Porous Silica Films

We present a reproducible, one-pot colloidal co-assembly approach that results in large-scale, highly-ordered porous silica films with embedded, uniformly-distributed, accessible gold nanoparticles. The unique coloration of these inverse opal films combines iridescence with plasmonic effects. The coupled optical properties are easily tunable either by changing the concentration of added nanoparticles to the solution before assembly or by localized growth of the embedded Au nanoparticles upon exposure to tetrachloroauric acid solution, after colloidal template removal. The presence of the selectively absorbing particles furthermore enhances the hue and saturation of the inverse opals color by suppressing incoherent diffuse scattering. The composition and optical properties of these films are demonstrated to be locally tunable using selective functionalization of the doped opals.Chemistry and Chemical Biolog

Bioinspired self-repairing slippery surfaces with pressure-stable omniphobicity

Creating a robust synthetic surface that repels various liquids would have broad technological implications for areas ranging from biomedical devices and fuel transport to architecture but has proved extremely challenging. Inspirations from natural nonwetting structures particularly the leaves of the lotus, have led to the development of liquid-repellent microtextured surfaces that rely on the formation of a stable air–liquid interface. Despite over a decade of intense research, these surfaces are, however, still plagued with problems that restrict their practical applications: limited oleophobicity with high contact angle hysteresis, failure under pressure and upon physical damage inability to self-heal and high production cost. To address these challenges, here we report a strategy to create self-healing, slippery liquid-infused porous surface(s) (SLIPS) with exceptional liquid- and ice-repellency, pressure stability and enhanced optical transparency. Our approach—inspired by Nepenthes pitcher plants—is conceptually different from the lotus effect, because we use nano/microstructured substrates to lock in place the infused lubricating fluid. We define the requirements for which the lubricant forms a stable, defect-free and inert ‘slippery’ interface. This surface outperforms its natural counterparts and state-of-the-art synthetic liquid-repellent surfaces in its capability to repel various simple and complex liquids (water, hydrocarbons, crude oil and blood), maintain low contact angle hysteresis (<2.5°), quickly restore liquid-repellency after physical damage (within 0.1–1 s), resist ice adhesion, and function at high pressures (up to about 680 atm). We show that these properties are insensitive to the precise geometry of the underlying substrate, making our approach applicable to various inexpensive, low-surface-energy structured materials (such as porous Teflon membrane). We envision that these slippery surfaces will be useful in fluid handling and transportation, optical sensing, medicine, and as self-cleaning and anti-fouling materials operating in extreme environments.Engineering and Applied Science

Clinical pharmacist services within intensive care unit recovery clinics: An opinion of the critical care practice and research network of the American College of Clinical Pharmacy

Intensive care unit recovery clinics (ICU- RCs) have been proposed as a potential mechanism to address the multifaceted unmet needs of intensive care unit (ICU) survivors and caregivers. The needs of this population include, but are not limited to, medication optimization, addressing physical function and psychological needs, coordination of care, and other interventions that may help in improving patient recovery and reducing the rate of preventable readmissions. The objective of this opinion paper is to identify and describe clinical pharmacy services for the management of ICU survivors and their caregivers in an ICU- RC. The goals are to guide the establishment and development of clinical pharmacist involvement in ICU- RCs and to highlight ICU recovery research and educational opportunities. Recommendations provided in this paper are based on the following: a review of published data on clinical pharmacist involvement in the ICU- RCs; a consensus of clinical pharmacists who provide direct patient care to ICU survivors and caregivers; and a review of published guidelines and literature focusing on the management of ICU survivors and caregivers. These recommendations define areas of clinical pharmacist involvement in ICU- RCs. Consequently, clinical pharmacists can promote education on Post Intensive Care Syndrome and Post Intensive Care Syndrome- Family; improve medication adherence; facilitate appropriate referrals to primary care providers and specialists; ensure comprehensive medication management and medication reconciliation; provide assessment of inappropriate and appropriate medications after hospitalization; address adverse drug events, medication errors, and drug interactions; promote preventive measures; and facilitate medication acquisition with the goal of improving patient outcomes and reducing health care system costs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163579/2/jac51311.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163579/1/jac51311_am.pd

Galactic star formation and accretion histories from matching galaxies to dark matter haloes

We present a new statistical method to determine the relationship between the stellar masses of galaxies and the masses of their host dark matter haloes over the entire cosmic history from z~4 to the present. This multi-epoch abundance matching (MEAM) model self-consistently takes into account that satellite galaxies first become satellites at times earlier than they are observed. We employ a redshift-dependent parameterization of the stellar-to-halo mass relation to populate haloes and subhaloes in the Millennium simulations with galaxies, requiring that the observed stellar mass functions at several redshifts be reproduced simultaneously. Using merger trees extracted from the dark matter simulations in combination with MEAM, we predict the average assembly histories of galaxies, separating into star formation within the galaxies (in-situ) and accretion of stars (ex-situ). The peak star formation efficiency decreases with redshift from 23% at z=0 to 9% at z=4 while the corresponding halo mass increases from 10^11.8M\odot to 10^12.5M\odot. The star formation rate of central galaxies peaks at a redshift which depends on halo mass; for massive haloes this peak is at early cosmic times while for low-mass galaxies the peak has not been reached yet. In haloes similar to that of the Milky-Way about half of the central stellar mass is assembled after z=0.7. In low-mass haloes, the accretion of satellites contributes little to the assembly of their central galaxies, while in massive haloes more than half of the central stellar mass is formed ex-situ with significant accretion of satellites at z<2. We find that our method implies a cosmic star formation history and an evolution of specific star formation rates which are consistent with those inferred directly. We present convenient fitting functions for stellar masses, star formation rates, and accretion rates as functions of halo mass and redshift.Comment: 20 pages, 12 figures, 1 table, submitted to MNRA

Heterozygosity for Pten Promotes Tumorigenesis in a Mouse Model of Medulloblastoma

BACKGROUND: Recent publications have described an important role for cross talk between PI-3 kinase and sonic hedgehog signaling pathways in the pathogenesis of medulloblastoma. METHODOLOGY/PRINCIPAL FINDINGS: We crossed mice with constitutive activation of Smoothened, SmoA1, with Pten deficient mice. Both constitutive and conditional Pten deficiency doubled the incidence of mice with symptoms of medulloblastoma and resulted in decreased survival. Analysis revealed a clear separation of gene signatures, with up-regulation of genes in the PI-3 kinase signaling pathway, including downstream activation of angiogenesis in SmoA1+/-; Pten +/- medulloblastomas. Western blotting and immunohistochemistry confirmed reduced or absent Pten, Akt activation, and increased angiogenesis in Pten deficient tumors. Down-regulated genes included genes in the sonic hedgehog pathway and tumor suppressor genes. SmoA1+/-; Pten +/+ medulloblastomas appeared classic in histology with increased proliferation and diffuse staining for apoptosis. In contrast, Pten deficient tumors exhibited extensive nodularity with neuronal differentiation separated by focal areas of intense staining for proliferation and virtually absent apoptosis. Examination of human medulloblastomas revealed low to absent PTEN expression in over half of the tumors. Kaplan-Meier analysis confirmed worse overall survival in patients whose tumor exhibited low to absent PTEN expression. CONCLUSIONS/SIGNIFICANCE: This suggests that PTEN expression is a marker of favorable prognosis and mouse models with activation of PI-3 kinase pathways may be important tools for preclinical evaluation of promising agents for the treatment of medulloblastoma

Large subglacial source of mercury from the southwestern margin of the Greenland Ice Sheet

The Greenland Ice Sheet is currently not accounted for in Arctic mercury budgets, despite large and increasing annual runoff to the ocean and the socio-economic concerns of high mercury levels in Arctic organisms. Here we present concentrations of mercury in meltwaters from three glacial catchments on the southwestern margin of the Greenland Ice Sheet and evaluate the export of mercury to downstream fjords based on samples collected during summer ablation seasons. We show that concentrations of dissolved mercury are among the highest recorded in natural waters and mercury yields from these glacial catchments (521–3,300 mmol km−2 year−1) are two orders of magnitude higher than from Arctic rivers (4–20 mmol km−2 year−1). Fluxes of dissolved mercury from the southwestern region of Greenland are estimated to be globally significant (15.4–212 kmol year−1), accounting for about 10% of the estimated global riverine flux, and include export of bioaccumulating methylmercury (0.31–1.97 kmol year−1). High dissolved mercury concentrations (~20 pM inorganic mercury and ~2 pM methylmercury) were found to persist across salinity gradients of fjords. Mean particulate mercury concentrations were among the highest recorded in the literature (~51,000 pM), and dissolved mercury concentrations in runoff exceed reported surface snow and ice values. These results suggest a geological source of mercury at the ice sheet bed. The high concentrations of mercury and its large export to the downstream fjords have important implications for Arctic ecosystems, highlighting an urgent need to better understand mercury dynamics in ice sheet runoff under global warming

The ENIGMA-Epilepsy working group: Mapping disease from large data sets

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller‐scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well‐established by the ENIGMA Consortium, ENIGMA‐Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event‐based modeling analysis. We explore age of onset‐ and duration‐related features, as well as phenomena‐specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA‐Epilepsy

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice