Active wetting of epithelial tissues

Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behavior of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between 2D epithelial monolayers and 3D spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phenomena. By combining an active polar fluid model with measurements of physical forces as a function of tissue size, contractility, cell-cell and cell-substrate adhesion, and substrate stiffness, we show that the wetting transition results from the competition between traction forces and contractile intercellular stresses. This competition defines a new intrinsic lengthscale that gives rise to a critical size for the wetting transition in tissues, a striking feature that has no counterpart in classical wetting. Finally, we show that active shape fluctuations are dynamically amplified during tissue dewetting. Overall, we conclude that tissue spreading constitutes a prominent example of active wetting --- a novel physical scenario that may explain morphological transitions during tissue morphogenesis and tumor progression

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain–behavior relationships after stroke

The goal of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well‐powered meta‐ and mega‐analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large‐scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided

Cognitive endpoints for therapy development for neuronopathic mucopolysaccharidoses: Results of a consensus procedure

The design and conduct of clinical studies to evaluate the effects of novel therapies on central nervous system manifestations in children with neuronopathic mucopolysaccharidoses is challenging. Owing to the rarity of these disorders, multinational studies are often needed to recruit enough patients to provide meaningful data and statistical power. This can make the consistent collection of reliable data across study sites difficult. To address these challenges, an International MPS Consensus Conference for Cognitive Endpoints was convened to discuss approaches for evaluating cognitive and adaptive function in patients with mucopolysaccharidoses. The goal was to develop a consensus on best practice for the design and conduct of clinical studies investigating novel therapies for these conditions, with particular focus on the most appropriate outcome measures for cognitive function and adaptive behavior. The outcomes from the consensus panel discussion are reported here

P-wave excited baryons from pion- and photo-induced hyperon production

We report evidence for $N(1710)P_{11}$, $N(1875)P_{11}$, $N(1900)P_{13}$, $\Delta(1600)P_{33}$, $\Delta(1910)P_{31}$, and $\Delta(1920)P_{33}$, and find indications that $N(1900)P_{13}$ might have a companion state at 1970\,MeV. The controversial $\Delta(1750)P_{31}$ is not seen. The evidence is derived from a study of data on pion- and photo-induced hyperon production, but other data are included as well. Most of the resonances reported here were found in the Karlsruhe-Helsinki (KH84) and the Carnegie-Mellon (CM) analyses but were challenged recently by the Data Analysis Center at GWU. Our analysis is constrained by the energy independent $\pi N$ scattering amplitudes from either KH84 or GWU. The two $\pi N$ amplitudes from KH84 or GWU, respectively, lead to slightly different $\pi N$ branching ratios of contributing resonances but the debated resonances are required in both series of fits.Comment: 22 pages, 28 figures. Some additional sets of data are adde

Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome

<p>Abstract</p> <p>Background</p> <p>Idiopathic membranous nephropathy (IMN) is one of the most common causes of primary nephrotic syndrome in adults. However, it is a relatively rare entity in the pediatric population and there is a paucity of data about the incidence, prognosis, and optimal treatment of IMN in children and adolescents. We conducted this study to evaluate pediatric patients with IMN in order to clarify the presentation, response to therapy, and clinical outcome.</p> <p>Methods</p> <p>A retrospective chart review was performed on patients identified with biopsy-proven IMN between 1988–2005. Patients with systemic lupus erythematosus or hepatitis-related lesions were excluded. The following data were tabulated: age, gender, ethnicity, presenting clinical and laboratory findings, proteinuria in a first morning urine specimen, estimated glomerular filtration rate (GFR_e), histopathology, type and duration of treatment, and clinical status at final evaluation.</p> <p>Results</p> <p>13 cases of IMN were identified out of 460 renal biopsies performed for evaluation of primary kidney disease during the study interval. Mean age was 9.6 ± 4.6, gender 6 M:7 F, ethnicity 8 W:2 B:3 H. At the initial visit hematuria was present in 9 patients, edema in 5, nephrotic-range proteinuria in 5, and hypertension in 3. Mean urinary protein:creatinine ratio 3.3 ± 2.5 and all patients had a normal GFR_e. Classic glomerular findings of IMN were seen in all renal specimens, with concomitant interstitial changes in 2 cases. Treatment included an angiotensin converting enzyme inhibitor or angiotensin receptor blocker in 11 cases. Most patients were also given immunosuppressive medications – prednisone in 10, a calcineurin inhibitor in 5, and mycophenolate mofetil or azathioprine in 3 patients. At the last follow-up, 42 ± 35 months after the diagnostic biopsy, 7 children were hypertensive and the urine protein:creatinine ratio was 2.3 ± 3.1. The mean GFR_ewas 127 ± 57 mL/min/m². Three patients had Chronic Kidney Disease Stage 3, all of whom were also hypertensive.</p> <p>Conclusion</p> <p>IMN is a rare but serious glomerulopathy in pediatrics. We estimate that it accounts for approximately 3% of renal biopsies. Long-term prognosis is guarded because approximately 50% of patients may have evidence of progressive kidney disease.</p

Radio emission from Supernova Remnants

The explosion of a supernova releases almost instantaneously about 10^51 ergs of mechanic energy, changing irreversibly the physical and chemical properties of large regions in the galaxies. The stellar ejecta, the nebula resulting from the powerful shock waves, and sometimes a compact stellar remnant, constitute a supernova remnant (SNR). They can radiate their energy across the whole electromagnetic spectrum, but the great majority are radio sources. Almost 70 years after the first detection of radio emission coming from a SNR, great progress has been achieved in the comprehension of their physical characteristics and evolution. We review the present knowledge of different aspects of radio remnants, focusing on sources of the Milky Way and the Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief overview of theoretical background, analyze morphology and polarization properties, and review and critical discuss different methods applied to determine the radio spectrum and distances. The consequences of the interaction between the SNR shocks and the surrounding medium are examined, including the question of whether SNRs can trigger the formation of new stars. Cases of multispectral comparison are presented. A section is devoted to reviewing recent results of radio SNRs in the Magellanic Clouds, with particular emphasis on the radio properties of SN 1987A, an ideal laboratory to investigate dynamical evolution of an SNR in near real time. The review concludes with a summary of issues on radio SNRs that deserve further study, and analyzing the prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London