Dense active matter model of motion patterns in confluent cell monolayers

Epithelial cell monolayers show remarkable displacement and velocity correlations over distances of ten or more cell sizes that are reminiscent of supercooled liquids and active nematics. We show that many observed features can be described within the framework of dense active matter, and argue that persistent uncoordinated cell motility coupled to the collective elastic modes of the cell sheet is sufficient to produce swirl-like correlations. We obtain this result using both continuum active linear elasticity and a normal modes formalism, and validate analytical predictions with numerical simulations of two agent-based cell models, soft elastic particles and the self-propelled Voronoi model together with in-vitro experiments of confluent corneal epithelial cell sheets. Simulations and normal mode analysis perfectly match when tissue-level reorganisation occurs on times longer than the persistence time of cell motility. Our analytical model quantitatively matches measured velocity correlation functions over more than a decade with a single fitting parameter.Comment: updated version accepted for publication in Nat. Com

Barriers to adequate follow-up during adjuvant therapy may be important factors in the worse outcome for Black women after breast cancer treatment

<p>Abstract</p> <p>Introduction</p> <p>Black women appear to have worse outcome after diagnosis and treatment of breast cancer. It is still unclear if this is because Black race is more often associated with known negative prognostic indicators or if it is an independent prognostic factor. To study this, we analyzed a patient cohort from an urban university medical center where these women made up the majority of the patient population.</p> <p>Methods</p> <p>We used retrospective analysis of a prospectively collected database of breast cancer patients seen from May 1999 to June 2006. Time to recurrence and survival were analyzed using the Kaplan-Meier method, with statistical analysis by chi-square, log rank testing, and the Cox regression model.</p> <p>Results</p> <p>265 female patients were diagnosed with breast cancer during the time period. Fifty patients (19%) had pure DCIS and 215 patients (81%) had invasive disease. Racial and ethnic composition of the entire cohort was as follows: Black (N = 150, 56.6%), Hispanic (N = 83, 31.3%), Caucasian (N = 26, 9.8%), Asian (N = 4, 1.5%), and Arabic (N = 2, 0.8%). For patients with invasive disease, independent predictors of poor disease-free survival included tumor size, node-positivity, incompletion of adjuvant therapy, and Black race. Tumor size, node-positivity, and Black race were independently associated with disease-specific overall survival.</p> <p>Conclusion</p> <p>Worse outcome among Black women appears to be independent of the usual predictors of survival. Further investigation is necessary to identify the cause of this survival disparity. Barriers to completion of standard post-operative treatment regimens may be especially important in this regard.</p

Hepatitis B and Hepatocellular Carcinoma Screening Among Asian Americans: Survey of Safety Net Healthcare Providers

BackgroundPhysician patterns of screening for hepatitis B (HBV) and hepatocellular carcinoma (HCC) among Asian Americans are not well described.AimsTo describe HBV and HCC screening practices among providers with large Asian American populations.MethodsProviders within San Francisco's safety net system were surveyed with respect to HBV and HCC screening practices as well as knowledge, attitudes, and barriers to HCC screening.ResultsAmong the 109 respondents (response rate = 72%), 62% were aged &gt;40, 65% female, 24% Asian, 87% primary care providers, and 48% had &gt;25% Asian patients. Only 76% had screened &gt;50% of their Asian patients for HBV and 43% had vaccinated &gt;50% of eligible patients against HBV. Although 94% knew Asians were disproportionately affected by HCC, only 79% had screened for HCC in &gt;50% of their Asian patients with chronic hepatitis B (CHB). A majority believed that HCC screening in CHB reduces HCC mortality (70%) and is cost-effective (57%). The most common HCC screening modality was AFP with abdominal ultrasound every 6-12 months (63%). Factors associated with HBV screening were familiarity with AASLD guidelines (OR 6.4, 95% CI 1.3-30.1, p = 0.02) and having vaccinated &gt;50% of eligible patients against HBV (OR 2.2, 95% CI 1.1-4.5, p = 0.03). Factors associated with HCC screening using abdominal ultrasound every 6-12 months were having &gt;25% Asian patients (OR = 4.5, 95% CI 1.3-15.3, p = 0.02) and higher HCC knowledge score (OR = 1.9 per item, 95% CI 1.01-3.6, p = 0.045).ConclusionsHBV and HCC screening rates and HBV vaccination among Asians from physician report is suboptimal. HCC screening is associated with having more Asian patients and higher provider knowledge. Provider education is essential in increasing rates of HBV and HCC screening among Asian Americans

San Francisco Hep B Free: A Grassroots Community Coalition to Prevent Hepatitis B and Liver Cancer

Chronic hepatitis B is the leading cause of liver cancer and the largest health disparity between Asian/Pacific Islanders (APIs) and the general US population. The Hep B Free model was launched to eliminate hepatitis B infection by increasing hepatitis B awareness, testing, vaccination, and treatment among APIs by building a broad, community-wide coalition. The San Francisco Hep B Free campaign is a diverse public/private collaboration unifying the API community, health care system, policy makers, businesses, and the general public in San Francisco, California. Mass-media and grassroots messaging raised citywide awareness of hepatitis B and promoted use of the existing health care system for hepatitis B screening and follow-up. Coalition partners reported semi-annually on activities, resources utilized, and system changes instituted. From 2007 to 2009, over 150 organizations contributed approximately $1,000,000 in resources to the San Francisco Hep B Free campaign. 40 educational events reached 1,100 healthcare providers, and 50% of primary care physicians pledged to screen APIs routinely for hepatitis B. Community events and fairs reached over 200,000 members of the general public. Of 3,315 API clients tested at stand-alone screening sites created by the campaign, 6.5% were found to be chronically infected and referred to follow-up care. A grassroots coalition that develops strong partnerships with diverse organizations can use existing resources to successfully increase public and healthcare provider awareness about hepatitis B among APIs, promote routine hepatitis B testing and vaccination as part of standard primary care, and ensure access to treatment for chronically infected individuals

Characterization of Changes in Serum Anti-Glycan Antibodies in Crohn's Disease – a Longitudinal Analysis

INTRODUCTION: Anti-glycan antibodies are a promising tool for differential diagnosis and disease stratification of patients with Crohn's disease (CD). We longitudinally assessed level and status changes of anti-glycan antibodies over time in individual CD patients as well as determinants of this phenomenon. METHODS: 859 serum samples derived from a cohort of 253 inflammatory bowel disease (IBD) patients (207 CD, 46 ulcerative colitis (UC)) were tested for the presence of anti-laminarin (Anti-L), anti-chitin (Anti-C), anti-chitobioside (ACCA), anti-laminaribioside (ALCA), anti-mannobioside (AMCA) and anti-Saccharomyces cerevisiae (gASCA) antibodies by ELISA. All patients had at least two and up to eleven serum samples taken during the disease course. RESULTS: Median follow-up time for CD was 17.4 months (Interquartile range (IQR) 8.0, 31.6 months) and for UC 10.9 months (IQR 4.9, 21.0 months). In a subgroup of CD subjects marked changes in the overall immune response (quartile sum score) and levels of individual markers were observed over time. The marker status (positive versus negative) remained widely stable. Neither clinical phenotype nor NOD2 genotype was associated with the observed fluctuations. In a longitudinal analysis neither changes in disease activity nor CD behavior led to alterations in the levels of the glycan markers. The ability of the panel to discriminate CD from UC or its association with CD phenotypes remained stable during follow-up. In the serum of UC patients neither significant level nor status changes were observed. CONCLUSIONS: While the levels of anti-glycan antibodies fluctuate in a subgroup of CD patients the antibody status is widely stable over time

Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension

The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human–AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret, and critically appraise the design and risk of bias for a planned clinical trial

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Identification of Potential Therapeutic Drugs for Huntington's Disease using Caenorhabditis elegans

The prolonged time course of Huntington's disease (HD) neurodegeneration increases both the time and cost of testing potential therapeutic compounds in mammalian models. An alternative is to initially assess the efficacy of compounds in invertebrate models, reducing time of testing from months to days.We screened candidate therapeutic compounds that were identified previously in cell culture/animal studies in a C. elegans HD model and found that two FDA approved drugs, lithium chloride and mithramycin, independently and in combination suppressed HD neurotoxicity. Aging is a critical contributor to late onset neurodegenerative diseases. Using a genetic strategy and a novel assay, we demonstrate that lithium chloride and mithramycin remain neuroprotective independent of activity of the forkhead transcription factor DAF-16, which mediates the effects of the insulin-like signaling pathway on aging.These results suggest that pathways involved in polyglutamine-induced degeneration are distinct from specific aging pathways. The assays presented here will be useful for rapid and inexpensive testing of other potential HD drugs and elucidating pathways of drug action. Additionally, the neuroprotection conferred by lithium chloride and mithramycin suggests that these drugs may be useful for polyglutamine disease therapy

Post Eclosion Age Predicts the Prevalence of Midgut Trypanosome Infections in Glossina

The teneral phenomenon, as observed in Glossina sp., refers to the increased susceptibility of the fly to trypanosome infection when the first bloodmeal taken is trypanosome-infected. In recent years, the term teneral has gradually become synonymous with unfed, and thus fails to consider the age of the newly emerged fly at the time the first bloodmeal is taken. Furthermore, conflicting evidence exists of the effect of the age of the teneral fly post eclosion when it is given the infected first bloodmeal in determining the infection prevalence. This study demonstrates that it is not the feeding history of the fly but rather the age (hours after eclosion of the fly from the puparium) of the fly when it takes the first (infective) bloodmeal that determines the level of fly susceptibility to trypanosome infection. We examine this phenomenon in male and female flies from two distinct tsetse clades (Glossina morsitans morsitans and Glossina palpalis palpalis) infected with two salivarian trypanosome species, Trypanosoma (Trypanozoon) brucei brucei and Trypanosoma (Nannomonas) congolense using Fisher's exact test to examine differences in infection rates. Teneral tsetse aged less than 24 hours post-eclosion (h.p.e.) are twice as susceptible to trypanosome infection as flies aged 48 h.p.e. This trend is conserved across sex, vector clade and parasite species. The life cycle stage of the parasite fed to the fly (mammalian versus insect form trypanosomes) does not alter this age-related bias in infection. Reducing the numbers of parasites fed to 48 h.p.e., but not to 24 h.p.e. flies, increases teneral refractoriness. The importance of this phenomenon in disease biology in the field as well as the necessity of employing flies of consistent age in laboratory-based infection studies is discussed

Human T-lymphotropic virus type 1 (HTLV-1) prevalence and quantitative detection of DNA proviral load in individuals with indeterminate/positive serological results

BACKGROUND: HTLV-1 infection is currently restricted to endemic areas. To define the prevalence of HTLV-1 infection in patients living in Italy, we first carried out a retrospective serological analysis in a group of people originating from African countries referred to our hospital from January 2003 to February 2005. We subsequently applied a real time PCR on peripheral blood mononuclear cells from subjects with positive or indeterminate serological results. METHODS: All the sera were first analysed by serological methods (ELISA and/or Western Blotting) and then the peripheral blood mononuclear cells from subjects with positive or inconclusive serological results were analyzed for the presence of proviral DNA by a sensitive SYBR Green real time PCR. In addition, twenty HTLV-I ELISA negative samples were assayed by real time PCR approach as negative controls. RESULTS: Serological results disclosed serum reactivity by ELISA (absorbance values equal or greater than the cut-off value) in 9 out of 3408 individuals attending the Sexually Transmitted Diseases Clinic and/or Oncology Department, and 2 out 534 blood donors enrolled as a control population. Irrespective of positive or inconclusive serological results, all these subjects were analyzed for the presence of proviral DNA in peripheral blood mononuclear cells by SYBR real time PCR. A clear-cut positive result for the presence of HTLV-1 DNA was obtained in two subjects from endemic areas. CONCLUSION: SYBR real time PCR cut short inconclusive serological results. This rapid and inexpensive assay showed an excellent linear dynamic range, specificity and reproducibility readily revealing and quantifying the presence of virus in PBMCs. Our results highlight the need to monitor the presence of HTLV-1 in countries which have seen a large influx of immigrants in recent years. Epidemiological surveillance and correct diagnosis are recommended to verify the prevalence and incidence of a new undesirable phenomenon