Distributed Domain Propagation

This is the final version. Available on open access from the publisher via the DOI in this record16th International Symposium on Experimental Algorithms (SEA 2017), 21-23 June 2017, London, UKPortfolio parallelization is an approach that runs several solver instances in parallel and terminates when one of them succeeds in solving the problem. Despite it’s simplicity portfolio parallelization has been shown to perform well for modern mixed-integer programming (MIP) and boolean satisfiability problem (SAT) solvers. Domain propagation has also been shown to be a simple technique in modern MIP and SAT solvers that effectively finds additional domain reductions after a variables domain has been reduced. This paper investigates the impact of distributed domain propagation in modern MIP solvers that employ portfolio parallelization. Computational experiments were conducted for two implementations of this parallelization approach. While both share global variable bounds and solutions they communicate differently. In one implementation the communication is performed only at designated points in the solving process and in the other it is performed completely asynchronously. Computational experiments show a positive performance impact of communicating global variable bounds and provide valuable insights in communication strategies for parallel solvers.German Federal Ministry of Education and Researc

Gene expression profiling and silencing reveal that monolignol biosynthesis plays a critical role in penetration defence in wheat against powdery mildew invasion

Cell wall apposition (CWA) formation is one of the first lines of defence used by plants to halt invading fungi such as powdery mildew. Lignin is a complex polymer of hydroxylated and methoxylated phenylpropane units (monolignols) and lignification renders the cell wall more resistant to pathogen attack. The role of monolignol biosynthesis in CWA-mediated defence against powdery mildew penetration into cereals is demonstrated here using RNA interference (RNAi)-mediated gene silencing and enzyme-specific inhibitors. Thirteen cDNAs representing eight genes involved in monolignol biosynthesis were cloned from an expression sequence tag (EST) library derived from the epidermis of diploid wheat (Triticum monococcum) infected with Blumeria graminis f. sp. tritici (Bgt). Differential expression patterns were found for these genes in susceptible and resistant plants after infection. Transcripts of phenylalanine ammonia lyase (PAL), caffeic acid O-methyltransferase (CAOMT), ferulic acid hydroxylase (FAH), caffeoyl-CoA O-methyltransferase (CCoAMT), and cinnamyl alcohol dehydrogenase (CAD) were accumulated, particularly in the epidermis. RNAi-mediated transient gene silencing in the epidermis led to a higher penetration efficiency of Bgt than in the controls. Gene silencing also compromised penetration resistance to varying degrees with different genes against an inappropriate pathogen, B. graminis f. sp. hordei (Bgh). Co-silencing led to greater penetration of Bgt or Bgh than when the genes were silenced separately. Fluorescence emission spectra analyses revealed that gene silencing hampered host autofluorescence response at fungal contact sites. These results illustrate that monolignol biosynthesis is critically important for host defence against both appropriate and inappropriate pathogen invasion in wheat

A novel isolator-based system promotes viability of human embryos during laboratory processing

In vitro fertilisation (IVF) and related technologies are arguably the most challenging of all cell culture applications. The starting material is a single cell from which one aims to produce an embryo capable of establishing a pregnancy eventually leading to a live birth. Laboratory processing during IVF treatment requires open manipulations of gametes and embryos, which typically involves exposure to ambient conditions. To reduce the risk of cellular stress, we have developed a totally enclosed system of interlinked isolator-based workstations designed to maintain oocytes and embryos in a physiological environment throughout the IVF process. Comparison of clinical and laboratory data before and after the introduction of the new system revealed that significantly more embryos developed to the blastocyst stage in the enclosed isolator-based system compared with conventional open-fronted laminar flow hoods. Moreover, blastocysts produced in the isolator-based system contained significantly more cells and their development was accelerated. Consistent with this, the introduction of the enclosed system was accompanied by a significant increase in the clinical pregnancy rate and in the proportion of embryos implanting following transfer to the uterus. The data indicate that protection from ambient conditions promotes improved development of human embryos. Importantly, we found that it was entirely feasible to conduct all IVF-related procedures in the isolator-based workstations

Beta-Catenin Phosphorylated at Threonine 120 Antagonizes Generation of Active Beta-Catenin by Spatial Localization in trans-Golgi Network

The stability and subcellular localization of beta-catenin, a protein that plays a major role in cell adhesion and proliferation, is tightly regulated by multiple signaling pathways. While aberrant activation of beta-catenin signaling has been implicated in cancers, the biochemical identity of transcriptionally active beta-catenin (ABC), commonly known as unphosphorylated serine 37 (S37) and threonine 41 (T41) β-catenin, remains elusive. Our current study demonstrates that ABC transcriptional activity is influenced by phosphorylation of T120 by Protein Kinase D1 (PKD1). Whereas the nuclear β-catenin from PKD1-low prostate cancer cell line C4-2 is unphosphorylated S37/T41/T120 with high transcription activity, the nuclear β-catenin from PKD1-overexpressing C4-2 cells is highly phosphorylated at T120, S37 and T41 with low transcription activity, implying that accumulation of nuclear β-catenin alone cannot be simply used as a read-out for Wnt activation. In human normal prostate tissue, the phosphorylated T120 β-catenin is mainly localized to the trans-Golgi network (TGN, 22/30, 73%), and this pattern is significantly altered in prostate cancer (14/197, 7.1%), which is consistent with known down regulation of PKD1 in prostate cancer. These in vitro and in vivo data unveil a previously unrecognized post-translational modification of ABC through T120 phosphorylation by PKD1, which alters subcellular localization and transcriptional activity of β-catenin. Our results support the view that β-catenin signaling activity is regulated by spatial compartmentation and post-translational modifications and protein level of β-catenin alone is insufficient to count signaling activity

C. albicans Colonization of Human Mucosal Surfaces

Background: Candida albicans is a low level commensal organism in normal human populations with the continuous potential to expand and cause a spectrum of clinical conditions. Methodology/Principal Findings: Using ex vivo human organ cultures and populations of primary human cells, we have developed several related experimental systems to examine early-stage interactions between C. albicans and mucosal surfaces. Experiments have been conducted both with exogenously added C. albicans and with overtly normal human mucosal surfaces supporting pre-existing infections with natural isolates of Candida. Under different culture conditions, we have demonstrated the formation of C. albicans colonies on human target cells and filament formation, equivalent to tissue invasion. Conclusions/Significance: These organ culture systems provide a valuable new resource to examine the molecular and cellular basis for Candida colonization of human mucosal surfaces

The effects of compression gloves on hand symptoms and hand function in rheumatoid arthritis and hand osteoarthritis : a systematic review

Objective: to evaluate the effects of compression gloves in adults with rheumatoid arthritis and hand osteoarthritis. Data sources: Systematic review of randomized controlled trials identified from MEDLINE, CINAHL, AMED, PEDro, OT Seeker, The Cochrane Library, ISI Web of Knowledge, Science Direct and PubMed from their inceptions to January 2015. Review methods: Methodological quality of identified trials was evaluated using the PEDro scale by three independent assessors. Effects were summarized descriptively. Results: Four trials (n=8-24; total n=74), comparing night wear of full-length finger compression gloves with placebo gloves, were assessed. Three were of moderate (PEDro score 4-5) and one low (score 3) methodological quality. Effect sizes or standardized mean differences could not be calculated to compare trials due to poor data reporting. In rheumatoid arthritis, finger joint swelling was significantly reduced, but results for pain and stiffness were inconclusive and no differences in grip strength and dexterity were identified. One study reported similar effects in pain, stiffness and finger joint swelling from both compression and thermal placebo gloves. Only one study evaluated gloves in hand osteoarthritis (n=5) with no differences. Conclusions: All the trials identified were small with a high risk of Type I and II errors. Evidence for the effectiveness of compression gloves worn at night is inconclusive in rheumatoid arthritis and hand osteoarthritis

Improving appropriate polypharmacy for older people in primary care: selecting components of an evidence-based intervention to target prescribing and dispensing

Background The use of multiple medicines (polypharmacy) is increasingly common in older people. Ensuring that patients receive the most appropriate combinations of medications (appropriate polypharmacy) is a significant challenge. The quality of evidence to support the effectiveness of interventions to improve appropriate polypharmacy is low. Systematic identification of mediators of behaviour change, using the Theoretical Domains Framework (TDF), provides a theoretically robust evidence base to inform intervention design. This study aimed to (1) identify key theoretical domains that were perceived to influence the prescribing and dispensing of appropriate polypharmacy to older patients by general practitioners (GPs) and community pharmacists, and (2) map domains to associated behaviour change techniques (BCTs) to include as components of an intervention to improve appropriate polypharmacy in older people in primary care. Methods Semi-structured interviews were conducted with members of each healthcare professional (HCP) group using tailored topic guides based on TDF version 1 (12 domains). Questions covering each domain explored HCPs’ perceptions of barriers and facilitators to ensuring the prescribing and dispensing of appropriate polypharmacy to older people. Interviews were audio-recorded and transcribed verbatim. Data analysis involved the framework method and content analysis. Key domains were identified and mapped to BCTs based on established methods and discussion within the research team. Results Thirty HCPs were interviewed (15 GPs, 15 pharmacists). Eight key domains were identified, perceived to influence prescribing and dispensing of appropriate polypharmacy: ‘Skills’, ‘Beliefs about capabilities’, ‘Beliefs about consequences’, ‘Environmental context and resources’, ‘Memory, attention and decision processes’, ‘Social/professional role and identity’, ‘Social influences’ and ‘Behavioural regulation’. Following mapping, four BCTs were selected for inclusion in an intervention for GPs or pharmacists: ‘Action planning’, ‘Prompts/cues’, ‘Modelling or demonstrating of behaviour’ and ‘Salience of consequences’. An additional BCT (‘Social support or encouragement’) was selected for inclusion in a community pharmacy-based intervention in order to address barriers relating to interprofessional working that were encountered by pharmacists. Conclusions Selected BCTs will be operationalised in a theory-based intervention to improve appropriate polypharmacy for older people, to be delivered in GP practice and community pharmacy settings. Future research will involve development and feasibility testing of this intervention

A feasibility study of a theory-based intervention to improve appropriate polypharmacy for older people in primary care

Background: A general practitioner (GP)-targeted intervention aimed at improving the prescribing of appropriate polypharmacy for older people was previously developed using a systematic, theory-based approach based on the UK Medical Research Council’s complex intervention framework. The primary intervention component comprised a video demonstration of a GP prescribing appropriate polypharmacy during a consultation with an older patient. The video was delivered to GPs online and included feedback emphasising the positive outcomes of performing the behaviour. As a complementary intervention component, patients were invited to scheduled medication review consultations with GPs. This study aimed to test the feasibility of the intervention and study procedures (recruitment, data collection). Methods: GPs from two general practices were given access to the video, and reception staff scheduled consultations with older patients receiving polypharmacy (≥4 medicines). Primary feasibility study outcomes were the usability and acceptability of the intervention to GPs. Feedback was collected from GP and patient participants using structured questionnaires. Clinical data were also extracted from recruited patients’ medical records (baseline and 1 month post-consultation). The feasibility of applying validated assessment of prescribing appropriateness (STOPP/ START criteria, Medication Appropriateness Index) and medication regimen complexity (Medication Regimen Complexity Index) to these data was investigated. Data analysis was descriptive, providing an overview of participants’ feedback and clinical assessment findings. Results: Four GPs and ten patients were recruited across two practices. The intervention was considered usable and acceptable by GPs. Some reservations were expressed by GPs as to whether the video truly reflected resource and time pressures encountered in the general practice working environment. Patient feedback on the scheduled consultations was positive. Patients welcomed the opportunity to have their medications reviewed. Due to the short time to follow-up and a lack of detailed clinical information in patient records, it was not feasible to detect any prescribing changes or to apply the assessment tools to patients’ clinical data. Conclusion: The findings will help to further refine the intervention and study procedures (including time to follow-up) which will be tested in a randomised pilot study that will inform the design of a definitive trial to evaluate the intervention’s effectiveness

Vibration Response Imaging: evaluation of rater agreement in healthy subjects and subjects with pneumonia

<p>Abstract</p> <p>Background</p> <p>We evaluated pulmonologists variability in the interpretation of Vibration response imaging (VRI) obtained from healthy subjects and patients hospitalized for community acquired pneumonia.</p> <p>Methods</p> <p>The present is a prospective study conducted in a tertiary university hospital. Twenty healthy subjects and twenty three pneumonia cases were included in this study. Six pulmonologists blindly analyzed images of normal subjects and pneumonia cases and evaluated different aspects of VRI images related to the quality of data aquisition, synchronization of the progression of breath sound distribution and agreement between the maximal energy frame (MEF) of VRI (which is the maximal geographical area of lung vibrations produced at maximal inspiration) and chest radiography. For qualitative assessment of VRI images, the raters' evaluations were analyzed by degree of consistency and agreement.</p> <p>Results</p> <p>The average value for overall identical evaluations of twelve features of the VRI image evaluation, ranged from 87% to 95% per rater (94% to 97% in control cases and from 79% to 93% per rater in pneumonia cases). Inter-rater median (IQR) agreement was 91% (82-96). The level of agreement according to VRI feature evaluated was in most cases over 80%; intra-class correlation (ICC) obtained by using a model of subject/rater for the averaged features was overall 0.86 (0.92 in normal and 0.73 in pneumonia cases).</p> <p>Conclusions</p> <p>Our findings suggest good agreement in the interpretation of VRI data between different raters. In this respect, VRI might be helpful as a radiation free diagnostic tool for the management of pneumonia.</p