34 research outputs found
Researching effective approaches to cleaning in hospitals: protocol of the REACH study, a multi-site stepped-wedge randomised trial
BackgroundThe Researching Effective Approaches to Cleaning in Hospitals (REACH) study will generate evidence about the effectiveness and cost-effectiveness of a novel cleaning initiative that aims to improve the environmental cleanliness of hospitals. The initiative is an environmental cleaning bundle, with five interdependent, evidence-based components (training, technique, product, audit and communication) implemented with environmental services staff to enhance hospital cleaning practices.Methods/designThe REACH study will use a stepped-wedge randomised controlled design to test the study intervention, an environmental cleaning bundle, in 11 Australian hospitals. All trial hospitals will receive the intervention and act as their own control, with analysis undertaken of the change within each hospital based on data collected in the control and intervention periods. Each site will be randomised to one of the 11 intervention timings with staggered commencement dates in 2016 and an intervention period between 20 and 50 weeks. All sites complete the trial at the same time in 2017. The inclusion criteria allow for a purposive sample of both public and private hospitals that have higher-risk patient populations for healthcare-associated infections (HAIs). The primary outcome (objective one) is the monthly number of Staphylococcus aureus bacteraemias (SABs), Clostridium difficile infections (CDIs) and vancomycin resistant enterococci (VRE) infections, per 10,000 bed days. Secondary outcomes for objective one include the thoroughness of hospital cleaning assessed using fluorescent marker technology, the bio-burden of frequent touch surfaces post cleaning and changes in staff knowledge and attitudes about environmental cleaning. A cost-effectiveness analysis will determine the second key outcome (objective two): the incremental cost-effectiveness ratio from implementation of the cleaning bundle.The study uses the integrated Promoting Action on Research Implementation in Health Services (iPARIHS) framework to support the tailored implementation of the environmental cleaning bundle in each hospital.DiscussionEvidence from the REACH trial will contribute to future policy and practice guidelines about hospital environmental cleaning. It will be used by healthcare leaders and clinicians to inform decision-making and implementation of best-practice infection prevention strategies to reduce HAIs in hospitals
Magnetic Fields toward Ophiuchus-B Derived from SCUBA-2 Polarization Measurements
We present the results of dust emission polarization measurements of Ophiuchus-B (Oph-B) carried out using the Submillimetre Common-User Bolometer Array 2 (SCUBA-2) camera with its associated polarimeter (POL-2) on the James Clerk Maxwell Telescope in Hawaii. This work is part of the B-fields in Star-forming Region Observations survey initiated to understand the role of magnetic fields in star formation for nearby star-forming molecular clouds. We present a first look at the geometry and strength of magnetic fields in Oph-B. The field geometry is traced over ~0.2 pc, with clear detection of both of the sub-clumps of Oph-B. The field pattern appears significantly disordered in sub-clump Oph-B1. The field geometry in Oph-B2 is more ordered, with a tendency to be along the major axis of the clump, parallel to the filamentary structure within which it lies. The degree of polarization decreases systematically toward the dense core material in the two sub-clumps. The field lines in the lower density material along the periphery are smoothly joined to the large-scale magnetic fields probed by NIR polarization observations. We estimated a magnetic field strength of 630 ± 410 μG in the Oph-B2 sub-clump using a Davis–Chandrasekhar–Fermi analysis. With this magnetic field strength, we find a mass-to-flux ratio λ = 1.6 ± 1.1, which suggests that the Oph-B2 clump is slightly magnetically supercritical
Robust estimation of bacterial cell count from optical density
Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Preventing infections through cleaner hospitals project
While many Australian hospitals have good infection control practices, research about the role cleaning in the hospital environment plays in preventing infections is limited
Neuropsychological findings from older premutation carrier males and their noncarrier siblings from families with fragile X syndrome.
Maternal age and risk for trisomy 21 assessed by the origin of chromosome nondisjunction: a report from the Atlanta and National Down Syndrome Projects
Abstract We examined the association between maternal age and chromosome 21 nondisjunction by origin of the meiotic error. We analyzed data from two populationbased, case-control studies: Atlanta Down Syndrome Project (1989Project ( -1999 and National Down Syndrome Project (2001)(2002)(2003)(2004). Cases were live born infants with trisomy 21 and controls were infants without trisomy 21 delivered in the same geographical regions. We enrolled 1,215 of 1,881 eligible case families and 1,375 of 2,293 controls. We report four primary Wndings. First, the signiWcant association between advanced maternal age and chromosome 21 nondisjunction was restricted to meiotic errors in the egg; the association was not observed in sperm or in post-zygotic mitotic errors. Second, advanced maternal age was signiWcantly associated with both meiosis I (MI) and meiosis II (MII). For example, compared to mothers of controls, mothers of infants with trisomy 21 due to MI nondisjunction were 8.5 times more likely to bȩ 40 years old than 20-24 years old at the birth of the index case (95% CI = 5.6-12.9). Where nondisjunction occurred in MII, mothers were 15.1 times more likely to be ¸40 years (95% CI = 8.4-27.3). Third, the ratio of MI to MII errors diVered by maternal age. The ratio was lower among women <19 years of age and those ¸40 years (2.1, 2.3, respectively) and higher in the middle age group (3.6). Lastly, we found no eVect of grand-maternal age on the risk for maternal nondisjunction. This study emphasizes the complex association between advanced maternal age and nondisjunction of chromosome 21 during oogenesis
The association of low socioeconomic status and the risk of having a child with Down syndrome: a report from the National Down Syndrome Project
Comparison of the relationship between hotspot usage between MI and MII cases and Controls.
<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099560#pone-0099560-g004" target="_blank">Figure 4A and 4B</a> represent MI and MII cases respectively with only one recombinant event on 21q. The solid line represents the relationship between the number of hotspots per bin and the proportion of recombination per bin along normally segregating chromosomes 21. The dotted line represents the relationship between the number of hotspots per bin and the proportion of recombination per bin along chromosomes 21 from MI errors (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099560#pone-0099560-g004" target="_blank">figure 4A</a>) and MII errors (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099560#pone-0099560-g004" target="_blank">figure 4B</a>).</p