Sensitivity of predicted bioaerosol exposure from open windrow composting facilities to ADMS dispersion model parameters

Bioaerosols are released in elevated quantities from composting facilities and are associated with negative health effects, although dose-response relationships are not well understood, and require improved exposure classification. Dispersion modelling has great potential to improve exposure classification, but has not yet been extensively used or validated in this context. We present a sensitivity analysis of the ADMS dispersion model specific to input parameter ranges relevant to bioaerosol emissions from open windrow composting. This analysis provides an aid for model calibration by prioritising parameter adjustment and targeting independent parameter estimation. Results showed that predicted exposure was most sensitive to the wet and dry deposition modules and the majority of parameters relating to emission source characteristics, including pollutant emission velocity, source geometry and source height. This research improves understanding of the accuracy of model input data required to provide more reliable exposure predictions

Clinical response to primary letrozole therapy in elderly patients with early breast cancer : possible role for p53 as a biomarker

Primary tamoxifen therapy has been widely used to treat elderly women with ER-positive breast cancer in the past. Aromatase inhibitors may be more beneficial than tamoxifen when used as primary endocrine therapy in elderly patients. We aimed to retrospectively evaluate a series of elderly women with ER-positive breast cancer treated with primary letrozole therapy as sole therapy with a minimum of 5 years follow up. To identify possible predictive biomarkers a pilot immunohistochemical analysis was performed to assess the expression of PR, HER2, EGFR, BCL2 and p53. A total of 45 women, aged more than 70 years with a diagnosis of ER-positive breast cancer that was treated with primary letrozole therapy were identified. A case note review was undertaken to obtain clinical information. Formalin fixed paraffin embedded tumour tissue from diagnostic core biopsies was available for all patients. Immunohistochemical analysis was performed to establish the protein expression status of p53, PR, HER2, EGFR and BCL2. The mean age of the 45 patients was 87 years (range 70–101). Clinical benefit was seen in 60% of the patients. Median progression free survival was 53 months (95% CI – 34–72) and the median time to progression was 43 months (95% CI – 22–64). BCL2 was expressed in 45/45 (100%); PR in 38/45 (84%); EGFR in 13/45 (28%); HER2 in 9/45 (20%) and p53 in 5/45 (11%) of tissue samples. Positive expression of p53 was associated with poor progression free survival (p = 0.03) in this pilot study. This study demonstrates that letrozole as sole treatment appears to be a suitable treatment option for elderly patients with ER-positive breast cancer who are not fit for, or decline, surgery. The analysis of p53 in a larger study is warranted in order to assess its role as a biomarker in this patient group

Effects of different types of classroom physical activity breaks on children’s on-task behaviour, academic achievement and cognition

Aim This study examined the effects of different types of classroom physical activity breaks on children’s on-task behaviour, academic achievement and cognition. Methods Participants were 87 Australian primary school students (mean age 9.11 ± 0.62 years), recruited from one school. Three classes were randomly assigned either to activity breaks only (n = 29), activity breaks and mathematics combined (n = 29), or control conditions involving only mathematical content (n = 29). Students were engaged in five minutes of classroom physical activity breaks, three times per week, for four weeks (divided into two minutes at the beginning of the usual mathematics curriculum lesson and three minutes in the middle of the lesson). Assessments were conducted at baseline and post-test. Results Significant group-by-time effects were found for on-task behaviour (active engagement: activity breaks and mathematics combined versus control, p ≤ 0.001; activity breaks versus control, p ≤ 0.001; activity breaks and mathematics combined versus activity breaks, p = 0.037; passive engagement: activity breaks and mathematics combined versus control, p ≤ 0.001) and mathematics scores (activity breaks versus control, p = 0.045). Conclusion Physical activity breaks with and without integrated mathematics content were effective in improving children’s on-task behaviour and learning scores

Assessment of dysphotopsia in pseudophakic subjects with multifocal intraocular lenses

Aim: To better understand the phenomenon of dysphotopsia in patients implanted with multifocal intraocular lenses (IOLs). Methods: Forty-five patients (aged 61.8±8.9 years) implanted bilaterally with Tecnis ZM900 (diffractive multifocal), Lentis Mplus MF30 (segmented refractive multifocal) or Softec-1 (monofocal) IOLs (each n=15) 4–6 months previously and who had achieved a good surgical outcome were examined. Each reported their dysphotopsia symptoms subjectively, identified its form (EyeVisPod illustrations), quantified retinal straylight (C-Quant) and halo perception (Aston halometer). Retinal straylight and halometry was repeated by a second masked clinician to determine interobserver repeatability. Results: Subjective dysphotopsia ratings were able to differentiate Tecnis ZM900 from Lentis Mplus MF30 (p0.10) quantification or between straylight and the halo area (p>0.30). Conclusions: Multifocal IOLs induce symptoms of dysphotopsia. Straylight did not differentiate between IOL designs, however halometry identified clear differences in light scatter due to the IOL optics. Whereas, subjective rating of overall dysphotopsia are not strongly associated with straylight or halo perception, the halometry polar diagram reflected the subjective descriptions of dysphotopsia

Predictive gene signatures:molecular markers distinguishing colon adenomatous polyp and carcinoma

Funding: This study was supported by the Scottish Government's Rural and Environment Science and Analytical Services Division Food, Land and People Programme GT403 (http://www.scotland.gov.uk/Topics/Research/About/EBAR/StrategicResearch/future-research-strategy/Themes), Scottish Universities Life Science Alliance Translational Biology Studentship 10/09, (http://www.sulsa.ac.uk/), NHS Grampian Endowment Fund 12/07 (http://www.nhsgrampian.co.uk/nhsgrampian/gra_display_hospital.jsp?pContentID=65&p_applic=CCC&p_service=Content.show&). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.Peer reviewedPublisher PD

Koinonia

Best Practice FeaturesLife on Life Learning: Steps Towards Authentic Mentoring, Brian Jensen The Heart of the Honor Code: I am My Brother\u27s Keeper, Emily J. Darnell Spotlight FeaturesOld People are Whole Persons, Too: Why Understanding Heritage is a Foundational Component of College Student Development, Philip Byers Ministry and Learning in Residence Life, Josh Arnold Shepherding in an Age of Edupunks, Drew Moser The Gap in the Curtain: Seeing Pieces of a Residential Community\u27s Future, David Johnstone InterviewsA Conversation with Juana Bordas, conducted by Rob Pepper Looking Into the Future: Two Educators\u27 Perspectives on Christian Higher Education, by Kim Stave and Ken Heffner (edited by Kirstin Vander Giessen-Reitsma) Book ReviewsThe Unlikely Disciple (by Kevin Roose), reviewed by Christopher Bohle ReflectionsSeven Greek Words that Mean the World to Me, Bob Crow FeaturesThe President\u27s Corner Editor\u27s Deskhttps://pillars.taylor.edu/acsd_koinonia/1013/thumbnail.jp

Covariance and correlation analysis of resting state functional magnetic resonance imaging data acquired in a clinical trial of mindfulness-based stress reduction and exercise in older individuals

We describe and apply novel methodology for whole-brain analysis of resting state fMRI functional connectivity data, combining conventional multi-channel Pearson correlation with covariance analysis. Unlike correlation, covariance analysis preserves signal amplitude information, which feature of fMRI time series may carry physiological significance. Additionally, we demonstrate that dimensionality reduction of the fMRI data offers several computational advantages including projection onto a space of manageable dimension, enabling linear operations on functional connectivity measures and exclusion of variance unrelated to resting state network structure. We show that group-averaged, dimensionality reduced, covariance and correlation matrices are related, to reasonable approximation, by a single scalar factor. We apply this methodology to the analysis of a large, resting state fMRI data set acquired in a prospective, controlled study of mindfulness training and exercise in older, sedentary participants at risk for developing cognitive decline. Results show marginally significant effects of both mindfulness training and exercise in both covariance and correlation measures of functional connectivity

Conservative management versus open reduction and internal fixation for mid-shaft clavicle fractures in adults - The Clavicle Trial: Study protocol for a multicentre randomized controlled trial

Background: Clavicle fractures account for around 4% of all fractures and up to 44% of fractures of the shoulder girdle. Fractures of the middle third (or mid-shaft) account for approximately 80% of all clavicle fractures. Management of this group of fractures is often challenging and the outcome can be unsatisfactory. In particular it is not clear whether surgery produces better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision.Methods/Design: We aim to undertake a multicentre randomised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults. Surgical treatment will be performed using the Acumed clavicle fixation system. Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union. We aim to recruit 300 patients. These patients will be followed-up for at least 9 months. The primary endpoint will be the rate of non-union at 3 months following treatment. Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm, Shoulder and Hand (DASH) Score at 3 and 9 months post-operatively.Discussion: This article presents the protocol for a multicentre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.Trial Registration: United Kingdom Clinical Research Network ID: 8665. The date of registration of the trial is 07/09/2006. The date the first patient was recruited is 18/12/2007. © 2011 Longo et al; licensee BioMed Central Ltd

Ionizable lipid nanoparticles for in utero mRNA delivery.

Clinical advances enable the prenatal diagnosis of genetic diseases that are candidates for gene and enzyme therapies such as messenger RNA (mRNA)-mediated protein replacement. Prenatal mRNA therapies can treat disease before the onset of irreversible pathology with high therapeutic efficacy and safety due to the small fetal size, immature immune system, and abundance of progenitor cells. However, the development of nonviral platforms for prenatal delivery is nascent. We developed a library of ionizable lipid nanoparticles (LNPs) for in utero mRNA delivery to mouse fetuses. We screened LNPs for luciferase mRNA delivery and identified formulations that accumulate within fetal livers, lungs, and intestines with higher efficiency and safety compared to benchmark delivery systems, DLin-MC3-DMA and jetPEI. We demonstrate that LNPs can deliver mRNAs to induce hepatic production of therapeutic secreted proteins. These LNPs may provide a platform for in utero mRNA delivery for protein replacement and gene editing