Structures and processes of care in ambulatory oncology settings and nurse-reported exposure to chemotherapy

PURPOSE: Oncology nurses in ambulatory settings are at increased risk for unintentional chemotherapy exposure due to the large volumes of agents delivered and the absence of regulatory enforcement. Given the limited data regarding the correlates of exposure, the authors sought to identify the relationship between the organisational structures and processes of care in ambulatory oncology settings associated with increased risk of unintentional chemotherapy. METHODS: Between April 2010 and June 2010, a state-wide sample of oncology nurses were surveyed who reported their employment outside of hospital inpatient units (n=1339). The survey examined the likelihood of self-reported exposure to chemotherapy as a function of perceived quality of the practice environment, nursing workload, and seven ambulatory chemotherapy administration safety standards. RESULTS: The response rate was 30.4%, with minimal demographic differences observed between respondents and non-respondents. The overall rate of exposure to the skin or eyes in the past year was 16.9%. In multivariable logistic regression models that controlled for demographic characteristics and clustering of nurses in practices, the likelihood of exposure decreased when nurses reported adequate staffing and resources (OR 0.35, 95% CI 0.17 to 0.73; p=0.001), and when nurses reported that chemotherapy doses were verified by two nurses frequently or very frequently (OR 0.17, 95% CI 0.05 to 0.59; p=0.001). CONCLUSIONS: Oncology nurses in the ambulatory setting report substantial unintentional skin and eye exposure to chemotherapy. Ensuring adequate staffing and resources and adherence to recognised practice standards may protect oncology nurses from harm.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94114/1/Structures and processes of care in ambulatory oncology settings and nurse-reported exposure to chemotherapy.pd

Grid-Based Atmospheric Retrievals for Reflected-Light Spectra of Exoplanets using PSGnest

Techniques to retrieve the atmospheric properties of exoplanets via direct observation of their reflected light have often been limited in scope due to computational constraints imposed by the forward-model calculations. We have developed a new set of techniques which significantly decreases the time required to perform a retrieval while maintaining accurate results. We constructed a grid of 1.4 million pre-computed geometric albedo spectra valued at discrete sets of parameter points. Spectra from this grid are used to produce models for a fast and efficient nested sampling routine called PSGnest. Beyond the upfront time to construct a spectral grid, the amount of time to complete a full retrieval using PSGnest is on the order of seconds to minutes using a personal computer. An extensive evaluation of the error induced from interpolating intermediate spectra from the grid indicates that this bias is insignificant compared to other retrieval error sources, with an average coefficient of determination between interpolated and true spectra of 0.998. We apply these new retrieval techniques to help constrain the optimal bandpass centers for retrieving various atmospheric and bulk parameters from a LuvEx-type mission observing several planetary archetypes. We show that spectral observations made using a 20\% bandpass centered at 0.73 microns can be used alongside our new techniques to make detections of $H_2O$ and $O_2$ without the need to increase observing time beyond what is necessary for a signal-to-noise ratio of 10. The methods introduced here will enable robust studies of the capabilities of future observatories to characterize exoplanets.Comment: 32 pages, 17 figures. Accepted for publication in The Astronomical Journa

Proxima Centauri b is not a transiting exoplanet

We report Spitzer Space Telescope observations during predicted transits of the exoplanet Proxima Centauri b. As the nearest terrestrial habitable-zone planet we will ever discover, any potential transit of Proxima b would place strong constraints on its radius, bulk density, and atmosphere. Subsequent transmission spectroscopy and secondary-eclipse measurements could then probe the atmospheric chemistry, physical processes, and orbit, including a search for biosignatures. However, our photometric results rule out planetary transits at the 200~ppm level at 4.5$~{\mu}m$, yielding a 3$\sigma$ upper radius limit of 0.4~R_\rm{\oplus} (Earth radii). Previous claims of possible transits from optical ground- and space-based photometry were likely correlated noise in the data from Proxima Centauri's frequent flaring. Follow-up observations should focus on planetary radio emission, phase curves, and direct imaging. Our study indicates dramatically reduced stellar activity at near-to-mid infrared wavelengths, compared to the optical. Proxima b is an ideal target for space-based infrared telescopes, if their instruments can be configured to handle Proxima's brightness.Comment: 8 pages, 3 figures, 2 tables, accepted for publication in MNRA

Winter Movements of Louisiana Pine Snakes (Pituophis ruthveni) in Texas and Louisiana

Despite concerns that the Louisiana Pine Snake (Pituophis ruthveni) has been extirpated from large portions of its historic range, only a limited number of studies on their movement patterns have been published. Winter movement patterns are of particular interest since it has been hypothesized that impacts of management practices would be reduced during the winter. Using radiotelemetry, we determined winter movement patterns of Louisiana Pine Snakes (11 males, 8 females) in 5 study areas (2 in Louisiana and 3 in Texas). Movements during winter (November–February) were greatly curtailed compared to the remainder of the year; however, snakes occasionally undertook substantial movements. Relocations were typically within the snake’s previous active-season home range, and movements were more frequent in the early portion of winter. All hibernation sites were within Baird’s Pocket Gopher (Geomys breviceps) burrow systems at depths ranging from 13–25 cm. Louisiana Pine Snakes did not use communal hibernacula, nor did individual snakes return to previously used sites in successive years

Genes contributing to Porphyromonas gingivalis fitness in abscess and epithelial cell colonization environments

Porphyromonas gingivalis is an important cause of serious periodontal diseases, and is emerging as a pathogen in several systemic conditions including some forms of cancer. Initial colonization by P. gingivalis involves interaction with gingival epithelial cells, and the organism can also access host tissues and spread haematogenously. To better understand the mechanisms underlying these properties, we utilized a highly saturated transposon insertion library of P. gingivalis, and assessed the fitness of mutants during epithelial cell colonization and survival in a murine abscess model by high-throughput sequencing (Tn-Seq). Transposon insertions in many genes previously suspected as contributing to virulence showed significant fitness defects in both screening assays. In addition, a number of genes not previously associated with P. gingivalis virulence were identified as important for fitness. We further examined fitness defects of four such genes by generating defined mutations. Genes encoding a carbamoyl phosphate synthetase, a replication-associated recombination protein, a nitrosative stress responsive HcpR transcription regulator, and RNase Z, a zinc phosphodiesterase, showed a fitness phenotype in epithelial cell colonization and in a competitive abscess infection. This study verifies the importance of several well-characterized putative virulence factors of P. gingivalis and identifies novel fitness determinants of the organism

ITGB5 and AGFG1 variants are associated with severity of airway responsiveness

Background: Airway hyperresponsiveness (AHR), a primary characteristic of asthma, involves increased airway smooth muscle contractility in response to certain exposures. We sought to determine whether common genetic variants were associated with AHR severity. Methods: A genome-wide association study (GWAS) of AHR, quantified as the natural log of the dosage of methacholine causing a 20% drop in FEV1, was performed with 994 non-Hispanic white asthmatic subjects from three drug clinical trials: CAMP, CARE, and ACRN. Genotyping was performed on Affymetrix 6.0 arrays, and imputed data based on HapMap Phase 2, was used to measure the association of SNPs with AHR using a linear regression model. Replication of primary findings was attempted in 650 white subjects from DAG, and 3,354 white subjects from LHS. Evidence that the top SNPs were eQTL of their respective genes was sought using expression data available for 419 white CAMP subjects. Results: The top primary GWAS associations were in rs848788 (P-value 7.2E-07) and rs6731443 (P-value 2.5E-06), located within the ITGB5 and AGFG1 genes, respectively. The AGFG1 result replicated at a nominally significant level in one independent population (LHS P-value 0.012), and the SNP had a nominally significant unadjusted P-value (0.0067) for being an eQTL of AGFG1. Conclusions: Based on current knowledge of ITGB5 and AGFG1, our results suggest that variants within these genes may be involved in modulating AHR. Future functional studies are required to confirm that our associations represent true biologically significant findings

Changes in γ-secretase activity and specificity caused by the introduction of consensus aspartyl protease active motif in Presenilin 1

Presenilin (PS1 or PS2) is an essential component of the active γ-secretase complex that liberates the Aβ peptides from amyloid precursor protein (APP). PS1 is regarded as an atypical aspartyl protease harboring two essential aspartic acids in the context of the sequence D257LV and D385FI, respectively, rather than the typical DTG...DTG catalytic motif of classical aspartyl proteases. In the present studies, we introduced the sequence DTG in PS1 at and around the catalytic D257 and D385 residues to generate three PS1 mutants: D257TG, D385TG, and the double-mutant D257TG/D385TG. The effects of these changes on the γ-secretase activity in the presence or absence of γ-secretase inhibitors and modulators were investigated. The results showed that PS1 mutants having D385TG robustly enhanced Aβ42 production compared to the wild type (wt), and were more sensitive than wt to inhibition by a classical aspartyl protease transition state mimic, and fenchylamine, a sulfonamide derivative. Unlike wt PS1 and some of its clinical mutants, all three PS1 artificial mutants decreased cleavage of Notch S3-site, suggesting that these artificial mutations may trigger conformational changes at the substrate docking and catalytic site that cause alteration of substrate specificity and inhibition pattern. Consistent with this notion, we have found that NSAID enzymatic inhibitors of COX, known modulators of the γ-secretase activity, cause PS1 mutants containing D385TG to produce higher levels of both Aβ38 and Aβ42, but to reduce levels of Aβ39, showing a pattern of Aβ formation different from that observed with wild type PS1 and its clinical mutants. This study provides an important structural clue for the rational design of drugs to inhibit processing of APP at the γ-site without interfering with Notch processing

Summer effects on body mass index (BMI) gain and growth patterns of American Indian children from kindergarten to first grade: a prospective study

<p>Abstract</p> <p>Background</p> <p>Overweight and obesity are highly prevalent among American Indian children, especially those living on reservations. There is little scientific evidence about the effects of summer vacation on obesity development in children. The purpose of this study was to investigate the effects of summer vacation between kindergarten and first grade on growth in height, weight, and body mass index (BMI) for a sample of American Indian children.</p> <p>Methods</p> <p>Children had their height and weight measured in four rounds of data collection (yielded three intervals: kindergarten, summer vacation, and first grade) as part of a school-based obesity prevention trial (Bright Start) in a Northern Plains Indian Reservation. Demographic variables were collected at baseline from parent surveys. Growth velocities (Z-score units/year) for BMI, weight, and height were estimated and compared for each interval using generalized linear mixed models.</p> <p>Results</p> <p>The children were taller and heavier than median of same age counterparts. Height Z-scores were positively associated with increasing weight status category. The mean weight velocity during summer was significantly less than during the school year. More rapid growth velocity in height during summer than during school year was observed. Obese children gained less adjusted-BMI in the first grade after gaining more than their counterparts during the previous two intervals. No statistically significant interval effects were found for height and BMI velocities.</p> <p>Conclusions</p> <p>There was no indication of a significant summer effect on children's BMI. Rather than seasonal or school-related patterns, the predominant pattern indicated by weight-Z and BMI-Z velocities might be related to age or maturation.</p> <p>Trial registration</p> <p>Bright Start: Obesity Prevention in American Indian Children Clinical Trial Govt ID# <a href="http://www.clinicaltrials.gov/ct2/show/NCT00123032">NCT00123032</a></p

Osteomacs interact with megakaryocytes and osteoblasts to regulate murine hematopoietic stem cell function

Networking between hematopoietic stem cells (HSCs) and cells of the hematopoietic niche is critical for stem cell function and maintenance of the stem cell pool. We characterized calvariae-resident osteomacs (OMs) and their interaction with megakaryocytes to sustain HSC function and identified distinguishing properties between OMs and bone marrow (BM)–derived macrophages. OMs, identified as CD45+F4/80+ cells, were easily detectable (3%-5%) in neonatal calvarial cells. Coculture of neonatal calvarial cells with megakaryocytes for 7 days increased OM three- to sixfold, demonstrating that megakaryocytes regulate OM proliferation. OMs were required for the hematopoiesis-enhancing activity of osteoblasts, and this activity was augmented by megakaryocytes. Serial transplantation demonstrated that HSC repopulating potential was best maintained by in vitro cultures containing osteoblasts, OMs, and megakaryocytes. With or without megakaryocytes, BM-derived macrophages were unable to functionally substitute for neonatal calvarial cell–associated OMs. In addition, OMs differentiated into multinucleated, tartrate resistant acid phosphatase–positive osteoclasts capable of bone resorption. Nine-color flow cytometric analysis revealed that although BM-derived macrophages and OMs share many cell surface phenotypic similarities (CD45, F4/80, CD68, CD11b, Mac2, and Gr-1), only a subgroup of OMs coexpressed M-CSFR and CD166, thus providing a unique profile for OMs. CD169 was expressed by both OMs and BM-derived macrophages and therefore was not a distinguishing marker between these 2 cell types. These results demonstrate that OMs support HSC function and illustrate that megakaryocytes significantly augment the synergistic activity of osteoblasts and OMs. Furthermore, this report establishes for the first time that the crosstalk between OMs, osteoblasts, and megakaryocytes is a novel network supporting HSC function