Maternal-Early-Warning-System Education to Improve Registered Nurse Knowledge of and Appropriate Responses to Triggers

The maternal early warning system (MEWS) is the single most reliable response tool to improve maternal outcomes in obstetrics. Recognition and response by nurses to the MEWS triggers was worrisome at the project site as the MEWS trigger to detect changes in the clinical conditions in obstetric patients was not applied consistently at the bedside. This project was developed to evaluate whether providing an education program on the application of MEWS to nurses in obstetrics at the practicum site would improve registered nurses’ knowledge of and appropriate responses to the MEWS trigger alarms. A literature search targeting the key words maternal early warning system, quality improvement, nursing competency, and health care outcomes in sources such as CINHAL, Medline, EBSCO, and Cochrane Reviews as well as federal, state, and local databases was used to inform the project. The four levels of the Kirkpatrick model, reaction, learning, behaviors, and results, served as the framework for educating the nurses on MEWS. The design for the project with 40 obstetrics nurses included a pretest, staff education, an immediate posttest, and a 2-week retest. Data were collected using a 5-level Likert Scale delivered on a Qualtrics platform. The responses were recoded into two categories, high confidence and low confidence, and a chi-squared analysis was used to detect any significant differences in knowledge attainment by nurses. The pretest Mean (M) = 22.00, immediate posttest Mean (M) = 36.33; the 2-week posttest follow-up Mean (M) = 35.16. The social change, supported by this project, was improvement of nurses’ recognition of MEWS trigger alarms and their reaction to reduce the occurrence of preventable maternal mortality and morbidity at the micro level

Maternal-Early-Warning-System Education to Improve Registered Nurse Knowledge of and Appropriate Responses to Triggers

The maternal early warning system (MEWS) is the single most reliable response tool to improve maternal outcomes in obstetrics. Recognition and response by nurses to the MEWS triggers was worrisome at the project site as the MEWS trigger to detect changes in the clinical conditions in obstetric patients was not applied consistently at the bedside. This project was developed to evaluate whether providing an education program on the application of MEWS to nurses in obstetrics at the practicum site would improve registered nurses’ knowledge of and appropriate responses to the MEWS trigger alarms. A literature search targeting the key words maternal early warning system, quality improvement, nursing competency, and health care outcomes in sources such as CINHAL, Medline, EBSCO, and Cochrane Reviews as well as federal, state, and local databases was used to inform the project. The four levels of the Kirkpatrick model, reaction, learning, behaviors, and results, served as the framework for educating the nurses on MEWS. The design for the project with 40 obstetrics nurses included a pretest, staff education, an immediate posttest, and a 2-week retest. Data were collected using a 5-level Likert Scale delivered on a Qualtrics platform. The responses were recoded into two categories, high confidence and low confidence, and a chi-squared analysis was used to detect any significant differences in knowledge attainment by nurses. The pretest Mean (M) = 22.00, immediate posttest Mean (M) = 36.33; the 2-week posttest follow-up Mean (M) = 35.16. The social change, supported by this project, was improvement of nurses’ recognition of MEWS trigger alarms and their reaction to reduce the occurrence of preventable maternal mortality and morbidity at the micro level

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P-Bonferroni <1.06 x 10(-7)). In additional analyses in 7,278 participants,Peer reviewe

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

In-situ estimation of ice crystal properties at the South Pole using LED calibration data from the IceCube Neutrino Observatory

The IceCube Neutrino Observatory instruments about 1 km3 of deep, glacial ice at the geographic South Pole using 5160 photomultipliers to detect Cherenkov light emitted by charged relativistic particles. A unexpected light propagation effect observed by the experiment is an anisotropic attenuation, which is aligned with the local flow direction of the ice. Birefringent light propagation has been examined as a possible explanation for this effect. The predictions of a first-principles birefringence model developed for this purpose, in particular curved light trajectories resulting from asymmetric diffusion, provide a qualitatively good match to the main features of the data. This in turn allows us to deduce ice crystal properties. Since the wavelength of the detected light is short compared to the crystal size, these crystal properties do not only include the crystal orientation fabric, but also the average crystal size and shape, as a function of depth. By adding small empirical corrections to this first-principles model, a quantitatively accurate description of the optical properties of the IceCube glacial ice is obtained. In this paper, we present the experimental signature of ice optical anisotropy observed in IceCube LED calibration data, the theory and parametrization of the birefringence effect, the fitting procedures of these parameterizations to experimental data as well as the inferred crystal properties.</p