Impact of Natural Blind Spot Location on Perimetry.

We study the spatial distribution of natural blind spot location (NBSL) and its impact on perimetry. Pattern deviation (PD) values of 11,449 reliable visual fields (VFs) that are defined as clinically unaffected based on summary indices were extracted from 11,449 glaucoma patients. We modeled NBSL distribution using a two-dimensional non-linear regression approach and correlated NBSL with spherical equivalent (SE). Additionally, we compared PD values of groups with longer and shorter distances than median, and larger and smaller angles than median between NBSL and fixation. Mean and standard deviation of horizontal and vertical NBSL were 14.33° ± 1.37° and -2.06° ± 1.27°, respectively. SE decreased with increasing NBSL (correlation: r = -0.14, p \u3c 0.001). For NBSL distances longer than median distance (14.32°), average PD values decreased in the upper central (average difference for significant points (ADSP): -0.18 dB) and increased in the lower nasal VF region (ADSP: 0.14 dB). For angles in the direction of upper hemifield relative to the median angle (-8.13°), PD values decreased in lower nasal (ADSP: -0.11 dB) and increased in upper temporal VF areas (ADSP: 0.19 dB). In conclusion, we demonstrate that NBSL has a systematic effect on the spatial distribution of VF sensitivity

Application of a Hybrid Statistical–Dynamical System to Seasonal Prediction of North American Temperature and Precipitation

Recent research demonstrates that dynamical models sometimes fail to represent observed teleconnection patterns associated with predictable modes of climate variability. As a result, model forecast skill may be reduced. We address this gap in skill through the application of a Bayesian postprocessing technique—the calibration, bridging, and merging (CBaM) method—which previously has been shown to improve probabilistic seasonal forecast skill over Australia. Calibration models developed from dynamical model reforecasts and observations are employed to statistically correct dynamical model forecasts. Bridging models use dynamical model forecasts of relevant climate modes (e.g., ENSO) as predictors of remote temperature and precipitation. Bridging and calibration models are first developed separately using Bayesian joint probability modeling and then merged using Bayesian model averaging to yield an optimal forecast. We apply CBaM to seasonal forecasts of North American 2-m temperature and precipitation from the North American Multimodel Ensemble (NMME) hindcast. Bridging is done using the model-predicted Niño-3.4 index. Overall, the fully merged CBaM forecasts achieve higher Brier skill scores and better reliability compared to raw NMME forecasts. Bridging enhances forecast skill for individual NMME member model forecasts of temperature, but does not result in significant improvements in precipitation forecast skill, possibly because the models of the NMME better represent the ENSO–precipitation teleconnection pattern compared to the ENSO– temperature pattern. These results demonstrate the potential utility of the CBaM method to improve seasonal forecast skill over North America

An Artificial Intelligence Approach to Detect Visual Field Progression in Glaucoma Based on Spatial Pattern Analysis.

Purpose: To detect visual field (VF) progression by analyzing spatial pattern changes. Methods: We selected 12,217 eyes from 7360 patients with at least five reliable 24-2 VFs and 5 years of follow-up with an interval of at least 6 months. VFs were decomposed into 16 archetype patterns previously derived by artificial intelligence techniques. Linear regressions were applied to the 16 archetype weights of VF series over time. We defined progression as the decrease rate of the normal archetype or any increase rate of the 15 VF defect archetypes to be outside normal limits. The archetype method was compared with mean deviation (MD) slope, Advanced Glaucoma Intervention Study (AGIS) scoring, Collaborative Initial Glaucoma Treatment Study (CIGTS) scoring, and the permutation of pointwise linear regression (PoPLR), and was validated by a subset of VFs assessed by three glaucoma specialists. Results: In the method development cohort of 11,817 eyes, the archetype method agreed more with MD slope (kappa: 0.37) and PoPLR (0.33) than AGIS (0.12) and CIGTS (0.22). The most frequently progressed patterns included decreased normal pattern (63.7%), and increased nasal steps (16.4%), altitudinal loss (15.9%), superior-peripheral defect (12.1%), paracentral/central defects (10.5%), and near total loss (10.4%). In the clinical validation cohort of 397 eyes with 27.5% of confirmed progression, the agreement (kappa) and accuracy (mean of hit rate and correct rejection rate) of the archetype method (0.51 and 0.77) significantly (P \u3c 0.001 for all) outperformed AGIS (0.06 and 0.52), CIGTS (0.24 and 0.59), MD slope (0.21 and 0.59), and PoPLR (0.26 and 0.60). Conclusions: The archetype method can inform clinicians of VF progression patterns

Nurse Practitioners' Use of Communication Techniques: Results of a Maryland Oral Health Literacy Survey

Funding for Open Access provided by the UMD Libraries Open Access Publishing Fund.Objectives: We examined nurse practitioners’ use and opinions of recommended communication techniques for the promotion of oral health as part of a Maryland state-wide oral health literacy assessment. Use of recommended health-literate and patient-centered communication techniques have demonstrated improved health outcomes. Methods: A 27-item self-report survey, containing 17 communication technique items, across 5 domains, was mailed to 1,410 licensed nurse practitioners (NPs) in Maryland in 2010. Use of communication techniques and opinions about their effectiveness were analyzed using descriptive statistics. General linear models explored provider and practice characteristics to predict differences in the total number and the mean number of communication techniques routinely used in a week. Results: More than 80% of NPs (N = 194) routinely used 3 of the 7 basic communication techniques: simple language, limiting teaching to 2–3 concepts, and speaking slowly. More than 75% of respondents believed that 6 of the 7 basic communication techniques are effective. Sociodemographic provider characteristics and practice characteristics were not significant predictors of the mean number or the total number of communication techniques routinely used by NPs in a week. Potential predictors for using more of the 7 basic communication techniques, demonstrating significance in one general linear model each, were: assessing the office for user-friendliness and ever taking a communication course in addition to nursing school. Conclusions: NPs in Maryland self-reported routinely using some recommended health-literate communication techniques, with belief in their effectiveness. Our findings suggest that NPs who had assessed the office for patient-friendliness or who had taken a communication course beyond their initial education may be predictors for using more of the 7 basic communication techniques. These self-reported findings should be validated with observational studies. Graduate and continuing education for NPs should increase emphasis on health-literate and patient-centered communication techniques to increase patient understanding of dental caries prevention. Non-dental healthcare providers, such as NPs, are uniquely positioned to contribute to preventing early childhood dental caries through health-literate and patient-centered communication

Designing optoelectronic properties by on-surface synthesis: formation and electronic structure of an iron-terpyridine macromolecular complex

Supramolecular chemistry protocols applied on surfaces offer compelling avenues for atomic scale control over organic-inorganic interface structures. In this approach, adsorbate-surface interactions and two-dimensional confinement can lead to morphologies and properties that differ dramatically from those achieved via conventional synthetic approaches. Here, we describe the bottom-up, on-surface synthesis of one-dimensional coordination nanostructures based on an iron (Fe)-terpyridine (tpy) interaction borrowed from functional metal-organic complexes used in photovoltaic and catalytic applications. Thermally activated diffusion of sequentially deposited ligands and metal atoms, and intra-ligand conformational changes, lead to Fe-tpy coordination and formation of these nanochains. Low-temperature Scanning Tunneling Microscopy and Density Functional Theory were used to elucidate the atomic-scale morphology of the system, providing evidence of a linear tri-Fe linkage between facing, coplanar tpy groups. Scanning Tunneling Spectroscopy reveals highest occupied orbitals with dominant contributions from states located at the Fe node, and ligand states that mostly contribute to the lowest unoccupied orbitals. This electronic structure yields potential for hosting photo-induced metal-to-ligand charge transfer in the visible/near-infrared. The formation of this unusual tpy/tri-Fe/tpy coordination motif has not been observed for wet chemistry synthesis methods, and is mediated by the bottom-up on-surface approach used here

The PKC, HOG and Ca2+ signalling pathways co-ordinately regulate chitin synthesis in Candida albicans

Open Access via PMC2649417Peer reviewedPublisher PD

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

Aberrant development corrected in adult-onset Huntington's disease iPSC-derived neuronal cultures via WNT signaling modulation

Aberrant neuronal development and the persistence of mitotic cellular populations have been implicated in a multitude of neurological disorders, including Huntington's disease (HD). However, the mechanism underlying this potential pathology remains unclear. We used a modified protocol to differentiate induced pluripotent stem cells (iPSCs) from HD patients and unaffected controls into neuronal cultures enriched for medium spiny neurons, the cell type most affected in HD. We performed single-cell and bulk transcriptomic and epigenomic analyses and demonstrated that a persistent cyclin D1+ neural stem cell (NSC) population is observed selectively in adult-onset HD iPSCs during differentiation. Treatment with a WNT inhibitor abrogates this NSC population while preserving neurons. Taken together, our findings identify a mechanism that may promote aberrant neurodevelopment and adult neurogenesis in adult-onset HD striatal neurons with the potential for therapeutic compensation