Annual Report of the National Coordinating Center for Public Health Services & Systems Research, Year Four

The National Coordinating Center for Public Health Services and Systems Research (PHSSR), together with the Public Health Practice-Based Research Networks (PBRN) Program, works to expand the production and application of evidence on how best to organize, finance and deliver public health strategies that improve population health. The Center designs and conducts research studies, provides technical assistance and direction for other researchers across the U.S., develops methodological advances in measurement and analysis, and accelerates the translation and dissemination of research findings for policy and practice stakeholders

The Boston equalens: A clinical evaluation for wear

Recent advances in gas permeable contact lens materials have accounted for their successful use in extended wear. In this study, 18 subjects were fitted with the Boston Equalens, a new silicon/acrylate lens which is combined with a flourinated monomer. The subjects wore one lens as a daily wear contact lens and the other lens as an extended wear contact lens for a period of 90 days. Four patients successfully completed the 90 days of extended wear and five patients completed between 30 and 90 days of extended wear. No significant differences of corneal curvature, refractive error, corrected visual acuity, or subjective responses were noted between the daily wear eye and the extended wear eye. Also there were no reports of lens adhesion on any of the subjects\u27 eyes

Feasibility of a unified approach to intensity-modulated radiation therapy and volume-modulated arc therapy optimization and delivery

Purpose: To study the feasibility of unified intensity-modulated arc therapy (UIMAT) which combines intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT)optimization and delivery to produce superior radiation treatment plans, both in terms of dosedistribution and efficiency of beam delivery when compared with either VMAT or IMRT alone. Methods: An inverse planning algorithm for UIMAT was prototyped within the pinnacle treatment planningsystem (Philips Healthcare). The IMRT and VMAT deliveries are unified within the same arc, with IMRT being delivered at specific gantry angles within the arc. Optimized gantry angles for the IMRT and VMAT phases are assigned automatically by the inverse optimization algorithm.Optimization of the IMRT and VMAT phases is done simultaneously using a direct apertureoptimization algorithm. Five treatment plans each for prostate, head and neck, and lung were generated using a unified optimization technique and compared with clinical IMRT or VMAT plans. Delivery verification was performed with an ArcCheck phantom (Sun Nuclear) on a Varian TrueBeam linear accelerator (Varian Medical Systems). Results: In this prototype implementation, the UIMAT plans offered the same target dose coverage while reducing mean doses to organs at risk by 8.4% for head-and-neck cases, 5.7% for lung cases, and 3.5% for prostate cases, compared with the VMAT or IMRT plans. In addition, UIMAT can bedelivered with similar efficiency as VMAT. Conclusions: In this proof-of-concept work, a novel radiation therapy optimization and delivery technique that interlaces VMAT or IMRT delivery within the same arc has been demonstrated. Initial results show that unified VMAT/IMRT has the potential to be superior to either standard IMRT or VMAT

Magnetic resonance imaging biomarkers of chronic obstructive pulmonary disease prior to radiation therapy for non-small cell lung cancer.

OBJECTIVE: In this prospectively planned interim-analysis, the prevalence of chronic obstructive lung disease (COPD) phenotypes was determined using magnetic resonance imaging (MRI) and X-ray computed tomography (CT) in non-small-cell-lung-cancer (NSCLC) patients. MATERIALS AND METHODS: Stage-III-NSCLC patients provided written informed consent for pulmonary function tests, imaging and the 6-min-walk-test. Ventilation defect percent (VDP) and CT lung density (relative-of-CT-density-histogram RESULTS: Seventeen stage-III NSCLC patients were evaluated (68 ± 7 years, 7 M/10 F, mean FEV1 = 77%pred) including seven current and 10 ex-smokers and eight patients with a prior lung disease diagnosis. There was a significant difference for smoking history (p = .02) and FEV1/FVC (p = .04) for subgroups classified using quantitative imaging. Patient subgroups classified using qualitative imaging findings were significantly different for emphysema (RA950, p \u3c .001). There were significant relationships for whole-lung VDP (p \u3c .05), but not RECIST or tumour-lobe VDP measurements with pulmonary function and exercise measurements. Preliminary analysis for non-tumour burden ventilation abnormalities using Reader-operator-characteristic (ROC) curves reflected a 94% classification rate for smoking pack-years, 93% for FEV1/FVC and 82% for RA950. ROC sensitivity/specificity/positive/negative likelihood ratios were also generated for pack-years, (0.92/0.80/4.6/0.3), FEV1/FVC (0.92/0.80/4.6/0.3), RA950 (0.92/0.80/4.6/0.3) and RECIST (0.58/0.80/2.9/1.1). CONCLUSIONS: In this prospectively planned interim-analysis of a larger clinical trial, NSCLC patients were classified based on COPD imaging phenotypes. A proof-of-concept evaluation showed that FEV1/FVC and smoking history identified NSCLC patients with ventilation abnormalities appropriate for functional lung avoidance radiotherapy

Aldosterone modulates the association between NCC and ENAC

Distal sodium transport is a final step in the regulation of blood pressure. As such, understanding how the two main sodium transport proteins, the thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC), are regulated is paramount. Both are expressed in the late distal nephron; however, no evidence has suggested that these two sodium transport proteins interact. Recently, we established that these two sodium transport proteins functionally interact in the second part of the distal nephron (DCT2). Given their co-localization within the DCT2, we hypothesized that NCC and ENaC interactions might be modulated by aldosterone (Aldo). Aldo treatment increased NCC and αENaC colocalization (electron microscopy) and interaction (coimmunoprecipitation). Finally, with co-expression of the Aldo-induced protein serum- and glucocorticoid-inducible kinase 1 (SGK1), NCC and αENaC interactions were increased. These data demonstrate that Aldo promotes increased interaction of NCC and ENaC, within the DCT2 revealing a novel method of regulation for distal sodium reabsorption

Nudibranch Range Shifts associated with the 2014 Warm Anomaly in the Northeast Pacific

Abstract.—The Northeast Pacific Ocean was anomalously warm in 2014, despite ENSO-neutral conditions in the tropical Pacific. We documented northern range shifts associated with this anomaly for 30 species of nudibranchs and other shallow-water, benthic heterobranch gastropods from southern California to southern Oregon. Nine of these (Placida cremoniana, Trapania velox, Doriopsilla fulva, Janolus anulatus, J. barbarensis, Flabellina cooperi, Anteaeolidiella chromosoma, A. oliviae, and Noumeaella rubrofasciata) were recorded from new northernmost localities, while the remainder were found at or near northern range limits established mainly during past El Niño events. All 30 species have planktotrophic larval development, and six were observed spawning at northern localities, increasing the likelihood that their ranges will continue to shift poleward as the strong 2015-16 El Niño develops. Notable among these was Okenia rosacea, usually found south of San Francisco and last observed in Oregon as a single specimen found during the 1997-98 El Niño. In 2015 this bright pink nudibranch reached high densities and was observed spawning throughout northern California and into southern Oregon. Okenia rosacea is therefore poised to exploit abundant prey resources previously out of its reach in northern Oregon and Washington. Our results not only demonstrate a striking biological response to the 2014 warm anomaly in the North Pacific Ocean, but also support early physical indications of a larger regional climate shift, one reinforced by long-term global warming. Combined with historical data, these results highlight how shallow-water nudibranchs, with their planktotrophic larvae, short life cycles, conspicuous coloration, and accessibility are excellent biological indicators of ocean climate in the region

Optimization of multi-electrode implant configurations and programming for the delivery of non-ablative electric fields in intratumoral modulation therapy.

PURPOSE: Application of low intensity electric fields to interfere with tumor growth is being increasingly recognized as a promising new cancer treatment modality. Intratumoral modulation therapy (IMT) is a developing technology that uses multiple electrodes implanted within or adjacent tumor regions to deliver electric fields to treat cancer. In this study, the determination of optimal IMT parameters was cast as a mathematical optimization problem, and electrode configurations, programming, optimization, and maximum treatable tumor size were evaluated in the simplest and easiest to understand spherical tumor model. The establishment of electrode placement and programming rules to maximize electric field tumor coverage designed specifically for IMT is the first step in developing an effective IMT treatment planning system. METHODS: Finite element method electric field computer simulations for tumor models with 2 to 7 implanted electrodes were performed to quantify the electric field over time with various parameters, including number of electrodes (2 to 7), number of contacts per electrode (1 to 3), location within tumor volume, and input waveform with relative phase shift between 0 and 2π radians. Homogeneous tissue specific conductivity and dielectric values were assigned to the spherical tumor and surrounding tissue volume. In order to achieve the goal of covering the tumor volume with a uniform threshold of 1 V/cm electric field, a custom least square objective function was used to maximize the tumor volume covered by 1 V/cm time averaged field, while maximizing the electric field in voxels receiving less than this threshold. An additional term in the objective function was investigated with a weighted tissue sparing term, to minimize the field to surrounding tissues. The positions of the electrodes were also optimized to maximize target coverage with the fewest number of electrodes. The complexity of this optimization problem including its non-convexity, the presence of many local minima, and the computational load associated with these stochastic based optimizations led to the use of a custom pattern search algorithm. Optimization parameters were bounded between 0 and 2π radians for phase shift, and anywhere within the tumor volume for location. The robustness of the pattern search method was then evaluated with 50 random initial parameter values. RESULTS: The optimization algorithm was successfully implemented, and for 2 to 4 electrodes, equally spaced relative phase shifts and electrodes placed equidistant from each other was optimal. For 5 electrodes, up to 2.5 cm diameter tumors with 2.0 V, and 4.1 cm with 4.0 V could be treated with the optimal configuration of a centrally placed electrode and 4 surrounding electrodes. The use of 7 electrodes allow for 3.4 cm diameter coverage at 2.0 V and 5.5 cm at 4.0 V. The evaluation of the optimization method using 50 random initial parameter values found the method to be robust in finding the optimal solution. CONCLUSIONS: This study has established a robust optimization method for temporally optimizing electric field tumor coverage for IMT, with the adaptability to optimize a variety of parameters including geometrical and relative phase shift configurations

Drought effects on composition and yield for corn stover, mixed grasses, and Miscanthus as bioenergy feedstocks

Drought conditions in 2012 were some of the most severe in recent history. The purpose of this study is to examine the impact of drought on quality, quantity, and theoretical ethanol yield (TEY) of three bioenergy feedstocks, corn stover, mixed grasses from Conservation Reserve Program lands, and Miscanthus ×giganteus. To assess drought effects on these feedstocks, samples from 2010 (minimal to no drought) and 2012 (severe drought) were compared from multiple locations in the US. In all feedstocks, drought significantly increased extractives and reduced structural sugars and lignin; subsequently, TEYs were reduced 10–15%. Biomass yields were significantly reduced for M. × giganteus and mixed grasses. When reduction in quality and quantity were combined, TEYs decreased 26–59%. Drought negatively affected biomass quality and quantity that resulted in significant TEY reductions. Such fluctuations in biomass quality and yield may have significant consequences for developing lignocellulosic biorefineries

The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance

We show that the mouse macrophage-restricted F4/80 protein is not required for the development and distribution of tissue macrophages but is involved in the generation of antigen-specific efferent regulatory T (T reg) cells that suppress antigen-specific immunity. In the in vivo anterior chamber (a.c.)–associated immune deviation (ACAID) model of peripheral tolerance, a.c. inoculation of antigen into F4/80−/− mice was unable to induce efferent T reg cells and suppress delayed-type hypersensitivity (DTH) responses. Moreover, the use of anti-F4/80 mAb and F4/80−/− APCs in an in vitro ACAID model showed that all APC cells in the culture must be able to express F4/80 protein if efferent T reg cells were to be generated. In a low-dose oral tolerance model, WT but not F4/80−/− mice generated an efferent CD8+ T reg cell population that suppressed an antigen-specific DTH response. Peripheral tolerance was restored in F4/80−/− mice by adoptive transfer of F4/80+ APCs in both peripheral tolerance models, indicating a central role for the F4/80 molecule in the generation of efferent CD8+ T reg cells