Defining a Minimum Set of Standardized Patient-centered Outcome Measures for Macular Degeneration

Purpose To define a minimum set of outcome measures for tracking, comparing, and improving macular degeneration care. Design Recommendations from a working group of international experts in macular degeneration outcomes registry development and patient advocates, facilitated by the International Consortium for Health Outcomes Measurement (ICHOM). Methods Modified Delphi technique, supported by structured teleconferences, followed by online surveys to drive consensus decisions. Potential outcomes were identified through literature review of outcomes collected in existing registries and reported in major clinical trials. Outcomes were refined by the working group and selected based on impact on patients, relationship to good clinical care, and feasibility of measurement in routine clinical practice. Results Standardized measurement of the following outcomes is recommended: visual functioning and quality of life (distance visual acuity, mobility and independence, emotional well-being, reading and accessing information); number of treatments; complications of treatment; and disease control. Proposed data collection sources include administrative data, clinical data during routine clinical visits, and patient-reported sources annually. Recording the following clinical characteristics is recommended to enable risk adjustment: age; sex; ethnicity; smoking status; baseline visual acuity in both eyes; type of macular degeneration; presence of geographic atrophy, subretinal fibrosis, or pigment epithelial detachment; previous macular degeneration treatment; ocular comorbidities. Conclusions The recommended minimum outcomes and pragmatic reporting standards should enable standardized, meaningful assessments and comparisons of macular degeneration treatment outcomes. Adoption could accelerate global improvements in standardized data gathering and reporting of patient-centered outcomes. This can facilitate informed decisions by patients and health care providers, plus allow long-term monitoring of aggregate data, ultimately improving understanding of disease progression and treatment responses

Recent Arctic climate change and its remote forcing of Northwest Atlantic shelf ecosystems

Author Posting. © The Oceanography Society, 2012. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 25, no. 3 (2012): 208-213, doi:10.5670/oceanog.2012.64.During recent decades, historically unprecedented changes have been observed in the Arctic as climate warming has increased precipitation, river discharge, and glacial as well as sea-ice melting. Additionally, shifts in the Arctic's atmospheric pressure field have altered surface winds, ocean circulation, and freshwater storage in the Beaufort Gyre. These processes have resulted in variable patterns of freshwater export from the Arctic Ocean, including the emergence of great salinity anomalies propagating throughout the North Atlantic. Here, we link these variable patterns of freshwater export from the Arctic Ocean to the regime shifts observed in Northwest Atlantic shelf ecosystems. Specifically, we hypothesize that the corresponding salinity anomalies, both negative and positive, alter the timing and extent of water-column stratification, thereby impacting the production and seasonal cycles of phytoplankton, zooplankton, and higher-trophic-level consumers. Should this hypothesis hold up to critical evaluation, it has the potential to fundamentally alter our current understanding of the processes forcing the dynamics of Northwest Atlantic shelf ecosystems.Funding for this research was provided by the National Science Foundation as part of the Regional and Pan-Regional Synthesis Phases of the US Global Ocean Ecosystem (GLOBEC) Program

In Vivo Methods for the Assessment of Topical Drug Bioavailability

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described

High incidence of Epstein-Barr virus, cytomegalovirus and human herpesvirus 6 infections in children with cancer

BACKGROUND: A prospective single-center study was performed to study infection with lymphotropic herpesviruses (LH) Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) in children with cancer. METHODS: The group of 186 children was examined for the presence of LH before, during and 2 months after the end of anticancer treatment. Serology of EBV and CMV was monitored in all children, serology of HHV-6 and DNA analysis of all three LH was monitored in 70 children. RESULTS: At the time of cancer diagnosis (pre-treatment), there was no difference between cancer patients and age-matched healthy controls in overall IgG seropositivity for EBV (68.8% vs. 72.0%; p = 0.47) and CMV (37.6% vs. 41.7%; p = 0.36). During anticancer therapy, primary or reactivated EBV and CMV infection was present in 65 (34.9%) and 66 (35.4%) of 186 patients, respectively, leading to increased overall post-treatment IgG seropositivity that was significantly different from controls for EBV (86.6% vs. 72.0%; p = 0.0004) and CMV (67.7% vs. 41.7%; p < 0.0001). Overall pre-treatment IgG seropositivity for HHV-6 was significantly lower in patients than in controls (80.6% vs. 91.3%; p = 0.0231) which may be in agreement with Greaves hypothesis of protective effect of common infections in infancy to cancer development. Primary or reactivated HHV-6 infection was present in 23 (32.9%) of 70 patients during anticancer therapy leading to post-treatment IgG seropositivity that was not significantly different from controls (94.3% vs. 91.3%; p = 0.58). The LH infection occurred independently from leukodepleted blood transfusions given. Combination of serology and DNA analysis in detection of symptomatic EBV or CMV infection was superior to serology alone. CONCLUSION: EBV, CMV and HHV-6 infections are frequently present during therapy of pediatric malignancy

Development and validation of a predictive model for American Society of Anesthesiologists Physical Status

Abstract Background The American Society of Anesthesiologists Physical Status (ASA-PS) classification system was developed to categorize the fitness of patients before surgery. Increasingly, the ASA-PS has been applied to other uses including justification of inpatient admission. Our objectives were to develop and cross-validate a statistical model for predicting ASA-PS; and 2) assess the concurrent and predictive validity of the model by assessing associations between model-derived ASA-PS, observed ASA-PS, and a diverse set of 30-day outcomes. Methods Using the 2014 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data File, we developed and internally cross-validated multinomial regression models to predict ASA-PS using preoperative NSQIP data. Accuracy was assessed with C-Statistics and calibration plots. We assessed both concurrent and predictive validity of model-derived ASA-PS relative to observed ASA-PS and 30-day outcomes. To aid further research and use of the ASA-PS model, we implemented it into an online calculator. Results Of the 566,797 elective procedures in the final analytic dataset, 8.9% were ASA-PS 1, 48.9% were ASA-PS 2, 39.1% were ASA-PS 3, and 3.2% were ASA-PS 4. The accuracy of the 21-variable model to predict ASA-PS was C = 0.77 +/− 0.0025. The model-derived ASA-PS had stronger association with key indicators of preoperative status including comorbidities and higher BMI (concurrent validity) compared to observed ASA-PS, but less strong associations with postoperative complications (predictive validity). The online ASA-PS calculator may be accessed at https://s-spire-clintools.shinyapps.io/ASA_PS_Estimator/ Conclusions Model-derived ASA-PS better tracked key indicators of preoperative status compared to observed ASA-PS. The ability to have an electronically derived measure of ASA-PS can potentially be useful in research, quality measurement, and clinical applications.https://deepblue.lib.umich.edu/bitstream/2027.42/152155/1/12913_2019_Article_4640.pd

The Impact of Error-Management Climate, Error Type and Error Originator on Auditors’ Reporting Errors Discovered on Audit Work Papers

We examine factors affecting the auditor’s willingness to report their own or their peers’ self-discovered errors in working papers subsequent to detailed working paper review. Prior research has shown that errors in working papers are detected in the review process; however, such detection rates only rarely exceed 50% of the seeded errors. Hence, measures that encourage auditors to be alert to their own (or their peers’) potential errors any time they revisit the audit working papers may be valuable in detecting such residual errors and potentially correcting them before damage occurs to the audit firm or its client. We hypothesize that three factors affect the auditor’s willingness to report post detailed review discovered errors: the local office error-management climate (open versus blame), the type of error (mechanical versus conceptual) and who committed the error (the individual who committed the error (self) or a peer). Local office error-management climate is said to be open and supportive where errors and mistakes are accepted as part of everyday life as long as they are learned from and not repeated. In alternative, a blame error-management climate focuses on a “get it right the first time” culture where mistakes are not tolerated and blame gets attached to those admitting to or found committing such errors. We find that error-management climate has a significant overall effect on auditor willingness to report errors, as does who committed the error originally. We find both predicted and unpredicted significant interactions among the three factors that qualify these observed significant main effects. We discuss implications for audit practice and further research

A search for new physics in low-energy electron recoils from the first LZ exposure

The LUX-ZEPLIN (LZ) experiment is a dark matter detector centered on a dual-phase xenon time projection chamber. We report searches for new physics appearing through few-keV-scale electron recoils, using the experiment's first exposure of 60 live days and a fiducial mass of 5.5t. The data are found to be consistent with a background-only hypothesis, and limits are set on models for new physics including solar axion electron coupling, solar neutrino magnetic moment and millicharge, and electron couplings to galactic axion-like particles and hidden photons. Similar limits are set on weakly interacting massive particle (WIMP) dark matter producing signals through ionized atomic states from the Migdal effect.Comment: 13 pages, 10 figures. See https://tinyurl.com/LZDataReleaseRun1ER for a data release related to this pape

Long-term passive acoustic recordings track the changing distribution of North Atlantic right whales (Eubalaena glacialis) from 2004 to 2014

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 7 (2017): 13460, doi:10.1038/s41598-017-13359-3.Given new distribution patterns of the endangered North Atlantic right whale (NARW; Eubalaena glacialis) population in recent years, an improved understanding of spatio-temporal movements are imperative for the conservation of this species. While so far visual data have provided most information on NARW movements, passive acoustic monitoring (PAM) was used in this study in order to better capture year-round NARW presence. This project used PAM data from 2004 to 2014 collected by 19 organizations throughout the western North Atlantic Ocean. Overall, data from 324 recorders (35,600 days) were processed and analyzed using a classification and detection system. Results highlight almost year-round habitat use of the western North Atlantic Ocean, with a decrease in detections in waters off Cape Hatteras, North Carolina in summer and fall. Data collected post 2010 showed an increased NARW presence in the mid-Atlantic region and a simultaneous decrease in the northern Gulf of Maine. In addition, NARWs were widely distributed across most regions throughout winter months. This study demonstrates that a large-scale analysis of PAM data provides significant value to understanding and tracking shifts in large whale movements over long time scales.This research was funded and supported by many organizations, specified by projects as follows: Data recordings from region 1 were provided by K. Stafford and this research effort was funded by the National Science Foundation #NSF-ARC 0532611. Region 2 data were provided by D. K. Mellinger and S. Nieukirk, funded by National Oceanic and Atmospheric Agency (NOAA) and the Office of Naval Research (ONR) #N00014–03–1–0099, NOAA #NA06OAR4600100, US Navy #N00244-08-1-0029, N00244-09-1-0079, and N00244-10-1-0047

Background Determination for the LUX-ZEPLIN (LZ) Dark Matter Experiment

The LUX-ZEPLIN experiment recently reported limits on WIMP-nucleus interactions from its initial science run, down to $9.2\times10^{-48}$ cm$^2$ for the spin-independent interaction of a 36 GeV/c$^2$ WIMP at 90% confidence level. In this paper, we present a comprehensive analysis of the backgrounds important for this result and for other upcoming physics analyses, including neutrinoless double-beta decay searches and effective field theory interpretations of LUX-ZEPLIN data. We confirm that the in-situ determinations of bulk and fixed radioactive backgrounds are consistent with expectations from the ex-situ assays. The observed background rate after WIMP search criteria were applied was $(6.3\pm0.5)\times10^{-5}$ events/keV$_{ee}$/kg/day in the low-energy region, approximately 60 times lower than the equivalent rate reported by the LUX experiment.Comment: 25 pages, 15 figure