Predictive modeling of riverine constituent concentrations and loads using historic and imposed hydrologic conditions

This research was principally concerned with the task of quantifying dissolved and suspended constituents carried in river water when direct measurements are not available. This is a question of scientific and societal relevance, and one with a long history of study and a great deal of remaining difficulty. The traditional approach to estimating these quantities, linear regression models (LMs), suffers from poor flexibility and high subsequent bias in many applications. This research applied semiparametric generalized additive models (GAMs), a more flexible class of regression models, evaluated their performance in various locations and conditions, and applied them in a proactive modeling effort in a major water-supply reservoir. Chapter 1 compared GAMs to LMs for estimating nutrient and organic carbon loads in three major tributaries of the Wachusett Reservoir in central Massachusetts. The relative performance of each model was determined using cross-validation. GAMs outperformed LMs in most cases, explaining an additional 2% of load variance and 5% of concentration variance in validation data on average. Relative differences between the two modeling approaches exceeded 100% depending on the time interval of the load estimate. Chapter 2 assessed the applicability of GAMs to the prediction of riverine solute concentrations during extreme high-flow events when such events are absent from the models\u27 calibration data. The models tended to overpredict extreme-event concentrations, with increasing bias and variance for increasingly extreme hydrologic conditions. Despite an overall increase in uncertainty for extreme-event concentration estimates, estimates under extreme hydrologic conditions could be improved by taking into account the observed bias in the aggregated regional database. Chapter 3 developed and applied a methodology to generate reservoir tributary discharge and constituent concentration time-series for an imposed extreme-event scenario. A multivariate probability model was developed for constituent concentration in an arbitrary number of tributaries and water-quality constituents, conditional on time and hydrologic condition. Two separate historical storm events were modified using 3 extreme precipitation depths on tributaries of the Wachusett Reservoir Watershed in Massachusetts, U.S. Quasi-Monte Carlo was used to propagate this uncertainty to a process-based model of the receiving water body

Quantifying and contextualizing disinfection byproducts during the Flint Water Crisis: a case study, and framework for broader application

Total trihalomethanes (TTHMs) and other disinfection byproducts (DBPs) have been a concern in Flint, Michigan, in both delivered water and water from home water heaters. Historical TTHM data and DBP sampling results from Flint were combined with models for predicting hot water TTHMs to assess the probability of certain DBP concentrations. Results were compared with hot and cold water DBPs from a water system in Florida. Flint results were used to estimate cancer risk resulting from chronic exposure to hot water TTHMs, and compared to similar risk assessments in other water systems. Results indicate TTHM concentrations decreased in Flint following a return to water from the Detroit Water and Sewerage Department, and were very near the mean value for public drinking water systems in the United States. Measurement of other unregulated DBPs also indicated levels within the typical ranges. Monte Carlo simulations coupled with modeling of hot water TTHMs indicated a low probability of TTHMs exceeding 80 μg/L in Flint in 2016. The estimated cancer risk from exposure to TTHMs in Flint is similar to other areas. The methods used in this work can apply broadly to other water systems to de-escalate perceptions of risk following a water crisis

Gynecologic oncology patient perspectives and knowledge on advance care planning: A quality improvement intervention

OBJECTIVES: Assess and improve advance care planning (ACP) awareness and uptake among gynecologic oncology patients. METHODS: Using a quality improvement Plan-Do-Check-Act framework, we completed a single institution needs assessment and intervention. The needs assessment was a 26-question survey assessing baseline ACP knowledge and preferences of gynecologic oncology patients. We used this survey to implement an outpatient intervention in which patients were offered ACP resources (pamphlet, discussion with their gynecologic oncologist, and/or social work referral). We conducted a post-intervention survey among patients who had and had not received ACP resource(s) to assess whether our intervention increased ACP knowledge, discussions, or uptake. RESULTS: Among 106 patients surveyed in the needs assessment, 33 % had ACP documents, 26 % had discussed ACP with a physician, and 82 % thought discussing ACP was important. The majority preferred these conversations in the outpatient setting (52 %) with their gynecologic oncologist (80 %) instead of nurses or trainees. In the intervention, 526 patients were offered ACP resources. Compared to women who did not receive resources (n = 324), patients who received ACP resource(s) (n = 202) were more likely to have ACP discussions with their gynecologic oncologist (38 % vs 68 %, CONCLUSIONS: ACP uptake among gynecologic oncology patients is low, but ACP discussions with an oncologist during outpatient visits are important to patients and improve their knowledge regarding completing ACP documents

Performance of Three LED-Based Fluorescence Microscopy Systems for Detection of Tuberculosis in Uganda

BACKGROUND: Direct smear microscopy using Ziehl-Neelsen (ZN) staining is the mainstay of tuberculosis (TB) diagnosis in most high burden countries, but is limited by low sensitivity in routine practice, particularly in high human immunodeficiency virus (HIV) prevalence settings. METHODS: We compared the performance of three commercial light emitting diode (LED)-based microscopy systems (Primostar™ iLED, Lumin™ and AFTER®) for fluorescent detection of Mycobacterium tuberculosis with ZN microscopy on slides prepared from sputum of TB suspects. Examination time for LED-based fluorescent microscopy (LED FM) and ZN slides was also compared, and a qualitative user appraisal of the LED FM systems was carried out. RESULTS: LED FM was between 5.6 and 9.4% more sensitive than ZN microscopy, although the difference was not statistically significant. There was no significant difference in the sensitivity or specificity of the three LED FM systems, although the specificity of Fraen AFTER was somewhat lower than the other LED FM methods. Examination time for LED FM was 2 and 4 times less than for ZN microscopy. LED FM was highly acceptable to Ugandan technologists, although differences in operational performance of the three systems were reported. CONCLUSIONS: LED FM compares favourably with ZN microscopy, with equivalent specificity and a modest increase in sensitivity. Screening of slides was substantially quicker using LED FM than ZN, and LED FM was rated highly by laboratory technologists. Available commercial systems have different operational characteristics which should be considered prior to programmatic implementation

RAD51 foci as a biomarker predictive of platinum chemotherapy response in ovarian cancer

PURPOSE: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples. EXPERIMENTAL DESIGN: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if \u3e10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated. RESULTS: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P \u3c 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P \u3c 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78-1.0; P \u3c 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P \u3c 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33-0.85; P \u3c 0.001) and overall survival (HR, 0.43; 95% CI, 0.25-0.75; P = 0.003) than RAD51-High status. CONCLUSIONS: RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials

Seabird Trophic Position Across Three Ocean Regions Tracks Ecosystem Differences

We analyze recently collected feather tissues from two species of seabirds, the sooty tern (Onychoprion fuscatus) and brown noddy (Anous stolidus), in three ocean regions (North Atlantic, North Pacific, and South Pacific) with different human impacts. The species are similar morphologically and in the trophic levels from which they feed within each location. In contrast, we detect reliable differences in trophic position amongst the regions. Trophic position appears to decline as the intensity of commercial fishing increases, and is at its lowest in the Caribbean. The spatial gradient in trophic position we document in these regions exceeds those detected over specimens from the last 130 years in the Hawaiian Islands. Modeling suggests that climate velocity and human impacts on fish populations strongly align with these differences

Hydrogenation properties of lithium and sodium hydride – closo-borate, [B10H10]2− and [B12H12]2−, composites

© 2018 the Owner Societies. The hydrogen absorption properties of metal closo-borate/metal hydride composites, M2B10H10-8MH and M2B12H12-10MH, M = Li or Na, are studied under high hydrogen pressures to understand the formation mechanism of metal borohydrides. The hydrogen storage properties of the composites have been investigated by in situ synchrotron radiation powder X-ray diffraction at p(H2) = 400 bar and by ex situ hydrogen absorption measurements at p(H2) = 526 to 998 bar. The in situ experiments reveal the formation of crystalline intermediates before metal borohydrides (MBH4) are formed. On the contrary, the M2B12H12-10MH (M = Li and Na) systems show no formation of the metal borohydride at T = 400 °C and p(H2) = 537 to 970 bar.11B MAS NMR of the M2B10H10-8MH composites reveal that the molar ratio of LiBH4or NaBH4and the remaining B species is 1:0.63 and 1:0.21, respectively. Solution and solid-state11B NMR spectra reveal new intermediates with a B:H ratio close to 1:1. Our results indicate that the M2B10H10(M = Li, Na) salts display a higher reactivity towards hydrogen in the presence of metal hydrides compared to the corresponding [B12H12]2-composites, which represents an important step towards understanding the factors that determine the stability and reversibility of high hydrogen capacity metal borohydrides for hydrogen storage

Expertise differences in anticipatory judgements during a temporally and spatially occluded dynamic task

There is contradictory evidence surrounding the role of critical cues in the successful anticipation of penalty kick outcome. In the current study, skilled and less-skilled soccer goalkeepers were required to anticipate spatially (full body; hip region) and temporally (–160 ms, –80 ms before, foot–ball contact) occluded penalty kicks. The skilled group outperformed the less-skilled group in all conditions. Both groups performed better in the full body, compared to hip region condition. Later temporal occlusion conditions were associated with increased performance in the correct response and correct side analysis, but not for correct height. These data suggest that there is enough postural information from the hip region for skilled goalkeepers to make highly accurate predictions of penalty kick direction, however, other regions are needed in order to make predictions of height. These data demonstrate the evolution of cues over time and have implications for anticipation training

Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma

Angiogenesis is not only dependent on endothelial cell invasion and proliferation, it also requires pericyte coverage of vascular sprouts for stabilization of vascular walls. Clinical efficacy of angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathway is still limited to date. We hypothesized that the level of vessel maturation is critically involved in the response to antiangiogenic therapies. To test this hypothesis, we evaluated the vascular network in spontaneously developing melanomas of MT/ret transgenic mice after using PTK787/ZK222584 for anti-VEGF therapy but also analyzed human melanoma metastases taken at clinical relapse in patients undergoing adjuvant treatment using bevacizumab. Both experimental settings showed that tumor vessels, which are resistant to anti-VEGF therapy, are characterized by enhanced vessel diameter and normalization of the vascular bed by coverage of mature pericytes and immunoreactivity for desmin, NG-2, platelet-derived growth factor receptor β, and the late-stage maturity marker α smooth muscle actin. Our findings emphasize that the level of mural cell differentiation and stabilization of the vascular wall significantly contribute to the response toward antiangiogenic therapy in melanoma. This study may be useful in paving the way toward a more rational development of second generation antiangiogenic combination therapies and in providing, for the first time, a murine model to study this