Acute and Late Esophageal Toxicity After SABR to Thoracic Tumors Near or Abutting the Esophagus.

PURPOSE: Our purpose was to evaluate the incidence of acute and late esophageal toxicity in patients with thoracic tumors near or abutting the esophagus treated with SABR. METHODS AND MATERIALS: Among patients with thoracic tumors treated with SABR, we identified those with tumors near or abutting the esophagus. Using the linear-quadratic model with an α/ß ratio of 10, we determined the correlation between dosimetric parameters and esophageal toxicity graded using the Common Terminology Criteria for Adverse Events, version 5.0. RESULTS: Out of 2200 patients treated with thoracic SABR, 767 patients were analyzable for esophageal dosimetry. We identified 55 patients with tumors near the esophagus (52 evaluable for esophagitis grade) and 28 with planning target volume (PTV) overlapping the esophagus. Dose gradients across the esophagus were consistently sharp. Median follow-up and overall survival were 16 and 23 months, respectively. Thirteen patients (25%) developed temporary grade 2 acute esophageal toxicity, 11 (85%) of whom had PTV overlapping the esophagus. Symptoms resolved within 1 to 3 months in 12 patients and 6 months in all patients. No grade 3 to 5 toxicity was observed. Only 3 patients (6%) developed late or persistent grade 2 dysphagia or dyspepsia of uncertain relationship to SABR. The cumulative incidence of acute esophagitis was 15% and 25% at 14 and 60 days, respectively. Acute toxicity correlated on univariate analysis with esophageal Dmax, D1cc, D2cc, Dmax/Dprescription, and whether the PTV was overlapping the esophagus. Esophageal Dmax (BED10) <62 Gy, D1cc (BED10) <48 Gy, D2cc (BED10) <43 Gy, and Dmax/Dprescription <85% were associated with <20% risk of grade 2 acute esophagitis. Only 2 local recurrences occurred. CONCLUSIONS: Although 25% of patients with tumors near the esophagus developed acute esophagitis (39% of those with PTV overlapping the esophagus), these toxicities were all grade 2 and all temporary. This suggests the safety and efficacy of thoracic SABR for tumors near or abutting the esophagus when treating with high conformity and sharp dose gradients.

Occupant-Based Injury Severity Prediction.

Road traffic injuries continue to be a leading cause of death around the world. Rapid emergency response is a key factor in improving occupant outcomes. Over the past ten years, Injury Severity Prediction (ISP) models have been developed and deployed to assist in effective dispatch of emergency medical services (EMS). Prior versions of ISP have relied on driver-based scenarios that are not relevant in many of the possible autonomous vehicle (AV) contexts. This paper describes the development and validation of occupant-based ISP models that predict injury severity for specific vehicle seat positions. Models show improved predictive performance, sensitivity 80% and specificity over 95%, for front row occupants. Second row occupant models have similar specificity, but sensitivity scores dropped due to occupant heterogeneity and small sample sizes of seriously injured occupants.

Improving the Insulin Pump Initiation Process for Pediatric Patients with Type 1 Diabetes through Application of Lean Quality Improvement Methods.

CONTEXT: Our pediatric diabetes center initiated insulin pump therapy for more than 250 patients with type 1 diabetes in 2014, but onboarding was inefficient. OBJECTIVE: To decrease time from the decision to initiate pump therapy to the ambulatory encounter after pump start (lead time) for new pump users from 132.5 days to less than 110 days within 5 months. DESIGN: Define, Measure, Analyze, Improve, Control method. We identified key problems: Long wait for training classes, unclear metrics, complicated scheduling, and nonstandardized processes. We then implemented 17 changes, including shortened classes, increased class offerings and space, clarified metrics, built a reporting dashboard, designated and cross-trained staff, created appeals letter templates, and educated clinicians. At project conclusion, we established a reaction plan if the processes were not performing as designed. MAIN OUTCOME MEASURES: Outcomes of pump orders placed before and after improvements were implemented. RESULTS: During this project, 229 patients initiated the pump start process. Median lead time decreased from 132.5 to 98.5 days (p = 0.007). Patients with lead time under 110 days increased from 37% to 60% (p = 0.001). There were 31 pump nonstarters, with no significant association between group and whether the patient was a starter or nonstarter (p = 0.58). Nonstarters had a longer diabetes duration (median = 3.43 vs 2.05 years, p = 0.001). CONCLUSION: Project goals were met. A high proportion of patients not starting pump therapy was discovered, but this was not affected by the project. We implemented further changes and a process-monitoring system.

Patterns of island change and persistence offer alternate adaptation pathways for atoll nations.

Sea-level rise and climatic change threaten the existence of atoll nations. Inundation and erosion are expected to render islands uninhabitable over the next century, forcing human migration. Here we present analysis of shoreline change in all 101 islands in the Pacific atoll nation of Tuvalu. Using remotely sensed data, change is analysed over the past four decades, a period when local sea level has risen at twice the global average (~3.90 ± 0.4 mm.yr-1). Results highlight a net increase in land area in Tuvalu of 73.5 ha (2.9%), despite sea-level rise, and land area increase in eight of nine atolls. Island change has lacked uniformity with 74% increasing and 27% decreasing in size. Results challenge perceptions of island loss, showing islands are dynamic features that will persist as sites for habitation over the next century, presenting alternate opportunities for adaptation that embrace the heterogeneity of island types and their dynamics.

Constitutive changes in pigment concentrations: implications for estimating isoprene emissions using the photochemical reflectance index.

The photochemical reflectance index (PRI), through its relationship with light use efficiency (LUE) and xanthophyll cycle activity, has recently been shown to hold potential for tracking isoprene emissions from vegetation. However, both PRI and isoprene emissions can also be influenced by changes in carotenoid pigment concentrations. Xanthophyll cycle activity and changes in carotenoid concentrations operate over different timescales, but the importance of constitutive changes in pigment concentrations for accurately estimating isoprene emissions using PRI is unknown. To clarify the physiological mechanisms behind the PRI-isoprene relationship, the light environment of potted Salix viminalis (osier willow) trees was modified to induce acclimation in photosynthetic rates, phytopigments, isoprene emissions and PRI. Acclimation resulted in differences in pigment concentrations, isoprene emissions and PRI. Constitutive changes in carotenoid concentration were significantly correlated with both isoprene emissions and PRI, suggesting that the relationship between PRI and isoprene emissions is significantly influenced by constitutive pigment changes. Consequently knowledge regarding how isoprene emissions are affected by both longer term changes in total carotenoid concentrations and shorter term dynamic adjustments of LUE is required to facilitate interpretation of PRI for monitoring isoprene emissions.

Crowdsourced earthquake early warning.

Earthquake early warning (EEW) can reduce harm to people and infrastructure from earthquakes and tsunamis, but it has not been implemented in most high earthquake-risk regions because of prohibitive cost. Common consumer devices such as smartphones contain low-cost versions of the sensors used in EEW. Although less accurate than scientific-grade instruments, these sensors are globally ubiquitous. Through controlled tests of consumer devices, simulation of an M w (moment magnitude) 7 earthquake on California's Hayward fault, and real data from the M w 9 Tohoku-oki earthquake, we demonstrate that EEW could be achieved via crowdsourcing.

Reframing the challenges to integrated care: a complex-adaptive systems perspective.

INTRODUCTION: Despite over two decades of international experience and research on health systems integration, integrated care has not developed widely. We hypothesized that part of the problem may lie in how we conceptualize the integration process and the complex systems within which integrated care is enacted. This study aims to contribute to discourse regarding the relevance and utility of a complex-adaptive systems (CAS) perspective on integrated care. METHODS: In the Canadian province of Ontario, government mandated the development of fourteen Local Health Integration Networks in 2006. Against the backdrop of these efforts to integrate care, we collected focus group data from a diverse sample of healthcare professionals in the Greater Toronto Area using convenience and snowball sampling. A semi-structured interview guide was used to elicit participant views and experiences of health systems integration. We use a CAS framework to describe and analyze the data, and to assess the theoretical fit of a CAS perspective with the dominant themes in participant responses. RESULTS: Our findings indicate that integration is challenged by system complexity, weak ties and poor alignment among professionals and organizations, a lack of funding incentives to support collaborative work, and a bureaucratic environment based on a command and control approach to management. Using a CAS framework, we identified several characteristics of CAS in our data, including diverse, interdependent and semi-autonomous actors; embedded co-evolutionary systems; emergent behaviours and non-linearity; and self-organizing capacity. DISCUSSION AND CONCLUSION: One possible explanation for the lack of systems change towards integration is that we have failed to treat the healthcare system as complex-adaptive. The data suggest that future integration initiatives must be anchored in a CAS perspective, and focus on building the system's capacity to self-organize. We conclude that integrating care requires policies and management practices that promote system awareness, relationship-building and information-sharing, and that recognize change as an evolving learning process rather than a series of programmatic steps.

Developing a strategic human resources plan for the Urban Angel.

In healthcare a significant portion of the budget is related to human resources. However, many healthcare organizations have yet to develop and implement a focused organizational strategy that ensures all human resources are managed in a way that best supports the successful achievement of corporate strategies. St. Michael's Hospital, in Toronto, Ontario, recognized the benefits of a strategic human resources management plan. During an eight-month planning process, St. Michael's Hospital undertook the planning for and development of a strategic human resources management plan. Key learnings are outlined in this paper.

The 2011 magnitude 9.0 Tohoku-Oki earthquake: mosaicking the megathrust from seconds to centuries.

Geophysical observations from the 2011 moment magnitude (M(w)) 9.0 Tohoku-Oki, Japan earthquake allow exploration of a rare large event along a subduction megathrust. Models for this event indicate that the distribution of coseismic fault slip exceeded 50 meters in places. Sources of high-frequency seismic waves delineate the edges of the deepest portions of coseismic slip and do not simply correlate with the locations of peak slip. Relative to the M(w) 8.8 2010 Maule, Chile earthquake, the Tohoku-Oki earthquake was deficient in high-frequency seismic radiation--a difference that we attribute to its relatively shallow depth. Estimates of total fault slip and surface secular strain accumulation on millennial time scales suggest the need to consider the potential for a future large earthquake just south of this event.

Time-course correlation of biofilm properties and electrochemical performance in single-chamber microbial fuel cells.

The relationship between anode microbial characteristics and electrochemical parameters in microbial fuel cells (MFCs) was analyzed by time-course sampling of parallel single-bottle MFCs operated under identical conditions. While voltage stabilized within 4days, anode biofilms continued growing during the six-week operation. Viable cell density increased asymptotically, but membrane-compromised cells accumulated steadily from only 9% of total cells on day 3 to 52% at 6weeks. Electrochemical performance followed the viable cell trend, with a positive correlation for power density and an inverse correlation for anode charge transfer resistance. The biofilm architecture shifted from rod-shaped, dispersed cells to more filamentous structures, with the continuous detection of Geobacter sulfurreducens-like 16S rRNA fragments throughout operation and the emergence of a community member related to a known phenazine-producing Pseudomonas species. A drop in cathode open circuit potential between weeks two and three suggested that uncontrolled biofilm growth on the cathode deleteriously affects system performance.

Using the balanced scorecard in the development of community partnerships.

The benefits of community partnerships have been well established in the health service literature. However, measuring these benefits and associated outcomes is relatively new. This paper presents an innovative initiative in the application of a balanced scorecard framework for measuring and monitoring partnership activity at the community level, while adopting principles of evidence-based practice to the partnership process. In addition, it serves as an excellent example of how organizations can apply scorecard methodology to move away from relationship-based partnerships and into new collaborations of which they can select - using a formal skill and competency assessment for partnership success.

Biogenic volatile organic compounds as a potential stimulator for organic contaminant degradation by soil microorganisms.

The effects of monoterpenes on the degradation of (14)C-2,4-dichlorophenol (DCP) were investigated in soils collected from areas surrounding monoterpene and non-monoterpene-emitting vegetation. Indigenous microorganisms degraded (14)C-2,4-DCP to (14)CO(2), after 1d contact time. Degradation was enhanced by prior exposure of the soils to 2,4-DCP for 32 d, increasing extents of mineralisation up to 60%. Monoterpene amendments further enhanced 2,4-DCP degradation, but only following pre-exposure to both 2,4-DCP and monoterpene, with total 2,4-DCP mineralisation extents of up to 71%. Degradation was greatest at the higher monoterpene concentrations (> or = 1 microg kg(-1)). Total mineralisation extents were similar between concentrations, but higher than the control and the 0.1 microg kg(-1) amendment, indicating that increases in monoterpene concentration has a diminishing enhancing effect. We suggest that monoterpenes can stimulate the biodegradation of 2,4-DCP by indigenous soil microorganisms and that monoterpene amendment in soils is an effective strategy for removing organic contaminants.

Biodegradation of 2,4-dichlorophenol in the presence of volatile organic compounds in soils under different vegetation types.

It has been suggested that monoterpenes emitted within the soil profile, either by roots or by decaying biomass, may enhance the biodegradation of organic pollutants. The aim of this study was to evaluate the effect of biogenic volatile organic compounds (VOCs) on the catabolism of 2,4-dichlorophenol in soils. Soils were collected from areas surrounding monoterpene (woodland) and nonmonoterpene (grassland)-emitting vegetation types. Soils were spiked with [UL-14C] 2,4-dichlorophenol at 10 mg kg(-1) and amended with alpha-pinene, p-cymene or a mix of monoterpenes (alpha-pinene, limonene and p-cymene in 1:1:1 ratio). The effects of monoterpene addition on the catabolism of [UL-14C] 2,4-dichlorophenol to 14CO2 by indigenous soil microbial communities were assessed in freshly spiked and 4-week-aged soils. It was found that aged woodland soils exhibited a higher level of [UL-14C] 2,4-dichlorophenol degradation, which was subsequently enhanced by the addition of monoterpenes (P<0.001), with the VOC mix and alpha-pinene amendments showing increased [UL-14C] 2,4-dichlorophenol catabolism. This study supports claims that the addition of biogenic VOCs to soils enhances the degradation of xenobiotic contaminants.

Biogenic volatile organic compounds as potential carbon sources for microbial communities in soil from the rhizosphere of Populus tremula.

Catabolism of a (14)C-labelled volatile monoterpene compound (geraniol) to (14)CO(2) was investigated in soils taken from the rhizosphere at distances up to 200 cm from the trunks of three small Populus tremula trees growing at different sites in Slovenia. Emissions of limonene of up to 18 microg m(-2) h(-1) were detected from the soil surface at each site. Evolution of (14)C-labelled CO(2) was measured as a product of catabolism of (14)C-labelled geraniol introduced into the soil samples. Indigenous soil microorganisms degraded the geraniol rapidly. There was a significant difference in relative lag times and rates of catabolism along the gradient from the tree trunks, with relatively longer lag times and lower rates occurring in soil samples from the farthest point from the tree.

Circadian control of isoprene emissions from oil palm (Elaeis guineensis).

The emission of isoprene from the biosphere to the atmosphere has a profound effect on the Earth's atmospheric system. Until now, it has been assumed that the primary short-term controls on isoprene emission are photosynthetically active radiation and temperature. Here we show that isoprene emissions from a tropical tree (oil palm, Elaeis guineensis) are under strong circadian control, and that the circadian clock is potentially able to gate light-induced isoprene emissions. These rhythms are robustly temperature compensated with isoprene emissions still under circadian control at 38 degrees C. This is well beyond the acknowledged temperature range of all previously described circadian phenomena in plants. Furthermore, rhythmic expression of LHY/CCA1, a genetic component of the central clock in Arabidopsis thaliana, is still maintained at these elevated temperatures in oil palm. Maintenance of the CCA1/LHY-TOC1 molecular oscillator at these temperatures in oil palm allows for the possibility that this system is involved in the control of isoprene emission rhythms. This study contradicts the accepted theory that isoprene emissions are primarily light-induced.

Amylin replacement therapy in patients with insulin-requiring type 2 diabetes.

Normally, the release of glucagon is halted at the beginning of a meal by a direct mechanism: insulin secretion from the beta cells within the pancreas inhibits the release of glucagon from the beta cells. An "indirect" mechanism--amylin (a neuroendocrine hormone also secreted from the beta cells)--suppresses the release of glucagon through the central nervous system. In type 2 diabetes, the first phase insulin release is absent, and as amylin is released in direct proportion to insulin, both mechanisms to suppress glucagon are absent. The result is that glucagon secretion and, ultimately, the stimulation of hepatic glucose release continue, resulting in extreme postprandial hyperglycemia. It has been shown that amylin supplementation with injections of the human amylin analogue pramlintide, in patients with insulin-requiring type 2 diabetes, helps limit postprandial hyperglycemia. Amylin supplementation not only suppresses glucagon secretion but also slows the absorption of glucose in the intestines and limits nutrient intake by providing a feeling of satiety, resulting in a moderate reduction in body weight for many patients. Recently approved by the FDA, pramlintide is now available for clinical use. However, it is important that pramlintide be prescribed only for selected patients and that these patients are thoroughly educated in the use of this agent, especially during initiation of treatment. Patients suited to pramlintide use are those who have not achieved adequate glycemic control despite optimal insulin use, are under the care of a professional health care provider skilled in the use of insulin and a diabetes educator, and are well-disciplined in diabetes self-management.

Development and application of an urban tree air quality score for photochemical pollution episodes using the Birmingham, United Kingdom, area as a case study.

An atmospheric chemistry model (CiTTyCAT) is used to quantify the effects of trees on urban air quality in scenarios of high photochemical pollution. The combined effects of both pollutant deposition to and emission of biogenic volatile organic compounds (BVOC) from the urban forest are considered, and the West Midlands, metropolitan area in the UK is used as a case study. While all trees can be beneficial to air quality in terms of the deposition of O3, NO2, CO, and HNO3, some trees have the potential to contribute to the formation of O3 due to the reaction of BVOC and NOx. A number of model scenarios are used to develop an urban tree air quality score (UTAQS) that ranks trees in order of their potential to improve air quality. Of the 30 species considered, pine, larch, and silver birch have the greatest potential to improve urban air quality, while oaks, willows, and poplars can worsen downwind air quality if planted in very large numbers. The UTAQS classification is designed with practitioners in mind, to help them achieve sustainable urban air quality. The UTAQS classification is applicable to all urban areas of the UK and other mid-latitude, temperate climate zones that have tree species common to those found in UK urban areas. The modeling approach used here is directly applicable to all areas of the world given the appropriate input data. It provides a tool that can help to achieve future sustainable urban air quality.

Opportunistic emissions of volatile isoprenoids.

Isoprene, monoterpenes and sesquiterpenes are synthesized and emitted by some plant species, but not all plant species have this ability. These volatile, nonessential isoprenoid compounds share the same biochemical precursors as larger essential isoprenoids such as gibberellic acids and carotenoids. They have many protective and ecological functions for the plant species that produce them, but plant species that do not produce these compounds also grow and reproduce successfully. Here, we develop an 'opportunist hypothesis' suggesting that (i) volatile isoprenoid production takes advantage of dimethylallyl diphosphate (DMAPP) and its isomer isopentenyl diphosphate (IPP), which are synthesized primarily to produce essential isoprenoids, and (ii) conditions affecting synthesis of the higher isoprenoids will affect the production and emission of volatile isoprenoids.