Cuvier's beaked whales (Ziphius cavirostris) are known as extreme divers, though behavioral data from this difficult-to-study species have been limited. They are also the species most often stranded ...in association with Mid-Frequency Active (MFA) sonar use, a relationship that remains poorly understood. We used satellite-linked tags to record the diving behavior and locations of eight Ziphius off the Southern California coast for periods up to three months. The effort resulted in 3732 hr of dive data with associated regional movements--the first dataset of its kind for any beaked whale--and included dives to 2992 m depth and lasting 137.5 min, both new mammalian dive records. Deep dives had a group mean depth of 1401 m (s.d. = 137.8, n = 1142) and duration of 67.4 min (s.d. = 6.9). The group mean time between deep dives was 102.3 min (s.d. = 30.8, n = 783). While the previously described stereotypic pattern of deep and shallow dives was apparent, there was considerable inter- and intra-individual variability in most parameters. There was significant diel behavioral variation, including increased time near the surface and decreased shallow diving at night. However, maximum depth and the proportion of time spent on deep dives (presumed foraging), varied little from day to night. Surprisingly, tagged whales were present within an MFA sonar training range for 38% of days locations were received, and though comprehensive records of sonar use during tag deployments were not available, we discuss the effects frequent acoustic disturbance may have had on the observed behaviors. These data better characterize the true behavioral range of this species, and suggest caution should be exercised when drawing conclusions about behavior using short-term datasets.
The ICARUS T600 detector is the largest liquid argon time projection chamber (LArTPC) to be built and operated 1. This detector was in operation in the INFN Gran Sasso underground laboratory until ...2012, exposed to the CERN Neutrino to Gran Sasso (CNGS) νµ beam, performing neutrino oscillation studies. The ICARUS T600 is presently under refurbishment in order to make it suitable for surface level operation, as it will serve as the far detector for the Short-Baseline Neutrino (SBN) Program at Fermilab 2. A major upgrade of the ICARUS detector in order to allow it to cope with a high cosmic background is the upgrade of the light collection system. The study presented here shows a simulation to optimize the PMT layout to allow for the localization and identification of interaction within the T600. An excellent performance can be obtained, with an error on the localization smaller than 20 cm and of the order of a few percent in the identification of cosmic rays.
ABSTRACT We apply a number of statistical and machine learning techniques to classify and rank gamma-ray sources from the Third Fermi Large Area Telescope Source Catalog (3FGL), according to their ...likelihood of falling into the two major classes of gamma-ray emitters: pulsars (PSR) or active galactic nuclei (AGNs). Using 1904 3FGL sources that have been identified/associated with AGNs (1738) and PSR (166), we train (using 70% of our sample) and test (using 30%) our algorithms and find that the best overall accuracy (>96%) is obtained with the Random Forest (RF) technique, while using a logistic regression (LR) algorithm results in only marginally lower accuracy. We apply the same techniques on a subsample of 142 known gamma-ray pulsars to classify them into two major subcategories: young (YNG) and millisecond pulsars (MSP). Once more, the RF algorithm has the best overall accuracy (∼90%), while a boosted LR analysis comes a close second. We apply our two best models (RF and LR) to the entire 3FGL catalog, providing predictions on the likely nature of unassociated sources, including the likely type of pulsar (YNG or MSP). We also use our predictions to shed light on the possible nature of some gamma-ray sources with known associations (e.g., binaries, supernova remnants/pulsar wind nebulae). Finally, we provide a list of plausible X-ray counterparts for some pulsar candidates, obtained using Swift, Chandra, and XMM. The results of our study will be of interest both for in-depth follow-up searches (e.g., pulsar) at various wavelengths and for broader population studies.
Implement and demonstrate feasibility of in situ simulations to identify latent safety threats (LSTs) at a higher rate than lab-based training, and reinforce teamwork training in a paediatric ...emergency department (ED).
Multidisciplinary healthcare providers responded to critical simulated patients in an urban ED during all shifts. Unannounced in situ simulations were limited to 10 min of simulation and 10 min of debriefing, and were video recorded. A standardised debriefing template was used to assess LSTs. The primary outcome measure was the number and type of LSTs identified during the simulations. Secondary measures included: participants' assessment of impact on patient care and value to participants. Blinded video review using a modified Anaesthetists Non-Technical Skills scale was used to assess team behaviours.
218 healthcare providers responded to 90 in situ simulations conducted over 1 year. A total of 73 LSTs were identified; a rate of one every 1.2 simulations performed. In situ simulations were cancelled at a rate of 28% initially, but the cancellation rate decreased as training matured. Examples of threats identified include malfunctioning equipment and knowledge gaps concerning role responsibilities. 78% of participants rated the simulations as extremely valuable or valuable, while only 5% rated the simulation as having little or no value. Of those responding to a postsimulation survey, 77% reported little or no clinical impact. Video recordings did not indicate changes in non-technical skills during this time.
In situ simulation is a practical method for the detection of LSTs and to reinforce team training behaviours. Embedding in situ simulation as a routine expectation positively affected operations and the safety climate in a high risk clinical setting.
Water security is a top concern for social well-being, and dramatic changes in the availability of freshwater have occurred as a result of human uses and landscape management. Elevated nutrient ...loading and perturbations to major ion composition have resulted from human activities and have degraded freshwater resources. This study addresses the emerging nature of streamwater quality in the 21st century through analysis of concentrations and trends in a wide variety of constituents in streams and rivers of the U.S. Concentrations of 15 water quality constituents including nutrients, major ions, sediment, and specific conductance were analyzed over the period 1982–2012 and a targeted trend analysis was performed from 1992 to 2012. Although environmental policy is geared toward addressing the long-standing problem of nutrient overenrichment, these efforts have had uneven success, with decreasing nutrient concentrations at urbanized sites and little to no change at agricultural sites. Additionally, freshwaters are being salinized rapidly in all human-dominated land use types. While efforts to control nutrients are ongoing, rapid salinity increases are ushering in a new set of poorly defined issues. Increasing salinity negatively affects biodiversity, mobilizes sediment-bound contaminants, and increases lead contamination of drinking water, but its effects are not well integrated into current paradigms of water management.
Neutrophil/lymphocyte ratio (NLR), defined as absolute neutrophils count divided by absolute lymphocytes count, has been reported as poor prognostic factor in several neoplastic diseases but only a ...few data are available about unresectable metastatic colorectal cancer (mCRC) patients (pts). The aim of our study was to evaluate the prognostic and predictive role of NLR in the TRIBE trial.
Pts enrolled in TRIBE trial were included. TRIBE is a multicentre phase III trial randomizing unresectable and previously untreated mCRC pts to receive FOLFOXIRI or FOLFIRI plus bevacizumab. A cut-off value of 3 was adopted to discriminate pts with low (NLR<3) versus high (NLR≥3) NLR, as primary analysis. As secondary analysis, NLR was treated as an ordinal variable with three levels based on terciles distribution.
NLR at baseline was available for 413 patients. After multiple imputation at univariate analysis, patients with high NLR had significantly shorter progression-free survival (PFS) hazard ratio (HR) 1.27 (95% CI 1.05–1.55), P=0.017 and overall survival (OS) HR 1.56 (95% CI 1.25–1.95), P<0.001 than patients with low NLR. In the multivariable model, NLR retained a significant association with OS HR 1.44 (95% CI 1.14–1.82), P=0.014 but not with PFS HR 1.18 (95% CI 0.95–1.46), P=0.375. No interaction effect between treatment arm and NLR was evident in terms of PFS (P for interaction=0.536) or OS (P for interaction=0.831). Patients with low HR 0.84 (95% CI 0.64–1.08) and high HR 0.73 (95% CI 0.54–0.97) NLR achieved similar PFS benefit from the triplet and consistent results were obtained in terms of OS HR 0.83 (95% CI 0.62–1.12) for low NLR; HR 0.82 (95% CI 0.59–1.12) for high NLR.
This study confirmed the prognostic role of NLR in mCRC pts treated with bevacizumab plus chemotherapy in the first line, showing the worse prognosis of pts with high NLR. The advantage of the triplet is independent of NLR at baseline.
Purpose
The purpose of this study was to assess the overall burden of pancreatic cancer in Europe, with a focus on survival time in a real-world setting, and the overall healthy life lost to the ...disease.
Methods
Real-world data were retrieved from peer-reviewed, observational studies identified by an electronic search. We performed two de novo analyses: a proportional shortfall analysis to quantify the proportion of healthy life lost to pancreatic cancer and an estimation of the aggregate life-years lost annually in Europe.
Results
Ninety-one studies were included. The median, age-standardised incidence of pancreatic cancer per 100,000 was 7.6 in men and 4.9 in women. Overall median survival from diagnosis was 4.6 months; median survival was 2.8–5.7 months in patients with metastatic disease. The proportional shortfall analysis showed that pancreatic cancer results in a 98 % loss of healthy life, with a life expectancy at diagnosis of 4.6 months compared to 15.1 years for an age-matched healthy population. Annually, 610,000–915,000 quality-adjusted life-years (QALYs) are lost to pancreatic cancer in Europe. Patients had significantly lower scores on validated health-related quality of life instruments versus population norms.
Conclusions
To the best of our knowledge, this is the first study to systematically review real-world overall survival and patient outcomes of pancreatic cancer patients in Europe outside the context of clinical trials. Our findings confirm the poor prognosis and short survival reported by national studies. Pancreatic cancer is a substantial burden in Europe, with nearly a million aggregate life-years lost annually and almost complete loss of healthy life in affected individuals.
Injury is the leading cause of childhood morbidity and mortality. Injury prevention (IP) initiatives are often created in isolation from the communities most affected. We hypothesized that the use of ...a comprehensive approach to injury prevention through community partnerships will result in a measurable reduction in pediatric injuries.
The IP program at our free-standing level 1 pediatric trauma center developed partnerships within eight targeted high-risk communities. IP coordinators and community partners implemented programs driven by community-specific injury data and community input. Programs focused on home, bike, playground, pedestrian, and child passenger safety. Program components included in–home education with free safety equipment and installation; free bike helmet fittings and distribution; community playground builds; and car seat classes with education, free car seat distribution and installation. Using trauma registry data, we compared injuries rates in targeted communities with non-intervention communities county-wide over an eight-year period.
Between 2012 and 2019, nearly 4000 families received home safety equipment and education through community partnerships. Approximately 2000 bike helmets, 900 car/booster seats, in addition to safety messages and education were provided across the intervention communities. Over this 8-year time period, the injury rates significantly decreased by 28.4%, across the eight targeted high-risk communities, compared to a 10.9% reduction in non-intervention communities across the county.
Effective injury prevention can be achieved through partnerships, working in solidarity with community members to address actual areas of concern to them. Sharing data, seeking ongoing community input, continuously reviewing learnings, and implementing identified changes are crucial to the success of such partnerships.
Level III.
Despite major advances in the management of metastatic colorectal cancer (mCRC) with liver-only involvement, relapse rates are high and reliable prognostic markers are needed.
To assess the ...prognostic impact of BRAF and RAS mutations in a large series of liver-resected patients, medical records of 3024 mCRC patients were reviewed. Eligible cases undergoing potentially curative liver resection were selected. BRAF and RAS mutational status was tested on primary and/or metastases by means of pyrosequencing and mass spectrometry genotyping assay. Primary endpoint was relapse-free survival (RFS).
In the final study population (N=309) BRAF mutant, RAS mutant and all wild-type (wt) patients were 12(4%), 160(52%) and 137(44%), respectively. Median RFS was 5.7, 11.0 and 14.4 months respectively and differed significantly (Log-rank, P=0.043). At multivariate analyses, BRAF mutant had a higher risk of relapse in comparison to all wt (multivariate hazard ratio (HR)=2.31; 95% CI, 1.09-4.87; P=0.029) and to RAS mutant (multivariate HR=2.06; 95% CI, 1.02-4.14; P=0.044). Similar results were obtained in terms of overall survival. Compared with all wt patients, RAS mutant showed a higher risk of death (HR=1.47; 95% CI, 1.05-2.07; P=0.025), but such effect was lost at multivariate analyses.
BRAF mutation is associated with an extremely poor median RFS after liver resection and with higher probability of relapse and death. Knowledge of BRAF mutational status may optimise clinical decision making in mCRC patients potentially candidate to hepatic surgery. RAS status as useful marker in this setting might require further studies.
Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC ...(mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers. Treatment decisions for patients with mCRC must be evidence-based. Thus, these ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.
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