The Complexity of the Practice of Ecosystem-Based Management.

In the United States, there are more than 20 federal agencies that manage over 140 ocean statutes (Crowder et al., 2006). A history of disjointed, single sector management has resulted in a one-dimensional view of ecosystems, administrative systems, and the socio-economic drivers that affect them. In contrast, an ecosystem-based approach to management is inherently multi-dimensional. Ecosystem-based approaches to management (EBM) are at the forefront of progressive science and policy discussions. Both the U.S. Commission on Ocean Policy (USCOP, 2004) and the Pew Oceans Commission (POC, 2003) reports called for a better understanding of the impact of human activities on the coastal ocean and the result was President Obama’s National Policy for the Stewardship of the Ocean, our Coasts, and the Great Lakes (2010). EBM is holistic by seeking to include all stakeholders affected by marine policy in decision-making. Stakeholders may include individuals from all levels of government, academia, environmental organizations, and marine-dependent businesses and industry. EBM processes require decision-makers to approach marine management differently and more comprehensively to sufficiently require a more sophisticated conceptual understanding of the process and the people involved. There are implicit cognitive, interpersonal, and intra-personal demands of EBM that are not addressed by current literature. This research seeks to understand the mental demands of EBM. A constructive developmental framework is used to illuminate how decision-makers reason or make sense of the ideals and values underlying EBM, the mutual relationships that must be built among natural resource management agencies, and the personal experiences and emotions that accompany change

Surgery or Non-surgical Treatment of <= 8 mm Non-small Cell Lung Cancer: A Population-Based Study

Background: Timing for intervention of small indeterminate pulmonary nodules has long been a topic of debate given the low incidence of malignancy and difficulty in obtaining a definite preoperative diagnosis. We sought to determine survival outcomes of surgical and non-surgical managements in non-small cell lung cancer (NSCLC) ≤8 mm, which may provide a reference for prospective decision-making for patients with suspected NSCLC. Method: A total of 1,652 patients with Stage IA NSCLC ≤8 mm were identified from the Surveillance, Epidemiology, and End Results (SEER) database and categorized into surgery and non-surgery groups. Chi-square test, t-test and Mann-Whitney U test were used to compare the baseline characteristics between groups. Survival curves were depicted using Kaplan-Meier method and compared by log-rank test. Cox proportional hazard model was used for univariate and multivariate analyses. Adjustment of confounding factors between groups was performed by propensity score matching. Results: The surgery and non-surgery groups included 1,438 and 208 patients, respectively. Patients in surgery group demonstrated superior survival outcome than patients in non-surgery group both before [overall survival (OS): HR, 16.22; 95% CI, 11.48–22.91, p < 0.001; cancer-specific survival (CSS): HR, 49.6; 95% CI, 31.09–79.11, p < 0.001] and after (OS: HR, 3.12; 95% CI, 2.40–4.05, p < 0.001; CSS: HR, 3.85; 95% CI, 2.74–5.40, p < 0.001) propensity score matching. The 30-day mortality rates were 3.1 and 12.0% in surgery and non-surgery groups, respectively. Multivariate analysis suggested age, sex, race, tumor size, grade, pathological stage were all independent prognostic factors in patients with ≤8 mm NSCLC. A comparison of surgical resections revealed a survival superiority of lobectomy over sub-lobectomy. In terms of CSS, no statistically significant difference was found between segmentectomy and wedge resection. Conclusion: The current SEER database showed better prognosis of surgical resection than non-surgical treatment in patients with ≤8 mm NSCLC. However, the factors that should be essentially included in the proper propensity-matched analysis, such as comorbidity, cardiopulmonary function and performance status were unavailable and the true superiority or inferiority should be examined further by ongoing randomized trial, especially comparing surgery and stereotactic body irradiation

Long-range interactions and non-extensivity in ferromagnetic spin models

The Ising model with ferromagnetic interactions that decay as $1/r^\alpha$ is analyzed in the non-extensive regime $0\leq\alpha\leq d$, where the thermodynamic limit is not defined. In order to study the asymptotic properties of the model in the $N\rightarrow\infty$ limit ($N$ being the number of spins) we propose a generalization of the Curie-Weiss model, for which the $N\rightarrow\infty$ limit is well defined for all $\alpha\geq 0$. We conjecture that mean field theory is {\it exact} in the last model for all $0\leq\alpha\leq d$. This conjecture is supported by Monte Carlo heat bath simulations in the $d=1$ case. Moreover, we confirm a recently conjectured scaling (Tsallis\cite{Tsallis}) which allows for a unification of extensive ($\alpha>d$) and non-extensive ($0\leq\alpha\leq d$) regimes.Comment: RevTex, 12 pages, 1 eps figur

Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease

Lung cancer diagnostics have progressed greatly in the previous decade. Development of molecular testing to identify an increasing number of potentially clinically actionable genetic variants, using smaller samples obtained via minimally invasive techniques, is a huge challenge. Tumour heterogeneity and cancer evolution in response to therapy means that repeat biopsies or circulating biomarkers are likely to be increasingly useful to adapt treatment as resistance develops. We highlight some of the current challenges faced in clinical practice for molecular testing of EGFR, ALK, and new biomarkers such as PDL1. Implementation of next generation sequencing platforms for molecular diagnostics in non-small-cell lung cancer is increasingly common, allowing testing of multiple genetic variants from a single sample. The use of next generation sequencing to recruit for molecularly stratified clinical trials is discussed in the context of the UK Stratified Medicine Programme and The UK National Lung Matrix Trial

Transient Inhibition of PI3Kδ Enhances the Therapeutic Effect of Intravenous Delivery of Oncolytic Vaccinia Virus

Tumor-targeting oncolytic viruses such as vaccinia virus (VV) are attractive cancer therapeutic agents that act through multiple mechanisms to provoke both tumor lysis and anti-tumor immune responses. However, delivery of these agents remains restricted to intra-tumoral administration, which prevents effective targeting of inaccessible and disseminated tumor cells. In the present study we have identified transient pharmacological inhibition of the leukocyte-enriched phosphoinositide 3-kinase δ (PI3Kδ) as a novel mechanism to potentiate intravenous delivery of oncolytic VV to tumors. Pre-treatment of immunocompetent mice with the PI3Kδ-selective inhibitor IC87114 or the clinically approved idelalisib (CAL-101), prior to intravenous delivery of a tumor-tropic VV, dramatically improved viral delivery to tumors. This occurred via an inhibition of viral attachment to, but not internalization by, systemic macrophages through perturbation of signaling pathways involving RhoA/ROCK, AKT, and Rac. Pre-treatment using PI3Kδ-selective inhibitors prior to intravenous delivery of VV resulted in enhanced anti-tumor efficacy and significantly prolonged survival compared to delivery without PI3Kδ inhibition. These results indicate that effective intravenous delivery of oncolytic VV may be clinically achievable and could be useful in improving anti-tumor efficacy of oncolytic virotherapy

The cross on rings performed by an Olympic champion

The cross is a key skill in Male Artistic Gymnastics rings routines. However, few researches were found about this skill. There is knowledge about the forces needed to perform the cross, or about muscles activation, separately. The aim of this paper was to accomplish a comprehensive research about the biomechanics of cross on rings, in order to obtain a descriptive model about this skill. Therefore, the currently Olympic champion on rings event volunteered in this research. He performed three crosses with the usual apparatus in his training gym. The measurement methods were combined: One digital video camera, one strain gauge in each cable and surface electromyography of nine right shoulder muscles were used. Statistical analyses were performed by parametric and non parametric tests and descriptive statistics. Symmetry values were calculated for shoulder angles and cables of right and left side. Coefficient of variation of muscle activation and co contraction were verified. Within gymnast variability was calculated using biological coefficient of variation (BCV), discretely for kinematic measures. Low variability values of shoulder angles and cable forces were verified and low values of asymmetry as well. Muscle activation varied according to muscle function, while co-contraction values were different among trials. These results pointed out the characteristics of the cross performed by an elite gymnast. Knowledge about the characteristics of cross can inform coaches, practitioners and clinicians how a successful skill should be presented

Evidence of exactness of the mean field theory in the nonextensive regime of long-range spin models

The q-state Potts model with long-range interactions that decay as 1/r^alpha subjected to an uniform magnetic field on d-dimensional lattices is analized for different values of q in the nonextensive regime (alpha between 0 and d). We also consider the two dimensional antiferromagnetic Ising model with the same type of interactions. The mean field solution and Monte Carlo calculations for the equations of state for these models are compared. We show that, using a derived scaling which properly describes the nonextensive thermodynamic behaviour, both types of calculations show an excellent agreement in all the cases here considered, except for alpha=d. These results allow us to extend to nonextensive magnetic models a previous conjecture which states that the mean field theory is exact for the Ising one.Comment: 10 pages, 4 figure

Imprints of the Quantum World in Classical Mechanics

The imprints left by quantum mechanics in classical (Hamiltonian) mechanics are much more numerous than is usually believed. We show Using no physical hypotheses) that the Schroedinger equation for a nonrelativistic system of spinless particles is a classical equation which is equivalent to Hamilton's equations.Comment: Paper submitted to Foundations of Physic

Implementation of the Time-to-Event Continuous Reassessment Method Design in a Phase I Platform Trial Testing Novel Radiotherapy-Drug Combinations-CONCORDE

\ua9 2022 by American Society of Clinical Oncology. PURPOSE CONCORDE is the first phase I drug-radiotherapy (RT) combination platform in non-small-cell lung cancer, designed to assess multiple different DNA damage response inhibitors in combination with radical thoracic RT. Time-to-event continuous reassessment method (TiTE-CRM) methodology will inform dose escalation individually for each different DNA damage response inhibitor-RT combination and a randomized calibration arm will aid attribution of toxicities. We report in detail the novel statistical design and implementation of the TiTE-CRM in the CONCORDE trial. METHODS Statistical parameters were calibrated following recommendations by Lee and Cheung. Simulations were performed to assess the operating characteristics of the chosen models and were written using modified code from the R package dfcrm. RESULTS The results of the simulation work showed that the proposed statistical model setup can answer the research questions under a wide range of potential scenarios. The proposed models work well under varying levels of recruitment and with multiple adaptations to the original methodology. CONCLUSION The results demonstrate how TiTE-CRM methodology may be used in practice in a complex dose-finding platform study. We propose that this novel phase I design has potential to overcome some of the logistical barriers that for many years have prevented timely development of novel drug-RT combinations

Changes in the Management of Patients having Radical Radiotherapy for Lung Cancer during the First Wave of the COVID-19 Pandemic in the UK.

AIMS: In response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I-III lung cancer from April to October 2020. MATERIALS AND METHODS: Lung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression. RESULTS: In total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease. CONCLUSIONS: The COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes