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We propose in this paper a method to assess the effects of a contaminant on a micro-ecosystem, integrating the population dynamics and the interactions between species. For that, we developed a dynamic model to describe the functioning of a microcosm exposed to a contaminant and to discriminate direct and indirect effects. Then, we get back from modelling to experimentation in order to identify which of the collected data have really been necessary and sufficient to estimate model parameters in order to propose a more efficient experimental design for further investigations. We illustrated our approach using a 2-L laboratory microcosm involving three species (the duckweed Lemna minor, the microalgae Pseudokirchneriella subcapitata and the daphnids Daphnia magna) exposed to cadmium contamination. We modelled the dynamics of the three species and their interactions using a mechanistic model based on coupled ordinary differential equations. The main processes occurring in this three-species microcosm were thus formalized, including growth and settling of algae, growth of duckweeds, interspecific competition between algae and duckweeds, growth, survival and grazing of daphnids, as well as cadmium effects. We estimated model parameters by Bayesian inference, using simultaneously all the data issued from multiple laboratory experiments specifically conducted for this study. Cadmium concentrations ranged between 0 and 50 μg.L-1 . For all parameters of our model, we obtained biologically realistic values and reasonable uncertainties. The cascade of cadmium effects, both direct and indirect, was identified. Critical effect concentrations were provided for the life history traits of each species. An example of experimental design adapted to this kind a microcosm was also proposed. This approach appears promising when studying contaminant effects on ecosystem functioning.

The presence of cervical lymph node metastasis in patients with head and neck cancer is associated with an unfavorable prognosis. Reports vary as to whether various conventional radiographic studies, such as computed tomography (CT) and magnetic resonance imaging, confer an advantage over physical examination in the patient without clinical findings of cervical metastasis (N0). Positron emission tomography (PET) is a functional imaging modality that has recently been used for head and neck neoplasms. The use of PET in the evaluation of the N0-staged neck in 14 consecutive patients with squamous cell carcinoma (SCC) of the upper aerodigestive tract is reported. Seven patients (50%) undergoing 13 neck dissections had pathologic evidence of disease. PET scans were positive in five patients with pathologically confirmed cervical metastasis. PET scans were negative in seven patients (11 neck dissections) with no pathologic evidence of disease. PET scans were positive for unilateral cervical metastasis in two of three patients with involvement of a single lymph node. PET scans were positive in two of three patients with more than two lymph nodes involved. PET had an accuracy of 100% in the eight patients with SCC of the oral cavity. In patients with oropharyngeal or hypopharyngeal carcinoma PET localized cervical metastasis in two of four patients with neck metastasis. In the patient with an N0-staged neck on clinical examination, PET was found to have an overall sensitivity of 78%, specificity of 100%, positive predictive value of 100%, negative predictive value of 88%, and accuracy of 92%. CT demonstrated sensitivity of 57%, specificity of 90%, positive predictive value of 80%, negative predictive value of 75%, and accuracy of 76%. PET showed a trend in increased accuracy (P = 0.11) over CT. PET appears to be a promising diagnostic aid that may be applied when evaluating the N0-staged neck, especially for SCC of the oral cavity. [ABSTRACT FROM AUTHOR]

"A Who's Who of pesticides is therefore of concern to us all. If we are going to live so intimately with these chemicals eating and drinking them, taking them into the very marrow of our bones - we had better know something about their nature and their power."-Rachel Carson, Silent Spring. In her day, Rachel Carson was right: plant protection products (PPP), like all the other chemical substances that humans increasingly release into the environment without further precaution, are among our worst enemies today (Bruhl and Zaller, 2019; Naidu et al., 2021; Tang et al., 2021; Topping et al., 2020). All compartments of the biosphere, air, soil and water, are potential reservoirs within which all species that live there are impaired. Birds are particularly concerned: PPP are recognized as a factor in the decline of their abundance and diversity predominantly in agricultural landscapes. Due to the restrictions on vertebrates testing, in silico-based approaches are an ideal choice alternative given input data are available. This is where the problem lies as we will illustrate in this paper. We performed an extensive literature search covering a long period of time, a wide diversity of bird species, a large range of chemical substances, and as many model types as possible to encompass all our future need to improve environmental risk assessment of chemicals for birds. In the end, we show that poultry species exposed to pesticides are the most studied at the individual level with physiologically based toxicokinetic models. To go beyond, with more species, more chemical types, over several levels of biological organization, we show that observed data are crucially missing (Gilbert, 2011). As a consequence, improving existing models or developing new ones could be like climbing Everest if no additional data can be gathered, especially on chemical effects and toxicodynamic aspects., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Radium-223 dichloride (Ra-223) is now frequently used to treat prostate cancer that has metastasized to bone, although patient selection continues to be suboptimal for determining who will benefit most from this novel treatment modality., Materials and Methods: Seventy-nine patients with metastatic castration-resistant prostate cancer (mCRPC) were treated with Ra-223 from 2012 to 2016. The burden of skeletal metastasis was determined for each using the Bone Scan Index (BSI) as a ratio of diseased to normal bone. Clinical, laboratory, and survival data were collected and examined for associations with BSI, and treatment tolerability was assessed., Results: Chemotherapy-naïve patients were significantly more likely to complete the full course of treatment. Median follow-up was 31 months (range 0.7-38.8 months) and median overall survival was 15.4 months (range 9.5-20.6 months). Overall survival was significantly associated with findings on bone scans (P < .05). Patients with higher BSI tended toward poorer outcomes. Nearly half the patients with low baseline BSI survived 3 years or more following Ra-223 treatment. By contrast, only 20% of the patients with high baseline BSI lived for 1 year, and none lived for an additional 3. Baseline BSI was significantly associated with decreased hemoglobin, higher serum PSA and alkaline phosphatase levels, and treatment-associated reductions in platelet and absolute neutrophil counts., Conclusion: Our results suggest better outcomes to Ra-223 therapy for patients who are chemotherapy-naïve and who undergo treatment earlier in the course of their disease as reflected by low BSI and concordant laboratory parameters., (© The Author(s) 2023. Published by Oxford University Press.)

New Approach Methodologies (NAMs) provide tools for supporting both human and environmental risk assessment (HRA and ERA). This short review provides recent insights regarding the use of NAMs in ERA of food and feed chemicals. We highlight the usefulness of tiered methods supporting weight-of-evidence approaches in relation to problem formulation (i.e., data availability, time, and resource availability). In silico models, including quantitative structure activity relationship models, support filling data gaps when no chemical property or ecotoxicological data are available, and biologically-based models (e.g., toxicokinetic-toxicodynamic models, dynamic energy models, physiologically-based models and species sensitivity distributions) are applicable in more data rich situations, including landscape-based modelling approaches. Particular attention is given to provide practical examples to apply the approaches described in real-world settings. We conclude with future perspectives, with regards to the need for addressing complex challenges such as chemical mixtures and multiple stressors in a wide range of organisms and ecosystems.

The role of 18F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computerized tomography (PET-CT) in evaluation of bone marrow involvement (BMI) in patients with T-cell lymphoma (TCL) is poorly understood. We investigated whether PET-CT could replace bone marrow aspiration and biopsy (BMAB) in TCL. Sixty patients with newly diagnosed TCL who underwent both diagnostic PET-CT and BMAB were identified. BMI was tissue-confirmed in 15 (25%) cases, however only 8 of these 15 showed BMI on PET-CT (sensitivity of 53.3%, specificity of 100%). BMI by BMAB was associated with lower progression-free survival (PFS) ( p  = 0.038 ) and overall survival (OS) ( p =  0.003) while PET-CT BMI was associated only with OS ( p =  0.02). BMI detected by BMAB in the setting of a negative PET-CT had similar inferior prognosis as BMI identified on PET-CT. Thus, PET-CT in TCL misses BMI in almost half of the cases detected by BMAB and hence cannot substitute BMAB in evaluation of TCL.

Aim/objectives/background: The goal of therapy with unsealed radiopharmaceutical sources is to provide either cure or significant prolongation of disease-specific survival, and effective reduction and/or prevention of adverse disease-related symptoms or untoward events while minimizing treatment-associated side effects and complications. Radium-223 dichloride (radium-223) is an alpha particle-emitting isotope used for targeted bone therapy. This practice parameter is intended to guide appropriately trained and licensed physicians performing therapy with radium-223. Such therapy requires close cooperation and communication between the physicians who are responsible for the clinical management of the patient and those who administer radiopharmaceutical therapy and manage the attendant side effects. Adherence to this parameter should help to maximize the efficacious use of radium-223, maintain safe conditions, and ensure compliance with applicable regulations., Methods: This practice parameter was developed according to the process described on the American College of Radiology (ACR) website ("The Process for Developing ACR Practice Parameters and Technical Standards," www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters of the ACR Commission on Radiation Oncology in collaboration with the American College of Nuclear Medicine (ACNM), the American Society for Radiation Oncology (ASTRO), and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). All these societies contributed to the development of the practice parameter and approved the final document., Results: This practice parameter addresses the many factors which contribute to appropriate, safe, and effective clinical use of radium-223. Topics addressed include qualifications and responsibilities of personnel, specifications of patient examination and treatment; documentation, radiation safety, quality control/improvement, infection control, and patient education., Conclusions: This practice parameter is intended as a tool to guide clinical use of radium-223 with the goal of facilitating safe and effective medical care based on current knowledge, available resources and patient needs. The sole purpose of this document is to assist practitioners in achieving this objective.

In the frame of a project which consists in modeling a laboratory microcosm under cadmium pressure, we initiated this study on the fate and effects of cadmium in the presence of either the microalga Pseudokirchneriella subcapitata or the duckweed Lemna minor, two organisms of the microcosm. For each organism, growth inhibition tests on a duration of 2-3 weeks were carried out with the objective of linking effects with total dissolved, ionic and internalized forms of cadmium. Numbers of organisms (algal cells or duckweed fronds) in 2-L beakers filled with synthetic nutritive medium containing EDTA were counted during the course of assays, while cadmium concentrations in the water and in the organisms were measured. Free cadmium fraction was calculated using PHREEQC, a computer program for chemical speciation. Results showed that cadmium toxicity to microalgae could be correlated to the free divalent fraction of this metal, limited by the presence of EDTA, and to its concentration in the organisms. Bioconcentration factors for our medium were suggested for P. subcapitata (111,000 on the basis of free cadmium concentration) and L. minor (17,812 on the basis of total dissolved concentration). No effect concentrations were roughly estimated around 400 µg/g for Pseudokirchneriella subcapitata and 200-300 µg/g for Lemna minor. This study is a first step towards a fate model based on chemical speciation for a better understanding of microcosm results.

Purpose: On the basis of preclinical data suggesting that the class I selective HDAC inhibitor entinostat exerts a synergistic antitumor effect in combination with high-dose IL2 in a renal cell carcinoma model by downregulating Foxp3 expression and function of regulatory T cells (Treg), we conducted a phase I/II clinical study with entinostat and high-dose IL2 in patients with metastatic clear cell renal cell carcinoma (ccRCC). Experimental Design: Clear cell histology, no prior treatments, and being sufficiently fit to receive high-dose IL2 were the main eligibility criteria. The phase I portion consisted of two dose levels of entinostat (3 and 5 mg, orally every 14 days) and a fixed standard dose of IL2 (600,000 U/kg i.v.). Each cycle was 85 days. The primary endpoint was objective response rate and toxicity. Secondary endpoints included progression-free survival and overall survival. Results: Forty-seven patients were enrolled. At a median follow-up of 21.9 months, the objective response rate was 37% [95% confidence interval (CI), 22%-53%], the median progression-free survival was 13.8 months (95% CI, 6.0-18.8), and the median overall survival was 65.3 months (95% CI, 52.6.-65.3). The most common grade 3/4 toxicities were hypophosphatemia (16%), lymphopenia (15%), and hypocalcemia (7%), and all were transient. Decreased Tregs were observed following treatment with entinostat, and lower numbers were associated with response ( P = 0.03). Conclusions: This trial suggests a promising clinical activity for entinostat in combination with high-dose IL2 in ccRCC patients and provides the first example of an epigenetic agent being rationally combined with immunotherapy. Clin Cancer Res; 23(23); 7199-208. ©2017 AACR ., (©2017 American Association for Cancer Research.)

In a single-arm, phase 2 clinical trial, bendamustine-rituximab (BR) demonstrated an overall response rate of 82% among 45 patients with relapsed or refractory mantle cell lymphoma (MCL), with manageable tolerability. A prespecified 18 F-FDG PET analysis was conducted to assess the predictive value of the metabolic response to BR compared with the response by International Working Group (IWG) criteria., Methods: Adult patients with relapsed or refractory MCL underwent 18 F-FDG PET at screening and after 6 cycles of BR therapy. Scans were reviewed by a central facility and scored using the 5-point Deauville scale, comparing uptake to the liver and mediastinum in up to 6 lesions, to determine metabolic response rates, indicated by negative posttreatment scans. Metabolic responses were compared with study outcomes assessed by IWG criteria., Results: Complete 18 F-FDG PET data were available for 32 of 45 patients. All patients had positive baseline scans, with baseline scores ranging from 4 to 5. Complete metabolic responses (CMR) were observed in 24 (75%) patients after 6 cycles of BR. Patients attaining a CMR had a 96% overall response rate by IWG criteria, with 62.5% achieving a complete response. Of the 8 patients not attaining a CMR, 6 responded to BR but none achieved a complete response. CMR was associated with a greater 1-y progression-free survival of 91.5%, compared with 12.5% without CMR; a longer median duration of response of 20.6 mo, compared with 7.8 mo; and improved overall survival at 1 y. 18 F-FDG PET data from patients with refractory or advanced disease demonstrated CMR in more than half., Conclusion: Compared with positive end-of-treatment 18 F-FDG PET, negative scans, indicating a CMR, were predictive of improved 1-y survival, duration of response, and overall survival for patients with relapsed or refractory MCL receiving BR., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Contaminant effects on species are generally assessed with single-species bioassays. As a consequence, interactions between species that occur in ecosystems are not taken into account. To investigate the effects of contaminants on interacting species dynamics, our study describes the functioning of a 2-L laboratory microcosm with two species, the duckweed Lemna minor and the microalgae Pseudokirchneriella subcapitata, exposed to cadmium contamination. We modelled the dynamics of both species and their interactions using a mechanistic model based on coupled ordinary differential equations. The main processes occurring in this two-species microcosm were thus formalised, including growth and settling of algae, growth of duckweeds, interspecific competition between the two species and cadmium effects. We estimated model parameters by Bayesian inference, using simultaneously all the data issued from multiple laboratory experiments specifically conducted for this study. Cadmium concentrations ranged between 0 and 50 μg·L(-1). For all parameters of our model, we obtained biologically realistic values and reasonable uncertainties. Only duckweed dynamics was affected by interspecific competition, while algal dynamics was not impaired. Growth rate of both species decreased with cadmium concentration, as well as competition intensity showing that the interspecific competition pressure on duckweed decreased with cadmium concentration. This innovative combination of mechanistic modelling and model-guided experiments was successful to understand the algae-duckweed microcosm functioning without and with contaminant. This approach appears promising to include interactions between species when studying contaminant effects on ecosystem functioning., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International Harmonization Project criteria (IHP), Deauville 5-point scale (D 5PS) with scores 1-3 considered negative (D 5PS > 3) and D 5PS with scores 1-4 considered negative (D 5PS = 5). Ratios of tumor maximum standardized uptake value (SUVmax) to liver SUVmax were also analyzed. We found no difference in progression-free survival (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS > 3. The 2-year PFS using D 5PS = 5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p = 0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET-positive and PET-negative patients in different prognostic groups.

Purpose: Negative [(18)F]fluorodeoxyglucose (FDG) -positron emission tomography (PET)/computed tomography (CT) after two cycles of chemotherapy indicates a favorable prognosis in Hodgkin lymphoma (HL). We hypothesized that the negative predictive value would be even higher in patients responding rapidly enough to be PET negative after one cycle. This prospective study aimed to assess the prognostic value of PET after one cycle of chemotherapy in HL and to assess the dynamics of FDG uptake after one cycle (PET1) and after two cycles (PET2)., Patients and Methods: All PET scans were read by two blinded, independent reviewers in different countries, according to the Deauville five-point scale. The main end point was progression-free survival (PFS) after 2 years., Results: A total of 126 patients were included, and all had PET1; 89 patients had both PET1 and PET2. The prognostic value of PET1 was statistically significant with respect to both PFS and overall survival. Two-year PFS for PET1-negative and PET1-positive patients was 94.1% and 40.8%, respectively. Among those with both PET1 and PET2, 2-year PFS was 98.3% and 38.5% for PET1-negative and PET1-positive patients and 90.2% and 23.1% for PET2-negative and PET2-positive patients, respectively. No PET1-negative patient was PET2 positive., Conclusion: PET after one cycle of chemotherapy is highly prognostic in HL. No other prognostic tool identifies a group of patients with HL with a more favorable outcome than those patients with a negative PET1. In the absence of precise pretherapeutic predictive markers, PET1 is the best method for response-adapted strategies designed to select patients for less intensive treatment., (© 2014 by American Society of Clinical Oncology.)

Objectives/hypothesis: To define the prevalence of tracheotomy tube complications and evaluate risk factors (RFs) associated with their occurrence., Study Design: Multi-institution historical cohort., Methods: Data regarding tracheotomy tube complications from consecutive surgeries performed across eight participating institutions between January 1, 2008 and December 31, 2009 were retrospectively collected. Patient demographics, comorbidities, physician specialty, and surgical technique were recorded and statistically analyzed to identify the incidence of surgical complications following tracheotomy and associated RFs., Results: The charts of 1,175 tracheotomy procedures were reviewed from eight academic institutions. Otolaryngologists performed 66.2% of the tracheotomies. Intraoperative, early (<1 week), and late complication rates were 1.4%, 5.6%, and 7.1%, respectively. Postoperative bleeding was identified as the most common early complication (2.6%), whereas airway stenosis was the most common late complication (1.7%). The use of outer flange security sutures to anchor the tracheostomy tube was negatively associated with the incidence of early complication (P<.0001). The use of large endotracheal tubes (size>7.5) and obesity were associated with the development of airway stenosis (P<.05).Twenty-two percent of patients undergoing tracheotomy died during hospitalization., Conclusions: Perioperative tracheotomy complications are rare; however, the rate of death for all causes is high (22%) in this population. Obesity and the use of endotracheal tubes over 7.5 in size are major risk factors for the development of airway stenosis. Although percutaneous tracheotomy resulted in a significantly higher rate of postoperative bleeding (6.6%) than the open method (1.9%) (P<.05), the use of outer flange tracheostomy tube sutures may reduce this complication., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Background: Information on differential renal function following abdominal chemoradiation is limited. This study evaluated the association between renal function as measured by biochemical endpoints and scintigraphy and dose volume parameters in patients with gastrointestinal malignancies., Materials and Methods: Patients who received abdominal chemoradiation between 2002 and 2009 were identified for this study. Technetium(99m) MAG-3 scintigraphy and laboratory data were obtained prior to and after chemoradiation in 6 month intervals. Factors assessed included age, gender, hypertension, diabetes, and dose volume parameters. Renal function was assessed by biochemical endpoints and renal scintigraphy., Results: Significant reductions in relative renal function of the primarily irradiated kidney and creatinine clearance were seen. Split renal function decreased from 49.75% pre-radiation to 47.74% and 41.28% at 6-12 months and >12 months post-radiation (P=0.0184). Creatinine clearance declined from 90.67ml/min pre-radiation to 82.23ml/min and 74.54ml/min at 6-12 months and >12 months post-radiation (P<0.0001). Univariate analysis of patients who had at least one post-radiation renogram showed the percent volumes of the primarily irradiated kidney receiving ≥ 25 Gy (V(25)) and 40 Gy (V(40)) were significantly associated with ≥5% decrease in relative renal function (P=0.0387 and P=0.0438 respectively)., Conclusion: Decline in split renal function using Technetium(99m) MAG-3 scintigraphy correlates with decrease in creatinine clearance and radiation dose-volume parameters following abdominal chemoradiation. Change in split perfusion can be detected as early as 6 months post-radiation. Scintigraphy may provide early determination and quantification of subclinical renal injury prior to clinical evidence of nephropathy.