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Panitumumab is a fully human monoclonal antibody that targets EGFR. We aimed to compare chemoradiotherapy plus panitumumab with chemoradiotherapy alone in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 41 sites in nine countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0–1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (three cycles of cisplatin 100 mg/m2) or panitumumab plus chemoradiotherapy (three cycles of intravenous panitumumab 9·0 mg/kg every 3 weeks plus cisplatin 75 mg/m2) using stratified randomisation with a block size of five. All patients received 70 Gy to gross tumour and 50 Gy to areas at risk for subclinical disease with standard fractionation. The primary endpoint was local-regional control at 2 years, analysed in all randomised patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00500760. Between Oct 26, 2007, and March 26, 2009, 153 patients were enrolled and 150 received treatment (63 in the chemoradiotherapy group and 87 in the panitumumab plus chemoradiotherapy group). Local-regional control at 2 years was 68% (95% CI 54–78) in the chemoradiotherapy group and 61% (50–71) in the panitumumab plus chemoradiotherapy group. The most frequent grade 3–4 adverse events were dysphagia (17 [27%] of 63 patients in the chemoradiotherapy group vs 35 [40%] of 87 in the panitumumab plus chemoradiotherapy group), mucosal inflammation (15 [24%] vs 48 [55%]), and radiation skin injury (eight [13%] vs 27 [31%]). Serious adverse events were reported in 20 (32%) of 63 patients in the chemoradiotherapy group and in 37 (43%) of 87 patients in the panitumumab plus chemoradiotherapy group. In patients with locally advanced squamous-cell carcinoma of the head and neck, the addition of panitumumab to standard fractionation radiotherapy and cisplatin did not confer any benefit, and the role of EGFR inhibition in these patients needs to be reassessed. Amgen.

The assessment of disturbance effects on wildlife and resulting mitigation efforts are founded on edge-effect theory. According to the classical view, the abundance of animals affected by human disturbance should increase monotonically with distance from disturbed areas to reach a maximum at remote locations. Here we show that distance-dependent movement taxis can skew abundance distributions toward disturbed areas. We develop an advection-diffusion model based on basic movement behavior commonly observed in animal populations and parameterize the model from observations on radio-collared caribou in a boreal ecosystem. The model predicts maximum abundance at 3.7 km from cutovers and roads. Consistently, aerial surveys conducted over 161,920 km2showed that the relative probability of caribou occurrence displays nonmonotonic changes with the distance to anthropogenic features, with a peak occurring at 4.5 km away from these features. This aggregation near disturbed areas thus provides the predators of this top-down-controlled, threatened herbivore species with specific locations to concentrate their search. The edge-effect theory developed here thus predicts that human activities should alter animal distribution and food web properties differently than anticipated from the current paradigm. Consideration of such nonmonotonic response to habitat edges may become essential to successful wildlife conservation.

Network theory increasingly informs wildlife conservation in disturbed landscapes, but with concern increasingly expressed about its application to real‐world situations. The theory predicts that the connectivity of scale‐free networks should be particularly sensitive to the disturbance of highly connected nodes (i.e. hubs). This expectation relies on complete patch removal, thus restraining its application to the last of several steps involved in habitat fragmentation, and overlooks potential reconnection of patches after disturbance (i.e. rewiring). We performed a landscape‐scale experiment to evaluate the robustness of scale‐free spatial networks of woodland caribou (Rangifer tarandus caribou) to logging activity. We built caribou networks before and after disturbance using a mechanistic model of inter‐patch movements and differentiated networks disturbed in their hubs and non‐hubs. We applied a reaction–advection–diffusion model to networks before and after disturbance to account for the spatio‐temporal dynamics of caribou movement within the networks and anticipate their space use. We validated network and space‐use predictions using empirical estimates from GPS relocations of caribou. Using the validated predictions, we compared topological network measures before and after disturbance to quantify changes in connectivity within the networks according to the type of disturbed nodes (i.e. hubs or non‐hubs) and assessed space‐use reorganization. We used control networks, for which no disturbance occurred in the before–after timeframe of the study, in the latter analysis to get a baseline rate of change. Disturbances due to logging activity typically resulted in fragmentation and shrinkage instead of complete patch removal. Independently to the type of disturbed nodes, caribou rewired their network using remnant patches from the fragmentation process. Consequently, topological network measures generally did not differ between before and after disturbance, such that caribou networks displayed some robustness to logging activity due to the rewiring process. Space‐use reorganization was greater, however, when hubs were disturbed in comparison with non‐hubs and controls. Even though caribou rewired their networks, they revisited less patches after the disturbance of hubs. A naive application of network theory (i.e. without potential rewiring and using complete patch removal), to assess spatial network robustness, may be inappropriate during most steps of the fragmentation process because of the rewiring process. Indeed, network rewiring facilitated by the presence of remnant patches can enhance spatial network robustness, in comparison with no rewiring. In addition, species‐specific functional connectivity should be accounted for when anticipating the rewiring process and animal space use within disturbed networks. A free Plain Language Summary can be found within the Supporting Information of this article. A free Plain Language Summary can be found within the Supporting Information of this article.

Biofilm formation on abiotic and biotic surfaces was studied with two hyphobacteria, strongly attached to the surface of the arbuscular mycorrhizal fungus (AMF) Rhizoglomus irregulare ( Ri ) DAOM 197198 and two mycorrhizobacteria, loosely attached to the roots of different mycorrhizal plants. When the sparingly soluble igneous phosphate rock (PR) from Quebec, or when the chemical hydroxyapatite were used as sole phosphorus (P) source, hyphobacteria Rhizobium miluonense Rm3 and Burkholderia anthina Ba8 produced significantly more biofilms than mycorrhizobacteria Rahnella sp. Rs11 and Burkholderia phenazinium Bph12, as indicated by the crystal violet assay or by quantifying biofilm exopolysaccharides. As previously observed with planktonic bacteria, biofilms mobilized P by lowering the pH and releasing gluconic acid. The high efficiency of P mobilization by the hyphobacteria Ba8 was linked to the presence of more viable cells in its biofilm as revealed by the hydrolysis of fluorescein diacetate. Scanning electron microscopy micrographs showed a high adherence of the best P-solubilizer hyphobacteria Ba8 on the surface of Quebec PR. Hydroxyapatite porous structure did not allow a good adherence of Ba8. Ba8 formed an important biofilm on the hyphae of Ri DAOM 197198 with low reactive Quebec PR while no biofilm was observed with the high reactive hydroxyapatite. Results confirm the possible presence of specificity between the Ri DAOM 197198 and the hyphobacteria and suggest that the interaction would be regulated by the availability of P.

Background The purpose of the study was to identify factors associated with weight loss during radiotherapy (RT) in patients with stage I or II head and neck (HN) cancer. Methods This study was conducted as part of a phase III chemoprevention trial. A total of 540 patients were randomized. The patients were weighed before and after RT. Patients’ characteristics, dietary intake, health-related quality of life (HRQOL), tumor characteristic, treatment characteristics, and acute adverse effects of RT were evaluated at baseline and during RT. Factors independently associated with weight loss during RT were identified using the multiple linear regression ( P  ≤ 0.05). Results The mean weight loss during RT was 2.2 kg (standard deviation, 3.4). In bivariate analyses, the occurrence of adverse effects of RT and most of the HRQOL dimensions evaluated during RT were correlated with weight loss. In the multivariate analysis, eight factors were associated with a greater weight loss: all HN cancer sites other than the glottic larynx ( P  < 0.001), TNM stage II disease ( P  = 0.01), higher pre-RT body weight ( P  < 0.001), dysphagia before RT ( P  < 0.005), higher mucosa adverse effect of RT ( P  = 0.03), lower dietary energy intake during RT ( P  < 0.001), lower score of the digestive dimension on the Head and Neck Radiotherapy Questionnaire ( P  < 0.001) and a higher score of the constipation symptom on the EORTC QLQ-C30 during RT ( P  = 0.02). Conclusions The results underline the importance of maintaining energy intake in early stage HN cancer patients during RT and the importance of preventing and treating adverse effects.

Reforestation of degraded lands in the boreal forest is challenging and depends on the direction and strength of the plant-soil feedback (PSF). Using a gradient in tree productivity (null, low and high) from a long-term, spatially replicated reforestation experiment of borrow pits in the boreal forest, we investigated the interplay between microbial communities and soil and tree nutrient stocks and concentrations in relation to a positive PSF induced by wood mulch amendment. Three levels of mulch amendment underlie the observed gradient in tree productivity, and plots that had been amended with a continuous layer of mulch 17 years earlier showed a positive PSF with trees up to 6 m tall, a closed canopy, and a developing humus layer. The average taxonomic and functional composition of the bacterial and fungal communities differed markedly betweenlow- and high-productivity plots. Trees in high-productivity plots recruited a specialized soil microbiome that was more efficient at nutrient mobilization and acquisition. These plots showed increases in carbon (C), calcium (Ca), nitrogen (N), potassium (K), and phosphorus (P) stocks and as well as bacterial and fungal biomass. The soil microbiome was dominated by taxa from the fungal genus Cortinarius and the bacterial family Chitinophagaceae, and a complex microbial network with higher connectivity and more keystone species supported tree productivity in reforested plots compared to unproductive plots. Therefore, mulching of plots resulted in a microbially mediated PSF that enhances mineral weathering and non-symbiotic N fixation, and in turn helps transform unproductive plots into productive plots to ensure rapid restoration of the forest ecosystem in a harsh boreal environment.

Engineered wood flooring (EWF) is a multilayer composite flooring product. The cross layered structure is designed to give good dimensional stability to the EWF under changing environmental conditions. However, during winter season in North America, the indoor relative humidity could decrease dramatically and generate an important cupping deformation. The main objective of this study was to characterize the interlaminar stresses ( σ 33 , σ 13 and σ 23 ) distribution at free-edges in EWF made with an OSB substrate. A three-dimensional (3D) finite element model was used to predict the cupping deformation and to characterize stresses developed in the EWF. The finite element model is based on an unsteady-state moisture transfer equation, a mechanical equilibrium equation and an elastic constitutive law. The physical and mechanical properties of OSB substrate were experimentally determined as a function of the density and moisture content. The simulated EWF deformations were compared against the laboratory observations. For both simulation and experimental results, the cupping deformation of EWF was induced by varying the ambient relative humidity from 50 to 20% at 20°C. A good agreement has been found between the numerical and experimental EWF cupping deformation. The stress distribution fields generated by the model correspond to the delaminations observed on the OSB substrate in the climate room. Delamination in EWF can occur principally under the action of the tension stress or a combination of tension and shear stresses. Finally, simulated results show that the levels of interlaminar stresses are maximal near the free-edges of EWF strips.

⿢GSVs in the MAP-Kinase and estrogen pathways were associated with OS in HNC patients.⿢ESRRG variant is a potential splicing site disruptor sequence at the transcript level.⿢Higher protein expression of ESRRG and CACNA2D1 is associated with poor OS. Carcinomas of the oral cavity, pharynx and larynx are referred to as head and neck cancers (HNC); together they account for 2⿿3% of all newly diagnosed cancers in North America. Between 40⿿50% of HNC are early diagnosed at stages I⿿II. The 5-year and 10-year relative survival rates are 61% and 50%, respectively. Germline genetic sequence variants (GSV) have become increasingly found to have prognostic implications in a variety of cancers. Identifying these variants may have important clinical and biological implications. We conducted a genome-wide association study (GWAS) in 531 Stage I⿿II radiation-treated HNC patients (originally recruited for α-tocopherol/β-carotene placebo-controlled secondary prevention study) and used a replication cohort of 566 HNC patients of all stages, of mostly non-HPV-related cancers. Survival rates were estimated by the Kaplan-Meier method. Cox proportional hazards models adjusted for potential clinical factors and principal components were used to test for associations between the GSV and overall survival (OS) in these tumors. The median follow-up time for OS was 9.21 years (GWAS cohort) and 2.37 years (replication cohort). In both cohorts, CACNA2D1:rs2299187, ESRRG:rs946465 and ESRRG:rs1416612 were each individually significantly associated with survival. In silico analysis of ESRRG:rs946465 identifies that it produces a splice variant in ESRRG. Variant alleles of CACNA2D1:rs2299187 and ESRRG:rs946465 were associated with higher expression of the corresponding protein. Putatively functional polymorphisms in the MAP-Kinase and estrogen pathways, identified through GWAS and replicated in an independent dataset were associated with the survival of HNC patients.

Women with breast cancer who are undergoing breast-conserving surgery were assigned to receive whole-breast irradiation with or without regional nodal irradiation. At 10 years, disease-free survival in the nodal-irradiation group was improved but overall survival was not. Many women with early-stage breast cancer undergo breast-conserving surgery followed by whole-breast irradiation, which reduces the rate of local recurrence. 1 – 3 Radiotherapy to the chest wall and regional lymph nodes, termed regional nodal irradiation, which is commonly used after mastectomy in women with node-positive breast cancer who are treated with adjuvant systemic therapy, reduces locoregional and distant recurrence and improves overall survival. 4 – 6 An unanswered question is whether the addition of regional nodal irradiation to whole-breast irradiation after breast-conserving surgery has the same effect. Whole-breast irradiation may involve irradiation of the lower axillary and internal mammary lymph nodes. 7 However, regional . . .