The changing causal foundations of cancer-related symptom clustering during the final month of palliative care: A longitudinal study

<p>Abstract</p> <p>Background</p> <p>Symptoms tend to occur in what have been called symptom clusters. Early symptom cluster research was imprecise regarding the causal foundations of the coordinations between specific symptoms, and was silent on whether the relationships between symptoms remained stable over time. This study develops a causal model of the relationships between symptoms in cancer palliative care patients as they approach death, and investigates the changing associations among the symptoms and between those symptoms and well-being.</p> <p>Methods</p> <p>Complete symptom assessment scores were obtained for 82 individuals from an existing palliative care database. The data included assessments of pain, anxiety, nausea, shortness of breath, drowsiness, loss of appetite, tiredness, depression and well-being, all collected using the Edmonton Symptom Assessment System (ESAS). Relationships between the symptoms and well-being were investigated using a structural equation model.</p> <p>Results</p> <p>The model fit acceptably and explained between 26% and 83% of the variation in appetite, tiredness, depression, and well-being. Drowsiness displayed consistent effects on appetite, tiredness and well-being. In contrast, anxiety's effect on well-being shifted importantly, with a direct effect and an indirect effect through tiredness at one month, being replaced by an effect working exclusively through depression at one week.</p> <p>Conclusion</p> <p>Some of the causal forces explaining the variations in, and relationships among, palliative care patients' symptoms changed over the final month of life. This illustrates how investigating the causal foundations of symptom correlation or clustering can provide more detailed understandings that may contribute to improved control of patient comfort, quality of life, and quality of death.</p

The processing and impact of dissolved riverine nitrogen in the Arctic Ocean

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Estuaries and Coasts 35 (2012): 401-415, doi:10.1007/s12237-011-9417-3.Although the Arctic Ocean is the most riverine-influenced of all of the world’s oceans, the importance of terrigenous nutrients in this environment is poorly understood. This study couples estimates of circumpolar riverine nutrient fluxes from the PARTNERS (Pan-Arctic River Transport of Nutrients, Organic Matter, and Suspended Sediments) Project with a regionally configured version of the MIT general circulation model to develop estimates of the distribution and availability of dissolved riverine N in the Arctic Ocean, assess its importance for primary production, and compare these estimates to potential bacterial production fueled by riverine C. Because riverine dissolved organic nitrogen is remineralized slowly, riverine N is available for uptake well into the open ocean. Despite this, we estimate that even when recycling is considered, riverine N may support 0.5–1.5 Tmol C year−1 of primary production, a small proportion of total Arctic Ocean photosynthesis. Rapid uptake of dissolved inorganic nitrogen coupled with relatively high rates of dissolved organic nitrogen regeneration in N-limited nearshore regions, however, leads to potential localized rates of riverine-supported photosynthesis that represent a substantial proportion of nearshore production.Funding for this work was provided through NSFOPP- 0229302 and NSF-OPP-0732985.Support to SET was additionally provided by an NSERC Postdoctoral Fellowship

Major Role of Microbes in Carbon Fluxes during Austral Winter in the Southern Drake Passage

Carbon cycling in Southern Ocean is a major issue in climate change, hence the need to understand the role of biota in the regulation of carbon fixation and cycling. Southern Ocean is a heterogeneous system, characterized by a strong seasonality, due to long dark winter. Yet, currently little is known about biogeochemical dynamics during this season, particularly in the deeper part of the ocean. We studied bacterial communities and processes in summer and winter cruises in the southern Drake Passage. Here we show that in winter, when the primary production is greatly reduced, Bacteria and Archaea become the major producers of biogenic particles, at the expense of dissolved organic carbon drawdown. Heterotrophic production and chemoautotrophic CO2 fixation rates were substantial, also in deep water, and bacterial populations were controlled by protists and viruses. A dynamic food web is also consistent with the observed temporal and spatial variations in archaeal and bacterial communities that might exploit various niches. Thus, Southern Ocean microbial loop may substantially maintain a wintertime food web and system respiration at the expense of summer produced DOC as well as regenerate nutrients and iron. Our findings have important implications for Southern Ocean ecosystem functioning and carbon cycle and its manipulation by iron enrichment to achieve net sequestration of atmospheric CO2

Nutrient Enrichment and Food Web Composition Affect Ecosystem Metabolism in an Experimental Seagrass Habitat

Food web composition and resource levels can influence ecosystem properties such as productivity and elemental cycles. In particular, herbivores occupy a central place in food webs as the species richness and composition of this trophic level may simultaneously influence the transmission of resource and predator effects to higher and lower trophic levels, respectively. Yet, these interactions are poorly understood.Using an experimental seagrass mesocosm system, we factorially manipulated water column nutrient concentrations, food chain length, and diversity of crustacean grazers to address two questions: (1) Does food web composition modulate the effects of nutrient enrichment on plant and grazer biomasses and stoichiometry? (2) Do ecosystem fluxes of dissolved oxygen and nutrients more closely reflect above-ground biomass and community structure or sediment processes? Nutrient enrichment and grazer presence generally had strong effects on biomass accumulation, stoichiometry, and ecosystem fluxes, whereas predator effects were weaker or absent. Nutrient enrichment had little effect on producer biomass or net ecosystem production but strongly increased seagrass nutrient content, ecosystem flux rates, and grazer secondary production, suggesting that enhanced production was efficiently transferred from producers to herbivores. Gross ecosystem production (oxygen evolution) correlated positively with above-ground plant biomass, whereas inorganic nutrient fluxes were unrelated to plant or grazer biomasses, suggesting dominance by sediment microbial processes. Finally, grazer richness significantly stabilized ecosystem processes, as predators decreased ecosystem production and respiration only in the zero- and one- species grazer treatments.Overall, our results indicate that consumer presence and species composition strongly influence ecosystem responses to nutrient enrichment, and that increasing herbivore diversity can stabilize ecosystem flux rates in the face of perturbations

A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis

Introduction: Bone is an integral part of the osteoarthritis (OA) process. We conducted a systematic literature review in order to understand the relationship between non-conventional radiographic imaging of subchondral bone, pain, structural pathology and joint replacement in peripheral joint OA. Methods: A search of the Medline, EMBASE and Cochrane library databases was performed for original articles reporting association between non-conventional radiographic imaging-assessed subchondral bone pathologies and joint replacement, pain or structural progression in knee, hip, hand, ankle and foot OA. Each association was qualitatively characterised by a synthesis of the data from each analysis based upon study design, adequacy of covariate adjustment and quality scoring. Results: In total 2456 abstracts were screened and 139 papers were included (70 cross-sectional, 71 longitudinal analyses; 116 knee, 15 hip, six hand, two ankle and involved 113 MRI, eight DXA, four CT, eight scintigraphic and eight 2D shape analyses). BMLs, osteophytes and bone shape were independently associated with structural progression or joint replacement. BMLs and bone shape were independently associated with longitudinal change in pain and incident frequent knee pain respectively. Conclusion: Subchondral bone features have independent associations with structural progression, pain and joint replacement in peripheral OA in the hip and hand but especially in the knee. For peripheral OA sites other than the knee, there are fewer associations and independent associations of bone pathologies with these important OA outcomes which may reflect fewer studies; for example the foot and ankle were poorly studied. Subchondral OA bone appears to be a relevant therapeutic target. Systematic review: PROSPERO registration number: CRD 4201300500

Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months

Monitoring the activity of 2-oxoglutarate dependent histone demethylases by NMR spectroscopy: direct observation of formaldehyde.

(Chemical Equation Presented) Formaldetected: Application of 1H- and 1D 13C HSQC NMR spectroscopy methods for monitoring the activity of a 2-oxoglutarate dependent histone Nε-emethyllysine demethylase (JMJD2E) enabled the in situ quantitative analysis of the different components of the reaction, including the direct observation of hydrated formaldehyde resulting from enzyme-catalysed demethylation. © 2010 Wiley-VCH Verlag GmbHand Co. KGaA