Neuroimaging, cancer, and cognition: state of the knowledge

OBJECTIVES: To review neuroimaging research concerning cancer- and cancer treatment-related changes in brain structure and function, clinical perspectives, and future directions. DATA SOURCES: Peer-reviewed literature. CONCLUSION: Cancer and chemotherapy are associated with cerebral structural and functional alterations in breast cancer patients that may persist for years; many of these changes are correlated with cognitive complaints or performance. In other cancers there is some evidence that metabolism is altered by cancer, but more research is needed. IMPLICATIONS FOR NURSING PRACTICE: Understanding the role of neuroimaging is important to identify the basis of cognitive changes associated with cancer and cancer treatment

Pasture Management in the US Midwest – An Assessment of Current Practices and Future Opportunities

Managed grazing offers significant potential to improve the sustainability of livestock farms in the US Midwest, however the benefits of managed grazing are largely influenced by the management practices employed on farm. The objective of this study was to gain an understanding of current grazing practices on Midwest farms and to identify the knowledge and support needs of graziers. A total of 185 responses were received from a range of different enterprises including dairy, beef, and sheep production. Results show a substantial degree of variation in grazing management practices between respondents and highlights significant scope for improvement on farms particularly in the areas of pasture measurement and budgeting, and grazing infrastructure. Reported benefits of managed grazing included lower environmental impact, better pasture and animal performance, better animal health and welfare, and lower costs. Challenges with managed grazing included time and labor input, maintaining pasture quantity and quality during the grazing season, adverse weather conditions such as excessive rain and drought, and animal health challenges such as heat stress, parasites and in some cases coyotes. The study highlighted opportunities for research and extension providers to better support farmers with information and advice and identified knowledge gaps in areas such as pasture species selection, soil fertility, grazing infrastructure, pasture budgeting, legumes, and pasture measurement. The study successfully gained an insight into graziers in the Midwest, the outputs of which, will be valuable to a number of key stakeholders going forward, including researchers, extension agents, farmers and policy makers

Differential affinity of FLIP and procaspase 8 for FADD’s DED binding surfaces regulates DISC assembly

Death receptor activation triggers recruitment of FADD, which via its death effector domain (DED) engages the DEDs of procaspase 8 and its inhibitor FLIP to form death-inducing signalling complexes (DISCs). The DEDs of FADD, FLIP and procaspase 8 interact with one another using two binding surfaces defined by α1/α4 and α2/α5 helices, respectively. Here we report that FLIP has preferential affinity for the α1/α4 surface of FADD, whereas procaspase 8 has preferential affinity for FADD's α2/α5 surface. These relative affinities contribute to FLIP being recruited to the DISC at comparable levels to procaspase 8 despite lower cellular expression. Additional studies, including assessment of DISC stoichiometry and functional assays, suggest that following death receptor recruitment, the FADD DED preferentially engages FLIP using its α1/α4 surface and procaspase 8 using its α2/α5 surface; these tripartite intermediates then interact via the α1/α4 surface of FLIP DED1 and the α2/α5 surface of procaspase 8 DED2

Discretization of variational regularization in Banach spaces

Consider a nonlinear ill-posed operator equation $F(u)=y$ where $F$ is defined on a Banach space $X$. In general, for solving this equation numerically, a finite dimensional approximation of $X$ and an approximation of $F$ are required. Moreover, in general the given data \yd of $y$ are noisy. In this paper we analyze finite dimensional variational regularization, which takes into account operator approximations and noisy data: We show (semi-)convergence of the regularized solution of the finite dimensional problems and establish convergence rates in terms of Bregman distances under appropriate sourcewise representation of a solution of the equation. The more involved case of regularization in nonseparable Banach spaces is discussed in detail. In particular we consider the space of finite total variation functions, the space of functions of finite bounded deformation, and the $L^\infty$--space

Perspectives in anaerobic digestion of lipid-rich wastewater

Lipid-rich wastewaters are ideal sources for methane production, but lipids are generally separated and removed prior to anaerobic treatment to avoid sludge flotation and microbial inhibition. In this work, we review the major technological and microbiological advances in the anaerobic digestion (AD) of lipids, while highlighting the most important breakthroughs in the field and identifying the future perspectives. In the past decades, several treatment processes have been developed for lipidrich wastewaters, moving from the upflow granular sludge based reactor designs to anaerobic membrane bioreactors and in situ flotation based bioreactors all now commercially available. Knowledge on the complexity of microbial communities and microbial interactions has increased greatly, allowing a better interpretation of lipids anaerobic biodegradation. However, there are still knowledge gaps and bottlenecks in lipids AD that need to be overcome to improve industrial applications. A multi-faceted approach with industrial and academic partners will provide a unique strategy for future widespread usage of waste-lipids as valuable resource for AD.The authors acknowledge the funding from EPA Research (Ireland), the Irish Dairy Processing Technology Centre, The Irish Research Council (EBPS2012) and the Microbiology Society; the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684), of Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462), POCI-01-0145-FEDER-007679 (UID/CTM/50011/2013), and by BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. The authors also acknowledge the financial support of the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 323009 and the funding of ANII-Uruguay, UNESCO-IHE and LATU (Uruguay).info:eu-repo/semantics/publishedVersio

Complex circular subsidence structures in tephra deposited on large blocks of ice: Varða tuff cone, Öræfajökull, Iceland

Several broadly circular structures up to 16 m in diameter, into which higher strata have sagged and locally collapsed, are present in a tephra outcrop on southwest Öræfajökull, southern Iceland. The tephra was sourced in a nearby basaltic tuff cone at Varða. The structures have not previously been described in tuff cones, and they probably formed by the melting out of large buried blocks of ice emplaced during a preceding jökulhlaup that may have been triggered by a subglacial eruption within the Öræfajökull ice cap. They are named ice-melt subsidence structures, and they are analogous to kettle holes that are commonly found in proglacial sandurs and some lahars sourced in ice-clad volcanoes. The internal structure is better exposed in the Varða examples because of an absence of fluvial infilling and reworking, and erosion of the outcrop to reveal the deeper geometry. The ice-melt subsidence structures at Varða are a proxy for buried ice. They are the only known evidence for a subglacial eruption and associated jökulhlaup that created the ice blocks. The recognition of such structures elsewhere will be useful in reconstructing more complete regional volcanic histories as well as for identifying ice-proximal settings during palaeoenvironmental investigations

Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study

Purpose To determine treatment and aging-related effects on longitudinal cognitive function in older breast cancer survivors. Methods Newly diagnosed nonmetastatic breast cancer survivors (n = 344) and matched controls without cancer (n = 347) 60 years of age and older without dementia or neurologic disease were recruited between August 2010 and December 2015. Data collection occurred during presystemic treatment/control enrollment and at 12 and 24 months through biospecimens; surveys; self-reported Functional Assessment of Cancer Therapy-Cognitive Function; and neuropsychological tests that measured attention, processing speed, and executive function (APE) and learning and memory (LM). Linear mixed-effects models tested two-way interactions of treatment group (control, chemotherapy with or without hormonal therapy, and hormonal therapy) and time and explored three-way interactions of ApoE (ε4+ v not) by group by time; covariates included baseline age, frailty, race, and cognitive reserve. Results Survivors and controls were 60 to 98 years of age, were well educated, and had similar baseline cognitive scores. Treatment was related to longitudinal cognition scores, with survivors who received chemotherapy having increasingly worse APE scores (P = .05) and those initiating hormonal therapy having lower LM scores at 12 months (P = .03) than other groups. These group-by-time differences varied by ApoE genotype, where only ε4+ survivors receiving hormone therapy had short-term decreases in adjusted LM scores (three-way interaction P = .03). For APE, the three-way interaction was not significant (P = .14), but scores were significantly lower for ε4+ survivors exposed to chemotherapy (−0.40; 95% CI, −0.79 to −0.01) at 24 months than ε4+ controls (0.01; 95% CI, 0.16 to 0.18; P < .05). Increasing age was associated with lower baseline scores on all cognitive measures (P < .001); frailty was associated with baseline APE and self-reported decline (P < .001). Conclusion Breast cancer systemic treatment and aging-related phenotypes and genotypes are associated with longitudinal decreases in cognitive function scores in older survivors. These data could inform treatment decision making and survivorship care planning

Abusive Supervision, Upward Maintenance Communication, and Subordinates\u27 Psychological Distress

This study reanalyzes data from Tepper\u27s (2000) two-wave study regarding the effects of subordinates\u27 perceptions of supervisory abuse to assess previously unexamined relationships. As predicted, we found that subordinates who more rather than less strongly perceived that they had been abused by supervisors tended to use regulative maintenance tactics with higher frequency. Further, the positive relationship between abusive supervision and subordinates\u27 psychological distress was exacerbated by subordinates\u27 use of regulative maintenance communications, and that relationship was reduced by subordinates\u27 use of direct maintenance communication. Theoretical and practical implications are discussed

Therapy-induced tumour secretomes promote resistance and tumour progression.

Drug resistance invariably limits the clinical efficacy of targeted therapy with kinase inhibitors against cancer. Here we show that targeted therapy with BRAF, ALK or EGFR kinase inhibitors induces a complex network of secreted signals in drug-stressed human and mouse melanoma and human lung adenocarcinoma cells. This therapy-induced secretome stimulates the outgrowth, dissemination and metastasis of drug-resistant cancer cell clones and supports the survival of drug-sensitive cancer cells, contributing to incomplete tumour regression. The tumour-promoting secretome of melanoma cells treated with the kinase inhibitor vemurafenib is driven by downregulation of the transcription factor FRA1. In situ transcriptome analysis of drug-resistant melanoma cells responding to the regressing tumour microenvironment revealed hyperactivation of several signalling pathways, most prominently the AKT pathway. Dual inhibition of RAF and the PI(3)K/AKT/mTOR intracellular signalling pathways blunted the outgrowth of the drug-resistant cell population in BRAF mutant human melanoma, suggesting this combination therapy as a strategy against tumour relapse. Thus, therapeutic inhibition of oncogenic drivers induces vast secretome changes in drug-sensitive cancer cells, paradoxically establishing a tumour microenvironment that supports the expansion of drug-resistant clones, but is susceptible to combination therapy