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

Decreasing initial telomere length in humans intergenerationally understates age-associated telomere shortening

Telomere length shortens with aging, and short telomeres have been linked to a wide variety of pathologies. Previous studies suggested a discrepancy in age-associated telomere shortening rate estimated by cross-sectional studies versus the rate measured in longitudinal studies, indicating a potential bias in cross-sectional estimates. Intergenerational changes in initial telomere length, such as that predicted by the previously described effect of a father's age at birth of his offspring (FAB), could explain the discrepancy in shortening rate measurements. We evaluated whether changes occur in initial telomere length over multiple generations in three large datasets and identified paternal birth year (PBY) as a variable that reconciles the difference between longitudinal and cross-sectional measurements. We also clarify the association between FAB and offspring telomere length, demonstrating that this effect is substantially larger than reported in the past. These results indicate the presence of a downward secular trend in telomere length at birth over generational time with potential public health implications

Shear wave reflection seismic yields subsurface dissolution and subrosion patterns: application to the Ghor Al-Haditha sinkhole site, Dead Sea, Jordan

Near-surface geophysical imaging of alluvial fan settings is a challenging task but crucial for understating geological processes in such settings. The alluvial fan of Ghor Al-Haditha at the southeast shore of the Dead Sea is strongly affected by localized subsidence and destructive sinkhole collapses, with a significantly increasing sinkhole formation rate since ca. 1983. A similar increase is observed also on the western shore of the Dead Sea, in correlation with an ongoing decline in the Dead Sea level. Since different structural models of the upper 50 m of the alluvial fan and varying hypothetical sinkhole processes have been suggested for the Ghor Al-Haditha area in the past, this study aimed to clarify the subsurface characteristics responsible for sinkhole development. For this purpose, high-frequency shear wave reflection vibratory seismic surveys were carried out in the Ghor Al-Haditha area along several crossing and parallel profiles with a total length of 1.8 and 2.1 km in 2013 and 2014, respectively. The sedimentary architecture of the alluvial fan at Ghor Al-Haditha is resolved down to a depth of nearly 200 m at a high resolution and is calibrated with the stratigraphic profiles of two boreholes located inside the survey area. The most surprising result of the survey is the absence of evidence of a thick (> 2–10 m) compacted salt layer formerly suggested to lie at ca. 35–40 m depth. Instead, seismic reflection amplitudes and velocities image with good continuity a complex interlocking of alluvial fan deposits and lacustrine sediments of the Dead Sea between 0 and 200 m depth. Furthermore, the underground section of areas affected by sinkholes is characterized by highly scattering wave fields and reduced seismic interval velocities. We propose that the Dead Sea mud layers, which comprise distributed inclusions or lenses of evaporitic chloride, sulfate, and carbonate minerals as well as clay silicates, become increasingly exposed to unsaturated water as the sea level declines and are consequently destabilized and mobilized by both dissolution and physical erosion in the subsurface. This new interpretation of the underlying cause of sinkhole development is supported by surface observations in nearby channel systems. Overall, this study shows that shear wave seismic reflection technique is a promising method for enhanced near-surface imaging in such challenging alluvial fan settings

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

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

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