CANcer BEhavioural nutrition and exercise feasibility trial (CanBenefit); phase I qualitative interview findings

Background: Older people with lung cancer are often frail and unfit due to their cancer and co-morbidities and may tolerate cancer treatments poorly. Physical activity (PA) and a healthy diet offer quality of life benefit to people with cancer before, during, and post treatment. However, older adults are poorly represented in the clinical trials on which recommendations were made. Objective: To assess the acceptability, usefulness, and practicality of delivering a tailored wellbeing (PA and nutrition) intervention for older adults with lung cancer before, during, and after cancer treatments (chemotherapy and/or immunotherapy). Methods: Semi-structured interviews conducted with nine patients with lung cancer and three patients with mesothelioma, ≥70 years and ten informal carers, and nine Multidisciplinary Team (MDT) members. A topic guide covered the acceptability, usefulness, and practicality of a wellbeing intervention as well as specific feedback on individual components. Data were subjected to thematic analysis. Findings: Four themes were generated: current lack of wellbeing care in clinical work; preferred “can have” dietary and “can do” PA advice; peer support as facilitating factor; and barriers to compliance including patients' psychological and physical issues as well as current cancer pathway and staffing issues. Conclusion: Older adults with lung cancer would welcome a proactive, clear and instructive, wellbeing intervention. Many barriers to compliance exist, particularly before and during cancer treatments due to the psycho-social impact of diagnosis, and the effects of cancer treatment. The intervention must be tailored to individual need and address physical limitations, psychological and social welfare in addition to PA and nutritional advice

Physical activity and nutrition interventions for older adults with cancer: a systematic review

Purpose: The aim of this review was to summarize the current literature for the effectiveness of activity and nutritional based interventions on health-related quality of life (HRQoL) in older adults living with and beyond cancer (LWBC). Methods: We conducted systematic structured searches of CINAHL, Embase, Medline, Cochrane CENTRAL databases, and bibliographic review. Two independent researchers selected against inclusion criteria: (1) lifestyle nutrition and/or activity intervention for people with any cancer diagnosis, (2) measured HRQoL, (3) all participants over 60years of age and (4) randomized controlled trials. Results: Searches identified 5179 titles; 114 articles had full text review, with 14 studies (participant n = 1660) included. Three had nutrition and activity components, one, nutrition only and ten, activity only. Duration ranged from 7days to 1year. Interventions varied from intensive daily prehabilitation to home-based gardening interventions. Studies investigated various HRQoL outcomes including fatigue, general and cancer-specific quality of life (QoL), distress, depression, global side-effect burden and physical functioning. Eight studies reported significant intervention improvements in one or more QoL measure. Seven studies reported using a psychosocial/theoretical framework. There is a gap in tailored nutrition advice. Conclusions: Among the few studies that targeted older adults with cancer, most were activity-based programmes with half reporting improvements in QoL. Future research should focus on or include tailored nutrition components and consider appropriate behaviour change techniques to maximize potential QoL improvement. Implications for Cancer Survivors: More research is needed to address the research gap regarding older adults as current recommendations are derived from younger populations

Does Graded Prognostic Assessment outperform Recursive Partitioning Analysis in patients with moderate prognosis brain metastases?

AIM: To compare the clinical utility of the Recursive Partitioning Analysis (RPA) and Graded Prognostic Assessment (GPA) in predicting outcomes for moderate prognosis patients with brain metastases. METHODS & MATERIALS: We reviewed 101 whole brain radiotherapy cases. RPA and GPA were calculated. Overall survival was compared. RESULTS: Sixty-eight patients had moderate prognosis. RPA patient characteristics for increased death hazard were ≤10 WBRT fractions or no surgery/radiosurgery. GPA patients had increased death risk with no surgery/radiosurgery or lower Karnofsky Performance Status. CONCLUSION: The indices have similar predicted survival. Patients scored by RPA with longer radiation schedules had longer survival; patients scored by GPA did not. This indicates GPA is more clinically useful, leaving less room for subjective treatment choices

Children with new onset seizures: A prospective study of parent variables, child behavior problems, and seizure occurrence

OBJECTIVE: Parent variables (stigma, mood, unmet needs for information and support, and worry) are associated with behavioral difficulties in children with seizures; however, it is not known how this relationship is influenced by additional seizures. This study followed children (ages 4-14 years) and their parents over a 24-month period (with data collected at baseline and 6, 12, and 24 months) and investigated the effect of an additional seizure on the relationship between parenting variables and child behavior difficulties. METHODS: The sample was parents of 196 children (104 girls and 92 boys) with a first seizure within the past 6 weeks. Child mean age at baseline was 8 years, 3 months (SD 3 years). Data were analyzed using t-tests, chi-square tests, and repeated measures analyses of covariance. RESULTS: Relationships between parent variables, additional seizures, and child behavior problems were consistent across time. Several associations between parent variables and child behavior problems were stronger in the additional seizure group than in the no additional seizure group. CONCLUSIONS: Findings suggest that interventions that assist families to respond constructively to the reactions of others regarding their child's seizure condition and to address their needs for information and support could help families of children with continuing seizures to have an improved quality of life

Forebay Computational Fluid Dynamics Modeling for The Dalles Dam to Support Behavior Guidance System Siting Studies

Computational fluid dynamics (CFD) models were developed to support the siting and design of a behavioral guidance system (BGS) structure in The Dalles Dam (TDA) forebay on the Columbia River. The work was conducted by Pacific Northwest National Laboratory for the U.S. Army Corps of Engineers, Portland District (CENWP). The CFD results were an invaluable tool for the analysis, both from a Regional and Agency perspective (for the fish passage evaluation) and a CENWP perspective (supporting the BGS design and location). The new CFD model (TDA forebay model) included the latest bathymetry (surveyed in 1999) and a detailed representation of the engineered structures (spillway, powerhouse main, fish, and service units). The TDA forebay model was designed and developed in a way that future studies could easily modify or, to a large extent, reuse large portions of the existing mesh. This study resulted in these key findings: (1) The TDA forebay model matched well with field-measured velocity data. (2) The TDA forebay model matched observations made at the 1:80 general physical model of the TDA forebay. (3) During the course of this study, the methodology typically used by CENWP to contour topographic data was shown to be inaccurate when applied to widely-spaced transect data. Contouring methodologies need to be revisited--especially before such things as modifying the bathymetry in the 1:80 general physical model are undertaken. Future alignments can be evaluated with the model staying largely intact. The next round of analysis will need to address fish passage demands and navigation concerns. CFD models can be used to identify the most promising locations and to provide quantified metrics for biological, hydraulic, and navigation criteria. The most promising locations should then be further evaluated in the 1:80 general physical model

Low HDL Cholesterol is Associated with Lower Gray Matter Volume in Cognitively Healthy Adults

Dyslipidemia is common in adults and contributes to high rates of cardiovascular disease and may be linked to subsequent neurodegenerative and neurovascular diseases. This study examined whether lower brain volumes and cognition associated with dyslipidemia could be observed in cognitively healthy adults, and whether apolipoprotein E (APOE) genotype or family history of Alzheimer's disease (FHAD) alters this effect. T1-weighted magnetic resonance imaging was used to examine regional brain gray matter (GM) and white matter (WM) in 183 individuals (58.4 ± 8.0 years) using voxel-based morphometry. A non-parametric multiple linear regression model was used to assess the effect of high-density lipoprotein (HDL) and non-HDL cholesterol, APOE, and FHAD on regional GM and WM volume. A post hoc analysis was used to assess whether any significant correlations found within the volumetric analysis had an effect on cognition. HDL was positively correlated with GM volume in the bilateral temporal poles, middle temporal gyri, temporo-occipital gyri, and left superior temporal gyrus and parahippocampal region. This effect was independent of APOE and FHAD. A significant association between HDL and the Brief Visuospatial Memory Test was found. Additionally, GM volume within the right middle temporal gyrus, the region most affected by HDL, was significantly associated with the Controlled Oral Word Association Test and the Center for Epidemiological Studies Depression Scale. These findings suggest that adults with decreased levels of HDL cholesterol may be experiencing cognitive changes and GM reductions in regions associated with neurodegenerative disease and therefore, may be at greater risk for future cognitive decline

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer\u27s disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants\u27 activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD. © 2007 The International Neuropsychological Society

Single-Molecule Imaging Reveals Aβ42:Aβ40 Ratio-Dependent Oligomer Growth on Neuronal Processes

AbstractSoluble oligomers of the amyloid-β peptide have been implicated as proximal neurotoxins in Alzheimer’s disease. However, the identity of the neurotoxic aggregate(s) and the mechanisms by which these species induce neuronal dysfunction remain uncertain. Physiologically relevant experimentation is hindered by the low endogenous concentrations of the peptide, the metastability of Aβ oligomers, and the wide range of observed interactions between Aβ and biological membranes. Single-molecule microscopy represents one avenue for overcoming these challenges. Using this technique, we find that Aβ binds to primary rat hippocampal neurons at physiological concentrations. Although amyloid-β(1–40) as well as amyloid-β(1–42) initially form larger oligomers on neurites than on glass slides, a 1:1 mix of the two peptides result in smaller neurite-bound oligomers than those detected on-slide or for either peptide alone. With 1 nM peptide in solution, Aβ40 oligomers do not grow over the course of 48 h, Aβ42 oligomers grow slightly, and oligomers of a 1:1 mix grow substantially. Evidently, small Aβ oligomers are capable of binding to neurons at physiological concentrations and grow at rates dependent on local Aβ42:Aβ40 ratios. These results are intriguing in light of the increased Aβ42:Aβ40 ratios shown to correlate with familial Alzheimer’s disease mutations

Associations between diffusion MRI microstructure and cerebrospinal fluid markers of Alzheimer's disease pathology and neurodegeneration along the Alzheimer's disease continuum

INTRODUCTION: White matter (WM) degeneration is a critical component of early Alzheimer's disease (AD) pathophysiology. Diffusion-weighted imaging (DWI) models, including diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and mean apparent propagator MRI (MAP-MRI), have the potential to identify early neurodegenerative WM changes associated with AD. METHODS: We imaged 213 (198 cognitively unimpaired) aging adults with DWI and used tract-based spatial statistics to compare 15 DWI metrics of WM microstructure to 9 cerebrospinal fluid (CSF) markers of AD pathology and neurodegeneration treated as continuous variables. RESULTS: We found widespread WM injury in AD, as indexed by robust associations between DWI metrics and CSF biomarkers. MAP-MRI had more spatially diffuse relationships with Aβ42/40 and pTau, compared with NODDI and DTI. DISCUSSION: Our results suggest that WM degeneration may be more pervasive in AD than is commonly appreciated and that innovative DWI models such as MAP-MRI may provide clinically viable biomarkers of AD-related neurodegeneration in the earliest stages of AD progression