Time-dependent response of a zonally averaged ocean–atmosphere–sea ice model to Milankovitch forcing

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Springer-Verlag for personal use, not for redistribution. The definitive version was published in Climate Dynamics 6 (2010): 763-779, doi:10.1007/s00382-010-0790-6.An ocean-atmosphere-sea ice model is developed to explore the time-dependent response of climate to Milankovitch forcing for the time interval 5-3 Myr BP. The ocean component is a zonally averaged model of the circulation in five basins (Arctic, Atlantic, Indian, Pacific, and Southern Oceans). The atmospheric component is a one-dimensional (latitudinal) energy balance model, and the sea-ice component is a thermodynamic model. Two numerical experiments are conducted. The first experiment does not include sea ice and the Arctic Ocean; the second experiment does. Results from the two experiments are used to investigate (i) the response of annual mean surface air and ocean temperatures to Milankovitch forcing, and (ii) the role of sea ice in this response. In both experiments, the response of air temperature is dominated by obliquity cycles at most latitudes. On the other hand, the response of ocean temperature varies with latitude and depth. Deep water formed between 45°N-65°N in the Atlantic Ocean mainly responds to precession. In contrast, deep water formed south of 60°S responds to obliquity when sea ice is not included. Sea ice acts as a time-integrator of summer insolation changes such that annual mean sea-ice conditions mainly respond to obliquity. Thus, in the presence of sea ice, air temperature changes over the sea ice are amplified, and temperature changes in deep water of southern origin are suppressed since water below sea ice is kept near the freezing point.This work was supported by an NSERC Discovery Grant awarded to L.A.M. We also thank GEC3 for a Network Grant

A pilot dose-response study of the acute effects of haskap berry extract (Lonicera caerulea L.) on cognition, mood and blood pressure in older adults

Purpose Haskap (Lonicera caerulea L. or blue honeysuckle) is a plant native to the low-lying wet areas and mountains of Siberia and northeastern Asia, but is now cultivated in Canada. The dark blue berries are rich in anthocyanins, particularly cyanidin-3-O-glucoside. Previously, anthocyanin-rich fruits have been observed to benefit cognitive performance during the immediate postprandial period following a single acute dose. However, no study has currently examined the potential for haskap berries to influence cognitive performance. Here, we investigate the acute cognitive benefits of an anthocyanin-rich haskap berry extract. Methods A double-blind, counterbalanced, crossover intervention study compared the acute effects of three separate haskap berry extract doses, containing 100mg, 200mg, and 400mg anthocyanins, with a sugar-matched placebo. Participants were an opportunity sample of 20 older adults, aged 62-81 years. Measures of cognition, mood, and blood pressure were recorded at baseline and 1.5 hours postprandially. Results Compared to placebo, the 400mg dose elicited significantly lower diastolic blood pressure and heart rate. Both 200mg and 400mg doses elicited significantly higher word recall, with the 400mg dose also significantly improving word recognition scores, on an episodic memory task. However, mood, working memory and executive function task results were more equivocal. Conclusions The findings provide evidence for improvements in episodic memory and blood pressure following acute supplementation with haskap berry extract, with higher doses appearing most effective. The cognitive findings concur with previous literature that suggests episodic memory effects, and not executive function effects, are most prevalent in older adults following anthocyanin-rich berry supplementation. The blood pressure outcome is consistent with a vasodilatory mechanism of action

White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia

Flavonoid-rich orange juice is associated with acute improvements in cognitive function in healthy middle-aged males

Purpose: Epidemiological evidence suggests that chronic consumption of fruit-based flavonoids is associated with cognitive benefits; however, the acute effects of flavonoid-rich (FR) drinks on cognitive function in the immediate postprandial period require examination. The objective was to investigate whether consumption of FR orange juice is associated with acute cognitive benefits over 6 h in healthy middle-aged adults. Methods: Males aged 30–65 consumed a 240-ml FR orange juice (272 mg) and a calorie-matched placebo in a randomized, double-blind, counterbalanced order on 2 days separated by a 2-week washout. Cognitive function and subjective mood were assessed at baseline (prior to drink consumption) and 2 and 6 h post consumption. The cognitive battery included eight individual cognitive tests. A standardized breakfast was consumed prior to the baseline measures, and a standardized lunch was consumed 3 h post-drink consumption. Results: Change from baseline analysis revealed that performance on tests of executive function and psychomotor speed was significantly better following the FR drink compared to the placebo. The effects of objective cognitive function were supported by significant benefits for subjective alertness following the FR drink relative to the placebo. Conclusions: These data demonstrate that consumption of FR orange juice can acutely enhance objective and subjective cognition over the course of 6 h in healthy middle-aged adults

Increasing the Depth of Current Understanding: Sensitivity Testing of Deep-Sea Larval Dispersal Models for Ecologists

Larval dispersal is an important ecological process of great interest to conservation and the establishment of marine protected areas. Increasing numbers of studies are turning to biophysical models to simulate dispersal patterns, including in the deep-sea, but for many ecologists unassisted by a physical oceanographer, a model can present as a black box. Sensitivity testing offers a means to test the models' abilities and limitations and is a starting point for all modelling efforts. The aim of this study is to illustrate a sensitivity testing process for the unassisted ecologist, through a deep-sea case study example, and demonstrate how sensitivity testing can be used to determine optimal model settings, assess model adequacy, and inform ecological interpretation of model outputs. Five input parameters are tested (timestep of particle simulator (TS), horizontal (HS) and vertical separation (VS) of release points, release frequency (RF), and temporal range (TR) of simulations) using a commonly employed pairing of models. The procedures used are relevant to all marine larval dispersal models. It is shown how the results of these tests can inform the future set up and interpretation of ecological studies in this area. For example, an optimal arrangement of release locations spanning a release area could be deduced; the increased depth range spanned in deep-sea studies may necessitate the stratification of dispersal simulations with different numbers of release locations at different depths; no fewer than 52 releases per year should be used unless biologically informed; three years of simulations chosen based on climatic extremes may provide results with 90% similarity to five years of simulation; and this model setup is not appropriate for simulating rare dispersal events. A step-by-step process, summarising advice on the sensitivity testing procedure, is provided to inform all future unassisted ecologists looking to run a larval dispersal simulation

Are Happiness and Life Satisfaction Different Across Religious groups? Exploring Determinants of Happiness and Life Satisfaction

This study explores whether different religions experience different levels of happiness and life satisfaction and in case this is affected by country economic and cultural environment. Using World Value Survey (from 1981 to 2014), this study found that individual religiosity and country level of development play a significant role in shaping people’s subjective well-being (SWB). Protestants, Buddhists and Roman Catholic were happier and most satisfied with their lives compared to other religious groups. Orthodox has the lowest SWB. Health status, household’s financial satisfaction and freedom of choice are means by which religious groups and governments across the globe can improve the SWB of their citizens. Keywords: happiness; life satisfaction; religion; religious differences; cultur

Response shift in patient-reported outcomes:definition, theory, and a revised model

International audiencePurpose The extant response shift definitions and theoretical response shift models, while helpful, also introduce predicaments and theoretical debates continue. To address these predicaments and stimulate empirical research, we propose a more specific formal definition of response shift and a revised theoretical model. Methods This work is an international collaborative effort and involved a critical assessment of the literature. Results Three main predicaments were identified. First, the formal definitions of response shift need further specification and clarification. Second, previous models were focused on explaining change in the construct intended to be measured rather than explaining the construct at multiple time points and neglected the importance of using at least two time points to investigate response shift. Third, extant models do not explicitly distinguish the measure from the construct. Here we define response shift as an effect occurring whenever observed change (e.g., change in patient-reported outcome measures (PROM) scores) is not fully explained by target change (i.e., change in the construct intended to be measured). The revised model distinguishes the measure (e.g., PROM) from the underlying target construct (e.g., quality of life) at two time points. The major plausible paths are delineated, and the underlying assumptions of this model are explicated. Conclusion It is our hope that this refined definition and model are useful in the further development of response shift theory. The model with its explicit list of assumptions and hypothesized relationships lends itself for critical, empirical examination. Future studies are needed to empirically test the assumptions and hypothesized relationships

A Cross-Species Analysis of a Mouse Model of Breast Cancer-Specific Osteolysis and Human Bone Metastases Using Gene Expression Profiling

<p>Abstract</p> <p>Background</p> <p>Breast cancer is the second leading cause of cancer-related death in women in the United States. During the advanced stages of disease, many breast cancer patients suffer from bone metastasis. These metastases are predominantly osteolytic and develop when tumor cells interact with bone. <it>In vivo </it>models that mimic the breast cancer-specific osteolytic bone microenvironment are limited. Previously, we developed a mouse model of tumor-bone interaction in which three mouse breast cancer cell lines were implanted onto the calvaria. Analysis of tumors from this model revealed that they exhibited strong bone resorption, induction of osteoclasts and intracranial penetration at the tumor bone (TB)-interface.</p> <p>Methods</p> <p>In this study, we identified and used a TB microenvironment-specific gene expression signature from this model to extend our understanding of the metastatic bone microenvironment in human disease and to predict potential therapeutic targets.</p> <p>Results</p> <p>We identified a TB signature consisting of 934 genes that were commonly (among our 3 cell lines) and specifically (as compared to tumor-alone area within the bone microenvironment) up- and down-regulated >2-fold at the TB interface in our mouse osteolytic model. By comparing the TB signature with gene expression profiles from human breast metastases and an <it>in vitro </it>osteoclast model, we demonstrate that our model mimics both the human breast cancer bone microenvironment and osteoclastogenesis. Furthermore, we observed enrichment in various signaling pathways specific to the TB interface; that is, TGF-β and myeloid self-renewal pathways were activated and the Wnt pathway was inactivated. Lastly, we used the TB-signature to predict cyclopenthiazide as a potential inhibitor of the TB interface.</p> <p>Conclusion</p> <p>Our mouse breast cancer model morphologically and genetically resembles the osteoclastic bone microenvironment observed in human disease. Characterization of the gene expression signature specific to the TB interface in our model revealed signaling mechanisms operative in human breast cancer metastases and predicted a therapeutic inhibitor of cancer-mediated osteolysis.</p

Multiple FadD Acyl-CoA Synthetases Contribute to Differential Fatty Acid Degradation and Virulence in Pseudomonas aeruginosa

A close interconnection between nutrient metabolism and virulence factor expression contributes to the pathophysiology of Pseudomonas aeruginosa as a successful pathogen. P. aeruginosa fatty acid (FA) degradation is complicated with multiple acyl-CoA synthetase homologs (FadDs) expressed in vivo in lung tissue during cystic fibrosis infections. The promoters of two genetically linked P. aeruginosa fadD genes (fadD1 and fadD2) were mapped and northern blot analysis indicated they could exist on two different transcripts. These FadDs contain ATP/AMP signature and FA-binding motifs highly homologous to those of the Escherichia coli FadD. Upon introduction into an E. coli fadD-/fadR- double mutant, both P. aeruginosa fadDs functionally complemented the E. coli fadD-/fadR- mutant, allowing degradation of different chain-length FAs. Chromosomal mutagenesis, growth analysis, induction studies, and determination of kinetic parameters suggested that FadD1 has a substrate preference for long-chain FAs while FadD2 prefers shorter-chain FAs. When compared to the wild type strain, the fadD2 mutant exhibited decreased production of lipase, protease, rhamnolipid and phospholipase, and retardation of both swimming and swarming motilities. Interestingly, fadD1 mutant showed only increased swarming motility. Growth analysis of the fadD mutants showed noticeable deficiencies in utilizing FAs and phosphatidylcholine (major components of lung surfactant) as the sole carbon source. This defect translated into decreased in vivo fitness of P. aeruginosa in a BALB/c mouse lung infection model, supporting the role of lipids as a significant nutrient source for this bacterium in vivo

Positive Psychology in Cancer Care: Bad Science, Exaggerated Claims, and Unproven Medicine

Claims of positive psychology about people with cancer enjoy great popularity because they seem to offer scientific confirmation of strongly held cultural beliefs and values. Our goal is to examine critically four widely accepted claims in the positive psychology literature regarding adaptational outcomes among individuals living with cancer. We examine: (1) the role of positive factors, such as a "fighting spirit" in extending the life of persons with cancer; (2) effects of interventions cultivating positive psychological states on immune functioning and cancer progression and mortality; and evidence concerning (3) benefit finding and (4) post-traumatic growth following serious illness such as cancer and other highly threatening experiences. Claims about these areas of research routinely made in the positive psychology literature do not fit with available evidence. We note in particular the incoherence of claims about the adaptational value of benefit finding and post-traumatic growth among cancer patients, and the implausibility of claims that interventions that enhance benefit finding improve the prognosis of cancer patients by strengthening the immune system. We urge positive psychologists to rededicate themselves to a positive psychology based on scientific evidence rather than wishful thinking