A cutting- plane approach for semi- infinite mathematical programming

Many situations ranging from industrial to social via economic and environmental problems may be cast into a Semi-infinite mathematical program. In this paper, the cutting-plane approach which lends itself better for standard non-linear programs is exploited with good reasons for grappling with linear, convex and geometric Semi-infinite programs. For each case, computational aspects are discussed and convergence statements established. Simple numerical examples are also provided for the sake of illustration. The paper ends by briefly comparing the cutting-plane approachdiscussed here with other existing approaches and by stressing the necessity of pushing forward a Decision Support System effectively capable for helping someone faced with a problem that can be formulated as a Semi-infinite mathematical program

An updated study-level meta-analysis of randomised controlled trials on proning in ARDS and acute lung injury

International audienceINTRODUCTION: In patients with acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS), recent randomised controlled trials (RCTs) showed a consistent trend of mortality reduction with prone ventilation. We updated a meta-analysis on this topic. METHODS: RCTs that compared ventilation of adult patients with ALI/ARDS in prone versus supine position were included in this study-level meta-analysis. Analysis was made by a random-effects model. The effect size on intensive care unit (ICU) mortality was computed in the overall included studies and in two subgroups of studies: those that included all ALI or hypoxemic patients, and those that restricted inclusion to only ARDS patients. A relationship between studies' effect size and daily prone duration was sought with meta-regression. We also computed the effects of prone positioning on major adverse airway complications. RESULTS: Seven RCTs (including 1,675 adult patients, of whom 862 were ventilated in the prone position) were included. The four most recent trials included only ARDS patients, and also applied the longest proning durations and used lung-protective ventilation. The effects of prone positioning differed according to the type of study. Overall, prone ventilation did not reduce ICU mortality (odds ratio = 0.91, 95% confidence interval = 0.75 to 1.2; P = 0.39), but it significantly reduced the ICU mortality in the four recent studies that enrolled only patients with ARDS (odds ratio = 0.71; 95% confidence interval = 0.5 to 0.99; P = 0.048; number needed to treat = 11). Meta-regression on all studies disclosed only a trend to explain effect variation by prone duration (P = 0.06). Prone positioning was not associated with a statistical increase in major airway complications. CONCLUSIONS: Long duration of ventilation in prone position significantly reduces ICU mortality when only ARDS patients are considered

Improving the Robustness of Difference of Convex Algorithm in the Research of a Global Optimum of a Nonconvex Differentiable Function Defined on a Bounded Closed Interval

International audienceIn this paper we present an algorithm for solving a DC problem non convex on an interval [a, b] of R. We use the DCA (Difference of Convex Algorithm) and the minimum of the average of two approximations of the function from a and b.This strategy has the advantage of giving in general a minimum to be situated in the attraction zone of the global minimum searched. After applying the DCA from this minimum we certainly arrive at the global minimum searched

New technique for solving univariate global optimization

summary:In this paper, a new global optimization method is proposed for an optimization problem with twice differentiable objective function a single variable with box constraint. The method employs a difference of linear interpolant of the objective and a concave function, where the former is a continuous piecewise convex quadratic function underestimator. The main objectives of this research are to determine the value of the lower bound that does not need an iterative local optimizer. The proposed method is proven to have a finite convergence to locate the global optimum point. The numerical experiments indicate that the proposed method competes with another covering methods

Persisting neuropsychiatric symptoms, Alzheimer's disease, and cerebrospinal fluid cortisol and dehydroepiandrosterone sulfate

INTRODUCTION Neuropsychiatric symptoms are important treatment targets in the management of dementia and can be present at very early clinical stages of neurodegenerative diseases. Increased cortisol has been reported in Alzheimer's disease (AD) and has been associated with faster cognitive decline. Elevated cortisol output has been observed in relation to perceived stress, depression, and anxiety. Dehydroepiandrosterone sulfate (DHEAS) has known anti-glucocorticoid effects and may counter the effects of cortisol. OBJECTIVES We aimed to examine whether CSF cortisol and DHEAS levels were associated with (1) neuropsychiatric symptoms at baseline, (2) changes in neuropsychiatric symptoms over 3 years, and (3) whether these associations were related to or independent of AD pathology. METHODS One hundred and eighteen participants on a prospective study in a memory clinic setting, including patients with cognitive impairment (n = 78), i.e., mild cognitive impairment or mild dementia, and volunteers with normal cognition (n = 40), were included. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). CSF cortisol and DHEAS, as well as CSF AD biomarkers, were obtained at baseline. Neuropsychiatric symptoms were re-assessed at follow-up visits 18 and 36 months from baseline. We constructed linear regression models to examine the links between baseline neuropsychiatric symptoms, the presence of AD pathology as indicated by CSF biomarkers, and CSF cortisol and DHEAS. We used repeated-measures mixed ANCOVA models to examine the associations between the neuropsychiatric symptoms' changes over time, baseline CSF cortisol and DHEAS, and AD pathology. RESULTS Higher CSF cortisol was associated with higher NPI-Q severity scores at baseline after controlling for covariates including AD pathology status (B = 0.085 [0.027; 0.144], p = 0.027; r = 0.277). In particular, higher CSF cortisol was associated with higher baseline scores of depression/dysphoria, anxiety, and apathy/indifference. Elevated CSF cortisol was also associated with more marked increase in NPI-Q scores over time regardless of AD status (p = 0.036, η$^{2}$ = 0.207), but this association was no longer significant after controlling for BMI and the use of psychotropic medications. CSF DHEAS was associated neither with NPI-Q scores at baseline nor with their change over time. Cortisol did not mediate the association between baseline NPI-Q and changes in clinical dementia rating sum of boxes over 36 months. CONCLUSION Higher CSF cortisol may reflect or contribute to more severe neuropsychiatric symptoms at baseline, as well as more pronounced worsening over 3 years, independently of the presence of AD pathology. Our findings also suggest that interventions targeting the HPA axis may be helpful to treat neuropsychiatric symptoms in patients with dementia

High Cortisol and the Risk of Dementia and Alzheimer's Disease: A Review of the Literature.

Introduction: Cortisol effects on the brain are exerted through two distinct receptors, inducing complex and even opposite effects on the cerebral structures implicated in the various cognitive functions. High cortisol may also have deleterious effects on the brain structures and contribute to neurodegeneration, in particular Alzheimer's disease (AD), via different mechanisms. Objective: To examine the interrelationships between cortisol, cognitive impairment and AD. Methods: Review of the literature. Results: Clinical studies found that elevated cortisol was associated with poorer overall cognitive functioning, as well as with poorer episodic memory, executive functioning, language, spatial memory, processing speed, and social cognition; while in animals, glucocorticoid administration resulted in cognitive impairment and abnormal behavior. In cognitively healthy subjects, higher cortisol levels have been associated with an increased risk of cognitive decline and AD. Subjects with dementia and Mild Cognitive Impairment (MCI) due to AD have been found to have higher CSF cortisol levels than cognitively healthy controls. Elevated CSF cortisol may also be associated with a more rapid cognitive decline in MCI due to AD. Elevated cortisol levels have been also found in delirium. High cortisol may mediate the impact of stressful life events, high neuroticism, depression, sleep disturbances, as well as cardiovascular risk factors on cognitive performance, neurodegeneration, and cognitive decline. High cortisol may also exert neurotoxic effects on the hippocampus, and promote oxidative stress and amyloid β peptide toxicity. Further possible underlying mechanisms include the interactions of cortisol with inflammatory mediators, neurotransmitters, and growth factors. Conclusion: Elevated cortisol levels may exert detrimental effects on cognition and contribute to AD pathology. Further studies are needed to investigate cortisol-reducing and glucocorticoidreceptor modulating interventions to prevent cognitive decline

Personality, Cortisol, and Cognition in Non-demented Elderly Subjects: Results from a Population-Based Study.

Certain personality traits, in particular higher neuroticism, have been associated, on one hand, with elevated cortisol levels, and on the other hand, with poorer cognitive performance. At the same time, several studies highlighted the association between high cortisol and poor cognitive functioning. Here, we hypothesized that increased cortisol may be associated with poorer cognition and with certain personality traits (mainly high neuroticism), and that personality might explain the association between cortisol and cognition. A cross-sectional analysis was conducted using data from Colaus/PsyColaus, a population-based study involving residents of Lausanne, Switzerland. Salivary cortisol samples (upon waking, 30 min after waking, at 11 am and at 8 pm) along with cognitive and personality measures were obtained from 643 non-demented participants aged at least 65. Personality traits were assessed using the NEO Five-Factor Inventory (NEO-FFI). We examined the links between the cortisol Area under the Curve (AUC), the Clinical Dementia Rating Sum of Boxes (CDRSOB) and the NEO-FFI scores. No association was found between personality traits and the CDRSOB or the MMSE score, controlling for age, sex, depression, education and BMI. However, the executive functioning domain z-score was negatively associated with agreeableness (p = 0.005; slope = -0.107 [-0.181; -0.033]) and openness (p = 0.029; slope = -0.081 [-0.154; -0.008]) after controlling for age, sex, depression, education and BMI. The CDRSOB score was positively associated with the cortisol AUC after controlling for age, sex, BMI, education and depression, (p = 0.003; slope = 0.686 [0.240; 1.333]). This association remained significant after controlling for personality traits and for the interaction between personality traits and the cortisol AUC (p = 0.006; slope = 0.792 [0.233; 1.352]. High agreeableness and openness might be associated with poorer executive performance in later life. Increased cortisol may be associated with both specific personality traits (high extraversion, low openness) and worse cognitive performance. Increased salivary cortisol does not mediate the relationship between personality traits and cognitive impairment

Life events, salivary cortisol, and cognitive performance in nondemented subjects: a population-based study.

Older people are particularly exposed to stressful events, known to activate the hypothalamus-pituitary-adrenal axis resulting in increased cortisol levels. High cortisol has been associated with deleterious effects on cognition. We hypothesized that stressful life events could increase cortisol secretion leading to cognitive impairment. A cross-sectional analysis was conducted using data from Colaus/PsyColaus, a longitudinal population-based study among Lausanne residents. Salivary cortisol samples were obtained from 796 nondemented subjects aged at least 65. A neuropsychological battery was used to assess cognitive performance and determine the Clinical Dementia Rating Sum of Boxes (CDRSOB). Lifetime life events and their subjective impact were assessed using a validated questionnaire. The total impact of life events was associated neither with cortisol area under the curve (AUC) nor with CDRSOB nor with any cognitive domain performance. The CDRSOB was associated with the cortisol AUC, controlling for age, sex, body mass index, education and depressive symptoms (p = 0.003; B = 0.686 [0.240; 1.333]; r = 0.114). This association between CDRSOB and the cortisol AUC remained significant after controlling for life events total impact (p = 0.040; B = 0.591 [0.027; 1.155]; r = 0.106). These findings do not support the hypothesis that stressful life events increase cortisol secretion leading to cognitive impairment. The association of higher cortisol levels with poorer cognition might be not a mere reflection of stressful events but rather explained by other factors, yet to be elucidated