239 research outputs found

    Random attractors for stochastic 2D-Navier-Stokes equations in some unbounded domains

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    We show that the stochastic flow generated by the Stochastic Navier-Stokes equations in a 2-dimensional Poincar\'e domain has a unique random attractor. This result complements a recent result by Brze\'zniak and Li [10] who showed that the flow is asymptotically compact and generalizes a recent result by Caraballo et al. [12] who proved existence of a unique pullback attractor for the time-dependent deterministic Navier-Stokes equations in a 2-dimensional Poincar\'e domain

    Atopic dermatitis: tacrolimus vs. topical corticosteroid use

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    Atopic dermatitis (AD), the dermatological manifestation of the atopic diathesis, has a variety of clinical presentations. It is a chronic and relapsing inflammatory disorder, requiring a multifaceted treatment approach. Topical corticosteroids are the backbone of therapy. However, concerns over adverse drug reactions associated with their long-term application limit their use. Tacrolimus, on the other hand, has been shown to be effective in stabilising the symptoms of AD in the long-term setting, without the side-effects that hamper the use of topical corticosteroids. Long-term safety data up to ten years are available in the literature. Despite this, the US Food and Drug Administration (FDA) black box warning of possible malignancies has resulted in much debate among experts. The main focus of this article is to compare the safety and efficacy of topical corticosteroids to calcineurin inhibitors, particularly tacrolimus. Furthermore, the aim is to evaluate the place of tacrolimus in AD therapy. A brief overview of the condition and other treatment modalities will also be discussed.Keywords: atopic dermatitis, tacroliums, topical corticosteroid us

    Depression, antidepressant medications, and risk of Clostridium difficile infection

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    Abstract Background An ancillary finding in previous research has suggested that the use of antidepressant medications increases the risk of developing Clostridium difficile infection (CDI). Our objective was to evaluate whether depression or the use of anti-depressants altered the risk of developing CDI, using two distinct datasets and study designs. Methods In Study 1, we conducted a longitudinal investigation of a nationally representative sample of older Americans (n = 16,781), linking data from biennial interviews to physician and emergency department visits, stays in hospital and skilled nursing facilities, home health visits, and other outpatient visits. In Study 2, we completed a clinical investigation of hospitalized adults who were tested for C. difficile (n = 4047), with cases testing positive and controls testing negative. Antidepressant medication use prior to testing was ascertained. Results The population-based rate of CDI in older Americans was 282.9/100,000 person-years (95% confidence interval (CI)) 226.3 to 339.5) for individuals with depression and 197.1/100,000 person-years for those without depression (95% CI 168.0 to 226.1). The odds of CDI were 36% greater in persons with major depression (95% CI 1.06 to 1.74), 35% greater in individuals with depressive disorders (95% CI 1.05 to 1.73), 54% greater in those who were widowed (95% CI 1.21 to 1.95), and 25% lower in adults who did not live alone (95% CI 0.62 to 0.92). Self-reports of feeling sad or having emotional, nervous or psychiatric problems at baseline were also associated with the later development of CDI. Use of certain antidepressant medications during hospitalization was associated with altered risk of CDI. Conclusions Adults with depression and who take specific anti-depressants seem to be more likely to develop CDI. Older adults who are widowed or who live alone are also at greater risk of CDI.http://deepblue.lib.umich.edu/bitstream/2027.42/112859/1/12916_2012_Article_763.pd

    Cognitive health among older adults in the United States and in England

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    <p>Abstract</p> <p>Background</p> <p>Cognitive function is a key determinant of independence and quality of life among older adults. Compared to adults in England, US adults have a greater prevalence of cardiovascular risk factors and disease that may lead to poorer cognitive function. We compared cognitive performance of older adults in the US and England, and sought to identify sociodemographic and medical factors associated with differences in cognitive function between the two countries.</p> <p>Methods</p> <p>Data were from the 2002 waves of the US Health and Retirement Study (HRS) (n = 8,299) and the English Longitudinal Study of Ageing (ELSA) (n = 5,276), nationally representative population-based studies designed to facilitate direct comparisons of health, wealth, and well-being. There were differences in the administration of the HRS and ELSA surveys, including use of both telephone and in-person administration of the HRS compared to only in-person administration of the ELSA, and a significantly higher response rate for the HRS (87% for the HRS vs. 67% for the ELSA). In each country, we assessed cognitive performance in non-hispanic whites aged 65 and over using the same tests of memory and orientation (0 to 24 point scale).</p> <p>Results</p> <p>US adults scored significantly better than English adults on the 24-point cognitive scale (unadjusted mean: 12.8 vs. 11.4, P < .001; age- and sex-adjusted: 13.2 vs. 11.7, P < .001). The US cognitive advantage was apparent even though US adults had a significantly higher prevalence of cardiovascular risk factors and disease. In a series of OLS regression analyses that controlled for a range of sociodemographic and medical factors, higher levels of education and wealth, and lower levels of depressive symptoms, accounted for some of the US cognitive advantage. US adults were also more likely to be taking medications for hypertension, and hypertension treatment was associated with significantly better cognitive function in the US, but not in England (P = .014 for treatment × country interaction).</p> <p>Conclusion</p> <p>Despite methodological differences in the administration of the surveys in the two countries, US adults aged ≥ 65 appeared to be cognitively healthier than English adults, even though they had a higher burden of cardiovascular risk factors and disease. Given the growing number of older adults worldwide, future cross-national studies aimed at identifying the medical and social factors that might prevent or delay cognitive decline in older adults would make important and valuable contributions to public health.</p

    Predicting progression of mild cognitive impairment to dementia using neuropsychological data: a supervised learning approach using time windows

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    Background: Predicting progression from a stage of Mild Cognitive Impairment to dementia is a major pursuit in current research. It is broadly accepted that cognition declines with a continuum between MCI and dementia. As such, cohorts of MCI patients are usually heterogeneous, containing patients at different stages of the neurodegenerative process. This hampers the prognostic task. Nevertheless, when learning prognostic models, most studies use the entire cohort of MCI patients regardless of their disease stages. In this paper, we propose a Time Windows approach to predict conversion to dementia, learning with patients stratified using time windows, thus fine-tuning the prognosis regarding the time to conversion. Methods: In the proposed Time Windows approach, we grouped patients based on the clinical information of whether they converted (converter MCI) or remained MCI (stable MCI) within a specific time window. We tested time windows of 2, 3, 4 and 5 years. We developed a prognostic model for each time window using clinical and neuropsychological data and compared this approach with the commonly used in the literature, where all patients are used to learn the models, named as First Last approach. This enables to move from the traditional question "Will a MCI patient convert to dementia somewhere in the future" to the question "Will a MCI patient convert to dementia in a specific time window". Results: The proposed Time Windows approach outperformed the First Last approach. The results showed that we can predict conversion to dementia as early as 5 years before the event with an AUC of 0.88 in the cross-validation set and 0.76 in an independent validation set. Conclusions: Prognostic models using time windows have higher performance when predicting progression from MCI to dementia, when compared to the prognostic approach commonly used in the literature. Furthermore, the proposed Time Windows approach is more relevant from a clinical point of view, predicting conversion within a temporal interval rather than sometime in the future and allowing clinicians to timely adjust treatments and clinical appointments.FCT under the Neuroclinomics2 project [PTDC/EEI-SII/1937/2014, SFRH/BD/95846/2013]; INESC-ID plurianual [UID/CEC/50021/2013]; LASIGE Research Unit [UID/CEC/00408/2013

    ¿Redefinición o adaptación? : el impacto de la COVID-19 en la acción humanitaria

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    Bibliografía: p. 26Resumen: Este informe presenta el escenario actual y futuro de la acción humanitaria a nivel internacional tras la declaración de situación de pandemia mundial por la COVID-19, en marzo de 2020. En el mismo se describen y analizan las consecuencias y efectos de la pandemia sobre las necesidades humanitarias y los desafíos que esta representa para la respuesta humanitaria en el futuro. De manera específica, este informe se centra en el estudio de las consecuencias de la COVID-19 sobre el sistema internacional humanitario, así como sobre los Objetivos de Desarrollo Sostenible (ODS) relacionados con la pobreza, el hambre y la salud

    Higher education delays and shortens cognitive impairment. A multistate life table analysis of the US Health and Retirement Study

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    Improved health may extend or shorten the duration of cognitive impairment by postponing incidence or death. We assess the duration of cognitive impairment in the US Health and Retirement Study (1992–2004) by self reported BMI, smoking and levels of education in men and women and three ethnic groups. We define multistate life tables by the transition rates to cognitive impairment, recovery and death and estimate Cox proportional hazard ratios for the studied determinants. 95% confidence intervals are obtained by bootstrapping. 55 year old white men and women expect to live 25.4 and 30.0 years, of which 1.7 [95% confidence intervals 1.5; 1.9] years and 2.7 [2.4; 2.9] years with cognitive impairment. Both black men and women live 3.7 [2.9; 4.5] years longer with cognitive impairment than whites, Hispanic men and women 3.2 [1.9; 4.6] and 5.8 [4.2; 7.5] years. BMI makes no difference. Smoking decreases the duration of cognitive impairment with 0.8 [0.4; 1.3] years by high mortality. Highly educated men and women live longer, but 1.6 years [1.1; 2.2] and 1.9 years [1.6; 2.6] shorter with cognitive impairment than lowly educated men and women. The effect of education is more pronounced among ethnic minorities. Higher life expectancy goes together with a longer period of cognitive impairment, but not for higher levels of education: that extends life in good cognitive health but shortens the period of cognitive impairment. The increased duration of cognitive impairment in minority ethnic groups needs further study, also in Europe

    Progressive Purkinje Cell Degeneration in tambaleante Mutant Mice Is a Consequence of a Missense Mutation in HERC1 E3 Ubiquitin Ligase

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    The HERC gene family encodes proteins with two characteristic domains: HECT and RCC1-like. Proteins with HECT domains have been described to function as ubiquitin ligases, and those that contain RCC1-like domains have been reported to function as GTPases regulators. These two activities are essential in a number of important cellular processes such as cell cycle, cell signaling, and membrane trafficking. Mutations affecting these domains have been found associated with retinitis pigmentosa, amyotrophic lateral sclerosis, and cancer. In humans, six HERC genes have been reported which encode two subgroups of HERC proteins: large (HERC1-2) and small (HERC3-6). The giant HERC1 protein was the first to be identified. It has been involved in membrane trafficking and cell proliferation/growth through its interactions with clathrin, M2-pyruvate kinase, and TSC2 proteins. Mutations affecting other members of the HERC family have been found to be associated with sterility and growth retardation. Here, we report the characterization of a recessive mutation named tambaleante, which causes progressive Purkinje cell degeneration leading to severe ataxia with reduced growth and lifespan in homozygous mice aged over two months. We mapped this mutation in mouse chromosome 9 and then performed positional cloning. We found a G⇔A transition at position 1448, causing a Gly to Glu substitution (Gly483Glu) in the highly conserved N-terminal RCC1-like domain of the HERC1 protein. Successful transgenic rescue, with either a mouse BAC containing the normal copy of Herc1 or with the human HERC1 cDNA, validated our findings. Histological and biochemical studies revealed extensive autophagy associated with an increase of the mutant protein level and a decrease of mTOR activity. Our observations concerning this first mutation in the Herc1 gene contribute to the functional annotation of the encoded E3 ubiquitin ligase and underline the crucial and unexpected role of this protein in Purkinje cell physiology

    Effect of diabetes on caregiver burden in an observational study of individuals with Alzheimer’s disease

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    Background The burden on caregivers of patients with Alzheimer’s disease (AD) is associated with the patient’s functional status and may also be influenced by chronic comorbid medical conditions, such as diabetes. This post-hoc exploratory analysis assessed whether comorbid diabetes in patients with AD affects caregiver burden, and whether caregivers with diabetes experience greater burden than caregivers without diabetes. Caregiver and patient healthcare resource use (HCRU) were also assessed. Methods Baseline data from the GERAS observational study of patients with AD and their caregivers (both n = 1495) in France, Germany and the UK were analyzed. Caregiver burden was assessed using the Zarit Burden Interview (ZBI). Caregiver time on activities of daily living (ADL: basic ADL; instrumental ADL, iADL) and supervision (hours/month), and caregiver and patient HCRU (outpatient visits, emergency room visits, nights hospitalized) were assessed using the Resource Utilization in Dementia instrument for the month before the baseline visit. Regression analyses were adjusted for relevant covariates. Time on supervision and basic ADL was analyzed using zero-inflated negative binomial regression. Results Caregivers of patients with diabetes (n = 188) were younger and more likely to be female (both p < 0.05), compared with caregivers of patients without diabetes (n = 1307). Analyses showed caregivers of patients with diabetes spent significantly more time on iADL (+16 %; p = 0.03; increases were also observed for basic ADL and total caregiver time but did not reach statistical significance) and had a trend towards increased ZBI score. Patients with diabetes had a 63 % increase in the odds of requiring supervision versus those without diabetes (p = 0.01). Caregiver and patient HCRU did not differ according to patient diabetes. Caregivers with diabetes (n = 127) did not differ from those without diabetes (n = 1367) regarding burden/time, but caregivers with diabetes had a 91 % increase in the odds of having outpatient visits (p = 0.01). Conclusions This cross-sectional analysis found caregiver time on iADL and supervision was higher for caregivers of patients with AD and diabetes versus without diabetes, while HCRU was unaffected by patient diabetes. Longitudinal analyses assessing change in caregiver burden over time by patient diabetes status may help clarify the cumulative impact of diabetes and AD dementia on caregiver burden
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