Sorption, Desorption and Exchange of Cesium on Glaciofluvial Deposits

Distribution ratios and isotherms for Sorption, desorption and isotope-exchange of cesium (labelled with Cs-137) were measured on grain size fractions (<2mm) of quatemary glaciofluvial deposits. Sediment materials from two locations within Switzerland and synthetic groundwaters of different compositions were used. The investigated concentration range for cesium was 10"" — 10"' M. Cesium introduced into the system with the solid phase may influence the measurements at the lowest concentrations. Depending on the experimental conditions, the distribution ratios vary between 3 and 30'000 ml/g. The isotherms are non-linear. Normalization of the cesium concentration in the solid with the cation-exchange capacity leads to nearly identical isotherms for all size fractions of the two geographic locations. Desorption and exchange are retarded at the higher cesium concentrations. This can be explained by structural changes in clay minerals which dominate the Sorption of cesium on this material. Variations in the composition of the groundwater influence the Sorption of cesium only sHghtly; potassium and hydrogen ions are the main competitors

Genetics-Based Population Pharmacokinetics and Pharmacodynamics of Risperidone in a Psychiatric Cohort.

BACKGROUND: High interindividual variability in plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, may lead to suboptimal drug concentration. OBJECTIVE: Using a population pharmacokinetic approach, we aimed to characterize the genetic and non-genetic sources of variability affecting risperidone and 9-hydroxyrisperidone pharmacokinetics, and relate them to common side effects. METHODS: Overall, 150 psychiatric patients (178 observations) treated with risperidone were genotyped for common polymorphisms in NR1/2, POR, PPARα, ABCB1, CYP2D6 and CYP3A genes. Plasma risperidone and 9-hydroxyrisperidone were measured, and clinical data and common clinical chemistry parameters were collected. Drug and metabolite concentrations were analyzed using non-linear mixed effect modeling (NONMEM(®)). Correlations between trough concentrations of the active moiety (risperidone plus 9-hydroxyrisperidone) and common side effects were assessed using logistic regression and linear mixed modeling. RESULTS: The cytochrome P450 (CYP) 2D6 phenotype explained 52% of interindividual variability in risperidone pharmacokinetics. The area under the concentration-time curve (AUC) of the active moiety was found to be 28% higher in CYP2D6 poor metabolizers compared with intermediate, extensive and ultrarapid metabolizers. No other genetic markers were found to significantly affect risperidone concentrations. 9-hydroxyrisperidone elimination was decreased by 26% with doubling of age. A correlation between trough predicted concentration of the active moiety and neurologic symptoms was found (p = 0.03), suggesting that a concentration &gt;40 ng/mL should be targeted only in cases of insufficient, or absence of, response. CONCLUSIONS: Genetic polymorphisms of CYP2D6 play an important role in risperidone, 9-hydroxyrisperidone and active moiety plasma concentration variability, which were associated with common side effects. These results highlight the importance of a personalized dosage adjustment during risperidone treatment

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

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

Effects of childhood multiple maltreatment experiences on depression of socioeconomic disadvantaged elderly in Brazil.

Childhood maltreatment is a risk factor for depression in nonelderly individuals. We investigated the effect of childhood abuse and neglect on the development of geriatric depression and its severity in socioeconomically disadvantaged individuals. A cross-sectional study investigated 449 individuals aged 60-103 years sorted by data using the enrollment list health coverage from the city of Porto Alegre, Brazil. The fifteen-item Geriatric Depression Scale was used to assess depression. The Childhood Trauma Questionnaire was used to identify emotional and physical neglect, in addition to emotional, physical, and sexual abuse. Geriatric depression was associated with emotional and physical abuse and neglect. Emotional abuse and neglect, as well as physical abuse, increased the odds of an individual developing severe depression. Correlations were observed for combined forms of maltreatment, with two to five maltreatment types producing mild to moderate symptoms. Similar trends were observed for severe symptoms in a limited number of cases. The cross-sectional design limit causal inference. Retrospective measurement of childhood maltreatment may increase recall and response bias. Late-life depression and its severity significantly correlated with the extent of childhood emotional and physical abuse and neglect. Thus, research should focus on supporting trauma survivors late in life, particularly when they come from low or middle income countries because these patients have higher rates of depression in elderly populations

The effect of neoadjuvant therapy on PD-L1 expression and CD8+lymphocyte density in non-small cell lung cancer.

PD-L1 expression is the routine clinical biomarker for the selection of patients to receive immunotherapy in non-small cell lung cancer (NSCLC). However, the application and best timing of immunotherapy in the resectable setting is still under investigation. We aimed to study the effect of chemotherapy on PD-L1 expression and tumor infiltrating lymphocytes (TILs), which is to date still poorly understood. Our retrospective, single-centre neoadjuvant cohort comprised 96 consecutive patients with NSCLC resected 2000-2016 after neoadjuvant therapy, including paired diagnostic chemo-naïve specimens in 53 cases. A biologically matched surgical cohort of 114 primary resected cases was included. PD-L1 expression, CD8 + TILs density and tertiary lymphoid structures were assessed on whole slides and correlated with clinico-pathological characteristics and survival. Seven/53 and 12/53 cases had lower respectively higher PD-L1 expressions after neoadjuvant therapy. Most cases (n = 34) showed no changes in PD-L1 expression, the majority of these harboring PD-L1 &lt; 1% in both samples (21/34 [61.8%]). Although CD8 + TILs density was significantly higher after chemotherapy (p = 0.031) in resections compared to diagnostic biopsies, this might be due to sampling and statistical bias. No difference in PD-L1 expression or CD8 + TILs density was detected when comparing the neoadjuvant and surgical cohort. In univariable analyses, higher CD8 + TILs density, higher numbers of tertiary lymphoid structures but not PD-L1 expression were significantly associated with longer survival. Increased PD-L1 expression after neoadjuvant chemotherapy was not significantly associated with shorter 5-year survival, but the number of cases was very low. In multivariable analysis, only pT category and age remained independent prognostic factors. In summary, PD-L1 expression was mostly unchanged after neoadjuvant chemotherapy compared to diagnostic biopsies. The sample size of cases with changed PD-L1 expression was too small to draw conclusions on any prognostic value

Optimising medication management for polymedicated home-dwelling older adults with multiple chronic conditions: a mixed-methods study protocol.

Optimal medication management is one of the basic conditions necessary for home-dwelling older adults living with multiple chronic conditions (OAMCC) to be able to remain at home and preserve their quality of life. Currently, the reasons for such high numbers of emergency department visits and the very significant rate of hospitalisations for OAMCC, due to medication-related problems (MRPs), is poorly explored. This study aims to reveal the current state of the medication management practices of polymedicated, home-dwelling OAMCC and to make proposals for improving clinical and medication pathways through an innovative and integrated model for supporting medication management and preventing adverse health outcomes. A mixed-methods study will address the medication management of polymedicated, home-dwelling OAMCC. Its explanatory sequential design will involve two major phases conducted sequentially over time. The quantitative phase will consist of retrospectively exploiting the last 5 years of electronic patient records from a local hospital (N ≈ 50 000) in order to identify the different profiles-made up of patient-related, medication-related and environment-related factors-of the polymedicated, home-dwelling OAMCC at risk of hospitalisation, emergency department visits, hospital readmission (notably for MRPs), institutionalisation or early death. The qualitative study will involve: (a) obtaining and understanding the medication management practices and experiences of the identified profiles extracted from the hospital data of OAMCC who will be interviewed at home (N ≈ 30); (b) collecting and analysing the perspectives of the formal and informal caregivers involved in medication management at home in order to cross-reference perspectives about this important dimension of care at home. Finally, the mixed-methods findings will enable the development of an innovative, integrated model of medication management based on the Agency for Clinical Innovation framework and Bodenheimer and Sinsky's quadruple aim. Ethical approval has been obtained from the Human Research Ethics Committee of the Canton Vaud (2018-02196). Findings will be disseminated in peer-reviewed journals, professional conferences and other knowledge transfer activities with primary healthcare providers, hospital care units, informal caregivers' and patients' associations

Epidemiology of at-risk alcohol use and associated comorbidities of interest among community-dwelling older adults: a protocol for a systematic review.

There is little epidemiological evidence and knowledge about at-risk alcohol use among community-dwelling older adults and their chronic and acute alcohol-related comorbidities of interest. This systematic review will summarise and examine relevant studies about the epidemiology of at-risk alcohol use and associated comorbidities of interest in this population. We will search the following databases, without language or date restrictions, from inception to 31 August 2019: Embase.com, Medline Ovid SP, Pubmed (NOT medline[sb]), CINAHL EBSCO, PsycINFO Ovid SP, Central-Cochrane Library Wiley and Web of Science (Core Collection). Search strategies will be developed in collaboration with a librarian. We will use predefined search terms for alcoholism, epidemiology, the elderly, living place and comorbidities of interest, as well as terms related to the identification of "measurements", "tools" or "instruments" for measuring harm from alcohol use. At-risk status will be determined by the amount of alcohol consumed and any comorbidities of interest associated with at-risk alcohol use, with the latter being documented separately or using an assessment tool for at-risk drinking. We will also examine the bibliographies of all the relevant articles found and search for unpublished studies. We will consider publications in all languages. No ethical approval is necessary. Results will be presented in national and international conferences on addiction and published in a peer-reviewed journal. CRD42018099965

Prediction of antipsychotics efficacy based on a polygenic risk score: a real-world cohort study.

Background: Response to antipsychotics is subject to a wide interindividual variability, due to genetic and non-genetic factors. Several single nucleotide polymorphisms (SNPs) have been associated with response to antipsychotics in genome-wide association studies (GWAS). Polygenic risk scores (PRS) are a powerful tool to aggregate into a single measure the small effects of multiple risk alleles. Materials and methods: We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRS &lt;sub&gt;response&lt;/sub&gt; ) in a real-world sample of patients (N = 460) with different diagnoses (schizophrenia spectrum, bipolar, depressive, neurocognitive, substance use disorders and miscellaneous). Two other PRSs composed of SNPs previously associated with risk of schizophrenia (PRS &lt;sub&gt;schizophrenia1&lt;/sub&gt; and PRS &lt;sub&gt;schizophrenia2&lt;/sub&gt; ) were also tested for their association with response to treatment. Results: PRS &lt;sub&gt;response&lt;/sub&gt; was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03-1.26, p = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02-1.37, p = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04-1.47, p = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04-1.55, p = 0.01, N = 149). Sensitivity and specificity were sub-optimal (schizophrenia 62%, 61%; schizophrenia spectrum 56%, 55%; schizophrenia spectrum plus bipolar disorder 60%, 56%; all patients 63%, 58%, respectively). PRS &lt;sub&gt;schizophrenia1&lt;/sub&gt; and PRS &lt;sub&gt;schizophrenia2&lt;/sub&gt; were not significantly associated with response to treatment. Conclusion: PRS &lt;sub&gt;response&lt;/sub&gt; defined from GWAS studies is significantly associated with response to antipsychotics in a real-world cohort; however, the results of the sensitivity-specificity analysis preclude its use as a predictive tool in clinical practice