Levels and determinants of inflammatory biomarkers in a Swiss population-based sample (CoLaus Study).

OBJECTIVE: to assess the levels and determinants of interleukin (IL)-1ß, IL-6, tumour necrosis factor (TNF)-a and C-reactive protein (CRP) in a healthy Caucasian population.METHODS: population sample of 2884 men and 3201 women aged 35 to 75. IL-1ß, IL-6 and TNF-a were assessed by a multiplexed particle-based flow cytometric assay and CRP by an immunometric assay.RESULTS: Spearman rank correlations between duplicate cytokine measurements (N?=?80) ranged between 0.89 and 0.96; intra-class correlation coefficients ranged between 0.94 and 0.97, indicating good reproducibility. Among the 6085 participants, 2289 (37.6%), 451 (7.4%) and 43 (0.7%) had IL-1ß, IL-6 and TNF-a levels below detection limits, respectively. Median (interquartile range) for participants with detectable values were 1.17 (0.48-3.90) pg/ml for IL-1ß; 1.47 (0.71-3.53) pg/ml for IL-6; 2.89 (1.82-4.53) pg/ml for TNF-a and 1.3 (0.6-2.7) ng/ml for CRP. On multivariate analysis, greater age was the only factor inversely associated with IL-1ß levels. Male sex, increased BMI and smoking were associated with greater IL-6 levels, while no relationship was found for age and leisure-time PA. Male sex, greater age, increased BMI and current smoking were associated with greater TNF-a levels, while no relationship was found with leisure-time PA. CRP levels were positively related to age, BMI and smoking, and inversely to male sex and physical activity.CONCLUSION: Population-based levels of several cytokines were established. Increased age and BMI, and to a lesser degree sex and smoking, significantly and differentially impact cytokine levels, while leisure-time physical activity has little effect.

Determinants of vaccine immunity in the cohort of human immunodeficiency virus-infected children living in Switzerland.

BACKGROUND: Human immunodeficiency virus (HIV)-infected children are at increased risk of infections caused by vaccine preventable pathogens, and specific immunization recommendations have been issued. METHODS: A prospective national multicenter study assessed how these recommendations are followed in Switzerland and how immunization history correlates with vaccine immunity. RESULTS: Among 87 HIV-infected children (mean age: 11.1 years) followed in the 5 Swiss university hospitals and 1 regional hospital, most (76%) had CD4 T cells >25%, were receiving highly active antiretroviral treatment (79%) and had undetectable viral load (60%). Immunization coverage was lower than in the general population and many lacked serum antibodies to vaccine-preventable pathogens, including measles (54%), varicella (39%), and hepatitis B (65%). The presence of vaccine antibodies correlated most significantly with having an up-to-date immunization history (P<0.05). An up-to-date immunization history was not related to age, immunologic stage, or viremia but to the referral medical center. CONCLUSIONS: All pediatricians in charge of HIV-infected children are urged to identify missing immunizations in this high-risk population.

Prevalence and determinants of obesity in children in public schools of Sintra, Portugal

OBJECTIVE: To assess the prevalence of and the factors related to overweight and obesity in a sample of children from the region of Sintra, Portugal. METHODS AND PROCEDURES: Cross-sectional study, stratified for freguesia with random selection of schools. Height, weight, triceps skinfold, upper arm and waist circumferences were measured, and overweight/obesity defined according to international criteria. Breast-feeding, number of daily meals and parents' height and weight data were also collected. RESULTS: One thousand two hundred and twenty-five children aged 6-10 years were assessed. Overall prevalence of overweight and obesity was 35.6% (23% overweight and 12.6% obesity). Overweight or obese children had higher triceps skinfold, upper arm circumference, arm muscle area, and waist circumference than their normal weight counterparts (P < 0.001). On multivariate analysis, relatively to a child without obese progenitors, a child with one obese progenitor had an obesity risk multiplied by 2.78 (95% confidence interval (CI): 1.76-4.38), while a child with two obese progenitors had a risk multiplied by 6.47 (95% CI: 5.59-16.19). Conversely, being picky was significantly related with a smaller risk of obesity: for boys, odds ratio (OR) = 0.15 (95% CI: 0.04-0.63); for girls, OR = 0.19 (95% CI: 0.06-0.64). Finally, no relationships were found between obesity, birth weight, birth height or breast-feeding. DISCUSSION: Prevalence of overweight and obesity are elevated among children of the Sintra region in Portugal compared to most other regions of Europe. The relationship with the parents' nutritional state stresses the need to target families for preventing obesity.

Determinants of the development of post-traumatic stress disorder, in the general population.

PURPOSE: To assess (1) the lifetime prevalence of exposure both to trauma and post-traumatic stress disorder (PTSD); (2) the risk of PTSD by type of trauma; and (3) the determinants of the development of PTSD in the community. METHODS: The Diagnostic Interview for Genetic Studies was administered to a random sample of an urban area (N = 3,691). RESULTS: (1) The lifetime prevalence estimates of exposure to trauma and PTSD were 21.0 and 5.0%; respectively, with a twice as high prevalence of PTSD in women compared to men despite a similar likelihood of exposure in the two sexes; (2) Sexual abuse was the trauma involving the highest risk of PTSD; (3) The risk of PTSD was most strongly associated with sexual abuse followed by preexisting bipolar disorder, alcohol dependence, antisocial personality, childhood separation anxiety disorder, being victim of crime, witnessing violence, Neuroticism and Problem-focused coping strategies. After adjustment for these characteristics, female sex was no longer found to be significantly associated with the risk of PTSD. CONCLUSIONS: The risk for the development of PTSD after exposure to traumatic events is associated with several factors including the type of exposure, preexisting psychopathology, personality features and coping strategies which independently contribute to the vulnerability to PTSD.

Determinants of the essential one-carbon metabolism metabolites, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine and folate, in cerebrospinal fluid.

BACKGROUND: Disturbances in the levels of one-carbon (1C) metabolism metabolites have been associated with a wide variety of neuropsychiatric diseases. Cerebrospinal fluid (CSF) levels of homocysteine (Hcy) and the other 1C metabolites, nor their interrelatedness and putative determinants, have been studied extensively in a healthy population. METHODS: Plasma and CSF samples from 100 individuals free from neuropsychiatric diseases were analyzed (55 male, 45 female; age 50±17 years). In blood, we measured plasma Hcy, serum folate and serum vitamin B12. In CSF, we measured total Hcy, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and 5-methyltetrahydrofolate (5-methylTHF). Highly selective analytical methods like liquid chromatography combined with either mass spectrometry or fluorescence detection were used. RESULTS: CSF Hcy was inversely correlated with CSF 5-methylTHF and positively with plasma Hcy, independent of serum folate status. CSF SAH correlated with age, lower CSF 5-methylTHF and higher CSF Hcy. CSF 5-methylTHF showed independent negative correlations with age and positive correlations with serum folate. CSF SAM did not correlate with any of the 1C metabolites. CONCLUSIONS: Aging is characterized by a reduction in CSF 5-methylTHF levels and increased CSF levels of the potentially neurotoxic transmethylation inhibitor SAH. CSF 5-methylTHF, which is itself determined in part by systemic folate status, is a powerful independent determinant of CSF levels of Hcy and SAH.

Determinants of the effect of existential behavioral therapy for bereaved partners: a qualitative study.

BACKGROUND: Informal caregivers of palliative patients took part in existential behavioral therapy (EBT), a group intervention comprising mindfulness exercises to reduce psychological distress and improve quality of life. OBJECTIVES: This study examined what the participants perceived as helpful to cope with their loss during the first year of bereavement, particularly with regard to the EBT intervention. DESIGN: Sixteen problem-centered, semi-structured interviews were evaluated with content analysis. RESULTS: Two main categories were found: social support and self-regulation. Social support includes sense of belonging as well as emotional, cognitive, and practical help experienced from others. Mindfulness and acceptance, a clear focus on the positive, and orientation toward the future were helpful strategies of self-regulation; these were also part of the EBT intervention. Mindfulness was understood as permitting emotions and acceptance of one's inner processes, even if they were not pleasant, and was found to be helpful to stop ruminative thinking. CONCLUSIONS: The categories considered as being helpful parallel core elements of EBT and recent grief theories. The intervention was found to be supportive and met the needs of the participants. The interviewees appreciated the continuity of EBT support from palliative care into bereavement.

Physical determinants of tennis performance in competitive teenage players

It is unclear how physical attributes influence tennis-specific performance in teenage players. The aims of this study were (a) to examine the relationships between speed, explosive power, leg stiffness, and muscular strength of upper and lower limbs; and (b) to determine to what extent these physical qualities relate to tournament play performance in a group of competitive teenage tennis players. A total of 12 male players aged 13.6 +/- 1.4 years performed a series of physical tests: a 5-m, 10-m, and 20-m sprint; squat jump (SJ); countermovement jump (CMJ); drop jump (DJ); multi-rebound jumps; maximum voluntary contraction of isometric grip strength; and plantar flexor of the dominant and nondominant side. Speed (r = 0.69, 0.63, and 0.74 for 5-, 10-, and 20-m sprints, respectively), vertical power abilities (r = -0.71, -0.80 and -0.66 for SJ, CMJ, and DJ, respectively), and maximal strength in the dominant side (r = -0.67 and -0.73 for handgrip and plantar flexor, respectively) were significantly correlated with tennis performance. However, strength in the nondominant side (r = -0.29 and -0.42 for handgrip and plantar flexor) and leg stiffness (r = -0.15) were not correlated with the performance ranking of the players. It seems that physical attributes have a strong influence on tennis performance in this age group and that an important asymmetry is already observed. By monitoring regularly such physical abilities during puberty, the conditioning coach can modify a program to compensate for the imbalances. This would in turn minimize the risks of injuries during this critical period.

Endothelial cells as key determinants of the tumor microenvironment: interaction with tumor cells, extracellular matrix and immune killer cells.

Besides tumor cells, the tumor microenvironment harbors a variety of host-derived cells, such as endothelial cells, fibroblasts, innate and adaptive immune cells. It is a complex and highly dynamic environment, providing very important cues to tumor development and progression. Tumor-associated endothelial cells play a key role in this process. On the one hand, they form tumor-associated (angiogenic) vessels through sprouting from locally preexisting vessels or recruitment of bone marrow-derived endothelial progenitor cells, to provide nutritional support to the growing tumor. On the other hand, they are the interface between circulating blood cells, tumor cells and the extracellular matrix, thereby playing a central role in controlling leukocyte recruitment, tumor cell behavior and metastasis formation. Hypoxia is a critical parameter modulating the tumor microenvironment and endothelial/tumor cell interactions. Under hypoxic stress, tumor cells produce factors that promote tumor angiogenesis, tumor cell motility and metastasis. Among these factors, VEGF, a main angiogenesis modulator, can also play a critical role in the control of immune tolerance. This review discusses some aspects of the role of endothelial cells within tumor microenvironment and emphasizes their interaction with tumor cells, the extracellular matrix and with immune killer cells. We will also address the role played by circulating endothelial progenitor cells and illustrate their features and mechanism of recruitment to the tumor microenvironment and their role in tumor angiogenesis.

Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin

Variation in cellular gene expression levels has been shown to be inherited. Expression is controlled at transcriptional and post-transcriptional levels. Internal ribosome entry sites (IRES) are used by viruses to bypass inhibition of cap-dependent translation, and by eukaryotic cells to control translation under conditions when protein synthesis is inhibited. We aimed at identifying genomic determinants of variability in IRES-mediated translation of viral [Encephalomyocarditis virus (EMCV)] and cellular IRES [X-linked inhibitor-of-apoptosis (XIAP) and c-myc]. Bicistronic lentiviral constructs expressing two fluorescent reporters were used to transduce laboratory and B lymphoblastoid cell lines [15 CEPH pedigrees (n = 205) and 50 unrelated individuals]. IRES efficiency varied according to cell type and among individuals. Control of IRES activity has a significant genetic component (h(2) of 0.47 and 0.36 for EMCV and XIAP, respectively). Quantitative linkage analysis identified a suggestive locus (LOD 2.35) on chromosome 18q21.2, and genome-wide association analysis revealed of a cluster of SNPs on chromosome 3, intronic to the FHIT gene, marginally associated (P = 5.9E-7) with XIAP IRES function. This study illustrates the in vitro generation of intermediate phenotypes by using cell lines for the evaluation of genetic determinants of control of elements such as IRES.

Précarité et déterminants sociaux de la santé: quel(s) rôle(s) pour le médecin de premier recours [Deprivation and social determinants of health: any role for the general practitioner?]

Social deprivation also exists in an industrialised country like Switzerland where there are many different social economic levels; social inequalities have increased in the past years having a major impact on social economic determinants of health. Being aware of these determinants and systematically identifying them in patients has become crucial for the general practitioner in order to improve the way s/he delivers care and interacts with more vulnerable populations. Because the general practitioner is often in contact with people of different socioeconomic levels, s/he is a key witness of social inequalities in health. S/he therefore has a responsibility to document them, to promote health, to prevent disease and be an advocate for the disadvantages in order to influence these social determinants of health.

Three essays on the determinants of output, inflation and interest rates

Résumé: Output, inflation and interest rates are key macroeconomic variables, in particular for monetary policy. In modern macroeconomic models they are driven by random shocks which feed through the economy in various ways. Models differ in the nature of shocks and their transmission mechanisms. This is the common theme underlying the three essays of this thesis. Each essay takes a different perspective on the subject: First, the thesis shows empirically how different shocks lead to different behavior of interest rates over the business cycle. For commonly analyzed shocks (technology and monetary policy errors), the patterns square with standard models. The big unknown are sources of inflation persistence. Then the thesis presents a theory of monetary policy, when the central bank can better observe structural shocks than the public. The public will then seek to infer the bank's extra knowledge from its policy actions and expectation management becomes a key factor of optimal policy. In a simple New Keynesian model, monetary policy becomes more concerned with inflation persistence than otherwise. Finally, the thesis points to the huge uncertainties involved in estimating the responses to structural shocks with permanent effects.

Determinants of school efficiency : The case of primary schools in the State of Geneva, Switzerland

Purpose The purpose of this paper is (1) to measure school technical efficiency and (2) to identify the determinants of primary school performance. Design/methodology/approach A two-stage Data Envelopment Analysis (DEA) of school efficiency is conducted. At the first stage, DEA is employed to calculate an individual efficiency score for each school. At the second stage, efficiency is regressed on school characteristics and environmental variables. Findings The mean technical efficiency of schools in the State of Geneva is equal to 93%. By improving the operation of schools, 7% (100 - 93) of inputs could be saved, representing 17'744'656.2 Swiss francs in 2010. School efficiency is negatively influenced by (1) operations being held on multiple sites, (2) the proportion of disadvantaged pupils enrolled at the school and (3) the provision of special education, but positively influenced by school size (captured by the number of pupils). Practical implications Technically, the determinants of school efficiency are outside of the control of the headteachers. However, it is still possible to either boost the positive impact or curb the negative impact. Potential actions are discussed. Originality/value Unlike most similar studies, the model in this study is tested for multicollinearity, heteroskedasticity and endogeneity. It is therefore robust. Moreover, one explanatory variable of school efficiency (operations being held on multiple sites) is a truly original variable as it has never been tested so far.

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Neuro-mechanical determinants of repeated treadmill sprints - Usefulness of an "hypoxic to normoxic recovery" approach.

To improve our understanding of the limiting factors during repeated sprinting, we manipulated hypoxia severity during an initial set and examined the effects on performance and associated neuro-mechanical alterations during a subsequent set performed in normoxia. On separate days, 13 active males performed eight 5-s sprints (recovery = 25 s) on an instrumented treadmill in either normoxia near sea-level (SL; FiO2 = 20.9%), moderate (MH; FiO2 = 16.8%) or severe normobaric hypoxia (SH; FiO2 = 13.3%) followed, 6 min later, by four 5-s sprints (recovery = 25 s) in normoxia. Throughout the first set, along with distance covered [larger sprint decrement score in SH (-8.2%) compared to SL (-5.3%) and MH (-7.2%); P < 0.05], changes in contact time, step frequency and root mean square activity (surface electromyography) of the quadriceps (Rectus femoris muscle) in SH exceeded those in SL and MH (P < 0.05). During first sprint of the subsequent normoxic set, the distance covered (99.6, 96.4, and 98.3% of sprint 1 in SL, MH, and SH, respectively), the main kinetic (mean vertical, horizontal, and resultant forces) and kinematic (contact time and step frequency) variables as well as surface electromyogram of quadriceps and plantar flexor muscles were fully recovered, with no significant difference between conditions. Despite differing hypoxic severity levels during sprints 1-8, performance and neuro-mechanical patterns did not differ during the four sprints of the second set performed in normoxia. In summary, under the circumstances of this study (participant background, exercise-to-rest ratio, hypoxia exposure), sprint mechanical performance and neural alterations were largely influenced by the hypoxia severity in an initial set of repeated sprints. However, hypoxia had no residual effect during a subsequent set performed in normoxia. Hence, the recovery of performance and associated neuro-mechanical alterations was complete after resting for 6 min near sea level, with a similar fatigue pattern across conditions during subsequent repeated sprints in normoxia.