Prevalence of normal weight obesity in Switzerland: effect of various definitions

BACKGROUND: Normal weight obesity (NWO) is defined as an excessive body fat associated with a normal body mass index (BMI < 25 kg/m(2)), but its prevalence in the general population is unknown. AIM OF THE STUDY: To assess the prevalence of NWO in Switzerland according to different cut points used to define excess body fat. METHODS: Cross-sectional study including 3,213 women and 2,912 men aged 35-75 years. Body fat was assessed by bioelectrical impedance analysis and prevalence of NWO was assessed using four previously published definitions for excess body fat. RESULTS: Percent body fat increased with age: in men, the values (mean +/- SD) were 20.2 +/- 5.4, 23.0 +/- 5.4, 26.3 +/- 5.2 and 28.2 +/- 4.6 for age groups 35-44, 45-54, 55-64 and 65-75 years, respectively; the corresponding values for women were 29.9 +/- 7.8, 33.1 +/- 7.4, 36.7 +/- 7.5 and 39.6 +/- 6.9. In men, prevalence of NWO was <1% irrespective of the definition used. Conversely, in women, a 1- to 20-fold difference (from 1.4 to 27.8%) in NWO prevalence was found. The prevalence of NWO increased with age when age-independent cut points were used in women, but not in men. CONCLUSIONS: Prevalence of NWO is low in the general population and higher in women than in men. The prevalence is highly dependent on the criteria used to define excess body fat, namely in women. The use of gender- and age-specific cut points to define excess body fat is better than fixed or gender-specific only cut points.

Quantifying the weight of fingerprint evidence through the spatial relationship, directions and types of minutiae observed on fingermarks

This paper presents a statistical model for the quantification of the weight of fingerprint evidence. Contrarily to previous models (generative and score-based models), our model proposes to estimate the probability distributions of spatial relationships, directions and types of minutiae observed on fingerprints for any given fingermark. Our model is relying on an AFIS algorithm provided by 3M Cogent and on a dataset of more than 4,000,000 fingerprints to represent a sample from a relevant population of potential sources. The performance of our model was tested using several hundreds of minutiae configurations observed on a set of 565 fingermarks. In particular, the effects of various sub-populations of fingers (i.e., finger number, finger general pattern) on the expected evidential value of our test configurations were investigated. The performance of our model indicates that the spatial relationship between minutiae carries more evidential weight than their type or direction. Our results also indicate that the AFIS component of our model directly enables us to assign weight to fingerprint evidence without the need for the additional layer of complex statistical modeling involved by the estimation of the probability distributions of fingerprint features. In fact, it seems that the AFIS component is more sensitive to the sub-population effects than the other components of the model. Overall, the data generated during this research project contributes to support the idea that fingerprint evidence is a valuable forensic tool for the identification of individuals.

Activity-dependent phosphorylation of SNAP-25 in hippocampal organotypic cultures.

Synaptosomal-associated protein of 25 kDa (SNAP-25) is thought to play a key role in vesicle exocytosis and in the control of transmitter release. However, the precise mechanisms of action as well as the regulation of SNAP-25 remain unclear. Here we show by immunoprecipitation that activation of protein kinase C (PKC) by phorbol esters results in an increase in SNAP-25 phosphorylation. In addition, immunochemical analysis of two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels shows that SNAP-25 focuses as three or four distinct spots in the expected range of molecular weight and isoelectric point. Changing the phosphorylation level of the protein by incubating the slices in the presence of either a PKC agonist (phorbol 12,13-dibutyrate) or antagonist (chelerythrine) modified the distribution of SNAP-25 among these spots. Phorbol 12,13-dibutyrate increased the intensity of the spots with higher molecular weight and lower isoelectric point, whereas chelerythrine produced the opposite effect. This effect was specific for regulators of PKC, as agonists of other kinases did not produce similar changes. Induction of long-term potentiation, a property involved in learning mechanisms, and production of seizures with a GABA(A) receptor antagonist also increased the intensity of the spots with higher molecular weight and lower isoelectric point. This effect was prevented by the PKC inhibitor chelerythrine. We conclude that SNAP-25 can be phosphorylated in situ by PKC in an activity-dependent manner.

The data treatment dependent variability of U-Pb zircon ages obtained using mono-collector, sector field, laser ablation ICP-MS

U-Pb dating of zircons by laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) is a widely used analytical technique in Earth Sciences. For U-Pb ages below 1 billion years (1 Ga), Pb-206/U-238 dates are usually used, showing the least bias by external parameters such as the presence of initial lead and its isotopic composition in the analysed mineral. Precision and accuracy of the Pb/U ratio are thus of highest importance in LA-ICPMS geochronology. We consider the evaluation of the statistical distribution of the sweep intensities based on goodness-of-fit tests in order to find a model probability distribution fitting the data to apply an appropriate formulation for the standard deviation. We then discuss three main methods to calculate the Pb/U intensity ratio and its uncertainty in the LA-ICPMS: (1) ratio-of-the-mean intensities method, (2) mean-of-the-intensity-ratios method and (3) intercept method. These methods apply different functions to the same raw intensity vs. time data to calculate the mean Pb/U intensity ratio. Thus, the calculated intensity ratio and its uncertainty depend on the method applied. We demonstrate that the accuracy and, conditionally, the precision of the ratio-of-the-mean intensities method are invariant to the intensity fluctuations and averaging related to the dwell time selection and off-line data transformation (averaging of several sweeps); we present a statistical approach how to calculate the uncertainty of this method for transient signals. We also show that the accuracy of methods (2) and (3) is influenced by the intensity fluctuations and averaging, and the extent of this influence can amount to tens of percentage points; we show that the uncertainty of these methods also depends on how the signal is averaged. Each of the above methods imposes requirements to the instrumentation. The ratio-of-the-mean intensities method is sufficiently accurate provided the laser induced fractionation between the beginning and the end of the signal is kept low and linear. We show, based on a comprehensive series of analyses with different ablation pit sizes, energy densities and repetition rates for a 193 nm ns-ablation system that such a fractionation behaviour requires using a low ablation speed (low energy density and low repetition rate). Overall, we conclude that the ratio-of-the-mean intensities method combined with low sampling rates is the most mathematically accurate among the existing data treatment methods for U-Pb zircon dating by sensitive sector field ICPMS.

Investigation of Improved Utility Cut Repair Techniques to Reduce Settlement in Repaired Areas, Phase II, TR-566, 2010

Trench maintenance problems are caused by improper backfill placement and construction procedures. This report is part of a multiphase research project that aims to improve long-term performance of utility cut restoration trenches. The goal of this research is to improve pavement patch life and reduce maintenance of the repaired areas. The objectives were to use field-testing data, laboratory-testing data, and long-term monitoring (elevation survey and falling weight deflectometer testing) to suggest and modify recommendations from Phase I and to identify the principles of trench subsurface settlement and load distribution in utility cut restoration areas by using instrumented trenches. The objectives were accomplished by monitoring local agency utility construction from Phase I, constructing and monitoring the recommended trenches from Phase I, and instrumenting trenches to monitor changes in temperature, pressure, moisture content, and settlement as a function of time to determine the influences of seasonal changes on the utility cut performance.

Loss of Prestress, Camber, and Deflection of Non-Composite and Composite Structures Using Different Weight Concretes, HR-137, 1970

General equations are presented for predicting loss of prestress and camber of both composite and non- composite prestressed concrete structures. Continuous time functins of all parameters needed to solve the equations are given, and sample results included. Computed prestress loss and camber are compared with experimental data for normal weight and lightweight concrete. Methods are also presented for predicting the effect of non-prestressed tension steel in reducing time-dependent loss of prestress and camber, and for the determination of short-time deflections of uncracked and cracked prestressed members. Comparisons with experimental results are indicated for these partially prestressed methods.

Bayesian genetic parameters for body weight and survival of Nile tilapia farmed in Brazil

The objective of this study was to estimate genetic parameters for survival and weight of Nile tilapia (Oreochromis niloticus), farmed in cages and ponds in Brazil, and to predict genetic gain under different scenarios. Survival was recorded as a binary response (dead or alive), during harvest time in the 2008 grow-out period. Genetic parameters were estimated using a Bayesian mixed linear-threshold animal model via Gibbs sampling. The breeding population consisted of 2,912 individual fish, which were analyzed together with the pedigree of 5,394 fish. The heritabilities estimates, with 95% posterior credible intervals, for tagging weight, harvest weight and survival were 0.17 (0.09-0.27), 0.21 (0.12-0.32) and 0.32 (0.22-0.44), respectively. Credible intervals show a 95% probability that the true genetic correlations were in a favourable direction. The selection for weight has a positive impact on survival. Estimated genetic gain was high when selecting for harvest weight (5.07%), and indirect gain for tagging weight (2.17%) and survival (2.03%) were also considerable.

Cell-permeable peptides induce dose- and length-dependent cytotoxic effects.

We have explored the threshold of tolerance of three unrelated cell types to treatments with potential cytoprotective peptides bound to Tat(48-57) and Antp(43-58) cell-permeable peptide carriers. Both Tat(48-57) and Antp(43-58) are well known for their good efficacy at crossing membranes of different cell types, their overall low toxicity, and their absence of leakage once internalised. Here, we show that concentrations of up to 100 microM of Tat(48-57) were essentially harmless in all cells tested, whereas Antp(43-58) was significantly more toxic. Moreover, all peptides bound to Tat(48-57) and Antp(43-58) triggered significant and length-dependent cytotoxicity when used at concentrations above 10 microM in all but one cell types (208F rat fibroblasts), irrespective of the sequence of the cargo. Absence of cytotoxicity in 208F fibroblasts correlated with poor intracellular peptide uptake, as monitored by confocal laser scanning fluorescence microscopy. Our data further suggest that the onset of cytotoxicity correlates with the activation of two intracellular stress signalling pathways, namely those involving JNK, and to a lesser extent p38 mitogen-activated protein kinases. These responses are of particular concern for cells that are especially sensitive to the activation of stress kinases. Collectively, these results indicate that in order to avoid unwanted and unspecific cytotoxicity, effector molecules bound to Tat(48-57) should be designed with the shortest possible sequence and the highest possible affinity for their binding partners or targets, so that concentrations below 10 microM can be successfully applied to cells without harm. Considering that cytotoxicity associated to Tat(48-57)- and Antp(43-58) bound peptide conjugates was not restricted to a particular type of cells, our data provide a general framework for the design of cell-penetrating peptides that may apply to broader uses of intracellular peptide and drug delivery.

Phosphorylation-dependent dimerization and subcellular localization of islet-brain 1/c-Jun N-terminal kinase-interacting protein 1.

Islet-brain 1 [IB1; also termed c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP-1] is involved in the apoptotic signaling cascade of JNK and functions as a scaffold protein. It organizes several MAP kinases and the microtubule-transport motor protein kinesin and relates to other signal-transducing molecules such as the amyloid precursor protein. Here we have identified IB1/JIP-1 using different antibodies that reacted with either a monomeric or a dimeric form of IB1/JIP-1. By immunoelectron microscopy, differences in the subcellular localization were observed. The monomeric form was found in the cytoplasmic compartment and is associated with the cytoskeleton and with membranes, whereas the dimeric form was found in addition in nuclei. After treatment of mouse brain homogenates with alkaline phosphatase, the dimeric form disappeared and the monomeric form decreased its molecular weight, suggesting that an IB1/JIP-1 dimerization is phosphorylation dependent and that IB1 exists in several phospho- forms. N-methyl-D-aspartate receptor activation induced a dephosphorylation of IB1/JIP-1 in primary cultures of cortical neurons and reduced homodimerization. In conclusion, these data suggest that IB1/JIP-1 monomers and dimers may differ in compartmental localization and thus function as a scaffold protein of the JNK signaling cascade in the cytoplasm or as a transcription factor in nuclei.

Dose and time-dependent selective neurotoxicity induced by mephedrone in mice.

Mephedrone is a drug of abuse marketed as 'bath salts'. There are discrepancies concerning its long-term effects. We have investigated the neurotoxicity of mephedrone in mice following different exposition schedules. Schedule 1: four doses of 50 mg/kg. Schedule 2: four doses of 25 mg/kg. Schedule 3: three daily doses of 25 mg/kg, for two consecutive days. All schedules induced, in some animals, an aggressive behavior and hyperthermia as well as a decrease in weight gain. Mephedrone (schedule 1) induced dopaminergic and serotoninergic neurotoxicity that persisted 7 days after exposition. At a lower dose (schedule 2) only a transient dopaminergic injury was found. In the weekend consumption pattern (schedule 3), mephedrone induced dopamine and serotonin transporter loss that was accompanied by a decrease in tyrosine hydroxylase and tryptophan hydroxylase 2 expression one week after exposition. Also, mephedrone induced a depressive-like behavior, as well as a reduction in striatal D2 density, suggesting higher susceptibility to addictive drugs. In cultured cortical neurons, mephedrone induced a concentration-dependent cytotoxic effect. Using repeated doses for 2 days in an elevated ambient temperature we evidenced a loss of frontal cortex dopaminergic and hippocampal serotoninergic neuronal markers that suggest injuries at nerve endings.

Dose and time-dependent selective neurotoxicity induced by mephedrone in mice.

Mephedrone is a drug of abuse marketed as 'bath salts'. There are discrepancies concerning its long-term effects. We have investigated the neurotoxicity of mephedrone in mice following different exposition schedules. Schedule 1: four doses of 50 mg/kg. Schedule 2: four doses of 25 mg/kg. Schedule 3: three daily doses of 25 mg/kg, for two consecutive days. All schedules induced, in some animals, an aggressive behavior and hyperthermia as well as a decrease in weight gain. Mephedrone (schedule 1) induced dopaminergic and serotoninergic neurotoxicity that persisted 7 days after exposition. At a lower dose (schedule 2) only a transient dopaminergic injury was found. In the weekend consumption pattern (schedule 3), mephedrone induced dopamine and serotonin transporter loss that was accompanied by a decrease in tyrosine hydroxylase and tryptophan hydroxylase 2 expression one week after exposition. Also, mephedrone induced a depressive-like behavior, as well as a reduction in striatal D2 density, suggesting higher susceptibility to addictive drugs. In cultured cortical neurons, mephedrone induced a concentration-dependent cytotoxic effect. Using repeated doses for 2 days in an elevated ambient temperature we evidenced a loss of frontal cortex dopaminergic and hippocampal serotoninergic neuronal markers that suggest injuries at nerve endings.

PPARα is Required for PPARδ action in regulation of body weight and hepatic steatosis in mice.

NlmCategory="UNASSIGNED">Peroxisome proliferator activated receptors alpha (PPARα) and delta (PPARδ) belong to the nuclear receptor superfamily. PPARα is a target of well established lipid-lowering drugs. PPARδ (also known as PPARβ/δ) has been investigated as a promising antidiabetic drug target; however, the evidence in the literature on PPARδ effect on hepatic lipid metabolism is inconsistent. Mice conditionally expressing human PPARδ demonstrated pronounced weight loss and promoted hepatic steatosis when treated with GW501516 (PPARδ-agonist) when compared to wild type mice. This effect was completely absent in mice with either a dominant negative form of PPARδ or deletion of the DNA binding domain of PPARδ. This confirmed the absolute requirement for PPARδ in the physiological actions of GW501516 and confirmed the potential utility against the human form of this receptor. Surprisingly the genetic deletion of PPARα also abrogated the effect of GW501516 in terms of both weight loss and hepatic lipid accumulation. Also the levels of the PPARα endogenous agonist 16:0/18:1-GPC were shown to be modulated by PPARδ in wild type mice. Our results show that both PPARδ and PPARα receptors are essential for GW501516-driven adipose tissue reduction and subsequently hepatic steatosis, with PPARα working downstream of PPARδ.

Detecting Heterogeneous Risk Attitudes with Mixed Gambles

We propose a task for eliciting attitudes toward risk that is close to real-world risky decisions which typically involve gains and losses. The task consists of accepting or rejecting gambles that provide a gain with probability p and a loss with probability 1−p . We employ finite mixture models to uncover heterogeneity in risk preferences and find that (i) behavior is heterogeneous, with one half of the subjects behaving as expected utility maximizers, (ii) for the others, reference-dependent models perform better than those where subjects derive utility from final outcomes, (iii) models with sign-dependent decision weights perform better than those without, and (iv) there is no evidence for loss aversion. The procedure is sufficiently simple so that it can be easily used in field or lab experiments where risk elicitation is not the main experiment.

Regression analysis of compositional data when both the dependent variable and independent variable are components

It is well known that regression analyses involving compositional data need special attention because the data are not of full rank. For a regression analysis where both the dependent and independent variable are components we propose a transformation of the components emphasizing their role as dependent and independent variables. A simple linear regression can be performed on the transformed components. The regression line can be depicted in a ternary diagram facilitating the interpretation of the analysis in terms of components. An exemple with time-budgets illustrates the method and the graphical features