HDL-C and HDL-C/ApoA-I predict long-term progression of glycemia in established type 2 diabetes

OBJECTIVE: Low HDL cholesterol (HDL-C) and small HDL particle size may directly promote hyperglycemia. We evaluated associations of HDL-C, apolipoprotein A-I (apoA-I), and HDL-C/apoA-I with insulin secretion, insulin resistance, HbA1c, and long-term glycemic deterioration, reflected by initiation of pharmacologic glucose control.

RESEARCH DESIGN AND METHODS: The 5-year Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study followed 9,795 type 2 diabetic subjects. We calculated baseline associations of fasting HDL-C, apoA-I, and HDL-C/apoA-I with HbA1c and, in those not taking exogenous insulin (n = 8,271), with estimated β-cell function (homeostasis model assessment of β-cell function [HOMA-B]) and insulin resistance (HOMA-IR). Among the 2,608 subjects prescribed lifestyle only, Cox proportional hazards analysis evaluated associations of HDL-C, apoA-I, and HDL-C/apoA-I with subsequent initiation of oral hypoglycemic agents (OHAs) or insulin.

RESULTS: Adjusted for age and sex, baseline HDL-C, apoA-I, and HDL-C/apoA-I were inversely associated with HOMA-IR (r = -0.233, -0.134, and -0.230; all P < 0.001; n = 8,271) but not related to HbA1c (all P > 0.05; n = 9,795). ApoA-I was also inversely associated with HOMA-B (r = -0.063; P = 0.002; n = 8,271) adjusted for age, sex, and HOMA-IR. Prospectively, lower baseline HDL-C and HDL-C/apoA-I levels predicted greater uptake (per 1-SD lower: hazard ratio [HR] 1.13 [CI 1.07-1.19], P < 0.001; and HR 1.16 [CI 1.10-1.23], P < 0.001, respectively) and earlier uptake (median 12.9 and 24.0 months, respectively, for quartile 1 vs. quartile 4; both P < 0.01) of OHAs and insulin, with no difference in HbA1c thresholds for initiation (P = 0.87 and P = 0.81). Controlling for HOMA-IR and triglycerides lessened both associations, but HDL-C/apoA-I remained significant.

CONCLUSIONS: HDL-C, apoA-I, and HDL-C/apoA-I were associated with concurrent insulin resistance but not HbA1c. However, lower HDL-C and HDL-C/apoA-I predicted greater and earlier need for pharmacologic glucose control.

TRPV2 Channels Contribute to Stretch-Activated Cation Currents and Myogenic Constriction in Retinal Arterioles

Purpose: Activation of the transient receptor potential channels, TRPC6, TRPM4, and TRPP1 (PKD2), has been shown to contribute to the myogenic constriction of cerebral arteries. In the present study we sought to determine the potential role of various mechanosensitive TRP channels to myogenic signaling in arterioles of the rat retina.

Methods: Rat retinal arterioles were isolated for RT-PCR, Fura-2 Ca2+ microfluorimetry, patch-clamp electrophysiology, and pressure myography studies. In some experiments, confocal immunolabeling of wholemount preparations was used to examine the localization of specific mechanosensitive TRP channels in retinal vascular smooth muscle cells (VSMCs).

Results: Reverse transcription-polymerase chain reaction analysis demonstrated mRNA expression for TRPC1, M7, V1, V2, V4, and P1, but not TRPC6 or M4, in isolated retinal arterioles. Immunolabeling revealed plasma membrane, cytosolic and nuclear expression of TRPC1, M7, V1, V2, V4, and P1 in retinal VSMCs. Hypoosmotic stretch-induced Ca2+ influx in retinal VSMCs was reversed by the TRPV2 inhibitor tranilast and the nonselective TRPP1/V2 antagonist amiloride. Inhibitors of TRPC1, M7, V1, and V4 had no effect. Hypoosmotic stretch-activated cation currents were similar in Na+ and Cs+ containing solutions suggesting no contribution by TRPP1 channels. Direct plasma membrane stretch triggered cation current activity that was blocked by tranilast and specific TRPV2 pore-blocking antibodies and mimicked by the TRPV2 activator, Δ9-tetrahydrocannabinol. Preincubation of retinal arterioles with TRPV2 blocking antibodies prevented the development of myogenic tone.

Conclusions: Our results suggest that retinal VSMCs express a range of mechanosensitive TRP channels, but only TRPV2 appears to contribute to myogenic signaling in this vascular bed.

Investigations on the structural, optical and magnetic properties of nanostructured cerium oxide in pure and doped forms and its polymer nanocomposites

In recent years, nanoscience and nanotechnology has emerged as one of the most important and exciting frontier areas of research interest in almost all fields of science and technology. This technology provides the path of many breakthrough changes in the near future in many areas of advanced technological applications. Nanotechnology is an interdisciplinary area of research and development. The advent of nanotechnology in the modern times and the beginning of its systematic study can be thought of to have begun with a lecture by the famous physicist Richard Feynman. In 1960 he presented a visionary and prophetic lecture at the meeting of the American Physical Society entitled “there is plenty of room at the bottom” where he speculated on the possibility and potential of nanosized materials. Synthesis of nanomaterials and nanostructures are the essential aspects of nanotechnology. Studies on new physical properties and applications of nanomaterials are possible only when materials are made available with desired size, morphology, crystal structure and chemical composition. Cerium oxide (ceria) is one of the important functional materials with high mechanical strength, thermal stability, excellent optical properties, appreciable oxygen ion conductivity and oxygen storage capacity. Ceria finds a variety of applications in mechanical polishing of microelectronic devices, as catalysts for three-way automatic exhaust systems and as additives in ceramics and phosphors. The doped ceria usually has enhanced catalytic and electrical properties, which depend on a series of factors such as the particle size, the structural characteristics, morphology etc. Ceria based solid solutions have been widely identified as promising electrolytes for intermediate temperature solid oxide fuel cells (SOFC). The success of many promising device technologies depends on the suitable powder synthesis techniques. The challenge for introducing new nanopowder synthesis techniques is to preserve high material quality while attaining the desired composition. The method adopted should give reproducible powder properties, high yield and must be time and energy effective. The use of a variety of new materials in many technological applications has been realized through the use of thin films of these materials. Thus the development of any new material will have good application potential if it can be deposited in thin film form with the same properties. The advantageous properties of thin films include the possibility of tailoring the properties according to film thickness, small mass of the materials involved and high surface to volume ratio. The synthesis of polymer nanocomposites is an integral aspect of polymer nanotechnology. By inserting the nanometric inorganic compounds, the properties of polymers can be improved and this has a lot of applications depending upon the inorganic filler material present in the polymer.

Impact of Thresholds and Load Patterns when Executing HPC Applications with Cloud Elasticity

Elasticity is one of the most known capabilities related to cloud computing, being largely deployed reactively using thresholds. In this way, maximum and minimum limits are used to drive resource allocation and deallocation actions, leading to the following problem statements: How can cloud users set the threshold values to enable elasticity in their cloud applications? And what is the impact of the application’s load pattern in the elasticity? This article tries to answer these questions for iterative high performance computing applications, showing the impact of both thresholds and load patterns on application performance and resource consumption. To accomplish this, we developed a reactive and PaaS-based elasticity model called AutoElastic and employed it over a private cloud to execute a numerical integration application. Here, we are presenting an analysis of best practices and possible optimizations regarding the elasticity and HPC pair. Considering the results, we observed that the maximum threshold influences the application time more than the minimum one. We concluded that threshold values close to 100% of CPU load are directly related to a weaker reactivity, postponing resource reconfiguration when its activation in advance could be pertinent for reducing the application runtime.

Low doses of a neonicotinoid insecticide modify pheromone response thresholds of central but not peripheral olfactory neurons in a pest insect

International audience

Determination of thresholds in marine molluscs as an alternative to the Environmental Quality Standards in marine water defined in the Water Framework Directive

The Water Framework Directive (WFD) establishes Environmental Quality Standards (EQS) in marine water for 34 priority substances. Among these substances, 25 are hydrophobic and bioaccumulable (2 metals and 23 organic compounds). For these 25 substances, monitoring in water matrix is not appropriate and an alternative matrix should be developed. Bivalve mollusks, particularly mussels (Mytilus edulis, Mytilus galloprovincialis), are used by Ifremer as a quantitative biological indicator since 1979 in France, to assess the marine water quality. This study has been carried out in order to determine thresholds in mussels at least as protective as EQS in marine water laid down by the WFD. Three steps are defined: - Provide an overview of knowledges about the relations between the concentrations of contaminants in the marine water and mussels through bioaccumulation factor (BAF) and bioconcentration factor (BCF). This allows to examine how a BCF or a BAF can be determined: BCF can be determined experimentally (according to US EPA or ASTM standards), or by Quantitative Activity-Structure Relationship models (QSAR): four equations can be used for mussels. BAF can be determined by field experiment; but none standards exists. It could be determined by using QSAR but this method is considered as invalid for mussels, or by using existing model: Dynamic Budget Model, but this is complex to use. - Collect concentrations data in marine water (Cwater) in bibliography for those 25 substances; and compare them with concentration in mussels (Cmussels) obtained through French monitoring network of chemicals contaminants (ROCCH) and biological integrator network RINBIO. According to available data, this leads to determine the BAF or the BCF (Cmussels /Cwater) with field data. - Compare BAF and BCF values (when available) obtained with various methods for these substances: BCF (stemming from the bibliography, using experimental process), BCF calculated by QSAR and BAF determined using field data. This study points out that experimental BCF data are available for 3 substances (Chlorpyrifos, HCH, Pentachlorobenzene). BCF by QSAR can be calculated for 20 substances. The use of field data allows to evaluate 4 BAF for organic compounds and 2 BAF for metals. Using these BAF or BCF value, thresholds in shellfish can be determined as an alternative to EQS in marine water.

Identifying and enhancing risk thresholds in the detection of elder financial abuse: A signal detection analysis of professionals' decision making

Background: Financial abuse of elders is an under acknowledged problem and professionals' judgements contribute to both the prevalence of abuse and the ability to prevent and intervene. In the absence of a definitive "gold standard" for the judgement, it is desirable to try and bring novice professionals' judgemental risk thresholds to the level of competent professionals as quickly and effectively as possible. This study aimed to test if a training intervention was able to bring novices' risk thresholds for financial abuse in line with expert opinion. Methods: A signal detection analysis, within a randomised controlled trial of an educational intervention, was undertaken to examine the effect on the ability of novices to efficiently detect financial abuse. Novices (n = 154) and experts (n = 33) judged "certainty of risk" across 43 scenarios; whether a scenario constituted a case of financial abuse or not was a function of expert opinion. Novices (n = 154) were randomised to receive either an on-line educational intervention to improve financial abuse detection (n = 78) or a control group (no on-line educational intervention, n = 76). Both groups examined 28 scenarios of abuse (11 "signal" scenarios of risk and 17 "noise" scenarios of no risk). After the intervention group had received the on-line training, both groups then examined 15 further scenarios (5 "signal" and 10 "noise" scenarios). Results: Experts were more certain than the novices, pre (Mean 70.61 vs. 58.04) and post intervention (Mean 70.84 vs. 63.04); and more consistent. The intervention group (mean 64.64) were more certain of abuse post-intervention than the control group (mean 61.41, p = 0.02). Signal detection analysis of sensitivity (Á) and bias (C) revealed that this was due to the intervention shifting the novices' tendency towards saying "at risk" (C post intervention -.34) and away from their pre intervention levels of bias (C-.12). Receiver operating curves revealed more efficient judgments in the intervention group. Conclusion: An educational intervention can improve judgements of financial abuse amongst novice professionals.

Water stress thresholds for regulated deficit irrigation in pistachio trees

The response of "Kerman" pistachio trees budded on three different rootstocks (Pistacia terebinthus, Pista-cia atlantica and Pistacia integerrima) to regulated deficit irrigation (RDI) in shallow soils was studied for3 years. The trees were either fully irrigated (C treatment) or subjected to deficit irrigation during Stage IIof fruit growth with two water stress thresholds (T1 and T2). The irrigation scheduling for fully-irrigatedtrees and water-stressed trees was managed by means of midday stem water potential (?stem) measure-ments. The use of direct measurements of the water status allowed estimating accurately the irrigationrequirements for pistachio trees, with water reductions ranging from 46 to 205 mm in fully-irrigatedtrees. The combination of the ?stemuse and the RDI regime saved 43?70% in T1 and 48?73% in T2 ofwater compared to the calculated crop evapotranspiration (ETc) for fully irrigated treatment (C).Deficit irrigation during Stage II significantly reduced the vegetative growth of the trees. Yield and fruitquality were not affected by any irrigation regime, except during the first year of the study. Thus, theresults indicate that full irrigation scheduling and RDI can be achieved successfully using ?stemtool onpistachio trees growing in shallow soils. A ?stemthreshold of ?1.5 MPa during stage II (T1) was suggestedfor RDI scheduling, as it did not reduce the yield or the production value. However a ?stemthresholdof ?2.0 MPa (T2) resulted in a significant reduction and an extensive delay in the recovery of stomatalconductance (gl),with negative effects on long-term pistachio production.P. integerrima showed a weaker capacity of adaptation to the study conditions compared to P. atlanticaand P. terebinthus, having a tendency to get more stressed and to produce a lower quality crop.

Quantification of standards of proof thresholds in criminal and civil litigation

Standards of proof in law serve the purpose of instructing juries as to the expected levels of confidence in determinations of fact. In criminal trials, to reach a guilty verdict a jury must be satisfied beyond a reasonable doubt, and in civil trials by a preponderance of the evidence. The purposes of this study are to determine the quantitative thresholds used to make these determinations; to ascertain the levels of juror agreement with basic principles of justice; and to try to predict thresholds and beliefs by juror personality characteristics. Participants read brief case descriptions and indicated thresholds in percentages, their beliefs in various principles, and completed three personality measures. A 92-94% threshold in criminal and an 80% threshold in civil matters was found; but prediction by personality was not supported. Significant percentages of jurors disavowed the presumptions of innocence and right to counsel.

Behavioral and molecular genetics of reading-related AM and FM detection thresholds

Auditory detection thresholds for certain frequencies of both amplitude modulated (AM) and frequency modulated (FM) dynamic auditory stimuli are associated with reading in typically developing and dyslexic readers. We present the first behavioral and molecular genetic characterization of these two auditory traits. Two extant extended family datasets were given reading tasks and psychoacoustic tasks to determine FM 2 Hz and AM 20 Hz sensitivity thresholds. Univariate heritabilities were significant for both AM (h2 = 0.20) and FM (h2 = 0.29). Bayesian posterior probability of linkage (PPL) analysis found loci for AM (12q, PPL = 81 %) and FM (10p, PPL = 32 %; 20q, PPL = 65 %). Bivariate heritability analyses revealed that FM is genetically correlated with reading, while AM was not. Bivariate PPL analysis indicates that FM loci (10p, 20q) are not also associated with reading.

Slow passage through thresholds in quantum dot lasers

A turn on of a quantum dot (QD) semiconductor laser simultaneously operating at the ground state (GS) and excited state (ES) is investigated both experimentally and theoretically. We find experimentally that the slow passage through the two successive laser thresholds may lead to significant delays in the GS and ES turn ons. The difference between the turn-on times is measured as a function of the pump rate of change and reveals no clear power law. This has motivated a detailed analysis of rate equations appropriate for two-state lasing QD lasers. We find that the effective time of the GS turn on follows an -1/2 power law provided that the rate of change is not too small. The effective time of the ES transition follows an -1 power law, but its first order correction in ln is numerically significant. The two turn ons result from different physical mechanisms. The delay of the GS transition strongly depends on the slow growth of the dot population, whereas the ES transition only depends on the time needed to leave a repellent steady state.

La négativité de l’aperception pure : une étude sur l’altérité dans la Critique de la raison pure

Cet article a pour objectif de déceler chez Kant, et plus précisément dans la Critique de la raison pure, une théorie d’altérité. Nous partons de ce que Kant nomme lui-même le « paradoxe » du sens interne, à savoir que le sujet vit son activité de pensée de manière passive, comme tout autre phénomène. C’est dire que le sujet se reçoit comme une intuition et il en est affecté, de même qu’il l’est par l’intuition des objets à l’extérieur de lui. Or si cette structure se présente comme en effet une structure d’altérité où le sujet vit son activité comme celle d’un autre, il nous faut encore tenir compte des remarques de Kant (notamment dans la seconde édition) où le sujet est présenté comme ayant un rapport direct (et donc préphénoménal) à soi. C’est à partir de cette tension interne au texte de la Critique que nous tenterons d’esquisser une théorie d’altérité. Nous voulons montrer que l’aperception pure est douée d’une forme de négativité qui rendra impossible toute immédiateté dans le rapport à soi.