BACKGROUND:Describing the undiagnosed HIV-infected population is essential for guiding HIV screening policy, implementing interventions, and resource planning.
METHODS:We used French national HIV ...surveillance data and a back-calculation approach to estimate the number of undiagnosed HIV-infected individuals in France and the distribution of time since HIV infection among undiagnosed individuals. We also used data on CD4 cell count decline to assess the CD4 cell count distribution among undiagnosed individuals.
RESULTS:We estimated that 29 000 95% confidence interval (CI)24 200–33 900 individuals were living with undiagnosed HIV infection at the end of 2010. Of these, 28.7% (95% CI27.1–30.4) were infected less than a year ago, 16.4% (95% CI15.0–17.8) more than 5 years ago, and 59.6% (95% CI59.2–59.8) were eligible for antiretroviral treatment (CD4 cell count less than 500 cells/μl) according to the 2010 French guidelines. Men represented 70.0% of the undiagnosed HIV-infected individuals and had lower CD4 cell counts than women. The numbers of undiagnosed infections in MSM, non-French national heterosexuals, and French national heterosexuals were similar (9200, 9300, 10 000, respectively). However, because of differences in group size, undiagnosed HIV prevalence varied significantly between these groups (2.95, 0.36, 0.03%, respectively; P less than 0.001).
CONCLUSION:Our findings suggest that many undiagnosed HIV-infected individuals were eligible for treatment and, thus, lack of HIV diagnosis is a lost chance for them; many more heterosexuals than MSM will need to be tested to find those undiagnosed; and universal screening of men may be cost-effective, especially in the areas most affected by the epidemic, such as the Paris region.
Abstract Since the publication of the 2012 guidelines new literature has emerged to inform decision-making. The 2016 guidelines primary panel selected a number of clinically relevant questions and ...has produced updated recommendations, on the basis of important new findings. In subjects with clinical atherosclerosis, abdominal aortic aneurysm, most subjects with diabetes or chronic kidney disease, and those with low-density lipoprotein cholesterol ≥ 5 mmol/L, statin therapy is recommended. For all others, there is an emphasis on risk assessment linked to lipid determination to optimize decision-making. We have recommended nonfasting lipid determination as a suitable alternative to fasting levels. Risk assessment and lipid determination should be considered in individuals older than 40 years of age or in those at increased risk regardless of age. Pharmacotherapy is generally not indicated for those at low Framingham Risk Score (FRS; <10%). A wider range of patients are now eligible for statin therapy in the FRS intermediate risk category (10%-19%) and in those with a high FRS (> 20%). Despite the controversy, we continue to advocate for low-density lipoprotein cholesterol targets for subjects who start therapy. Detailed recommendations are also presented for health behaviour modification that is indicated in all subjects. Finally, recommendation for the use of nonstatin medications is provided. Shared decision-making is vital because there are many areas in which clinical trials do not fully inform practice. The guidelines are meant to be a platform for meaningful conversation between patient and care provider so that individual decisions can be made for risk screening, assessment, and treatment.
The Energetic Particle Detector (EPD) Investigation is one of 5 fields-and-particles investigations on the Magnetospheric Multiscale (MMS) mission. MMS comprises 4 spacecraft flying in close ...formation in highly elliptical, near-Earth-equatorial orbits targeting understanding of the fundamental physics of the important physical process called magnetic reconnection using Earth’s magnetosphere as a plasma laboratory. EPD comprises two sensor types, the Energetic Ion Spectrometer (EIS) with one instrument on each of the 4 spacecraft, and the Fly’s Eye Energetic Particle Spectrometer (FEEPS) with 2 instruments on each of the 4 spacecraft. EIS measures energetic ion energy, angle and elemental compositional distributions from a required low energy limit of 20 keV for protons and 45 keV for oxygen ions, up to >0.5 MeV (with capabilities to measure up to >1 MeV). FEEPS measures instantaneous all sky images of energetic electrons from 25 keV to >0.5 MeV, and also measures total ion energy distributions from 45 keV to >0.5 MeV to be used in conjunction with EIS to measure all sky ion distributions. In this report we describe the EPD investigation and the details of the EIS sensor. Specifically we describe EPD-level science objectives, the science and measurement requirements, and the challenges that the EPD team had in meeting these requirements. Here we also describe the design and operation of the EIS instruments, their calibrated performances, and the EIS in-flight and ground operations. Blake et al. (The Flys Eye Energetic Particle Spectrometer (FEEPS) contribution to the Energetic Particle Detector (EPD) investigation of the Magnetospheric Magnetoscale (MMS) Mission,
this issue
) describe the design and operation of the FEEPS instruments, their calibrated performances, and the FEEPS in-flight and ground operations. The MMS spacecraft will launch in early 2015, and over its 2-year mission will provide comprehensive measurements of magnetic reconnection at Earth’s magnetopause during the 18 months that comprise orbital phase 1, and magnetic reconnection within Earth’s magnetotail during the about 6 months that comprise orbital phase 2.
The Jupiter Energetic Particle Detector Instruments (JEDI) on the Juno Jupiter polar-orbiting, atmosphere-skimming, mission to Jupiter will coordinate with the several other space physics instruments ...on the Juno spacecraft to characterize and understand the space environment of Jupiter’s polar regions, and specifically to understand the generation of Jupiter’s powerful aurora. JEDI comprises 3 nearly-identical instruments and measures at minimum the energy, angle, and ion composition distributions of ions with energies from H:20 keV and O: 50 keV to >1 MeV, and the energy and angle distribution of electrons from <40 to >500 keV. Each JEDI instrument uses microchannel plates (MCP) and thin foils to measure the times of flight (TOF) of incoming ions and the pulse height associated with the interaction of ions with the foils, and it uses solid state detectors (SSD’s) to measure the total energy (
E
) of both the ions and the electrons. The MCP anodes and the SSD arrays are configured to determine the directions of arrivals of the incoming charged particles. The instruments also use fast triple coincidence and optimum shielding to suppress penetrating background radiation and incoming UV foreground. Here we describe the science objectives of JEDI, the science and measurement requirements, the challenges that the JEDI team had in meeting these requirements, the design and operation of the JEDI instruments, their calibrated performances, the JEDI inflight and ground operations, and the initial measurements of the JEDI instruments in interplanetary space following the Juno launch on 5 August 2011. Juno will begin its prime science operations, comprising 32 orbits with dimensions 1.1×40 RJ, in mid-2016.
We report the development of laboratory based hyperspectral X-ray computed tomography which allows the internal elemental chemistry of an object to be reconstructed and visualised in three ...dimensions. The method employs a spectroscopic X-ray imaging detector with sufficient energy resolution to distinguish individual elemental absorption edges. Elemental distributions can then be made by K-edge subtraction, or alternatively by voxel-wise spectral fitting to give relative atomic concentrations. We demonstrate its application to two material systems: studying the distribution of catalyst material on porous substrates for industrial scale chemical processing; and mapping of minerals and inclusion phases inside a mineralised ore sample. The method makes use of a standard laboratory X-ray source with measurement times similar to that required for conventional computed tomography.
Abstract Many developments have occurred since the publication of the widely-used 2009 Canadian Cardiovascular Society (CCS) Dyslipidemia guidelines. Here, we present an updated version of the ...guidelines, incorporating new recommendations based on recent findings and harmonizing CCS guidelines with those from other Societies. The G rading of R ecommendations A ssessment, D evelopment and E valuation (GRADE) system was used, per present standards of the CCS. The total cardiovascular disease Framingham Risk Score (FRS), modified for a family history of premature coronary disease, is recommended for risk assessment. Low-density lipoprotein cholesterol remains the primary target of therapy. However, non-high density lipoprotein cholesterol has been added to apolipoprotein B as an alternate target. There is an increased emphasis on treatment of higher risk patients, including those with chronic kidney disease and high risk hypertension. The primary panel has recommended a judicious use of secondary testing for subjects in whom the need for statin therapy is unclear. Expanded information on health behaviours is presented and is the backbone of risk reduction in all subjects. Finally, a systematic approach to statin intolerance is advocated to maximize appropriate use of lipid-lowering therapy. This document presents the recommendations and principal conclusions of this process. Along with associated Supplementary Material that can be accessed online, this document will be part of a program of knowledge translation. The goal is to increase the appropriate use of evidence-based cardiovascular disease event risk assessment in the management of dyslipidemia as a fundamental means of reducing global risk in the Canadian population.
Quantum computers promise to solve certain problems that are forever intractable to classical computers. The first of these devices are likely to tackle bespoke problems suited to their own ...particular physical capabilities. Sampling the probability distribution from many bosons interfering quantum-mechanically is conjectured to be intractable to a classical computer but solvable with photons in linear optics. However, the complexity of this type of problem means its solution is mathematically unverifiable, so the task of establishing successful operation becomes one of gathering sufficiently convincing circumstantial or experimental evidence. Here, we develop scalable methods to experimentally establish correct operation for this class of computation, which we implement for three, four and five photons in integrated optical circuits, on Hilbert spaces of up to 50,000 dimensions. Our broad approach is practical for all quantum computational architectures where formal verification methods for quantum algorithms are either intractable or unknown.
Display omitted
Variation of self-diffusion coefficient (D) of sodium 1-decanesulfonate as a function of its concentration in TA solution (■) or ChCat solution (●) at 30°C (ChCat=4gL−1 in water). ...Included photographs show the evolution of polymer solution (precipitation occurring) during surfactant addition.
•Diffusion NMR allows to simultaneously study quaternized chitosan and surfactant diffusion coefficients.•Consistent conclusions obtained whatever the used technique (diffusion NMR and conductivity).•Electrostatic nature of interactions can be detected by DOSY experiments.•For concentration ratio of ionic charges larger than 1, surfactant molecules are free and have the same properties than pure surfactant in water solution.
Surfactant-polysaccharide complexes (SPEC) based on oppositely charged sodium 1-decanesulfonate and quaternized chitosan were studied using two techniques. The first one, the conductivity, is a very often used even when diffusion NMR (DOSY) technique was considered for the first time for such systems involving surfactant and chitosan derivatives and more generally polysaccharides. The physico-chemical characteristics of pure surfactant solutions as well as SPECs were determined and compared according to the considered experimental technique. Close results were obtained and the great advantage of DOSY technique is the capacity to study simultaneously the two components of the systems, allowing more information on the nature of interactions between the surfactant and the polysaccharide as well as the mechanism involved during these interactions. This may be of great interest to understand how these complexes can alter the properties of formulations in which these components are involved, which is one of the big challenges of the industrial research.
To propose two new indicators for monitoring access to antiretroviral treatment (ART) for human immunodeficiency virus (HIV); (i) the time from HIV seroconversion to ART initiation, and (ii) the time ...from ART eligibility to initiation, referred to as delay in ART initiation. To estimate values of these indicators in Cameroon.
We used linear regression to model the natural decline in CD4+ T-lymphocyte (CD4+ cell) numbers in HIV-infected individuals over time. The model was fitted using data from a cohort of 351 people in Côte d'Ivoire. We used the model to estimate the time from seroconversion to ART initiation and the delay in ART initiation in a representative sample of 4154 HIV-infected people who started ART in Cameroon between 2007 and 2010.
In Cameroon, the median CD4+ cell counts at ART initiation increased from 140 cells/μl (interquartile range, IQR: 66 to 210) in 2007-2009 to 163 cells/μl (IQR: 73 to 260) in 2010. The estimated average time from seroconversion to ART initiation decreased from 10.4 years (95% confidence interval, CI: 10.3 to 10.5) to 9.8 years (95% CI: 9.6 to 10.0). Delay in ART initiation increased from 3.4 years (95% CI: 3.1 to 3.7) to 5.8 years (95% CI: 5.6 to 6.2).
The estimated time to initiate ART and the delay in ART initiation indicate that progress in Cameroon is insufficient. These indicators should help monitor whether public health interventions to accelerate ART initiation are successful.
Pancreas organogenesis is regulated by the interaction of distinct signaling pathways that promote or restrict morphogenesis and cell differentiation. Previous work has shown that activin, a ...TGF(beta+) signaling molecule, permits pancreas development by repressing expression of Sonic hedgehog (Shh), a member of the hedgehog family of signaling molecules that antagonize pancreas development. Here we show that Indian hedgehog (Ihh), another hedgehog family member, and Patched 1 (Ptc1), a receptor and negative regulator of hedgehog activity, are expressed in pancreatic tissue. Targeted inactivation of Ihh in mice allows ectopic branching of ventral pancreatic tissue resulting in an annulus that encircles the duodenum, a phenotype frequently observed in humans suffering from a rare disorder known as annular pancreas. Shh(â)(/)(â) and Shh(â)(/)(â) Ihh(+/)(â) mutants have a threefold increase in pancreas mass, and a fourfold increase in pancreatic endocrine cell numbers. In contrast, mutations in Ptc1 reduce pancreas gene expression and impair glucose homeostasis. Thus, islet cell, pancreatic mass and pancreatic morphogenesis are regulated by hedgehog signaling molecules expressed within and adjacent to the embryonic pancreas. Defects in hedgehog signaling may lead to congenital pancreatic malformations and glucose intolerance.
PDF
