A 3-sided Pyramid Wavefront Sensor Controlled by a Neural Network for Adaptive Optics to reach diffraction-limited Imaging of the Retina

In-vivo imaging of the eye's fundus is the basis for the diagnosis of retinal diseases in ophthalmology. However, the resolution of the images is limited - besides the inevitable diffractive limitation by the finite size of the pupil - by the imperfect optical elements of the eye, causing aberrations. In astronomy, first test measurements of atmospheric aberrations with the novel 4-sided pyramid sensor have confirmed the benefits of this sensor compared with conventional wavefront sensors. This work presents a pyramid wavefront sensor for the measurement of aberrations and their compensation on a confocal laser scanning ophthalmoscope. By contrast, a 3-sided pyramid prism is used and it is demonstrated experimentally, that this prism, which is easier to manufacture than the 4-sided prism, reveals to be an equivalent sensor. The control of the deformable mirror which can compensate the aberrations is implemented by an artificial neural network based on the acquired sensor data. With the trained neural network, aberrations of 150nm RMS could already be reduced to half the error. The neural network is composed of a convolutional S_C-net of 2x4 layers, which extracts feature information out of the signal images of the pyramid, and a 3-layer, feed-forward backpropagation net, that determines the required deflection of the mirror in order to compensate for a given aberration

Atomic Interferometer with Amplitude Gratings of Light and its Applications to Atom Based Tests of the Equivalence Principle

We have developed a matter wave interferometer based on the diffraction of atoms from effective absorption gratings of light. In a setup with cold rubidium atoms in an atomic fountain the interferometer has been used to carry out tests of the equivalence principle on an atomic basis. The gravitational acceleration of the two isotopes 85Rb and 87Rb was compared, yielding a difference Dg/g =(1.2 +-1.7)x10^{-7}. We also perform a differential free fall measurement of atoms in two different hyperfine states, and obtained a result of Dg/g =(0.4 +-1.2)x10^{-7}.Comment: 4 Pages, 4 figures, accepted for Physical Review Letter

Impact of patatin-like phospholipase domain-containing 3 gene polymorphism (rs738409) on severity of liver disease in HIV/hepatitis C virus-coinfected patients

Objective: To analyze the association between patatin-like phospholipase domain-containing 3 gene (PNPLA3) rs738409 polymorphism and severity of liver disease in HIV/hepatitis C virus-coinfected patients. Methods: We performed a cross-sectional study of 215 patients who underwent a liver biopsy. PNPLA3 rs738409 polymorphism was genotyped using GoldenGate assay. The outcome variables were as follows: advanced fibrosis (F ≥3 and FIB-4 ≥3.25), rapid fibrosis progression (FPR ≥0.10 fibrosis units/year), severe activity grade (A≥3), and steatosis (fatty hepatocytes ≥10%). The genetic association analysis was carried out according to an additive genetic model through logistic regressions adjusted by the most significant covariables. Results: Overall, 21.4% had F at least 3, 8.9% had FIB-4 at least 3.25, 11.4% had A at least 3, 60.6% had steatosis, and 32.5% had FPR at least 0.10. For each rs738409 G allele, we found an increased frequency of patients with advanced fibrosis (F at least 3) (0% CC, 18.5% CG, and 25.2% GG; P = 0.049) and FIB-4 at least 3.25 (0% CC, 3.8% CG, and 13.2% GG; P = 0.016). Furthermore, for each rs738409 G allele, the odds of having F at least 3 increased 2.15 times (95% confidence interval=1.07; 4.35; P = 0.029) and having FIB-4 at least 3.25 increased 8.77 times (95% of confidence interval = 1.11; 69.0; P = 0.039). Note that rs738409 G allele carriers tended to higher likelihood of having FPR at least 0.10, but statistical significance was not reached (P = 0.054). Finally, we did not find any association for A at least 3 and liver steatosis. Conclusion: PNPLA3 rs738409 polymorphism was associated with the severity of liver fibrosis in patients coinfected with HIV and hepatitis C virus, suggesting that this polymorphism might also play a significant role in the progression of hepatic fibrosis in this group of patients.This work has been supported by grants given by Fondo de Investigación de Sanidad en España (FIS) (Spanish Health Founds for Research) (grant numbers PI11/01556, PI14/01094, PI11/00245, PI14CIII/00011), and ‘Fundación para la Investigación y la Prevención del Sida en España’ (FIPSE) (grant number 361020/10). This work has been (partially) funded by the RD12/0017/0024 and RD12/0017/0004 projects as part of the Plan Nacional R+D+I and cofinanced by ISCIII – Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). ‘Instituto de Salud Carlos III’ (grant numbers CD12/00442, CD13/00013 and RD12/0017/0024, respectively). This work has been (partially) funded by the RD12/0017 project as part of the Plan Nacional R+D+I and cofinanced by ISCIII – Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER).S

rs7903146 polymorphism at transcription factor 7 like 2 gene is associated with total cholesterol and lipoprotein profile in HIV/hepatitis C virus-coinfected patients

Transcription factor 7 like 2 (TCF7L2) rs7903146 polymorphism has been associated with metabolic disturbance and cardiovascular disease. The aim of this study was to analyze the association between TCF7L2 rs7903146 polymorphism and potential disturbances on the lipid profile in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. We performed a cross-sectional study on 263 HIV/HVC-coinfected patients. TCF7L2 polymorphism was genotyped by GoldenGate assay. The analysis was performed by linear and logistic regression under a dominant model of inheritance. The variables analyzed were total cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), non-HDL-C, and triglycerides. Patients harboring the rs7903146 TT/TC genotype showed a diminished concentration of TC (p=0.003), LDL-C (p=0.004), HDL-C (p=0.012), and non-HDL-C (p=0.013), a lower percentage of TC≥200 mg/dl (p=0.038), and a higher percentage of HDL≤40 mg/dl (p=0.023). In addition, we observed that rs7903146 was differently related to fasting serum lipid levels according to the HCV-genotype (HCV-GT). With regard to HCV-GT1 patients, the rs7903146 TT/TC genotype was associated with lower levels of HDL-C [adjusted arithmetic mean ratio (aAMR)=0.91; p=0.049] and an elevated percentage of patients with HDL-C≤40 mg/dl [adjusted odds ratio (aOR)=3.26; p=0.003]. For HCV-GT3 patients, the rs7903146 TT/TC genotype was associated with lower serum values of TC (aAMR=0.81; p=0.037), LDL-C (aAMR=0.67; p=0.001), and non-HDL-C (aAMR=0.75; p=0.002) and a reduced percentage of TC≥200 mg/dl (aOR=0.089; p=0.037). In conclusion, the TCF7L2 rs7903146 TT/TC genotype was associated with lower levels of TC, LDL, and HDL in HCV-GT3 patients, and lower levels of HDL-C in HCV-GT1 patients, suggesting a role in cardiovascular disease and a potential use as a biomarker in HIV/HCV-coinfected patients.D.P.T., M.A.JS., and M.G.A. have received research funding from “Instituto de Salud Carlos III” [grants CM12/00043, CM10/00105, and CD12/00442, respectively]. J.B. is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS). This work has been supported by grants from Fondo de Investigación de Sanidad en España (FIS) [Spanish Health Funds for Research] [grants PI08/0738, PI11/00245; PI08/0928, and PI11/01556], and “Fundación para la Investigación y la Prevención del Sida en España” (FIPSE) [grant 361020/10]. This work has been (partially) funded by the RD12/0017/0024 and RD12/0017/0004 projects as part of the Plan Nacional R+D+I and cofinanced by ISCIII––Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER).S

Variabilidad de la prescripción de antibióticos en atención primaria de los sectores sanitarios de Aragón

Fundamentos: La resistencia a los antibióticos puede contenerse con una mejor utilización, para lo que debemos conocer cómo se usan. El objetivo del estudio es describir la prevalencia del consumo de antibióticos y la variabilidad en su utilización en los diferentes sectores sanitarios de Aragón. Métodos: Estudio descriptivo de la prescripción de antibióticos en los sectores sanitarios de Aragón en 2008. Los datos se obtuvieron del Sistema de Información de Consumo Farmacéutico de Aragón, que recoge las recetas dispensadas en oficinas de farmacia. Se calcularon las tasas de utilización de antibióticos por cada mil habitantes ajustadas por sexo y edad mediante el método directo e indirecto. La utilización de los subgrupos de antibióticos se midió en dosis diarias definidas (DDD) por mil habitantes/día (DHD). En el análisis de la variabilidad se utilizaron la razón de variación (RV), el coeficiente de variación (CV), el coeficiente de variación ponderado (CVw) y el componente sistemático de la variación (SCV). Resultados: La tasa ajustada de utilización de antibióticos osciló entre 279,8 y 382 por cada 1.000 habitantes, mostrando un CVw=0,12. La tasa de utilización en mujeres fue 364,9 por 1.000 y en hombres 300,0 por 1.000. Los subgrupos que presentaron las mayores variaciones fueron cefalosporinas (RV 2,42 y CVw 0,37) y las quinolonas (RV 1,84 y CVw 0,22). Conclusiones: La tasa de utilización fue mayor en las mujeres que en los hombres.Por subgrupos la mayor variabilidad en la prescripción de antibióticos entre los sectores sanitarios de Aragón se produce en las cefalosporinas y las quinolonas. BACKGROUND: Resistance to antibacterial drugs can be contained by judicious utilization, so we must know about its use. The objective is to describe the prevalence of antibiotic consumption and the variability in the use of antibiotics among outpatients in the different health areas of Aragon. METHODS: Study of the prescription of antibiotics in the health areas of Aragon in 2008. Data were extracted from the Aragon Pharmaceutical Consumption Database, a complete register of all dispensed prescriptions. Prescription rates per 1000 individuals adjusted by sex and age were calculated using a direct and indirect standardization method. The subgroups utilization were calculated in Defined Daily Dose per 1000 inhabitants per day (DID). In the variation analysis were used: extremal quotient (EQ), coefficient of variation (CV), weighted coefficient of variation (CVw). RESULTS: The adjusted rate of antibiotic varied between 279,8 and 382 per 1000 inhabitants, showing a CVw=0,12. The utilization rate in women was 364.9 per 1,000 and in men 300.0 per 1,000. Cephalosporins have a EQ=2,42 and CVw=0,37; and quinolones have EQ=1,84 and CVw=0,22. CONCLUSIONS: The utilization rate was higher in women than men. The higher variability in the prescription of antibiotics among health areas in Aragon was in cephalosporins and quinolones

Water intake, hydration status and 2-year changes in cognitive performance: a prospective cohort study

BackgroundWater intake and hydration status have been suggested to impact cognition; however, longitudinal evidence is limited and often inconsistent. This study aimed to longitudinally assess the association between hydration status and water intake based on current recommendations, with changes in cognition in an older Spanish population at high cardiovascular disease risk.MethodsA prospective analysis was conducted of a cohort of 1957 adults (aged 55-75) with overweight/obesity (BMI between >= 27 and = 300 mmol/L (dehydrated). Water intake was assessed as total drinking water intake and total water intake from food and beverages and according to EFSA recommendations. Global cognitive function was determined as a composite z-score summarizing individual participant results from all neuropsychological tests. Multivariable linear regression models were fitted to assess the associations between baseline hydration status and fluid intake, continuously and categorically, with 2-year changes in cognitive performance.ResultsThe mean baseline daily total water intake was 2871 +/- 676 mL/day (2889 +/- 677 mL/day in men; 2854 +/- 674 mL/day in women), and 80.2% of participants met the ESFA reference values for an adequate intake. Serum osmolarity (mean 298 +/- 24 mmol/L, range 263 to 347 mmol/L) indicated that 56% of participants were physiologically dehydrated. Lower physiological hydration status (i.e., greater serum osmolarity) was associated with a greater decline in global cognitive function z-score over a 2-year period (beta: - 0.010; 95% CI - 0.017 to - 0.004, p-value = 0.002). No significant associations were observed between water intake from beverages and/or foods with 2-year changes in global cognitive function.ConclusionsReduced physiological hydration status was associated with greater reductions in global cognitive function over a 2-year period in older adults with metabolic syndrome and overweight or obesity. Future research assessing the impact of hydration on cognitive performance over a longer duration is needed

Haplotype analysis of the internationally distributed BRCA1 c.3331_3334delCAAG founder mutation reveals a common ancestral origin in Iberia

Background: TheBRCA1c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluateBRCA1c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. Methods: BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity aroundBRCA1c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surroundingBRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia. Results: The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was similar to 100 generations in Iberia and that it was introduced to South America early during the European colonization period. Conclusions: Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum