Therapy with ombitasvir/paritaprevir/ritonavir plus dasabuvir is effective and safe for the treatment of genotypes 1 and 4 hepatitis C virus (HCV) infection in patients with severe renal impairment: A multicentre experience.

Limited data are available on direct-acting antivirals for treating hepatitis C virus (HCV) infection in patients with severe renal impairment. The aim of this study was to evaluate the effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) in patients with stage 4 or 5 chronic kidney disease (CKD) and HCV genotype 1 or 4 infection in real clinical practice, and to investigate pharmacological interactions. This retrospective study included patients treated with OBV/PTV/r+DSV±RBV or OBV/PTV/r+RBV with CKD stage 4 (eGFR: 15-29 mL/min/1.73m2 ) or 5 (eGFR<15 mL/min/1.73m2 or requiring dialysis) and HCV infection by genotypes 1 and 4 between April 2015 and October 2015 in nine Spanish centres. Sustained virological response at 12 weeks (SVR12) was assessed, and clinical and laboratory data, fibrosis stage, adverse events and pharmacological interactions were reported. Forty-six patients were included: 10 (21.7%) had CKD stage 4 and 36 (78.2%) CKD stage 5. Seventeen (36.9%) had cirrhosis. SVR12 rate in the intention-to-treat population was 95.7%. Twenty-one (45.6%) received RBV, which was discontinued in two (9.5%) patients. Anaemia (haemoglobin <10 g/dl) occurred in 12 patients (57.1%) with RBV vs 10 (40.0%) without RBV (P=.246). Renal function remained stable during antiviral therapy. Nine patients (19.5%) experienced serious adverse events unrelated to antiviral therapy. Concomitant medication was discontinued or modified in 41.3% of patients. In conclusion, the effectiveness of OBV/PTV/r±DSV±RBV in patients with CKD 4-5 was similar to that observed in those with normal renal function and was not associated with severe adverse events.

Changes in air quality in Mexico City, London and Delhi in response to various stages and levels of lockdowns and easing of restrictions during COVID-19 pandemic.

The impacts of COVID-19 lockdown restrictions have provided a valuable global experiment into the extent of improvements in air quality possible with reductions in vehicle movements. Mexico City, London and Delhi all share the problem of air quality failing WHO guideline limits, each with unique situations and influencing factors. We determine, discuss and compare the air quality changes across these cities during the COVID-19, to understand how the findings may support future improvements in their air quality and associated health of citizens. We analysed ground-level PM10, PM2.5, NO2, O3 and CO changes in each city for the period 1st January to August 31, 2020 under different phases of lockdown, with respect to daily average concentrations over the same period for 2017 to 2019. We found major reductions in PM10, PM2.5, NO2 and CO across the three cities for the lockdown phases and increases in O3 in London and Mexico City but not Delhi. The differences were due to the O3 production criteria across the cities, for Delhi production depends on the VOC-limited photochemical regime. Levels of reductions were commensurate with the degree of lockdown. In Mexico City, the greatest reduction in measured concentration was in CO in the initial lockdown phase (40%), in London the greatest decrease was for NO2 in the later part of the lockdown (49%), and in Delhi the greatest decrease was in PM10, and PM2.5 in the initial lockdown phase (61% and 50%, respectively). Reduction in pollutant concentrations agreed with reductions in vehicle movements. In the initial lockdown phase vehicle movements reduced by up to 59% in Mexico City and 63% in London. The cities demonstrated a range of air quality changes in their differing geographical areas and land use types. Local meteorology and pollution events, such as forest fires, also impacted the results.

Discriminability measures for predicting readability of text on textured backgrounds.

Several discriminability measures were examined for their ability to predict reading search times for three levels of text contrast and a range of backgrounds (plain, a periodic texture, and four spatial-frequency-filtered textures created from the periodic texture). Search times indicate that these background variations only affect readability when the text contrast is low, and that spatial frequency content of the background affects readability. These results were not well predicted by the single variables of text contrast (Spearman rank correlation = -0.64) and background RMS contrast (0.08), but a global masking index and a spatial-frequency-selective masking index led to better predictions (-0.84 and -0.81, respectively).

Changes on computed cranial tomography with aging: intracranial fluid volume.

A semiautomated computer analysis was developed to estimate fluid volumes in each hemicranium from computed tomography scans. The method was used to estimate total ventricular and sulcal fluid in 123 normal subjects aged 23-88 years. A wide range of normal values was found. The trend was for the estimated ventricular and sulcal fluid volumes to remain relatively constant until age 60 and then to increase at an increasing rate thereafter. Ventricular enlargement occurred in the absence of sulcal enlargement and vice versa. The estimate of the volume of the ventricles was related to skull size. When this was taken into account, the size of the ventricles showed no sex difference. The cranial cavity was larger in men than in women, and, in both genders, the left hemicranium and the left ventricle were larger on the average than their right counterparts. The limitations of computed cranial tomography as a quantitative tool are discussed in detail.

Object detection in natural backgrounds predicted by discrimination performance and models.

Many models of visual performance predict image discriminability, the visibility of the difference between a pair of images. We compared the ability of three image discrimination models to predict the detectability of objects embedded in natural backgrounds. The three models were: a multiple channel Cortex transform model with within-channel masking; a single channel contrast sensitivity filter model; and a digital image difference metric. Each model used a Minkowski distance metric (generalized vector magnitude) to summate absolute differences between the background and object plus background images. For each model, this summation was implemented with three different exponents: 2, 4 and infinity. In addition, each combination of model and summation exponent was implemented with and without a simple contrast gain factor. The model outputs were compared to measures of object detectability obtained from 19 observers. Among the models without the contrast gain factor, the multiple channel model with a summation exponent of 4 performed best, predicting the pattern of observer d's with an RMS error of 2.3 dB. The contrast gain factor improved the predictions of all three models for all three exponents. With the factor, the best exponent was 4 for all three models, and their prediction errors were near 1 dB. These results demonstrate that image discrimination models can predict the relative detectability of objects in natural scenes.

Effects of solvent medium on solubility. V: Enthalpic and entropic contributions to the free energy changes of di-substituted benzene derivatives in ethanol:water and ethanol:cyclohexane mixtures.

The solubility at four different temperatures in water, cyclohexane, and mixtures of water and ethanol and ethanol and cyclohexane of nine derivatives of the structure pX1-C6H4-X2, together with their heats of fusion are reported. The enthalpy and entropy of mixing (delta HM and delta SM, respectively), and also the excess free energy (delta GE) for pure solvents and several compositions of solvent mixtures were calculated. The enthalpic and entropic contribution to the free energy of transfer for water:solvent mixtures was also calculated for each compound. Solvent systems may be classified by means of the enthalpic-entropic relationships exhibited by the series in each case.

Effects of solvent medium on solubility IV: Comparison of the hydrophilic-lipophilic character exhibited by functional groups in ethanol-water and ethanol-cyclohexane mixtures.

Solvent effects on the solubility of a set of structurally related solid compounds (Ax, Ay, etc.) in ethanol-water (system 1) and ethanol-cyclohexane (system 2) are compared by the equation, log Sy = Py log Sx + C. For a given structural change, Ax----Ay, it yields the respective medium-effects parameters, Py1 and Py2. They are used to compare the sensitivity of both solvent systems with the structural changes in the substrates by the equation, delta 12 = (Py1 - 1) - (1 - Py2). Structural changes involving the full replacement of the hydrogen atoms bonded to either O or N afford delta 12 less than 0, while those involving solely an increase in the alkyl chain of the substrates yield delta 12 greater than 0. A structural change where the donor-acceptor capacity of hydrogen bonding is maintained yields a delta 12 approaching zero.

Effects of solvent medium on solubility III: Hydrophilic-lipophilic character exhibited by some functional groups having oxygen or nitrogen in ethanol-water.

Solubility data of nine derivatives of the structure p-X1-C6H4-X2 in ethanol-water at 25 degrees C are reported. The correlation of such sets of data by log Sy = Py X log Sx + C yields the medium effect parameter Py for a variety of functional groups possessing either oxygen or nitrogen. Py accounts for the hydrophilic-lipophilic character exhibited by each group.

CT measures of cerebrospinal fluid volume in alcoholics and normal volunteers.

Cranial computed tomography (CT) scans were obtained in 46 male chronic alcoholics and 31 normal male volunteers. Automated methods were used to estimate the cerebrospinal fluid (CSF) volume in various intracranial zones. Measures of the ventricular fluid volume, the volume of fluid in cortical areas on CT sections at the level of the ventricles, and the sulcal fluid volumes on two convexity sections were computed. The alcoholic group, excluding subjects with chronic liver disease, had significantly more fluid than the control group on all sulcal measures. The group difference on the ventricular measure fell short of significance. Within the alcoholic group, no significant correlation was found between the number of years of alcoholism and any fluid measure when normal age effects were taken into account. A striking degree of variability in the sulcal volumes was observed within the alcoholic group, with many subjects showing normal values while a large group showed markedly elevated values. Further studies will be necessary to determine the significance of these variations.

A hexagonal orthogonal-oriented pyramid as a model of image representation in visual cortex.

Retinal ganglion cells represent the visual image with a spatial code, in which each cell conveys information about a small region in the image. In contrast, cells of primary visual cortex employ a hybrid space-frequency code in which each cell conveys information about a region that is local in space, spatial frequency, and orientation. Despite the presumable importance of this transformation, we lack any comprehensive notion of how it occurs. Here we describe a mathematical model for this transformation. The hexagonal orthogonal-oriented quadrature pyramid (HOP) transform, which operates on a hexagonal input lattice, employs basis functions that are orthogonal, self-similar, and localized in space, spatial frequency, orientation, and phase. The basis functions, which are generated from seven basic types through a recursive process, form an image code of the pyramid type. The seven basis functions, six bandpass and one low-pass, occupy a point and a hexagon of six nearest neighbors on a hexagonal sample lattice. The six bandpass basis functions consist of three with even symmetry, and three with odd symmetry. The three even kernels are rotations of 0, 60, and 120 degrees of a common kernel; likewise for the three odd kernels. At the lowest level, the inputs are image samples. At each higher level, the input lattice is provided by the low-pass coefficients computed at the previous level. At each level, the output is subsampled in such a way as to yield a new hexagonal lattice with a spacing square root 7 larger than the previous level, so that the number of coefficients is reduced by a factor of seven at each level. In the biological model, the input lattice is the retinal ganglion cell array. The resulting scheme provides a compact, efficient code of the image and generates receptive fields that resemble those of the primary visual cortex.

Live attenuated malaria vaccine designed to protect through hepatic CD8⁺ T cell immunity.

Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8(+) T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8(+), IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.

Hemorragia posparto y ascariasis: presentación de un caso / Postpartum hemorrhage and ascariasis: a case reporte

Resumen La hemorragia posparto es una de las principales complicaciones maternas que genera morbimortalidad. Se asocia diversas causas, como atonía uterina, retención de restos placentarios y coagulopatías. Una poco conocida es la infección por Ascarislumbricoides. Se realiza la revisión de un caso clínico de paciente de 16 años de edad, que evolucionó a histerectomía secundaria a ascariasis y muerte materna, que ingresó al Servicio de Urgencias Obstétricas del Hospital de la Universidad del Norte. Según nuestro conocimiento, es el primer caso descrito en nuestro país en el que se sospecha la asociación de hemorragia posparto y la infección por Ascarislumbricoides.

Abstract Postpartum hemorrhage is one of the most important obstetrical complications, having a high morbidity and mortality rate. It is associated to different causes such as uterine atony, placental birth alterations, and coagulopathy. One not so well-known cause is the infestation with the parasite Ascarislumbricoides. We report a case of a 16-year-old patient who required an emergency postpartum hysterectomy until progressing to death due to ascariasis. To our current knowledge, this is the first reported case in Colombia where there is a suspected association between the infestation with Ascarislumbricoides and postpartum hemorrhage.

Putting the visual system noise back in the picture.

Computable expressions for the input-picture-equivalent contrast noise of the visual system are provided for the locally linear subclass of nonlinear models, where the internal model noise is allowed to be signal dependent. The equivalent-noise concept is thereby extended to many of the models developed to explain masking and discrimination among suprathreshold stimuli. For these models the equivalent noise depends on the masking stimulus, and its structure can be strongly determined by the representation of the masker at the level of the system at which the performance-limiting noise is generated. The expressions are applicable to the case of less-than-full-rank transformations. Pictures that have hypothetical visual-system noise projected back into them can provide insights into efficient picture-coding algorithms.

A new microassay for the determination of alkaline phosphatase activity in early mouse concepti.

A new enzymatic assay for the determination of alkaline phosphatase (APase) activity in preimplantation mouse concepti is described. This method allows estimation of APase activity of concepti extracts using the fluorogenic substrate, 3,6-fluorescein diphosphate (FDP). For measuring APase activity, 0.1% Nonidet P-40 was used to solubilize the enzyme. Control assays showed that this procedure does not modify the enzyme activity. According to the Km obtained for APase from mouse concepti (between 1-2 microM), the initial concentration of FDP was 20 microM, which is 10 fold the Km. The assay sensitivity allows continuous recording of the product generated and a reliable determination in less than 20 min. Results show that APase activity in mouse concepti may be detected from the 2-cell stage, increasing exponentially towards the blastocyst stage.

Detection in fixed and random noise in foveal and parafoveal vision explained by template learning.

Foveal and parafoveal contrast detection thresholds for Gabor and checkerboard targets were measured in white noise by means of a two-interval forced-choice paradigm. Two white-noise conditions were used: fixed and twin. In the fixed noise condition a single noise sample was presented in both intervals of all the trials. In the twin noise condition the same noise sample was used in the two intervals of a trial, but a new sample was generated for each trial. Fixed noise conditions usually resulted in lower thresholds than twin noise. Template learning models are presented that attribute this advantage of fixed over twin noise either to fixed memory templates' reducing uncertainty by incorporation of the noise or to the introduction, by the learning process itself, of more variability in the twin noise condition. Quantitative predictions of the template learning process show that it contributes to the accelerating nonlinear increase in performance with signal amplitude at low signal-to-noise ratios.

Model of human visual-motion sensing.

We propose a model of how humans sense the velocity of moving images. The model exploits constraints provided by human psychophysics, notably that motion-sensing elements appear tuned for two-dimensional spatial frequency, and by the frequency spectrum of a moving image, namely, that its support lies in the plane in which the temporal frequency equals the dot product of the spatial frequency and the image velocity. The first stage of the model is a set of spatial-frequency-tuned, direction-selective linear sensors. The temporal frequency of the response of each sensor is shown to encode the component of the image velocity in the sensor direction. At the second stage, these components are resolved in order to measure the velocity of image motion at each of a number of spatial locations and spatial frequencies. The model has been applied to several illustrative examples, including apparent motion, coherent gratings, and natural image sequences. The model agrees qualitatively with human perception.

Equivalent-noise model for contrast detection and discrimination.

Models for the detection and the discrimination of low-contrast signals by human observers typically assume that the observer is limited by the filtering action of the visual system and by the noisy character of its processing. For some models both the filtering and the noise can be represented by a noise in the stimulus domain, the input equivalent noise of the model. We derive some formulas for computing this noise, describe the calculation of a sample, and discuss some implications of this approach.