Country-report pattern corrections of new cases allow accurate 2-week predictions of COVID-19 evolution with the Gompertz model.

Accurate short-term predictions of COVID-19 cases with empirical models allow Health Officials to prepare for hospital contingencies in a two-three week window given the delay between case reporting and the admission of patients in a hospital. We investigate the ability of Gompertz-type empiric models to provide accurate prediction up to two and three weeks to give a large window of preparation in case of a surge in virus transmission. We investigate the stability of the prediction and its accuracy using bi-weekly predictions during the last trimester of 2020 and 2021. Using data from 2020, we show that understanding and correcting for the daily reporting structure of cases in the different countries is key to accomplish accurate predictions. Furthermore, we found that filtering out predictions that are highly unstable to changes in the parameters of the model, which are roughly 20%, reduces strongly the number of predictions that are way-off. The method is then tested for robustness with data from 2021. We found that, for this data, only 1-2% of the one-week predictions were off by more than 50%. This increased to 3% for two-week predictions, and only for three-week predictions it reached 10%.

Low-density colloid centrifugation removes bacteria from boar semen doses after spiking with selected species.

Single-layer centrifugation (SLC) with a low-density colloid is an efficient method for removing contaminating microorganisms from boar semen while recovering most spermatozoa from the original sample. This study tested the performance of this technique, using 50-ml tubes, by spiking commercial semen doses prepared without antibiotics with selected bacterial species followed by storage at 17 °C. The doses were spiked up to 102/ml CFU (colony forming units) of the bacteria Burkholderia ambifaria, Pseudomonas aeruginosa, and Staphylococcus simulans. The semen was processed by SLC (15 ml of sample and 15 ml of colloid) with the colloid Porcicoll at 20% (P20) and 30% (P30), with a spiked control (CTL) and an unspiked control (CTL0), analyzing microbiology and sperm quality on days 0, 3 and 7. SLC completely removed B. ambifaria and S. simulans, considerably reducing P. aeruginosa and overall contamination (especially P30, ∼104 CFU/ml of total contamination on day 7, median). Sperm viability was lower in P20 and P30 samples at day 0, with higher cytoplasmic ROS. Still, results were similar in all groups on day 3 and reversed on day 7, indicating a protective effect of SLC (possibly directly by removal of damaged sperm and indirectly because of lower bacterial contamination). Sperm chromatin was affected by the treatment (lower DNA fragmentation and chromatin decondensation) and storage (higher overall condensation on day 7 as per chromomycin A3 and monobromobimane staining). In conclusion, SLC with low-density colloids can remove most bacteria in a controlled contamination design while potentially improving sperm quality and long-term storage at practical temperatures.

Use of the flavonoid taxifolin for sperm cryopreservation from the threatened Bermeya goat breed.

Taxifolin is a plant flavonoid effective as an antioxidant. This study aimed to assess the effect of adding taxifolin to the semen extender during the cooling period before freezing on the overall post-thawing sperm variables of Bermeya goats. In the first experiment, a dose-response experiment was performed with four experimental groups: Control, 10, 50, and 100 µg/ml of taxifolin using semen from 8 Bermeya males. In the second experiment, semen from 7 Bermeya bucks was collected and extended at 20 °C using a Tris-citric acid-glucose medium supplemented with different concentrations of taxifolin and glutathione (GSH): control, 5 µM taxifolin, 1 mM GSH, and both antioxidants. In both experiments, two straws per buck were thawed in a water bath (37 °C, 30 s), pooled, and incubated at 38 °C. Motility (CASA) was assessed at 0, 2, and 5 h, and sperm physiology was assessed at 0 and 5 h by flow cytometry (viability, intact acrosome membrane, mitochondria membrane potential, capacitation, intracellular reactive oxygen species -ROS-, mitochondrial superoxide, and chromatin status). In experiment 2, an artificial insemination trial (AI) was included with 29 goats for testing the taxifolin 5-µM treatment on fertility. Data were analyzed with the R statistical environment using linear mixed-effects models. In experiment 1 and compared to the control, T10 increased progressive motility (P < 0.001) but taxifolin decreased total and progressive motility at higher concentrations (P < 0.001), both post-thawing and after the incubation. Viability decreased post-thawing in the three concentrations (P < 0.001). Cytoplasmic ROS decreased at 0 and 5 h at T10 (P = 0.049), and all doses decreased mitochondrial superoxide post-thawing (P = 0.024). In experiment 2, 5 µM taxifolin or 1 mM GSH (alone or combined) increased total and progressive motility vs. the control (P < 0.01), and taxifolin increased kinematic parameters such as VCL, ALH, and DNC (P < 0.05). Viability was not affected by taxifolin in this experiment. Both antioxidants did not significantly affect other sperm physiology parameters. The incubation significantly affected all the parameters (P < 0.004), overall decreasing sperm quality. Fertility after artificial insemination with doses supplemented with 5 µM taxifolin was 76.9% (10/13), not significantly different from the control group (69.2%, 9/13). In conclusion, taxifolin showed a lack of toxicity in the low micromolar range and could benefit goat semen cryopreservation.

Low density Porcicoll separates spermatozoa from bacteria and retains sperm quality.

Antibiotics are added to semen extenders to control the growth of bacteria contaminating semen during collection but may contribute to the development of antibiotic resistance. An alternative would be physical separation of spermatozoa from bacteria. The objective of the present study was to evaluate two low densities of Porcicoll for removal of bacteria, and for their effect on sperm recovery and sperm quality. Semen was collected from boars at a commercial station. Aliquots of 8 extended ejaculates were subjected to colloid centrifugation through 20% Porcicoll (P20) and 30% Porcicoll (P30) in 500 mL tubes and then stored at 17 °C. Microbiological examination and sperm quality evaluation (computer assisted sperm analysis and flow cytometry) were carried out on controls and all colloid-selected samples immediately after preparation and again after storage for 3 and 7 days. The microorganisms found were mainly bacteria from the environment, gut or skin. There was a considerable reduction or complete removal of some bacteria by both colloids. Recovery rates were 86% for P20 and 81% for P30. Sperm quality was not adversely affected by colloid centrifugation on day 0, and thereafter showed a more gradual deterioration in colloid centrifuged samples than in controls, possibly due to lower bacterial contamination. There were no differences in sperm quality between the two colloid treatments. Thus, these results show that contaminating bacteria in semen can be controlled by centrifugation through low density colloids.

Slow and fast pulses in 1-D cultures of excitatory neurons.

We analyze the characteristics of front propagation in activity of 1-D neuronal cultures by numerical simulations, using only excitatory dynamics. Experimental results in 1-D cultures of hippocampal neurons from rats have shown the spontaneous generation of a slow, low amplitude pulse that precedes a high amplitude, fast pulse that propagates through all the system. Notably, this transition appears both with and without the presence of functioning inhibitory synapses. In accordance with previous work, we demonstrate that purely excitatory integrate and fire neurons with depression in the synapses suffice to produce fast and uniform pulses but cannot explain the appearance of slow, weak pulses. We propose to explain the slow pulses by increasing the complexity of the neuron model in a purely excitatory network with connectivity as close to the experiments as possible. This approach allows us to show that spike frequency adaptation is a fundamental ingredient for the initiation process of the pulse. The introduction of a slow variable that mimics the presence of the slow K(+) channels in the soma and produces spike frequency adaptation increases strongly the persistence of the transient activity before the emergence of the fast pulse up to temporal and spatial scales comparable with the experiments. Finally, we demonstrate that proper levels of additive white noisy currents generate such pulses spontaneously, fully reproducing the experimental results.

Global coupling in excitable media provides a simplified description of mechanoelectrical feedback in cardiac tissue.

Cardiac mechanoelectric feedback can play an important role in different heart pathologies. In this paper, we show that mechanoelectric models which describe both the electric propagation and the mechanic contraction of cardiac tissue naturally lead to close systems of equations with global coupling among the variables. This point is exemplified using the Nash-Panfilov model, which reduces to a FitzHugh-Nagumo-type equation with global coupling in the linear elastic regime. We explain the appearance of self-oscillatory regimes in terms of the system nullclines and describe the different dynamical attractors. Finally, we study their basin of attraction in terms of the system size and the strength of the stretch-induced currents.

[The pharmacist, rare diseases and orphan medicines]. / El farmacéutico en el contexto de las enfermedades raras y los medicamentos huérfanos.

Treatment of rare diseases is often complicated due to the difficulties posed by the research and development of medicines by the pharmacological industry. One of the greatest concerns of this group of patients, which is both scarce and diverse, is access to available medicines. The European Medicine Agency establishes the term orphan medicines and the incentives and bases for their commercialisation. Due to their special characteristics, the majority of orphan medicines require suitable vigilance and control. The hospital pharmacy services are actively involved in their management and supply, as well as in a correct pharmacotherapeutic monitoring of the patients.

Relevance of dynamic wetting in viscous fingering patterns.

We demonstrate that wetting effects at moving contact lines have a strong impact in viscous fingering patterns. Experiments in a rotating Hele-Shaw (HS) cell, dry or prewetted, show consistent morphological differences. When the wetting fluid invades a dry region, contact angle dynamics yield a kinetic contribution to the interface pressure drop that scales with capillary number as Ca(2/3) but is significantly larger than the Park-Homsy kinetic correction. Numerical results are in very good agreement with experiments and show that standard HS equations work best for prewetted cells.

Cardiac contraction induces discordant alternans and localized block.

In this paper we use a simplified model of cardiac excitation-contraction coupling to study the effect of tissue deformation on the dynamics of alternans, i.e., alternations in the duration of the cardiac action potential, that occur at fast pacing rates and are known to be proarrhythmic. We show that small stretch-activated currents can produce large effects and cause a transition from in-phase to off-phase alternations (i.e., from concordant to discordant alternans) and to conduction blocks. We demonstrate numerically and analytically that this effect is the result of a generic change in the slope of the conduction velocity restitution curve due to electromechanical coupling. Thus, excitation-contraction coupling can potentially play a relevant role in the transition to reentry and fibrillation.

Systematic weakly nonlinear analysis of interfacial instabilities in Hele-Shaw flows.

We develop a systematic method to derive all orders of mode couplings in a weakly nonlinear approach to the dynamics of the interface between two immiscible viscous fluids in a Hele-Shaw cell. The method is completely general: it applies to arbitrary geometry and driving. Here we apply it to the channel geometry driven by gravity and pressure. The finite radius of convergence of the mode-coupling expansion is found. Calculation up to third-order couplings is done, which is necessary to account for the time-dependent Saffman-Taylor finger solution and the case of zero viscosity contrast. The explicit results provide relevant analytical information about the role that the viscosity contrast and the surface tension play in the dynamics of the system. We finally check the quantitative validity of different orders of approximation and a resummation scheme against a physically relevant, exact time-dependent solution. The agreement between the low-order approximations and the exact solution is excellent within the radius of convergence, and is even reasonably good beyond this radius.

Systematic weakly nonlinear analysis of radial viscous fingering.

We present a weakly nonlinear analysis of the interface dynamics in a radial Hele-Shaw cell driven by both injection and rotation. We extend the systematic expansion introduced in [E. Alvarez-Lacalle et al., Phys. Rev. E 64, 016302 (2001)] to the radial geometry, and compute explicitly the first nonlinear contributions. We also find the necessary and sufficient condition for the uniform convergence of the nonlinear expansion. Within this region of convergence, the analytical predictions at low orders are compared satisfactorily to exact solutions and numerical integration of the problem. This is particularly remarkable in configurations (with no counterpart in the channel geometry) for which the interplay between injection and rotation allows that condition to be satisfied at all times. In the case of the purely centrifugal forcing we demonstrate that nonlinear couplings make the interface more unstable for lower viscosity contrast between the fluids.

[Carcinoid tumor of the Vater's ampulla]. / Tumor carcinoide de la ampolla de Vater.

We report a patient with biliary obstruction of two years evolution. Blood chemistry evaluation was compatible with obstructive jaundice. Endoscopy and CT were suggestive of ampullary tumor. At laparotomy, the biopsy specimen was diagnosed as carcinoid tumor, and was treated by a Whipple's procedure.

Identification of intracellular calcium dynamics in stimulated cardiomyocytes.

We have developed an automatic method for the analysis and identification of dynamical regimes in intracellular calcium patterns from confocal calcium images. The method allows the identification of different dynamical patterns such as spatially concordant and discordant alternans, irregular behavior or phase-locking regimes such as period doubling or halving. The method can be applied to the analysis of different cardiac pathologies related to anomalies at the cellular level such as ventricular reentrant arrhythmias.

Pinch-off singularities in rotating Hele-Shaw flows at high viscosity contrast.

We study the evolution of a family of dumbbell-shaped liquid patches surrounded by air inside a rotating Hele-Shaw cell with lubrication methods and numerical simulations. Depending on initial conditions, the dumbbell either stretches to infinity, pinches off at the neck to form a droplet, or collects into a circular drop at the center of rotation. Whether or not pinch-off occurs results from a subtle interplay between centrifugal and capillary forces. In particular, rotation may delay or even prevent pinch-off from occurring owing to stretching and smoothing of the fluid neck. However, frequently rotation may have the opposite effect leading to pinch-off where the relaxation toward a circular drop would be observed in an ordinary Hele-Shaw cell.

Pattern formation and interface pinch-off in rotating Hele-Shaw flows: a phase-field approach.

Viscous fingering dynamics driven by centrifugal forcing is studied for arbitrary viscosity contrast. Theoretical methods, including exact solutions, and numerics based on a phase-field approach are used. Both confirm that pinch-off singularities in patterns originated from the centrifugally driven instability may occur spontaneously and be inherent to the two-dimensional Hele-Shaw dynamics. They are systematically more frequent for lower viscosity contrasts consistently with experimental evidence. The analytical insights provide an interpretation of this fact in terms of the asymptotic matching of the different regions of the fingering patterns. The phase-field numerical scheme is shown to be particularly adequate to elucidate the existence of finite-time singularities through the dependence of the singularity time on the interface thickness, in particular for varying viscosity contrast.

Hierarchical structures induce long-range dynamical correlations in written texts.

Thoughts and ideas are multidimensional and often concurrent, yet they can be expressed surprisingly well sequentially by the translation into language. This reduction of dimensions occurs naturally but requires memory and necessitates the existence of correlations, e.g., in written text. However, correlations in word appearance decay quickly, while previous observations of long-range correlations using random walk approaches yield little insight on memory or on semantic context. Instead, we study combinations of words that a reader is exposed to within a "window of attention," spanning about 100 words. We define a vector space of such word combinations by looking at words that co-occur within the window of attention, and analyze its structure. Singular value decomposition of the co-occurrence matrix identifies a basis whose vectors correspond to specific topics, or "concepts" that are relevant to the text. As the reader follows a text, the "vector of attention" traces out a trajectory of directions in this "concept space." We find that memory of the direction is retained over long times, forming power-law correlations. The appearance of power laws hints at the existence of an underlying hierarchical network. Indeed, imposing a hierarchy similar to that defined by volumes, chapters, paragraphs, etc. succeeds in creating correlations in a surrogate random text that are identical to those of the original text. We conclude that hierarchical structures in text serve to create long-range correlations, and use the reader's memory in reenacting some of the multidimensionality of the thoughts being expressed.

Molecular model of the contractile ring.

We present a model for the actin contractile ring of adherent animal cells. The model suggests that the actin concentration within the ring and consequently the power that the ring exerts both increase during contraction. We demonstrate the crucial role of actin polymerization and depolymerization throughout cytokinesis, and the dominance of viscous dissipation in the dynamics. The physical origin of two phases in cytokinesis dynamics ("biphasic cytokinesis") follows from a limitation on the actin density. The model is consistent with a wide range of measurements of the midzone of dividing animal cells.

Nonlinear Saffman-Taylor instability.

We show, both theoretically and experimentally, that the interface between two viscous fluids in a Hele-Shaw cell can be nonlinearly unstable before the Saffman-Taylor linear instability point is reached. We identify the family of exact elastica solutions [Nye et al., Eur. J. Phys. 5, 73 (1984)]] as the unstable branch of the corresponding subcritical bifurcation which ends up at a topological singularity defined by interface pinchoff. We devise an experimental procedure to prepare arbitrary initial conditions in a Hele-Shaw cell. This is used to test the proposed bifurcation scenario and quantitatively asses its practical relevance.