Mathematical modeling of the proliferation gradient in multicellular tumor spheroids.

MultiCellular Tumor Spheroids are 3D cell cultures that can accurately reproduce the behavior of solid tumors. It has been experimentally observed that large spheroids exhibit a decreasing gradient of proliferation from the periphery to the center of these multicellular 3D models: the proportion of proliferating cells is higher in the periphery while the non-proliferating quiescent cells increase in depth. In this paper, we propose to investigate the key mechanisms involved in the establishment of this gradient with a Partial Differential Equations model that mimics the experimental set-up of growing spheroids under different nutrients supply conditions. The model consists of mass balance equations on the two cell populations observed in the data: the proliferating cells and the quiescent cells. The spherical symmetry is used to rewrite the model in radial and relative coordinates. Thanks to a rigorous data postprocessing the model is then fit and compared quantitatively with the experimental quantification of the percentage of proliferating cells from EdU immunodetection on 2D spheroid cryosection images. The results of this calibration show that the proliferation gradient observed in spheroids can be quantitatively reproduced by our model.

New objective measurements of semen wave motion are associated with fertility in sheep.

In sheep, wave motion in semen is currently used by AI centres to select ejaculates for insemination. Despite its low cost, convenience and established ability to predict fertility, the subjectivity of this assessment is a limiting factor for its applicability. The aims of the present study were to establish an objective method for the analysis of wave motion and to assess the associations of objective parameters with fertility after cervical insemination. Collective sperm motion in undiluted semen was observed by phase contrast microscopy at low magnification in a 100-µm deep glass chamber. Images of moving dark waves over a grey background were recorded and analysed by the optic flow method, producing several velocity-related parameters. Turbulence was assessed from the motion of fluorescent polystyrene beads. Among objective parameters, optical flow entropy and the average speed of beads were both able to discriminate ejaculates suitable for insemination. Two synthetic variables of optic flow and bead motion and a global objective variable were computed from linear combinations of individual parameters and compared with the subjective motion score for their predictive value. These were as efficient as the wave motion score for assessing fertility and can be proposed for the assessment of ram semen in routine AI procedures.

Influence of Poisson's ratio on elastographic direct and inverse problems.

We consider the displacement of an elastic material under an external compression (axial or almost axial stress). We assume that only one component of the displacement is observed, in the direction of compression (axial displacement), or alternatively, that two components are observed in a plane. These hypotheses are in accordance with an imaging modality, namely ultrasonic elastography. In the case of a homogeneous medium we show that any value of Poisson's ratio allows us to predict the observed value of the axial displacement. When two components of the displacement are measured in a plane, the Poisson's ratio of the plane strain model that predicts the observed displacement is not the same as the tri-dimensional material. These facts are illustrated by numerical experiments in the case of an inhomogeneous medium. We also present results on experimental phantom data, where the inverse problem of reconstructing the Young's modulus is solved assuming different values for Poisson's ratio.

Derivation and validation of guidelines for stool cultures for enteropathogenic bacteria other than Clostridium difficile in hospitalized adults.

CONTEXT: The yield of in-hospital stool cultures performed more than 72 hours after admission is low, and a commonly used policy dictates that laboratories reject these cultures to save costs. However, enteropathogenic bacteria other than Clostridium difficile (EPB) may cause nosocomial illness that would be missed by use of such a "3-day rule." OBJECTIVE: To develop guidelines for hospital use of stool cultures that are sensitive to clinically relevant cases of sporadic and epidemic nosocomial diarrhea. DESIGN: Five-part study that incorporated a derivation sample based on retrospective chart review and a prospective cohort study (including cost savings analysis), and a validation sample based on retrospective chart review. SETTING: Four European academic health care centers. PATIENTS: Derivation sample: 1735 adult inpatients from whom 3416 stool cultures were obtained during a 19-month period (1995-1997) and 68 adult inpatients for whom EPB were grown from stool cultures during a 10-year period (1988-1998); validation sample: 65 patients with sporadic isolation of EPB (1993-1998), 56 patients involved in 2 nosocomial Salmonella outbreaks (1992 and 1997), and 330 patients who had stool cultures performed (1998). MAIN OUTCOME MEASURE: Performance of derived criteria in detecting pathogenic bacteria and outbreaks and reducing total number of stool cultures performed. RESULTS: Stool cultures grew EPB in 3.3% of samples obtained 72 hours after admission was not associated with clinical symptoms or signs but was associated with community-acquired diarrhea (24%), age 65 years or older with preexisting comorbid disease (25%), neutropenia (13%), HIV infection (10%), and nondiarrheal manifestations of enteric infections (16%). Twelve percent were asymptomatic carriers. These characteristics were used to create criteria for selecting patients for whom stool cultures would be indicated. These criteria were applied post hoc to a series of 1025 stool cultures; the number of stool cultures would have been reduced by 52% and no clinically significant cases would have been missed. Annual savings to a 355-bed institution would be approximately $7800 for reagent costs and 75 hours of technician time. In the validation samples, only 2 patients of 65 who had EPB would not have been identified, and neither required treatment. If the 3-day rule had been applied, 52 cases would not have been identified, 28 of which required antibiotic treatment. CONCLUSION: Our modified 3-day rule for use in selecting cases for stool culture is sensitive to sporadic and epidemic cases of nosocomial diarrhea in hospitalized adults.

Acute and long-term efficacy of antituberculous treatment in HIV-seropositive patients with tuberculosis: a study of 36 cases.

Thirty-six consecutively observed HIV-seropositive patients with tuberculosis, including 31 patients with AIDS, who received antituberculous treatment, were followed up to evaluate its efficacy. Treatment with standard antituberculous regimens was intended except when an individual's condition required a modified therapeutic approach. Therapeutic failure occurred in five patients (14%) while on treatment, one also had a post-treatment relapse. Treatment failure was associated with drug resistance and non-compliance in three patients and in another two, both of whom died early in the course of their disease, with HIV-related conditions other than tuberculosis. The median relapse-free post-treatment follow-up time in 24 patients in whom treatment did not fail was 13 months (range 4-67). Standard antituberculous treatment is highly effective in the immediate and long-term treatment of HIV-related tuberculosis provided that drug susceptibility and treatment compliance are confirmed.