Contrarian compulsions produce time dependent flocking of active particles

Animals having a trend to align their velocities to an average of their neighbors' may flock as illustrated by the Vicsek model and its variants. If, in addition, they feel a systematic contrarian trend, the result may be a time periodic adjustment of the flock or period doubling in time. This is demonstrated by analyzing a modified Vicsek model of self-propelled particles and its corresponding kinetic equation valid for a large number of particles. We have carried out a stability and bifurcation analysis of the order-disorder transition to spatially uniform stationary or time periodic solutions that are characterized by their complex order parameters. Direct numerical simulations differing from theoretical predictions indicate the formation of spatiotemporal structures. Strikingly, we have found that increasing the usual alignment noise may favor flocking and an optimum noise produces the strongest possible order parameter.Comment: 21 pages, 12 figures, revised versio

Crossover between parabolic and hyperbolic scaling, oscillatory modes and resonances near flocking

A stability and bifurcation analysis of a kinetic equation indicates that the flocking bifurcation of the two-dimensional Vicsek model exhibits an interplay between parabolic and hyperbolic behavior. For box sizes smaller than a certain large value, flocking appears continuously from a uniform disordered state at a critical value of the noise. Because of mass conservation, the amplitude equations describing the flocking state consist of a scalar equation for the density disturbance from the homogeneous particle density (particle number divided by box area) and a vector equation for a current density. These two equations contain two time scales. At the shorter scale, they are a hyperbolic system in which time and space scale in the same way. At the longer, diffusive, time scale, the equations are parabolic. The bifurcating solution depends on the angle and is uniform in space as in the normal form of the usual pitchfork bifurcation. We show that linearization about the latter solution is described by a Klein-Gordon equation in the hyperbolic time scale. Then there are persistent oscillations with many incommensurate frequencies about the bifurcating solution, they produce a shift in the critical noise and resonate with a periodic forcing of the alignment rule. These predictions are confirmed by direct numerical simulations of the Vicsek model.Comment: 17 pages, 4 figures, minor typos correcte

Tracking collective cell motion by topological data analysis

By modifying and calibrating an active vertex model to experiments, we have simulated numerically a confluent cellular monolayer spreading on an empty space and the collision of two monolayers of different cells in an antagonistic migration assay. Cells are subject to inertial forces and to active forces that try to align their velocities with those of neighboring ones. In agreement with experiments, spreading tests exhibit finger formation in the moving interfaces, swirls in the velocity field, and the polar order parameter and correlation and swirl lengths increase with time. Cells inside the tissue have smaller area than those at the interface, as observed in recent experiments. In antagonistic migration assays, a population of fluidlike Ras cells invades a population of wild type solidlike cells having shape parameters above and below the geometric critical value, respectively. Cell mixing or segregation depends on the junction tensions between different cells. We reproduce experimentally observed antagonistic migration assays by assuming that a fraction of cells favor mixing, the others segregation, and that these cells are randomly distributed in space. To characterize and compare the structure of interfaces between cell types or of interfaces of spreading cellular monolayers in an automatic manner, we apply topological data analysis to experimental data and to numerical simulations. We use time series of numerical simulation data to automatically group, track and classify advancing interfaces of cellular aggregates by means of bottleneck or Wasserstein distances of persistent homologies. These topological data analysis techniques are scalable and could be used in studies involving large amounts of data. Besides applications to wound healing and metastatic cancer, these studies are relevant for tissue engineering, biological effects of materials, tissue and organ regeneration.Comment: 34 pages, 25 figures, the final version will appear in PLoS Computational Biolog

Retrospective real-world pilot data on transcranial pulse stimulation in mild to severe Alzheimer's patients

Transcranial pulse stimulation (TPS) is a non-invasive neuromodulation therapy that uses short, repetitive shockwaves through a neuro-navigated device. Current research suggests that these pulses lead to a wide range of vascular, metabolic, and neurotrophic changes. This relatively new CE-marked treatment provided first promising results in a clinical pilot study for improving cognition in mild-to-moderate Alzheimer's. Data from other centers is lacking, so here we analyzed safety and pilot real-world short-term results of TPS from the first center in Germany. To gain information about effects in different stages, patients with not only mild but also moderate-to-severe Alzheimer's were analyzed

No effect of subthalamic deep brain stimulation on metacognition in Parkinson’s disease

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a powerful treatment in Parkinson’s disease (PD), which provides a positive effect on motor symptoms although the way it operates on high cognitive processes such as metacognition remains unclear. To address this issue, we recorded electroencephalogram (EEG) of PD patients treated with STN-DBS that performed a reversal learning (RL) paradigm endowed with metacognitive self-assessment. We considered two stimulation conditions, namely DBS-ON (stimulation on) and DBS-OFF (stimulation off), and focused our EEG-analysis on the frontal brain region due to its involvement on high cognitive processes. We found a trend towards a significant difference in RL ability between stimulation conditions. STN-DBS showed no effect on metacognition, although a significant association between accuracy and decision confidence level held for DBS OFF, but not in the case of DBS ON. In summary, our study revealed no significant effect of STN-DBS on RL or metacognition

Factors associated with unprotected anal intercourse among men who have sex with men in Douala, Cameroon

Objectives Research on men who have sex with men (MSM) in sub-Saharan Africa was neglected for a long time. The objective of this study was to understand factors associated with unprotected anal intercourse (UAI) with male partners among a group of MSM living in the city of Douala, Cameroon. Methods In 2008, a survey on the sexual activity and practices of MSM was set up in Douala in collaboration with a local community-based organisation. Data were collected among a convenience sample of 168 MSM during face-to-face interviews with trained interviewers. Results A total of 142 individuals reported sexual activity during the previous 6 months, among whom 80 (57%) reported UAI with male partners. In a multivariate logistic regression model adjusted for the frequency of sexual intercourse, not having had access to prevention interventions and not knowing any HIV-infected person were both independently associated with a higher risk of UAI. Other factors associated with this higher risk included having had a stable male partnership at some point in one's life and not having been out of Douala for more than 4 weeks during the previous year. Conclusions This community-based research is the first study of MSM in Cameroon and the HIV transmission risks they face. Results show the importance of HIV prevention interventions from peers, and underline the need to maintain efforts to develop specific interventions targeting MSM more efficiently in the African context

Novel regulatory therapies for prevention of Graft-versus-host disease

Graft-versus-host disease is one of the major transplant-related complications in allogeneic hematopoietic stem cell transplantation. Continued efforts have been made to prevent the occurrence of severe graft-versus-host disease by eliminating or suppressing donor-derived effector T cells. Conventional immunosuppression does not adequately prevent graft-versus-host disease, especially in mismatched transplants. Unfortunately, elimination of donor-derived T cells impairs stem cell engraftment, and delays immunologic reconstitution, rendering the recipient susceptible to post-transplant infections and disease relapse, with potentially lethal consequences. In this review, we discuss the role of dynamic immune regulation in controlling graft-versus-host disease, and how cell-based therapies are being developed using regulatory T cells and other tolerogenic cells for the prevention and treatment of graft-versus-host disease. In addition, advances in the design of cytoreductive conditioning regimens to selectively target graft-versus-host disease-inducing donor-derived T cells that have improved the safety of allogeneic stem cell transplantation are reviewed. Finally, we discuss advances in our understanding of the tolerogenic facilitating cell population, a phenotypically and functionally distinct population of bone marrow-derived cells which promote hematopoietic stem cell engraftment while reducing the risk of graft-versus-host disease

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study.

BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)