Definitions and classification of malformations of cortical development: practical guidelines.

Malformations of cortical development are a group of rare disorders commonly manifesting with developmental delay, cerebral palsy or seizures. The neurological outcome is extremely variable depending on the type, extent and severity of the malformation and the involved genetic pathways of brain development. Neuroimaging plays an essential role in the diagnosis of these malformations, but several issues regarding malformations of cortical development definitions and classification remain unclear. The purpose of this consensus statement is to provide standardized malformations of cortical development terminology and classification for neuroradiological pattern interpretation. A committee of international experts in paediatric neuroradiology prepared systematic literature reviews and formulated neuroimaging recommendations in collaboration with geneticists, paediatric neurologists and pathologists during consensus meetings in the context of the European Network Neuro-MIG initiative on Brain Malformations (https://www.neuro-mig.org/). Malformations of cortical development neuroimaging features and practical recommendations are provided to aid both expert and non-expert radiologists and neurologists who may encounter patients with malformations of cortical development in their practice, with the aim of improving malformations of cortical development diagnosis and imaging interpretation worldwide.

Building Bridges Between the Clinic and the Laboratory: A Meeting Review - Brain Malformations: A Roadmap for Future Research.

In the middle of March 2019, a group of scientists and clinicians (as well as those who wear both hats) gathered in the green campus of the Weizmann Institute of Science to share recent scientific findings, to establish collaborations, and to discuss future directions for better diagnosis, etiology modeling and treatment of brain malformations. One hundred fifty scientists from twenty-two countries took part in this meeting. Thirty-eight talks were presented and as many as twenty-five posters were displayed. This review is aimed at presenting some of the highlights that the audience was exposed to during the three-day meeting.

Current Directions in the Auricular Vagus Nerve Stimulation II - An Engineering Perspective.

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging electroceutical technology in the field of bioelectronic medicine with applications in therapy. Artificial modulation of the afferent vagus nerve - a powerful entrance to the brain - affects a large number of physiological processes implicating interactions between the brain and body. Engineering aspects of aVNS determine its efficiency in application. The relevant safety and regulatory issues need to be appropriately addressed. In particular, in silico modeling acts as a tool for aVNS optimization. The evolution of personalized electroceuticals using novel architectures of the closed-loop aVNS paradigms with biofeedback can be expected to optimally meet therapy needs. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the scope of EU COST Action "European network for innovative uses of EMFs in biomedical applications (BM1309)." Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on engineering aspects - a discussion of physiological aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

Current Directions in the Auricular Vagus Nerve Stimulation I - A Physiological Perspective.

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging technology in the field of bioelectronic medicine with applications in therapy. Modulation of the afferent vagus nerve affects a large number of physiological processes and bodily states associated with information transfer between the brain and body. These include disease mitigating effects and sustainable therapeutic applications ranging from chronic pain diseases, neurodegenerative and metabolic ailments to inflammatory and cardiovascular diseases. Given the current evidence from experimental research in animal and clinical studies we discuss basic aVNS mechanisms and their potential clinical effects. Collectively, we provide a focused review on the physiological role of the vagus nerve and formulate a biology-driven rationale for aVNS. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the framework of EU COST Action "European network for innovative uses of EMFs in biomedical applications (BM1309)." Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on physiological aspects - a discussion of engineering aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

Computer analysis of histopathological images for tumor grading. 2.

OBJECTIVE: We have upgraded our own original color filtration pixel-by-pixel (CFPP) method (Klonowski et al 2018a Physiol. Meas. 39 034002) to enable not only automatic and rapid assessment of the proliferation index of a tumor or neoplasm but also quick automatic location of hot-spots (regions of interest, ROIs) in immunohistochemically stained microscopic images of neoplasms and tumors. APPROACH: Neoplastic cells stain differently from normal cells. By counting in a given window the number of pixels belonging to the given subspaces of (R,G,B) color space which correspond, respectively, to proliferating cells (which are mostly neoplastic) and non-proliferating cells (which are mostly normal) we calculate the local proliferation index in this window. The window is moved all around the whole histopathological virtual slide (WSI) or around a chosen part of the WSI. By adding the respective numbers calculated for all the windows covering the WSI or the chosen part of it one can easily calculate the global proliferation index. MAIN RESULTS: The method is rapid and does not require the time-consuming step of selecting ROIs manually nor does it need computationally complicated detection of hot-spots, both of which attempt to emulate a pathologist's way of thinking. We apply our method to a set of slide images of diffuse large B-cell lymphoma. SIGNIFICANCE: By appropriate changes in the (R,G,B) color filtration thresholds, our method may be adapted to the analysis of other types of tumors. It may also be adapted for analysis of microscopic images in neuropathology. Because of its rapidity and simplicity it may also used for analysis of series of images to assess local dynamics of image complexity in network physiology applications.

Higuchi Fractal Dimension of Heart Rate Variability During Percutaneous Auricular Vagus Nerve Stimulation in Healthy and Diabetic Subjects.

Analysis of heart rate variability (HRV) can be applied to assess the autonomic nervous system (ANS) sympathetic and parasympathetic activity. Since living systems are non-linear, evaluation of ANS activity is difficult by means of linear methods. We propose to apply the Higuchi fractal dimension (HFD) method for assessment of ANS activity. HFD measures complexity of the HRV signal. We analyzed 45 RR time series of 84 min duration each from nine healthy and five diabetic subjects with clinically confirmed long-term diabetes mellitus type II and with diabetic foot ulcer lasting more than 6 weeks. Based on HRV time series complexity analysis we have shown that HFD: (1) discriminates healthy subjects from patients with diabetes mellitus type II; (2) assesses the impact of percutaneous auricular vagus nerve stimulation (pVNS) on ANS activity in normal and diabetic conditions. Thus, HFD may be used during pVNS treatment, to provide stimulation feedback for on-line regulation of therapy in a fast and robust way.

Computer analysis of histopathological images for tumor grading.

OBJECTIVE: We developed a new method that enables automatic and rapid assessment of a tumor's proliferation index from immunohistochemically (IHC) stained microscopic images. APPROACH: The method is based on computer-aided analysis of images - color filtration pixel-by-pixel (CFPP method) of the whole histopathological virtual slides. MAIN RESULTS: The method is simple, rapid, and does not require the time consuming step of selecting manually areas of interest nor the need for computationally complicated detection of hot-spots, both of which attempt to emulate a pathologist's way of estimating a proliferation index. We apply our method to a set of diffuse large B-cell lymphoma (DLBCL) slide images. SIGNIFICANCE: By appropriate changes in the color filtration thresholds, our method may be adapted to the analysis of other types of tumors. It may also be adapted for analysis of microscopic images in neuropathology, like biopsies of dystrophic muscles. Because of its simplicity and rapidity it may also be applied for analysis of series of images to assess dynamics of image complexity in network physiology.

Peritoneal adhesions as a cause of mechanical small bowel obstruction based on own experience.

UNLABELLED: Bowel obstruction is a condition which has been known for many years. As time goes by, the problem is still often encountered at surgical emergency rooms. More than 20% of emergency surgical interventions are performed because of symptoms of digestive tract obstruction with the disease mostly situated in the small bowel. Rates of causative factors of the disease have changed over recent years and there have been increasingly more cases of small bowel obstruction caused by peritoneal adhesions, i.e., adhesive small bowel obstruction (ASBO). The aim of the study to analyse the reasons and incidence of adhesive small bowel obstruction during two periods of time (1990-1995 and 2005-2010). MATERIAL AND METHODS: We performed a retrospective analysis of medical records of patients hospitalized at the 1st Department of General Surgery and Surgical Oncology of the Provincial Polyclinic Hospital in Plock between 1990 and 1995. The outcomes were compared with another period of 2005-2010. RESULTS: We found that the incidence of adhesive small bowel obstruction increased from 58 cases in the first period to 215 cases in the second one, and the outcomes improved. The proportion of patients who underwent surgery diminished from 38% to 13%. The mean hospitalization time shortened and was 11.3 days and 6.95 days during 1990-1995 and 2005-2010 periods of time, respectively. In the first group, patients who had a surgery were hospitalized for 17.8 days and those who were treated conservatively for 8.08 days. In the second group, the mean hospital stay decreased to 15.6 days and 5.7 days in the case of surgical and conservative treatment, respectively. The age of onset declined from 56.63 years in the first period to 52.54 years in the other one. CONCLUSIONS: Analysed data show an increasing number of patients with adhesive small bowel obstruction. The highest risk of the disease was associated with operations on the large bowel and gynaecological procedures.

Fractals in the neurosciences, Part II: clinical applications and future perspectives.

It has been ascertained that the human brain is a complex system studied at multiple scales, from neurons and microcircuits to macronetworks. The brain is characterized by a hierarchical organization that gives rise to its highly topological and functional complexity. Over the last decades, fractal geometry has been shown as a universal tool for the analysis and quantification of the geometric complexity of natural objects, including the brain. The fractal dimension has been identified as a quantitative parameter for the evaluation of the roughness of neural structures, the estimation of time series, and the description of patterns, thus able to discriminate different states of the brain in its entire physiopathological spectrum. Fractal-based computational analyses have been applied to the neurosciences, particularly in the field of clinical neurosciences including neuroimaging and neuroradiology, neurology and neurosurgery, psychiatry and psychology, and neuro-oncology and neuropathology. After a review of the basic concepts of fractal analysis and its main applications to the basic neurosciences in part I of this series, here, we review the main applications of fractals to the clinical neurosciences for a holistic approach towards a fractal geometry model of the brain.

Econobiophysics - game of choosing. Model of selection or election process with diverse accessible information.

We propose several models applicable to both selection and election processes when each selecting or electing subject has access to different information about the objects to choose from. We wrote special software to simulate these processes. We consider both the cases when the environment is neutral (natural process) as well as when the environment is involved (controlled process).

Higuchi's fractal dimension for analysis of the effect of external periodic stressor on electrical oscillations in the brain.

This study addresses application of Higuchi's fractal dimension (FD) as a measure to evaluate the effect of external periodic stressor on electrical oscillations in the brain. Modulated microwave radiation was applied as a weak periodic stressor with strongly inhomogeneous distribution inside the brain. Experiments were performed on a group of 14 volunteers. Ten cycles (1 min on, 1 min off) of 450-MHz microwave radiation modulated at 40 Hz were applied. Higuchi's FD was calculated in eight symmetric electroencephalographic (EEG) channels located in frontal, temporal, parietal, and occipital areas. FD values averaged over a group detected a small (1-2%) but statistically significant increase with exposure in all EEG channels. FD increased for 12, decreased for one, and was constant for one subject. FD showed the most remarkable effect in temporal and parietal regions of the left hemisphere where the microwave field was maximal. Changes of FD in these regions of the right hemisphere were much higher than expected in accordance with the field distribution. Correlation of FD between different EEG channels was high and retained its value in exposed conditions. Spreading of disturbance between different brain areas is supposed to be crucial for the effect of exposure on the electrical oscillations in the brain.

Simple fractal method of assessment of histological images for application in medical diagnostics.

We propose new method of assessment of histological images for medical diagnostics. 2-D image is preprocessed to form 1-D landscapes or 1-D signature of the image contour and then their complexity is analyzed using Higuchi's fractal dimension method. The method may have broad medical application, from choosing implant materials to differentiation between benign masses and malignant breast tumors.

Signatures of depression in non-stationary biometric time series.

This paper is based on a discussion that was held during a special session on models of mental disorders, at the NeuroMath meeting in Stockholm, Sweden, in September 2008. At this occasion, scientists from different countries and different fields of research presented their research and discussed open questions with regard to analyses and models of mental disorders, in particular depression. The content of this paper emerged from these discussions and in the presentation we briefly link biomarkers (hormones), bio-signals (EEG) and biomaps (brain-maps via EEG) to depression and its treatments, via linear statistical models as well as nonlinear dynamic models. Some examples involving EEG-data are presented.

Some computational aspects of the brain computer interfaces based on inner music.

We discuss the BCI based on inner tones and inner music. We had some success in the detection of inner tones, the imagined tones which are not sung aloud. Rather easily imagined and controlled, they offer a set of states usable for BCI, with high information capacity and high transfer rates. Imagination of sounds or musical tunes could provide a multicommand language for BCI, as if using the natural language. Moreover, this approach could be used to test musical abilities. Such BCI interface could be superior when there is a need for a broader command language. Some computational estimates and unresolved difficulties are presented.

Everything you wanted to ask about EEG but were afraid to get the right answer.

We answer several important questions concerning EEG. We also shortly discuss importance of nonlinear methods of contemporary physics in EEG analysis. Basic definitions and explanation of fundamental concepts may be found in my previous publications in NBP.It is a magnificent feeling to recognize the unity of complex phenomena which appear to be things quite apart from the direct visible truth.Albert Einstein.

Why nonlinear biomedical physics?

The two goals of Nonlinear Biomedical Physics are: firstly to show how nonlinear methods can shed new light on biological phenomena and medical applications and secondly to bridge the technical, mathematical, and cultural divides between the physical disciplines where these methods are being developed and the audience for their use in the biological and medical sciences.

From conformons to human brains: an informal overview of nonlinear dynamics and its applications in biomedicine.

Methods of contemporary physics are increasingly important for biomedical research but, for a multitude of diverse reasons, most practitioners of biomedicine lack access to a comprehensive knowledge of these modern methodologies. This paper is an attempt to describe nonlinear dynamics and its methods in a way that could be read and understood by biomedical professionals who usually are not trained in advanced mathematics. After an overview of basic concepts and vocabulary of nonlinear dynamics, deterministic chaos, and fractals, application of nonlinear methods of biosignal analysis is discussed. In particular, five case studies are presented: 1. Monitoring the depth of anaesthesia and of sedation; 2. Bright Light Therapy and Seasonal Affective Disorder; 3. Analysis of posturographic signals; 4. Evoked EEG and photo-stimulation; 5. Influence of electromagnetic fields generated by cellular phones.