Technical innovations for the diagnosis and the rehabilitation of motor and perceptive impairments of the child with Cerebral Palsy

The treatment of the Cerebral Palsy (CP) is considered as the “core problem” for the whole field of the pediatric rehabilitation. The reason why this pathology has such a primary role, can be ascribed to two main aspects. First of all CP is the form of disability most frequent in childhood (one new case per 500 birth alive, (1)), secondarily the functional recovery of the “spastic” child is, historically, the clinical field in which the majority of the therapeutic methods and techniques (physiotherapy, orthotic, pharmacologic, orthopedic-surgical, neurosurgical) were first applied and tested. The currently accepted definition of CP – Group of disorders of the development of movement and posture causing activity limitation (2) – is the result of a recent update by the World Health Organization to the language of the International Classification of Functioning Disability and Health, from the original proposal of Ingram – A persistent but not unchangeable disorder of posture and movement – dated 1955 (3). This definition considers CP as a permanent ailment, i.e. a “fixed” condition, that however can be modified both functionally and structurally by means of child spontaneous evolution and treatments carried out during childhood. The lesion that causes the palsy, happens in a structurally immature brain in the pre-, peri- or post-birth period (but only during the firsts months of life). The most frequent causes of CP are: prematurity, insufficient cerebral perfusion, arterial haemorrhage, venous infarction, hypoxia caused by various origin (for example from the ingestion of amniotic liquid), malnutrition, infection and maternal or fetal poisoning. In addition to these causes, traumas and malformations have to be included. The lesion, whether focused or spread over the nervous system, impairs the whole functioning of the Central Nervous System (CNS). As a consequence, they affect the construction of the adaptive functions (4), first of all posture control, locomotion and manipulation. The palsy itself does not vary over time, however it assumes an unavoidable “evolutionary” feature when during growth the child is requested to meet new and different needs through the construction of new and different functions. It is essential to consider that clinically CP is not only a direct expression of structural impairment, that is of etiology, pathogenesis and lesion timing, but it is mainly the manifestation of the path followed by the CNS to “re”-construct the adaptive functions “despite” the presence of the damage. “Palsy” is “the form of the function that is implemented by an individual whose CNS has been damaged in order to satisfy the demands coming from the environment” (4). Therefore it is only possible to establish general relations between lesion site, nature and size, and palsy and recovery processes. It is quite common to observe that children with very similar neuroimaging can have very different clinical manifestations of CP and, on the other hand, children with very similar motor behaviors can have completely different lesion histories. A very clear example of this is represented by hemiplegic forms, which show bilateral hemispheric lesions in a high percentage of cases. The first section of this thesis is aimed at guiding the interpretation of CP. First of all the issue of the detection of the palsy is treated from historical viewpoint. Consequently, an extended analysis of the current definition of CP, as internationally accepted, is provided. The definition is then outlined in terms of a space dimension and then of a time dimension, hence it is highlighted where this definition is unacceptably lacking. The last part of the first section further stresses the importance of shifting from the traditional concept of CP as a palsy of development (defect analysis) towards the notion of development of palsy, i.e., as the product of the relationship that the individual however tries to dynamically build with the surrounding environment (resource semeiotics) starting and growing from a different availability of resources, needs, dreams, rights and duties (4). In the scientific and clinic community no common classification system of CP has so far been universally accepted. Besides, no standard operative method or technique have been acknowledged to effectively assess the different disabilities and impairments exhibited by children with CP. CP is still “an artificial concept, comprising several causes and clinical syndromes that have been grouped together for a convenience of management” (5). The lack of standard and common protocols able to effectively diagnose the palsy, and as a consequence to establish specific treatments and prognosis, is mainly because of the difficulty to elevate this field to a level based on scientific evidence. A solution aimed at overcoming the current incomplete treatment of CP children is represented by the clinical systematic adoption of objective tools able to measure motor defects and movement impairments. A widespread application of reliable instruments and techniques able to objectively evaluate both the form of the palsy (diagnosis) and the efficacy of the treatments provided (prognosis), constitutes a valuable method able to validate care protocols, establish the efficacy of classification systems and assess the validity of definitions. Since the ‘80s, instruments specifically oriented to the analysis of the human movement have been advantageously designed and applied in the context of CP with the aim of measuring motor deficits and, especially, gait deviations. The gait analysis (GA) technique has been increasingly used over the years to assess, analyze, classify, and support the process of clinical decisions making, allowing for a complete investigation of gait with an increased temporal and spatial resolution. GA has provided a basis for improving the outcome of surgical and nonsurgical treatments and for introducing a new modus operandi in the identification of defects and functional adaptations to the musculoskeletal disorders. Historically, the first laboratories set up for gait analysis developed their own protocol (set of procedures for data collection and for data reduction) independently, according to performances of the technologies available at that time. In particular, the stereophotogrammetric systems mainly based on optoelectronic technology, soon became a gold-standard for motion analysis. They have been successfully applied especially for scientific purposes. Nowadays the optoelectronic systems have significantly improved their performances in term of spatial and temporal resolution, however many laboratories continue to use the protocols designed on the technology available in the ‘70s and now out-of-date. Furthermore, these protocols are not coherent both for the biomechanical models and for the adopted collection procedures. In spite of these differences, GA data are shared, exchanged and interpreted irrespectively to the adopted protocol without a full awareness to what extent these protocols are compatible and comparable with each other. Following the extraordinary advances in computer science and electronics, new systems for GA no longer based on optoelectronic technology, are now becoming available. They are the Inertial and Magnetic Measurement Systems (IMMSs), based on miniature MEMS (Microelectromechanical systems) inertial sensor technology. These systems are cost effective, wearable and fully portable motion analysis systems, these features gives IMMSs the potential to be used both outside specialized laboratories and to consecutive collect series of tens of gait cycles. The recognition and selection of the most representative gait cycle is then easier and more reliable especially in CP children, considering their relevant gait cycle variability. The second section of this thesis is focused on GA. In particular, it is firstly aimed at examining the differences among five most representative GA protocols in order to assess the state of the art with respect to the inter-protocol variability. The design of a new protocol is then proposed and presented with the aim of achieving gait analysis on CP children by means of IMMS. The protocol, named ‘Outwalk’, contains original and innovative solutions oriented at obtaining joint kinematic with calibration procedures extremely comfortable for the patients. The results of a first in-vivo validation of Outwalk on healthy subjects are then provided. In particular, this study was carried out by comparing Outwalk used in combination with an IMMS with respect to a reference protocol and an optoelectronic system. In order to set a more accurate and precise comparison of the systems and the protocols, ad hoc methods were designed and an original formulation of the statistical parameter coefficient of multiple correlation was developed and effectively applied. On the basis of the experimental design proposed for the validation on healthy subjects, a first assessment of Outwalk, together with an IMMS, was also carried out on CP children. The third section of this thesis is dedicated to the treatment of walking in CP children. Commonly prescribed treatments in addressing gait abnormalities in CP children include physical therapy, surgery (orthopedic and rhizotomy), and orthoses. The orthotic approach is conservative, being reversible, and widespread in many therapeutic regimes. Orthoses are used to improve the gait of children with CP, by preventing deformities, controlling joint position, and offering an effective lever for the ankle joint. Orthoses are prescribed for the additional aims of increasing walking speed, improving stability, preventing stumbling, and decreasing muscular fatigue. The ankle-foot orthosis (AFO), with a rigid ankle, are primarily designed to prevent equinus and other foot deformities with a positive effect also on more proximal joints. However, AFOs prevent the natural excursion of the tibio-tarsic joint during the second rocker, hence hampering the natural leaning progression of the whole body under the effect of the inertia (6). A new modular (submalleolar) astragalus-calcanear orthosis, named OMAC, has recently been proposed with the intention of substituting the prescription of AFOs in those CP children exhibiting a flat and valgus-pronated foot. The aim of this section is thus to present the mechanical and technical features of the OMAC by means of an accurate description of the device. In particular, the integral document of the deposited Italian patent, is provided. A preliminary validation of OMAC with respect to AFO is also reported as resulted from an experimental campaign on diplegic CP children, during a three month period, aimed at quantitatively assessing the benefit provided by the two orthoses on walking and at qualitatively evaluating the changes in the quality of life and motor abilities. As already stated, CP is universally considered as a persistent but not unchangeable disorder of posture and movement. Conversely to this definition, some clinicians (4) have recently pointed out that movement disorders may be primarily caused by the presence of perceptive disorders, where perception is not merely the acquisition of sensory information, but an active process aimed at guiding the execution of movements through the integration of sensory information properly representing the state of one’s body and of the environment. Children with perceptive impairments show an overall fear of moving and the onset of strongly unnatural walking schemes directly caused by the presence of perceptive system disorders. The fourth section of the thesis thus deals with accurately defining the perceptive impairment exhibited by diplegic CP children. A detailed description of the clinical signs revealing the presence of the perceptive impairment, and a classification scheme of the clinical aspects of perceptual disorders is provided. In the end, a functional reaching test is proposed as an instrumental test able to disclosure the perceptive impairment. References 1. Prevalence and characteristics of children with cerebral palsy in Europe. Dev Med Child Neurol. 2002 Set;44(9):633-640. 2. Bax M, Goldstein M, Rosenbaum P, Leviton A, Paneth N, Dan B, et al. Proposed definition and classification of cerebral palsy, April 2005. Dev Med Child Neurol. 2005 Ago;47(8):571-576. 3. Ingram TT. A study of cerebral palsy in the childhood population of Edinburgh. Arch. Dis. Child. 1955 Apr;30(150):85-98. 4. Ferrari A, Cioni G. The spastic forms of cerebral palsy : a guide to the assessment of adaptive functions. Milan: Springer; 2009. 5. Olney SJ, Wright MJ. Cerebral Palsy. Campbell S et al. Physical Therapy for Children. 2nd Ed. Philadelphia: Saunders. 2000;:533-570. 6. Desloovere K, Molenaers G, Van Gestel L, Huenaerts C, Van Campenhout A, Callewaert B, et al. How can push-off be preserved during use of an ankle foot orthosis in children with hemiplegia? A prospective controlled study. Gait Posture. 2006 Ott;24(2):142-151.

New path integral simulation algorithms and their application to creep in the quantum sine-Gordon chain

A path integral simulation algorithm which includes a higher-order Trotter approximation (HOA)is analyzed and compared to an approach which includes the correct quantum mechanical pair interaction (effective Propagator (EPr)). It is found that the HOA algorithmconverges to the quantum limit with increasing Trotter number P as P^{-4}, while the EPr algorithm converges as P^{-2}.The convergence rate of the HOA algorithm is analyzed for various physical systemssuch as a harmonic chain,a particle in a double-well potential, gaseous argon, gaseous helium and crystalline argon. A new expression for the estimator for the pair correlation function in the HOA algorithm is derived. A new path integral algorithm, the hybrid algorithm, is developed.It combines an exact treatment of the quadratic part of the Hamiltonian and thehigher-order Trotter expansion techniques.For the discrete quantum sine-Gordon chain (DQSGC), it is shown that this algorithm works more efficiently than all other improved path integral algorithms discussed in this work. The new simulation techniques developed in this work allow the analysis of theDQSGC and disordered model systems in the highly quantum mechanical regime using path integral molecular dynamics (PIMD)and adiabatic centroid path integral molecular dynamics (ACPIMD).The ground state phonon dispersion relation is calculated for the DQSGC by the ACPIMD method.It is found that the excitation gap at zero wave vector is reduced by quantum fluctuations. Two different phases exist: One phase with a finite excitation gap at zero wave vector, and a gapless phase where the excitation gap vanishes.The reaction of the DQSGC to an external driving force is analyzed at T=0.In the gapless phase the system creeps if a small force is applied, and in the phase with a gap the system is pinned. At a critical force, the systems undergo a depinning transition in both phases and flow is induced. The analysis of the DQSGC is extended to models with disordered substrate potentials. Three different cases are analyzed: Disordered substrate potentials with roughness exponent H=0, H=1/2,and a model with disordered bond length. For all models, the ground state phonon dispersion relation is calculated.

Enabling a direct path from end-user specifications to executable protocols in a biology laboratory environment

Biomedical analyses are becoming increasingly complex, with respect to both the type of the data to be produced and the procedures to be executed. This trend is expected to continue in the future. The development of information and protocol management systems that can sustain this challenge is therefore becoming an essential enabling factor for all actors in the field. The use of custom-built solutions that require the biology domain expert to acquire or procure software engineering expertise in the development of the laboratory infrastructure is not fully satisfactory because it incurs undesirable mutual knowledge dependencies between the two camps. We propose instead an infrastructure concept that enables the domain experts to express laboratory protocols using proper domain knowledge, free from the incidence and mediation of the software implementation artefacts. In the system that we propose this is made possible by basing the modelling language on an authoritative domain specific ontology and then using modern model-driven architecture technology to transform the user models in software artefacts ready for execution in a multi-agent based execution platform specialized for biomedical laboratories.

On the path of Exploratory Search Users - A Semantic Web tool

L’Exploratory Search, paradigma di ricerca basato sulle attività di scoperta e d’apprendimento, è stato per diverso tempo ignorato dai motori di ricerca tradizionali. Invece, è spesso dalle ricerche esplorative che nascono le idee più innovative. Le recenti tecnologie del Semantic Web forniscono le soluzioni che permettono d’implementare dei motori di ricerca capaci di accompagnare gli utenti impegnati in tale tipo di ricerca. Aemoo, motore di ricerca sul quale s’appoggia questa tesi ne è un esempio efficace. A partire da quest’ultimo e sempre con l’aiuto delle tecnologie del Web of Data, questo lavoro si propone di fornire una metodologia che permette di prendere in considerazione la singolarità del profilo di ciascun utente al fine di guidarlo nella sua ricerca esplorativa in modo personalizzato. Il criterio di personalizzazione che abbiamo scelto è comportamentale, ovvero basato sulle decisioni che l’utente prende ad ogni tappa che ritma il processo di ricerca. Implementando un prototipo, abbiamo potuto testare la validità di quest’approccio permettendo quindi all’utente di non essere più solo nel lungo e tortuoso cammino che porta alla conoscenza.

Conjugation of Toll Like Receptor 7 agonist through conjugation to immunogenic proteins. Synthesis, characterization, formulation and pre-clinical evaluation

The next generation of vaccine adjuvant are represented by a wide ranging set of molecules called Toll like agonists (TLR’s). Although many of these molecules are complex structures extracted from microorganisms, small molecule TLR agonists have also been identified. However, delivery systems have not been optimized to allow their effective delivery in conjunction with antigens. Here we describe a novel approach in which a small molecule TLR agonist has been conjugated directly to antigens to ensure effective co delivery. We describe the conjugation of a relevant protein, a recombinant protective antigen from S.pneumoniae (RrgB), which is linked to a TLR7 agonist. Following thorough characterization to ensure there was no aggregation, the conjugate was evaluated in a murine infection model. Results showed that the conjugate extended animals’ survival after lethal challenge with S.pneumoniae. Comparable results were obtained with a 10 fold lower dose than that of the native unconjugated antigen. Notably, the animals immunized with the same dose of unconjugated TLR7 agonist and antigen showed no adjuvant effect. The increased immunogenicity was likely a consequence of the co-localization of TLR7 agonist and antigen by chemical binding and is was more effective than simple co-administration. Likely, this approach can be adopted to reduce the dose of antigen required to induce protective immunity, and potentially increase the safety of a broad variety of vaccine candidates

Silk Fibroin: a biopolymer platform for innovative pharmaceutical formulation and biomedical devices.

The protein silk fibroin (SF) from the silkworm Bombyx mori is a FDA-approved biomaterial used over centuries as sutures wire. Importantly, several evidences highlighted the potential of silk biomaterials obtained by using so-called regenerated silk fibroin (RSF) in biomedicine, tissue engineering and drug delivery. Indeed, by a water-based protocol, it is possible to obtain protein water-solution, by extraction and purification of fibroin from silk fibres. Notably, RSF can be processed in a variety of biomaterials forms used in biomedical and technological fields, displaying remarkable properties such as biocompatibility, controllable biodegradability, optical transparency, mechanical robustness. Moreover, RSF biomaterials can be doped and/or chemical functionalized with drugs, optically active molecules, growth factors and/or chemicals In this view, activities of my PhD research program were focused to standardize the process of extraction and purification of protein to get the best physical and chemical characteristics. The analysis of the chemo-physical properties of the fibroin involved both the RSF water-solution and the protein processed in film. Chemo-physical properties have been studied through: vibrational (FT-IR and Raman-FT) and optical (absorption and emission UV-VIS) spectroscopy, nuclear magnetic resonance (1H and 13C NMR), thermal analysis and thermo-gravimetric scan (DSC and TGA). In the last year of my PhD, activities were focused to study and define innovative methods of functionalization of the silk fibroin solution and films. Indeed, research program was the application of different methods of manufacturing approaches of the films of fibroin without the use of harsh treatments and organic solvents. New approaches to doping and chemical functionalization of the silk fibroin were studied. Two different methods have been identified: 1) biodoping that consists in the doping of fibroin with optically active molecules through the addition of fluorescent molecules in the standard diet used for the breeding of silkworms; 2) chemical functionalization via silylation.

Synthesis, characterization and formulation of a cathode active material: Copper nitroprusside

Nowadays, rechargeable Li-ion batteries play an important role in portable consumer devices. Formulation of such batteries is improvable by researching new cathodic materials that present higher performances of cyclability and negligible efficiency loss over cycles. Goal of this work was to investigate a new cathodic material, copper nitroprusside, which presents a porous 3D framework. Synthesis was carried out by a low-cost and scalable co-precipitation method. Subsequently, the product was characterized by means of different techniques, such as TGA, XRF, CHN elemental analysis, XRD, Mössbauer spectroscopy and cyclic voltammetry. Electrochemical tests were finally performed both in coin cells and by using in situ cells: on one hand, coin cells allowed different formulations to be easily tested, on the other operando cycling led a deeper insight to insertion process and both chemical and physical changes. Results of several tests highlighted a non-reversible electrochemical behavior of the material and a rapid capacity fading over time. Moreover, operando techniques report that amorphisation occurs during the discharge.

Modeling multiple state electrostatically formed nanowire transistors

The present thesis work proposes a new physical equivalent circuit model for a recently proposed semiconductor transistor, a 2-drain MSET (Multiple State Electrostatically Formed Nanowire Transistor). It presents a new software-based experimental setup that has been developed for carrying out numerical simulations on the device and on equivalent circuits. As of 2015, we have already approached the scaling limits of the ubiquitous CMOS technology that has been in the forefront of mainstream technological advancement, so many researchers are exploring different ideas in the realm of electrical devices for logical applications, among them MSET transistors. The idea that underlies MSETs is that a single multiple-terminal device could replace many traditional transistors. In particular a 2-drain MSET is akin to a silicon multiplexer, consisting in a Junction FET with independent gates, but with a split drain, so that a voltage-controlled conductive path can connect either of the drains to the source. The first chapter of this work presents the theory of classical JFETs and its common equivalent circuit models. The physical model and its derivation are presented, the current state of equivalent circuits for the JFET is discussed. A physical model of a JFET with two independent gates has been developed, deriving it from previous results, and is presented at the end of the chapter. A review of the characteristics of MSET device is shown in chapter 2. In this chapter, the proposed physical model and its formulation are presented. A listing for the SPICE model was attached as an appendix at the end of this document. Chapter 3 concerns the results of the numerical simulations on the device. At first the research for a suitable geometry is discussed and then comparisons between results from finite-elements simulations and equivalent circuit runs are made. Where points of challenging divergence were found between the two numerical results, the relevant physical processes are discussed. In the fourth chapter the experimental setup is discussed. The GUI-based environments that allow to explore the four-dimensional solution space and to analyze the physical variables inside the device are described. It is shown how this software project has been structured to overcome technical challenges in structuring multiple simulations in sequence, and to provide for a flexible platform for future research in the field.

Clinical and antibacterial effect of an anti-inflammatory toothpaste formulation with Scutellaria baicalensis extract on experimental gingivitis

It was the aim of the study to evaluate the clinical and antibacterial effect of a dentifrice containing an anti-inflammatory plant extract (SB) versus a placebo (PLA) using an experimental gingivitis model. Forty subjects (20 per group) discontinued all oral hygiene measures for four teeth for a period of 21 days using a shield (to generate a possible gingivitis) while they could brush the other teeth normally. After brushing, the shield was removed and teeth were treated with the randomly assigned toothpaste slurry for 1 min. Löe and Silness gingival index (GI), Silness and Löe plaque index (PI), and biofilm vitality (VF%) were assessed at days 0, 14, and 21, respectively. Subjects of the PLA group developed a GI of 0.82?±?0.342 (day 14) and 1.585?±?0.218 (day 21), while the data of the SB group were significantly reduced (0.355?±?0.243 and 0.934?±?0.342, p?formulation was able to significantly reduce the extent of gingivitis, plaque development, and vital flora.

Anti insulin-like growth factor I receptor immunoliposomes: a single formulation combining two anticancer treatments with enhanced therapeutic efficiency

Context: Through overexpression and aberrant activation in many human tumors, the IGF system plays a key role in tumor development and tumor cell proliferation. Different strategies targeting IGF-I receptor (IGFI-R) have been developed, and recent studies demonstrated that combined treatments with cytostatic drugs enhance the potency of anti-IGFI-R therapies. Objective: The objective of the study was to examine the IGFI-R expression status in neuroendocrine tumors of the gastroenteropancreatic system (GEP-NETs) in comparison with healthy tissues and use potential overexpression as a target for novel anti-IGFI-R immunoliposomes. Experimental Design: A human tumor tissue array and samples from different normal tissues were investigated by immunohistochemistry. An IGFI-R antagonistic antibody (1H7) was coupled to the surface of sterically stabilized liposomes loaded with doxorubicin. Cell lines from different tumor entities were investigated for liposomal association studies in vitro. For in vivo experiments, neuroendocrine tumor xenografts were used for evaluation of pharmacokinetic and therapeutic properties of the novel compound. Results: Immunohistochemistry revealed significant IGFI-R overexpression in all investigated GEP-NETs (n = 59; staining index, 229.1 +/- 3.1%) in comparison with normal tissues (115.7 +/- 3.7%). Furthermore, anti-IGFI-R immunoliposomes displayed specific tumor cell association (44.2 +/- 1.6% vs. IgG liposomes, 0.8 +/- 0.3%; P < 0.0001) and internalization in human neuroendocrine tumor cells in vitro and superior antitumor efficacy in vivo (life span 31.5 +/- 2.2 d vs. untreated control, 19 +/- 0.6, P = 0.008). Conclusion: IGFI-R overexpression seems to be a common characteristic of otherwise heterogenous NETs. Novel anti-IGFI-R immunoliposomes have been developed and successfully tested in a preclinical model for human GEP-NETs. Moreover in vitro experiments indicate that usage of this agent could also present a promising approach for other tumor entities.

GSR deposition along the bullet path in contact shots to composite models

In contact shots, all the materials emerging from the muzzle (combustion gases, soot, powder grains, and metals from the primer) will be driven into the depth of the entrance wound and the following sections of the bullet track. The so-called "pocket" ("powder cavity") under the skin containing soot and gunpowder particles is regarded as a significant indicator of a contact entrance wound since one would expect that the quantity of GSR deposited along the bullet's path rapidly declines towards the exit hole. Nevertheless, experience has shown that soot, powder particles, and carboxyhemoglobin may be found not only in the initial part of the wound channel, but also far away from the entrance and even at the exit. In order to investigate the propagation of GSRs under standardized conditions, contact test shots were fired against composite models of pig skin and 25-cm-long gelatin blocks using 9-mm Luger pistol cartridges with two different primers (Sinoxid® and Sintox®). Subsequently, 1-cm-thick layers of the gelatin blocks were examined as to their primer element contents (lead, barium, and antimony as discharge residues of Sinoxid® as well as zinc and titanium from Sintox®) by means of X-ray fluorescence spectroscopy. As expected, the highest element concentrations were found in the initial parts of the bullet tracks, but also the distal sections contained detectable amounts of the respective primer elements. The same was true for amorphous soot and unburned/partly burned powder particles, which could be demonstrated even at the exit site. With the help of a high-speed motion camera it was shown that for a short time the temporary cavitation extends from the entrance to the exit thus facilitating the unlimited spread of discharge residues along the whole bullet path.

A Kinetostatic Formulation for Load-Flow Visualization in Compliant Mechanisms

Load flow visualization, which is an important step in structural and machine assembly design may aid in the analysis and eventual synthesis of compliant mechanisms. In this paper, we present a kineto-static formulation to visualize load flow in compliant mechanisms. This formulation uses the concept of transferred forces to quantify load flow from input to the output of a compliant mechanism. The magnitude and direction of load flow in the constituent members enables functional decomposition of the compliant mechanism into (i) Constraints (C): members that are constrained to deform in a particular direction and (ii) Transmitters (T): members that transmit load to the output. Furthermore, it is shown that a constraint member and an adjacent transmitter member can be grouped together to constitute a fundamental building block known as an CT set whose load flow behavior is maximally decoupled from the rest of the mechanism. We can thereby explain the deformation behavior of a number of compliant mechanisms from literature by visualizing load flow, and identifying building blocks.