Classical Criteria Research Articles

Constructing training sets for genomic selection to identify superior genotypes in candidate populations.

Approaches for constructing training sets in genomic selection are proposed to efficiently identify top-performing genotypes from a breeding population. Identifying superior genotypes from a candidate population is a key objective in plant breeding programs. This study evaluates various methods for the training set optimization in genomic selection, with the goal of enhancing efficiency in discovering top-performing genotypes from a breeding population. Additionally, two approaches, inspired by classical optimal design criteria, are proposed to expand the search space for the best genotypes and compared with methods focusing on maximizing accuracy in breeding value prediction. Evaluation metrics such as normalized discounted cumulative gain, Spearman's rank correlation, and Pearson's correlation are employed to assess performance in both simulation studies and real trait analyses. Overall, for candidate populations lacking a strong subpopulation structure, a ridge regression-based method, referred to as is recommended. For candidate populations with a strong subpopulation structure, a heuristic-based version of generalized coefficient of determination and a D-optimality-like method that maximizes overall genomic variation are preferred approaches for the primary objective of plant breeding. For populations with a large number of candidates, a proposed ranking method ( ) can first be used to down-scale the candidate population, after which a heuristic-based method is employed to identify the best genotypes. Notably, the proposed has been verified to be equivalent to the original version, known as , but its implementation is much more computationally efficient.

Quantum-inspired Attribute Selection Algorithms

Abstract In this study, we propose the use of quantum information gain and fidelity as quantum splitting criteria to construct an efficient and balanced quantum decision tree. Quantum information gain is a circuit-based criterion in which angle embedding is used to construct a quantum state, which utilizes quantum mutual information to compute the information between a feature and the class attribute. For the fidelity-based criterion, we construct a quantum state using the occurrence of random events in a feature and its corresponding class. We use the constructed state to further compute fidelity for determining the splitting attribute among all features. Using numerical analysis, our results clearly demonstrate that the fidelity-based criterion ensures the construction of a balanced tree. We further compare the efficiency of our quantum information gain and fidelity-based quantum splitting criteria with different classical splitting criteria on balanced and imbalanced datasets. Our analysis shows that the quantum splitting criteria lead to quantum advantage in comparison to classical splitting criteria for different evaluation metrics.

SWOT analysis as a tool for selecting text materials for the formation of English communicative competence of students of non-linguistic specialties

The study is devoted to the implementation of SWOT analysis as an auxiliary criterion for the selection of text material in the formation of English communicative competence for students of non-linguistic specialties. The article examines the concept of communicative competence, as a complex phenomenon of students’ availability of appropriate abilities and skills for high-quality foreign language communication. The main groups of criteria for the selection of text material have been outlined, including 1) subject-scientific ones; 2) linguistic stylistic; 3) methodological; 4) person-oriented. The concept of SWOT analysis has been summarized and the components of the matrix of this analysis have been analyzed, namely: the factors of positive influence of the internal environment are – Strengths, the negative factors – Weaknesses, and the factors of external influence are Opportunities, and the negative ones are Threats. The use of SWOT analysis, based on the classic qualitative criteria for text selection has been proposed as follows: Strengths – linguistic stylistic criteria of variety of types and genres and professionally oriented lexical units; Weaknesses – methodological criteria of authenticity, accessibility, adaptability, etc.; Opportunities – subject-scientific criteria of novelty, informational value and the presence of paralinguistic components; Threats are person-oriented criteria of relevance and practical value. An analysis of the English-language text has been carried out according to the proposed SWOT-analysis model and qualitative criteria for the selection of text material have been highlighted as well.

Stochastic Processes with Expected Stopping Time

Markov chains are the de facto finite-state model for stochastic dynamical systems, and Markov decision processes (MDPs) extend Markov chains by incorporating non-deterministic behaviors. Given an MDP and rewards on states, a classical optimization criterion is the maximal expected total reward where the MDP stops after T steps, which can be computed by a simple dynamic programming algorithm. We consider a natural generalization of the problem where the stopping times can be chosen according to a probability distribution, such that the expected stopping time is T, to optimize the expected total reward. Quite surprisingly we establish inter-reducibility of the expected stopping-time problem for Markov chains with the Positivity problem (which is related to the well-known Skolem problem), for which establishing either decidability or undecidability would be a major breakthrough. Given the hardness of the exact problem, we consider the approximate version of the problem: we show that it can be solved in exponential time for Markov chains and in exponential space for MDPs.

Enhanced Oscillation Criteria for Non-Canonical Second-Order Advanced Dynamic Equations on Time Scales

This study aims to establish novel iterative oscillation criteria for second-order half-linear advanced dynamic equations in non-canonical form. The results extend and enhance recently established criteria for this type of equation by various authors and also encompass the classical criteria for related ordinary differential equations. Our methodology involves transforming the non-canonical equation into its corresponding canonical form. The inherent symmetry of these canonical forms plays a pivotal role in deriving our new criteria. By employing techniques from the theory of symmetric differential equations and utilizing symmetric functions, we establish precise conditions for oscillation. Several illustrative examples highlight the accuracy, applicability, and versatility of our results.

Impact of new definition on the prognosis of patients with pulmonary hypertension compared to classic definition

Abstract Background The recent European Society of Cardiology (ESC)/European Respiratory Society (ERS) 2022 pulmonary hypertension (PH) guidelines have updated the definition of PH from a mean pulmonary arterial pressure (mPAP) ≥ 25mmHg to > 20mmHg, and the pulmonary vascular resistance (PVR) threshold for pre-capillary PH (Pre-PH) from > 3 wood units (WU) to > 2 WU. Little is known regarding the implication of this new criteria in all PH subgroups in Asia. Purpose In this study, we aim to evaluate the impact of the new PH definition on the prevalence and prognosis of PH subgroups in as Asian cohort. Methods A retrospective analysis of a single-center RHC registry (April 2016 - July 2023) was conducted. 314 patients (median age 62.5, 50.3% men) were included. Patients were categorized into PH subgroups as defined by both the classic and new criteria. The primary outcome included cardiovascular mortality or heart failure hospitalizations, assessed over a maximum follow-up period of 5 years. Clinical outcomes of different PH subgroups using the classic and new definitions were compared using Kaplan-Meier methods, log-rank tests, and Cox proportional hazards models. Continuous parameters were analyzed using restrictive cubic splines within Cox models. Results Based on the new cutoffs (mPAP > 20mmHg, PVR > 2 WU), 76 patents (24.2%) were reclassified. PH increased to 233 (+ 41, +13.1%), Pre-PH increased to 92 (+ 30, +9.6%), Ipc-PH decreased to 27 (- 21, -6.7%), and Cpc-PH increased to 108 (+33, +10.5%). Over a median follow-up of 238.5 days, 65 primary outcomes occurred. Under the new PH definition, 5-year survival rates for Pre-PH, Ipc-PH, and Cpc-PH are 73.2%, 57.5%, and 47.0%, improved from 67.0%, 53.3%, and 44.3% in the classic definition. In the Cox regression analysis, using the Non-PH as a reference, the risk of primary outcome for PH subgroups was lower in the new definition compared to the classic definition (Table 1). Using the classic mPAP cut-off [<25 vs. ≥25 mmHg], patients with PH had a significantly higher risk for primary outcome (HR 2.25, 95% CI 1.26-4.00, p=0.006) compared with patients without PH. However, using the new mPAP cut-off [<20 vs. ≥20 mmHg], it didn’t show significant difference between two groups (HR 1.62, 95% CI 0.86-3.04, p=0.132). Spline analyses suggested a linear relation between the risk of primary outcome and mPAP considering mPAP between 20 and 45mmHg, and a plateau of events for mPAP values over 45mmHg. In patients with PVR > 2 WU, we observed a linear relation between PVR and events for values and a plateau of events for PVR values over 7.5 WU (Figure 1). Conclusion The new definition increased the diagnosis of PH, particularly in Pre-PH and Cpc-PH. This definition faciliates earlier diagnosis, encompassing milder disease states, and demonstrated better prognosis in PH subgroups. However, it dose not identify additional patients at increased risk of primary outcomes.Table 1Figure 1

Singular loci of algebras over ramified discrete valuation rings

AbstractWhen is a field, the classical Jacobian criterion computes the singular locus of an equidimensional, finitely generated ‐algebra as the closed subset of an ideal generated by appropriate minors of the so‐called Jacobian matrix. Recently, Hochster‐Jeffries and Saito have extended this result for algebras over any unramified discrete valuation ring of mixed characteristic via the use of ‐derivations. Motivated by these results, in this paper, we state and prove an analogous Jacobian criterion for algebras over ramified discrete valuation rings of mixed characteristic.

Are information criteria good enough to choose the right the number of regimes in hidden Markov models?

Selecting the number of regimes in Hidden Markov models is an important problem. Many criteria are used to do so, such as Akaike information criterion (AIC), Bayesian information criterion (BIC), integrated completed likelihood (ICL), deviance information criterion (DIC), and Watanabe-Akaike information criterion (WAIC), to name a few. In this article, we introduced goodness-of-fit tests for general Hidden Markov models with covariates, where the distribution of the observations is arbitrary, i.e. continuous, discrete, or a mixture of both. A selection procedure is proposed based on this goodness-of-fit test. The main aim of this article is to compare the classical information criterion with the new criterion when the outcome is either continuous, discrete or zero-inflated. Numerical experiments assess the finite sample performance of the goodness-of-fit tests, and comparisons between the different criteria are made.

Hyers–Ulam stability of Nipah virus model using Atangana–Baleanu–Caputo fractional derivative with fixed point method

In this study, we present a novel investigation into the dynamics of the Nipah virus through the lens of fractional differential equations (FDEs), employing the Atangana–Baleanu–Caputo fractional derivative (ABCFD) and the fixed-point approach (FPA). The core contribution of this work lies in establishing the existence and uniqueness of solutions to the proposed FDEs, a critical step for validating the model. Furthermore, we explore the Hyers–Ulam (HU) stability of these generalized FDEs, providing a rigorous mathematical foundation for the stability analysis within the context of viral dynamics. By leveraging the ABCFD, our work extends the classical stability criteria, offering new insights into the role of memory effects in disease modeling. Additionally, we present approximate solutions across various compartments and fractional orders, highlighting the sensitivity of the system to key parameters. Numerical simulations, conducted using the Cullis method, illustrate the impact of fractional orders and validate the theoretical findings, positioning this work as a significant advancement in the application of fractional calculus to epidemiological models.

Peculiarities of granulocyte-macrophage and macrophage colony-stimulating factors receptors expression in subpopulations of peripheral blood monocytes of patients with chronic obstructive pulmonary disease

Introduction. To analyze of the severity of respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD), depending on the presence of an exacerbation or novel coronavirus infection (NCVI), taking into account the activity of acute phase blood parameters.Materials and methods. The medical documentation of 162 patients with COPD was studied, which were divided into 3 groups: group 1 (n=61) ‒ COPD and NCVI, group 2 (n=53) – stable COPD, group 3 (n=48) ‒ COPD exacerbation. The severity of respiratory symptoms was assessed using points. To assess the activity of inflammation the following biochemical indicators were used ‒ C-reactive protein (CRP) and fibrinogen (g/L).Results. According to the severity of cough and the intensity of dyspnea on the mMRC scale, the first, second and third groups did not differ statistically (p=0.07). Patients of the first group (82.5%) characterized by the absence of classical criteria for exacerbation of COPD. In terms of the severity of sputum production, the first, second and third groups are statistically different (p=0.0001). The first, second and third groups differ significantly in the level of serum CRP (p=0.0001) and fibrinogen (p=0.009). According to the results of the correlation analysis, some relationships found between respiratory symptoms and the level of CRP and fibrinogen.Conclusion. The clinical feature of the associated course of stable COPD and NCVI is the presence of severe dyspnea and the absence of classic criteria for exacerbation of COPD. Systemic inflammation in NCVI and stable COPD are more pronounced than in isolated stable COPD or exacerbation and correlates with cough and dyspnea. Practitioners for the differential diagnosis of NCVI in stable COPD can use the data obtained.

Adrenal tumours in patients with pathogenic APC mutations: a retrospective study

BackgroundAdrenal tumours are associated with familial adenomatous polyposis (FAP). In the literature, most studies use the clinical definition of FAP (more than 100 adenomatous polyps found in endoscopic studies). However, not all patients that meet clinical criteria for FAP carry pathogenic mutations in the adenomatous polyposis coli (APC) gene, as there is genetic heterogeneity responsible for FAP with the polyposis sometimes explained by genetic and environmental factors other than pathogenic APC mutations. Reciprocally, not all the patients with pathogenic APC variants will fulfil the classic criteria of FAP.ObjectiveThis study aims to investigate the characteristics of adrenal tumours in patients with pathogenic or likely pathogenic APC variants and explore the hormonal function of these patients.MethodThis is a retrospective cohort study. Patients with pathogenic or likely pathogenic APC variants were recruited and their radiological assessments were reviewed. Patient demographic data, APC variants, adrenal mass characteristics and hormonal testing results were collected.ResultThe prevalence of adrenal mass was 26.7% (24/90) among patients with pathogenic or likely pathogenic APC variants. Using the classic definition, the prevalence was 32.4% (22/68). Four patients had adrenal hormone testing, two of which had Conn’s syndrome and two had nonspecific subclinical results.ConclusionIn our cohort, the prevalence of adrenal tumours among patients with pathogenic and likely pathogenic APC mutations is at least twice to three times higher than the general population prevalence reported from international population-based studies. The hormonal functions of patients with pathogenic APC variants and adrenal tumours can be investigated with routine testing in further research.

High-resolution versus conventional manometry for the diagnosis of small bowel motor dysfunction.

The diagnosis of small bowel motility disorders is performed by manometric evaluation of the contractile patterns of the small intestine. Conventional intestinal manometry systems include few pressure sensors at relatively long intervals. We have recently shown that high-resolution jejunal manometry, with multiple closely spaced recording sites, allows the analysis of propagation patterns of intestinal motility in healthy subjects that cannot be detected with conventional manometry. The objective of this pilot study was to explore the feasibility and diagnostic value of high-resolution intestinal manometry in patients with suspected small bowel dysmotility. Prospective pilot study evaluating intestinal motility patterns in 16 consecutive patients (16-61 years; 11 women) with severe, chronic digestive symptoms referred for the evaluation of intestinal motility and in 18 healthy controls (21-38 years; 8 women). A 36-channel high-resolution manometry catheter was orally placed under radiological guidance in the jejunum. Intestinal motility was continuously recorded for 3 h fasting and 2 h after a 450 kcal meal. The manometric recordings were analyzed in two formats: (a) with the high-resolution data from 34 channels and (b) showing only the recordings from 5 channels separated by 7 cm intervals, mimicking a conventional manometry recording. In the analysis mimicking conventional manometry, abnormal motility criteria were detected in six patients and in no healthy subject [bursts (n = 3), postprandial minute rhythm (n = 1) and myopathic pattern (n = 2)]. These classical dysmotility criteria were also detected by high-resolution manometry. High-resolution analysis detected one or more abnormal findings in seven additional patients that were not observed in any healthy subject, specifically: (a) abnormal propagation of Phase III (n = 3); (b) reduced propagated activity during Fasting Phase II (n = 4); (c) increased propagated activity during Fasting Phase II and postprandial phase (n = 1). This pilot study suggests that high-resolution intestinal manometry may improve the sensitivity of conventional manometry in the detection of intestinal motor dysfunction.

Development of a Health-State Classification System for the Pediatric Quality-of-Life Inventory Version 4.0 Generic Core Scales for Preference-Based Valuation in Australia

ObjectivesPediatric Quality-of-Life Inventory Version 4.0 Generic Core Scales (PedsQL GCS), comprising 23 items covering 4 subscales (physical, emotional, social, and school functioning), is a widely applied generic measure of childhood health-related quality of life but does not provide health utilities for cost-effectiveness-based decision making. This study aimed to develop a reduced item version of PedsQL GCS amenable to health utility derivation in Australia. MethodsData sources were 2 cohorts of the Longitudinal Study of Australian Children, including proxy responses for all PedsQL GCS versions (Toddlers, Young Children, Children, and Teens), and the CheckPoint sample containing child self-report to the Children version. Three analytic samples were CheckPoint sample (n = 1874); Mallinson sample containing 1 measurement per child from one of the Young Children, Children, or Teens versions (n = 7855); and Toddlers sample (n = 7401). Exploratory and confirmatory factor analyses assessed dimensionality. Psychometric analyses used Rasch and classical criteria on 3 randomly selected subsamples (n = 500) per sample. Item selection prioritized psychometric performance in the CheckPoint sample, also considering performance in other samples and conceptual content. ResultsDimensionality assessments did not generate an alternative empirical structure for the measure, and psychometric analyses were conducted on the original 4 subscales. The selected items were: “Get aches and pains” for physical functioning; “Feel sad/blue” for emotional functioning; “Other kids not friends” for social functioning; and “Keeping up with school work” for school functioning. ConclusionsThe final 4-item set, pending further psychometric validation and valuation, can generate health utilities from the widely used PedsQL GCS to inform cost-effectiveness-based decision making.

The relationships between tensile strength, mode I and mode II fracture toughness of rock: An empirical and microcracking perspective

The empirical relationships between tensile strength, mode I and mode II fracture toughness obtained by previous studies have the problem of a small amount of data for fitting, and more data are needed for further study. There is a discrepancy between the theoretical prediction and the experimental results of the relationship between mode II and mode I fracture toughness. Because of this, a review is conducted to determine the relationships among tensile strength, mode I fracture toughness, and mode II fracture toughness from the data gathered from the available literature. The results indicate that the mode I and mode II fracture toughness have linear relationships with tensile strength with the linear coefficient of 0.141 and 0.219, respectively. The linear coefficient between mode II and mode I fracture toughness is 2.389, indicating that the classical mixed mode criteria are mistaken the empirical relationship between mode II and mode I fracture toughness. The microcracking mechanism and failure model are quantified and compared in detail among tensile test, mode I and mode II fracture toughness tests based on moment tensor. It found that the nature of the source can be related to each other, which gives some light on the reason for the existence of certain relationships between these macroscopic parameters from a microcracking perspective.

On the synthesis and formability of high-entropy oxides

This paper reports on a straightforward and general solution-based synthesis method for high-entropy oxides (HEOs) of different types and compositions. The flexibility and simplicity of this method are hoped to drive development of new HEOs and study of their properties and applications. Thirteen HEOs with rock salt, fluorite, spinel, and perovskite structures were synthesized using a Pechini-type synthesis at temperatures significantly lower than those necessary in solid-state synthesis (400–900 °C). Metal nitrates, nitrites, chlorides, and even water-sensitive alkoxides were used as the metal precursors with the present method. The HEOs were characterized using powder X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Relaxation of cation size and charge rules and formability of HEOs are also discussed. The present results indicate that the classical criteria for material stability do not readily translate to high-entropy systems. For example, the well-known criteria for Goldschmidt and octahedral tolerance factors established for ordinary perovskites do not seem to describe formability of perovskite HEOs well. The discussed relaxation of cation size and charge rules will contribute to the understanding of HEO systems and development of new HEO phases.

A New Critical Plane Multiaxial Fatigue Criterion with an Exponent to Account for High Mean Stress Effect

The mean stress effect remains a critical aspect in multiaxial fatigue analysis. This work presents a new criterion that, based on the classical Findley criterion, applies a material-dependent exponent to the mean normal stress term and includes the ultimate tensile stress as a fitting parameter. This way of considering the non-linear effect of the mean stress, with a material-dependent rather than a fixed exponent, is totally innovative among the multiaxial fatigue criteria found in the literature. In order to verify its accuracy, the new criterion has been checked against an extended version of the Papuga database of multiaxial experimental tests with 485 results, and compared with the criteria by Findley, Robert, and Papuga. The new criterion provides outstanding results for pure uniaxial cases, with multiaxial performance similar to the Robert criterion with a smaller range of error and a conservative trend, even surpassing the popular Papuga method in several relevant loading scenarios. These features enhance the applicability and versatility of the criterion for its use in the fatigue design of structural components.

Caffeine removal using brewery’s spent grain modified with H3PO4: experimental observation and statistical analysis

This work studied the performance and reusability of the biosorbent obtained from a brewery’s spent grain (BSG), applying experimental observation and statistical analysis to caffeine removal from the real matrix. A study of caffeine removal on a batch scale, through kinetic and isotherm models, applying classical and Bayesian statistic criteria, was performed to choose the most adequate model and estimate the maximum amount adsorbed (qmax) and the equilibrium constant (Ke). The biosorbent regeneration through ultrasound and thermal oxidation and the biosorbent characteristics—including the structural changes after the regeneration cycles—were also evaluated. The best operational conditions for caffeine removal (above 80%) were obtained at natural pH and adsorbent dosage of 20 g L−1, with the qmax ranging from 5.86 to 8.83 mg g−1. Results demonstrate that acid sites disappear after adsorption indicating that caffeine binds to the adsorbent surface through hydrogen bonds (chemisorption occurrence hypothesis). The biosorbent was regenerated eight consecutive times and kept the adsorption performance above 60%. Besides, it was efficient in the alkalinity removal (80%), inorganic carbon (95%), and caffeine (98%), which shows the potential for application in the treatment of aqueous matrices.

Exploring the Clinical Utility of Targeted MECP2 Testing in Real-World Practice

BackgroundThis study aimed to explore the clinical utility of targeted MECP2 testing in a large cohort of females with neurodevelopmental delays. Our aim was to identify suitable candidates for testing based on prevailing diagnostic criteria. MethodsEligible participants with global developmental delay/arrest or regression before age 36 months underwent MECP2 testing. MECP2-positive patients were further categorized based on Rett syndrome (RTT) diagnostic criteria, including typical, atypical, possible, and unclassified, to assess disease typicality and progression with respect to age. ResultsOf the 683 patients, 162 (23.7%) were diagnosed with MECP2-related RTT. Global developmental delay was the predominant initial symptom in approximately 75% of the cohort with developmental arrest/regression at testing. Symptoms emerged before age six months in 14 patients (8.6%). The average age at the time of MECP2 testing was 3.7 years, with 31.5% of the patients tested under two years. Of those under two years, 15 were initially categorized into the unclassified group; however, 12 were later reclassified into the typical/atypical RTT groups based on follow-up evaluation. Among the 119 patients monitored beyond age five years, 80% displayed typical RTT symptoms, 10 remained unclassified, and 9.8% had exonic deletions, posing challenges for detection using next-generation sequencing. ConclusionsTargeted MECP2 testing has emerged as a clinically valuable tool with a high diagnostic yield, including the identification of small deletions. Given that younger patients may not always meet the classic RTT criteria, this study recommends targeted MECP2 testing in younger patients without typical RTT features.

Morphological and Molecular Characterization of Three Myxosporean Species of the Genera Myxobolus, Henneguya, and Myxidium (Cnidaria: Myxozoa) Infecting Freshwater Fish, Isolated for the First Time in Japan.

The majority of myxosporean species (Cnidaria: Myxozoa) of the genera Myxobolus (35 species), Henneguya (8 species), and Myxidium (9 species) from freshwater or brackish fish in Japan were recorded more than 30 years ago (accumulatively 81.1% [43/53]). The re-discovery and molecular-genetic characterization of these species is a current research priority. During our myxosporean survey in Japanese freshwater fish, we detected three species that had never been recorded in Japan, but in the Russian Far East (Sakhalin Island, and Maritime Province): Myxobolus tribolodonus sp. n., forming cysts in the gills of Tribolodon sachalinensis (syn. M. marinus sensu Aseeva, 2000; M. marinus sensu Sokolov et Frolova, 2015, recorded from the gills of Pseudaspius (syn. Tribolodon) spp.); Henneguya pungitii Achmerov, 1953, forming cysts in the subcutis of external skin and buccal submucosa of Pungitius sinensis; and Myxidium salvelini Konovalov et Shulman, 1966, in the urinary bladder of Oncorhynchus masou ishikawae. These new isolates were characterized by integrated taxonomic approaches, i.e., myxospore morphology and molecular-genetic characterization of the small subunit ribosomal RNA gene (SSU rDNA). These new isolates were phylogenetically differentiated from any species whose SSU rDNA sequences were deposited in the DNA databases, and concurrently compared with recorded species based on classical morphological criteria. All three species were differentiated from myxosporeans previously recorded in Japan, indicating new distribution records out of the Russian Far East. For reliable species identification, accumulation of at least SSU rDNA sequences of known species worldwide is critically important.

Adenosine triphosphate: a new player in complex regional pain syndrome type 1.

The complex regional pain syndrome type 1 (CRPS-1) is one of the most discussed painful syndromes due to the variability and severity of its symptoms. CRPS-1 generally occurs after a trauma, a fracture or a sprain followed by an immobilization. Classical diagnostic criteria are not always clear; hence, the diagnosis is difficult. The definition of CRPS itself defines and considers the pain as key symptom neglecting the bone damage. Early CRPS involves the activation of the innate cutaneous immune system with altered sensory and sympathetic signaling, activation and proliferation of keratinocytes and mast cells in addition to the release of inflammatory mediators and pain. The role of the immune system and the response to the disease is becoming clearer as the microglia is activated as a result of injury and can induce a central sensitization while astrocytes can maintain the process. Adenosine triphosphate (ATP) exerts a fundamental role in the activation of innate cutaneous immune system, in the proliferation of keratinocytes and mast cells, in the release of several proinflammatory cytokines and in the microglia activation. It is essential to intervene on this pathology as soon as possible with drugs, as clodronate, able to reduce bone marrow edema and pain through the inhibition of the primary inflammatory process and the immune reaction, limiting the activation of macrophages and the release of cytokines activating nuclear growth factor (NGF). In this review the role of ATP, bisphosphonates and rehabilitation are discussed.