Randomized clinical trial comparing survival after D1 or D2 gastrectomy for gastric cancer.

BACKGROUND: It is still unclear whether D2 lymphadenectomy improves the survival of patients with gastric cancer and should therefore be performed routinely or selectively. The aim of this multicentre randomized trial was to compare D2 and D1 lymphadenectomy in the treatment of gastric cancer. METHODS: Between June 1998 and December 2006, patients with gastric adenocarcinoma were assigned randomly to either D1 or D2 gastrectomy. Intraoperative randomization was implemented centrally by telephone. Primary outcome was overall survival; secondary endpoints were disease-specific survival, morbidity and postoperative mortality. RESULTS: A total of 267 eligible patients were allocated to either D1 (133 patients) or D2 (134) resection. Morbidity (12.0 versus 17.9 per cent respectively; P = 0.183) and operative mortality (3.0 versus 2.2 per cent; P = 0.725) rates did not differ significantly between the groups. Median follow-up was 8.8 (range 4.5-13.1) years for surviving patients and 2.4 (0.2-11.9) years for those who died, and was not different in the two treatment arms. There was no difference in the overall 5-year survival rate (66.5 versus 64.2 per cent for D1 and D2 lymphadenectomy respectively; P = 0.695). Subgroup analyses showed a 5-year disease-specific survival benefit for patients with pathological tumour (pT) 1 disease in the D1 group (98 per cent versus 83 per cent for the D2 group; P = 0.015), and for patients with pT2-4 status and positive lymph nodes in the D2 group (59 per cent versus 38 per cent for the D1 group; P = 0.055). CONCLUSION: No difference was found in overall 5-year survival between D1 and D2 resection. Subgroup analyses suggest that D2 lymphadenectomy may be a better choice in patients with advanced disease and lymph node metastases. REGISTRATION NUMBER: ISRCTN11154654 (http://www.controlled-trials.com).

Pattern formation in auxin flux.

The plant hormone auxin is fundamental for plant growth, and its spatial distribution in plant tissues is critical for plant morphogenesis. We consider a leading model of the polar auxin flux, and study in full detail the stability of the possible equilibrium configurations. We show that the critical states of the auxin transport process are composed of basic building blocks, which are isolated in a background of auxin depleted cells, and are not geometrically regular in general. The same model was considered recently through a continuous limit and a coupling to the von Karman equations, to model the interplay of biochemistry and mechanics during plant growth. Our conclusions might be of interest in this setting, since, for example, we establish the existence of Lyapunov functions for the auxin flux, proving in this way the convergence of pure transport processes toward the set of equilibrium points.

On Gait Consistency Quantification Through ARX Residual Modeling and Kernel Two-Sample Testing.

OBJECTIVE: The quantification of the way an individual walks is key to the understanding of diseases affecting the neuromuscular system. More specifically, to improve diagnostics and treatment plans, there is a continuous interest in quantifying gait consistency, allowing clinicians to distinguish natural variability of the gait patterns from disease progression or treatment effects. To this end, the current article presents a novel objective method for assessing the consistency of an individual's gait, consisting of two major components. METHODS: Firstly, inertial sensor accelerometer data from both shanks and the lower back is used to fit an AutoRegressive with eXogenous input model. The model residuals are then used as a key feature for gait consistency monitoring. Secondly, the non-parametric maximum mean discrepancy hypothesis test is introduced to measure differences in the distributions of the residuals as a measure of gait consistency. As a paradigmatic case, gait consistency was evaluated both in a single walking test and between tests at different time points in healthy individuals and those affected by multiple sclerosis (MS). RESULTS: It was found that MS patients experienced difficulties maintaining a consistent gait, even when the retest was performed one-hour apart and all external factors were controlled. When the retest was performed one-week apart, both healthy and MS individuals displayed inconsistent gait patterns. CONCLUSION: Gait consistency has been successfully quantified for both healthy and MS individuals. SIGNIFICANCE: This newly proposed approach revealed the detrimental effects of varying assessment conditions on gait pattern consistency, indicating potential masking effects at follow-up assessments.

Work-Related Stress Questionnaire: confirmatory factor analysis for construct validation by the PHRASI study.

OBJECTIVE: The purpose of this study is to validate the 13-item version of the Work-Related Stress Questionnaire (WRSQ) on a representative sample of Italian public health residents. MATERIALS AND METHODS: The WRSQ was administered as part of the Public Health Residents' Anonymous Survey in Italy (PHRASI) from 14 June to 26 July 2022. Collinearity between each questionnaire item was assessed with Kendall's τ statistic. The latent factors identified associating similar items based on the authors' observations were workplace, job demand, support and unpleasant workplace. Goodness-of-fit was assessed with confirmatory factor analysis calculating: Comparative Fit Index (CFI), Tucker-Lewis Index (TLI), Root Mean Square Error of Approximation (RMSEA), Standardized Root-Mean-Residual (SRMR). Cronbach's alpha (α) and Omega McDonald (ω) were calculated to evaluate the reliability of the questionnaire. R 4.2.2 was used to perform the analyses. RESULTS: 379 Public Health residents (58% women) responded to the questionnaire. No significant collinearity was found between the items (τ range -0.31 to 0.49). Confirmatory Factor Analysis showed CFI = 0.975, TLI = 0.967, RMSEA = 0.041 and SRMR = 0.051. Internal consistency of the WRSQ Total Score was α = 0.80 and ω = 0.85. CONCLUSIONS: Although validated in a sectorial subpopulation of healthcare workers, the WRSQ proved to be an excellent tool for assessing work-related stress. Unpleasant workplace latent factors showed lower factor loading and internal consistency than others. This could be due to the fact that topics investigated with unpleasant workplace items (e.g., abuse and discrimination) are experienced on a less regular basis than the ones assessed through the other items.

Molecular background and genotype-phenotype correlation in autoimmune-polyendocrinopathy-candidiasis-ectodermal-distrophy patients from Campania and in their relatives.

BACKGROUND: Autoimmune-polyendocrinopathy-candidiasis- ectodermal-distrophy (APECED) is a recessive disease, caused by mutations in the AutoImmune REgulator (AIRE) gene. Different mutations are peculiar of particular populations. In Italy, 3 hot spots areas where APECED shows an increased prevalence, have been identified in Sardinia, Apulia, and in the Venetian region. AIM: In this study, we analyzed AIRE mutations and genotype-phenotype correlation in APECED patients originating from Campania and in their relatives. PATIENTS AND METHODS: In 6 patients affected with APECED clinical findings, genetic analysis of AIRE, and APECED-related autoantibodies were performed. RESULTS: All patients carried at least 1 mutation on exon 1 or on splice-site flanking exon 1. Two siblings carried a complex homozygous mutation [IVS1 + 1G>C; IVS1 + 5delG] on intron 1; 2 patients were compound heterozygous for [T16M]+[W78R] (exons 1+2); 1 patient was compound heterozygous for [A21V]+[C322fs] (exons 1+8) and another was homozygous for [T16M]+[T16M] on exon 1. Expression of the disease showed wide variability while circulating autoantibodies paralleled to phenotype in each patient. Analysis of relatives allowed the identification of 8 heterozygotes. None of heterozygous subjects presented major findings of APECED. CONCLUSIONS: Mutations localized on exon 1 and the region flanking exon 1 are common in APECED patients originating from Campania. Genotype-phenotype correlation failed to reveal a relationship between detected mutations and clinical expression. Mutations in heterozygosis in AIRE gene are not associated to major findings of APECED.

Algorithms for Walking Speed Estimation Using a Lower-Back-Worn Inertial Sensor: A Cross-Validation on Speed Ranges.

Walking/gait speed is a key measure for daily mobility characterization. To date, various studies have attempted to design algorithms to estimate walking speed using an inertial sensor worn on the lower back, which is considered as a proper location for activity monitoring in daily life. However, these algorithms were rarely compared and validated on the same datasets, including people with different preferred walking speed. This study implemented several original, improved, and new algorithms for estimating cadence, step length and eventually speed. We designed comprehensive cross-validation to compare the algorithms for walking slow, normal, fast, and using walking aids. We used two datasets, including reference data for algorithm validation from an instrumented mat (40 subjects) and shanks-worn inertial sensors (88 subjects), with normal and impaired walking patterns. The results showed up to 50% performance improvements. Training of algorithms on data from people with different preferred speeds led to better performance. For the slow walkers, an average RMSE of 2.5 steps/min, 0.04 m, and 0.10 m/s were respectively achieved for cadence, step length, and speed estimation. For normal walkers, the errors were 3.5 steps/min, 0.08 m, and 0.12 m/s. An average RMSE of 1.3 steps/min, 0.05 m, and 0.10 m/s were also observed on fast walkers. For people using walking aids, the error significantly increased up to an RMSE of 14 steps/min, 0.18 m, and 0.27 m/s. The results demonstrated the robustness of the proposed combined speed estimation approach for different speed ranges. It achieved an RMSE of 0.10, 0.18, 0.15, and 0.32 m/s for slow, normal, fast, and using walking aids, respectively.

A method for gait events detection based on low spatial resolution pressure insoles data.

The accurate identification of initial and final foot contacts is a crucial prerequisite for obtaining a reliable estimation of spatio-temporal parameters of gait. Well-accepted gold standard techniques in this field are force platforms and instrumented walkways, which provide a direct measure of the foot-ground reaction forces. Nonetheless, these tools are expensive, non-portable and restrict the analysis to laboratory settings. Instrumented insoles with a reduced number of pressure sensing elements might overcome these limitations, but a suitable method for gait events identification has not been adopted yet. The aim of this paper was to present and validate a method aiming at filling such void, as applied to a system including two insoles with 16 pressure sensing elements (element area = 310 mm2), sampling at 100 Hz. Gait events were identified exploiting the sensor redundancy and a cluster-based strategy. The method was tested in the laboratory against force platforms on nine healthy subjects for a total of 801 initial and final contacts. Initial and final contacts were detected with low average errors of (about 20 ms and 10 ms, respectively). Similarly, the errors in estimating stance duration and step duration averaged 20 ms and <10 ms, respectively. By selecting appropriate thresholds, the method may be easily applied to other pressure insoles featuring similar requirements.

A wearable multi-sensor system for real world gait analysis.

Gait analysis is commonly performed in standardized environments, but there is a growing interest in assessing gait also in ecological conditions. In this regard, an important limitation is the lack of an accurate mobile gold standard for validating any wearable system, such as continuous monitoring devices mounted on the trunk or wrist. This study therefore deals with the development and validation of a new wearable multi-sensor-based system for digital gait assessment in free-living conditions. In particular, results obtained from five healthy subjects during lab-based and real-world experiments were presented and discussed. The in-lab validation, which assessed the accuracy and reliability of the proposed system, shows median percentage errors smaller than 2% in the estimation of spatio-temporal parameters. The system also proved to be easy to use, comfortable to wear and robust during the out-of-lab acquisitions, showing its feasibility for free-living applications.

PTX3 genetic variations affect the risk of Pseudomonas aeruginosa airway colonization in cystic fibrosis patients.

Cystic fibrosis (CF) is a common life-threatening autosomal recessive disorder in the Caucasian population, and the gene responsible is the CF transmembrane conductance regulator (CFTR). Patients with CF have repeated bacterial infection of the airways caused by Pseudomonas aeruginosa (PA), which is one of the predominant pathogen, and endobronchial chronic infection represents a major cause of morbidity and mortality. Pentraxin 3 (PTX3) is a gene that encodes the antimicrobial protein, PTX3, which is believed to have an important role in innate immunity of lung. To address the role of PTX3 in the risk of PA lung colonization, we investigated five single nucleotide polymorphisms of PTX3 gene in 172 Caucasian CF patients who were homozygous for the F508del mutation. We observed that PTX3 haplotype frequencies were significantly different between patients with PA colonization, as compared with noncolonized patients. Moreover, a protective effect was found in association with a specific haplotype (odds ratio 0.524). Our data suggest that variations within PTX3 affect lung colonization of Pseudomonas in patients with CF.

Effects of toluidine blue-mediated photodynamic therapy on periopathogens and periodontal biofilm: in vitro evaluation.

Photodynamic therapy (PDT) is a selective modality of killing targeted cells, mostly known for its application in neoplasms. PDT can be considered to be an alternative method for the elimination of periodontal bacteria from the pocket without harms for the resident tissues. Therefore, PDT may replace systemic antibiotics and enhance the effect of mechanical treatments of periodontal defects. This effort focused on the in vitro sensitization of periopathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia ) Toluidine Blue mediated and on the use of a Diode laser emitting source. The objective of this research was to evaluate the bactericidal in vitro effect of laser diodes 830 nm (as the light source) after photosensitization with Toluidine Blue (TBO) on the following periopathogenic bacteria: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia. After evaluating the effect on the single bacterial strain, the ability of Diode Laser to disrupt the structure of biofilms produced by A. actinomycetemcomitans after photosensitization with TBO was also analyzed. The study suggests that the association of TBO and diode laser light 830 nm is effective for the killing of bacteria strains and determines the photoinactivation of Aggregatibacter biofilms. In summary, photodynamic therapy has effectively shown its capabilities and, therefore, it can be considered a valid alternative approach to antimicrobial therapy of periodontitis.

Inter-leg Distance Measurement as a Tool for Accurate Step Counting in Patients with Multiple Sclerosis.

Step detection is commonly performed using wearable inertial devices. However, methods based on the extraction of signals features may deteriorate their accuracy when applied to very slow walkers with abnormal gait patterns. The aim of this study is to test and validate an innovative step counter method (DiSC) based on the direct measurement of inter-leg distance. Data were recorded using an innovative wearable system which integrates a magneto-inertial unit and multiple distance sensors (DSs) attached to the shank. The method allowed for the detection of both left and right steps using a single device and was validated on thirteen people affected by multiple sclerosis (0 <; EDSS <; 6.5) while performing a six-minute walking test. Two different measurement ranges for the distance sensor were tested (DS200: 0-200 mm; DS400: 0-400 mm). Accuracy was evaluated by comparing the estimates of the DiSC method against video recordings used as gold standard. Preliminary results showed a good accuracy in detecting steps with half the errors in detecting the step of the instrumented side compared to the non-instrumented (mean absolute percentage error 2.4% vs 4.8% for DS200; mean absolute percentage error 2% vs 5.4% for DS400). When averaging errors across patients, over and under estimation errors were compensated, and very high accuracy was achieved (E%<; 1.2% for DS200; E%<; 0.7% for DS400). DS400 is the suggested configuration for patients walking with a large base of support.

WITHDRAWN: Assessment of the inter-laboratory repeatability of gait analysis measurements in patients with multiple sclerosis.

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Steady-state expression of self-regulated genes.

MOTIVATION: Regulatory gene networks contain generic modules such as feedback loops that are essential for the regulation of many biological functions. The study of the stochastic mechanisms of gene regulation is instrumental for the understanding of how cells maintain their expression at levels commensurate with their biological role, as well as to engineer gene expression switches of appropriate behavior. The lack of precise knowledge on the steady-state distribution of gene expression requires the use of Gillespie algorithms and Monte-Carlo approximations. METHODOLOGY: In this study, we provide new exact formulas and efficient numerical algorithms for computing/modeling the steady-state of a class of self-regulated genes, and we use it to model/compute the stochastic expression of a gene of interest in an engineered network introduced in mammalian cells. The behavior of the genetic network is then analyzed experimentally in living cells. RESULTS: Stochastic models often reveal counter-intuitive experimental behaviors, and we find that this genetic architecture displays a unimodal behavior in mammalian cells, which was unexpected given its known bimodal response in unicellular organisms. We provide a molecular rationale for this behavior, and we implement it in the mathematical picture to explain the experimental results obtained from this network.

Should the instructions issued to the subject in traditional static posturography be standardised?

The postural ability of a subject is usually evaluated through the observation of the centre of pressure parameters obtained through posturography. These parameters are known to be sensitive to various factors and standards have consequently been proposed for data acquisition and analysis. A factor usually not taken into due consideration but likely to influence the postural exam is the kind of standing posture (e.g. natural or immobile) a subject is instructed to maintain. This study aimed at investigating whether instructions issued in a traditional static posturographic test influence its outcome and hence should be considered in the standardisation of the posturography protocols. Two groups of young healthy subjects were each issued one of two common instructions, "stand quietly" or "stand as still as possible", by means of projected instructions. Differences between the two groups were investigated for commonly calculated centre of pressure parameters. All these parameters, but the mean frequency, were significantly different, with variations in the range between 8% (mean velocity) and 71% (confidence circle area). These results suggest that instructions given to the subjects strongly influence the outcome of posturography and should, hence, be standardised.

Validation of a model-based inverse kinematics approach based on wearable inertial sensors.

Wearable inertial measurement units (IMUs) are a promising solution to human motion estimation. Using IMUs 3D orientations, a model-driven inverse kinematics methodology to estimate joint angles is presented. Estimated joint angles were validated against encoder-measured kinematics (robot) and against marker-based kinematics (passive mechanism). Results are promising, with RMS angular errors respectively lower than 3 and 6 deg over a minimum range of motion of 50 deg (robot) and 160 deg (passive mechanism). Moreover, a noise robustness analysis revealed that the model-driven approach reduces the effects of experimental noises, making the proposed technique particularly suitable for application in human motion analysis.

Prevalence of reticular pseudodrusen in age-related macular degeneration with newly diagnosed choroidal neovascularisation.

AIM: To investigate the prevalence of reticular pseudodrusen (RPD) in eyes of patients presenting with newly diagnosed choroidal neovascularisation (CNV) in age-related macular degeneration (AMD), and to analyse the association between RPD, age-related maculopathy (ARM) and AMD. METHOD: Two observational consecutive prospective series. In series 1, patients with AMD with newly diagnosed CNV were sampled to determine the incidence of RPD. Eyes with and without RPD were compared by the Mann-Whitney non-parametric test and Fisher's exact test for age, sex of patients, the eye involved and type of CNV. Series 2 comprised 100 patients referred for fundus photography, fluorescein and/or indocyanine green angiography, for whom pictures showed RPD. This second cohort was then selected from a larger group of patients. RESULTS: Patients with newly diagnosed CNV in series 1 comprised 67 women and 33 men, aged 57-96 years (mean 79.5). CNV was "classic" (32 eyes), "occult" (41) or exhibited vascularised pigment epithelial detachment (PED, 11), retinal angiomatous proliferation (RAP) with or without PED (13), or haemorrhagic or fibrovascular scarring (3). In all, 24 (24%) eyes had RPD. The prevalence of RAP was significantly higher in eyes with RPD than in those without (p = 0.0128), despite the small number of patients with RAP. In series 2, 100 patients with RPD were enrolled in 3 months, and corresponded to 8% of the overall cases referred to our centre (Centre Ophtalmologique d'Imagerie et de Laser, Paris, France). There were 77 women and 23 men, aged 54-93 years (mean 79.2). Eyes with RPD (n = 155) usually exhibited signs of ARM or AMD, including soft drusen (101 eyes) and/or retinal pigment epithelium abnormalities (70), geographical atrophy (27) and/or CNV (61). In both studies, examination of blue-light fundus pictures was extremely helpful in diagnosing RPD. CONCLUSION: RPD have a high prevalence among patients with AMD with newly diagnosed CNV (24% of cases). RPD were commonly associated with ARM or AMD. This study suggests that eyes with RPD could be classified as a phenotype of ARM.

Mobility assessment of patients with facioscapulohumeral dystrophy.

BACKGROUND: Facioscapulohumeral muscular dystrophy is the third most common form of inherited myopathies with a prevalence of 1:20,000. Since both muscle involvement and disease progression are heterogeneous and unpredictable, quantitative assessment tools are needed to evaluate the effects of pharmacological and physical training treatments. METHODS: The instrumented movement analysis of 12 patients with facioscapulohumeral dystrophy and 12 control subjects was conducted using a 9-camera stereophotogrammetric system and 2 force platforms. Subjects performed four tasks of different difficulties: arm movement, level walking, step ascending, and squatting. Manual muscle test, clinical severity scale and magnetic resonance imaging were used to clinically assess the patients. FINDINGS: Walking speed and centre of mass vertical displacement during squatting were reduced in patients and can be used to assess their motor capacity. Features common in the patient sample were: the reduction of shoulder range of motion, the excessive ankle plantar-flexion during walking and step ascending, and the reduction of knee flexion-extension moment during squatting. These parameters were correlated with magnetic resonance imaging results at relevant structure level and can be used to assess the corresponding body functioning. Furthermore, instrumented movement analysis was able to distinguish from normal controls also a group of patients in which clinical assessments did not show any obvious abnormalities and had been evaluated as normal. INTERPRETATION: The quantitative assessment tool devised in this study provides suitable information in terms of both motor capacity and impairment severity of patients with facioscapulohumeral dystrophy, and, thus, encouraging its use for the evaluation of therapeutic trial outcomes for this disease.

Extraction of information on elder motor ability from clinical and biomechanical data through data mining.

This study aimed at evaluating the additional knowledge provided by a biomechanical test coupled with clinical tests for motor ability assessment. A database including clinical test scores and sit-to-stand test variables obtained from 110 medically stable elderly subjects was submitted to data mining by searching for association rules. The presence of rules revealed some redundancies due to sample homogeneity, as mainly observed in the joint analysis of a questionnaire for daily activities assessment (Nottingham test) and the sit-to-stand, and due to similar evaluated information, as resulted from the joint analysis of a balance and gait scale (Tinetti test) and the sit-to-stand. Conversely, when no association rules were found, the tests carried unrelated information. The associations mined while analysing these clinical tests encouraged the integration of biomechanical tests, increasing significantly its clinical applicability and reducing the information redundancy. The information extracted also allowed to highlight rules typical of elderly persons that may serve as a knowledge-based tool for the detection of possible deviation from normality.