Methodology to gauge a four-bar linkage prosthetic knee mechanism based on gait analysis and genetic algorithms

El objetivo de esta investigación es desarrollar una metodología para dimensionar un mecanismo policéntrico de rodilla de 4 barras para máxima estabilidad. Basado en el hecho de que la estabilidad del mecanismo durante la respuesta a la carga depende de la posición del centro instantáneo de rotación (CIR) respecto la fuerza de reacción del piso (FRP) durante la fase de apoyo, se desarrolló una plataforma de cómputo que representa el movimiento real de la pierna, el vector FRP y el mecanismo con su CIR. Para obtener los datos de entrada a la plataforma, se realizó un análisis de marcha a una paciente con amputación transfemoral unilateral, obteniendo la FRP, el ángulo de flexo-extensión de rodilla y la cinemática de los miembros inferiores. Por otra parte, a través de los algoritmos genéticos (AGs), se obtienen las dimensiones y configuración de los eslabones del mecanismo requeridas para iterar con la plataforma en la cual, comparando la ubicación de la FRP respecto al CIR en el plano sagital, se determinan las dimensiones funcionales adecuadas. El mecanismo se dimensionó exitosamente utilizando la metodología desarrollada, garantizando estabilidad de la rodilla después del contacto inicial y flexión voluntaria antes del despegue de punta.This research was aimed to develop a methodology for establishing the proper dimensions of a four-bar linkage prosthetic knee mechanism for maximum stability. Based on the fact that the stability of a four-bar knee during load-bearing is determined by the location of the instantaneous center of rotation (ICR) with respect to the ground reaction force (GRF) vector, a computational platform was developed to simulate the movement of the leg, the GRF vector and the position of the ICR of the mechanism. On one hand, a gait analysis was carried out on a subject with unilateral transfemoral amputation, from which the GRF, the knee flexion-extension angle and the kinematics of the lower limbs were determined. On the other hand, genetic algorithms (GAs) technique provided the dimensions and mechanism links configuration required to iterate with the platform on which, comparing the location of the GRF and the ICR in the sagittal plane, the functional dimensions of the mechanism were obtained. The polycentric knee mechanism was gauged successfully by ensuring knee stability during the initial contact and load response as well as the ability to initiate voluntary flexion toward late stance before the toe-off

Cultural adaptation of the Italian version of the Patient-Reported Outcomes Common Terminology Criteria for Adverse Event (PRO-CTCAE®)

Introduction: US National Cancer Institute's (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) is a library of 78 symptom terms and 124 items enabling patient reporting of symptomatic adverse events in cancer trials. This multicenter study used mixed methods to develop an Italian language version of this widely accepted measure, and describe the content validity and reliability in a diverse sample of Italian-speaking patients. Methods: All PRO-CTCAE items were translated in accordance with international guidelines. Subsequently, the content validity of the PRO-CTCAE-Italian was explored and iteratively refined through cognitive debriefing interviews. Participants (n=96; 52% male; median age 64 years; 26% older adults; 18% lower educational attainment) completed a PRO-CTCAE survey and participated in a semi-structured interview to determine if the translation captured the concepts of the original English language PRO-CTCAE, and to evaluate comprehension, clarity and ease of judgement. Test-retest reliability of the finalized measure was explored in a second sample (n=135). Results: Four rounds of cognitive debriefing interviews were conducted. The majority of PRO-CTCAE symptom terms, attributes and associated response choices were well-understood, and respondents found the items easy to judge. To improve comprehension and clarity, the symptom terms for nausea and pain were rephrased and retested in subsequent interview rounds. Test-retest reliability was excellent for 41/49 items (84%); the median intraclass correlation coefficient was 0.83 (range 0.64-0.94). Discussion: Results support the semantic, conceptual and pragmatic equivalence of PRO-CTCAE-Italian to the original English version, and provide preliminary descriptive evidence of content validity and reliability

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

The effects of post-translational side-chain modifications on the stimulatory activity, serum stability and conformation of synthetic peptides carrying T helper cell epitopes

AbstractPeptides 31D and VF 13, corresponding to the rabies virus nucleo- and glycoproteins, respectively, vigorously stimulate T helper cells of the appropriate specificity. Earlier we showed how internal and external glycosylation affects the major histocompatibility complex molecule (MHC)-binding ability and conformation of these T-cell epitopes (Otvos et al. (1994) Biochim. Biophys. Acta 1224, 68–76; Otvos et al. (1995) Biochim. Biophys. Acta 1267, 55–64). In the current report, we examined the T-helper cell stimulatory ability after introduction of a new set of post-translational modifications. To obtain general information concerning the effects of amino acid side-chain modifications on other biochemical properties of protein fragments, we studied the serum stability and the conformation of the 31D and VF13 peptides. We found that the extent of the reduction of the T-cell stimulatory activity depends upon the location in the sequence of the host amino acid residue. Generally, (β-linked sugars in mid-chain positions had a greater inhibitory effect than a-linked sugars attached to identical amino acids. In a case where mid-chain glycosylation just marginally reduced the T-cell stimulatory activity, the β-linked glycopeptide was significantly more resistant to serum proteases. This finding suggests that addition of β-linked carbohydrates might be superior to the addition of a-linked sugars for vaccine development, and generally for peptide agonist drug design. In addition, data presented here provide the first documentation that phosphorylation and sulfation of tyrosine residues may retain the MHC-binding ability and T-cell stimulatory activity of class II epitopes. The sulfated and the phosphorylated 31D peptides exhibited considerably increased serum stability compared to the unmodified parent peptide. Finally, all post-translational modifications destabilized the dominant α-helical or turn structures of the peptides presented in aqueous trifluoroethanol mixtures. While the circular dichroism spectra of the α- and β-linked VF13 glycopeptides with monosaccharides were almost indistinguishable, the structure of the glycopeptides depended upon the length of the sugar moiety. Significantly, incorporation of sulfate or phosphate groups resulted in identical peptide conformations