Gold nanoparticles as enablers of cell membrane permeabilization by time-varying magnetic field: influence of distance and geometry.

This study is based on the quantification of the influence of the presence of gold nanoparticles (Au NPs), of their geometry and their distance from cell membrane during time-varying electromagnetic fields cell membrane permeabilization on the pores opening dynamics. Results showed that the combined use of Au NPs and time-varying magnetic field can improve significantly the permeabilization of cell membrane. The presence of Au NPs allowed to reach transmembrane potential values enabling the cell membrane permeabilization only when placed at very short distance, equal to 20 nm. Both geometry and variability of the positioning in proximity of the cell membrane showed a strong influence on the probability of enabling pores opening. Clinical Relevance- This study provides a better comprehension about the mechanisms, still not completely understood, underlying cell membrane permeabilization by combining Au NPs and time-varying magnetic fields.

Application of Stochastic Dosimetry for assessing the Human RFEMF Exposure in a 5G indoor Scenario.

In recent years the introduction of 5G networks is causing a drastically change of human exposure levels in the radio frequency range. The aim of this paper is on expanding the knowledge on this issue, assessing the exposure levels for a particular case of indoor 5G scenario, where the presence of an Access Point (AP) was simulated. Coupling the traditional deterministic computational method with an innovative stochastic approach, called Polynomial Chaos Kriging, allowed to evaluate the exposure variability of an user considering the 3D beamforming capability of the antenna. The exposure levels, expressed in terms of specific absorption rate (SAR) in specific tissues, showed low values compared to ICNIRP guidelines.

Contactless Cell Permeabilization by Time-Varying Magnetic fields: Modelling Transmembrane Potential and Mechanical Stress in in- vitro Experimental Set-Up.

The feasibility of using time-varying magnetic field as a contactless cells permeabilization method was demonstrated by experimental results, but the underlying mechanism is still poorly understood. In this study a numerical analysis of the transmembrane potential (TMP) at cell membranes during permeabilization by time-varying magnetic fields was proposed, and a first quantification of mechanical stress induced by the magnetic and electric fields and hypothesized to play an important role in the permeabilization mechanism was carried out. TMP values induced by typical in-vitro experimental conditions were far below the values needed for membrane permeabilization, with a strong dependence on distance of the cell from the coil. The preliminary assessment of the mechanical pressure and potential deformation of cells showed that stress values evaluated in conditions in which TMP values were too low to cause membrane permeabilization were comparable to those known to influence the pore opening mechanisms.Clinical Relevance- Results represent a significant step towards a better comprehension of the mechanism underlying cell membrane permeabilization by time-varying magnetic fields.

Computational simulation of electromagnetic fields on human targets for magnetic targeting applications.

In the last few years, the use of nanoparticles for therapeutic applications has attracted the interest of many scientists, who are looking for effective methods to target nanoparticles linked to drugs directly to the diseased organs. Among them, magnetic targeting consists of magnetic systems (magnets or coils) which can impress high gradient magnetic fields and then magnetic forces on the magnetic nanoparticles. Despite some studies have reported an effective improvement in drug delivery by using this technique, there is still a paucity of studies able to quantify and explain the experimental results. In this scenario, "in silico" models allow to analyze and compare different magnetic targeting systems in their ability to generate the required magnetic field gradient for specific human targets.In this paper we then evaluated, by means of computational electromagnetics techniques, the attitude of various ad-hoc designed magnetic systems in targeting the heart tissues of differently aged human anatomical models.

Assessment of Children Exposure Variability to Near-Field Sources using Stochastic Dosimetry.

In this paper, the exposure of a child to a hairdryer model is evaluated. Nowadays, the assessment of children exposure to near-field sources has become in fact a topic of high interest, because it was found that even domestic appliances could be relevant for children exposure level. Therefore, the aim of the present work is to use a method based on stochastic dosimetry to assess the exposure variability due to near-field sources, not limiting it only on some worst-case exposure scenario. In particular, electric field amplitudes induced in specific tissues composing the central nervous system and the peripheral nervous system (following the ICNIRP guidelines) were analyzed. The results highlight a high exposure variability depending on the hairdryer position in respect with the child.

Clinical Data Reuse or Secondary Use: Current Status and Potential Future Progress.

Objective: To perform a review of recent research in clinical data reuse or secondary use, and envision future advances in this field. Methods: The review is based on a large literature search in MEDLINE (through PubMed), conference proceedings, and the ACM Digital Library, focusing only on research published between 2005 and early 2016. Each selected publication was reviewed by the authors, and a structured analysis and summarization of its content was developed. Results: The initial search produced 359 publications, reduced after a manual examination of abstracts and full publications. The following aspects of clinical data reuse are discussed: motivations and challenges, privacy and ethical concerns, data integration and interoperability, data models and terminologies, unstructured data reuse, structured data mining, clinical practice and research integration, and examples of clinical data reuse (quality measurement and learning healthcare systems). Conclusion: Reuse of clinical data is a fast-growing field recognized as essential to realize the potentials for high quality healthcare, improved healthcare management, reduced healthcare costs, population health management, and effective clinical research.

Evolution of Italian Universal Newborn Hearing Screening Programs.

BACKGROUND: The aim of this study was to evaluate the state of implementation of the Universal Newborn Hearing Screening Programs in Italy and to determine the effect that an ad hoc legislation may have on the percentage of infants screened for detection of hearing impairment in nurseries. MATERIAL AND METHODS: Italian Newborn Hearing Screening data were obtained during four national surveys (years 2003, 2006, 2008, and 2011). The screening rates obtained by the Regions which adopted or did not adopt a legislation to increase the newborns' coverage were compared. RESULTS: In 2011, the average coverage rate was 78.3%, but in 12 out of 20 Regions it exceeded 95%. Coverage rate was greater in Regions that implemented an ad hoc legislation compared to Regions that did not. As a matter of fact, Regions which passed the legislation screened more than 95% of infants, whereas Regions without legislation reported a mean screening rate of nearly 67% of newborns. CONCLUSION: Current results seem to confirm that a specific legislation might have a decisive effect on the increase of rate of coverage of newborn hearing screenings.

Objective measures of perceptual quality for predicting speech intelligibility in sensorineural hearing loss.

An objective method to predict speech intelligibility in sensorineural hearing loss of different types and increasing degrees of severity is proposed and validated with experimental data. The novel approach is based on the combined use of acoustic simulations of impaired perception and objective measures of perceptual speech quality (PESQ). Acoustic simulations were obtained after degradation of the original, non distorted, speech waveforms by spectral smearing, expansive nonlinearity, and level scaling. PESQ was used to measure perceptual quality of the acoustic simulations obtained by varying the degree of the simulated hearing loss. A logistic function was applied to transform PESQ scores into predicted intelligibility scores. A set of CV and VC syllables in /a/, /u/, and /i/ contexts was used as reference test material. The method was validated with subjective measures of intelligibility of the degraded speech obtained in a group of 10 normal hearing subjects. Overall, prediction of experimental speech intelligibility through the transformed PESQ measures was good (R(2)=0.7; RMSE=0.08) revealing that the proposed approach could be a valuable aid in real clinical applications.

Susceptibility of linear and nonlinear otoacoustic emission components to low-dose styrene exposure.

OBJECTIVE: To investigate potential susceptibility of active cochlear mechanisms to low-level styrene exposure by comparing TEOAEs in workers and controls. DESIGN: Two advanced analysis techniques were applied to detect sub-clinical changes in linear and nonlinear cochlear mechanisms of OAE generation: the wavelet transform to decompose TEOAEs into time-frequency components and extract signal-to-noise ratio and latency of each component, and the bispectrum to detect and extract nonlinear TEOAE contributions as quadratic frequency couplings (QFCs). STUDY SAMPLE: Two cohorts of workers were examined: subjects exposed exclusively to styrene (N = 9), and subjects exposed to styrene and noise (N = 6). The control group was perfectly matched by age and sex to the exposed group. RESULTS: Exposed subjects showed significantly lowered SNR in TEOAE components at mid-to-high frequencies (above 1.6 kHz) and a shift of QFC distribution towards lower frequencies than controls. No systematic differences were observed in latency. CONCLUSION: Low-level styrene exposure may have induced a modification of cochlear functionality as concerns linear and nonlinear OAE generation mechanisms. The lack of change in latency seems to suggest that the OAE components, where generation region and latency are tightly coupled, may not have been affected by styrene and noise exposure levels considered here.

Influence of tinnitus sound therapy signals on the intelligibility of speech.

OBJECTIVE: To assess the influence on speech intelligibility of various signals used in tinnitus sound therapy. MATERIALS AND METHODS: We measured, in normal hearing subjects, the intelligibility of speech in the presence of three different sound therapy signals: wide-band noise, a recording of moving water, and a combination of tones. RESULTS: For a given level of stimulation, speech intelligibility was worst in the presence of wide-band noise, compared with the other sound therapy signals. When the stimulation level of the three different signals was increased, speech intelligibility deteriorated more rapidly with wide-band noise, compared with the other two signals. The combination of tones had the least influence on speech intelligibility. CONCLUSION: The use of different tinnitus sound therapy signals can lead to significantly different effects on the intelligibility of speech. The use of natural sound recordings or combinations of tones may provide the patient with more flexibility to change the stimulation level during treatment.

Functional evaluation and rehabilitation engineering.

Life is complex and all about movement, which allows us to interact with the environment and communicate with each other. The human nervous system is capable of performing a simultaneous and integrated control of 100-150 mechanical degrees of freedom of movement in the body via tensions generated by about 700 muscles. In its widest context, movement is carried out by a sensory motor system comprising multiple sensors (visual,auditory, and proprioceptive),multiple actuators (muscles acting on the skeletal system),and an intermediary processor that can be summarized as a multiple-input­multiple-output nonlinear dynamic time-varying control system. This grand control system is capable of responding with remarkable accuracy,speed, appropriateness,versatility, and adaptability to a wide spectrum of continuous and discrete stimuli and conditions and is certainly orders of magnitude more complex and sophisticated than the most advanced robotic systems currently available. In the last decades,a great deal of research has been carried out in the fields of functional evaluation of human performance and rehabilitation engineering. These fields combine knowledge, concepts, and methods from across many disciplines (e.g., biomechanics,neuroscience, and physiology), with the aim of developing apparatuses and methods fort he measurement and analysis of complex sensory motor performance and the ultimate goal of enhancing the execution of different tasks in both healthy people and persons with reduced capabilities from different causes (injury, disease, amputation,and neural degeneration).

SUN-test (Speech Understanding in Noise): A Method for Hearing Disability Screening.

The SUN-test (Speech Understanding in Noise) is a speech-in-noise test to screen adults and older adults for hearing disability. The SUN-test consists in a short list of intervocalic consonants (VCV, vowel-consonant-vowel) in noise that are presented in a three-alternatives forced choice (3AFC) paradigm by means of a touch-screen interface. Based on the number of stimuli correctly identified, the tested subject gets one of three possible test outcomes: no listening difficulties, a hearing check would be advisable, or a hearing check is recommended. This paper reviews the main results obtained with the SUN-test in the Italian language in a population of nearly 1,300 adults and older adults with varying degrees of audiometric thresholds and audio-metric configurations, tested both in low and in high ambient noise settings. Results obtained in the tested population revealed that the outcomes of the SUN-test were in line with the outcomes of pure-tone testing, and that the test performance was similar both in low and in high ambient noise (up to 65 dB A). Results obtained with the SUN-test were not biased by the age of the subject because the performance of younger and older subjects in the test was similar. The mean duration of the SUN-test was nearly 40 s/ear, and was lower than 1 minute per ear even in subjects older than 80 years so that both ears could be tested, on average, in 2 minutes. The SUN-test was considered easy or slightly difficult by nearly 90% of subjects; test duration was judged short or fair by nearly 95% of subjects, and the overall evaluation of the test was pleasant, or neutral, in more than 90% of subjects. Overall, results of this study indicated that the SUN-test might be feasible for application in adult hearing screening. The test is fast, easy, self convincing, and reflects differences in hearing sensitivity between the tested subjects. The outcomes of the SUN-test were not influenced by the noise level in the test room (up to 65 dB A) indicating that the test, as such, might be feasible to screen adults and older adults both in clinical and in non clinical settings, such as convenient care clinics, hearing aid providers, or pharmacies, where the ambient noise is, typically, not controlled.

Pilot Initiatives of Adult Hearing Screening in Italy.

A series of pilot initiatives of adult hearing screening programs were organized in eight large and small-size cities in Italy in the past two years. The screening initiatives were held in public places, supermarkets, drugstores, and in some universities of the third age, and involved an overall population of 2,278 screened subjects with age ranging from 13 to 93 years. Three different screening tests were used to assess hearing ability in the participants, i.e.: screening pure tone audiometry (PTA), an automated speech-in-noise screening test (the SUN-test), and a screening questionnaire of self-perceived hearing handicap (the HHIE-S). This paper describes the organization and management of these screening initiatives and reviews the main results obtained in the screened population, using the three different screening tests. Results obtained in these pilot initiatives showed that screening adults for hearing problems might be feasible, on a local level, in non clinical settings and can be performed quite easily with the support of local coordinators and partners, such as associations or local authorities. It is recognized that further initiatives and studies will have to be performed to better define the key aspects related to the organization and management of adult hearing screening programs, either at a local, regional, or national level.

Influence of compact disk recording protocols on reliability and comparability of speech audiometry outcomes: acoustic analysis.

OBJECTIVE: To assess whether different compact disk recording protocols, used to prepare speech test material, affect the reliability and comparability of speech audiometry testing. MATERIAL AND METHODS: We conducted acoustic analysis of compact disks used in clinical practice, to determine whether speech material had been recorded using similar procedures. To assess the impact of different recording procedures on speech test outcomes, normal hearing subjects were tested using differently prepared compact disks, and their psychometric curves compared. RESULTS: Acoustic analysis revealed that speech material had been recorded using different protocols. The major difference was the gain between the levels at which the speech material and the calibration signal had been recorded. Although correct calibration of the audiometer was performed for each compact disk before testing, speech recognition thresholds and maximum intelligibility thresholds differed significantly between compact disks (p < 0.05), and were influenced by the gain between the recording level of the speech material and the calibration signal. CONCLUSION: To ensure the reliability and comparability of speech test outcomes obtained using different compact disks, it is recommended to check for possible differences in the recording gains used to prepare the compact disks, and then to compensate for any differences before testing.

Universal newborn hearing screening programs in Italy: survey of year 2006.

CONCLUSION: Our results suggest a rapid diffusion of newborn hearing screening programs in Italy and indicate that three conditions seem to play a crucial role in the implementation of Universal Newborn Hearing Screening (UNHS) programs: the size (>800 births/year) and location (metropolitan urban areas) of the hospital, and the presence of an audiologist in the UNHS coordinating team. OBJECTIVES: The aim of this paper is to provide data on the degree of implementation and coverage of UNHS programs in Italy. MATERIALS AND METHODS: Data were collected through a Screening Survey Questionnaire that was sent to all birthing hospitals active in Italy in 2006 and was filled in by the chief of the hospital or by the UNHS program coordinator. RESULTS: In Italy UNHS coverage had undergone a steep increase from 29.3% in 2003 (156,048 newborns screened) to 48.4% in 2006 (262,103 screened). The majority of UNHS programs were implemented in the two most economically developed areas, i.e. in the north-west area (79.5%, 108,200 of 136,109 births), and in the north-east area (57.2%, 52,727 of 92,133 births), while a limited diffusion still remains in some areas, typically in the islands (11.3%, 7158 of 63,460 births).

Influence of cochlear implant-like operating conditions on wavelet speech processing.

This study assessed the influence of 'non-ideal' operating conditions typical of cochlear implants (CIs) on the behavior of the wavelet transform (WT) when used to process speech. Particular attention was given to the effect of limited stimulation rate and limited number of channels, typical of CI speech processing, on the performance of the WT. Computer simulations and psychoacoustic recognition tests of WT-processed speech were implemented. The crucial role played by the 'non-ideal' operating conditions on WT speech processing was put in evidence. Psychoacoustic recognition tests proved to be fundamental to evaluate feasibility of WT speech processing for CIs.

Auditory cortical responses in patients with cochlear implants.

Currently, the most commonly used electrophysiological tests for cochlear implant evaluation are Averaged Electrical Voltages (AEV), Electrical Advisory Brainstem Responses (EABR) and Neural Response Telemetry (NRT). The present paper focuses on the study of acoustic auditory cortical responses, or slow vertex responses, which are not widely used due to the difficulty in recording, especially in young children. Aims of this study were validation of slow vertex responses and their possible applications in monitoring postimplant results, particularly restoration of hearing and auditory maturation. In practice, the use of tone-bursts, also through hearing aids or cochlear implants, as in slow vertex responses, allows many more frequencies to be investigated and louder intensities to be reached than with other tests based on a click as stimulus. Study design focused on latencies of N1 and P2 slow vertex response peaks in cochlear implants. The study population comprised 45 implant recipients (aged 2 to 70 years), divided into 5 different homogeneous groups according to chronological age, age at onset of deafness, and age at implantation. For each subject, slow vertex responses and free-field auditory responses (PTAS) were recorded for tone-bursts at 500 and 2000 Hz before cochlear implant surgery (using hearing aid amplification) and during scheduled sessions at 3rd and 12th month after implant activation. Results showed that N1 and P2 latencies decreased in all groups starting from 3rd through 12th month after activation. Subjects implanted before school age or at least before age 8 yrs showed the widest latency changes. All subjects showed a reduction in the gap between subjective thresholds (obtained with free field auditory responses) and objective thresholds (obtained with slow vertex responses), obtained in presurgery stage and after cochlear implant. In conclusion, a natural evolution of neurophysiological cortical activities of the auditory pathway, over time, was found especially in young children with prelingual deafness and implanted in preschool age. Cochlear implantation appears to provide hearing restoration, demonstrated by the sharp reduction of the gap between subjective free field auditory responses and slow vertex responses threshold obtained with hearing aids vs. cochlear implant.

The generation mechanisms and repeatability of 2F1-F2 distortion product otoacoustic emissions: study on normally hearing subjects.

The 2F1-F2 distortion product otoacoustic emission (DPOAE) is considered to consist of two generation mechanisms, the so-called place-fixed and wave-fixed mechanisms, depending on the frequency ratio F2/F1. The general assumption is that for a small frequency ratio there is a predominantly place-fixed emission mechanism, while with a larger frequency ratio there is a predominantly wave-fixed mechanism. There is also a lack of published data on the repeatability of the two components when separated. One aim of this study was therefore to identify the wave-fixed and place-fixed components of the 2F1-F2 DPOAE using a time-window separation method. The second aim was to quantify the test-retest repeatability of the separated 2F1-F2 DPOAE components in a group of normally hearing subjects. Results confirmed the presence of wave-fixed and place-fixed components for 2F1-F2 and a predominance of place or wave-fixed DPOAE as a function of frequency ratio. This pattern varied somewhat among subjects. Moreover, regardless of which component was stronger for any F2/F1, both components were highly repeatable across time within individual ears.