Simple technique for integrating compact silicon devices within optical fibers.

In this work, we present a simple fabrication process enabling the integration of a subwavelength amorphous silicon layer inside optical fibers by means of the arc discharge technique. To assess our method, we have fabricated a compact in-line Fabry-Perot interferometer consisting of a thin (<1 µm) a-Si:H layer completely embedded within a standard single-mode optical fiber. The device exhibits low loss (1.3 dB) and high interference fringe visibility (~80%) both in reflection and transmission, due to the high refractive index contrast between silica and a-Si:H. A high linear temperature sensitivity up to 106 pm/°C is demonstrated in the range 120°C-400°C. The proposed interferometer is attractive for point monitoring applications as well as for ultrahigh-temperature sensing in harsh environments.

Metasurface-assisted Lab-on-fiber optrode for highly sensitive detection of vitamin D.

The increasing demand for vitamin D status assessment has highlighted the need for rapid, sensitive, and user-friendly methods for its detection in biological samples potentially integrated in Point-of-Care (PoC) diagnostic devices. Detection of the major circulating form of vitamin D, 25-hydroxyvitamin D3-25(OH)D3, is particularly challenging due to the laborious procedures for sample preparation and its low molecular weight (∼400 Da), which requires highly sensitive detection methods. In this study, we developed a novel label-free Lab-on-Fiber biosensing platform for highly sensitive detection of 25(OH)D3 based on the integration of plasmonic metasurfaces (MSs) on the tip of a single-mode optical fiber (OF). A dedicated pipeline was carefully designed and developed to optimize the bio-functionalization of the plasmonic sensor tip to specifically detect the target biomolecule. The resulting MS-assisted Lab-on-fiber platform enables direct and highly sensitive detection of 25(OH)D3 in clinically relevant ranges (4-160 ng/mL), both in buffer solution and complex matrix, with limits of detection (LOD) of 1.40 ng/mL in saline buffer and 0.85 ng/mL in complex matrix. Overall, these results demonstrate that our platform can successfully and specifically detect small molecules in label-free configuration, with performances comparable to those of conventional methods used in clinical practice. The high degree of miniaturization combined with its high sensitivity makes our platform an exceptional building block for realizing valid diagnostic alternatives for label-free detection of clinically relevant analytes, which can be transformed into new low-cost, fast, simple, and ready-to-use PoC diagnostic devices with improved processability and performance compared to current methods.

Sexuality in breast cancer survivors: sexual experiences, emotions, and cognitions in a group of women under hormonal therapy.

BACKGROUND: Earlier diagnosis and improved treatments have led to better outcomes in breast cancer, making quality of life a key issue. Sexuality represents a pillar of quality of life, although it is often neglected by both healthcare providers and patients when it comes to cancer. This study aims to explore the differences in sexual functioning, distress, psychopathology, emotions, and cognitions between breast cancer patients under hormonal treatment and controls. METHODS: Seventy-nine women (age range between 24 and 69 years) in hormonal therapy for breast cancer completed a self-reported protocol. A matched control group of 103 women was randomly extracted from an Italian general population database. Eight self-report questionnaires exploring biopsychosocial factors were administered. RESULTS: The current study showed an impaired sexuality in breast cancer patients compared to controls. Breast cancer women under hormonal treatment were characterized by diminished or absent sexual activity (chi2 = 36.16; p < 0.001), lower level of sexual functioning in all areas except for pain (F(1,180) = 8.1; p < 0.01), higher sexual (F(1,180) = 10.08; p < 0.001) and psychological distress (F(1,180) = 6.23; p < 0.05), higher scores in Difficulties in Identifying Feelings (F(1,180) = 7.31; p < 0.01) and Externally Oriented Thinking (F(1,180) = 6.64; p < 0.05), higher level of negative emotions related to sexuality (F(1,180) = 11.13; p < 0.001), and more rigid cognition towards peculiar aspects of sexuality, such as Failure Disengagement Thoughts (F(1,180) = 22.01; p < 0.001) and Age related Beliefs (F(1,180) = 5.7; p < 0.05). CONCLUSIONS: Health care providers do not usually assess those issues in their routine practice, so that sexuality remains an unmet need with remarkable effects on general health and quality of life.

Offspring from endogamic vs. exogamic matings: Absence of anthropometric differences among Sardinian children (Italy).

This study evaluates possible differences in body dimensions among children from matings of different exogamy levels. The cross-sectional sample consisted of 867 children, 435 males, and 432 females, 6-10 years old, attending elementary schools in the metropolitan area of Cagliari, the capital of Sardinia (Italy). The children were divided into two groups according to the level of exogamy. The first group consisted of children of parents born in the same Sardinian municipality and was considered endogamous sensu stricto. The second group included children of parents born in municipalities from different Sardinian linguistic domains and was considered exogamous. The Mann-Whitney test did not reveal significant differences between the two groups of children in the mean rank values of the 36 anthropometric variables considered, with the exception of cephalic circumference in males and chest depth in females. In particular, there were no significant differences for anthropometric variables considered to be indirect indicators of nutritional status: sum of skinfolds, waist/hip ratio, body mass index, total upper arm area, upper arm muscle area, and upper arm fat area. The results indicate that Sardinian children from marriages of different exogamy levels do not differ in body dimensions if they grow up with similar nutritional and socioeconomic conditions.

Light-microgel interaction in resonant nanostructures.

Combination of responsive microgels and photonic resonant nanostructures represents an intriguing technological tool for realizing tunable and reconfigurable platforms, especially useful for biochemical sensing applications. Interaction of light with microgel particles during their swelling/shrinking dynamics is not trivial because of the inverse relationships between their size and refractive index. In this work, we propose a reliable analytical model describing the optical properties of closed-packed assembly of surface-attached microgels, as a function of the external stimulus applied. The relationships between the refractive index and thickness of the equivalent microgel slab are derived from experimental observations based on conventional morphological analysis. The model is first validated in the case of temperature responsive microgels integrated on a plasmonic lab-on-fiber optrode, and also implemented in the same case study for an optical responsivity optimization problem. Overall, our model can be extended to other photonic platforms and different kind of microgels, independently from the nature of the stimulus inducing their swelling.

Microgel assisted Lab-on-Fiber Optrode.

Precision medicine is continuously demanding for novel point of care systems, potentially exploitable also for in-vivo analysis. Biosensing probes based on Lab-On-Fiber Technology have been recently developed to meet these challenges. However, devices exploiting standard label-free approaches (based on ligand/target molecule interaction) suffer from low sensitivity in all cases where the detection of small molecules at low concentrations is needed. Here we report on a platform developed through the combination of Lab-On-Fiber probes with microgels, which are directly integrated onto the resonant plasmonic nanostructure realized on the fiber tip. In response to binding events, the microgel network concentrates the target molecule and amplifies the optical response, leading to remarkable sensitivity enhancement. Moreover, by acting on the microgel degrees of freedom such as concentration and operating temperature, it is possible to control the limit of detection, tune the working range as well as the response time of the probe. These unique characteristics pave the way for advanced label-free biosensing platforms, suitably reconfigurable depending on the specific application.

Optical fiber tip templating using direct focused ion beam milling.

We report on a method for integrating sub-wavelength resonant structures on top of optical fiber tip. Our fabrication technique is based on direct milling of the glass on the fiber facet by means of focused ion beam. The patterned fiber tip acts as a structured template for successive depositions of any responsive or functional overlay. The proposed method is validated by depositing on the patterned fiber a high refractive index material layer, to obtain a 'double-layer' photonic crystal slab supporting guided resonances, appearing as peaks in the reflection spectrum. Morphological and optical characterizations are performed to investigate the effects of the fabrication process. Our results show how undesired effects, intrinsic to the fabrication procedure should be taken into account in order to guarantee a successful development of the device. Moreover, to demonstrate the flexibility of our approach and the possibility to engineering the resonances, a thin layer of gold is also deposited on the fiber tip, giving rise to a hybrid photonic-plasmonic structure with a complementary spectral response and different optical field distribution at the resonant wavelengths. Overall, this work represents a significant step forward the consolidation of Lab-on-Fiber Technology.

Impairment of lung volumes and respiratory muscle strength in adult patients with growth hormone deficiency.

Little is known of the respiratory function in patients with growth hormone (GH) deficiency. The aim of the present study was to evaluate lung volumes and respiratory muscle strength in patients diagnosed as GH deficient in childhood. Ten patients diagnosed as GH deficient in childhood and ten healthy subjects entered the study. For each subject the evaluation of respiratory function followed the same standard approach, consisting of respiratory muscle strength assessment, recording of flow-volume curves, measurement of static lung volumes and lung diffusing capacity. Both maximal inspiratory and expiratory mouth pressures were decreased in GH deficiency. Vital capacity, N2 functional residual capacity and total lung capacity were significantly reduced when compared to healthy subjects. Conversely, the residual volume and diffusing lung capacity to CO did not show any significant change. No significant change of percentage forced expiratory volume in 1 s/forced vital capacity ratio was observed. The decrease of respiratory mouth pressures was not correlated to the decrease of lung volumes. In conclusion, the results of this study show that adult patients affected with childhood onset GH deficiency suffer from impairment of ventilatory function and a decrease of respiratory muscle pressures, probably due to reduction of respiratory muscle strength.

Lung volumes and respiratory muscle strength in adult patients with childhood- or adult-onset growth hormone deficiency: effect of 12 months' growth hormone replacement therapy.

We have described impairment of the respiratory function in adult patients with childhood-onset growth hormone (GH) deficiency. The aim of the present study was to evaluate lung volumes and respiratory muscle strength in patients diagnosed as GH deficient before and after 6 and 12 months of recombinant GH treatment. Ten adults diagnosed as GH deficient in childhood, ten adults diagnosed as GH deficient in adulthood and ten healthy subjects entered the study. For each subject, evaluation of respiratory function followed the same standard approach, consisting of respiratory muscle strength assessment, record of flow-volume curves, measurement of static lung volumes and lung diffusing capacity. Childhood-onset GH-deficient patients had a significant reduction of maximal inspiratory (p < 0.01) and maximal expiratory (p < 0.05) mouth pressures. Total lung capacity, vital capacity and functional residual capacity were significantly reduced compared to healthy subjects (p < 0.05). Conversely, residual volume and diffusing lung capacity did not show any significant change. No significant change of the ratio between the percentage forced expiratory volume in 1 s and the forced vital capacity was observed. The decrease of respiratory mouth pressures was not correlated to the decrease of lung volumes. Adult-onset GH-deficient patients had only a significant reduction of maximal expiratory pressure compared to healthy subjects (p < 0.05). After 6 months of treatment no significant differences in any of the evaluated parameters were found. After 12 months of treatment patients with childhood-onset GH deficiency show a significant improvement of lung volumes (p < 0.01) and maximal respiratory mouth pressures (p < 0.005), whereas adult-onset GH-deficient patients show a significant improvement of maximal expiratory pressure (p < 0.05). In conclusion, the results of this study showed that adult patients affected with childhood-onset GH deficiency suffer from an impairment of the ventilatory function due to a reduction of lung volumes and a decrease of respiratory pressures probably due to a reduction of respiratory muscle strength. This impairment was reversed after 12 months of treatment with recombinant GH. Conversely, adult-onset GH-deficient patients had only an impairment of the maximal expiratory pressure, probably due to respiratory muscle weakness re-established after 12 months of GH therapy.

Endothelin abnormalities in patients with pulmonary embolism.

BACKGROUND: Endothelin (ET) is an endothelium-derived multifunctional peptide involved in the local regulation of the vascular tone. STUDY OBJECTIVES: To assess changes of endogenous ET production/excretion in the acute phase (36 h from the event) of pulmonary embolism (PE). PARTICIPANTS: Ten patients with acute PE, nine patients with acute lung injury (ALI), and 12 healthy volunteers (HVs). MEASUREMENTS AND RESULTS: ET was detected by radioimmunoassay in venous and arterial blood as well as in 24-h urine specimens. For each subject, arterial/venous immunoreactive ET (ir-ET) ratio was evaluated as an index of its pulmonary extraction/synthesis. Creatinine clearance was employed in each case to obtain a corrected renal ir-ET clearance. Renal ir-ET clearance was comparable in all three groups. Arterial/venous ir-ET ratio was comparable in PE and in ALI patients (1.31 +/- 0.25 vs 1.24 +/- 0.20; p = 0.7), while it was significantly higher in PE patients than in HV subjects (0.85 +/- 0.07; p = 0.0001). Accordingly, 24-h urine ir-ET excretion was higher in PE (120.50 +/- 27.36 ng/24 h) and ALI patients (135.80 +/- 21.60 ng/24 h) than in HV subjects (68.33 +/- 9.31 ng/24 h; p = 0.0001). CONCLUSIONS: Abnormalities of ET metabolism-mainly related to increased synthesis and/or defective pulmonary handling-occur in the acute phase of PE. The relevance of this finding with respect to the pathogenesis and/or management of pulmonary thromboembolism remains to be elucidated.

Rapid onset of hypoxic vasoconstriction in isolated lungs.

A fast-response O2 analyzer that samples air at low flow rates allows the quasi-instantaneous measurement of O2 concentration change in the airways of isolated blood-perfused rat lungs. This instrument and an oximeter were used to measure the stimulus-response delay time of hypoxic pulmonary vasoconstriction when the lungs were challenged with 10, 5, or 3% O2. The estimate for the shortest delay time between accomplished fall in airway O2 concentration and the onset of hypoxia-induced vasoconstriction was approximately 7 s. We found that the slope of pressure rise, but not the stimulus-response delay time, correlated with the magnitude of hypoxic vasoconstriction. Oscillations in pulmonary arterial pressure were observed when the lungs were challenged with 10% O2 but not when the challenge was 12, 5, or 3%, indicating perhaps that these oscillations were a threshold phenomenon. Established hypoxic vasoconstriction was sensitive to brief changes in airway O2 concentration. Vasodilation occurred when the gas mixture was switched from 3 to 21% O2 for two to five breaths, and vasoconstriction occurred when the gas was changed during a single breath from 5 to 3% O2.

Low acute hypoxic ventilatory response and hypoxic depression in acute altitude sickness.

Persons with acute altitude sickness hypoventilate at high altitude compared with persons without symptoms. We hypothesized that their hypoventilation was due to low initial hypoxic ventilatory responsiveness, combined with subsequent blunting of ventilation by hypocapnia and/or prolonged hypoxia. To test this hypothesis, we compared eight subjects with histories of acute altitude sickness with four subjects who had been asymptomatic during prior altitude exposure. At a simulated altitude of 4,800 m, the eight susceptible subjects developed symptoms of altitude sickness and had lower minute ventilations and higher end-tidal PCO2's than the four asymptomatic subjects. In measurements made prior to altitude exposure, ventilatory responsiveness to acute hypoxia was reduced in symptomatic compared to asymptomatic subjects, both when measured under isocapnic and poikolocapnic (no added CO2) conditions. Diminution of the poikilocapnic relative to the isocapnic hypoxic response was similar in the two groups. Ventilation fell, and end-tidal PCO2 rose in both groups during 30 min of steady-state hypoxia relative to values observed acutely. After 4.5 h at 4,800 m, ventilation was lower than values observed acutely at the same arterial O2 saturation. The reduction in ventilation in relation to the hypoxemia present was greater in symptomatic than in asymptomatic persons. Thus the hypoventilation in symptomatic compared to asymptomatic subjects was attributable both to a lower acute hypoxic response and a subsequent greater blunting of ventilation at high altitude.

Headache at high altitude is not related to internal carotid arterial blood velocity.

The cause of headache in persons going to high altitude is unknown. Relatively severe hypoxemia in susceptible subjects could induce large increases in cerebral blood flow that then could initiate the headache. Thus we measured noninvasively, by Doppler ultrasound, changes in internal carotid arterial blood velocity (velocity) in 12 subjects in Denver (1,600 m) and repeatedly up to 7 h at a simulated altitude of 4,800 m (barometric pressure = 430 Torr). Six subjects, selected because of prior history of high-altitude headache, developed comparatively severe headache at 4,800 m, and four subjects, without such history, remained well. Two subjects developed moderate headache. Velocity at 4,800 m did not correlate with symptom development, arterial O2 saturation, or end-tidal PCO2. Also, neither velocity nor blood pressure was consistently elevated above the Denver base-line values. During measurements of hypercapnic ventilatory response in Denver, velocity increased linearly with end-tidal PCO2, confirming that our Doppler method could demonstrate an increase. Also, 30 min of isocapnic or poikilocapnic hypoxia caused small increases in velocity (+8 and +6%) during the base-line measurement at low altitude. Although even a small increase in cerebral perfusion could contribute to headache symptoms at high altitude, cerebral blood flow does not appear to play a primary role.

Venous occlusion plethysmography reduces arterial diameter and flow velocity.

The measurement of peripheral blood flow by plethysmography assumes that the cuff pressure required for venous occlusion does not decrease arterial inflow. However, studies in five normal subjects suggested that calf blood flow measured with a plethysmograph was less than arterial inflow calculated from Doppler velocity measurements. We hypothesized that the pressure required for venous occlusion may have decreased arterial velocity. Further studies revealed that systolic diameter of the superficial femoral artery under a thigh cuff decreased from 7.7 +/- 0.4 to 5.6 +/- 0.7 mm (P less than 0.05) when the inflation pressure was increased from 0 to 40 mmHg. Cuff inflation to 40 mmHg also reduced mean velocity 38% in the common femoral artery and 47% in the popliteal artery. Inflation of a cuff on the arm reduced mean velocity in the radial artery 22% at 20 mmHg, 26% at 40 mmHg, and 33% at 60 mmHg. We conclude that inflation of a cuff on an extremity to low pressures for venous occlusion also caused a reduction in arterial diameter and flow velocity.

Internal carotid flow velocity with exercise before and after acclimatization to 4,300 m.

Cerebral blood flow and O2 delivery during exercise are important for well-being at altitude but have not been studied. We expected flow to increase on arrival at altitude and then to fall as O2 saturation and hemoglobin increased, thereby maintaining cerebral O2 delivery. We used Doppler ultrasound to measure internal carotid artery flow velocity at sea level and on Pikes Peak, CO (4,300 m). In an initial study (1987, n = 7 men) done to determine the effect of brief (5-min) exercises of increasing intensity, we found at sea level that velocity [24.8 +/- 1.4 (SE) cm/s rest] increased by 15 +/- 7, 30 +/- 6, and 22 +/- 8% for cycle exercises at 33, 71, and 96% of maximal O2 uptake, respectively. During acute hypobaric hypoxia in a decompression chamber (inspired PO2 = 83 Torr), velocity (23.2 +/- 1.4 cm/s rest) increased by 33 +/- 6, 20 +/- 5, and 17 +/- 9% for exercises at 45, 72, and 98% of maximal O2 uptake, respectively. After 18 days on Pikes Peak (inspired PO2 = 87 Torr), velocity (26.6 +/- 1.5 cm/s rest) did not increase with exercise. A subsequent study (1988, n = 7 men) of the effect of prolonged exercise (45 min at approximately 100 W) found at sea level that velocity (24.8 +/- 1.7 cm/s rest) increased by 22 +/- 6, 13 +/- 5, 17 +/- 4, and 12 +/- 3% at 5, 15, 30, and 45 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Breathing and brain blood flow during sleep in patients with chronic mountain sickness.

Chronic mountain sickness (CMS) patients have lower arterial O2 saturation (SaO2) during sleep compared with healthy high-altitude residents, but whether nocturnal arterial O2 content (CaO2) and brain O2 delivery are reduced is unknown. We measured SaO2, CaO2, sleep-disordered breathing (SDB), and internal carotid artery flow velocity in 8 CMS patients, 8 age-matched healthy CMS controls, 11 healthy younger-aged Han, and 11 healthy younger-aged Tibetan male residents of Lhasa, Tibet (3,658 m). CMS patients spent a greater portion of the night in SDB (total no. of episodes of apnea, hypopnea, and hypoventilation) than did the CMS controls, young Han, or young Tibetans (15% vs. 5, 1, and 1%, respectively; P < 0.05) because of more frequent apnea and hypoventilation episodes and longer duration of all types of episodes. SDB and unexplained arterial O2 desaturation caused nocturnal SaO2 to be lower and more variable in CMS patients than in CMS controls or in younger-aged Han or Tibetan men. Average CaO2 was similar, but the CMS patients spent 29%, whereas the other groups spent < 4%, of the night at values < 18 ml O2/100 ml whole blood. Internal carotid artery flow velocity during wakefulness was similar in CMS patients and CMS controls despite higher end-tidal PcO2 values in the CMS patients. When contiguous sleep stages are compared, flow velocity rose from stage 2 to rapid-eye-movement sleep in both groups. Whereas flow velocity remained elevated from awake to rapid-eye-movement sleep in the CMS controls, it fell in the CMS patients. During episodes of SDB, internal carotid flow velocity increased in CMS controls but did not change in the CMS patients such that values were lower in the CMS patients than in CMS controls at the end and after SDB episodes. We concluded that SDB and episodes of unexplained desaturation lowered nocturnal SaO2 and CaO2, which, together with a lack of compensatory increase in internal carotid artery flow velocity, likely decreased brain O2 delivery in CMS patients during a considerable portion of the night.

Internal carotid and vertebral arterial flow velocity in men at high altitude.

Cerebral blood flow increases at high altitude, but the mechanism of the increase and its role in adaptation to high altitude are unclear. We hypothesized that the hypoxemia at high altitude would increase cerebral blood flow, which would in turn defend O2 delivery to the brain. Noninvasive Doppler ultrasound was used to measure the flow velocities in the internal carotid and the vertebral arteries in six healthy male subjects. Within 2-4 h of arrival on Pikes Peak (4,300 m), velocities in both arteries were slightly and not significantly increased above sea-level values. By 18-44 h a peak increase of 20% was observed (combined P less than 0.025). Subsequently (days 4-12) velocities declined to values similar to those at sea level. At altitude the lowest arterial O2 saturation (SaO2) and the highest end-tidal PCO2 was observed on arrival. By day 4 and thereafter, when the flow velocities had returned toward sea-level values, hemoglobin concentration and SaO2 were increased over initial high-altitude values such that calculated O2 transport values were even higher than those at sea level. Although the cause of the failure for cerebral flow velocity to increase on arrival is not understood, the subsequent increase may act to defend brain O2 transport. With further increase in hemoglobin and SaO2 over time at high altitude, flow velocity returned to sea-level values.

Internal carotid arterial flow velocity during exercise in Tibetan and Han residents of Lhasa (3,658 m).

Cerebral blood flow increases with acute exposure to high altitude, but the effect of hypoxia on the cerebral circulation at rest and during exercise appears influenced by the duration of high-altitude exposure. To determine whether internal carotid artery flow velocity increased with exercise in long-term residents of high altitude and whether resting values and the response to exercise differed in lifelong vs. acclimatized newcomer male residents of high altitude, we studied 15 native Tibetan and 11 Han ("Chinese") 6 +/- 2-yr residents of Lhasa (3,658 m), Tibet Autonomous Region, China. Noninvasive Doppler ultrasound was used to measure internal carotid artery diameter, mean flow velocity, and, in combination, hemoglobin and arterial O2 saturation to assess cerebral O2 delivery. Tibetan and Han groups were similar in body size and resting internal carotid artery diameter, blood pressure, hemoglobin concentration, internal carotid artery mean flow velocity, and calculated cerebral O2 delivery. Submaximal exercise increased internal carotid artery mean flow velocity and cerebral O2 delivery in the Tibetan and Han subjects. At peak exercise, the Tibetans sustained the increase in flow velocity and cerebral O2 delivery, whereas the Hans did not. Across all exercise levels up to and including peak effort, the Tibetans demonstrated a greater increase in internal carotid artery flow velocity and cerebral O2 delivery relative to resting values than did the Hans. The greater cerebral O2 delivery was accompanied by increased peak exercise capacity in the Tibetan compared with the Han group. Our findings suggest that the cerebral blood flow response to exercise is maintained in Tibetan lifelong residents of high altitude.

The mismatch negativity cortical evoked potential elicited by speech in cochlear-implant users.

The mismatch negativity (MMN) event-related potential is a non-task related neurophysiologic index of auditory discrimination. The MMN was elicited in eight cochlear implant recipients by the synthesized speech stimulus pair /da/ and /ta/. The response was remarkably similar to the MMN measured in normal-hearing individuals to the same stimuli. The results suggest that the central auditory system can process certain aspects of speech consistently, independent of whether the stimuli are processed through a normal cochlea or mediated by a cochlear prosthesis. The MMN shows promise as a measure for the objective evaluation of cochlear-implant function, and for the study of central neurophysiological processes underlying speech perception.

Speech-evoked cortical potentials in children.

Event-related potentials (ERPs) were obtained to synthesized speech stimuli in 16 school-aged children (7-11 years) and compared to responses in 10 adults. P1, N1, and P2 event-related potentials were elicited by the phoneme /ga/. The mismatch negativity (MMN) was elicited by variants of /da/ and /ga/, which differ in the onset frequency of the second and third formant transitions. In general, the well-defined N1/P2 complex characteristic of the adult response, was not found in children. Waves P1 and N1 had longer peak latencies in children than in adults. Wave P2 amplitude was smaller in children than in adults. In contrast to the often poorly delineated earlier cortical potentials, the MMN was well defined in children. Significant MMNs were obtained in all subjects tested. MMN magnitude (peak amplitude and area) was significantly larger in the children. No significant differences were found in peak latency and duration of the MMN in children compared to the adult response. Another negative wave occurring at 400 msec was also observed in response to the deviant stimuli. This negative wave occurred at a similar latency in adults and children and was significantly larger and more robust in children. Results support the view that development of ERPs does not involve a hierarchical process with respect to latency. That is, earlier occurring waves do not necessarily mature before later occurring waves. The latencies of P1, N1, and P2 and overall morphology of these waves may provide a measure of maturation of central pathways. The early development of the MMN, its apparent robustness in school-aged children, and its reflection of the processing of acoustic differences in speech stimuli suggest its possible use in the assessment of central auditory function.