Demographics and anthropometrics impact benefits of health intervention: data from the Reduce Obesity and Diabetes Project.

OBJECTIVE: To determine the efficacy of a 4-month school-based health, nutrition and exercise intervention on body fatness and examine possible effects of demographic and anthropometric covariates. METHODS: Height, weight, waist circumference and body composition were measured in a diverse population of 644 NYC middle school students (mean ± SD age 12.7 ± 0.9 years; 46% male; 38% Hispanic, 17% East Asian, 15% South Asian, 13.5% African American, 8.5% Caucasian, 8% other) during the fall and spring semesters. Year 1 participants (n = 322) were controls. Experimental participants (year 2, n = 469) received a 12-session classroom-based health and nutrition educational programme with an optional exercise intervention. RESULTS: Groups were demographically and anthropometrically similar. The intervention resulted in significant reductions in indices of adiposity (ΔBMI z-scores [-0.035 ± 0.014; p = 0.01], Δ% body fat [-0.5 ± 0.2; p < 0.0001] and Δwaist circumference [-0.73 ± 0.30 cm; p < 0.0001]). Intervention effects were greater (p = 0.01) in men (ΔBMI z-score = -0.052 ± 0.015) versus women (0.022 ± 0.018), participants who were obese (ΔBMI z-score -0.083 ± 0.022 kg m-2) versus lean (-0.0097 ± 0.020 kg m-2) and South Asians (Δ% body fat -1.03 ± 0.35) versus total (-0.49 ± 0.20%) participants (p = 0.005). CONCLUSION: A 4-month school-based health intervention was effective in decreasing measures of adiposity in middle school students, particularly in men, participants who were obese and South Asians.

Effect of nasal continuous positive airway pressure on the pharyngeal swallow in neonates.

OBJECTIVE: Feeding neonates orally while on nasal continuous positive airway pressure (nCPAP) is a common practice. We hypothesize that pressurized airflow provided by nCPAP will alter the swallowing mechanism in neonates, increasing the risk of aspiration during oral feeding. STUDY DESIGN: Infants receiving nCPAP with a RAM cannula and tolerating at least 50% of their feeding orally were included in the study (one term; six preterm infants). Each participant underwent a videofluoroscopic swallow study while on nCPAP and off nCPAP. A non-parametric signed-rank test was used for paired data. RESULT: The incidence of deep penetration (P=0.03) and aspiration (P=0.01) decreased significantly off-nCPAP compared with on-nCPAP. However, the incidence of mild penetration (P=0.65) and nasopharyngeal reflux (P=0.87) remained the same under both conditions. CONCLUSION: Oral feeding while on-nCPAP significantly increases the risk of laryngeal penetration and tracheal aspiration events. We recommend caution when initiating oral feedings on nCPAP.

Should gentamicin trough levels be routinely obtained in term neonates?

OBJECTIVE: Gentamicin is a common antibiotic used to treat sepsis in neonates. We hypothesize that obtaining routine gentamicin trough levels may not be necessary in low-risk, term infants. STUDY DESIGN: We performed a retrospective cohort study of term infants (n=346) treated with gentamicin in a single level III neonatal intensive care unit (NICU). The results of gentamicin trough levels and the correlation with risk factors and potential side effects were recorded. In addition, we conducted a survey of 75 academic NICUs across the United States regarding their gentamicin monitoring practice. RESULTS: Routine trough levels did not predict potential gentamicin toxicity in neonates with low risk factors. Regression analysis demonstrated a positive correlation between gentamicin trough levels and serum creatinine. The survey of the NICUs in the United States demonstrated significant inconsistency in gentamicin monitoring practice. CONCLUSION: Obtaining gentamicin trough levels guided by risk factors is more appropriate than obtaining routine trough levels in low-risk term neonates.

Plasma advanced glycation end products (AGEs), receptors for AGEs and their correlation with inflammatory markers in middle school-age children.

AIM: Advanced glycation end products (AGEs) and/or their receptors (RAGE) are significantly positively correlated with adiposity, inflammation, dyslipidemia, and insulin resistance in adults. However, the relationships between AGEs, RAGE, and adiposity-related comorbidites in children have not been well studied. METHODS: In a cross-sectional study of 88 children (age 11-15 years) from the New York area enrolled in the Reduce Obesity and Diabetes (ROAD) study, we examined the correlation of the AGE N(ε)-(carboxymethyl)lysine (CML), soluble RAGE (sRAGE), and endogenous secretory RAGE (esRAGE) with adiposity, inflammatory markers [interleukin-6 (IL-6), C-reactive protein, tumor necrosis factor-α], adiponectin, lipids, insulin sensitivity, and insulin secretory capacity. RESULTS: Pediatric CML levels were ~20% below average adult levels. CML was significantly (p < 0.05) positively correlated with age and insulin sensitivity and negatively with adiposity, dyslipidemia and IL-6. sRAGE correlated positively with esRAGE and negatively with adiposity and IL-6. Both sRAGE and esRAGE correlated negatively with insulin secretory capacity. CONCLUSION: Our findings suggest that unlike adults, CML is negatively associated with adiposity and adiposity-related comorbidity risk in children. As in adults, sRAGE and esRAGE were, to varying degrees, negatively correlated with body fatness and risk factors for adiposity-related comorbidities.

Highly efficient state-selective submicrosecond photoionization detection of single atoms.

We experimentally demonstrate a detection scheme suitable for state analysis of single optically trapped atoms in less than 1 µs with an overall detection efficiency η exceeding 98%. The method is based on hyperfine-state-selective photoionization and subsequent registration of the correlated photoion-electron pairs by coincidence counting via two opposing channel electron multipliers. The scheme enables the calibration of absolute detection efficiencies and might be a key ingredient for future quantum information applications or precision spectroscopy of ultracold atoms.

Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years.

BACKGROUND: Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. METHODS: Women aged 15-25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6.4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with ClinicalTrials.gov, number NCT00120848. FINDINGS: For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95.3% (95% CI 87.4-98.7) and against 12-month persistent infection was 100% (81.8-100). Vaccine efficacy against CIN2+ was 100% (51.3-100) for lesions associated with HPV-16/18 and 71.9% (20.6-91.9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred. INTERPRETATION: Our findings show excellent long-term efficacy, high and sustained immunogenicity, and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6.4 years. FUNDING: GlaxoSmithKline Biologicals (Belgium).

Randomized, controlled, dose-ranging trial of carisbamate for partial-onset seizures.

OBJECTIVE: To evaluate the efficacy, safety, and tolerability of carisbamate (CRS), an investigational drug, as adjunctive treatment for partial-onset seizures in adults. METHODS: A randomized, double-blind, placebo-controlled, multicenter, dose-ranging study was conducted in 12 countries. Patients counted seizures during an 8-week baseline period, and then, if eligible, entered a double-blind phase consisting of a 4-week dose-titration period (target CRS doses: 100, 300, 800, or 1,600 mg/d or placebo in two divided doses) and a 12-week maintenance period. The primary efficacy variable was percent reduction in partial-onset seizure frequency during the double-blind phase compared with pretreatment baseline. Safety data and responder rates were also assessed. RESULTS: Five hundred thirty-seven patients were randomized, and 82% completed the study. In the intent-to-treat population (n = 533), CRS at doses of > or =300 mg/d (p < or = 0.006) reduced the frequency of partial-onset seizures vs placebo: 6% (placebo) vs 24% (300 mg/d), 21% (800 mg/d), and 29% (1,600 mg/d) for CRS. Adverse events consisted primarily of CNS effects, and led to discontinuation of drug in 8% of the placebo group vs 5% (100 mg/d), 6% (300 mg/d), 12% (800 mg/d), and 19% (1,600 mg/d) of the CRS groups. CONCLUSIONS: Carisbamate at doses of 300, 800, and 1,600 mg/d was effective as adjunctive therapy for reducing the frequency of partial-onset seizures.

Towards long-distance atom-photon entanglement.

We report the observation of entanglement between a single trapped atom and a single photon at remote locations. The degree of coherence of the entangled atom-photon pair is verified via appropriate local correlation measurements, after communicating the photon via an optical fiber link of 300 m length to a receiver 3.5 m apart. In addition, we measured the temporal evolution of the atomic density matrix after projecting the atom via a state measurement of the photon onto several well-defined spin states. We find that the state of the single atom dephases on a time scale of 150 micros, which represents an important step towards long-distance quantum networking with individual neutral atoms.

Coherence properties and quantum state transportation in an optical conveyor belt.

We have prepared and detected quantum coherences of trapped cesium atoms with long dephasing times. Controlled transport by an "optical conveyor belt" over macroscopic distances preserves the atomic coherence with slight reduction of coherence time. The limiting dephasing effects are experimentally identified, and we present an analytical model of the reversible and irreversible dephasing mechanisms. Our experimental methods are applicable at the single-atom level. Coherent quantum bit operations along with quantum state transport open the route towards a "quantum shift register" of individual neutral atoms.

Brain perfusion monitoring with frequency-domain and continuous-wave near-infrared spectroscopy: a cross-correlation study in newborn piglets.

The newborn piglet brain model was used to correlate continuous-wave (CW) and frequency-domain (FD) near-infrared spectroscopy. Six ventilated and instrumented newborn piglets were subjected to a series of manipulations in blood oxygenation with the effects on brain perfusion known to be associated with brain hypoxia-ischaemia. An excellent agreement between the CW and FD was demonstrated. This agreement improved when the scattering properties (determined by the FD device) were employed to calculate the differential pathlength factor, an important step in CW data processing.

Contraception.

Prescribing and reviewing contraceptive methods with adolescents involves a significant amount of time and resources. Health care providers need to be familiar with how teens think about sex and birth control, what their beliefs are, and how individual teens may make different choices based on their lifestyles. Barrier methods remain popular in that they are accessible and do not require a clinician visit. The hormonal choices need to be explained fully in plain language and selections based on these sessions made appropriately. Teens can be effective users of contraception if they are given the appropriate tools, access, and knowledge.

Oxcarbazepine monotherapy for partial-onset seizures: a multicenter, double-blind, clinical trial.

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) 2,400 mg/day versus OXC 300 mg/day monotherapy in patients with medically refractory partial epilepsy. BACKGROUND: OXC is primarily metabolized by reductase enzymes and, consequently, has a low propensity to inhibit or induce oxidative enzymes and a minimal potential for drug-drug interactions. The efficacy of OXC as monotherapy was shown in several comparative trials in patients with newly diagnosed epilepsy and in hospitalized patients undergoing evaluation for epilepsy surgery. METHODS: A multicenter, double-blind, randomized, parallel-group trial design was chosen to assess the antiepileptic efficacy of OXC as monotherapy in a refractory epilepsy patient population. Outpatients aged 12 years or older with inadequately controlled partial seizures, with or without secondarily generalized seizures, were enrolled. Patients finished the trial by completing the double-blind phase or by meeting one of four predefined exit criteria: a twofold increase in partial seizure frequency in any 28-day period relative to baseline; a twofold increase in the highest consecutive 2-day partial seizure frequency relative to baseline; occurrence of a single generalized seizure if none occurred during the 6 months prior to randomization; or prolongation or worsening of generalized seizure duration or frequency requiring intervention. Adverse events (AEs), vital signs, and clinical laboratory tests were evaluated. RESULTS: The percentage of patients meeting one of the exit criteria was significantly lower (p < 0.0001) for the OXC 2400 mg/day group (14/34; 41%) than the OXC 300 mg/day group (42/45; 93%). In addition, there was a significant difference in time to exit in favor of the OXC 2400 mg/day group (p = 0.0001). In the intent-to-treat analysis, 12% of patients in the OXC 2400 mg/day group were seizure-free compared with none in the 300 mg/day group. OXC was well-tolerated, with dizziness, fatigue, somnolence, and nausea being the most frequent AEs. Most of these AEs were transient and rated as mild to moderate in intensity. CONCLUSION: OXC is safe and effective in the treatment of patients with partial epilepsy previously receiving treatment with other antiepileptic drugs. The results of this trial are consistent with previous monotherapy trials with OXC.

Role of frequency domain optical spectroscopy in the detection of neonatal brain hemorrhage--a newborn piglet study.

OBJECTIVE: Inability of continuous wave (CW) optical spectroscopy to measure changes in scattering, and the use of an arbitrary rather than an actual baseline, makes the CW method highly susceptible to errors that can lead to a false-positive or false-negative diagnosis. Our objective was to assess whether, and to what extent, the use of quantitative frequency domain spectroscopy would improve our ability to detect and monitor the development of brain hemorrhage. METHODS: A dual-channel frequency-domain tissue spectrometer (Model 96208, ISS, Inc., Champaign, IL) was used to monitor the development of experimental subcortical and periventricular-intraventricular hemorrhage (IVH) in 10 newborn piglets (blood injection model). The multidistance approach was employed to calculate the absorption and reduced scattering coefficients and hemoglobin changes from the ac, dc, and phase values acquired at four different source-detector distances and at 752 nm and 830 nm. RESULTS: There were significant absorption and scattering changes in the subcortical hematoma (n = 5) and the IVH groups (n = 5). The smallest detectable amount of blood in the brain was 0.04 ml. Changes associated with subcortical hematoma were several times higher than those associated with IVH, and correlated better with the estimated cross-sectional area of the hematoma than with the volume of the injected blood. As opposed to IVH, there was a significant absorption difference between the injured (subcortical hematoma) and normal side of the brain, probably because in case of IVH a significant volume of the injected blood had accumulated/spread beyond the reach of the probe. CONCLUSION: Clearly, frequency-domain spectroscopy cannot increase our ability to quantify the volume (size) or the oxygenation of the injected blood, especially in the case of IVH. However, the ability to quantify the baseline tissue absorption and scattering would significantly improve diagnostic performance, and may allow for early identification and treatment of neonatal brain hemorrhage.

Long-term follow-up of premature infants treated with prophylactic, intratracheal recombinant human CuZn superoxide dismutase.

OBJECTIVE: To examine the long-term effects of treatment with recombinant human CuZn superoxide dismutase (rhSOD) in infants enrolled previously in two placebo-controlled trials. STUDY DESIGN: Records for 46 (88%) infants were examined, with 19 infants having received either single or multiple intratracheal (i.t.) doses of placebo, 12 having received a single i.t. dose of rhSOD, and 15 having received multiple i.t. doses of rhSOD. Mean age at follow-up was 28 months corrected age. Records were examined for neurologic dysfunction, developmental delay, and any significant medical disorders. RESULTS: Four placebo infants (21%) had evidence of neurodevelopmental abnormalities and four infants developed asthma. Four single-dose rhSOD infants (33%) had neurodevelopmental abnormalities and two infants developed asthma. One multiple-dose rhSOD infant had evidence of neurodevelopmental abnormalities and one developed asthma. No other differences were found between the placebo and rhSOD groups. CONCLUSION: Preliminary data suggest that rhSOD is safe and not associated with any long-term adverse effects. Further results will depend on the results of multicenter trials of rhSOD in preterm infants.

Alternating antipyretics: is this an alternative?

OBJECTIVES: To identify current fever management strategies and their basis, and to assess the frequency of alternating acetaminophen and ibuprofen. BACKGROUND: Practicing pediatricians confront the dilemma of elevated temperature and the anxiety this creates for parents. An informal survey of pediatricians revealed a variety of management strategies, including alternating acetaminophen and ibuprofen. There are no scientific data regarding alternating these 2 products. Design. During professional meetings, pediatricians voluntarily filled out a 15-item questionnaire. RESULTS: One hundred sixty-one completed surveys were reviewed. Respondents were mostly general pediatricians (67.7%), with >/=20 years in practice (55.9%). Most respondents chose a temperature of 101(o)F to start antipyretic treatment (61.9%). A small percentage used discomfort alone as the indication (13%). The antipyretic of choice was temperature-dependent in 50% of respondents; 57% used ibuprofen for temperature >/=102 degrees F. Fifty percent of respondents advised parents to alternate acetaminophen and ibuprofen. The method of alternation varied. The most common answers given for choosing a particular antipyretic regime were recommendations of the American Academy of Pediatrics (29%) and opinions of colleagues and mentors (25%). Physicians with <5 years of practice were significantly more likely to alternate antipyretics (69.7%). CONCLUSION: Acetaminophen and ibuprofen are commonly being used in an alternating manner for management of fever. There is presently no scientific evidence that this combination is safe or achieves faster antipyresis than either agent alone. There is evidence that the improper use of these agents may cause harm. Despite 29% of participants citing American Academy of Pediatrics recommendations as the basis for fever management, no such policy or recommendations exist. The observation that this practice is more common in younger practitioners may reflect their continued anxiety about fever (fever phobia). Until properly controlled studies have assessed the risk of combining these 2 products, practitioners should proceed with caution.

Nonfocal generalized tonic-clonic seizures: response during long-term topiramate treatment. Topiramate YTC/YTCE Study Group.

PURPOSE: A total of 131 adults and children (mean age, 27 years; range, 3-59 years) with generalized tonic-clonic seizures (GTCS) of nonfocal origin resistant to other antiepileptic drugs (AEDs) were treated with open-label topiramate (TPM) after completing double-blind placebo-controlled trials. RESULTS: The mean duration of open-label TPM treatment was 387 days (range, 14-909 days); the mean TPM dose was 7 mg/kg/day (range, 1-16 mg/kg/day). At the last study visit, the frequency of GTCS was reduced > or =50% from baseline in 63% of patients and by > or =75% in 44%. Among patients treated > or =6 months, 16% were GTCS free > or =6 months despite a pretreatment seizure frequency of one GTCS/week (median). Treatment with TPM was being continued in 82% of patients (n = 107) at the last visit. During treatment periods of up to 2.5 years, 11 (8%) patients discontinued TPM because of adverse events and seven (5%) because of inadequate seizure control. CONCLUSIONS: TPM therapy was well tolerated, and seizure control was maintained with long-term, open-label therapy in patients with GTCS, leading to prolonged seizure-free intervals in some patients with seizures previously resistant to AED therapy.

The potential role of an adult mentor in influencing high-risk behaviors in adolescents.

BACKGROUND: While mentorship programs, which connect adolescents with adults to whom they can turn to for help and advice, are proliferating in an attempt to prevent high-risk behaviors in teenagers, there are few data to show that mentorship actually makes a difference. OBJECTIVE: To determine if there is an association between having an adult mentor and high-risk behaviors in adolescents. HYPOTHESIS: Adolescents who have an adult mentor would be less likely to engage in high-risk behaviors than those without an adult mentor. DESIGN: Cross-sectional study. A self-administered, anonymous questionnaire was developed to assess demographics, involvement in risk behaviors, and the prevalence of a mentor in the life of a young person. PARTICIPANTS: A convenience sample of 294 adolescents, seen consecutively (93% of those approached), receiving outpatient medical care. Participants were predominantly female (68%), of mixed race/ethnicity, aged between 12 and 23 years (mean +/- SD age, 16.9 +/- 2.4), and from diverse socioeconomic backgrounds. SETTING: An adolescent health service in a suburban community-based teaching hospital. MAIN OUTCOME MEASURES: Adolescent smoking, alcohol and drug use, sexual practices, and weapon carrying. RESULTS: Adolescents with mentors were significantly less likely to participate in 4 of the 5 measured risk behaviors: ever carrying a weapon (odds ratio, 0.41; P< or =.01), illicit drug use in the past 30 days (odds ratio, 0.44; P< or =.01), smoking more than 5 cigarettes per day (odds ratio, 0.54; P< or =.05), and sex with more than 1 partner in the past 6 months (odds ratio, 0.56; P< or =.05). No significant difference was found with alcohol use (> or =3 drinks in the past 30 days). CONCLUSION: A strong positive relationship was found between adolescents having an adult mentor and decreased participation in 4 of the 5 risk behaviors evaluated.

An open-label study of repeated use of diazepam rectal gel (Diastat) for episodes of acute breakthrough seizures and clusters: safety, efficacy, and tolerance. North American Diastat Group.

PURPOSE: To assess safety of diazepam rectal gel (DZPRG) for control of acute seizures in epilepsy patients and to evaluate tolerance with repeated use of DZPRG at intervals of > or =5 days. METHODS: Subjects were persons with epilepsy, age 2 years or older, with seizure clusters or prolonged seizures. Onset of a treatable episode was defined; caregivers were trained to administer DZPRG and to monitor respiration, seizures, and adverse effects (AEs). DZPRG was dispensed in a single-use, prefilled syringe; dosage was determined by age and weight. Maximal use was > or =5-day intervals, < or =5 times/month. After use, caregivers returned data booklets and syringe. Caregivers and physicians completed global ratings yearly. RESULTS: In 149 subjects treated, 77% of 1,578 administrations resulted in seizure freedom for the next 12 h. One hundred twenty-five received two or more treatments (two to 78; median, 8), 0.03-4.3/month (median, 0.4). To evaluate tolerance, subjects with two or more episodes were divided into low (two to seven episodes) and high use (eight to 78 episodes treated). There was no difference in proportion seizure free 12 h after the first administration versus last administration, for either infrequent or frequent administration. Sedation occurred in 17%, attributed to DZPRG in 9%. No respiratory depression was attributable to DZPRG. Three subjects withdrew because of AEs attributable to (agitation) or possibly attributable to DZPRG (chest pain, rash). Five subjects withdrew because of AEs unrelated to DZPRG. Caregiver and physician global ratings were highly positive at both 12 and 24 months. CONCLUSIONS: DZPRG is safe and effective in children and adults with epilepsy with breakthrough seizures. Neither tolerance nor significant medication-related AEs were seen with repeated DZPRG administration at intervals > or =5 days.

Real-time optical imaging of experimental brain ischemia and hemorrhage in neonatal piglets.

Our objective was to study the development of experimental brain ischemia and hemorrhage by real-time optical imaging. Optical imaging is based on the ability of near infrared light to non-invasively penetrate through the intact scalp and skull and measure brain concentrations of oxy- and deoxyhemoglobin, dominant brain absorbers. Optical imaging was performed in 7 anesthetized, instrumented, and ventilated newborn piglets subjected to the injection of 0.3 cc of saline followed by 2 cc of blood into the left frontal subcortical brain region via a needle inserted through the skull with stereotactic guidance. The image-acquisition rate of 5.26 images per sec allowed for real-time imaging. The detection threshold of the imager at the estimated depth of 1-1.5 cm was approximately 70 microL for saline and approximately 40 microL for blood. The imager readily detected five subcortical hematomas and two large bilateral subarachnoid hemorrhages. The imager detected a global decrease in brain absorption associated with the volume-injection-related increase in intracranial pressure in the surrounding ipsilateral and contralateral brain. Any decrease in brain absorption is an equivalent to brain ischemia. This study demonstrates the capability of optical imaging in detecting brain ischemia and hemorrhage in real-time with high temporal and spatial resolution.

Non-invasive optical monitoring of the newborn piglet brain using continuous-wave and frequency-domain spectroscopy.

We have used continuous-wave (CW) and frequency-domain spectroscopy to investigate the optical properties of the newborn piglet brain in vivo and non-invasively. Three anaesthetized, intubated, ventilated and instrumented newborn piglets were placed into a stereotaxic instrument for optimal experimental stability, reproducible probe-to-scalp optical contact and 3D adjustment of the optical probe. By measuring the absolute values of the brain absorption and reduced scattering coefficients at two wavelengths (758 and 830 nm), frequency-domain spectroscopy provided absolute readings (in contrast to the relative readings of CW spectroscopy) of cerebral haemoglobin concentration and saturation during experimentally induced perturbations in cerebral haemodynamics and oxygenation. Such perturbations included a modulation of the inspired oxygen concentration, transient brain asphyxia, carotid artery occlusion and terminal brain asphyxia. The baseline cerebral haemoglobin saturation and concentration, measured with frequency-domain spectroscopy, were about 60% and 42 microM respectively. The cerebral saturation values ranged from a minimum of 17% (during transient brain asphyxia) to a maximum of 80% (during recovery from transient brain asphyxia). To analyse the CW optical data, we have (a) derived a mathematical relationship between the cerebral optical properties and the differential pathlength factor and (b) introduced a method based on the spatial dependence of the detected intensity (dc slope method). The analysis of the cerebral optical signals associated with the arterial pulse and with respiration demonstrates that motion artefacts can significantly affect the intensity recorded from a single optode pair. Motion artefacts can be strongly reduced by combining data from multiple optodes to provide relative readings in the dc slope method. We also report significant biphasic changes (initial decrease and successive increase) in the reduced scattering coefficient measured in the brain after the piglet had been sacrificed.