Iowa Brain-Behavior Modeling Toolkit: An Open-Source MATLAB Tool for Inferential and Predictive Modeling of Imaging-Behavior and Lesion-Deficit Relationships.

The traditional analytical framework taken by neuroimaging studies in general, and lesion-behavior studies in particular, has been inferential in nature and has focused on identifying and interpreting statistically significant effects within the sample under study. While this framework is well-suited for hypothesis testing approaches, achieving the modern goal of precision medicine requires a different framework that is predictive in nature and that focuses on maximizing the predictive power of models and evaluating their ability to generalize beyond the data that were used to train them. However, few tools exist to support the development and evaluation of predictive models in the context of neuroimaging or lesion-behavior research, creating an obstacle to the widespread adoption of predictive modeling approaches in the field. Further, existing tools for lesion-behavior analysis are often unable to accommodate categorical outcome variables and often impose restrictions on the predictor data. Researchers therefore often must use different software packages and analytical approaches depending on whether they are addressing a classification vs. regression problem and on whether their predictor data correspond to binary lesion images, continuous lesion-network images, connectivity matrices, or other data modalities. To address these limitations, we have developed a MATLAB software toolkit that supports both inferential and predictive modeling frameworks, accommodates both classification and regression problems, and does not impose restrictions on the modality of the predictor data. The toolkit features both a graphical user interface and scripting interface, includes implementations of multiple mass-univariate, multivariate, and machine learning models, features built-in and customizable routines for hyper-parameter optimization, cross-validation, model stacking, and significance testing, and automatically generates text-based descriptions of key methodological details and modeling results to improve reproducibility and minimize errors in the reporting of methods and results. Here, we provide an overview and discussion of the toolkit's features and demonstrate its functionality by applying it to the question of how expressive and receptive language impairments relate to lesion location, structural disconnection, and functional network disruption in a large sample of patients with left hemispheric brain lesions. We find that impairments in expressive vs. receptive language are most strongly associated with left lateral prefrontal and left posterior temporal/parietal damage, respectively. We also find that impairments in expressive vs. receptive language are associated with partially overlapping patterns of fronto-temporal structural disconnection, and that the associated functional networks are also similar. Importantly, we find that lesion location and lesion-derived network measures are highly predictive of both types of impairment, with predictions from models trained on these measures explaining ~30-40% of the variance on average when applied to data from patients not used to train the models. We have made the toolkit publicly available, and we have included a comprehensive set of tutorial notebooks to support new users in applying the toolkit in their studies.

Antidepressant Exposure and DNA Methylation: Insights from a Methylome-Wide Association Study.

Importance: Understanding antidepressant mechanisms could help design more effective and tolerated treatments. Objective: Identify DNA methylation (DNAm) changes associated with antidepressant exposure. Design: Case-control methylome-wide association studies (MWAS) of antidepressant exposure were performed from blood samples collected between 2006-2011 in Generation Scotland (GS). The summary statistics were tested for enrichment in specific tissues, gene ontologies and an independent MWAS in the Netherlands Study of Depression and Anxiety (NESDA). A methylation profile score (MPS) was derived and tested for its association with antidepressant exposure in eight independent cohorts, alongside prospective data from GS. Setting: Cohorts; GS, NESDA, FTC, SHIP-Trend, FOR2107, LBC1936, MARS-UniDep, ALSPAC, E-Risk, and NTR. Participants: Participants with DNAm data and self-report/prescription derived antidepressant exposure. Main Outcomes and Measures: Whole-blood DNAm levels were assayed by the EPIC/450K Illumina array (9 studies, N exposed = 661, N unexposed = 9,575) alongside MBD-Seq in NESDA (N exposed = 398, N unexposed = 414). Antidepressant exposure was measured by self- report and/or antidepressant prescriptions. Results: The self-report MWAS (N = 16,536, N exposed = 1,508, mean age = 48, 59% female) and the prescription-derived MWAS (N = 7,951, N exposed = 861, mean age = 47, 59% female), found hypermethylation at seven and four DNAm sites (p < 9.42x10 -8 ), respectively. The top locus was cg26277237 ( KANK1, p self-report = 9.3x10 -13 , p prescription = 6.1x10 -3 ). The self-report MWAS found a differentially methylated region, mapping to DGUOK-AS1 ( p adj = 5.0x10 -3 ) alongside significant enrichment for genes expressed in the amygdala, the "synaptic vesicle membrane" gene ontology and the top 1% of CpGs from the NESDA MWAS (OR = 1.39, p < 0.042). The MPS was associated with antidepressant exposure in meta-analysed data from external cohorts (N studies = 9, N = 10,236, N exposed = 661, f3 = 0.196, p < 1x10 -4 ). Conclusions and Relevance: Antidepressant exposure is associated with changes in DNAm across different cohorts. Further investigation into these changes could inform on new targets for antidepressant treatments. 3 Key Points: Question: Is antidepressant exposure associated with differential whole blood DNA methylation?Findings: In this methylome-wide association study of 16,536 adults across Scotland, antidepressant exposure was significantly associated with hypermethylation at CpGs mapping to KANK1 and DGUOK-AS1. A methylation profile score trained on this sample was significantly associated with antidepressant exposure (pooled f3 [95%CI]=0.196 [0.105, 0.288], p < 1x10 -4 ) in a meta-analysis of external datasets. Meaning: Antidepressant exposure is associated with hypermethylation at KANK1 and DGUOK-AS1 , which have roles in mitochondrial metabolism and neurite outgrowth. If replicated in future studies, targeting these genes could inform the design of more effective and better tolerated treatments for depression.

Light-induced anomalous Hall effect in graphene.

Many non-equilibrium phenomena have been discovered or predicted in optically-driven quantum solids1. Examples include light-induced superconductivity2,3 and Floquet-engineered topological phases4-8. These are short lived effects that should lead to measurable changes in electrical transport, which can be characterized using an ultrafast device architecture based on photoconductive switches9. Here, we report the observation of a light-induced anomalous Hall effect in monolayer graphene driven by a femtosecond pulse of circularly polarized light. The dependence of the effect on a gate potential used to tune the Fermi level reveals multiple features that reflect a Floquet-engineered topological band structure4,5, similar to the band structure originally proposed by Haldane10. This includes an approximately 60 meV wide conductance plateau centered at the Dirac point, where a gap of equal magnitude is predicted to open. We find that when the Fermi level lies within this plateau, the estimated anomalous Hall conductance saturates around 1.8±0.4 e2/h.

Depolarization and decreased surface expression of K+ channels contribute to NSAID-inhibition of intestinal restitution.

Non-steroidal anti-inflammatory drugs (NSAIDs) contribute to gastrointestinal ulcer formation by inhibiting epithelial cell migration and mucosal restitution; however, the drug-affected signaling pathways are poorly defined. We investigated whether NSAID inhibition of intestinal epithelial migration is associated with depletion of intracellular polyamines, depolarization of membrane potential (E(m)) and altered surface expression of K(+) channels. Epithelial cell migration in response to the wounding of confluent IEC-6 and IEC-Cdx2 monolayers was reduced by indomethacin (100 microM), phenylbutazone (100 microM) and NS-398 (100 microM) but not by SC-560 (1 microM). NSAID-inhibition of intestinal cell migration was not associated with depletion of intracellular polyamines. Treatment of IEC-6 and IEC-Cdx2 cells with indomethacin, phenylbutazone and NS-398 induced significant depolarization of E(m), whereas treatment with SC-560 had no effect on E(m). The E(m) of IEC-Cdx2 cells was: -38.5+/-1.8 mV under control conditions; -35.9+/-1.6 mV after treatment with SC-560; -18.8+/-1.2 mV after treatment with indomethacin; and -23.7+/-1.4 mV after treatment with NS-398. Whereas SC-560 had no significant effects on the total cellular expression of K(v)1.4 channel protein, indomethacin and NS-398 decreased not only the total cellular expression of K(v)1.4, but also the cell surface expression of both K(v)1.4 and K(v)1.6 channel subunits in IEC-Cdx2. Both K(v)1.4 and K(v)1.6 channel proteins were immunoprecipitated by K(v)1.4 antibody from IEC-Cdx2 lysates, indicating that these subunits co-assemble to form heteromeric K(v) channels. These results suggest that NSAID inhibition of epithelial cell migration is independent of polyamine-depletion, and is associated with depolarization of E(m) and decreased surface expression of heteromeric K(v)1 channels.

Reversible Chemical Dimerization by rCD1.

An optimal tool to unravel the role of a specific player within a cellular network or process requires its spatiotemporally resolved perturbation. Chemically induced dimerization (CID) by the rapamycin system has proven useful to induce protein dimerization or translocation with high spatiotemporal precision. Recently, we and others have added reversibility of the dimerization event as a novel feature to CID approaches. Among those, our reversible chemical dimerizer (rCD1) shows the fastest release kinetics observed, comparable to optogenetic methods. Induction and termination of enzyme activities, including phosphatidylinositol 3-kinase (PI3K) and 5-phosphatase (5Ptase), therefore allowed us to monitor the relaxation of the downstream effectors within living cells by imaging and traditional biochemical methods. Because switching off the rCD1-induced enzyme activity is sufficiently fast, it is possible to estimate kinetic parameters for enzyme activity and metabolism. Fast reversible CIDs are therefore unique tools for performing semiquantitative biochemistry in intact cells. In this chapter, we discuss advantages and constraints for the design of reversible CID applications. We provide detailed protocols for rCD1 synthesis, CID component expression in and delivery to mammalian cells and the determination of enzyme kinetics inside intact cells by a specially designed image acquisition and data analysis method.

Orientation relationship of eutectoid FeAl and FeAl2.

Fe-Al alloys in the aluminium range of 55-65 at.% exhibit a lamellar microstructure of B2-ordered FeAl and triclinic FeAl2, which is caused by a eutectoid decomposition of the high-temperature Fe5Al8 phase, the so-called ∊ phase. The orientation relationship of FeAl and FeAl2 has previously been studied by Bastin et al. [J. Cryst. Growth (1978 ▸), 43, 745] and Hirata et al. [Philos. Mag. Lett. (2008 ▸), 88, 491]. Since both results are based on different crystallographic data regarding FeAl2, the data are re-evaluated with respect to a recent re-determination of the FeAl2 phase provided by Chumak et al. [Acta Cryst. (2010 ▸), C66, i87]. It is found that both orientation relationships match subsequent to a rotation operation of 180° about a 〈112〉 crystallographic axis of FeAl or by applying the inversion symmetry of the FeAl2 crystal structure as suggested by the Chumak data set. Experimental evidence for the validity of the previously determined orientation relationships was found in as-cast fully lamellar material (random texture) as well as directionally solidified material (∼〈110〉FeAl || solidification direction) by means of orientation imaging microscopy and global texture measurements. In addition, a preferential interface between FeAl and FeAl2 was identified by means of trace analyses using cross sectioning with a focused ion beam. On the basis of these habit planes the orientation relationship between the two phases can be described by ([Formula: see text]01)FeAl || (114)[Formula: see text] and [111]FeAl || [1[Formula: see text]0][Formula: see text]. There is no evidence for twinning within FeAl lamellae or alternating orientations of FeAl lamellae. Based on the determined orientation and interface data, an atomistic model of the structure relationship of Fe5Al8, FeAl and FeAl2 in the vicinity of the eutectoid decomposition is derived. This model is analysed with respect to the strain which has to be accommodated at the interface of FeAl and FeAl2.

Lathyrus hirsutus (Caley Pea) intoxication in a herd of horses.

BACKGROUND: Caley Pea (Lathyrus hirsutus) is potentially toxic to horses, but large case series are not reported. OBJECTIVES: To describe the clinical signs of horses intoxicated with Lathyrus hirsutus and speculate on the neuroanatomical lesion localization and pathogenesis based upon the observed clinical signs. ANIMALS: Twenty-two of 25 horses ranging in age from 6 to 34 months were affected. Five affected horses were presented to the OSUCHVS for evaluation and treatment after having been attended at the ranch by a local veterinarian (ALA). An additional horse that had been euthanized was also presented for necropsy. METHODS: A case series is presented. Diagnostic evaluation included: physical examination, complete blood count, serum biochemistry, CSF analysis, EMG, ERG, upper airway endoscopy, muscle biopsy, and serum vitamin E analysis. The grain ration consumed by the affected horses was analyzed for ionophores and cultured for fungi: the hay was examined for toxic plants. RESULTS: Bermuda grass hay consumed by the horses contained large quantities of mature Lathyrus hirsutus. Acute clinical signs conform to earlier descriptions of Lathyrus hirsutus intoxication in cattle. Residual neurologic signs were characterized by incoordination in the rhythmicity of multiple gaits. Evidence of mild neurogenic muscle atrophy was recognized in 1 of 5 horses biopsied. CONCLUSIONS AND CLINICAL IMPORTANCE: Caley Pea intoxication may occur within days of seed pod consumption. The neurologic signs are unique and suggest involvement of the upper motor neuron system and regions of the spinal cord influencing voluntary motor movement. Drought conditions during plant growth may increase the risk of toxicosis.

Bioavailability of enteric-coated sodium fluoride tablets as affected by the administration of calcium supplements at different time intervals.

The gastrointestinal absorption of enteric-coated (EC) tablets of sodium fluoride (NaF) with respect to different time schedules of administration of calcium supplements in solution was tested. It was found that the simultaneous administration of these two medications under these formulations did not interfere with fluoride absorption. The calcium was also well absorbed as shown by the rise in serum ionized calcium concentration. Other schedules were studied as well, such as EC NaF tablets taken 1 hour after or 3 hours before the administration of calcium supplements. No superiority was shown, on the contrary, compared with the simultaneous administration of both medications. It was concluded that EC tablets of NaF and calcium supplements in solution can be provided simultaneously to enhance compliance.

Energy metabolism, nitrogen balance, and substrate utilization in critically ill children.

BACKGROUND: Critically ill patients are characterized by a hypermetabolic state, a catabolic response, higher nutritional needs, and a decreased capacity for utilization of parenteral substrate. OBJECTIVE: We sought to analyze the relation between a patient's metabolic state and their nutritional intake, substrate utilization, and nitrogen balance (NB) in mechanically ventilated, critically ill children receiving parenteral nutrition. DESIGN: This was a cross-sectional study in which resting energy expenditure (REE) and NB were measured and substrate utilization and the metabolic index (MI) ratio (REE/expected energy requirements) were calculated. RESULTS: Thirty-three children (mean age: 5 y) participated. Their average REE was 0.23 +/- 0.10 MJ x kg(-1) x d(-1) and their average MI was 1.2 +/- 0.5. Mean energy intake, protein intake, and NB were 0.25 +/- 0.14 MJ x kg(-1) x d(-1), 2.1 +/- 1 g x kg(-1) x d(-1), and -89 +/- 166 mg x kg(-1) x d(-1), respectively. Patients with an MI >1.1 (n = 19) had a higher fat oxidation than did patients with an MI <1.1 (n = 14; P < 0.05). Patients with lipogenesis (n = 13) had a higher carbohydrate intake than did patients without lipogenesis (n = 20; P < 0.05). Patients with a positive NB (n = 12) had a higher protein intake than did patients with a negative NB (n = 21; P < 0.001) and lower protein oxidation (P < 0.01). CONCLUSIONS: Critically ill children are hypermetabolic and in negative NB. In this population, fat is used preferentially for oxidation and carbohydrate is utilized poorly. A high carbohydrate intake was associated with lipogenesis and less fat oxidation, a negative NB was associated with high oxidation rates for protein, and a high protein intake was associated with a positive NB.

The Perlman familial nephroblastomatosis syndrome.

In 1973, Perlman et al described a familial syndrome of bilateral renal hamartomas with or without nephroblastomatosis, macrosomia, islet cell hypertrophy, unusual facies, and early lethality. Two additional sibs were recently reported by Neri et al [1984]. We report on two sibs with polyhydramnios, fetal ascites, and abdominal muscular hypoplasia, visceromegaly, and subsequent development of Wilms tumor in one of them. Delineated features of this syndrome include visceromegaly, macrosomia, renal hamartomas, nephroblastomatosis, cryptorchidism in males, unusual facial appearance, polyhydramnios, fetal ascites, and Wilms tumor but do not include hemihypertrophy, omphalocele or umbilical abnormalities, aniridia, or other conditions known to be associated with Wilms tumor. This condition should be considered primarily in the differential diagnosis of fetal ascites without hydrops and possibly in the differential diagnosis of familial Wilms tumor, polyhydramnios, congenital hepatomegaly, or nephromegaly.

Effect of acute exposure to hypergravity (GX vs. GZ) on dynamic cerebral autoregulation.

We examined the effects of 30 min of exposure to either +3GX (front-to-back) or +GZ (head-to-foot) centrifugation on cerebrovascular responses to 80 degrees head-up tilt (HUT) in 14 healthy individuals. Both before and after +3 GX or +3 GZ centrifugation, eye-level blood pressure (BP(eye)), end tidal PCO2 (PET(CO2)), mean cerebral flow velocity (CFV) in the middle cerebral artery (transcranial Doppler ultrasound), cerebral vascular resistance (CVR), and dynamic cerebral autoregulatory gain (GAIN) were measured with subjects in the supine position and during subsequent 80 degrees HUT for 30 min. Mean BP(eye) decreased with HUT in both the GX (n = 7) and GZ (n = 7) groups (P < 0.001), with the decrease being greater after centrifugation only in the GZ group (P < 0.05). PET(CO2) also decreased with HUT in both groups (P < 0.01), but the absolute level of decrease was unaffected by centrifugation. CFV decreased during HUT more significantly after centrifugation than before centrifugation in both groups (P < 0.02). However, these greater decreases were not associated with greater increases in CVR. In the supine position after centrifugation compared with before centrifugation, GAIN increased in both groups (P < 0.05, suggesting an autoregulatory deficit), with the change being correlated to a measure of otolith function (the linear vestibulo-ocular reflex) in the GX group (r = 0.76, P < 0.05) but not in the GZ group (r = 0.24, P = 0.60). However, GAIN was subsequently restored to precentrifugation levels during postcentrifugation HUT (i.e., as BP(eye) decreased), suggesting that both types of centrifugation resulted in a leftward shift of the cerebral autoregulation curve. We speculate that this leftward shift may have been due to vestibular activation (especially during +GX) or potentially to an adaptation to reduced cerebral perfusion pressure during +GZ.

Orthostatic intolerance and motion sickness after parabolic flight.

Because it is not clear that the induction of orthostatic intolerance in returning astronauts always requires prolonged exposure to microgravity, we investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy subjects before and after the brief micro- and hypergravity of parabolic flight. Concomitantly, we investigated the effect of parabolic flight-induced vomiting on orthostatic tolerance, R-wave-R-wave interval and arterial pressure power spectra, and carotid-cardiac baroreflex and Valsalva responses. After parabolic flight 1) 8 of 16 subjects could not tolerate 30 min of upright tilt (compared to 2 of 16 before flight); 2) 6 of 16 subjects vomited; 3) new intolerance to upright tilt was associated with exaggerated falls in total peripheral resistance, whereas vomiting was associated with increased R-wave-R-wave interval variability and carotid-cardiac baroreflex responsiveness; and 4) the proximate mode of new orthostatic failure differed in subjects who did and did not vomit, with vomiters experiencing comparatively isolated upright hypocapnia and cerebral vasoconstriction and nonvomiters experiencing signs and symptoms reminiscent of the clinical postural tachycardia syndrome. Results suggest, first, that syndromes of orthostatic intolerance resembling those developing after space flight can develop after a brief (i.e., 2-h) parabolic flight and, second, that recent vomiting can influence the results of tests of autonomic cardiovascular function commonly utilized in returning astronauts.

Simultaneous transcranial Doppler and arterial blood pressure response to lower body negative pressure.

Microgravity induces fluid shifts which can alter the cardiovascular responses of astronauts both during space flight and on return to Earth. The decrease in orthostatic tolerance in astronauts returning from a weightless environment can be modelled in ground-based studies using lower body negative pressure (LBNP). This study examined the physiological changes induced by LBNP and determined a reliable method of predicting the onset of presyncope to enable evaluation of countermeasures for loss of orthostatic tolerance, such as glycerol-induced hyperhydration. Six healthy male subjects, aged 18 to 45 years, were each subjected to two LBNP tests, with or without glycerol ingestion. Continuous, non-invasive measurements of middle cerebral artery blood flow velocities (CBF) by transcranial Doppler, arterial blood pressure (Finapres ABP), ECG and LBNP box pressures were recorded during each test. Negative pressure was increased in three minute intervals until symptoms of presyncope were observed. An increase in heart rate (HR), a relatively constant mean ABP and a steady decline in mean CBF were consistently observed as the box pressure was decreased. The continuous on-line measurements clearly showed consistent dynamic changes in both CBF and ABP waveforms in response to changes in LBNP. At the onset of presyncope, sudden drops in mean ABP, HR and mean CBF were typically noted, the latter providing the earliest indication of presyncope. The time required to re-establish original baseline values of CBF and ABP after release of box pressure varied widely from six to over ten minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral blood flow velocities by transcranial Doppler during parabolic flight.

Microgravity is produced for 20 to 30 seconds in NASA's KC-135 aircraft at the end of a 2 G pullup for each of 40 parabolas per flight. Continuous transcranial Doppler ultrasound, arterial blood pressure, and acceleration levels were recorded for 12 male and 8 female healthy subjects without known cardiovascular or cerebrovascular disease. Recordings were made throughout 10 parabolas per subject in each of the supine, sitting, and standing postures. The data were digitized for off-line analysis using Fast Fourier Transform and other signal processing methods. A phase lag in changes to transcranial Doppler waveforms from the onset of acceleration was more pronounced in the standing position than in the sitting position. There was less of a phase lag in the supine position. These ultrasound changes preceded the more delayed variations in arterial blood pressure. The KC-135 provides a unique short-term environment that allows measurement of the human response to variations in acceleration but limits physiological monitoring of responses to a steady state of microgravity.

Transcranial Doppler studies of flow velocity in middle cerebral artery in weightlessness.

Physiological adaptation to weightlessness requires changes in cardiovascular system parameters to maintain homeostasis in the presence of cephalic fluid shifts. The cerebral circulation must respond immediately to these systemic changes or impairment of cerebral function will occur. Blood flow velocities of the middle cerebral artery were measured by transcranial Doppler (TCD) ultrasound in NASA's KC-135 aircraft from four healthy subjects in the supine position. Transcranial Doppler data with accompanying acceleration information were analyzed in three segments in each parabola. Cardiac cycles for each segment of all 20 parabolas were pooled for individual subjects. A Student's t test on the data revealed statistically significant differences in the mean and peak frequencies, systolic/diastolic ratios and Doppler power between positive 2 gz and microgravity (10(-2) gz) as well as between positive 2 gz and negative 2 gz. Velocity waveform profiles differed for the first one third of each segment, with a more resistive waveform developing during the last two thirds. Changes in systemic arterial resistance and/or raised intracranial pressure may contribute to these TCD waveform changes.

Device for extradural monitoring of intracranial pressure: technical note.

An ICP-monitoring device utilizing an extradural method is described. Clinical and laboratory use has shown it to be easily installed, safe, accurate, and reliable. It can be used with currently available transducers and monitoring equipment. It is hoped that this simple device will encourage the increased use of ICP monitoring.

Respiratory system mechanics in patients receiving aerosolized ribavirin during mechanical ventilation for suspected respiratory syncytial viral infection.

Respiratory syncytial virus (RSV) is an important respiratory pathogen for infants. Aerosolized ribavirin (AR) has been used in mechanically ventilated (MV) patients with RSV bronchiolitis. The purpose of this study was to measure respiratory system mechanics (RSM) in pediatric patients requiring MV and receiving AR for suspected RSV. Patients were prospectively randomized to receive AR, either at a regular dose (RD) (6 g/300 mL over 18 hr/day) or a high dose (HD) (6 g/100 mL over 2 hr, three times a day). To measure changes in RSM, a passive exhalation technique was used before and after each dose of AR; time constant (tc) in s, resistance (Rrs) in cmH(2)O/mL/kg/s, and quasistatic compliance (Crs) in mL/cmH(2)O/kg were measured. Airway pressure and flow signals were obtained and analyzed using a pneumotachograph, a differential pressure transducer, and a computer interface. Statistical analysis was done by Mann-Whitney and Wilcoxon rank tests. Thirteen patients were enrolled: 5 patients in the HD group (mean age of 52 months), and 8 patients in the RD group (mean age of 10 months). Four and 5 patients were positive for RSV by ELISA in the HD and RD groups, respectively. The RSM in the HD group were: tc, 0.58 +/- 0.15 s and 0.55 +/- 0.20 s before and after AR, respectively; Rrs, 0.03 +/- 0. 03 cmH(2)0/mL/kg/s and 0.02 +/- 0.02 cmH(2)0/mL/kg/s, respectively; and Crs, 0.63 +/- 0.21 mL/cmH(2)O/kg and 0.70 +/- 0.13 mL/cmH(2)O/kg, respectively. In the RD group, the RSM were: tc, 0.37 +/- 0.12 s and 0.31 +/- 0.10 s before and after AR, respectively; Rrs, 0.03 +/- 0.02 cmH(2)0/mL/kg/s and 0.02 +/- 0.01 cmH(2)0/mL/kg/s, respectively (P < 0.05); and Crs, 0.46 +/- 0.20 mL/cmH(2)O/kg and 0.46 +/- 0.19 mL/cmH(2)O/kg, respectively. We conclude that the use of AR for bronchiolitis in infants and young children during mechanical ventilation does not worsen RSM.

Rectal-scalp temperature difference predicts brain death in children.

When brain death in children occurs, commonly the scalp feels cold despite a normal core temperature. This phenomenon might reflect absent cerebral blood flow and metabolic activity. The authors, therefore, measured rectal-scalp temperature differences in critically ill comatose children to test the hypothesis that a particular temperature difference may correlate with clinical brain death. In a prospective cohort study set in a pediatric intensive care unit, rectal-scalp, rectal-abdomen, and rectal-mastoid temperatures in critically ill comatose children older than 18 months of age were measured before and during brain death evaluations. Twelve children were enrolled. Clinical criteria for brain death were met by seven patients, and five patients survived. All of the seven children who died had rectal-scalp temperature differences greater than 4 degrees C (mean = 6.7, range = 6.0-7.4) at the time of clinical brain death. No survivor had a rectal-scalp temperature difference of 4 degrees C at any time (mean = 3.4, range = 2.9-3.9). Rectal-scalp temperature differences of those who died and those who survived were significantly different at the P < 0.005 level. Rectal-abdomen and rectal-mastoid temperature differences did not correlate with clinical brain death or rectal-scalp temperature difference. In this preliminary study a rectal-scalp temperature difference of greater than 4 degrees C correlates with clinical criteria for brain death in children.

Nosocomial infections in the pediatric intensive care unit.

Pediatric intensive care units have contributed considerably to the management of children with severe diseases and life-threatening conditions. The use of mechanical ventilation, invasive monitoring, and indwelling catheters increase the risk for nosocomial infection. Improving infection control practices and surveillance can significantly reduce the incidence of nosocomial infections.