Nuclear Magnetic Resonance Chemical Shift as a Probe for Single-Molecule Charge Transport.

Existing modelling tools, developed to aid the design of efficient molecular wires and to better understand their charge-transport behaviour and mechanism, have limitations in accuracy and computational cost. Further research is required to develop faster and more precise methods that can yield information on how charge transport properties are impacted by changes in the chemical structure of a molecular wire. In this study, we report a clear semilogarithmic correlation between charge transport efficiency and nuclear magnetic resonance chemical shifts in multiple series of molecular wires, also accounting for the presence of chemical substituents. The NMR data was used to inform a simple tight-binding model that accurately captures the experimental single-molecule conductance values, especially useful in this case as more sophisticated density functional theory calculations fail due to inherent limitations. Our study demonstrates the potential of NMR spectroscopy as a valuable tool for characterising, rationalising, and gaining additional insights on the charge transport properties of single-molecule junctions.

Structure determination and crystal chemistry of large repeat mixed-layer hexaferrites.

Hexaferrites are an important class of magnetic oxides with applications in data storage and electronics. Their crystal structures are highly modular, consisting of Fe- or Ba-rich close-packed blocks that can be stacked in different sequences to form a multitude of unique structures, producing large anisotropic unit cells with lattice parameters typically >100 Šalong the stacking axis. This has limited atomic-resolution structure solutions to relatively simple examples such as Ba2Zn2Fe12O22, whilst longer stacking sequences have been modelled only in terms of block sequences, with no refinement of individual atomic coordinates or occupancies. This paper describes the growth of a series of complex hexaferrite crystals, their atomic-level structure solution by high-resolution synchrotron X-ray diffraction, electron diffraction and imaging methods, and their physical characterization by magnetometry. The structures include a new hexaferrite stacking sequence, with the longest lattice parameter of any hexaferrite with a fully determined structure.

Photochemical CO2 reduction in water using a co-immobilised nickel catalyst and a visible light sensitiser.

A dye-sensitised CO2 reduction photocatalyst that operates in water is reported. Transient spectroscopy demonstrates that the facile co-immobilisation of a Ru dye and a Ni CO2 reduction electrocatalyst enables efficient on-particle electron transfer leading to photocatalytic activity that greatly exceeds the equivalent solution based system.

The synthesis and structure of chiral enamine N-oxides.

Chiral enamine N-oxides have been synthesised by a diastereoselective intermolecular reverse-Cope cycloaddition reaction between chiral hydroxylamines and activated acetylenes. Their structures have been investigated by NMR, X-ray crystallography and computational methods.

Reliability of lower extremity alignment measurement using radiographs and PACS.

PURPOSE: Lower extremity alignment is an important consideration prior to cartilage surgery and/or osteotomy about the knee. This is measured on full length standing hip to ankle radiographs, which has traditionally been done using hard copy radiographs. However, the advent of PACS (Picture Archiving and Communication Systems) has allowed these measurements to be done on computer based digital radiographs. The objectives of this study were to evaluate the intra- and inter-observer reliability of lower limb alignment measures manually obtained from hard copy radiographs versus using the Philips Easy Vision system, and to assess the subjective ease of use for the two methods. METHODS: Forty-two patients who underwent surgery and who had a standing hip to ankle radiograph on file were identified. Four raters, including two radiologists and two orthopaedic surgeons, measured each hard copy radiograph and computer image on two separate occasions. Three measurements were recorded for each hard copy radiograph and computer image-width of tibial plateau, the distance from the medial aspect of the tibial plateau to the weight-bearing line, and the mechanical axis. RESULTS: All correlations for this study were high. For tibial plateau data, the hard copy radiographs compared to PACS demonstrated intra-class correlation coefficients (ICC) ranging from 0.93 to 0.99 for inter-rater reliability for the four raters. The ICC for intra-rater reliability for hard copies ranged from 0.90 to 0.99 and for PACS from 0.94 to 0.99. The inter-rater data comparing raters ranged from 0.87 to 0.98 for hard copy radiographs and from 0.98 to 0.99 for PACS. For mechanical axis data, the ICC for hard copy radiograph compared to PACS ranged from 0.93 to 0.97 for the intra-rater reliability for the four raters. The intra-rater reliability for mechanical axis data on hard copy radiograph ranged from an ICC of 0.86 to 0.96, and for PACS the ICC ranged from 0.93 to 0.99. The inter-observer data for hard copy radiographs using the mechanical axis ranged from 0.88 to 0.94 and for PACS ranged from 0.93 to 0.97. The physicians rated PACS as statistically significantly easier to use when compared to hard copy (P = 0.03). CONCLUSION: Evaluation of lower extremity alignment using two techniques prior to knee surgery was found to have higher inter- and intra-observer reliability using PACS software. PACS is now used prior to cartilage surgery and/or osteotomy to measure both alignment and the location of the weight bearing line on the tibial plateau both before and after surgery. LEVEL OF EVIDENCE: Diagnostic study, Level I.

Early interventions involving parents to improve neurodevelopmental outcomes of premature infants: a meta-analysis.

OBJECTIVE: To determine in a systematic review, whether interventions for infant development that involve parents, improve neurodevelopment at 12 months corrected age or older. STUDY DESIGN: Randomized trials were identified where an infant intervention was aimed to improve development and involved parents of preterms; and long-term neurodevelopment using standardized tests at 12 months (or longer) was reported. RESULT: Identified studies (n=25) used a variety of interventions including parent education, infant stimulation, home visits or individualized developmental care. Meta-analysis at 12 months (N=2198 infants) found significantly higher mental (N=2198) and physical (N=1319) performance scores favoring the intervention group. At 24 months, the mental (N=1490) performance scores were improved, but physical (N=1025) performance scores were not statistically significant. The improvement in neurodevelopmental outcome was not sustained at 36 months (N=961) and 5 years (N=1017). CONCLUSION: Positive clinically meaningful effects (>5 points) are seen to an age of 36 months, but are no longer present at 5 years.

Epithelial apoptosis in mechanistically distinct methods of injury in the murine small intestine.

Gut epithelial apoptosis is involved in the pathophysiology of multiple diseases. This study characterized intestinal apoptosis in three mechanistically distinct injuries with different kinetics of cell death. FVB/N mice were subjected to gamma radiation, Pseudomonas aeruginosa pneumonia or injection of monoclonal anti-CD3 antibody and sacrificed 4, 12, or 24 hours post-injury (n=10/time point). Apoptosis was quantified in the jejunum by hematoxylin and eosin (H&E), active caspase-3, terminal deoxynucleotidyl transferase dUTP-mediated nick end labeling (TUNEL), in situ oligoligation reaction (ISOL,) cytokeratin 18, and annexin V staining. Reproducible results were obtained only for H&E, active caspase-3, TUNEL and ISOL, which were quantified and compared against each other for each injury at each time point. Kinetics of injury were different with early apoptosis highest following radiation, late apoptosis highest following anti CD3, and more consistent levels following pneumonia. ISOL was the most consistent stain and was always statistically indistinguishable from at least 2 stains. In contrast, active caspase-3 demonstrated lower levels of apoptosis, while the TUNEL assay had higher levels of apoptosis in the most severely injured intestine regardless of mechanism of injury. H&E was a statistical outlier more commonly than any other stain. This suggests that regardless of mechanism or kinetics of injury, ISOL correlates to other quantification methods of detecting gut epithelial apoptosis more than any other method studied and compares favorably to other commonly accepted techniques of quantifying apoptosis in a large intestinal cross sectional by balancing sensitivity and specificity across a range of times and levels of death.

Progressive symptoms and signs following institution of highly active antiretroviral therapy and subsequent antituberculosis therapy: immune reconstitution syndrome or infection?

A 36 year old man presented with weight loss, cough, fever, and exertional dyspnoea shortly after a diagnosis of HIV infection. Symptoms and initial radiological abnormalities worsened after highly active antiretroviral therapy was started. An eventual diagnosis was established but multiple problems occurred throughout the treatment period. Differentiation between immune reconstitution inflammatory syndrome and an infective cause was problematic.

Characterization of pro-apoptotic and matrix-degradative gene expression following induction of osteoarthritis in mature and aged rabbits.

OBJECTIVE: The genetic and molecular changes leading to the distinctive alterations of aged cartilage and its propensity for developing osteoarthritis (OA) are unknown. We hypothesized that pro-apoptotic and matrix-degradative gene expression in a rabbit model of induced OA using mature and aged animals might elucidate this relationship. METHODS: Groups of six mature and aged rabbits underwent anterior cruciate ligament transection (ACLT) and were sacrificed 4 weeks after surgery to create an Outerbridge grade II OA. RNA was extracted from the articular cartilage and menisci of the affected knee and was examined with regard to expression of the following genes: Caspase 8, Fas, Fas ligand (Fas-L), p53, aggrecanase, matrix metalloproteinase (MMP)-1, and MMP-3-MMP-13. A second cohort of mature and aged animals was sacrificed with no intervention to the joint and gene expression was assessed in a similar manner. RESULTS: Fas and Caspase 8 showed significantly increased expression in the cartilage of mature animals with induced OA when compared to unoperated controls while induction of OA in aged rabbits did not significantly increase expression of any of the apoptosis genes. Among unoperated animals, the aged cohort showed significantly increased expression of MMP-1 and aggrecanase in cartilage when compared to mature animals. MMP-13 expression was upregulated in aged cartilage following induction of OA. Although ACLT animals showed gross thinning and irregularities within the meniscus, only the expression of Caspase 8 in the aged rabbits was significantly increased after induction of OA. CONCLUSIONS: Aging of articular cartilage shares some qualities with the development of OA, as seen in the parallel increases in gene expression of Caspase 8 and Fas. Although this may imply a common mechanism of cartilage degeneration in aging and OA or even a spectrum of disease, both are complex processes requiring further study.

Isolated mental developmental delay in very low birth weight infants: association with prolonged doxapram therapy for apnea.

OBJECTIVE: We investigated factors associated with isolated mental delay in infants weighing < 1250 g at birth. STUDY DESIGN: With a case-control design, matching variables for 40 cases included gestation, birth weight, sex, grade of intraventricular hemorrhage, and socioeconomic status. Case subjects had a mental developmental index < 70, and controls had a mental developmental index > or = 85, according to the Bayley Scales of Infant Development II at 18 months' corrected age. RESULTS: There were no differences between the case and control subjects for neonatal complications and antenatal or postnatal steroid use. There was a marked difference in the cumulative dosage and duration of doxapram therapy used for apnea of prematurity (total dose 2233 +/- 1927 mg vs 615 +/- 767 mg, P < .001; duration 45.2 +/- 32.5 days vs 19.4 +/- 23.4 days, P < .001 for case subjects and control subjects, respectively). Multivariate analysis did not identify additive predictive variables. CONCLUSION: Isolated mental delay in infants weighing < 1250 g at birth was associated with the total dosage and duration of doxapram therapy for severe apnea. Although this may be a marker for cerebral dysfunction manifesting as apnea of prematurity, possible adverse effects of doxapram or its preservative, benzyl alcohol, on the developing brain deserve further study.

Cerebral infarction in the term newborn: clinical presentation and long-term outcome.

OBJECTIVE: We evaluated the long-term neurodevelopmental outcome of cranial computed tomography (CT)-documented cerebral infarction in term neonates to ascertain factors that would help to predict the risk of subsequent neurodevelopmental sequelae in early childhood. STUDY DESIGN: From 1983 to 1997, all surviving neonates from two level III neonatal intensive care units were prospectively identified and subsequently assessed in childhood. Clinical presentation was characterized by retrospective chart review and blinded re-reading of computed tomography (CT) scans. Perinatal events were compared with neurodevelopmental outcome. RESULTS: Forty-six children were followed up for a mean of 42.1 months (range, 18-164 months). Neurodevelopmental outcome was normal in 15 and abnormal in 31. A single disability was present in 8, and multiple disabilities were present in 23. Cerebral palsy was present in 22 and cognitive impairment in 19. Abnormal findings on neurologic examination at discharge and seizures in the neonatal period were associated with the presence of one or more childhood disabilities. The site or laterality of the vascular distribution of the lesion on neonatal CT did not correlate with long-term outcome. CONCLUSION: After cerebral infarction in the neonatal period, one third of term infants have normal long-term development. Neonatal seizure history and the findings on neurologic examination at discharge help in counseling parents about the possible long-term outcome of neonatal stroke.

A cost-effectiveness analysis of the application of nitric oxide versus oxygen gas for near-term newborns with respiratory failure: results from a Canadian randomized clinical trial.

OBJECTIVE: To conduct a cost-effectiveness analysis of the use of inhaled nitric oxide (NO) vs. oxygen administered to near-term (gestational age > or =34 wks) newborns with severe respiratory illness that were referred for consideration of extracorporeal membrane oxygenation (ECMO). DESIGN: The cost-effectiveness analysis is based on outcome and utilization data from two multicentered randomized clinical trials conducted by the Canadian Inhaled Nitric Oxide Study group, one for patients with congenital diaphragmatic hernia (CDH) and one for patients without CDH. Data from the western Canadian ECMO center were used to establish costs. SETTING: Patients were cared for in Canadian regional neonatal intensive care units, including two ECMO centers. Air transport was used for transporting patients between centers. PATIENTS: Term and near-term newborns with severe respiratory illness who were receiving maximum conventional therapy and whose oxygenation index was >40. INTERVENTIONS: Patients randomly received NO or oxygen. If their conditions deteriorated, they qualified for ECMO. Not all that qualified for ECMO received it because of individual parent/ physician preferences. MEASUREMENTS AND MAIN RESULTS: The cost-effectiveness ratio was the ratio of net cost (including neonatal intensive care, ECMO, and transport) to net outcome (survival) for the two interventions. For non-CDH cases, the cost-effectiveness ratio was $36,613 (Canadian) per life saved; the confidence intervals were wide and the results were not statistically significant. For CDH patients, the death rate was lower for oxygen and the oxygen patients cost less; the results were not statistically significant. CONCLUSIONS: The small numbers of patients in the trials precluded significant results. Further, our results have a short-term time horizon (discharge to home or death). Thus, for non-CDH patients, the favorable ratio provides very qualified evidence in favor of NO.

Prolonged use of pancuronium bromide and sensorineural hearing loss in childhood survivors of congenital diaphragmatic hernia.

Sensorineural hearing loss (SNHL) is a significant neurologic morbidity in survivors of neonatal congenital diaphragmatic hernia (CDH), with a reported incidence of up to 60%. In a historical cohort study of 37 neonates with CDH, we investigated the use of pancuronium bromide (PB) and common ototoxic drugs during the neonatal period and their relationship to SNHL in childhood survivors. Survivors with SNHL (n = 23) had significantly higher cumulative dose of PB administered during the neonatal illness than survivors without SNHL (n = 14). The cumulative dose and duration of PB use significantly correlated (r = 0.66-0.81) and independently predicted (adjusted r (2) = 0.42-0.64) the greatest intensity (in decibels) and the widest band (lowest frequency in hertz) loss of SNHL. No differences were identified between survivors with and without SNHL regarding demographic and neonatal characteristics (including oxygenation and ventilation variables and the cumulative dose and duration of therapy with aminoglycosides, vancomycin, and furosemide), although survivors with SNHL had received a modestly higher cumulative dose of ethacrynic acid than survivors without SNHL. Although we show that prolonged administration of PB during the neonatal period is associated with SNHL in childhood survivors of CDH, further multicenter studies are required to investigate the possible etiologies of SNHL in this high-risk population.

EEG and long-term outcome of term infants with neonatal hypoxic-ischemic encephalopathy.

OBJECTIVE: The prognostic value of a burst suppression pattern (BSP) on the electroencephalograph (EEG) in the prediction of long-term outcome for full term newborns with hypoxic-ischemic encephalopathy (HIE) is well established. The purpose of our study was to compare the patterns of burst suppression on EEG with long-term neurological outcome in term infants with HIE. METHODS: We retrospectively analyzed all records of all full-term newborn infants born at the University of Alberta Hospital between January 1, 1991 and December 31, 1992, who had clinical evidence of HIE and had at least one EEG during the first week of life. The EEGs were reviewed and blindly subclassified into a BSP, or if the pattern was not continuous or was incomplete, a modified burst suppression pattern (MBSP), based on specified electrophysiological criteria. The long-term neurological outcome was then correlated with the EEG pattern. RESULTS: Twenty-three full-term infants were studied. Fifteen had a BSP on EEG and 8 had a MBSP. Six of 15 infants with a BSP died. Of the 9 survivors with a BSP, 7 are disabled and two are normal. Of the 8 infants in the MBSP group, one infant died, two are disabled and 5 are normal. In the BSP group, 6/7 disabled infants developed cerebral palsy while in the MBSP group, only one developed cerebral palsy. CONCLUSION: The results are suggestive of a better outcome for infants with neonatal HIE and MBSP on EEG compared with those with a BSP. Subclassification of the EEG changes of neonatal HIE into BSP and MBSP may give a more accurate prediction of outcome in perinatal asphyxia and assist in discussion with parents about prognosis.

Early childhood neurodevelopment in very low birth weight infants with predischarge apnea.

Apnea commonly occurs in preterm infants and may persist beyond term. We prospectively investigated the relationship between apnea that persisted beyond 35 weeks post-conceptional age and subsequent neurodevelopment in early childhood. Between January, 1990-November, 1993, we performed predischarge respiratory recordings, using 24-hr, 4-channel pneumography, at 35 weeks or more of postconceptional age in 164 infants (birth weight, <1,250 g; gestational age, < or = 32 weeks), who subsequently underwent multidisciplinary neurodevelopmental assessment at 15-64 (median 24) months of adjusted age. The duration of initial artificial ventilation for respiratory distress syndrome and the grade of intraventricular hemorrhage were independent predictors of neurodevelopmental outcome. Mean oximetry desaturation and frequency of predischarge apnea correlated with mental and motor developmental scores. Mean oximetry desaturation during apnea was an independent predictor for motor score in the total population, and for both mental and motor scores in 50 infants with grade 3 or 4 intraventricular hemorrhage, but not in 114 infants without grade 3 or 4 intraventricular hemorrhage. Despite its limited predictability for early childhood neurodevelopment, predischarge respiratory recordings may be useful in predicting subsequent neurodevelopment of high-risk preterm infants, especially those with severe intraventricular hemorrhage.

The outcome of very low birth weight neonates (

Although inhaled nitric oxide (INO) improves oxygenation in critically ill neonates, the neurodevelopmental outcome of premature neonates with severe hypoxemic respiratory failure treated with INO has not been reported. Mortality and prospective neurodevelopmental assessment in early childhood were studied in a cohort of 24 very low birth weight neonates (

High prevalence of sensorineural hearing loss among survivors of neonatal congenital diaphragmatic hernia. Western Canadian ECMO Follow-up Group.

OBJECTIVE: This study aimed to determine the prevalence of sensorineural hearing loss (SNHL) in 2-5-year-old survivors with neonatal respiratory failure due to congenital diaphragmatic hernia (CDH) with or without the need for extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: The study design was a prospective, multicenter, longitudinal outcome study of consecutively surviving neonates admitted to a single tertiary intensive care unit. SETTING: The study was conducted at four audiologic departments affiliated with tertiary-level intensive care follow-up programs. PATIENTS: Thirty-seven surviving children receiving neonatal intensive care from February 1989 through January 1995 for neonatal respiratory failure due to CDH were studied. Excluded were 15 children with early death and I child lost to follow-up. INTERVENTION: The initial treatment depended on the severity of neonatal respiratory failure: ECMO-treated (n=31, 20 survivors) (death before ECMO initiation, 2) and non-ECMO treated (n=20, 17 survivors, another survivor lost to follow-up). MAIN OUTCOME MEASURE: Early childhood audiologic test results were measured. RESULTS: Sensorineural hearing loss was found in almost 60% of subjects: ECMO-treated, 12 (60%) of 20; non-ECMO-treated, 10 (59%) of 17. Of the 22 children with SNHL, 16 had mild- to-moderate low-frequency sloping to moderate-to-severe high-frequency loss. Of the remaining, six had severe-to-profound loss at 500 Hz and above. Seventeen children had normal responses to sound as newborns or in infancy. Five children were not tested. Documented progression was found in nine children. Twenty children currently are using amplification, and 2 have had cochlear implantation. CONCLUSIONS: Of children with CDH in this area presenting early with severe neonatal respiratory failure, SNHL developed in 60% by 2-5 years of life. Ongoing monitoring of the hearing status of children with CDH is imperative.