Construct validity of the continuous attention test for children.

The purpose of this study was to evaluate the construct validity of the Continuous Attention Test for Children (the CAT), a clinical measure of vigilance. To examine convergent and discriminant validity, a multitrait-multimethod matrix was used. It was predicted that the CAT would correlate with other neuropsychological measures involving vigilance, but not with measures involving potential confounds (e.g., short-term memory). Participants were 47 children, aged 6 to 11, referred for neuropsychological assessment. Results partially supported discriminant validity, but convergent validity was weak. That is, findings suggest that the CAT measures an ability distinct from those assessed by some other popular tests involving vigilance. However, method-related confounds may remain. The CAT appears to add useful information in the context of clinical evaluations.

Sustained attention and impulsivity in children with Tourette syndrome: comorbidity and confounds.

We sought to determine whether Tourette syndrome (TS) was related to attentional disturbance independent of Attention Deficit Hyperactivity disorder (ADHD) and obsessive-compulsive symptoms (OCS), two comorbid conditions associated with attentional problems in other populations. Participants were 74 children [21 with uncomplicated TS (TS-Only), 14 with TS and ADHD (TS-ADHD), 21 with ADHD, and 18 controls]. Impaired sustained attention and impulsivity on a Continuous Performance Task were uncommon in the TS-Only group, but common in TS-ADHD and ADHD. The TS-ADHD group was less impulsive than the ADHD group, but had a higher rate of whole-body tics than the TS-Only group, raising questions about the diagnosis of ADHD in TS. OCS was not an independent risk factor for attention problems. However, the association of tic severity and impulsivity was consistent with the theory that TS involves dysfunction in cortical-subcortical circuits mediating behavioral inhibition.

Femtosecond infrared pulses tunable from 9 to 18 mum at an 88-MHz repetition rate.

Femtosecond mid-infrared laser pulses that are continuously tunable in the wavelength range from 9 to 18mum are demonstrated. These nearly bandwidth-limited pulses are generated by phase-matched difference-frequency mixing within the broad spectrum of 20-fs pulses from a mode-locked Ti:sapphire laser in GaSe. A direct determination of the pulse duration at 11.5mum gives a value of 140 fs. The average mid-infrared power of 1muW is ~100 times greater than that for infrared generation by non-phase-matched optical rectification.

Enhancement of radiation-induced regrowth delay by gemcitabine in a human tumor xenograft model.

Gemcitabine, a cytidine nucleoside analogue, has schedule-dependent antitumor activity in vitro and in vivo. Gemcitabine also has dose- and time-dependent radiosensitization properties in vitro. Thus it may have therapeutic application in combination with radiation. The aims of this study were to investigate whether gemcitabine could enhance radiation-induced tumor regrowth delay in a human squamous carcinoma (FaDu) xenograft in nude mice and to examine the effect of gemcitabine on radiation-induced apoptosis in in vivo tumors. Radiation was given locally to the tumors twice daily in 2 Gy fractions over 2 weeks for 5 days/week. Significant regrowth delay enhancement was observed which was dependent on gemcitabine schedule. Effective schedules using maximum tolerated gemcitabine doses were twice weekly and once weekly, but not daily. Significant toxicity occurred with radiation plus twice weekly gemcitabine, but enhancement was seen using gemcitabine doses well below the maximum tolerated dose. Both gemcitabine and radiation led to apoptotic cell death, but this was not increased when both treatments were combined. These results indicate that gemcitabine may be of therapeutic value as a radiation enhancer in the treatment of human cancers. Preliminary studies suggest that increased apoptotic cell death is not a mechanism leading to this enhancement.

Radioenhancement by cisplatin with accelerated fractionated radiotherapy in a human tumour xenograft.

The aim of the present study was to investigate whether cisplatin would enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation therapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tumours were exposed to twice-daily 2-Gy fractions, applied 6 h apart over 2 weeks, 5 days a week, alone or combined with cisplatin given at maximally tolerated doses in three different schedules: (1) i.p. as a single bolus (SB) or (2) i.p. as a daily bolus at 30 min before the first daily radiation fraction or (3) s.c. as a continuous infusion through a mini-osmotic pump over 13 days, commencing 24 h prior to the first daily radiation fraction. The end point for the study was tumour growth delay (TGD), calculated as the difference between the delay in regrowth to 200% of the initial tumour size in treated versus control mice. SB cisplatin plus radiation showed only an additive effect on TGD, whereas daily-bolus and continuous-infusion cisplatin demonstrated a greater than additive effect when combined with accelerated fractionated radiation in this human tumour model. Cisplatin appears to be especially beneficial as a radiation enhancer when given throughout the course of radiation.

Generation of 16-fs pulses at 425 nm by extracavity frequency doubling of a mode-locked Ti:sapphire laser.

An efficient doubling scheme capable of producing 16-fs pulses centered at 425 nm with an average power of 40 mW is described. The system uses 15-fs pulses from a continuous-wave mode-locked Ti:sapphire oscillator centered at 850 nm. The pulse characteristics resulting from doubling with beta-barium borate crystals of various lengths are presented. The results compare favorably with previous attempts at intracavity doubling and provide a more convenient route to femtosecond experiments with fully synchronized second-harmonic radiation.

The teratogenic effects of salicylic acid on the developing nervous system in rats in vitro.

Aspirin ingestion in humans and animals has been reported to lead to a range of undesirable outcomes, including fetal death, growth retardation, and congenital abnormalities. Rat embryos were cultured for 48 h in 100-300 micrograms/ml of salicylic acid, a metabolite of aspirin, days 9.5-11.5 of gestation. When compared to growth in control embryos, a significant dose-dependent decrease in crown-rump lengths, somite numbers, and yolk sac diameters was observed. There was also a significant increase in overall dysmorphology, including eye, brachial arch, and heart anomalies, and an absence of forelimb buds. The neural tube was especially vulnerable and had frequently failed to close. Cellular and ultrastructural examination revealed extensive cell death in the neuroepithelium, with a lesser effect on the mesenchymal cells. Large condensed blebs projected into the ventricular lumen, and cell membranes as well as the basal lamina were severely disrupted, with all cytoplasmic organelles affected in dying cells. It is likely that the extensive cell necrosis and blebbing in the developing neuroepithelium at the site of neural tube fusion may be involved in failed neurulation, while necrosis at other sites in the cranial neuroepithelium may be linked with previously reported intellectual and behavioural abnormalities.

A quantitative and morphological study of ectodermal microvilli in ten areas in the control and experimental prenatal rat.

This study provides a baseline of mainly quantitative morphologic information in relation to the ectodermal microvilli in ten areas in the control and experimental prenatal rat with special reference to the period of neural tube closure. Embryos from six litters were used and ten areas were examined mainly with the scanning electron microscope. Statistical analysis showed no significant difference between litters nor between the ten areas examined. In the 376 hr (day 15.6) fetus only the ectodermal cells of the nostril region demonstrated a rich population of microvilli, a fact possibly associated with late maturation of that region. Some evidence is provided to show that there is an increase in the population of microvilli in the 276 hr (day 11.5) embryo following experimentally induced zinc deficiency and introduction of nicotine in the culture medium. The possible mechanisms underlying the increase in ectodermal microvilli are i) an attempt by ectodermal cells to absorb nutrients, ii) a reflection of cells under stress, iii) failure of early embryonic ectodermal cells to shed microvilli normally associated with developmental changes, and iv) a generalized developmental delay rather than some cellular response to a trace element nutritional deficiency and a teratogen.

The teratogenic effects of nicotine in vitro in rats: a light and electron microscope study.

Cigarette smoking in pregnant women has been shown to lead to intrauterine growth retardation and fetal death, and possibly also to neural dysmorphology and long-term learning deficits in the offspring. Because the teratogenic agent in cigarette smoke remains controversial, the present study on rat embryos in culture examined specifically whether nicotine can cause neural dysmorphology and, hence, act as a nervous system teratogen. This in vitro study confirmed previous reports in utero that nicotine leads to growth retardation, and, in addition, demonstrated that development of the nervous system, particularly the forebrain, as well as the branchial arches was impaired, possibly leading to microcephaly and cleft palate respectively in term fetuses. Cellular disruption and necrosis occurred in the neuroepithelium and underlying mesenchyme, with the effect being dose dependent. Ultrastructurally, there was severe disruption of cell and organelle membranes, with many healthy cells containing engulfed, whole condensed or remnants of dead cells. This study demonstrates that nicotine acts as a nervous system teratogen leading to gross and cellular dysmorphology. Suggested mechanisms for nicotine action include the possibility that the highly lipid soluble teratogen may exert its effects directly on the membranes or indirectly through oxidative membrane damage.

Evidence of difficulties in sustained attention in children with ADDH.

It has been suggested that children with ADDH have specific difficulties in sustained attention. Despite some early studies supporting this position, many recent reports using continuous performance tests (CPTs) have failed to confirm this hypothesis. Possible reasons for this discrepancy are outlined and an attempt to corroborate and extend an earlier study (Sykes, Douglas, & Morgenstern, 1973) was undertaken. CPT results in normal children indicated that changes in performance over time, although not affected by gender, were influenced by age. Data from ADDH subjects indicated that they performed significantly more poorly with time on task than did controls. These results suggest that the ability to sustain attention increases with age and does not vary by gender. Furthermore, difficultues in the ability to sustain attention can be demonstrated in children with ADDH. Finally, it is suggested that within-age-level comparisons between groups of ADDH and controls would be more clinically sensitive than across-age-group comparisons.

Psychosocial research and the hospitalized adolescent: approaches and challenges.

Hospitalized adolescents regularly become participants in psychosocial research within acute-care hospital settings. Examples of studies within the four common approaches used to examine and describe the behaviors of this group (instructional, theoretical, informational, experimental) are briefly described. The impact of various illness states (acute, chronic, terminal) and the readiness of the adolescent to be involved in such research are also discussed. The measurement of adolescent behavior and appropriate instrumentation are presented as areas of challenge for future psychosocial research.

Cortico-cortical connections of the motor cortex in the brushtailed possum (Trichosurus vulpecula).

Cortico-cortical connections of motor cortex in the marsupial brushtailed possum were traced by making injections of horseradish peroxidase (HRP) into two parts of motor cortex: the rostral agranular part which does not overlap somatosensory cortex, and the caudal part which does. Following injections in motor cortex, labelled neurons were observed on the same side of the brain within somatosensory areas 1 and 2 and in parietal cortex just caudal to S1, with most neurons in cortical Layers 2-4. Commissural connections were found in half of the experiments, with many labelled neurons in cortical Layer 5. We have compared the pattern of cortico-cortical connections in the possum with those seen in some other mammals, which appear generally similar.