Vestibular testing in children - The suppression head impulse (SHIMP) test.

INTRODUCTION: The incidence of vestibular disorders and vertigo during childhood is increasing and pediatric clinicians have become more sensitive to children's balance disorders; thus, there is a need for appropriate detection test procedures for peripheral vestibular hypofunction. In order to ensure a reliable diagnosis and minimize misdiagnosis, a standardized clinical procedure via careful history and clinical examination is recommended. However, children, especially, are often unable to verbalize "vertigo" in a concrete manner, which often necessitates a consultation with a pediatrician holding nonspecific symptoms. The so-called suppression of the head impulse test (SHIMPs) represents a modification of the video head impulse test (HIMP) and is used for a more sensitive assessment of residual vestibular functions. In adults, SHIMPs are already an established diagnostic method. Nevertheless, to date, nothing is known about the applicability and standard values in childhood. MATERIAL AND METHODS: In this monocentric, prospective study, we investigated whether SHIMPs enable a sensitive functional analysis of the vestibular system in healthy children of different ages. For this purpose, SHIMPs were performed in 40 children aged 3-18 years. RESULTS: In this study, we demonstrated that SHIMPs can be easily performed in children (3-18 years). It is vital that the test be appropriately explained for children to ensure sufficient test tolerance and compliance. CONCLUSION: SHIMPs are a helpful supplement to clinically established vestibular tests such as the HIMP in pediatric vestibular balance disorder diagnostics and can be integrated into the clinical routine, especially in children who have minimal verbal abilities or understanding of the instructions for HIMP. Similar to the HIMP, SHIMPs are characterized by a short test duration and a high tolerance.

Accurate Mass Measurement of a Levitated Nanomechanical Resonator for Precision Force-Sensing.

Nanomechanical resonators are widely operated as force and mass sensors with sensitivities in the zepto-Newton (10-21) and yocto-gram (10-24) regime, respectively. Their accuracy, however, is usually undermined by high uncertainties in the effective mass of the system, whose estimation is a nontrivial task. This critical issue can be addressed in levitodynamics, where the nanoresonator typically consists of a single silica nanoparticle of well-defined mass. Yet, current methods assess the mass of the levitated nanoparticles with uncertainties up to a few tens of percent, therefore preventing to achieve unprecedented sensing performances. Here, we present a novel measurement protocol that uses the electric field from a surrounding plate capacitor to directly drive a charged optically levitated particle in moderate vacuum. The developed technique estimates the mass within a statistical error below 1% and a systematic error of ∼2%, and paves the way toward more reliable sensing and metrology applications of levitodynamics systems.

Wiring up pre-characterized single-photon emitters by laser lithography.

Future quantum optical chips will likely be hybrid in nature and include many single-photon emitters, waveguides, filters, as well as single-photon detectors. Here, we introduce a scalable optical localization-selection-lithography procedure for wiring up a large number of single-photon emitters via polymeric photonic wire bonds in three dimensions. First, we localize and characterize nitrogen vacancies in nanodiamonds inside a solid photoresist exhibiting low background fluorescence. Next, without intermediate steps and using the same optical instrument, we perform aligned three-dimensional laser lithography. As a proof of concept, we design, fabricate, and characterize three-dimensional functional waveguide elements on an optical chip. Each element consists of one single-photon emitter centered in a crossed-arc waveguide configuration, allowing for integrated optical excitation and efficient background suppression at the same time.

A new HLA-B*15 allele, B*15:220, found in three individuals sharing the HLA-A*66:01, HLA-C*12:03 and HLADRB1*07:01 alleles.

The new allele HLA-B*15:220 is associated with a conserved haplotype.

A phase II study of sorafenib in patients with chemo-naive castration-resistant prostate cancer.

BACKGROUND: The purpose of this trial was to evaluate the antitumor activity of sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, in patients with castration-resistant prostate cancer. PATIENTS AND METHODS: This was a multicenter, two-stage, phase II study. Sorafenib 400 mg was administered orally twice daily continuously. Primary end point was prostate-specific antigen (PSA) 'response' defined as a > or =50% decrease for > or =4 weeks. RESULTS: In all, 28 patients were enrolled. Eastern Cooperative Oncology Group performance status was zero or one in 19 and 9 patients. Two patients had no metastases, and 26 had bone and/or lymph node disease. A median of two cycles (range 1-8) was delivered. Adverse events were typical for sorafenib. The PSA response rate was 3.6% [95% confidence interval (CI) 0.1% to 18.3%] with response occurring in one patient (baseline = 10 000 and nadir = 1643 microg/l). No measurable disease responses occurred in eight patients. Time to PSA progression was 2.3 months (95% CI 1.8-6.4). Of 16 patients who discontinued sorafenib and then did not receive any immediate therapy, 10 had postdiscontinuation PSA declines of 7%-52%. CONCLUSIONS: Sorafenib has limited activity using current PSA criteria. The declines in PSA observed on treatment discontinuation indicate an effect on PSA production/secretion. Further study may be warranted but needs to consider the limitations of PSA as an indicator of progression and response.

Attentional stages of information processing during a continuous performance test: a startle modification analysis.

This study of 31 college students employed the startle eye-blink modification (SEM) technique to index both early and later stages of attentional processing during a memory-load version of the Continuous Performance Test (CPT). Participants viewed a series of digits and pressed a button after the digit 7 of each 3-7 sequence. A startling noise burst was presented either 120 or 1,200 ms following three preselected prepulses: target (3), nontarget (non-3 and non-7 digits), or target plus distractor (3 and simultaneous tone distractor). Greater startle inhibition occurred 120 ms following target and target-plus-distractor prepulses compared with nontargets, indicating early selective attention. No difference was observed between SEM during target and target-plus-distractor prepulses, suggesting the distractor was effectively ignored. At 1,200 ms, the three prepulse types produced nondifferential inhibition, suggesting that modality-specific selective attention occurs in anticipation of the presentation of the next CPT prepulse. These findings indicate that SEM distinguishes between different early selective attention and later anticipatory attention subprocesses underlying the CPT.

Startle reactivity and PTSD symptoms in a community sample of women.

Exaggerated startle and PTSD symptoms have been investigated primarily in relation to acute or Type I stressors. The present study examined PTSD symptoms and startle eyeblink response in relation to chronic or Type II stressors. Type II stressors were operationally defined as high levels of childhood corporal punishment and high levels of current partner aggression. This study recruited a sample of 52 women from a metropolitan community and administered several questionnaires assessing experience of corporal punishment in childhood, current intimate partner aggression and level of PTSD symptoms. Following questionnaires, women were presented with eight auditory startle probes (white noise). Results showed that both childhood corporal punishment and intimate partner aggression were associated with women's PTSD symptom scores. However, only PTSD symptom scores were associated with reduced startle. Results are discussed in light of Type I and Type II stressors, and recent suggestions in the PTSD literature that a subgroup of individuals may experience physiological suppression rather than heightened physiological reactivity.

On the clinical and cognitive meaning of impaired sensorimotor gating in schizophrenia.

Schizophrenia patients have been shown to have a defective sensorimotor gating process as indexed by impaired prepulse inhibition of the startle eyeblink reflex. Moreover, we have previously reported that schizophrenia patients have dysfunctional attentional modulation of prepulse inhibition. The present experiment combined our previous sample of 14 schizophrenia outpatients and 12 demographically matched control subjects with a new sample of 10 outpatients and 6 control subjects. All participants performed a tone-length judgement task that involved attending to one pitch of tone (the attended prepulse) and ignoring another pitch of tone (the ignored prepulse). During this task the acoustic startle eyeblink reflex was electromyographically recorded from the orbicularis oculi muscle. The results replicated the finding of impaired attentional modulation of prepulse inhibition in the new sample of schizophrenia outpatients compared to demographically matched control subjects. Specifically, the new control group exhibited greater startle modification during the attended prepulse, whereas the new patient group failed to show this differential effect. In addition, impaired prepulse inhibition following the attended prepulse was significantly correlated with heightened delusions, conceptual disorganization, and suspiciousness as measured with the expanded Brief Psychiatric Rating Scale. These correlations were significant with prepulse inhibition to the attended prepulse but not with prepulse inhibition to the ignored prepulse. Impaired prepulse inhibition was not correlated with negative symptoms. All in all, the results support the hypothesis that impaired attentional modulation of startle prepulse inhibition reflects basic neurocognitive processes related to thought disorder in schizophrenia.

The PDE inhibitor zaprinast enhances NO-mediated protection against vascular leakage in reperfused lungs.

Disruption of endothelial barrier properties with development of noncardiogenic pulmonary edema is a major threat in lung ischemia-reperfusion (I/R) injury that occurs under conditions of lung transplantation. Inhaled nitric oxide (NO) reduced vascular leakage in lung I/R models, but the efficacy of this agent may be limited. We coadministered NO and zaprinast, a cGMP-specific phosphodiesterase inhibitor, to further augment the NO-cGMP axis. Isolated, buffer-perfused rabbit lungs were exposed to 4.5 h of warm ischemia. Reperfusion provoked a transient elevation in pulmonary arterial pressure and a negligible rise in microvascular pressure followed by a massive increase in the capillary filtration coefficient and severe lung edema formation. Inhalation of 10 parts/million of NO or intravascular application of 100 microM zaprinast on reperfusion both reduced pressor response and moderately attenuated vascular leakage. Combined administration of both agents induced no additional vasodilation at constant microvascular pressures, but additively protected against capillary leakage paralleled by a severalfold increase in perfusate cGMP levels. In conclusion, combining low-dose NO inhalation and phosphodiesterase inhibition may be suitable for the maintenance of graft function in lung transplantation by amplifying the beneficial effect of the NO-cGMP axis and avoiding toxic effects of high NO doses.

Automatic and controlled attentional processes in startle eyeblink modification: effects of habituation of the prepulse.

The effect of prehabituation of the prepulse on startle eyeblink modification was studied in two experiments. In Experiment 1, college student participants were either prehabituated or nonhabituated to a tone that served as a prepulse in a startle modification passive attention paradigm. Neither short lead interval (60 and 120 ms) prepulse inhibition (PPI) nor long lead interval (2,000 ms) prepulse facilitation (PPF) was affected by the prehabituation procedure. In Experiment 2, participants were presented with an active attention paradigm in which one of two tone prepulses was attended while the other was ignored. One group was prehabituated to the prepulses and the other was not. Unlike the results with the passive paradigm in Experiment 1, prehabituation did significantly diminish attentional modulation of PPI and PPF. These results are consistent with the hypothesis that passive PPI and PPF are primarily automatic processes, whereas attentional modulation involves controlled cognitive processing.

Discrete and continuous prepulses have differential effects on startle prepulse inhibition and skin conductance orienting.

The effectiveness of different types of auditory prepulses in eliciting skin conductance orienting and in producing prepulse inhibition (PPI) of the acoustic startle eyeblink was studied in two experiments. A discrete white noise prepulse produced greater PPI than either a continuous white noise, a discrete tone, or a continuous tone. The discrete white noise advantage was not due to similarity in bandwidth to the startle pulse or to a refractory effect of the prepulse. Moreover, a dissociation between PPI and skin conductance orienting was seen in both experiments. PPI using auditory prepulses appears to be dependent primarily on the acoustic characteristics of the transient portion of the prepulse, whereas skin conductance orienting is more dependent on the sustained portions of the stimulus.

Attentional modulation of short- and long-lead-interval modification of the acoustic startle eyeblink response: comparing auditory and visual prestimuli.

Studies in our laboratory have shown that modification of startle by lead stimuli with short- and long-lead-intervals is modulated by stimulus significance. The significant stimulus in a tone duration judgement task generates enhanced short-lead-interval startle inhibition as well as pronounced long-lead-interval startle facilitation. The present study was designed to compare tones with simple visual stimuli as lead stimuli in a counterbalanced within-subjects design (Experiment I) or between-subjects design (Experiment II). The results show that auditory compared to visual lead stimuli generate more short-lead-interval inhibition but comparable amounts of long-lead-interval startle facilitation, which was significantly enhanced on to-be-attended trials independent of sensory modality. The attentional manipulation did not yield short-lead-interval effects in Experiment I, but previously reported attention effects were replicated in Experiment II. The results suggest early modality effects on startle modification, reflected by the differing levels of inhibition. Late effects of both modality and attention, however, seem to reflect a sensory modality independent process in startle modification.

A null HLA-A*68 allele in a bone marrow donor.

The authors describe an A*68 allele present at the molecular level but not expressed at the cell surface. This non expression results from the deletion of one nucleotide in exon 1, which causes a shift of the reading frame leading to an early non-sense codon in the same exon.

Formation of macrocyclic oligoferrocenes: a matrix-assisted laser desorption/ionization mass spectrometric study.

Oligomeric ferrocenes were investigated simultaneously by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOFMS). The oligomers were obtained by the reaction of tetrahydro-4,4,8,8-tetramethyl-4,8-disila-s-indacene-3a,7a-diyldilithium (Li(2)L) with FeCl(2).1.5 THF (THF = tetrahydrofuran). Depending on the reaction conditions up to ten linear-chain and eleven cyclic ferrocene oligomers with masses between 1139 and 5071 Da could be detected unambiguously. The most abundant macrocycles contained ten and seven iron atoms when the reactions were carried out at -20 and 25 degrees C, respectively. The chains had cyclopentadienes as end groups and formally resulted from replacing one iron of a cycle by two hydrogens, which corresponds to a mass difference of 54 Da. Copyright 1999 John Wiley & Sons, Ltd.

The psychological significance of human startle eyeblink modification: a review.

The human startle eyeblink reflex is reliably modified by both cognitive and emotional processes. This review provides a comprehensive survey of the current literature on human startle modification and its psychological significance. Issues raised for short lead interval startle inhibition include its interpretation as a measure of protection of processing, sensorimotor gating and early attentional processing. For long lead interval effects, interpretations related to attentional and emotional processing are discussed. Also reviewed are clinical applications to information processing dysfunctions in the schizophrenia spectrum disorders, and to emotional processing disorders. Finally, an integrative summary that incorporates most of the cognitive findings is presented and directions for future research are identified regarding both cognitive and emotional modification of startle.

A prospective study of hyperactive boys with conduct problems and normal boys: adolescent and adult criminality.

OBJECTIVE: To examine the relationship between attention deficit disorder with hyperactivity in childhood and criminality in adolescence and adulthood in 89 hyperactive and 87 normal control subjects. METHOD: In this prospective study, adolescent follow-up intervals ranged from 13 to 21 years and adult follow-up ranged from 18 to 23 years. The official arrest records for all subjects were obtained. RESULTS: Hyperactive subjects had significantly higher juvenile (46% versus 11%) and adult (21% versus 1%) arrest rates. Juvenile and adult incarceration rates were also significantly higher. Childhood conduct problems predicted later criminality, and serious antisocial behavior in adolescence predicted adult criminality. CONCLUSIONS: Hyperactive children are at risk for both juvenile and adult criminality. The risk for becoming an adult offender is associated with conduct problems in childhood and serious antisocial behavior (repeat offending) in adolescence. Hyperactive children who do not have conduct problems are not at increased risk for later criminality.

Autonomic orienting and the allocation of processing resources in schizophrenia patients and putatively at-risk individuals.

The differential allocation of attentional resources to attended and ignored stimuli was examined by measuring skin conductance orienting responses and secondary reaction time in relatively asymptomatic schizophrenia outpatients, demographically matched normal controls, college students putatively at risk for psychosis, and a college student control group. At-risk participants were those with extreme scores on scales for either anhedonia or perceptual aberration-magical ideation (per-mags). Compared to control groups, the patients and per-mags showed secondary reaction time results suggesting a delay in the differential allocation of attentional resources. This deficit was observed particularly in patients and matched controls with few or no skin conductance orienting responses, suggesting that impaired autonomic orienting is related to underlying cognitive-attentional vulnerability factors.

A nucleotide insertion in exon 4 is responsible for the absence of expression of an HLA-A*01 allele.

HLA class I typing performed in parallel by molecular biology and serology has revealed cases where an HLA class I allele was identified whereas the corresponding antigen was not detected on the cell surface. In the present report, we describe four members of a family in whom an HLA-A1 allele identified at the molecular level was typed as A "blank" by lymphocytotoxicity. This serologically blank antigen was undetectable by isoelectric focusing (IEF). Sequencing of the HLA-A*01 allele from the promoter region to the eighth exonic region revealed insertion of a "C" nucleotide at the beginning of the fourth exon as compared to the common HLA-A*0101 allele. This mutation causes a frame shift, giving rise to an early stop codon in the fourth exon.

The varying time courses of attentional and affective modulation of the startle eyeblink reflex.

In previous research on modulation of the startle eyeblink reflex, emotional effects have been demonstrated only at late probe positions, whereas attentional effects have been found at both early and late positions but only when the prepulses were affectively neutral. In Experiment 1, participants viewed emotionally valenced pictures and were instructed to attend to the duration of half of the slides. Affective modulation of the startle eyeblink occurred at long lead intervals, but attentional modulation also occurred late. In Experiment 2, participants viewed the same slides used in Experiment 1 but were instructed to attend to the duration of only the positive or the negative slides. Affective modulation occurred at both early and late probe positions, whereas attentional effects occurred only following slide offset. Early (250 ms) affective modification of startle eyeblink has not been previously reported. These results suggest that the time courses of emotional and attentional modulation of startle are variable and can occur at both early and late startle probe positions, depending on task requirements.