Impaired communication ability in SOX11 syndrome.

BACKGROUND: Speech and language skills are important for social interaction and learning. This study characterised the communication abilities of verbal individuals with SOX11 syndrome using a standardised parent/carer questionnaire, the Children's Communication Checklist (CCC-2). METHOD: Thirteen parent/carers of verbal individuals (aged 5-19 years) diagnosed with SOX11 syndrome completed the CCC-2. In order to contextualise findings, responses were compared to norms and to data from Noonan syndrome, a relatively well-known genetic diagnosis associated with communication impairment. RESULTS: For all individuals, the CCC-2 composite score indicated significant communication difficulties. Language structure (speech, syntax, semantics and coherence), pragmatic language (inappropriate initiation, stereotyped language use of context and non-verbal communication) and autistic features (social relations and interests) scores were lower than typically developing norms. Subscale comparisons revealed relative difference in use of context compared to other pragmatic domains (stereotyped language and inappropriate initiation). Individual scores showed substantial variation, particularly in regard to language structure profile. Differences were more pronounced than for Noonan syndrome, specifically in domains of speech, syntax, non-verbal communication and social relations. CONCLUSIONS: SOX11 syndrome is associated with communication impairment. It is important to assess communication abilities as part of the management of individuals with SOX11 syndrome and understand individual strengths and difficulties in order to provide targeted support.

Observations on early fungal infections with relevance for replant disease in fine roots of the rose rootstock Rosa corymbifera 'Laxa'.

Replant disease is a worldwide phenomenon affecting various woody plant genera and species, especially within the Rosaceae. Compared to decades of intensive studies regarding replant disease of apple (ARD), the replant disease of roses (RRD) has hardly been investigated. The etiology of RRD is also still unclear and a remedy desperately needed. In greenhouse pot trials with seedlings of the RRD-sensitive rootstock Rosa corymbifera 'Laxa' cultured in replant disease affected soils from two different locations, early RRD symptom development was studied in fine roots. In microscopic analyses we found similarities to ARD symptoms with regards to structural damages, impairment in the root hair status, and necroses and blackening in the cortex tissue. Examinations of both whole mounts and thin sections of fine root segments revealed frequent conspicuous fungal infections in association with the cellular disorders. Particularly striking were fungal intracellular structures with pathogenic characteristics that are described for the first time. Isolated fungi from these tissue areas were identified by means of ITS primers, and many of them were members of the Nectriaceae. In a next step, 35 of these isolates were subjected to a multi-locus sequence analysis and the results revealed that several genera and species were involved in the development of RRD within a single rose plant. Inoculations with selected single isolates (Rugonectria rugulosa and Ilyonectria robusta) in a Perlite assay confirmed their pathogenic relationship to early necrotic host plant reactions, and symptoms were similar to those exhibited in ARD.

Data processing in NMR relaxometry using the matrix pencil.

The matrix pencil method (MPM) is explored for stable, reproducible data processing in nuclear magnetic resonance (NMR) relaxometry. Data from one-dimensional and two-dimensional relaxometry experiments designed to measure transverse relaxation T2, longitudinal relaxation T1, diffusion coefficient D values, and their correlations in a standard olive oil/water mixture serve as a platform available to any NMR spectroscopist to compare the performance of the MPM to the benchmark inverse Laplace transform (ILT). The data from two practical examples, including the drying of a solvent polymer system and the enzymatic digestion of polysialic acid, were also explored with the MPM and ILT. In the cases considered here, the MPM appears to outperform the ILT in terms of resolution and stability in the determination of fundamental constants for complex materials and mixtures.

Dynamic inversion enables external magnets to concentrate ferromagnetic rods to a central target.

The ability to use magnets external to the body to focus therapy to deep tissue targets has remained an elusive goal in magnetic drug targeting. Researchers have hitherto been able to manipulate magnetic nanotherapeutics in vivo with nearby magnets but have remained unable to focus these therapies to targets deep within the body using magnets external to the body. One of the factors that has made focusing of therapy to central targets between magnets challenging is Samuel Earnshaw's theorem as applied to Maxwell's equations. These mathematical formulations imply that external static magnets cannot create a stable potential energy well between them. We posited that fast magnetic pulses could act on ferromagnetic rods before they could realign with the magnetic field. Mathematically, this is equivalent to reversing the sign of the potential energy term in Earnshaw's theorem, thus enabling a quasi-static stable trap between magnets. With in vitro experiments, we demonstrated that quick, shaped magnetic pulses can be successfully used to create inward pointing magnetic forces that, on average, enable external magnets to concentrate ferromagnetic rods to a central location.

A Prototype Body-Mounted MRI-Compatible Robot for Needle Guidance in Shoulder Arthrography.

A novel compact and lightweight patient-mounted MRI-compatible robot has been designed for MRI image-guided interventions. This robot is intended to enable MRI-guided needle placement as done in shoulder arthrography. The robot could make needle placement more accurate and simplify the current workflow by converting the traditional two-stage arthrography procedure (fluoroscopy-guided needle insertion followed by a diagnostic MRI scan) to a one-stage procedure (streamlined workflow all in MRI suite). The robot has 4 degrees of freedom (DOF), two for orientation of the needle and two for needle positioning. The mechanical design was based on several criteria including rigidity, MRI compatibility, compact design, sterilizability, and adjustability. The proposed workflow is discussed and initial MRI compatibility experiments are presented. The results show that artifacts in the region of interest are minimal and that MRI images of the shoulder were not adversely affected by placing the robot on a human volunteer.

Resistively detected nuclear magnetic resonance in n- and p-type GaAs quantum point contacts.

We present resistively detected NMR measurements in induced and modulation-doped electron quantum point contacts, as well as induced hole quantum point contacts. While the magnitude of the resistance change and associated NMR peaks in n-type devices is in line with other recent measurements using this technique, the effect in p-type devices is too small to measure. This suggests that the hyperfine coupling between holes and nuclei in this type of device is much smaller than the electron hyperfine coupling, which could have implications in quantum information processing.

A real-time PCR assay for the differentiation of Candida species.

AIMS: We established a real-time PCR assay for the detection and strain identification of Candida species and demonstrated the ability to differentiate between Candida albicans the most common species, and also Candida parapsilosis, Candida glabrata, Candida tropicalis and Candida dubliniensis by LightCycler PCR and melting curve analysis. METHODS AND RESULTS: The DNA isolation from cultures and serum was established using the QIAmp Tissue Kit. The sensitivity of the assay was ≥ 2 genome equivalents/assay. It was possible to differentiate all investigated Candida species by melting curve analysis, and no cross-reaction to human DNA or Aspergillus species could be observed. CONCLUSIONS: The established real-time PCR assay is a useful tool for the rapid identification of Candida species and a base technology for more complex PCR assays. SIGNIFICANCE AND IMPACT OF THE STUDY: We carried out initial steps in validation of a PCR assay for the detection and differentiation of medically relevant Candida species. The PCR was improved by generating PCR standards, additional generation of melting curves for species identification and the possibility to investigate different specimens simultaneously.

1H MRS identifies symptomatic and asymptomatic subjects with partial ornithine transcarbamylase deficiency.

OBJECTIVE: To evaluate brain metabolism in subjects with partial ornithine transcarbamylase deficiency (OTCD) utilizing (1)H MRS. METHODS: Single-voxel (1)H MRS was performed on 25 medically-stable adults with partial OTCD, and 22 similarly aged controls. Metabolite concentrations from frontal and parietal white matter (FWM, PWM), frontal gray matter (FGM), posterior cingulate gray matter (PCGM), and thalamus (tha) were compared with controls and IQ, plasma ammonia, glutamine, and disease severity. RESULTS: Cases ranged from 19 to 59 years; average 34 years; controls ranged from 18 to 59 years; average 33 years. IQ scores were lower in cases (full scale 111 vs. 126; performance IQ 106 vs. 117). Decreased myoinositol (mI) in FWM (p=0.005), PWM (p<0.001), PCGM (p=0.003), and tha (p=0.004), identified subjects with OTCD, including asymptomatic heterozygotes. Glutamine (gln) was increased in FWM (p<0.001), PWM (p<0.001), FGM (p=0.002), and PCGM (p=0.001). Disease severity was inversely correlated with [mI] in PWM (r=-0.403; p=0.046) and directly correlated with [gln] in PCGM (r=0.548; p=0.005). N-Acetylaspartate (NAA) was elevated in PWM (p=0.002); choline was decreased in FWM (p=0.001) and tha (p=0.002). There was an inverse relationship between [mI] and [gln] in cases only. Total buffering capacity (measured by [mI/mI+gln] ratio, a measure of total osmolar capacity) was inversely correlated with disease severity in FWM (r=-0.479; p=0.018), PWM (r=-0.458; p=0.021), PCGM (r=-0.567; p=0.003), and tha (r=-0.345; p=0.037). CONCLUSION: Brain metabolism is impaired in partial OTCD. Depletion of mI and total buffering capacity are inversely correlated with disease severity, and serve as biomarkers.

Enhanced perceived responsibility decreases metamemory but not memory accuracy in obsessive-compulsive disorder (OCD).

Mixed findings have been obtained in prior research with respect to the presence and severity of memory and metamemory deficits in obsessive-compulsive disorder (OCD). We tested the hypothesis that experimentally induced increments of subjective responsibility would lead to a disproportionately strong decline of memory confidence and enhanced response latencies in OCD while leaving memory accuracy unaffected. Twenty-eight OCD patients and 28 healthy controls were presented a computerized memory test framed with two different scenarios. In the neutral scenario, the participant was requested to imagine purchasing 15 items from a do-it-yourself store. In the recognition phase, the 15 needed items were presented along with 15 distractor items. The participant was asked to decide whether items were on his or her shopping list or not, graded by subjective confidence. In the responsibility scenario, the general experimental setup was analogous except that the participant now had to envision that he or she was a helper in a region recently struck by an earthquake, dispatched to provide 15 urgently needed goods from a nearby town. In line with prior work by our group, samples did not differ in either condition on memory accuracy in a subsequent recognition task. As hypothesized, OCD participants were less certain in their responses for the high responsibility condition than controls. Whereas patients and controls did not differ in their subjective estimates for memorized items, patients expressed stronger doubt that their earthquake mission was successful. The findings indicate that low memory confidence in OCD may only be elicited in situations where perceived responsibility is high and that patients may share higher performance standards ("good is not good enough") than controls when perceived responsibility is inflated.

Symptom dimensions in obsessive-compulsive disorder: prediction of cognitive-behavior therapy outcome.

OBJECTIVE: A significant number of patients with obsessive-compulsive disorder (OCD) fail to benefit sufficiently from treatments. This study aimed to evaluate whether certain OCD symptom dimensions were associated with cognitive-behavioral therapy (CBT) outcome. METHOD: Symptoms of 104 CBT-treated in-patients with OCD were assessed with the clinician-rated Yale-Brown Obsessive-Compulsive Scale symptom checklist. Logistic regression analyses examined outcome predictors. RESULTS: The most frequent OCD symptoms were aggressive and contamination obsessions, and compulsive checking and cleaning. Patients with hoarding symptoms at baseline (n = 19) were significantly less likely to become treatment responders as compared to patients without these symptoms. Patients with sexual and religious obsessions tended to respond less frequently, although this failed to reach statistical significance (P = 0.07). Regression analyses revealed that higher scores on the hoarding dimension were predictive of non-response, even after controlling for possible confounding variables. CONCLUSION: Our results strongly indicate that in-patients with obsessive-compulsive hoarding respond poorly to CBT.

Consistent and reproducible slice selection in rodent brain using a novel stereotaxic device for MRI.

Typically small animal radiological images are obtained after placing the animal in the center of the imaging device using beds or platforms, and then adjusting the position after obtaining a scout image. Such a process does not permit the reproducible visualization of the same anatomical plane with repeated examinations. We have developed a device that allows stereotaxic placement of an animal in precisely the same position for repeated examinations. The instrument incorporates a full range of physiological monitoring and life support systems including temperature control, anesthesia delivery and respiratory monitoring. Using magnetic resonance imaging (MRI), the accuracy and reliability of this device is demonstrated in a rat traumatic brain injury (TBI) model.

Impact of comorbid depressive symptoms on neuropsychological performance in obsessive-compulsive disorder.

There is indirect evidence from previous research that several executive disturbances in obsessive-compulsive disorder (OCD) are mediated by comorbid depressive symptoms. For the present study, the authors investigated whether OCD patients with elevated Hamilton Rating Scale for Depression (HRSD) scores would exhibit deficits in tasks sensitive to the medial and dorsolateral frontal cortex as well as other executive tasks. The 36 OCD patients were split along the median according to their HRSD scores and compared with matched control subjects. Patients with high HRSD scores performed significantly worse than control subjects and patients with low HRSD scores on the Wisconsin Card Sorting Test, the Trail-Making Test (TMT, Part B), and the TMT difference score. Moreover, patients with high HRSD scores exhibited deficits on a (creative) verbal fluency task. It is suggested that comorbid depressive symptoms may have artificially inflated some executive deficit scores in previous studies.

Attempted and completed suicide in older subjects: results from the WHO/EURO Multicentre Study of Suicidal Behaviour.

OBJECTIVE: The authors present an analysis of findings for the 65 years and over age group from the WHO/EURO Multicentre Study of Suicidal Behaviour (1989-93). METHODS: Multinational data on non-fatal suicidal behaviour is derived from 1518 subjects in 16 European centres. Local district data on suicide were available from 10 of the collaborating centres. RESULTS: Stockholm (Sweden), Pontoise (France) and Oxford (UK) had the highest suicide attempts rates. In most centres, the majority of elderly who attempted suicide were widow(er)s, often living alone, who used predominantly voluntary drug ingestion. Non-fatal suicidal behaviour decreased with increasing age, whereas suicide rates rose. The ratio between fatal and non-fatal behaviours was 1:2, that for males/females almost 1:1. In the years considered, substantial stability in suicide and attempted suicide rates was observed. As their age increased, suicidal subjects displayed only a limited tendency to repeat self-destructive acts. Moreover, there was little correlation between attempted suicide and suicide rates, which carries different clinical implications for non-fatal suicidal behaviour in the elderly compared with younger subjects in the same WHO/EURO study.

Expression of soluble, recombinant alphavbeta3 integrin fragments in Escherichia coli.

No prokaryotic expression of integrin alphavbeta3 has been reported so far. We report here the expression of C-terminally truncated alphavbeta3 receptors in E. coli considering the known features required for dimerization and ligand binding. The expressed protein was insoluble despite of the addition of 'solubilizers' to the culture medium. Osmotic stress conditions combined with added exogenous solutes resulted in a small part of soluble receptor. The alphavbeta3 variants were purified from inclusion bodies or from soluble cytoplasmic maltose binding protein fusions. Heterodimerization of the subunits was proved by immunoprecipitation assays. Receptor-ligand binding was found to depend on the concentration. A competition assay with RGD peptides referred to unspecific receptor-ligand interaction. The latter fact was consistent with the finding that soluble receptors did not bind on RGD peptide-coupled sepharose (GRGDSPK sepharose).

Suicide among German federal and state police officers.

Most American studies report higher police officer suicide rates in comparison to age-matched populations. In the Federal Republic of Germany police organizations are comprised of Federal Customs, 16 state police, and 2 federal police organizations. A survey carried out in 1997 yielded higher suicide rates for police officers also in Germany in comparison to rates of the comparable age group (25 per 100,000 vs 20 per 100,000). The most commonly used suicide method was firearms (66-71%). Hypotheses often attribute this high suicidality among police officers to higher work stress than in other professions. Other hypotheses implicate individual variables such as psychiatric illnesses, alcoholism, and interpersonal and marital problems. A transactional model might explain these different views.

Attempted suicide in Europe: rates, trends and sociodemographic characteristics of suicide attempters during the period 1989-1992. Results of the WHO/EURO Multicentre Study on Parasuicide.

The World Health Organization/EURO Multicentre Project on Parasuicide is part of the action to implement target 12 of the WHO programme, "Health for All by the Year 2000', for the European region. Sixteen centres in 13 European countries are participating in the monitoring aspect of the project, in which trends in the epidemiology of suicide attempts are assessed. The highest average male age-standardized rate of suicide attempts was found for Helsinki, Finland (314/100,000), and the lowest rate (45/100,000) was for Guipuzcoa, Spain, representing a sevenfold difference. The highest average female age-standardized rate was found for Cergy-Pontoise, France (462/100,000), and the lowest (69/100,000) again for Guipuzcoa, Spain. With only one exception (Helsinki), the person-based suicide attempt rates were higher among women than among men. In the majority of centres, the highest person-based rates were found in the younger age groups. The rates among people aged 55 years or over were generally the lowest. For the majority of the centres, the rates for individuals aged 15 years or over decreased between 1989 and 1992. The methods used were primarily "soft' (poisoning) or cutting. More than 50% of the suicide attempters made more than one attempt, and nearly 20% of the second attempts were made within 12 months after the first attempt. Compared with the general population, suicide attempters more often belong to the social categories associated with social destabilization and poverty.