IMMUNOCYTOCHEMICAL AND RADIOIMMUNOMETRICAL DEMONSTRATION OF SEROTONIN-IMMUNOREACTIVITIES AND NEUROPEPTIDE-IMMUNOREACTIVITIES IN THE ADULT-RAT TAPEWORM, HYMENOLEPIS-DIMINUTA (CESTODA, CYCLOPHYLLIDEA)

Standard indirect immunocytochemical techniques have been interfaced with confocal scanning laser microscopy (for whole-mount preparations) and epifluorescence microscopy (for cryosections) to investigate the occurrence and distribution of serotoninergic and peptidergic nerve elements in adult H. diminuta. Serotonin (5-HT)-immunoreactivity (IR) was widespread throughout the worm, occurring in the paired cerebral ganglia, transverse commissure, the 10 longitudinal nerve cords and in a plethora of small nerve fibres of the peripheral nervous system. An abundance of serotoninergic nerve cell bodies was found in association with the lateral nerve cords. The genital atrium and accessory reproductive ducts were richly innervated with serotoninergic nerve fibres. Thirty-five antisera to 20 vertebrate regulatory peptides and 1 invertebrate peptide (FMRFamide) were used to screen the worm for neuropeptide IR. Immunostaining was obtained with antisera raised to pancreatic polypeptide (PP), peptide YY (PYY), neuropeptide Y (NPY), substance P (SP), peptide histidine isoleucine (PHI), xenopsin (XP) and FMRFamide. The most extensive pattern of IR occurred with antisera to PP and PYY, IR being evident in the cerebral ganglia, transverse commissure, longitudinal nerve cords and in small nerve fibres that ramified throughout the parenchyma. A series of bipolar nerve cell bodies between the median nerve cords displayed PP/PYY-IR. The distribution of FMRFamide-IR was reminiscent of the PP/PYY pattern but was less extensive. Comparison of the serotoninergic and peptidergic nervous systems has revealed general similarities and some distinct differences, especially with regard to the distribution of immunoreactive nerve cell bodies. Quantitative data are presented on the levels of PP-, SP-, PHI-, and gastrin-releasing peptide (GRP)-immunoreactivities demonstrable in acid-alcohol extracts of whole worms. The highest level of peptide IR determined was recorded for PP.

Lateral electron transport in high-intensity laser-irradiated foils diagnosed by ion emission

An experimental investigation of lateral electron transport in thin metallic foil targets irradiated by ultraintense (>= 10(19) W/cm(2)) laser pulses is reported. Two-dimensional spatially resolved ion emission measurements are used to quantify electric-field generation resulting from electron transport. The measurement of large electric fields (similar to 0.1 TV/m) millimeters from the laser focus reveals that lateral energy transport continues long after the laser pulse has decayed. Numerical simulations confirm a very strong enhancement of electron density and electric field at the edges of the target.

Adaptations of lateral hand movements to early and late visual occlusion in catching

Recent studies suggested that the control of hand movements in catching involves continuous vision-based adjustments. More insight into these adjustments may be gained by examining the effects of occluding different parts of the ball trajectory. Here, we examined the effects of such occlusion on lateral hand movements when catching balls approaching from different directions, with the occlusion conditions presented in blocks or in randomized order. The analyses showed that late occlusion only had an effect during the blocked presentation, and early occlusion only during the randomized presentation. During the randomized presentation movement biases were more leftward if the preceding trial was an early occlusion trial. The effect of early occlusion during the randomized presentation suggests that the observed leftward movement bias relates to the rightward visual acceleration inherent to the ball trajectories used, while its absence during the blocked presentation seems to reflect trial-by-trial adaptations in the visuomotor gain, reminiscent of dynamic gain control in the smooth pursuit system. The movement biases during the late occlusion block were interpreted in terms of an incomplete motion extrapolation--a reduction of the velocity gain--caused by the fact that participants never saw the to-be-extrapolated part of the ball trajectory. These results underscore that continuous movement adjustments for catching do not only depend on visual information, but also on visuomotor adaptations based on non-visual information.

Autobiographical memory specificity, depression, and trauma in bipolar disorder

Objectives. In a bipolar disorder (BD) sample, the present study investigated: (i) the prevalence of trauma; (ii) the specificity of autobiographical memory (AM); (iii) the influence of childhood trauma on AM specificity, current inter-episode depressive mood, and BD severity; (iv) if AM specificity moderates the influence of childhood trauma on current inter-episode depressive mood and BD severity.

Methods. Fifty-two participants were recruited from a geographically well-defined mental health service in Northern Ireland. The AM test, self-report measures of lifetime experience of trauma, childhood trauma, and depression were administered. Severity of BD was estimated utilizing a systematic tool for reviewing all available clinical data of participants.

Results. A high prevalence of trauma was found. A total of 94.2% (49/52) of participants reported experiencing a traumatic event in either childhood or adulthood. AM specificity was significantly lower than previous reports of such in major depression. However, whilst childhood trauma predicted current inter-episode depressive mood, childhood trauma was not predictive of BD severity or AM specificity. Moreover, the association between childhood trauma and depressed mood was not moderated by AM specificity.

Conclusions. The findings of this study suggest a relationship between early psychosocial adversity and current inter-episode depressive mood in BD. In addition, levels of overgeneral AM are similar to that reported for depression, but are unrelated to childhood trauma, current inter-episode depressive mood, or BD severity. Clinical implications include the importance of routine assessment of trauma in BD and the need for adjunctive evidenced-based psychological therapies.

Enquiring about traumatic experiences in bipolar disorder: A case note and self- report comparison

Objectives: This study examined: (i) the prevalence of lifetime trauma, childhood trauma and trauma related to civil unrest in a Bipolar Disorder sample, and (ii) the agreement between rates of disclosure of trauma in case notes and self-report questionnaires.

Methods: The case notes of sixty participants, recruited from a geographically well-defined mental health service in Northern Ireland, were examined for reports of experiences of lifetime, childhood and traumatic events related to civil conflict. The participants also completed self-report measures of trauma.

Results: Considerable differences were found between the prevalence of trauma as measured by self-report questionnaires and case notes reports. The prevalence of lifetime trauma as measured by the Trauma History Questionnaire was 61.7% (compared to case notes prevalence of 33.3%). The prevalence of moderate and severe levels of childhood trauma as measured by the Childhood Trauma Questionnaire was 65% (case notes 21.7%). Rates of trauma related to civil unrest were 35% (case notes 3.3%). Poor levels of agreement were found between all self-report trauma measures and case notes reports. Agreement on two categories of trauma (childhood emotional neglect and childhood physical neglect) reached statistical significance but kappa scores suggest this agreement was poor (kappa = .14. p<.05; kappa = .127, p<.05). © 2011 Elsevier B.V. All rights reserved.

Conclusions: It is probable that the increased rate of trauma disclosed in the self-report questionnaire arises because clinicians during initial assessment and subsequent treatment do not consistently enquire about trauma. The need for staff training is discussed. (C) 2011 Elsevier B.V. All rights reserved.

A Phase I Trial of Bortezomib in Combination with Epirubicin, Carboplatin and Capecitabine (VECarboX) in Advanced Gastric and Gastro-oesophageal Junction Adenocarcinoma

PURPOSE:
The protease inhibitor bortezomib attenuates the action of NF-κB and has shown preclinical activity alone and in combination with chemotherapy.

DESIGN:
A Phase I dose-escalation study was performed administering bortezomib (0.7, 1.0, 1.3 and 1.6 mg m(-2) on days 1 and 8 from cycle 2 onwards) in combination with Epirubicin 50 mg m(-2) intravenously on day 1, Carboplatin AUC 5 day 1 and Capecitabine 625 mg m(-2) BD days 1-21 every 21 days (VECarboX regimen), in patients with advanced oesophagogastric adenocarcinoma. The primary objective was to define the maximum tolerated dose (MTD) of Bortezomib when combined with ECarboX.

RESULTS:
18 patients received bortezomib 0.7 (n = 6), 1.0 (n = 3), 1.3 (n = 6) and 1.6 mg m(-2) (n = 3) and a protocol amendment reducing the capecitabine dose to 500 mg m(-2) BD was enacted due to myelotoxicity. Common treatment-related non-haematological adverse events of any grade were fatigue (83.3 %), anorexia (55.6 %), constipation (55.6 %) and nausea (55.6 %). Common Grade 3/4 haematological toxicities were neutropenia (77.8 %) and thrombocytopenia (44.4 %). Objective responses were achieved in 6 patients (33.3 %) and a further 5 patients (27.8 %) had stable disease for >8 weeks.

CONCLUSIONS:
The addition of Bortezomib to ECarboX is well tolerated and response rates are comparable with standard chemotherapy.

A novel device to measure acetabular inclination with patients in lateral decubitus

The ability to measure acetabular cup orientation accurately during total hip arthroplasty represents a significant challenge. The aim of this research was to develop and evaluate a novel low cost mechanical device for measuring operative acetabular inclination. Cup implantation was simulated in two trials using the novel device: firstly involving surgeons and engineers orientating acetabular cups with sawbone pelves at a range of inclination angles (20°-55° in 5° increments); secondly in a simulated intra-operative scenario with surgeons. Target angles were compared with achieved angles and deviations from desired angles were recorded. In addition, all participants orientated cups under the same conditions using two other techniques: freehand and with a propriatory Mechanical Alignment Guide. In the first trial, the mean errors (deviations) using freehand technique, the mechanical alignment guide and the new device were 5.2° +/- 4.3° (range 0.1-22.0), 3.6° +/- 3.9° (range 0.1°-33.6°) and 0.5° +/- 0.4° (range 0.0-1.9) respectively. In the second trial, the mean error for freehand technique, mechanical alignment guide and the new device were 6.2° +/- 4.2° (range 0.2-18.2), 3.8° +/- 3.3° (range 0.0-19.1) and 0.6° +/- 0.5° (range 0.0-1.8) respectively. The new device has the potential to allow the surgeon to choose and record operative inclination accurately during total hip arthroplasty in the lateral decubitus position.

Genome scan meta-analysis of schizophrenia and bipolar disorder, part II:Schizophrenia

Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk

Development and validation of the first high performance-lateral flow immunoassay (HP-LFIA) for the rapid screening of domoic acid from shellfish extracts

A lateral flow immunoassay (LFIA) has been developed and fully validated to detect the primary amnesic shellfish poisoning (ASP) toxin, domoic acid (DA). The performance characteristics of two versions of the test were investigated using spiked and naturally contaminated shellfish (mussels, scallops, oysters, clams, and cockles). The tests provide a qualitative result, to indicate the absence or presence of DA in extracts of shellfish tissues, at concentrations that are relevant to regulatory limits. The new rapid assay (LFIA version 2) was designed to overcome the performance limitations identified in the first version of the assay. The improved test uses an electronic reader to remove the subjective nature of the generated results, and the positive cut-off for screening of DA in shellfish was increased from 10 ppm (version 1) to 17.5 ppm (version 2). A simple extraction and test procedure was employed, which required minimal equipment and materials; results were available 15 min after sample preparation. Stability of the aqueous extracts at room temperature (22 C) at four time points (up to 245 min after extraction) and across a range of DA concentrations was 100.3±1.3% and 98.8±2.4% for pre- and post-buffered extracts, respectively. The assay can be used both within laboratory settings and in remote locations. The accuracy of the new assay, to indicate negative results at or below 10 ppm DA, and positive results at or above 17.5 ppm, was 99.5% (n=216 tests). Validation data were obtained from a 2-day, randomised, blind study consisting of multiple LFIA lots (n=3), readers (n=3) and operators (n=3), carrying out multiple extractions of mussel tissue (n=3) at each concentration (0, 10, 17.5, and 20 ppm). No matrix effects were observed on the performance of the assay with different species (mussels, scallops, oysters, clams, and cockles). There was no impact on accuracy or interference from other phycotoxins, glutamic acid or glutamine with various strip incubations (8, 10, and 12 min). The accuracy of the assay, using naturally contaminated samples to indicate negative results at or below 12.5 ppm and positive results at or above 17.5 ppm, was 100%. Variability between three LFIA lots across a range of DA concentrations, expressed as coefficient of variation (% CV), was 1.1±0.4% (n=2 days) based on quantitative readings from the electronic reader. During an 8 week stability study, accuracy of the method with test strips stored at various temperatures (6, 22, 37 and 50 C) was 100%. Validation for both versions included comparisons with results obtained using reference LC-UV methods. © 2013 Elsevier B.V.

Morphological consequences of lateral outfracture of the inferior turbinate

Objective: We report three cases of lateral outfracture of the inferior turbinate, which demonstrate a range of changes in the size, position and shape of the inferior turbinate.

Method: During a study of the validity of computer modelling of nasal airflow, computed tomography scans of the noses of patients who had undergone lateral outfracture of the inferior turbinate were collected. The pre-operative scan was compared with the post-operative scan six weeks later.

Results: In one patient, there was only a small lateral displacement of the inferior turbinate. In the other two cases, appreciable reduction in the volume of one inferior turbinate was noted, in addition to minor changes in the shape.

Conclusion: Lateral outfracture of the inferior turbinate produces varied and inconsistent changes in morphology which may affect the shape, size and position of the turbinate.

Ultimate lateral load resistance of laterally loaded pile

Several methods are available for predicting ultimate lateral load resistance of laterally loaded pile. These methods often produce significantly different ultimate lateral resistance. This makes it difficult to select an appropriate method in designing/predicting ultimate lateral resistance of pile. This paper presents a review of two different methods; Meyerh of and Patra & Pise for predicting lateral resistance of pile. Then, the predicted ultimate lateral resistances by these two methods are compared with the experimental results. It is found that Meyerhof's method gives better prediction for single pile with smaller L/d ratio whereas Patra & Pise method gives better predictions for pile groups with higher L/d. Thus, none of these methods can be applicable universally for all possible conditions. Also the parametric study on ultimate lateral resistance revealed that length to diameter ratio, pile spacing, pile configuration in a pile group are important parameters for prediction of lateral load resistance. © 2009 Taylor & Francis Group.