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The 24-week extension of AIDS Clinical Trials Group Protocol 359, a study of human immunodeficiency virus (HIV)‐infected, indinavir-experienced patients, was designed to study the durability of “salvage” treatment regimens. Patients received saquinavir in combination with either ritonavir or nelfinavir and, in addition, delavirdine, adefovir, or both. Patients who demonstrated a virologic response at weeks 12‐16 were eligible to continue therapy in the extension through week 48. Of the 105 eligible subjects who were enrolled in the extension, 86 (82%) completed 48 weeks, and 49 (57%) of those 86 had HIV RNA levels 500 copies/ mL at week 48. For these 86 subjects who completed 48 weeks, the median change in CD4 cell count from baseline was +72 cells/mm 3 . Greater body weight, higher CD4 cell count, and greater degree of phenotypic susceptibility to indinavir and saquinavir at baseline were significantly associated with durable virologic suppression. These results show that some patients who experience treatment failure can demonstrate durable virologic and immunologic responses with salvage antiretroviral regimens. Current treatment guidelines recommend starting therapy for human immunodeficiency virus (HIV) infection with 2 nucleoside analogue reverse-transcriptase inhibitors in combination with 1 or 2 protease inhibitors or a nonnucleoside analogue reversetranscriptase inhibitor [1, 2]. However, 20%‐63% of patients from clinical cohorts experience virologic treatment failure while receiving combination antiretroviral therapy [3‐7]. Recent prospective studies have attempted to identify strategies for treatment of the treatment-experienced patient [8‐13], but these studies have focused primarily on 8‐24-week virologic responses to treatment. The durability of virologic and immunologic re

Summary Aim: Until now scintimammography did not achieve any definite role in the assessment of breast lesions. Purpose of this study was to elaborate its use as well as the limitations of scintimammography after 500 examinations completed. Methods: Scintigraphic findings were correlated with the histopathologic outcome of 219 patients, who underwent surgery or biopsy for histopathological confirmation. The results were determined with respect to palpability of the lesion and tumour size. Additionally, a distinct analysis was performed for the patient subpopulation with indeterminate results of previously performed physical examination, mammography, and sonography. Results: Overall sensitivity for scintimammography was 82.1% at a specificity of 87.5%. For palpable lesions sensitivity was 91.7% which was evidently higher as compared to 64.9% for non palpable lesions. For palpable lesions specificity was 81.1% and 88.6% for non palpable lesions. According to tumour size sensitivity ranged between 65.2% for carcinoma with a diameter 1 cm. In the patients subgroup with indeterminate preliminary diagnosis (n = 143) sensitivity decreased to 71.7% at a specificity of 87.8%. Patients undergoing neoadjuvant chemotherapy showed decreasing sestamibi uptake as early as 8 days after therapy if tumour response was evident. However, small residual invasive tumours in patients with complete remission could not be visualised. Conclusion: Scintimammography is neither suited for screening, nor early diagnosis of breast cancer, nor for the further evaluation of small and unclear mammographic findings. Scintimammography should not be used whenever histopathological clarification of a suspicious lesion is necessary. It is useful to further investigate patients with unclear or probably benign findings in physical examination and/or mammography and to monitor tumour response to neoadjuvant chemotherapy.

In engineering applications, one of the actual scientific challenges is a development of sensor systems with complex adaptive behaviour and operating sensitivity. Smart materials like magneto-sensitive elastomers (MSEs) offer great potential for designing such intelligent devices, because they possess unique magnetic-field dependent properties. This paper deals with the investigation of the free vibrational behaviour displayed by cantilever beams made of MSEs containing magnetically soft particles in the presence of a uniform magnetic field. The presented setup is considered as a prototype of a sensitive unit for transforming mechanical stimuli of the base into vibrations of the MSE element, which could be converted in a facile way into electromagnetic signals for measuring and analysing. It is shown experimentally that for the MSE beams of several different lengths and compositions, the first eigenfrequency depends strongly on the strength of the applied magnetic field. The developed theoretical model extends the conventional vibrational dynamics of thin rods to allow for the ponderomotive torque induced by magneto-mechanical interactions experienced by an MSE beam. The model has two adjustable parameters that characterise the geometric configuration of the cantilever beam and its magnetic material properties. It is found that the values of these parameters are 'universally' valid, i.e., they provide good agreement between the theoretical eigenfrequency dependencies and the experimental results for all used MSE beams. The evidence presented ensures a good basis for further investigations of the sensitivity and amplitude–frequency characteristics of MSE vibration sensor elements.

Innovative developments in the pharmacotherapy of juvenile idiopathic arthritis and especially biologics allow the formulation of new therapeutic targets, such as the rapid induction of remission with shortening of the period of active disease and therefore preventing damage and disability. These new therapies also represent a challenge to the monitoring of drug safety, the pharmacovigilance. For this purpose the Society for Paediatric and Adolescent Rheumatology has set up an early register to record achievements in treatment improvement and in addition to independently assess information on drug safety, acute tolerance and long-term safety.

is well-known that eye movements are central to visual perception [1]. Visual acuity decreases dramatically in the periphery of vision, and precise eye movements to specific locations are vital to foveate objects of interest and identify them with high accuracy [1–4]. Given the importance of eye movements for visual perception, there has been a surge of interest in the topic, with numerous studies being conducted to clarify the variables that determine our eye movements (for a historical review see [5]). In fact, Google Scholar shows that eye movements are discussed in over a million publications, and a Web of Science search reveals 17,000 publications with eye movement in the title or abstract. As shown in Figure 1, the number of publications with eye movement in the title or abstract has also steadily increased over years, culminating in about 200 papers published in 2013. Figure 1 The number of publications with the “eye movement” in the title or abstract, according to a Web of Science search 2014. Despite the surge of interest in eye movements, many questions remain unresolved. This is also reflected in this special issue on eye movement control. First, there are a variety of different eye movements [2, 4]. Among the most widely known eye movements are the fast, ballistic saccades (including superfast express saccades) (e.g., B. de Gelder et al., this issue), smooth-pursuit eye movements (J. N. van der Geest et al., this issue), and vergence eye movements (e.g., P. M. Grove et al., this issue) required to fixate objects at different depths. Less well-known and yet intensely researched are microsaccades, tremor, slow drift, and vestibuloocular and optokinetic eye movements that stabilize gaze during motions of the head and motions of large regions of the image on the retina [2, 4]. Secondly and more importantly for the current special issue, eye movements are also controlled by a variety of different factors [1, 4]. Apart from being subject to diverse muscular and ocular constraints, successful voluntary control over eye movements critically depends on the quality of the visual input, which in turn depends on a variety of internal and external factors [1, 6, 7]. The contributions to the present special issue clarify key elements of both internal and external factors in eye movement control (G. W. Alpers et al., U. Ansorge et al., B. de Gelder et al., P. M. Grove et al., D. R. Hardwick et al., W. E. Huddlestone et al., J. Kassubek et al., A. Khan et al., A. Piras et al., N. D. Smith et al., J. N. van der Geest et al., and D. Venini et al., this issue). In the present contributions, eye movements have also been used to provide new insights into ocular and neurological disorders (J. Kassubek et al., N. D. Smith et al., this issue) and shed new light on the relationship between covert attention and eye movements (e.g., G. W. Alpers et al., U. Ansorge et al., D. R. Hardwick et al., and A. Khan et al., this issue; see also [6–9]). Together, the papers in this special issue provide a timely update on eye movement control that reflects current hot topics in the field, spanning the range from cognitive science over applied psychology to clinical psychology and neuroscience. Stefanie I. Becker Gernot Horstmann Arvid Herwig

In visual search, responses are slowed, from one trial to the next, both when the target dimension changes (e.g., from a color target to a size target) and when the target feature changes (e.g., from a red target to a green target) relative to being repeated across trials. The present study examined whether such feature and dimension switch costs can be attributed to the same underlying mechanism(s). Contrary to this contention, an EEG study showed that feature changes influenced visual selection of the target (i.e., delayed N2pc onset), whereas dimension changes influenced the later process of response selection (i.e., delayed s-LRP onset). An fMRI study provided convergent evidence for the two-system view: Compared with repetitions, feature changes led to increased activation in the occipital cortex, and superior and inferior parietal lobules, which have been implicated in spatial attention. By contrast, dimension changes led to activation of a fronto-posterior network that is primarily linked with response selection (i.e., pre-motor cortex, supplementary motor area and frontal areas). Taken together, the results suggest that feature and dimension switch costs are based on different processes. Specifically, whereas target feature changes delay attention shifts to the target, target dimension changes interfere with later response selection operations.

Recently, D.V. Becker, Anderson, Mortensen, Neufeld, and Neel (2011) proposed recommendations to avoid methodological confounds in visual search studies using emotional photographic faces. These confounds were argued to cause the frequently observed Anger Superiority Effect (ASE), the faster detection of angry than happy expressions, and conceal a true Happiness Superiority Effect (HSE). In Experiment 1, we applied these recommendations (for the first time) to visual search among schematic faces that previously had consistently yielded a robust ASE. Contrary to the prevailing literature, but consistent with D.V. Becker et al. (2011), we observed a HSE with schematic faces. The HSE with schematic faces was replicated in Experiments 2 and 3 using a similar method in discrimination tasks rather than fixed target searches. Experiment 4 isolated background heterogeneity as the key determinant leading to the HSE.

In visual search for pop-out targets, search times are shorter when the target and non-target colors from the previous trial are repeated than when they change. This priming effect was originally attributed to a feature weighting mechanism that biases attention towards the target features, and away from the non-target features. However, more recent studies have shown that visual selection is strongly context-dependent: According to a relational account of feature priming, the target color is always encoded relative to the non-target color (e.g., as redder or greener). The present study provides a critical test of this hypothesis, by varying the colors of the search items such that either the relative color or the absolute color of the target always remained constant (or both). The results clearly show that color priming depends on the relative color of a target with respect to the non-targets but not on its absolute color value. Moreover, the observed priming effects did not change over the course of the experiment, suggesting that the visual system encodes colors in a relative manner from the start of the experiment. Taken together, these results strongly support a relational account of feature priming in visual search, and are inconsistent with the dominant feature-based views.

Borna disease (BD) is a severe endemic and fatal disorder caused by the neurotropic Borna disease virus (BDV) which mainly occurs in horses and sheep. Borna disease virus belongs to the order Mononegavirales, which includes many reservoir-bound viruses with high zoonotic and pathogenic properties including the filoviruses and lyssaviruses. Clinically manifest BD occurs in endemic areas of Germany, Switzerland, Liechtenstein, and Austria. A seasonal accumulation of cases in spring and summer, incidences that vary from year to year, and the recent detection of BDV in bicolored shrews (Crocidura leucodon) in Swiss endemic areas argue for a natural reservoir. We established a geographic information system analysis of the distribution of 485 equine BD cases in Bavarian (Germany) endemic areas and of the occurrence of 285 records of C. leucodon captured in Bavaria. Boosted regression trees were used to identify driving factors of habitat choice and virus prevalence. The distribution model of C. leucodon and the prevalence model for BDV had very good accuracy. Mean annual precipitation900 mm, mean annual temperatures of 8 C, elevation350 m, low forest cover, and a high percentage of urban fabric and arable land describe the optimal habitat for C. leucodon. Occurrence probability of C. leucodon was significantly higher in Bavarian BDV-endemic areas than in random areas in Bavaria. The prevalence of BD was higher in urban areas with annual mean precipitation of 800-900 mm, annual mean temperature of 8 C, and elevation500 m. Our results indicate that the distribution model can accurately predict BD occurrence. Based on these results, practical safety precautions could be derived. The BDV model represents a suitable system for reservoir-bound, neurotropic Mononegavirales because it allows analyzing ecologic and biologic aspects that determine virus abundance, maintenance in reservoir species, and transmission to end host species.

The approval of etanercept for the treatment of the juvenile idiopathic arthritis (JIA) categories extended oligoarthritis (ExtOA), enthesitis-related arthritis (ERA) and psoriasis arthritis (PsA) was recently added to the approval for the treatment of polyarticular-course JIA (PA). This study aims to evaluate the efficacy and safety of etanercept in a large number of patients with the additional JIA categories. The Biologika in der Kinderrheumatologie (BIKER) registry documents baseline demographics, clinical characteristics and disease activity parameters. Efficacy was determined using the PedACR 30/50/70 response criteria and the Juvenile Arthritis Disease Activity Score (JADAS)-10. Safety assessments were based on adverse events’ reports. Until December 2012, a total of 1,678 JIA patients, incorporating 238 ERA, 315 ExtOA and 127 PsA patients were included. JADAS-10 demonstrated marked improvement compared to baseline after 3 to 24 months in ExtOA [16.1 ± 7.6 (baseline), 5.1 ± 5.2 (3 months), 3.0 ± 3.5 (24 months)]; ERA (15.3 ± 7.2, 4.4 ± 4.7, 4.0 ± 4.9) and PsA (14.7 ± 6.4, 5.0 ± 4.6, 5.3 ± 6.4). Compared to patients with PA, the rate of serious adverse events [relative risk (RR) 1.39 (0.95–2.03, p = 0.08)] and nonserious [1.18 (1.02–1.35; p = 0.03)] adverse events were elevated. The rate of uveitis flares was significantly higher in PsA (3.3/100 patient-years), ExtOA (2.8/100 patient-years) and ERA (2.7/100 patient-years) than in rheumatoid factor (RF)-negative polyarticular JIA (1.3/100 pat.yrs) or RF-positive polyarticular JIA (0.27/100 patient-years). Reports on chronic inflammatory bowel disease were numerically more frequent in ExtOA, ERA and PsA. Administration of etanercept in patients with the JIA categories ExtOA, ERA and PsA is safe and very efficacious in children. Attention should be paid to the occurrence of extraarticular autoimmunopathies.

In visual search, some fixations are made between stimuli on empty regions, commonly referred to as “centre-of-gravity” fixations (henceforth: COG fixations). Previous studies have shown that observers with task expertise show more COG fixations than novices. This led to the view that COG fixations reflect simultaneous encoding of multiple stimuli, allowing more efficient processing of task-related items. The present study tested whether COG fixations also aid performance in visual search tasks with unfamiliar and abstract stimuli. Moreover, to provide evidence for the multiple-item processing view, we analysed the effects of COG fixations on the number and dwell times of stimulus fixations. The results showed that (1) search efficiency increased with increasing COG fixations even in search for unfamiliar stimuli and in the absence of special higher-order skills, (2) COG fixations reliably reduced the number of stimulus fixations and their dwell times, indicating processing of multiple distractors, and (3) the proportion of COG fixations was dynamically adapted to potential information gain of COG locations. A second experiment showed that COG fixations are diminished when stimulus positions unpredictably vary across trials. Together, the results support the multiple-item processing view, which has important implications for current theories of visual search.

European Vegetation Archive (EVA) was announced as a new initiative of the European Vegetation Survey at the EVS Meeting in Vienna in 2012. The aim of EVA is to create a centralized database of European vegetation plots by storing copies of national and regional databases on a single software platform using a unified taxonomic reference database. EVA does not affect the ongoing independent developments of source databases and it guarantees that data property rights of the original contributors are respected. EVA Data Property and Governance Rules were approved and the EVA website (www.euroveg.org/eva-database) was established in 2012. Since then several European vegetation-plot databases joined EVA. In the framework of the parallel Braun-Blanquet project, we obtained experience with handling multiple databases based on different taxonomies, and a prototype of Turboveg 3 was developed as a software tool for joint management of multiple databases. This prototype has recently been accepted as the platform for technical management of EVA according to the approved Rules. A specific challenge for EVA is joining multiple species lists with different taxonomies used in national and regional databases. To solve this issue, EVA took over the SynBioSys Taxon Database, developed earlier for the SynBioSys Europe project, which is a system of taxon names and concepts used in the individual databases and their matches to a unified list of European flora. This taxon database is currently being extended to account for new vegetation-plot databases and revised by taxonomic experts working in a newly established EVA Taxonomic Advisory Board. These technical developments made it possible that after two years since its formal establishment, first data sets could be uploaded to EVA, forming a basis for large-scale analyses of European vegetation diversity for both scientific purposes and applications.

Wir berichten uber einen 59-jahrigen Patienten, bei dem vor 2 Jahren eine reaktiv perforierende Kollagenose anhand des klinischen Bildes und der dazu passenden Histologie diagnostiziert wurde. Eine deutliche Verschlechterung des Allgemeinempfindens und der Hautlasionen fuhrte zu einer stationaren Aufnahme des Patienten. Die Abstriche von den Hautlasionen konnten eine Superinfektion mit Candida albicans, Pseudomonas aeruginosa, Enterokokken, koagulasenegativen Staphylokokken sowie methizillinresistenten Staphylokokken (MRSA) nachweisen. In der Folge kam es zu einem septischen Multiorganversagen mit delirantem Zustandsbild, katecholaminpflichtiger Kreislaufinsuffizienz und Funktionsstorungen von Leber und Niere, welches durch testgerechte Antibiose, der in den Hautlasionen isolierten Keime, gut therapierbar war. Dies zeigt, dass die reaktiv perforierende Kollagenose durch bakterielle Superinfektion einen potentiell lebensbedrohlichen, septischen Verlauf nehmen kann, der durch rasche und testgerechte Antibiose der in den Hautlasionen isolierten Keime behandelt werden sollte. Trotz fehlendem Nachweis der Keime in den Blutkulturen spricht der klinische Verlauf fur eine Ursachlichkeit der isolierten Keime und gegen eine irrelevante Kollonisation der Hautlasionen.

The susceptibility of Trypanosoma cruzi epimastigotes to lysis by normal or immune sera in a complement-dependent reaction has been reported, but the effects induced directly by immune serum depleted of complement remain unstudied. The aim of this work was to study the ultrastructural alterations induced in T. cruzi epimastigotes by immune mouse or rabbit sera with or without complement. A local isolate of T. cruzi (Queretaro) was used in all experiments. Immune sera were raised in both mouse and rabbit by immunization with T. cruzi epimastigote antigens. Light microscopy showed intense agglutination of epimastigotes when incubated with decomplemented mouse or rabbit immune sera. A distinctive ultrastructural feature of this agglutination pattern was the fusion of plasma membranes and a pattern of intercrossing between subpellicular microtubules. Agglutination was associated with fragmentation of nuclear membranes and swelling of cytoplasm, Golgi cisternae, endoplasmic reticulum, mitochondria and kinetoplast membranes. Agglutinated parasites also incorporated trypan blue stain. Results of [3H]-thymidine incorporation confirmed that epimastigotes exposed to specific antibodies in the absence of complement were incapable of proliferating. Ultrastructural changes observed in epimastigote micrographs incubated with decomplemented immune mouse sera were statistically significant (P

Different salvage strategies have been used to regain control in patients with HIV who have virological failure on combination antiretroviral therapy. We conducted a cohort study of 63 extensively antiretroviral pretreated patients who initiated nelfinavir as part of salvage therapy, to determine predictors of virological response. The maximum HIV RNA response was >0.5 log10 copies/ml reduction in 43 patients (68%), including 21 patients (33%) who had suppression to

We examined the role of yeast transcription initiation factor IIE (TFIIE) in eukaryotic transcription-coupled repair (TCR), the preferential removal of DNA damage from the transcribed strands of genes over non-transcribed sequences. TFIIE can recruit the transcription initiation/repair factor TFIIH to the RNA polymerase II (RNA pol II) initiation complex to facilitate promoter clearance. Following exposure to UV radiation, the RNA pol II elongation complex is blocked at sites of UV-induced DNA damage, and may be recognized by nucleotide excision repair proteins, thus enabling TCR. The TFA1 gene encodes the large subunit of TFIIE. We determined how DNA repair is affected by TFA1 conditional mutations. In particular, we find proficient TCR in a heat-sensitive tfa1 mutant at the non-permissive temperature during which growth is inhibited and overall RNA pol II transcription is reported to be inhibited. We demonstrate that transcription of the RPB2 gene was reduced, but readily detectable, in the heat-sensitive tfa1 mutant at the non-permissive temperature and thereby prove that TCR does occur in an expressed gene in the absence of TFIIE in vivo. We demonstrate that TCR occurs even at low levels of transcription.

Background Consistent long-term viral suppression has been difficult to achieve in children with human immunodeficiency virus type 1 (HIV-1) infection. We tested the safety and antiviral efficacy of a novel combination consisting of efavirenz, nelfinavir, and one or more nucleoside reverse-transcriptase inhibitors in 57 children previously treated with only nucleoside reverse-transcriptase inhibitors. Methods The children were monitored for 48 weeks after the initiation of therapy. We assessed plasma concentrations of efavirenz and nelfinavir, plasma HIV-1 RNA levels, and lymphocyte subpopulations. Results At base line, the 57 HIV-1–infected children (age range, 3.8 to 16.8 years) had a median of 699 CD4 cells per cubic millimeter and 10,000 copies of HIV-1 RNA per milliliter of plasma. The most common treatment-related effects of at least moderate severity were rash (in 30 percent of children), diarrhea (in 18 percent), neutropenia (in 12 percent), and biochemical abnormalities (in 12 percent). Serious s...

Twenty human immunodeficiency virus-infected patients experiencing virologic failure of an indinavir- or ritonavir-containing treatment regimen were evaluated in a prospective, open-label study. Subjects received nelfinavir, saquinavir, abacavir, and either another nucleoside analog (n=10) or nevirapine (n=10). Patients treated with the nevirapine-containing regimen experienced significantly greater virologic suppression at week 24 than those not treated with nevirapine (P=.04). Baseline phenotypic drug susceptibility was strongly correlated with outcome in both treatment arms. Subjects with baseline virus phenotypically sensitive to 2 or 3 drugs in the salvage regimen experienced significantly greater virus load suppression than those with baseline virus sensitive to 0 or 1 drug (median week-24 change=-2.24 log and -0.35 log, respectively; P=.01). In conclusion, non-nucleoside reverse transcriptase inhibitors may represent a potent drug in salvage therapy regimens after failure of an indinavir or ritonavir regimen. Phenotypic resistance testing may provide a useful tool for selecting more effective salvage regimens.

The melanocortin-4 receptor gene (MC4-R) has been implicated in weight regulation. Recently, two independent groups reported frameshift mutations associated with a dominant form of obesity (1, 2). We screened the coding region of the MC4-R in 306 extremely obese children and adolescents (mean body mass index: BMI 34.4 +/- 6.6 kg/m2), 25 healthy underweight students (mean BMI 17.1 +/- 0.8 kg/m2), 52 normal weight individuals (mean BMI 22.0 +/- 1.0 kg/m2), 51 inpatients with anorexia nervosa (AN, DSM IV criteria, mean BMI 14.3 +/- 1.5 kg/m2) and 27 patients with bulimia nervosa (BN, DSM IV criteria, mean BMI 21.7 +/- 5.8 kg/m2) by single strand conformation polymorphism analysis (SSCP). Several mutations were identified, including the frameshift mutation described (1). The mutations were as follows: a) The deletion of 4 bp (delta of CTCT at codon 211) results in a frameshift, thus rendering a truncated protein. This mutation has been assumed to be associated with dominantly-inherited morbid obesity in humans (1). Both the index patient (BMI 42.06 kg/m2, height 171 cm, age 19.6 years) and her mother (BMI 37.55 kg/m2, height 164 cm, age 42.5 years) were heterozygous for the deletion. b) A nonsense mutation at position 35 of the MC4-R was detected in two obese probands (BMI 31.29 kg/m2 and BMI 45.91 kg/m2). This mutation leads to a truncated protein that encompasses the N-terminal extracellular domain. Both carriers additionally showed (c) a missense mutation (Asp-37-Val). In both of these cases Tyr-35-Stop and Asp-37-Val were maternally transmitted, thus these variations form a haplotype. d) e) A male obese proband harbored two missense mutations (Ser-30-Phe, Gly-252-Ser). f)-i) Four different missense mutations (Pro-78-Leu, Thr-112-Met, Arg-165-Trp, Ile-317-Thr) were detected in four different male probands, respectively. All of these mutations (a to i) were found solely in extremely obese individuals whose BMIs were all above the 99th percentile. j) A silent mutation (C-579-T, Val-193-Val) was detected in a male underweight individual. k) A previously described polymorphism (Val-103-Ile; 3) was detected with similar frequencies in all different study groups. 1) We identified a novel polymorphism (Ile-251-Leu) with similar allele frequencies in all groups under study. In conclusion, our data indicate that mutations in the MC4-R are not uncommon. Whereas our data support the evidence for dominantly inherited obesity as revealed by the three obese probands with haplo-insufficiency, the functional significance of the missense mutations remains to be determined.

Most frequently the ependymomas of the central nervous system affect the Conus medullaris and Filum terminale. Ependymomas of the thoracic spine with association of a tumor-caused syringomyelia are extremely rare. The reported 50 years old patient with a thoracic ependymoma realized first symptoms as a shoulder-arm pain caused by the tumor-syrinx. The case report indicates that MRI is the superior imaging modality for primary tumors of the central nervous system. All relevant diagnostic and therapeutic informations derived from the MRI. The article describes the clinical manifestations, the diagnostic way and therapeutic procedure in the problem region thoracic spine.

The Space Telescope Imaging Spectrograph (STIS) instrument was installed on the Hubble Space Telescope (HST) during the second servicing mission, in 1997 February. Four bands cover the wavelength range of 115–1000 nm, with spectral resolving powers between 26 and 200,000. Camera modes are used for target acquisition and deep imaging. Correction for HST's spherical aberration and astigmatism is included. The 115–170 nm range is covered by a CsI MAMA (Multianode Microchannel Array) detector and the 165–310 nm range by a Cs2Te MAMA, each with a format of \documentclass{aastex} \usepackage{amsbsy} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{bm} \usepackage{mathrsfs} \usepackage{pifont} \usepackage{stmaryrd} \usepackage{textcomp} \usepackage{portland,xspace} \usepackage{amsmath,amsxtra} \usepackage[OT2,OT1]{fontenc} \newcommand\cyr{ \renewcommand\rmdefault{wncyr} \renewcommand\sfdefault{wncyss} \renewcommand\encodingdefault{OT2} \normalfont \selectfont} \DeclareTextFontCommand{\textcyr}{\cy...

The magnetic fields emitted by electronic article surveillance (EAS) systems (shoplifting gates) are a source of interference for implanted medical devices. In the Study of Pacemaker and Implantable Cardioverter Defibrillator Triggering by Electronic Article Surveillance Devices (SPICED TEAS), 25 adult volunteers with ICDs and 50 with pacemakers were exposed to the fields of six different EAS systems. These EAS systems used three modes of operation: magnetic audio frequency, swept radiofrequency, and acoustomagnetic technology. No ICD exhibited interference mimicking sensing of tachyarrhythmias with any EAS system. Pacemakers interacted variably, depending on the type of EAS system. Swept radiofrequency systems produced no interaction with any implanted medical device. One magnetic audio frequency system interacted with 2 of 50 pacemakers. The acoustomagnetic system interacted with 48 of 50 pacemakers. Interactions included asynchronous pacing, atrial oversensing (producing "EAS induced tachycardia" in the ventricle), ventricular oversensing (with pacemaker inhibition), and paced beats resulting from the direct induction of current in the pacemaker ("EAS induced pacing"). These interactions produced symptoms in some patients (palpitations, presyncope) only while patients were in the EAS field. No pacemaker was reprogrammed. We conclude that high energy, pulsed low frequency EAS systems such as acoustomagnetic systems interfere with most pacemakers. Pacemaker patients should be advised to minimize exposure to the fields of such systems to prevent the possibility of serious clinical events.

Pro-opiomelanocortin (POMC) is the precursor of melanocortins (adrenocorticotropin: ACTH, beta-endorphin, beta-lipotropin: beta-LPH, corticotropin like intermediate peptide, alpha-, beta- and gamma-melanocyte-stimulating hormone: alpha-, beta- and gamma-MSH) some of which act in the brain to reduce food intake and are potential mediators of leptin action. Recently, three different mutations in the POMC gene (POMC) were identified in two unrelated children that lead to early-onset extreme obesity, adrenal insufficiency, and red hair pigmentation. In the present study we systematically screened the coding region of POMC in 96 extremely obese children and adolescents, 60 healthy underweight individuals and 46 patients with anorexia nervosa (AN) and identified several variants. a) A 9 and an 18 base pair insertion (9bp and 18bp: AGC AGC GGC and AGC AGC GGC AGC AGC GGC, respectively, between codon 73 and 74; 1,2). These in-frame variants lead to the insertion of three or six amino acids (Ser-Ser-Gly; Ser-Ser-Gly-Ser-Ser-Gly) carboxy-terminal to gamma-MSH. Frequencies of the 9bp insertion allele varied between 3 and 5% among the different study groups (Pearson's chi2 P>0.5). b) Both an out-of-frame 6 bp insertion (within codon 176: GGG CCC) leading to the insertion of two amino acids (Arg-Ala) and a premature stop-codon (G-7316-T: Glu-180-Stop) within the gamma-LPH sequence were maternally inherited in an obese female proband. This proband inherited another missense mutation from her father (Glu-188-Gly). c) A missense mutation (G-7016-A; Asp-80-Asn) was observed in a single patient with AN who also harboured the 9bp insertion on a paternally derived haplotype. d) The allelic co-occurence of two silent mutations (C-6982-T and C-7285-T) was detected in two obese subjects. e) Two further silent mutations (C-3832-T; C-7111-G) were detected in an underweight and an obese subject, respectively. We conclude that the POMC gene harbors several different polymorphisms and mutations, none of which can readily be associated with the phenotypes under study.

The partitioning of a rectangular grid graph with weighted vertices into p connected components such that the component of smallest weight is as heavy as possible (the max-min problem) is considered. It is shown that the problem is NP-hard for rectangles with at least three rows. A shifting algorithm is given which approximates the optimal solution. Bounds for the relative error are determined under a posteriori hypotheses. A further shifting algorithm is also given which allows for error estimates under a priori hypotheses and for asymptotic error estimates. A similar approach can be taken with the problem of finding the partition whose largest component is as small as possible (the min-max problem). The case of rectangles with two rows has a polynomial algorithm and is dealt with in another paper.

Immunization of mice with DNA vaccines encoding the full-length form and C and N termini of Plasmodium yoelii merozoite surface protein 1 provided partial protection against sporozoite challenge and resulted in boosting of antibody titers after challenge. In C57BL/6 mice, two DNA vaccines provided protection comparable to that of recombinant protein consisting of the C terminus in Freund’s adjuvant.

The Space Telescope Imaging Spectrograph (STIS) was successfully installed into the Hubble Space Telescope (HST) in 1997 February, during the second HST servicing mission, STS-82. STIS is a versatile spectrograph, covering the 115-1000 nm wavelength range in a variety of spectroscopic and imaging modes that take advantage of the angular resolution, unobstructed wavelength coverage, and dark sky offered by the HST. In the months since launch, a number of performance tests and calibrations have been carried out and are continuing. These tests demonstrate that the instrument is performing very well. We present here a synopsis of the results to date.

What factors determine which stimuli of a scene will be visually selected and become available for conscious perception? Current models of attention assume that top-down control over visual selection is achieved by tuning attention to specific feature values (e.g. red, green, blue). This modulates the output of feature-specific sensory neurons (‘feature maps’) that guide attention to locations that contain the sought-after feature. Contrary to this prevalent view, it has been proposed that visual selection depends on the context. According to a new relational account, features are appraised in a context-dependent manner, so that items are selected in virtue of their relationship to the context (e.g. redder, larger, darker) rather than their absolute feature values (e.g. red vs. green). The present chapter argues that the feature map concept is untenable in view of recent evidence for the relational account, as feature map theories would have to propose an unrealistically large number of additional feature maps to account for guidance by feature relationships. Moreover, it is argued that top-down tuning to feature relationships is neurologically plausible and that the relational theory can potentially replace current feature-based theories of attention.

Visual search is typically faster when the target from the previous trial is repeated than when it changes. This priming effect is commonly attributed to a selection bias for the target feature value or against the nontarget feature value that carries over to the next trial. By contrast, according to a relational account, what is primed in visual search is the target-nontarget relationship-namely, the feature that the target has in relation to the features in the nontarget context (e.g., larger, darker, redder)-and switch costs occur only when the target-nontarget relations reverse across trials. Here, the relational account was tested against current feature-based views in three eye movement experiments that used different shape search tasks (e.g., geometrical figures varying in the number of corners). For all tested shapes, reversing the target-nontarget relationships produced switch costs of the same magnitude as directly switching the target and nontarget features across trials ("full-switch"). In particular, changing only the nontargets produced large switch costs, even when the target feature was always repeated across trials. By contrast, no switch costs were observed when both the target and nontarget features changed, such that the coarse target-nontarget relations remained constant across trials. These results support the relational account over feature-based accounts of priming and indicate that a target's shape can be encoded relative to the shapes in the nontarget context.

Mammals use five main, mutually nonexclusive mechanisms to balance energy budgets: torpor, metabolic compensation, change in activity patterns, change in ingested energy, and/or variability in digestive efficiency. Bats, as small and actively flying mammals, have a high mass-specific energy demand; therefore, balancing mechanisms should be pronounced in this group. We found that male Myotis daubentonii exhibited marked variation in the relative importance of these different mechanisms during their period of seasonal activity in response to extrinsic (ambient temperature, insect abundance) and intrinsic (reproduction, body condition) factors. Cold ambient temperatures in spring facilitated long and frequent daily torpor bouts, whereas in early summer, increased energy intake was the dominant factor in energy balancing. Intake was further increased in late summer, when insect abundance was highest, and daily torpor bouts were shorter and less frequent than in early summer. In autumn, males used metabolic compensation to reduce their resting metabolic rate in addition to daily torpor. Metabolic compensation might be one of the mechanisms that allow males to maintain high body temperature during the day while decreasing the need for foraging time at night, thus maximizing their opportunities to mate.

Task switch costs often show an asymmetry, with switch costs being larger when switching from a difficult task to an easier task. This asymmetry has been explained by difficult tasks being represented more strongly and consequently requiring more inhibition prior to switching to the easier task. The present study shows that switch cost asymmetries observed in arithmetic tasks (addition vs. subtraction) do not depend on task difficulty: Switch costs of similar magnitudes were obtained when participants were presented with unsolvable pseudo-equations that did not differ in task difficulty. Further experiments showed that neither task switch costs nor switch cost asymmetries were due to perceptual factors (e.g., perceptual priming effects). These findings suggest that asymmetrical switch costs can be brought about by the association of some tasks with greater difficulty than others. Moreover, the finding that asymmetrical switch costs were observed (1) in the absence of a task switch proper and (2) without differences in task difficulty, suggests that present theories of task switch costs and switch cost asymmetries are in important ways incomplete and need to be modified.

Eye fixations allow the human viewer to perceive scene content with high acuity. If fixations drive visual memory for scenes, a viewer might repeat his/her previous fixation pattern during recognition of a familiar scene. However, visual salience alone could account for similarities between two successive fixation patterns by attracting the eyes in a stimulus-driven, task-independent manner. In the present study, we tested whether the viewer's aim to recognize a scene fosters fixations on scene content that repeats from learning to recognition as compared to the influence of visual salience alone. In Experiment 1 we compared the gaze behavior in a recognition task to that in a free-viewing task. By showing the same stimuli in both tasks, the task-independent influence of salience was held constant. We found that during a recognition task, but not during (repeated) free viewing, viewers showed a pronounced preference for previously fixated scene content. In Experiment 2 we tested whether participants remembered visual input that they fixated during learning better than salient but nonfixated visual input. To that end we presented participants with smaller cutouts from learned and new scenes. We found that cutouts featuring scene content fixated during encoding were recognized better and faster than cutouts featuring nonfixated but highly salient scene content from learned scenes. Both experiments supported the hypothesis that fixations during encoding and maybe during recognition serve visual memory over and above a stimulus-driven influence of visual salience.

Visual search studies have shown that attention can be top-down biased to a specific target color, so that only items with this color or a similar color can capture attention. According to some theories of attention, colors from different categories (i.e., red, green, blue, yellow) are represented independently. However, other accounts have proposed that these are related--either because color is filtered through broad overlapping channels (4-channel view), or because colors are represented in one continuous feature space (e.g., CIE space) and search is governed by specific principles (e.g., linear separability between colors, or top-down tuning to relative colors). The present study tested these different views using a cueing experiment in which observers had to select one target color (e.g., red) and ignore two or four differently colored distractors that were presented prior to the target (cues). The results showed clear evidence for top-down contingent capture by colors, as a target-colored cue captured attention more strongly than differently colored cues. However, the results failed to support any of the proposed views that different color categories are related to one another by overlapping channels, linear separability, or relational guidance (N = 96).

Bipolar disorder (BPD), probably the most prevalent psychotic disorder in adults, has been relatively neglected or controversial in children and adolescents over the past century. We reviewed the literature on early-onset BPD. Estimates of prevalence, particularly before puberty, are limited by historical biases against pediatric mood disorders and by formidable diagnostic complexity and comorbidity. Although clinical features of pediatric and adult BPD have similarities, pediatric cases probably cannot be defined solely by features characteristic of adult cases. Onset was before age 20 years in at least 25% of reported BPD cases, with some increase in this incidence over the past century. Pediatric BPD is familial more often than is adult-onset BPD, may be associated with a premorbid cyclothymic or hyperthymic temperament, and can be precipitated by antidepressant treatment. Pediatric BPD episodes frequently include irritability, dysphoria, or psychotic symptoms; they are commonly chronic and carry high risks of substance abuse and suicide. BPD is often recognized in adolescents, but the syndrome or its antecedents are almost certainly underrecognized and undertreated in children. Controlled studies of short- and long-term treatment, course, and outcome in this disorder remain strikingly limited, and the syndrome urgently requires increased clinical and scientific interest.

In three experiments, we tested whether sequentially coding two visual stimuli can create a spatial misperception of a visual moving stimulus. In Experiment 1, we showed that a spatial misperception, the flash-lag effect, is accompanied by a similar temporal misperception of first perceiving the flash and only then a change of the moving stimulus, when in fact the two events were exactly simultaneous. In Experiment 2, we demonstrated that when the spatial misperception of a flash-lag effect is absent, the temporal misperception is also absent. In Experiment 3, we extended these findings and showed that if the stimulus conditions require coding first a flash and subsequently a nearby moving stimulus, a spatial flash-lag effect is found, with the position of the moving stimulus being misperceived as shifted in the direction of its motion, whereas this spatial misperception is reversed so that the moving stimulus is misperceived as shifted in a direction opposite to its motion when the conditions require coding first the moving stimulus and then the flash. Together, the results demonstrate that sequential coding of two stimuli can lead to a spatial misperception whose direction can be predicted from the order of coding the moving object versus the flash. We propose an attentional sequential-coding explanation for the flash-lag effect and discuss its explanatory power with respect to related illusions (e.g., the Fröhlich effect) and other explanations.

The Arg residue at position 8 of mammalian GnRH is necessary for high affinity binding to mammalian GnRH receptors. This requirement has been postulated to derive from an electrostatic interaction of Arg8 with a negatively charged receptor residue. In order to identify such a residue, 8 conserved acidic residues of the mouse GnRH receptor were mutated to isosteric Asn or Gln. Mutant receptors were tested for decreased preference for Arg8-containing ligands by ligand binding and inositol phosphate production. One of the mutants, in which the Glu301 residue was mutated to Gln, exhibited a 56-fold decrease in apparent affinity for mammalian GnRH. The mutant receptor also exhibited decreased affinity for [Lys8]GnRH, but its affinity for [Gln8]GnRH was unchanged compared with the wild type receptor. The apparent affinity of the mutant receptor for the acidic analogue, [Glu8]GnRH, was increased more than 10-fold. The mutant receptor did not, therefore, distinguish mammalian GnRH from analogues with amino acid substitutions at position 8 as effectively as the wild type receptor. This loss of discrimination was specific for the residue at position 8, because the mutant receptor did distinguish mammalian GnRH from analogues with favorable substitutions at positions 5, 6, and 7. These findings show that Glu301 of the GnRH receptor plays a role in receptor recognition of Arg8 in the ligand and are consistent with an electrostatic interaction between these 2 residues.

We tested whether color word cues automatically primed attentional control settings during visual search, or whether color words were used in a strategic manner for the control of attention. In Experiment 1, we used color words as cues that were informative or uninformative with respect to the target color. Regardless of the cue’s informativeness, distractors similar to the color cue captured more attention. In Experiment 2, the participants either indicated their expectation about the target color or recalled the last target color, which was uncorrelated with the present target color. We observed more attentional capture by distractors that were similar to the participants’ predictions and recollections, but no difference between effects of the recollected and predicted colors. In Experiment 3, we used 100%-informative word cues that were congruent with the predicted target color (e.g., the word “red” informed that the target would be red) or incongruent with the predicted target color (e.g., the word “green” informed that the target would be red) and found that informative incongruent word cues primed attention capture by a word-similar distractor. Together, the results suggest that word cues (Exps. 1 and 3) and color representations (Exp. 2) primed attention capture in an automatic manner. This indicates that color cues automatically primed temporary adjustments in attention control settings.

The ability to attribute mental states to others is crucial for social competency. To assess mentalizing abilities, in false-belief tasks participants attempt to identify an actor’s belief about an object’s location as opposed to the object’s actual location. Passing this test on explicit measures is typically achieved by 4 years of age, but recent eye movement studies reveal registration of others’ beliefs by 7 to 15 months. Consequently, a 2-path mentalizing system has been proposed, consisting of a late developing, cognitively demanding component and an early developing, implicit/automatic component. To date, investigations on the implicit system have been based on single-trial experiments only or have not examined how it operates across time. In addition, no study has examined the extent to which participants are conscious of the belief states of others during these tasks. Thus, the existence of a distinct implicit mentalizing system is yet to be demonstrated definitively. Here we show that adults engaged in a primary unrelated task display eye movement patterns consistent with mental state attributions across a sustained temporal period. Debriefing supported the hypothesis that this mentalizing was implicit. It appears there indeed exists a distinct implicit mental state attribution system.

Waves of spontaneous electrical activity propagate across many regions of the central nervous system during specific stages of early development. The patterns of wave propagation are critical in the activation of many activity-dependent developmental programs. It is not known how the mechanisms that initiate and propagate spontaneous waves operate during periods in which major changes in neuronal structure and function are taking place. We have recently reported that spontaneous waves of activity propagate across the neonatal mouse cerebral cortex and that these waves are initiated at pacemaker sites in the septal nucleus and ventral cortex. Here we show that spontaneous waves occur between embryonic day 18 (E18) and postnatal day 12 (P12), and that during that period they undergo major changes in transmitter dependence and propagation patterns. At early stages, spontaneous waves are largely GABA dependent and are mostly confined to the septum and ventral cortex. As development proceeds, wave initiation depends increasingly on AMPA-type glutamate receptors, and an ever increasing fraction of waves propagate into the dorsal cortex. The initiation sites and restricted propagation of waves at early stages are highly correlated with the position of GABAergic neurons in the cortex. The later switch to a glutamate-based mechanism allows propagation of waves into the dorsal cortex, and appears to be a compensatory mechanism that ensures continued wave generation even as GABA transmission becomes inhibitory.

Can a stimulus capture attention independent of the observer's goals and intentions? In a recent review, (Burnham, Psychonomic Bulletin & Review, 14, 392-422, 2007) argued that there is no convincing evidence that attention capture is ever completely independent of the goals and intentions of the observer. By contrast, surprise capture studies have shown that a color singleton can capture attention on its unannounced first occurrence, if it is new and unexpected, and hence is not part of the intentional set. However, the evidence from surprise capture studies has been criticized on methodological grounds. Here, we tested surprise capture in a new paradigm that avoids previous methodological complications. The results refute the prior criticisms and reinstate surprise capture as prime evidence for goal-independent capture.

The present study examined the factors that determine the dwell times in a visual search task, that is, the duration the gaze remains fixated on an object. It has been suggested that an item’s similarity to the search target should be an important determiner of dwell times, because dwell times are taken to reflect the time needed to reject the item as a distractor, and such discriminations are supposed to be harder the more similar an item is to the search target. In line with this similarity view, a previous study shows that, in search for a target ring of thin line-width, dwell times on thin linewidth Landolt C’s distractors were longer than dwell times on Landolt C’s with thick or medium linewidth. However, dwell times may have been longer on thin Landolt C’s because the thin line-width made it harder to detect whether the stimuli had a gap or not. Thus, it is an open question whether dwell times on thin line-width distractors were longer because they were similar to the target or because the perceptual decision was more difficult. The present study de-coupled similarity from perceptual difficulty, by measuring dwell times on thin, medium and thick line-width distractors when the target had thin, medium or thick line-width. The results showed that dwell times were longer on target-similar than target-dissimilar stimuli across all target conditions and regardless of the line-width. It is concluded that prior findings of longer dwell times on thin linewidth-distractors can clearly be attributed to target similarity. As will be discussed towards the end, the finding of similarity effects on dwell times has important implications for current theories of visual search and eye movement control.

Dispersed rat gastric mucosal cells (F0) were separated into five fractions (F1-F5) by counterflow elutriation, with F1 representing the smallest and F5 the largest cell diameters. In F0-F5, leukotriene B4 (LTB4) release in response to 10(-5) M calcium ionophore A-23187 was 7.68 +/- 1.26, 51.6 +/- 10.8, 72.4 +/- 10.4, 7.1 +/- 0.7, 5.7 +/- 0.6, and 11.6 +/- 3.4 pg.10(6) cells-1 x 30 min-1. In the identical fractions, sulfidopeptide release in response to A-23187 was 200.6 +/- 20.5, 1,116.0 +/- 166.6, 1,309.4 +/- 163.2, 189.8 +/- 25.8, 108.0 +/- 18.0, and 158.4 +/- 54.0 pg.10(6) cells-1 x 30 min-1. High-pressure liquid chromatography verified the radioimmunologically determined LTB4 and identified LTC4 as the only sulfidopeptide LT released. LT release from F2 cells in response to A-23187 was time and dose dependent, reaching maximal stimulation at 10(-5) M A-23187. This response was blocked by the dual inhibitor of cyclooxygenase and lipoxygenases, BW755C (2 x 10(-5)-2 x 10(-4) M), by the selective 5-lipoxygenase inhibitor L-651,392 (10(-7)-10(-5) M), and by MK-886 (10(-9)-10(-7) M), which blocks translocation of 5-lipoxygenase. The postreceptor stimuli dibutyryl adenosine 3',5'-cyclic monophosphate, forskolin, 12-O-tetradecanoyl-phorbol-13-acetate, and oleyl-acetyl-glycerol failed to induce LT release. However, 10(-4) M arachidonic acid increased basal LT release up to eightfold and increased A-23187-stimulated LT release by an additional 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

The cloned sheep gonadotropin-releasing hormone (GnRH) receptor was analysed for sequence homology/differences among mammalian receptors and its pharmacology characterized in COS-1 cells. Transmembrane domains TM2, TM3, TM5, TM6 and TM7, and extracellular loop 1 are most highly conserved (>90%) in this G-protein coupled receptor. The Kd of the sheep receptor in binding assays (4.9 nM) was similar to the human and rat receptors, but lower than the mouse receptor. The rank order of potency of a series of GnRH analogues for binding and inositol phosphate stimulation in transfected COS-1 cells was identical to that of the receptor characterized in sheep pituitary gonadotropes. Northern blot analysis identified four transcripts sized 5.4 kb, 3.6 kb, 2.3 kb and 1.3 kb in sheep pituitanes which were upregulated by castration.

Let T = (V,E) be a rooted tree with n edges. We associate nonnegative weight w(v) and size s(v) with each vertex v in V. A q-partition of T into q connected components T1,T2,…,Tq is obtained by deleting k = q−1 edges of T, 1 ≤ k < n. The weight W(Ti) (or size S(Ti)) of component Ti is then the sum o weights (sizes) of the vertices of Ti. The height h(T) is the maximum number of edges of paths having one end at the root. If P is a partition with components T1…,Tq let WP = max1 ≤ i ≤ q W(Ti). The following two problems are considered: 1.Size-constrained min-max problem: Find a q-partition of T for which WP is a minimum over all partitions P satisfying S(Ti) ≤ M (M > 0).2.Height-constrained min-max problem: Find a q-partition of T for which WP is a minimum over all partitions P satisfying height h(Ti) ≤ H (H is a positive integer).The first problem is shown to be NP-complete, while a polynomial algorithm is presented for the second problem.