Weak Measurement Protocols for Majorana Bound State Identification.

We propose a continuous weak measurement protocol testing the nonlocality of Majorana bound states through current shot noise correlations. The experimental setup contains a topological superconductor island with three normal-conducting leads weakly coupled to different Majorana states. Putting one lead at finite voltage and measuring the shot noise correlations between the other two (grounded) leads, devices with true Majorana states are distinguished from those without by strong current correlations. The presence of true Majorana states manifests itself in unusually high noise levels or the near absence of noise, depending on the chosen device configuration. Monitoring the noise statistics amounts to a weak continuous measurement of the Majorana qubit and yields information similar to that of a full braiding protocol, but at much lower experimental effort. Our theory can be adapted to different platforms and should allow for the clear identification of Majorana states.

Occipital nerve stimulation for chronic migraine: a randomized trial on subthreshold stimulation.

INTRODUCTION: Occipital nerve stimulation (ONS) may provide pain relief in migraine patients. In this double-blinded trial we investigated the significance of paresthesia and possible placebo effects. METHODS: Patients already treated with ONS reporting stable treatment effect were included. "Effective stimulation," "subthreshold stimulation" and "no stimulation" were compared. Patients cycled through all three treatment groups. Outcome was measured using the visual analog scale (VAS) for pain, McGill Pain Questionnaire and SF-36. RESULTS: Eight patients were included, mean preoperative VAS was 8.20 ± 1.22. A significant improvement in pain was observed in favor of suprathreshold stimulation compared to subthreshold stimulation (1.98 ± 1.56 vs 5.65 ± 2.11). Pain also significantly improved under subthreshold stimulation compared to no stimulation (5.65 ± 2.11 vs 8.45 ± 0.99). No changes in SF-36 were observed. CONCLUSIONS: Paresthesia is not required to achieve pain reduction but suprathreshold stimulation yields better results, underlining the significance of stimulation parameter customization.

The impact of brain shift in deep brain stimulation surgery: observation and obviation.

BACKGROUND: The impact of brain shift on deep brain stimulation surgery is considerable. In DBS surgery, brain shift is mainly caused by CSF loss. CSF loss can be estimated by post-surgical intracranial air. Different approaches and techniques exist to minimize CSF loss and hence brain shift. The aim of this survey was to investigate the extent and dynamics of CSF loss during DBS surgery, analyze its impact on final electrode position, and describe a simple and inexpensive method of burr hole closure. METHODS: Sixty-six patients being treated with deep brain stimulation were retrospectively analyzed for this treatise. During surgery, CSF loss was minimized using bone wax as a burr hole closure. Intracranial air volume was calculated based on early post-surgery stereotactic 3D CT and correlated with duration of surgery and electrode deviations derived from post-surgery image fusion. RESULTS: Median early post-surgery intracranial air was 2.1 cm(3) (range 0-35.7 cm(3), SD 8.53 cm(3)). No correlation was found between duration of surgery and CSF-loss (R = 0.078, p = 0.534), indicating that CSF loss mainly occurs early during surgery. Linear regression analysis revealed no significant correlations regarding volume of intracranial air and electrode displacement in any of the three principal axes. No significant difference regarding electrode deviations between first and second side of surgery were observed. CONCLUSIONS: CSF loss mainly occurs during the early phase of DBS surgery. CSF loss during a later phase of surgery can be effectively averted by burr hole closure. Postoperative intracranial air volumes up to 35 cm(3) did not result in significant electrode displacement in our series. Comparing our results to studies previously published on this subject, burr hole closure using bone wax is highly effective.

Epstein-Barr virus transcription activator R upregulates BARF1 expression by direct binding to its promoter, independent of methylation.

Epstein-Barr virus (EBV) BamHI-A rightward frame 1 (BARF1) is considered a major viral oncogene in epithelial cells and has immune-modulating properties. However, in B cells and lymphomas, BARF1 expression is restricted to the viral lytic replication cycle. In this report, the transcriptional regulation of BARF1 during lytic replication is unraveled. Bisulfite sequencing of various cell lines indicated a high level of methylation of the BARF1 gene control region. A BARF1 promoter luciferase reporter construct was created using a CpG-free vector, enabling true assessment of promoter methylation. Induction of the EBV lytic cycle is mediated by the immediate-early proteins BZLF1 (Z) and BRLF1 (R). R was found to activate expression of the BARF1 promoter up to 250-fold independently of Z and unaffected by BARF1 promoter methylation. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), and specific mutagenesis of the R-responsive elements (RREs) demonstrated direct binding of R to RREs between nucleotides -554 and -327 relative to the BARF1 transcriptional ATG start site. The kinetics of BARF1 expression upon transactivation by R showed that BARF1 mRNA was expressed within 6 h in the context of the viral genome. In conclusion, expression of the BARF1 protein during lytic replication is regulated by direct binding of R to multiple RREs in the gene control region and is independent of the promoter methylation status. The early kinetics of BARF1 upon transactivation by R confirm its status as an early gene and emphasize the necessity of early immune modulation during lytic reactivation.

[A capillary-based perfusion phantom for the simulation of brain perfusion for MRI]. / Ein kapillarbasiertes Phantom zur Simulation der Gehirnperfusion mit der Magnet-Resonanz-Tomografie.

PURPOSE: The measurement of the CBF is a non-standardized procedure and there are no reliable gold standards. This abstract shows a capillary-based perfusion-phantom for CE-DSC-MRI. It has equivalent flow properties to those within the tissue capillary system of the human brain and allows the validation of the Siemens Perfusion (MR) software. MATERIALS AND METHODS: The perfusion phantom consists of a dialyzer for the simulation of the capillary system, a feeding tube for simulation of the AIF and a pulsatile pump for simulation of the heart. Using this perfusion phantom, the exact determination of the gold standard CBF due to the well-known geometry of the phantom is easy. It was validated based on different perfusion measurements. These measurements were investigated with standard software (Siemens Perfusion MR). The software determined the CBF within the capillary system. Based on this CBF, a comparison to the gold standard was made with several different flow speeds. After AIF selection, a total of 726 CBF data points were automatically extracted by the software. RESULTS: This results in a comparison of the gold standard CBF to these 726 CBF values. Therefore, a reproducible and reliable deviation estimation between gold standard CBF and measured CBF using the software was computed. It can be shown that the deviation between gold standard and software-based evaluation ranges between 1 and 31 %. CONCLUSION: There is no significance for any correlation between flow speed and amount of deviation. The mean measured CBF is 11.4 % higher than the gold standard CBF (p-value < 0.001). Using this kind of perfusion-phantom, the validation of different software systems allows reliable conclusions about their quality.

Retrospective analysis of treatment outcome in 315 patients with oligodendroglial brain tumors.

Although chemotherapy with procarbazine, lomustine and vincristine (PCV) is considered to be well tolerated, side effects frequently lead to dose reduction or even discontinuation of treatment of oligodendroglial brain tumors. The primary objective of the analysis was to retrospectively compare progression-free survival (PFS) after PCV vs. PC chemotherapy (without vincristine to avoid side effects). Patients were retrospectively identified from a database containing our patients between 1990 and 2003. For the selected cases, all histopathology reports were re-evaluated by a local neuropathologist. Based on the updated histology data, patients were included in the study if they had at least one histological diagnosis of an oligodendroglial tumor. PFS after start of PCV (n = 61) and PC (n = 84) chemotherapy identical (median 30 months). Multivariate analysis adjusting for prognostic imbalances favouring the PC group showed a minor, statistically non-significant benefit for PCV (hazard ratio 0.81, 95% confidence interval 0.53-1.25; p = 0.346). Younger age (< 50 y) was a statistically significant predictor of longer PFS. Significant advantages in terms of overall survival after first diagnosis of oligodendroglial tumor (OS, n = 315) were found for patients < 50 y (p < 0.001), oligodendrogliomas versus oligoastrocytomas (p = 0.002), and WHO degrees II vs. degrees III (p < 0.001). Three risk groups regarding OS were identified. Findings support the hypothesis that PC may be as effective as PCV chemotherapy, while avoiding the additional risks of vincristine. Younger age, lower tumor grade and histology of an oligodendroglioma were identified to be favorable prognostic factors.

Current concepts in stereotactic radiosurgery - a neurosurgical and radiooncological point of view.

Stereotactic radiosurgery is related to the history of "radiotherapy" and "stereotactic neurosurgery". The concepts for neurosurgeons and radiooncologists have been changed during the last decade and have also transformed neurosurgery. The gamma knife and the stereotactically modified linear accelerator (LINAC) are radiosurgical equipments to treat predetermined intracranial targets through the intact skull without damaging the surrounding normal brain tissue. These technical developments allow a more precise intracranial lesion control and offer even more conformal dose plans for irregularly shaped lesions. Histological determination by stereotactic biopsy remains the basis for any otherwise undefined intracranial lesion. As a minimal approach, it allows functional preservation, low risk and high sensitivity. Long-term results have been published for various indications. The impact of radiosurgery is presented for the management of gliomas, metastases, brain stem lesions, benign tumours and vascular malformations and selected functional disorders such as trigeminal neuralgia. In AVM's it can be performed as part of a multimodality strategy including resection or endovascular embolisation. Finally, the technological advances in radiation oncology as well as stereotactic neurosurgery have led to significant improvements in radiosurgical treatment opportunities. Novel indications are currently under investigation. The combination of both, the neurosurgical and the radiooncological expertise, will help to minimize the risk for the patient while achieving a greater treatment success.

[Multimodal group therapy for the elderly with chronic pain: concept and results in a before and after comparison]. / Multimodale Gruppentherapie bei Senioren mit chronischen Schmerzen : Konzept und Ergebnisse im Prä-post-Vergleich.

BACKGROUND: Multimodal pain therapy programs are increasingly being recommended as an effective treatment option also for elderly patients with chronic pain. However, data from Germany are limited. PATIENTS AND METHODS: A multimodal group program adapted to the specific needs of elderly pain patients over 70 years old (20 treatment days, over 10 weeks) was started in our pain clinic in June 2005. We evaluated clinical, psychometric and physical data at the beginning and at the end of the treatment program, and compared outcome results with a waiting list control group. RESULTS: A total of 24 patients (mean age 76.2+/-4.79 years) could be evaluated of which 21 patients suffered from musculoskeletal pain, 2 from neuropathic pain syndromes and 1 from headache. In the waiting-list control group 13 patients were included. There were no significant between-group differences regarding age, stages of chronification, pain intensity, duration of pain and pain diagnosis. CONCLUSIONS: A multimodal pain therapy program for elderly patients (over 70 years old) is an effective treatment option to reduce pain intensity and pain disability. Furthermore, life quality and physical performance improved. Long-term effects still have to be evaluated.

[Metered-dose inhaler with spacer vs nebulization for severe and potentially severe acute asthma treatment in the pediatric emergency department]. / Traitement aux urgences des crises d'asthme par nébulisations vs chambres d'inhalation.

OBJECTIVE: To compare treatment with beta 2 agonist delivered either by a spacer device or a nebulizer in children with severe or potentially severe acute asthma. METHODS: In this randomized trial, children 4 to 15 years, cared for in the emergency department for severe or potentially severe acute asthma, received 6 times either nebulizations of salbutamol (0.15mg/kg) or puffs of a beta 2 agonist (salbutamol 50 microg/kg or terbutaline 125 microg/kg). The primary outcome was the hospitalization rate. Secondary outcomes included percentage improvement in Bishop score, in PEF, SaO(2), respiratory and heart rates, side effects, length of stay and relapses 10 and 30 days later. RESULTS: Groups did not differ for baseline data. There were no significant differences between the 2 groups (nebulizer N=40, spacer N=39) for baseline characteristics before emergency department consultation except for length of acute asthma in the spacer group. Clinical evolution after treatment, hospitalization rate, relapse were similar including the more severe subgroup. In the spacer group, tachycardia was less frequent (P<0.02). The overall length of stay in the emergency department was significantly shorter (148+/-20 vs 108+/-13 min, P<10(-9)). CONCLUSIONS: The administration of beta 2 agonist using a metered-dose inhaler with spacer is an effective alternative to nebulizers for the treatment of children with severe or potentially severe acute asthma in the emergency department. Time gained can be used for asthma education.

[Oral morphine administration for children's traumatic pain]. / Utilisation de la morphine orale pour les douleurs post-traumatiques de l'enfant.

OBJECTIVES: To study the compliance of prescription, the efficacity and the adverse events of oral morphine used in the pediatric emergency department (ED) in traumatic pains. METHOD: This prospective study was conducted in the ED from october 2002 to september 2003. Children aged six months to 16 years with a visual analogic scale (VAS) score higher than 70 or with a traumatic member deformation received oral morphine (0,5 mg/kg). Pain was assessed every 30 minutes using two scales: behavioral observation by the faces scale and objective pain scale (OPS) for children less than five years, behavioral observation by the faces scale and self-report by VAS for children older than five years. The compliance of prescription, the pain scores and the adverse events were studied. RESULTS: Ninety-one children received oral morphine and seventy-four children were studied. Seventy per cent of prescriptions were in accordance with the recommendations. For patients younger than five years a rapid decrease of pain was observed in thirty minutes. The pain's reduction was respectively 79 and 84% with faces scale and OPS when they left ED. For children older than five years, pain's reduction was more important and more rapid when pain assessment was made by nurses than when it was self-reported in the first hour (pain reduction 58,2 and 36,1%). When leaving, pain reduction was the same with the two different assessments. No major adverse event was noted. CONCLUSION: Use of oral morphine in ED is simple, with a few numbers of adverse events. None was severe. Efficiency is correct after 30 to 60 minutes.

Long-term suppression of extrapyramidal motor symptoms with deep brain stimulation (DBS).

Deep Brain Stimulation (DBS) was investigated for the treatment of extrapyramidal motor symptoms. Both tremor and rigidity as well as akinesia are known to be permanently suppressed by applying a high-frequency current to different basal ganglia nuclei. Chronic DBS was performed in 113 patients using stereotactically implanted quadripolar electrodes in the ventrolateral thalamus (n = 43), the globus pallidus internus (n = 15), or the subthalamic nucleus (n = 55). Subcutaneous implantation of the generator occurred during a second procedure following correct positioning of the electrodes and confirmation of effectiveness by external stimulation. Patients were followed up using standardized rating scales before and after surgery. Deep Brain Stimulation significantly suppresses extrapyramidal symptoms such as tremor (p < 0.001), rigidity (p < 0.001), dyskinesia (p < 0.01), akinesia, and dystonia (p < 0.05). Permanent side effects were avoided by changing the stimulation parameters. Severe complications occurred in only two patients (n = 2, 1.8 %). DBS is a safe and effective long-term treatment for tremor, rigidity, dyskinesia, akinesia and dystonia.

[Effect of racecadotril in the management of acute diarrhea in infants and children]. / Effet du racécadotril sur le recours aux soins dans le traitement des diarrhées aiguës du nourrisson et de l'enfant.

BACKGROUND: The treatment of diarrhoea relies on the maintenance or restoration of hydration with maintenance of an adequate nutritional intake. Racecadotril has been shown to reduce the stools output during acute diarrhoea. The present work was aimed at measuring the number of emergency department visits for acute diarrhoea either the children received racecadotril or not. METHOD: Racecadotril and rehydration were compared with rehydration alone in children aged three months to three years who had acute diarrhoea and were evaluated in the emergency department (ED). The primary end point was the number of medical exams during the week after starting treatment. Secondary end points were the number of stools during the first 48 hours, the duration of the diarrhoea and the weight on day 7. RESULTS: One hundred and sixty-six children were alternatively randomized to the treated and the control groups. There was no difference for age, degree of dehydration and length of illness before the first visit between the groups. Whatever type of rehydration (oral or i.v.), the treated group had a significant lower number of stools (p < 0.001) and a faster recovery (p < 10(-9)). The children receiving racecadotril needed less additional ED visits for the same episode (p < 0.05). There was no difference for the weight-gain on day 7. CONCLUSIONS: This study demonstrates the efficacy of racecadotril as adjuvant therapy to oral and i.v. rehydration in the treatment of acute diarrhoea and a fewer emergency department second visit before recovery.

[Benefits of ipratropium bromide in the management of asthmatic crises in the emergency department]. / Apport du bromure d'ipratropium dans la prise en charge des crises d'asthme aux urgences.

BACKGROUND: To determine if the addition of ipratropium bromide in the emergency department (ED) for the treatment of childhood asthma reduces rates of hospitalization and relapses for moderate and severe exacerbations. METHODS: Patients were given an oral corticosteroid treatment (2 mg/kg) and received every 20 minutes either three nebulizations with albuterol (0.15 mg/kg) and ipratropium bromide (250 micrograms) or six nebulizations with albuterol alone (control group). The primary end point was the need for hospitalization, additional nebulizations or a relapse during the following week. Secondary end point included the effect of age. RESULTS: One hundred and forty three children, two to 15 years old, were randomized to ipratropium or control groups and 121 were evaluated on day seven. As a whole, the control group was less often hospitalized or in relapse than those treated with three nebulizations of albuterol and ipratropium (17.5% vs 37.9%, p < 0.02). The ipratropium group reached the same result after three additional albuterol nebulizations. The benefit of anticholinergic therapy was observed for children less than six years of age who had a similar rate of success (73.5 vs 75.7%). CONCLUSION: The association of ipratropium bromide to the first three doses of the albuterol protocol for acute asthma did not act as well as six nebulizations of albuterol alone. The effect was age dependent and two to six years old children needed more attention. Nevertheless the hospitalization rate did not support the use of ipratropium compared with repeated albuterol nebulizations.

[Assessing the cost of the first episode of bronchiolitis]. / Evaluation du coût du premier épisode de bronchiolite.

BACKGROUND: Each year, a quarter of the children younger than 24 months has respiratory syncytial virus bronchiolitis. The morbidity among high-risk infants and the possible association with the development of asthma lead to propose preventive measures whose cost-effectiveness relationship is unknown. The present work was aimed at measuring costs of a first attack of bronchiolitis. METHOD: For children less than two years visited in the emergency department, direct and indirect costs were measured according to the 'Sécurité Sociale' prices. Associated morbidity, the management of care (inpatient versus outpatient), outpatients' outcome two weeks after the visit, socioeconomic data were recorded. RESULTS: One hundred eighty three children have been studied. The length of stay for 40 hospitalizations was 7.6 +/- 4.3 days. Direct costs were 37,200 +/- 22,000 FF for inpatients, and 1286 +/- 633 F for outpatients. For 113 outpatients' families, indirect costs were 49 working days lost. The way the child was looked after and the unemployment rate in the study were similar to data provided by the National Institute of Statistics and Economic Studies. CONCLUSION: Because of the variability of the hospitalization rate from one setting to another, overall costs of the epidemic cannot be evaluated. For the policymaker, the greatest costs come from the outpatient care. Others studies will be necessary to evaluate the price of future preventive measures.

[Patient security through algorithm standardization in a urology practice--account of practical experience and medical certification]. / Patientensicherheit durch algorithmische Standardisierung in einer urologischen Praxis--Erfahrungsbericht einer Praxiszertifizierung.

Visiting a physician means taking a risk, of which our patients (clients) know too little. Those who run the practice know about critical points and have the duty to protect their clients. One way of doing so is to standardize working routines. An even better way is to have the practice certified and audited (controlled) annually by an objective institution (e.g., the German TUV).

Waterjet dissection of the brain: experimental and first clinical results. Technical note.

Control of bleeding during dissection is a problem that is still not completely resolved in neurosurgical procedures. To overcome this problem in some settings, the authors, in close collaboration with their institution, developed a new device for blunt dissection of brain tumors that is based on a waterjet technique. This report describes their first experimental and clinical experience with this new method. Numerous cutting experiments were performed in porcine cadaver brains. The best results were obtained using pressures from 4 to 6 bars with a 100-microm tip, which produced very small, precise cuts. Histological evaluation showed no disruption or vacuolization of the surrounding tissue. The authors have used the new device in nine patients (seven with gliomas and two undergoing temporal lobe resections for epilepsy), and no complications have been observed. The waterjet device allowed dissection of the brain tissue while even small exposed vessels were spared injury. The instrument was found to be easy to use. Future investigations will concentrate on adapting this new method to endoscopic surgery and evaluating fluids with low surface tension to avoid foaming and bubbling during open surgery.

The integrin alpha 2 beta 1 (GPIa/IIa)-I-domain inhibits platelet-collagen interaction.

The integrin alpha 2 beta 1 is a major cellular receptor for collagen. The alpha 2 subunit contains an +/- 200 amino acids inserted domain (I-domain) in the N-terminal region. A certain degree of homology exists between the I-domains found in integrins, collagen and the A-domains of vWF. The alpha 2-I-domain encoding region (aa residues D145 to S334) was obtained by RT-PCR from mRNA of non stimulated human PBL's. The primers were designed to introduce the necessary restriction sites for cloning of the DNA fragment in frame downstream of the malE gene, as well as a stop codon after the last triplet. The resulting construct pMAL-c2-alpha 2-I allows the expression of the I-domain, fused to the C-terminus of maltose binding protein (mal). The alpha 2-I-mal is purified from the bacterial extract by affinity chromatography on an amylose column. The purified alpha 2-I-mal has been characterized by ELISA's. The alpha 2-I-mal bound to immobilised collagen type I in a concentration dependent manner and could be blocked by the functional monoclonal anti-alpha 2 beta 1 antibody 6F1. The interaction of alpha 2-I-mal with collagen furthermore is Mg(2+)-dependent since the binding was inhibited in the presence of 10 mM EDTA or 10 mM Ca2+ but sustained in the presence of 10 mM Mg2+. Finally, alpha 2-I-mal itself was able to inhibit adhesion of washed platelets to collagen immobilised on a microtiterplate in a dose-dependent manner (alpha 2-I-mal IC50:0.7 microM) as well as platelet aggregation induced by collagen type I (alpha 2-I-mal IC50:0.7 microM). With these results we could confirm that the alpha 2-I-domain represents the collagen-binding site of alpha 2 beta 1 and we furthermore could indicate that this domain is able to prevent platelet adhesion to collagen and collagen-induced platelet aggregation, pointing to the primordial role of alpha 2-I-mal and hence of alpha 2 beta 1 in platelet-collagen interaction.

Changes of ganglioside pattern during cerebellar development of normal and staggerer mice.

The total amount of gangliosides per cerebellum of a wild-type mouse increased 126-fold during postnatal development. Although all major gangliosides were synthesized, the relative amount of individual ganglioside species changed during this period. In the developing wild-type cerebellum a transient accumulation of GD3 occurred between birth and postnatal day 20 (P20) with the largest portion (23%) of the total ganglioside content at postnatal day 7 (P7). In the adult cerebellum GD3 was only a minor component (3.2%) of the ganglioside pattern. As demonstrated by immunofluorescence the accumulation of GD3 was predominantly associated with premigratory and early postmigratory granule cells. The ganglioside GD3 was found in two alkali-stable forms in the young cerebellum, whereas the ganglioside species with the higher Rf value (migrating in the same position as the upper GD3 band) in the adult cerebellum was alkali labile. The cerebellum of the neurological mutant staggerer (sg/sg) was characterized by a low amount of GD1a in adult animals, due to the massive death of neurons in the postnatal cerebellar cortex. The neonatal loss of sialic acid residues from cerebellar cell surfaces in wild-type mice and the maintenance of embryonic sialoglycoconjugates in the staggerer cerebellum cannot be explained by the alterations of ganglioside patterns observed during postnatal development.