Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial.

BACKGROUND: Three small trials suggest that intravenous immunoglobulin can affect biomarkers and symptoms of mild-to-moderate Alzheimer's disease. We tested the safety, effective dose, and infusion interval of intravenous immunoglobulin in such patients. METHODS: We did a multicentre, placebo-controlled phase 2 trial at seven sites in the USA and five in Germany. Participants with probable Alzheimer's disease aged 50-85 years were randomly assigned (by a computer-generated randomisation sequence, with block sizes of eight) to infusions every 4 weeks (0·2, 0·5, or 0·8 g intravenous immunoglobulin per kg bodyweight, or placebo) or infusions every 2 weeks (0·1, 0·25, or 0·4 g/kg, or placebo). Patients, caregivers, investigators assessing outcomes, and staff at imaging facilities and the clinical research organisation were masked to treatment allocation, but dispensing pharmacists, the statistician, and the person responsible for final PET analyses were not. Treatment was masked with opaque pouches and infusion lines. The primary endpoint was median area under the curve (AUC) of plasma amyloid β (Aβ)(1-40) between the last infusion and the final visit (2 weeks or 4 weeks depending on infusion interval) in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). FINDINGS: 89 patients were assessed for eligibility, of whom 58 were enrolled and 55 included in the primary analysis. Median AUC of plasma Aβ(1-40) was not significantly different for intravenous immunoglobulin compared with placebo for five of the six intervention groups (-18·0 [range -1347·0 to 1068·5] for 0·2 g/kg, -364·3 [-5834·5 to 1953·5] for 0·5 g/kg, and -351·8 [-1084·0 to 936·5] for 0·8 g/kg every 4 weeks vs -116·3 [-1379·0 to 5266·0] for placebo; and -13·8 [-1729·0 to 307·0] for 0·1 g/kg, and -32·5 [-1102·5 to 451·5] for 0·25 g/kg every 2 weeks vs 159·5 [51·5 to 303·0] for placebo; p>0·05 for all). The difference in median AUC of plasma Aβ(1-40) between the 0·4 g/kg every 2 weeks group (47·0 [range -341·0 to 72·5]) and the placebo group was significant (p=0·0216). 25 of 42 (60%) patients in the intervention group versus nine of 14 (64%) receiving placebo had an adverse event. Four of 42 (10%) patients in the intravenous immunoglobulin group versus four of 14 (29%) receiving placebo had a serious adverse event, including one stroke in the intervention group. INTERPRETATION: Intravenous immunoglobulin may have an acceptable safety profile. Our results did not accord with those from previous studies. Longer trials with greater power are needed to assess the cognitive and functional effects of intravenous immunoglobulin in patients with Alzheimer's disease.

Spatial filtering for pilot-aided WCDMA systems: a semi-blind subspace approach

This paper proposes a spatial filtering technique forthe reception of pilot-aided multirate multicode direct-sequencecode division multiple access (DS/CDMA) systems such as widebandCDMA (WCDMA). These systems introduce a code-multiplexedpilot sequence that can be used for the estimation of thefilter weights, but the presence of the traffic signal (transmittedat the same time as the pilot sequence) corrupts that estimationand degrades the performance of the filter significantly. This iscaused by the fact that although the traffic and pilot signals areusually designed to be orthogonal, the frequency selectivity of thechannel degrades this orthogonality at hte receiving end. Here,we propose a semi-blind technique that eliminates the self-noisecaused by the code-multiplexing of the pilot. We derive analyticallythe asymptotic performance of both the training-only andthe semi-blind techniques and compare them with the actual simulatedperformance. It is shown, both analytically and via simulation,that high gains can be achieved with respect to training-onlybasedtechniques.

On the inclusion of channel's time dependence in a hidden Markov model for blind channel estimation

In this paper, the theory of hidden Markov models (HMM) isapplied to the problem of blind (without training sequences) channel estimationand data detection. Within a HMM framework, the Baum–Welch(BW) identification algorithm is frequently used to find out maximum-likelihood (ML) estimates of the corresponding model. However, such a procedureassumes the model (i.e., the channel response) to be static throughoutthe observation sequence. By means of introducing a parametric model fortime-varying channel responses, a version of the algorithm, which is moreappropriate for mobile channels [time-dependent Baum-Welch (TDBW)] isderived. Aiming to compare algorithm behavior, a set of computer simulationsfor a GSM scenario is provided. Results indicate that, in comparisonto other Baum–Welch (BW) versions of the algorithm, the TDBW approachattains a remarkable enhancement in performance. For that purpose, onlya moderate increase in computational complexity is needed.

Probabilistic algorithms for blind adaptive multiuser detection

In this paper, two probabilistic adaptive algorithmsfor jointly detecting active users in a DS-CDMA system arereported. The first one, which is based on the theory of hiddenMarkov models (HMM’s) and the Baum–Wech (BW) algorithm,is proposed within the CDMA scenario and compared withthe second one, which is a previously developed Viterbi-basedalgorithm. Both techniques are completely blind in the sense thatno knowledge of the signatures, channel state information, ortraining sequences is required for any user. Once convergencehas been achieved, an estimate of the signature of each userconvolved with its physical channel response (CR) and estimateddata sequences are provided. This CR estimate can be used toswitch to any decision-directed (DD) adaptation scheme. Performanceof the algorithms is verified via simulations as well as onexperimental data obtained in an underwater acoustics (UWA)environment. In both cases, performance is found to be highlysatisfactory, showing the near–far resistance of the analyzed algorithms.

Blind channel estimation and data detection using hidden Markov models theory

In this correspondence, we propose applying the hiddenMarkov models (HMM) theory to the problem of blind channel estimationand data detection. The Baum–Welch (BW) algorithm, which is able toestimate all the parameters of the model, is enriched by introducingsome linear constraints emerging from a linear FIR hypothesis on thechannel. Additionally, a version of the algorithm that is suitable for timevaryingchannels is also presented. Performance is analyzed in a GSMenvironment using standard test channels and is found to be close to thatobtained with a nonblind receiver.

Power quality improving with virtual flux-based voltage source line converter

Line converters have become an attractive AC/DC power conversion solution in industrial applications. Line converters are based on controllable semiconductor switches, typically insulated gate bipolar transistors. Compared to the traditional diode bridge-based power converters line converters have many advantageous characteristics, including bidirectional power flow, controllable de-link voltage and power factor and sinusoidal line current. This thesis considers the control of the lineconverter and its application to power quality improving. The line converter control system studied is based on the virtual flux linkage orientation and the direct torque control (DTC) principle. A new DTC-based current control scheme is introduced and analyzed. The overmodulation characteristics of the DTC converter are considered and an analytical equation for the maximum modulation index is derived. The integration of the active filtering features to the line converter isconsidered. Three different active filtering methods are implemented. A frequency-domain method, which is based on selective harmonic sequence elimination, anda time-domain method, which is effective in a wider frequency band, are used inharmonic current compensation. Also, a voltage feedback active filtering method, which mitigates harmonic sequences of the grid voltage, is implemented. The frequency-domain and the voltage feedback active filtering control systems are analyzed and controllers are designed. The designs are verified with practical measurements. The performance and the characteristics of the implemented active filtering methods are compared and the effect of the L- and the LCL-type line filteris discussed. The importance of the correct grid impedance estimate in the voltage feedback active filter control system is discussed and a new measurement-based method to obtain it is proposed. Also, a power conditioning system (PCS) application of the line converter is considered. A new method for correcting the voltage unbalance of the PCS-fed island network is proposed and experimentally validated.

Cefuroxime prophylaxis is effective in noninstrumented spine surgery : a double-blind, placebo-controlled study

Rapport de synthèse : Plusieurs investigateurs ont démontré que l'utilisation d'une antibiothérapie prophylactique lors d'interventions neurochirurgicales en terrain non infecté (chirurgie propre) réduisait le taux d'infection. Toutefois, ces taux d'infections sont très variables en fonction des types de chirurgie et de la durée des interventions. Les craniotomies, la mise en place ou le remplacement de shunt ventriculo-cardiaque, l'extirpation de méningiomes intracrâniens et les interventions d'une durée de plus de quatre heures sont grevées d'un taux d'infections post-opératoires plus élevé. Si une prophylaxie antibiotique est maintenant reconnue et utilisée dans ce type de chirurgie, il n'a jamais été démontré que cette pratique amène un bénéfice dans les cas de chirurgie pour hernie discale. Des études ont montré que de nombreux organismes potentiellement pathogènes pouvaient être collectés et cultivés à proximité voire dans le champ opératoire. Malgré ces observations, le taux d'infections post-opératoires reste peu important (entre 1-4% selon les centres). Il n'est actuellement pas possible de distinguer le rôle respectif d'une antibiothérapie prophylactique et des pratiques d'asepsie habituelles (y compris l'usage de solutions de rinçage antiseptiques) dans la faible incidence des infections post-opératoires en ce qui concerne la chirurgie des hernies discales. Lorsque des opérations de chirurgie dite «propre » sont grevées d'un taux de complications aussi bas, une prophylaxie antibiotique n'est généralement pas recommandée, en raison d'un rapport coût-bénéfice défavorable. Le but de cette étude est d'évaluer la nécessité d'une antibiothérapie prophylactique par une céphalosporine de seconde génération (cefuroxime 1,5 g intraveineuse) dans la prévention des infections post-opératoires au cours d'une chirurgie pour hernie discale. Il s'agit d'un essai clinique prospectif, contrôlé contre placebo en insu réciproque, à répartition aléatoire. L'étude a été conduite dans les services de neurochirurgie de l'Hôpital Universitaire de Genève et du Centre Hospitalier Universitaire Vaudois de Lausanne. L'ensemble des patients admis dans ces deux services pour une opération de hernie discale et ayant donné leur consentement ont été inclus dans l'étude qui s'est déroulé sur une période de 6 ans. Mille trois cent soixante-neuf patients opérés pour une hernie discale ont été inclus dans cet essai et 132 patients ont été exclus de l'analyse pour diverses raisons. Au total 1'237 patients ont été analysés, respectivement 613 et 624 patients dans le groupe cefuroxime et le groupe placebo. Les patients des deux groupes présentaient des caractéristiques identiques. Nous n'avons objectivé aucun effet secondaire indésirable attribuable à la cefuroxime ou au placebo. Huit (1.3%) patients du groupe cefuroxime et 18 patients (2.8%) du groupe placebo ont développé une infection du site opératoire (P=0.073). Neuf des patients infectés dans le groupe placebo présentaient une infection profonde du site opératoire (spondylodiscite, abcès épidural) et aucun dans le groupe cefuroxime (P<0.01). Tous les patients avec infection profonde du site opératoire ont été traités par antibiothérapie par voie intraveineuse pour au moins 4 semaines et il a été procédé à une reprise chirurgicale chez deux patients. Ces résultats montrent qu'il faut traiter 69 patients avec une antibiothérapie prophylactique de cefuroxime pour prévenir une infection du site opératoire. En conclusion, l'administration d'une dose de cefuroxime 1.5 g intraveineuse comme prophylaxie lors d'opération de hernie discale, permet de réduire significativement le risque d'infection profonde du site opératoire.

Kaukokäyttöliittymä liikkuvalle robotille

Lappeenrannan teknillinen yliopiston Tietotekniikan osaston Tietojenkäsittelytieteen laitoksen tutkimuskäytössä olevaan liikkuvaan robottiin toteutettiin tässä työssä graafinen kaukokäyttöliittymä. Työlle on motivaationa laajennettavuus, jota olemassaoleva suljetun lähdekoodin käyttöliittymä ei pysty tarjoamaan. Työssä olennaisin on olio-ohjelmointitekniikalla toteutettu robotin datamallin, ja sen graafisen esityksen arkkitehtuurillinen erottaminen. Lisäksi tarkastellaan lyhyesti liikkuvien robottien kaukokäyttöliittymien teoriaa, ja WLAN-tekniikan soveltuvuutta robotin ja käyttöliittymän välisen yhteyden toteuttamiseen.

The genome of the recently domesticated crop plant sugar beet (Beta vulgaris)

Sugar beet (Beta vulgaris ssp. vulgaris) is an important crop of temperate climates which provides nearly 30% of the world's annual sugar production and is a source for bioethanol and animal feed. The species belongs to the order of Caryophylalles, is diploid with 2n = 18 chromosomes, has an estimated genome size of 714-758 megabases and shares an ancient genome triplication with other eudicot plants. Leafy beets have been cultivated since Roman times, but sugar beet is one of the most recently domesticated crops. It arose in the late eighteenth century when lines accumulating sugar in the storage root were selected from crosses made with chard and fodder beet. Here we present a reference genome sequence for sugar beet as the first non-rosid, non-asterid eudicot genome, advancing comparative genomics and phylogenetic reconstructions. The genome sequence comprises 567 megabases, of which 85% could be assigned to chromosomes. The assembly covers a large proportion of the repetitive sequence content that was estimated to be 63%. We predicted 27,421 protein-coding genes supported by transcript data and annotated them on the basis of sequence homology. Phylogenetic analyses provided evidence for the separation of Caryophyllales before the split of asterids and rosids, and revealed lineage-specific gene family expansions and losses. We sequenced spinach (Spinacia oleracea), another Caryophyllales species, and validated features that separate this clade from rosids and asterids. Intraspecific genomic variation was analysed based on the genome sequences of sea beet (Beta vulgaris ssp. maritima; progenitor of all beet crops) and four additional sugar beet accessions. We identified seven million variant positions in the reference genome, and also large regions of low variability, indicating artificial selection. The sugar beet genome sequence enables the identification of genes affecting agronomically relevant traits, supports molecular breeding and maximizes the plant's potential in energy biotechnology.

Separation mechanisms in nanofiltration and retention changes of organic compounds

Orgaanisten yhdisteiden negatiivinen retentio nanosuodatuksessa on ilmiö, jota eiole kovin paljon tutkittu. Negatiivisen retentioon vaikuttavat syyt tai tekijäteivät ole kovin hyvin tiedossa. Erotusmenetelmänä negatiivinen retentio voi olla käyttökelpoinen tietyissä sovelluksissa. Työn kirjallisuusosa käsittelee nanosuodatuksen erotusmekanismeja ja retentioon vaikuttavia tekijöitä. Myös joitakin malleja on esitetty. Nanosuodatus on monimutkainen prosessi, josta ei voida löytää vain yhtä erotusmekanismia tai retentioon vaikuttavaa tekijää. Prosessit ovat kokonaisuuksia, joissa erottumiseen vaikuttavat syöttöliuoksen, erotettavan komponentin ja kalvon ominaisuudet, ja niiden väliset vuorovaikutukset. Työn kokeellisessa osassa koottiin mahdollisimman paljon esimerkkejä, joissa monosakkaridien negatiivinen retentio ilmenee. Muita orgaanisia ja epäorgaanisia yhdisteitä käytettiin 'häiriöyhdisteinä' syöttöliuoksessa monosakkaridien kanssa. Kokeet suoritettiin kahdella laboratoriomittakaavan suodatuslaitteella käyttäen kahta kaupallista nanosuodatuskalvoa. Negatiivinen retentio ilmeni useissa tapauksissa. Permeaattivuon ja 'häiriöyhdisteiden' pitoisuuksien havaittiin vaikuttavan voimakkaasti negatiivisen retention ilmenemiseen.

Study of isotopic variations in black powder: reflections on the use of stable isotopes in forensic science for source inference.

Isotope ratio mass spectrometry (IRMS) has recently made its appearance in the forensic community. This high-precision technology has already been applied to a broad range of forensic fields such as illicit drugs, explosives and flammable liquids, where current, routinely used techniques have limited powers of discrimination. The conclusions drawn from the majority of these IRMS studies appear to be very promising. Used in a comparative process, as in food or drug authentication, the measurement of stable isotope ratios is a new and remarkable analytical tool for the discrimination or the identification of a substance with a definite source or origin. However, the research consists mostly of preliminary studies. The significance of this 'new' piece of information needs to be evaluated in light of a forensic framework to assess the actual potential and validity of IRMS, considering the characteristics of each field. Through the isotopic study of black powder, this paper aims at illustrating the potential of the method and the limitations of current knowledge in stable isotopes when facing forensic problems.

Electrical source imaging for presurgical focus localization in epilepsy patients with normal MRI.

PURPOSE: Patients with magnetic resonance (MR)-negative focal epilepsy (MRN-E) have less favorable surgical outcomes (between 40% and 70%) compared to those in whom an MRI lesion guides the site of surgical intervention (60-90%). Patients with extratemporal MRN-E have the worst outcome (around 50% chance of seizure freedom). We studied whether electroencephalography (EEG) source imaging (ESI) of interictal epileptic activity can contribute to the identification of the epileptic focus in patients with normal MRI. METHODS: We carried out ESI in 10 operated patients with nonlesional MRI and a postsurgical follow-up of at least 1 year. Five of the 10 patients had extratemporal lobe epilepsy. Evaluation comprised surface and intracranial EEG monitoring of ictal and interictal events, structural MRI, [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), ictal and interictal perfusion single photon emission computed tomography (SPECT) scans. Eight of the 10 patients also underwent intracranial monitoring. RESULTS: ESI correctly localized the epileptic focus within the resection margins in 8 of 10 patients, 9 of whom experienced favorable postsurgical outcomes. DISCUSSION: The results highlight the diagnostic value of ESI and encourage broadening its application to patients with MRN-E. If the surface EEG contains fairly localized spikes, ESI contributes to the presurgical decision process.

Language variation in source texts and their translations: the case of L3 in film translation

In addition to the two languages essentially involved in translation, that of the source text (L1) and that of the target text (L2), we propose a third language (L3) to refer to any other language(s) found in the text. L3 may appear in the source text (ST) or the target text (TT), actually appearing more frequently inSTs in our case studies. We present a range of combinations for the convergence and divergence of L1, L2 and L3, for the case of feature films and their translations using examples from dubbed and subtitled versions of films, but we are hopeful that our tentative conclusions may be relevant to other modalities of translation, audiovisual and otherwise. When L3 appears in an audiovisual ST,we find a variety of solutions whereby L3 is deleted from or adapted to the TT.In the latter case, L3 might be rendered in a number of ways, depending on factors such as the audience’s familiarity with L3, and the possibility that L3 inthe ST is an invented language.

Ignition of a human body by a modest external source: a case report.

A case of sustained combustion of a human body that occurred in 2006 in Geneva, Switzerland, is presented. The body of a man was discovered at home and found to have been almost completely incinerated between the knees and the mid-chest, with less damage to the head, arms, lower legs and feet. His dog was also found dead just behind the house door. The external source of ignition was most likely a cigarette or a cigar. The chair in which the man had been sitting was largely consumed while other objects in the room exhibited only a brown oily or greasy coating and were virtually undamaged. Toxicological analyses carried out on the blood from the lower legs showed low levels of desalkylflurazepam. Alcohol concentration was 1.10 per thousand, carboxyhaemoglobin levels were 12% and cyanide concentration was 0.05 mg/L. Toxicological analyses carried out on the dog's blood showed carboxyhaemoglobin levels at 65%.

Blind docking of 260 protein-ligand complexes with EADock 2.0.

Molecular docking softwares are one of the important tools of modern drug development pipelines. The promising achievements of the last 10 years emphasize the need for further improvement, as reflected by several recent publications (Leach et al., J Med Chem 2006, 49, 5851; Warren et al., J Med Chem 2006, 49, 5912). Our initial approach, EADock, showed a good performance in reproducing the experimental binding modes for a set of 37 different ligand-protein complexes (Grosdidier et al., Proteins 2007, 67, 1010). This article presents recent improvements regarding the scoring and sampling aspects over the initial implementation, as well as a new seeding procedure based on the detection of cavities, opening the door to blind docking with EADock. These enhancements were validated on 260 complexes taken from the high quality Ligand Protein Database [LPDB, (Roche et al., J Med Chem 2001, 44, 3592)]. Two issues were identified: first, the quality of the initial structures cannot be assumed and a manual inspection and/or a search in the literature are likely to be required to achieve the best performance. Second the description of interactions involving metal ions still has to be improved. Nonetheless, a remarkable success rate of 65% was achieved for a large scale blind docking assay, when considering only the top ranked binding mode and a success threshold of 2 A RMSD to the crystal structure. When looking at the five-top ranked binding modes, the success rate increases up to 76%. In a standard local docking assay, success rates of 75 and 83% were obtained, considering only the top ranked binding mode, or the five top binding modes, respectively.