Cutting edge: Natalizumab blocks adhesion but not initial contact of human T cells to the blood-brain barrier in vivo in an animal model of multiple sclerosis

The humanized anti-alpha(4) integrin Ab Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis. Natalizumab is thought to exert its therapeutic efficacy by blocking the alpha(4) integrin-mediated binding of circulating immune cells to the blood-brain barrier (BBB). As alpha(4) integrins control other immunological processes, natalizumab may, however, execute its beneficial effects elsewhere. By means of intravital microscopy we demonstrate that natalizumab specifically inhibits the firm adhesion but not the rolling or capture of human T cells on the inflamed BBB in mice with acute experimental autoimmune encephalomyelitis (EAE). The efficiency of natalizumab to block T cell adhesion to the inflamed BBB was found to be more effective in EAE than in acute systemic TNF-alpha-induced inflammation. Our data demonstrate that alpha(4) integrin-mediated adhesion of human T cells to the inflamed BBB during EAE is efficiently blocked by natalizumab and thus provide the first direct in vivo proof of concept of this therapy in multiple sclerosis.

Approximating method of frames

In this paper, the well-known method of frames approach to the signal decomposition problem is reformulated as a certain bilevel goal-attainment linear least squares problem. As a consequence, a numerically robust variant of the method, named approximating method of frames, is proposed on the basis of a certain minimal Euclidean norm approximating splitting pseudo-iteration-wise method.

Weighted Majoritarian Rules for the Location of Multiple Public Facilities

We consider collective decision problems given by a profile of single-peaked preferences defined over the real line and a set of pure public facilities to be located on the line. In this context, Bochet and Gordon (2012) provide a large class of priority rules based on efficiency, object-population monotonicity and sovereignty. Each such rule is described by a fixed priority ordering among interest groups. We show that any priority rule which treats agents symmetrically — anonymity — respects some form of coherence across collective decision problems — reinforcement — and only depends on peak information — peakonly — is a weighted majoritarian rule. Each such rule defines priorities based on the relative size of the interest groups and specific weights attached to locations. We give an explicit account of the richness of this class of rules.

Treatment of multiple adjacent Miller class I and II gingival recessions with a Modified Coronally Advanced Tunnel (MCAT) technique and a collagen matrix or palatal connective tissue graft: a randomized, controlled clinical trial

BACKGROUND A newly developed collagen matrix (CM) of porcine origin has been shown to represent a potential alternative to palatal connective tissue grafts (CTG) for the treatment of single Miller Class I and II gingival recessions when used in conjunction with a coronally advanced flap (CAF). However, at present it remains unknown to what extent CM may represent a valuable alternative to CTG in the treatment of Miller Class I and II multiple adjacent gingival recessions (MAGR). The aim of this study was to compare the clinical outcomes following treatment of Miller Class I and II MAGR using the modified coronally advanced tunnel technique (MCAT) in conjunction with either CM or CTG. METHODS Twenty-two patients with a total of 156 Miller Class I and II gingival recessions were included in this study. Recessions were randomly treated according to a split-mouth design by means of MCAT + CM (test) or MCAT + CTG (control). The following measurements were recorded at baseline (i.e. prior to surgery) and at 12 months: Gingival Recession Depth (GRD), Probing Pocket Depth (PD), Clinical Attachment Level (CAL), Keratinized Tissue Width (KTW), Gingival Recession Width (GRW) and Gingival Thickness (GT). GT was measured 3-mm apical to the gingival margin. Patient acceptance was recorded using a Visual Analogue Scale (VAS). The primary outcome variable was Complete Root Coverage (CRC), secondary outcomes were Mean Root Coverage (MRC), change in KTW, GT, patient acceptance and duration of surgery. RESULTS Healing was uneventful in both groups. No adverse reactions at any of the sites were observed. At 12 months, both treatments resulted in statistically significant improvements of CRC, MRC, KTW and GT compared with baseline (p < 0.05). CRC was found at 42% of test sites and at 85% of control sites respectively (p < 0.05). MRC measured 71 ± 21% mm at test sites versus 90 ± 18% mm at control sites (p < 0.05). Mean KTW measured 2.4 ± 0.7 mm at test sites versus 2.7 ± 0.8 mm at control sites (p > 0.05). At test sites, GT values changed from 0.8 ± 0.2 to 1.0 ± 0.3 mm, and at control sites from 0.8 ± 0.3 to 1.3 ± 0.4 mm (p < 0.05). Duration of surgery and patient morbidity was statistically significantly lower in the test compared with the control group respectively (p < 0.05). CONCLUSIONS The present findings indicate that the use of CM may represent an alternative to CTG by reducing surgical time and patient morbidity, but yielded lower CRC than CTG in the treatment of Miller Class I and II MAGR when used in conjunction with MCAT.

Radiofrequency ablation of multiple accessory pathways

The aim of the study was to review the clinical and electrophysiological characteristics and results of radiofrequency catheter ablation in patients with multiple accessory pathways to compare them with those of patients with single accessory pathways. Electrophysiological study and radiofrequency catheter ablation were performed in 1010 consecutive cases with Wolff Parkinson White Syndrome. Presence of multiple accessory pathways was documented in 31 patients (3.1%); 30 had two, and 1 had three accessory pathways. Of the 63 accessory pathways, 42 were manifest and 21 concealed. Nine patients had Ebstein's anomaly associated with atrioventricular bypass tracts. The most common combination was right posteroseptal with right free wall bypass tracts (15 patients with 30 accessory pathways). Fifty-one of the sixty-three accessory pathways (81%) were ablated successfully without complications. The duration of the procedure was 100 +/- 58 min and the fluoroscopic time 40 +/- 17 min. A follow up of 5 +/- 3 years after ablation, demonstrated recurrences of six accessory pathways (9.5%). In conclusion, patients with multiple accessory pathways can be treated by radiofrequency ablation in only one session with a high success rate although slightly less than that in patients with a single accessory pathway (81% vs 93%, P<0.01).

The Assessment of Multiple Processes Underlying the Attentional Blink: A Fixed - links Modeling Approach based on Behavioral and Electrophysiological Data

When observers are presented with two visual targets appearing in the same position in close temporal proximity, a marked reduction in detection performance of the second target has often been reported, the so-called attentional blink phenomenon. Several studies found a similar decrement of P300 amplitudes during the attentional blink period as observed with detection performances of the second target. However, whether the parallel courses of second target performances and corresponding P300 amplitudes resulted from the same underlying mechanisms remained unclear. The aim of our study was therefore to investigate whether the mechanisms underlying the AB can be assessed by fixed-links modeling and whether this kind of assessment would reveal the same or at least related processes in the behavioral and electrophysiological data. On both levels of observation three highly similar processes could be identified: an increasing, a decreasing and a u-shaped trend. Corresponding processes from the behavioral and electrophysiological data were substantially correlated, with the two u-shaped trends showing the strongest association with each other. Our results provide evidence for the assumption that the same mechanisms underlie attentional blink task performance at the electrophysiological and behavioral levels as assessed by fixed-links models.

Validation of multiple-breath washout equipment for infants and young children.

INTRODUCTION The new ATS/ERS consensus report recommends in vitro validation of multiple-breath inert gas washout (MBW) equipment based on a lung model with simulated physiologic conditions. We aimed to assess accuracy of two MBW setups for infants and young children using this model, and to compare functional residual capacity (FRC) from helium MBW (FRCMBW ) with FRC from plethysmography (FRCpleth ) in vivo. METHODS The MBW setups were based on ultrasonic flow meter technology. Sulfur hexafluoride and helium were used as tracer gases. We measured FRC in vitro for specific model settings with and without carbon dioxide and calculated differences of measured to generated FRC. For in vivo evaluation, difference between FRCMBW and FRCpleth was calculated in 20 healthy children, median age 6.1 years. Coefficient of variation (CV) was calculated per FRC. RESULTS In the infant model (51 runs, FRC 80-300 ml), mean (SD) relative difference between generated and measured FRCs was 0.7 (4.7) %, median CV was 4.4% for measured FRCs. In the young child model, one setting (8 runs, FRC 400 ml) showed a relative difference of up to 13%. For the remaining FRCs (42 runs, FRC 600-1,400 ml), mean (SD) relative difference was -2.0 (3.4) %; median CV was 1.4% for measured FRCs. In vivo FRCpleth exceeded FRCMBW values by 37% on average. CONCLUSIONS Both setups measure lung volumes in the intended age group reliably and reproducibly. Characteristics of different techniques should be considered when measuring lung volumes in vivo. Pediatr Pulmonol. © 2014 Wiley Periodicals, Inc.

Persistence of biological traces at inside parts of a firearm from a case of multiple familial homicide

Backspatter from wounds caused by contact shots against a biological target had before been shown to be propelled into firearms' barrels where they can persist and be retrieved from as relevant forensic evidence. Herein, that insight was applied to the investigation of a case of multiple familial homicide with a firearm. Samples of backspatter were collected from the firearm using DNA-free swabs. DNA was extracted from the swabs, and 16 STR systems were PCR-amplified to generate DNA profiles of all victims shot by the firearm. The quality of the resulting DNA profiles was sufficient to exclude the perpetrator as donor and to differentiate the three closely related victims thereby proving that all three victims had been shot by the same firearm from very close or contact distance. A key insight gained from this case was that not only a firearms' barrel inside but other inner surfaces may be charged with profilable DNA.

The effect of nontemporal stimulus size on perceived duration as assessed by the method of reproduction

Perceived duration is assumed to be positively related to nontemporal stimulus magnitude. Most recently, the finding that larger stimuli are perceived to last longer has been challenged to represent a mere decisional bias induced by the use of comparative duration judgments. Therefore, in the present study, the method of temporal reproduction was applied as a psychophysical procedure to quantify perceived duration. Another major goal was to investigate the influence of attention on the effect of visual stimulus size on perceived duration. For this purpose, an additional dual-task paradigm was employed. Our results not only converged with previous findings in demonstrating a functional positive relationship between nontemporal stimulus size and perceived duration, but also showed that the effect of stimulus size on perceived duration was not confined to comparative duration judgments. Furthermore, the effect of stimulus size proved to be independent of attentional resources allocated to stimulus size; nontemporal visual stimulus information does not need to be processed intentionally to influence perceived duration. Finally, the effect of nontemporal stimulus size on perceived duration was effectively modulated by the duration of the target intervals, suggesting a hitherto largely unrecognized role of temporal context for the effect of nontemporal stimulus size to become evident.