The use of magnetic resonance imaging in multiple sclerosis treatment trials: power calculations for annual lesion load measurement

Phase III definitive treatment trials of new multiple sclerosis (MS) therapies now routinely incorporate an annual magnetic resonance imaging protocol, with change in T2-weighted brain lesion load providing an important outcome measure. To date the accepted strategy has been to perform a core imaging protocol on all patients in such studies. The aim of this study was to provide power calculations based on this MRI endpoint. Serial MRI data from 128 patients with either relapsing remitting (RR) or secondary progressive (SP) MS were used to calculate sample size requirements using a repeated measures analysis of variance design. We provide sample size calculations based on various follow-up intervals and effect sizes. Sample sizes for the SPMS cohort were substantially larger than for the RRMS group, reflecting the greater variance in lesion load changes between patients in the SPMS group. With a follow-up of 3 years, we estimate that only 12 and 33 patients per arm are needed to show stabilisation of MRI lesion load in the RRMS and SPMS groups, respectively. Our results suggest that ongoing phase III treatment trials are more than adequately powered to detect even subtle treatment effects, and indicate that incorporating measurements from longer follow-up durations increases power substantially. We conclude that an annual imaging protocol provides a robust and powerful tool for assessing effects on the radiological appearance of the disease process. Received: 11 February 1999/Received in revised form: 28 July 1999/Accepted: 10 October 1999     

A novel approach to identify antigens recognized by CD4 T cells using complement-opsonized bacteria expressing a cDNA library.

In patients with hematological malignancies receiving HLA-matched stem cell transplantation, T cells specific for minor histocompatibility antigens play a major role in graft rejection, induction of graft-versus-host disease and beneficial graft-versus-leukemia reactivity. Several human minor histocompatibility antigens recognized by T cells have been identified, but only two are presented by HLA class II molecules. In search of an efficient approach to identify antigenic peptides processed through the HLA class II pathway, we constructed a cDNA library in bacteria that were induced to express proteins. Bacteria were opsonized with complement to enforce receptor-mediated uptake by Epstein-Barr virus immortalized B cells that were subsequently used as antigen-presenting cells. This approach was validated with an HLA class II-restricted antigen encoded by gene DBY. We were able to identify bacteria expressing DBY diluted into a 300-fold excess of bacteria expressing a nonrelevant gene. Screening of a bacterial library using a DBY-specific CD4 T cell clone resulted in the isolation of several DBY cDNAs. We propose this strategy for a rapid identification of HLA class II-restricted antigenic peptides recognized by CD4 T cells.     

Pore Narrowing of Mesoporous Silica Materials

To use mesoporous silicas as low-k materials, the pore entrances must be really small to avoid diffusion of metals that can increase the dielectric constant of the low-k dielectric. In this paper we present a new method to narrow the pores of mesoporous materials through grafting of a cyclic-bridged organosilane precursor. As mesoporous material, the well-studied MCM-41 powder was selected to allow an easy characterization of the grafting reactions. Firstly, the successful grafting of the cyclic-bridged organosilane precursor on MCM-41 is presented. Secondly, it is demonstrated that pore narrowing can be obtained without losing porosity by removing the porogen template after grafting. The remaining silanols in the pores can then be end-capped with hexamethyl disilazane (HMDS) to make the material completely hydrophobic. Finally, we applied the pore narrowing method on organosilica films to prove that this method is also successful on existing low-k materials.     

Attention modulates the dorsal striatum response to love stimuli

In previous functional magnetic resonance imaging (fMRI) studies concerning romantic love, several brain regions including the caudate and putamen have consistently been found to be more responsive to beloved‐related than control stimuli. In those studies, infatuated individuals were typically instructed to passively view the stimuli or to think of the viewed person. In the current study, we examined how the instruction to attend to, or ignore the beloved modulates the response of these brain areas. Infatuated individuals performed an oddball task in which pictures of their beloved and friend served as targets and distractors. The dorsal striatum showed greater activation for the beloved than friend, but only when they were targets. The dorsal striatum actually tended to show less activation for the beloved than the friend when they were distractors. The longer the love and relationship duration, the smaller the response of the dorsal striatum to beloved‐distractor stimuli was. We interpret our findings in terms of reinforcement learning. By virtue of using a cognitive task with a full factorial design, we show that the dorsal striatum is not activated by beloved‐related information per se, but only by beloved‐related information that is attended. Hum Brain Mapp 35:503–512, 2014. © 2012 Wiley Periodicals, Inc.     

Resorbable scaffold based chronic neural electrode arrays

We have developed a novel type of neural electrode array for future brain-machine interfaces (BMI) and neural implants requiring high resolution recording and stimulation on the surface of brain lesions or on the cortex. The devices differ on two points from commonly used thin film electrode arrays: first, the thin film backbone of the implant is exceptionally thin (down to 5 microns) and finely patterned into spring-like structures. This increases the flexibility of the electrode array and allows stretching and conforming better to a quasi spherical cavity surface. Second, the thin film backbone of the device is reinforced with a porous layer of resorbable chitosan. This design aims at minimal invasiveness and low mechanical irritation during prolonged use, while the chitosan matrix ensures the implant is stiff enough for practical handling during the implantation procedure and dissolves afterwards. Furthermore, the chitosan adds haemostatic and antiseptic properties to the implant and improves adhesion. In the article, the design and fabrication process are presented. In vitro and long term in vivo test results over a 12 month period are shown. By adopting the use of a resorbable scaffold-like material as main constituent of neural implants, the presented work opens up the possibility of applying tissue engineering techniques to further improve neural implant technology.     

Fetal Movement Counting—Maternal Concern and Experiences: A Multicenter,Randomized, Controlled Trial

Abstract: Background: Fetal movement counting may improve timely identification of decreased fetal activity and thereby contribute to prevent adverse pregnancy outcomes, but it may also contribute to maternal concern. This study aimed to test whether fetal movement counting increased maternal concern. Methods: In a multicenter, controlled trial 1,013 women with a singleton pregnancy were randomly assigned either to perform daily fetal movement counting from pregnancy week 28 or to follow standard Norwegian antenatal care where fetal movement counting is not encouraged. The primary outcome was maternal concern, measured by the Cambridge Worry Scale. Analysis was by intention-to-treat. Results: The means and SDs on Cambridge Worry Scale scores were 0.77 (0.55) and 0.90 (0.62) for the intervention and the control groups, respectively, a mean difference between the groups of 0.14 (95% CI: 0.06–0.21, p < 0.001). Decreased fetal activity was of concern to 433 women once or more during pregnancy, 45 and 42 percent in the intervention and control groups, respectively (relative risk = 1.1, 95% CI: 0.9–1.2). Seventy-nine percent of the women responded favorably to the use of counting charts. Conclusions: Women who performed fetal movement counting in the third trimester reported less concern than those in the control group. The frequency of maternal report of concern about decreased fetal activity was similar between the groups. Most women considered the use of a counting chart to be positive. (BIRTH 39:1 March 2012)