Exploiting the Time-Reversal Operator for Adaptive Optics, Selective Focusing and Scattering Pattern Analysis

We report on the experimental measurement of the backscattering matrix of a weakly scattering medium in optics, composed of a few dispersed gold nanobeads. The DORT method (Decomposition of the Time Reversal Operator) is applied to this matrix and we demonstrate selective and efficient focusing on individual scatterers, even through an aberrating layer. Moreover, we show that this approach provides the decomposition of the scattering pattern of a single nanoparticle. These results open important perspectives for optical imaging, characterization and selective excitation of nanoparticles.Comment: 10 page

USPIO-enhanced MRI for preoperative staging of gynecological pelvic tumors: preliminary results

The aim of this study was to assess nodal enhancement with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) during preoperative staging of gynecological pelvic tumors within the same imaging session for the primary tumor. Pelvic MRI was performed 18-28h after intravenous infusion of USPIO (Combidex/Sinerem, 2.6mg Fe/kg body weight) in 13 women (mean age 51 years) scheduled for surgery for biopsy proven (n=11) or clinically suspected (n=2) uterine carcinoma. Axial T1-weighted spin-echo (SE), T2-weighted fast SE (FSE; with fat saturation), fast spoiled gradient-recalled (FSPGR) echo, sagittal and oblique T2-weighted FSE sequences were acquired on a 1.5-T system. Lymph nodes were prospectively staged using standard criteria, i.e., size and shape, as well as USPIO enhancement. Results were correlated with histology findings. MRI correctly staged all primary uterine tumors. In one case, the preoperative diagnosis of stage IV switched the therapeutic approach to radiochemotherapy. Ninety-one (86 benign, 5 malignant) of the histologically characterized nodes could be correlated with their MRI counterparts. One node was false positive; three micrometastases greater than 5mm and one 5-mm metastasis were missed. On a nodal basis, the sensitivity score was 0.33 and the specificity score, 0.99. On a patient basis, the sensitivity score was 0.25 and the specificity score, 0.80. Our preliminary results indicate that USPIO-enhanced pelvic MRI for preoperative nodal assessment is feasible within one imaging session for primary tumors and that it has a high specificity. However, the low sensitivity in the present study is a limitation for the clinical application of this techniqu

My migraine voice survey. aA global study of disease burden among individuals with migraine for whom preventive treatments have failed

Background: Migraine is associated with many debilitating symptoms that affect daily functioning. My Migraine Voice is a large global cross-sectional study aimed at understanding the full burden and impact of migraine directly from patients suffering from ≥4 monthly migraine days (MMDs) with a history of prophylactic treatment failure. Methods: This study was conducted worldwide (31 countries across North and South Americas, Europe, the Middle East and Northern Africa, and the Asia-Pacific region) using an online survey administered to adults with migraine who reported ≥4 MMDs in the 3 months preceding survey administration, with pre-specified criteria of 90% having used preventive migraine treatment (80% with history of ≥1 treatment failure). Prophylactic treatment failure was defined as a reported change in preventive medication by individuals with migraine for any reason, at least once. Results: In total, 11,266 individuals participated in the survey. Seventy-four percent of the participants reported spending time in darkness/isolation due to migraine (average: 19 h/month). While 85% of all respondents reported negative aspects of living with migraine (feeling helpless, depressed, not understood), sleeping difficulties (83%), and fear of the next attack (55%), 57% shared ≥1 positive aspect (learning to cope, becoming a stronger person). Forty-nine percent reported feeling limited in daily activities throughout all migraine phases. Migraine impact on professional, private, or social domains was reported by 87% of respondents (51% in all domains). In the previous 12 months, 38% of respondents had visited the emergency department (average: 3.3 visits), whereas 23% stayed in hospital overnight (average: 3.2 nights) due to migraine. Conclusions: The burden of migraine is substantial among this cohort of individuals with at least 4 migraine days per month and for whom at least 1 preventive migraine treatment had failed. Interestingly, respondents reported some positive aspects in their migraine journey; the greater resilience and strength brought on by coping with migraine suggests that if future treatments could address existing unmet needs, these individuals with migraine will be able to maximize their contribution to society

Upwelling couples chemical and biological dynamics across the littoral and pelagic zones of Lake Tanganyika, East Africa

We studied the effects of upwelling on nutrient and phytoplankton dynamics in the pelagic and littoral zones of Lake Tanganyika near Kigoma, Tanzania. During the dry season of 2004, a rise in the thermocline and sudden drop in surface water temperatures indicated a substantial upwelling event. Increases in concentrations of nitrate, soluble reactive phosphorus, and silica in the surface waters occurred simultaneously after the temperature drop. Within days, chlorophyll a concentrations increased and remained elevated, while inorganic nutrient concentrations returned to preupwelling levels and organic nutrient concentrations peaked. We observed parallel temporal patterns of water temperature, nutrient concentrations, and phytoplankton chlorophyll in both the pelagic and the littoral zones, demonstrating that upwelling strongly affects the nearshore ecosystem as well as the pelagic zone. Concurrent records from 12 littoral sites indicated spatial variation in the timing, magnitude, and biological response to upwelling. There was no discernable latitudinal pattern in the timing of upwelling, suggesting that mixing did not result from a progressive wave. Our monitoring, as well as other multiyear studies, suggests that dry-season upwelling occurs during most years in northern Lake Tanganyika. The observed sensitivity of littoral nutrients and phytoplankton to upwelling suggests that reductions in upwelling due to global climate change could strongly affect the dynamics of the spectacular nearshore ecosystem of Lake Tanganyika, as has been proposed for the pelagic zone

The size of electron-hole pairs in pi conjugated systems

We have performed momentum dependent electron energy-loss studies of the electronic excitations in sexithiophene and compared the results to those from parent oligomers. Our experiment probes the dynamic structure factor S(q,omega)and we show that the momentum dependent intensity variation of the excitations observed can be used to extract the size of the electron-hole pair created in the excitation process. The extension of the electron-hole pairs along the molecules is comparable to the length of the molecules and thus maybe only limited by structural constraints. Consequently, the primary intramolecular electron-hole pairs are relatively weakly bound. We find no evidence for the formation of excitations localized on single thiophene units.Comment: RevTex, 3 figures, to appear in Physical Review Letter

On the neural origin of pseudoneglect: EEG-correlates of shifts in line bisection performance with manipulation of line length

Healthy participants tend to show systematic biases in spatial attention, usually to the left. However, these biases can shift rightward as a result of a number of experimental manipulations. Using electroencephalography (EEG) and a computerized line bisection task, here we investigated for the first time the neural correlates of changes in spatial attention bias induced by line-length (the so-called line-length effect). In accordance with previous studies, an overall systematic left bias (pseudoneglect) was present during long line but not during short line bisection performance. This effect of line-length on behavioral bias was associated with stronger right parieto-occipital responses to long as compared to short lines in an early time window (100–200 ms) post-stimulus onset. This early differential activation to long as compared to short lines was task-independent (present even in a non-spatial control task not requiring line bisection), suggesting that it reflects a reflexive attentional response to long lines. This was corroborated by further analyses source-localizing the line-length effect to the right temporo-parietal junction (TPJ) and revealing a positive correlation between the strength of this effect and the magnitude by which long lines (relative to short lines) drive a behavioral left bias across individuals. Therefore, stimulus-driven left bisection bias was associated with increased right hemispheric engagement of areas of the ventral attention network. This further substantiates that this network plays a key role in the genesis of spatial bias, and suggests that post-stimulus TPJ-activity at early information processing stages (around the latency of the N1 component) contributes to the left bias

Cellular Ser/Thr-Kinase Assays Using Generic Peptide Substrates

High-throughput cellular profiling has successfully stimulated early drug discovery pipelines by facilitating targeted as well as opportunistic lead finding, hit annotation and SAR analysis. While automation-friendly universal assay formats exist to address most established drug target classes like GPCRs, NHRs, ion channels or Tyr-kinases, no such cellular assay technology is currently enabling an equally broad and rapid interrogation of the Ser/Thr-kinase space. Here we present the foundation of an emerging cellular Ser/Thr-kinase platform that involves a) coexpression of targeted kinases with promiscuous peptide substrates and b) quantification of intracellular substrate phosphorylation by homogeneous TR-FRET. Proof-of-concept data is provided for cellular AKT, B-RAF and CamK2δ assays. Importantly, comparable activity profiles were found for well characterized B-Raf inhibitors in TR-FRET assays relying on either promiscuous peptide substrates or a MEK1(WT) protein substrate respectively. Moreover, IC50-values correlated strongly between cellular TR-FRET assays and a gold standard Ba/F3 proliferation assay for B-Raf activity. Finally, we expanded our initial assay panel by screening a kinase-focused cDNA library and identified starting points for >20 cellular Ser/Thr-kinase assays