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Background For patients with acute ischemic stroke undergoing endovascular mechanical thrombectomy with x-ray angiography, the use of adjuncts to maintain vessel patency, such as stents or antiplatelet medications, can increase risk of periprocedural complications. Criteria for using these adjuncts are not well defined. Purpose To evaluate use of MRI to guide critical decision making by using a combined biplane x-ray neuroangiography 3.0-T MRI suite during acute ischemic stroke intervention. Materials and Methods This retrospective observational study evaluated consecutive patients undergoing endovascular intervention for acute ischemic stroke between July 2019 and May 2020 who underwent either angiography with MRI or angiography alone. Cerebral tissue viability was assessed by using MRI as the reference standard. For statistical analysis, Fisher exact test and Student t test were used to compare groups. Results Of 47 patients undergoing acute stroke intervention, 12 patients (median age, 69 years; interquartile range, 60-77 years; nine men) underwent x-ray angiography with MRI whereas the remaining 35 patients (median age, 80 years; interquartile range, 68-86 years; 22 men) underwent angiography alone. MRI results influenced clinical decision making in one of three ways: whether or not to perform initial or additional mechanical thrombectomy, whether or not to place an intracranial stent, and administration of antithrombotic or blood pressure medications. In this initial experience, decision making during endovascular acute stroke intervention in the combined angiography-MRI suite was better informed at MRI, such that therapy was guided in real time by the viability of the at-risk cerebral tissue. Conclusion Integrating intraprocedural 3.0-T MRI into acute ischemic stroke treatment was feasible and guided decisions of whether or not to continue thrombectomy, to place stents, or to administer antithrombotic medication or provide blood pressure medications. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lev and Leslie-Mazwi in this issue.

Evidence is growing to support minimally invasive surgical evacuation of intraparenchymal hematomas, particularly those with minimal residual hematoma volumes following evacuation. To maximize the potential for neurologic recovery, it is imperative that the trajectory for access to the hematoma minimizes disruption of normal parenchyma. Flat panel detector CT-based navigation and needle guidance software provides a platform that uses flat panel detector CT imaging obtained on the angiography table to aid reliable and safe access to the hematoma. In addition to providing a high degree of accuracy, this method also allows convenient and rapid re-imaging to assess navigation accuracy and the degree of hematoma evacuation prior to procedural completion. We provide a practical review of the syngo iGuide needle guidance software and the methodology for incorporating its use, and the software of other vendors, in a variety of minimally invasive methods for evacuation of intraparenchymal hematomas.

Background Digital subtraction angiography (DSA) remains the gold standard for angiographic evaluation of cerebrovascular pathology, however, multiple acquisitions requiring additional time and radiation are often needed. In contrast, 3D-DSA provides volumetric information from a single injection but neglects temporal information. Four-dimensional-DSA (4D-DSA) combines temporal information of 2D-DSA with volumetric information of 3D-DSA to provide time-resolved tomographic 3D reconstructions, potentially reducing procedure time and radiation. This work evaluates the diagnostic quality of virtual single-frame 4D-DSA relative to 2D-DSA images by assessing clinicians’ ability to evaluate cerebrovascular pathology. Methods Single-frame images of four projections from 4D-DSA and their corresponding 2D-DSA images (n = 15) were rated by two neurointerventional radiologists. Images were graded based on diagnostic quality (0 = non-diagnostic, 1 = poor, 2 = acceptable, 3 = good). Dose area product (DAP) for each case was recorded for all 2D-DSA, 4D-DSA acquisitions, and the overall procedure. Results The mean diagnostic quality of all four 4D-DSA projections from both raters was 1.75 while the mean of 2D-DSA projections was 2.8. Student’s t-test revealed significant difference in diagnostic quality between 4D-DSA and 2D-DSA at all four projections (p Conclusions The difference in image quality between virtual single-frame 4D-DSA and their respective 2D-DSA images is statistically significant. Furthermore, 4D-DSA acquisitions require less radiation dose than conventional procedures with 2D-DSA acquisitions.

The simultaneous growth of robotic-assisted surgery and telemedicine in recent years has only been accelerated by the recent coronavirus disease 2019 pandemic. Robotic assistance for neurovascular intervention has garnered significant interest due to opportunities for tele-stroke models of care for remote underserved areas. Lessons learned from medical robots in interventional cardiology and neurosurgery have contributed to incremental but vital advances in medical robotics despite important limitations. In this article, we discuss robot types and their clinical justification and ethics, as well as a general overview on available robots in thoracic/abdominal surgery, neurosurgery, and cardiac electrophysiology. We conclude with current clinical research in neuroendovascular intervention and a perspective on future directions.

Background and ObjectivesRas–mitogen-activated protein kinase (MAPK) signaling abnormalities occur in most brain arteriovenous malformations (bAVMs). No means exist to molecularly profile bAVMs without open surgery, limiting precision medicine approaches to treatment. Here, we report use of endoluminal biopsy of the vessel lumen of bAVMs to characterize gene expression and blood flow–mediated transcriptional changes in living patients.MethodsEndoluminal biopsy and computational fluid dynamic modeling (CFD) were performed in adults with unruptured AVMs with cerebral angiography. Each patient underwent surgical resection and cell sampling from a contiguous arterial segment. Fluorescence-assisted cell sorting enriched endothelial cells, which were sequenced on an Illumina HiSeq 4000 sequencer. Gene expression was quantified with RNA sequencing (RNAseq). Differential gene expression, ontology, and correlative analyses were performed. Results were validated with quantitative reverse transcription PCR (RT-qPCR).ResultsEndoluminal biopsy was successful in 4 patients without complication. Endoluminal biopsy yielded 269.0 ± 79.9 cells per biopsy (control 309.2 ± 86.6 cells, bAVM 228.8 ± 133.4 cells). RNAseq identified 106 differentially expressed genes (DEGs) in bAVMs (false discovery rate ≤0.05). DEGs were enriched for bAVM pathogenic cascades, including Ras-MAPK signaling (p< 0.05), and confirmed with RT-qPCR and a panel predictive of MAPK/extracellular signal-regulated kinase inhibitor response. Compared to patient-matched surgically excised tissues, endoluminal biopsy detected 83.3% of genes, and genome-wide expression strongly correlated (Pearsonr= 0.77). Wall shear stress measured by CFD correlated with inflammatory pathway upregulation. Comparison of pre-embolization and postembolization samples confirmed flow-mediated gene expression changes.DiscussionEndoluminal biopsy allows molecular profiling of bAVMs in living patients. Gene expression profiles are similar to those of tissues acquired with open surgery and identify potentially targetable Ras-MAPK signaling abnormalities in bAVMs. Integration with CFD allows determination of flow-mediated transcriptomic alterations. Endoluminal biopsy may help facilitate trials of precision medicine approaches to bAVMs in humans.

BACKGROUND AND PURPOSE: Hemodynamic features of brain AVMs may portend increased hemorrhage risk. Previous studies have suggested that MTT is shorter in ruptured AVMs as assessed on quantitative color-coded parametric DSA. This study assesses the interrater reliability of MTT measurements obtained using quantitative color-coded DSA. MATERIALS AND METHODS: Thirty-five color-coded parametric DSA images of 34 brain AVMs were analyzed by 4 neuroradiologists with experience in interventional neuroradiology. Hemodynamic features assessed included MTT of the AVM and TTP of the dominant feeding artery and draining vein. Agreement among the 4 raters was assessed using the intraclass correlation coefficient. RESULTS: The interrater reliability among the 4 raters was poor (intraclass correlation coefficient = 0.218; 95% CI, 0.062–0.414; P value = .002) as it related to MTT assessment. When the analysis was limited to cases in which the raters selected the same image to analyze and selected the same primary feeding artery and the same primary draining vein, interrater reliability improved to fair (intraclass correlation coefficient = 0.564; 95% CI, 0.367–0.717; P

Introduction Improved functional outcome has been shown in carefully selected patients who are directly transferred to the interventional suite for immediate access to recanalization therapy, bypassing the emergency department (ED) and diagnostic multidetector CT (MDCT). For stroke patients transferred directly to the interventional suite, flat panel CT (FPCT) may provide the necessary diagnostic information regarding intracranial hemorrhage, large vessel patency, clot extent, and collateral supply. However, the large amount of data acquired, typically including 10 phases of contrast-enhancement, can be difficult to review and interpret quickly in the acute stroke setting, and its diagnostic equivalence to MDCT has not been validated. A display format that incorporates all of the multiphasic information into a single time-variant color map may be helpful in facilitating rapid interpretation. Materials and Methods Between January and October 2019, six acute ischemic stroke patients at a tertiary urban hospital underwent multiphasic FPCT after conventional stroke evaluation with MDCT in the ED. IRB approval was obtained. Data was post-processed on a separate workstation, allowing dynamic visualization of ten 3D volumes in different phases of contrast enhancement, enabling evaluation for hemorrhage, occlusion site, clot extent, and collateral flow. We retrospectively processed these multiphasic scans in a fully automated workflow including rigid motion correction, orbitomeatal line alignment, mask image subtraction, maximum intensity projection (MIP) generation, and production of a single color-coded MIP volume condensing the data contained in the 10 phases of contrast enhancement. Results Intracranial hemorrhage was not detected in any case, either on MDCT or FPCT. Color-coded MIP images enabled confident diagnosis of large vessel occlusion, clot extent, and collateral flow. The time to acquire FPCT in IR was faster than that to acquire MDCT in the ED (2 vs 17 min). Theoretical time savings averaged 68 min. All patients underwent subsequent mechanical thrombectomy (with TICI 2b/3 results). FPCT perfusion maps were equivalent to MDCT perfusion maps, and accurately predicted core infarct volume on follow-up MRI/CT, as compared by manual segmentation methods. Conclusion Flat panel CT angiography is a promising tool to enable one-stop shop management of acute ischemic stroke in the interventional suite. Color-coded MIP images enable rapid diagnosis and interpretation of large multiphasic CTA data. Disclosures K. Narsinh: None. K. Mueller: 5; C; Siemens Healthineers. M. Manhart: 5; C; Siemens Healthineers. S. Hetts: 1; C; Siemens Healthineers, NIH. 2; C; Imperative Medical, MicroVention Terumo, Route 92 Medical. T. Moore: None. E. Chaney: None. D. Cooke: 1; C; Siemens Healthineers.

Introduction Intracranial atherosclerotic disease (ICAD) is sometimes discovered during mechanical thrombectomy for acute ischemic stroke. In the event of partial or failed recanalization, termination of the procedure is typically determined by interpretation of the angiogram. Although some retrospective studies have suggested that rescue intracranial stenting is safe and effective in this setting, others have suggested that intracranial stenting may increase risk of intracranial hemorrhage. In difficult cases that result in partial or failed recanalization, MRI would be helpful to definitively discriminate viable from infarcted cerebral tissue and determine operative course. Methods We performed a retrospective single institution review of all acute stroke patients who underwent thrombectomy and intraprocedural MRI. From October 2019 to March 2020, eight patients underwent intraprocedural 3 Tesla MRI during mechanical thrombectomy for acute ischemic stroke intervention in a hybrid angiography-MRI suite. Diffusion-weighted (DWI; b-value=1000 s/mm2) and T2-weighted sequences were obtained. The electronic medical record was reviewed to determine clinical outcomes. Results In all cases, the intraprocedural MRI was obtained to determine the extent of core infarct, and played a pivotal role in decision-making. In particular, operators used the MRI to make decisions regarding intracranial stent placement, administration of antiplatelet medications or heparin, and blood pressure parameters. p { margin-bottom: 0.1in; line-height: 115%; background: transparent } In four patients who underwent partial recanalization (TICI 2a or less), intracranial stents were placed in 2 based on MRI results. In the remaining patients, MRI informed the time course for postoperative initiation of anticoagulant medications and blood pressure parameters. Conclusion Hybrid angiography-MRI units offer a unique capability to inform neurointerventionalists of the viability of the tissue they are attempting to salvage during complex cerebrovascular interventions. Integrating MRI into the stroke treatment angiography suite may thereby improve individual patient selection and treatment selection. Disclosures K. Narsinh: None. B. Kilbride: None. K. Mueller: 5; C; Siemens Healthineers. J. Vitt: None. J. Massachi: None. M. Amans: 1; C; NIH. D. Cooke: 1; C; Siemens Healthineers. M. Wilson: None. S. Hetts: 1; C; Siemens Healthineers, NIH. 2; C; Imperative Medical, MicroVention Terumo, Route 92 Medical.

Summary First‐line treatments for classical Hodgkin lymphoma (HL) include ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and BEACOPP escalated (escalated dose bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone). To further improve overall outcomes, positron emission tomography‐driven strategies and ABVD or BEACOPP variants incorporating the antibody‐drug conjugate brentuximab vedotin (BV) or anti‐PD1 antibodies are under investigation in advanced‐stage patients. The present study aimed to elicit preferences for attributes associated with ABVD, BEACOPP escalated and BV‐AVD (BV, adriamycin, vinblastine and dacarbazine) among patients and physicians. Cross‐sectional online discrete choice experiments were administered to HL patients (n = 381) and haematologists/oncologists (n = 357) in France, Germany and the United Kingdom. Included attributes were progression‐free survival (PFS), overall survival (OS), and the risk of neuropathy, lung damage, infertility and hospitalisation due to adverse events. Whereas 5‐year PFS and OS were the most important treatment attributes to patients, the relative importance of each attribute and preference weights for each level varied among physicians according to the description of the hypothetical patient for whom treatment was recommended. PFS and OS most strongly influenced physicians’ recommendations when considering young female patients who did not want children or young male patients. Infertility was more important to physicians’ treatment decision than PFS when considering young women with unknown fertility preferences, whereas hospitalisations due to adverse events played the largest role in treatment decisions for older patients.

Purpose To review available evidence for use of cone-beam CT during transcatheter arterial chemoembolization in hepatocellular carcinoma (HCC) for detection of tumor and feeding arteries. Materials and Methods Literature searches were conducted from inception to May 15, 2016, in PubMed (MEDLINE), Scopus, and Cochrane Central Register of Controlled Trials. Searches included "cone beam," "CBCT," "C-arm," "CACT," "cone-beam CT," "volumetric CT," "volume computed tomography," "volume CT," AND "liver," "hepatic*," "hepatoc*." Studies that involved adults with HCC specifically and treated with transcatheter arterial chemoembolization that used cone-beam CT were included. Results Inclusion criteria were met by 18 studies. Pooled sensitivity of cone-beam CT for detecting tumor was 90% (95% confidence interval [CI], 82%–95%), whereas pooled sensitivity of digital subtraction angiography (DSA) for tumor detection was 67% (95% CI, 51%–80%). Pooled sensitivity of cone-beam CT for detecting tumor feeding arteries was 93% (95% CI, 91%–95%), whereas pooled sensitivity of DSA was 55% (95% CI, 36%–74%). Conclusions Cone-beam CT can significantly increase detection of tumors and tumor feeding arteries during transcatheter arterial chemoembolization. Cone-beam CT should be considered as an adjunct tool to DSA during transcatheter arterial chemoembolization treatments of HCC.

The detection and analysis of rare blood biomarkers is necessary for early diagnosis of cancer and to facilitate the development of tailored therapies. However, current methods for the isolation of circulating tumour cells (CTCs) or nucleic acids present in a standard clinical sample of only 5–10 ml of blood provide inadequate yields for early cancer detection and comprehensive molecular profiling. Here, we report the development of a flexible magnetic wire that can retrieve rare biomarkers from the subject’s blood in vivo at a much higher yield. The wire is inserted and removed through a standard intravenous catheter and captures biomarkers that have been previously labelled with injected magnetic particles. In a proof-of-concept experiment in a live porcine model, we demonstrate the in vivo labelling and single-pass capture of viable model CTCs in less than 10 s. The wire achieves capture efficiencies that correspond to enrichments of 10–80 times the amount of CTCs in a 5-ml blood draw, and 500–5,000 times the enrichments achieved using the commercially available Gilupi CellCollector.

Synovial sarcoma (SS) is an aggressive malignancy which accounts for approximately 5–10% of all soft-tissue sarcomas. SS has pathologic and genomic characteristics that define it as a distinct subtype of soft tissue sarcoma (STS). STS subtypes continue to be recognized as distinct entities with specific characteristics, including differential chemo-sensitivity. The objective of this study was to conduct a descriptive review of current data on survival outcomes of systemic anti-cancer therapy specific to SS. A systematic literature review was conducted, using a custom search strategy to search EMBASE, Medline and CENTRAL for clinical trials and observational studies reporting overall survival (OS), progression-free survival (PFS) and/or response for cohorts of at least 50 SS patients. We identified 28 studies meeting these criteria, 25 of which were retrospective studies. Only three prospective studies were identified. Survival reports varied widely between studies based on the population, in particular on the disease stage, and reporting was heterogeneous in terms of the time points reported on. For patients with localized disease, reports of five-year PFS ranged from 26% to 80.7% and five-year OS from 40% to 90.7%, whereas five-year OS for patients with metastatic disease was very low at around 10%; and in one case, 0% was reported. Only four of the included publications reported outcomes by type of systemic anti-cancer therapy received. Our study draws attention to the fact that additional prospective studies to better define the most appropriate treatment for SS in all stages and lines of therapy are still needed.

Purpose Hepatocellular carcinomas (HCCs) bridging two or more Couinaud–Bismuth segments of the liver ("watershed tumors") can recruit multiple segmental arteries. The primary hypothesis of this study was that fewer watershed tumors show complete response (CR) after chemoembolization, with shorter time to local recurrence. Secondary analysis on the impact on transplantation eligibility in the presence of progressive disease was also performed. Materials and Methods A total of 155 transplantation-eligible patients whose HCC met Milan criteria (watershed, n=83; nonwatershed, n=72) and was treated with chemoembolization were included. Cone-beam computed tomography (CT) was used for guidance and for confirmation of circumferential uptake. Local response to chemoembolization per modified Response Evaluation Criteria In Solid Tumors and local disease-free survival (DFS) for the index tumor were calculated. Differences were assessed by univariate and multivariate analyses. Results CR after a single of chemoembolization was observed in 55.4% of watershed tumors and in 72.2% of nonwatershed tumors ( P = .045). Estimated DFS intervals were 151 days (95% confidence interval [CI], 93–245 d) and 336 days (95% CI, 231–747 d; P = .040) in the watershed and nonwatershed groups, respectively. Worse DFS was observed with a Model for End-Stage Liver Disease score > 20 ( P = .0001), higher Child–Pugh–Turcotte score ( P = .049), and watershed location ( P = .040). Waiting list drop-off rates were statistically similar between groups. Conclusions Hepatocellular carcinomas located in the watershed region of the liver have a poorer response to chemoembolization than those located elsewhere. These tumors are associated with worse DFS and require additional treatments to maintain transplantation eligibility per Milan criteria. Cone-beam CT can identify crossover supply and confirm complete geographic drug uptake, possibly reducing (but not eliminating) the risk of incomplete response.

In this article, I employ the notion of a Holocaust performative developed by Vivian Patraka and modifies it to accommodate German cultural production about the memory of Germans as Holocaust perpetrators. Rather than engage with the irretrievable absence of the Holocaust victims, many cultural products produced for German audiences highlight the reappearance of the perpetrators in postwar decades. With this as my framework, I analyze the performative strategies involved in cultural texts that invoke the family—and by extension the nation—as a site of memory, including the utilization of photographs. I explore the ways in which such “family albums” have been used in the context of a variety of media, such as the first and the revised Wehrmacht exhibit, the drama Vor dem Ruhestand (1979) by the Austrian writer Thomas Bernhard, who wrote this play specifically for the theater in Stuttgart, and Michael Verhoeven’s documentary film Der unbekannte Soldat (2006). My discussion underscores how each of these media perform in intermedial ways to highlight the Germans’ conflicted and difficult engagement with the Nazi past, affecting German cultural and memory politics.

Rezumat. Ideea principală promovată de autor este că în procesul integrării europene este importantă conservarea tradiţiilor naţionale şi promovarea intereselor naţionale. Autorul menţionează că migraţia este un factor influent în formarea şi perceperea interesului naţional şi, în acest context, poate influenţa procesul de integrare. Experienţa statelor europene, mai ales a Germaniei, oferă noi oportunităţi pentru statele candidate la integrare. Înţelegând că evenimentele tragice ale istoriei Europei moderne nu pot şi nu trebuie repetate, francezii şi nemţii au decis să depăşească şi să înlăture din viaţa lor ideologiile duşmănoase ale statelor uninaţionale, să refuze parţial la suveranitatea naţională şi să creeze instituţii supranaţionale. Prin aceasta Franţa a sacrificat o parte din propria suveranitate în favoarea uniunii cu Germania. Abstract. Thema in idea promoted by the authoris that in the process of European integration it is important for national traditions to be preserved and national interests to be promoted. The author noted that migration is an influential factor in shaping the perception of the national interest and in this context can influence the integration process. The experience of European countries, especially Germany, offers new opportunities for the candidate to integration. Since tragic events of modern European history cannot and should not be repeated, the French and the Germans decided to overcome and remove from their lives hostile ideologies of uninational states, to partially refuse national sovereignty and create supranational institutions. Through this, France has sacrificed some of its sovereignty in favour of union with Germany

Rationale and Objectives Intra-procedural measurement of hepatic perfusion following liver embolization continues to be a challenge. Blood volume imaging before and after interventional procedures would allow identifying the treatment end point or even allow predicting treatment outcome. Recent liver oncology studies showed the feasibility of parenchymal blood volume (PBV) imaging using an angiographic C-arm system. This study was done to evaluate the reproducibility of PBV measurements using cone beam computed tomography (CBCT) before and after embolization of the liver in a swine model. Materials and Methods CBCT imaging was performed before and after partial bland embolization of the left lobe of the liver in five adult pigs. Intra-arterial injection of iodinated contrast with a 6-second x-ray delay was used with a two-sweep 8-second rotation imaging protocol. Three acquisitions, each separated by 10 minutes to allow for contrast clearance, were obtained before and after embolization in each animal. Post-processing was carried out using dedicated software to generate three-dimensional (3D) PBV maps. Two region-of-interest measurements were placed on two views within the right and left lobe on each CBCT 3D PBV map. Variation in PBV for scans acquired within each animal was determined by the coefficient of variation and intraclass correlation. A Wilcoxon signed-rank test was used to test post-procedure reduction in PBV. Results The CBCT PBV maps showed mean coefficients of variation of 7% (range: 2%–16%) and 25% (range: 13%–34%) for baseline and embolized PBV maps, respectively. The intraclass correlation for PBV measurements was 0.89, demonstrating high reproducibility, with measurable reduction in PBV displayed after embolization ( P = 0.007). Conclusions Intra-procedural acquisition of 3D PBV maps before and after liver embolization using CBCT is highly reproducible and shows promising application for obtaining intra-procedural PBV maps during locoregional therapy.

Non-technical summary Imaging of slow, long-lasting changes in intracellular Ca2+ levels ([Ca2+]i) is a common method to assess neuronal activity. We found that fast [Ca2+]i imaging (≥200 Hz sampling rate) may be a new option to record fast neuronal events including spike discharge and fast synaptic transmission in enteric neurones. These [Ca2+]i peaks required opening of voltage-gated sodium and calcium channels as well as Ca2+ release from intracellular stores. Abstract Slow changes in [Ca2+]i reflect increased neuronal activity. Our study demonstrates that single-trial fast [Ca2+]i imaging (≥200 Hz sampling rate) revealed peaks each of which are associated with single spike discharge recorded by consecutive voltage-sensitive dye (VSD) imaging in enteric neurones and nerve fibres. Fast [Ca2+]i imaging also revealed subthreshold fast excitatory postsynaptic potentials. Nicotine-evoked [Ca2+]i peaks were reduced by ω-conotoxin and blocked by ruthenium red or tetrodotoxin. Fast [Ca2+]i imaging can be used to directly record single action potentials in enteric neurones. [Ca2+]i peaks required opening of voltage-gated sodium and calcium channels as well as Ca2+ release from intracellular stores.

German authors have consistently broken the cultural taboo against discussing the Nazi legacy within the family in the so-called Vaterliteratur and later Enkelliteratur. While the former typically assumes an accusatory stance toward the parent generation, the latter has been characterized as forgiving and empathetic toward wartime Germans. Filmmakers have also contributed to this discourse, with autobiographical documentaries that explore their families' Nazi legacies. Jens Schanze's Winterkinder—Die schweigende Generation (2005) is a prime example of the grandchildren's empathetic yet critical examination of their family's past, especially when compared with Malte Ludin's 2 oder 3 Dinge, die ich von ihm weis (2005), which displays the confrontational, accusatory stance typically attributed to works of the children of the war generation. Both films impressively highlight what Sigrid Weigel calls a telescoping effect that allows for certain modes of denial to be passed on, and they expose the after effects on succeeding generations caused by such transferred silences and denials.

Introduction: The standard of care for previously untreated classical Hodgkin lymphoma (HL) in the United States has been combination chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or with radiotherapy depending on clinical characteristics. Other treatment programs exist, including intensified chemotherapy regimens, and substitution of brentuximab vedotin for bleomycin recently received FDA approval as first-line therapy for advance stage HL. The objective of this study was to understand how specific treatment attributes impact preferences among patients and physicians for choice of first-line treatment of HL. Methods: An online survey including a discrete choice experiment (DCE) was administered both to oncologists who manage patients with HL and to patients diagnosed within HL within the last two years in the United States. Participants were identified via online research panels. The attributes and levels of the hypothetical treatments presented in the DCE were informed by targeted literature review and physician and patient interviews. For physicians, six attributes were included: two-year overall survival (OS); two-year progression free survival (PFS); risk of side effects requiring hospitalization; risk of peripheral neuropathy (PN); risk of pulmonary toxicity; and patient out-of-pocket cost. The patient DCE included four attributes: OS, PFS, risk of PN and risk of pulmonary toxicity. DCE scenarios were developed using a d-efficient design. Participants reviewed 10 scenarios, and selected their preference between two hypothetical treatments. Patients considered themselves when selecting their preference; physicians considered four different advanced HL patient profiles that differed in age (30 or 65 years), smoking status, and the presence of baseline PN. The DCE data were analyzed using a mixed logit model (MXL). The relative importance of each attribute was calculated by determining the differences between the maximum and minimum coefficients of each attribute. These were then normalized and presented as percentages. Results: A total of 200 physicians and 141 patients were included in the analysis. Physicians had a mean of 15 years' experience and 71% practiced in a community setting. Patients had a median age of 35 years (range 19 to 69), 60% were male, and 34% were diagnosed with advanced stage HL. In the DCE, the most important attributes to both patients and physicians were OS and PFS. Based on the coefficients from the MXL model, a 1% increase in OS was more important to both groups than a 1% increase in PFS. The coefficients and level ranges for each attribute were used to calculate preference weights (see methods). Based on preference weights, PFS was the most important attribute for patients, followed by OS, risk of pulmonary toxicity, and risk of PN (Table 1). Compared to male patients, there was a trend for female patients to have a lower preference for a 1% decrease in risk of progression (p=0.077). Patients above the median age of 35 years had a significant preference (p=0.048) for a lower risk of pulmonary toxicity, and a trend for a higher preference for a 1% increase in OS (p=0.059) was observed. OS was also marginally more important to patients diagnosed with advanced stage HL versus those diagnosed in earlier stages. For physicians, preferences for treatment attributes differed based on the patient profile presented. PFS outweighed OS for a healthy 35 year-old patient (Table 2), whereas OS had a higher relative preference weight for a 35 year old smoker and older patients. For smokers, physicians ranked pulmonary toxicity as the most important attribute. Among older patients, side effects requiring hospitalization were more important to physicians' preferences than both OS and PFS. There were no major differences in preferences between academic and community oncologists. Conclusion: Patients are willing to accept treatments with worse short and long-term side effects in exchange for improved OS or PFS. Physicians' treatment preferences are patient-specific, with age and comorbidities impacting both the relative weight of OS and PFS attributes and the importance of pulmonary toxicity and short-term side effects. These results underscore the importance of assessing and sharing patient and physician preferences in creating a treatment plan for the management of newly diagnosed Hodgkin lymphoma. Disclosures Feliciano: Seattle Genetics: Employment, Equity Ownership. Mueller:ICON plc: Employment. Korol:ICON plc: Employment. He:ICON plc: Employment. Matasar:Seattle Genetics: Honoraria.

The nanoscale chemical composition variations of the surfaces of thin films of polystyrene- b-poly(methyl methacrylate) (PS- b-PMMA) diblock copolymers are investigated using apertureless near-field IR microscopy. The scattering of the incident infrared beam from a modulated atomic force microscopy (AFM) tip is probed using homodyne detection and demodulation at the tip oscillation frequency. An increase in the IR attenuation is observed in the PMMA-rich domains with a wavenumber dependence that is consistent with the bulk absorption spectrum. The results indicate that even though a small topography-induced artifact can be observed in the near-field images, the chemical signature of the sample is detected clearly.

A novel experimental technique, combining near-field optics and femtosecond pump–probe spectroscopy, is demonstrated to analyse the coherent nonlinear optical response of single quantum dots on ultrafast time scales. The technique is used to study the effects of strong non-resonant light fields on the optical spectra of single excitons in interface quantum dots. Transient reflectivity spectra show dispersive line shapes reflecting the light-induced shift of the quantum dot resonance. The nonlinear spectra are governed by the phase shift of the coherent quantum dot polarization acquired during the interaction with the light field. The phase shift is measured and ultrafast control of the quantum dot polarization is demonstrated.

Background: Liquid biopsies have long promised to enable earlier cancer diagnosis and tailored therapy. However, circulating tumor cells (CTCs) are extremely rare (1-10 cells per mL blood), limiting their clinical utility. There are too few CTCs in a standard 5-10 mL blood sample for culture and drug susceptibility testing, or for comprehensively profiling a molecularly heterogeneous cancer and its metastases for drug resistance mutations. To achieve large-scale CTC enrichment, new strategies are needed that can rapidly and effectively interrogate large blood volumes. Aim: To design a flexible magnetic wire capable of high-throughput intravascular enrichment and retrieval of rare biomarkers, including CTCs, from the entire circulating blood volume to attain a much higher biomarker yield for earlier cancer detection and personalized treatment. Methods: We present a promising platform for in vivo enrichment of rare biomarkers, the Magnetic Wire for Intravascular Retrieval and Enrichment (MagWIRE): a flexible, self-contained magnetic wire consisting of a string of small magnets with alternating polarities, achieving high local field gradients along its entire length to capture magnetically labeled targets from a large surrounding volume. The platform is proposed to work as follows: Blood biomarkers are immunomagnetically labeled by injecting a patient with antibody-coated magnetic particles (MPs), similar to FDA-approved Feraheme®. The MagWIRE is then inserted through a standard IV catheter into a superficial vein in the arm or through an existing chemotherapy port to magnetically capture passing MP-bound biomarkers. Within an hour, ~5 liters has circulated through a 2-3-mm-diameter human vein, allowing most of the patient’s blood volume to be sampled. The magnets can then be displaced from the MagWIRE sheath to elute the bound targets into buffer for downstream analysis. We performed proof-of-concept demonstrations in: 1) a closed-loop blood circulation system consisting of a pump, tubing, and a blood reservoir, and 2) in vivo within a porcine ear vein model. To model CTC capture, we targeted H1650 lung cancer cells with 1-μm superparamagnetic iron oxide particles coated with antibodies against epithelial cell adhesion molecule (EpCAM), a commonly used CTC marker. We couple the MagWIRE with a unique approach for rapid ( Results: Considerable gains are achievable by sampling from large volumes, even at relatively low capture efficiencies. In our closed-loop setup, the MagWIRE demonstrated capture efficiencies in whole blood of 56.14+/-15.80% for pre-labeled cells and 10.17+/-5.41% for cells labeled in flow. In a porcine ear model, we captured cells with efficiencies up to 8%, corresponding to 80-fold enrichment when integrated over a 5-liter blood volume compared with a 5 mL blood draw. Citation Format: Ophir Vermesh, Amin Aalipour, Tianjia J. Ge, Yamil Saenz, Yue Guo, Seung-min Park, Yoshiaki Mitsutake, Michael Bachmann, Chin Chun Ooi, Kerstin Mueller, Hamed Arami, Alfredo Green, Shan X. Wang, Sanjiv S. Gambhir. An intravascular magnetic wire for high-throughput in vivo enrichment of rare circulating cancer biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3796. doi:10.1158/1538-7445.AM2017-3796

Within pharmaceutical industry charge heterogeneity testing of biopharmaceuticals has to be reproducible and fast. It should pass method validation according to ICH Q2. Classical approaches for the analysis of the charge heterogeneity of biopharmaceuticals are ion exchange chromatography (IEC) and isoelectric focusing (IEF). As an alternative approach, also capillary zone electrophoresis (CZE) was expected to allow reliable charge heterogeneity profiling by separation according to the analyte's net charge and hydrodynamic radius. Aim of this study was to assess if CZE possesses all of the required features. Therefore, beside lab internal validation of this method also an international cross company study was organized. It was shown that CZE is applicable across a broad pI range between 7.4 and 9.5. The coefficient of correlation was above 0.99 which demonstrated linearity. Precision by repeatability was around 1% (maximum relative standard deviation per level) and accuracy by recovery was around 100% (mean recovery per level). Accuracy was further verified by direct comparison of IEC, IEF and CZE, which in this case showed comparable %CPA results for all three methods. However, best resolution for the investigated MAb was obtained with CZE. In dependence on sample concentration the detection limit was between 1 and 3%. Within the intercompany study for CZE the same stressed and non-stressed samples were analyzed in each of the 11 participating labs. The finally obtained dataset contained more than 1000 separations which provided an extended dataset for further statistical evaluation. Among the different labs no significant differences between the peak profiles were observed. Mean driver for dropouts in quantitative evaluation was linked to the performance of some participating labs while the impact of the method performance was negligible. In comparison to a 50cm capillary there was a slightly better separation of impurities and drug substance related compounds with a 30cm capillary which demonstrates that an increased stability indicating potential can be combined with the increased separation velocity and high throughput capability of a shorter capillary. Separation can be performed in as little as approx. 3min allowing high throughput applications. The intercompany study delivered precise results without explicit training of the participating labs in the method prior to the study (standard deviations in the range of 1%). It was demonstrated that CZE is an alternative platform technology for the charge heterogeneity testing of antibodies in the pharmaceutical industry.

It is known that a reduction of the field-of-view in 3-D X-ray imaging is proportional to a reduction in radiation dose. The resulting truncation, however, is incompatible with conventional reconstruction algorithms. Recently, a novel method for region of interest reconstruction that uses neither prior knowledge nor extrapolation has been published, named approximated truncation robust algorithm for computed tomography (ATRACT). It is based on a decomposition of the standard ramp filter into a 2-D Laplace filtering and a 2-D Radon-based residual filtering step. In this paper, we present two variants of the original ATRACT. One is based on expressing the residual filter as an efficient 2-D convolution with an analytically derived kernel. The second variant is to apply ATRACT in 1-D to further reduce computational complexity. The proposed algorithms were evaluated by using a reconstruction benchmark, as well as two clinical data sets. The results are encouraging since the proposed algorithms achieve a speed-up factor of up to 245 compared to the 2-D Radon-based ATRACT. Reconstructions of high accuracy are obtained, e.g., even real-data reconstruction in the presence of severe truncation achieve a relative root mean square error of as little as 0.92% with respect to nontruncated data.

Compared to pre-operative imaging modalities, it is more convenient to estimate the current cardiac physiological status from C-arm angiocardiography since C-arm is a widely used intra-operative imaging modality to guide many cardiac interventions. The 3D shape and motion of the left ventricle (LV) estimated from rotational angiocardiography provide important cardiac function measurements, e.g., ejection fraction and myocardium motion dyssynchrony. However, automatic estimation of the 3D LV motion is difficult since all anatomical structures overlap on the 2D X-ray projections and the nearby confounding strong image boundaries (e.g., pericardium) often cause ambiguities to LV endocardium boundary detection. In this paper, a new framework is proposed to overcome the aforementioned difficulties: (1) A new learning-based boundary detector is developed by training a boosting boundary classifier combined with the principal component analysis of a local image patch; (2) The prior LV motion model is learned from a set of dynamic cardiac computed tomography (CT) sequences to provide a good initial estimate of the 3D LV shape of different cardiac phases; (3) The 3D motion trajectory is learned for each mesh point; (4) All these components are integrated into a multi-surface graph optimization method to extract the globally coherent motion. The method is tested on seven patient scans, showing significant improvement on the ambiguous boundary cases with a detection accuracy of 2.87 +/- 1.00 mm on LV endocardium boundary delineation in the 2D projections.

In X-ray imaging, a reduction of the field of view (FOV) is proportional to a reduction in radiation dose. The resulting truncation, however, is incompatible with conventional tomographic reconstruction algorithms. This problem has been studied extensively. Very recently, a novel method for region of interest (ROI) reconstruction from truncated projections with neither the use of prior knowledge nor explicit extrapolation has been published, named Approximated Truncation Robust Algorithm for Computed Tomography (ATRACT). It is based on a decomposition of the standard ramp filter into a 2D Laplace filtering (local operation) and a 2D Radon-based filtering step (non-local operation). The 2D Radon-based filtering that involves many interpolations complicates the filtering procedure in ATRACT, which essentially limits its practicality. In this paper, an optimization for this shortcoming is presented. That is to apply ATRACT in one dimension, which implies that we decompose the standard ramp filter into the 1D Laplace filter and a 1D convolutionbased filter. The convolution kernel was determined numerically by computing the 1D impulse response of the standard ramp filtering coupled with the second order anti-derivative operation. The proposed algorithm was evaluated by using a reconstruction benchmark test, a real phantom and a clinical data set in terms of spatial resolution, computational efficiency as well as robustness of correction quality. The evaluation outcomes were encouraging. The proposed algorithm showed improvement in computational performance with respect to the 2D ATRACT algorithm and furthermore maintained reconstructions of high accuracy in presence of data truncation.

The transcriptional co-activator BOB.1/OBF.1 was originally identified in B cells and is constitutively expressed throughout B cell development. BOB.1/OBF.1 associates with the transcription factors Oct1 and Oct2, thereby enhancing octamer-dependent transcription. In contrast, in T cells, BOB.1/OBF.1 expression is inducible by treatment of cells with PMA/Ionomycin or by antigen receptor engagement, indicating a marked difference in the regulation of BOB.1/OBF.1 expression in B versus T cells. The molecular mechanisms underlying the differential expression of BOB.1/OBF.1 in T and B cells remain largely unknown. Therefore, the present study focuses on mechanisms controlling the transcriptional regulation of BOB.1/OBF.1 and Oct2 in T cells. We show that both calcineurin- and \(NF-\kappa B\)-inhibitors efficiently attenuate the expression of BOB.1/OBF.1 and Oct2 in T cells. In silico analyses of the BOB.1/OBF.1 promoter revealed the presence of previously unappreciated combined NFAT/\(NF-\kappa B\) sites. An array of genetic and biochemical analyses illustrates the involvement of the \(Ca^{2+}\)/calmodulin-dependent phosphatase calcineurin as well as NFAT and \(NF-\kappa B\) transcription factors in the transcriptional regulation of octamer-dependent transcription in T cells. Conclusively, impaired expression of BOB.1/OBF.1 and Oct2 and therefore a hampered octamer-dependent transcription may participate in T cell-mediated immunodeficiency caused by the deletion of NFAT or \(NF-\kappa B\) transcription factors.

Compared to pre-operative imaging modalities, it is more convenient to estimate the current cardiac physiological status from C-arm angiocardiography since C-arm is a widely used intra-operative imaging modality to guide many cardiac interventions. The 3D shape and motion of the left ventricle (LV) estimated from rotational angiocardiography provide important cardiac function measurements, e.g., ejection fraction and myocardium motion dyssynchrony. However, automatic estimation of the 3D LV motion is difficult since all anatomical structures overlap on the 2D X-ray projections and the nearby confounding strong image boundaries (e.g., pericardium) often cause ambiguities to LV endocardium boundary detection. In this paper, a new framework is proposed to overcome the aforementioned difficulties: (1) A new learning-based boundary detector is developed by training a boosting boundary classifier combined with the principal component analysis of a local image patch; (2) The prior LV motion model is learned from a set of dynamic cardiac computed tomography (CT) sequences to provide a good initial estimate of the 3D LV shape of different cardiac phases; (3) The 3D motion trajectory is learned for each mesh point; (4) All these components are integrated into a multi-surface graph optimization method to extract the globally coherent motion. The method is tested on seven patient scans, showing significant improvement on the ambiguous boundary cases with a detection accuracy of 2.87±1.00 mm on LV endocardium boundary delineation in the 2D projections.

182 Background: In 2006, maintenance therapy was added as a treatment guideline for patients with advanced non-squamous (nsq) NSCLC. This study aimed to identify patient- and disease-related factors that impact maintenance therapy decision making. Methods: An online discrete choice survey was administered to physicians currently managing patients with advanced nsq NSCLC in the US. Physicians viewed 12 patient profiles differing in levels of the following attributes: 1st line treatment response (complete, partial, stable, progression), adverse events during 1st line therapy (none, mild, moderate, severe), comorbidities (none, mild renal, severe renal, other), patient motivation/convenience (+/+, +/-, -/+, -/-), patient insurance co-pay rate (0, 5, 10, 20%), and age (45, 58, 68, 80 years). No specific maintenance treatments were stated. For each profile, physicians indicated if they would recommend maintenance therapy. Recommendations were analyzed using a mixed-effects logistic regression model. Odds ratios (ORs) were calculated to estimate the relative odds of a maintenance therapy recommendation for levels of each attribute. Results: The survey was completed by 100 physicians (81% male; mean years of experience: 15.4). The study design was balanced and orthogonal. Maintenance therapy was recommended for 75% of the profiles; 98% of physicians recommended maintenance therapy for at least 1 profile, with 26% recommending it for all profiles. The odds of recommending maintenance therapy were significantly lower when the patient profile included disease progression relative to stable response (OR: 0.17; p

Proteases play a decisive role in health and disease. They fulfil diverse functions and have been associated with the pathology of gastrointestinal disorders such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). The current knowledge focuses on host-derived proteases including matrix metalloproteinases, various serine proteases and cathepsins. The possible contribution of bacterial proteases has been largely ignored in the pathogenesis of IBD and IBS, although there is increasing evidence, especially demonstrated for proteases from pathogenic bacteria. The underlying mechanisms extend to proteases from commensal bacteria which may be relevant for disease susceptibility. The intestinal microbiota and its proteolytic capacity exhibit the potential to contribute to the pathogenesis of IBD and IBS. This review highlights the relevance of host- and bacteria-derived proteases and their signalling mechanisms.

The real time X-ray angiography based on C-arm cone beam system is the workhorse imaging modality for interventional cardiac procedures. These images are two-dimensional (2D) projections of three dimensional (3D) objects along the X-ray direction. The organ of interest (OOI), such as left ventricle (LV) endocardium, in the projection image is superimposed with other anatomical structures and often has low contrast. In this study, a novel approach is proposed to isolate the OOI in projection images by subtracting with a background image, which is generated by numerical projection of 3D tomographic image with OOI masked out. Study based on one patient and one pig image is taken. About two to three-fold increase in the contrast-to-noise ratio (CNR) is achieved for LV endocardium, compared to an unprocessed image.

Proteases play a decisive role in health and disease. They fulfil diverse functions and have been associated with the pathology of gastrointestinal disorders such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). The current knowledge focuses on host-derived proteases including matrix metalloproteinases, various serine proteases and cathepsins. The possible contribution of bacterial proteases has been largely ignored in the pathogenesis of IBD and IBS, although there is increasing evidence, especially demonstrated for proteases from pathogenic bacteria. The underlying mechanisms extend to proteases from commensal bacteria which may be relevant for disease susceptibility. The intestinal microbiota and its proteolytic capacity exhibit the potential to contribute to the pathogenesis of IBD and IBS. This review highlights the relevance of host- and bacteria-derived proteases and their signalling mechanisms.

In this paper, we propose an automatic method to directly extract 3D dynamic left ventricle (LV) model from sparse 2D rotational angiocardiogram (each cardiac phase contains only five projections). The extracted dynamic model provides quantitative cardiac function for analysis. The overlay of the model onto 2D real-time fluoroscopic images provides valuable visual guidance during cardiac intervention. Though containing severe cardiac motion artifacts, an ungated CT reconstruction is used in our approach to extract a rough static LV model. The initialized LV model is projected onto each 2D projection image. The silhouette of the projected mesh is deformed to match the boundary of LV blood pool. The deformation vectors of the silhouette are back-projected to 3D space and used as anchor points for thin plate spline (TPS) interpolation of other mesh points. The proposed method is validated on 12 synthesized datasets. The extracted 3D LV meshes match the ground truth quite well with a mean point-to-mesh error of 0.51 +/- 0.11 mm. The preliminary experiments on two real datasets (included a patient and a pig) show promising results too.

Background & Aims Protease-activated receptors (PARs) are expressed in the enteric nervous system. Excessive release of proteases has been reported in functional and inflammatory bowel diseases. Studies in several animal models indicate the involvement of neural PARs. We studied the actions of different PAR-activating peptides (AP) in the human submucous plexus and performed comparative studies in guinea pig submucous neurons. Methods We used voltage- and calcium-sensitive dye recordings to study the effects of PAR1-AP, PAR2-AP, PAR4-AP, the PAR1 activator thrombin, and the PAR2 activator tryptase on neurons and glia in human and guinea pig submucous plexus. Human preparations were derived from surgical resections. Levels of mucosal secretion evoked by PAR-APs were measured in Ussing chambers. Results PAR1-AP and thrombin evoked a prominent spike discharge and intracellular Ca 2+ concentration ([Ca] i ) transients in most human submucous neurons and glia. PAR2-AP, tryptase, and PAR4-AP caused significantly weaker responses in a minor population. In contrast, PAR2-AP evoked much stronger responses in enteric neurons and glia of guinea pigs than did PAR1-AP or PAR4-AP. PAR1-AP, but not PAR2-AP or PAR4-AP, evoked a nerve-mediated secretion in human epithelium. The PAR1 antagonist SCH79797 inhibited the PAR1-AP, and thrombin evoked responses on neurons, glia, and epithelial secretion. In the submucous layer of human intestine, but not guinea pig intestine, PAR2-AP evoked [Ca] i signals in CD68 + macrophages. Conclusions In the human submucous plexus, PAR1, rather than PAR2 or PAR4, activates nerves and glia. These findings indicate that PAR1 should be the focus of future studies on neural PAR-mediated actions in the human intestine; PAR1 might be developed as a therapeutic target for gastrointestinal disorders associated with increased levels of proteases.

Excitonic and spin excitations of single semiconductor quantum dots currently attract attention as possible candidates for solid state based implementations of quantum logic devices. Due to their rather short decoherence times in the picosecond to nanosecond range, such implementations rely on using ultrafast optical pulses to probe and control coherent polarizations. In this article, we review our recent work on combining ultrafast spectroscopy and near-field microscopy to probe the nonlinear optical response of a single quantum dot and of a pair of dipolecoupled quantum dots on a femtosecond time scale. We demonstrate coherent control of both amplitude and phase of the coherent quantum dot polarization by studying Rabi oscillations and the optical Stark effect in an individual dot. By probing Rabi oscillations in a pair of dots, we identify couplings between permanent excitonic dipole moments. Our results show that although semiconductor quantum dots resemble in many respects atomic systems, Coulomb many-body interactions can contribute significantly to their optical nonlinearities on ultrashort time scales. This paves the way towards the realization of potentially scalable nonlocal quantum gates in chains of dipole-coupled dots, but also means that decoherence phenomena induced by many-body interactions need to be carefully controlled.

Excitonic and spin excitations of single semiconductor quantum dots currently attract attention as possible candidates for solid state based implementations of quantum logic devices. Due to their rather short decoherence times in the picosecond to nanosecond range, such implementations rely on using ultrafast optical pulses to probe and control coherent polarizations. In this article, we review our recent work on combining ultrafast spectroscopy and near-field microscopy to probe the nonlinear optical response of a single quantum dot and of a pair of dipolecoupled quantum dots on a femtosecond time scale. We demonstrate coherent control of both amplitude and phase of the coherent quantum dot polarization by studying Rabi oscillations and the optical Stark effect in an individual dot. By probing Rabi oscillations in a pair of dots, we identify couplings between permanent excitonic dipole moments. Our results show that although semiconductor quantum dots resemble in many respects atomic systems, Coulomb many-body interactions can contribute significantly to their optical nonlinearities on ultrashort time scales. This paves the way towards the realization of potentially scalable nonlocal quantum gates in chains of dipole-coupled dots, but also means that decoherence phenomena induced by many-body interactions need to be carefully controlled.© (2005) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Excitonic and spin excitations of single semiconductor quantum dots currently attract attention as possible candidates for solid state based implementations of quantum logic devices. Due to their rather short decoherence times in the picosecond to nanosecond range, such implementations rely on using ultrafast optical pulses to probe and control coherent polarizations. We combine ultrafast spectroscopy and near-field microscopy to probe the nonlinear optical response of a single quantum dot on a femtosecond time scale. Transient reflectivity spectra show pronounced oscillations around the quantum dot exciton line. These oscillations reflect phase-disturbing Coulomb interactions between the exitonic quantum dot polarization and continuum excitations. The results show that although semiconductor quantum dots resemble in many respects atomic systems, Coulomb many-body interactions can contribute significantly to their optical nonlinearities on ultrashort time scales.

We report the first experimental study of the optical Stark effect in single semiconductor quantum dots (QD). For below band gap excitation, two-color pump-probe spectra show dispersive line shapes caused by a light-induced blueshift of the excitonic resonance. The line shape depends strongly on the excitation field strength and is determined by the pump-induced phase shift of the coherent QD polarization. Transient spectral oscillations can be understood as rotations of the QD polarization phase with negligible population change. Ultrafast control of the QD polarization is demonstrated.

Background H2S actions in the gut involve neural activation. This study aimed to reveal the signaling mechanisms responsible for the pro-secretory effect of H2S by using TRPV1 and unselective TRP blockers and inhibitors of other signaling cascades hitherto described to be targeted by H2S elsewhere. Methods Ussing chamber voltage clamp technique was used to study actions of the H2S donor NaHS on secretion in guinea-pig and human colon. NaHS effects on guinea-pig primary afferents were also evaluated. Key Results NaHS evoked secretion was significantly reduced in guinea-pig and human tissue by the selective TRPV1 blockers capsazepine, AMG9801, SB705498, BCTC; LY294002 (Phosphatidylinositol-3 kinase (PI3K) inhibitor), SKF96365 (store operated calcium channel blocker), 2-APB (inositol triphosphate blocker), and atropine but not by HC030031 (TRPA1 blocker) or L- and T-type calcium channel antagonists. Actions of TRPV1 antagonists suggested non-competitive inhibition at multiple sites. In guinea-pig colon, Gd 3+ and La 3+ (unselective TRP blockers) had no effects while ruthenium red reduced NaHS effects; in human colon Gd 3+ attenuated NaHS response. NaHS response was inhibited by neurokinin-1 and -3 receptor blockers in guinea-pig and neurokinin-1 and -2 receptor blockade in human tissue. There was cross-desensitization between NaHS and capsaicin responses. NaHS induced capsazepine and LY294002 sensitive afferent discharge. Conclusions & Inferences H2S evokes mucosal secretion by targeting TRPV1 expressing afferent nerves which activate cholinergic secretomotor neurons via release of substance P acting in a species dependent manner on neurokinin-1, -2 or -3 receptors. Besides TRPV1 signaling H2S may target intracellular calcium dependent pathways and PI3K.