MRI-guided endovascular intervention: current methods and future potential.

INTRODUCTION: Image-guided endovascular interventions, performed using the insertion and navigation of catheters through the vasculature, have been increasing in number over the years, as minimally invasive procedures continue to replace invasive surgical procedures. Such endovascular interventions are almost exclusively performed under x-ray fluoroscopy, which has the best spatial and temporal resolution of all clinical imaging modalities. Magnetic resonance imaging (MRI) offers unique advantages and could be an attractive alternative to conventional x-ray guidance, but also brings with it distinctive challenges. AREAS COVERED: In this review, the benefits and limitations of MRI-guided endovascular interventions are addressed, systems and devices for guiding such interventions are summarized, and clinical applications are discussed. EXPERT OPINION: MRI-guided endovascular interventions are still relatively new to the interventional radiology field, since significant technical hurdles remain to justify significant costs and demonstrate safety, design, and robustness. Clinical applications of MRI-guided interventions are promising but their full potential may not be realized until proper tools designed to function in the MRI environment are available. Translational research and further preclinical studies are needed before MRI-guided interventions will be practical in a clinical interventional setting.

Endoluminal Biopsy for Molecular Profiling of Human Brain Vascular Malformations.

BACKGROUND AND OBJECTIVES: Ras-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. METHODS: Endoluminal 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). RESULTS: Endoluminal 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 (Pearson r = 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. DISCUSSION: Endoluminal 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.

Identifying cow - level factors and farm characteristics associated with locomotion scores in dairy cows using cumulative link mixed models.

Lameness is a tremendous problem in intensively managed dairy herds all over the world. It has been associated with considerable adverse effects on animal welfare and economic viability. The majority of studies have evaluated factors associated with gait disturbance by categorising cows into lame and non-lame. This procedure yet entails a loss of information and precision. In the present study, we extend the binomial response to five categories acknowledging the ordered categorical nature of locomotion assessments, which conserves a higher level of information. A cumulative link mixed modelling approach was used to identify factors associated with increasing locomotion scores. The analysis revealed that a low body condition, elevated somatic cell count, more severe hock lesions, increasing parity, absence of pasture access, and poor udder cleanliness were relevant variables associated with higher locomotion scores. Furthermore, distinct differences in the locomotion scores assigned were identified in regard to breed, observer, and season. Using locomotion scores rather than a dichotomised response variable uncovers more refined relationships between gait disturbances and associated factors. This will help to understand the intricate nature of gait disturbances in dairy cows more deeply.

Robotics for neuroendovascular intervention: Background and primer.

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.

How to iGuide: flat panel detector, CT-assisted, minimally invasive evacuation of intracranial hematomas.

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.

Combined Use of X-ray Angiography and Intraprocedural MRI Enables Tissue-based Decision Making Regarding Revascularization during Acute Ischemic Stroke Intervention.

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.

Virtual 2D angiography from four-dimensional digital subtraction angiography (4D-DSA): A feasibility study.

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 < 0.001). On average 4D-DSA acquisitions accounted for 30% dose compared to the overall average aggregated dose per procedure. 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.

Factors Associated With Lameness in Tie Stall Housed Dairy Cows in South Germany.

Lameness remains a major concern for animal welfare and productivity in modern dairy production. Even though a trend toward loose housing systems exists and the public expects livestock to be kept under conditions where freedom of movement and the expression of natural behavior are ensured, restrictive housing systems continue to be the predominant type of housing in some regions. Factors associated with lameness were evaluated by application of multiple logistic regression modeling on data of 1,006 dairy cows from 56 tie stall farms in Bavaria, South Germany. In this population, approximately every fourth cow was lame (24.44% of scored animals). The mean farm level prevalence of lameness was 23.28%. In total, 22 factors were analyzed regarding their association with lameness. A low Body Condition Score (BCS) (OR 1.54 [95%-CI 1.05-2.25]) as well as increasing parity (OR 1.41 [95%-CI 1.29-1.54]) entailed greater odds of lameness. Moreover, higher milk yield (OR 0.98 [95%-CI 0.96-1.00]) and organic farming (OR 0.48 [95%-0.25-0.92]) appeared to be protectively associated with lameness. Cows with hock injuries (OR 2.57 [95%-CI 1.41-4.67]) or with swellings of the ribs (OR 2.55 [95%-CI 1.53-4.23]) had higher odds of lameness. A similar association was observed for the contamination of the lower legs with distinct plaques of manure (OR 1.88 [95%-CI 1.14-3.10]). As a central aspect of tie stall housing, the length of the stalls was associated with lameness; with stalls of medium [(>158-171 cm) (OR 2.15 [95%-CI 1.29-3.58]) and short (≤158 cm) length (OR 4.07 [95%-CI 2.35-7.05]) increasing the odds compared with long stalls (>171 cm). These results can help both gaining knowledge on relevant factors associated with lameness as well as approaching the problem of dairy cow lameness in tie stall operations.

Randomised clinical trial showing the curative effect of bandaging on M2-stage lesions of digital dermatitis in dairy cows.

OBJECTIVES AND DESIGN: This trial evaluated the effect of bandaging of acute painful ulcerative bovine digital dermatitis (DD) lesion (stage M2) in dairy cows, tested using two different topical treatments. DESIGN: Randomised clinical trial. SETTING: This study was conducted using Holstein-Friesian cows ranging in age from heifers to fourth lactation in a single dairy herd and diagnosed with acute ulcerative DD lesions (stage M2) on the first examination (week 0). Cows were randomly assigned into either a non-bandaged or bandaged group across two treatment conditions: topical chlortetracycline spray (CTC) and Intra Hoof-Fit Gel (IHF). Lesions received standardised bandaging and treatment on a weekly basis. Unhealed lesions could receive up to five repeated treatments, at weekly intervals, within a four-week period. Both M-stage and locomotion were also evaluated and scored weekly. Cows with healthily formed skin (stage M0) were deemed healed and subsequently released from the study. RESULTS: In total, 163 M2 lesions were diagnosed at week 0. Bandaged M2 lesions had a significantly higher probability of cure than non-bandaged lesions regardless of treatment type (HR: 4.1; P<0.001; 95 per cent CI: 2.5 to 6.8). Most healing occurred within the first three weeks of trial. Furthermore, bandaged lesions (group 2 and group 4) were significantly less likely to progress into the chronic hyperkeratotic or proliferative stage (M4) than non-bandaged lesions in group 1 and group 3 (HR: 0.10; P<0.001; 95 per cent CI: 0.04 to 0.22). Out of concern for the cow's wellbeing, this study investigated the effects of bandaging on locomotion. Bandaging had no effect on locomotion for either cows treated with CTC (group 1: median Sprecher score, 2; IQR=1-2; group 2: median Sprecher score, 2; IQR=1-3; P=0.3) or IHF (group 3: median Sprecher score, 2; IQR=1-2; group 4: median Sprecher score, 2; IQR=1-3; P=0.3).

Patient and physician preferences for first-line treatment of classical Hodgkin lymphoma in Germany, France and the United Kingdom.

First-line treatments for classical Hodgkin lymphoma (HL) include ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and BEACOPPescalated (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, BEACOPPescalated 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.

An intravascular magnetic wire for the high-throughput retrieval of circulating tumour cells in vivo.

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.

Systemic Anti-Cancer Therapy in Synovial Sarcoma: A Systematic Review.

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.

The Role of Cone-Beam CT in Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

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.

Reproducibility of Parenchymal Blood Volume Measurements Using an Angiographic C-arm CT System.

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.

Watershed Hepatocellular Carcinomas: The Risk of Incomplete Response following Transhepatic Arterial Chemoembolization.

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.

Evaluation of capillary zone electrophoresis for charge heterogeneity testing of monoclonal antibodies.

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.

Partner choice and fidelity stabilize coevolution in a Cretaceous-age defensive symbiosis.

Many insects rely on symbiotic microbes for survival, growth, or reproduction. Over evolutionary timescales, the association with intracellular symbionts is stabilized by partner fidelity through strictly vertical symbiont transmission, resulting in congruent host and symbiont phylogenies. However, little is known about how symbioses with extracellular symbionts, representing the majority of insect-associated microorganisms, evolve and remain stable despite opportunities for horizontal exchange and de novo acquisition of symbionts from the environment. Here we demonstrate that host control over symbiont transmission (partner choice) reinforces partner fidelity between solitary wasps and antibiotic-producing bacteria and thereby stabilizes this Cretaceous-age defensive mutualism. Phylogenetic analyses show that three genera of beewolf wasps (Philanthus, Trachypus, and Philanthinus) cultivate a distinct clade of Streptomyces bacteria for protection against pathogenic fungi. The symbionts were acquired from a soil-dwelling ancestor at least 68 million years ago, and vertical transmission via the brood cell and the cocoon surface resulted in host-symbiont codiversification. However, the external mode of transmission also provides opportunities for horizontal transfer, and beewolf species have indeed exchanged symbiont strains, possibly through predation or nest reuse. Experimental infection with nonnative bacteria reveals that--despite successful colonization of the antennal gland reservoirs--transmission to the cocoon is selectively blocked. Thus, partner choice can play an important role even in predominantly vertically transmitted symbioses by stabilizing the cooperative association over evolutionary timescales.

Towards clinical application of a Laplace operator-based region of interest reconstruction algorithm in C-arm CT.

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.

Biogeography of a defensive symbiosis.

Mutualistic microorganisms play important roles in nutrition, reproduction and defense of many insects, yet the factors contributing to their maintenance and dispersal remain unknown in most cases. Theory suggests that collaboration can be maintained by repeated interaction of the same partners (partner fidelity) or by selective discrimination against non-cooperative partners (partner choice). In the defensive mutualism between solitary beewolf wasps and their antibiotic-producing Streptomyces bacteria, partner choice by host control of vertical symbiont transmission reinforces partner fidelity and has helped to maintain this highly specific association since it originated in the late Cretaceous. However, co-phylogenetic and biogeographic analyses suggest that there has also been considerable horizontal transmission of the symbionts. While the beewolves clearly have a paleotropic or palearctic origin, with later colonization of the nearctic and neotropics via Beringia and the Aves ridge, respectively, the bacteria show only weak geographical clustering, implying global dispersal or vicariance within the confines of an otherwise apparently exclusive symbiotic relationship. We discuss several hypotheses that may explain these patterns. Future studies investigating the occurrence of beewolf symbionts in the environment could yield broadly applicable insights into the relative impact of animal-vectored and free-living dispersal on the distribution of microorganisms in nature.

Octamer-dependent transcription in T cells is mediated by NFAT and NF-κB.

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-κB-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-κB 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-κB 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-κB transcription factors.