A multiway analysis for identifying high integrity bovine BACs

Background: In large genomics projects involving many different types of analyses of bacterial artificial chromosomes (BACs), such as fingerprinting, end sequencing (BES) and full BAC sequencing there are many opportunities for the identities of BACs to become confused. However, by comparing the results from the different analyses, inconsistencies can be identified and a set of high integrity BACs preferred for future research can be defined. Results: The location of each bovine BAC in the BAC fingerprint-based genome map and in the genome assembly were compared based on the reported BESs, and for a smaller number of BACs the full sequence. BACs with consistent positions in all three datasets, or if the full sequence was not available, for both the fingerprint map and BES-based alignments, were deemed to be correctly positioned. BACs with consistent BES-based and fingerprint-based locations, but with conflicting locations based on the fully sequenced BAC, appeared to have been misidentified during sequencing, and included a number of apparently swapped BACs. Inconsistencies between BESbased and fingerprint map positions identified thirty one plates from the CHORI-240 library that appear to have suffered substantial systematic problems during the end-sequencing of the BACs. No systematic problems were identified in the fingerprinting of the BACs. Analysis of BACs overlapping in the assembly identified a small overrepresentation of clones with substantial overlap in the library and a substantial enrichment of highly overlapping BACs on the same plate in the CHORI-240 library. More than half of these BACs appear to have been present as duplicates on the original BAC-library plates and thus should be avoided in subsequent projects. Conclusion: Our analysis shows that ~95% of the bovine CHORI-240 library clones with both a BAC fingerprint and two BESs mapping to the genome in the expected orientations (~27% of all BACs) have consistent locations in the BAC fingerprint map and the genome assembly. We have developed a broadly applicable methodology for checking the integrity of BAC-based datasets even where only incomplete and partially assembled genomic sequence is available

Treatment of Cerebral Vasospasm in an Infant Using a Modified Dotter Technique

An 8-month old female presented with spontaneous subarachnoid hemorrhage and was treated successfully with endovascular coil embolization of the ruptured aneurysm. Transcranial Doppler ultrasound performed four days later demonstrated middle cerebral artery (MCA) velocities greater than 350 cm/sec on the right and greater than 200 cm/sec on the left, despite medical management. The patient demonstrated no focal neurological deficits, though examination was limited by our patient's sedation and intubation. Angiography revealed severe vasospasm of the supraclinoid internal carotid and MCA territories, bilaterally. The vasospasm was refractory to the administration of intra-arterial verapamil. Balloon angioplasty was attempted, but the device could not be advanced safely due to the small size of the patient's vessels and the stiffness of the device. A microcatheter (0.0165" diameter) was advanced over a J-shaped soft microwire (0.014" diameter) to perform mechanical angioplasty in the internal carotid artery and MCA vessels bilaterally. Dramatic improvement was seen angiographically and on transcranial Doppler, and no complications were seen

Transradial Interventional Procedures

The majority of neurointerventions can be performed via the radial approach, even with the femoral catheters. The specific case setup depends on the goals of the intervention. If using the femoral catheters, one is limited to the 6F and 8F systems. The former offers the protection of a radial sheath, the latter must be performed sheathlessly. The size of the radial artery and difficulty and support demands of the case dictate the preferred setup. With minimal experience, once diagnostic angiography is mastered, interventions can easily be learned. The technical pearls and nuances of performing complex neurointervention via the radial approach are reviewed

“Micro-introducer access” intra-arterial chemotherapy for retinoblastoma in an 8-week-old infant

Intra-arterial chemotherapy (IAC) for retinoblastoma has emerged as a standard therapy to facilitate globe salvage in patients with retinoblastoma. However, transfemoral endovascular catheterization of the ophthalmic artery is typically reserved for infants aged 3 months or older due to size of the patient and vascular anatomy. Here, the authors report a successful case of transfemoral intra-arterial chemotherapy delivery performed for group E retinoblastoma in an infant at 8 weeks of age who weighed only 4.1 kg using “micro-introducer sheath” technique to minimize the size of the arteriotomy. The patient received Melphalan, Topotecan, and Carboplatin via infusion through a microcatheter placed in the right ophthalmic artery. The procedure was tolerated well, and the patient went on to have two additional IAC procedures. Follow-up examinations under anesthesia showed tumor regression in response to chemotherapy. While typically reserved for older and larger patients, with proper technical expertise, transfemoral intra-arterial chemotherapy can be considered in such small infants with highly advanced disease. Keywords: Retinoblastoma, Intra-arterial chemotherapy, Endovascular, Ophthalmic artery, Pediatric

Transradial access: lessons learned from cardiology

Innovations in interventional cardiology historically predate those in neuro-intervention. As such, studying trends in interventional cardiology can be useful in exploring avenues to optimise neuro-interventional techniques. One such cardiology innovation has been the steady conversion of arterial puncture sites from transfemoral access (TFA) to transradial access (TRA), a paradigm shift supported by safety benefits for patients. While neuro-intervention has unique anatomical challenges, the access itself is identical. As such, examining the extensive cardiology literature on the radial approach has the potential to offer valuable lessons for the neuro-interventionalist audience who may be unfamiliar with this body of work. Therefore, we present here a report, particularly for neuro-interventionalists, regarding the best practices for TRA by reviewing the relevant cardiology literature. We focused our review on the data most relevant to our audience, namely that surrounding the access itself. By reviewing the cardiology literature on metrics such as safety profiles, cost and patient satisfaction differences between TFA and TRA, as well as examining the technical nuances of the procedure and post-procedural care, we hope to give physicians treating complex cerebrovascular disease a broader data-driven understanding of TRA

Current applications and future perspectives of robotics in cerebrovascular and endovascular neurosurgery

Advances in robotic medicine have been adopted by various surgical subspecialties as the benefits of this technology become more readily apparent: precision in narrow operative windows, tremor controlled movements, and modestly improved outcomes, among others. Vascular neurosurgery, in particular, remains open to newer and more cutting edge treatment options for complex pathologies, and robotics may be on the horizon for such advances. We seek to provide a broad overview of these innovations in vascular neurosurgery for both practitioners well acquainted with robotics and those seeking to become more familiar. Technologies under development for cerebrovascular and endovascular neurosurgery include robot assisted angiography, guided operative microscopes, coil insertion systems, and endoscopic clipping devices. Additionally, robotic systems in the fields of interventional cardiology and radiology have potential applications to endovascular neurosurgery but require proper modifications to navigate complex intracerebral vasculature. Robotic technology is not without drawbacks, as broad implementation may lead to increased cost, training time, and potential delays in emergency situations. Further cultivation of current multidisciplinary technologies and investment into newer systems is necessary before robotics can make a sizable impact in clinical practice

Delayed ischemic stroke following spontaneous thrombosis of an arteriovenous malformation

Spontaneous obliteration of an arteriovenous malformation (SOAVM) is a rare event that is not completely understood. Less than 100 cases of SOAVMs have been reported in the literature. We present a unique case of a middle-aged patient with spontaneous obliteration of a cerebral arteriovenous malformation (AVM) who developed an ischemic stroke due to thrombosis of the stagnant proximal segment of the inferior branch of the middle cerebral artery feeder. Although the pathophysiology is not well understood, the arterial feeder hemodynamic changes post SOAVM may behave similarly to what occurs in rare cases after surgical resection of AVMs. Our case raises the hypothesis that stagnation of flow in spontaneous AVM obliteration may lead to delayed ischemic stroke in the territory of the feeding artery

A multiway analysis for identifying high integrity bovine BACs

Abstract Background In large genomics projects involving many different types of analyses of bacterial artificial chromosomes (BACs), such as fingerprinting, end sequencing (BES) and full BAC sequencing there are many opportunities for the identities of BACs to become confused. However, by comparing the results from the different analyses, inconsistencies can be identified and a set of high integrity BACs preferred for future research can be defined. Results The location of each bovine BAC in the BAC fingerprint-based genome map and in the genome assembly were compared based on the reported BESs, and for a smaller number of BACs the full sequence. BACs with consistent positions in all three datasets, or if the full sequence was not available, for both the fingerprint map and BES-based alignments, were deemed to be correctly positioned. BACs with consistent BES-based and fingerprint-based locations, but with conflicting locations based on the fully sequenced BAC, appeared to have been misidentified during sequencing, and included a number of apparently swapped BACs. Inconsistencies between BES-based and fingerprint map positions identified thirty one plates from the CHORI-240 library that appear to have suffered substantial systematic problems during the end-sequencing of the BACs. No systematic problems were identified in the fingerprinting of the BACs. Analysis of BACs overlapping in the assembly identified a small overrepresentation of clones with substantial overlap in the library and a substantial enrichment of highly overlapping BACs on the same plate in the CHORI-240 library. More than half of these BACs appear to have been present as duplicates on the original BAC-library plates and thus should be avoided in subsequent projects. Conclusion Our analysis shows that ~95% of the bovine CHORI-240 library clones with both a BAC fingerprint and two BESs mapping to the genome in the expected orientations (~27% of all BACs) have consistent locations in the BAC fingerprint map and the genome assembly. We have developed a broadly applicable methodology for checking the integrity of BAC-based datasets even where only incomplete and partially assembled genomic sequence is available.</p

Genetic associations of intracranial aneurysm formation and sub-arachnoid hemorrhage

Risk factors for cerebral aneurysms typically include age, hypertension, smoking, and alcohol usage. However, the possible connection of aneurysms with genetic conditions such as Marfan's syndrome, polycystic kidney disease, and neurofibromatosis raises the question of possible genetic risk factors for aneurysm, and additionally, genetic risk factors for rupture. We conducted a literature review using the PubMed database for studies regarding genetic correlation with cerebral aneurysm formation as well as rupture from December 2008 to Jun 2015. Twenty-one studies related to IA formation and 10 concerning IA rupture that met our criteria were found and tabulated. The most studied gene and the strongest association was 9p21/CDKN2, which is involved in vessel wall remodelling. Other possible genes that may contribute to IA formation include EDNRA and SOX17; however, these factors were not studied as robustly as CDKN2. Multiple factors contribute to aneurysm formation and rupture and the contributions of blood flow dynamics and comorbidities as mentioned previously, cannot be ignored. While these elements are important to development and rupture of aneurysms, genetic influence may predispose certain patients to formation of aneurysms and eventual rupture