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Introduction: Deep venous stent placement has developed into a primary treatment modality for venous obstruction in recent decades. Reported rates of complications are low in the literature and are based mainly on case reports and single-centre cohorts. Interventionalists performing these procedures must be aware of the occurrence of complications associated with stent placement to counsel patients adequately and promote avoidance through optimal procedural approach. This study aims to determine the incidence of serious complications associated with iliocaval and iliofemoral stent placement in a cohort of patients from 3 major tertiary deep venous referral centres., Methods: Data were collated from January 2014 to September 2023. The following major complications were included in the analysis: death, major bleeding requiring transfusion, massive pulmonary embolism, any complication which required endovascular or open surgical intervention, vessel rupture, acute kidney injury requiring dialysis, stent crushing, fracture, migration, involution or erosion., Results: One thousand eight hundred fourteen (1814) patients were treated for acute or chronic deep venous pathology during the 9-year study period. Sixty-one patients (3.3%) experienced a major stent-related complication. The most frequently reported complication was stent crushing (n = 18, 29.5%), followed by stent fracture (n = 10, 16.4%) and erosion of the stent through the vessel wall (n = 8, 13.1%). Death was a rare event (0.2%)., Conclusion: Deep venous stent placement is a safe procedure with low rates of major complications. It is incumbent upon operators to be aware of the risks associated with these procedures, however, rare, so that they may obtain fully informed consent from patients., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Consent for Publication: Consent for publication was obtained for every individual person’s data included in the study. Ethical Approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed Consent: Informed consent was obtained from all individual participants included in the study., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Objective: Interventional treatments for acute iliofemoral deep vein thrombosis (DVT) remain controversial after publication of the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) study. Interventions have been shown to reduce post-thrombotic syndrome severity and improve quality of life in DVT patients, but have been accompanied by risk of major bleeding from thrombolytics. We describe thrombus removal using a novel combined basket-rotational thrombectomy device that minimizes the need for thrombolytics or repeat procedures., Methods: The aim of this prospective, nonrandomized, multicenter, first-in-human study of 19 patients with acute iliofemoral DVT was to evaluate the safety and performance of the Pounce venous thrombectomy system ≤12 months after treatment. The primary performance end point was defined as procedural success through achievement of Society of Interventional Radiology (SIR) grade II lysis in treated vessels with freedom from procedural adverse events. Secondary end points included venous disease severity assessments using the Villalta scale and the Venous Clinical Severity Score, patient quality-of-life measurement using the Venous Insufficiency Epidemiological and Economic Study-Quality of Life questionnaire, and calf circumference measurements taken at baseline, 24 hours, and 1 month., Results: The primary end point of complete or near-complete thrombus removal (Society of Interventional Radiology grade II or III) was achieved in all patients. All study device-related safety end points were met, with no major bleeding or device-related adverse events. Of the 19 patients treated, 16 (84.2%) did not receive thrombolytics during the procedure. Post-thrombotic syndrome (Villalta scale >4) was identified in 17 of 19 patients (89.5%) at baseline, 4 of 13 patients (30.8%) available for follow-up at 6 months, and 2 of 11 patients (18.2%) at 12 months. The median Venous Clinical Severity Score decreased (P < .001) from 8.5 (interquartile range [IQR], 7-10) at baseline to 4 (IQR, 2-4) at 1 month after the procedure and was similar at 6 months (2; IQR, 2-5) and 12 months (2; IQR, 1.5-3) after the procedure. The median Venous Insufficiency Epidemiological and Economic Study-Quality of Life questionnaire score improved (P < .001) by 39 from baseline (57; IQR, 53.5-74) to 1 month (96; IQR, 86-101) after the procedure, and remained high at 6 months (99; IQR, 75-103) and 12 months (98; IQR, 94.5-100). The median calf circumference decreased (P = .089) from 39 cm (IQR, 35-47.8 cm) at baseline to 36 cm (IQR, 32.5-40.5 cm) at 24 hours after the procedure and was 34.5 cm (IQR, 33.2-38.5 cm) at 1 month., Conclusions: The Pounce device is safe and effective for removal the of thrombus in patients with acute iliofemoral DVT. Initial results demonstrate improvements in venous disease severity and patient quality of life., Competing Interests: Disclosures S.B. acknowledges Consulting/Speakers fees from Surmodics and Vetex. M.L. acknowledges consulting fees from Vetex and Surmodics. G.S. acknowledges stock options in Vetex., (Copyright © 2024. Published by Elsevier Inc.)

Marine phosphatization events cause episodic carbonate fluorapatite (CFA) precipitation on seamounts, and are commonly linked to growth hiatuses in ferromanganese (Fe-Mn) crusts. However, the complete record of these events and their paleoenvironmental significance remains poorly understood, in large part due to poor age constraints. Here, we apply U-Pb dating to CFA in Fe-Mn crusts from Western Pacific seamounts. These data exhibit good alignment with Sr isotope ages, revealing six potential phosphatization events. This established CFA chronology tightens the timespan of phosphatization events and refines the age framework of Fe-Mn crusts. We subsequently utilize a multiproxy approach to demonstrate that the phosphatization events occurred coeval with the expansion of oceanic oxygen minimum zones. The Western Pacific Fe-Mn crusts thus document major perturbations in global oceanic phosphorus cycling, which appear to have been driven by climate-induced increases in primary productivity linked to changes in global ocean circulation., (© 2024. The Author(s).)

Endovascular treatment of iliofemoral deep vein thrombosis (IF DVT) can become more complex when thrombus extends below the knee. This article discusses various techniques that can be used to treat IF DVT with distal involvement.

This review article provides an overview of acute and chronic venous occlusion, a condition that can cause significant morbidity and mortality if not diagnosed and treated promptly. The article begins with an introduction to the anatomy of the venous system, followed by a discussion of the causes and clinical features of venous occlusion. The diagnostic tools available for the assessment of venous occlusion, including imaging modalities such as ultrasound, CT, and MRI, are then discussed, along with their respective advantages and limitations. The article also covers the treatment options for acute and chronic venous occlusion, including anticoagulant therapy and endovascular interventions. This review aims to provide radiologists with an updated understanding of the pathophysiology, diagnosis, and management of acute and chronic venous occlusion., Competing Interests: Competing interestsGO’S: Paid medical advisor/speakers bureau for Cook Medical, BSCI, Bard, Medtronic, Merit, Marvao, Versono, Intact Vascular, Creagh Medical, Vetex.

Venous stents are being used with increasing frequency, with a multitude of dedicated venous stents now well established or emerging onto the market. This review explores the multifaceted aspects of venous stenting. We discuss the history of venous stents, indications for their use, the imaging required before, during and after stenting, as well as some technical tips and tricks which we have found to be helpful in our own daily practice with a particular focus on iliofemoral venous stenting. Ultimately, this article seeks to enhance the understanding of venous stenting, offering insights into what we feel are best practices, challenges, and prospects for improved patient outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Interventions for thrombotic and nonthrombotic venous disorders have increased with technical advances and more trained venous specialists. Antithrombotic therapy is essential to clinical and procedural success; however, postprocedural therapeutic regimens exhibit significant heterogeneity due to limited prospective randomized data and incomplete mechanistic understanding of the critical factors driving long-term patency. Postinterventional antithrombotic therapy for thrombotic venous disorders should adhere to existing venous thromboembolism management guidelines, which include 3-6 months of therapeutic anticoagulation at minimum and consideration of extended therapy in patients with higher risk of thrombosis because of procedural or patient factors. The added benefit of antiplatelet agents in the acute and intermediate period is unknown, having shown improved long-term stent patency in some retrospective studies. Dual- and/or triple-agent therapy should be limited based on individual risks of thrombosis and bleeding. The treatment of nonthrombotic disorders is more heterogeneous, though patients with limited flow, extensive stent material, or underlying prothrombotic states such as malignancy or chronic inflammation may benefit from single-agent or multiagent antithrombotic therapy. However, the agent, dose, and duration of therapy remain indeterminate. Future prospective studies are warranted to improve patient risk stratification and standardize postprocedural anti-thrombotic therapy in patients receiving venous interventions.

Purpose of Review: Venous thromboembolic disease causes significant mortality and morbidity in the oncologic patient population. Recently, minimally invasive endovascular technologies have been developed as an adjunct to antithrombotic therapy for the management of DVT and PE. The current and potential roles for endovascular treatment of cancer-associated venous thromboembolism (VTE) will be reviewed in this article., Recent Findings: The recent NCCN guidelines recommend endovascular therapy in patients eligible for therapeutic anticoagulation who present with life-, organ-, or limb-threatening thrombosis. However, symptomatic non-life-threatening VTE can negatively affect QOL and physical function, both of which have prognostic implications in the cancer population. Endovascular therapies have been shown to improve physical function and QOL in prospective trials performed in a non-oncologic patient population as well as small retrospective studies in the cancer population. In addition to treating life- and limb-threatening thrombosis, endovascular therapy for VTE can improve QOL and physical function in comparison to anticoagulation alone. Prospective trials are warranted to assess the benefit of endovascular therapy for quality of life-years, performance status, and overall survival in the oncologic patient population., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: Percutaneous endovenous stenting has emerged during the past decade as the primary method of treating symptomatic venous outflow obstruction. A recognized complication of venous stenting is stent migration. The aim of the present systematic review was to identify the number of cases of stent migration in reported studies to recognize the risk factors that might be associated with this complication and the outcomes following migration., Methods: A review was conducted in accordance with the MOOSE (meta-analyses of observational studies in epidemiology) and PRIMSA (preferred reporting items for systematic review and meta-analysis) guidelines and registered in the PROSPERO. MEDLINE, EMBASE, and PubMed databases. Key references were searched using specified keywords. All relevant data for the primary procedure and subsequent presentation with stent migration were retrieved. The data were assessed as too low in quality to allow for statistical analysis., Results: Between 1994 and 2020, 31 studies were identified, including 29 case reports and 2 case series, providing data for 54 events of venous stent migration with some data provided regarding the stent used for 47 of the events. The mean age of the 52 patients with stent migration was 50 years (range, 19-88 years) and 30 were men (57.6%). The stents for most of the reported cases were ≤60 mm in length (38 of 46; 82.6%). Only three of the reports were of stents >14 mm in diameter (3 of 47; 3.6%). None of the studies had reported migration of stents >100 mm long. In 85% of the migrated stent events, retrieval was attempted, with 65.2% via an endovascular approach. The immediate outcome was satisfactory for 100% of the reported attempts, whether by an endovascular or open surgical approach., Conclusions: The findings from our literature review suggest that the risk of migration is rare but might be underreported. Most of reported cases had occurred with shorter and smaller diameter stents. The paucity of reported data and the short-term follow-up provided suggest that more formal data collection would provide a truer reflection of the incidence. However, clear strategies to avoid migration should be followed to prevent this complication from occurring., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the performance of the Zilver® Vena™ Venous Stent in the treatment of patients with symptomatic iliofemoral outflow obstruction., Methods: Between August 2012 and January 2015, 35 patients (mean age of 45.1 ± 15.5 years; 77.1% female) with symptomatic iliofemoral venous outflow obstruction were treated with the Zilver Vena Venous Stent (Cook Ireland, Ltd.) as part of this prospective, single arm, multicenter study. Study assessments included procedural success, major adverse events (MAEs), freedom from occlusion and qualitative patency at 6 and 12 month post-procedure, clinical symptoms of venous insufficiency, and reintervention with the treated venous segment., Results: The rate of freedom from occlusion at 6 month and 12 month was 88.2%. The rate of qualitative patency was 88.2% at 6 month and 85.2% at 12 month. Three MAEs were reported: one symptomatic pulmonary embolism and two clinically-driven reinterventions. Following stenting, clinical symptoms of venous insufficiency improved significantly from baseline at each follow-up, as measured by VDS (p < 0.0001), CEAP "C" (p ≤ 0.0001), VCSS (p < 0.0001), and CIVIQ (p < 0.0001)., Conclusion: Clinical results with the Zilver Vena Venous Stent were favorable through 12 month, with high patency rates, reduction of venous insufficiency symptoms, and low morbidity., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: Venous leg ulceration is a widespread, debilitating pathology with high recurrence rates. Conservative treatment using graduated compression dressings may be associated with unacceptable ulcer recurrence rates. Early superficial venous ablation encourages ulcer healing and reduces recurrence. However, many of this cohort display concomitant ilio-caval stenosis, which further contributes to lower limb venous hypertension and ulceration. An approach that combines early superficial venous ablation with early treatment of ilio-caval stenotic disease may significantly improve ulcer healing and recurrence rates. We question whether early iliac vein interrogation with intravascular ultrasound (IVUS), stenting of significant occlusive disease plus superficial venous ablation, in patients with active venous leg ulceration, will produce superior ulcer healing to standard therapy., Methods: This is a prospective, multi-centre, randomised controlled, feasibility trial recruiting patients with lower limb venous ulceration and saphenous venous incompetence. Patients will be randomised to undergo either truncal ablation and compression therapy or truncal ablation, simultaneous iliac interrogation with intravascular ultrasound and stenting of significant (> 50%) iliac vein lesions plus compression therapy. The primary feasibility outcome will be the rate of eligible patient participation while the primary clinical outcomes will be ulcer healing and procedural safety. Secondary outcomes include time to healing, quality of life and clinical scores, ulcer recurrence rates and rates of post-thrombotic syndrome. Follow-up will be over a 5-year period. This feasibility trial is designed to include 60 patients. Should it be practicable a total of 594 patients would be required to adequately power the trial to definitively address ulcer-healing rates., Discussion: This trial will be the first randomised trial to examine the role iliac interrogation and intervention in conjunction with standard operative therapy in the management of venous ulceration related to superficial truncal venous incompetence., Ethical Committee Reference: C.A. 2111 Galway Clinical Research Ethics Committee REGISTRATION: Clinical Trials.gov registration NCT03640689 , Registered on 21 August 2018.

Cardiac output during exercise increases by as much as fivefold in the untrained man, and by as much as eightfold in the elite athlete. Increasing venous return is a critical but much overlooked component of the physiological response to exercise. Cardiac disorders such as constrictive pericarditis, restrictive cardiomyopathy and pulmonary hypertension are recognised to impair preload and cause exercise limitation; however, the effects of peripheral venous obstruction on cardiac function have not been well described. This manuscript will discuss how obstruction of the iliocaval venous outflow can lead to impairment in exercise tolerance, how such obstructions may be diagnosed, the potential implications of chronic obstructions on sympathetic nervous system activation, and relevance of venous compression syndromes in heart failure with preserved ejection fraction.

Purpose: To report an iliac venous stent landing technique using only fluoroscopy in patients with May-Thurner syndrome (MTS)., Material and Methods: Sixty-five patients (69% female) who had self-expanding nitinol stents deployed for symptomatic MTS were retrospectively analyzed. Mean age was 50 years (range 18-80). The cephalic stent right lower corner was deployed to the right of the lumbar vertebra spinous process (SP), but not as far to the right as the right pedicle lateral border. Mode stent diameter and length were 14 mm (range 12-18) and 120 cm (range 60-180), determined by venography, respectively. The anatomical positions of the right common iliac artery, inferior vena cava (IVC), and stent were assessed relative to these bony landmarks on computed tomography venography., Results: Position of the proximal right common iliac artery right lateral border lay a mean distance of 12 mm (±8 to the right of the SP and 13 mm (±7) left of the right pedicle lateral border. Mean position of the IVC right lateral wall lay 1 mm (±6) to the right of the right pedicle lateral border. Mean position of the cephalic stent right lower corner was 6 mm (±6) to the left of the right pedicle lateral border and 19 mm (±7) to the right of the SP. The mean space left between the cephalic stent right lower corner and the IVC right lateral wall was 5 mm (±5). Primary patency rate at 1 year was 88%., Conclusions: Important vascular structures lie in predictable locations relative to bony landmarks, facilitating accurate venous stent placement using fluoroscopy only., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Objective: To describe clinical practice experience of 11 C-Metomidate PET/CT as an adjunct to adrenal vein sampling (AVS) in the lateralization of aldosterone-producing adenomas (APA) in primary aldosteronism (PA)., Context: Accurate lateralization of APA in the setting of PA offers the potential for surgical cure and improved long-term cardiovascular outcomes. Challenges associated with AVS, the current gold standard lateralization modality, mean that only a small proportion of potentially eligible patients currently make it through to surgery. This has prompted consideration of alternative strategies for lateralization, including the application of novel molecular PET tracers such as 11 C-Metomidate., Design: Clinical Service Evaluation/Retrospective audit., Patients: Fifteen individuals with a confirmed diagnosis of PA, undergoing lateralization with 11 C-Metomidate PET/CT prior to final clinical decision on surgical vs medical management., Measurements: All patients underwent screening aldosterone renin ratio (ARR), followed by confirmatory testing with the seated saline infusion test, according to Endocrine Society Clinical Practice Guidelines. Adrenal glands were imaged using dedicated adrenal CT. 11 C-Metomidate PET/CT was undertaken due to equivocal or failed AVS. Management outcomes were assessed by longitudinal measurement of blood pressure, ARR, number of hypertensive medications following adrenalectomy or institution of medical therapy., Results: We describe the individual lateralization and clinical outcomes for 15 patients with PA., Conclusion: 11 C-Metomidate PET/CT in conjunction with adrenal CT and AVS provided useful information which aided clinical decision-making for PA within a multidisciplinary hypertension clinic., (© 2019 John Wiley & Sons Ltd.)

Objective: To investigate the feasibility and efficacy of localized, subtotal, cortical-sparing microwave thermal ablation (MTA) as a potential curative management for primary aldosteronism. The study investigated with equal importance the selected ablation of small volumes of adrenal cortex while sparing adjacent cortex. Method: An in-vivo study was carried out in swine ( n  = 8) where MTA was applied under direct visualization, to the adrenal glands at 45 W or 70 W for 60 s, using a lateral, side-firing probe and a non-penetrative approach. Animals were survived for 48 h post-procedurally. Animals were investigated for markers of histological, immunohistochemical and biochemical evidence of adrenal function and adrenal damage by assessing samples drawn intra-operatively and at the time of euthanasia. Results: Selected MTA (70 W for 60 s) successfully ablated small adrenocortical volumes (∼0.8 cm 3 ) characterized by coagulative necrosis and abnormal expression of functional markers (CYP11B1 and CYP17). Non-ablated, adjacent cortex was not affected and preserved normal expression of functional markers, without increased expression of markers of heat damage (HSP-70 and HMGB-1). Limited adrenal medullary damage was demonstrated histologically, clinically and biochemically. Conclusion: MTA offers potential as an efficient methodology for delivering targeted subtotal cortical-sparing adrenal ablation. Image-guided targeted MTA may also represent a safe future modality for curative management of PA, in the setting of both unilateral and bilateral disease.

Venous thromboembolism (VTE) is a major public health issue; deep vein thrombosis (DVT) affects about 1/1000 patients. Each year, VTE kills more patients in Western Europe than breast cancer, prostate cancer, acquired immune deficiency syndrome (AIDS) and road traffic accidents combined and is responsible for the deaths of approximately 370,000 European citizens (Cohen et al. in Thromb Haemost 98:756-764, 2007; Bĕlohlávek et al. in Exp Clin Cardiol 18(2):129-138, 2013). The recently published ATTRACT trial (Acute Venous Thrombosis Thrombus Removal with Adjunctive Catheter-directed Thrombolysis) (Vedantham et al. in N Engl J Med 377:2240-2252, 2017) concluded that the addition of catheter-directed thrombolysis to standard therapy with anticoagulation and compression stockings offers no significant clinical benefit over standard therapy in terms of reduction in the rate of post-thrombotic syndrome (PTS) at 2 years. It is the largest, prospective, multi-centre, randomised controlled trial (RCT) and represents the culmination over a decade of planning, execution and analysis. In this opinion article, we analyse why it was needed, what it demonstrated, some limitations, and the directions in which this important publication will take us.

Purpose: The purpose of this work was to describe the results of a technique of simultaneous antegrade and retrograde vascular access ("criss-cross") to the popliteal vein to achieve venous recanalization in patients with acute, extensive, iliofemoral DVT with concomitant popliteal and calf vein thrombosis., Materials and Methods: Seven patients were treated using this technique, in three patients as a bailout option after failed posterior tibial vein puncture and in four as a first option. Antegrade popliteal venous access was performed according to the usual technique using duplex ultrasound (DUS) guidance and thrombolysis (CDT), or thrombectomy (PMT) was performed. Following this, the retrograde sheath was placed under DUS guidance, a tibial vein was selectively catheterized and CDT, and/or a PMT was performed., Results: Three patients underwent isolated CDT, another three had associated PMT, and one patient underwent iliofemoral PMT and catheter thromboaspiration of the popliteal and calf veins. Median thrombolysis duration was 72 h (24-72 h). SIR grade III thrombolysis was achieved in six patients and grade II in one patient. All patients underwent subsequent stenting of their iliac vein lesions. Minor complications were observed in two patients (ecchymosis), while one patient developed a hematoma on the popliteal fossa., Conclusion: This "criss-cross" technique represents a safe alternative to the distal (anterior or posterior tibial) vein access both as a bailout option after failed distal venous access as well as a primary approach due to its potential advantage of clearing larger thrombus volume. Experience in ultrasound-guided popliteal vein puncture is crucial to avoid complications., Level of Evidence: Case series, Level IV.

Background: The majority of iliac venous obstructions occur on the left side, and endovascular therapy has become the first line treatment for this condition. A left common iliac venous stent will protrude into the inferior vena cava (IVC) to some extent, thereby covering the contralateral common iliac vein (CIV) outflow. This may increase the risk of thrombosis of the contralateral iliac vein. The aim of this paper was to determine the rate of, and factors associated with, contralateral lower limb venous thrombosis after stenting, and to evaluate the results of salvage revascularisation., Methods: A total of 376 patients (102 from UCH, Galway, Ireland, 2008-16, and 274 from, CHU Nord, Marseille, France, 2000-15) with symptomatic acute or chronic left iliocaval venous obstruction were retrospectively evaluated. Either duplex ultrasound scanning (DUS) or computed tomographic venography (CTV) was used for pre- and post-operative imaging. Data were collected from the PACS system (IMPAX, Agfa, BE) of the Radiology Department, UCH, Galway, and from the electronic medical records of Vascular Surgery department, CHU Nord, Marseille., Results: The median age of stented patients was 46 (range 15-86 years), 80% were female (301/376). Following left CIV stent placement, 10 patients later presented with a right (contralateral) iliac deep venous thrombosis (DVT) resulting in a cumulative incidence of contralateral DVT of 4% according to Kaplan-Meier analysis. Acute DVT (p=.001), non-compliance with the prescribed 6 months anticoagulation (p = 0.05), pre-operative contralateral internal iliac vein (IIV) thrombosis (p = 0.001), and pre-existing IVC filter placement (p = 0.003) were all statistically significantly associated with contralateral DVT. All patients with symptomatic contralateral iliac DVT underwent clot removal in the acute phase. The primary patency of these limbs was 100% at 3 years., Conclusion: Stent placement across the iliocaval confluence from the left CIV is associated with a low but definite rate of contralateral iliac vein thrombosis. Acute DVT, pre-operative contralateral IIV thrombosis, pre-existing IVC filters, and anticoagulation non-compliance are significant risk factors., (Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Semaphorins are secreted or membrane-bound proteins implicated in neurodevelopmental processes of axon guidance and cell migration. Exploratory behaviour and motor learning was examined ethologically in Semaphorin 6A (Sema6A) mutant mice. The ethogram of initial exploration in Sema6A knockout mice was characterised by increased rearing to wall with decreased sifting; over subsequent habituation, locomotion, sniffing and rearing to wall were increased, with reduced habituation of rearing seated. Rotarod analysis indicated delayed motor learning in Sema6A heterozygous mutants. Disruption to the axonal guidance and cell migration processes regulated by Sema6A is associated with topographically specific disruption to fundamental aspects of behaviour, namely the ethogram of initial exploration and subsequent habituation to the environment, and motor learning., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Deep vein thrombosis, and the resultant development of post-thrombotic syndrome, is a significant health issue. Recent evidence demonstrates that the severity of post-thrombotic syndrome symptoms is directly related to the level of venous thrombosis and following treatment these subsequent symptoms are inversely related to the degree of thrombus removal. If we can improve, and preferably standardise the terminology associated with pre-treatment assessment of thrombus load and post-treatment success of thrombus removal techniques, we should then be able to choose more tailor-made techniques to greater benefit our patients. A number of scoring systems have been devised for the assessment of venous thrombus burden, with a majority impractical for everyday usage. In order to provide a more practical solution, the lower extremity thrombosis classification has been developed, using information on anatomical location for venous thrombus combined with a clinical indicator as to the likely sequelae. Anatomical success following venous thrombolysis can be defined by assessing restoration of anterograde flow in the treated vein or the percentage degree of thrombolysis, using venography. The second option is the method most frequently utilised, with the Venous Registry grading system applied. Data from recent trials have given us conflicting and confusing data mainly because we are not using standardised terminology. We urgently need to agree on a standard method of description of thrombus removal before stent placement which also incorporates the likely clinical impact of the area involved in the thrombosis., (© The Author(s) 2016.)

Objectives: The aim of this study was to assess factors influencing the clinical outcome and morphological changes of acute and chronic type B aortic dissection after thoracic endovascular aortic repair (TEVAR)., Background: Aortic remodeling after TEVAR may be associated with clinical outcome, complications, and endoleak development., Methods: Sixty cases of TEVAR for complicated type B acute aortic dissection (AAD) (n = 29) and chronic aortic dissection (CAD) (n = 31) with a minimum follow-up of 3 years were retrospectively reviewed. Using computed tomography images, we assessed true lumen, false lumen, and total aortic short-axis diameters. Six procedural factors were analyzed in relation to aortic remodeling and other outcomes. Analysis of variance was used to compare short-axis, false lumen, and true lumen diameters during the follow-up period. Univariate and multivariate analyses were used to assess the relationship between procedural factors and multiple outcomes., Results: A total of 100 stent grafts were implanted in 60 consecutive patients with acute aortic dissection (AAD) and CAD. Aortic remodeling consisting of false lumen thrombosis and shrinkage was more prominent in AAD than in CAD, especially within the first 18 months. Of note, the entire aortic diameter increased significantly cephalad to the stent graft in AAD. Only in the AAD group there was increased aortic remodeling related to post-dilation of the stent graft. Type I and II endoleaks occurred in 17 patients (28%); in AAD, embolization of the left subclavian artery after stent graft deployment was significantly associated with a lower risk of endoleak development, but this was not evident in CAD., Conclusions: Aortic remodeling and clinical outcome after TEVAR can be influenced by procedural techniques (post-dilation and embolization of the left subclavian artery in patients with acute but not chronic aortic dissection)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Early detection of skeletal metastasis is critical for accurate staging and optimal treatment. This paper briefly reviews our current understanding of the biological mechanisms through which tumours metastasise to bone and describes the available imaging methods to diagnose bone metastasis and monitor response to treatment. Among the various imaging modalities currently available for imaging skeletal metastasis, hybrid techniques which fuse morphological and functional data are the most sensitive and specific, and positron emission tomography (PET)/computed tomography and PET/magnetic resonance imaging will almost certainly continue to evolve and become increasingly important in this regard.

Purpose: To assess the effects of iliofemoral vein stent placement on symptomatic lower extremity swelling (LES), presumed to be lymphedema, in patients with cancer., Materials and Methods: During the period 2005-2013, 62 patients (38 female; age, 60.4 y ± 15.4) with histology-proven metastatic disease and LES resistant to standard therapies were evaluated and found to have venous outflow obstruction. Stents were placed in the iliofemoral veins or inferior vena cava, or both, and evaluated by color Doppler ultrasound or contrast-enhanced computed tomography during the follow-up period. Patient symptoms were assessed using the Venous Disability Score (VDS) and the Galway Limb Swelling score, a patient-directed, 5-question symptom scoring system., Results: Stents were successfully placed in all patients. During the follow-up period, in-stent thrombosis occurred in 13 patients, and additional stents were placed in 3 patients to treat luminal narrowing. The mean VDS improved significantly (P < .05): from 3.0 ± 0 on the day of the procedure to 2.95 ± 0.22 on day 3, 2.0 ± 0.33 on day 7, and 1.87 ± 0.34 on day 30. The mean Galway Limb Swelling score also improved significantly (P < 0.001): from 3.6 ± 0.74 on the day of the procedure to 1.96 ± 0.91 on day 3, 1.06 ± 0.78 on day 7, and 0.6 ± 0.66 on day 30. During the follow-up period, 60 patients died as a result of their underlying malignancy (mean, 230 d; range, 5-1,080 d)., Conclusions: Iliofemoral or iliocaval venous stent placement may have a valuable role in patients with metastatic disease and symptomatic LES associated with venous obstruction., (Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.)

Chronic venous insufficiency (CVI) as an advanced stage of chronic venous disease is a common problem that occurs in approximately 1-5 % of the adult population. CVI has either a nonthrombotic (primary) or postthrombotic (secondary) cause involving reflux, obstruction, or a combination of both. The role of venous obstruction is increasingly recognized as a major cause of CVI, with obstructive lesions in the iliocaval segment being markedly more relevant than lesions at the levels of the crural and femoral veins. Approximately 70-80 % of iliac veins develop a variable degree of obstruction following an episode of acute deep venous thrombosis. Nonthrombotic iliac vein obstruction also known as May-Thurner or Cockett's syndrome is the most common cause of nonthrombotic iliac vein occlusion. While compression therapy is the basis of therapy in CVI, in many cases, venous recanalization or correction of obstructive iliac vein lesions may result in resolution of symptoms. This document reviews the current evidence on iliocaval vein recanalization and provides standards of practice for iliocaval stenting in primary and secondary causes of chronic venous disease.

Aim: The aim of the study was to assess the early clinical experience with the Zilver Vena stent in treating patients with iliofemoral venous obstruction at a tertiary referral hospital., Methods: Demographic, procedural, and follow-up data of 20 patients (12 women; mean age of 59 ± 17 years) treated for iliofemoral vein obstruction between January 2011 and December 2012 were retrospectively reviewed. Most patients presented with acute obstruction (N.=14; 70%), and 10 patients (50%) had an active malignancy. Patency was established venographically at procedure end, and was evaluated with Duplex ultrasound in follow-up., Results: Venous obstructions were attributed primarily to extrinsic compression from a malignant or other mass in the pelvis (N.=9) and May-Thurner (N.=5). Flow was re-established through the obstructed venous segment in all patients at procedure end. In follow-up, three patients experienced early stent thrombosis (<30 days); the clinical patency rate was 85% (17/20 patients). Clinical improvement was demonstrated by decreased leg swelling in the remaining 17 patients., Conclusion: The Zilver Vena stent performed favorably in this challenging patient population; these results need to be confirmed in multicenter studies.

Activation of dopamine D1 receptors (D1Rs) has been shown to induce epileptiform activity. We studied the molecular changes occurring in the hippocampus in response to the administration of the D1-type receptor agonist, SKF 81297. SKF 81297 at 2.5 and 5.0 mg/kg induced behavioural seizures. Electrophysiological recordings in the dentate gyrus revealed the presence of epileptiform discharges peaking at 30-45 min post-injection and declining by 60 min. Seizures were prevented by the D1-type receptor antagonist, SCH 23390, or the cannabinoid CB1 receptor agonist, CP 55,940. The effect of SKF 81297 was accompanied by increased phosphorylation of the extracellular signal-regulated protein kinases 1 and 2 (ERK), in the granule cells of the dentate gyrus. This effect was also observed in response to administration of other D1-type receptor agonists, such as SKF83822 and SKF83959. In addition, SKF 81297 increased the phosphorylation of the ribosomal protein S6 and histone H3, two downstream targets of ERK. These effects were prevented by genetic inactivation of D1Rs, or by pharmacological inhibition of ERK. SKF 81297 was also able to enhance the levels of Zif268 and Arc/Arg3.1, two immediate early genes involved in transcriptional regulation and synaptic plasticity. These changes may be involved in forms of activity-dependent plasticity linked to the manifestation of seizures and to the ability of dopamine to affect learning and memory.

Orofacial movements involve complex processes that include generators for down-stream patterns, with up-stream regulatory mechanisms. While the neurotransmitter dopamine plays a fundamental role, the role of individual dopamine receptor subtypes and their associated transduction mechanisms is unclear. Here we review systematic, comparative studies of orofacial function in mutant mice with "knockout" of D1, D2, D3, D4 or D5 receptors, or of their critical transduction component DARPP-32 at four levels: general orofacial behaviors within the mouse repertoire, as assessed naturalistically; individual components of orofacial movement, as assessed under non-naturalistic conditions; each of the above, as assessed also under challenge with a D1-like vs a D2-like agonist. Studies in these "knockouts" provide novel insights into the motoric "building blocks" that regulate orofacial function., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To report a combined procedure that opens the acutely thrombosed superior vena cava (SVC) to rapidly alleviate symptoms in seriously ill patients with SVC syndrome., Case Reports: Four patients aged 54 to 63 years old with underlying malignancies were referred for treatment of SVC syndrome. All received isolated pharmacomechanical thrombolysis (IPMT) with tissue plasminogen activator delivered in a Trellis Peripheral Infusion System that removed obstructive clot in minutes versus the 24 to 48 hours required for traditional catheter-directed thrombolysis. In each case, stents were inserted immediately following IPMT in a combined procedure lasting <1 hour. Patients exhibited near-immediate relief of debilitating symptoms; completion venography demonstrated patent vessels with excellent blood flow., Conclusion: Combining IPMT with immediate stenting during the same session is an effective method for managing acute thrombotic SVC syndrome and limiting the exposure time and number of interventions performed on seriously ill patients.

Neuregulin-1 (NRG1) has been shown to play a role in glutamatergic neurotransmission and is a risk gene for schizophrenia, in which there is evidence for hypoglutamatergic function. Sensitivity to the behavioural effects of the psychotomimetic N-methyl-D-aspartate receptor antagonists MK-801 and phencyclidine (PCP) was examined in mutant mice with heterozygous deletion of NRG1. Social behaviour (sociability, social novelty preference and dyadic interaction), together with exploratory activity, was assessed following acute or subchronic administration of MK-801 (0.1 and 0.2 mg/kg) or PCP (5 mg/kg). In untreated NRG1 mutants, levels of glutamate, N-acetylaspartate and GABA were determined using high-performance liquid chromatography and regional brain volumes were assessed using magnetic resonance imaging at 7T. NRG1 mutants, particularly males, displayed decreased responsivity to the locomotor-activating effects of acute PCP. Subchronic MK-801 and PCP disrupted sociability and social novelty preference in mutants and wildtypes and reversed the increase in both exploratory activity and social dominance-related behaviours observed in vehicle-treated mutants. No phenotypic differences were demonstrated in N-acetylaspartate, glutamate or GABA levels. The total ventricular and olfactory bulb volume was decreased in mutants. These data indicate a subtle role for NRG1 in modulating several schizophrenia-relevant processes including the effects of psychotomimetic N-methyl-D-aspartate receptor antagonists.

Objective: We sought to assess the probability that a new suspicious bone lesion is an alternative diagnosis, that is, a benign lesion or a second malignant tumor as opposed to metastatic disease from the malignant tumor, in a person with known primary malignant disease., Materials and Methods: We reviewed the radiologic and pathologic records of bone biopsies scheduled at our institution between 2002 and 2007. The following parameters were recorded: indication, type of primary cancer, date of diagnosis, complications of biopsy, whether the sample was of diagnostic quality, pathologic finding, and thus whether the primary malignant tumor was concordant with the lesion sampled., Results: Fifty-four of 55 patients (17 men, 37 women; mean age, 67 years) with known primary cancer and suspicious bone lesions underwent biopsy. One of the 55 patients did not undergo biopsy because a sacral insufficiency fracture was confidently diagnosed at CT. The primary malignant disease had been diagnosed up to 16 years before the new bone lesion was suspected and bone biopsy performed. Cancer types included those of genitourinary tract, breast, thyroid, gastrointestinal tract, and lung and lymphoma and myeloma. Diagnostic material was obtained in 43 of 54 cases (80%), and nondiagnostic material was obtained in 11 of 54 cases (20%). Forty-two of 43 positive biopsy findings (98%) were consistent with the primary malignant tumor. The other positive finding was a new malignant tumor. This new tumor was myelofibrosis in a man with chronic myelocytic leukemia. The primary diagnosis correlated highly with that of the new bone lesion (Spearman's test, R = 0.842; p < 0.001). No complications, including hemorrhage, infection, sinus track formation, fracture, and pneumothorax, were encountered., Conclusion: In a patient with known primary malignant disease, the probability is low (2%) that biopsy of a new suspicious bone lesion will show the lesion is other than metastasis from the primary tumor.

Isolated limb infusion (ILI) is a recently described minimally invasive technique indicated in the management of regionally advanced cancers refractory to systemic therapy and surgery. The present report describes the initial single-center experience of three patients with regionally advanced peripheral melanoma and one with lower-extremity cutaneous T-cell lymphoma treated over a period of 1 year. It is feasible to perform the complete ILI procedure in a single 60-100-minute session, solely in the interventional radiology suite, without a requirement for patient transfer to the operating room or extra waiting time between catheter insertion and chemotherapy infusion treatment.

As the techniques for endovascular treatment of aortic bifurcation disease become more widely known, it is not enough for interventional radiologists (IR) to be merely technically excellent at the procedural aspects of this important intervention. They must also become expert at managing the patient, and establishing direct contact not only with the patient, but also with the patient's primary doctor, usually their general practitioner. Younger IR physicians may have not had the opportunity to perform as many arterial catheter studies as their grayer counterparts for two main reasons: the shift towards non-invasive studies (US/CTA/MRA), and the encroachment of other specialties on the endovascular field of play. This is not a cause for despair. If you offer the best service, with the best results, you will, in time, get the referrals. However, you must be prepared to offer more than a glorified angiography service: critical to this is the establishment of an Interventional Radiology Clinic, as this then becomes the target for referrals from a variety of other specialties.

Studies in antipsychotic-naïve patients with schizophrenia indicate a baseline level of spontaneous involuntary movements, particularly orofacial dyskinesia. Neuregulin-1 is associated with risk for schizophrenia and its functional role can be studied in 'knockout' mice. We have shown previously that neuregulin-1 'knockouts' evidence disruption in social behaviour. Neuregulin-1 'knockouts' were assessed for four topographies of orofacial movement, both spontaneously and under challenge with the D(1)-like dopamine receptor agonist SKF 83959. Neuregulin-1 'knockouts' evidenced an increase in spontaneous incisor chattering, particularly among males. SKF 83959 induced incisor chattering, vertical jaw movements and tongue protrusions; the level of horizontal jaw movements was increased and that of tongue protrusions decreased in neuregulin-1 'knockouts'. These findings indicate that the schizophrenia risk gene neuregulin-1 is involved in the regulation of not only social behaviour but also orofacial dyskinesia. Orofacial dyskinesia in neuregulin-1 mutants may indicate some modest genetic relationship between risk for schizophrenia and vulnerability to spontaneous movement disorder.

Catechol-O-methyltransferase is an important enzyme in the metabolism of dopamine and an important regulator of aspects of dopamine-dependent working memory in prefrontal cortex that are disturbed in schizophrenia. This study investigated the phenotype of mice with heterozygous deletion vs. homozygous knockout of the catechol-O-methyltransferase gene across paradigms that access processes relevant for psychotic illness. Homozygotes evidenced improved performance in spontaneous alternation, an index of immediate spatial working memory; this effect appeared more substantive in males and was reflected in performance in aspects of the Barnes maze, an index of spatial learning/memory. Heterozygotes evidenced impaired performance in object recognition, an index of recognition memory; this effect was evident for both sexes at a retention interval of 5 min but appeared more enduring in males. There were no material effects for either genotype in relation to sociability or social novelty preference. While homozygous catechol-O-methyltransferase deletion results in improvement in spatial learning/working memory with little effect on social behavior, heterozygous deletion results in impairment of recognition memory. We have reported recently, using similar methods, that mice with deletion of the schizophrenia risk gene neuregulin-1 evidence disruption to social behavior, with little effect on spatial learning/working memory. The data suggest that catechol-O-methyltransferase and neuregulin-1 may influence, respectively, primarily cognitive and social endophenotypes of the overall schizophrenia syndrome.

The apparent incidence of iliopsoas muscle abnormalities is currently rapidly increasing secondary to the increased number of immuno-compromised patients, malignancies, chemotherapy, immunotherapy, multi-systemic disease and the wide availability of cross-sectional imaging. Disease of the iliopsoas compartment can present with non-specific or indolent clinical features, particularly where normal immune responses are attenuated. Delay in diagnosis can lead to inappropriate initial treatment and, in some cases, serious complications. Wider availability and application of modern cross-sectional imaging offers rapid, confident diagnosis. An understanding of iliopsoas compartment anatomy and pathways of disease spread are essential to recognising these clinically important conditions. We review the anatomy, clinical presentation and common imaging findings of iliopsoas disease as it presents through the emergency room.

Recent reports have shown that the selective dopamine D(1)-like agonist SKF 83822 [which stimulates adenylate cyclase, but not phospholipase C] induces prominent behavioral seizures in mice, whereas its benzazepine congener SKF 83959 [which stimulates phospholipase C, but not adenylate cyclase] does not. To investigate the relative involvement of D(1) vs D(5) receptors in mediating seizures, ethological behavioral topography and cortical EEGs were recorded in D(1), D(5) and DARPP-32 knockout mice in response to a convulsant dose of SKF 83822. SKF 83822-induced behavioral and EEG seizures were gene dose-dependently abolished in D(1) knockouts. In both heterozygous and homozygous D(5) knockouts, the latency to first seizure was significantly increased and total EEG seizures were reduced relative to wild-types. The majority (60%) of homozygous DARPP-32 knockouts did not have seizures; of those having seizures (40%), the latency to first seizure was significantly increased and the number of high amplitude, high frequency polyspike EEG events was reduced. In addition, immunoblotting was performed to investigate downstream intracellular signalling mechanisms at D(1)-like receptors following challenge with SKF 83822 and SKF 83959. In wild-types administered SKF 83822, levels of ERK1/2 and GluR1 AMPA receptor phosphorylation increased two-fold in both the striatum and hippocampus; in striatal slices DARPP-32 phosphorylation at Thr34 increased five-fold relative to vehicle-treated controls. These findings indicate that D(1), and to a lesser extent D(5), receptor coupling to DARPP-32, ERK1/2 and glutamatergic signalling is involved in mediating the convulsant effects of SKF 83822.

Clinical genetic studies have implicated neuregulin-1 [NRG1] as a leading susceptibility gene for schizophrenia. NRG1 is known to play a significant role in the developing brain, which is consistent with the prevailing neurodevelopmental model of schizophrenia. Thus, the emotional and social phenotype of adult mice with heterozygous 'knockout' of transmembrane [TM]-domain NRG1 was examined further in both sexes. Emotional/anxiety-related behaviour was assessed using the elevated plus-maze and the light-dark test. Social behaviour was examined in terms of dyadic interactions between NRG1 mutants and an unfamiliar C57BL6 conspecific in a novel environment. There was no effect of NRG1 genotype on performance in either test of emotionality/anxiety. However, previous reports of hyperactivity in NRG1 mutants were confirmed in both paradigms. In the test of social interaction, aggressive following was increased in NRG1 mutants of both sexes, together with an increase in walkovers in female mutants. These findings elaborate the specificity of the NRG1 phenotype for the social rather than the emotional/anxiety-related domain. They indicate that NRG1 is involved in the regulation of reciprocal social interaction behaviour and thus suggest a putative role for NRG1 in a schizophrenia-related endophenotype.

Catechol-O-methyltransferase (COMT) inactivates dopamine in prefrontal cortex and is associated clinically with a schizophrenia endophenotype. Using an ethologically based approach, the phenotype of mice with heterozygous COMT deletion was characterised by decreased rearing with increased sifting and chewing. Heterozygous COMT deletion is associated with a distinctive phenotype. This differs from that which we have reported previously for heterozygous deletion of the schizophrenia risk gene neuregulin-1.

The effect of inferior vena cava (IVC) stents crossing the ostia of the renal veins on renal function has not been reported. The purpose of this study is to report a single-institution experience with four cases of IVC stent implantation for malignant compression and/or invasion of the IVC causing severe lower-extremity edema. The patients' symptoms were successfully relieved, and follow-up imaging and serum creatinine measurements for the remainder of their lives revealed no evidence of renal impairment or renal vein thrombosis.

Neuregulin-1 (NRG1) has been identified as a candidate susceptibility gene for schizophrenia. In the present study the functional role of the NRG1 gene, as it relates to cognitive and social processes known to be disrupted in schizophrenia, was assessed in mice with heterozygous deletion of transmembrane (TM)-domain NRG1 in comparison with wildtypes (WT). Social affiliative behavior was assessed using the sociability and preference for social novelty paradigm, in terms of time spent in: (i) a chamber containing an unfamiliar conspecific vs. an empty chamber (sociability), or (ii) a chamber containing an unfamiliar conspecific vs. a chamber containing a familiar conspecific (preference for social novelty). Social dominance and aggressive behavior were examined in the resident-intruder paradigm. Spatial learning and memory were assessed using the Barnes maze paradigm, while spatial working memory was measured using the continuous variant of the spontaneous alternation task. Barnes maze data revealed intact spatial learning in NRG1 mutants, with elevated baseline latency to enter the escape hole in male NRG1 mutants reflecting an increase in activity level. Similarly, although a greater number of overall arm entries were found, spontaneous alternation was unaffected in NRG1 mice. Social affiliation data revealed NRG1 mutants to evidence a specific loss of WT preference for spending time with an unfamiliar as opposed to a familiar conspecific. This suggests that NRG1 mutants show a selective impairment in response to social novelty. While spatial learning and working memory processes appear intact, heterozygous deletion of TM-domain NRG1 was associated with disruption to social novelty behavior. These data inform at a novel phenotypic level on the functional role of this gene in the context of its association with risk for schizophrenia.

Purpose: To evaluate the performance of the Trellis-8 isolated thrombolysis catheter during single-session pharmacomechanical thrombectomy (PMT) combined with low-dose thrombolysis with tissue plasminogen activator (TPA) in the treatment of patients with acute deep vein thrombosis (DVT) and multiple comorbidities., Materials and Methods: Retrospective analysis was performed of 19 consecutive patients with acute above-knee DVT treated by PMT with the Trellis device followed by venous angioplasty and stent placement. Isolated thrombolysis with low-dose TPA was used with all patients. Concurrent therapies included retrievable inferior vena cava filter insertion (n = 4). The primary endpoint was restoration of rapid inline venous flow; the secondary endpoint was thrombus clearance., Results: Restoration of rapid inline venous flow was achieved in all cases; thrombus removal was less than 50% in one case (4%), 50%-95% in 18 cases (82%), and at least 95% in three cases (14%). The median administered dose of TPA was 13.4 mg per patient. The mean treatment time was 91 minutes per limb (range, 61-129 min), with a mean of 21 minutes per thrombosed segment (range, 8-31 min). There were no major complications. Primary patency rate of the treated venous segments at 2 days was 86% (n = 19) and the primary assisted patency rate was 100% at 30 days. Two patients died of advanced malignancy at 17 and 24 days., Conclusions: The Trellis system was an effective method for the treatment of acute DVT. Based on the present data, the Trellis system could prove to be a safe and feasible single-session PMT method for the treatment of acute DVT in a broader patient population and warrants further investigation in a large-scale study.

Recent advances in pharmacotherapeutics and interventional techniques have resulted in resurgence in interest regarding the optimal means of management of hemodynamically significant pulmonary embolic disease. However, these various techniques have many associated disadvantages, and it is of paramount importance that the responsible physician has a detailed understanding of each of these so that the appropriate intervention be requested and performed. By way of background discussion and relevant cases in point, we consider each of these management options in turn, with particular reference to the advantages, disadvantages, and application of each.

Over the last decade, sequencing and characterisation of the mouse genome has been accompanied by unparalleled advances in functional genomics. In the context of drug action, we analyse the strengths and limitations of classical mutagenesis and gene targeting techniques, as well as alternative approaches such as chemical mutagenesis, gene trap, recombineering, transposon-mediated mutagenesis, chromosomal engineering, viral transgenesis and RNA interference. This review also focuses on the emerging importance of genetic manipulation in other species and related logistical issues of experimental work using mutants.:, (� 2006 Elsevier Ltd . All rights reserved.)