Imaging features of intraosseous hemangiomas: beyond the mobile spine and calvarium.

OBJECTIVE: Describe imaging features of intraosseous hemangiomas located outside of the mobile spine and calvarium. MATERIALS AND METHODS: Imaging and medical records were retrospectively reviewed for cases of intraosseous hemangiomas located outside of the calvarium and mobile spine. Evaluation included patient demographics, histologic confirmation, and imaging characteristics. RESULTS: Thirty-six patients were included (25 F, 11 M; mean age 54 ± 17 years, range 10-84 years) with 37 total lesions (70% axial and 30% appendicular skeleton). Mixed lytic and sclerotic features were identified on 83-85% radiographs and CTs. Amorphous increased density mimicking osteoid matrix was present on 38-45% radiographs and CTs. Classic honeycomb or radial pattern was identified on 45% of CTs. Osseous expansion and cortical permeation were common features. CT identified periosteal reaction in 24% of lesions. All hemangiomas had heterogeneous MRI signal and most moderately or avidly enhanced. Intralesional fat was identified on 78% MRIs, often as a minor component and only detected on 24% of CTs. A soft tissue mass was present on 52% of MRIs. FDG PET/CT mean SUVmax of 3.2 ± 0.6 (range 1.9-5.0). Lesional FDG activity relative to background marrow was increased in 75% of lesions. Lesions with cortical permeation had higher metabolic activity versus those without (3.5 ± 0.7 versus 2.2 ± 0.3, p = 0.041). CONCLUSION: Intraosseous hemangiomas outside of the mobile spine and calvarium demonstrate more aggressive imaging features compared to vertebral hemangiomas, including cortical permeation, soft tissue mass, amorphous increased density mimicking osteoid matrix, and increased FDG activity.

Sonographic evaluation of the lateral femoral cutaneous nerve in meralgia paresthetica.

OBJECTIVE: Identify sonographic features of the lateral femoral cutaneous nerve (LFCN) in meralgia paresthetica (MP) and report therapeutic outcomes in sonographically confirmed cases. MATERIALS AND METHODS: Retrospective review of 50 patients with clinically suspected MP and 20 controls. Ultrasounds were reviewed for characteristics of the LFCN and compared between groups. When available, MRIs were reviewed. In cases of sonographically pathologic LFCN, subsequent therapeutic interventions were recorded. RESULTS: Thirty-five of the suspected MP cases (70%) had ultrasound findings suggestive of MP, 10 (20%) were negative, and in 5 (10%) the LFCN was not seen. Sonographic findings in positive cases included nerve enlargement in all cases (mean cross-sectional area 9 mm2 (standard deviation (SD) ± 5.59) versus 4 mm2 (SD ± 2.31) and 3 mm2 (SD ± 2.31) in negative cases and normal controls, respectively; p < 0.01), nerve hypoechogenicity (30 of 35 cases, 86%), and focal lesion (7 of 35 cases, 20%). Sixteen ultrasounds positive for MP had MRIs with only 4 (25%) reporting a concordant LFCN abnormality (enlargement or T2 hyperintensity). Twenty-five of the 35 (71%) patients with positive sonographic findings for MP had a US-guided LFCN block (local anesthetic ± corticosteroid), with 24 of 25 (96%) patients reporting immediate symptomatic improvement. Eighteen of 35 (51%) underwent LFCN neurectomy or neurolysis, all of whom experienced symptomatic improvement. CONCLUSION: Ultrasound is a useful modality for LFCN assessment in clinically suspected MP and is more sensitive for abnormalities than MRI. Nearly all patients who received perineural analgesia and/or neurectomy or neurolysis had symptomatic improvement.

A phase Ib/II translational study of sunitinib with neoadjuvant radiotherapy in soft-tissue sarcoma.

BACKGROUND: Preoperative radiotherapy (RT) is commonly used to treat localised soft-tissue sarcomas (STS). Hypoxia is an important determinant of radioresistance. Whether antiangiogenic therapy can 'normalise' tumour vasculature, thereby improving oxygenation, remains unknown. METHODS: Two cohorts were prospectively enrolled. Cohort A evaluated the implications of hypoxia in STS, using the hypoxic tracer (18)F-azomycin arabinoside (FAZA-PET). In cohort B, sunitinib was added to preoperative RT in a dose-finding phase 1b/2 design. RESULTS: In cohort A, 13 out of 23 tumours were hypoxic (FAZA-PET), correlating with metabolic activity (r(2)=0.85; P<0.001). Two-year progression-free (PFS) and overall (OS) survival were 61% (95% CI: 0.44-0.84) and 87% (95% CI: 0.74-1.00), respectively. Hypoxia was associated with radioresistance (P=0.012), higher local recurrence (Hazard ratio (HR): 10.2; P=0.02), PFS (HR: 8.4; P=0.02), and OS (HR: 41.4; P<0.04). In Cohort B, seven patients received sunitinib at dose level (DL): 0 (50 mg per day for 2 weeks before RT; 25 mg per day during RT) and two patients received DL: -1 (37.5 mg per day for entire period). Dose-limiting toxicities were observed in 4 out of 7 patients at DL 0 and 2 out of 2 patients at DL -1, resulting in premature study closure. Although there was no difference in PFS or OS, patients receiving sunitinib had higher local failure (HR: 8.1; P=0.004). CONCLUSION: In STS, hypoxia is associated with adverse outcomes. The combination of sunitinib with preoperative RT resulted in unacceptable toxicities, and higher local relapse rates.

Pea aphid biotype performance on diverse Medicago host genotypes indicates highly specific virulence and resistance functions.

Aphid-plant interactions depend on genotypes of both organisms, which determine the two-way molecular exchange that leads to compatible or incompatible outcomes. The underlying genes are mostly unknown, making it difficult to predict likelihood of aphid success or host resistance, and hampering crop genetic improvement. Here we screened eight pea aphid clonal genotypes collected from diverse legume hosts, on a species-wide panel of Medicago truncatula (Mt) genotypes. Aphid virulence was measured by survival, fecundity and growth rate, together with scores for chlorosis and necrosis as host response indicators. Outcomes were highly dependent on the specific aphid-host genotype combinations. Only one Mt line was fully resistant against all clones. Aphid-induced host chlorosis and necrosis varied greatly, but correlated with resistance only in a few combinations. Bi-clustering analysis indicated that all aphid clones could be distinguished by their performance profiles across the host genotypes tested, with each clone being genetically differentiated and potentially representing a distinct biotype. Clones originating from Medicago sativa ranged from highly virulent to almost completely avirulent on both Medicago species, indicating that some were well adapted, whereas others were most likely migrants. Comparisons of closely related pairs of Australian Mt genotypes differing in aphid resistance revealed no enhanced resistance to European pea aphid clones. Based on the extensive variation in pea aphid adaptation even on unfamiliar hosts, most likely reflecting multiple biotype-specific gene-for-gene interactions, we conclude that robust defences require an arsenal of appropriate resistance genes.

Does phloem-based resistance to aphid feeding affect host-plant acceptance for reproduction? Parturition of the pea aphid, Acyrthosiphon pisum, on two near-isogenic lines of Medicago truncatula.

Probing behaviour (prior to parturition) and parturition of two clones (PS01 and N116) of the pea aphid, Acyrthosiphon pisum on two genotypes (near-isogenic lines (NILs)) (Q174_5.13 and Q174_9.10) of Medicago truncatula were investigated using electrical penetration graph (EPG) coupled with simultaneous visual monitoring for parturition. Line Q174_5.13 has been reported to show a phloem-based resistance to feeding in the clone PS01 but to be susceptible to the clone N116, whereas Q174_9.10 has shown to be susceptible to both aphid clones. The time taken to first parturition by clone PS01 was similar on Q174_5.13 and Q174_9.10. Prior to parturition, no aphids on Q174_5.13 contacted phloem, but 5% of the aphids on Q174_9.10 showed phloem salivation (recognized by EPG pattern E1). No phloem contact was observed with aphid clone N116 on either NILs of Medicago before first parturition occurred, and the time taken to first larviposition was similar on Q174_5.13 and Q174_9.10. The results indicate that the initiation of parturition of the clone PS01 and N116 on both NILs does not require the phloem contact and seems unchanged by a phloem-based resistance mechanism to feeding on Medicago. This finding suggests that host recognition and decisions about parturition occur before phloem contact or ingestion, and act independently on R-gene-mediated resistance.

Image analysis of hyperchromatic crowded cell groups in SurePath cervical cytology.

OBJECTIVE: The discrimination of hyperchromatic crowded cell groups (HCCGs) in cervical cytology is a difficult and error-prone interpretive task. While the classic features of dyskaryosis are of undoubted value, the contribution of size, shape and colour intensity of HCCGs is less certain. This study employed morphometric analysis to determine whether HCCG area, shape and colour intensity are useful in categorising them. METHODS: Seventy-five digital images from each of six categories of HCCG were subjected to image analysis. Ten variables relating to HCCG size, shape and colour intensity were assessed by discriminant function analysis. A further 28 cases were employed as a test set to determine the classification accuracy of the discriminant model. All samples were SurePath liquid-based cytology preparations. RESULTS: Nine of the 10 variables contributed significantly to the model (P<0.001) but no single variable had sufficient discriminative ability. Classification accuracy was highest for abnormal endocervical HCCGs and lowest for squamous metaplastic cells (64.0 vs. 17.3% correct classification rate). The accuracy of the model for distinguishing normal and abnormal HCCGs was 70.0%, which was significantly higher than chance (P<0.0001), but this reduced to 64.3% for the test cases, which was no better than chance (P>0.05). CONCLUSIONS: The area, shape and colour intensity of HCCGs, either alone or in combination, have little discriminative value. Practitioners and trainers should focus on the well-established features of dyskaryosis, such as chromatin pattern, nuclear membrane irregularities and group architecture. In terms of morphometric analysis, DNA ploidy and chromatin texture analysis may be more fruitful avenues of investigation.

Spinal dural arteriovenous fistulas--presentation, management and outcome in a single neurosurgical institution.

OBJECTIVE: To compare the outcome, with respect to treatment modality, of patients treated with spinal dural arteriovenous fistulas (SDAVF). METHOD: Retrospective cohort study of patients with SDAVF assessed at a single tertiary referral centre, between 1999 and 2009. Intervention type, pre-/ post-intervention Aminoff-Logue disability score (ALDS) and recurrence rate were obtained from medical records. RESULTS: 26 patients were identified with 23 receiving intervention. All patients initially received super selective angiogram, with 13 undergoing endovascular embolization at this stage, after discussion between the surgeon and interventional radiologist. Six patients who underwent embolization had a recurrence. The remaining 10 patients had fistulas marked during angiography, and were then treated surgically, after discussion. One of these recurred. The difference in recurrence rate between the two intervention types was not statistically significant. Fistulas treated with the embolization material onyx were twice as likely to recur as those treated with the alternative material, histoacryl-lipiodol. There was a statistically significant difference between the modes of intervention in relation to clinical outcome. Surgeries lead to an improvement in neurology, whereas treatment via embolization did not. Neurological improvement was seen in non-recurring cases, however deterioration in neurological function occurred with fistula recurrence. CONCLUSION: Super selective angiography is effective in defining the relevant vascular anatomy and allows for precise fistula localization during any potential subsequent surgery. Onyx was associated with a higher recurrence rate, suggesting it is less suitable as an embolization material for SDAVF treatment. Surgery appeared to correlate to reversal of neurological impairment seen at presentation, possibly due to a lower recurrence rate. The study is limited by small patient numbers, emphasizing the need for further studies of SDAVF patients.

Radiographic and MRI Assessment of the Thrower's Elbow.

PURPOSE OF REVIEW: Throwing athletes are vulnerable to elbow injuries, especially in the medial elbow, related to high stress and valgus load in both acute and chronic settings as a result of this complex biomechanical action. This current review details the relevant anatomy and imaging features of common elbow pathology identified with radiographs and MRI in throwing athletes. RECENT FINDINGS: Although elbow pathology in throwing athletes is well documented, advances in imaging technology and technique, particularly with MRI, have allowed for more detailed and accurate imaging description and diagnosis. Pathology of thrower's elbow occurs in predictable patterns and can be reliably identified radiologically. Clinical history and physical examination should guide radiologic evaluation initially with radiographs and followed by an MRI optimized to the clinical question. Constellation of clinical, physical, and radiologic assessments should be used to guide management.

Using routinely recorded data in a UK RCT: a comparison to standard prospective data collection methods.

BACKGROUND: Routinely recorded data held in electronic health records can be used to inform the conduct of randomised controlled trials (RCTs). However, limitations with access and accuracy have been identified. OBJECTIVE: Using epilepsy as an exemplar condition, we assessed the attributes and agreement of routinely recorded data compared to data collected using case report forms in a UK RCT assessing antiepileptic drug treatments for individuals newly diagnosed with epilepsy. METHODS: The case study RCT is the Standard and New Antiepileptic Drugs II (SANAD II) trial, a pragmatic, UK multicentre RCT assessing the clinical and cost-effectiveness of antiepileptic drugs as treatments for epilepsy. Ninety-eight of 470 eligible participants provided consent for access to routinely recorded secondary care data that were retrieved from NHS Digital Hospital Episode Statistics (N=71) and primary and secondary care data from The Secure Anonymised Information Linkage Databank (N=27). We assessed data items relevant to the identification of individuals eligible for inclusion in SANAD II, baseline and follow-up visits. The attributes of routinely recorded data were assessed including the degree of missing data. The agreement between routinely recorded data and data collected on case report forms in SANAD II was assessed using calculation of Cohen's kappa for categorical data and construction of Bland-Altman plots for continuous data. RESULTS: There was a significant degree of missing data in the routine record for 15 of the 20 variables assessed, including all clinical variables. Agreement was poor for the majority of comparisons, including the assessments of seizure occurrence and adverse events. For example, only 23/62 (37%) participants had a date of first-ever seizure identified in routine datasets. Agreement was satisfactory for the date of prescription of antiepileptic drugs and episodes of healthcare resource use. CONCLUSIONS: There are currently significant limitations preventing the use of routinely recorded data for participant identification and assessment of clinical outcomes in epilepsy, and potentially other chronic conditions. Further research is urgently required to assess the attributes, agreement, additional benefits, cost-effectiveness and 'optimal mix' of routinely recorded data compared to data collected using standard methods such as case report forms at clinic visits for people with epilepsy. TRIAL REGISTRATION: Standard and New Antiepileptic Drugs II (SANAD II (EudraCT No: 2012-001884-64, registered 05/09/2012; ISRCTN Number: ISRCTN30294119 , registered 03/07/2012)).

Functional mutants of Azospirillum brasilense elicit beneficial physiological and metabolic responses in Zea mays contributing to increased host iron assimilation.

Iron (Fe), an essential element for plant growth, is abundant in soil but with low bioavailability. Thus, plants developed specialized mechanisms to sequester the element. Beneficial microbes have recently become a favored method to promote plant growth through increased uptake of essential micronutrients, like Fe, yet little is known of their mechanisms of action. Functional mutants of the epiphytic bacterium Azospirillum brasilense, a prolific grass-root colonizer, were used to examine mechanisms for promoting iron uptake in Zea mays. Mutants included HM053, FP10, and ipdC, which have varying capacities for biological nitrogen fixation and production of the plant hormone auxin. Using radioactive iron-59 tracing and inductively coupled plasma mass spectrometry, we documented significant differences in host uptake of Fe2+/3+ correlating with mutant biological function. Radioactive carbon-11, administered to plants as 11CO2, provided insights into shifts in host usage of 'new' carbon resources in the presence of these beneficial microbes. Of the mutants examined, HM053 exhibited the greatest influence on host Fe uptake with increased plant allocation of 11C-resources to roots where they were transformed and exuded as 11C-acidic substrates to aid in Fe-chelation, and increased C-11 partitioning into citric acid, nicotianamine and histidine to aid in the in situ translocation of Fe once assimilated.

Comparison of skin prick tests with specific serum immunoglobulin E in the diagnosis of fungal sensitization in patients with severe asthma.

BACKGROUND: It has been shown that patients with allergic bronchopulmonary aspergillosis (ABPA) and patients with severe asthma with fungal sensitization (SAFS) can benefit from antifungal therapy. It is not known whether allergy skin prick tests (SPT) or specific IgE tests are more sensitive in the identification of patients who are sensitized to fungi and who are therefore candidates for antifungal therapy. OBJECTIVES: To compare SPT and specific serum IgE tests for fungal sensitization in patients with severe asthma. METHODS: We have undertaken SPT and specific serum IgE tests to six fungi (Aspergillus fumigatus, Candida albicans, Penicillium notatum, Cladosporium herbarum, Alternaria alternata and Botrytis cineria) and specific serum IgE test for Trichophyton in 121 patients with severe asthma (British Thoracic Society/SIGN steps 4 and 5). RESULTS: Sixty-six percent of patients were sensitized to one or more fungi based on SPT and/or specific serum IgE results. Positivity to SPT and/or specific serum IgE was as follows: A. fumigatus 45%, C. albicans 36%, P. notatum 29%, C. herbarum 24%, A. alternata 22%, B. cineria 18%, Trichophyton 17% (specific serum IgE only). Concordance between the tests was 77% overall but only 14-56% for individual fungi. Twenty-nine (24%) patients were sensitized to a single fungus and seven (6%) were sensitized to all seven fungal species. Fifty percent of patients were sensitized to fungal and non-fungal extracts, 21% were sensitized only to non-fungal extracts, 16% were sensitized only to fungal extracts and 13% had no positive tests. CONCLUSION: This study is consistent with previous reports that fungal sensitization is common in patients with severe asthma. At present, it remains necessary to undertake both SPT and specific serum IgE testing to identify all cases of fungal sensitization. This may be important in the identification of patients with ABPA and SAFS who may benefit from antifungal therapy.

Enzyme specificity as a factor in regulation of fatty acid chain length in Escherichia coli.

Various acyl-acyl carrier protein intermediates in saturated and unsaturated fatty acid biosynthesis were tested as substrates for beta-ketoacyl-acyl carrier protein synthetase. With both classes of substrates the condensing enzyme in fatty biosynthesis demonstrates specificities which indicate that it might be an important factor in determining fatty acid chain length in Escherichia coli.

Arabidopsis NPH1: a flavoprotein with the properties of a photoreceptor for phototropism.

The NPH1 gene of Arabidopsis thaliana encodes a 120-kilodalton serine-threonine protein kinase hypothesized to function as a photoreceptor for phototropism. When expressed in insect cells, the NPH1 protein is phosphorylated in response to blue light irradiation. The biochemical and photochemical properties of the photosensitive protein reflect those of the native protein in microsomal membranes. Recombinant NPH1 noncovalently binds flavin mononucleotide, a likely chromophore for light-dependent autophosphorylation. The fluorescence excitation spectrum of the recombinant protein is similar to the action spectrum for phototropism, consistent with the conclusion that NPH1 is an autophosphorylating flavoprotein photoreceptor mediating phototropic responses in higher plants.

The synthesis and enzymic hydrolysis of (E)-2-[2,3-2H2]propenyl glucosinolate: confirmation of the rearrangement of the thiohydroximate moiety.

(E)-2-[2,3-2H2]propenyl glucosinolate was synthesised starting from (E)-[3,4-2H2]but-3-en-1-ol, which was produced by reduction of but-3-yn-1-ol with deuterium gas in the presence of Lindlar's catalyst. The synthesis of (E)-2-[2,3-2H2]propenyl glucosinolate was completed via the nitro intermediate to form the basic desulphoglucosinolate skeleton. The (E)-2-[2,3-2H2]propenyl glucosinolate was fully characterised and deuterium NMR spectroscopy used to examine the rearrangement of the thiohydroximate to the isothiocyanate and thiocyanate.

Salvaging the limb salvage: management of complications following endoprosthetic reconstruction for tumours around the knee.

INTRODUCTION: Limb-salvage surgery, including endoprosthetic reconstruction after tumour resection, has become the standard management for local control of tumours around the knee. As the nature of surgery is technically complex and demanding, there is potential for significant morbidity arising from complications. This study describes our experience with complications following endoprosthetic reconstruction around the knee. METHODS: Retrospective analysis of consecutive resections and endoprosthetic reconstructions for tumours around the knee between 1996 and September 2005 performed at St Vincent's Hospital, Melbourne. RESULTS: Fifty consecutive cases were reviewed, with a median follow-up of 24.5 (range, 2-124) months. Median age was 41 (range, 13-79) years. Tumour types included 38 primary musculoskeletal malignancies, 8 metastatic tumours, 2 bony lymphomas and 2 benign lesions. There were eight deaths, nine cases of subsequent metastatic spread and no local recurrences. There were six cases of deep infection, two each of non-resolving nerve palsy, fracture and mechanical wear, and one each of symptomatic patellofemoral impingement, aseptic loosening and intraoperative popliteal artery trauma. Five patients required endoprosthetic revision, and three subsequent amputations were described. Excellent functional outcome and emotional acceptance was observed amongst patients that underwent revision. CONCLUSION: Resection and endoprosthetic reconstruction of tumours around the knee is both technically challenging and resource-intensive. It is imperative that morbidity from complications is limited through the minimisation of their incidence and the provision of optimal management. This series demonstrates that good patient outcomes can be achieved in specialist centres with experienced surgeons and adoption of a multidisciplinary approach.

Risk of a seizure recurrence after a breakthrough seizure and the implications for driving: further analysis of the standard versus new antiepileptic drugs (SANAD) randomised controlled trial.

OBJECTIVES: A breakthrough seizure is one occurring after at least 12 months seizure freedom while on treatment. The Driver and Vehicle Licensing Agency (DVLA) allows an individual to return to driving once they have been seizure free for 12 months following a breakthrough seizure. This is based on the assumption that the risk of a further seizure in the next 12 months has dropped <20%. This analysis considers whether the prescribed 1 year off driving following a breakthrough seizure is sufficient for this and stratifies risk according to clinical characteristics. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS AND MAIN OUTCOME MEASURES: The multicentre UK-based Standard versus New Antiepileptic Drugs (SANAD) study was a randomised controlled trial assessing standard and new antiepileptic drugs for patients with newly diagnosed epilepsy. For participants aged at least 16 with a breakthrough seizure, data have been analysed to estimate the annual seizure recurrence risk following a period of 6, 9 and 12 months seizure freedom. Regression modelling was used to investigate how antiepileptic drug treatment and a number of clinical factors influence the risk of seizure recurrence. RESULTS: At 12 months following a breakthrough seizure, the overall unadjusted risk of a recurrence over the next 12 months is lower than 20%, risk 17% (95% CI 15% to 19%). However, some patient subgroups have been identified which have an annual recurrence risk significantly greater than 20% after an initial 12-month seizure-free period following a breakthrough seizure. CONCLUSIONS: This reanalysis of SANAD provides estimates of seizure recurrence risks following a breakthrough seizure that will inform policy and guidance about regaining an ordinary driving licence. Further guidance is needed as to how such data should be used. TRIAL REGISTRATION NUMBER: SANAD is registered with the International Standard Randomised Controlled Trial Number Register ISRCTN38354748.

Using routinely recorded data in the UK to assess outcomes in a randomised controlled trial: The Trials of Access.

BACKGROUND: In the UK, routinely recorded data may benefit prospective studies including randomised controlled trials (RCTs). In an on-going study, we aim to assess the feasibility of access and agreement of routinely recorded clinical and non-clinical data compared to data collected during a RCT using standard prospective methods. This paper will summarise available UK routinely recorded data sources and discuss our experience with the feasibility of accessing routinely recorded data for participants of a RCT before finally proposing recommendations for improving the access and implementation of routinely recorded data in RCTs. METHODS: Setting: the case study RCT is the Standard and New Antiepileptic Drugs II (SANAD II) trial, a pragmatic, UK, multicentre, phase IV RCT assessing the clinical and cost-effectiveness of antiepileptic drug treatments for newly diagnosed epilepsy. PARTICIPANTS: 98 participants have provided written consent to permit the request of routinely recorded data. Study procedures: routinely recorded clinical and non-clinical data were identified and data requested through formal applications from available data holders for the duration that participants have been recruited into SANAD II. The feasibility of accessing routinely recorded data during a RCT is assessed and recommendations for improving access proposed. RESULTS: Secondary-care clinical and socioeconomic data is recorded on a national basis and can be accessed, although there are limitations in the application process. Primary-care data are recorded by a number of organisations on a de-identified basis but access for specific individuals has not been feasible. Access to data recorded by non-clinical sources, including The Department for Work and Pensions and The Driving and Vehicle Licensing Agency, was not successful. CONCLUSIONS: Recommendations discussed include further research to assess the attributes of routinely recorded data, an assessment of public perceptions and the development of strategies to collaboratively improve access to routinely recorded data for research. TRIAL REGISTRATION: International Standard Randomised Controlled Trials, ISRCTN30294119 . Registered on 3 July 2012. EudraCT No: 2012-001884-64. Registered on 9 May 2012.