On-Disc Observations of Flux Rope Formation Prior to Its Eruption.

Coronal mass ejections (CMEs) are one of the primary manifestations of solar activity and can drive severe space weather effects. Therefore, it is vital to work towards being able to predict their occurrence. However, many aspects of CME formation and eruption remain unclear, including whether magnetic flux ropes are present before the onset of eruption and the key mechanisms that cause CMEs to occur. In this work, the pre-eruptive coronal configuration of an active region that produced an interplanetary CME with a clear magnetic flux rope structure at 1 AU is studied. A forward-S sigmoid appears in extreme-ultraviolet (EUV) data two hours before the onset of the eruption (SOL2012-06-14), which is interpreted as a signature of a right-handed flux rope that formed prior to the eruption. Flare ribbons and EUV dimmings are used to infer the locations of the flux rope footpoints. These locations, together with observations of the global magnetic flux distribution, indicate that an interaction between newly emerged magnetic flux and pre-existing sunspot field in the days prior to the eruption may have enabled the coronal flux rope to form via tether-cutting-like reconnection. Composition analysis suggests that the flux rope had a coronal plasma composition, supporting our interpretation that the flux rope formed via magnetic reconnection in the corona. Once formed, the flux rope remained stable for two hours before erupting as a CME. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11207-017-1093-4) contains supplementary material, which is available to authorized users.

Indications and efficacy of continuous subcutaneous insulin infusion (CSII) therapy in Type 1 diabetes mellitus: a clinical audit in a specialist service.

AIM: To determine if current guidelines correctly identify patients who will benefit from continuous subcutaneous insulin infusion (CSII) therapy by comparing outcomes between Type 1 diabetic patients with recurrent severe hypoglycaemia (SH) indications with those without; and between patients without and with classic contraindications to CSII managed in a single multidisciplinary pump clinic. METHODS: Changes in biomedical outcomes [glycated haemoglobin (HbA1c), hypoglycaemia, diabetic ketoacidosis (DKA) rates], from before CSII to the end of the study (median duration 20.5 months, range 1-192), were analysed retrospectively from data collected from notes and interviews of 40 patients. Quality of life was assessed by three validated questionnaires at study end (33 patients). RESULTS: Twenty-five out of forty patients were started for reasons other than SH and 15 out of 40 had contraindications to CSII. Overall, CSII was associated with a reduction in HbA1c (9.6 +/- 2.7% to 8.3 +/- 1.2%, P = 0.011), SH (6.45 +/- 16.15/year to 0.34 +/- 1.01/year, P = 0.034) and DKA (1.83 +/- 4.48/year to 0.27 +/- 1.12/year, P = 0.036). The fall in SH was greater for patients started for SH (P < 0.001). However, only patients started for other indications showed a fall in HbA1c (P = 0.001). The fall in DKA rate was greater in patients with contraindications (P = 0.042), and they did not lose the other benefits of CSII therapy, including quality of life. CONCLUSIONS: In the setting of a specialist multidisciplinary service, CSII can be an effective and safe therapy. It confers benefit outside the setting of severe hypoglycaemia and can confer benefit in some patients with classic contraindications. This questions the validity of criteria that may exclude these patients in such a service.

Renal cancer and malformations in relatives of patients with Bardet-Biedl syndrome.

BACKGROUND: Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder with five loci identified thus far. The spectrum of disease includes diverse malformations of the kidney and lower urinary tract. The incidence of BBS is approximately 1/100,000 with a predicted heterozygote frequency of 1/160, and it has been suggested that heterozygotes are at increased risk of obesity and hypertension. METHODS: We describe renal disease in relatives of 109 UK BBS patients. Using PCR with fluorescent microsatellite markers we amplified DNA derived from renal tumours of affected parents to determine whether there was loss of heterozygosity at any of four BBS loci and two other gene loci associated with clear cell renal cell carcinoma (CC-RCC). RESULTS: CC-RCC was diagnosed in three of 180 BBS parents and there was loss of heterozygosity at BBS1 (11q13) in the tumour tissue of one of these subjects. In addition, there was a high incidence of renal agenesis in siblings of BBS patients and two BBS families were identified with apparently dominant inheritance of renal malformations. In one family we were able to demonstrate that renal malformations segregated with the BBS2 locus (16q21). CONCLUSIONS: Since all parents and two-thirds of siblings of BBS patients must be heterozygous for BBS mutations, our observations may implicate BBS genes in the pathogenesis of both renal cancer and malformations, both disorders of precursor cell growth and differentiation. We suggest these observations may have important implications for screening potential BBS carriers for kidney disease and may lead to a greater understanding of the aetiology of renal disease in the general population.

Metastatic malignant melanoma in a mandarin duck (Aix galericulata).

A biopsy taken from a mass on the dorsal surface of the bill of an adult female mandarin duck (Aix galericulata) was diagnosed as a malignant melanoma by light microscopy. Two months later, the tumor had enlarged considerably; the duck developed severe dyspnea and was euthanatized. At necropsy, there were metastases to lymphoid tissues in the lower regions of the neck. To our knowledge, this is the first report of a malignant melanoma in a mandarin duck.

Protective effect of snake venom antibodies in sera of previous snake bite victims.

Three out of seven serum samples from Ecuadorian Indians had very high antibody levels against Bothrops nasutus venom, and IgG concentrates of these sera effectively neutralized this venom when subsequently injected into mice. It is concluded that the high mortality rate among these Indians would be even higher if there were not such natural protection. Further research into active immunization of humans should be encouraged.

Severe neurotoxic envenoming by the Malayan krait Bungarus candidus (Linnaeus): response to antivenom and anticholinesterase.

Five patients were bitten by the Malayan krait Bungarus candidus (Linnaeus) in eastern Thailand or north western Malaya. Two patients were not envenomed but the other three developed generalised paralysis which progressed to respiratory paralysis in two cases, one of which ended fatally. One patient showed parasympathetic abnormalities. Anticholinesterase produced a dramatic improvement in one patient. Another patient probably benefited from paraspecific antivenom. The efficacy of antivenoms and adjuvants such as anticholinesterases in patients with neurotoxic envenoming requires further study.

Renal oncocytoma. A review of the literature and report of an unusual multicentric case.

Renal oncocytoma is a rare tumour of the kidney composed exclusively of large polygonal cells with eosinophilic, granular cytoplasm. Ultrastructurally they are distinguished by the presence of large numbers of mitochondria and histochemically by abundant oxidative enzymes and adenosine triphosphate. Macroscopically these tumours are usually light brown in colour and commonly exhibit a dense central area of fibrous scarring, with fibrous trabeculae extending from this central zone in a stellate fashion. Renal oncocytomas are commoner in males than females (sex ratio 2:1) and although the age range at presentation is wide, there is a peak incidence in the seventh decade. The prognosis following surgical removal is excellent, despite the fact that many of these tumours are large. Invasion of the perirenal fat and the renal vein and metastatic spread to regional lymph nodes is documented, but death from metastatic disease is rare. The great majority of renal oncocytomas reported are solitary. We describe a multicentric renal oncocytoma, the sixth so far reported.

The management of snake bite.

The present article reviews current knowledge on the epidemiology, pathophysiology, and treatment of snake bite, with particular reference to the situation in developing countries. There is little reliable information on the incidence of snake bite in many parts of the world, and epidemiological studies are needed, using enzyme-linked immunosorbent assay to identify and quantify serum levels of venom antigen and antibody. The pathophysiology and clinical features of envenoming by medically important snakes are discussed. Antivenom, if used correctly, can reverse systemic poisoning even if given days after the bite. It is therefore wise to wait for the appearance of signs of systemic poisoning before administering antivenom, rather than using it routinely. WHO has designated the Liverpool School of Tropical Medicine as a Collaborating Centre for the Control of Antivenoms, and this Centre now holds a collection of reference venoms from several important snake species. Characterization of these and of standard antivenoms should significantly improve the management of snake bite throughout the world.

Development of simple standard assay procedures for the characterization of snake venom.

In accordance with the recommendations of the report of a WHO Coordination Meeting on Venoms and Antivenoms, methods have been developed for the assessment of lethal, defibrinogenating, procoagulant, haemorrhagic, and necrotizing properties of venoms, and used to study 53 venoms from 30 different species of snakes of medical importance throughout the world. The venoms studied included Echis carinatus (Iran), Naja naja kaouthia (Thailand), Notechis scutatus (Australia), Trimeresurus flavoviridis (Japan), Vipera russelli (Thailand), and Crotalus atrox (USA), which comprise six of the eight venoms designated by WHO as international reference venoms (IRVs). (C. atrox venom replaced C. adamanteus venom, as an adequate supply of the latter was not available.) The tests used were simple and should be reproducible in other laboratories throughout the world. Procedures for assaying neuromuscular paralytic activity and systemic myotoxic activity have yet to be developed.The tests will be used to assay the neutralizing potency of both international standard antivenoms (raised using the IRVs) and new and currently available commercial antivenoms. Such studies should result in the production of more potent antivenoms for use in both developing and developed countries, and improve the understanding and management of snake bite throughout the world.

Neuroblastoma arising in a mature cystic teratoma of the ovary.

A case is described of a neuroblastoma which appeared to arise in a mature cystic teratoma of the ovary. The literature concerning neural tumours of the ovary is briefly reviewed and the grounds for believing that the development of such neoplasms is an indication of the presence of immature neuroepithelial components in a teratoma, rather than a result of malignant change in a fully mature teratoma, are discussed.

Snake venom antibodies in Ecuadorian Indians.

Serum samples from 223 Waorani Indians, a tribe in eastern Ecuador, were investigated by enzyme-linked immunosorbent assay for antibodies to snake venom. Seventy-eight per cent were positive, confirming the highest incidence and mortality from snake bite poisoning yet recorded in the world. Most samples were positive for more than one venom antibody. Antibodies were found to venoms of Bothrops viper in 60% of positive cases, of Micrurus coral snake in 21%, and of the bushmaster, Lachesis muta, in 18%. Further studies are needed to determine whether high venom-antibody levels afford protection against further snake envenoming.