The cascading origin of the 2018 Kilauea eruption and implications for future forecasting.

The 2018 summit and flank eruption of Kilauea Volcano was one of the largest volcanic events in Hawai'i in 200 years. Data suggest that a backup in the magma plumbing system at the long-lived Pu'u 'O'o eruption site caused widespread pressurization in the volcano, driving magma into the lower flank. The eruption evolved, and its impact expanded, as a sequence of cascading events, allowing relatively minor changes at Pu'u 'O'o to cause major destruction and historic changes across the volcano. Eruption forecasting is inherently challenging in cascading scenarios where magmatic systems may prime gradually and trigger on small events.

Cyclic lava effusion during the 2018 eruption of Kilauea Volcano.

Lava flows present a recurring threat to communities on active volcanoes, and volumetric eruption rate is one of the primary factors controlling flow behavior and hazard. The time scales and driving forces of eruption rate variability, however, remain poorly understood. In 2018, a highly destructive eruption occurred on the lower flank of Kilauea Volcano, Hawai'i, where the primary vent exhibited substantial cyclic eruption rates on both short (minutes) and long (tens of hours) time scales. We used multiparameter data to show that the short cycles were driven by shallow outgassing, whereas longer cycles were pressure-driven surges in magma supply triggered by summit caldera collapse events 40 kilometers upslope. The results provide a clear link between eruption rate fluctuations and their driving processes in the magmatic system.

The 2018 rift eruption and summit collapse of Kilauea Volcano.

In 2018, Kilauea Volcano experienced its largest lower East Rift Zone (LERZ) eruption and caldera collapse in at least 200 years. After collapse of the Pu'u 'O'o vent on 30 April, magma propagated downrift. Eruptive fissures opened in the LERZ on 3 May, eventually extending ~6.8 kilometers. A 4 May earthquake [moment magnitude (M w) 6.9] produced ~5 meters of fault slip. Lava erupted at rates exceeding 100 cubic meters per second, eventually covering 35.5 square kilometers. The summit magma system partially drained, producing minor explosions and near-daily collapses releasing energy equivalent to M w 4.7 to 5.4 earthquakes. Activity declined rapidly on 4 August. Summit collapse and lava flow volume estimates are roughly equivalent-about 0.8 cubic kilometers. Careful historical observation and monitoring of Kilauea enabled successful forecasting of hazardous events.

A method for the morphological analysis of the regurgitant mitral valve using three dimensional echocardiography.

BACKGROUND: Atrial en-face reconstructions are commonly used to assess mitral valve morphology in three dimensional (3D) echocardiography but may miss important abnormalities. OBJECTIVE: To present a systematic method for the analysis of the regurgitant mitral valve using a combination of en-face and longitudinal views for better anatomical evaluation. METHODS: Detailed 3D assessment was done on 58 patients undergoing mitral valve repair. En-face and longitudinal views were compared for detection and location of primary pathology. The quality of acquisitions under general anaesthesia and sedation was also compared. RESULTS: Recognition of valve structure was significantly better with longitudinal reconstruction for both mitral leaflets but not for the commissures. Accurate identification of pathology was possible in 95% cases, compared with 50% for en-face reconstruction (p < 0.001). There was no significant difference between imaging under sedation and anaesthesia. CONCLUSION: En-face reconstructions alone are inadequate. Additional longitudinal reconstructions are necessary to ensure full inspection of valve morphology.

Readability and content of supplementary written drug information for patients used by Australian rheumatologists.

OBJECTIVE: To determine the readability and content of supplementary written drug information currently being given to patients by rheumatologists in Australia. DESIGN AND PARTICIPANTS: Blinded standardised review by two independent reviewers of supplementary written drug information routinely provided to patients by the 195 fully registered members of the Australian Rheumatology Association (ARA). MAIN OUTCOME MEASURES: FOG and SMOG readability scores to estimate readability; critical appraisal of content according to predetermined criteria. RESULTS: 84 rheumatologists responded (43%), 45 of whom reported providing copies of written drug information to patients. Overall, 91 different documents were reviewed. Drugs most commonly considered were methotrexate (17), gold (16), sulfasalazine (10), penicillamine (10) and prednisolone (8). Level of agreement between reviewers for FOG and SMOG scores was fair to good (intraclass correlation coefficient, 0.61 and 0.51, respectively). Mean (95% CI) FOG and SMOG scores were 12.6 (12.2-12.9) and 11 (10.7-11.2), respectively (implying that half of those in Year 12 [or aged 17 years] and Year 11 [or aged 16 years] according to the FOG and SMOG mean scores, respectively, will comprehend half of the text or more). For the same medication, there was a wide variation in the information provided, including which side effects were discussed. While 98% included some information about side effects, fewer considered dose (74%), drug interactions if applicable (70%), purpose of drug (67%), how and when to take the drug (62%), expected time to improvement (54%), what to do in the event of side effects (44%), the expected duration of therapy (18%) and what to do if a dose was missed (5%). CONCLUSIONS: The reading level required to understand supplementary written drug information used by Australian rheumatologists is much higher than the average reading ability of the Australian population (estimated at Year 8 level). The content of this information varies widely and often omits important information.

In vitro characterization of a recombinant 32P-phosphorylated anti-(carcinoembryonic antigen) single-chain antibody.

The major limitations of monoclonal antibody conjugates as therapeutic agents have been their poor tumour targeting, inadequate tumour penetration and immunogenicity. More even and deeper tissue penetration has been demonstrated with smaller antibody fragments. The smaller size and absence of an Fc segment may contribute to a lowered immunogenicity with single-chain antibodies (scFv) and also permit their recombinant engineering and bacterial expression. We describe the successful engineering, expression and pre-clinical characterisation of a phosphorylatable "kemptide" (Leu-Arg-Arg-Ala-Ser-Gly) anti-carcinoembryonic antigen (anti-CEA) scFv (PKS-scFv), for use as a radioimmunotherapeutic agent. Specifically, a yield of 6 mg/l induced culture was obtained. Site-specific phosphorylation was demonstrated without loss of specificity. In vitro assays revealed a selective cytotoxicity of 32P-PKS-scFv for high-CEA-expressing LS-174T cells compared to the low-CEA-expressing HT-29 cells, with a rapid internalisation rate.

Preclinical characterization and in vivo imaging studies of an engineered recombinant technetium-99m-labeled metallothionein-containing anti-carcinoembryonic antigen single-chain antibody.

UNLABELLED: We describe the engineering of a novel single-chain fragment (scFv) metallothionein (MET) containing anti-carcinoembryonic antigen (CEA) antibody (referred to as MET-scFv) for use as a diagnostic imaging agent in colorectal cancer. METHODS: Site-directed cloning of annealed oligonucleotides, containing both the MET and a c-myc tag sequence, into a pUC19-based expression vector enabled soluble secreted protein expression from Escherichia coli. Affinity purification was used to purify the protein using an anti-c-myc affinity column. The specificity of both the unlabeled and labeled MET-scFv for CEA was demonstrated by solid-phase enzyme-linked immunosorbent assay and radioimmunoassay and by fluorescence-activated cell sorting analysis on CEA-expressing human colorectal LS-174T cells. Technetium-99m labeling was achieved using a Zn2+ transchelation step, enabling direct 99mTc transfer without separate reduction of MET. In vitro stability was demonstrated by fast protein liquid chromatography analysis of labeled MET-scFv, incubated with bovine serum albumin (BSA), transferrin and mouse serum. Last, in vivo pharmacokinetics, biodistribution and imaging were performed. RESULTS: Yields of 6 mg/liter induced culture purified protein were achieved. Successful site-specific labeling was demonstrated using a Zn2+ transchelation modification of a pretinning method, which also enabled lower amounts of the reducing agent to be used. The specificity for CEA was retained after labeling. Despite a rapid serum clearance (t(1/2alpha) = 2.8 min), adequate localization to tumor of 5.37% injected dose/g at 4 hr was demonstrated. Moreover, the short-lived t(1/2alpha) of scFv, its early tumor targeting and rapid blood-pool clearance gave tumor-to-blood ratios of 2.07 by 4 hr, enabling early gamma camera imaging. Successful and specific imaging was achieved using LS-174T xenografts in nude mice by 3-6 hr. CONCLUSION: A recombinant MET containing scFv was successfully expressed, purified and labeled with 99Tc. The stable site-specific labeling of 99Tc, combined with the rapid plasma clearance of the scFv, led to successful early in vivo imaging of xenografted mice.

A comparative multicentre trial of spinal needles for caesarean section.

We studied 681 patients in a randomised, multicentre, double-blind, parallel group trial designed to assess the incidence of headache following spinal anaesthesia for Caesarean section using four different pencil point spinal needles. The needles used were: Whitacre 25G (n = 170), Polymedic 25G (n = 170), Sprotte 24G (n = 173) and Polymedic 24G (n = 168). The incidence of all headaches prior to discharge was 11.1%. Only five headaches (0.75%) were severe with features of post dural puncture headache (PDPH) and required an epidural blood patch: Whitacre 25G = 0, Polymedic 25G = 1 (0.6%), Sprotte 24G = 2 (1.2%), Polymedic 24G = 2 (1.2%). There was no statistically significant difference between the four groups for PDPH. We conclude that all four needles studied performed satisfactorily and comparably.

Fibromyalgia antirheumatic drug trials: Effects of a standardized instructional videotape on the reliability of observer-dependent outcome measures.

AIMS: A study was designed to assess the effects of a standardized instructional videotape on reducing interobserver variability for several commonly used observer-dependent outcome measures. METHODS: During a single day, six rheumatologists independently examined six patients with fibromyalgia (FM) in a predetermined order using a Latin square design, before and after viewing a standardized videotape which demonstrated methods for performing dolorimetry and for detecting skinfold tenderness and reactive hyperaemia. Reliability coefficients were calculated based on the variance components of the analysis of variance (ANOVA) table. RESULTS: Prestandardization reliability coefficients were <0.80 for 8 measures. Following standardization all reliability coefficients approximated to or exceeded 0.80. CONCLUSIONS: An important and beneficial effect of the standardization procedure was noted for several outcome variables. Such reductions in observer variability have the potential to diminish sample size requirements for FM antirheumatic drug studies. The use of a videotape to achieve this goal has obvious cost and convenience advantages over one-on-one training procedures.

The effect of a cervical collar on the tidal volume of anaesthetised adult patients.

Semi-rigid cervical collars may be used to assist the stabilisation of the cervical spine during transport in patients suffering from major trauma. We have attempted to evaluate the effect of one such collar on airway patency in the presence of depressed airway reflexes. Thirty-eight patients undergoing anaesthesia via face mask with spontaneous ventilation were studied. Tidal volume was measured with the airway in three different positions, both with and without a collar. The collar made no statistically significant difference to tidal volume in any position. Changing support of the airway increased tidal volume both with and without the collar. Patients fitted with an incorrectly sized collar may develop upper airway obstruction in the presence of impaired consciousness. Experience should be gained in the correct fitting of semi-rigid collars.

Circulating interleukin 1 beta and soluble interleukin 2 receptor: evaluation as markers of disease activity in scleroderma.

OBJECTIVES: To investigate whether circulating levels of interleukin 1 beta (IL-1 beta) or soluble interleukin 2 receptor (sIL-2R) reflect clinical disease status and response to therapy in scleroderma. METHODS: Plasma IL-1 beta and serum sIL-2R were measured by ELISA in 19 patients with limited cutaneous scleroderma (9 with extraesophageal internal organ involvement), 5 patients with diffuse cutaneous scleroderma and internal organ involvement, and 11 healthy controls, as well as serially over 12 months in 4 patients with scleroderma treated with cyclosporine. RESULTS: IL-1 beta levels were similar in scleroderma and control subject groups. sIL-2R levels were significantly higher in subjects with scleroderma involving internal organs (elevated in 93%), and correlated with erythrocyte sedimentation rate. sIL-2R levels decreased over 12 months in 2 of 4 patients taking cyclosporine in whom other variables remained unchanged. CONCLUSIONS: Elevated serum sIL-2R is a marker of internal organ involvement in scleroderma and warrants further investigation in assessing disease prognosis and response to therapy.

Influence of glyceryl trinitrate and nifedipine on coronary sinus blood flow and global myocardial metabolism during coronary artery operation.

The effects of intravenous infusions of glyceryl trinitrate and nifedipine on systemic haemodynamic function, coronary haemodynamic function, and global myocardial metabolism were compared in two groups of eleven patients with unimpaired left ventricular function undergoing elective coronary artery operation who were anaesthetised with high dose fentanyl. Severe post-sternotomy hypertension developed in three patients in the glyceryl trinitrate group who were resistant to the hypotensive effect of this agent. All patients given nifedipine remained haemodynamically stable. Coronary sinus blood flow and myocardial oxygen consumption increased and coronary vascular resistance decreased after sternotomy in the nifedipine group but not in the glyceryl trinitrate group. There is no satisfactory explanation for the apparently paradoxical increase in myocardial oxygen consumption in the patients given nifedipine. This phenomenon did not appear to be associated with any detrimental effect of left ventricular function. Thus nifedipine was better than glyceryl trinitrate for the control of post-sternotomy hypertension in patients with good left ventricular function. Intravenous nifedipine is not recommended, however, for the intraoperative control of blood pressure in patients with unstable angina or impaired left ventricular function.

A comparison of the haemodynamic effects of propofol ('Diprivan') and thiopentone in patients with coronary artery disease.

Twenty patients scheduled for elective coronary surgery received either propofol ('Diprivan') 1.5 mg/kg in emulsion or thiopentone 2 mg/kg for induction of anaesthesia. Vecuronium was used for neuromuscular blockade. Cardiovascular dynamics were recorded every minute until 6 min after intubation. Anaesthesia with propofol was accompanied by a reduction in arterial pressure, the decrease being severe in two patients. This was largely due to a decrease in systemic vascular resistance. Thiopentone anaesthesia resulted in a smaller decrease in arterial pressure, but a marked increase in arterial pressure followed endotracheal intubation. Although the absence of haemodynamic changes following intubation during propofol anaesthesia is advantageous to the ischaemic myocardium, this has to be balanced by the variable and sometimes severe reduction in arterial pressure that occurred on induction.

Early extubation of the trachea after open heart surgery for congenital heart disease. A review of 3 years' experience.

The results of early extubation after open heart surgery for congenital heart disease in 209 consecutive patients have been reviewed. No patient younger than 3 months of age, 52% of those between 3 and 12 months, and 88% of those older than 12 months had the tracheal tube removed in the operating theatre. Four patients required reintubation of the trachea, three because of respiratory difficulty and one because of cerebral oedema. There were two deaths in the extubated group. Twelve patients had PaO2 values less than 8.0 kPa after operation, despite adequate oxygen therapy. In four of these, this was related to persistent intracardiac shunting. It is concluded that early extubation after open heart surgery for congenital heart disease has minimal risk in carefully selected patients.

Study of diarrhea in critically ill patients.

There has been an impression that diarrhea occurs commonly in seriously ill patients treated in ICUs. In view of the sparsity of published work on the problem, we embarked on a prospective study of all patients admitted to the ICU for more than 48 h over a 12-month period. Three factors were examined in detail: nasogastric feeding, cimetidine administration, and antibiotic treatment. Other factors also were considered, notably the nature of the underlying illness and the spread of a possible infective agent by cross-infection. There was a 41% incidence of diarrhea. A significant increase in the incidence of diarrhea occurred in patients on nasogastric feeding (p less than 0.01) and in those receiving cimetidine (p less than 0.05); there was no increased incidence in those receiving antibiotic therapy. The cytotoxin of Clostridium difficile was specifically looked for in all patients with diarrhea, but was not detected.