Consultant and trainee attitudes towards supervision of operative procedures in the UK and Ireland.

The e-logbook is used to monitor progression through training and to assess training within teaching units. We document consultant and trainee opinions with regards to supervision status, and to inform guidelines for trainees and trainers using the e-logbook. A questionnaire was sent to consultants and trainees in the UK and Ireland. Eight theatre scenarios were described and respondents were asked to state what they felt was the appropriate supervision status for the trainee. Significantly more consultants in the UK use the e-logbook than those based in Ireland (58.5%:14.5%). There were differences in consensus response to the scenarios between consultants and trainees, and between Irish and UK based surgeons. We have documented the opinions of consultants and trainees from across the UK and Ireland with regards to supervision status for trainees under certain theatre situations. This information should support formal guidelines for all users of the logbook.

Annually recurring parthenogenesis in a zebra shark Stegostoma fasciatum.

A zebra shark, Stegostoma fasciatum, held in captivity at the Burj Al Arab aquarium, produced embryos and pups in the absence of a male. A total of 15 pups were produced from eggs laid within the aquarium over a period of four consecutive years commencing 2007. Parthenogenesis was confirmed through DNA analysis for three pups sampled during the first two consecutive egg cycles and is presumed to be the method of reproduction responsible thereafter.

Earthquake rupture stalled by a subducting fracture zone.

We showed that the rupture produced by the great Peru earthquake (moment magnitude 8.4) on 23 June 2001 propagated for approximately 70 kilometers before encountering a 6000-square-kilometer area of fault that acted as a barrier. The rupture continued around this barrier, which remained unbroken for approximately 30 seconds and then began to break when the main rupture front was approximately 200 kilometers from the epicenter. The barrier had relatively low rupture speed, slip, and aftershock density as compared to its surroundings, and the time of the main energy release in the earthquake coincided with the barrier's rupture. We associate this barrier with a fracture zone feature on the subducting oceanic plate.

Functional analysis of CpG methylation in the BRCA1 promoter region.

Understanding the role for DNA methylation in tumorigenesis has evolved from defining the location and extent of methylation in a variety of cancer-related genes to clarifying the functional and site-specific effects of aberrant methylation on gene expression. Our objectives were to characterize the functional effects of DNA methylation in the BRCA1 promoter and to clarify the functional status of the BRCA1 CRE (cAMP response element) motif. Luciferase reporter assays confirm that an intact CRE is important for BRCA1 expression in transient transfections. Luciferase activities were decreased in constructs where the CRE recognition sequence was altered and when constructs were methylated in vitro. Gel mobility shift and competition assays identified a DNA-protein complex recognizing the CRE motif that we were able to supershift using CREB-specific antibody. Furthermore this CRE is methylation sensitive, and we localized this methylation effect to a CpG dinucleotide within the BRCA1 CRE motif. The consequences of aberrant DNA methylation at specific transcription factor motifs, along with the multiple mutational events that can occur in a variety of essential genes such as BRCA1, paint a complex picture where both genetic and epigenetic changes contribute to tumour formation.

Simultaneous rupture along two conjugate planes of the Wharton Basin earthquake.

Analysis of broadband teleseismic data shows that the 18 June 2000 Wharton Basin earthquake, a moment magnitude 7.8 intraplate event in the region of diffuse deformation separating the Indian and Australian plates, consisted of two subevents that simultaneously ruptured two near-conjugate planes. This mode of rupture accommodates shortening by a mechanism different from that previously known elsewhere in the region. The larger subevent occurred on a fossil fracture zone, with a relatively high stress drop of about 20 megapascals, showing that large stresses can accumulate in regions of distributed deformation.

Zanamivir in the prevention of influenza among healthy adults: a randomized controlled trial.

CONTEXT: The neuraminidase inhibitor zanamivir, a sialic acid analog administered directly to the respiratory tract, has been demonstrated in clinical studies to be effective in treatment of type A and B influenza. It has also been shown to prevent influenza infection and disease in an experimental model. OBJECTIVE: To examine the efficacy of zanamivir, administered once daily, in the prevention of influenza infection and disease. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Two midwestern university communities. PARTICIPANTS: A total of 1107 healthy adults (mean age [range], 29 [18-69] years) were recruited in November 1997, before the influenza season. INTERVENTION: At the start of the influenza outbreak, 554 subjects were randomized to receive placebo and 553 to receive zanamivir. The drug, 10 mg once per day, or identical placebo was administered by oral inhalation for a 4-week period. MAIN OUTCOME MEASURES: Illness occurrence was recorded by participants daily and records were evaluated weekly. Specimens were collected for viral isolation when symptoms were reported within 3 days of illness onset. Infection was also identified by testing paired serum samples for rise in antibody titer against the circulating influenza viruses. RESULTS: Zanamivir was 67% efficacious (95% confidence interval [CI], 39%-83%; P<.001) in preventing laboratory-confirmed clinical influenza meeting the case definition and 84% efficacious (95% CI, 55%-94%; P=.001) in preventing laboratory-confirmed illnesses with fever. All influenza infections occurring during the season, with or without symptoms, were prevented with an efficacy of 31% (95% CI, 4%-50%; P=.03). The nature and incidence of adverse events in the zanamivir group did not differ from placebo. Compliance with the once-daily dosage was high. CONCLUSIONS: Zanamivir administered once daily is efficacious and well tolerated in the prevention of influenza for a 4-week period in healthy adults.

Cloning and expression of the ApaLI, NspI, NspHI, SacI, ScaI, and SapI restriction-modification systems in Escherichia coli.

The genes encoding the ApaLI (5'-GTGCAC-3'), NspI (5'-RCATGY-3'), NspHI (5'-RCATGY-3'), SacI (5'-GAGCTC-3'), SapI (5'-GCTCTTCN1-3', 5'-N4GAAGAGC-3') and ScaI (5'-AGTACT-3') restriction-modification systems have been cloned in E. coli. Amino acid sequence comparison of M.ApaLI, M.NspI, M.NspHI, and M.SacI with known methylases indicated that they contain the ten conserved motifs characteristic of C5 cytosine methylases. NspI and NspHI restriction-modification systems are highly homologous in amino acid sequence. The C-termini of the NspI and NlaIII (5'-CATG-3') restriction endonucleases share significant similarity. 5mC modification of the internal C in a SacI site renders it resistant to SacI digestion. External 5mC modification of a SacI site has no effect on SacI digestion. N4mC modification of the second base in the sequence 5'-GCTCTTC-3' blocks SapI digestion. N4mC modification of the other cytosines in the SapI site does not affect SapI digestion. N4mC modification of ScaI site blocks ScaI digetion. A DNA invertase homolog was found adjacent to the ApaLI restriction-modification system. A DNA transposase subunit homolog was found upstream of the SapI restriction endonuclease gene.

Three-dimensional structure of the adenine-specific DNA methyltransferase M.Taq I in complex with the cofactor S-adenosylmethionine.

The Thermus aquaticus DNA methyltransferase M.Taq I (EC 2.1.1.72) methylates N6 of adenine in the specific double-helical DNA sequence TCGA by transfer of --CH3 from the cofactor S-adenosyl-L-methionine. The x-ray crystal structure at 2.4-A resolution of this enzyme in complex with S-adenosylmethionine shows alpha/beta folding of the polypeptide into two domains of about equal size. They are arranged in the form of a C with a wide cleft suitable to accommodate the DNA substrate. The N-terminal domain is dominated by a nine-stranded beta-sheet; it contains the two conserved segments typical for N-methyltransferases which form a pocket for cofactor binding. The C-terminal domain is formed by four small beta-sheets and alpha-helices. The three-dimensional folding of M.Taq I is similar to that of the cytosine-specific Hha I methyltransferase, where the large beta-sheet in the N-terminal domain contains all conserved segments and the enzymatically functional parts, and the smaller C-terminal domain is less structured.

Pancreatic function testing: serum PABA measurement is a reliable and accurate measurement of exocrine function.

A comparison between the NBT-PABA/14C-PABA test (NBT-PABA, n-benzoyl-tyrosyl para-aminobenzoic acid) using the PABA excretion index (PEI) and serum PABA estimation at 90 minutes has been made in 42 consecutive subjects attending for investigation of possible pancreatic disease to a District General Hospital (DGH). The PEI was unobtainable or incorrect on 38% of occasions compared with 9% for the serum test. Sensitivity, specificity, and efficiency for the PEI (n = 33 valid results) were 71%, 88%, and 79% respectively and for the serum PABA (n = 41 valid results), 95%, 90%, and 93% respectively. These results confirm that measurement of serum PABA is a simpler, more reliable, and a more accurate method of assessing pancreatic function.

Functional somatic complaints in adolescents: relationship to negative life events, self-concept, and family characteristics.

While recurrent somatic complaints are commonly encountered in children and adolescents, occult organic disease is rarely found in patients with these complaints. Recent studies have confirmed the clinical impression that a relationship exists between functional somatic complaints and negative life events in adolescents. Our goal was to investigate additional psychosocial characteristics that may be associated with functional complaints. One hundred fifteen adolescents coming for the first time to an adolescent medicine clinic completed standard measures of negative life events, psychophysiologic symptoms, self-esteem, peer social comparison, and family functioning before an independent evaluation by a physician. Patients with functional somatic complaints (chest pain, recurrent abdominal pain, limb pain, and hyperventilation syndrome) reported significantly more negative life events, lower self-esteem, more psychophysiologic symptoms and a lower self-evaluation than did patients coming for physical examination or routine health maintenance. Functional somatic complaints in adolescents may be associated with poor psychosocial adjustment and reaction to negative life events. In addition to ruling out organic disease, physicians dealing with these patients should evaluate other areas, including stressful life events, peer relations, and self-esteem.

Frequency of Entamoeba gingivalis in human gingival scrapings.

A survey was made of gingival scrapings stained by the Papanicolaou method to assess the occurrence of Entamoeba gingivalis, a nonpathogenic-oral amoeba. Positive findings were recorded in 59% of 113 dental patients, and 32% of 96 healthy controls. These figures showed no significant changes during the last 20 years when compared with data published in 1960 and 1963. The existence of E. gingivalis and its rare appearance in the sputum should be known to cytologists because of the morphologic resemblance to Entamoeba histolytica, a pathogenic amoeba. Morphologic features are described to differentiate E. gingivalis from similar structures found in sputum.

Towards a definitive assay of creatinine in serum and in urine: separation by high-performance liquid chromatography.

A fast and sensitive method for the separation of serum and urinary creatinine is described. For the preliminary purification of serum and urine, a cation-exchange column is used to remove protein, anions and neutral compounds prior to isolation of creatinine by high-performance liquid chromatography. A reversed-phase system with 0.01 M ammonium acetate solution as the mobile phase can separate creatinine in 7.5 min at a flow-rate of 1 ml/min. The purity of the separated creatinine is proved by derivatization using trifluoracetic anhydride, followed by gas chromatography and mass spectrometry. Although this method of purification was designed for incorporation into a definitive assay, the ease and speed of analysis makes is very attractive for routine clinical use.