Short length scale oxygen isotope heterogeneity in the icelandic mantle: Evidence from plagioclase compositional zones

Using a new high-resolution dataset, this study presents evidence for short length scale 18O/16O heterogeneity in the mantle source region of young (age ≲12 ka bp) Icelandic basalts. The dataset comprises secondary ion mass spectrometry determinations of 18O/16O in single compositional zones of plagioclase crystals from the primitive Borgarhraun flow in northern Iceland, along with trace and major element data from the same zones. The presence of mantle under Iceland with δ18O below typical mid-ocean ridge basalt (MORB) values of ∼5·5 ± 0·3‰ (VSMOW) has previously been disputed, because variability in δ18O in many Icelandic basalts is also known to be caused by the interaction of basaltic melts with crustal lithologies that have been altered by low-δ18O meteoric water. Primitive basalt flows, such as Borgarhraun, and their macrocrysts are the most likely candidates to retain a mantle δ18O signature. However, the role of crustal processes in generating the low δ18O in olivine crystals from these flows has not unequivocally been ruled out. By making intra-crystal analyses in Borgarhraun plagioclase it has been possible in this study to obtain a detailed record of the chemical and isotopic compositions of the melts that crystallized the plagioclase zones. The variability observed in trace element compositions of the early crystallized anorthitic plagioclase zones (80·9–89·4 mol % anorthite) is firstly shown to arise from melt compositional variability, and equilibrium melt concentrations of Sr, La and Y are then calculated from the crystal concentrations of these elements using carefully selected partition coefficients. The ranges of incompatible trace element ratios (La/Y, Sr/Y) in these equilibrium melts reflect a range of compositions of fractional mantle melts, a result that is in agreement with previous proposals for the cause of variability in trace element indices of Borgarhraun olivine-hosted melt inclusions and clinopyroxene compositional zones. Correlations observed between La/Y and Sr/Y in the melts in equilibrium with the Borgarhraun plagioclase zones and the δ18O of these zones therefore support the hypothesis that the mantle under Iceland is heterogeneous in 18O/16O. Such correlations have not previously been observed in intra-crystal data from Iceland, and provide strong evidence that mantle material with abnormally low δ18O may exist in the form of readily fusible heterogeneities alongside ambient mantle with MORB-like δ18O (≈+5·5‰) on a length scale of <100 km. The lowest δ18O of plagioclase that is attributed to a mantle origin in this study is 4·5 ± 0·4‰, equating to a melt equivalent value of 4·3 ± 0·5‰ or an olivine equivalent value of 3·8 ± 0·5‰.This work was supported by a Natural Environment Research Council studentship to B.W. (NE/F007183/1), a Natural Environment Research Council young investigator grant to J.M. (NE/E001254/1) and a Natural Environment Research Council Ion Microprobe Facility award (IMF 365/1008).This is the final published version. It first appeared at http://petrology.oxfordjournals.org/content/55/12/2537.abstract

Baseline characteristics of participants in the Treatment of Advanced Glaucoma Study (TAGS): A multicentre randomised controlled trial

PURPOSE: To report the baseline characteristics of participants enrolled in the Treatment of Advanced Glaucoma Study (TAGS) DESIGN: Pragmatic randomised control trial (RCT). PARTICIPANTS: Patients with open angle glaucoma presenting with advanced glaucoma in at least one eye as defined by the Hodapp-Parrish-Anderson (HPA) criteria of severe defect. METHODS: Participants with newly diagnosed advanced glaucoma in at least one eye were recruited. Participants were randomly allocated to receive either primary augmented trabeculectomy or primary medical management. When both eyes were eligible, the same intervention was undertaken in both eyes and the index eye for analysis was the eye with the less severe visual field mean deviation (MD). MAIN OUTCOME MEASURES: Visual field profile defined by the HPA classification, clinical characteristics, Quality of life measured by the National Eye Institute Visual Function Questionnaire 25 (VFQ-25), EuroQual-5 Dimension (EQ-5D 5L), Health Utility Index-3 (HUI-3) and Glaucoma Profile Instrument (GPI) RESULTS: Four hundred and fifty-three patients were recruited. The mean visual field MD was -15.0dB (SD 6.3) in the index eye and -6.2dB in the non-index eye. Of index eyes (HPA ‘severe’ classification) at baseline, over 70% had a mean deviation < -12.00dB and nearly 90% had more than 20 points defective at the 1% level. The mean LogMAR visual acuity of the index eye was 0.2 (SD 0.3), CONCLUSIONS: TAGS is the first RCT to compare medical and surgical treatments for patients presenting with advanced open angle glaucoma in a publicly funded health service. It will provide clinical, health related quality of life and economic outcomes to inform future treatment choices for those presenting with advanced glaucom

Meaning behind measurement : self-comparisons affect responses to health related quality of life questionnaires

Purpose The subjective nature of quality of life is particularly pertinent to the domain of health-related quality of life (HRQOL) research. The extent to which participants’ responses are affected by subjective information and personal reference frames is unknown. This study investigated how an elderly population living with a chronic metabolic bone disorder evaluated self-reported quality of life. Methods Participants (n = 1,331) in a multi-centre randomised controlled trial for the treatment of Paget’s disease completed annual HRQOL questionnaires, including the SF-36, EQ-5D and HAQ. Supplementary questions were added to reveal implicit reference frames used when making HRQOL evaluations. Twenty-one participants (11 male, 10 female, aged 59–91 years) were interviewed retrospectively about their responses to the supplementary questions, using cognitive interviewing techniques and semi-structured topic guides. Results The interviews revealed that participants used complex and interconnected reference frames to promote response shift when making quality of life evaluations. The choice of reference frame often reflected external factors unrelated to individual health. Many participants also stated that they were unclear whether to report general or disease-related HRQOL. Conclusions It is important, especially in clinical trials, to provide instructions clarifying whether ‘quality of life’ refers to disease-related HRQOL. Information on selfcomparison reference frames is necessary for the interpretation of responses to questions about HRQOL.The Chief Scientist Office of the Scottish Government Health Directorates, The PRISM funding bodies (the Arthritis Research Campaign, the National Association for the Relief of Paget’s disease and the Alliance for Better Bone Health)Peer reviewedAuthor final versio

UKMenCar4: A cross-sectional survey of asymptomatic meningococcal carriage amongst UK adolescents at a period of low invasive meningococcal disease incidence.

Carriage of Neisseria meningitidis, the meningococcus, is a prerequisite for invasive meningococcal disease (IMD), a potentially devastating infection that disproportionately afflicts infants and children. Humans are the sole known reservoir for the meningococcus, and it is carried asymptomatically in the nasopharynx of ~10% of the population. Rates of carriage are dependent on age of the host and social and behavioural factors. In the UK, meningococcal carriage has been studied through large, multi-centre carriage surveys of adolescents in 1999, 2000, and 2001, demonstrating carriage can be affected by immunisation with the capsular group C meningococcal conjugate vaccine, inducing population immunity against carriage. Fifteen years after these surveys were carried out, invasive meningococcal disease incidence had declined from a peak in 1999.  The UKMenCar4 study was conducted in 2014/15 to investigate rates of carriage amongst the adolescent population during a period of low disease incidence. The protocols and methodology used to perform UKMenCar4, a large carriage survey, are described here

Primary trabeculectomy versus primary glaucoma eye drops for newly diagnosed advanced glaucoma: TAGS RCT

Background: Patients diagnosed with advanced primary open-angle glaucoma are at a high risk of lifetime blindness. Uncertainty exists about whether primary medical management (glaucoma eye drops) or primary surgical treatment (augmented trabeculectomy) provide the best and safest patient outcomes. // Objectives: To compare primary medical management with primary surgical treatment (augmented trabeculectomy) in patients with primary open-angle glaucoma presenting with advanced disease in terms of health-related quality of life, clinical effectiveness, safety and cost-effectiveness. // Design: This was a two-arm, parallel, multicentre, pragmatic randomised controlled trial. // Setting: Secondary care eye services. // Participants: Adult patients presenting with advanced primary open-angle glaucoma in at least one eye, as defined by the Hodapp–Parrish–Anderson classification of severe glaucoma. // Intervention: Primary medical treatment – escalating medical management with glaucoma eye drops. Primary trabeculectomy treatment – trabeculectomy augmented with mitomycin C. // Main outcome measures: The primary outcome was health-related quality of life measured with the Visual Function Questionnaire-25 at 2 years post randomisation. Secondary outcomes were mean intraocular pressure; EQ-5D-5L; Health Utilities Index 3; Glaucoma Utility Index; cost and cost-effectiveness; generic, vision-specific and disease-specific health-related quality of life; clinical effectiveness; and safety. // Results: A total of 453 participants were recruited. The mean age of the participants was 67 years (standard deviation 12 years) in the trabeculectomy arm and 68 years (standard deviation 12 years) in the medical management arm. Over 65% of participants were male and more than 80% were white. At 24 months, the mean difference in Visual Function Questionnaire-25 score was 1.06 (95% confidence interval –1.32 to 3.43; p = 0.383). There was no evidence of a difference between arms in the EQ-5D-5L score, the Health Utilities Index or the Glaucoma Utility Index. At 24 months, the mean intraocular pressure was 12.40 mmHg in the trabeculectomy arm and 15.07 mmHg in the medical management arm (mean difference –2.75 mmHg, 95% confidence interval –3.84 to –1.66 mmHg; p < 0.001). Fewer types of glaucoma eye drops were required in the trabeculectomy arm. LogMAR visual acuity was slightly better in the medical management arm (mean difference 0.07, 95% confidence interval 0.02 to 0.11; p = 0.006) than in the trabeculectomy arm. There was no evidence of difference in safety between the two arms. A discrete choice experiment updated the utility values for the Glaucoma Utility Index. The within-trial economic analysis found a small increase in the mean EQ-5D-5L score (0.04) and that trabeculectomy has a higher probability of being cost-effective than medical management. The incremental cost of trabeculectomy per quality-adjusted life-year was £45,456. Therefore, at 2 years, surgery is unlikely to be considered cost-effective at a threshold of £20,000 per quality-adjusted life-year. When extrapolated over a patient’s lifetime in a model-based analysis, trabeculectomy, compared with medical treatment, was associated with higher costs (average £2687), a larger number of quality-adjusted life-years (average 0.28) and higher incremental cost per quality-adjusted life-year gained (average £9679). The likelihood of trabeculectomy being cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life year gained was 73%. // Conclusions: Our results suggested that there was no difference between treatment arms in health-related quality of life, as measured with the Visual Function Questionnaire-25 at 24 months. Intraocular pressure was better controlled in the trabeculectomy arm, and this may reduce visual field progression. Modelling over the patient’s lifetime suggests that trabeculectomy may be cost-effective over the range of values of society’s willingness to pay for a quality-adjusted life-year

Relationship between Antibody Susceptibility and Lipopolysaccharide O-Antigen Characteristics of Invasive and Gastrointestinal Nontyphoidal Salmonellae Isolates from Kenya

Background: Nontyphoidal Salmonellae (NTS) cause a large burden of invasive and gastrointestinal disease among young children in sub-Saharan Africa. No vaccine is currently available. Previous reports indicate the importance of the O-antigen of Salmonella lipopolysaccharide for virulence and resistance to antibody-mediated killing. We hypothesised that isolates with more O-antigen have increased resistance to antibody-mediated killing and are more likely to be invasive than gastrointestinal. Methodology/Principal findings: We studied 192 NTS isolates (114 Typhimurium, 78 Enteritidis) from blood and stools, mostly from paediatric admissions in Kenya 2000-2011. Isolates were tested for susceptibility to antibody-mediated killing, using whole adult serum. O-antigen structural characteristics, including O-acetylation and glucosylation, were investigated. Overall, isolates were susceptible to antibody-mediated killing, but S. Enteritidis were less susceptible and expressed more O-antigen than Typhimurium (p\u3c0.0001 for both comparisons). For S. Typhimurium, but not Enteritidis, O-antigen expression correlated with reduced sensitivity to killing (r = 0.29, 95% CI = 0.10-0.45, p = 0.002). Both serovars expressed O-antigen populations ranging 21-33 kDa average molecular weight. O-antigen from most Typhimurium were O-acetylated on rhamnose and abequose residues, while Enteritidis O-antigen had low or no O-acetylation. Both Typhimurium and Enteritidis O-antigen were approximately 20%-50% glucosylated. Amount of S. Typhimurium O-antigen and O-antigen glucosylation level were inversely related. There was no clear association between clinical presentation and antibody susceptibility, O-antigen level or other O-antigen features. Conclusion/Significance: Kenyan S. Typhimurium and Enteritidis clinical isolates are susceptible to antibody-mediated killing, with degree of susceptibility varying with level of O-antigen for S. Typhimurium. This supports the development of an antibody-inducing vaccine against NTS for Africa. No clear differences were found in the phenotype of isolates from blood and stool, suggesting that the same isolates can cause invasive disease and gastroenteritis. Genome studies are required to understand whether invasive and gastrointestinal isolates differ at the genotypic level

Systematic reviews of complementary therapies - an annotated bibliography. Part 1: Acupuncture

Background Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with acupuncture. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of acupuncture; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pretested form and summarized descriptively. Results From a total of 48 potentially relevant reviews preselected in a screeening process 39 met the inclusion criteria. 22 were on various pain syndromes or rheumatic diseases. Other topics addressed by more than one review were addiction, nausea, asthma and tinnitus. Almost unanimously the reviews state that acupuncture trials include too few patients. Often included trials are heterogeneous regarding patients, interventions and outcome measures, are considered to have insufficient quality and contradictory results. Convincing evidence is available only for postoperative nausea, for which acupuncture appears to be of benefit, and smoking cessation, where acupuncture is no more effective than sham acupuncture. Conclusions A large number of systematic reviews on acupuncture exists. What is most obvious from these reviews is the need for (the funding of) well-designed, larger clinical trials

Is annual surveillance of all treated hypothyroid patients necessary?

Peer reviewedPublisher PD