Metformin in polycystic ovary syndrome: systematic review and meta-analysis

The original publication may be found at www.bmj.comObjective To assess the effectiveness of metformin in improving clinical and biochemical features of polycystic ovary syndrome. Design Systematic review and meta-analysis. Data sources Randomised controlled trials that investigated the effect of metformin compared with either placebo or no treatment, or compared with an ovulation induction agent. Selection of studies 13 trials were included for analysis, including 543 women with polycystic ovary syndrome that was defined by using biochemical or ultrasound evidence. Main outcome measure Pregnancy and ovulation rates. Secondary outcomes of clinical and biochemical features of polycystic ovary syndrome. Results Meta-analysis showed that metformin is effective in achieving ovulation in women with polycystic ovary syndrome, with odds ratios of 3.88 (95% confidence interval 2.25 to 6.69) for metformin compared with placebo and 4.41 (2.37 to 8.22) for metformin and clomifene compared with clomifene alone. An analysis of pregnancy rates shows a significant treatment effect for metformin and clomifene (odds ratio 4.40, 1.96 to 9.85). Metformin has an effect in reducing fasting insulin concentrations, blood pressure, and low density lipoprotein cholesterol. We found no evidence of any effect on body mass index or waist:hip ratio. Metformin was associated with a higher incidence of nausea, vomiting, and other gastrointestinal disturbance. Conclusions Metformin is an effective treatment for anovulation in women with polycystic ovary syndrome. Its choice as a first line agent seems justified, and there is some evidence of benefit on variables of the metabolic syndrome. No data are available regarding the safety of metformin in long term use in young women and only limited data on its safety in early pregnancy. It should be used as an adjuvant to general lifestyle improvements and not as a replacement for increased exercise and improved diet.Jonathan M Lord, Ingrid H K Flight, Robert J Norma

A Computational Framework for High-Throughput Isotopic Natural Abundance Correction of Omics-Level Ultra-High Resolution FT-MS Datasets

New metabolomics applications of ultra-high resolution and accuracy mass spectrometry can provide thousands of detectable isotopologues, with the number of potentially detectable isotopologues increasing exponentially with the number of stable isotopes used in newer isotope tracing methods like stable isotope-resolved metabolomics (SIRM) experiments. This huge increase in usable data requires software capable of correcting the large number of isotopologue peaks resulting from SIRM experiments in a timely manner. We describe the design of a new algorithm and software system capable of handling these high volumes of data, while including quality control methods for maintaining data quality. We validate this new algorithm against a previous single isotope correction algorithm in a two-step cross-validation. Next, we demonstrate the algorithm and correct for the effects of natural abundance for both 13C and 15N isotopes on a set of raw isotopologue intensities of UDP-N-acetyl-D-glucosamine derived from a 13C/15N-tracing experiment. Finally, we demonstrate the algorithm on a full omics-level dataset

Method and System for Identification of Metabolites Using Mass Spectra

A method and system is provided for mass spectrometry for identification of a specific elemental formula for an unknown compound which includes but is not limited to a metabolite. The method includes calculating a natural abundance probability (NAP) of a given isotopologue for isotopes of non-labelling elements of an unknown compound. Molecular fragments for a subset of isotopes identified using the NAP are created and sorted into a requisite cache data structure to be subsequently searched. Peaks from raw spectrum data from mass spectrometry for an unknown compound. Sample-specific peaks of the unknown com- pound from various spectral artifacts in ultra-high resolution Fourier transform mass spectra are separated. A set of possible isotope-resolved molecular formula (IMF) are created by iteratively searching the molecular fragment caches and combining with additional isotopes and then statistically filtering the results based on NAP and mass-to-charge (m/2) matching probabilities. An unknown compound is identified and its corresponding elemental molecular formula (EMF) from statistically-significant caches of isotopologues with compatible IMFs

Decision support and the effectiveness of web-based delivery and information tailoring for bowel cancer screening : an exploratory study

Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females throughout the developed world. Population screening using fecal occult blood tests (FOBTs) facilitates early detection and greater chance of survival, but participation rates are low. We developed a Web-based decision tool to provide information tailored to an individual&rsquo;s decision stage for CRC screening and attitude toward screening utilizing the Preventive Health Model (PHM) and Precaution Adoption Process Model (PAPM) as theoretical frameworks for screening behavior. We describe the practical steps employed in the tool&rsquo;s design and the subsequent conduct of an exploratory study.Objective: To design a decision tool for CRC screening and conduct an exploratory study among average-risk men and women to (1) test the impact of message type (tailored vs non-tailored) and message delivery modality (Web-based vs paper-based) on attitudes toward screening and screening uptake, and (2) investigate the acceptability of the decision tool and relevance of materials.Methods: Participants (n = 100), recruited from a population sample of men and women aged 50-76 residing in urban Adelaide, Australia, were randomly assigned to a control group or one of 4 interventions: (1) Web-based and tailored information, (2) paper-based and tailored information, (3) Web-based and non-tailored (generic) information, or (4) paper-based and non-tailored information. Participation was augmented by snowball recruitment (n = 19). Questionnaires based on PHM variables were administered pre- and post-intervention. Participants were given the opportunity to request an FOBT. Following the intervention, participants discussed the acceptability of the tool.Results: Full data were available for 87.4% (104/119) of participants. Post-intervention, perceived susceptibility scores for individuals receiving tailored information increased from mean 10.6 (SD 2.1) to mean 11.8 (SD 2.2). Scores on self-efficacy increased in the tailored group from mean 11.7 (SD 2.0) to mean 12.6 (SD 1.8). There were significant time x modality x message effects for social influence and salience and coherence, reflecting an increase in these scores for tailored Web-based participants only; social influence scores increased from mean 11.7 (SD 2.6) to mean 14.9 (SD 2.3), and salience and coherence scores increased from mean 16.0 (SD 2.2) to mean 17.7 (SD 2.1). There was no greater influence of modality or message type on movement toward a decision to screen or screening uptake, indicating that neither tailored messages nor a Web modality had superior effect. Overall, participants regarded tailored messages positively, but thought that the Web tool lacked &ldquo;media richness.&rdquo;Conclusions: This exploratory study confirms that tailoring on PHM predictors of CRC screening has the potential to positively address attitudes toward screening. However, tailoring on these variables did not result in significantly increased screening uptake. Future research should consider other possible psychosocial influences. Mode of delivery did not affect outcomes, but as a delivery medium, the Web has economic and logistical advantages over paper.<br /

Interesting magnetic properties of Fe1−x_{1-x}Cox_xSi alloys

Solid solution between nonmagnetic narrow gap semiconductor FeSi and diamagnetic semi-metal CoSi gives rise to interesting metallic alloys with long-range helical magnetic ordering, for a wide range of intermediate concentration. We report various interesting magnetic properties of these alloys, including low temperature re-entrant spin-glass like behaviour and a novel inverted magnetic hysteresis loop. Role of Dzyaloshinski-Moriya interaction in the magnetic response of these non-centrosymmetric alloys is discussed.Comment: 11 pages and 3 figure

Mapping from visual acuity to EQ-5D, EQ-5D with vision bolt-on, and VFQ-UI in patients with macular edema in the LEAVO trial

Objectives Mappings to convert clinical measures to preference-based measures of health such as the EQ-5D-3L are sometimes required in cost-utility analyses. We developed mappings to convert best-corrected visual acuity (BCVA) to the EQ-5D-3L, the EQ-5D-3L with a vision bolt-on (EQ-5D V), and the Visual Functioning Questionnaire-Utility Index (VFQ-UI) in patients with macular edema caused by central retinal vein occlusion. Methods We used data from Lucentis, Eylea, Avastin in vein occlusion (LEAVO), which is a phase-3 randomized controlled trial comparing ranibizumab, aflibercept, and bevacizumab in 463 patients with observations at 6 time points. We estimated adjusted limited dependent variable mixture models consisting of 1 to 4 distributions (components) using BCVA in each eye, age, and sex to predict utility within the components and BCVA as a determinant of component membership. We compared model fit using mean error, mean absolute error, root mean square error, Akaike information criteria, Bayesian information criteria, and visual inspection of mean predicted and observed utilities and cumulative distribution functions. Results Mean utility scores were 0.82 for the EQ-5D-3L, 0.79 for the EQ-5D V, and 0.88 for the VFQ-UI. The best-fitting models for the EQ-5D and EQ-5D V had 2 components (with means of approximately 0.44 and 0.85), and the best-fitting model for VFQ-UI had 3 components (with means of approximately 0.95, 0.74, and 0.90). Conclusions Models with multiple components better predict utility than those with single components. This article provides a valuable addition to the literature, in which previous mappings in visual acuity have been limited to linear regressions, resulting in unfounded assumptions about the distribution of the dependent variable

Patterns of participation over four rounds of annual fecal immunochemical test-based screening for colorectal cancer: what predicts rescreening?

Published online: 01 August 2017Background: Participation at the recommended intervals is critical for screening to be effective in reducing colorectal cancer (CRC) incidence. This study describes patterns of screening participation over four rounds of fecal immunochemical testing (FIT) to identify whether demographic variables and prior screening satisfaction are significantly associated with patterns of re-participation. Methods: Baseline surveys were mailed to 4000 South Australians randomly selected from the electoral-roll. Respondents (n = 1928/48.2%) were offered four annual FIT rounds. Screening participation and satisfaction at each round were recorded. Results: Study participation was 58.5, 66.9, 73.1 and 71.4% respectively over four rounds. Three participation patterns were described: consistent participation (43.1%), consistent non-participation (26.4%) and inconsistent participation (changeable; 30.5%), including intermittent and sustained change patterns. Sustained change described those who changed participatory behavior and then maintained for at least two rounds (n = 375/19.5%). Older people, and those not working were most likely to sustain participation. Younger invitees, especially men, were more likely to change participatory behavior and sustain the change. People with higher disadvantage, less education, not working and with no prior (pre-trial) screening experience were more likely to start participating and drop out. People dissatisfied with a prior screening test, including finding aspects embarrassing or unpleasant, were also more likely not to participate in annual screening or to drop out. Conclusions: The findings identify those at risk of non- or inconsistent participation in rescreening. They should aid targeting of interventions for demographic groups at risk and ensuring screening experiences are not perceived as unpleasant or difficult.Joanne M. Osborne, Carlene Wilson, Amy Duncan, Stephen R. Cole, Ingrid Flight, Deborah Turnbull, Donna L. Hughes and Graeme P. Youn

Long-Term Trends in Phytoplankton Chlorophyll a and Size Structure in the Benguela Upwelling System

This is the final version. Available from American Geophysical Union (AGU) via the DOI in this record.The Benguela Upwelling System (BUS) is among the most productive ecosystems globally, supporting numerous fisheries and ecosystem services in Southern Africa. Sea-viewing Wide Field-of-view Sensor and Moderate-resolution Imaging Spectroradiometer-Aqua chlorophyll a (Chla) concentrations between September 1997 and February 2018 were used to investigate long-term trends in phytoplankton biomass and size structure (microphytoplankton [>20 μm], nanophytoplankton [2–20 μm], and picophytoplankton [<2 μm]) in the Northern Benguela, Southern Benguela (SB), and Agulhas Bank (AB) shelf and open ocean regions of the BUS. Trends in upwelling and correlations with Chla and size structure were examined. Increasing Chla and microphytoplankton trends occurred in the Northern Benguela shelf and open ocean, while decreases were evident on the SB shelf in all seasons. In the SB open ocean, small increases occurred during austral winter, with a decrease in spring. On the AB shelf, increases in Chla and microphytoplankton occurred in summer with decreases during the other seasons. Patterns differed in the AB open ocean, with increases in winter and spring and decreases in summer and autumn. Although R 2 values indicated that linear trends accounted for a reasonable portion of the variance, and most trends were statistically significant, they showed only small changes on the shelf domains and little to no change in the open ocean. Strong correlations between upwelling, Chla, and the size classes were observed, but distinct seasonal differences occurred in each region. This is the first 20-year analysis of phytoplankton biomass and community structure in the BUS and provides a baseline against which future changes can be monitored.NERC National Centre for Earth ObservationSouth African National Research Foundation (NRF)South African Department of Environmental Affair