Measuring research impact: a large cancer research funding programme in Australia

Background: Measuring research impact is of critical interest to philanthropic and government funding agencies interested in ensuring that the research they fund is both scientifically excellent and has meaningful impact into health and other outcomes. The Beat Cancer Project (BCP) is a AUD $34 m cancer research funding scheme that commenced in 2011. It was initiated by an Australian charity (Cancer Council SA), and supported by the South Australian Government and the state’s major universities. Methods: This study applied Buxton and Hanney’s Payback Framework to assess research impact generated from the BCP after 3 years of funding. Data sources were an audit of peer-reviewed publications from January 2011 to September 2014 from Web of Knowledge and a self-report survey of investigators awarded BCP research funding during its first 3 years of implementation (2011–2013). Of the 104 surveys, 92 (88 Results: The BCP performed well across all five categories of the Payback Framework. In terms of knowledge production, 1257 peer-reviewed publications were generated and the mean impact factor of publishing journals increased annually. There were many benefits to future research with 21 respondents (23$1 that the cancer charity invested, the BCP gained an additional AUD $6.06. Five projects (5%) had informed policy and 5 (5%) informed product development, with an additional 31 (34%) and 35 (38%) projects, respectively, anticipating doing so. In terms of health and sector and broader economic benefits, 8 (9%) projects had influenced practice or behaviour of health staff and 32 (34%) would reportedly to do so in the future. Conclusions: Research impact was a priority of charity and government funders and led to a deliberate funding strategy. Emphasising research impact while maintaining rigorous, competitive processes can achieve the joint objectives of excellence in research, yielding good research impact and a high rate of leverage for philanthropic and public investment, as indicated by these early results

Understanding barriers to involving community midwives in identifying research participants; experience of the first Steps randomised controlled trial

- Objective: To explore barriers to the involvement of community midwives in identifying women in early pregnancy as potential participants in the XX, a randomised controlled trial of a new intervention to provide health and parenting support to potentially vulnerable women. - Design: Descriptive qualitative investigation using semi-structured audio-recoded interviews. - Setting: Community midwifery offices. - Participants: Volunteer sample of 13 community midwives. - Measurement: Themes derived from content analysis. - Findings: Understanding of their role in the research process was unclear to many midwives. Confusion arose about the difference between potential participant identification and trial recruitment. There were concerns about the eligibility criteria and it was suggested that there was insufficient time during booking appointments, and sometimes insufficient information, to determine potential eligibility. Midwives had concerns about some aspects of the intervention, which incorporated routine midwifery care, and had expectations that women may not like a group programme. This may have led some not to mention the trial. They were, however positive about the programme's potential for beneficial impacts on mothers and infants. - Key conclusions: Dedicated research midwives may be the best option if research studies need to identify potential participants early in pregnancy, so that they can communicate with all their colleagues. - Implications for practice: If community midwives are asked to be involved in time-critical research they are likely to need additional local resources and support

ALMA Reveals the Molecular Medium Fueling the Nearest Nuclear Starburst

We use ALMA to derive the mass, length, and time scales associated with the nuclear starburst in NGC 253. This region forms ~2 M_sun/yr of stars and resembles other starbursts in scaling relations, with star formation consuming the gas reservoir 10 times faster than in galaxy disks. We present observations of CO, the high effective density transitions HCN(1-0), HCO+(1-0), CS(2-1), and their isotopologues. We identify ten clouds that appear as peaks in line emission and enhancements in the HCN-to-CO ratio. These clouds are massive (~10^7 M_sun) structures with sizes (~30 pc) similar to GMCs in other systems. Compared to disk galaxy GMCs, they show high line widths (~20-40 km/s) given their size, with implied Mach numbers ~90. The clouds also show high surface (~6,000 M_sun/pc^2) and volume densities (n_H2~2,000 cm^-3). Given these, self-gravity can explain the line widths. This short free fall time (~0.7 Myr) helps explain the more efficient star formation in NGC 253. We also consider the starburst region as a whole. The geometry is confused by the high inclination, but simple models support a non-axisymmetric, bar-like geometry with a compact, clumpy region of high gas density embedded in an extended CO distribution. Even for the whole region, the surface density still exceeds that of a disk galaxy GMC. The orbital time (~10 Myr), disk free fall time (<~ 3 Myr), and disk crossing time (<~ 3 Myr) are each much shorter than in a normal spiral galaxy disk. Some but not all aspects of the structure correspond to predictions from assuming vertical dynamical equilibrium or a marginally stable rotating disk. Finally, the CO-to-H2 conversion factor implied by our cloud calculations is approximately Galactic, contrasting with results showing a low value for the whole starburst region. The contrast provides resolved support for the idea of mixed molecular ISM phases in starburst galaxies.Comment: Accepted for publication in the Astrophysical Journal. 31 pages, 16 Figure

Management of Chlamydia Cases in Australia (MoCCA): protocol for a non-randomised implementation and feasibility trial

INTRODUCTION: The sexually transmitted infection chlamydia can cause significant complications, particularly among people with female reproductive organs. Optimal management includes timely and appropriate treatment, notifying and treating sexual partners, timely retesting for reinfection and detecting complications including pelvic inflammatory disease (PID). In Australia, mainstream primary care (general practice) is where most chlamydia infections are diagnosed, making it a key setting for optimising chlamydia management. High reinfection and low retesting rates suggest partner notification and retesting are not uniformly provided. The Management of Chlamydia Cases in Australia (MoCCA) study seeks to address gaps in chlamydia management in Australian general practice through implementing interventions shown to improve chlamydia management in specialist services. MoCCA will focus on improving retesting, partner management (including patient-delivered partner therapy) and PID diagnosis. METHODS AND ANALYSIS: MoCCA is a non-randomised implementation and feasibility trial aiming to determine how best to implement interventions to support general practice in delivering best practice chlamydia management. Our method is guided by the Consolidated Framework for Implementation Research and the Normalisation Process Theory. MoCCA interventions include a website, flow charts, fact sheets, mailed specimen kits and autofills to streamline chlamydia consultation documentation. We aim to recruit 20 general practices across three Australian states (Victoria, New South Wales, Queensland) through which we will implement the interventions over 12–18 months. Mixed methods involving qualitative and quantitative data collection and analyses (observation, interviews, surveys) from staff and patients will be undertaken to explore our intervention implementation, acceptability and uptake. Deidentified general practice and laboratory data will be used to measure pre-post chlamydia testing, retesting, reinfection and PID rates, and to estimate MoCCA intervention costs. Our findings will guide scale-up plans for Australian general practice. ETHICS AND DISSEMINATION: Ethics approval was obtained from The University of Melbourne Human Research Ethics Committee (Ethics ID: 22665). Findings will be disseminated via conference presentations, peer-reviewed publications and study reports

The burden of diabetes mellitus during pregnancy in low- and middle-income countries : a systematic review

Peer reviewedPublisher PD

Optimal Dose of Spinal Bupivacaine on Maternal and Fetal Outcomes in Parturients Undergoing Combined Technique for Labor Analgesia: A Randomized Double Blinded Prospective Study

Study Objectives: Maternal hypotension and fetal bradycardia (FB) are recognized complications of combined spinal epidural. Our purpose was to ascertain which of 3 common doses of spinal bupivacaine results in optimal analgesia with minimal side effects, assuming the lowest dose fills all criteria. Design: Prospective, randomized clinical trial. Setting: Labor and Delivery Unit of 514-bed urban teaching hospital. Patients, Interventions and Measurements: Patients were assigned to receive an intrathecal dose of 20 mcg of fentanyl with either 2.5 mg, 1.66 mg, or 1.25 mg of isobaric bupivacaine. Visual Analog Scale (VAS) Pain Score, fetal heart rate (FHR), maternal blood pressure (BP), number of hypotensive episodes, doses of vasopressors, nitroglycerin and mode of delivery were recorded at various time points. Main results: 164 patients were enrolled: 66 receiving 1.25 mg, 50 in the 1.66 mg group and 48 in the 2.5 mg. At 6 and 10 minutes, we recorded in the 1.66 mg group: 4.7% and 4.6%, 18.9% and 23.9% fewer hypotensive episodes compared with the 1.25 mg and the 2.5 mg groups respectively and significantly more hypotensive episodes in the 2.5 mg group (p = 0.025 and 0.019 respectively). There was no statistical difference in vasopressors use, mode of delivery or FB. The VAS decreased equally by an average of 7–10 points among all groups. Conclusion: The 1.66 mg spinal dose was associated with the least hypotensive episodes and equivalent pain relief as the 2.5 mg. The 1.25 mg and 1.66 mg doses allowed for adequate BP and FHR stability. Clinical Trial: Study registered on the ClinicalTrial.gov website under the NCT number NCT02159807

Magnetic resonance imaging phantoms for quality-control of myocardial T1 and ECV mapping: specific formulation, long-term stability and variation with heart rate and temperature

Background: Magnetic resonance imaging (MRI) phantoms are routinely used for quality assurance in MRI centres; however their long term stability for verification of myocardial T1/ extracellular volume fraction (ECV) mapping has never been investigated. Methods: Nickel-chloride agarose gel phantoms were formulated in a reproducible laboratory procedure to mimic blood and myocardial T1 and T2 values, native and late after Gadolinium administration as used in T1/ECV mapping. The phantoms were imaged weekly with an 11 heart beat MOLLI sequence for T1 and long TR spin-echo sequences for T2, in a carefully controlled reproducible manner for 12 months. Results: There were only small relative changes seen in all the native and post gadolinium T1 values (up to 9.0 % maximal relative change in T1 values) or phantom ECV (up to 8.3 % maximal relative change of ECV, up to 2.2 % maximal absolute change in ECV) during this period. All native and post gadolinium T2 values remained stable over time with <2 % change. Temperature sensitivity testing showed MOLLI T1 values in the long T1 phantoms increasing by 23.9 ms per degree increase and short T1 phantoms increasing by 0.3 ms per degree increase. There was a small absolute increase in ECV of 0.069 % (~0.22 % relative increase in ECV) per degree increase. Variation in heart rate testing showed a 0.13 % absolute increase in ECV (~0.45 % relative increase in ECV) per 10 heart rate increase. Conclusions: These are the first phantoms reported in the literature modeling T1 and T2 values for blood and myocardium specifically for the T1mapping/ECV mapping application, with stability tested rigorously over a 12 month period. This work has significant implications for the utility of such phantoms in improving the accuracy of serial scans for myocardial tissue characterisation by T1 mapping methods and in multicentre work

A medical device-grade T1 and ECV phantom for global T1 mapping quality assurance - the T1_1 Mapping and ECV Standardization in cardiovascular magnetic resonance (T1MES) program

$\textbf{Background:}$ T$_1$ mapping and extracellular volume (ECV) have the potential to guide patient care and serve as surrogate end-points in clinical trials, but measurements differ between cardiovascular magnetic resonance (CMR) scanners and pulse sequences. To help deliver T$_1$ mapping to global clinical care, we developed a phantom-based quality assurance (QA) system for verification of measurement stability over time at individual sites, with further aims of generalization of results across sites, vendor systems, software versions and imaging sequences. We thus created T1MES: The T1 Mapping and ECV Standardization Program. $\textbf{Methods:}$ A design collaboration consisting of a specialist MRI small-medium enterprise, clinicians, physicists and national metrology institutes was formed. A phantom was designed covering clinically relevant ranges of T$_1$ and T$_2$ in blood and myocardium, pre and post-contrast, for 1.5 T and 3 T. Reproducible mass manufacture was established. The device received regulatory clearance by the Food and Drug Administration (FDA) and Conformité Européene (CE) marking. $\textbf{Results:}$ The T1MES phantom is an agarose gel-based phantom using nickel chloride as the paramagnetic relaxation modifier. It was reproducibly specified and mass-produced with a rigorously repeatable process. Each phantom contains nine differently-doped agarose gel tubes embedded in a gel/beads matrix. Phantoms were free of air bubbles and susceptibility artifacts at both field strengths and T$_1$ maps were free from off-resonance artifacts. The incorporation of high-density polyethylene beads in the main gel fill was effective at flattening the $B_1$ field. T$_1$ and T$_2$ values measured in T1MES showed coefficients of variation of 1 % or less between repeat scans indicating good short-term reproducibility. Temperature dependency experiments confirmed that over the range 15-30 °C the short-T$_1$ tubes were more stable with temperature than the long-T$_1$ tubes. A batch of 69 phantoms was mass-produced with random sampling of ten of these showing coefficients of variations for T$_1$ of 0.64 ± 0.45 % and 0.49 ± 0.34 % at 1.5 T and 3 T respectively. $\textbf{Conclusion:}$ The T1MES program has developed a T$_1$ mapping phantom to CE/FDA manufacturing standards. An initial 69 phantoms with a multi-vendor user manual are now being scanned fortnightly in centers worldwide. Future results will explore T$_1$ mapping sequences, platform performance, stability and the potential for standardization.This project has been funded by a European Association of Cardiovascular Imaging (EACVI part of the ESC) Imaging Research Grant, a UK National Institute of Health Research (NIHR) Biomedical Research Center (BRC) Cardiometabolic Research Grant at University College London (UCL, #BRC/ 199/JM/101320), and a Barts Charity Research Grant (#1107/2356/MRC0140). G.C. is supported by the National Institute for Health Research Rare Diseases Translational Research Collaboration (NIHR RD-TRC) and by the NIHR UCL Hospitals Biomedical Research Center. J.C.M. is directly and indirectly supported by the UCL Hospitals NIHR BRC and Biomedical Research Unit at Barts Hospital respectively. This work was in part supported by an NIHR BRC award to Cambridge University Hospitals NHS Foundation Trust and NIHR Cardiovascular Biomedical Research Unit support at Royal Brompton Hospital London UK

Unveiling the Sigma-Discrepancy in IR-Luminous Mergers I: Dust & Dynamics

Mergers in the local universe present a unique opportunity for studying the transformations of galaxies in detail. Presented here are recent results, based on multi-wavelength, high-resolution imaging and medium resolution spectroscopy, which demonstrate how star-formation and the presence of Red Supergiants and/or Asymptotic Giant Branch stars has lead to a serious underestimation of the dynamical masses of infrared-bright galaxies. The dominance of a nuclear disk of young stars in the near-infrared bands, where dust obscuration does not block their signatures, can severely bias the global properties measured in a galaxy, including mass. This explains why past studies of gas-rich Luminous & Ultraluminous Infrared Galaxies, which have measured dynamical masses using the 1.62 or 2.29 micron CO band-heads, have found that these galaxies are forming m < m* ellipticals. On the other hand, precisely because of dust obscuration, I-band photometry and central velocity dispersions obtained with the Calcium II triplet at 0.85 microns reflect the global properties of the mergers and suggest that all types of merger remnants, including infrared-bright ones, will form m > m* ellipticals. Moreover, merger remnants, including LIRGs, are placed on the I-band Fundamental Plane for the first time and appear to be virtually indistinguishable from elliptical galaxies.Comment: Accepted for publication in The Astrophysical Journal, to appear Feb 20, 2010 v710. 82 pages, 19 Figures, 2 Appendices Minor update to reference